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I. TRIETHYLCARBINOL AND RELATED COMPOUNDS. II. STUDIES ON STEROIDAL SAPOGENINS

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THE PENNSYLVANIA STATE COLLEGE
The Graduate School
Department of Chemistry
I.
II.
TRIETHYLCARBINOL AND RELATED COMPOUNDS
STUDIES ON STEROIDAL SAPOGENINS
A Thesis
by
ELDON MELTON JONES
Submitted in partial fulfillment
of the requirements
for the degree of
DOCTOR OF PHILOSOPHY
June, 1940
Approved:
May
, 1940
epartment of Chemistry
May
, 1940 -
May
, 1940
(Km m j l I/ <T.
‘Department or Onemlstrv
Head', Department o r u q ^ m T s t r y
ACKNOWLEDGEMENT
• The author takes this opportunity to express
his warmest appreciation to Dr. P. C. Whitmore and
to Professor R. E. Marker, the directors of these
studies, for their suggestion of the problems and
for the stimulating interest which they have shown
during the course of the investigations.
TABLE OF CONTENTS
Part I - Trlethylcarblnol and Related Compounds.
Introduction
page 1
Historical----------------------------------------- page 2
D i s c u s s i o n ---------------------------------------- page 2
Experimental ------------------------------------- page 5
Distilling Equipment
page 5
Source of M a t e r i a l s ------------------------- page 6
Preparation of Trlethylcarblnol
page 7
Dehydration of Trlethylcarblnol
page 8
Ozonolysls of 3-Ethyl-3-pentene
page 9
Pilot Huns of the Polymerization of
3-Ethyl-2-pentene
page 10
Polymerization of 3-Ethyl -3- pentene
page 13
Fractionation of the P o l y m e r s -------------- page 15
Refractionation of the P o l y m e r s ----------- page 18
Densities and Molecular Refractions of
the P o l y m e r s ---------- page 23
Summary of the Polymerization Products
page 23
Preparation of Triethylcarbinyl Chloride - page 35
Preparation of Triethylcarblnylmagneslum
Chloride
page 25
Preparation of Trlethylacetic A c i d
page 26
Preparation of Trlethylacetamide
page 27
Preparation of
page 28
3,3-Diethyl-2-pentanone
Bromination of Trlethylcarblnol ---------- page 29
Hydrolysis of 3,3-Dibromo-3-ethylpentane - page 30
Solid By-product from the Preparation
of Trlethylcarblnol - page 31
Preparation of Stannic C h l o r i d e -------------page 32
Treatment of 3-Ethyl-3-pentene with
Acetyl C h l o r i d e
page 33
Oxidation of 3-Ethyl-l-butanol---------------page 34
Preparation of Dlethylacetamide-------------page 35
Preparation of Methyl-t-butylacetyl
C h l o r i d e --------------page 36
Attempted Preparation of Diethylp l n a colylcarbinol
page 36
Treatment of Ethylpinacolyl Ketone with
Ethylmagneslum B r o m i d e
page 37
Summary
page 39
B i b l i o g r a p h y ---------------------------------------- page 40
Part II - Studies on Steroidal Sapogenlns
I n t r o d u c t i o n ---------------------------------------- page 41
H i s t o r i c a l ------------------------------------------ page 42
D i s c u s s i o n ------------------------------------------ page 60
A.
S a r s a s a p o g e n ln---------------------------page 60
B.
C h l o r o g e n i n ------------------------------ page 66
Experimental
A.
Sarsasapogenln —
page 69
----------------------- page 69
Preparation of Pseudosarsasapogenin
page 69
Oxidation of Pseudosarsasapogenin
page 69
Sa r s a sapogenone
page 70
Pseudosarsasapogenone
page 70
Oxidation of Pseudosarsasapogenone ----- page 71
Desoxysarsasapogenin--------------------- page 71
Pseudodesoxysarsasapogenin -------------- page 71
Dihydropseudodesoxysarsasapogenln
page 72
Oxidation of Pseudodesoxysarsasapogenin
page 73
epl-Sarsasapogenin
page 73
epi-Pseudosarsasapogenln
page 73
epi-Dlhydropseudosarsasapogenln
page 74
p-Nitrobenzoate of epi-Dlhydropseudosarsasapogenin-------- page 74
Oxidation of epi-Pseudosarsasapogenin —
page 75
Oxidation of epl-Sarsasapogenin with
Persulfuric a c i d
page 75
Benzoate of Pregnanetriol-3(
) ,16,30 —
page 76
Prepara.tion of Tetrahydrosarsasapogenln
page 77
Clemmensen Reduction of Tetrahydrosarsasapogenin-------- page 77
16-Acetoxy-tetrahydrosarsasapogenin ---- page 77
Oxidation of Sarsasapogenln Acetate
with Hydrogen
P e r o x i d e --------------- page 79
Action of Hydrogen Peroxide on Pseudosarsasapogenin-------- page 79
C h l o r o g e n i n --------— ---------------------- page 81
Preparation of Pseudochlorogenin ------- page 81
Acid Isomerization of Pseudochlorogenin
page 81
Preparation of Chlorogenone ------------
page 81
Oxidation of Cholestanediol-3,6 --------
page 82
Reduction of Gholestanedione-3,6 -------
page 82
Reduction of Chlorogenone with Sodium
In e t h a n o l ----------- page 83
Acetate of Chlorogenin .
page 83
Catalytic Reduction of Chlorogenone
page 84
Acetate of beta-Chlorogenin
page 84
Benzoate of beta-Chlorogenin
page 85
Reduction of beta-Chlorogenin ----------
Page 85
----------------------
!p age 87
-
Summary
B i b l i o g r a p h y --------------------------------------page 88
PART I
TRIETHYLG ARBINOL AMD RELATED COMPOUNDS
INTRODUCTION
Numerous studies of dehydration of alcohols
and polymerization of the resulting olefins have been
made in this laboratory.
The polymers actually ob­
tained were those predicted according to Whitmorels
theory of polymerization (l) as, for example, in the
case of isobutene (3) and of tetramethylethylene (3 ) i(4).
Trlethylcarblnol can be dehydrated to 3-ethyl3-pentene.
Polymerization of this olefin to the dimer
yields a mixture of tetradecenes which, theoretically,
should consist principally of 3,5,5,-triethyl-4-methyl3-heptene and 3,5,5-triethyl-4-methyl-3-heptene.
The purpose of the present study was to prepare
and identify the polymers of 3-ethyl-3-pentene.
preliminary work the polymers were prepared,
In'the
separated
by careful fractional distillation, the physical con­
stants of the fractions were determined, and certain
related compounds useful in the identification of the
polymers were prepared.
The work on the identification
of the polymers Is being continued by H. D. Zook of
this laboratory.
d
2
HISTORICAL
The literature on trlethylcarblnol - Its prep­
aration, dehydration, and attempts at polymerization
of the resulting olefin - has been reviewed by W. C.
Smith (5).
DISCUSSION
The trlethylcarblnol used in this work was pre­
pared by the action of ethylmagnesium bromide on ethyl
propionate (6), with an average yield of about 75$.
Trlethylcarblnol was dehydrated by dropping it
onto a 5:1 mixture of copper sulfate and pumice at
180°.
An average yield of about 90$ of the purified olefin,
3-etliyl-3-pentene, was obtained.
Ozonolysis of the olefin yielded only acetaldehyde
and diethyl ketone.
This proved that 3-ethyl-3-pentene
was the only olefin formed.
Because of the symmetry of
the carbinol molecule the formation of other olefins
would not be expected.
Six pilot runs were made to determine the best
conditions for the polymerization of 3-ethyl-3-pentene
to the dimer.
The best results were obtained using
equal volumes of 84$ sulfuric acid and olefin at a
temperature of -8° to -10°.
Two large runs, using 11 moles of olefin in each,
yielded 3070 g. of crude polymer.
The product was
3
fractionated through Column W and refractionated through
Column EMJ.
The yield of dimer was 54$.
The refractive
index-weight curve for the distillation showed the
presence of seven isomers.
Triethylcarbinyl chloride was prepared by treating
triethylcarbinol with dry hydrogen chloride.
This was
converted to the Grignard reagent, with a yield of 66$.
Treatment of triethylcarbinylmagnesium chloride with
carbon dioxide gas at -5° and 60 mm. pressure (gauge)
gave a 13$ yield of trlethylacetlc acid.
In addition
to the acid a 67$ yield of 3-ethylpentane was obtained,
indicating incomplete reaction between the carbon dioxide
and the G-rignard reagent.
Triethylacetic acid reacted with thionyl chloride
to give the acid chloride, which, upon treatment with
dry ammonia gas, gave a 73$ yield of triethylacetamide.
Triethylacetamide was treated with methylmagnesium
chloride to form 3,3-diethyl-2-pentanone.
This ketone
was characterized by the preparation of a 2,4-dinitrophenylhydrazone.
Trlethylcarblnol was brominated by treatment with
bromine at 50°.
After an induction period of about
15 minutes the reaction proceeded quite rapidly with
the evolution of heat.
The yield of 2,3-dibromo-3-ethyl-
pentane obtained was 47$. An attempt to hydrolyze the
dibromide by refluxing with water was unsuccessful.
4
An attempt was made to Identify a crystalline
material which forms in the preparation of trlethylcarblnol
The crystals appear in the condenser after the steam
distillation of the carbinol.
Melting point, molecular
weight, and solubility in organic and inorganic solvents
were determined.
were made.
Elementary analysis and ignition tests
Oxidation with alkaline potassium permanganate
and reduction with sodium in moist ether were attempted.
The material did not decolorize a solution of bromine in
carbon tetrachloride.
The identification of the sub­
stance was not completed.
Diethylacetamide was prepared by treating diethylacetic acid with thionyl chloride and adding ammonia.
The over-all yield was 67$.
Methyl-t-butylacetic acid was separated by careful
fractionation of a crude mixture of acids obtained from
W. R. Wheeler of this laboratory.
The acid was treated
with thionyl chloride to form the acid chloride, which,
in turn was treated with ethylmagneslum bromide.
None
of the expected diethylpinacolylcarbinol was obtained.
Instead, ethyl pinacolyl ketone was formed in 56$ yield.
The ketone was recovered unchanged after treatment with
ethylmagnesium bromide, methylmagnesium chloride, and
methylmagnesium iodide.
Addition of the Grignard
reagent is prevented b y enolization of the ketone.
5
EXPERIMENTAL
DISTILLING EQUIPMENT
All of the fractionating columns used In this
work were of the total condensation, Partial take-off
type except JPC, which was a partial condensation
column.
Columns W and EMJ were packed with 3/33 in.
stainless steel helices and the others were packed
with 5/33 in. glass helices.
Length
Diameter
E
63.5 cm.
1.5 cm.
12
L
40.0 cm.
0.8 cm.
11
B
80.0 cm.
2.0 cm.
11
W
108 in.
EMJ
100 cm.
Column
JPC
48.0 cm.
Theoretical
87
.75 in.
1.0 cm.
35
1.0 cm.
9
All refractive Indices were taken on an Abbe
refractometer kept at 2 0 °.
Jr
.0 1 ° by means of an
electrically controlled thermostats.
6
Source of Materials
The fethyl bromide used in all the Grignard
reactions was Eastman Practical, which had been
dried over calcium chloride.
The ethyl propionate used in the preparation
of the triethylcarbinol was redistilled Eastman
Technical grade.
The material used boiled at 77-79°/740
mm. and had an index of refractions of 1.3840-1.3842.
Dlethylacetic acid was obtained from W. 0.
Osborn.
It boiled at 100°/ 18 mm. and had a re­
fractive index of 1.4133.
Methyl-t-butylacetic acid was obtained from
a mixture of acids prepared by W. R. Wheeler by the
oxidation of nonenes from stock t-amyl and t-butyl
alcohols.
4
7
Preparation of Materials
Preparation of Trlethylcarblnol.-
A total of twenty
runs was made in the following manner:
In a 3-neck,
5 liter, flask equipped with reflux condenser, dropping
funnel, and mercury sealed stirrer, were placed 6 moles
of magnesium and 1000 cc. of dry ether.
A solution of
6 moles, 654 g. , of ethyl bromide ln.-lOOO cc. of dry
ether was added through the dropping funnel during 10
hours with vigorous stirring.
The mixture was stirred
overnight and a solution of 3 moles, 306 g . , of ethyl
propionate in 500 cc. of dry ether was added through
the dropping funnel during 8 hours.
The flask was
cooled in a water bath during the addition of the
ester.
The mixture was stirred overnight and was
decomposed by the addition of 1300 g. of ice.
The
ether was distilled and the remainder was steam
distilled to effect a separation of the carbinol.
The water layer of the distillate was extracted twice
with 150 cc. portions of ether.
The extracts were
combined with the oil layer and the ether was
distilled.
After drying over potassium carbonate,
the product was fractionated through Column E.
8
Time
Cut
3:45.: PM" 1
3
3:56
3
3:13
4
3:31
5
4:04
6
4:35
7
4:55
5:30
8
11:19 AM
11:43
13:00
13:37
13:57
1:33
1:53
-3:34
3:58
3? 26
4:60
4:33
4:43
5:03
5:17
5.:33
residue
Bath
117°
117
117
117
116
115
115.
115
115.
9
10
114
114
11
116
13
118
13
14
118
15
117
16
117
117
17
18
119
130
19
130
30
31
131
134
33
137
33
34
149
- 3 g-
Head
11°
85
85.
85
85
85:
853
85
Index
1.3918
1.4316
1.4388
1.4394
1.4296:
1.4296
1.4296
1.4296
Weight
7.1g.
3.7
6.0
8.1
13.9
11.7
11.9
13.3
86
86
86
86
86
86
86
86
86
86
86
86
86
86
86
86
1.4296
1.4396
1.4296
1.4396
1.4296
1.4396
1.4296
1.4296
1.4396
1.4396
1.4396
1.4296
1.4296
1.4296
1.4296
1.4296
10.3
13.0
14.0
13.0
13.6
12.0
14.1
13.9
13.1
12.0
13.4
12.6
12.6
13.2
9.9
6.2
Pressure
100 mm.
100 mm.
100 mm.
100 mm.
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
Guts 3- 34, 358.7 g. , 3.33 moles, 74 .3fo of trlethylcs
The carbinol had a boiling point of 143° at an
atmospheric pressure of 74-4 mm.
Dehydration of the carbinol frequently took place
upon distillation, and in many cases the olefin was ob­
tained in this manner.
Dehydration of T r i e t h y l c a r b i n o l A 5:1 mixture of copper
sulfate - pumice, 30 g . , was placed in 3-neck, 500 cc.
flask attached to Column E.
The column jacket was kept
at 90° and the flask was heated in an oil bath at 180°.
During eight hours, four moles, 464- g., of triethylcarbinol
was added to the flask through a dropping funnel.
As the
<t
9
carbinol was dehydrated the water and the olefin distilled
out and were separated.
The olefin was dried over sodi
sulfate and distilled through Column E.
Cut
Time
7 :3& PM "T"
2
7:43
3
7:53
4
8:09
8:37
5
6
9:32
7
10:23
10:44
8
11:03
9
10'
11:26
11:40
11
Bath
108
107
106
108
111
113
116
120 128
139
Head
93°
94
94
95
95
95
95
95
95
95
96':
Index
1.4123
1.4140
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
Weight
2.2g.
4.1
6.0
14.7
41.0
86.0
86.0
39.0
38.0
37.0
5.6
Pressure
742 mm.
742
742
742
742
742
74-2
742
742
742
742
Cuts 3-11, 356••3 g. , 3 .64 ;
moles, 91$ of 3-Ethyl-2-pentei
A total of 34 moles of the above olefin were prepared.
Ozonolysls of 3-EthyJ- 2-pentene.-
3-•Ethyl-2--pentene, 0
moles, 39.2 g . , was dissolved in 300 cc. of low boiling
hydrocarbon solvent and a stream of ozonized oxygen was
passed through the solution for 13.5 hours at the rate of
16 liters per hour.
The ozonide was decomposed by dropping
it into a boiling mixture of 500 cc. of water and 0.4 moles
of zinc, which contained traces of silver nitrate and
hydroquinone.
