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Dialkyldioxanes and the structure of glycolaldehyde dimer

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DATE
NORTHWESTERN UNIVERSITY
DIALKYLDIOXANES AMD THE STRUCTURE
OF GLYCOLALDEHYDE DIMER
A DISSERTATION
SUBMITTED TO THE GRADUATE SCHOOL
PARTIAL FULFILLMENT OF THE REQUIREMENTS
for the degree
DOCTOR OF PHILOSOPHY
DEPARTMENT OF CHEMISTRY
BY
LEO KANT ROCHEN
EVANSTON,
ILLINOIS
JUNE, 1940
ProQuest Number: 10101899
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ACKNOWLEDGEMENT
To Professor Robert K. Summerbell,
as an encouraging adviser and sympathetic
friend, the author takes this opportunity
to express his deepest gratitude and most
sincere appreciation.
TABLE OF CONTENTS
B age
INTRODUCTION
I. HISTORICAL
A#
Pialkyldioxanes.
1.
2.
3.
B.
Significance of Dioxane .................. 3
Synthesis of dioxane and some of
its h o m o l o g s .............................. 5
Preparation of alpha- and betahalogene t h e r s .......................... 8
Glycolaldehyde Dimer,
1,
2m
Synthesis of glycolaldehyde ...............10
Structure of glycolaldehyde dimer . . . .11
II. DISCUSSION OF RESULTS
Am
Dialkyldioxanesa
1.
Synthesis of 2,3-dialkyldioxanes
. . . .16
. • .22
Properties of a l k y l d i o x a n e s ...............26
2m Synthesis of 2,6-dialkyldioxanes ,.
3*
B.
Glyc olaldehyde Dime r.
1„
2*
3.
4.
5.
6*
7.
Dioxadiene
• • • . • • • • • • • . • • • 3 9
Structure of 2,5-dihalogendioxanes
. . .42
Dioxene .
......................
.44
Attempted synthesis of p-nitrophenylhydrazone of diglycolaldehyde
......... 46
4 - P e n t e n e - l ~ c l ............................ 51
Structure of glycolaldehyde dimer . . . .52
Chlorination of dioxane and 2,5-dichlor o d i o x a n e ..................................57
IIIo EXPERIMENTAL
A.
Di alkyldioxanes.
1.
2,3-Diethyldioxane Q
a. o<-Chlorobutyl- ps-chloroethyl ether .62
b.
R -Dibromobutyl -9 !-chloroethyl
e t h e r ...................
63
c.
-Ethyl- 9 -bromobutyl- (3 ‘-chloro­
ethyl et her ...........
64
d.
Synthesis of 2,3-diethyldioxane . . .65
Page
B.
2.
2-Ethyl- 3-me thy Id i ox an e
.
a. oi -Me thyl- 9 -bromobutyl - “
ch.loroeth.yl ether . . .................. 65
to* Synthesis of 2— ethyl-3-methyldioxane
,66
5,
2-Ethyl-6-methyldioxane
a. o( -Chloroethyl- (9 '-chloroisopropyl
ether • • • • • * •
• • . . , . . • • 6 7
b.
cS,9 -Dibromoethyl-/? i-chloroisopropyl ether
. . . . . . . ............68
c.
^-Ethyl- p-bromoethyl • (9*-chloro­
isopropyl ether ........... , . . * . . 6 9
d.
Synthesis of 2-ethyl-6-methyldioxane. .69
4.
2-Propyl-6-methyIdioxone.
a,
o( - Propyl- P -bromoe thyl- (? £■-chloro­
isopropyl ether . . . . * . . . . . * . 7 0
h.
Synthesis of 2-propyl-6-methyldioxane .71
Glycolaldehyde Dimer,
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Preparation of glycolaldehyde dimer . . . .72
Glycol aldehyde dimer d i ' b r o m i d e ............73
Glycol aldehyde dimer di acetate
. . . . • .73
Dioxadiene
a. From, crystalline 2,3, 5, 6-tetrachlorodioxane
......... 74
b. From high boiling chlorinated liquid
dioxanes
......................... 75
2,5 - D i b r o m o d i o x a n e ............. ........... 76
Structure of 2,5-dibromod.ioxane............ 77
Identity of 2,5-dibromodioxane with
Fischer*s glycolaldehyde dimer bromide
. .77
Identity of 2,5-diacetoxydioxane with
Fischer*s glycolaldehyde dimer diacetate. .78
2,5-Dihydrofur an
79
Attempted synthesis of p-nitrophenylhydrazone of diglycolaldehyde
. . . . . . . .
.79
4 - P e n t e n e - l - o l .............................. 81
Dioxene
a.
At room temperature
................. 82
b.
At 140°C..........
83
c.
By means of a zinc r e a g e n t ...........84
5 -Hydroxy-3-oxapentanal p-nitrophenylhydrazone
...................
.35
Oxidation of 5-hydroxy-3-oxapentanal p-nitr ophenylhydr az o n e .................... 86
P
15.
16.
IV.
V.
VI.
Cblorination of Dioxane.
a. Isolation of 2,5-dich.lorodioxane . . .87
b. With. s u l f u r y l c h l o r i d e in the presence
................ 88
of peroxides.
(1) Excess sulfuryl chloride
(2) Excess dioxane
CEl or in at I on of 2, 5-Dichlorodioxane
a. Preparation of 2, 3, 5 ,6- tetr achlorodioxane
91
b* With sulfuryl chloride in the
.............. 91
presence of peroxides
.........................................................9 5
BIBLIOGRAPHY
VITA
INTRODUCTION
Although dioxane has heen known since 1863,'
It was
3 4
not until its commercial production in 1928 ' that it assumed
its present importance*
The work presented in this thesis
is a continuation of the study of the chemistry of dioxane
and related compounds carried out at Northwestern
6
6 f7
University.
The first published investigations from
8
this laboratory appeared in 1932.
The difficulty of obtaining pure diaIkyldioxanes of
known structure has prevented the continuation of the study
of the physical and chemical properties of these compounds*
The properties of the 2,3-dialkyldioxanes have indicated
some peculiarities in the behavior of these dioxane homologs.
However, not until the isomeric 2,5-dialkyldioxanes and
2,6-dialkyldioxanes have been synthesized and their properties
studied, can any valid generalizations be drawn concerning
the characteristic properties of the dioxanes*
Consequently,
a purpose of this investigation was to synthesize a series
of 2,6-dialky ldi oxanes and to study some of their physical
and chemical properties*
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
Lourenco, Ann. chim. phys., [3], 67, 288 (1863)
Wurtz, ibid., T3D, 323 (1863)
U* S. Patent, 1,681,861*
Chem. Abstr*, 22, 3893 (1928)
Schrader, Z* angew. Chem., 42, 541 (1929"T”
Bauer, Ph. D. Dissertation, Northwestern University (1936)
Umhoefer, Ph. D. Disseifetion, Northwestern University (1938)
Nelson, M. S. Dissertation, Northwestern University (1938)
Christ and Summerbell, J. Am. Chem* Soc*, 54, 3777 (1932)
Since the realization, during the last forty years,
that the simplest diose and trioses exist both in the
monomeric and dimeric states, many investigators have
attempted to explain the chemical structure of the dimeric
form*
Evidence accumulated that these dimers had a dioxane
_
nucleus#
Recent organic texts
9,10
go so far as to show the
structural formulae of the dimeric forms with a dioxane
nucleus as the skeleton structure*
Unfortunately, all such
evidence was based on physical chemical data and on chemical
reactions udiich indicated only the absence of the character­
istic groups of the monomer*
No direct evidence for the
assumed basic structure had ever been obtained*
Hence,
another purpose of these investigations was to prove or
disprove the assumption that diose and triose dimers were
substituted dioxanes*
The investigations were to be
conducted from a synthetic approach so that more definite
conclusions could be drawn*
(9) Vfhitmore, "Organic Chemistry", p. 398. D. Van Nostrand
Company, Inc*, New York (1937)
(10) Karrer,
Organic Chemistry”, p* 230*
Nordemann Pub*
Company, Inc., New York (1938)
-3-
I.
A*
HISTORICAL
Dialkyldioxanes
1*
Significance of Dioxane.
The increasing uses for dioxane In organic syntheses
and in chemical industry have provided the incentives for
the continued study of this compound and its homologs*
1,4-Dioxane is a heterocyclic ether having the chemical
structure (I)*
0
H sCe
t
Kj3^ 6
S CHS
I
s CH<3
I
Because of Its unusual solvent properties of fats,
11 , 133
13
rubber, plastics, cellulose esters, dyes, and salts,
dioxane is used extensively in industry and is available
n o w in large quantities*
(11)
(12)
(13)
It has also become quite useful
British Pat., 245,098, Chem* Abstr., 2 1 , 292 (1927)
Davison, Ind* Eng* Chem., 18, 669 (1926)
Meyer and Punkel, Z* physik. Chem., BodensteinFestband, 553— 73 (1931)% Chem* Abstr*, 2 5 , 5332 (1931)
-4-
in the laboratory* where it finds application in molecular
14,16,16
weight determinations,
in the study of Grignard
17
reagents,
_
and in the preparation of water solutions of
IS , 19
known dielectric constants*
The fact that dioxane has a
zero moment permits the preparation of dioxane-w&ter
solutions having a large range of dielectric constants*
Although oxygen almost invariably behaves as a bivalent
atom, in dioxane it sometimes exhibits the properties of a
tri- and a quadricovalent atom*
This is evidenced by its
1 7 , 2o"3(
unusual ability to form definite oxonium addition compounds.
The dioxane-sulfur trioxide addition product has been found
to be an excellent sulfonating and sulfating reagent for
30
various compounds when used in anhydrous media.
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
(28)
(29)
(30)
Oxford, Biochem. J., 28
1325 (1934)
Anshutz and Broeker, B e r * , 59, 2844 (1926)
Kraus and Fingee, J* Am. Chem* Soc*, 56_, 511 (1934)
Schlenk and Schlenk, Ber., 62, 920 (1929)
Schwingel and Greene, J. Am. Chem. Soc*, 56, 653 (1934)
Williams, ibid., 52, 1831, 1838 (1930)
Faworsky, Chem. Zentr., (I) 15, (1907)
Paterno and Spallio, Chem. Abstr., 2 , 1123 (1908)
Kehrmann and Falke, Helv. Chim. Acta., 7 992 (1924)
Rheinboldt and Boy, J. prakt. Chem., (2*7, 129, 268 (1931)
Van Alphen, Rec. trav. chim., 49, 1041 (1930)
Evans and Dehn, J. Am. Chem. Soc., 5 2 , 3204 (1930)
Hepworth, J. Chem. Soc., 1 1 9 , 1252 T^931)
Bergmann and Suchardt, Ann., 4 8 7 , 229 (1931)
Muller, Ber., 65
1051 (1932)
Doak, J. Am. Pharm. Soc., 23, 541 (1934); Chem* Abstr.,
29 2539 (1935)
Suter, Evans and Kiefer, J. Am. Chem. Soc., BO, 538 (1938)
-5 -
2*
Synthesis of dioxane and some of its homologs*
p-Dioxane is now manufactured commercially in a con­
tinuous process by boiling glycol in the presence of such
etherification catalysts as zinc chloride, phosphoric acid,
benzenesulphbnidc acid, or sulfuric acid.
The glycol is
added to the mixture at a rate corresponding to that at
31
which the dioxane distills*
Other glycols may be sub32
stituted, but mixtures of products result from the reaction.
34
35
36
By using propylene glycol, Levene and Walti
obtained
mixtures of 2,5— and 2,6-dimethyldioxane (II) and (III)*
This method has its limitations for the preparation of pure
dioxane homologs*
The reaction tends to produce cyclic
acetals (IV) and by-products of the type CHS *CH(OH)•CH2 *0 ‘
CH2 -CH(CH3 )•0-CH s3-CH(0H)*CHs .
O
/ \
H EC
CHCHa
I I
CHa *HC
CHa
\ /
\ /
(IX)
(III)
O
(31)
(32)
(33)
(34)
(35)
(36)
,0
/ \
CH3 -HC CH*CH3
I I
H 2C CHa
^ 0 — CHS
CH3— CH
|
^ o — ch3
0
(IV)
U* S* Patent*, 1,681,861, Chem* Abstr*, 22
3893 (1928)
German Pat., 500,223, ibid., 24
4307 (1930)
U. S. Patent, 1,939,189, ibid*, 28, 1366 (1934)
German Pat., 516,844, ibid., 2J3, 1841 (1931)
British Pat*, 318,758, Chem* Zentr. , (I), 2012 (1930)
Levene and Walti, J. Biol. Chem., 7_5, 325 (1927)
33 ,
-6 -
37
Tellegen also obtained a mixture of the 2,5- and 2,6dimethyldioxanes by heating propylene glycol with four
percent sulfuric acid.
Dioxane and its alkyl derivatives
have also been prepared by catalytic treatment of ethylene
3 6 36 3 9
and propylene oxides. ' 9
Dioxane may again result from
the polymerization of formaldehyde*
40
dioxane arises from acetaldehyde*
Similarly, dimethyl-
As is evident, few of these methods have been applicable
to the preparation of pure higher substituted dioxane
derivatives*
A step in that direction was taken when
Suramerbell, Christ, and Bauer prepared the 2,3-diaryldioxanes
in excellent yields by the action of aryl Grignard reagents
41,4S ^48
on 2,3-dichlorodioxane*
The same reaction has been
44
employed to synthesize 2,3-dialkyldioxanes but in low yields.
Higher yields may be obtained through the substitution
of alkyl zinc or alkyl cadmium compounds for the Grignard
reagent.
