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A continuous flow microwave reactor for organic synthesis

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A CONTINUOUS FLOW MICROWAVE REACTOR FOR
ORGANIC SYNTHESIS
by
Jennifer Marja Sauks
A thesis submitted in conformity with the requirements
for the degree of Masters of Applied Science
Chemical Engineering and Applied Chemistry
University of Toronto
© Copyright by Jennifer Marja Sauks 2011
UMI Number: 1571182
All rights reserved
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UMI 1571182
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A Continuous Flow Microwave Reactor for Organic Synthesis
Jennifer Marja Sauks
Masters of Applied Science
Chemical Engineering and Applied Chemistry
University of Toronto
2011
Abstract
Microwave reactors are important tools in chemical synthesis, as they can lead to unprecedented
reductions in reaction times and improved reaction yields. In order to scale-up the technology
for greater throughput and industrial application, reactor types are moving from batch form to
continuous flow reactors. The purpose of this research was to design, build, verify and model a
continuous flow microwave reactor. The reactor was required to operate under high temperature
and high pressure conditions, and to be connected to in-line gas chromatography/mass
spectrometry, for real time sample analysis.
Specifically, a pressure creating device was developed to enable the reactor to run under high
pressure conditions (< 1100 psi) without the use of a conventional back-pressure device. The
reactor design was verified using two chemical reactions, and an in-line analytic apparatus was
developed to assess the potential for this reactor to operate with in-line GC/MS. Additionally, a
computational fluid dynamic model was developed to better understand the heat and mass
transfer inside the reactor tube.
ii
***
To my parents,
Toomas & Jo Ann Sauks,
my sisters,
Emilie & Katie Sauks,
for all of their love, laughter, and support.
*
Special thanks to
Emma Brisson & Paul O’Brien,
for their friendship and creative insight.
*
Thanks to
Dr. Y. Lawryshyn, Dr. T. Bender, & Dr. M. Organ,
for the unparalleled learning experience.
***
iii
Table of Contents
Table of Contents ........................................................................................................................... iv Nomenclature ............................................................................................................................... viii List of Tables ................................................................................................................................. xi List of Figures ............................................................................................................................... xii List of Appendices ...................................................................................................................... xvii Chapter 1 ......................................................................................................................................... 1 1 Introduction ................................................................................................................................ 1 1.1 Microwave Irradiation......................................................................................................... 2 1.1.1 Dielectric Heating ................................................................................................... 4 1.1.2 Penetration Depth .................................................................................................... 6 1.1.3 ‘Specific’ Microwave Effects ................................................................................. 6 1.2 Microwaves and Chemistry ................................................................................................ 7 1.2.1 Microwave Reactors versus Conventionally Heated Reactors ............................... 7 1.2.2 Types of Microwave Reactors ................................................................................ 8 1.3 Reactors with In-Line Analytics ....................................................................................... 14 1.4 Reactor Modeling .............................................................................................................. 15 1.5 Challenges ......................................................................................................................... 16 Chapter 2 ....................................................................................................................................... 17 2 Research Problem..................................................................................................................... 17 2.1 Motivation and Goals ........................................................................................................ 17 Chapter 3 ....................................................................................................................................... 18 3 The Design of a Continuous Flow Microwave Reactor ........................................................... 18 3.1 Reactor Summary .............................................................................................................. 18 3.2 Reactor Components ......................................................................................................... 20 iv
3.2.1 Syringe Pumps ...................................................................................................... 20 3.2.2 Microwave Zone ................................................................................................... 20 3.2.3 Novel Pressure Creating Device ........................................................................... 25 3.2.4 In-Line Analytics .................................................................................................. 31 Chapter 4 ....................................................................................................................................... 35 4 Reactor Process Variables ........................................................................................................ 35 4.1 Power and Temperature .................................................................................................... 35 4.2 Pressure ............................................................................................................................. 41 4.3 Flow Characteristics and Residence Time ........................................................................ 42 Chapter 5 ....................................................................................................................................... 44 5 Chemistry to Verify the Reactor Design and Operation .......................................................... 44 5.1 Claisen Rearrangement ..................................................................................................... 44 5.1.1 Development of the Reactor Standard Operating Procedure (SOP) ..................... 45 5.1.2 Development of the In-Line Analytics Standard Operating Procedure ................ 48 5.1.3 Long Reactor Operation ........................................................................................ 52 5.1.4 Reactor Mass Balance ........................................................................................... 57 5.2 Benzimidazole Synthesis .................................................................................................. 58 5.2.1 Background ........................................................................................................... 58 5.2.2 Results ................................................................................................................... 59 5.3 Conclusions on the Reactor Design Based on Chemistry ................................................. 60 Chapter 6 ....................................................................................................................................... 62 6 Reactor Model .......................................................................................................................... 62 6.1 Modeling Methodology..................................................................................................... 62 6.1.1 Geometry ............................................................................................................... 63 6.1.2 Model Assumptions .............................................................................................. 65 6.1.3 Modeling Equations .............................................................................................. 66 v
6.1.4 Mesh ...................................................................................................................... 69 6.2 Modeling Results .............................................................................................................. 72 6.2.1 Temperature Profile .............................................................................................. 73 6.2.2 Flow Profile........................................................................................................... 79 6.2.3 Reaction ................................................................................................................ 82 6.3 Discussion ......................................................................................................................... 86 6.3.1 Thermal Results .................................................................................................... 86 6.3.2 Flow Results.......................................................................................................... 87 6.3.3 Reaction Results .................................................................................................... 87 6.4 Model Summary ................................................................................................................ 89 Chapter 7 ....................................................................................................................................... 90 7 Conclusion................................................................................................................................ 90 7.1 Key Features of the Reactor Design and Future Work ..................................................... 91 7.1.1 Silicon Carbide Tube ............................................................................................ 91 7.1.2 Pressure Creating Device ...................................................................................... 92 7.1.3 In-Line Analytics .................................................................................................. 94 7.2 Critique of the Mechanical Aspects of the Reactor Design and Future Work .................. 95 7.3 Critique of the Reactor Standard Operating Procedure and Future Work ........................ 99 7.4 Future Experimental Work.............................................................................................. 100 7.5 Future Work for the Model ............................................................................................. 101 References ................................................................................................................................... 103 Appendix A: Literature Review .................................................................................................. 108 Appendix B: Reactor Parts .......................................................................................................... 116 Appendix C: Process Variables................................................................................................... 125 Appendix D: Experiments ........................................................................................................... 127 D.1 Developing the Standard Operating Procedure ............................................................... 127 vi
D.2 The Standard Operating Procedure for Reactor Configuration A................................... 131 D.3 Experimental Section ...................................................................................................... 133 2-Allylphenol (2, Scheme 1) ........................................................................................... 133 2-Methylbenzimidazole (4, Scheme 2) ........................................................................... 133 D.4 Cleaning the Reactor between Experiments ................................................................... 134 D.5 In-Line Analytics Cleaning ............................................................................................. 135 D.6 The Standard Operating Procedure for Reactor Configuration B ................................... 137 Appendix E: Modeling Details ................................................................................................... 141 E.1 Convection Heat Transfer Coefficient ............................................................................ 141 E.2 Material Properties .......................................................................................................... 142 E.3 Sensitivity Analysis for Material Properties ................................................................... 143 E.4 Mesh Dependency Test ................................................................................................... 145 E.5 Mesh Coordinates ........................................................................................................... 146 E.6 Details of the Model Boundary Conditions .................................................................... 147 vii
Nomenclature
Symbols:
A
– o-Phenylenediamine
B
– 2-Methylbenzimidazole
Di,m
– Mass diffusion coefficient for species i in a mixture
E
– Internal energy
Fr
– Drag force (radial direction)
Fx
– Drag force (axial direction)
g
– Gravity
Gr
– Grashof number
h
– Convective heat transfer coefficient and sensible enthalpy
ℎ!!
– Enthalpy of formation of species j
!!
– Diffusion flux of species i
k
– Thermal conductivity
L
– Length
M
– Molar
Nu
– Nusselt number
P
– Product
p
– Pressure
Pr
– Prandtl number
r
– Radius
Ri
– Net rate of production of species i by chemical reaction
Rj
– Volumetric rate of creation of species j
SM
– Starting material
Sh
– Heat of chemical reaction
viii
Tref
– Reference temperature
!
– Velocity
!!
– Radial velocity
!!
– Axial velocity
x
– Penetration depth
Yi
– Mass fraction of species i
Yj
– Mass fraction of species j
β
– Thermal expansion coefficient
ε’
– Dielectric constant
ε”
– Dielectric loss
µ
– Viscosity
ρ
– Density
tan δ
– Loss tangent
Abbreviations:
CFD
– Computational Fluid Dynamics
GC
– Gas Chromatography
GC/MS
– Gas Chromatography/Mass Spectrometry
GPC
– Gel Permeation Chromatography
HPLC
– High Performance Liquid Chromatography
ID
– Inner Diameter
IR
– Infrared
MACOS
– Microwave Assisted Continuous Organic Synthesis
NMR
– Nuclear Magnetic Resonance
NPT
– National Pipe Thread
OD
– Outer Diameter
PC
– Personal Computer
ix
PCD
– Pressure Creating Device
PEEK
– Polyether Ether Ketone
PFA
– Perfluoroalkoxy
PTFE
– Polytetrafluoroethylene
SiC
– Silicon Carbide
SOP
– Standard Operating Procedure
UHPLC
– Ultra High Performance Liquid Chromatography
UV-Vis
– Ultraviolet Visible Spectroscopy
x
List of Tables
Table 1. Loss tangents for various solvents and solids (for 2.45 GHz, 20ºC) (Kappe et al., 2009).
......................................................................................................................................................... 5 Table 2. Commercially available batch microwaves.................................................................... 10 Table 3. Examples of continuous flow reactors with in-line analytics. ....................................... 15 Table 4. Specifications of the SiC reactor tubes used in this apparatus. ...................................... 24 Table 5. The size of samples collected using the sample loop. .................................................... 49 Table A.1. Literature review of continuous flow microwave reactors published to date. ......... 108 Table B.1. Reactor parts list. ...................................................................................................... 116 Table D.1. Detailed standard operating procedure for Reactor Configuration A (Figure 15, page
38). .............................................................................................................................................. 131 Table D.2. Detailed standard operating procedure for Reactor Configuration B (Figure 5, page
19). .............................................................................................................................................. 137 Table E.1. Material Properties for all liquid materials used in this model................................. 142 Table E.2. Material properties of silicon carbide. ...................................................................... 142 Table E.3. Material properties of the reaction mixture used in this model. ............................... 143 Table E.4. Mesh sizes tested in the dependency test.................................................................. 145 Table E.5. Details of the boundary conditions used for the SiC tube in this model. ................. 147 xi
List of Figures
Figure 1. The electromagnetic spectrum, microwaves highlighted in grey (Kappe et al., 2009). . 2 Figure 2. a) Dipolar polarization: dipoles constantly try to align themselves to an alternating
field, b) ionic conduction: ions constantly moving in the electric field (Kappe et al., 2009). ........ 3 Figure 3. Cross sections of a Pyrex vessel heated by conduction and by microwave irradiation. . 8 Figure 4. Schematics and picture of Organ’s first MACOS reactor. a) Single reactor setup; b,c)
parallel reactor setup (Comer & Organ, 2005a). ........................................................................... 13 Figure 5. Cross-sectional schematic of Reactor Configuration B – the finalized reactor design. 19 Figure 6. Biotage Initiator™ batch microwave (left) and modifications made to the unit (right).
....................................................................................................................................................... 21 Figure 7. An IR camera image taken of a SiC tube heating up under microwave irradiation. .... 22 Figure 8. Reactor tubes (left to right- SiC, aluminum oxide, and quartz).................................... 23 Figure 9. Process flow path in a typical back-pressure regulator (Plast-O-Matirc, 2011). The blue
line represents the flow path through the regulator....................................................................... 26 Figure 10. Schematic of the PCD. ................................................................................................ 28 Figure 11. CombiPAL autosampler shown installed on a GC/MS with the flow cell sitting in the
GC/MS sample tray. ...................................................................................................................... 31 Figure 12. Rotary valve port configurations for the in-line analytic setup. a) Position for
sampling products from the reactor, and b) position for collecting products from the reactor. ... 32 Figure 13. Flow cell a) photograph and b) cross-sectional schematic. ........................................ 34 Figure 14. An image of the SiC tube under microwave irradiation, taken with the IR camera. The
vertical and horizontal temperature profiles of interest are indicated. .......................................... 36 Figure 15. Cross-sectional schematic of Reactor Configuration A.............................................. 38 xii
Figure 16. The heating of air, acetic acid, and toluene in the SiC reactor tube exposed to
microwave irradiation over a range of power values (30 W – 70 W). .......................................... 39 Figure 17. Toluene heated in a SiC reactor tube exposed to microwave irradiation at 50 W over a
range of flow rates......................................................................................................................... 40 Figure 18. Power/temperature curve for a SiC tube heated using microwave irradiation. .......... 41 Figure 19. Vapour pressure curves for common solvents used in organic reactions (Perry &
Green, 2008).................................................................................................................................. 42 Figure 20. Residence time versus flow rate for the SiC reactor tube. .......................................... 43 Scheme 1. The Claisen rearrangement of allyl phenol ether 1 to 2-allyl phenol 2. ..................... 45 Figure 21. Initial experiments of the Claisen rearrangement to determine the baseline operation
of the reactor. Experiments were completed at a flow rate of 25 µL/min at 240˚C (580 psi
pressure) using Reactor Configuration A...................................................................................... 46 Figure 22. Results for the Claisen rearrangement performed over a range of temperatures at a
flow rate of 25 µL/min and 580 psi pressure using Reactor Configuration A. ............................. 48 Figure 23. The area count of starting material and product for repeated sampling using the inline analytics SOP. Area count determined by GC/MS. ............................................................... 51 Figure 24. Percent starting material in each sample taken during the in-line analytics
reproducibility tests. Area count determined by GC/MS. ............................................................. 51 Figure 25. Percent product in each sample taken during the in-line analytics reproducibility tests.
Area count determined by GC/MS................................................................................................ 52 Figure 26. Starting material area count for the Samples and both flow cell injections taken at
each hour during the Long Reaction. Area count determined by GC/MS. ................................... 54 Figure 27. Product area count for the Samples and both flow cells injections taken at each hour
during the Long Reaction. Area count determined by GC/MS..................................................... 55 xiii
Figure 28. The composition of starting material in the Samples and both flow cell injections
taken at each hour during the Long Reaction. Area count determined by GC/MS. ..................... 56 Figure 29. The composition of product in the Samples and both flow cell injections taken at each
hour during the Long Reaction. Area count determined by GC/MS. ........................................... 56 Scheme 2. The synthesis of 2-methylbenzimidazole from o-phenylenediamine and acetic acid. 59 Figure 30. The synthesis of 2-methylbenzimidazole performed over a range of temperatures at a
flow rate of 200 µL/min (30 second residence time) and 650 psi pressure in Reactor
Configuration A. ........................................................................................................................... 60 Figure 31. The synthesis of 2-methylbenzimidazole performed over a range of flow rates at
130˚C and 650 psi pressure in Reactor Configuration A. ............................................................. 60 Figure 32. a) Geometry of the SiC tube studied in this model, b) 2D axisymmetric model of the
SiC tube with domains labeled, and c) boundary zones. .............................................................. 64 Figure 33. The SiC tube (left) and a close up of the mesh (right)................................................ 70 Figure 34. The boundary conditions set on the SiC tube studied in this model. .......................... 71 Figure 35. Model results of the wall and fluid temperature profiles in the SiC tube with 100˚C
hot zone surface temperature at 200 µL/min. ............................................................................... 75 Figure 36. Model results of the wall and fluid temperature profiles in the SiC tube with 200˚C
hot zone surface temperature at 200 µL/min. ............................................................................... 76 Figure 37. Model results of the wall and fluid temperature profiles in the SiC tube with 200˚C
hot zone surface temperature for a flow rate of 25 µL/min. ......................................................... 78 Figure 38. Reactor heating efficiency of the reaction mixture. The models were completed for
the reaction at 100˚C and 200˚C hot zone surface temperature over a range of flow rates. The
plot shows the volume of fluid heated to within 10˚C of the hot zone surface temperature for the
reaction completed. The ideal case is shown in green, which represents the total volume of fluid
found adjacent to the hot zone wall (33.3 %). .............................................................................. 79 xiv
Figure 39. Velocity profiles for the reaction model at 100˚C hot zone surface temperature for a
flow rate of 200 µL/min. ............................................................................................................... 80 Figure 40. Velocity profiles for the reaction model at 200˚C hot zone surface temperature for a
flow rate of 200 µL/min. ............................................................................................................... 81 Figure 41. Model results of the concentration profiles in the SiC tube at 100˚C hot zone surface
temperature (28 % conversion of A into B) for 200 µL/min. ....................................................... 84 Figure 42. Model results of the concentration profiles in the SiC tube at 200˚C hot zone surface
temperature (>99 % conversion of A into B) for 200 µL/min. ..................................................... 85 Figure 43. Experimental versus model results showing the percent conversion of A into B over a
range of temperatures for a residence time of 30 seconds. Experimental results are from Chapter
5. .................................................................................................................................................... 86 Figure 44. Experimental versus model results showing the percent conversion of A into B over
three flow rates. Experimental results are from Chapter 5. .......................................................... 86 Figure 45. A plot of the maximum operating pressure and temperature for continuous flow
microwave reactors found in the literature. Data point 17 is the reactor described in this thesis. 92 Figure 46. The Biotage Initiator™ built-in IR sensor placement for the batch vials and for the
SiC tube. The red circle indicates the area over which the sensor gathers temperature data. The
sensor reports an average temperature value of the entire circle. ................................................. 98 Figure B.1. Schematic of the reactor tube holder....................................................................... 118 Figure B.2. Explosion view of the pressure creating device. ..................................................... 119 Figure B.3. Schematic of the outage tube (OT-1). ..................................................................... 120 Figure B.4. Schematic of the flow cell (FC-1): main view. ....................................................... 121 Figure B.5. Schematic of the flow cell (FC-1): Side A. ............................................................. 122 Figure B.6. Schematic of the flow cell (FC-1): side B............................................................... 123 xv
Figure B.7. Schematic of the flow cell (FC-1): top view. .......................................................... 124 Figure C.2. A typical screen shot from the IR camera software, demonstrating the heating of a
SiC tube at 100 W. The blue graph shows 3 horizontal temperature profiles of the SiC tube,
demonstrating that the horizontal surface temperature is nearly constant. ................................. 126 Figure D.1. Results from the Claisen rearrangement performed with bubble removal and a
reactor prime. Experiments were completed at a flow rate of 25 µL/min for 260˚C (580 psi
pressure) for Reactor Configuration A........................................................................................ 129 Figure D.2. Tracking the removal of starting material during the reactor wash sequence. The
area count represents the total count of the starting material peak from the GC/MS. Reactor
Configuration B was used in this experiment. ............................................................................ 135 Figure D.3. Tracking the removal of starting material during the in-line analytic wash sequence.
Samples were taken from the flow cell using the CombiPAL autosampler. The area count
represents the total count of the starting material peak from the GC/MS. Reaction Configuration
B was used in this experiment..................................................................................................... 136 Figure E.1. The results of the sensitivity analysis on the outlet fluid temperature. The figure
shows the percent difference between the reactions completed with the baseline case (baseline
values for the properties) versus the reactions completed with the properties varied by +/- 25 %.
..................................................................................................................................................... 144 Figure E.2. The results of the sensitivity analysis on the outlet mole fraction of species A. The
figure shows the percent difference between the reactions completed with the baseline case
(baseline values for the properties) versus the reactions completed with the properties varied by
+/- 25 %....................................................................................................................................... 144 Figure E.3. The coordinates used to generate the domain of the SiC tube and generate the mesh
used in this model. ...................................................................................................................... 146 xvi
List of Appendices
Appendix A: Literature Review .................................................................................................. 108 Appendix B: Reactor Parts .......................................................................................................... 116 Appendix C: Process Variables................................................................................................... 125 Appendix E: Modeling Details ................................................................................................... 141 xvii
1
Chapter 1
1
Introduction
Microwave reactors for organic synthesis were first introduced to chemists in the late 1980’s, as
an alternative to hot plates and oil bathes (Kappe, 2004). These reactors use microwave
irradiation, which is part of the electromagnetic spectrum, to heat a sample based on its dielectric
heating properties. For organic chemistry, microwave irradiation poses significant advantages
over conventional heating methods (hot plate, oil bath, etc.) through decreased reaction time,
increased product yield, improved selectivity, and higher bulk operating temperatures (Kappe et
al., 2009). The mechanism by which microwave irradiation improves reaction results is a subject
of great debate, with parties divided over whether thermal effects alone, or ‘special microwave
effects’ are the cause of the improvement (Kappe, 2004; Kappe et al., 2009; Obermayer et al.,
2009).
The first publication that used microwave irradiation for organic chemistry was by Gedye
(1986). Gedye demonstrated significantly reduced reaction times when compared to conventional
heating methods for several reactions (Gedye et al., 1986). At this time, however, microwave
chemistry was conducted using domestic microwave ovens that had little ability to control
process conditions, such as temperature and pressure (Kappe et al., 2009). As a result, reactions
were difficult to perform, results were hard to reproduce, and laboratory accidents were common
due to the excessive pressure build up in the reactors (Kappe et al., 2009). In light of these
difficulties, microwave reactors were largely overlooked by chemists for many years (Kappe et
al., 2009). However, over the past decade, large strides have been made in developing safer and
more reliable dedicated microwave reactors for organic synthesis. Several different reactor
configurations have become commercially available, all with the ability to monitor and control
pressure and temperature. Microwave reactors have become increasingly common in chemical
laboratories, and thousands of reactions have been processed successfully using this technology,
and often with improved results over traditional reactors (Glasnov & Kappe, 2007; Kappe et al.,
2009). Microwave reactors have proven to be useful in fields such as medicinal chemistry,
polymer synthesis, and material sciences (Kappe et al., 2009).
2
This chapter provides an overview on microwave reactors. First an explanation of microwave
irradiation and how it heats up a reaction sample is provided. Next, the benefits and challenges of
using the technology are discussed, and its application for organic chemistry is examined in more
detail, as the technology is compared to conventionally heated reactors. Looking more closely at
microwave systems, batch reactors are highlighted as the most commonly found microwave
reactor to date. However, issues in scaling-up the technology has led to increased interest in
continuous flow microwave reactors, which are discussed in full detail. Specifically, a first
generation MACOS (Microwave Assisted Continuous Organic Synthesis) reactor developed by
Organ and coworkers is discussed. As the chapter concludes, future work for including in-line
analysis in continuous flow microwave reactors is highlighted as an essential move forward to
complete the ideal reactor system. Furthermore, it is noted that modeling of the microwave
reactors can provide important insight into how to improve the reactor designs. Finally, the
challenges faced by the field of MACOS reactors are discussed.
1.1 Microwave Irradiation
Microwave reactors heat samples using electromagnetic irradiation with a frequency between 0.3
to 300 GHz (Figure 1). The main use of microwave irradiation is in the telecommunication and
energy transmission sector, however specific frequencies of 2.45 GHz (12.25 cm wavelength)
have been assigned to household and reactor microwaves in order to avoid interference with
telecommunication applications.
Figure 1. The electromagnetic spectrum, microwaves highlighted in grey (Kappe et al., 2009).
3
The energy carried by electromagnetic irradiation at 2.45 GHz is too low to break molecular
bonds, is lower than that of Brownian motion, and therefore cannot ‘induce’ chemical reactions
by means of direct absorption of the energy (Kappe et al., 2009). Instead, energy is transferred to
a sample through a dielectric heating response. This response is dependent on the medium having
ideal characteristics for microwave absorption (i.e. must contain dipoles). The electronic portion
of the irradiation is responsible for heating by two mechanisms including dipolar polarization
and ionic conduction. Dipolar polarization is an interaction of the sample with the electric field
and it occurs when the sample has a dipole moment (Figure 2a). The dipoles in the sample align
themselves in the presence of the electric field, and as the field alternates, the dipoles continue to
realign. The constant motion causes molecular friction and dielectric loss, and therefore
generates heat. The degree of heating in a material is dependent on how well the dipoles align in
the electric field (Kappe et al., 2009).
Figure 2. a) Dipolar polarization: dipoles constantly try to align themselves to an alternating
field, b) ionic conduction: ions constantly moving in the electric field (Kappe et al., 2009).
Ionic conduction occurs when solvated charged particles (ions) oscillate and collide in the
presence of the electromagnetic field and therefore generate heat by friction (see Figure 2b). The
heat generated by ionic conduction is much greater than heat generated by the dipolar heating
mechanism. Strongly conducting materials, such as metals, graphite or silicon carbide, are heated
by a related mechanism. Microwave irradiation induces a flow of electrons along the surface of
4
the material. As a result of the resistance caused by the flow of the electrons, these materials
heat up very efficiently when exposed to microwave irradiation. The intense heating has led to
the use of thin film catalyst such as palladium (Comer & Organ, 2005b; He et al., 2004) and gold
(He et al., 2004, 2005), and passive heating elements made of silicon carbide (SiC) (Kremsner &
Kappe, 2006), as aids in driving microwave chemistry (Kappe et al., 2009).