The products distilled out during the re­
action, and the more vola.tile material was collected in
an ether trap at the end of the system.
The ether was
dried over sodium sulfate and dry ammonia was passed
through for six hours,giving 13 g . , 53$, of the acetaldehyde-ammonia complex.
The water layer of the distillate
was extracted twice with 25 cc. portions of ether which
10
were combined with the oil layer and dried over sodium
sulfate.
The ether was distilled and the residue was
fractionated through Column L.
Fractionation of the oil products from the ozonolysis of
olefini
Cut
Bath
Time
T3TS0 T "
us*
13:08
3
133
12:17
136
3
13:27
4
138
5
128
12:31
13:41
6
133
140
13:51
7
1:08
8
158
184
1:28
9
195
1:38 10
1:50 11
303
residue - 1.3 g.
Head
63
70
94
98
99
100
100
100
101
103
Index
TT3SS0
1.3738
1.3774
1.3888
1.3918
1.3918
1.3930
1.3930
1.3933
1.3930
1.3933
Weight
1 .lg.
1.2
.8
.8
1.3
3.4
4.4
•4.3
4.3
1.3
1.3
Pressure
740 mm.
740
740
740
740
740
740
740
740
740
740
Cuts 5-11, 19.3 g . , .334 moles, 56.1$ of diethyl ketone.
The 3,4-dinitrophenylhydrazone of cut 8 was made and
found to melt at 155-156°.
A mixture with an authentic
sample of the same derivative of diethyl ketone gave no
depression in melting point.
Pilot runs of the polymerization of 3-Ethyl-3-pentene.No.
\
- 3-Ethyl-S pentene, 0.5 moles, 49 g . , was placed
in a 3 neck, 300 cc. flask equipped with dropping funnel,
reflux condenser, and stirrer.
The flask and contents
were cooled to 0° and an equal volume, 70 cc., of 75$
sulfuric acid at 0 ° was added through the dropping
funnel during 30 minutes.
During the addition of the
acid the flask was kept in a bath of ice-HCl at - 8 to
-10°.
The yellowish mixture was stirred for 15 minutes
11
and the cooling bath was removed.
The mixture was
stirred for another 15 minutes and then allowed to stand
at room temperature for 3 hours.
At the end of this time
the oil layer was colorless and the acid layer was orange.
The oil layer was washed with 15 cc. of 10$ sodium carbonate and then with 30 cc. of water.
weighed 44 g.
The crude material
After drying over potassium carbonate thi
was distilled through. Column> L.
Cut
Time
13:40 PM T “
3
13:49
1:00
3
4
1 :15
5
1:39
1:38
6
7
1:48
8
1:58
3:07
9
10
3;33
3:37
11
3:48
13
Bath
119°
119
119
119
131
133
133
135
136
134
138
300
Head
“ S30,
94
94
94
94
94
94
94
94
94
101
105
Index
1T5177
1.4150
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4148
1.4534
1;4593
Weight
l.b g.
1.6
3.3
4.6
5.3
4.3
4.7
4.8
4.3
5.3
.5
1.7
Pressure
730 mm.
730
730
730
730
730
730
730
730
730
13 mm.
13
Cuts 3t *10 represent 37 g . , or 75$ recovered olefin.
No. 3 - same as No. 1 except that 81$ acid was used.
The
crude material was distilled through Column L.
Weight
Time
Cut
B ath
Head
Index
3.3 g.
Y7S1
35
8:36 AM 1
93®
15 3 *
3.5
94
1.4135
8:51
3
159
1.4130
3.5
9:10
170
95
3
3.1
1.4143
4
185
99
9:31
3.4
1.4156
334
5
110
9:33
-74
1.4370
1.3
6
119
10:33
1.4450
3.3
10:45
7
134
, 85
3.6
1.4516
97
11:44
8
118
3.0
1.4536
9
103
13:15
133
3.5
1.4533
1
0
130:
99
13:33
3.8
1.4537
13:50
103
11
131
3.3
1.4546
99
114
1:05 PM 13
1.4546
5.3
117
1:43
13'
103'
5.3
1.4554
104
14
3:00
134
3.0
1.4563
106
130
15
3:37
1.7
1.4576
, 108
163
16
3:03
.6
1.4578
1
1
0
330
17
3.35
Residue - .3 g . , Total take-•off -44.3 g.
Pressure
733 mm
733
733
733
733
13 mm
13
13
16
13
14
13
13
13
13
13
13
13
No. 3 same as No. 1 but with 84$ acid.
The crude material
was distilled through Oolumn L.
Bath
Head
Cut
Weight
Index
Time
100°
1.4167
3.3 g.
5:30 M
1
3 03 6
110
1.4300
75
10:08
3
1.3
87
1.437D
10:15
110
1.1
3
120
1.4470
4
92
3.9
16:36
3.0
94
10:40
5
113
1.4493
1.4510
97
118
3.9
6
10:53
97
1.4513
11:08
7
131
3.3
109
98
4.7
11:50
1.4532
8
5.0
137
98
1.4528
9
13:35
1.4534
5.7
10
139
103
13:51
5.0
136106
1.4544
1:14 PM 1 1
110
149
1:30
1.4555
3.3
13
177
115
1.4565
3.03
1.7
13
1.4580
230
14
132
3.35
1.3
44.0
Residue - .8 g. , Total talce-off
g.
Pressure
736 mm.
12 mm.
12
12
13:
12
13
12
12
12
13
12
13
13
No. 4 - same as No. 1 except that no external cooling
bath was applied during the addition of the cold acid to
the cold olefin.
The mixture was stirred for 30 minutes
after the addition of the acid.
temperature.
There was no rise in
The crude material was distilled through
Column L.
Weight
Pressure
Index
Cut
Bath Head
Time
735 mnn
1.4148
2 .8 g.
118°
5:oo AM 1
93°
1.4146
4.6
725 mm.
94
9:18
133
3
735
4.5
1.4146
124
94
9:38
3
4.7
1.4146
735
94
9:59
4
133
1,4146
725
5.2
134
10:25
94
5
5.5
1.4146
735
94
135
10:49
6
4.6
'735
1.4148
130
94
11:45
7
1.4150
735
3.7
20 0
94
13 :45
8
1.7
13 mm.
1.4514
100
133
3:08 PM 9
1.4554
3.8
13
160
3:45
10
103
15
1.4570
.6
300
3:07
103
11
Residue - .7 g . , Fractions 1-8, 35.6 g., represent"a
recovery of 74$ of the original olefin.
No. 5 - Similar to No- 4 but with 81$ acid.
The tem­
perature of the mixture at the end of the addition of
the acid was 53° and a sharp odor was noticed.
The
13
crude material was distilled through Column L.
Cut
Bath Head
Weight
Time
Index
75.*
1.4300
3755 PM '"1 ~
1136
5. 8 g.
118
87
3
7:33
1.4431
5.3
130
93
1.4487
7:37
3
5.5
4
118
97
7:53
1.4503
3.3
97
1.4510
5
119
5.0
8 :11
1
0
0
6
1.4514
3.7
133
8:31
7
135
103
1.4519
4.1
8:53
105
9:30
8
1.4539
3.5
133
109
140
9
1.4533
1.3
9:35
144
10
1.4537
9:44
111
1.3
160
1.4544
1.4
10:07
113
11
135
10:30
195
1.4556
1. 1
13
Residue - 1. g . , Total take-off - 39.9 g.
No. 6 - similar to No. 4 but with 84$ acid.
odor produced in the reaction mixture.
Pressure
13 mm.
11 mm.
11
11
11
11
11
11
11
11
11
11
Very sharp
The crude product
was fractionated through Column L.
Weight
Bath Head
Index
1080 ~Td 5 0’
T. 4339
l.lg.
1.4330
1.0
65
9:16
105
3
3.0
77
1.4377
115
9:31
3
9:40
1.4434
130
1.9
4
83
1.4444
1.7
9:49
85
5
133
3.4
134
89
1.4458
6
10:03
1.4480
3.0
10:11
7
135:
93
94
1.4488
10:31
137
8
3.1
3.4
96
1.4495
10:36
137
9
130
1.4507
11:10
10
5.1
93
1.4514
4.9
100
11:44
11
133
1.9
13:07
1.4533
'103
13
143
1.4536
1.6
13:30
106
148
13
107
1.9
1.4533
13:47
14
156
1.
0
1.4536
115
1:05
160
15
1.4544
1.6
160
119
16
1:33
1.7
130
1.4553
180
1:46
17
1.4584
1.3
140
1:55
194
18
Residue - 1 . 8 g . , Total take- off - 37. ? g.
Time
9:08 AM
Cut
1
Pressure
11 mm.
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
The conditions used in run No. 3 were chosen as the best
for the polymerization of the olefin in large amounts.
Polymerization of 3 -Ethyl- 3 -pentene.made, using 11 moles of olefin in each.
Two runs were
The olefin was
14
placed In a 5 liter flask equipped with a stirrer and a
dropping funnel.
The flask was packed in an ice-HCl
bath and cooled for 1 l/S hours.
An equal volume
(1510 cc.) of pre-cooled 84% sulfuric acid was added
through the dropping funnel, with vigorous stirring,
during 6 hours.
The mixture was stirred for 17 hours,
during which time the temperature was allowed to rise
to 25°.
At the end of the stirring the acid layer was
cherry-red in color and the olefin layer was a clear,
colorless liquid.
The oil layer was removed and
washed with 250 cc. of 10% sodium carbonate solution,
then with 250 cc. of water.
The odor of sulfur dioxide
disappeared during the washing.
The products from two
such runs were combined and dried over potassium
carbonate.
The yield of crude, dry product was 2,07Q g . ,
while the theoretical amount would be 2,156 grams.
The
crude material was separated roughly into two large
fractions by fractionation through Column B.
The first
cut, weighing 1218 g . , consisted of material boiling up
to 103°/13 mm.
The second fraction weighed 715 g. and
was distilled off rapidly,
was desired at this point.
since no further separation
The residue from this
distillation weighed 27 grams.
It was not investigated.
The acid layers from the polymerization, upon
treatment with 2 0 0 0 g. of ice and extraction with ether,
gave about 20 g. of a dark, evil-smelling oil.
This oil
distilled from 60° to 231°, and was not investigated
further.
15
Fractionation of the polymers of 3-Ethyl-2-pentene.The mixture of polymers from above was fractionated
through Column W.
The first fraction from the rough
fractionation through Column B was charged to the column
first.
After about half of the material had been
distilled the remaining 715 g. were added.
The
following data were obtained.
Fractionation III.
Cut Pot
139°
139
139
145
143
144
144
144
146
150
152
149
5 25
13 152
14 152
7 35
9 00
15 153
1 0 00
16 152
1 1 15
17 150
150
1 2 20 AM 18
1 30
19 151
20
2 45
152
3 45
21
152
4 45
22
152
6 05
23 153
7 00
24 153
7 50
25 153
1 0 45
26 152
1
0
PM
1
27 154
4 35
28 151
6 25
29 154
9 15
30 154
1 0 15
31 154
11 0 0
32 154
0
0
12
33 155
Time
1
1 0 0 AM
00
2
2
3
3 00
4
4 00
5
5 00
6
6 00
7 00
7
8
8 00
9
9 00
1 0 30
10
1 15 PM 1 1
3 25
12
Head
63°
74
84
87
92
97
98
100
100
100
103
104
107
108
110
111
112
113
115
115
115:
115
115
116
116
116
117
117
117
118
118
118
119
Index
1 .40^7
1.4204
1.4280
1.4308
1.4334
1.4353
1.4359
1.4360
1.4386
1.4400
1.4402
1.4414
1.4420
1.4420
1.4420
1.4420
1.4420
1.4420
1.4430
JE1.4437
1.4444
1.4450
1.4453
1.4456
1.4460
1.4464
1.4466
1.4470
1.4473
1.4476
1.4476
1.4476
1.4476
Weight
13 g.
15
15.2
15.. 3
12.4
13.4
14.3
13.5
13.6
10.2
12.4
12.7
14.3
13.5
13.5
15.2
13.9
12.6
14.7
15.6
14.8
15.0
12.3
13.4
'9.1
14.6
12.8
13.5
14.5
15.2
14.6
13.7
12.3
(Continued on next page)
Pressure
50 mm.
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
16
Head Index
Cut Pot
Welgl
Time
i£ 0 6 1.4476
1 05 Alt 34 155°
12.7
35 156
131
1.4476
15.0
3 00
36 156
14.0
133
3 00
1.4478
4 00
37 156
133
1.4481
10.6
134
38 156
5 00
1.4486
14.9
134
1.4490
6 00
13.9
39 157
40 157
135
7 00
1.4490
14.5
41 156
135
1.4490
8 00
13.6
43 156
135
1.4490
9 00
11.3
10 35
136
43 153
1.4490
16.8
136
1.4490
13 30 PM 44 153
16.3
flooded
13 40
3 35
133
134
1.4490
45 154
4 30
13.4
30
146
134
6
46
1.4490
13.5
8 00
47 153
135
1.4490
13.5
9 00
1.4490
48 153
135
16.3
10 00
49 153
135
1.4490
15.8
50 153
11 00
135
1.4490
17.1
1.4490
13 00
51 156
136'
17.4
Distillation stopped and the remaining
1 30 AM
Column all flooded
3 30
53 161
133
8.8
1.4485
4 30
1.4490
53 161
9.1
133
5 30
54 161
1.4490
13.7
133
6 30
55 161
1.4490
133
14.5
7 45
56 163
1.4491
133
11.1
9 30
57 163
134
1.4493
13.3
11 35
58 163
134
1.4495
13.5
1 30 PM
14.1
59 163
135
1.4498
3 30
60 163
125:
15.0
1.4498
5 30
1.4500
134
61 164
14.2
7 30
124
1.4500
63 164
14.6
9 30
124
1.4504
63 164
14.7
11 30
64 164
125:
1.4506
14.3
1 30 AM
65 165
135
14.6
1.4508
3 30
66 166
1.4510:
125
14.5
5 35
14.9
67 166
1.4514
125
7 30
15.0
6 8 166'
1.4514
135
9 35
69 166
125
1.4514
14.3
11 30
70 165
12.7
1.4514
126
3 0 0 PM 71 166
17.1
126
1.4517
4 00
13.9
125
1.4518
73 166
6 00
13.4
126
1.4520
73 166
8 00
1.4520
14.4
74 166
137
10 0 0
13.6
753 167
127
1.4522
13.7
13 00
128
1.4522
76 167
3 00 AM 77 167
14.3
129
1.4532
4 00
13.9
1.4523
78 167
129
(Continued on next page)
Pressure
56 mm.
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
added.
50 mm.
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
17
Cut Pot
Time
6:00 AM
167°
80 167
8:00
81 168
10:00
83 169
12 TOO''
3:10 PM 83 169
84 169
4:15
6:00
85 169
86 169
8:00
87 169
10:00
12:00
88 169
2:00 AM 89 169
90 171
4:00
6:00
91 172
8:0 0
93 172
10:00
93 170
94 173
12:00
3:05 PM 95. 172
96 173
4:05
6:00
97 173
8: 0 0
98 173
10:00
99 176
13:00
1 0 0 176
2:00 AM 1 0 1 175
4:00
103 178
6:00
103 178
8 :00
104 180
10:00
105 181
12:00
106 182
1:00 PM
flooded
3:00
107 180
108 181
109 181
1 1 0 182
12:00
1 1 1 182
1:30 AM 113 183
3:05
113 185
4:40
114 183
6:15
115 183
7:45
116 184
117 184
9:20
118 187
10:20
11:30
119 188
4.35
6:35
8:30
10:15
Head
Index
1.45&3
129
1.4522
1.4523
109
1.4522
139
1.4533
129
1.4523
129
1.4523
129
1.4522
129
1.4523
139
129
1.4532
129
1.4523
1.4523
129
130
1.4532
1.4530
130
130
1.4537
1.4546
131
1.4550
130
130
1.4550
1.4550
131
1.4550
131
1.4544
133
1.4538
132
1.4533
133
1.4530
134
135 • 1.4530
1.4528
136
1.4-524
137
1.4524
140
134
135
136
1367.
137
138
138
138
138
138
137
137
134.