The low yields in the Grignard reaction are due
to the formation of p-dioxene (V) as the major product*
(37)
(38)
(39)
(40)
(41)
(42)
(43)
(44)
Tellegen, **Dioxan en Derivaten”, p* 26, Technical
University, Delft, Holland (1934)
German Pat., 597,496, Chem. Abstr*, 28, 5080 (1934)
German Pat*, 598,952, ibid*, 28, 6446 (1934)
French Pat*, 772,154, Chem* Abstr*, 2 9 , 1440 (1935)
Christ and Summerbell, J. Am* Chem. Soc., 55, 4547 (1933)
Christ and Summerbell, ibid., 54, 3777 (1932)
Summerbell and Bauer, ibid, 5 7 , 2364 (1935)
Summerbell and Bauer, ibid*, 58, 759 (1936)
0
'
o
\
H aC
„ L
H aC
N
/
CHG1
CHC1
HSC
\
CH
|f + MgBra + MgCla
CH
/
+ C aH s + C aH4
I
+ 2CaH 5MgBr
---------- *
HaC
\
S
o
0
(V)
Using an analogous method, both the monoaryl and mono^ «3-
alkyl dioxanes have been synthesised from monochlorodioxane * *
The yields in the latter syntheses are lowered due to the fact
that side reactions take place.
One of the by-products
isolated in the alkylation reaction was a 2-alkyl-3~dioxanyl~
dioxane(VI).
A probable mechanism for such formation is
4s
shown by the equation.
CH£“ CHC1
•
»
0
0
I f
CHa- C H a
CH— CH
*
*
ZnCla)
+ 0
0
I I
C H s- C H q
C H a—
I
0
I
CHa—
CHa- CH — CH — CHC1
I I
j
I
o
o
o
o
I
I
I
1
CH a— C H S CHa — CIia
C H — C H — CH —
I
I
I
0
0
0
I
I
I
CHa
CH a
RZnCl^
R
(V I )
Further discussion of methods of preparing substituted
dioxanes Is deferred until later.
When ft -chloroethyl ether is heated at 200°C. with 5%
46
sodium hydroxide, dioxane is one of the products.
This
reaction led to the synthesis of ethyldioxane in an analagous
45
manner.
Light metals such as sodium and copper have also
(45)
Summerbell and Umhoefer,
ibid, 61, 3016 (1939)
(46)
French Pat., 711,596, Chem. Abstr.,
26, 1947 (1932)
-8 -
been employed in the synthesis or dioxane and its homologs
from @ -halogenated dialkyl ethers#
3*
4 *7
Preparation of alpha- and beta-halogen
The direct action of chlorine on alkyl ethers nearly
always results in the formation of an alpha-chloroether or
a mixture of di-alpha-chloroethers#
The synthesis of
dichlorodioxane presents an unusual case since it may be
B0
considered both an alpha-, and a beta-chloroether*
Mono­
chlorodioxane, indirectly synthesized b y the addition of h y ­
drogen chloride to dioxene, may also be looked upon as both
an alpha-, and a beta-chloroether*
Further chlorination
of the alpha-chloroethers results in the formation of
mixtures of highly halogenated ethers, both in the alpha
63.
and beta positions*
With but few exceptions, pure halogenated ethers have
b e e n synthesized indirectly without the aid of direct halogenation*
A method of preparing alpha-chloroethers was
52
first described by Wurtz and Frapoli
and later improved
53
64
by Henry and Gauthier*
(47)
(48)
(49)
(50)
(51)
(52)
(53)
(54)
Similar experiments were later
British Pat*, 435,110, Chem* Abstr®, 30, 1387 (1936)
Friedel, Compt* rend., 84, 247 (1877)
Fritsche and Schumacher, Ann*, 279, 301 (1894)
Boeseken, Tellegen, and Henriquez, Hec* trav. chim*,
50, 909 (1931)
Oddo and Cusmano, Gazz® chim* ital*, 4 1 , II, 224,
Chem* Abstr*, jS, 229 (1912)
Wurtz and Frapoli, Ann*, 1 0 8 , 226 (1858)
Henry, Bull* soc* chim*, (2) 44, 458 (1885)
Gauthier, Aron* chim. phys* (8"? 16, 311 (1909)
-986
^5 6 ,5 7 ,5 8 , 5 9
conducted in other laboratories#
60
Stappers,
in 1905, was the first to use substituted alcohols in
this type of condensation and succeeded in condensing
.
33
formaldehyde with propylene chlorohydrin*
Later,
^ - d i c h l o r o e t h y l ether was synthesized from paraldehyde
and ethylene chlorohydrin#
Since then, many investigators
63-6 6
have effected analogous condensations#
,7 . 4 5
The remarkable difference in the reactivity of the
halogen atom when in an alpha or beta position of an
aliphatic ether led Boord to synthesize a series of
ft
67,68
-bromoethers •
He noted that a Grignard reagent
will only substitute the alpha halogen in an
ether#
@ -dihalogen
This method of synthesis was actually an adaptation
67
of the method of Houben and Fuhrer.
(55)
(56)
(57)
(58)
(59)
(60)
(61)
(62)
(63)
(64)
(65)
(66)
(67)
Beta-halogenated ethers
Wedekind, Ber., 36, 1383 (1903)
Clark, Cox, and Mark, J# Am. Chem. Soc#,39, 712 (1917)
Boord and Swallen, ibid., 5 2 , 651 (1930)
Boord and Soday, ibid., 55, 3297 (1933)
Henze and Murchison, ibid., 5 3 , 4077 (1931)
Stappers, Hec. trav. chim., 24, 256 (1905)
Grignard and Purdy, Bull. soc. chim., 31, 982 (1922)
Farren, Fife, Clark, and Garland, J. Am.. Chem. Soc., 4 7 ,
2412 (1925)
Allen and Henze, ibid., _59, 540 (1937)
Speer and Henze, ibid., 63., 1226 (1939)
Lingo and Henze, ibid., 61, 1574 (1939)
Blanchard, Bull. soc. chim., 39,1119 (1926)
Houben and Fuhrer, Ber., 40, 4993 (1907)
10-
may also "be prepared b y the dehydration of* halogenated
60 0 0 q
alcohols#
* 9
An unusual means for making f f -halogenated
71
ethers was recently reported by some Russian investigators#
By condensing ethylene glycol or ethylene chlorohydrin
with butenes in the presence of benzenesulf onanide dichloride,
they succeeded in preparing P , {3 f-dichloro- and
(3 -chloro-/? -hydroxyethers#
B#
Glycolaldehyde Dimer
1#
Synthesis of Glycolaldehyde
Qlycolaldehyde is the simplest and most interesting
of the monohydroxy aldehydes and may be also regarded as
the simplest aldose#
The formation of carbohydrates in
plants possibly takes place through glycolaldehyde as an
intermediate.
The compound was first synthesized by
753
Fischer
through the action of barium hydroxide on
bromoacetaldehyde.
In the same year, Marckwald and
Ellinger prepared it by the hydrolysis of glycol acetal with
dilute acids.
73
The yields were extremely low in both
cases, while the starting materials were not easily available#
74,75
Finally, Fenton
obtained sizeable amounts of the
aldehyde through the mild oxidation of tartaric acid (VII)
(68)
(69)
(70)
(71)
(72)
(73)
(74)
(75)
Karam and Waldo, J# Am. Chem. Soc., 43, 2223 (1921)
Can. Pat., 359,236, Chem. Abstr., 30, 6011 (1936)
Fr. Pat., 773,140, Chem. Abstr., 29, 1432 (1935)
Likhosherstov, Zhabotinskaya, Pavlovskaya, and Ponomarenko,
J. Gen. Chem* (U.S.S.R.), 8, 997 (1938), Chem. Abstr.
33, 3761 (1939)
Fischer and Landsteiner, Ber., 85, 2549 (1892)
Marckwald and Ellinger, ibid, 25, 2984 (1892)
Fenton, J. Chem. Soc., 67, 780 (*1895)
Fenton, and Jackson, ibTd, 75, 575 (1899)
-11-
and subsequent decarboxylation of the resulting dihydroxymaleic acid (VIII)•
COOH
COOH
*
*
CHOH
H 20 s
COH
It
COH
>
I
CHOH
PeS04
$
i
GOOH
COOH
(VII)
(VIII)
Other
-2C0S
*
CHgOH - CHO
50°
methods for the synthesis of glycolaldehyde depend
on the oxidation of an ethylene bond adjacent to an ether
76
oxygen*
Milas
oxidized divinyl ether, vinyl bromide,
and vinyl acetate with a hydrogen peroxide reagent in
the presence of osmic oxide catalyst*
Yields were reported
as high as 96% based on the weight of glyoxal osazone
77
isolated*
Hurd and Pilachione
reported the aldehyde to
result from the oxonolysis of allyl acetate*
It m a y also
be obtained through the ozonalysis of allyl alcohol and
cinnamyl alcohol*
Another.*:synthesis has been accomplished
by the condensation of formaldehyde through the use of
78
calcium hydroxide*
2*
Structure of Glycolaldehyde Dimer
75
It was Fenton
who first showed that glycolaldehyde
existed both in the monomeric and in the dimeric states*
Since then,
several other investigators have demonstrated
the existence of the two forms by various methods*79*80
(76)
(77)
(78)
'79)
[80)
Milas, Sussman, and Mason, J* Am* Chem. Soc* 61, 1844 (1939)
Hurd and Pilachione, ibid*, 6 1 , 1156 (1939)
Kuzin, J* Gen* Chem* (U.S. S.RT7 8, 592 (1938) Chem* Abstr*,
33, 1271 (1939)
McClelland., J* Chem* Soc*, 99, 1827 (1911)
Wohl and Neuberg, Ber*, 33,^5099 (1900)
-1 2 -
This phenomenon however is not limited to glycolaldehyde
but has been found to exist in its derivatives as well.
Thus, the ethyl and methyl glycoside, acetate, thioacetate,
8 2, SJ3, 83 ,Q4z
and bromide, are found as dimers,
Similar obser­
vations have been made in the cases of acetol,
acetoin,
dihydroxyacetone, glyceraldehyde, methyl glyoxal,
and
85,86,87,88
certain .of their derivatives.
The suggested structures for the dimers are numerous
and have varied with the extending knowledge of the chemical
and physical behavior of these substances.
The first attempt
to attack the structural problem of these dimers was made
8©
by Emil Fischer
in 1895.
For the dimer of benzoylcarJbinol.
methy1 acetal, he proposed a dioxane structure
2,5-diphenyl-2,5-dimethoxydioxane.
(IX), or
The next fifteen years
saw no change in the commonly accepted structures for the
dimeric compounds.
dihydroxyacetone
dimeric
Dimeric glycolaldehyde
(X), dimeric
(XI), dimeric glyceraldehyde(XII), and
acetol methylacetal (XIII), were all considered
8 o ,86
to be derivatives of dioxane.
(81)
(82)
(83)
(84)
(85)
(86)
(87)
(88)
(89)
7©
In 1911, McClelland,
Gehrke and Kohler, Ber., 64-B, 2700 (1931)
Bergmann and Miekely, ibid, 54-B, 2150 (1921)
Fischer and Taube, ibid,, 60-B, 1704 (1927)
Bergmann and Ludewig, Ann., 4 3 6 , 173 (1924)
Bertrand, Compt. rend*, 129, 341 (1899)
Nef, Ann., 3 5 5 , 257 (190<T}
Fischer and Llildbrand, Ber., 57-B, 707 (1924)
Fischer and Taube, Ibid., 59-E, 857 (1926)
Fischer, E., Ber*, 28, 1161 (1895)
-15-
not satisfied with the suggestions that these substances
v\rere new definite chemical compounds,
off erred a four-atom
unstable heterocyclic ring as a possible structure
0
/ \
H ®G
s*
G ^ OCH,
0 -P
C H o0 v
/
0
• 0
/
\
H SC
I
HOHG
\
0
/
(X)
0
/ \
0
/ \ /0HS
H SG~
Gs
CH3 I
■ OCH,
SxC
CH,s
/ \
/
C H 3o x 0
HOGH2-HG
I
HOHG
\
CHOH
I
CH-CHjaOH
0
/
(XII)
0
/ \ /OH
H SG
CxcHgOH
HO |
I
CHHOGH« \ /
0
CHOH
I
CHS
(IX)
(xIV),
(XI)
0
/
\
N
/
HOCH q -HC
(XIV)
(XIII)
for glycolaldehyde dimer.
0
CH-CH b 0H
The uncertainty of investigators
in this field as to the structure of these substances is
8<4
emphasized by the work of Bergmann
9o
91
and Fischer
.
Dimeric acetoin (XV) and the dimer of methylacetal of acetoin
(XVI) were considered to be highly associated compounds.
Although all derivatives of glycolaldehyde synthesized by
Fischer were dimeric, he made no attempt to explain their
structures.
Glycolaldehyde, its acetate, bromide,
glycoside were indicated by (XVII),
respectively,
(90)
(91)
(XVIII),
(XIX),
and called dimeric.
Bergmann and Miekely, Ber., 62-B, 2297 (1929)
Fischer, PI.O.L., ibid., 60-B, 1704 (1927)
and ethyl
(XX),
-14-
GH3
I
GHe — C — 0
1^0
C H S -C'
H
GH
I
--0— G — C H a
° o
G — GHS
H
OCKa
/
CHa— C
I
c h 3— c
H
or
0-
0
OCH;
I
G ■CH.
I
C — 'CHS
E
(XVI)
2CHS - GH - C - CH
»
H
OH
0
2 C H S - GH - G - GH;
\
/ ^
0
OH
OH
0
GH
HC
GH
(XV)
/JHOH
0 I
VC H S
(XVII)
.GHOAc
° x 'C H S
(XVIII)
/CHBr
0 I
v CHa
0.