1.1.1
Dielectric Heating
The extent of heating in a microwave reactor is dependent on how a material responds to
microwave irradiation. The dielectric property of a material, called the loss tangent (tan δ),
describes the ability of the material to heat up when exposed to microwave irradiation (Kappe et
al., 2009). The loss tangent is described by:
!"
tan ! = !!
where ε” is the dielectric loss and ε’ is the dielectric constant (Kappe et al., 2009).
A material or mixture that has a high loss tangent is considered to be an effective absorber, and
therefore will heat up efficiently in the presence of microwave irradiation (Kappe et al., 2009).
Table 1 outlines the loss tangents for common solvents used in organic chemistry, as well as for
solid materials typically used as the reactor vessel in microwave reactors. The loss tangent is a
function of microwave frequency and temperature. As a result, a material that is highly
microwave absorbing at low temperatures may experience a decrease in its loss tangent as the
temperature rises, and therefore will require more power to maintain and increase the
temperature past this point (Kappe et al., 2009). Alternatively, a material’s loss tangent may
increase with increasing temperature, and therefore may lead to thermal runaway (Kappe et al.,
2009). For reaction mixtures that absorb microwaves poorly, polar additives such as ionic liquids
or passive heating elements (generally made of SiC) can be added to help boost the heating
efficiency (Kappe et al., 2009; Kremsner & Kappe, 2006).
5
Table 1. Loss tangents for various solvents and solids (for 2.45 GHz, 20ºC) (Kappe et al., 2009).
Ability to Absorb
Microwave
Irradiation
High
Medium
Low
Ability to Absorb
Microwave
Irradiation
Low
Solvent
Loss Tangent (tan δ)
Ethylene glycol
Ethanol
DMSO
2-propanol
Formic acid
Methanol
Nitrobenzene
1-butanol
2-butanol
1,2-dichlorobenzene
NMP
Acetic acid
DMF
1,2-dichloroethane
Water
Chlorobenzene
Chloroform
Acetonitrile
Ethyl acetate
Acetone
Tetrahydrofuran
Dichloromethane
Toluene
Hexane
1.350
0.941
0.825
0.799
0.722
0.659
0.589
0.571
0.447
0.280
0.275
0.174
0.161
0.127
0.123
0.101
0.091
0.062
0.059
0.054
0.047
0.042
0.040
0.020
Solid
Loss Tangent (tan δ)
(x 10-4)
Plexiglass
Phosphate glass
Polyethylene
Polyester
Porcelain
Borosilicate glass
Ceramic
Polystyrene
Teflon
Quartz
57
46
31
28
11
10
5.5
3.3
1.5
0.6
6
1.1.2
Penetration Depth
A key concern for using microwave irradiation for heating is how deep the irradiation penetrates
into the reactor. The exact definition of penetration depth is the point where 37 % of the initial
irradiation power is still present in the sample (Nüchter et al., 2004). It is a function of
temperature and microwave frequency, and generally materials with a high loss tangent have low
penetration depths, as tan δ ~ 1/x where x is the penetration depth (Nüchter et al., 2004). Water,
for example, has a penetration depth of 1.4 cm at 25˚C and 5.7 cm at 95˚C (Nüchter et al., 2004).
Beyond the penetration depth, heating will occur only as a result of conduction and convection.
The limited penetration depth makes it difficult to scale-up microwave reactor technology. As a
result, batch reactors do not typically exceed 5 L, as even with sufficient stirring the efficiency of
heating the system is no longer comparable to conventionally heated batch reactors (Kappe et al.,
2009). In order to overcome the issue of penetration depth, sequential small batches or narrow
channels with continuous flow can be used to increase the throughput in an effective and safe
manner.
1.1.3
‘Specific’ Microwave Effects
The question as to why microwaves favourably enhance chemical reactions has been a hot topic
of debate. Some claim enhancements are a result of purely thermal/kinetic effects (Kappe et al.,
2009; Mingos & Baghurst, 1991; Obermayer et al., 2009), while others claim improvements in
reactions are the combined work of thermal/kinetic effects and ‘specific’ or ‘non-thermal’
microwave effects (Kappe et al., 2009; Loupy, 2002; Perreux & Loupy, 2001). The former group
claims that microwave irradiation rapidly heats the reaction sample to a high bulk temperature
while under pressure (Kappe et al., 2009; Mingos & Baghurst, 1991; Obermayer et al., 2009). As
a result, the solvent is rapidly superheated to temperatures well above its normal boiling point,
therefore creating temperature profiles unattainable by conventional heating methods (Kappe et
al., 2009; Mingos & Baghurst, 1991; Obermayer et al., 2009). However, the latter group suggests
the improvements are a result of ‘non-thermal’ microwave effects (Kappe et al., 2009; Loupy,
2002; Perreux & Loupy, 2001). The ‘non-thermal’ effects include the direct interaction of the
electric field with molecules in the reaction mixture, leading to changes to the pre-exponential
factor or activation energy of a reaction (Kappe et al., 2009; Loupy, 2002; Perreux & Loupy,
2001).
7
Perhaps one of the most significant studies on the existence of ‘non-thermal’ microwave effects
was published by Obermayer and coworkers (2009). In the study, it was demonstrated that
silicon carbide (SiC) acts as a microwave shield, in that it absorbs microwaves very efficiently
and blocks them from passing through the material (Obermayer et al., 2009). Knowing this, they
used a SiC reaction vessel (irradiation heats the sample inside indirectly) and a standard Pyrex
vessel (microwaves heat sample directly), to conduct a series of reactions in parallel in order to
compare the results of full microwave penetration versus microwave irradiation as an indirect
heat source (Obermayer et al., 2009). Both samples had identical operating temperatures,
pressures, and residence times, and thus the results of these experiments could be directly
compared (Obermayer et al., 2009). It was demonstrated that the reaction results for both vessels
were nearly identical, and as such it was concluded that ‘non-thermal’ microwave effects did not
play a role in accelerating the reaction rate (Obermayer et al., 2009).
1.2 Microwaves and Chemistry
1.2.1
Microwave Reactors versus Conventionally Heated Reactors
Microwave reactors offer an alternative method to perform chemical reactions. They also offer
several advantages when compared to the operation of conventionally heated reactors (hot plate,
oil bath, etc). Microwave reactors have increased energy efficiency over conventional reactors,
which are limited by conduction and convection heat transfer through a sample (Figure 3)
(Kappe et al., 2009). Reactors that use microwave irradiation heat samples dielectrically,
meaning the whole sample is heated to the same degree (given the proper dimensions).
Furthermore, these reactors can quickly heat samples to high temperatures, and when operating
under pressure, the solvents can superheat, which has been demonstrated to improve reaction
conditions (Chemat & Esveld, 2001). Additionally, microwave reactors can offer faster reaction
optimization and on-the-fly control of reaction conditions. However, some of the most
interesting advantages to using this technology include those relating to improvements to
reaction results such as increased yields, selectivity, and/or decreased reaction time (Kappe,
2004; Kappe et al., 2009).
8
Figure 3. Cross sections of a Pyrex vessel heated by conduction and by microwave irradiation.
Although there is a strong case for using microwave irradiation for chemical reactions, there are
still some disadvantages to using this technology. Typically, the reaction cannot be monitored
directly and cannot be visually inspected as it progresses (Kappe et al., 2009). Furthermore,
reagents or catalysts cannot be easily added to a reaction part way through a run without
disrupting the entire process (Kappe et al., 2009). With current technology, it is not possible to
scale-up a reaction to large production scale, due to issues of irradiation penetration depth
(Kappe et al., 2009). Lastly, the equipment is expensive when compared to costs attributed with
conventional heating methods (Kappe et al., 2009).
1.2.2
Types of Microwave Reactors
There are two types of microwave reactors that are used to perform chemical reactions, including
batch and continuous flow reactors. Batch reactors have been around the longest and the
technology has infiltrated the commercial market to a much wider degree than continuous flow
systems. However, limitations in reactor scale-up and safety concerns in using large batch
reactors have encouraged the growth of continuous flow reactors.
1.2.2.1
Batch Reactors
To date, the most common microwave reactor for chemistry is the batch reactor. A batch
microwave reactor consists of a microwave generator that sends microwaves through a
9
waveguide to the microwave cavity. The microwave cavity has been specially constructed to
focus the irradiation on the reaction vessel, which is typically a Pyrex sealed vessel containing
anywhere from 200 µL to 10 mL sample (Kappe et al., 2009). The reactor is controlled by
software that regulates the microwave power applied to the sample, based on user inputs for
desired operating temperature and time. There are several commercially available units (Table
2), which can offer a wide range of features including continuous power control, pressure
monitoring and control (through automatic venting), temperature measurement (infrared sensor
or fiber-optic probe), stirring (built-in mechanical or magnetic mechanism), cooling (for postreaction), software for programming reaction methods, and explosion proof microwave cavities
(Kappe et al., 2009). Depending on the supplier, batch microwave reactors have different
operating ranges for temperature and pressure, but typical upper limits are 300ºC and 290 psi
pressure (Kappe et al., 2009). Reaction monitoring is generally not possible in sealed microwave
reactors, and to date only one system has been developed which incorporates inlet and outlet
ports for sampling during a reaction (Kappe et al., 2009).
10
Table 2. Commercially available batch microwaves.
CEM Corporation – Discover Platform,
ExplorerPLS Systems, Voyager Systems,
Peptide Synthesizers (CEM, 2011)
Biotage AB – Initiator Platform
(Biotage, 2011)
Milestone s.r.l. (Milestone Inc., 2011)
Anton Paar GmbH (Anton Paar, 2011)
1.2.2.1.1
Scale-Up of Batch Vessels
Most batch reactors are equipped to produce milligram to gram quantities from processing
volumes of 1-5 mL, however there is great interest in producing kilograms of products from
these reactors.
Although there are dedicated systems that allow for scaled-up processing,
systems are still limited to only a few liters in size. Some of the issues that prevent the scale-up
of batch microwave reactors include safety issues in processing large volumes under high
pressures in a microwave cavity (Kappe et al., 2009). Furthermore, as sample size increases, the
11
limited penetration depth of microwave irradiation leads to poor field homogeneity in the
sample, meaning a greater volume remains unheated by the irradiation (Kappe et al., 2009).
Stirring is required (either mechanical or magnetic) in order to keep conditions homogenous in
the large sample (Kappe et al., 2009). Furthermore, in order to heat large volumes, higher
microwave power is required to heat up the sample, and as a result, the overall efficiency of
heating the reactor decreases (Kappe et al., 2009). Overall, the design and function of the
microwave cavity would need to be re-examined in order to heat larger reaction vessels more
effectively (Kappe et al., 2009).
In order for industry to implement microwave technology, solutions to the above issues on
production scale-up are needed. Potential solutions include using continuous flow, sequential
batch or stop flow reactors. In these systems, the reaction volume under high pressure and high
temperature is kept to a minimum (Kappe et al., 2009; Glasnov & Kappe, 2007).
1.2.2.2
Continuous Flow Reactors
Continuous flow reactors are being considered for microwave chemistry, as they offer increased
throughput compared to batch reactors while maintaining safe volumes. The reactors have been
developed in a variety of channel sizes, including microfluidic channels, mesofluidic channels,
stop-flow systems, or larger scale flow reactors. Continuous flow reactor designs developed to
date include a tubular coil (Wilson et al., 2004; Chen et al., 1990; Cablewski et al., 1994), a Ushaped tube (He et al., 2004, 2005; Baxendale et al., 2006; Pillai et al, 2004), a straight tube
(Comer & Organ, 2005a, 2005b), or a bead-filled vessel (Bagley et al., 2005; Glasnov et al,
2006) made from Pyrex or Teflon. These reactors are placed inside a microwave cavity, and
reactants are pumped through using a syringe or HPLC pump. Process pressure is controlled
using a back-pressure valve, and temperature is monitored using either thermocouples on the
inlet and outlet streams, or the built-in IR sensor of the microwave unit. Some reactor designs
include heat exchangers at the outlet to cool products quickly, in-line analytics for on-the-fly
sample analysis, or recycle loops to increase residence time. Table A1 found in Appendix A
provides a literature review of continuous flow microwave reactors published to date, and
provides a brief outline of the important operating parameters that are relevant to this thesis. It
was found that generally reactors are limited by the materials of construction used for the reactor
tubes and fittings, which cannot withstand temperatures above 200ºC and pressures greater than
12
200 to 300 psi. Although there was a great range in the processing volumes for these reactors,
generally systems could process several liters per hour, which allowed for upwards of several
hundred grams to be produced (as opposed to a few gram scale typically found in batch
microwave reactors). In the survey of literature, it was discovered that some reactors were
limited to homogeneous reactions, as blockages could occur if solids formed (Cablewski et al.,
1994; Wilson et al., 2004). Some designs could support catalysts either immobilized on walls
(Comer & Organ, 2005a, 2005b; He et al., 2004, 2005), beads (Baxendale et al., 2006), or
scaffolds (Chemat et al., 1996; Kirschning et al., 2006), thus enabling the processing of different
heterogeneous reactions. It should be noted that most continuous flow reactors developed to date
have been adapted to fit inside a modified batch microwave unit (Bagley et al., 2005; Baxendale
et al., 2006; Chemat et al., 1996; Chen et al., 1990; Comer & Organ, 2005a, 2005b; Glasnov et
al., 2006; He et al., 2004a, 2004b, 2005; Jachuck et al., 2006; Kirschning et al., 2006; Pillai et al.,
2004; Pipus et al., 2000; Savin et al., 2003; Wilson et al., 2004). There exists only one company
that commercially offers a continuous flow microwave platform at the mesoscale level
(Milestone FlowSYNTH, 2011).
1.2.2.2.1
Microwave Assisted Continuous Organic Synthesis
Microwave Assisted Continuous Organic Synthesis (MACOS) is a field of study dedicated to
developing continuous flow microwave reactors. The reactors address the scale-up issues of
batch reactors, while helping to decrease the total time required to optimize and scale-up a
reaction. MACOS reactors use a novel combination of microwave irradiation to heat a sample,
continuous flow for optimal processing, and narrow channels to enhance heat and mass transfer.
This combination creates a robust technology that can help in the ‘process intensification’ of
chemical laboratories. The goals of MACOS are to increase the speed of reactions through the
use of microwave irradiation and increase throughput by using continuous flow, while taking
advantage of the improved heating and mixing as a result of using narrow channels.
1.2.2.3
Organ’s Prototype: A First Generation MACOS Reactor
A microwave reactor design by Organ’s group focuses on using a straight capillary tube placed
inside a microwave cavity (Comer & Organ, 2005a, 2005b; Kappe et al., 2009). The simplistic
design boasts the novel combination of both microscale flow and microwave irradiation, and
results published to date have demonstrated great potential in the reactor design (Comer &
13
Organ, 2005a, 2005b; Kappe et al., 2009). The initial design included a syringe pump that
infused reactants through a glass capillary tube located within the cavity of a modified Biotage
Initiator™ microwave (Figure 4).
Figure 4. Schematics and picture of Organ’s first MACOS reactor. a) Single reactor setup; b,c)
parallel reactor setup (Comer & Organ, 2005a).
The reactor system demonstrated the potential to produce libraries of compounds, and
experimental optimization could be easily achieved through the ability to change reaction
temperature and residence time on-the-fly (Comer & Organ, 2005a, 2005b; Kappe et al., 2009).
The initial design boasted many benefits over other continuous flow microwave designs. Since a
straight capillary tube was used, it was easier to prevent clogging compared to other reactors,
such as the U-shape or coil reactor designs (Comer & Organ, 2005a, 2005b; Kappe et al., 2009).
The tubes were inexpensive, easy to replace glass capillaries that, if needed, could be coated with
metal films to enhance heating and provide catalytic reaction conditions (Comer & Organ,
2005a, 2005b; Kappe et al., 2009). However, the initial design also had some challenges,
including leaking and/or failing reactor tube fittings, leaking plumbing, and unknown and
uncontrolled pressure of the reactor. At high temperatures, a portion of the reaction could
vapourize and be lost through these leaks, meaning there was uncontrolled residence time and
mass loss, so yield was often lower than expected.
14
1.3 Reactors with In-Line Analytics
MACOS would benefit from in-line analytical capabilities. There are few examples in the
literature of continuous flow reactors coupled to in-line analytical techniques, such as nuclear
magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), and high performance
liquid chromatography (HPLC) (Table 3). In-line analytics allows for continuous monitoring of
reactions in real time. Without in-line analytics, continuous flow reactors will only speed up the
chemical process to the point of analytics, where a bottleneck will form as analysis of samples
would still be one-at-a-time. By coupling analytical techniques to reactors, sampling becomes
less of an afterthought and more of a sequence that happens during the reaction. The whole
process will help to speed up the optimization stage of a reaction, as analysis could occur as soon
as the first products had been processed at steady state conditions. Typically in-line analytic
designs involve either a flow cell device to permit sampling (Table 3a), a direct stream of
products sent through an instrument (Table 3c), or a rotary valve to divert a portion of the
products to analytics (Table 3b and 3d).
15
Table 3. Examples of continuous flow reactors with in-line analytics.
a) Gel permeation chromatography (GPC)
– gas chromatography (GC) used with a
sequential batch microwave reactor
(Hoogenboom & Shubert, 2005).
b) High performance liquid
chromatography (HPLC) used with a
microfluidic continuous flow microwave
reactor (McMullen et al., 2010).
c) Ultraviolet visible spectroscopy (UVVis) used with a mesofluidic continuous
flow microwave reactor (Cáceres et al.,
2005).
d) Ultra high performance liquid
chromatography (UHPLC) used with a
microfluidic continuous flow microwave
reactor (Fang et al., 2010).
UV-Vis
Microwave
Reactor
1.4 Reactor Modeling
Modeling is an essential tool used to understand how reactors operate in terms of heat and mass
transfer, as well as to assess the efficiency of the design. Specifically, computational fluid
dynamic (CFD) modeling is a useful software tool to model fluid flow, kinetics, and other
physical phenomena, and it is widely used in academia and industry to verify reactor designs.
Typically, the modeling of microwave reactors involves complex mathematics due to the
complicated heating mechanism, as described in Section 1.1. There are many examples in the
literature of different models that have been developed to try and predict microwave heating
(Acierno et al., 2004; Ayappa et al., 1992; Franca & Haghighi, 1996; Zhu et al., 2007). However,
the microwave reactor described in this thesis uses a silicon carbide reactor tube, which
16
essentially acts as a shield against microwaves (Obermayer et al., 2009), and as such, the heating
process could be greatly simplified in a CFD model. A simple model would help to describe
how a flowing reaction solution inside the reactor tube is affected by the heated walls, and how
this translates to reaction completion.
1.5 Challenges
Currently, continuous flow microwave reactors are limited by their maximum operating
temperature and pressure. Based on an extensive literature survey, documented in Table A1 in
Appendix A, it was discovered that for continuous flow microwave reactors published to date,
the maximum operating conditions are typically capped at 300ºC and 500 psi. It appears that
these reactors are limited to this operating window as a result of the chosen materials of
construction. Usually the reactor is made of Pyrex or Teflon, and system components such as
tubing and fittings are made of Teflon. Teflon has a melting point of 342°C (Lewis, 2004), but
begins to soften approaching this temperature, especially in the presence of some solvents. As
well, these systems are pressurized by pumps, usually high performance liquid chromatography
(HPLC) or syringe pumps that work in conjunction with a back-pressure regulator, which creates
pressure upstream by restricting the flow. The back-pressure regulators chosen for the job are
often made of Teflon, and so not only have a temperature limitation, but also have a low pressure
rating as well. Additionally, many reactors have not been connected to in-line analytics and
therefore lose efficiency when analytics are required in real time.
17
Chapter 2
2
Research Problem
2.1 Motivation and Goals
A first MACOS (Microwave Assisted Continuous Organic Synthesis) reactor was designed by
Organ and co-workers and has demonstrated the potential to continuously produce compounds
either individually or as small collections (Comer & Organ, 2005a, 2005b). The reactor produced
compounds in less time, with improved yield and selectivity when compared to traditional
methods using hot plates, oil baths or batch microwave reactors (Comer & Organ, 2005a,
2005b). However, the reactor faced several challenges in its design, including leaking
components, unregulated and unknown operating pressure, and unknown thermal characteristics
in the reactor tube. Additionally, it was desired to have the reactor designed with in-line analytics
so it would be connected to gas chromatography/mass spectrometry (GC/MS), enabling reaction
monitoring in real time, and therefore help to accelerate process optimization of a reaction.
This thesis describes the next generation MACOS reactor that has overcome these challenges by
meeting the following design requirements. The reactor had to regulate and withstand high
temperatures and high pressures, so that organic reactions could be conducted completely in the
liquid phase while operating at elevated temperatures. The system had to incorporate in-line
monitoring using gas chromatography/mass spectrometry (GC/MS), so that reactions could be
monitored in real time, as this allows for on-the-fly optimization of reactions. Furthermore, a
computational fluid dynamic model of the heat and mass transfer inside the reactor tube was
required in order to completely understand the operation of the reactor tube. The final reactor
design was to improve reaction efficiency and decrease the overall time spent in traditional
chemical laboratories, as the discovery, optimization, and scale-up of a reaction could be
completed in this one setup.
18
Chapter 3
3
The Design of a Continuous Flow Microwave Reactor
3.1 Reactor Summary
The reactor that has been designed, constructed and commissioned during this thesis is a
continuous flow microwave reactor with in-line analytics that can operate under high
temperature and high pressure conditions. A cross-sectional schematic of the final reactor design
is shown in Figure 5. The reactor can be broken down into four general parts including syringe
pumps, microwave zone, pressure creating device (PCD), and in-line analytics. The operation of
the reactor starts with a pair of syringe pumps continuously infusing reactants through a straight
SiC reactor tube located inside a microwave cavity. Here, the reaction sample is exposed to
microwave irradiation and the reaction takes place. The sample exits the reactor tube and
continues through the PCD, where high pressure nitrogen gas is used to keep the entire reactor
under constant high pressure. The reaction sample passes through a rotary valve, which diverts
the sample to collection or to a flow cell that enables sampling by gas chromatography/mass
spectrometry (GC/MS). The design can withstand temperatures up to 450˚C, pressures up to
1100 psi, and flow rates up to 1000 µL/min. The following sections describe each component,
and a complete list of all reactor components and their specifications can be found in Table B.1
in Appendix B.
19
Figure 5. Cross-sectional schematic of Reactor Configuration B – the finalized reactor design.
20
3.2 Reactor Components
3.2.1
Syringe Pumps
The reactants are pumped into and through the reactor using syringe pumps.
In order to
continuously pump reactants, pairs of pumps are required, so that while one pump infuses
reactants into the reactor, the other pump is in refill mode. The pumps are used in conjunction
with 2.5 mL stainless steel syringes and are capable of withstanding pressures of over several
thousand pounds per square inch, which is well above the system maximum operating pressure
(1100 psi). The pumps are controlled using a personal computer (PC) and an in-house written
program that allows the user to control the flow rate, syringe diameter, and target volume. The
pumps are vertically oriented to ensure that all bubbles can be removed while filling the syringes.
The syringes are connected to the reactor using 1/8” outer diameter (OD) stainless steel tubing
and a 3-way ball valve.
3.2.2
Microwave Zone
The microwave zone is the part of the apparatus that is responsible for heating the reactions. It
consists of a microwave generator and cavity, infrared (IR) camera, reactor tube, and reactor
fittings.
3.2.2.1
Microwave Generator and Cavity
A microwave generator is required to introduce microwave irradiation into a cavity, through
which the reactor tube is located. The irradiation from the generator produces the heating
required to heat a reaction. The microwave unit used in this design was a Biotage Initiator™
which has been modified to accommodate a flow through system. The microwave can operate
between 1 - 400 W and has a microwave irradiation cavity that is 43 mm tall. Several physical
and programming changes were made to the unit in order to allow for the tube to pass through
the cavity. The physical changes included opening up a section of the cavity base to allow the
tube through, machining a window (3.5 cm tall by 3.0 cm wide) into the side wall of the cavity to
allow for an external IR camera to view the reactor tube, disabling the automatic lid and pulling
the internal IR sensor out of the microwave cavity. Programming changes included disabling the
pressure sensor and lid open error message. As a result of these changes, the automatic power
21
setting was also removed and the user had to select the power manually. Please refer to Figure 6
for a picture of the reactor setup using the modified Biotage Initiator™.
Figure 6. Biotage Initiator™ batch microwave (left) and modifications made to the unit (right).