136
1.4524
1.4534
1.4534
1.4534
1.4536
1,4536
1.4538
1.4538
1.4538
1.4532
1.4536
1.4540
1.4540
Weight
14.0
14.2
13.4
13.9
15.4
15.1
13.0
14.8
14.6
14.8
14.5
14.4
14.3
14.0
13.7
13.9
15.3
13.6
13.3
13.8
14.1
14.3
14.5
15.0
15.0
14.2
14.6
13.5
10.6
13.4
16.3
15.9
15.6
13.6
14.7
14.6
14.'3
13.2
14.6
rs;s
11.7
Pressure
50 him.
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
40 mm.
40
The fractionation was stopped at t h i s point and the
residue of 348 g. was transferred to Column EMJ (page
5
) for completion of the distillation.
(Continued on next page)
18
Head Index
Cut Pot
Weight;
column all flooded
130 180®
141° 1.4538
3.4
9 00
1.4540
13.0
143
10 00
131 181
1.4540
9.6
133 181
143
11 00
1.4540
13.5
143
133 181
13 00
1.4540
144
15; 11
1 00 AM 134 181
1.4540
135 183
145
11.7
1 33
1.4540
136
185
147
13.7
39
3
1.4544
30
137
11.7
187
148
3
1.4546
138 189
13.3
4 30
149
150
1.4548
11.6
139 193
5 30
11.5
130 198
1.4553
6 30
153
154
1.4555
11.4
131 198
7 30
1.4558
156
11.3
133 300
8 35
8.0
133 303
158
1.4563
9 30
1.4570 .
134 303
8.5
10 30
163
170
30
135
300
13.8
1.4583
11
Total take-off, 1834.3 g •
Time
T
PM
Press.
33 mm.
35
35
35
35
35
35
35
35
35
35
35
35.
35
35
35
35
Residue - 60 g.
Refractionation of the polymers of 3-Eth.yl-3-pentene.Fractionation III-A.
Outs 10-18 of fractionation III, 118.3 g . , were combined
and fractionated through Column EMJ.
Weigh.t
Cut Bath Head
Press
Time
Index
50 mm
9 55 AM ~ T ~ 155® 103®
1.4403
3.5 g.
50
10 35
6.0
1.4400
104
3
158
50
10 50
7.3
1.4408
155
104
3
6.4
1.4410
50
11 15
4
104
157
5.8
1.4410
50
11 55
5
154
105
50
1.4414
7.7
13 33
6
106
153
8.7
1.4416
13 45
7
156
50
107
50
1 15 PM 8
1.4414
5.7
157
107
8.0
50
1.4415
1 45
108
9
154
6.9
10
1.4416
3 15
109
158
50
8.9
1.4416
3 45
110
11
158
50
8.5
1.4416
160
3 15
13
111
50
50
8.5
1.4415
3 35
13
163
113
50
4 05
8.5
1.4414
14
178
113
5.0
50
1.4414
4 30
15
350
113
—
50
1.4434
7.3
5 00
370
16
Cuts 6>-15, 69 g. of almost constant I n d e x material.
19
Fractionation III-B.- Outs 19-38 of fractionation III,
3 7 3 g . , were combined and fractionated t h r o u g h Column EMJ.
Time
5 30
e 30
7 15
8
9
10
11
11
13
1
3
3
4
4
5
6
7
8
9
9
10
11
12
13
1
Cut
purr
3
3
4
00
00
5
00
6
00
7
50
8
50 AM 9
10
25
30
11
15
12
00 13
50
14
40
15
30
16
35
17
15
18
00
19
30
47
21
33
30
32
10
23
50
24
10PM 25-.
Bath
150 6
158
155
154
156
156
156
156
155
155
156
157
157
159
160
159
157
156
130
163
166
178
178
295
300
Head
115*
116
116
116
116
116
117
117
117
117
117
117
117
118
118
118
118
119
119
119
120
122
123
124
—
Index
1.4440
1.4445
1.4448
1.4448
1.4448
1.4449
1.4453
1.4457
1.4456
1.4458
1.4458
1.4458
1.4461
1.4463
1.4464
1.4465
1.4467
1.4467
1.4469
1.4470
1.4470
1.4473
1.4473
1.4478
1.4490
Weight
6.7 g.
10.8
10.6
7.7
9.6
9.8
13.4
12.7
10.0
11.1
9.3
11.6
11.8
12.0
13.7
13.8
12.6
11.5
11.5
11.5
11.7
12.3
12.9
10.3
3.6
Pressure
50 mm.
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
Fractionation III-C. - Cuts 39-59 of fractionation III,
3 8 8 g . , were combined and fractionated t h r o u g h Column
E M J.
Cut
Time
8 :00PM ;L
8 :30
2
9 :30
3
I O :30
4
1 1 :20
5
12 :15AM 6
1 :00
7
2 :00
8
2 :45
9
3 :30 10
4- :05 11
4, :55 12
5 :35 13
6 :00 14
6 :35 15
7 :05 16
Bath
Head
124°
169
135
169
125
126
165
137
164
137
158
128
155
138
155
128
155
128
155
128
155
128
156
138
155
138
155
138
155
128
154
(Continued on
Index
1.4460
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485
1.4485:
1.4485
1.4485
Weight
3.7 g.
6.5
10.5
9.8
11.1
12.1
11.5
13.4
12.8
11.7
13.6
12.1
13.4
13.7
13.5
14^4
next page)
Pressu
50 mm
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
20
Weight
Cut
Bath Head
Index
Pressure
Time
bu mra.
154° 128°
1.4485
13.9 g.
8:00AM 17
50
128
1.4485
9:10
18
153
13.2
50
128
1.4485
19
153
14.3
9:45
50
20
128
1.4485
14.7
153
10:40
50
138
1.4487
154
14.7
11:40
31
50
1.4489
139
12:40
22
13.2
153
50
1.4494
139
1:30
23
158
11.1
50
24
220
139
1.4497
1:45
7.9
50
—
25
234
2:15
3.3
1.4531
Cuts 2-•20, 233.2 g., of constant index material •
Fractionation III-D. - 'Cuts 60-72 of III and 23-35
of
III-C, 212 g . , weres combined and frafctlonated through
Column EMJ.
Time
0730PM
7:30
8:30
9 :i0
9:50
10:30
11:10
8:32AM
10:00
10$j55
3.1 : 4 0
12:33
1 :38AM
2:30 3:10
4:05
5:45
Cut
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
B ath
155
155
155
157
157
157
157
157*
161
166
158
157
160
158
165
165
220
Head
139
130
130
130
131
131
131
131
130
130
130
130
130
130
130
130
—
Index
1.445*8
1.4500
1.4505
1.4505
1.4505
1.4505
1.4505
1.4505
1.4498
1.4504
1.4505
1.4508
1.4508
1.4510
1.4510
1.4510
1.4513
Weight
6.3 g.
12.6
13.1
13.7
13.7
14.7
13.2
10.2
6.3
14.0
12.4
13.1
15.0
13.9
11.8
12.7
6.8
Pressure
50 mm.
50
50
50
50
50
50
50 mm.
50
50
50
50
50
50
50
50
50
Fractionation III-E,- Cuts 73-91 of III, 361.7 g . , were
combined and fractionated through Column EMJ.
Cut
Time
1:05PM
1:35
2
3:15
3
3:15
4
4:15
5
5:10
6
5:55
7
6:45
8
Bath
170*
165
165
167
175
170
181
175
Head
130°
131
131
131
131
131
132
132
Index
1.4494
1.4520
1.4520
1.4520
1.4520
1.4530
1.4530
1.4530
Weight
2.9 g.
8.8
12.1
12.5
17.0
15.4
15.1
15.6
(Continued on next page)
Pressure
50 mm.
50
50
50
50
50
50
50
31
Weight
B ath Head
Cut
Index
Time
Pressure
1.4530
15.0
50 mm.
9
7135
r m 132?
1.4520
15.7
17D
10
132
50
8:20
170
1.4520
132
15.3
11
50
9:05
170
16.0
1.4520
9:50
132
50
13
170
1.4530
133
16.8
10:30
13
50
1.4630
' 160
132
15.6
50
8: Z l M 14
14.0
165
132
9:38
15
1.4530
50
1.4530
165
132
18.5
16
50
10.23
1.4520
164
14.1
12:01
17
132
50
1.4530
175
12.8
1:26PM 18
132
50
1.4520
240
19
133
5.2
50
2:02
—
2:30
30 ‘ 253
1.4526
2.1
50
Cuts 2--19, 254.5 g,., of constant index material.
Fractionation III-F, - Cuts 93-104 of fractionation III,
184.5 g . , were combined and fractionated through Column EMJ.
Weight
Cut
B ath Head
Index
Time
Pressure
1U712AM
T.T5I4
175* 1 2 5 *
3.8 g.
6(5 mm.
50
11:10
175
1.4540 13.8
135
2
50
12:05
178
1.4540 13.6
136
3
50
1 :05PM 4
1.4540 12.2
175
136
1:50
50
5
176
137
1.4543 13*6
50
3:40
6
177
137
1.4542 11.9
50
3:25
7
177
137
1.4542 12.8
50
4:30
8
176
137
1.4542 13.8
5:30
50
176
13.0
137
9
1.4542
50
6:30
10
179
1.4541 12.8
137
50
180
7:33
138
1.4538 13.9
11
50
1.4534 13.4
186
138
8:31
13
50
9:10
13.7
198
1.4526
13
138
50
6.4
9:35
1.4524
14
312
139
50
1.4530
10:15
327
140
6.1
15
—
50
10:40
1.4537
16
3.1
242
almost
constant
index.
Cuts 3--11, 130 g. Of material of
Fractionation III-G-,- Cuts 105-116 of fractionation III,
170 g. , were combined and fractionated through Column EMJ.
Time
Cut
3:45PM 1
4:30
2
5:05
3
6:00
4
7:00
5
7:50
6
8:30
7
Bath
187*
179
179
179
179
178
178
Head
134°
139
143
142
143
143
142
Index
1.4464
1.4522
1.4534
1.4524
1.4524
1.4524
1.4526
Weight
2.3 g.
3.3
8.6
10.5
12.8
13.2
14.8
(Continued on next page)
Pressure
50 mm.
50
50
50
50
50
50
Cut
Bath H e a d
Weight:
Indear.
Pressure
Time
50 mm.
ICO*
1.4524
X42~6‘
12.2 gg.
372ft
1.4524
X42
9
182
13.4
50
10:00
1.4524
10.7
1 :4 5 PM 10 ' ‘ 17ft"" 1 4 2
5o mm.
1.4524
178
10.6
50
11
X42
2:45
1.4524
183
X43
12.6
50
12
3 :37
1.4524
185
X44
12.4
50
13
4:33
216
1.4526
14
X45
15.1
50
6:05
227
15
X46
1.4532
50
8.2
6:50
3.0
16
272
1.4582
50
7:30
Cuts 2--14, 150 g. o±* constant index m a t e r i a l
“
f t "
—
•
Fractionation I I I - H , — Cuts 117-130 of fractionation III,
160.7 g . , were c o m b i n e d and fractionated
through Column
EMJ.
Bath
Time Cut
13ft*
ftnftAurr*
9:40
182
2
185
10:35
3
11:20
4
186
12 T05PM 5
188
12:50
187
6'
184
1 :16
7
8
1:45
184
190
2:40
9
3:30 10
192
208
4 :15 11
215
4:45 12
5:15 . 13
263
Cuts 3-11, 135 g . ,
Head
X426
X46
X48
X50
X50
X51
X52
X52
X52
X55
X56
X57
The densities
were determined for*
Index
Weight:
Pressure
50 mm :
3.7 g
1.4484
50
1.4530
6;0
10;©
1.4536
50
50
1.4536
12.6
50
1.4536
13.9
1.4536
50
15.3
15.4
50
1.4536
50
1.4536
14.9
50
1.4536
13.8
1.4536
15.0
50
1.4536
50
17.1
50
1.4545
10.4
—
50
5.6
1.4562
o f constant index mat e rial.
and molecular refractions,
at 20°,
the material from th.e various
constant index r a n g e s of the refractions."ted polymers.
A small glass p y k n o m e t e r was used in det ermining the
densities, and the
molecular refractions
were calculated
by means of the L o r e n z and Lorentz equation.
33
*2°
<%
*20
D
III-A-9
.7827
1.4415
66.2
III-C-10
.7974
1.4485
65.9
III-D-6
.8008
1.4505
65.9
II1-E-10
.8023
1.4520
65.9
III-F-7
.8059
1.4543
65.9
I I 1-0-8
.8023
1.4534
65.9
III-H-7
.8046
1.4536
65.9
Fraction
M;
I n all cases except one, the experimentally determined
values are one half a unit lower than the theoretical
value of 66.4, which was calculated from Eisenlohr- s
constants.
This discrepancy has also been n o t i c e d by
W. R. Wheeler in his study of the nonenes.
Summary of the Polymerization of 3-Ethyl-3-pentene.
Polymerization of 22 moles of 3-Ethyl-3-pentene gave
2,070 g. of crude polymers.
After fractional:ion through
Qolumn W and refractionation through Column E M J the
following products were obtained:
G-rams
Moles
Boiling Point
at 50 mm.
Density a1
1.4415
.7827
138°
1.4485
.7974
1.00
130°
1.4505
.800§
1.30
131-133°
1.4530
.8032
135-138°
1.4542
.8059
69
.35
333
1.19
196
255
130
n 20
D
.663
106-113°
(Continued on next page)
Grams
Moles
Bolling P o i n “fc
n~
D
at 50 mra.
150 -
.765
138
.66
Density at 30°
143°
1.4534
.8033
148-156°
1.4536
.8046
Total - 1161 g . , 5.S3, moles o f dimer as above.
(54$)
Intermediate fractions araountecl to 733.5 g., 3.74
moles, with 1.38 moles of t h i s
material in one large
fraction boiling between 115° a.nd
134° at 50 mm.
Total d i s t i l l a t e
9.67 moles, 91.4$
R e s i d u e s -------------Total P r o d u c t
1893.5 g . ,
87.0 g . ,
.44 moles
1980.5 g. ,10.11
4.3$
moles, ,.95.''6$
Preparation of Trlethylcarblnyl Chloride.-
Trlethylcarblnpl,
two moles, 238 g . , was placed in a 300 cc. flask and a
stream of dry hydrogen chloride was passed into the
carhinol for six hours.
The mixture was allowed to
stand for 12 hours and was again treated with dry
hydrogen chloride for 12 hours.
The oil layer was
separated and placed over anhydrous potfcssiura carbonate.
The yield of crude chloride was 260 g „ , or 97$, of the
theoretical.
The crude material was fractionated
through Column E to give 211.7 g . , 1.58 moles, of
trlethylcarblnyl chloride having a boiling point of
64°/60 mm. and an index of refraction of 1.4330.
Preparation of Trlethylcarblnylmagneslum Chloride.A 3 neck, one liter flask was equipped with a dropping
funnel, mercury-sealed stirrer, and a reflux condenser.
A few crystals of iodine and 1.6 moles of magnesium
were placed in the flask and the iodine was vaporized
by heating the bottom of the flask with a low flame.
The flask was cooled and 40 cc. of a solution of 210 g . ,
1.5 moles, of trlethylcarblnyl chloride in 200 cc. of
dry ether was introduced.
After the reaction had
started 85 cc. of ether was added to the contents of
the flask, and 185 cc. of the ether-halide solution
was added through the dropping funnel during 7 hours.
The remainder of the solution was diluted
with 125 cc.
of ether and added through the dropping funnel during
36
nine hours.
After stlr»aring for eight hours, a five cc.
sample of the mixture w a s
1.031 N sulfuric acid.
removed and titrated with
The yield of triethylcarbinylmagnes-
lum chloride was 1.04 m o l e s or 66$ of the theoretical.
Preparation of T r l e t h y l a c e t l c A c i d .-
The triethylcarblnyl-
magnesium chloride s o l u t i o n from above was transferred to
a two liter, 3 neck f l a s k ,
of ether.
The flask w a s
and was diluted with 650 cc.
packed in a bath of ice and
salt and the contents c o o l e d to -5°.
With vigorous
stirring, a stream of d.x*y carbon dioxide was passed
into the flask'"fa? five
(gauge).
iiours at a pressure of 60 mm.