(XIX)
CHOEt
I
GH a
(XX)
The reversion to the dioxane nucleus for these struc9o
tures v/as heralded by Bergmann in 1929
, in his study of
the methylketal of acetol which he indicated as being
2,5-dimethyl-2,5-dimethoxydioxane
(XXI).
Pyrolysis of this
compound at 140°C» and 3 mm. yielded a substance whose
structure was uncertain.(XXII).
A double bond was Indicated
93
by its ability to add bromine.
Two years later,
he com­
pletely abandoned all structures for the dimers but that
(92)
Bergmann and Miekely, Ber., 64-B , 803 (1931)
-15-
of a dioxane nucleus, when he reported the synthesis of1
2,5-dimethoxydioxane
(XXIII) from the pyrolysis of the
methylacetal of glycolaldehyde
0
/ \ ^
HaC
CHa
G ^ OCHs
CHS|
I
CHS
/
C H 30 \
0
(XXIV).
0
/ \
CHa
-CHaOH H aC
3
r\ tt |
i
I
~ ~—
z — > cn3
IfI
^ p
CH
C H sO \ /
0
or
E C —
C-CH
I
I
r\
r0
0
\
^
C H
I
CHS 0 - C -
CH.
(XXI)
or
HC^C-CH,LS
I
*
0 0
V C — CHS
(XXII)
I
C H S— OCHs
OCHs
/
2 CHoOH - CH
y
-2CHS0H
-- ^
^
H aG CHOCHs
OCH s
(XXIV)
0
GHs OHC CHg
\/
0
(XXIII)
No evidence has been presented since then which permits one
to question the commonly accepted thesis that these dimeric
compounds are dioxane derivatives.
But on the other hand,
no one has demonstrated that these compounds can be synthe­
sized using a dioxane nucleus as the starting material*
»3L6«
II*
A*
Discussion
Di alkyldiox ane s .
1*
Synthesi s of 2, 5-di alkyldioxanes .
Unusually small yields of 2,3~dialkyldioxanes had been
obtained by Summerbell and Bauer
through the action of
alkylmagneslum halides on 2,3-dichlorodioxane.
Subsequent
Investigations enabled them to Improve the yields by using
alkyl cadmium or alkyl zinc reagents in place of the
G-rignard reagents*
Their method of synthesis, however,
precluded the possibility of obtaining any unsymrnetrieal
2,3-di alkyldioxanes.
this clear*
A glance
The action of any alkyl metallic compounds on the
0
/ \
0
/ \
H SC
H aC
GHG1
+ 2RT5X
H SC
CHC1
\ /
0
at the reaction will make
—»
CHR
|
H aG
\
|
0
+ IJXg + ItCls
CHR
/
dichlorodloxane would immediately substitute the same
alkyl groups In positions 2 and 3 on the dioxane nucleus.
It is impossible with this method to make them different.
The synthesis of a 2,3-unsymmetrie ally substituted dioxane
offered an interesting problem In the study of the physical
and chemical properties of this series.
Examination of the structural formulae of polysubstituted
dioxanes will Immediately reveal the possibility of both
optical and cis-trans isomerism.
Ilonosubstituted dioxanes
should exhibit optical isomerism only*
0
0
/ \3£
HjgG HG R
I
H SG RG H
\ y
0
/
H aG
»
H SC
\
0
HG R
»
GHS
/
0
/ \ X
E aC HG-R
I
*x
H sC H G-R
\ s
0
trans.
cis,
In the above case only the trans form should demonstrate
optical isomerism*
The existence of two isomeric 2*3-
dimethyldioxanes was the first evidence in that direction*
although both isomers had been prepared in the same way from
2*3-dichlorodioxane*
Isomerism could not be demonstrated
in the cases of the other members of this series.
It was
hoped that the other isomers could be prepared by some
other synthetic method*
The obvious method had already been used for the
46
46
/->
preparation of dioxane
and ethyldioxane.
A /o ,(?*-*
dihalogen ether was converted Into the cyclic ether by
treatment with five to ten percent sodium hydroxide at
200°.
The use of a substituted Q , f? i-dihalogen ether
should obviously result In the formation of the correspond­
ingly substituted dioxane.
This method of synthesis has been successfully applied
in preparing 2*3-diethyldioxane and 2-ethy1-3-methyldioxane
from
*<-e thyl— /?-br omobutyl- (3 *-chloroe thyl ether and
c^ -me thy l-^ - b r o m o b u t y l - Q i -chloroethyl ether* respectively.
(X) Designates an asymmetric carbon atom
These ethers were prepared Toy modifying Boordt s synthesis
67
of unsaturated hydrocarbons.
A mixture of equivalent
amounts of butyraldehyde and ethylene chlorohydrin was
treated with dry hydrogen chloride at 0°.
The product
was ©^-chlorobutyl- (3 *-chloroethyl ether.
CHgGl
i
I
CHa
1
OH
*_
+
CHg—C
gH e
.
1
+
tt/^
n
HC1
CH
n
0
O
0°
*
Cl
CH.,
^
I
CIIS
^
PH —P
H
S
S— &
1 “
8
+ hoh
CHC1
0^
By treating alphachloro-ethers with bromine at 0°,
betabromo-ether results.
an alpha
In this way, bromination of
chlorobutyl“ |J '-chloroethyl ether yielded U > (2 -dibromobutyl
(5 T-chloroethyl ether.
Cl
1
CHS
C H S- C SH 5
*
*
CHg
GHC1
^
+
Bre— >
Cl
I
I
CHj3
Br
CH
\
\
GHg
0 x
-C s H 5
CHBr
^
+ HC1
0 ^
There was the chance that the reaction may not have pro­
ceeded in the usual manner.
Analysis for total halogen
in the bromination product indicated that it was
dibromobutyl-
<?(,
f-chloroethyl ether.
Of the three halogen atoms in the above molecule,
the bromine atom in the alpha position to the oxygen is
much more active than the other two.
Consequently, when
•«19w
the compound is treated with a G-rignard reagent the reaction
should involve the alpha "bromine atom exclusively.
In this
manner the action of methylmagnesium bromide on the alphabromoether produced
Similarly,
e^-methyl- ^-bromobutyl-
— chloroethyl ether.
the action of ethylmagnesium "bromide yleld_ed ®^~ethyl*
/S>-bromobutyl~ (3 1-chloroethyl ether.
Cl
1
CHS
1
CHe
\
Br
1
CH-C s H 5
1
CHBr
+
C H sMgBr — ^
/
Cl
I
CHa
1
CIi8
X
0
Br
I
CH-C s H 5
Cl
1
CHS
1
GHa
+
1
C sH 5MgBr
CHBr
Br
1
c h -c s h
\
5
+
CH-CHa
0
S'
Cl
1
CHS
1
CH*
Br
1
CH — C s H 5
I
CH-C s H 5
+ MgBr q
/
0
0
Yields in the foregoing reactions were good.
It has been
recommended that corresponding steps in similar syntheses
are preferably carried out without the purification of the
93
intermediate products.
By heating the
o^-ethyl- j^-br omobutyl-'(3 '-chloroethyl
ether with ten percent potassium hydroxide at 200° for
three hours,
there was obtained a fifteen percent yield
(93)
J. Am. Chem. Soc., 52, 3399
Boord,
(1930)
-20-
of 2,3-diethyldioxane.
When the
^-methyl-^-toromobutyl •
Q i-chloroethyl ether was refluxed for forty-two hours
Cl
I
CHo
I
CHS
^
Br
0
I
C H - C 3H 5
I
C H - C bH 6
+ 2K0H
/ '
H aC
CH-CaH s
— > I I
*
H aC
CH-CaH 5
o
+
KC1 + KBr + HOH
o
with an approximately five percent solution of potassium
hydroxide,
a six and one-half percent yield of 2-ethyl-3-
methyldioxane was obtained.
Cl
I
CHo
J
CHa
Br
I
CH-CaH B
|
CH-GHS
0
/'
+ 2K0H — > H aC CH-CaH 5
| |
H aC CH-CHS
0
+ KC1 + KBr + HOH
0
Evidently, heating at 200° with a ten percent alkali
solution tends to increase the yield of the dioxane.
Obvious competing reactions with that of cyclization are
those of complete hydrolysis and olefin formation..
possible result is the splitting of the ether bond.
Another
Any
one of the above reactions may be equally prooable under
the conditions tried.
Examination of the structure of the
ft' —dihalogen ether will reveal a primary chlorine atom,
a secondary bromine atom,
a primary ether bond,
and a
secondary ether bond.
The rate of formation of the dioxane will depend on
the rate of hydrolysis of either the chlorine atom,
the
ni
^X-
bromine atom, or both..
glycol,
Should both hydrolyze to form the
the only way in which the dioxane may be formed
would be by the removal of a molecule of water.
01
I
CH0
Br
I
CH — C sH 5
I
CH-CHe
t
CHa
\
OH
I
I
CHa
0
+ 2K0H — >
OH
C H — C eH 5
I
0H-CH s
\
CHa
x
/
0
-HOH
^
/
0
/
\
H SC
I
CH-CaH 5
h sg
c h -c h 3
t
0
This tendency should be minimized since the alkali solution
is quite dilute.
As a secondary bromine atom can be more
easily hydrolyzed than a primary chlorine atom, the
probability is that the dioxanes are formed mainly through
the removal of a molecule of hydrogen chloride from the
intermediate
-hydroxy- ($ »-chioro-ether.
0
Cl
I
CHa
Br
I
CH - C aH 5
I
I
CHa
X
GH-CH3
o
/
Cl
OH
I
CH - C aH 5
I
CH-CHS
I
CHa
K0Hv
*
I
CHa
\
o
/
S
H aC
/
K 0 H t H SC
*
\
/
The f ormation of a double bond' by the removal of a
halogen scad. molecule is quite probable in as much as the
CH-CaH 5
\
CH-CHa
/
0
-22
compounds contain adjacent secondary bromine and hydrogen
atoms.
The dilute alkali solution would not be the most
favorable factor for such formation*.
Yet,
the low yields
of the cyclisized ethers may be partially accounted for by
such side reactions.
Cl
Br
I
Cl
I
I
CHQ
CH — C s H 5
|
CH-CHa
f
C.Ha
\
0
OH
/
I
CHs
KOH„ I
-HBr C H s
X
CH-C 8Ii5
I*
C-CHa
0
/
KOH*
CHs
C H- C aH 5
I
II
CHS
C-CHS
\
0
X
When one considers all possible reactions which may
occur under the conditions of cyclization,
of the dioxanes are not too- surprising.
the low yields
Evidence for the
course of the other reactions might be found by an examination
of the other products of the reaction.
Since the yields of
the intermediates in this synthesis of the dioxanes are
reasonably good, determination of the proper conditions
for the last step would result in an excellent method for
such syntheses.
2.
Synthesis of 2,6-dialkyldioxanes
A knowledge of the physical properties of an organic
compound is of great service in the characterization of that
substance.
In any homologous series these physical properties
generally undergo a uniform change as the molecular weight
-23-
increases.
The monoalkyIdioxanes and the 2,3-dialkyldioxanes
have proved no exceptions in such considerations.
plete the story of the dialkylated dioxanes,
To com­
it was neces­
sary to prepare the isomeric 2,6- and 2,5-dialkyldioxanes•
It would then he an easy matter to predict the simple
physical properties of any unknown members of these
homologous series.
An obvious method of synthesis of the 2,6— and 2,5—
alkyldioxanes was again the use of the correctly substituted
(3 , (3t-dihalogen
ether.
The preparation of the
2 ,5-dialkyldiox­
anes was abandoned when the preparation of pure 2-chloropropanol-1 met with little success.
This known substance was
essential to the synthesis of the necessary alphachloroether, but it could not be prepared free of Its Isomer,
l-chloropropanol-2.
There appeared to be two possible methods for
obtaining the
-dihalogen ether necessary for the
synthesis of the
2 , 6-di alkyldioxanes
^
An
ct'- ft, P '-
tetr abromoethyl ether may be prepared by the direct
9 4i
bromination of vinyl ether.
Taking advantage of the
greater reactivity of the alpha bromine atoms,
dialkyl-
9,
an
o(,
-dibromoether may be prepared by the action
of an alkylmagnesium halide on the tetrabromoethyl ether.
(94)
Major and Ruigh,
J. Am. Chem. Soc.,
53_, 3133 (1931)
24-
This method was abandoned when experiments by Nelson
showed that the yie3.ds of* the
7
9 (3*—dihalogen e ther* were
very low*
These halogenated ethers were finally prepared in good
yields through the same series of reactions previously
outlined for the synthesis of the 2,3-dialkyIdioxanes.
In this way,
2— ethyl-3—me thyldioxane and 2—propyl— 3—methyl-
dioxane have been prepared f rom o^-ethyl- (3 -bromoethyl- /? =chloroisopropyl ether and
^-propyl-^--bromoethyl- (3 —
chloroisopropyl ether respectively,
The
•C-chloroethyl- (?•~
chloroisopropyl ether was prepared in the usual manner from
paraldehyde and propylene chlorohydrin
(l-chloropropanol-2)„
Bromination of the product at G°C. yielded
Q n-chloroisopropyl ether.
o(9 /9-dibromoethyl-
The action of propylmagnesium
chloride and e thylmagneslum bromide on the
d» (9-dibromoethyl-
J-chloroisopropyl ether resulted in the formation of the
necessary
9 , 9 \-dihalogen
By heating the
ethers*
c^-propyl- /9-bromoethyl- @-i-chloroisopropyl
ether with ten percent potassium hydroxide for three and onehalf hours at 200° there was obtained an 3.3 percent yield
of 2-propyl-6-methyldloxane»
The same treatment of
«^-ethyl-
(?.-brornoethyl- ft *-chloroisopropyl ether at 230° for six and
one-half hours resulted in a 19.6 percent yield of 2-ethyl-6-
me thyldioxane •
The same factors are involved in these
syntheses that have been discussed in connection with the
synthesis of 2,3-diethyldioxane and 2-ethyl-3-methyldioxane.