In order to ensure safe operation of the microwave, tin foil was wrapped around the machined
window to prevent microwaves from leaking, and as an additional check, microwave irradiation
levels outside the reactor were monitored using a Microwave Leakage Detector MD-2000 Digital
Readout device. It should be noted that although experiments in this thesis were conducted using
the Biotage Initiator™, any microwave unit with the ability to place a vertical tube inside the
cavity and room for process lines above and below would be compatible with the apparatus.
A stainless steel tube holder (Figure 6 and schematics in Figure B.1 in Appendix B) was
designed to align the reactor tube in the centre of the microwave cavity. Initially, it was believed
that the position of the tube within the microwave cavity could impact how the microwave
irradiation was focused on the tube, and therefore would affect the extent of heating. However,
after numerous experiments were performed with and without the tube holder, it was observed
that the temperature of the tube at various power levels was consistent. As such, it was
determined that the holder was not necessary. By excluding the tube holder, the reactor tube
length that extends beyond the microwave zone could be reduced, and therefore help to reduce
total process line volume.
22
3.2.2.2
Infrared Camera
An IR camera (ThermoVision™ A-Series A320, FLIR Systems) and accompanying software
was used to monitor the surface temperature of the reactor tube in the microwave cavity. An
external IR camera was required due to the inaccuracy of the microwave unit’s built-in IR
camera. Generally the built-in camera reported temperatures anywhere from 25-100°C less than
the actual temperature, as determined using the external IR camera. The inaccurate readings was
a result of the placement and size of the IR sensor with respect to the tube. The built-in IR sensor
was designed to capture the full diameter of a batch vessel, however the tube used in this design
had a much smaller diameter. The temperature readout from the built-in IR camera therefore not
only sensed the tube, but also the air around the tube, which resulted in a lower average
temperature than actually present. Regular temperature sensors (thermocouples) could not be
used in the microwave zone as they are made of metal and would cause arcing in the cavity. As a
result, a viewing window was machined on the outer most wall of the microwave cavity of the
Biotage Initiator™ and an external IR camera placed on a stand in front of the window in order
to continuously monitor the surface temperature. Using the camera software, the average surface
temperature of the SiC tube could be monitored. Please refer to Figure 7 for an example of the IR
camera image.
Figure 7. An IR camera image taken of a SiC tube heating up under microwave irradiation.
23
3.2.2.3
Reactor Tube
A straight SiC tube was selected as the reactor tube in this design. Initial work completed by
Organ and coworkers identified the effectiveness and ease of using short straight narrow tubes in
the microwave cavity (2005a, 2005b). In the literature, continuous flow reactors are usually coils
of Pyrex or Teflon, however these reactors can face issues with blockages due to the formation of
solids (Cablewski et al., 1994; Wilson et al., 2004). Additionally, by using Teflon, the maximum
temperature rating is 342°C (Lewis, 2004), and Pyrex coils could face issues with high pressures.
As a result, it was decided that a straight reactor tube would be most effective in this design.
Three tubes of interest for use in the reactor including straight tubes made of quartz, aluminum
oxide, and SiC (Figure 8).
Figure 8. Reactor tubes (left to right- SiC, aluminum oxide, and quartz).
Pressure tests were conducted using the reactor setup to determine the maximum operating
pressure for each type of tube. It was hypothesized that the weakest point in the reactor design
was the reactor tube to tube fitting connection (reactor tube fittings discussed further in Section
3.2.2.4), as all of the other connections were made with Swagelok fittings rated to pressures in
excess of 2000 psi, which is well above the operating pressure for this reactor. Pressure tests
were conducted by installing each tube in the reactor and then slowly increasing the pressure up
to a maximum pressure of 1100 psi (this is the maximum outlet pressure permitted by the
24
pressure regulator), unless failure occurred first. Pressure tests were conducted in a closed fume
hood and behind a blast shield in order to ensure complete safety in the event of tube or fitting
failure. The results of the tests indicated that the aluminum oxide and SiC tubes and the tube
fitting connection could withstand pressures up to 1100 psi. However, the quartz tube was found
to fracture when tightened in the stainless steel fittings. In addition, when the quartz tube was
pressure tested, it failed at 900 psi pressure. The failure was the result of the top fitting sliding
off of the tube and pressure released through this opening. The tube itself did not shatter during
the failure.
As a result of the pressure tests, it was determined that the reactor could be safely used with
either aluminum oxide or SiC tubes. However, for the purposes of this thesis, SiC tubes were
identified as being most effective as they couple strongly with microwave irradiation, and
therefore heat up exceptionally well under microwave irradiation. This was an attractive feature
for heating reactions containing non-polar solvents or compounds, as the reaction would
otherwise couple poorly with microwave irradiation and would not heat up sufficiently on its
own. In using the silicon carbide reactor tube, a reaction could heat up regardless of it dielectric
constant or polarity.
The specifications of the SiC tubes used in this reactor are outlined below in Table 4.
Table 4. Specifications of the SiC reactor tubes used in this apparatus.
Total Installed Length 17 cm
Total Length in Microwave 4.3 cm
Cavity (Hot Zone)
Tube OD 5 mm
Tube ID 1.75 mm
Reactor Volume in Hot Zone 103.4 µL
3.2.2.4
Reactor Fittings
The reactor design required a connection between SiC reactor tubes and stainless steel tubing
under high temperature and high pressure conditions. In a previous design used by Organ and
coworkers (2005a, 2005b), Upchurch fittings made from Teflon were used. However, these
fittings could not withstand the high temperature environment (reactor tube heating up above
300°C), and fitting failure resulted in loss of pressure and product loss as the reaction mixture
25
evaporated through the fittings. Teflon ferrules were tested in the reactor described in this thesis,
however certain solvents like toluene, under high temperatures and pressures caused the material
to flow, and therefore the seal was compromised. Moving away from Teflon, it was therefore
determined that stainless steel would provide the temperature and pressure limits required, and
was also a good candidate for chemical compatibility. However, with the hard materials
involved (ceramic reactor tubes), conventional ferrules made from stainless steel could not be
used in the fittings, as they would not form a seal against the hard SiC.
In order to use stainless steel tube fittings for the connection between the SiC tube and the rest of
the process lines, a different ferrule material was required. The first successful seal was created
using 100 % graphite straight ferrules (usually used in the application of sealing glass HPLC
columns). Graphite was highly moldable, which allowed it to seal against the ceramic tube, could
withstand high temperatures (500ºC) and was completely inert to chemicals (Restek, 2011).
However, the graphite ferrule connection was unreliable and was found to form very slow leaks,
as a result of the porous nature of the graphite pieces (Restek, 2011). However, a commercially
available ferrule made of a Vespel®/graphite mixture was reported to be better suited for high
pressure applications, as it had less porosity than pure graphite (Restek, 2011). The ferrule still
had enough pliability that it could mould to the hard ceramic surface, and had a temperature
rating of 450˚C and excellent chemical compatibility (Restek, 2011). Additionally, the ferrules
came in a one piece design, which required no back ferrule, and could be retightened multiple
times. Overall it was determined that the best seal for the SiC tubes was the Vespel®/graphite
ferrules used in the stainless steel tube fittings.
3.2.3
Novel Pressure Creating Device
The pressure creating device (PCD) was the apparatus responsible for setting and maintaining the
reactor pressure. The PCD designed in this thesis was able to maintain operating pressures up to
1100 psi using nitrogen gas. Typically, back-pressure regulators (Figure 9) are used in
continuous flow reactors to control pressure upstream. Pressure is created and maintained
upstream of the regulator by using a restriction to the flow path. The restriction, in conjunction
with the presence of dead volumes and the possibility for clogging in the device, made them less
than ideal to use with organic reactions. Furthermore, many back-pressure regulators designed
26
for small volumes and flow paths had relatively low maximum operating pressures and
temperatures, as a result of the choice of materials of construction.
Figure 9. Process flow path in a typical back-pressure regulator (Plast-O-Matirc, 2011). The blue
line represents the flow path through the regulator.
As a result, it became clear that a new method of pressure regulation was needed that could
create and maintain pressure in the reactor up to 1000 psi. Having this pressure limit would allow
many common solvents to remain in liquid phase while heated well above their boiling points.
Ideally the new device would not introduce any restriction to the process flow path, would be
tolerant to high temperatures, and have excellent chemical compatibility.
With these design parameters in mind, a PCD was designed and built with the following
specifications. The final design could pressurize the reactor up to 1100 psi using nitrogen gas,
could withstand high temperatures, and had excellent chemical compatibility due to the materials
of construction (all parts made from 316 stainless steel). The device did not obstruct or place a
restriction in the process flow path in order to create pressure, like in conventional back-pressure
regulators. For safety considerations, the system components were pressure rated to over 2000
27
psi when heated to several hundred degrees Celsius (Swagelok, 2011). Furthermore, the design
closed off the nitrogen gas cylinder from the reactor during the course of a reaction in order to
protect it in the event of reactor failure or vaporization of solvents. For future work, the PCD
could be fully automated with automatic valves and regulators. A cross-sectional view of the
PCD is depicted in Figure 10, and an explosion view of all the PCD components can be found in
Figure B.2 in Appendix B.
28
Figure 10. Schematic of the PCD.
29
3.2.3.1
PCD Operation
The pressure ballast (PB-1) is filled from a gas cylinder to the desired operating pressure prior to
the start of an experiment. The gas cylinder is then isolated from the pressure ballast (PB-1)
using the shut off valve (V-1). Valve V-2 is opened to pressurize the reactor using the nitrogen
gas stored in the pressure ballast (PB-1). This method of pressure regulation replicates the event
of performing chemistry in an open vessel, but under high pressure conditions. The PCD also
isolates the product stream from any expensive equipment required for gas regulation, and
enables the use of any solvent/reaction mixture, as it will only ever come into contact with
stainless steel. After an experiment, pressure is relieved through opening the pressure relief valve
(V-3). The products can be collected out of the base of the sample cylinder (PB-2) at any time by
opening valve (V-6) and directing the rotary valve (RV-1) to the desired position (Figure 5, page
19). Each component in the PCD (Figure 10) is explained further in the following sections.
3.2.3.2
Outage Tube (OT-1)
The purpose of the outage tube is to create an unobstructed flow path from the base of the SiC
tube through the PCD. The tube guides the flow of products into a high pressure environment in
the sample cylinder (PB-2). The outage tube is a stainless steel straight fitting with a male
connecter. The part is a 1/4” OD tube fitting coupled to a 1/4” male NPT connecter. The fitting
uses a Vespel®/graphite reducing ferrule from 1/4” to 3/16”. A 15 cm length of 1/8” OD stainless
steel tubing and bushing is soldered inside the tube fitting, aligned to the very base of the tube
fitting side, as depicted in Figure B.3 in Appendix B.
3.2.3.3
Pressure Tee (PT-1)
The pressure tee is a stainless steel female run tee with a 1/4" female NPT connection that the
outage tube screws into, and two 3/8” OD tube fittings. The tee is the entry point for both the
products from the reactor and the high pressure gas from the pressure ballast (PB-1). The tee has
been sized such that the outage tube (OT-1) extends its tube through the pressure tee with room
around it for the gas to flow through.
3.2.3.4
Sample Cylinder (PB-2)
The sample cylinder is a stainless steel double ended cylinder with a total volume of 50 cm3.
The top opening is attached to the pressure tee (PT-1), and is the entry point for the extended
30
tube from the outage tube (OT-1), and the bottom opening is attached to a 2-way ball (V-6) valve
leading to a rotary valve (RV-1). Products from the reactor drip from the extended outage tube
(OT-1) into the base of the sample cylinder against a closed 2-way ball valve (V-6). The sample
cylinder serves to create a high pressure environment in which the reactor can operate. This
method of exposing the reaction material to pressure does not require an obstruction in the flow
path, but rather provides a high pressure nitrogen gas environment as a means to create pressure.
3.2.3.5
Pressure Relief Tee (PT-2) and Valve (V-3)
The pressure relief tee and the pressure relief ball valve are both stainless steel. The pressure
relief tee directs high pressure gas into the pressure tee and the reactor, or allows for pressure
discharge through opening of the pressure relief ball valve. The valve is used to decrease system
pressure if the operating pressure is too high, as well for depressurizing the reactor at the end of
an experiment.
3.2.3.6
Pressure Ballast (PB-1)
The pressure ballast is a stainless steel 1 L double ended cylinder. The purpose of the ballast is to
regulate the pressure in the reactor. The vessel is filled with nitrogen gas to the desired operating
pressure (as read from the pressure gauge PG-3) and then is disconnected from the nitrogen
pressure cylinder using the shut off valve (V-1). The reactor therefore operates under the
pressure from the pressure ballast. This ensures that in the case of a reactor failure, such as a leak
in a seal or broken reactor tube, the nitrogen gas cylinder is protected against a sudden and
potentially damaging increase in flow rate, while also preventing unnecessary venting of the gas
cylinder. The volume of the pressure ballast is approximately 500 times greater than the reaction
flow path (syringe pumps to the bottom of the outage tube). Having such a large gas environment
compared to the flow path ensures that there are no pressure fluctuations during an experiment.
3.2.3.7
Rupture Disk (RD-1), Pressure Shut Off Valve (V-1) and
Compressed Nitrogen Gas Cylinder
The rupture disk is stainless steel and is rated to 1900 psi. The rupture disk is rated below the
maximum pressure ratings of many of the system components, but above the regular operating
pressure of the system, and thus acts as an extra safety precaution in the event that the system
pressure builds in excess of 1900 psi. The pressure shut off valve disconnects the entire PCD and
31
reactor from the nitrogen pressure cylinder in order to protect it from damage due to either
chemical vapours (if the reactor is operated incorrectly), or in the case of a sudden potentially
damaging increase in flow rate (due to a sudden decrease in pressure due to a system leak or
failure). The compressed nitrogen gas cylinder fills the pressure ballast (PB-1) with nitrogen gas
in order to create a high pressure environment to perform chemistry.
3.2.4
In-Line Analytics
The purpose of the in-line analytics apparatus is to allow for a direct sampling mechanism from
the reactor to gas chromatography/mass spectrometry (GC/MS). The in-line analytics includes a
rotary valve, flow cell, syringe pump, and a GC/MS equipped with a robotic autosampler
(CombiPAL) (Figure 5, page 19). Although the operation of the in-line analytics is currently
manual, the system (pumps, valves, etc.) could be automated, thus allowing for complete
automated sampling from the reactor.
Figure 11. CombiPAL autosampler shown installed on a GC/MS with the flow cell sitting in the
GC/MS sample tray.
3.2.4.1
Operation
The products from the reactor are directed to the 4-port rotary valve. Products can either be sent
to collection, or can be sent to the flow cell for sampling. During sampling, a small volume (0.55
+/-0.02 mL) of products is collected from the reactor and a syringe pump uses solvent (same as
the solvent used in the reaction) to push the sample through to the flow cell. The flow cell has
been designed to allow for the CombiPAL autosampler to take a 1 µL sample of the products,
32
which is then injected into the GC/MS. Between sampling runs, the plumbing and flow cell is
washed using the syringe pump and pure solvent.
3.2.4.2
Rotary Valve (RV-1)
The rotary valve used in the design was a four port, two position valve, with 1/8” x 0.75 mm
ports, 5000 psi pressure limit and was operated manually using a standard electric actuator (VICI
Valco Instruments Canada Corporation). Please refer to Figure 12 for the port configuration of
the rotary valve.
Figure 12. Rotary valve port configurations for the in-line analytic setup. a) Position for
sampling products from the reactor, and b) position for collecting products from the reactor.
When sampling the products for analysis by GC/MS, the valve is set to position (1-2, 3-4)
(products in red in Figure 12a) and approximately 0.55 +/-0.02 mL of products flow from the
reactor into the process lines leading to a closed 3-way ball valve (V-10). The rotary valve is
then set back to position (1-4, 2-3) (Figure 12b), V-10 is set open to the flow cell and a syringe
pump is used to push solvent (shown in blue) through port (3-2) toward the plug of products. The
syringe pump is set to a target volume of 2.0 mL, therefore pumping the plug of products into the
vertical sampling channel of the flow cell where it can be sampled by the CombiPAL. When
collecting products, the rotary valve is set to position (1-4, 2-3). At this time, the products
(shown in red in Figure 12b) are sent to collection. There are 2-way ball valves (V-6 and V-11)
located just outside of ports 1 and 4 to prevent the reactor from completely emptying and to
prevent pressure from escaping while the rotary valve is activated.
33
3.2.4.3
Flow Cell
The flow cell was a device designed to allow for a CombiPAL autosampler to take a sample of
the products from the reactor. The flow cell sat in a GC/MS sample tray and acted as a GC vial.
The CombiPAL autosampler had been programmed to locate and pierce the septa on the top of
the flow cell in order to take a sample of products. The flow cell was designed as a stainless steel
block with an internal vertical sampling channel (0.037 mL volume) with an inlet port at the
bottom of the vertical channel and outlet port near the top, as depicted in Figure 13. Sampling
occurred from the top through a GC/MS injector lid and septa that were screwed into the flow
cell. An additional port located at the top of the sampling channel usually remained closed but
could be opened to allow for additional cleaning if required. The flow cell was attached to the
rotary valve using stainless steel tubing with 1/8” OD. A detailed schematic of the flow cell is
presented in Figures B.4-B.7 in Appendix B.
34
a)
b)
Figure 13. Flow cell a) photograph and b) cross-sectional schematic.
35
Chapter 4
4
Reactor Process Variables
4.1 Power and Temperature
In order to accurately monitor the temperature of the silicon carbide reactor tube under
microwave irradiation, an external infrared camera was used (setup described in Section 3.2.2.2).
Since the power level, and thus the heating, was controlled manually (see Section 3.2.2.1), it was
important to determine what power level would be required to reach a desired average surface
temperature over a variety of conditions. These conditions included different solvents and flow
rates.
In order to monitor the temperature of the SiC tube, a picture of the surface temperature was
taken using the IR camera, and analyzed using the camera software. Pictures of the SiC tube
were taken over a variety of power values and examined. It was found that the vertical and
horizontal temperature profiles (Figure 14) of the tube were nearly constant, meaning the tube
surface heated up to a constant temperature (examples shown in Figure C.1 and C.2 in Appendix
C). As a result, the operational temperature of the SiC tube was taken as the average surface
temperature. It should be noted that as the SiC tube was constantly monitored, the camera
continuously updated the thermal image. The camera had an accuracy of +/- 2˚C (FLIR, 2011) as
stated by the manufacturer, and was also observed to fluctuate +/- 5˚C around an average
temperature value throughout an experiment.
36
Figure 14. An image of the SiC tube under microwave irradiation, taken with the IR camera.
The vertical and horizontal temperature profiles of interest are indicated.
With a method in place to determine the surface temperature of the SiC tube during an
experiment, further tests were conducted to determine how the average surface temperature
changed with different solvents, flow rates and power levels.
The reactor setup used for the following experiments was Reactor Configuration A (Figure 15).
The first experiment studied the effect of different solvents running through the SiC tube during
heating. It was hypothesized that due to the nature of SiC, which absorbs microwave irradiation
very well and essentially shields the contents of the tube to irradiation (Obermayer et al., 2009),
the reactor tube should heat up to the same degree at a given power setting, regardless of what
was flowing through it. This hypothesis was tested by pumping air, acetic acid, and toluene
through the SiC tube over a range of power settings (30 W to 70 W) and at a flow rate of 100
µL/min (Figure 16). It was observed that the SiC tube had approximately the same average
temperature at each power setting, regardless of the type of material flowing through the tube.
The first set of experiments was completed using the following procedure. R-1 was filled with
the solvent (acetic acid, toluene or left open to the atmosphere for air), and V-5 was set to R-1.
Pump P-1 was then filled with 2 mL of solvent or air from R-1. With V-2 closed, PB-1 was filled
with nitrogen gas to 650 psi (acetic acid), and 580 psi (toluene) pressure by opening V-1 and
regulating the nitrogen gas cylinder using PR-1. For the experiment using air, the reactor was
studied at atmospheric conditions, so the reactor was not pressurized using nitrogen gas. Setting
37
V-3 and V-6 closed, V-2 was opened to pressurize the reactor. The microwave MW-1 was turned
on (30 W to 70 W), and the external IR camera was set to monitor the surface temperature of the
SiC tube. V-5 was set to RT-1 and the pump P-1 was then set to infuse at 100 µL/min to a 2 mL
endpoint. Every 30 seconds, an average surface temperature was read from the IR camera and
recorded (Figure 16). After 5 minutes, the microwave MW-1 and pump was turned off, and the
system pressure relieved using V-3.
38
Figure 15. Cross-sectional schematic of Reactor Configuration A.
39
Figure 16. The heating of air, acetic acid, and toluene in the SiC reactor tube exposed to
microwave irradiation over a range of power values (30 W – 70 W).
However, the first set of experiments was conducted at only one flow rate, and therefore the
effects of heating the SiC tube at the same power level but over a range of flow rates had to be
determined. In the second set of experiments, toluene was used to study the effects of flow rate
on surface temperature over a range of 0 – 300 µL/min at a power setting of 50 W (Figure 17).
The second set of experiments was completed using the following procedure. R-1 was filled with
the solvent (toluene), and V-5 was set to R-1. Pump P-1 was then filled with 2 mL of solvent
from R-1. With V-2 closed, PB-1 was filled with nitrogen gas to 580 psi pressure by opening V-1
and regulating the nitrogen gas cylinder using PR-1. Setting V-3 and V-6 closed, V-2 was
opened to pressurize the reactor. The microwave MW-1 was turned on to 50 W, and the external
IR camera was set to monitor the surface temperature of the SiC tube. V-5 was set to RT-1 and
the pump P-1 was then set to infuse to a 2 mL endpoint at 50 µL/min. Every 30 seconds, an
average surface temperature was read from the IR camera and recorded (Figure 17). After 3
minutes, the microwave MW-1 and pump was turned off, and the system pressure relieved using
V-3. This experiment was repeated for flow rates of 100, 200 and 300 µL/min. The final
experiment involved the same procedure as above, but the microwave was not turned on until the
2 mL of toluene had been fully infused and the pump had stopped, in order to take a reading for 0
µL/min.
40
It was observed that once steady state conditions were achieved, the irradiation heated the SiC
tube to the same average surface temperature regardless of the flow rate between 0 – 300
µL/min. It was also concluded from these results that it required 2-3 minutes to reach the desired
steady state temperature.
Figure 17. Toluene heated in a SiC reactor tube exposed to microwave irradiation at 50 W over a
range of flow rates.
Overall, it was concluded that the SiC tube would reach the same average surface temperature at
a given power level, regardless of the speed or type of material flowing through it. With this
conclusion, a power/temperature curve (Figure 18) was generated for the SiC tube. The plot was
generated using the average temperature value attained from three experiments using acetic acid,
toluene, and air at a flow rate of 100 µL/min. The experimental procedure used for these
experiments followed the same method as the experiments described above.
41
Figure 18. Power/temperature curve for a SiC tube heated using microwave irradiation.
When running a reaction, the power required to achieve a desired operating temperature was
determined using Figure 18. All experiments were constantly monitored using the IR camera to
ensure that the proper average surface temperature was maintained.
Throughout the above experiments, the temperatures reported were the surface temperatures of
the SiC tube. Due to the excellent thermal conductivity of SiC (102.6 W/mK) (Saint-Gobain
Ceramics, 2011) the heat would be conducted through the SiC tube very efficiently, however the
temperature of the fluid inside was unknown. In order to determine the temperature profile
within the SiC tube over a range of operating conditions, a more in depth analysis was completed
using computational fluid dynamic modeling (Chapter 6).
4.2 Pressure
The reactor pressure was set and maintained using the PCD (described in Section 3.2.3), which
could sustain operating pressures up to 1100 psi. In order to set the operating pressure for a
reaction, the solvent vapour pressure curve was referenced (Figure 19). The operating pressure
chosen for any particular experiment was set to 50 psi greater than the vapour pressure at the
desired operating temperature of the solvent.
42
Figure 19. Vapour pressure curves for common solvents used in organic reactions (Perry &
Green, 2008).
4.3 Flow Characteristics and Residence Time
The flow rate was set by the syringe pumps, which could be controlled to operate at any flow
rate. However, given that the syringes used in this reactor system only held 2 mL, the flow rate
was limited to a range between 10 µL/min (10 minute residence time) and 1000 µL/min (6
seconds residence time) (Figure 20). At these flow rates, the Reynolds numbers varied from 1 –
120, which indicated that the reactor operates under laminar flow conditions.
43
Figure 20. Residence time versus flow rate for the SiC reactor tube.
44
Chapter 5
5
Chemistry to Verify the Reactor Design and Operation
The Claisen rearrangement of allyl phenyl ether was used to commission the reactor and in-line
analytics. It was also used to develop the standard operating procedure (SOP) for Reactor
Configuration A (Figure 15, page 38). A second reaction between o-phenylenediamine and acetic
acid to produce 2-methylbenzimidazole was used to demonstrate the reproducibility of the SOP.