A solution of*
350 cc. of concentrated sulfuric
acid in 500 cc. of w a t e r was added to the reaction
mixture.
The water l a y e r was extracted five times with
100 cc. portions of ettxer, and the extracts were com­
bined with the oil layer*.
a liquid residue which
carbonate solution.
Evaporation of the ether gave
w a s neutralized with 10$ sodium
A c i d i f i c a t i o n of the water layer
with dilute sulfuric a c i d gave a white precipitate.
The yield of crude aclcL
theoretical.
was 19 g . , or 13$ of the
The m e l t i n g point was 40-41°.
liquid remaining after
The
"the extraction of the acid was
washed with water and cLnied over sodium sulfate.
The
dried product was distilLled through Column L to give 67.4
g. of 3-ethylpentane.
T h e hydrocarbon was produced by the
action of the water on
nnreacted trlethylcarbinylmagneslum
37
chloride.
Preparation of Trlethylaoe~fcamlde.flask was equipped with a
ping funnel.
A two neck, 300 cc.
^reflux condenser and a drop­
The c o n d e n s e s was connected to a trap
for dissolving the hydrogexi chloride vapors in water.
Thionyl chloride, 16 g r ams , .135 moles, was placed in
the flask, which was h e a t e d on the steam bath.
During
twenty minutes a solution
o f 18 g . , 0.125 moles,
triethylacetic acid in 50
cc. of ether was added through
the dropping funnel.
mixture was heated for three
The
of
hours, during which time a_!_l volatile material distilled
out of the flask.
The tri_ ethylacetyl chloride was
dissolved in 300 cc. of e t h e r and transferred to
three neck, 500 cc. flask
a
-which was equipped with, a
stirrer and inlet and outZLet tubes for passing ammonia
through the flask.
With v i g o r o u s stirring, a stream of
ammonia gas was passed o v e r the surface of the solution
for 1 1/3 hours.
The r e a c t i o n mixture was treated with
75 cc. of water and the lawyers were separated.
water layer was extracted
of ether, and the e x t r a c t s
bined.
The
twice with 50 cc. portions
and oil layer were c o m ­
The ether was evaioorated and the residue was
dissolved in 30 cc. of 5 0 ^
bone black.
methanol and treated with
Recrystallizs.tion from chloroform gave
13.1 g. of tr l e t h y l a c e tamide which had a melting point
of 108°.
The yield was 7 3 # of the theoretical.
A
38
second run, starting with 39 g. of the acid, gave only
a 54,5$> yield of the amide.
In the second run the pro­
duct was crystallized from hot water Instead of chloro­
form.
Preparation of 3,3-Dlethyl-3-pentanone.-
Methyl-
magnesium chloride was prepared by passing methyl chloride
into a flask containing 0.6 moles of magnesium and 400 cc.
of ether.
The flask contsining the methylmagneslum
chloride was packed in ice and a solution of 31 g., 0.147
moles of triethylacetamlde in 500 cc. of ether was added
during three hours.
The mixture was refluxed for 34 hours
and decomposed by the addition of 1000 g. of ice.
The
ether was distilled and the remainder was steam distilled
in order to effect the removal of the ketone.
The water
layer of the distillate was extracted twice with 50 cc.
portions of ether.
The oil layer and the extracts were
combined and dried over sodium sulfate.
The ether was
distilled and the residue was fractionated through
Column L to give 13.3 g . , 0.094 moles, of 3 ,3-dlethyl-3pentanone, which had a boiling point of 93°/50 mm.
and an index of refraction of 1.4330.
The ketone was
found to have the following physical properties:
Bolling point at 739
mm.
174°
Freezing point --------------- 10.3°- 10.9°
Density at 3 0 ° --------------- .8387g./cc.
Molecular refraction at 30° - 43.67
Calculated
--------------- 43.79
29
The ketone gave a 2,4-dinitrophenylhydrazone which melted
at 94°.
No semicarbazone was obtained.
Bromination of Triethylcarbinol.-
Triethylcarbinol,
0.4 moles, 46.5 g. , was placed in a 3 neck, 200 cc.
flask equipped with a stirrer, thermometer, and drop­
ping funnel.
The flask was heated to 50° on a steam
bath and 0.4 moles of bromine was added through the
dropping funnel during two hours.
The temperature was
maintained at 50-60° during the addition of the bromine.
After an induction period of about 15 minutes, the re­
action proceeded cjuite rapidly and external heating was
not required.
The oil layer was separated, washed with
water, and dried over calcium chloride.
The dried
product was fractionated through Column L.
Bath
Time Cut
9 45AMT ~
91*
10 06
94
2
10 17
96
3
10 46
4
102
11 14
5
106
11 46
6
113
1 10PM 7
122
1 23
8
117
1 40
9
119
1 55 10
113
2 17 11
110
2 50 12
122
3 05 13
123
3 25 14
124
3 45 15
125
4 05 16
131
4 23 17
134
4 45 18
136
5 05 19
150
Residue - 14 g.
Head
58®
59
58
60
59
71
88
95"
96
98
98
95
96
95
97
96
96
95
—
Index
1.4600
1.4610
1.4618
1.4630
1.4630
1.4660
1.4792
1.4950
1.5057
1.5125
1.5127
1.5128
1.5128
1.5128
1.5128
1.5128
1.5128
1.5128
1.5130
Weight
4.2 g.
2.1
6.0
5.6
3.0
2.0
2.8
3.2
3.4
3.5
3.6
4.3
4.3
5.9
5.9
5.7
5.6
5.3
4.9
Pressu
18 mm
19
17
19
17
17
18
17
17
17
17
16
16
15
17
16
16
15
15
Fractions 10-19, 48.6 g. , 47# of 2,3-dibromo-3-ethylpentane
30
Attempted Hydrolysis o f S,3~Dlbromo-3-ethylpentane.The dibromoheptane f r o m the bromination of triethylcar­
binol, 48.6 g. , was p l a c e d In a 300 cc. , 3 neck flask
equipped with a stirrer and a reflux condenser..
One
hundred cubic centimeters of water was added to the
flask and the mixture was refluxed for nine hours,
with vigorous stirring.
At the end of this time there
was an oil layer on t o p of the water.
The condenser was
set downward, and with vigorous stirring, the oil layer
was steam distilled.
At first, the oil layer of the
distillate was decid e d l y lighter than water, but as the
distillation proceeded the oil became heavier and tended
to string out from top to bottom in the distillate.
The addition of 5 cc.
of ether caused the oil to collect
in one layer on the surface of the water.
The distillate
was treated with sodium bicarbonate and the layers were
separated.
The water layer was extracted with 35 cc. of
ether, and the extract was washed with 15 cc. of water.
The wash water was counter--extracted with 10 cc. of
ether which was combined with the oil layer and the other
extract.
After d r y i n g over calcium chloride, the material
was charged to Column L for fractionation.
Five small
fractions were obtained which were highly colored and
fumed in air, indicating the presence of hj'drogen bromide.
The residue was a black, tarry mass.
In a second run of the
same size, the dibromide
was n o t purified but was treated with water directly after
the br*omination of the carblnol.
up i n
The product was worked
the manner just described and was fractionated
throu.gh Oolumn L.
Cut Bath
Time
§713 A M " T “ 143*
9:43
3
153
156
9:53
3
10:01
4
157
165
5
10:33
11:05
6
169
13:36
7
196
Resiclue - 4.5 g.
None
Head
95*
95
135
<J-130
139
83
7D
Index
1.4174
1.4330
1.4360
1.4158
1.4178
1.4188
1.4307
Weight
1.3 g.
3:0
1.9
3.5
4.4
4.5
3.0
Pressure
737 mm.
737
737
737
737
737
737
of the expected product, 3-ethyl-3-pentanone, was
obtained.
Sollcl Material Obtained in the Preparation of Triethyl­
c a r b i n o l .-
It was noticed that in the preparation of
triethylcarbinol a small amount of crystalline solid
appeared in the condenser after all of the carbinol h’
ad
been
steam distilled.
The amounts varied, but averaged
a b o u t 0.5 g. for each run o f three moles.
was
This solid
also noticed by W. C. Smith in his work with tri­
ethylcarbinol.
The solid, hereafter referred to as XX,
m e l t e d at 136° after crystallization from aqueous
methianol.
Elementary analysis showed the absence of
sulfur, nitrogen, and halogens.
f l a m e and leaves no residue.
XX burns with a blue
XX is soluble in benzene,
toluxene, chloroform, carbon tetrachloride, ether, methanol,
33
ethanol,
ligroin, acetone, and.
dioxane.
It is Insoluble
in water and 5# sodium hydroxlcde solution, but dissolves
in dilute hydrochloric acid whien heated.
It dissolves
in sulfuric acid to give a y e l l o w i s h color.
The sulfuric acid soILntion of XX loses Its
yellow color upon n e u t r a l i z a t i o n and an oil separates.
XX
was not oxidized by alkaline p»otassium permanganate
solution.
XX was not un s a t u r a t e d to bromine and dissolved
inacetyl chloride without the
evolution of heat.
A
solution of XX in dry ether d i d not react with sodium.
XX gave no oxime, but gave a 3 ,5-dinitrophenylhydrazone
which crystallized from e t h a n o l and melted 154°.
Values for the molecular weigtat of XX, determined b y
the Rast method, were 188 and
189.
Preparation of Stannic Chloricie.-
Mossy tin, one mole,
118 g . , was placed in a 250 c o .
distilling flask equipped
with a condenser and receiver* .
The tin was melted with
a low flame and chlorine was p a s s e d into the flask for
7 1/2 hours.
An Immediate r e a c t i o n took place and a
yellowish liquid collected in. .the receiver.
distillate was placed over a
to stand for 48 hours.
was colorless.
The
f e w pieces of tin and allowed
At tire end of this time the liquid
It was distilLled from a small distilling
flask to give 338 g. , 0.915 m o l e s ,
of clear, colorless
stannic chloride, which b o i l e d at 111° at 734 mm. pressure.
33
Treatment of 3-Ethyl-3-pentene with Acetyl Chloride,3-Ethyl~3-pentnen, 0.5 moles, and 0.33 moles of acetyl
chloride were placed in a one liter,
2 neck flask
equipped with a dropping funnel and a reflux condenser.
During eight minutes 0.5 g. of stannic chloride was
added through the dropping funnel.
A vigorous reaction
took place with the evolution of much heat and the
production of an orange color which turned to a dark,
reddish-brown.
The reaction subsided in a short time
and the mixture was allowed to stand until cool.
The
mixture was shaken with 200 cc. of 15$ hydrochloric acid
and the oil layer was shaken with sodium bicarbonate
solution and then water.
The product was dried over
sodium sulfate and then refluxed for one hour with
50 g. of dimethylaniline to split out hydrogen chloride,
from the chlorinated ketone.
The mixture was washed
twice with 50 cc. portions of 15$ hydrochloric acid and
once with 50 cc. 10$ sodium bicarbonate solution.
product was then washed with 50 cc.
The.
of water, dried
over sodium sulfate, and fractionated through Column L.
Time
Cut
4:l3PM T
4:37
2
4:51
3
5:08
4
5
6:02
6
s r r w
7
9:34
9:50
8
10:02
9
Bath
155°166
169
177
185
133
133
121
135
Head
96°
96
96
97
98
"61
65
65
68
Index
r.41^3
1.4140
1.4140
1.4146
1.4146
1.4336
1.4391
1.4330
1.4333
height
3.3 g.
3.1
3.6
3.6
3.5
575
Pressure
?37 mm.
737
737
737
737
bd "mm.
50
50
50
34
Time
10:16
10.48
11:23
11:48
13:13
12:45
1:50
2:50
3:45
Cut
Tt5
11
12
13
14
15
16
17
18
Bath
132°
135
136
136
140
145
169
190
199
Head
736
82
93
93
93
95
104
122
126
Index
1.4333
1.4354
1.4429
1.4433
1.4443
1.4448
1.4456
1.4492
1.4556
Fractions 3-5 are recovered olefin.
Weight
3.8 g.
3.8
2.9
3.9
2.8
3.1
2.9
3.3
1.9
Pressure
50 mm.
50
50
50
50
50
50
50
50
None of the expected
product was obtained.
Oxidation of 3-Sthyl-l-butanol.-
A solution of 320 g.
of sodium dichromate in 400 cc. of water was placed in
a 3 neck, 2 liter flask equipped with a stirrer, reflux
condenser,
and dropping funnel.
With stirring, 300 cc.
of concentrated sulfuric acid was added slowly through
the dropping funnel.
During two hours 153 g . , 1.5
moles, of 2-ethyl-l-butanol was added through the dropping
funnel.
A vigorous reaction took place with the evolution
of much heat.
The mixture was stirred for 18 hours and
then steam distilled.
The water layer of the distillate
was extracted twice with 75 cc. portions of ether which
were combined with the oil layer and treated with 300 cc.
of 10# sodium carbonate solution.
There was no evolution
of carbon dioxide, indicating that none of the desired
acid was obtained.
If any of the acid were formed it
probably reacted with more alcohol to form an ester.
35
Preparation of P i e t h y l a c e t a m i d e .-
A two neck, 200 cc.
flask was equipped with a. reflux condenser and a drop­
ping funnel.
The c o n d e n s e r was connected to a trap for
dissolving the hydrogen c h l o r i d e vapors in water.
five grams, 0.21 moles,
o f
Twenty-
thlonyl chloride was placed in
the flask, which was hea-fced on the steam bath.
25 minutes 22 g . , 0.19 m o l e s ,
During
of diethylacetic acid was
added through the d r o p p i n g funnel,
^he mixture was
heated for 1 1/2 hours,
s.nd the acid chloride was
dissolved in 500 cc. of
e t h e r and transferred to a 1
liter, 3 neck flask whicii was equipped with a stirrer
and inlet and outlet t u b e s for passing ammonia through
the flask.
With v i g o r o u s
stirring a stream of ammonia
was passed over the s u r f a c e of the solution for two
hours.
The reaction m i x t u r e was treated with 100 cc.
of water and the layers
-were separated.
layer was extracted t w i c e
ether and the ether was
The water
with 50 cc. portions of
evaporated.
The white solid
remaining after the e v a p o r a t i o n of the ether was
dissolved in 50 cc. of 5 0 $ methanol and treated with
bone black.
C r y s t a l l i z a t i o n from chloroform gave 14.6 g . ,
67$, of d i e t h y l a c e t a m i d e , which had a melting point of
111-112°.
36
Preparation of Methyl-t-butylacetyl Chloride.-
A mixture
of crude acids was obtained from W. R. Wheeler.
These
acids were from oxidations 3 and. 4 of the nonenes from
stock alcohols (report 38-19, p a g e 98, W. R. W . ).
By
fractionation and refractionation of the mixture of
acids, 177.8 g . , 1.37 moles, of pure methyl-t-butylacetlc
acid were obtained.
All of t h i s acid was dissolved in
50 cc. of ether and added, d u r i n g two hours, to 300 g. ,
1.68 moles, of thionyl chloride
flask on the steam bath.
in a 3 neck, one liter
The mixture was stirred over
night and then fractionated through Column E.
The yield
of the acid chloride was 163.1 g . , 1.09 moles, 79.5$.
The chloride had a boiling point: of 61°/35 mm. and
index of refraction of 1.4313 a"t 30°.
Attempted Preparation of Dlethylplnacolylcarblnol. During 8 1/3 hours, a solution
of 1 mole, 149 g . , of
methyl-t-butylacetyl chloride i n 250 cc. of dry ether
was added to two moles of ethylmagnesium bromide in
800 cc. of ether.
The mixture
was stirred for 18 hours
and then refluxed for an additional 30 hours.
mixture was treated with 500 g.
was distilled.
The
of ice and the ether
The remainder w a s steam distilled for
4 hours in order to effect a separation of the reaction
product.
The water layer of th.e distillate was extracted
twice with 100 cc. of ether, a n d the extracts were combined
37
j
with the oil layer and dried over sodium sulfate.
The
dried product was fractionated through Column L.