In addition to varying the conditions of cyclization,
the
use of silver oxide instead of potassium hydroxide might
increase the yield.
Although the low yields of the dioxanes are discouraging,,
inspection of other possible methods of synthesis leave much
to be desired.
As has been emphasized previously, no other
method offered the advantage of the preparation of a pure
alkylated dioxane with a known structure.
Of course,
use of chlorinated dioxanes is an exception.
the
But synthesis
by this method is limited to the preparation of symmetrically
substituted dioxanes.
The action of RMJC on 2,3-, 2,5-,
and
2,6- dlchloro or dibromodioxane will result In the formation
of 2,3-,
2,5-,
and 2,6- symmetrically substituted dioxanes.
The usefulness of the cyclization method for preparing
various dioxane homologs is obvious.
By varying the starting
substances and the Grignard reagent used,
it becomes apparent
that this is a very general method, for the synthesis of many
substitilted dioxanes.
-26-
3.
Properties of Alkyldiox anes •
Table I
2 36-Dialkyld ioxanes
so
alkyl groups
d
b.p.
(°C, , ram.
So
d^
nD
)
a
C ale
3VI«R .
"j
,
F oun d
123.5-124/743
.941
1.4191
30.98
30.77
etliyl rn.eth.yl
144.5 / 747
.923
1.4241
35.62
35.79
propyl methyl
165 / 750
.915
1.4284
40,23
40.57
dime thyl
Table II
■
2 , 3-Dialkyldioxanes
b.p.
(°C , ,mm.)
e thyl me thy1
diethyl
nD
127.7-129/751
.958
1.4237
30.95
130.2-132.7/751
.965
1.4259
30.98
150-151/746
.940
1.4305
35*62
35.74
166-167.5/746
.941
1.4351
40.23
40.01
166•5— 168•5/739
.938
1.4342
40.23
40.05
.927
1.4414
49.40
49.08
.916
1.4465
58 .60
58.32
.963
1.4650
48.61
48.26
c
diethyl
c
di-n-propyl
Found
d4
c
dime thyl
a M.R.
G ale.
CO
•
o
to
alkyl groups
So
w
o
•
CD
0>
SO
87/12
202-205/744
c
di-n-butyl
129-130/22
238-240/744
diallylc
90.2-90.7 /16
-27-
Table III
e
Mon o alkyId i ox ane s
3o
b.p.
<3-4
nD
(° C .,mm)
alkyl groups
Calc .
0
Pound
me thyl
109-110/746.5
.977
1.4186
26.38
26.39
ethyl
132.5-133/750
.955
1.4263
30.99
31.17.
n-propyl
155.6-157.1/746 .943
1.4298
35.61
35 .64
n-butyl
178-179/735
.932
1.4336
40.23
40.26
allyl
156-158/747.6
.937
1.4442
35.14
36.35
The physical properties of the three known homologous
series of alkyldioxanes are listed in Tables I, II, and III*
As In the oases of the monoalkyldioxanes and the 2,3-dialky 1dioxanes,
the properties of the members of the 2, 6—di alkyldiox-
anes are closely related.
Is quite uniform.
The difference In boiling points
The addition of a CHa group Increases the
boiling point approximately 20 degrees.
The density of these
dialkyldioxanes decrease with increase in molecular weight
while the refractive index shows a nearly uniform increase
as the alkyl groups become larger.
(a)
(b)
(c)
(d)
(e)
The calculated values were obtained by using the atomic
values from Gilman, Organic Chemistry, p. 1738.
The found values were calculated from the formula of
Lorenz and Lorentz, given on the same page.
So
Bauer, ref. 5. Density as d§° recalculated for d4 .
Nelson, ref. 7.
Umhoefer, ref. 6.
-28-
W l t h the synthesis of this third series of alkyldiox anes
accomplished and some of the physical properties of its members
determined,
a much broader concept of the relationships
between dioxane homologs may be attempted.
it becomes of
interest then to ascertain whether any clear connection can
be seen between the state of alkyl substitution on the one
hand and such permanent physical properties as refractive
index and density on the other.
Inspection of the data in Table IV will reveal many
interesting relationships.
It has been so compiled that
the differences in the properties of isomeric alkyldioxanes
may be visualized more clearly.
Monoalkyldioxanes have
higher boiling points than dialkyldioxanes of the same
molecular weight.
There seem to be no appreciable changes
in the refractive Indices or densities between the monoalkyl­
dioxanes and the 2,3-dialkyldioxanes.
It is to be noted
also that the 2,6-dialkyldioxanes as compared to the other
isomeric dioxanes of the same molecular weight exhibit
definite decreases In all three properties.
boiling points,
lower densities,
They have lower
and lower refractive Indices.
The regular differences In boiling point as we Increase
the number of alkyl groups serves as another Indication
that the boiling point of dioxane is higher than one would
ordinarily expect.
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-31-
of a hydrated molecule
11
s
(XXV) accounts for the
miscibxlity
of dioxane in water in all proportions,
CHa —
h
:o ;h :o :
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CHa
:o :h :o :h
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ghs
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(H:o:i-i)n
(XXV)
Unlike dioxane, dioxene and dioxadiene are quite insoluble
in water at room temperature.
The introduction of double
bonds into the molecule seems to change the properties of the
oxygen atoms so that hydrogen bonds are no longer important.
It may be argued that the introduction of double bonds
tends toward the formation of a conjugated system with
the oxygen atoms.
The unpaired electrons of the oxygen
atom may then be considered as taking part in the resonating
structures of dioxene and dioxadiene.
Consequently,
there
would be little opportunity for these resonating electrons
to act as donors to the hydrogen atoms of a water molecule.
The result- would obviously be a tendency toward decreased
water solubility.
The Insolubility of dioxene and dioxadiene
Is partial evidence for such an hypothesis.
The abnormally high boiling point of dioxane and the
lower boiling points of 2,6-dialkyldioxanes compared with
their isomers may also be explained on the basis of molecular
association.
Molecular association Is frequently responsible
for apparent deviations from generalized rules applying to
(113)
Hildebrand, Sci., 33, 21 (1936)
*■*o2 **
various physical properties.
Thus, it is often responsible
for boiling points being higher than predicted and for similar
changes in density and refractive index.
Dioxane,
in the
liquid state, may be considered associated or polymerized
(XXVI)
and these molecular complexes must be broken down
before complete vaporization can take place.
.CHS— -CHS
*0— C H a .
C H a— C H S
>o.-H:CH '
.hc:h:o1
>o:
C H S— CHg^
'CHjg— C H a^
:o1
etc.
(XXVI)
The reaction
(C*H8O a )n
n C 4H Q03
absorbs a considerable amount of heat which must be added
to the normal heat of vaporization.
An abnormally high
boiling point may thus result.
The lower boiling points of the 2,6-dialkyldioxanes
may be explained through a similar reasoning.
The presence
of alkyl groups on either side of an oxygen atom will have
a shielding effect, decreasing the electron donating properties
of that atom.
A methyl group alpha to the oxygen atom may
Induce resonance between the two types of linkage to their
common carbon atom,
again reducing the electron donating
properties of the oxygen atom.
Another molecule will have
a more difficult time in reaching the oxygen atom in order
to associate with it.
Hence,
The result Is less association*
in the consideration of the boiling point of two
-35-
isomers,
the compound with, the smaller association tenden­
cies will have the lower boiling point.
Examination of data on alkylated b e n z e n e s .and alkylcyclohexanes seem to bear out the general belief that the
dioxane ring is more closely related to the cyclohexane
ring than to the benzene ring.
from conclusive,
ihough\ the evidence is far
it does enable one to reach another step
in the study of cyclic structures.
As in the alkyldioxanes,
the monoalkylcyclohexanes exhibit higher boiling points
than the polyalkyl derivatives of the same molecular weight.
The reverse is true when alkylbenzenes are considered.
All
of the xylenes boil at a higher temperature than ethylbenzene.
Mesitylene distills at 165°, while propylbenzene boils at
159°.
The relationship of the refractive indices to the
densities of the alkyldioxanes is best illustrated by
Figure I.
Since there is a fairly constant variation of
both refractive indices and densities,
it is not surprising
.to find a linear relationship between the two properties.
The most commonly used relationship expressing density and
refractive index is the formula of Lorenz and Lorentz
(95)
Gilman, Organic Chemistry,
95
John Wiley and Sons, p. 1738.
-34O
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used in calculating molar refractivity•
The vallies for the
molar refractivities of alkyldioxanes have been tabulated in
Table IV.
Experimental molar refractivities do not always
check the theoretical values.
Comparison of the two values
for the alkyldioxanes indicate that no uniform correction
to the molar refractivity for the dioxane ring has been
found.
It has also been demonstrated that the values for
isomeric compounds are not constant nor do they show any
uniform relationships.
Recently the concept of refractivity intercept has been
introduced to represent a more constant relationship between
the densities and refractive indices of the members of
96
an homologous series.
The refractivity intercept, b, is
&
empirically defined by the equation:
b = n - g .
This is the equation of a straight line with a positive
slope of one-half.
The refractivity intercept becomes
then the hypothetical refractive index at zero density.
Kurtz and Ward have determined the refractive intercept
for several homologous series of hydrocarbons and have found
a constant value for each series.
This relationship has
been proposed as being useful because it does provide a
constant characteristic of each homologous series.
(96)
This
Kurtz and Ward, J. Prank. Inst., 222, 563 (1936);
224, 583, 697 (1937).
-36-
constant is practically independent of boiling point or
molecular weight.
It can be used to great advantage as a
means of determining errors in data or as a criterion of
the purity of a compound.
By plotting the values of the refractive indices of
each series of alkyldioxanes against the densities,
an
unusual fact is brought to light.
The slope of the plot
6
is negative.
Umhoefer was the first to show this with
the monoalkyldioxanes•
tions.
The dialkyldioxanes are no excep­
He further demonstrated that the formula best
fitting the data on the mono alkyldiox anes is of the form:
, = » + §
Thus, both the sign of the slope and the value of the
intercept are changed.
The same formula has been applied
to the di alkyldiox ane s , giving a constant for each series.
The individual values for the refractivity intercept are
listed in Table IV.
Note the extremely high values for
dioxadiene, dioxene, dioxane,
dioxanes.
and the two allyl substituted
Excluding these values, the calculated average
value for the monoalkyldioxanes is 1.7443,
dialkyldioxanes it is 1,7474.
For the 2,3-
For the 2,6-dialkyldiox anes,
the average refractivity intercept is 1.7326.
from the average are listed in Table IV.
The deviations
Only In the case of
the 2,3-dialkyldioxanes do the values vary by more than
+0.001•
-37-
Inspection of Figure I will Immediately reveal a pos­
sible explanation for the larger variation In the refractivity
intercepts of the 2,3-dialkyldioxanes.
methyl, one of the two diethyl,
Values for the ethyl
and one of the two dimethyl
derivatives do not fall on the line for the 2,3-dialkyldioxanes♦
Whether the line is drawn from point 11 to either 5 or 6,
three points will never fall on that line.
Those three points
correspond to the 2-ethyl-3-methyldioxane, a 2,3-dimethyl­
dioxane,
and a 2,3-diethyldioxane.
The possible explanation
may be that these are values for the isomeric 2,3-dialkyldi­
oxanes.
The cis and trans Isomers may each provide a series
of 2,3-dialkyldioxanes with different boiling points,
densities, and refractive indices.
A determination of the
refractive Intercept has possibly resulted In the first
Indication that such may be the case.
isomers are possible for one substance,
There two geometric
two different
methods of synthesis of this compound may conceivably result
in the two geometric isomers or different mixtures of these
isomers.
The different mixtures would exhibit different
physical properties.
With this in mind, it is to be
noted that one of the 2,3-diethyldioxanes and the 2-ethyl3-rnethyldioxane were synthesized through the /? , (9 1-dihalogen
ether cyclization.
However,
the two 2,3-dimethyldioxanes
of Bauer apparently came from the same source.
-38-
An explanation may be offered for the fact that the
average refractivity intercept for the 2,6-dialkyldioxanes
is much lower than that for the 2,3-dialkyldioxanes.
The
values of Kurtz Indicate that the Introduction of one or
more double bonds tends to Increase the refractivity intercept
of 'hydrocarbons•
The presence of an alkyl group on one of
the carbons of the double bond tends to decrease the value.
On the assumption that the oxygen atom with its free electrons
Is equivalent to an unsaturated bond, the lower value for
the 2,6-dialkyldioxanes Is evident.
The presence of alkyl
groups on both sides of the oxygen atom would tend to
minimize any of its effect on the properties of the molecule.
A useful method of attack for the organic chemist is
the fact that most organic compounds may be Identified by
a characteristic reaction or the preparation of a derivative
with.properties which immediately Identify that compound.
This is especially-true when he is working with substances
which have reactive functional groups.
Unfortunately,
such
Is not the case with respect to the alkyldioxanes.
Since no ready method of making derivatives of these
alkyldioxanes is available nor can they be characterised
through other specific reactions,
their physical properties
are the only criteria by which they may be identified.
The
correlations between their densities and refractive indices
may not be perfect but they offer the first concrete tool
available for future studies of-compounds of a similar type.
B.
G-lycol aldehyde Dimer
1.
Diox adiene.
The discovery
that an ether solution of LIg-MgIs may
be used with good results for the preparation of dioxene
from 2,3-dichlorodioxane focused attention on its possible
97
use for the synthesis of dioxadiene.