This chapter outlines these experiments and furthermore characterizes the current state of the
reactor design (Reactor Configuration B – Figure 5, page 19) in terms of its operation and
functionality.
5.1 Claisen Rearrangement
With heat, allyl phenyl ether (1) undergoes the Claisen rearrangement to give 2-allylphenol (2)
(Scheme 1). The reaction is a simple A → B reaction which has been studied extensively in the
literature (Goering & Jacobson, 1958; Klyuchareva et al., 2009; Ziegler, 1988) and is often used
as a standard reaction to verify reactor designs (Bagnell et al., 1996; Kremsner & Kappe, 2006;
Razzaq et al., 2009a), similar to the one described in this thesis. Using a conventionally heated
batch reactor (hot plate, oil bath, etc.), this reaction required many hours at high temperatures
(<200˚C) in toluene in order to reach completion (Kremsner & Kappe, 2006). When translated to
a batch Pyrex vessel heated by microwave irradiation, the reaction did not proceed, as there was
insufficient heat generated by the toluene and reactant 1, which were nonpolar and had a low loss
tangent (see Section 1.1.1) (Kremsner & Kappe, 2006). However, the reaction did proceed to full
conversion under microwave irradiation when a SiC passive heating element was added to the
reaction mixture in the batch Pyrex vessel, at conditions of 250˚C (189 psi pressure) for 105
minutes (Kremsner & Kappe, 2006). Similarly, in using the ionic liquid N-butyl-N’methylimidazolium hexafluorophosphate (bmimPF6) with toluene under microwave irradiation,
the reaction mixture was brought to 250˚C and the transformation was completed in 105 minutes
(Kremsner & Kappe, 2006). With these two methods, the heating element had to be removed
prior to workup and analysis (Kremsner & Kappe, 2006). More recently, it was reported that a
high temperature/high pressure conventionally heated microreactor (X-Cube Flash™) achieved a
45
high yield and purity (<5 % by-products) using toluene as the solvent at 240˚C (1450 psi
pressure) with a 4 minute residence time (Razzaq et al., 2009a, 2009b).
Scheme 1. The Claisen rearrangement of allyl phenol ether 1 to 2-allyl phenol 2.
5.1.1
Development of the Reactor Standard Operating Procedure (SOP)
The Claisen rearrangement was used to develop the SOP of Reactor Configuration A (Figure 15,
page 38). Using literature reaction conditions as a starting point (Kremsner & Kappe, 2006), the
reaction was completed over a range of temperatures at a single flow rate in order to track the
conversion of 1. It was determined that the SOP of the reactor required a three step process
including a reactor prime, followed by the reaction, and then ending with a reactor flush. Using
these three steps, the reactor was found to operate with reproducible results. The following
section outlines the development of the SOP.
To start, several Claisen experiments were completed in order to determine the baseline
operation of the reactor, prior to the development of a SOP. The experiments were completed
using the following procedure. R-1 was filled with Claisen reactants and V-5 was set to R-1.
Pump P-1 was then filled with 2 mL reactants from R-1. With V-2 closed, PB-1 was filled with
nitrogen gas to 580 psi pressure by opening V-1 and regulating the nitrogen gas cylinder using
PR-1. Setting V-3 and V-6 closed, V-2 was opened to pressurize the reactor. The microwave
MW-1 was turned on to 75 W to achieve a 240˚C average surface temperature, and once at
steady state temperature, V-5 was set to RT-1 and the pump was set to infuse to a 2 mL endpoint
at a flow rate of 25 µL/min (4 minute residence time). At the end of the reaction, once the full 2
mL had been infused, the pump P-1 and microwave MW-1 was turned off. The reactor was
allowed to sit for 10 minutes, and then the pressure was relieved to the fume hood by slowly
opening V-3. Products were collected from the base of the reactor by opening V-6 and allowing
the solution to drain out. The sample was then analyzed without further workup or purification
using NMR.
46
The results of the experiments indicated that there was poor reproducibility from experiment to
experiment, as the conversion of 1 varied up to 75 % for the same operating conditions (Figure
21). It was believed that the variation was not a factor of the microwave heating itself, as the
reaction was continuously monitored using the external IR camera and the temperature remained
constant over the experiments. Instead, it was hypothesized that due to the large volume of
process lines from the syringe pumps to the SiC tube, a large volume of the reactants remained in
the process lines at the completion of the reaction and did not make it through to the SiC tube.
Some of the unreacted starting material in the process lines before the SiC tube could have
drained out when the products were collected at the end of the reaction. Furthermore, the
possibility of bubbles in the process lines was thought to have affected the residence time of the
mixture, which also could have affected the reproducibility of the reaction.
Figure 21. Initial experiments of the Claisen rearrangement to determine the baseline operation
of the reactor. Experiments were completed at a flow rate of 25 µL/min at 240˚C (580 psi
pressure) using Reactor Configuration A.
In order to address these issues and arrive at the current SOP, a sequential study was completed
using the Claisen rearrangement. Experiments were conducted using Reactor Configuration A
(Figure 15, page 38) and are documented in Appendix D, Section D.1. A summary of the SOP
derived from these experiments is summarized below and full details of the SOP for Reactor
Configuration A can be found in Appendix D, Section D.2.
47
The SOP for the reactor involved three steps: a reactor prime, the reaction, and a flush sequence.
The reactor prime filled all the process lines with pure solvent (the same that was used in the
reaction), in order to remove any air bubbles in the process lines. It was believed that air bubbles
could cause variable residence time for the reaction mixture, and thus lead to irreproducible
reaction results. The system was primed 2 x 2 mL per pump to ensure all bubbles had been
removed. The prime sequence ended with a plug of pure solvent in the process lines. Next was
the reaction sequence, which began by refilling the pumps with the reactants and starting up all
process equipment. The reactants were then infused into the reactor at a set flow rate,
temperature and pressure. At the end of the reaction, a flush sequence was completed, which
involved the pump refilling with 2 mL of pure toluene, which would subsequently be infused
into the reactor at the same reaction conditions. The flush sequence ensured that all of the
reactants would have passed through the SiC tube and been exposed to irradiation.
Using the SOP described above for Reactor Configuration A, the Claisen rearrangement was
performed over a range of temperatures for a flow rate of 25 µL/min (4 minute residence time)
and 580 psi pressure. The reaction was analyzed without further purification or workup using
NMR spectrometry, and the conversion of 1 with temperature is shown in Figure 22. From these
results, >99 % conversion of starting material was achieved for a 2 mL Claisen reaction sample
processed at a flow rate of 25 µL/min (4 minute residence time), at 260ºC (88 W) and 580 psi
pressure. The experimental procedure can be found in Appendix D, Section D.3.
48
Figure 22. Results for the Claisen rearrangement performed over a range of temperatures at a
flow rate of 25 µL/min and 580 psi pressure using Reactor Configuration A.
In Chapter 3, claims were made of the reactor operation window spanning up to 1100 psi and
450°C. The experiments for the Claisen rearrangement did not use the full potential of the
reactors operating window because the rearrangement is known to produce several side products
when heated above 260°C (Razzaq et al., 2009a).In an attempt to only produce the product 2allyl phenol, temperatures were limited to 260˚C for these experiments.
The Claisen reaction was also used to develop a cleaning sequence for the finalized reactor,
Reactor Configuration B (Figure 5, page 19). It was determined that a total of 100 mL of solvent
was required to clean out the reactor between experiments. Please refer to Appendix D, Section
D.4 for complete details on the development of the cleaning sequence.
5.1.2
Development of the In-Line Analytics Standard Operating
Procedure
The in-line analytic setup, from the collection of products after the rotary valve, to sampling
from the flow cell, required verification of its SOP. Three experiments using the Claisen
rearrangement were conducted in Reaction Configuration B (Figure 5, page 19) to help
characterize the operation of the in-line analytic setup. The first experiment examined the
variability of the sample size collected from the reactor. The second experiment examined the
reproducibility of sampling the same mixture repeatedly from the flow cell. The third experiment
49
determined if the composition of the sample was changed as a result of the in-line analytics SOP.
The results of the final experiment are deferred to Section 5.1.3.1.
The first experiment determined the size of a Claisen reaction sample taken from the reactor
using the in-line analytic setup. The SOP for sampling using the in-line analytics was followed
and was repeated four times to determine the reproducibility of sample size collected. A Claisen
mixture that had just been reacted was sitting in the base of the sample cylinder (PB-2) against a
closed valve V-6. The reactor was still under 580 psi pressure from the reaction just completed.
All process lines in the in-line analytic setup were cleared of all liquids by pumping air through
the lines using PB-3. This included process lines from the solvent pump to the rotary valve and
from the rotary valve to the flow cell. In order to take a sample, the rotary valve was set to
position (1-2, 3-4), and V-10 was closed. V-6 was opened to allow the Claisen mixture to be
pushed by the reactor pressure into the sample loop between the rotary valve and V-10. After 10
seconds, V-6 was closed, and V-10 was opened slowly to drain the collected sample into a
weighed vial. In addition, the rotary valve was set to position (2-3, 1-4), and the solvent pump
(P-3) was set to push 15 mL air through the lines, therefore ensuring that the remaining liquid
sitting in the lines was pushed into the vial. The vial was weighed, and the difference in weight
from before and after the experiment was taken as the total sample collected from the reactor.
The experiment was repeated four times, and the results are presented in Table 5. The average
sample collected using the in-line analytics setup was 0.55 g +/- 0.017 g, which translate to
approximately 0.60 mL of products.
Table 5. The size of samples collected using the sample loop.
Sample Weight of Sample Collected (g)
1
0.564
2
0.540
3
0.538
4
0.571
Average
0.55 +/- 0.017
The second experiment examined the reproducibility of sampling from the flow cell using the inline analytics setup. The reproducibility was tested by repeating the in-line analytics SOP eight
times using the same stock solution of Claisen mixture each time. By comparing the GC/MS
results between each sample injected, the reproducibility of the setup could be assessed. The
experiments involved pumping 10 mL of a Claisen rearrangement mixture of starting materials
50
and products into the base of the sample cylinder (PB-2) against a closed V-6. The reactor was
then pressurized to 580 psi. To sample, V-10 was closed and the rotary valve was switched to
position (1-2, 3-4). The solvent pump (P-3) was filled with toluene, and set to infuse to a 4 mL
endpoint, so the process lines from the solvent pump to the rotary valve were primed. Excess
prime was allowed to flow out of port 4 of the rotary valve and out of V-11 into waste (W-1).
The system was then ready to sample. V-6 was opened to allow the sample to flow into the
sample loop against a closed V-10. After 10 seconds, V-6 was closed. Simultaneously, the
solvent pump (P-3) was started at 5 mL/min for a target volume of 2.0 mL, the rotary valve was
switched to position (2-3, 1-4), and V-10 set open to the flow cell. A target volume of 2.0 mL
was determined to be the minimum volume required to get the very front of the products into the
vertical channel of the flow cell without sampling air bubbles. As soon as the pump was started,
the CombiPAL autosampler was also started. The CombiPAL went through a wash procedure (3
rinses with wash solution, followed by 2 rinses from the flow cell solution) prior to a sample
injection. Once the pump reached its target volume and stopped (after 24 seconds), and the
CombiPAL had completed its wash cycle (1 minute), the CombiPAL took a 1 µL sample from
the flow cell and injected it into the GC/MS for analysis. Each injection taken from the flow cell
was monitored for bubbles. The solvent pump (P-3) was then turned on to 15 mL/min for a target
volume of 30 mL, V-9 was opened, and the whole system was cleaned out using pure toluene.
The wash cycle was repeated with an additional 30 mL with V-9 closed, and the flow cell was
verified to be clean by sampling toluene from the flow cell using the CombiPAL and injecting it
into the GC/MS for analysis. For complete details on the development of the cleaning sequence
for the in-line analytics, please refer to Appendix D, Section D.5. The in-line analytic sampling
procedure was completed 8 times using the same Claisen mixture in order to determine the
reproducibility of the in-line analytics SOP. The results are shown in Figure 23 to 25. Looking at
the reproducibility of the area count from sample to sample, with the exception of sample 4,
there appears to be only a small variation in concentration of samples (Figure 23). The variation
is believed to be a result of the GC/MS method used to analyze the samples, as well as a result of
the high concentration of the samples injected into the GC/MS detector. The highly concentrated
samples could lead to a varied area count reading by the GC/MS from sample to sample. The
results shown in Figure 22 and 23 indicate that the composition of the injections from sample to
sample was very consistent, meaning the in-line analytics had excellent sampling reproducibility.
51
Figure 23. The area count of starting material and product for repeated sampling using the inline analytics SOP. Area count determined by GC/MS.
Figure 24. Percent starting material in each sample taken during the in-line analytics
reproducibility tests. Area count determined by GC/MS.
52
Figure 25. Percent product in each sample taken during the in-line analytics reproducibility tests.
Area count determined by GC/MS.
5.1.3
Long Reactor Operation
With the successful creation of a SOP for Reactor Configuration A and an SOP verified for the
in-line analytics, a final test to determine how the system operated over an extended period of
time was required. This was completed using the Claisen rearrangement in Reactor
Configuration B (Figure 5, page 19) over a Long Reaction (6 hours), over which a study to
further verify the in-line analytics also took place. During the Long Reaction experiment, two
syringe pumps were used to continuously infuse reactants into the reactor. Furthermore, the
reactor was primed using a sample of the initial reaction mixture instead of pure solvent, in order
to reduce dilution effects from the prime. The experiment was completed using the SOP outlined
for Reaction Configuration B in Appendix D, Section D.6.
The power was set to 95 W, which corresponded to an average surface temperature of 275˚C,
and pressure was 580 psi. The experiment was completed at a flow rate of 75 µL/min (1 minute,
20 second residence time), which was chosen so that a large sample would accumulate every
hour. As a result, 6 samples (called Samples A-F) of approximately 0.5 g (Section 5.1.2) were
collected every hour. Samples A, C-F were all collected by draining a sample from V-10. All of
these samples were directly injected into the GC/MS without any workup or dilution. In addition,
Sample A and Sample F were injected in triplicate into the GC/MS in order to verify the GC/MS
method. Sample B was taken using the flow cell setup. Two injections were taken from the flow
53
cell each hour using the CombiPAL autosampler. The first injection was taken using the SOP for
the in-line analytics. While this injection was being processed by the GC/MS (a process that took
approximately 10 minutes), Sample B was held in the flow cell, so that a second injection from
this sample could be made. To ensure that there was still enough Sample B in the flow cell for
the second injection, the solvent pump was set to push an additional 0.2 mL of solvent through
the lines. It should be noted that the microwave had an unexpected power down at 4 hours and
30 minutes, which caused it to shutdown automatically for 8 minutes, 20 seconds. The shutdown
impacted the conversion of starting material to product for the 5th and 6th hour samples.
Furthermore, when sampling from the flow cell, each injection was visually inspected for
bubbles during the injection process. It was observed that on the 3rd hour, the second flow cell
injection contained bubbles, as well as both flow cell injections for the 4th and 5th hour. Having
bubbles in the injection meant less sample was injected in the GC/MS, which translated to a
lower than normal total area count for the starting material and product peaks.
5.1.3.1
Results
The data collected during the Long Reaction was analyzed by GC/MS, which provided an area
count for each species (starting material 1 (SM) and product 2 (P)) at each hour. To evaluate the
results, an average of the SM count and P count for Samples A, C-F was calculated for each hour
(now referred to as Samples). The standard deviation of these values was included in the data as
error bars, in order to show how Samples A, C-F varied at each hour. The first plot of SM area
count (Figure 26) shows large error bars for the Samples at the 1st and 5th hours, which means
that there was a large variation in concentration between Samples A, C-F for these two hours.
Additionally, the variation was confirmed in the second plot of P area count (Figure 27). The
variation in sample concentration is likely a result of the GC/MS method used in this experiment.
Furthermore, as mentioned earlier, these samples were directly injected into the GC/MS without
further dilution, meaning the samples were very concentrated going into the GC/MS detector.
The concentrated samples could have also led to the GC/MS reading inconsistent concentrations
between the samples.
The Samples for each hour were also compared to flow cell samples 1 and 2 (Figures 26 and 27).
Overall, the flow cell samples had lower SM and P area counts compared to the Samples. This
makes sense as the flow cell sampling technique involved the use of toluene to push the product
54
sample from the reactor to the flow cell, and thus would dilute the sample. It should be noted that
the 2nd flow cell sample for the 3rd hour, as well as both flow cell samples for the 4th and 5th
hours have substantially lower area counts than the other flow cell samples. The lower area
counts were a result of the injections containing bubbles, which directly affected the area count,
as less material was injected into the GC/MS.
Figure 26. Starting material area count for the Samples and both flow cell injections taken at
each hour during the Long Reaction. Area count determined by GC/MS.
55
Figure 27. Product area count for the Samples and both flow cells injections taken at each hour
during the Long Reaction. Area count determined by GC/MS.
Also of interest was the composition of the Samples over time (Figure 28 for starting material
and Figure 29 for product). The error bars on these figures represent the variation in the
composition of Samples A, C-F at each hour. The results indicate that the reactor came to steady
state by the 3rd hour, and remained so for the 4th hour. Why the reactor takes 3 hours to achieve
steady state is believed to be a factor of ‘thermal drift’ throughout the entire apparatus. ‘Thermal
drift’ is defined as the slow heating of the PCD and surrounding apparatus over the duration of
the experiment, due to conduction of heat up and down from the SiC tube. Since the system is
made of stainless steel, which is highly conductive, the heat is transferred into the apparatus over
time and thus acts as a pre and post heater for the reaction. In particular, the outage tube (OT-1),
which is a 15 cm long stainless steel tube directly connected to the base of the SiC tube (Figure
B.3 in Appendix B), could have heated up to a high temperature over the course of the reaction,
and therefore continued to expose the reaction mixture to high temperatures. By the 3rd hour,
this ‘thermal drift’ has appeared to have reached its steady state condition. The 5th and 6th hour
data indicate more starting material was present, as a result of the microwave shutdown that
occurred at 4.5 hours.
Examining the data collected from the Samples versus the flow cell samples 1 and 2, the flow
cell samples, with the exception of the 1st and 5th hour, had nearly identical composition. This
56
indicated that the in-line analytics SOP is effective and by using this protocol, reaction samples
can be accurately analyzed.
Figure 28. The composition of starting material in the Samples and both flow cell injections
taken at each hour during the Long Reaction. Area count determined by GC/MS.
Figure 29. The composition of product in the Samples and both flow cell injections taken at each
hour during the Long Reaction. Area count determined by GC/MS.
Overall, the Long Reaction demonstrated the ability of Reactor Configuration B to perform over
an extended period of time. It was determined that the reactor achieved steady state operation
after the 2nd hour, which is thought to be the result of ‘thermal drift’ or the slow heating of the
PCD over time. The Long Reaction was also used to verify the in-line analytics, and it was
57
determined that the system could provide accurate analyses of the reaction mixtures. Overall, the
Long Reaction was essential to determine how the current reactor configuration operates, and to
highlight the challenges faced by the current design.
5.1.4
Reactor Mass Balance
A mass balance of the reactor was conducted using the Claisen rearrangement in Reactor
Configuration A (Figure 15, page 38), in order to determine if any mass was escaping into the
vapour phase and becoming stuck in the PCD. Although the operating pressure was greater than
the vapour pressure of the solvents used, meaning the solvents should remain in liquid phase, an
experiment to verify this was still required. A series of Claisen reactions were conducted in order
to determine the mass balance of the reaction mixture.
The experiments were completed using the following procedure. R-1 was filled with toluene, the
solvent used in the Claisen reaction, and V-5 was set to R-1. Pump P-1 was then filled with 2 mL
solvent from R-1. The pump was then set to infuse the solvent to a 2 mL endpoint back into R-1,
therefore pushing out any bubbles in the pump. Pump P-1 was then refilled with 2 mL solvent
from R-1. V-5 was set to RT-1 and pump P-1 infused the solvent to a 2 mL endpoint into the
reactor. V-6 was set open and any prime overflow was collected into W-1. V-5 was set back to
R-1 and P-1 set to refill with solvent to a 2 mL endpoint. V-5 was switched to RT-1 and pump P1 was set to infuse 2 mL of solvent into the reactor. The refilling and infusing of the pump with
priming solvent was repeated a total of 4 times, meaning 8 mL of solvent was infused into the
reactor. Once the excess solvent had drained into W-1, and no more solution came out of the
reactor, V-6 was closed. R-1 was then filled with Claisen reactants, the vial was weighed, and V5 set open to R-1. P-1 was set to refill to 2 mL endpoint with reactants. R-1 was then weighed
again to determine the total mass into the reactor. For the first set of experiments, there was no
heat and no pressure used, so V-5 was set to RT-1, and P-1 was set to infuse 2 mL of the
reactants into the reactor. Once the pump was done, V-6 was opened, and the solution was
allowed to drain out of the reactor into C-1. The C-1 vial was weighed before and after collecting
the sample to determine the total mass out of the reactor. For the second set of experiments, the
above procedure was followed, but heat and pressure were applied to the Claisen mixture. The
sequence continued from the above procedure (starting after R-1 was weighed) with V-2 closed,
PB-1 filled with nitrogen gas to 580 psi pressure by opening V-1 and regulating the nitrogen gas
58
cylinder using PR-1. V-3 was set to close, and V-2 was opened to pressurize the reactor. The
microwave MW-1 was turned on to 80 W to achieve a 260˚C average surface temperature, and
once at steady state temperature, V-5 was set to RT-1 and the pump was set to infuse to a 2 mL
endpoint at a flow rate of 200 µL/min. At the end of the reaction, once the full 2 mL had been
infused, the pump P-1 and microwave MW-1 was turned off. The reactor was allowed to sit for
10 minutes, and then the pressure was relieved to the fume hood by slowly opening V-3.
Products were collected into a weighed C-1 vial, from the base of the reactor by opening V-6 and
allowing the solution to drain out. C-1 was then weighed to get the final weight of products
collected or mass out of the reactor. These experiments were completed 3 times each. The total
mass balance was calculated by the weight of the products collected divided by the weight of the
reactants infused into the reactor.
The results of these experiments showed that the overall mass balance of the system was nearly
equal, with up to 5 % mass loss. It was determined that this mass loss was not a result of
vapourization of reaction mixtures and accumulation in the PCD, as no evidence of condensation
in the pressure ballast (PB-1) was ever found. It was concluded that due to the small scale of the
experiments, which involved samples no greater than 1.5 g, a 5 % error could be a result of both
weighing error, and varying amounts of liquid film remaining in the process lines.
5.2 Benzimidazole Synthesis
5.2.1
Background
The preparation of 2-methylbenzimidazole by the condensation of o-phenylenediamine with
acetic acid is a valuable reaction for the preparation of molecules possessing important biological
activity (Scheme 2) (Damm et al., 2010). It was reported that a high temperature/high pressure
conventionally heated microreactor (X-Cube Flash™) could process a 1 M solution of ophenylenediamine in acetic acid at 270oC (1885 psi pressure) with a 30 second residence time to
achieve a product yield of 50.7 g (94 % yield) (Damm et al., 2010). It was found that any attempt
to increase flow rate or concentration lead to pumping failure, as the mixture became extremely
viscous (Damm et al., 2010). To date, no report has been published on the continuous flow
microwave synthesis of 2-methylbenzimidazole. The reaction was conducted using the reactor
described in this thesis, as well as using the SOP developed in Section 5.1.1, in order to further
assess the reproducibility of the SOP.
59
Scheme 2. The synthesis of 2-methylbenzimidazole from o-phenylenediamine and acetic acid.
5.2.2
Results
Using Reactor Configuration A (Figure 15, page 38) and the SOP described in Appendix D,
Section D.2, the synthesis of 2-methylbenzimidazole was completed over a range of
temperatures for a flow rate of 200 µL/min (30 second residence time) and 650 psi pressure. The
reaction was analyzed without further purification or workup using NMR spectrometry, and the
conversion of 3 with temperature is shown in Figure 30. Each experiment was performed in
triplicate. From these results, >99 % conversion of 3 was achieved for a 2 mL reaction sample
processed at a flow rate of 200 µL/min (30 second residence time), at 170ºC (48 W) and 650 psi
pressure. The results also show the high degree of reproducibility when using the reactor SOP. It
should be noted that there are error bars for each data point, but for data points 170˚C and 200˚C
the bars are so small that they are not visible in this graph. Additional experiments were
completed to demonstrate the effect of changing the flow rate (and thus residence time) for the
reaction completed at 130°C (Figure 31). As expected, as the flow rate was decreased, meaning a
longer residence time, the reaction result improved and there was a higher degree of conversion
of 3. With an increase in flow rate, the reaction was found to proceed more slowly, as the
residence time decreased, and there was not sufficient time to fully react. The experimental
procedure can be found in Appendix D, Section D.3.
60
Figure 30. The synthesis of 2-methylbenzimidazole performed over a range of temperatures at a
flow rate of 200 µL/min (30 second residence time) and 650 psi pressure in Reactor
Configuration A.