Cut
Bath
Time
TSTCJlPM: 1
79°
81
13:15
3
81
3
12:39
1:00
4
81
5
1:45
83
3:10
6
85
7
§:37
88
8
3:05
93
9
3:47
103
10
4:40
127
5:05 11
158
5:15 13
159
5:30 13
163
Residue - 6.6 g.
Head
53*”
53
53
53
53
53
53
53
53
54
67
70
90
Index
1.4216
1.4318
1.4319
1.4219
1.4219
1.4319
1.4319
1.4219
1.4319
1.4319
1.4389
1.4387
1.4398
Weight
3.3 g.
5.1
12.1
5.4
7.8
9..7
10.8
11.3
10.1
4.1
2.3
3.1
3.6
Pressure
14 mm.
14
14
14
14
14
14
14
14
14
14
14
14
None of the desired carbinol was obtained.
Fractions 1-10, 79.6 g . , are ethyl pinacolyl ketone.
The ketone gives a 3,4 dinitrophenylhydrazone melting
at 75-76°.
The density of the ketone was found to be
0.8349 at 30° and the molecular refraction was 43.73.
The theoretical value for the molecular refraction,
using Eisenlohr s constants is 43.79, while that for
the carbinol would be 45.3.
Treatment of Ethylplnacolyl Ketone with Ethylmagneslum
Bromide.-
A solution of 43.6 g. , 0.3 moles, of ethyl
pinacolyl ketone in 75 cc. of dry ether was added, during
two hours,
to a solution of 0.3 m o l e s of ethylmagneslum
bromide in 300 cc. of ether.
A gas
collector was attached
to the apparatus throughout the reaction time.
The flask
was cooled with tap water d u r i n g the addition of the ketone.
The total volume of gas c o lle c t e d during the addition of
the ketone was 4500 c c . , but: after refluxing the mixture
for 7 hours, the volume of g a s Increased to 7100 cc.
more gas was given off when
150 cc. of water.
No
the mixture was treated with
The m i x t u r e was steam distilled and
the water layer of the distillate was extracted twice
with 35 cc. portions of ether.
The combined extracts
and oil layer were dried o v e r sodium sulfate and the
ether was distilled.
The r e s i d u e was fractionated through
Column L to give a yield of
35.4 g . , 0.349 moles of re­
covered ketone, but none of
the expected carbinol.
ketone boiled at 80°/50 mm.
and had an index of refraction
of 1.4331.
The
The gas which w a s given off during the re­
action contained 30$ air a n d no unsaturated compounds.
The remaining 70$ must be e "thane.
Since the ketone did
react with the ethylmagneslum bromide, as shown by a
negative Gilman test after “the reaction was finished, it
had to react as the enol form.
The ketone was obtained
from the treatment of the r e a c t i o n mixture with water.
Treatment of ethylplnacolyl ketone with methylmagnesium iodide gave no carbinol but gave a 67$ recovery
of the ketone.
M e t h y lmagnesium chloride likewise gave no
carbinol, but gave only a 5 0 $ recovery of the ketone.
39
SUMMARY
1.
Triethylcarbinol has been p r e p a r e d and
2.
It has been shown
dehydrated.
that the dehydration of triethyl­
carbinol gives only one olefin;
3-ethyl-2-pentene.
3.
3-Ethyl-S-pentene
has been po l y m e r i z e d to a mixture
of
dimers, which were f r a c t i o n a t e d to give seven Isomers.
4.
Physical constants of the d i m e r s of 3-ethyl-2-pentene
h a v e been determined.
5.
Certain compounds related t o
triethylcarbinol have
b e e n prepared.
6.
This study is being c o n t i n u e d by H. D. Zook in this
laboratory.
4
40
BIBLIOGRAPHY
1;
Whitmore, P. C. , Ind. Eng. Chem. 26, 94 (1934) .
3.
Whitmore, F. G. , and Wrenn, S. N. , J. Am. Chem.
Soc. 53, 3136
(l93l)-J Tongberg, C. 0.,
J. D. , Fenske, M. R. , Whitmore, F. G.,
Pickens,
ibid. 5 4 ,
3706 (l933) } Whitmore, F. C. , and Ghurch, J. M . ,
ibid. 54, 3710 (1932).
3.
Brunner, H., and Farmer, E. H. , J. Chem. Soc.
1309 (193?).
4.
Meunier, P. L. , Thesis (Ph. D.), The Pennsylvania
State College, 1936.
5.
Smith, W.
C., Thesis (M. S.), The Pennsylvania
State College, 1937.
6.
Boeseken,
J.,
and Wildschut, A.
Chim. 51,
168
(1932).
J., Rec. trav.
PART II
STUDIES ON STEROIDAL SAPOG-ENINS
INTRODUCTION
The steroidal sapogenins are a group of compounds
having the cyclopentanoperhydrophenanthrene nucleus and
an eight carbon side chain.
This nucleus is common to
sterols, bile acids, and the steroidal sapogenins.
The
side chain contains two oxygen atoms which exhibit no
reactivity except in acid solutions, and which are present
in a spiro-ketal structure.
The various sapogenins differ
in the number and configuration of the hydroxy groups in
the nucleus and the spatial arrangement of the groups or
atoms at G-5 and C-33.
Z ~\CHCH,
I.
Sarsasapogenin
II.
Chlorogenin
The structural relationship between the steroidal
sapogenins and the sterols suggests their usefulness as
starting materials for the preparation of hormones.
Sarsasapogenin has been converted to pregnanediol from
which progesterone, testosterone, and desoxycorticosterone
can be synthesized.
The present study was undertaken to obtain additional
information on these compounds and their derivatives.
%
HISTORICAL
An excellent review of the earlier work on the
steroidal sapogenins can be found in "Chemistry of
Natural Products related to Phenanthrene", by Fieser (l).
Since
the appearance of this book, rapid strides have
been made in the study of these compounds and much has
been contributed to the knowledge of their structure
and reactions.
Paralleling the work of Tschesche and Hagedorn (3 )
on tigogenin,
the C 2S desoxy. lactone from sarsasapogenin
has been degraded to etio-bilianic acid by Farmer and
Kon ( 3 ).
The reactions are shown in the following scheme:
§ Steps
III.
IV;
C2 2 Lactone
Desoxy Lactone
qoH
qqH
CH
CrO
V.
Diphenylcarbinol
VI.
etio-Bilianic Acid
Of the various structures proposed for the side chain
of the sapogenins, the most acceptable was that put forth
by Marker and Rohrmann (4) in which the two oxygen atoms
are present in a spiro-ketal structure (VII).
VII,
Sapogenin Side Chain (Marker and Rohrmann)
They found that the two oxygen atoms were reactive in
acidic solution and that sarsasapogenin could be hydro­
genated cata lytically to give a dihydro compound (VIII)
which contained two free hydroxyl groups.
A tetrahydro
compound (IX) was obtained by Clemmensen reduction of
sarsasapogenin, while dihydrosarsasapogenin was unchanged
when treated in the same manner.
This tetrahydro com­
pound contained only two hydroxyl groups which formed
esters under the usual conditions.
The third, at C 1 6 ,
should not be capable of esterification under any but
the most drastic conditions, due to steric hindrance.
Sarsasapogenin, upon refluxing with alcoholic
hydrogen chloride, isomerized to a different compound
having the same composition as sarsasapogenin.
This
isomerization could take place at C-22 if the spiroketal structure were correct.
Isosarsasapogenin (X)
gave the same reduction products as sarsasapogenin,
would be expected from the spiro-ketal structure.
sasapogenin acetate was oxidized quite readily by
as
Sar­
selenium dioxide
in acetic acid,
whereas dihydro and
tetrahydrt)sarsasapogenin were unchanged by such treat­
ment.
ch3
cMj
VIII. Dihydrosarsasapogenin
IX.
Tetrahydro sarsasapogenin
)cnc h3
X.
Isosarsasapogenin
45
Sarsasapogenin reacts readily with bromine to form
a monobromo derivative
(4 ) (5 ), from which the bromine
atom is not removed b y boiling pyridine or b y treatment
with pyridine and silver nitrate in the cold.
Sarsasapo-
genone gives the same monobromo derivative that is obtained
by oxidizing broraosarsasapogenin.
The bromine atom is re­
moved quite easily, however, by other reactions.
Treat­
ment of bromosarsasapogenin acetate with zinc dust and
acetic acid gives sarsasapogenin acetate, while treatment
with sodium and ethanol or sodium and amyl alcohol gives
sarsasapogenin.
Bromosarsasapogenin, upon Clemmensen
reduction, gives a good yield of tetrahydrosarsasapogenin,
Desoxysarsasapogenln (XI) has been prepared by the
sodium reduction of sarsasapogenyl chloride
from sarsasapogenone
(XII)
(6), and
(XIII) by the Clemmensen reduction
(8) (7) and the Wolff-Kishner reduction (8).
Upon re­
duction it underwent reactions analogous to those of
sarsasapogenin to give a dihydro compound and a tetra­
hydro compound.
Desoxy sarsasapogenin also reacted with
bromine to give a monobromo derivative.
While the nuclear configuration of sarsasapogenin
was proved definitely by Farmer and Kon (3 ) by their
degradation of the substance to etio-billanlc acid, no
very conclusive evidence has been offered which would
establish the position of the nuclear hydroxy group.
Askew, Farmer, and Kon (9) on the basis of surfa.ce film
measurements concluded that the hydroxy group must be in
46
the first ring and probably occupies the favored C-3
position since it precipitated digitonin.
XII:
Sarsasapogenyl Chloride
XI.
Desoxysarsasapogenin
Clemmensen
reduction
(Zn,HCl)
C
u
j
XIII.
ch4
XV
o-crfz.
"<«>
w
Sarsasapogenin
1
,0 ~CHx^
Sarsasapogenone
H 2 ,Pt03
or
Na, moist ether
Al(O-i-pr)
^
5
cw
Ct<3
C>?51h-c '°~C *WCH3
XIV. epi-Sarsasapogenin
47
Reduction of sarsasapogenone
ether (9) gave epi-sarsasapogenin
with sodium and moist
(XIV) , a substance
differing from sarsasapogenin o n l y in the configuration
of the nuclear hydroxy group.
Thj_s compound gave
sarsasapogenone upon mild oxidation, and did not give
a precipitate with digitonin.
Marker and Rohrmann- (l0) f o u n d that sarsasapogenin
behaves as a 3
(p)-hydroxy
configuration at C-5.
c o m p o u n d having the regular
Treatment
o f sarsasapogenin with
sodium and amyl alcohol gave epi- sarsasapogenin, by epimerization at 0-3.
The catalytic hydrogenation
(lO) of sarsasapogenone
gives approximately a 75$ yield o f epi-sarsasapogenin.
With aluminum isopropylate (lO)
sarsasapogenone gives
almost quantitative yields of e q u a l amounts of the two
isomers of sarsasapogenin.
epi-Sarsasapogenin behaves
similarly to sarsasapogenin
on catalytic hydrogenation, r e a c t i o n with bromine, and
oxidation with selenium dioxide.
All attempts to prepare
its tetrahydro derivative by Clemmensen reduction have
been unsuccessful.
Marker and Rohrmann (11) extended the reactions
characteristic or Sarsasapogenin
to tigogenin and found
that the results were similar i n
all cases except one.
Tigogenin did not give a crystalline tetrahydro compound,
when subjected to Clemmensen reduction.
The structural
relationship between tigogenin a n d sarsasapogenin was
48
shown (12) by a study of their hydroxy lactones.
Con­
version of sarsaspogenin lactone into its alio form gave
a product identical with tigogenin lactone.
This trans­
formation indicates that the two lactones differ only in
regard to the configuration at C-5 and that the hydroxy
groups are at C-3.
The chemistry of digitogenin (XVI) and gitogenin
(XVIl) is still in a rather confused state, although they
were the first
steroidal sapogenins to be studied (l).
The formation of methylsuccinic acid and cx-methylglutarlc
acid in the oxidation of these two sapogenins was formerly
explained b y assuming an oxidation of the nucleus.
The
formation of these two acids can be explained better on
the basis of the spiro-ketal structure for the side chain.
Digitogenin a n d gitogenin (l3) were found to resemble
sarsasapogenin in their behavior toward digitonin,
catalytic hydrogenation, bromlnation, and oxidation with
selenium dioxide.
Like tigogenin (XVIII) , they are in­
active toward isomerization with hydrochloric acid and
toward Clemmensen reduction.
In their investigation of the chromic anhydride
oxidation products of sarsasapogenin acetate Fieser and
Jacobsen (l4)
obtained an acid, C a7H 420s , which they
designated as
sarsasapogenoic acid.
They found that
under rather vigorous treatment it gave a dioxime, indi­
cating two canbonyl groups.
gave an acid,
Catalytic hydrogenation
C27H 4404 , designated as anhydrotetrahydro-
49
/cH*CHy"'c.ucHt
) O C *7 C . ^ a .
o
c h
3
HO
HO'
XVI.
Digitogenin
XVII:
CH3
G-itogenin
CHsCH'C-^ o-C-H*
1 ‘ O
lsO'Cnj
C H 3
nK "•,
io'X/!
XVIII;
H°
Tigogenin
XIX.
Diosgenin
sarsasapogenoic acid.
When heated with alcoholic
alkali, sarsasapogenoic acid gave anhydrosarsa­
sapogenoic acid; which was shown to contain an
alpha-beta unsaturated ketone group (15, 16).
Marker and Rohrmann (4) obtained anhydrotetrahydrosarsasapogenoic acid by the oxidation
of the acetate of dlhydrosarsasapogenin.
By the
use of various reducing agents (17) on sarsa­
sapogenoic acid they obtained anhydro sarsasapogenoic
acid, anhydrotetrahydrosarsasapogenoic acid, and
tetrahydroanhydrosarsasapogenoic acid.
The last
compound was obtained originally b y Fieser and
Jacobsen b y the reduction of sarsasapogenoic
acid.
On the basis of the spiro-ketal side chain
the formation of the acids would be explained as
shown by the following scheme.
(The compounds
are represented by partial formulas).
51
,vC^-C-Hx
J
CH3
in- C H - t H a - c H t C.H-CHtoH
h2
PtO.
“
^
XX.
Sarsasapogenin
XXI. Dihydrosarsasapogenin
CrO,
CrO,
Cfi 3
CH,
cH3
cH~c.rt-cHx*cri>--?t4'cooH
'
XXII. Sarsasapogenoic Acid
I
c»3
XXIII. Anhydrotetrahydrosarsasapogenoic Acid
alkali
Na + ethanol
*
Anhydrosarsasapogenoic
acid
Ha
PtO.
Tetrahydroanhydrosarsasapo­
genoic acid
52
A neutral p r o d u c t formed In t h e
oxidation of
sarsasapogenin ace*tate was Isolated t > y Fleser and Jacob­
sen (14,15)
and b y
Marker and Rohrmars.n (17) .
This com­
pound formed an a c e t a t e and a semicar-tazone.
Clemmensen
reduction gave t e t r a h y d r o s a r s a s a p o g e r d n , while catalytic
hydrogenation in a c i d i c
solution g a v e
compound of u n k n o w n structure.
A n a l y s e s indicate that
the empirical f o r m u l a of the neutral
or 0 27H 440 4 , but i t s
In studying
a tetrahydro
compound is
structure is s t i l l unknown.
the chromic a n h y d r i . d e oxidation products
of sarsasapogenin
acetate Marker and.
Bohrmann (l8) ob­
tained, in a d d i t i o n to the C 22 l a c t o x i e of Farmer and Kon
(3 ) and the C27 a c i d and C27 neutral.
compound of Fieser
and Jacobsen, a kieto acid of the cona."position C 22H 340 4 .
The acid was o b t a i n e d in yields of o n l y 1 - 2 $
when the
oxidation was c a r r i e d out at 60®, bua-t slightly better
yields were o b t a i n e d at 80°.
carbazone r e a d i l y .
The a d d
formed a semi-
Upon catalytic haydrogenation in
neutral medium t h e acid yielded largsgely a neutral product
melting at 197 -
198° which was I d e n t i c a l with the C22
lactone first o b t a i n e d by Farmer anci. K0n (3 ) by the
direct oxidation
of sarsasapogenin
steetate.