Summerbell and Umhoefer
finally succeeded in preparing dioxadiene from 2, 3, 5, 6tetrachlorodioxane in an analogous manner.
’
The temporary
appearance of the iodine color during the reaction led to
their suggestion of the following mechanism for the formation
%
of dio x e n e .
0
H aC
/
X
I
0HC1
I
H aC
CHC1
Mgl8
---- *
/
\
X
H aC
MgCla +
|
H SC
X
o
0
\
0
/ x
CHI
H SC
CII
I
—>
I
II
CHI
H aC
CH
/
\
/
0
0
+ I a + HgCl
Mg + 1 3'
— ^ Mgls
Thus the formation of dioxene from 2,3-dichlorodioxane occurs
through the intermediate formation of 2,3-diiododioxane.
The
diiododioxane then loses iodine to form dioxene.
The synthesis of dioxene was carried out in ethyl ether,
but the synthesis of dioxadiene under the same conditions
met with no success.
(9*7)
This failure was attributed to the
Summerbell and Umhoefer,
J. Am. Cnem. Soc», 6 1 , 30(d0 (19o9)
-40-
difference in reactivity between the two halogenated
dioxanes.
Eventually, by the use of the higher boiling
n —butyl ether
(b.p. 140°),
the successful preparation of
dioxadiene was accomplished.
A mechanism,
similar to that
for the formation of dioxene, may be proposed for the
formation of dioxadiene.
0
G1HG
i
C1HC
/
\
0
\
0
GHC1
I
CHC1
2MgIs
---- >
\
IHC
2MgC 1 s +
I
IHC
/
0
\
0
CHI
I
CHI
— »
HC
1/
/ s
hc
/
\
0
CH
l|
CH
/
+ 21 a + 2I'.TsCli
Mg + I3
Mgl 3
It is obvious from these equations that the magnesium
iodide is being continually regenerated.
Hence,
a small
amount of this substance should be sufficient for the
reaction between equivalent large amounts of magnesium
and the 2,3,5,6-tetrachlorodioxane or the 2,3-dichlorodioxane.
Yet, Umhoefer discovered that the use of relatively larger
amounts of magnesium Iodide produces larger yields of
dioxene.
By changing the molar ratio of iodine to 2,3-
dichlorodioxane from 1:20 to 1:5 he Increased the yield
of dioxene from 31.6/o to 49.0>o„
If the reaction mechanism was correct a change of
the same ratio in the synthesis of dioxadiene should also
influence the final yield of the unsaturated cyclic ether.
This was found to he true.
A 47.8,1 yield of dioxadiene had
been reported using iodine and symmetrical tetrachlorodioxane
in the ratio of 2.1:1 respectively.
Increasing the ratio
of iodine to tetrachlorodioxane to 2*3:1 resulted In a
73.3^ yield of dioxadiene.
The ratio increase may be the only reason for the
increase In the yield of dioxadiene.
factor must be considered.
However,
another
The previously reported synthesis
of dioxadiene was based on the use of the 143° Isomer of
symmetrical- tetrachlorodioxane.
59-60°,
A mixture of the 101°,
and 143° isomers were used in the preparation
which yielded 73.3/S.
There Is no evidence yet to indicate
whether the rates of dehalogenation of all possible
isomers of 2,3,5,6-tetrachlorodioxane are equivalent.
Bhould they be equivalent,
then the increased yields of
dioxadiene may be attributed to the change In the iodine
ratio*
The difficulty in obtaining any of the isomeric crystal­
line symmetrical tetr achlorodioxane s In substantial amounts
is the factor which limits the availability of dioxadiene.
It was thought that part of the liquid chlorinated dioxanes
might contain dissolved tetrachlorodioxan.es.
Then again,
there was the possibility that the unknown fifth isomer
of 2,3,5,6-tetrachlorodioxane was a liquid.
The urgent
-42-
need for dioxadiene stimulated the attempt to prepare it
by the dehalogenation of these high-boiling liquid chlori­
nated dioxan.es*
Conditions for the preparation from the
crystalline substance were simulated as far as possible
in the preparation from the liquid fraction.
The isolation
of 2.1 g. dioxadiene from the reaction has presented definite
proof that the liquid fractions do contain one or more
symmetrical tetrachlorodioxanes•
The unsaturation of all
fractions Isolated from the reaction mixture offers numerous
possibilities in the further study of these higher boiling
liquid chlorinated dioxanes and their reactions.
2*
Structure of dihalogendioxanes.
Dioxadiene reacts with dry hydrogen chloride in dry
97
chloroform solution to form 2,5-dichlorodioxane.
Dry
hydrogen bromide adds in the same manner to form 2*5dibromodioxane In excellent yields.
2*5-DIchlorodioxane
had been previously isolated as a product of the chlorination
of dioxane.
Both the structures of the 2*5-dichlorodioxane
and the 2,5-dibromodioxane were proven by hydrolysis at 100°
and quantitative conversion of the resulting glycolaldehyde
to the p-nitrophenylosazone.
The addition of two molecules of hydrogen halide to
dioxadiene might lead to the formation of either 2*5- or
2*6-dihalogendicxane*
The 2*6- compound (XXVII) will be
hydrolyzed to one mole of diglycolaldehyde
(XXVIII), while
the 2,5 compound (XXIX) will yield two moles of glycolaldehyde
(XXX).
On treatment of the hydrolyzed solution
0
HoC
I
BrHC
s
CHBr
(
CHa
0
PIG
2HBr
/
II
HG
/
CH
II
CH
H SC
2HBn
CHa
I
CHBr
/
BrHG
/
\
\
0
0
/
CHa
1
CHBr
H SC
2HaC>
|
---- *
HC
/
0
\
CKS
1
CH
Jf
0
II
0
0
(XXVII)
/
0
0
N
/
H SC
1
BrHG
\
N
(XXVIII)
with p-nitrophenylhydrazine,
\
/
H SC
1
BrHC
\
CHBr
1
CHa
2Ha0
2CHa0HCH0
/
(XXX)
0
(XXIX)
either one mole of the dihy-
drazone of diglycolaldehyde or two moles of the glyoxal
osazone will be formed.
The weight of the precipitate
corresponded to two moles of the osazone.
The derivative
9Q
melted at 311°
(cor.).
It also gave the characteristic
blue color for p-nitrophenylosazone of glyoxal when treated
with an alcoholic sodium hydroxide solution.
This experiment
indicates the original presence of a. 2,5-dihalogendioxane.
(98)
Fischer, F. G-. , Ann., 4 6 4 , 36 (1928)
-44
5,
Dioxene.
The resulting high yields of dioxadiene depends partially
on the fact that it is removed from the reaction mixture
as soon as it is formed.
It was hoped that a similar
procedure would increase the yields of dioxene.
was tc remove the dioxene
The theory
as soon as It was formed so as to
prevent any possible polymerization.
The method follov/ed
was that used for the synthesis of dioxadiene.
An Iodine/
2,3-dichlorodioxane ratio of 1:5 was used and n-butyl ether
was the solvent.
The reaction failed to yield any dioxene.
Apparently a temperature of 14-0°C« tends to either
the destruction or polymerization of dioxene as soon as It
is formed,
A more probable explanation may be that 2,3-
dichlorodioxane decomposes at 140° in the presence of
Mg-Mgls .
Considerable tarring had been noted soon after
the start of the reaction.
This effect was not demonstrated
during the similar preparation of dioxadiene.
The difference
in the stability of 2,3-di chi or odiox: ane from that of sym­
metrical tetrachlorodioxane may be the factor accounting
for the temperature effect In the preparation.
The preparation of cyclopropane from 1,3-dichloropropane
99
in yields as high as 95g suggested another possible
means of obtaining dioxene in appreciable quantities.
Haas
used anhydrous acetamide as a solvent and carried out the
reaction at 125°.
(99)
One mole of 1,3-dichloropropane was added
Haas, McBee, Hinds,
2 8 , H 7 8 (1936)
and Gluesenkamp,
Ind. Eng. Chem
-'-to—
dropwlse to a mixture of one rnole of sodium carbonate^
moles zinc dust,
andone-sixth
in molten acetamide.
The
of a mole of sodium
rate of addition of
two
iodide
thedichloro-
propane was adjusted to the rate of distillation of the
cyclopropane*
The method of the above synthesis was
duplicated with respect to the preparation of dioxene,
The starting materials used were one mole 2,3-dichlorodioxane,
one mole sodium carbonate,
two moles zinc dust,
tenths of a mole of sodium iodide,
resulted,
and two-
A yield of 17p> dioxene
A mechanism similar to that proposed for the
cyclopropane formation may be assumed for the dioxene
formation*
1.0
/ \
H gC
CHG1
|
|
H SC
CIICl
V
0
+
0
/ \
H SC
2Na+ + 2I~->
|
HgC
/
\
2 . 0
/ \
3*
0
I
2N aC 1
+
I#
/
CHI
I
CHI
H aC
I
H SC
^
/
/ \
\
I g + Zn
— ^
CH
H
CH
/
0
Zn I g
+
mm
4.
+
CHI
0
H SC
I
H aC
N
0
CHI
Znlg +x C H sC0NHe
The presence of
— *
the iodine
21
color
+ Zn
(CH3C0I-:hs )x
as soon as
the dichloro-
dioxane hits the surface of the reaction mixture is evi­
dence of its temporary existence as an Intermediate.
Apparently iodine ion is the active dehalogenating agent
and it must be regenerated to continue the reaction.
use of acetamide facilitates such regeneration.
The
The value
of x Is believed to be 4.
The isolation of dioxene from this reaction is the
first evidence that this zinc reagent may be used to remove
hemiacetal type halogens.
Optimum conditions for the
preparation have not been determined but its successful
use in this type of a synthesis may warrant further
experimentation along similar -lines.
4.
Attempted synthesis of diglycolaldehyde p-nitrophenyl-
hydrazone.
As has been pointed out previously,
the hydrolysis of
a 2,6-dihalogenether would result in the formation of
diglycolaldehyde.
This substance has never been prepared,
nor have any of its derivatives been Identified.
To
further demonstrate that the p-nitroxohenylhydrazine deri­
vative of the hydrolyzed dihalogen compound was not the
diglycolaldehyde p-nitrophenylhydrazone, the synthesis of
the latter was attempted.
A possible method was by the
hydrolysis of a 2,6-dihalogendioxane•
Unfortunately, no
such dioxane derivative has as yet been identified.
Another
possible method seemed to be through the ozonolysis of 2,5dihydrofuran.
Ozonolysis of the double bond in 2,5-dihydro-
fur an (XXXI) and subsequent hydrolysis of the ozonide
(XXXII)
in a reducing atmosphere should yield diglycolaldehyde
(XXXIII).
0
H aC
/
0
N
|
PI G
CHa
I
=s=
CH
0S
H 2G
7
/
0
s
,
|
HC
---
I
CH
I
0
(XXXI)
GH2
0
5H30
---- >
/
H sG
\
CHa
|
,
HG
+
CIi
ii
n
0
0
/
\
0
(XXXII)
(XXXIII)
By reacting the dlaldehyde with p-nitrophenylhydrazine the
hydrazone should be obtained.
An attempt to isolate the
pure diglycolaldehyde failed.
Attempts to prepare the h y ­
drazone without Isolating the aldehyde resulted either in
the recovery ofp-nitrophenylhydrazine or the formation of
glyoxal p-nitrophenylosazone.
The osazone was obtained
when the reaction was carried out at 100° while at room
temperature the original hydrazine was recovered.
The isolation of the glyoxal osazone from this reaction
presents an unusual problem,
since it may possibly result
from the splitting of the ether link,
and the oxidation of
the resulting alcohol (XXXIV) to an aldehyde, with the
subsequent formation of the osazone.
It may also arise
through the oxidation of a hydrogen atom alpha to the
ether oxygen and hydrolysis of the resulting hemiacetal (XXX
to the aldehyde with subsequent formation of the osazone(XXX
'These steps may be outlined by the following equations:
1.
CH0-CHa-0-CHa-CH0 + 2p-N0B-CaH 4-lTI-IiTHB -- )
p - N O a- C sH 4-NHN=CH-CHB-0-CHa-CH=H-NH-CsH4-p-NOa (A).
2.
(A) + H a0 — »
2p-NOa-C aH 4-NHN=CH-CHBOH
(XXXIV).
3.
(XXXIV) + 2p-NOa- C sH 4-NHNHs — ^ p - H O a-GGH 4-Kl-m=GH-GH=IJWK-CaH 4'
p - N O a (XXXV).
4.
(A) + p - N O B- C aH 4-NHNHB — »
p - N O B- C aH 4-NHN=CH-CH-0-CHB-CH=N-NH-CaH 4-p-NOa (XXXVI).
OH
5.
(XXXVI) + H aO + p-NOa-C0H 4-KHNHB
— >
(XXXV).
The osazone was identified by its melting point (308°) and
the fact that a mixed melting point with the known osazone
showed no depression.
In order to further study this unusual reaction it was
deemed necessary to start with a known derivative of a betaaldehydo-ether.
A derivative of this type can be obtained
from the hydrolysis of dioxene.
Hydrolysis of dioxene
should yield 5-hydroxy-3-oxapentanal
(XXXVII)
(XXXVIII) which on
treatment with p-nitrophenylhydrazine will result in the
necessary type of compound,
0
H aC
/
\
|
0
CH
II
HC
(XXXIX)
CH
\ 0/
H s0
H aC
^
/
0
\
I
CHa
I
H aC
CHOH
—^
(XXXVII)
|
H aC
I
OH
CI-IB
I
1
OH
'i0
CH
(a a H V I I I )
q
/
\
I
H aG
V 0^
(XXXVIII) + p-WOB-CaH4-HHKHB — >
/
H aC
\
CH a
|
C = 1TIIH-C aH 4—p-I!Oa
I
C'iXXIX)
The hydrolysis of 2 g. dioxene and subsequent treatment of
the solution with p-nitrophenylhydrazine resulted in the
isolation of 3.1 g. of orange needles melting at 142°.