Figure 31. The synthesis of 2-methylbenzimidazole performed over a range of flow rates at
130˚C and 650 psi pressure in Reactor Configuration A.
5.3 Conclusions on the Reactor Design Based on Chemistry
Overall, the Claisen rearrangement and the synthesis of 2-methylbenzimidazole were used to
establish and verify the SOP for both Reactor Configuration A (Figure 15, page 38) and Reactor
Configuration B (Figure 5, page 19). It was determined that Reactor Configuration B achieves
steady state operation at 3 hours, and this is believed to be a result of a ‘thermal drift’ that slowly
heats up the PCD and remaining apparatus. The ‘thermal drift’ is thought to be responsible for
61
pre and post heating of the reaction. The in-line analytic setup and SOP were also verified for
Reactor Configuration B, and demonstrated to provide consistent and accurate in-line sample
analysis. The results obtained throughout the experiments revealed that the reactor operates as
well or better than commercially available continuous flow units that employ electric resistance
heating, and can surpass results obtained using conventional batch microwave reactors. The use
of the SiC reactor tube allowed for a unique environment to perform chemistry using microwave
irradiation. Furthermore, the PCD introduced in this thesis offered a new method to effectively
pressurize a continuous flow reactor without any of the potential mechanical failures or clogging
issues that all conventional, and currently available back-pressure regulators face. To date, there
have been no other continuous flow microwave reactors capable of performing these reactions to
the same degree.
62
Chapter 6
6
Reactor Model
It is very difficult to measure the temperature of a reaction mixture that is heated using
microwave irradiation. Reaction samples are confined to a microwave cavity, in which
traditional thermocouples cannot be used, as metal arcs in the presence of microwave irradiation.
Attempts at monitoring temperature using internal fiber-optic probes, shielded thermocouples or
gas balloon thermometers are effective in only a few instances and otherwise are expensive,
fragile and have a limited temperature range that they can operate in (Kappe, 2009). As a result,
microwave reactors are generally monitored using IR cameras or sensors, which detect the
surface temperature of an object in the microwave reactor. Modeling can therefore be a useful
aid to help understand the thermal profiles within the microwave reactor. Computational fluid
dynamics (CFD) is a numerical modeling technique that can solve mass, energy, and momentum
equations for a given problem. The modeling software (FLUENT version 12.0.1) was used to
develop a model of the SiC reactor tube described in this thesis (Section 3.2.2.3). The model
investigated the temperature, velocity, and concentration profiles in the reactor tube during the
reaction between o-phenylenediamine (A) and acetic acid to produce 2-methylbenzimidazole
(B). The results were compared to experimental results (discussed in Chapter 5) in order to verify
the accuracy of the model. In the following sections, the assumptions and settings for the
development of the model are discussed along with a description of the SiC reactor tube
geometry and its associated mesh. The results discuss how the temperature, velocity, and
concentration profiles developed within the flow domain over a range of temperatures and flow
rates, and the model results are compared to the experimental results.
6.1 Modeling Methodology
In order to develop the CFD model of the SiC reactor tube, the following was required. First, the
assumptions for the reactor system were established. Next, the governing equations that
pertained to the reactor were selected. A mesh was then created of the SiC tube geometry, which
subdivided the entire domain into discrete control volumes. Finally, boundary conditions were
applied to the mesh, and the geometry was imported into the CFD software. At this point, the
software required all of the details of the boundary conditions and material properties. The CFD
63
model then solved the governing equations over the entire domain. These steps are outlined in
detail below for the SiC reactor tube. First, the geometry of the SiC reactor tube studied in the
model is presented.
6.1.1
Geometry
The microwave reactor described in this thesis used a SiC reactor tube. The SiC tube was placed
through the microwave cavity, with a length of 43 mm inside the actual cavity and exposed to
microwave irradiation. This portion of the tube is referred to as the hot zone. The geometry of the
SiC tube used is shown in Figure 32a. As a result of the axisymmetric nature of the SiC tube, the
geometry could be simplified to a two dimensional axisymmetric domain (Figure 32b). The
geometry consists of two domains – the fluid zone and the wall zone. The surfaces of the walls
and the outer bounds of the fluid zone are all assigned boundary zones (Figure 32c). For the fluid
zone, the inlet and outlet mark the bounds of the fluid flowing in and out of the model. The wall
surface adjacent to the fluid zone is comprised of three boundary layers, including the inlet wall,
the hot zone wall, and the outlet wall. These three zones are the inner surface of the SiC tube
wall. The outer most surface of the SiC tube wall has three adjacent boundary zones,
appropriately named the outer inlet wall, the hot zone surface, and the outer outlet wall. The last
two boundary zones are the very top edge of the SiC tube wall, called the top edge wall, and the
very bottom of the SiC tube wall, the bottom edge wall. Each boundary zone has been assigned a
boundary condition, which is further discussed in Section 6.1.4.1.
64
Figure 32. a) Geometry of the SiC tube studied in this model, b) 2D axisymmetric model of the
SiC tube with domains labeled, and c) boundary zones.
65
6.1.2
Model Assumptions
The following assumptions were used in this model:
•
Microwave irradiation: Typically, modeling a substance under microwave irradiation is a
very difficult and data intensive exercise (Acierno et al, 2004; Ayappa et al., 1992;
Franca & Haghighi, 1996; Zhu et al., 2007). This is partially a result of the complex
nature by which substances absorb microwave irradiation. The loss tangent describes the
materials ability to absorb microwaves, is a function of both the microwave frequency
used and the temperature, and varies largely from substance to substance (Section 1.1.1).
Furthermore, the loss tangent can fluctuate greatly throughout a reaction depending on
the microwave, the substances reacting, and the heating profiles in the sample, and thus
are very difficult to model (Kappe et al., 2009). Specifically in this work, in order to
model the effects of microwave irradiation on the SiC tube, experiments were first run to
determine how the SiC tube heated up over a range of microwave irradiation values
(Section 4.1). From these experiments, it was concluded that the vertical and horizontal
temperature profiles of the tube were nearly constant. Furthermore, since SiC acted as a
microwave shield, in that it absorbed microwaves but did not allow for irradiation to
penetrate inside the tube (Obermayer et al., 2009), the model did not have to account for
the effects of microwave irradiation on the contents of the reactor tube. With these
observations, it was determined that the microwave irradiation could be simplified to a
constant surface temperature which would be assigned to the outer most wall of the SiC
tube – denoted as the hot zone.
•
Inlet Wall Boundary Condition: In the reactor setup, the inlet portion of the reactor tube
(labeled outer inlet wall) was located within the tube fitting and a tube holder. The
temperature of the tube surface was unknown and was assumed to be at room temperature
or 300 K. The constant surface temperature assumption was applied for both the outer
inlet wall as well as the top wall edge of the reactor tube.
•
Outlet Wall Boundary Condition: In the reactor setup, the outlet portion of the reactor
tube (labeled outer outlet wall) was exposed to the surrounding air, and therefore
convection occurred between the reactor tube and the air. As a result, a convection wall
boundary condition was used for the outer outlet wall and the bottom edge wall of the
66
reactor tube. Calculations to approximate a value for the convection heat transfer
coefficient can be found in Appendix E, Section E.1.
•
Material Properties: Some of the material properties were not available and so
assumptions were made for any values required by the model. These cases are
highlighted in the material properties section in Appendix E, Section E.2. Additionally, a
sensitivity analysis was completed for each input to determine how much error could
have been introduced into the model. Details of the sensitivity analysis can be found in
Appendix E, Section E.3.
6.1.3
Modeling Equations
The governing equations solved in the model included continuity and momentum, as there was
fluid flow through the SiC tube, an energy conservation equation, as there was heat transfer
throughout the reactor, and a species conservation equation, to account for the reaction that took
place in the fluid zone. The following section explains the governing equations that the CFD
model used. As mentioned earlier, the SiC tube geometry can be simplified to a 2D axisymmetric
model, and therefore the equations are stated in cylindrical coordinates. The system was also
modeled at steady state, and therefore the steady state assumption has been applied to all
equations.
For fluid flow, the conservation of mass equation (continuity equation) was solved for the 2D
axisymmetric geometry using:
!
!"
!
ρ!! + !" ρ!! + !!!
!
= 0
where !! is the axial velocity and !! is the radial velocity. The conservation of momentum
equations were solved for the 2D axisymmetric geometry using the axial momentum
conservation equation (Navier-Stokes):
1 !
1 !
rρ!! !! +
rρ!! !!
! !"
! !"
!"
1 !
!!! 2
1 !
!!! !!! = − + !" (2
− (∇ ∙ !) + !"
+
!"
! !"
!"
3
! !"
!!
!"
+ !!
67
and the radial momentum conservation equation:
1 !
1 !
rρ!! !! +
rρ!! !!
! !"
! !"
!"
1 !
!!! !!!
1 !
!!! 2
= − + !" (
+ + !" 2
− (∇ ∙ !
!"
! !"
!"
!"
! !"
!"
3
2!
+ ∇ ∙ ! + !!
3!
− 2!
!!
!!
The terms on the left hand side represent convection of momentum, and the terms on the right
hand side represent the effects of forces from pressure, shear stress, and drag on momentum.
Note that for cylindrical coordinates:
∇ ∙ ! = !!!
!!! !!
+ + !"
!"
!
For heat transfer, both convection and conduction were considered in the model. As a result, the
energy equation solved in the model was:
∇ ∙ ! !" + !
= ∇ ∙ k∇! + !!
The left hand side term is the energy transfer due to convection, and the term on the right
represent energy transfer due to conduction. In this model, the energy transfer due to species
diffusion and viscous dissipation were not included, as they were assumed to be negligible. Note
that k is the thermal conductivity and Sh represents the heat of chemical reaction, which is
represented by:
!!,!"# = −
!
ℎ!!
!
!! !
In this equation, h!! is the enthalpy of formation of species j, and Rj is the volumetric rate of
creation of species j. Note that:
! !!
! = ℎ − + !
2
68
Where h is the sensible enthalpy, which for incompressible flow is:
ℎ = !! ℎ! + !
!
!
Here Yj is the mass fraction of species j and ℎ! is:
!
ℎ! = !!"#
!!,! !"
with a reference temperature of Tref = 298.15 K.
For solid regions, such as the SiC tube wall, the applicable energy equation was for heat flux due
to conduction. The reduced equation for heat transfer in the SiC walls is:
0 = ∇ ∙ !∇!
For species transport and finite-rate chemistry, the mixing and transport of the chemical species
was modeled by solving the conservation equations for convection, diffusion, and reaction
sources for each chemical species. The volumetric reactions were modeled using the species
transport equation:
∇ ∙ !!!! = − ∇ ∙ !! + !!
In this equation, Yi was the mass fraction of species i and the diffusion flux of species i, !! ,
appears due to the gradients of concentration. The solver used the dilute approximation (i.e.
Fick’s Law) to model the mass diffusion due to the concentration gradients using:
!! = −!!!,! ∇!!
Here, Di,m was the mass diffusion coefficient for species i in the mixture. For this particular
model, the mass diffusion was defined to be a constant using the dilute approximation, and
effects by thermal diffusion were not considered.
Ri was the net rate of production of species i by chemical reaction, which for this reaction is:
!! = !!,! !!,!
69
Where !!,! is the molecular weight of species i, and !!,! is the Arrhenius molar rate of
creation/destruction of species i in the reaction r. !!,! , is solved using:
!
!!,! = (!
!!
!,! − !
!
!,! )(!!,!
!!,!
(!! !,! !!!! !,! )
)
!!!
Where !!,! is the molar concentration of species j in reaction r (kmol/m3), !!!,! is the rate
exponent for reactant species j in reaction r, and !!!!,! is the rate exponent for product species j in
reaction r.
The reaction is specified in the general form with only forward reactions considered:
!
!
!′!,! ℳ! !!!
!!,!
!′′!,! ℳ! !!!
Where N is the number of chemical species in the system, !′!,! is the stoichiometric coefficient
for reactant i in reaction r, !′′!,! is the stoichiometric coefficient for product i in reaction r, ℳ!
denotes species i, and !!,! is the forward rate constant for reaction r. !!,! is calculated using the
Arrhenius expression as follows:
!!,! = !! !!! ! !!! /!"
Here !! is the pre-exponential factor, !! is the temperature exponent, !! is the activation energy
for the reaction, and R is the universal gas constant.
6.1.4
Mesh
In order to model the SiC tube using CFD, the geometry of the reactor had to be made into a
mesh. A mesh is the subdivision of a domain into discrete control volumes, which are used in the
CFD program to solve the governing equations on. The reactor tube was built as a 2D
axisymmetric model using meshing software GAMBIT (version 2.4.6) (Figure 33).
The
geometry was fit with a structured mesh using a rectangular mesh shape totaling 203,175 cells. A
mesh dependence test was performed in order to determine if the mesh resolution was fine
enough to not interfere with the final solution (see Appendix E, Section E.4 for details). It was
70
determined that the mesh provided adequate detail and results were independent of the mesh size.
Sizing and coordinates used to build the mesh can be found in Appendix E, Section E.5.
Figure 33. The SiC tube (left) and a close up of the mesh (right).
71
6.1.4.1
Boundary Conditions
Boundary conditions had to be applied to the mesh of the SiC tube. The boundary conditions
used in the model are shown in Figure 34 and included a velocity inlet and outflow for the fluid
zone, along with an axisymmetric centerline. For the wall zone, the top edge wall along with the
outer inlet wall was set to a constant temperature (300 K) or room temperature. The hot zone was
set to a constant temperature (to match the average surface temperature of the reactor), and the
outer outlet wall and bottom edge wall were set to convection to the surroundings. The boundary
conditions are shown in Figure 34, and complete details are described in Appendix E, Section
E.6.
Figure 34. The boundary conditions set on the SiC tube studied in this model.
6.1.4.2
Other Settings
All models were run using a pressure-based solver under steady state conditions. Gravity was set
in the x-direction as -9.81 m/s2. Please refer to Appendix E, Section E.2 for details outlining all
72
material properties used in these models. A species transport and reaction model was used to
model
the
reaction
between
o-phenylenediamine
and
acetic
acid
to
produce
2-
methylbenzimidazole. The reaction was performed as a volumetric reaction, and the Arrhenius
rate expression was adapted from Damm et al. (2010) which provided complete kinetic
information for the reaction. Values included the pre-exponential factor (3.1 x 108), activation
energy (7.343 x 107 j/kgmol) and a temperature exponent of 0 (Damm et al., 2010). The solution
method used in all of the models included a SIMPLE pressure-velocity coupling scheme, least
squares cell based spatial discretization gradient, standard pressure, while the momentum,
energy, and species were all solved using second order upwind (ANSYS FLUENT, 2011).
Solution controls of the under-relaxation factors were all used at their default values, and model
solutions were initialized using all zones (ANSYS FLUENT, 2011).
6.1.4.3
Convergence Check
The convergence or completion of the model was determined using a number of methods. While
the model was underway, a plot of the residuals (calculated imbalance of each of the conserved
variables) was used to show how the solution evolved with time. For convergence, the residuals
had to lower by a factor of 1 x 10-3 (ANSYS FLUENT, 2011). In addition, while the modeling
was running, real time plots of specific boundary values, such as velocity or temperature, could
be monitored. When a model had converged, the values no longer changed from iteration to
iteration (ANSYS FLUENT, 2011). Finally, at the end of a simulation, a flux report on the mass
and energy balance was generated for the fluid zone in order to determine the mass and energy
balance. For convergence, the difference or error of this flux report had to be less than 0.01 %
(ANSYS FLUENT, 2011).
6.2 Modeling Results
The CFD model created of the SiC reactor tube provided insights into the temperature, velocity,
and concentration profiles for the reaction of o-phenylenediamine (A) and acetic acid to produce
2-methylbenzimidazole (B). The reaction was studied over a hot zone surface temperature range
of 100˚C and 200˚C, for a flow rate of 200 µL/min, as well as studied at 130˚C over a flow rate
range of 50 µL/min to 200 µL/min. All reactions were completed at 0.1 M, meaning the inlet
mole fraction of o-phenylenediamine (A) was 0.005698. The reaction conversion was determined
73
by studying the average mole fraction of o-phenylenediamine (A) found at the outlet of the
reactor tube in the model.
6.2.1
Temperature Profile
The temperature profile was studied for each reaction completed using the model. In each case,
an axial cross section of the reactor tube was taken, and contours of the temperature profile
within the wall zone and fluid zone were analyzed. Of particular interest were the temperature
profiles for the reaction completed at a hot zone surface temperature of 100˚C and 200˚C for a
flow rate at 200 µL/min, as these represent the minimum and maximum temperatures studied. It
was determined that a large portion of the flow remained significantly below the temperature of
the hot zone for 200 µL/min, regardless of the hot zone temperature. As a result of these
findings, the effects of flow rate on heating were also examined. Insights into the effects of the
flow rate on the temperature profile will be presented by examining the reactor at a hot zone
surface temperature of 100˚C and 200˚C for flow rates between 25 µL/min and 200 µL/min.
The temperature profiles for the reaction conducted at a hot zone surface temperature of 100˚C at
200 µL/min are displayed in Figure 35. Looking at the wall zone, it can be confirmed that the hot
zone surface was set to 100˚C (373 K). From this point, the heat conducted through the wall to
the inner surface (adjacent to the fluid zone), as well as axially upwards and down the SiC tube.
The outer inlet wall was set to a constant temperature of 27˚C (300 K), and therefore the inlet
wall remained almost entirely at this temperature. The outer outlet wall had convection heat
transfer to the surroundings, which resulted in the outlet wall heating up as the conduction down
from the hot zone was greater than the convection of heat to the surroundings. The fluid zone
had an inlet fluid temperature set to a temperature of 27˚C (300 K), and so remained at this
temperature until the fluid began to heat as a result of conduction from the tube walls as it
entered the hot zone. The temperature profiles in the fluid zone are long, stretched, parabolic
profiles, and the center of the fluid flow heats minimally over the course of the reactor tube.
Overall, in analyzing the total volume of fluid in the reactor tube, only 4.4 % of the fluid volume
reached within 10˚C of the hot zone surface temperature. A total of 33.3 % of the fluid is located
adjacent to the hot zone.
The temperature profiles for the reaction conducted at a hot zone surface temperature of 200˚C at
200 µL/min are displayed in Figure 36. Looking at the wall zone, it can be confirmed that the hot
74
zone surface was set to 200˚C (473 K). From this point, the heat conducted through the wall to
the inner surface (adjacent to the fluid zone), as well as axially upwards and down the SiC tube.
The outer inlet wall was set to a constant temperature of 27˚C (300 K), and therefore the inlet
wall remained almost entirely at this temperature. The outer outlet wall had convection heat
transfer to the surroundings, which resulted in the outlet wall heating up as the conduction down
from the hot zone was greater than the convection of heat to the surroundings. The fluid zone
had an inlet fluid temperature set to a temperature of 27˚C (300 K), and so remained at this
temperature until the fluid began to heat as a result of conduction from the tube walls as it
entered the hot zone. The temperature profiles in the fluid zone are long, stretched, parabolic
profiles, and the center of the fluid flow heats minimally over the course of the reactor tube.
Overall, in analyzing the total volume of fluid in the reactor tube, only 2.0 % of the fluid volume
reached within 10˚C of the hot zone surface temperature. A total of 33.3 % of the fluid is located
adjacent to the hot zone.
Comparing the temperature profiles between the reaction completed at 100˚C and 200˚C for 200
µL/min flow rate, many similarities can be drawn. Both models demonstrated the same shape of
temperature profile in the walls and fluid zones. In both cases, the temperature profile developed
into a long, stretched parabolic profile. For both models, the center of the flow remained well
below the temperature of the hot zone, and only a small fraction of the overall volume of fluid
reached within 10˚C of the hot zone surface temperature. Ideally the entire flow field in the hot
zone would have heated to the temperature of the hot zone surface temperature.
75
Figure 35. Model results of the wall and fluid temperature profiles in the SiC tube with 100˚C
hot zone surface temperature at 200 µL/min.
76
Figure 36. Model results of the wall and fluid temperature profiles in the SiC tube with 200˚C
hot zone surface temperature at 200 µL/min.
77
The next set of models examined the effects of flow rate on the heating efficiency of the reactor.
The model was completed for the reaction at 100˚C and 200˚C, for flow rates of 25, 50, 100, and
300 µL/min.
The temperature profiles for the reaction conducted at a hot zone surface temperature of 200˚C at
25 µL/min are displayed in Figure 37. A quick look at the results demonstrates that the shape of
the temperature profiles in the wall zone is similar to the previous models. However, the
temperature profile in the fluid zone has changed dramatically. The parabolic profiles are shorter,
and the entire width of the flow field reaches the hot zone surface temperature. Overall, in
analyzing the total volume of fluid in the reactor tube, 27.0 % of the fluid volume reached within
10˚C of the hot zone surface temperature. A total of 33.3 % of the fluid is located adjacent to the
hot zone.
Overall, the results demonstrate that the efficiency of heating the reaction is largely based on the
flow rate. Figure 38 demonstrates the effects of flow rate on the heating efficiency of the fluid
zone. The reactor developed in this model operates ideally at flow rates of 50 µL/min or less. For
flow rates greater than 50 µL/min, the efficiency of heating the fluid decreases dramatically.
With faster flow rates, there is not sufficient time for heat to penetrate fully, through conduction,
into the center of the flow path.
78
Figure 37. Model results of the wall and fluid temperature profiles in the SiC tube with 200˚C
hot zone surface temperature for a flow rate of 25 µL/min.
79
Figure 38. Reactor heating efficiency of the reaction mixture. The models were completed for
the reaction at 100˚C and 200˚C hot zone surface temperature over a range of flow rates. The
plot shows the volume of fluid heated to within 10˚C of the hot zone surface temperature for the
reaction completed. The ideal case is shown in green, which represents the total volume of fluid
found adjacent to the hot zone wall (33.3 %).
6.2.2
Flow Profile
The velocity profile was studied for each reaction completed using the model. In each case, an
axial cross section of the reactor tube was taken, and contours of the velocity profile within the
fluid zone were analyzed. Of particular interest were the velocity profiles for the reaction
completed at a hot zone surface temperature of 100˚C and 200˚C for a flow rate of 200 µL/min,
as these represent the minimum and maximum temperatures studied (Figure 39 and 40). Note
that given the geometry of the reactor tube, a flow rate of 200 µL/min is equal to a velocity of
0.0139 m/s. The results show that the model predicts the flow to be laminar, which is what would
be expected given that turbulence was not modeled and that the Reynolds number is well below
100 (see Section 4.3).
80
Figure 39. Velocity profiles for the reaction model at 100˚C hot zone surface temperature for a
flow rate of 200 µL/min.
81
Figure 40. Velocity profiles for the reaction model at 200˚C hot zone surface temperature for a
flow rate of 200 µL/min.
82
6.2.3
Reaction
The profile of species A mole fraction was examined for each reaction completed using the
model. In each case, an axial cross section of the reactor tube was taken, and contours of the
species A mole fraction in the fluid zone were analyzed. Of particular interest were the profiles
for the reaction completed at a hot zone surface temperature of 100˚C and 200˚C for a flow rate
at 200 µL/min, as these represent the minimum and maximum temperatures studied. Also of
interest were the profiles of species A mole fraction for the reaction completed at a hot zone
surface temperature of 130˚C for flow rates of 100, 200, and 300 µL/min. With these results, a
direct correlation between the model results and the experimental results could be made. It was
determined that the general trend of the experimental data was reflected in the model, however
the model generally over predicted the reactor results.
The profile of species A mole fraction for the reaction conducted at a hot zone surface
temperature of 100˚C at 200 µL/min is displayed in Figure 41. The species profile in the fluid
zone indicate that species A was converting to species B along the walls where the heating was
most pronounced (blue and green indicates the areas with the lowest mole fraction of species A,
and therefore the most reactive regions in the flow field). As the fluid in the center of the flow is
not heated sufficiently to induce a reaction, the reaction remains incomplete in the center of the
flow field. The reaction results were determined by taking the average mole fraction of A at the
fluid outlet of the tube. For this reaction, the average mole fraction of A was 0.004123 at the tube
outlet, meaning that 28 % of species A had converted to species B.
The profile of species A mole fraction for the reaction conducted at a hot zone surface
temperature of 200˚C at 200 µL/min is displayed in Figure 42. The species profile in the fluid
zone indicated that species A was converting to species B along the walls where the heating was
most pronounced. However, in this model, the temperature is nearly high enough throughout the
flow field that the reaction runs almost to completion. For this reaction, the average mole fraction
of A was 8.58 x 10-6 at the tube outlet, meaning that > 99 % of species A had converted to
species B.
Comparing the species profiles between the reaction completed at 100˚C and 200˚C for 200
µL/min, it was found that the profiles were similar in shape, with the reaction most pronounced
in the hottest regions by the walls. Overall, the conversion of species A to species B improved
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with temperature, as would be expected for this reaction. The results of all the models completed
for this reaction are shown in Figure 43 and 44. Overall, the model predicted the general trends
of the experimental results, but over predicted the conversion of A. The results also demonstrated
that although the model demonstrates the same general trends as the experimental model, there is
a large discrepancy in the model results when conducted over a range of flow rates.