In the same
hydrogenation a l a c t o n e melting at ^ _ 8 6 — 188° was ob­
tained, which a p p e a r e d to be a p o l y m o r p h o u s form of the
lactone,
since i i
melting form.
gave no d e p r e s s i o n with the higher
W h e n the hydrogenati o n was carried out in
acidic ethanol o n l y the lower m e l t i n g form was obtained
in good yield.
Approximately equal,
amounts of both forms
53
were obtained when the acid was reduced with sodium in
ethanol.
The keto acid was unchanged by Cleminensen re­
duction.
All of the steroidal sapogenins which have been
extensively studied form lactones upon oxidation, after
protection of the nuclear hydroxy groups (3,3,9,13, 19).
That the lactone has a slight tendency to exist as a
/-hydroxy acid is indicated by the fact that the lactone
acetate upon vigorous oxidation with chromic anhydride
gives rise to some of the C 33 Keto acid (30).
Marker
and Rohrmann (20) degraded the hydroxy lactone to 3hydroxy-etlo-blllanic acid using the method of Tschesche
and Hagedorn
(3).
In extending their investigation of the acidic
products from the chromic anhydride oxidation of sar­
sasapogenin acetate Marker and Rohrmann (2l) Isolated
from the hydrolyzed acidic fra.ction, in addition to the
C 33 lactone, the C 19 dibasic acid 3-hydroxy-etio-bilianlo
acid.
This acid was also obtained by the oxidation of
dihydrosarsasapogenin acetate
genin (23).
(22) and 33-ethylsarsasapo-
The latter compound was obtained by the
treatment of sarsasapogenin acetate with ethylmagneslum
bromide (23).
Using the method of Litvan and Robinson (34),
Marker and Rohrmann (23)
converted 3 -hydroxy-eti^o-blllanlc
acid to etlo-cholanol-3(/g )-one-17.
This was converted
to etio-cholandiol-3( * )-!?( * ), from which
54
etio-cholanone-3-ol-17 was prepared.
This substance was
readily converted to testosterone by bromination and
subsequent removal of hydrogen bromide with pyridine.
Chlorogenin, a sapogenin isomeric with gitogenin,
was isolated along with tigogenin from the acid hydrolysis
products of extracts of the bulbs of Chlorogalum pomeri&ianum by Liang and Noller (35).
They reported that
chlorogenin gave no precipitate with digitonin, indicating
that the hydroxy group at C-3 had the aloha configuration.
In more recent work Noller (26) postulated that the two
hydroxy groups occupy the positions at C-3 and C-12.
Contrary to the findings of Noller, Marker and
Rohrmann (27) found that chlorogenin gives a digitonide
which is quite insoluble in 80fo ethanol.
This suggests
that one of the hydroxy groups is at C-3, but has the beta
configuration.
Marker and Rohrmann found that chlorogenone
gives a pyridazine derivative when treated with hydrazine
hydrate.
On the basis of this reaction they suggested
that the. hydroxy groups of chlorogenin are at C-3 and C-6.
Chlorogenone and tigenone yield the same desoxy
compound upon Clemmensen reduction (38) showing that the
nuclear configurations are the same.
Since tigogenin is
known to have the alio configuration, chlorogenin must
also belong to the alio series, and differs from tigogenin
only by the nresence of an additional hydroxy group.
Tsukamoto and his
co—
workers(29), in their studies
on diosgenin (XIX) an unsaturated sapogenin, obtained a
55
diketone which proved to be identical with chlorogenone
(38).
By the method of preparation of their ketone the
carbonyl groups should be at 0-3 and 0-6, which is fur­
ther evidence that the hydroxy groups in chlorogenin are
at C-3 and C-6.
Chlorogenin was found to resemble tigogenin when
subjected to the reactions characteristic of sarsasapo­
genin (28).
It showed little tendency to isomerize with
hydrochloric acid in ethanol and did not reduce by the
Clemmensen method.
In other respects it reacted similarly
to sarsasapogenin.
The fact that tigogenin, chlorogenin, gitogenin,
and digitogenin show no tendency to react with boiling
alcoholic hydrochloric acid indicates that the side
chains of these sapogenins differ in configuration from
that of sarsasapogenin, which by similar treatment is
isomerized to isosarsasapogenin (smilagenin (30)).
Marker
and Rohrmann (3l) obtained evidence which showed conclus­
ively that tigogenin differs from sarsasapogenin not only
in its configuration at C-5 but also in the configuration
of the side chain.
Sarsasapogenone upon bromination with
two moles of bromine gave dlbromosarsasapogenone, a sub­
stance having a bromine atom at C-4 as well as in the side
chain.
This ketone lost hydrogen bromide upon treatment
with boiline: oyridine to give a /^—unsaturated ketone.
Reduction of this product with sodium in ethanol and
separation of the isomers with digitonin gave a digioonin
56
precipitable compound which was different from tigogenin
hut identical with neotigogenin, an isomer of tigogenin
which was isolated from Ohlorogalum pomeridianum extracts
hy Goodson and Noller (32).
These results indicate that the side chain of
neotigogenin is of the
sarsasapogenin configuration.
Inasmuch as tigogenin (28), chlorogenin (28), and diosgenin (33) have all been converted to the same desoxy com­
pound it follows that these sapogenins all have the same
side chain configuration, that of the
configuration.
isosarsasapogenin
The stability of gitogenin and digito­
genin to alcoholic hydrochloric acid suggests that these
sapogenins likewise have the
isosarsasapogenin side chain
configuration.
The conversion of sarsasapogenin to pregnanedlol by
Marker and Rohrmann (34) in good yields showed that
sarsasapogenin is a good starting material for the prep­
aration of pregnane compounds, from which it is possible
to make progesterone,
one.
testosterone, and desoxycorticoster-
They treated sarsasapogenin with acetic anhydride
at 200° and obtained an isomeric substance, which they
designated as pseudosarsasapogenin.
This substance upon
mild oxidation with chromic anhydride yielded an un­
saturated ketone, /^6-pregnenedione-3,20, which gave
pregnanediol-3(c*) ,20(<*) when reduced with sodium in
ethanol.
The isomerization of sarsasapogenin to pseudo-
57
sarsasapogenin is also effected by other a c i d anhydrides
(35).
Propionic anhydride is quite e f f e c t i v e ,
while In
the case of n-butyric anhydride the i s o m e r i z a t i o n is
effected b y simple refluxing.
It is of i n t e r e s t that
acid products were encountered in all of tiiese isomerisation reactions.
In the case of acetic aniiydride, the
acid fraction yielded largely the 0 22 l a c t o n e .
All of the evidence, which is d e r i v e <3. largely
from oxidation and reduction studies, i n d i c a t e s that pseudosarsasapogenin is best represented by s t r m c t u r e XXIV, or
one of its eouivalents, XXV of XXVI.
CHj OH
CHsk-i-c^-cricCri-ciUOH
CH^
3r
1
./■
HO'
XXV
XXIV
,1
p u, C1Hj 0h
w ° rHo.vrHCK
3
*
XXVI
Neither pseudosarsasapogenin or its a c e t a t e
(36) react
with semicarbazide acetate under the usu.s.1 conditions.
Pseudosarsasapogenin upon catalytic hydr-ogenation
yields dihydropseudosarsasapogenin, whicli gives a di­
acetate.
Acetylated p s e udosarsasapogenin upon catalytic
58
hydrogenation yields a compound identical with the di­
acetate of dihydropseudosarsasapogenin.
This fact does
not seem to be in accordance with structure XXVI for
pseudo sarsasapogenin.
Dihydropseudo sarsasapogenin upon
oxidation at 15° with chromic anhydride readily yields
& 16 -pregnenedione
and an acid, C B7 H 4 a0 4 .
The fact
that this acid forms a disemicarbazone while pseudosarsasapogenin does not react with semicarbazide acetate
does not seem to be in accordance with structure XXV,
It seems strange that pseudosarsasapogenin and
dihydropseudosarsasapogenin form bis rather than the
expected tris derivatives.
This is probably due to
hindrance at the C-33 position.
The acid anhydride isomerization reaction was
extended to include tigogenin and chlorogenin (37).
All o f these pseudosapogenins have been found to be
readily converted to the sapogenins by treatment with
hydrochloric acid in ethanol (38).
In previous work
Marker and Rohrmann showed that the side chains of
tigogenin,
chlorogenin,
and diosgenin, and probably
gitogenin and digitogenin differ in configuration from
that of sarsasapogenin.
That the sapogenins derived
from the acid isomerization of pseudosapogenins is deter­
mined largely by the configuration at C-5 is indicated
by the fact that pseudosarsasapogenin yields largely
sarsasapogenin rather than isosarsasapogenin, while
pseudotigogenln yields largely tigogenin rather than
59
neotigogenin.
Thus it may b e generalized that pseudo­
sapogenins having the r e g u l a r configuration at C-5 give
rise to a spiro-ketal side chain of the sarsasapogenin
configuration (XXVIIl) , w h i l e those of the alio series
give rise to one having the
isosarsasapogenln con­
figuration (XXIX) .
c h
C=
3
oH
C - c-H<cR*-1 rt-£,H,,QH
XXVII. Pseudosapogenins
CNs
O-cHj.
CH-C
)CHCH3
7 pCH^Crt/
3
CH3
r*-c -cHx
u
C.H-C.0
.O
XXVIIl.
Side Chain of
XXIX.
Side Chain of
Sarsasapogenin
1 sosarsasapogenin
Configuration
Configuration.
Xt seems most p r o b a b l e that these reactions are
of an equilibrium nature a n d that the Isomerization of
pseudosarsasapogenin gives
sapogenin.
small amounts of isosarsa­
Likewise, the isomerization of pseudotigo-
genin probably gives small
addition to tigogenin.
amounts of neotigogenin in
*
DISCUSSION
A.
Sarsasapogenin.
The sarsasapogenin used in this work was obtained
by the acid hydrolysis of extracts of the Mexican sarsa­
parilla root, Radix sarsasaparillae.
It was purified by
conversion to the acetate and crystallization from ethyl
acetate.
The pure acetate exists in two forms, one
melting at 135° and one at 143°.
The higher melting
material may be obtained from the lower by seeding its
solutions with crystals of the higher melting form.
Pseudosarsasapogenin was prepared by the action
of acetic anhydride on sarsasapogenin acetate at 300°.
The yield for this reaction was approximately 60$ of
purified pseudosarsasapogenin.
In the oxidation of pseudosarsasapogenin with
chromic anhydride a considerable amount of acids are
formed, along with
^^-pregnenedione, arising from the
oxidative rupture of the 5-membered ring.
Since
potassium permanganate has less tendency to oxidize these
rings than does chromic anhydride, the oxidation of
pseudosarsasapogenin was carried out using a solution
of potassium permanganate in 60$ acetic acid at 15°.
Under these conditions no acid fraction was obtained,
61
the only neutral product being
seems rather strange
A 16- p r e g n e n e d i o n e .
that the permanganate
act with the double b o n d between C-16 and
this double bond has been shown to be
Mild oxidation
It
d i d not re­
C — 17.
very-
However,
inactive (36).
of sarsasapogenin witli
chromic
anhydride gave an 8 8 % yield of s a r s a s a p o g e n o n e which
was converted to pseudosarsasapogenone by
acetic anhydride at 200°.
"treatment with
As would be e x p e c t e d ,
A-^-pregnenedione-3,30 was formed by the
chromic an-,
hydride oxidation of p s e u d osar s a s a p o g e n o n e .
Mild Clemmensen reduction of s a r s a s a p o g e n o n e in
ethanol solution, u s i n g unamalgaraated z i n c ,
gave
desoxysarsasapogenin in yields of a p p r o x i m a t e l y 50$.
Pseudodesoxysarsasapogenin was obtained b y
of acetic anhydride
the action
at 300° on desoxysarsasapogenin.
Upon catalytic hydrogenation pseudodesoxysarsasapogenin
gave a dihydro compound having the same m e l t i n g point
as the starting material, 130°.
However,
a mixture of
the two compounds m e l t e d at 105-112°.
Pseudodesoxysar sasapogenin did not;
expected
give the
pregnenone-30 upon oxidati_on at 25° with
chromic anhydride.
The oxidation p r o d u c e s
were not in­
vestigated further.
Catalytic hydrogenation of s a r s a s a p o g e n o n e in
ethanol gave approximately 80$ yields of episarsasapogenin.
This c ompound gave epi-pseudo-
sarsasapogenin when t r e a t e d in the usual manner.
As w o u l d be expected, oxidation of epi-pseudosarsasapogenin with chromic
nenedlone.
anhydride gave
A
1 ft
-preg-
epi-Dihydropseudosarsasapogenin was
obtained b y the catalytic hydrogenation of epipseudosarsasapogenin i n
pound
readily formed a
acetic acid.
This com­
di-P-nitrobenzoate when
t r e a t e d with p-nitrobenzoyl chloride in pyridine
at 60 ° .
Treatment of epi-sarsasapogenin acetate
with persulfuric acid I n acetic acid gave
pregnanetriol-3(c*^) , 1 6 , 20, and a small amount
of l a ctonic material m e l t i n g at 312-214°.
triol
The
was characterized, by the preparation of its
tribenzoate, which was
obtained b y treating the
triol with benzoyl chloride in pyridine.
The cleavage of
c h a i n with persulfuric
as f o l l o w s ;i
the sarsasapogenin side
acid probably proceeds
63
’
c
h -r ^y
CHj;C^ ' C N C H j
OH- C- CHi- Crit-CH-CHiOH
I
CH,
Postulated Intermediate
k*s*ob
Hx.SO%
CH3C00H
CH3 0
’h-o -c -c^
ch3
CrtoH
hr
cz/
x-ch -ch.o A c
Yh
OAt
AM&H
CH,
Not Isolated
Tetrahydrosarsasapogenin i s obtained by the
Olennensen reduction of sarsasapogenin acetate, using
amalgamated zinc.
However, if the reaction is pro­
longed, low yields of the tetrahydro compound are
obtained", the main product b e i n g uncrystallizable
gums.
The logical assumption is that tetrahydro-
sarsasapogenin is sensitive to prolonged boiling
with zinc and hydrochloric acid in ethanol.
not the case, however,
This is
since it was found that tetra-
hydrosarsasapogenin was recovered unchanged after
boiling in ethanol with zinc a n d hydrochloric acid
for 48 hours.
Tetrahydrosarsasapogenin,
although having hydroxy
groups at C-3, C-16, and C-37, under the usual conditions
64
of esteriflcatlon forms esters only with the hydroxy
groups at C-3 and C-37, leaving a free hydroxy groun
at C-16 which can be oxidized to a ketonic group.
By
heating tetrahydrosarsasapogenin with acetic anhydride
at 200°, a product was obtained which upon prolonged
refluxing with alcoholic potassium hydroxide retains
its acetyl-group at C-16 without hydrolysis, whereas
the diesters are readily saponified.
The unreactivity
of a substituent at C-16 evidently depends to a great
extent upon the nature of the side chain on the molecule,
for the acetoxy group at C-16 in the triacetate of allopregnanetriol -3,16,30 can be hydrolyzed by the ordinary
procedures.
(39)
Hydrogen peroxide in acetic acid reacted with
pseudosarsasapogenin to give a neutral compound of the
formula C37H 440 B .
The same compound was obtained by
the action of hydrogen peroxide on dihydropseudosarsasapogenin.
The structure of the neutral material was not de­
termined, since no crystalline derivatives could be
obtained.
Because of the ease of isomerization of pseudo—
sarsasapogenin to sarsasapogenin under the influence of
acids,
sarsasapogenin was treated with hydrogen peroxide.
The only product obtained was pregnanetriol -3,16,30, a
compound previously obtained by the action of persulfuric
acid on sarsasapogenin.
(40).
65
Dihydrosarsasapogenin and bromosarsasapogeninwere recovered unchanged after treatment with hydrogen
peroxide in acetic acid.
Upon similar treatment
sarsasapogenone gave only non-crystalline material.
B. Chlorogenin.
The chlorogenin used in t h i s work was obtained
from the bulbs of the C a l i f o r n i a soap plant, Chlorogalum
pomeridianum.
It was found tbis/t the best way to p u r i f y
the chlorogenin was to convert
the crude hydrolysis
products to the pseudo c o m p o u n d s by treatment with
acetic anhydride.