Analysis for nitrogen by the Itjeldahl method gave values
of 15.05, 15.19, 14.91.
of diglycolaldehyde,
Calculated values for the hydrazone
22.57; for 5-hydroxy-3-oxapentanal
hydrazone, 17.57; for 5-hydroxy-3-oxapentanal hydrazone
monohydrate, 16.33; for the dihydrate, 15.26; for the
monoalcoholate,
14,73.
This list of compounds includes
most of possibilities resulting from the treatment of
hydrolyzed dioxene with p-nitrophenylhydrazine.
possibilities,
Of these
the dihydrate of 5-hydroxy-3-oxapentanal p-
nitrophenylhydrazone is indicated to be the most probable.
Of the theoretical 13.01/O water in the dihydrate,
only
8.65/ii could be removed by drying under 15 mm. pressure at
134°.
Refluxing the above hydrazone with excess p-nitroifnenylhydrazine in 25/o acetic acid resulted in the p-nitr ophenylosazone, confirming the probable reaction with diglycolaldehyde.
The osazone isolated melted at 310°
and showed no depression
when mixed with the known osazone.
The characteristic blue
color was obtained when the red needles of the osazone v.^ere
treated with a.lcoholic sodium hydroxide,
-50-
It may be of course that the ether may be split by
re fluxing with 25 /
co acetic
acid, since both reactions were
conducted in that solvent.
That observation does not alter
the fact that an ether linkage beta to a functional group
may be split by comparatively mild reagents.
It would be
of interest to learn whether the p-nitrophenylhydrazones
of ethoxy- and methoxyacetaldehyde can be treated similarly
to yield the osazones.
That these
(3
-ether linkages are more reactive than an
ordinary ether link of the same type may be indicated by
certain observations of Drake et, a l . °°
They found that
a Grignard reagent will act on me thoxyacet aldehyde in' the
ratio of 1,4 moles to one mole at 100°.
It was believed
that part of the methoxyl group in addition to the carbonyl
group reacted under those conditions.
Indications that such
might be the case could be obtained by examination of the
products of the reaction of the Grignard reagent with
methoxyacetaldehyde.
secondary alcohol
In addition to the expected /? - oxy-
(XL) one might also expect to find s.
simple substituted secondary alcohol (XLI),
RMgX + C H o-0-CHa-CH0
— >
C H o-0-CHa-CHR
I
(XL)
OH
+ R - C H a—CH—R (XLI) + MgX0CHa
/
OH
(100)
Drake, Duvall,
Jacobs, Thompson,
Chem. Goc., 60, 73,
(1933)
and Gonnichsen,
J, Am,
-51-
5.
4-Pentene-l-ol.
The preparation of 2,5-dihydrofuran focused attention
on the fact that the isomeric 2*3— dihydrofuran had never
been synthesized.
A study of the ozonolysis of this compound
might reveal peculiarities of the furan ring.
The compound
was also desired in connection with another study.
It was
hoped that this could be accomplished by starting with
hydroxybutyraldehyde which exists mainly in its cyclic
form as
c<~hydroxytetrahydrofuran.
Dehydration of the
furan should yield 2,3-dihydrofuran.
The
^-chlorotetra-
hydrofuran might also be synthesized from the hydroxy
compound by treating the latter with dry hydrogen chloride.
Bromination of the
^-chlorotetrahydrofuran at 0 ° G . might
conceivably result In the formation of
(9-dibromotetra-
hydrofuran which could then be dehalogen ated to 2*3-dihydrofuran.
y-Hydroxybutyraldehyde has been prepared by HeiferIch
and Schafer by ozonolysis of 4-pentene-l-ol and. hydrolysis
of the ozonide.
3-0 1
Careful repetition of their directions
for the same preparation met with complete failure.
Since
the synthesis of 2,3-dihydrofuran was not absolutely neces­
sary for the solution of our problem* further efforts in
that direction were abandoned.
In the course of these experiments* however*
(101)
Heiferich and Schafer* Eer.* 57-B, 1911
it was
(1924)
necessary to prepare 4-pentene-ol-1 in appreciable amounts
and In the most convenient manner.
This compound had first
loS
been synthesized In 1904
by the reduction of ethyl allyl
acetyl acetate.
Paul Improved upon the yield by reducing
the ethyl ester of allyl acetic acid to the unsaturated
103
alcohol.
lo4
Robinson
duplicated Paul's yields of 50#
by heating tetrahydrofurfurylmagneslum- bromide for two hours
at 100°.
In all of these preparations the starting materials
were not easily available nor were the overall yields very
high.
By reacting an allyl Grignard reagent with ethylene
oxide*
there was obtained a 61.2# yield of 5-pentene-ol-1,
a definite improvement on all previous methods of synthesis.
A further advantage lies in the ready accessibility of the
starting materials.
6.
Structure of glycolaldehyde dimer.
ho concrete synthetic evidence for the numerous sug­
gested structures of glycolaldehyde dimer and analogous
7 9 j
compounds has ever been presented.
8 9 , 9 0
Some investigators
consider them to be derivatives of dioxane and thus place
them In the category of definite chemical compounds.
(102)
(103)
(104)
Others
Bouveault and Blanc, Bull, soc. chim., ol (3), 1215
Paul, Ann. de chim., (10) 18, 332 (19327“
Robinson, J. Chem. Soc., (1936) 195.
(190
-53-
point to their dissociation at higher temperatures
and lower
pressures, relegating them to the status of strongly associated
1 0 5
c ompounds.
,9 1 ^7 0 ^8 1 , 8 8
Ho definite structures are proven
hut associated forms of the monomolecular type are assumed.
Many admit the anomalies and place them somewhere in be­
tween the two types of substances.
The evidence used has been the physico-chemical properties
of the dimers.
Dissociation in many solvents and dissociation
into the monomolecular form in the vapor state with the
return to a bimolecular order on condensation, point to the
conclusion that we are dealing with strong bimolecular
association.
sociation,
However,
the variance in the speed of dis­
the abnormal effect of temperature and dilution
on solvent action, indicate that a type of structural change
is brought about during the transition of dimer to monomer.
Bergmann
9o
has further demonstrated that the dimer methyl
lactolid of acetol (XLII) does not dissociate in the vapor
state if he eliminates all possible catalytic effects.
Fischer
lO 6
has shown that dimeric glyceraldehyde will not
dissociate in the vapor state.
2 CHS —
(105)
(106)
0CHo
)
C —
CH2
Bergmann and Ludewig, Ann., 456 , 173 (1924)
(1927)
Fischer, Taube, and Baer, Ber., 60-B , 479 (
Evidence for the existence of the dimer as a definite
compound is strongest from a strictly chemical standpoint.
Some of the dimers do not undergo many typical free carbonyl
reactions unless dissociated by various solvents.
Thus the
identity of the carbonyl grouping must be lost in the dimer
state.
The assumption of a dioxane nucleus for these dimers
explains most of their anomalous properties.
glycolaldehyde cannot be acetonated.
s o
Dimeric
Structure
(XLIII),
eliminating the possibility of free adjacent hydroxyl groups,
explains such failure.
Both the monomer and the dimer of
dihydroxyacetone may be acetonated to form a dimeric derivative.
Such action easily follows on the assumption of structures
(XLIV) for dimeric dihydroxyacetone and (XLV) for the dimeric
acetone derivative.
0
0
/
\ CHOH
H 2C
HO v I
» v C H sOH
CH0
,CHa
HOHC
HOCHg
0
(XLIII)
X
/
0
(XLIV)
2 (CH5 )sCO
-55-
The availability ol dioxadiene enabled us to approach,
the problem from a different point of view,
that of an
actual synthesis of a dimer with a definite structure.
It has already been shown that dioxadiene reacts with dry
hydrogen chloride in dry chloroform solution to form 2*5dichlorodioxane.
Dry hydrogen bromide adds in the same
manner to form 2* 5-dibromod.ioxane * which may be reacted with
silver acetate In dry toluene to yield the 2*5-diacetoxydioxane
The equations for these reactions will present a clearer
picture of these steps.
0
HC
/
\
{I
CH
ft
HC
CH
\
0
/
/
HgC
2HBr
I
* BrHC
x
Fischer
QS
0
V
/
0
CHBr
|
CHS
0
/ V
AgOAcv
H SC
|
AcOHC
\
CHOAc
\
+ 2AgBr
CHa
o
/
had synthesized a glycol aldehyde bromide from
the aldehyde dimer through the acetate dimer.
He pointed
out that neither the bromide formation nor the acetate form­
ation involved a rearrangement of the basic structures of
the original ald.eh.yde or Its derivatives,
mis evidence i or
this belief is an experiment whereby the bromide Is con­
verted to the ethyl glycoside of glycolaldehyde by treatment
with silver carbonate and ethyl alconol.
The glycoside
63
proved to be Identical with that syn the sized by Bergmann
from ethyl vinyl ether by oxidation with benzoyl peroxide.
- 56-
All of the above derivatives were found to exist as dimers*
Fischer represented them by such formulas as:
CHS
CH»
iv o
CHS
io °
HC
w o
HC
HC
I
I
»
OH
Br
OEt
The glycolaldehyde dimer diacetate was synthesized
according to Fischer and it proved to be identical with
the 2,5-diacetoxydioxane synthesized from, dioxadiene through
2,5-dibromodioxane,
Both compounds melt at 157-158°.
Mixed
melting points showed no depression.
The bromide was also synthesized according to Fischer
through the glyc ol aldehyde acetate.
It proved to be the
same as the 2,5-dibromodioxane synthesized from dioxadiene.
Both compounds darken at 104° and decompose completely at
154°.
A mixed melting point was not depressed.
Both
compounds decompose rapidly on standing at room temperature,
with the evolution of hydrogen bromide.
structures, long -white rectangles,
the microscope.
appear Identical under
Using the »Becke line” method, the average
refractive index for
2 ,5-dibromodioxane
dimer dibromide it Is 1.609.
attributed
Their crystal
is 1.618.
For the
The discrepancy may be
to the difficulty of working with a substance
which decomposes readily and Is somewhat soluble in the
liquids used for the determination.
In as much as Fischer is bromide is aeoually ^,o—
-57-
dibromodioxane,
and his acetate is 2, 5-diace toxydloxene,
we may conclude tliat dimeric glycol aldehyde is 2,5-dihydroxydioxane.
V«
Chlorination of dioxane and 2,3-dichlorodioxane.
In order to synthesize dioxadiene it was necessary to
prepare symmetrical tetrachlorodioxane,
intermediate in the preparation.
the necessary
Studies on the methods
of obtaining higher chlorinated dioxanes have been the
concern of many investigators.
Q > X o r7
>
lo6^ lo9
*
llO, 111
Usually their efforts led to the synthesis of 2,3-dichlorodioxane,
liquid unsymmetrical tetrachlorodioxanes, and small
yields of the 2,3,5,6-tetrachlorodioxanes.
In an effort to find a method that would lead to
6
greater yields of the symmetrical products, Umhoefer
carried out a number of chlorinations under a variety of
conditions.
ful.
His efforts in this direction v/ere unsuccess­
In the course of his experiments, however, he dis­
covered the existence of a new dichlorodioxane and a new
tetrachlorodioxane.
Chlorination at temperatures above
150° yielded 2, 2,3,3-tetrachlorodiox ane.
(107)
(108)
(109)
(110)
(111)
Chlorination using
Boeseken, Tellegen and Henriquez, J. Am. Chern. Soc.,
55 , 1284 (1933)
Kucera and Carpenter, ibid., 5J7, 2346 (1935)
Butler and Cretcher, ibid., 54, 2987 (1932)
Baker and Shannon, J. Chem, Soc., 1598 (1953)
Baker, ibid., 2666 (1932)
-53—
carbon tetrachloride as a solvent yielded a new dichlorodloxane , the 2,2— dichlor odloxane •
lie also made the obser­
vation that any symmetrIcal tetrachlorodloxane obtained
by the chlorination of dioxane In carbon tetrachloride was
exclusively the isomer melting at 101°.
The new chlorinated dioxanes were not Isolated and
characterized.
Their presence was indicated by an, exam­
ination of their hydrolytic products.
The 2,2—dichlorodloxane
yielded ^-hydroxyethoxyace tic acid while the 2,2,3,3-tetrachlorodioxane yielded oxalic acid and ethylene glycol on hydrolysis.
A renewed attack on the problem of finding a duplica.ble
method for obtaining the symmetrical tetrachlorodioxanes
In greater yields has
again been unsuccessful.
that were varied Include temperature,
time of chlorination,
agent.
The factors
effect of peroxides,
starting materials,
and chlorinating
The products were usually complex mixtures of liquid
chlorinated dioxanes which were difficult to fractionate*
As a result of one of the chlorinations,
there was
Isolated from the reflux condenser a solid which was
a
eventually proven to be 2,5-dichlorodloxane.
The substance
was crystallized from petroleum ether to yield v/hite needles
melting at 118-119°.
It v/as proven to be 2,5-dichlor odiox ane
by hydrolysis and quantitative conversion of the resulting
(a)
This substance has since been synthesized by hr. V/. LI.
bmedley by the chlorination of dioxane In carbon
tetrachloride at temperatures below 0 ° G .
glycolaldehyde to the p-nitrophenylosazone of glyoxal.
In 1939, Kharasch and coworkers published a new
technique for the chlorination of aliphatic type compounds.
1 IS
They used sulfuryl chloride with benzoyl peroxide as a catalyst.