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Figure 41. Model results of the concentration profiles in the SiC tube at 100˚C hot zone surface
temperature (28 % conversion of A into B) for 200 µL/min.
85
Figure 42. Model results of the concentration profiles in the SiC tube at 200˚C hot zone surface
temperature (>99 % conversion of A into B) for 200 µL/min.
86
Figure 43. Experimental versus model results showing the percent conversion of A into B over a
range of temperatures for a residence time of 30 seconds. Experimental results are from Chapter
5.
Figure 44. Experimental versus model results showing the percent conversion of A into B over
three flow rates. Experimental results are from Chapter 5.
6.3 Discussion
6.3.1
Thermal Results
It would be ideal if the reactor would heat the majority of the flow field adjacent to the hot zone
to within 10˚C of the hot zone temperature. However, the temperature profiles developed using
this model indicated that for flow rates in excess of 50 µL/min, a large volume of fluid in the
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center of the flow field did not reach within 10˚C of the hot zone surface temperature. This was a
result of the long, stretched parabolic temperature profiles that developed in the fluid zone,
which meant the fluid by the walls heated up, while the center of the flow field remained largely
unheated. For flow rates of 25 and 50 µL/min, a significant volume of the fluid did reach to
within 10˚C of the hot zone temperature, as the slower flow rates did not allow for the heat to
penetrate fully, through conduction, into the center of the flow path. This is an important finding,
as the temperature profile developed in the reactor for flow rates above 50 µL/min has the
potential to lead to incomplete reactions due to the inconsistent heating across the fluid zone.
Evaluating the accuracy of the thermal boundary conditions used in the model, it is believed that
the inlet wall assumption of constant temperature at 300 K was greatly under approximating the
actual temperature condition of the wall. In reality, significant conduction occurs upwards from
the hot zone, and this has been verified during experiments using the reactor, as the top tube
fitting became hot to the touch.
6.3.2
Flow Results
The reactor operated under laminar flow conditions, as determined by Reynolds number
calculations (Section 4.3) and was therefore modeled as such. As a result of the reactor operating
under laminar flow conditions, mixing in the fluid zone was minimal, and the flow did very little
to aid the already very slow diffusion processes. Ideally a mixer of some form could be
integrated into the reactor to improve mixing, thereby improving thermal diffusion and the
reaction results. However, there are many challenges associated with installing a static or
mechanical mixer in the SiC reactor tube. The reactor tube is very narrow (1.75 mm ID) and is
ceramic, therefore making it very difficult to implement a conventional mixer in the hot zone
area of the SiC tube.
6.3.3
Reaction Results
Overall, the model predicted the general trends of the experimental results, but was found to over
predict the conversion of species A. The difference between the model and the experimental
results could have been a factor of both the model development and the experimental results.
There were many assumptions made in developing the model and many physical values that had
to be assumed due to lack of data available. Specifically, data for the density of 2-
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methylbenzimidazole (B) could not be located. As a result it was assumed that the density was
the same as the starting material (o-phenylenediamine, 1030 kg/m3). Furthermore, the viscosity
of both the starting material (o-phenylenediamine, A) and product (2-methylbenzimidazole, B)
was not available, and therefore assumed to have the same viscosity as acetic acid (0.00122
kg/ms). In addition, the specific heat capacity and thermal conductivity for the reaction mixture
was assumed to be the same as values for acetic acid at 300 K (2148 J/kgK and 0.159 W/mK
respectively). The results of the sensitivity analysis are shown in detail in Appendix E, Section
E.3. Overall, the sensitivity analysis demonstrated that there was little impact on the overall
reaction results when the density of B and the viscosity of A and B were changed by +/- 25 %
from their assumed values. However, the analysis did conclude that there was a large impact on
the model results when the values assumed for the specific heat capacity and thermal
conductivity of the reaction mixture were changed by +/- 25 %. The magnitude of this impact
would be expected, however, given the importance of these thermal properties in the overall
model. Overall, the sensitivity analysis demonstrated that considerable error could have been
introduced into the model from assuming the values of the thermal conductivity and specific heat
capacity of the reaction mixture.
However, looking at the overall result from the perspective of the experimental data, a large
portion of the error could have come from the experimental results. These experiments were
conducted using 2 mL volumes of reactants, meaning a total reaction time of 20 minutes for a
200 µL/min flow rate. From the Long Reaction (Section 5.1.3), the reactor was found to reach
steady state conditions after 2 hours, which was predicted to be a result of ‘thermal drift’ or the
heating of the PCD, and in particular the outage tube, over the duration of an experiment. As a
result, the data generated to compare to the model were collected when the reactor had not
reached steady state conditions. In the Long Reaction results, the data collected at the first hour
showed approximately 17 % more starting material than the steady state data at the third hour.
Although this data was collected for the Claisen rearrangement, no doubt similar conclusions
could be drawn to the reaction studied in this model.
This implies that the experiments
completed for this model may have shown higher amounts of starting material than what the
steady state condition of the reactor would have actually produced. If so, the model may have
actually had a much more accurate prediction of the reactor dynamics. Further testing will be
required in order to test this hypothesis.
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6.4
Model Summary
Overall, the model discussed in this thesis was developed to try to predict reaction conditions as
well as to uncover the thermal, velocity, and concentration profiles within the reactor tube during
a reaction. The model was found to predict the general trends of the experimental reaction results
for the synthesis of 2-methylbenzimidazole, but over predicted the conversion of the starting
material. However, despite these discrepancies, the model still provided key insight into the
development of the thermal profile in the reactor tube. It was found that for flow rates greater
than 50 µL/min, the temperature profiles became less and less ideal, as the centerline fluid
remained largely unheated. The development of these temperature profiles at high flow rates has
the potential to lead to incomplete reactions. Flow rates of 50 µL/min or less demonstrated
improved conduction throughout the fluid, which resulted in a higher and more uniform
temperature profile. This is an important finding for understanding the efficiency of heating in
this reactor when using microwave irradiation and SiC tubes. There is great potential for this
model to be developed further and expanded so as to better correlate the model results to the
experimental data. Notes on future work for this model development can be found in Chapter 7,
Section 7.5.
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Chapter 7
7
Conclusion
A continuous flow microwave reactor for organic synthesis was designed, built, and
commissioned. The system, that was a second generation MACOS reactor, addressed all of the
challenges faced by the first generation reactor produced by the Organ group. These challenges
included leaking components, unregulated and unknown operating pressure, and unknown
thermal characteristics in the reactor tube. In the new reactor (Figure 5, page 19), improved
system plumbing and high pressure components allowed for a sealed system under high
temperature and high pressure conditions. A novel pressure creating device was introduced that
regulated the reactor to operate up to 1100 psi pressure using nitrogen gas. In addition, the
reactor was connected to gas chromatography/mass spectrometry via an in-line analytic setup. In
order to understand the thermal and mass profiles in the reactor tube, a computational fluid
dynamic model was constructed. The model shed light on how efficiently the reactor operated.
The reactor was commissioned using two chemical reactions: the Claisen rearrangement and the
synthesis of 2-methylbenzimdazole. Using the Claisen reaction, the standard operating procedure
for the reactor and in-line analytics was developed and verified to be reproducible. The results of
these studies indicated that the reactor required 3 hours to come to steady state, possibly due to a
‘thermal drift’ throughout the reactor apparatus, which caused the slow heating of the PCD over
longer reaction periods. As well, the studies indicated that the in-line analytics could provide
accurate and reproducible analyses of reactor samples.
The reaction to produce 2-
methylbenzimidazole was used to demonstrate the high degree of reproducibility of the SOP.
The finalized SOP for the reactor and in-line analytics can be found in Appendix D, Section D.6.
The following chapter is a critique of the entire reactor design and operation, as well as a
discussion for future work for the reactor and the model. First, an assessment of the key features
of the reactor design is discussed, including the silicon carbide reactor tube, the PCD, and the inline analytics. Then the mechanical aspects of the design are fully analyzed, followed by an
evaluation of the operational aspects of the reactor.
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7.1 Key Features of the Reactor Design and Future Work
7.1.1
Silicon Carbide Tube
The reactor design included a SiC tube (Figure 8, page 23) that was exposed to microwave
irradiation in order to heat up the flowing reaction solution. The reactor was designed to work
with either a SiC tube or alumina tube, however it was decided that a SiC tube would be the
focus of the studies in this thesis (Section 3.2.2.3). The SiC tube was chosen because of its
excellent thermal properties, its material strength to withstand high pressures, but most notably,
its ability to absorb microwave irradiation as a wide gap semiconductor. SiC is also known to act
as a barrier to microwave irradiation, meaning it shields the reactor contents from the irradiation
(Obermayer et al., 2009). As a result, the reaction solution is heated by conduction from the SiC
tube. Heating by conduction is contrary to the type of heating in a typical microwave reactor that
uses a Pyrex or alumina reaction vessel. Since these materials are nearly invisible to microwave
irradiation and therefore do not heat up, the reaction solution must have a high loss tangent, or
passive heating elements must be added in order for the solution to heat. SiC reactors, however,
can be used with any material, polar or non-polar because it heats by conduction. A prime
example was the non-polar Claisen reaction mixture, which would not proceed to completion in
typical batch microwave reactors without a heating aid, as its components are all weak absorbers
of microwave irradiation (Kremsner & Kappe, 2006). In this thesis, the Claisen rearrangement
could be completed using microwave irradiation with the SiC reactor tube without any
modifications to the composition of the reaction mixture. However, for reactions where the
components are highly microwave absorbing, the SiC tube may prove not as useful for the
following reason. From the CFD results discussed in Chapter 6, it was observed that for this
reactor, flow rates in excess of 50 µL/min could lead to considerable heating gradients in the
flow path of the tube. At higher flow rates, there was not enough time for heat to penetrate fully,
through conduction, into the center of the flow path. For species that can heat up efficiently
under microwave irradiation, it might be more effective to have the solution exposed to the
irradiation directly. Alumina is nearly microwave invisible, and thus if used as the reactor tube
material, would allow the entire reaction solution to heat up through dielectric means, which
could lead to improved thermal profiles compared to the SiC tubes. Although the work in this
thesis focused on using the SiC tube, alumina tubes could be easily interchanged into the design.
As a result, for future experiments, a choice between the two tubes could be made based on the
92
components of the reaction, and whether the mixture would benefit from conduction heating
from the SiC tube, or dielectric heating from using the alumina tube.
7.1.2
Pressure Creating Device
The PCD was designed to keep the reactor under pressure using nitrogen gas, rather than using
traditional back-pressure regulators that create pressure by restricting the flow path, and can
become clogged or damaged by reaction mixtures. The PCD withstood temperatures up to
450˚C and operating pressures up to 1100 psi, allowing it to attain higher operating pressures and
operate with higher temperatures than any other continuous flow microwave reactor published to
date (Figure 45, data point 17). The PCD created an operating window of heat and pressure more
than three times greater than any of the other continuous flow microwave reactors published to
date.
Figure 45. A plot of the maximum operating pressure and temperature for continuous flow
microwave reactors found in the literature. Data point 17 is the reactor described in this thesis.
1 – Wilson et al., 2004
2 –Baxendale et al., 2006
3 – Chemat et al., 1996
4 – Benali et al., 2008
5 – Bondiloi et al., 2008; Braun et al, 1998;
Corradi et al., 2005; Dressen et al., 2010
6 – Cablewski et al., 1993
7 – Glasnov et al., 2005
8 – Groisman & Gedanken, 2008 9 – He et al., 2004a, 2004b
10 – Marquie et al., 2001
11 – Comer & Organ, 2005
12 – Paulus et al., 2007
13 – Pipus et al., 2000
14 – CEM Flow / Scale-up Voyager Overview,
2011
15 – CEM Organic/Medicinal Chemistry MARS
Instrument, 2011
16 – Milestone - FlowSYNTH, 2011 93
However, there were several challenges with the design of the PCD. From a safety perspective,
the system was operating under high pressure conditions, meaning if a seal was compromised,
the high pressure nitrogen gas and any reactants that vapourized would escape from the
compromised seal. Due to the potential safety hazard, special precautions were set in place to
ensure operator safety.
The user wore typical laboratory personal protective equipment,
including a laboratory coat, safety glasses, and gloves, in addition to a face shield. Additionally,
a blast shield was placed between the operator and the reactor during experiments. From a
design perspective, the PCD was designed to operate from pressure supplied from a pressure
ballast (PB-1), instead of from the nitrogen cylinder directly. This was an important safety
feature that ensured the total amount of nitrogen gas vented would be limited to the gas
contained in the pressure ballast, if a seal was compromised, and would not include venting the
nitrogen cylinder. To improve upon safety for future designs, a flow rate meter could be
connected to an automated V-2. Therefore, in the case of a compromised seal, the flow rate meter
would detect a sudden increase in the flow out of the pressure ballast and would automatically
shut V-2, therefore isolating the pressure ballast from the rest of the reactor. This would further
minimize the total amount of gas that would be vented, and therefore make the system more safe.
In addition, the size of the pressure ballast was 1 L, and whether this volume of gas was actually
required should be determined. Moving to a smaller pressure ballast may be just as efficient, and
would further minimize the total volume of high pressure gas in the system.
Another challenge of the PCD design was that it was made of stainless steel, which is highly
conductive and was found to heat up over the duration of a reaction. Initially, stainless steel was
selected as the material of construction for the PCD as it provided excellent pressure ratings and
chemical compatibility. However, the challenges associated with the conductive nature of the
stainless steel were not fully realized until the Long Reaction was completed. At this time, it
became apparent that the PCD could heat the reactants and products after they had passed
through the reactor, in particular from the stainless steel outage tube (15 cm of additional heated
tubing) (see Figure B.3 in Appendix B). Ideally the reaction would have been contained to the
microwave irradiation zone, so that conditions could be tightly controlled. In order to ensure that
the reaction is not heated as it passes through the PCD, cooling around the pressure tee (PT-1)
would be required. Cooling would help to minimize the effects of the ‘thermal drift’ through the
reactor and ensure that the reaction would stop as soon as the mixture flowed out of the SiC tube.
94
The final challenge of the PCD design was in its operation. The design of the PCD allowed for
continuous flow through the microwave reactor under pressure, however ultimately led to semicontinuous sampling and collection from the PCD. The products from the reactor did not flow
continuously to analytics or collection, but rather had to be removed from the system in small
batches using the rotary valve, making product collection semi-continuous. Ideally the entire
system, from the infusing pumps to the sampling system, would operate continuously, however
this was not possible with the PCD design, as the nitrogen gas used to pressurize the system
caused operational and design restrictions.
7.1.3
In-Line Analytics
The finalized reactor design (Figure 5, page 19) included in-line analytics, which made it
possible to collect a sample from the reactor and analyze it with GC/MS, without having to
physically handle the sample. It was determined through experiments with the Claisen
rearrangement that the in-line analytics operated well and in a reproducible manner. Using the
setup, a sample of the Claisen products could be taken from the reactor during a reaction, and
sent to the flow cell for autosampling by the CombiPAL. Within ten minutes of sampling from
the reactor (1 minute of automatic syringe cleaning, 7 minutes of the actual GC/MS sample run,
2 minutes of the detector cooling and method equilibrating), an analysis of the reaction mixture
was complete and the system was ready for another sampling.
However there were several aspects of the design that were not ideal. The design included very
long process lines from the rotary valve to the flow cell (approximately 90 cm of stainless steel
tubing of 1.75 mm ID). The length of tubing was required due to the physical limitations of the
current setup. Given the laboratory bench and space to work with, it was not possible to set the
base of the reactor next to the GC/MS sample tray (where the flow cell was located). As a result,
tubing was used to bridge the gap between the reactor and the GC/MS. In the future, the flow cell
should be located next to the rotary valve in order to minimize process lines. To do so, a multitiered custom made laboratory bench will be required to place all components in the ideal spatial
arrangement. However with the current layout, in order to send a small plug of sample from the
reactor to the flow cell, with such a distance to travel, solvent was required to push the sample
into the flow cell. Although it was demonstrated that this method was an effective way to move
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the sample to the flow cell, it did introduce a dilution factor, which could vary from experiment
to experiment and led to inconsistent sample concentrations.
Another challenge of the in-line analytic setup was the design of the flow cell. The base of the
flow cell was designed to sit like a vial would in the GC/MS sample tray, however the tolerance
on the base of the flow cell was too great, meaning the flow cell could move freely in its
position. Furthermore, the sample port on the flow cell was not positioned in the exact center of
the vial position, meaning every time the flow cell moved, so did the sample port with respect to
where the CombiPAL was programmed to sample from. Therefore, every time the flow cell
shifted position, the CombiPAL had to be re-calibrated for the new flow cell position, in order to
prevent breaking the expensive sampling syringes. In addition to this design flaw, the flow cell
contained an additional outlet port, located near the sample port. The outlet port was connected
to a 2-way ball valve, which was closed during sampling, and opened during cleaning. However,
it was never determined if the port actually served any function during the cleaning cycle. The
function of this additional outlet port should be examined before the next iteration of design is
built.
There were also some challenges in using the flow cell. On a few occasions, air bubbles were
sampled by the CombiPAL from the flow cell. The bubbles are a result of a low liquid level in
the flow cell vertical channel (see Figure 13b, page 34), and thus air is sampled by the
CombiPAL. With the current setup, the operator watched each flow cell injection to determine if
there were bubbles in the sample. The bubbles would translate to a lower than expected area
count in the GC/MS analysis, because less sample is being injected than should be. Although the
composition of the samples was not affected by air bubbles (as demonstrated in the Long
Reaction, Section 5.1.3), it would be desirable to have no variation in volume between sample
injections.
7.2 Critique of the Mechanical Aspects of the Reactor Design
and Future Work
Overall, the reactor was demonstrated to work well and provide consistent reaction results.
Although the mechanical aspects of the design had improved from the first generation reactor
developed by Organ and coworkers, there were still some challenges with the design, and some
changes that could be made to further improve the system and operation. Described below is a
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critique of the mechanical aspects of the Reactor Configuration B (Figure 5, page 19), beginning
with the syringe pumps, and working through the reactor to sample collection. It should be noted
that all comments on the SiC tube, PCD, and in-line analytics were previously discussed in the
above sections, and therefore are not included in the following critique.
The reactants were introduced into the reactor using syringe pumps. The syringe pumps and
stainless steel syringes were found to work well for this design. They could withstand the high
pressure conditions, and were shown to work effectively over long periods of time (as
demonstrated in the Long Reaction). The syringe pumps were connected to the rest of the
apparatus using 3-way ball valves, which were manually operated. In order to continuously run
the reactor, one pump would infuse the reactants into the reactor while the other pump was
refilling. Every time the pump switched from refill to infuse mode, the 3-way ball valves had to
be switched manually. Given that the current stainless steel syringes are 2.5 mL, the switching
of the valves had to occur frequently. As a result, it would be useful to have the valves
automated, so that constant intervention by the user would not be required every time the pumps
switched directions. This will become a greater issue when longer experiments are conducted.
Automated valves would streamline the reactor operation and allow the operator to focus on
other important aspect of the reactor.
Connecting the syringe pumps and 3-way ball valves to the reactor was stainless steel tubing.
The length of tubing required to connect the pumps to the reactor was quite long (approximately
50 cm), contributing to unnecessary process line volumes and longer cleaning cycles. Ideally, the
pumps would be located as close to the microwave cavity as possible, in order to minimize the
length of process lines needed. With the current setup, it was not possible to move the pumps any
closer because of the design of the Biotage Initiator™ microwave used in this thesis. The
microwave cavity in the Biotage Initiator™ was located in a position that made access to it
difficult. However, work is currently underway in developing a new, compact microwave unit
that will be better suited to work with the reactor setup described in this thesis. The new
microwave unit, built by WaveCraft™, has a much smaller footprint than the Biotage Initiator™,
and has unrestricted access to the top and bottom of the microwave cavity, meaning that the
pumps can be situated close by.
97
The Biotage Initiator™ was intended for irradiating a sealed Pyrex batch vessel. As a result, the
system had many features that were created to operate only with these vessels. For the design
described in this thesis, the microwave was modified (see Section 3.2.2.1) to adapt to the SiC
tube, and as a result there were a few challenges in its operation. In particular, it was found that
the built-in IR sensor did not provide accurate temperatures of the SiC tube. The sensor was
designed to capture the entire surface of a wide Pyrex batch vessel, and therefore when used with
the SiC tube, would take an average temperature of the SiC tube and the surrounding air, which
resulted in lower than actual temperature values (Figure 46). However, the IR sensor was
required to report a temperature value to the microwave in order to keep the power on, so the IR
sensor was pulled out of the microwave cavity and set to point into the surrounding air. An
external IR camera was used to monitor the surface temperature through a machined window in
the microwave cavity (Figure 6, page 21). However, the microwave would sometimes shutdown
unexpectedly as a result of sudden changes to the built-in IR sensor readings. As the system did
not have an alarm for such a scenario, the microwave shutdown could go unnoticed unless the
microwave operating screen was regularly checked for error notifications. Furthermore, since the
microwave was built for a Pyrex batch vessel, the microwave cavity only spanned 43 mm tall,
meaning that only this much of the reactor tube was being irradiation. Having such a small
irradiation zone meant that slow flow rates (i.e. 25 µL/min) were required to ensure 2 – 4
minutes of residence time. Although the CFD model proved that the reactor heats more
efficiently at slow flow rates, from a production and throughput perspective, slow flow rates are
not ideal. The new microwave unit designed by WaveCraft™, as previously mentioned, has been
designed to work with a continuous flow setup. The unit has a long and narrow microwave
cavity, which has been built to hold a tube reactor. By using this microwave unit, the length of
tube exposed to microwave irradiation will be greatly increased, ultimately translating to
increased reaction throughput.
98
Figure 46. The Biotage Initiator™ built-in IR sensor placement for the batch vials and for the
SiC tube. The red circle indicates the area over which the sensor gathers temperature data. The
sensor reports an average temperature value of the entire circle.
After a reaction mixture passed through the SiC tube and entered the PCD, the solution collected
at the base of the sample cylinder (PB-2). Product collection from the PCD occurred by draining
the mixture through V-6 and the rotary valve (RV-1). This draining process was slow, and
therefore it would be ideal to have a secondary pressure system to allow for the rapid emptying
of the PCD and process lines. Furthermore, the 4-port rotary valve used in the design could
withstand the high pressure and high temperature conditions, however the 4-port configuration
required the process lines out of port 2 to act as a sample loop for product collection. By using
the process lines between port 2 of the rotary valve and V-10 for sample collection, this meant
that only small samples (0.5 g) could be collected from the reactor at a time while the reactor was
under pressure. The reactor could not be opened completely to the atmosphere to drain a larger
sample, as this would lead to a sudden rush of the pressurized nitrogen gas out of the system.
Ideally, the sample cylinder (PB-2) would be continually drained, leading to more precise sample
characterization over time, while also ensuring that the reaction will have terminated, as the
sample would be cooled completely upon removal from the PCD. In addition, the 4-port rotary
valve should be switched to a 6-port rotary valve, which would have the same 4 ports as the
99
current design, but would also contain a proper sample loop for product collection between the
remaining two ports. This could improve sampling from the reactor, as well as help to minimize
the contamination from the product sample in the in-line analytic process lines.
7.3 Critique of the Reactor Standard Operating Procedure and
Future Work
The SOP that was created for the Reactor Configuration B (Figure 5, page 19) was shown to
work effectively, with reproducible reaction and sampling results (for complete SOP, see
Appendix D, Section D.6). This section outlines a critique of the SOP and gives insight into why
certain procedures were necessary, while also discussing the impact of other aspects of reactor
operation, such as flow direction through the reactor tube.
The SOP started with a reactor prime, which was an essential procedure that filled the process
lines with bubble free solution. This ensured that there was no variation in the residence time for
a reaction sample. Initially, the prime was completed using pure solvent, however concerns over
reaction dilution by the priming solution led to simply using the reactants to prime the system.
However, this affected the conversion of the first sample collected from the reactor, as starting
materials in the process lines in and below the SiC tube were not fully reacted. That being said,
the presence of straight solvent also led to erroneous conversion in the first samples collected.
The next step of the SOP was the reaction, which was found to proceed smoothly, and there were
no issues in the procedure used. However, the reactor was designed to operate with a downward
flow through the microwave cavity. The downward flow was used because of the design of the
PCD, which required the flow to drip down from the outage tube (OT-1) to the base of the
sample cylinder (Figure 10, page 28). As a result, it was not possible to change the flow rate to
the upward direction. However, it was not clear that flow directed upwards would actually
produce better results. By allowing the flow to move upwards, there is definite control over the
flow rate of the fluid as there is no concern over material leaking out due to gravity. The user
knows that the process lines are filled, and that the fluid will flow based on the action of the
pumps. However, because this system was operated by pumping the reactants into high pressure
nitrogen, meaning the fluid encountered a wall of high pressure nitrogen gas as it moved through
the process lines, it was believed that the flow rate in the reactor tube was fully regulated by the
pumps, thus there may be no difference if the setup could operate by pumping upwards.