Pseudochlor-ogenin is much less
soluble than the o.ther p s e u d o s a p o g e n i n s present and
can easily be separated from -fcliem by crystallization
the mixture from acetone.
of
Ps-sudochlorogenin is con­
verted to chlorogenin by shorts
refluxing with alcoholic
hydrochloric acid.
Upon oxidation with c h r o m i c anhydride at 35°,
chlorogenin gives good yields
of chlorogenone.
care must be taken during the
oxidation, or only n o n -
crystalline material is o b t a i n e d .
However,
Chlorogenone is
quite
sensitive to alkali and shoul_<d not be allowed to s t a n d
long in contact with concentr»ated solutions of s o d i u m
hydroxide or potassium h y d r o x i d e .
By a comparison of the
reduction products of
cholestanedione -3,6 and chlorogenone,
additional
evidence was obtained indicatr. ing that the hydroxy
groups of chlorogenin are at
C-3 and C-S and that "the
hydroxy group at C-3 has the
beta configuration.
67
Windaus (41)
r e d u c e d cholegtanol -3-one-6 with sodium in
ethanol and o b t a i n e d a diol m e l t i n g at 316°.
The re­
duction of cholestanedione -3,6 w i t h sodium in ethanol
was carried o u t and found to give
216°.
the diol melting at
When clilorogenone was reduced in the same manner,
a product w a s
obtained which was identical with the
original n a t u r a l l y occurring chlorogenin.
Since the
method of r e d u c t i o n was the same as that of the reduction
of cholestanedione,
the 3-OH is o f the beta type.
was to be expected,
for in all k n o w n cases the reduction
of a 3-keto
This
sterol in which the configuration at C-5 is
alio gives r i s e to a 3-OH of the beta configuration.
R e d u c t i o n of chole stanol - 3 — one-5 (42) and cholestanone - 3 - o l - 6 (43) with hydro g e n in the presence of
platinum o x i d e catalyst gave a cholestanedlol, melting
at 190°, w h i c h is isomeric with that obtained by Windaus,
differing o n l y in the configuration of the hydroxy groups
at C-6. I n b o t h of these diols th e hydroxy groups at C-3
have the b e t a configuration.
genone wi t h
U p o n reduction of chloro­
hydrogen and platinum oxide catalyst a com­
pound was obtained, melting at 346-248°, which is iso­
meric with
chlorogenin, differing only in the configur­
ation of th.e hydroxy group, at C — S.
This compound is
called beta-chlorogenin.
A f u r t h e r confirmation of* the conclusions from
these reductions is the fact that allft-hyodesoxychollc
acid was formed b y the reduction of 3,Q-diketo-allocholanic acid with hydrogen and platinum oxide catalyst
(44).
The same acid was also formed by the oxidation ciDf
the diacetate (43) o f .cholestanediol of melting point
190°, showing that the hydroxy groups inithis diol have
the same configuration as those of allo— hyodesoxychollc
acid, in which b o t h are b e t a .
Correspondingly, the
hydroxy groups of beta-chlorogenin are both of the beta
configuration.
Since chlorogenin and beta-chlorogenin
differ only in the configuration of the hydroxy groups
at C-6, the hydroxy groups of the naturally occurring chlorogenin are beta at C-3 and alpha at; C-6.
EXPERIMENTAL
A.
Sarsasapogenin
Preparation of Pseudosarsasapogenin.-
A mixture of 15 g.
of sarsasapogenin acetate and 50 cc. of acetic anhydride
was heated in a sealed tube for 10 hours at 200°.
The
excess anhydride was evaporated in vacuo and the residue
was hydrolyzed by boiling with excess 5$ methanolic
potassium hydroxide solution.
The mixture was diluted
with water and the solid was filtered and washed with
water.
Crystallization of the solid from acetone gave
fine, white needles of pseudosarsasapogenin, melting
point 169°.
The yield from 60 g. of sarsasapogenin
acetate was 37.5 grams.
Oxidation of Pseudosarsasapogenin.-
To a solution of
3 g. of pseudosarsasapogenin in 200 cc. of acetic acid
was added a solution of 6 g. of potassium permanganate
in 500 cc. of
QOfo
acetic acid over a period of 15 minutes
The temperature was maintained at 15° during the addition
The mixture was allowed to stand at room temperature
5 hours, poured into water and extracted with ether.
for
The
extract was washed with water and then thoroughly shaken
with a 5$ solution of sodium hydroxide.
The ether layer
was washed with water and the solvent was evaporated.
The residue was treated with bone black in methanol and
was then crystallized from aqueous methanol.
It m e l t e d
at 194-196° and gave no depression in melting poind: when
mixed with an authentic sample of
A 16-Pregnenedio:ne-3,20.
Anal. Calcd. for 0 31H 3OO 2 : G, 80.2; H, 9.6
Pound: C, 80.1; H, 9.6
Sarsasapogenone.-
Sarsasapogenin obtained from ths_e
hydrolysis of 35 g. of sarsasapogenin acetate was
dis­
solved in 1.5 liters of acetic acid and a s o l u t i o n of 30
g. of chromium trioxide in 1000 cc.. of 80$ acetic
was added with stirring during 40 minutes.
acid
The m i x t u r e
was allowed to stand at room temperature for two inours,
then was diluted with water and extracted with etlner.
The extract was washed with water and sodium carb o n a t e
solution and the ether was evaporated.
The residrue was
crystallized from aqueous acetone to give 26.5 g.
of
sarsasapogenone, melting point 224-226°.
Pseudosarsasapogenone.-
A mixture of 5 g. of sar*sasapo-
genone and 35 cc. of acetic anhydride was heated
in a
sealed tube for 10 hours at 200°, and the excess
an­
hydride was evaporated in vacuo«
The residue w a s hydro­
lyzed by boiling with excess 5$ methanolic p o t a s s i u m
hydroxide solution, poured into water and e x t r a c t e d with
ether.
The extract was washed with water and t h e
was evaporated.
solvent
The residue was crystallized fr-om
aqueous acetone as white needles, melting point
3_65-loS°.
71
Oxidation
of Pseudosarsasapogenone.-
To a solution of
1.5 g. of
pseudosarsasapogenone In 50 cc. of acetic acid
was added
a solution of 1.5 g. of chromium trioxide in
25 cc. of
80fo acetic acid.
After standing at room
temperature for 90 minutes the mixture was diluted and
the p r e c i p i t a t e d solid was taken up in ether and washed
with a 5
sodium hydroxide solution.
The ether was
evaporated, and the residue was crystallized from acetone
to give wtiite plates, melting point 199-301°.
material
This
gave no depression in melting point when mixed
with an authe n t i c sample of
Desoxysar* sasapogenin.-
A16-pregnenedione-3,20.
During three hours 100 cc. of
concentratied hydrochloric acid was added to a boiling
mixture o f 6 g. of sarsasapogenone, 100 g. of 20 mesh
zinc, a n d
600 cc. of ethanol.
The mixture was poured
into w a t e r and extracted with ether.
The extract was
washed wi_th sodium carbonate solution and water, and
the solvent was evaporated.
The residue was crystal­
lized f r o m ethyl acetate to give white needles of
desoxysansasapogenin, melting point 213-315°.
From
three s u c h runs, 10 g. of the product was obtained.
Pseudodesoxysarsasapogenin.-
A mixture of 9 g. of
desoxysa.3rsasapogenin and 40 cc. of acetic anhydride was
heated i n a sealed tube for 10 hours at 200°.
The
acetic anhydride was evaporated in. vacuo and the
residue was hydrolyzed by boiling w i t h excess methanolic
potassium hydroxide for 30 minutes.
Water was added and
the mixture was extracted with ether.
The ether was
evaporated and the residue was crystallized from aqueous
acetone, melting point 130°.
Anal. Calcd.
for Cs7H 440 2 :
Found:
The y i e l d was 5.3 grams.
C, 80.9;
H, 11.1
C, 80.8;
H, 11.0
Dlhydropseudodesoxysarsasapogenin.-
A mixture of 600
mg. of pseudodesoxysarsasapogenin, 3 0 0 mg. of platinum
oxide catalyst,
and 80 cc. of acetic
acid was shahen
with hydrogen at room temperature a n d 3 atmospheres
pressure for 16 hours.
The mixture was filtered and
the solvent was evaporated in v a cuo.
The residue was
hydrolyzed by boiling with methanolic potassium hydrox­
ide solution, poured into water and
extracted with
ether.
with water and the
The extract was washed well
ether was evaporated.
The residue w a s crystallized
from acetone to give a product m e l t i n g at 129-130°.
A
mixture with the starting material melted at 105-112°.
Anal. Calcd.
for C27H 460 2 :
Found:
C, 80.5; H, 11.5
C, 80.7, H, 11.4
Oxidation of Pseudodesoxysarsasapogenin.-
A solution
of 1.3 g. of chromium trioxide in 3 5 cc. of 80fc acetic
acid was added to a solution of 1.3
g. of pseudodesoxy­
sarsasapogenin in 50 cc. of acetic acid and the mixture
was allowed to stand at room temperature for one hour.
Water was added and the mixture was extracted with ether.
The extract was washed with water and 5# sodium hydroxide
solution and the ether was evaporated.
The residue was
crystallized twice from acetone-ether to give a neutral
product which melted at 216-318°.
Anal. Found; G, 80.93! H, 11.15
■I £
This product is not the expected
epl-Sarsasapogenin.-
A
-pregnenone-20.
A mixture of 3 g. of sarsasapo­
genone 350 cc. of ethanol, and 300 mg. of platinum
oxide catalyst.was shaken with hydrogen at room temper­
ature ahd 3 atmospheres pressure for two hours.
After
filtration of the catalyst, the solvent was evaporated
and the residue was crystallized twice from acetone.
A total of 14 g. of epi-sarsasapogenln, melting at 305°,
was obtained from 18 g. of the starting material.
epl-Pseudosarsasaoogentn.-
A mixture of 9 g. of epl-
sarsasapogenin and 50 cc. of acetic anhydride was
heated in a sealed tube for 10 hours at 300°,
The
excess anhydride was evaporated in vacuo and the
residue was hydrolyzed by boiling with methanolic
potassium hydroxide.
The mixture was poured into water
and extracted with ether.
The extract was washed with
water and the ether was evaporated.
The residue was
crystallized from acetone to give 4.8 g. of white
needles, melting point 211-313°.
Anal. Calcd.
for C 3 7H 44b 3 :
Found*
C, 77.8; H, 10.6
C, 77.6; H, 10.6
epl-Dlhydropssudosarsasapogenin.-
A mixture of 1.5 g.
of epi-pseudosarsasapogenin, 1 g. of platinum oxide
catalyst, and 150 cc. of acetic acid was shaken with
hydrogen at room temperature and 3 atmospheres
pressure for 17 hours.
The mixture was filtered and
the solvent was evaporated in vacuo.
The residue was
hydrolyzed by boiling with methanolic potassium hy­
droxide solution, poured into water, and extracted with
ether.
The extract was washed with water and the ether
was evaporated.
The residue was crystallized from
acetone to give white needles, melting point 135-137°.
Anal. Calcd.
for
Cg 7 H 4 g 0 3 :
Found:
C, 77.4-; H, 11.1
C, 77.3; H, 11.0
p-Nitrobenzoate of epl-Dlhydropseudosarsasapogenin.-
A
solution of 500 mg. of epl-dihydropseudosarsasapogenin
and 700 mg. of p—nitrobenzoyl chloride in 10 cc. of dry
pyridine was heated for 6 hours at 60° and then allowed
to stand at room
temperature over night.
Thesolution
was diluted with
water and extracted with ether.
The
extract was washed with dilute hydrochloric acid, sodium
carbonate solution, and water.
The ether was evaporated
and the residue was crystallized three times from acetone
to give white needles of the di-p-nitrobenzoate, which
75
melted at 207° .
Anal.
Calcd. f o r C 41H 520 9N 2 :
C, 68.7:
Pound:
H, 7.3
C, 68.6; H, 7.3
Oxidation of epl-Pseudosarsasapogenln.-
To a solution
of 100 mg. of* epi-pseudosarsasapogenin in 10 cc. of
acetic acid w a s added a solution o f 300 mg. of chromium
trioxide in 8
cc. of 80$ acetic acid.
The mixture was
allowed to s t a n d at room temperature for one hour, then
diluted with
-water and extracted with ether.
The extract
was washed wjLth 5$ sodium hydroxide solution and water,
and the ether* was evaporated.
T h e residue was crystal­
lized from a c e t o n e to give white
crystals of
A ^ - p r e g n e n e d i o n e - S ^ O , melting point 199-201°.
Anal.
Calcd. for C21H 300 2 :
Pound:
Oxidation of
C, 80.2; H, 9.6
0,79.9;
H, 9.5
epl-Sarsasapogenin with Persulfurlc Aold.-
epi— Sarsasapogenin, 4.3 g. , was
transformed to the
acetate by r*efluxing with 50 cc.
for 45 m i nutes.
of acetic anhydride
The excess anhydride was evaporated
in vacuo and. the residue was t a h e n up in 750 cc. of
90$ acetic acid.
To this solution was added 20 g. of
potassium p e r s ulfate and 5 cc.
mixture was
o f sulfuric acid.
The
refluxed for two hours, poured into water
and e x t r a c t e d with ether.
The extract was washed with
3$ p o t a s s i u m hydroxide solution, and the ether was
*
76
evaporated.
The residue was hydrolyzed with hot
methanolic potassium hydroxide and poured into water.
The mixture was extracted with ether and the extract was
washed well with water.
The ether was evaporated and -the
residue was crystallized four times from acetone to give
300 mg. of crystalline pregnanetriol-3(
) , 16, 30, melt­
ing point 206-307°.
Anal.
Calcd.
for
G 21H 3S0 3 :
Found:
The alkaline
C, 74.9;
H, 10.8
C, 74.9;
H, 10.7
solution from the hydrolysis wasacidified
and extracted with, ether.
The extract was washed with
water and the e t h e r was evaporated.
The residue was
crystallized t h r e e times from acetone to give a small
amount of lac t o n i c material which melted at 212-314°.
Anal. Found:
0,
76.3
;
H, 9.53
Benzoate of P r e g nanetrlol-3( ^ ) , 16, 3 0 .-
A solution
of 100 rag. of pregnanetriol-3( 00 ) , 16,20 in 5 cc. of
pyridine was treated writh 6 drops of benzoyl chloride
and allowed to stand at room temperature for 34 hours.
Water was added a n d the mixture was extracted with
ether.
The extract was washed with water and dilute
hydrochloric acicl, and the ether was evaporated.
The
residue was crystallized from acetone three times to
give the tribenzoate, melting point 154°.
Anal. Calcd.
for
C43H4806 :
Found:
C, 77.7,
H, 7.5
C, 77.3;
H, 7.4
7?
Preparation of Tetrahydrosarsasapogenin.-
During four
hours 45 cc. of concentrated hydrochloric acid was added
a boiling mixture of 2 g. of sarsasapogenin acetate, 40 g.
of amalgamated zinc, a n d 250 cc. of ethanol.
The mixture
was decanted into water and extracted with ether.
The
extract was washed with, sodium carbonate solution and
water, and the ether was evaporated.
The residue
crystallized from ethyl acetate as small, compact
crystals, melting point 190-192°.
A total of 10.2 g.
of tetrahydrosarsasapogenin was obtained from 23 g. of
the starting material.
Clemmensen Reduction of Tetrahydrosarsasapogenin.-
Dur­
ing 48 hours 50 cc. of concentrated hydrochloric acid
was added to a boiling mixture of 2 g. of tetrahydro­
sarsasapogenin, 30 g.
of ethanol.
of amalgamated zinc,
and 300 cc.
The mixture was poured into water and
extracted with ether.
The extract was washed with
water and the ether was evaporated.
The residue
crystallized from ethyl acetate as small,
compact
crystals, which m e l t e d at.188-190° and gave no de­
pression in melting point when mixed with the start­
ing material.
16-Acetoxy-tetrahyd.rosarsasapogenin.-
A mixture of
2.5 g. of tetrahydrosarsasapogenin and 25 cc. of acetic
anhydride was heated in a sealed tube for 10 hours at
200°.