The use of excess sulfuryl chloride on dioxane resulted in
only a very small yield of symmetrical tetrachlorodloxane•
When 2,3-dichlorodloxane was chlorinated under similar
conditions the yield of the needed tetrachloro compound
was only slightly Increased.
The main products are high
boiling liquids.
When excess dioxane is used In the same
type of reaction,
2,3-dichlorodloxane is the only apparent
product.
Another interesting observation is that the symmetrical
tetrachlorodloxane obtained by the chlorination of dioxane
with sulfuryl chloride Is exclusively the Isomer melting
at 100°.
The same conclusion was drawn by Umhoefer when
carbon tetrachloride was the solvent In an ordinary
chlorination.
Evidently,
chlorination under 70°C. tends
toward the exclusive formation of the 100° melting Isomer
of 2,3,5,5-tetrachlorodioxane.
The difficulties Inherent In this problem of dioxane
chlorination may be realized when one learns that there are
approximately forty-five possible geometrical and structural
isomers, excluding the stereochemical Isomers of the
(112)
Kharasch et a l ., J.Am.Chem.3oc., 61., 2112, 3039, 5452 (1339)
chlorinated dioxanes.
situation.
These latter further complicate the
The data in Table V reveals that only twelve
isomers have been identified to date.
Table V
Chlorinated Isomers of Dioxane
Chlorine atoms
IylonochloroDichloro2,32,52,62,2Trichloro2,3,52,2,32,2,52,2,6Tetrachloro2,2,3,3.2,2,3,52, 2,3,62,2,5,5—
2,2,6, 62,2,5, 6—
2,3,5,6Pentachloro2,2,3,3,52, 2,3,5,52, 2, 3, 6, 62,2,3,5,6Hex achl or o2,2,3,3,5,52, 2,3,3,5,62,2,3,5,5,62,2,3,5,6,6HeptachloroOc tachloro-
(*)
^
Possible Isomers
Known Isomers
1
1
2
2
2
1
1
1
0
1
4
1
1
1
0
0
0
o'
..
1
2
2
1
1
2
5
1
2
0"
0
0
0*
4
1
1
1
4
0
0
0
0
1<J
0
0
0
0
0
0
1
2
2
2
1
1
Two isomers of unsymmetrical tetrachlorodloxane are Known
whose structures may be any one of these.
J The structure of the existing liexacnlor ociioxane i^» ^oi>
lcnown .
A review of the conditions of various chlorinations
together with an examination of the structures of the known
isomers of chlorinated dioxanes permits one to draw only
one definite conclusion.
chlorination.
There is no one mechanism of
Chlorination at low temperatures favors
progressive substitution.
Higher temperatures may shift
the reaction to a combination of substitution, halogen acid
removal,
and addition.
The isolation of 2,5-dichlorodioxane
presupposes the existence of monochlorodioxane as a primary
reaction product in some of the chlorin a tions•
It was
previously thought that its extreme instability would
prevent its isolation from a chlorinating mixture.
High
temperatures favor the splitting out of hydrogen halide
and halide
addition.
The formation of 2, 2,-3,3-tetr achloro-
dioxane at high temperatures may be explained by postulating
primary substitution,
hydrogen halide
and then alternate splitting out of
and chlorine addition.
-62-
III.
A*
EXPERIMENTAL
Dialkyldioxanes
1.
Synthesis of 2 ,5-diethyldioxane.
a.
Preparation of ®C-chlorobutyl~/5 *-chloroethyl ether*
A mixture of 165 g. (1*42 moles)
of dry redistilled
ethylene chlorohydrin and 102 g* (1*42 moles) dry redistilled
butyraldehyde was cooled to -5°C.
Dry hydrogen chloride
was passed into it at a rapid rate with continuous stirring.
The temperature of the reaction was kept slightly below 0°C.
and at the end of five hours two distinct layers appeared*
The lower layer was discarded while the upper layer was dried
over calcium chloride at 0° for twenty-four hours*
crude
6
2
Yield of
^ -chl o r o b u t y l - P ’-chloroethyl ether was 153 g* or
of the theoretical.
A portion was redistilled twice under diminished pressure,
yielding a fraction boiling at 74-76° at 18 mm.
The oily,
colorless liquid has an ethereal odor and In contact with
air underwent rapid decomposition with the evolution of
hydrogen chloride.
So
It soon darkened and deposited a black,
So
^
tarry mass*
d 4 1*103
; n-Q 1*4490
; M*R* calcd*, 41*29;
a
found, 41.47.
The pure material was analyzed for chlorine
20
(a) Lingo and Henze, ref. 65, reported:
M.H. found, 41.51; b.p. 71° at 10 mm.
Sq
d 4 1.1009; nD 1.4471;
by the Volhard method.
Anal. Subst., 0.2894 g.; cc. of 0.1501 N
AgNOs , 22.90.
Calc, for C6H 1J30C1S ; Cl, 41.73; found: Cl, 41.51.
b*
Preparation of
V ,/5—dibromobutyl
-chloroethyl ether.
With continual stirring at 0°, 353.3 g. (2.06 moles)
the
of
«<-chlorobuty 1 - -chloroethyl ether were reacted with 329.6 g
(2.06 moles)
of bromine.
The bromine was added dropwise over
the course of three hours at such a rate that the color of the
reaction was never darker than amber.
The reaction was then
stirred at room temperature for one and one-half hours and the
hydrogen chloride removed by placing the product under reduced
pressure.
The substance fumed considerably in air.
Yield,
600.7 g. or nearly quantitative.
Eighty-one grams of the crude ether was fractionally
distilled under vacuum.
A fraction weighing 47 g. was obtained
at 84-86° under 8 mm. pressure.
The substance was colorless
when freshly distilled but turned dark yellow on standing.
fraction represents a 54.0^ yield of
/^-dibromobutyl
This
-
chloroethyl ether based on the «<-chlorobutyl- 0 -chloroethyl
ether.
This yield Is probably much higher since the crude
substance was left in the refrigerator for ten days before
distillation.
Even at 0°, the tendency toward decomposition
was quite large.
A small portion of the distilled ether was
refractionated at 8 mm. and the fraction boiling at 85-86° was
analyzed for total halogen.
Excessive decomposition prevented
the accurate determination of density or refractive index.
-64-
Anal. Subst., 0.2765 g.; cc. of 0.1501 N AgN03 , 18.88.
Calc, for C6HxiOClBrs :
total halogen, 66.35; found, total
halogen, 66.74.
c.
Preparation of <^-ethyl-^-bromobutyl-/?1-chloroethyl ether.
A solution of ethylmagnesium bromide was prepared from
250 cc. of dry ether* 18 g. of magnesium turnings, and 83 g.
(0.75 mole) of ethyl bromide.
To this solution was added a
solution of 147 g. (0.5 mole) of the
chloroethyl ether.
«^,/3-dibromobutyl ^ -
The reaction was carried out at 0° and
required three hours.
At the end of that time, the reaction
was stirred for one and one-half hours at room temperature.
The excess Grignard reagent was destroyed by hydrolysis with
dilute hydrochloric acid.
The ether layer was separated from
the water layer and dried over calcium chloride for twenty
four hours.
The ether was removed by distillation from a steam
bath and the dark brown liquid residue was fractionally
distilled at 20 mm.
A 39.6 g. fraction distilled at 98^107°
and represents a 32.5$? yield of
chloroethyl ether.
*(-ethy 1-^-bromobuty 1-/3^ -
A small portion was redistilled over
sodium hydroxide pellets to facilitate purification.
A fraction
boiling at 96-7°/7mm. was collected and analyzed for total
halogen.
It was colorless when freshly distilled but turned
® O
dark on standing.
d4
S
q
1.304; n-p
1.4819; M.R. calculated,
53.42; found, 53.35.
Anal. Subst., 0*2382 g.; cc. of 0.1501 N AgNOa , 13.05.
Calc, for CeH l60ClBr; total halogen, 47.38; found, 47.29.
d.
Preparation of 2,3-diethyldioxane.
A ten percent potassium hydroxide solution was prepared
from 15 g. potassium hydroxide and 150 cc* water*
solution and 24*3 g*
(0*1 mole) of
This
ethyl—/?—bromobutyl-/? -
chloroethyl ether were placed in a steel bomb (300 cc.
capacity)
hours.
and heated in an oil bath at 200-210° 0. for three
The cooled solution was extracted with three 100 cc.
portions of ether.
After drying the ether solution for one
day over sodium sulfate, the ether was removed by distillation
from a steam bath.
The liquid residue was fractionally
distilled, yielding 2.1 g. of 2,3-diethyldioxane distilling at
166-167.5° under 746 mm.
This represents a 15.07$ yield based on
the (3 ,£ 1-dihalogen ether.
The substance had the characteristic
2O
Q,
So
o
odor of the dioxane homologs.
d 4 0.941
; n^ 1.4351
;
a
b
M.R. calculated, 40.23; found, 40.01.
Analysis for carbon
and hydrogen gave the following percentage composition:
calculated for CsH l60s ; C, 66.61; H, 11.19.
Found: C, 66.48;
H, 11.08.
2.
Synthesis of 2-e thy 1-3-me thy ldioxane.
a.
Preparation of °(-methyl-^-bromobutyl-(3 -chloroethyl
ether.
A grignard reagent was prepared from 200 g. (21 moles)
of methyl bromide,
50.1 g. of magnesium turnings, and 400 cc.
2©
20
(,a) Summerbell and Bauer, ref. 44, reported: d4 0.940; n~ 1.4342;
M.H. found, 40.05; b.p. 166.5-168.5 at 759 mm.
(b) Analysis by Mr. E.L. Washburn.
dry ethyl ether*
(1*0 mole)
To the clear solution were added 294*5 g*
of a/,/£-dIbromobutyl-/Pl-chloroethyl ether dissolved
In an equal volume of dry ether*
Complete addition required
three hours, the solution being continually stirred at 0°*
There was an immediate reaction as soon as the dibromoether
touched the surface of the Grignard.
When all of the ether
had been added, the reaction mixture was stirred at room
temperature for one hour and then hydrolyzed with dilute
hydrochloric acid*
The product was worked up in the usual
manner and distilled*
A 72*8 g* fraction was obtained distilling
at 74-79° under 5 mm* pressure*
31*4$ yield of
This fraction represents a
«^-methyl-^-bromobutyl- Ql-chloroethyl ether*
Re fractionation over sodium hydroxide pellets yielded the
pure substance boiling at 78-79° under .4 mm*
Freshly distilled,
the ether was colorless but turned azure blue on standing in
So
20
the cold*
d 4 1*322 ; n^ 1*4759; H.R. calculated, 48*80;
found, 49*03*
Anal* Subst*, 0*3930 g*, cc* of 0*1501 N AgN03 , 22*82*
Calculated for C 7H 140ClBr; total halogen, 50.27; found, 50*05.
b.
Preparation of 2-ethyl-3-methyldioxane*
To a solution o f 43 g. of potassium hydroxide in 900 cc.
of water were added 83.5 g. (0.362 mole) of the above crude
ether and the mixture was refluxed for forty-two hours.
At the end of that time most of the halogenated ether had
gone into solution, leaving a small amount of a yellow oil
floating on the top#
The entire solution was extracted with,
three 200 cc* portions of ether*
up in the usual way and distilled.
The product was then worked
Hefractionation at 746 ram.
yielded 2*9 g. of 2-ethyl-3-methyldioxane boiling at 150-151°.
.
ao
so
This represents a 6*6% yield*
d 4 0*940;
1*4305; M*R*
calculated, 35*62; found, 35*74.
Analysis for carbon and
hydrogen gave the following percentage composition:
lated for C 7H i 40s ; C, 64*56; H, 10*85*
calcu­
Found: C, 64*41;
H, 10*79.
5*
Synthesis of 2-ethyl-6-methyl dioxane*
a
a*
Preparation of
chloroethyl^ ( 3 1-chloroisopropyl ether.
Dry hydrogen chloride was passed into a mixture of 475 g*
(5 moles) of freshly distilled dry propylene chlorohydrin and
a
220 g* (l/3 moles) dry, redistilled paraldehyde at 0° with
continual stirring*
The reaction period was five hours, the
reaction mixture separating into two layers at the end of that
time*
The upper layer was separated and dried over calcium
chloride*
Yield of crude product was 535 g* or 68*6% of
theoretical*
yielding pure
A portion was purified by fractional distillation
chloroethyl- (9 *-chloroisopropyl ether boiling
at 54-55° -under 7 mm.
The ether is a colorless, oily liquid
and decomposes markedly when exposed to air at room temperature
d 4 °1.130; np°l*4433; M.R. calculated, 36.67; found, 36.85*
(a)
This work performed in conjunction with Mr* B. A* Nelson.
-63-
Anal. Subst., 0.2657 g.; cc. of 0.1501 N AgH03 , 22.43.
Calculated fop C 5H 1 o 0G1j3$
b.
45.17; founds Cl, 44.94.
Preparation of Y,^-dibromo ethyl- (9f-chloroisopropyl
ether.a
The
above crude, driecU^-chloro ethyl- (3*-chloroisopropyl
ether (430 g* or 2.75 moles) was cooled to 0° in a h
bath and 441 g.
(2.75 moles)
with continuous stirring.
ice
of bromine were slowly added
The reaction required three hours,
the color never being permitted to become darker than amber.
Further reaction was allowed to take place at room temperature
with stirring of one and one-half hours.
product was theoretical or 770 g.
Yield of crude
A 201 g. portion of this
crude ether was distilled under vacuum, yielding a 160 g.
fraction boiling 106-108° at 12 mm.
This represents a 79.8^
yield of pure <*,(?-dibromo ethyl - 0r~chloro isopropyl ether.
It is a viscous, colorless liquid with lachrymatory character­
istics, and tends toward rapid decomposition when exposed to
air at room temperature.
for analysis.