100
However, if upward flow was desired, the PCD would have to be redesigned to account for such
an operation.
After the reaction was the reactor flush, which was initially used in Reactor Configuration A
(Figure 15, page 38) prior to the development of the in-line analytics. The reactor flush consisted
of pushing a 2 mL sample of pure solvent through the reactor right after a reaction and at the
same reaction conditions. It was found that the flush was instrumental to ensure the entire
reaction sample had been exposed to microwave irradiation. The flush was of particular
importance for reaction samples of 2 mL or less, since the process line volume from the pumps
to the reactor was approximately 1.1 mL, leaving only 0.9 mL of the reactants to enter the
reactor. As a result, the flush was important as it pushed the entire reaction sample through the
SiC reactor tube. However, because the flush was completed using pure solvent, there were
concerns of the flush solution diluting the reaction. Once the in-line analytics had been setup in
Reactor Configuration B (Figure 5, page 19), the flush was found to be less important, as the
products could be collected while the reactor was still under pressure and larger reactions
(greater than 4 mL) were processed. Since the volume of the reaction had increased to greater
than 4 mL, this ensured that at least 2 mL had been fully processed by the reactor and moved into
the sample cylinder (PB-2).
The operation of the in-line analytics was found to be effective and reproducible. The longest
part of the SOP was the sampling by GC/MS, which from the start of the sample injection into
the instrument, to receiving the sample analysis, took 10 minutes for the Claisen reaction. This
time could be decreased by programming the CombiPAL autosampler syringe to have a quicker
and more efficient wash cycle. It was found that the syringe took 1 minute to clean the syringe
prior to injecting a sample into the GC/MS. In the future, when faster analysis is required, this
wash cycle could be analyzed to see if it could be reduced, however the actual sample run time in
the GC/MS cannot be shortened, as the analysis, cooling, and method equilibrating times are all
fixed.
7.4 Future Experimental Work
To wrap up the investigation of the reactor described in this thesis, the following experiments
should be conducted. The synthesis of 2-methylbenzimidazole should be completed using both
the SiC tube and alumina tube, in order to compare the results of using conduction heating versus
101
dielectric heating for this reactor. As well, it would be useful to run a series of experiments to
determine how quickly the reactor re-establishes steady state conditions when flow rate or
temperature is changed mid-run. This would evaluate how well the reactor and setup would work
for on-the-fly process optimization. Finally, a complete study and optimization of the Claisen
rearrangement and the synthesis of 2-methylbenzimidazole should be completed over a range of
flow rates and temperatures in order to determine if the reaction results can exceed results for
these reactions using state-of-the-art systems in the literature.
7.5 Future Work for the Model
The model created in this thesis was an effective tool for predicting how the new reactor system
operates. However, there is a lot of work that can be done to further verify and improve the
model. It would be useful to re-run the synthesis of 2-methylbenzimidazole experiments using
the reactor in order to determine what the actual steady state results are. The experiments
conducted in this thesis only examined a 2 mL reaction sample meaning that, at the flow rates
used, the entire reaction took only 20 minutes. According to the results of the Long Reaction
(Section 5.1.3), the reactor did not come to full steady state conditions until after the 2nd hour. As
a result, it would be interesting to see if this was also true for the synthesis of 2methylbenzimidazole, and if so, how the changed reaction results would correlate to the model
predictions.
It would also be useful to verify the model using a different reaction altogether. A reaction with
known kinetics could be completed in the microwave reactor over a range of flow rates and
temperatures and results could be compared to the model predictions. This exercise would help
to determine if the model was applicable to other reactions.
Other future works for the model include verifying the boundary conditions. The conditions used
in the model were largely based on assumptions, and not actual reactor conditions, as they were
not known. However, by installing thermocouples on the inlet wall and outlet wall of the SiC
tube just outside of the microwave cavity, the surface temperatures at these locations could be
verified and measured over a range of power settings. Using this data, better approximations of
the inlet wall and outlet wall boundary conditions could be made. Furthermore, investigations
into the unknown thermal properties of the reaction mixture should be considered, specifically
the thermal conductivity and specific heat capacity. For the model described in this thesis, these
102
values were assumed, however a sensitivity analysis revealed that changing these values by +/25 % can have a large impact on the model results.
Finally, through calculations made in this thesis, it was determined that the reactor operated
under laminar flow conditions. As a result, there was poor mixing throughout the reactor tube. In
order to improve mixing, and potentially improve heat and mass transfer through the SiC tube, it
would be ideal to install a mixer. A model would be useful to predict the design and efficiency of
a mixer prior to its implementation in the reactor. However, as mentioned earlier, adapting a
mixer to this system may prove to be a very difficult task. However, work is currently underway
in the Organ lab that involves the use of reactor tubes loaded with spheres containing catalysts. If
implemented, this setup might provide a packed bed effect in the reactor and thus may aid in the
mixing process. It would be interesting to conduct CFD modeling of these spheres in the SiC
tube to determine how much they could contribute to mixing in the fluid zone.
103
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Appendix A: Literature Review
Table A.1. Literature review of continuous flow microwave reactors published to date.
Reactor
Comments
-He et al., 2004a
Construction:
-Glass micro reactors
-PEEK tubing used for system
plumbing
(OD: 1.58 mm, ID: 0.18 mm)
-Sealed using Torr seals (Varian)
Flow:
-Syringe pump
Microwave:
-Placed in a Discover microwave
from CEM
Temperature Measurement:
- IR sensor (pointed at base of chip)
-He et al., 2004b, 2005
Construction:
-U-shaped glass capillary
(ID: 800 µm, OD: 1.2 mm,
L: 138 mm)
-Connected to plumbing using tube
fittings, used PTFE tubing
Flow:
-Syringe pump
Microwave:
-Placed in Discover microwave from
CEM
Temperature Measurement:
-IR sensor used at the bend in the U
-Pt wire electrodes placed around the
tube fittings at the inlet and outlet of
the U reactor
Other:
-Capillary coated with metal
109
-Jachuck et al., 2006
Construction:
-Made of a PTFE and an alumina
plate
Microwave:
-Placed in a domestic microwave
ovens (Westpointe)
Temperature Measurement:
-Pico type-K thermocouple used at
fluid inlet and outlet ports
-Comer & Organ, 2005a, 2005b
Construction:
-Straight glass capillaries
-ID: 200-1,200 µm
Flow:
-HPLC pumps
-Flow rate range: 2 – 40 µL/min
Microwave:
-Placed through a Emrys Synthesizer
(Biotage)
Other:
-Thin Pd film on inner surface of
capillary used as an immobilized
catalyst
110
-Kirschning et al., 2006
Construction:
-Reactor made from PEEK
Microwave:
-Placed in a CEM Voyager system
Other:
-Pdº catalyst immobilized in Raschig
rings
-Rings used in batch and flow
microwave chemistry
a) Honeycomb monolithic composite
b, c) Raschig rings
-Wilson et al., 2004
Construction:
-22 x 3 mm2 borosilicate glass coil
(1/8” ID) in a 100 x 10 mm2
borosilicate glass tube
-Omni glass threaded connectors,
PTFE end fittings containing PTFE
frits, TFE Teflon tubing (1/8” ID)
-100 psi back-pressure regulator at
outlet
-4 mL total flow cell volume
Flow:
-HPXL pump
Microwave:
-Placed in a Emrys Synthesizer
(Biotage)
Temperature Measurement:
-Used the microwave’s built-in IR
sensor
Other:
-Over-pressurization occurred when
solvents were superheated
-Clogging of lines had been observed
Max. Temp. (ºC): 200
Max. Pressure (psi): 100
111
-Baxendale et al., 2006
Construction:
-U-shaped reactor
-Used a 580 psi back-pressure
regulator
Flow:
-Syringe pump
Microwave:
-Reactor must be used with pulsed
microwave irradiation with short gasjet cooling
Other:
-Contained polyurea
microencapsulated palladium catalyst
which collapsed under continuous
microwave irradiation
-Bagley et al., 2005
Construction:
-Standard pressure-rated glass tube
used (10 mL)
-Tube filled with ~10 g sand in order
to create microchannels, and filled
with ~5 mL solvent
-Sealed with PTFE washers and
custom built steel head
-Used a back-pressure regulator
Flow:
-HPLC pump
Microwave:
-Placed in a CEM Voyager
microwave
Temperature Measurement:
-Used the microwave’s built-in IR
sensor
No image available.
-Savin et al., 2003
Construction:
-Used PTFE 1 mm tube sheathed in
Kevlar® fiber
Microwave:
-Placed in a CEM Voyager
microwave
Temperature Measurement:
-Used the microwave’s built-in
thermocouple probe
Other:
-10 mL volume processed
112
-Glasnov et al., 2006
Construction:
-Standard 10 mL reaction vessel
-Filled with 2 mm sized glass beads
-Teflon tubing
-250 psi maximum back-pressure
regulator used at reactor outlet
Flow:
-HPLC pumps
Microwave:
-Placed in a CEM Voyager CF
microwave
Temperature Measurement:
-Used the microwave’s built-in IR
sensor
Other:
Max. Pressure (psi): 250
-Pillai et al., 2004
Construction:
-U-shaped quartz tube reactor
(1.1 cm diameter, 12.5 cm length)
-Stirred
-15 mL volume processed
Flow:
-Pressure pump
Microwave:
-Placed in a CEM Voyager
microwave
Temperature Measurement:
-Fiber-optic temperature sensor
Other:
-Charged with heterogeneous catalyst
-Chen et al., 1990
Construction:
-Teflon reactor coil
Microwave:
-Kitchen microwave oven
Other:
-Produced > 20 g samples
-10 mL processed volume
113
-Cablewski et al., 1994
Construction:
-Reactor coils were PFA Teflon (1/8”
ID, 3 m length) or PTFE
-Pressure gauge at inlet
-Pressure regulating valve at outlet
Flow:
-Metering pump
Temperature Measurement:
-Thermocouples at inlet and outlet of
microwave cavity
Other:
-Solids caused blockages, slurries
could be used if it had very fine
particles
-24 mL processed volume
-Max. Temp. (˚C): 200
-Max. Pressure (psi): 205
-Chemat et al., 1996
Flow:
-Operated in open or closed loop
mode
-Variable-flow piston pump
-Flow rate range: 30 – 335 mL/min
-Residence time: 12 seconds to more
than 2 minutes
Microwave:
-A modified Maxidigest 350 Prolabo
microwave
Temperature Measurement:
-Gas thermometer at the reactor
outlet
Other:
-Catalyst supported in a perforated
plate for heterogeneous reactions
-Samples can be taken from the
sample loop using a Dewar vessel
-500 mL volume processed
-Max. Temp. (˚C): 200
-Max. Pressure (psi): 14
114
-Pipus et al., 2000
Construction:
-Pyrex glass tube (1.07 cm ID),
42 cm long
-Pressure regulating valve
Microwave:
-Conventional microwave oven
(Panasonic NE-1780)
Temperature Measurement:
-NiCr-Ni thermocouples at both the
inlet and outlet of the reactor
-Temperature distribution along the
reactor measured by radiation
thermometry using a IR detector
(Topscan 808)
Other:
-Glass reactor could be filled with
catalyst
-Max. Temp. (˚C): 140
-Max. Pressure (psi): 103
-Bierbaum et al., 2005
Construction:
-Pilot-plant scale microwave
-Alumina reactor tube
-Equipped with two stirrers
-Packed with saddle packing made
from microwave-inactive ceramics
Microwave:
-Microwave reactor specially built by
MLS GmbH
Temperature Measurement:
-4 IR sensors at different locations
along the reactor
-2 Ni-Cr/Ni thermocouples at reactor
inlet and outlet
Other:
-Inline HPLC analysis
-Produced up to 25 kg on a 2.2 L/h
basis
-880 mL processed volume
115
-Milestone - FlowSYNTH, 2011
Construction:
-Reactor tube made of PTFE-TFM
-In-line pressure control valve
-Contains a magnetically drive
paddle stirrer
Flow:
-Flow rate: 12 – 100 mL/min
Microwave:
- Milestone ETHOS-CFR continuous
flow reactor
Temperature Measurement:
-In-line thermal sensor
Other:
-Produces on the scale of hundreds of
grams
-Max. Temp. (˚C): 200
-Max. Pressure (psi): 435
116
Appendix B: Reactor Parts
Table B.1. Reactor parts list.
Process
Part I.D.
PR-1
--
Item
Catalog #
Quantity
Company
Nitrogen Pressure Regulator
Nitrogen Gas Cylinder
C3030-580
1
1
A-5
V-1
RD-1
A-4
H-1
PT-3
PG-3
Union
Plug Valve
Rupture Disk
Connector
T Series PTFE Hose
T Connector
Pressure Gauge
1
1
1
1
1
1
1
A-3
PB-1
Union
Pressure Cylinder
1
1
Swagelok
Swagelok
E-1
V-2
PT-2
A-2
V-3
A-7
--
Elbow
On-Off 2-way Ball Valve
T Connector
Hex Reducing Nipple
On-Off 2-way Ball Valve
Hose Connector
Plastic Hose
SS-4-HCG
SS-4P4T5
SS-RTM4-F4-1
SS-400-1-4
SS-4BHT-48
SS-400-3-4TTF
PGI-63BPG1500-LAOX
SS-4-TA-1-8
304L-HDF81000
SS-8-ME
SS-45F8
SS-8-ST
SS-8-HRN-2
SS-42GF2
SS-5-HC-1-2
14-169-7F
Linde
University
Supplier
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
1
1
1
1
1
1
50 ft
A-1
PT-1
OT-1
F-1
SC-1, SC2
V-4, V-5,
V-7
A-8
PB-2
A-9
V-6, V-9,
V-10, V11
RT-1
Connector
T Connector
Connector
Connector
Connector
SS-6-TA-1-8
TSS-600-3TFT
SS-400-1-4
SS-400-6-2
SS-200-R-1
1
1
1
1
2
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
Fisher
Scientific
Company
Swagelok
Swagelok
Swagelok
Swagelok
Swagelok
On-Off 3-way Ball Valve
SS-41GXS2
4
Swagelok
Connector
Pressure Cylinder
Connector
On-Off 2-way Ball Valve
SS-6-TA-1-4
304L-HDF4-50
SS-200-1-4
SS-41GS2
1
1
1
4
Swagelok
Swagelok
Swagelok
Swagelok
Silicon Carbide Tubes
--
--
Saint-Gobain
Ceramics
--
Reducing Ferrules 1/4”- 3/16”
RK20258
2
Chromatograp
117
RV-1
4 Port, 2 Position Rotary Valve
H-E4UW24VDC
1
FC-1
Flow Cell
--
1
---
CR298713
SS-T2-S-028-20
--
Flow Cell Septa
Stainless Steel Tubing – 1/8” OD,
0.028” ID
Snoop
---
PTFE Tape Pipe Thread Sealant
Giant Jack
MS-SNOOP8OZ
MS-STR-4
S63083
P-1, P-2
High Force Syringe Pump
70-2202
2
SS-1, SS2
PS-1
2.5 mL Stainless Steel Syringes
70-2269
2
30 mL Syringe
--
1
hic Specialties
Inc.
VICI Valco
Instruments
Canada
Corporation
Built by
University of
Toronto
Machine Shop
Varian Inc.
Swagelok
4
1 (20ft
min order)
1
Swagelok
1
4
Swagelok
Fisher
Scientific
Harvard
Apparatus
Harvard
Apparatus
Henke – Sass.
Wolf GMBH
118
Figure B.1. Schematic of the reactor tube holder.
119
Figure B.2. Explosion view of the pressure creating device.
120
Figure B.3. Schematic of the outage tube (OT-1).
121
Figure B.4. Schematic of the flow cell (FC-1): main view.
122
Figure B.5. Schematic of the flow cell (FC-1): Side A.
123
Figure B.6. Schematic of the flow cell (FC-1): side B.
124
Figure B.7. Schematic of the flow cell (FC-1): top view.
125
Appendix C: Process Variables
Figure C.1. A typical screen shot from the IR camera software, demonstrating the heating of a
SiC tube at 100 W. The blue graph shows 3 vertical temperature profiles of the SiC tube,
demonstrating that the vertical surface temperature is nearly constant.
126
Figure C.2. A typical screen shot from the IR camera software, demonstrating the heating of a
SiC tube at 100 W. The blue graph shows 3 horizontal temperature profiles of the SiC tube,
demonstrating that the horizontal surface temperature is nearly constant.
127
Appendix D: Experiments
D.1 Developing the Standard Operating Procedure
The Claisen rearrangement was used to develop the SOP for Reactor Configuration A (Figure 15,
page 38). Below is a detailed account of the steps taken to optimize the reactor operation.
1. Removing Bubbles
As a result of the hypothesis that bubbles could lead to variable residence time, and therefore
variable reaction results, the first set of Claisen reactions were performed with a bubble removal
step. Bubble removal was accomplished by placing the syringe pump vertically (so all air
bubbles would rise up out of the reaction sample) and by flushing out bubbles prior to a reaction.
Step 1 experiments were completed using the following procedure. R-1 was filled with Claisen
reactants and V-5 was set to R-1. Pump P-1 was then filled with 2 mL reactants from R-1. The
pump was then set to infuse the reactant to a 2 mL endpoint back into R-1, therefore pushing out
any bubbles in the pump. Pump P-1 was then refilled with 2 mL reactants from R-1. With V-2
closed, PB-1 was filled with nitrogen gas to 580 psi pressure by opening V-1 and regulating the
nitrogen gas cylinder using PR-1. Setting V-3 and V-6 closed, V-2 was opened to pressurize the
reactor. The microwave MW-1 was turned on to 75 W to achieve a 240˚C average surface
temperature, and once at steady state temperature, V-5 was set to RT-1 and the pump was set to
infuse to a 2 mL endpoint at a flow rate of 25 µL/min (4 minute residence time). At the end of
the reaction, once the full 2 mL had been infused, the pump P-1 and microwave MW-1 was
turned off. The reactor was allowed to sit for 10 minutes, and then the pressure was relieved to
the fume hood by slowly opening V-3. Products were collected from the base of the reactor by
opening V-6 and allowing the solution to drain out. The sample was analyzed without further
workup or purification using NMR.
Running three Claisen experiments using this technique, the reproducibility of the reactor results
improved compared to initial experiments. However, between the three experiments, the reaction
results still spanned a 20 % range for the conversion of starting material. Furthermore, only very
small samples were collected from the reactor, as the majority of the sample was stuck in the
process lines and never made it through the SiC tube. It was hypothesized that although the
128
removal of the bubbles in the reaction mixture itself may have partially improved results, the
encounter of the reaction mixture to valves, tube bends, and fittings in the process lines could
result in bubble formation in the reaction mixture while it was being pumped through the empty
process lines.
2. Priming The Reactor
As a result of the results in step 1, which stated that the possible issues of reproducibility were
due to the presence of bubbles located in the reactor plumbing, the next set of experiments were
performed with a full reactor prime using pure solvent (the same solvent that was used in the
reaction), as well as a bubble removal step. The prime involved the pumping of 8 mL of toluene
into the reactor, after the bubbles had been removed from the syringe using the bubble removal
technique described in step 1.
Step 2 experiments were completed using the following procedure. R-1 was filled with toluene,
the solvent used in the Claisen reaction and V-5 was set to R-1. Pump P-1 was then filled with 2
mL solvent from R-1. The pump was then set to infuse the solvent to a 2 mL endpoint back into
R-1, therefore pushing out any bubbles in the pump. Pump P-1 was then refilled with 2 mL
solvent from R-1. V-5 was set to RT-1 and pump P-1 infused the solvent to a 2 mL endpoint into
the reactor. V-6 was set open and any prime overflow was collected into W-1. V-5 was set back
to R-1 and P-1 set to refill with solvent to a 2 mL endpoint. V-5 was switched to RT-1 and pump
P-1 was set to infuse 2 mL of solvent into the reactor. The refilling and infusing of the pump
with solvent was repeated a total of 4 times, meaning 8 mL of solvent was pushed through the
reactor. Once the excess solvent had drained into W-1, and no more solution came out of the
reactor, V-6 was closed. R-1 was then filled with Claisen reactants and V-5 set open to R-1. P-1
was set to refill to 2 mL endpoint with reactants. With V-2 closed, PB-1 was then filled with
nitrogen gas to 580 psi pressure by opening V-1 and regulating the nitrogen gas cylinder using
PR-1. Setting V-3 closed, V-2 was opened to pressurize the reactor. The microwave MW-1 was
turned on to 75 W to achieve a 240˚C average surface temperature, and once at steady state
temperature, V-5 was set to RT-1 and the pump was set to infuse to a 2 mL endpoint at a flow
rate of 25 µL/min (4 minute residence time). At the end of the reaction, once the full 2 mL had
been infused, the pump P-1 and microwave MW-1 was turned off. The reactor was allowed to sit
for 10 minutes, and then the pressure was relieved to the fume hood by slowly opening V-3.
129
Products were collected from the base of the reactor by opening V-6 and allowing the solution to
drain out. The sample was analyzed without further workup or purification using NMR.
The results of the above experiments are shown in Figure D.1, which indicates that there was still
approximately a 20 % range in conversion of species A for the same operating conditions.
However the overall conversion was improving and approaching literature values (Razzaq et al.,
2009b). The remaining issues with reproducibility were no longer attributed to bubbles, as the
procedure in place (priming and bubble removal) was believed to have removed all bubbles. It
was hypothesized that the variability in the results could be from unreacted starting material left
over in the process lines that drained out when the final products were collected.
Figure D.1. Results from the Claisen rearrangement performed with bubble removal and a
reactor prime. Experiments were completed at a flow rate of 25 µL/min for 260˚C (580 psi
pressure) for Reactor Configuration A.
3. Flushing the Reactor After a Reaction
As a result of the hypothesis in step 2, stating that starting material found in the process lines
could contaminate the final products, a post-reaction flush was introduced. This involved
flushing the reactor with 2 mL solvent (the same solvent that was used in the reaction) at the
same reaction conditions. The flush pushed the remaining starting material found in the process
130
lines before the reactor tube through the SiC tube and allowed the material to fully react. The
flush sequence was tested three times using the Claisen reaction.
Step 3 experiments were completed using the following procedure. R-1 was filled with toluene,
the solvent used in the Claisen reaction, and V-5 was set to R-1. Pump P-1 was then filled with 2
mL solvent from R-1. The pump was then set to infuse the solvent to a 2 mL endpoint back into
R-1, therefore pushing out any bubbles in the pump. Pump P-1 was then refilled with 2 mL
solvent from R-1. V-5 was set to RT-1 and pump P-1 infused the solvent to a 2 mL endpoint into
the reactor. V-6 was set open and any prime overflow was collected into W-1. V-5 was set back
to R-1 and P-1 set to refill with solvent to a 2 mL endpoint. V-5 was switched to RT-1 and pump
P-1 was set to infuse 2 mL of solvent into the reactor. The refilling and infusing of the pump
with solvent was repeated a total of 4 times, meaning 8 mL of solvent was pushed through the
reactor. Once the excess solvent had drained into W-1, and no more solution came out of the
reactor, V-6 was closed. R-1 was then filled with Claisen reactants and V-5 set open to R-1. P-1
was set to refill to 2 mL endpoint with reactants. With V-2 closed, PB-1 was filled with nitrogen
gas to 580 psi pressure by opening V-1 and regulating the nitrogen gas cylinder using PR-1.
Setting V-3 closed, V-2 was opened to pressurize the reactor. The microwave MW-1 was turned
on to 80 W to achieve a 260˚C average surface temperature, and once at steady state temperature,
V-5 was set to RT-1 and the pump was set to infuse to a 2 mL endpoint at a flow rate of 25
µL/min (4 minute residence time). Once P-1 had completely infused the 2 mL of reactants into
the reactor, V-5 was set to R-1, which had been filled with toluene. P-1 was set to refill with
solvent to a 2 mL endpoint. V-5 was then set open to RT-1, and P-1 set to infuse pure solvent
into the reactor to a 2 mL endpoint. At the end of the reaction, once the final 2 mL of solvent had
been infused, the pump P-1 and microwave MW-1 was turned off. The reactor was allowed to sit
for 10 minutes, and then the pressure was relieved to the fume hood by slowly opening V-3.
Products were collected from the base of the reactor by opening V-6 and allowing the solution to
drain out. The sample was analyzed without further workup or purification using NMR. The
results of these experiments showed improved conversion and reproducibility, with a 95-97 %
conversion of starting material for all three experiments.
131
D.2 The Standard Operating Procedure for Reactor
Configuration A
Table D.1. Detailed standard operating procedure for Reactor Configuration A (Figure 15, page
38).
Reactor Priming Sequence
Note: All valves start in the open position, all process equipment turned on.