The acetic anhydride was evaporated in vacuo and
the residue was refluxed for 45 minutes with 5# alcoholic
potassium hydroxide solution.
Water was added and the
mixture was extracted with ether.
The extract was
washed with water and the residue was crystallized from
acetone to give 3 g. of 16-acetoxy-tetrahydrosarsasapogenin, melting point 154°.
Anal. Calcd. for C29H 500 4 :
Found:
C, 75.27; H,10.89
C, 75.28; H, 10.90
Oxidation of Sarsasapogenin Acetate with Hydrogen Peroxide.
A mixture of 6 g. of sarsaspogenin acetate, 50 cc. of
30$ hydrogen peroxide and 300 cc. of acetic acid was
heated at 70° for 7 hours.
The solution was concen­
trated in vacuo, diluted with water, and extracted with
ether.
The extract was washed with water and the ether
was evaporated.
The residue was hydrolyzed with hot
methanolic potassium hydroxide solution and poured into
water.
This was extracted with ether and the extract was
washed with water.
The ether was evaporated and the
residue was crystallized from acetone to give 1.55 g.
of pregnanetriol-3,16,20 melting at 321-223°.
This
gave no depression in melting point when mixed with an
authentic sample of pregnanetriol-3,16,30 prepared by
the action of persulfurlc acid on sarsasapogenin acetatse.
Bromosarsasapogenin acetate and dihydrosarsasapogenin
were recovered unchanged when treated in the above
manner.
79
Oxidation of Sarsasapogenone with Hydrogen Peroxide.-. A
mixture of 1 g. of pseudosarsasapogenone, 10 cc. of 30$ hydro­
gen peroxide, and 150 cc. of acetic acid was heated at 70°
for 5 hours.
The reaction mixture was worked up as described
for sarsasapogenin acetate.
The product could not be obtained
in a crystalline form.
Action of Hydrogen Peroxide on Pseudosarsasapogenin.- A
mixture of 1 g. of pseudosarsasapogenin, 10 cc.
gen peroxide and
5 hours.
of 30$ hydro­
300 cc. of acetic acid was heated
at70° for
The solution was concentrated in vacuo and diluted
with water.
It was extracted with ether, washed with water,
and the ether was evaporated.
The residue was hydrolyzed
with hot methanolic potassium hydroxide
water, and extracted with ether.
solution, poured into
The extract was washed with
water, and the ether was evaporated.
The residue crystallized
from aqueous methanol as tiny, white needles, which melted at
353-354°.
Yield:
Anal. Calcd. for
350 mg.
Cg 7 H 4 4 0 g : C, 73»26, H, 9.9
Found:
C,73.39;
73.56;
H, 10:01
9.99
The same product was1,obtained when dihydro sarsasapo­
genin was treated with hydrogen peroxide in the same manner.
The alkaline solution from the above hydrolysis was
acidified and extracted with ether.
The extract was
80
washed with water and the ether was evaporated.
The
residue was crystallized from aqueous m s t h a n o l
to give
a small amount of lactonic material, w h i c h melted at
382-285°.
Anal. Found;
C, 72.57; H, 9.44
When refluxed with acetic anhydricle the neutral
product gave only non-crystalline m a t e r i a l .
Oxidation
with chromium trioxide gave both neutralL and acid
products, neither of which was obtained
crystalline.
It
did not give a benzoate or a p-nitroben zoate when treated
in the usual manner.
its melting point.
It is stable to sliort heating at
No change was o b s e r v e d when it was
allowed to stand for 34 hours with alcoliolic hydrogen
chloride.
It was unaffected by c a t a l y t i c hydrogenation
in acetic acid with platinum oxide catalyst.
B. Chlorogenin
Preparation of Pseudochlorogenin.-
A mixture of 15 g. of
chlorogenin and 50 cc. of acetic anhydride was heated for
t e n hours at 300° in a sealed tube.
The material from
two such runs was combined and the excess anhydride
w a s evaporated in vacuo.
The residue was hydrolyzed b y
"boiling with a 5$> solution of potassium hydroxide in
methanol.
The crystalline product which separated upon
cooling the solution was filtered and recrystallized
from acetone to give 13.1 g. of pseudochlorogenin, which
h a d a melting point of 268-370°.
Acid Isomerization of Pseudochlorogenin.-
A mixture
of 7 g. of pseudochlorogenin, 25 cc. of concentrated
hydrochloric acid, and 1000 cc. of ethanol was refluxed
for three hours.
The solution was concentrated in vacuo
to a volume of 400 c c . , then cooled in an ice bath.
The
solid was filtered and recrystallized from ethanol to
give 5.1 g. of chlorogenin which had a melting point of
272-375°.
Preparation of Chlorogenone.-
A solution of 4 g. of
chromium trioxide in 100 cc. of 80$> acetic acid was added
with stirring to a solution of 4 g. of chlorogenin in
150 cc. of acetic acid during 20 minutes.
The mixture
was allowed to stand at room temperature for 1 hour and
83
was diluted with water.
T he resulting mixture was
extracted with ether and th e extract was washed with
water and sodium carbonate solution.
The residue
remaining from the evaporation of the ether was
crystallized twice from acetone.
Chlorogenone was 3.3 g.
The yield of
M elting point 334-336°.
Oxidation of Cholestanediol-3,6.-
A solution of 6 g.
of chromium trioxide in 1 5 0 cc. of 80$ acetic acid was
added, with stirring, to a
solution of 5 g. of
cholestanediol-3,6 in 300 cc. of acetic acid during
30 minutes.
The mixture w a s stirred for three hours
and poured into water.
T h i s was extracted with ether,
and the extract was washed with water and sodium
carbonate solution.
The ether was evaporated and
the residue was crystallized from ethanol.
The yield
of cholestanedione-3,6 w a s 1.6 g.j- melting point 169170°.
Reduction of Oholestanedlone-3,6.-
To a boiling
solution of 1.3 g. of cholestanedione-3,6 in 300 cc.
of absolute ethanol was added 13 g. of sodium during
1 hour.
The solution was diluted with water and
extracted with ether.
T h e extract was washed with
water and the ether was evaporated.
The residue
remaining after the evaporation of the ether was
treated with bone black in acetone and they crystal­
lized twice from acetone
and twice from aqueous
83
acetone.
The product melted at 316°.
Anal. Calcd. for C27H 4a0 3 :
Found
C,80.S ; H, 11.9
C,79.8 ; H, 11.86
Reduction of Chlorogenone with Sodium In E thanol.To a boiling solution of 1 g. of chlorogenone in 300
cc. of absolute ethanol was added 13 g. of sodium
during 1 1/3 hours.
The mixture was diluted with
water and extracted with ether.
The extract was
washed with water and the residue was treated with bone
black in acetone.
After one crystallization from
acetone the product melted at 371°, and gave no
depression in melting point when mixed with an authen­
tic sample of chlorogenin.
A n a l . Calcd.
for
C2 7H 44 0 4 : C, 74.9^
Found:
C,75.3;
H> 10.3
H, 10.4
Preparation of the Acetate of the Reduction Product
of Chlorogenone.-
A mixture of 10 cc. of acetic
anhydride and 100 mg. of the above reduction product
wa.s refluxed for 30 minutes and then poured into
water.
This was extracted with ether and the
was washed with water.
extract
Evaporation of the ether gave
a residue which was crystallized twice from aqueous
methanol.
The resulting product was a diacetate
which melted at 151-153° and did not give a de­
pression in melting point when mixed with an authentic
84
sample of chlorogenin diacetate.
Anal. Calcd.
for C 3XH 48O s ;
Found:
C, 73.05; H, 9.37
0, 73.13, H, 9.54
Catalytic Reduction of Chlorogenone.-
A mixture of 1.5
g. of chlorogenone, 300 cc. of ethanol, and 300 mg. of
platinum oxide cat&lyst was shaken with hydrogen at
room temperature and 3 atmospheres pressure for 4
hours.
The catalyst was filtered and the solvent was
evaporated in vacuo.
The residue,after crystallization
from ethanol, melted at 343-247°.
Recrystallization
from acetone raised the melting point to 346-348°.
A
mixture of this product with chlorogenin, m.p. 372°,
melted at 233-350°, and a mixture with chlorogenone,
m.p. 334-236°, melted at 3©5-234°.
This substance is
a new compound and is assigned the name beta-chlorogenin.
Anal. Calcd.
for C 37H440 4 :
Found:
C, 74.9 ; Hi,.10.3
C, 74.53; H, 10,3
Acetate of beta-Chlorogenln.-
A mixture of 200 mg.
of beta-chlorogenin and 5 cc. of acetic anhydride was
refluxed for 20 minutes and the excess anhydride was
evaporated in, vacuo.
Various solvents were tried but
it was quite difficult to obtain the acetate in good
crystalline form.
methanol.
at 120°.
The best solvent found was aqueous
After two crystallizations the acetate melted
85
Anal. Calcd. for C 3XH 4806 ;
Found:
C, 73.05; H, 9.37
C, 73.4 ; H, 9.43
Benzoate of beta-Chlorogenin.-
To a solution of 100
mg. of beta-chlorogenin in 5 cc. of dry pyridine was
added 8 drops of benzoyl chloride.
The mixture was
allowed to stand for 36 hours at room temperature,
then poured into water and extracted with ether.
The
extract was washed with dilute hydrochloric acid and
water, and the ether was evaporated.
The residue was
crystallized 3 times from aqueous acetone; melting
point 198-300°.
Anal. Calcd.
for C 4xH S20 6 :
Found:
C,
76.87;
C,
77.13; H, 8.37
Reduction of beta-Chlorogenln.of beta-chlorogenin, 75 cc.
A mixture of 500 mg.
of acetic
of platinum oxide catalyst was
H, 8.13
acid, and 300 mg.
shaken with hydrogen at
room temperature and 3 atmospheres pressure for 15 hours.
After removal of the catalyst the solvent was evaporated,
and the residue was-hydrolyzed with hot methanolic
potassium hydroxide.
After the addition of water the
mixture was extracted with ether, and the extract was
washed with water.
The residue remaining from the
evaporation of the ether was crystallized twice from
aqueous acetone; melting point 309-310°.
A mixture
with diEiydrochlorogenin, m.p.
233-335°, melted at
193-225°.
Anal. Calcd.
for C37H460*:
Founds
C, 74.6j H, 10.7
C, 7 4 . 4 j H, 10.75
87
Summary
1.
Pseudosarsasapogenin has been oxidized with
potassium permanganate in acetic acid solution.
3.
Pseudosarsasapogenone, Pseudodesoxysarsasapo­
genin,- and epi-pseudosarsasapogenin have been prepared
and studied.
3.
epi-Sarsasapogenin has been oxidized to
pregnanetriol-3( ) ,16,30 by means of persulfuric a d d .
4.
Tetrahydrosarsasapogenin has been shown to
be stable toward Clemmensen reduction.
5.
16-Acetoxy-tetrahydrosarsasapogenin has been
shown to be unreactive toward alcoholic potassium
hydroxide.
6.
The action of hydrogen peroxide on sarsa-
sapogenin and some of its derivatives has been studied.
7.
An Isomer of chlorogenin, beta-chlorogenin,
has been prepared and characterized.
8.
Evidence has been obtained showing that the
hydroxy groups in chlorogenin are beta at C-3 and
alpha at 0-6.
88
BIBLIOGRAPHY
I.
Fieser, L. F., Chemistry of Natural Products related
to Phenanthrene, 3d ed. New York, Reinhold
Publishing Corp., 1937.
3.
Tschesche, R. , and Hagedorn, A., Ber. 68_, 1413 (1935).
3.
Farmer,
S. N . , and Kon, G. A. R . , J. Chera. Soc.
414 (1937).
4.
Marker, R. E . , and Rohrmann, E . , J. Am. Chem. Soc.
61, 846 (1939).
5.
Marker, R. E . , and Rohrmann, E . , J. Am. Chem. Soc.
61, 1931 (1939).
6.
Simpson, J. C. E . , and Jacobs, W. A., J. Biol. Chem.
1 1 0 , 565 (1935).
7.
Fieser, L. F . , and Jacobsen, R. P., J. Am. Chem. Soc.
60, 3761 (1938).
8.
Marker, R. E. , and Rohrmann, E. , Ibid. 6_1, 1384
9.
Askew, F. A., Farmer, S. N . , and Kon, G. A. R . , J.
Chem.
10.
(1939) .
Soc. 1399 (1936).
Marker, R. E . , and Rohrmann, E . , J. Am. Chem.
Soc. 6 1 ,
943 (1939).
II.
Marker, R. E . ,
and Rohrmann, E . , Ibid. 61, 1516 (1939).
13.
Marker, R. E . ,
and Rohrmann, E . , Ibid. 61, 1391 (1939).
13.
Marker, R. E . ,
and Rohrmann, E . , Ibid. 61, 3734 (1939).
14.
Fieser, L. F . ,
and Jacobsen, R. P., Ibid. 60, 38 (1938).
15.
Fieser, L. F.,
and Jacobsen, R. P., Ibid. 60, 3753 (1938) .
89
16.
Fieser, L. F . , and Jones, R. N., J. Am. Chem. Soc.
61, 532 (1939).
17.
Marker, R. E . , and Rohrmann, E . , Ibid. 61, 2073 (1939).
18.
Marker, R. E . , and Rohrmann, E . , Ibid. 61, 1385 (1939).
19.
McMillan, F. M . , and Noller, C. R . , Ibid. 60, 1630 (1938)
20.
Marker, R. E . , and Rohrmann, E . , Ibid. 62, 76 (1940).
31.
Marker, R. E . , and Rohrmann, E . , Ibid. 61, 2723 (1939).
22.
Marker, R. E . , and Rohrmann, E., Ibid. 61, 3477 (1939).
33.
Marker, R. E . , and Rohrmann, E . , Ibid. 62, 900 (1940).
24.
Litvan, F . , and Robinson, R . , J. Chem.
25.
Liang, P., and Noller, C. R . , J. Am. Chem. Soc. 5 7 ,
525
26.
Soc. 1997 (1938).
(1935).
Noller, C. R . , Ibid. 60, 1639 (1938).
27.
Marker, R. E. , and Rohrmann, E. , Ibid. 61L, 946 (1939) .
38.
Marker, R. E. , and Rohrmann, E. , Ibid. 61, 3479 (1939) .
29.
Tsukamoto, T., Ueno, Y. , Ota, Z . , and Tschesche,
J. Pharm.
30.
Soc. Japan j57, 383 (1937) .
Kon, G. A. R. , Soper, H. R. , and Woolman, A. M. ,
J. Chem. Soc. 12Q1 (1939).
31.
Marker, R. E . , and Rohrmann, E . , J. Am. Chem. Soc. 62,
647 (1940).
32.
Goodson, L. A., and Noller, C. R. , Ibid. 61_, 2430 (1939)
33.
Tsukamoto, T., Ueno, Y . , and Ota, J., J. Pharm.
Soc.
Japan 57, 985: (1937) .
34.
Marker, R. E. , and R o h m a n n , E . , J. Am. Chem. Soc. 6JL,
3593 (1939).
90
35.
Marker, R. E . , and Rohrmann, E. , J. Am. Chem.
Soc. 6 3 ,
518 (1940).
36.
Marker, R. E . , and Rohrmann, E . , Ibid. 63, 531 (1940).
.
37.
\
Marker, R. E . , Rohrmann, E . , and Jones, E. M . ,
J. Am. Chem. Soc. 63_, 648 (1940) .
38..
Marker, R. E. ,and Rohrmann, E. , Ibid. 63, 896 (1940) .
39.
Marker, R. E . ,and Wlttle, E. L. , Ibid. 61, 855 (1939).
40.
Marker, R. E . ,Rohrmann, E . , Crooks, H. M. , Wlttle,
E. L . , Jones, E. M . , and Turner, D. L . , Ibid. 63,'
535 (1940).
41.
Windaus, A., Ber.
50, 133 (1917).
43.
Marker, R. E . ,and Krueger,
J., Ibid. 63, 79 (1940).
43.
Marker, R. E . ,Krueger, J.,
Adams, J. R . , and Jones,
E. M., Ibid. 63, 645 (1940).
44.
Windaus, A., Ann. 4 4 7 , 333 (1936).
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