Step
Operation
Notes
1
Fill reservoir R-1 with solvent.
Same solvent used in the
reaction.
2
Close V-2 and V-3. Open V-1 and regulate nitrogen
Charges PB-1 with nitrogen gas
gas cylinder to fill PB-1 to 50 psi above desired
to the desired operating
operating pressure using PR-1.
pressure.
3
Close V-1.
4
Set V-5 open to R-1 and V-4 open to P-1.
5
P-1 set to refill mode to a 2 mL endpoint.
6
P-1 set to infuse to 2 mL endpoint.
This sequence removes bubbles
from the reactants in the
pumps.
7
P-1 set to refill mode to 2 mL endpoint.
8
Set V-5 to RT-1.
9
P-1 set to infuse mode to 2 mL endpoint. Collect
P-1 priming the reactor with 2
prime overflow in W-1.
mL solvent.
10 Set V-5 to R-1.
11 P-1 set to refill mode to 2 mL endpoint.
12 Repeat steps 8 – 11 four times.
This is equal to 4 x 2 mL of
priming.
13 Close V-6. Open V-2.
Pressurizes reactor.
After priming, valves are in the following positions:
Closed: V-1, V-3, V-6 // Open: V-2, V-4 (open to P-1), V-5 (open to R-1)
132
Reaction and Flush Sequence
Note: All valves in same position when priming finished.
Step
Operation
1
Fill R-1 with reaction mixture.
2
P-1 set to refill mode to 2 mL endpoint.
3
Set MW-1 to power rating that will achieve
desired temperature.
4
Monitor reactor with IR camera to determine
when the tube is at desired operating temperature.
Throughout the reaction, monitor tube surface
temperature with IR camera and adjust MW-1
power settings as appropriate.
5
Set V-5 to RT-1.
6
P-1 set to infuse mode to 2 mL endpoint.
7
Fill R-1 with solvent. Set V-5 to R-1.
8
P-1 set to refill mode to 2 mL endpoint.
9
Set V-5 to RT-1.
10 P-1 set to infuse mode to 2 mL endpoint.
11 Close V-4. Turn off MW-1 and stop pump
program.
12 Allow ten minutes for cooling.
13 Slowly open V-3.
14
Open V-6. Allow products to drain from the
reactor into C-1.
Notes
Once at desired temperature,
proceed to step 5.
Reaction.
Reactor flush.
Vents the nitrogen gas from the
reactor to the fume hood.
133
D.3 Experimental Section
Starting materials and solvents were obtained from commercial suppliers and were used without
further purification. 1H NMR spectra were recorded from a Bruker 300 MHz spectrometer. All
experiments listed below were carried out using Reactor Configuration A (Figure 15, page 38),
and Reactor Configuration A SOP (Table D.1).
2-Allylphenol (2, Scheme 1)
A solution of 10 mL of toluene and 6.71 g allyl phenyl ether 1 was prepared. The reactor was
initially primed with toluene before being pressurized to 580 psi. The 2.5 mL syringe pump was
filled with reactants to the 2 mL mark, and the microwave was powered up to 95 W initially to
get the average surface temperature to 260°C, as indicated by the IR camera. Once at steady state
temperature, the pump was turned on to a flow rate of 25 µL/min. Over the course of the
reaction, the average surface temperature was monitored and the power setting on the microwave
adjusted as necessary to maintain 260°C. After the reactants had completely infused, the pump
was refilled with 2 mL of pure toluene, which was infused into the reactor at the same reaction
conditions in order to flush the lines and completely irradiate all of the reactants. At the
completion of the flush, the microwave was turned off, all valves were closed and the reactor
was allowed to cool for 10 minutes before venting the pressure through the vent valve V-3. The
product valve V-6 was opened to collect the product/solvent mixture (a yellowish oil). The crude
mixture was taken without further workup or purification for analysis by 1H NMR spectroscopy
at 300 MHz in CDCl3.
2-Methylbenzimidazole (4, Scheme 2)
A solution of 10 mL of acetic acid and 0.108 g of o-phenylendiamine 3 was prepared. The
reactor was initially primed with acetic acid before being pressurized to 650 psi pressure. The 2.5
mL syringe pump was filled with reactants to the 2 mL mark. The microwave was powered up
to 50 W initially and was reduced to 48 W over the course of the reaction in order to achieve an
average surface temperature of 170ºC, as indicated by the IR camera. Once at steady state
temperature, the pump was turned on to a flow rate of 200 µL/min. Over the course of the
reaction, the average surface temperature was monitored and the power setting on the microwave
adjusted as necessary to maintain 170°C. After the reactants had completely infused, the pump
134
was refilled with 2 mL of pure acetic acid, which was infused into the reactor at the same
reaction conditions in order to flush the lines and completely irradiate all of the reactants. At the
completion of the flush, the microwave was turned off, all valves were closed and the reactor
was allowed to cool for 10 minutes before venting pressure through vent valve V-3. The product
valve V-6 was opened to collect the product/solvent mixture (a yellowish oil). The crude mixture
was taken without further workup or purification for analysis by 1H NMR spectroscopy at 300
MHz in DMSO-d6.
D.4 Cleaning the Reactor between Experiments
The Reactor Configuration B (Figure 5, page 19), from the syringe pumps (P-1 and P-2) to the
rotary valve (RV-1), was cleaned by pumping pure solvent through the system. An experiment
was conducted to determine how much solvent was required to clean the reactor after a Claisen
reaction had been performed. Several samples were taken throughout the wash and analyzed
using GC/MS, in order assess the cleaning process. The GC/MS provided area counts of the
starting material and product peaks. These peaks were compared from sample to sample in order
to track the disappearance of the materials throughout the wash process.
The experiment started after a reaction had been completed, pressure had been relieved from the
reactor by opening V-3, and products had been collected into C-1 by opening V-6 and V-11, and
setting RV-1 to position (1-4, 2-3). P-1 and P-2 were refilled with air, which was then pushed
through the process lines using the pumps in order to clear out any remaining fluid into W-1. R-1
and R-2 were then filled with pure solvent (toluene). P-1 was set to infuse solvent into the reactor
to a 2 mL endpoint, while P-2 was set to refill to 2 mL endpoint. The flow rate used was 25
mL/min. Once the 2 mL endpoint was reached, the pumps switched actions, so P-2 was set to
infuse, while P-1 was set to refill. The alternating pump sequence was repeated so each pump
delivered 5 x 2 mL of solvent into the reactor. After the wash solution had drained from the
reactor into W-1, an additional 2 mL of solvent was pumped from each pump and collected in a
vial and analyzed using GC/MS. The reactor was cleaned and sampled in this manner 5 times, in
order to ensure the complete removal of the starting material and products of the Claisen reaction
(Figure D.2). Note that all products and by-products of the Claisen reaction were undetected after
the first wash. Overall, a total of 100 mL of solvent was required to remove the residual starting
material from the reactor.
135
Figure D.2. Tracking the removal of starting material during the reactor wash sequence. The
area count represents the total count of the starting material peak from the GC/MS. Reactor
Configuration B was used in this experiment.
D.5 In-Line Analytics Cleaning
The in-line analytics, as shown in Reactor Configuration B (Figure 5, page 19) including the
solvent pump (P-3) and rotary valve (RV-1) to the flow cell, was cleaned by pumping pure
solvent through the system. An experiment was conducted to determine how much solvent was
required to clean the entire system after a Claisen reaction had been sampled from the flow cell.
The experiment involved analyzing several samples from the wash throughout the cleaning
process that had been taken from the flow cell using the GS/MS and CombiPAL autosampler.
The solvent pump (P-3) was set to deliver a total of 15 mL of solvent at a flow rate of 25 mL/min
through the system. Note that for these experiments, V-9 was opened for the first 15 mL of
solvent that was pumped through, and then it was closed for the remainder of the experiment. An
injection was then made by sampling the flow cell using the CombiPAL and analyzed by
GC/MS. The GC/MS provided area counts of the starting material and product peaks. These
peaks were compared from sample to sample in order to track the disappearance of the materials
throughout the wash process. Note that all products and by-products of the Claisen reaction were
undetected after the first wash. Overall, a total of 60 mL of solvent was required to remove the
residual starting material from the in-line analytics (Figure D.3).
136
Figure D.3. Tracking the removal of starting material during the in-line analytic wash sequence.
Samples were taken from the flow cell using the CombiPAL autosampler. The area count
represents the total count of the starting material peak from the GC/MS. Reaction Configuration
B was used in this experiment.
137
D.6 The Standard Operating Procedure for Reactor
Configuration B
Table D.2. Detailed standard operating procedure for Reactor Configuration B (Figure 5, page
19).
Reactor Cleaning Sequence
Note: Start with all valves opened, however, if the clean sequence occurs right after a reaction
has been completed, keep V-1 and V-2 closed to preserve the nitrogen gas in PB-1. Turn on all
process equipment. The pumps will start in opposite positions, so P-1 is set to infuse (meaning
the syringe is empty but ready to infuse) and P-2 is set to refill.
Step
Operation
Notes
1
Fill reservoir R-1 and R-2 with pure solvent.
Pure solvent is the solvent
used in the reaction.
2
Close V-1, V-2 and V-3. Set RV-1 to position (1-4, 2-3).
3
Set V-4 open to P-2, set V-5 open to R-1, and set V-7
open to R-2.
4
Start pump program. P-1 starts with infuse mode, P-2
starts with refill mode to 2 mL endpoint.
5
Set V-7 to RT-1.
6
P-1 set to refill mode and P-2 set to infuse to 2 mL
Automated by pump program.
endpoint. Collect reactor effluent in waste W-1.
P-2 cleaning the reactor.
7
Set V-4 to P-1, set V-5 to RT-1 and set V-7 to R-2.
8
P-1 set to infuse mode and P-2 set to refill to 2 mL
Automated by pump program.
endpoint. Collect reactor effluent in waste W-1.
P-1 cleaning the reactor.
9
Set V-4 open to P-2, set V-5 open to R-1, and set V-7
open to RT-1.
10 Repeat steps 6 – 9 twenty five times.
This is equal to 50 mL of
cleaning per pump.
11 Remove R-1 and R-2 and repeat steps 6 – 9 four times
This sequence helps to clear
using air, and keep V-6 open.
out all solvent from the
process lines.
After cleaning, valves are in the following positions:
Closed: V-1, V-2, V-3 // Open: V-4 (open to P-2), V-5 (open to R-1), V-6, V-7 (open to RT-1),
V-8 (open to R-3), V-9, V-10, V-11, RV-1 (1-4, 2-3)
138
Reactor Priming Sequence
Note: All valves start in same position when cleaning finished. The pumps will start in
opposite positions, so P-1 is set to infuse (meaning the syringe is empty but ready to infuse)
and P-2 is set to refill.
Step
Operation
1
Fill reservoir R-1 and R-2 with reactants.
2
Open V-1 and regulate nitrogen gas cylinder to fill
PB-1 to 50 psi above desired operating pressure
using PR-1.
3
Close V-1.
4
Set V-7 open to R-2.
5
Start pump program. P-1 starts with infuse mode, P-2
starts with refill mode to 2 mL endpoint.
6
P-1 set to refill mode and P-2 set to infuse to 2 mL
endpoint.
7
P-1 set to infuse mode, P-2 set to refill mode to 2 mL
endpoint.
8
9
Set V-7 to RT-1.
P-1 set to refill mode and P-2 set to infuse to 2 mL
endpoint.
Set V-4 open to P-1, set V-5 to RT-1, and set V-7 to
R-2.
P-1 set to infuse mode and P-2 set to refill to 2 mL
endpoint. Collect prime overflow in W-1.
Set V-4 open to P-2, set V-5 open to R-1, and set V-7
open to RT-1.
Repeat steps 9 – 12 two times.
10
11
12
13
Notes
Charges PB-1 with nitrogen gas
to the desired operating
pressure.
Automated by pump program.
This sequence removes bubbles
from the reactants in the
pumps.
Automated by pump program.
This sequence removes bubbles
from the reactants in the
pumps.
Automated by pump program.
P-2 priming the reactor.
Automated by pump program.
P-1 priming the reactor.
This is equal to 2 x 2 mL of
priming per pump.
Pressurizes reactor.
14 Close V-6. Open V-2.
After priming, valves are in the following positions:
Closed: V-1, V-3, V-6 // Open: V-2, V-4 (open to P-2), V-5 (open to R-1), V-7 (open to RT1), V-8 (open to R-3), V-9, V-10, V-11, RV-1 (1-4, 2-3)
P-1 is in position to be refilled, while P-2 is full and ready to infuse reactants into the reactor.
139
Reaction Sequence
Note: All valves in same position when priming finished.
Step
Operation
1
Set MW-1 to power rating that will achieve
desired temperature.
2
Monitor reactor with IR camera to determine
when the tube is at desired operating temperature.
Throughout the reaction, monitor tube surface
temperature with IR camera and adjust MW-1
power settings as appropriate.
3
P-1 set to refill mode and P-2 set to infuse to 2
mL endpoint.
4
5
6
7
8
9
10
11
12
13
Set V-4 open to P-1, set V-5 to RT-1, and set V-7
to R-2.
P-1 set to infuse mode and P-2 set to refill to 2
mL endpoint.
Notes
Once at desired temperature,
proceed to step 3.
Automated by pump program.
P-2 pumps reactants into the
reactor.
Automated by pump program.
P-1 pumps reactants into the
reactor.
Set V-4 open to P-2, set V-5 open to R-1, and set
V-7 open to RT-1.
Repeat steps 3 - 6 for as many times as required to Each time steps 3 – 6 are
pump entire reaction mixture through the reactor. repeated, 4 mL of reactants have
been pumped into the reactor.
To take a sample using the in-line analytics, see
In-Line Analytic Sequence below. Otherwise,
proceed to step 9 to end reaction sequence.
Close V-2. Turn off MW-1 and stop pump
program.
Allow ten minutes for cooling.
Slowly open V-3.
Vents the nitrogen gas from the
reactor to the fume hood.
Open V-6. Allow products to drain from the
reactor into C-1.
After collection, proceed to Clean Sequence to
clean out the reactor.
140
In-Line Analytics Sequence
Step
Operation
Notes
1
Close V-9, V-10, and set RV-1 to position (1-2, 34).
2
Fill R-3 with pure solvent.
Same solvent that is used in the
reaction.
3
Set P-3 to refill to 30 mL endpoint from R-3.
4
Set V-8 to RV-1.
5
Set P-3 to infuse to 5 mL endpoint. Collect
Primes process lines from P-3 to
overflow of prime in W-1.
RV-1.
6
Open V-6. Wait 10 seconds.
7
Close V-6.
8
Open V-10, set RV-1 to position (2-3, 1-4), and
Flow rate: 5 mL/min
set P-3 to infuse to 2 mL endpoint. Start
Sample taken from flow cell by
CombiPAL to take injection.
CombiPAL.
9
After CombiPAL has taken an injection from the
Sequence to start cleaning the inflow cell, open V-9 and set P-3 to infuse to 20 mL line analytics. Flow rate: 25
endpoint. Collect cleaning solution in W-2.
mL/min.
10 Set V-8 to R-3. Set P-3 to refill to 30 mL
endpoint.
11 Close V-9. Set V-8 to RV-1. Set P-3 to infuse to
Sequence to continue cleaning
30 mL endpoint. Collect cleaning solution in W-2. the in-line analytics.
Flow rate: 25 mL/min.
12 Set V-8 to R-3. Set P-3 to refill to 10 mL
endpoint.
13 Set V-8 to RV-1. Set P-3 to infuse to 10 mL
Final sequence to continue
endpoint. Collect cleaning solution in W-2.
cleaning the in-line analytics.
Flow rate: 25 mL/min.
14 Start CombiPAL to take solvent injection from
Sample taken from flow cell by
flow cell.
CombiPAL. This checks to see if
the system is clean before the
next sample is taken.
15 Remove R-3. Set V-8 to the atmosphere. Set P-3
to refill to 30 mL endpoint.
16 Set V-8 to RV-1. Set P-3 to infuse to 30 mL
Removes all solvent in the
endpoint. Collect cleaning solution in W-2.
process lines using air pumped
through the system. Flow rate: 25
mL/min.
141
Appendix E: Modeling Details
E.1 Convection Heat Transfer Coefficient
The CFD model of the SiC tube included a convection boundary condition on the outer outlet
wall. For the convection boundary condition, a heat transfer coefficient was required. In order to
approximate its value, the following equations describing natural convection from the outside of
a vertical wall were assumed to apply to the SiC tube model.
The dimensionless Grashof number, which describes the ratio between buoyant forces and
viscous forces for free convection, is described by:
!" =
!! !! !"Δ!
!!
where L is the length of the tube (0.43 m), ρ is the density of the fluid surrounding the tube (air:
1.2 kg/m3), g is the gravitational constant, β is the thermal expansion coefficient of the fluid
(3.43 x 10-3 1/K), ∆T is the temperature difference between the wall of the tube and the fluid
(assumed to be on average 70˚C), and µ is the dynamic viscosity of the fluid (air: 18.1 x 10-6
kg/ms) (Annaratone, 2010). Solving for the Grashof number, Gr = 8.23 x 108, and with a Prandtl
number for air (Pr = 0.73), GrPr can be determined (6.0 x 108), and because it is between 104 and
109, the natural convection is laminar and the following assumption can be made for the Nusselt
number:
Nu = 0.59Gr0.25Pr0.25
which is equal to Nu = 92.4 for this model (Annaratone, 2010). Using the definition of the
Nusselt number:
!" =
ℎ!
!
the convective heat transfer coefficient (h) can be solved for. Here, L is the length of the tube
(0.43 m), and k is the thermal conductivity of air (0.0233 W/mK). For this model, h is
approximated to be 5.0 W/m2K.
142
E.2 Material Properties
Table E.1. Material Properties for all liquid materials used in this model.
Fluid
Acetic Acid
o-phenylenediamine
(A)
2-Methylbenzimidazole
(B)
Liquid Water
Density
(kg/m3)
Viscosity
(kg/ms)
Molecular
Weight
(kg/kgmol)
10491
0.001221
60.05
Standard
State
Enthalpy
(j/kgmol)
-4.8451E82
10303
0.00122†
108.14
3.91E74
298.154
1030*
0.00122†
132.16
2.69E75
298.155
998.26
0.0010036
18.02
-2.858412E86
2986
Reference
Temperature
(K)
298.152
Note:
*Data not available, therefore substance assumed to have the same density as o-phenylenediamine.
†Data not available, therefore substance assumed to have the same viscosity as acetic acid.
1 – Lewis, 2007
2 – Steele et al., 1997
3 – Sigma-Aldrich, 2011
4 – Contineanu et al., 1982
5 – Jiménez et al., 2004
6 – ANSYS FLUENT, 2011
Table E.2. Material properties of silicon carbide.
Silicon Carbide Properties
Density (kg/m3)
Specific Heat - Cp (J/kgK)
Thermal Conductivity
(W/mK)
Model Inputs
31001
6701
102.61
1 – Saint-Gobain Ceramics, 2011
143
Table E.3. Material properties of the reaction mixture used in this model.
Mixture
Template
Density
(kg/m3)
Viscosity
(kg/ms)
Specific
Heat (j/kgK)
Thermal
Conductivity
(W/mK)
Mass
Diffusivity
(m2/s)
Acetic acid in
excess, A, B,
water
Volume
weighted
mixing law1
Mass
weighted
mixing law1
21482*
0.1592†
1.21E-9
Notes:
* - Specific heat is for acetic acid at 300 K and is assumed to be representative of the reaction mixture.
†Thermal conductivity is for acetic acid at 300 K and is assumed to be representative of the reaction
mixture.
1 – ANSYS FLUENT, 2011
2 – Perry & Green, 2008
3 – Wilke & Chang, 1955
E.3 Sensitivity Analysis for Material Properties
A sensitivity analysis was completed for the CFD model of the SiC tube. There were five
material properties that were unknown, but required as model inputs, and therefore values were
assumed (called the baseline values) based off of other materials used in the model. In order to
determine how the assumed values may have impacted the final reaction results, a sensitivity
analysis was completed for each property. The sensitivity analysis examined the effects of
varying the baseline values by +/- 25 %. The quantities that were assessed include the following:
the density of 2-methylbenzimidazole (B) was assumed to have the density of the starting
material (o-phenylenediamine, 1030 kg/m3), the viscosity of both the starting material (ophenylenediamine, A) and product (2-methylbenzimidazole, B) was assumed to have the
viscosity of acetic acid (0.00122 kg/ms), and the specific heat capacity and thermal conductivity
for the reaction mixture was assumed to have the same values as acetic acid at 300 K (2148
J/kgK and 0.159 W/mK respectively).
The sensitivity analysis was completed by studying the effects of varying these values by
+/- 25 % for the reaction model completed at 150˚C and 200 µL/min. In particular, the effects on
the outlet mole fraction of species A and the outlet fluid temperature were examined for each
case. The results of the analysis are shown in Figure E.1 and Figure E.2. Overall, it was
determined that changing the density of B, and the viscosity of A and B, +/- 25 % from the
baseline value had little effect on the fluid temperature profile and mole fraction of species A at
the outlet of the SiC tube. However, for the specific heat and thermal conductivity of the mixture,
144
changing the baseline values had a large impact on the results, mainly for the outlet mole fraction
of species A.
Figure E.1. The results of the sensitivity analysis on the outlet fluid temperature. The figure
shows the percent difference between the reactions completed with the baseline case (baseline
values for the properties) versus the reactions completed with the properties varied by +/- 25 %.
Figure E.2. The results of the sensitivity analysis on the outlet mole fraction of species A. The
figure shows the percent difference between the reactions completed with the baseline case
(baseline values for the properties) versus the reactions completed with the properties varied by
+/- 25 %.
145
Overall, the sensitivity analysis demonstrated that little error was introduced into the model from
the density of 2-methylbenzimidazole (B), that was assumed to be the same as the density of the
starting material (o-phenylenediamine, 1030 kg/m3), and from the viscosity of both the starting
material (o-phenylenediamine, A) and product (2-methylbenzimidazole, B), that was assumed to
have the same viscosity as acetic acid (0.00122 kg/ms). However, there is a possibility for error
in the model from the assumed values for specific heat capacity and thermal conductivity for the
reaction mixture, which was assumed to be the same as values as acetic acid at 300 K (2148
J/kgK and 0.159 W/mK respectively). These thermal properties play a significant role in the
model results, and therefore may have impacted the final result. A future investigation into
estimating the specific heat capacity and thermal conductivity of the mixture should be
completed in order to create a more accurate model.
E.4 Mesh Dependency Test
A mesh dependency test was conducted in order to determine if the solution of the model was
dependent on the size of the mesh. In order to test this, four models were run at the same reaction
conditions, but with varying mesh coarseness, as determined by the total number of cells in the
mesh (Table E.4). Each mesh was tested with the reaction model of the synthesis of 2methylbenzimidazole, at 130˚C and 200 µL/min. In order to determine if the solution was
dependent on the mesh, the temperature, velocity, and species A mole fraction profiles were
compared for the outlet of the SiC tube. It was concluded that for all of the meshes, the reaction
results for the temperature, velocity, and specie A mole fraction profiles for the outlet of the SiC
tube were identical. As a result, it was concluded that the model result was independent of the
mesh coarseness, within this range.
Table E.4. Mesh sizes tested in the dependency test.
Mesh
1
2
3
4
Type Size (Number of cells)
Quad
40,152
Quad
131,580
Quad
203,175
Quad
356,817
146
E.5 Mesh Coordinates
The geometric coordinates used to develop the mesh of the SiC are shown in Figure E.3.
Figure E.3. The coordinates used to generate the domain of the SiC tube and generate the mesh
used in this model.
147
E.6 Details of the Model Boundary Conditions
Table E.5. Details of the boundary conditions used for the SiC tube in this model.
Boundary
Zones
Axis
Inlet
Boundary
Condition
Axis
Velocity inlet
Outlet
Inlet Wall
Outflow
Coupled wall
Hot Zone Wall
Coupled wall
Outlet Wall
Coupled wall
Outer Inlet Wall Constant
temperature
Hot Zone
Constant
Surface
temperature
Outer Outlet
Convection
Wall
heat transfer
Top edge wall
Constant
temperature
Bottom edge
Convection
wall
heat transfer
Fluid Zone
Interior
Thermal
Condition
Fluid
Fluid
-300 K (room
temperature)
Fluid
Silicon
carbide
Silicon
carbide
Silicon
carbide
Silicon
carbide
Silicon
carbide
Silicon
carbide
Silicon
carbide
Silicon
carbide
Fluid
-Coupled
Momentum
Condition
-Assigned a
flow rate in
m/s
Outflow
--
Coupled
--
No slip
Coupled
--
No slip
300 K (room
temperature)
Assigned a
temperature
h = 5 W/m2K
--
No slip
--
No slip
--
No slip
300 K (room
temperature)
h = 5 W/m2K
--
--
--
--
--
--
--
Material
Other
---No slip
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