A small sample was refractionated
B. P. 105— 105.5° at 4 mm; d4 1.782; n^ 1.5271;
M.R. calculated, 47.33; found, 48.40.
Anal. Subst., 0.2516 g.; cc. 0.1501 N AgROs , 17.78.
Calculated for C6H Q0ClBrs ; total halogen, 69.63; found, total
halogen,
69.21.
(a) This work performed in conjunction with Mr. B. A. Uelson.
-69-
c* Preparation of ^-ethyl-^-bromoethyl-i!?-chloroisopropyl
ether*
A Grignard reagent was prepared from 165 g*
(1*5 moles)
of ethyl bromide, 36 g* magnesium turnings, and 400 cc* dry
ether*
To the clear solution were added 280*5 g* (1 mole)
of the above crude ether dissolved in an equal volume of
dry ethyl ether*
The reaction was conducted at 0° and
required three hours for completion*
the mixture
At the end of that time,
was stirred at room temperature for one hour
and then hydrolyzed with dilute hydrochloric acid*
Working
u p the mixture in the usual manner resulted in a 158 g*
fraction distilling at 88-95° under 9 mm*
a 69.8^ yield of
ether.
This represents
e thy l-/?-bromo ethyl-(3T-chloroisopropyl
Refractionation over sodium hydroxide pellets
yielded the pure ether at 93*5° under 9 mm*
The product
is colorless and possesses a sweetish odor*
When pure, it
does not undergo decomposition when exposed to air at room
temperatures*
d 4 1*327; n ^ 01*4712; M*R* calculated, 48.80;
found, 48*35*
Anal* Subst*, 0*3165 g*, cc* of 0*1501 N AgN03 , 13*05*
Calculated for C7H 140ClBr; total halogen, 50*27; found, 49.94*
d*
Preparation of 2-ethyl-6 -me thy ldioxane.
A solution of 15 g* (0*27 mole) of potassium hydroxide
In 150 cc* water and 22*95 g* (0*1 mole) of °<-ethyl-/?-bromoethylp i -chloroisopropyl ether were heated for six and one-half
hours in a bomb at an oil bath temperature of 230° •
The
-70-
cooled reaction mixture was salted out with sodium chloride
and extracted with, three 100 cc# portions of ether.
Working
up the ether extraction in the usual manner yielded 2*55 g.
of 2- ethy 1-6-methyldioxane.
This represents a 19,7# yield.
The dioxane was refractionated over metallic sodium for
analysis; h.p. 144.5° at 747 mm.
In water and possesses the
homologs.
characteristic odor of dioxane
d®°0.923; n£°1.4241; M.R. calculated, 35.62;
found, 35.02.
Analysis for carbon and hydrogen gave the
following percentage composition:
C, 64.56; H, 10.85.
4.
It Is partially soluble
Pound:
calculated for C7H X40e :
C, 64.32; H, 10.81.
Synthesis of 2-propyl-6-methyIdioxane.
a.
Preparation of
—propyl— (3 -bromoethy 1
chloroisopropyl
ether.
A solution of propylmagneslum chloride was prepared from
78.5 g. (1 mole) propyl chloride, 24 g. magnesium turnings,
and 300 cc. dry ether.
To the cooled solution at 0° was
added a solution of 140.3 g. (0.5 mole) ©f
p /3—dibromoethyl
*
(? -chloroisopropyl ether in 150 cc. dry ether.
The addition
was carried out dropwise with continual stirring.
When all
of the ether had been added, the mixture was stirred at
room temperature for one hour and then hydrolyzed with dilute
hydrochloric acid.
When the mixture was worked up in the usual
way there was obtained 62.1 g. of a liquid product
-71-
distilling at 109° under 7 mm* pressure*
This fraction
represents a 51.0^ yield of pure <^-propyl-£>-bro mo ethyl-£> chloroisopropyl ether.
It is colorless,
and possesses a sweetish odor when pure#
M.H. calculated,
slightly viscous,
d*°1.316; n^°1.4712;
53*42; found, 52.85.
Anal* Subst., 0.3061 g.; cc. of 0.1051 N AgN03 , 16.66.
Calculated for C8H 160ClBr; total halogen, 47.38; found,
total halogen, 47.28.
d.
Preparation of 2-propyl-6-methyldioxane.
A mixture of 15 g. potassium hydroxide, 150 cc. water,
and 24.35 g. (0.1 mole)
of <^-propyl- f t -bromoethyl
/? 1-chloroisopropyl
ether were heated in a bomb for three hours at an oil bath
temperature of 200°.
The cooled mixture was worked up in the
usual way to yield 1.2 g. of pure 2 —propyl— 6—methyldioxane.
This represents an 8.3^ yield from the halogenated ether.
dioxane was refractionated over metallic sodium,
The
b.p. 165° at
750 m m . ; d4 °0.915; n^°1.4284; M. R. calculated, 40.23; found,
40.57.
Analysis for carbon and hydrogen gave the following
percentage composition:
H, 11.19.
calculated for C8H l60s : C, 66.61;
Found: C, 66.52; H, 11.12.
-72-
B.
Glycolaldehyde Dimer.
A_»
Preparation of glycolaldehyde dimer.
113
The directions of Fischer and Feldman
to a slight extent.
were varied
In our hands a modified procedure
seemed to facilitate Increased yields.
A solution of 200 g.
of tartaric acid in 140 cc. water was cooled to -30°C. by an
alcohol-carbon dioxide bath.
Then solutions of 4 g. of ferrous
sulfate in 40 cc. water and 5 g. of sodium potassium tartrate
in 40 cc. water were added.
Over a period of five to six
hours, 145 cc. of 30^ hydrogen peroxide were added.
The reac­
tion mixture was continually stirred while the temperature
was never permitted to rise above -10°C.
After stirring for
two mor e hours, the solution was set In the refrigerator for
seven days.
The crystallized dihydroxymaleic acid was then
filtered and dried in a vacuum desiccator over sulfuric
acid.
Yield was 36 g. or 18.0^ of theoretical.
Thirty-seven g. of dihydroxymaleic acid were covered
with 92 cc. of dry pyridine.
carbon dioxide occurred.
A copious evolution of
After standing for two hours
at 50°, carbon dioxide ceased coming off and the mixture
was filtered free of unreacted insoluble ferric dihydroxymaleate.
The filtrate was evaporated under vaoftum at
(lig) Fischer and Feldman, Ber., 62, 854 (1929)
30° and the residue placed in a vacuum dessicator over
sulfuric acid to remove the last traces of pyridine.
The residue was then triturated with cold acetone and
filtered.
Yield of glycolaldehyde dimer was 8.5 g. or
56*6% of theoretical.
No attempt was made to purify the
dimer since it was used In further preparations.
Preparation of glycolaldehyde dimer diacetate.88
Five grams of the glycolaldehyde dimer were dissolved in
25 cc. of dry pyridine and the solution cooled to 0°.
With
vigorous stirring at that temperature, 15 cc. acetic anhydride
were added dropwise.
The solution was stirred for one hour
and placed in the refrigerator for one day.
The solid was
then filtered and recrystallized from absolute alcohol.
Yield of the acetate dimer was 1.8 g . , m.p. 157°-8°.
Fischer reported a yield of 3.8 g. under similar conditions.
3.
Preparation of glycolaldehyde dimer dibromide.
Three and one-half grains
03
of glycolaldehyde dimer
diacetate were triturated for five minutes with 25 cc. of a
saturated solution of hydrogen bromide in glacial acetic
acid.
The mass was permitted to stand for one-half hour at
room temperature and filtered quickly.
The solid was
triturated with three 15 cc. portions of dry, cold ether and
again filtered.
The residue was recrystallized from chloro-
fonn to yield 2.4 g. of glycolaldehyde dimer dibromide.
-74-
Hecrystallization was accomplished by dissolving the solid
In chloroform, filtering, and placing the filtrate in a
vacuum dessicator until crystals appeared.
If the crystal­
lization was done slowly, by removing the solvent under
vacuum, the crystals appeared as fine white needles.
They
decomposed at 134°, with slight darkening at 104-106°.
4.
a.
Preparation of dioxadiene.
From crystalline 2,3,5,6— tetrachlorodioxane.
The synthesis of dioxadiene was essentially the same as
that carried out by Summerbell and Uimhoefer.
A variation
in the iodine-tetrachlorodioxane ratio and the final isolation
of the product resulted in an increased yield.
Thirty grams (1.25 moles) of magnesium turnings and
500 cc. of dry n-butyl ether were placed in a one-liter,
three-necked flask equipped with an efficient, mercury-sealed
stirrer and a bent tube of large diameter,
so arranged as to
connect with a condenser set for distillation.
then placed in an oil bath at 80° and 120 g.
The flask was
(0*472 mole) of
iodine were added in small portions over the course of one
hour.
The bath temperature was raised to 145° and maintained
there during the entire reaction.
With rapid stirring, 32.g.
(0.141 mole) of symmetrical tetrachlorodioxane were added In
small portions over a period of two hours.
Distillation
of both the dioxadiene and the n-butyl ether occurred as
soon as the crystals hit the surface of the reaction mixture.
Two 120 cc* portions of dry n-butyl ether were added during
the course of the reaction to replace that lost by distillation
After all of the tetrachlorodioxane had been added, the bath
temperature was raised to 165° to facilitate complete
distillation*
The distillate (370cc.) was redistilled
through a 40 cm* Podblelnlak column*
obtained distilling up to 110°*
A 15 g# fraction was
This fraction was redistilled
through the same column yielding 8*8 g. dioxadiene, boiling
at 75°-76°/757 mm.
This represents a 73.3^ yield of dioxadiene
from symmetrical tetrachlorodioxane.
b.
From high boiling, chlorinated, liquid dioxanes.
The procedure followed in this
as outlined above.
preparation was exactly
The dehalogenating reagent was prepared
from 30 g. of magnesium turnings,
500 cc. of dry n-butyl
ether, and 120 g. (0.472 mole) of iodine.
A mixture of
high boiling chlorinated fractions of dioxane (120°-140°/25mm.)
(50 g.), was added dropwise in the usual manner.
Fractionation
of the 450 cc. distillate resulted in 1.0 g. of a product
distilling up to 73° at atmospheric pressure and 2.1 g. of
dioxadiene (73-75°)•
Another fraction weighing 4.6 g. was
obtained boiling at 75-120°•
All fractions, Including the
large amount of butyl ether in the residue were unsaturated
to bromine in carbon tetrachloride.
Only the dioxadiene and
lower boiling fraction are heavier than water.
boiling fractions float when mixed with water.
The higher
5.
Preparation of 2,5-Dibromodioxane.
Dry hydrogen bromide was passed into a solution of
2.26 g. (0.026 mole) of dioxadiene in 50 ml. dry chloroform.
At the end of one hour the source of hydrogen bromide was
removed and the mixture filtered rapidly*
The solid was
placed temporarily in the refrigerator, while the filtrate
was put in a vacuum dessicator to facilitate further crystal­
lization.
As soon as crystals appeared, the mixture was
placed in the refrigerator for three hours, after which the
solid was quickly filtered.
6.0
All solids were combined, yielding
g. of crude 2,5-dibromodioxane.
yield of the theoretical.
chloroform.
This represents a 93.7^
The solid was recrystallized from
Enough solvent was added to effect complete
solution at room temperature.
The solution was then placed
In a salt ice bath and the chloroform evaporated under vacuum
until crystallization occurred.
and air dried.
The solid was quickly filtered
Care must be exercised to prevent decomposition,
on recrystallization,
since even at room temperature such action
takes place readily.
If the chloroform is removed at a
slow rate, crystal growth takes place, the solid consisting
of fine white needles.
There is slight darkening at 104-106°,
with complete decomposition at 134°.
Anal. Subst., 0.2946 g., cc. AgN03 (1 cc. = .0252 g.),
15.92.
Calculated for C4H 60sBr2 ; Br, 65.01.
Found, 64.85.
- 77
— — P y r o l y s i s and proof of structure of 2 , 5-dibromodioxane.
Thirty ml. of distilled water were added to 0.0416 g. of
2,5-dibromodioxane and the mixture heated over a steam bath
for two hours with occasional stirring.
To the cooled
solution was then added 0.35 g. of p-nitrophenylhydrazine
hydrochloride in 50 ml. of a 2b% acetic acid solution*
The
mixture was heated on a steam bath for one hour and the red
precipitate filtered and washed with water, alcohol, and
ether in succession.
constant weight.
The precipitate was dried at 110° to
Weight of substance, 0.1122 g.
Calculated
weight, for two equivalent moles p-nitrophenylosazone of
0.1102 g.
Calculated weight, assuming product to
bep-nitrophenylhydrazone of diglycolaldehyde, 0.0625g.
... Identity of 2,5-dibromodioxane with F i s c h e r ^ glycolaldehyde
dimer dibromide.
The dibromide synthesized from glycolaldehyde dimer and
2 , 5-dibro modi oxane are identical in many respects.
Both
compounds darkened at 104° and decomposed completely at 134°.
A mixed melting point was not depressed.
Both substances
decompose rapidly on standing at room temperature,
evolution of hydrogen bromide.
occurs even at 0°.
with the
Considerable decomposition
Their crystal structures, long white
rectangles, appear to be identical under the microscope.
the f,Becke line*1 method,
Using
the average refractive index for the
2,5-dibromodioxane crystal is 1.618.
The average for the
glycolaldehyde dimer dibromide crystal is 1.609.
This slight
discrepancy is probably due to the difficulty of working with
a substance which decomposes readily and is somewhat soluble
in the liquids used for the determination*
Paralleling the hydrolysis procedure for 2,5-dibromodioxane,
the treatment of the glycolaldehyde dimer dibromide resulted
in the followings
weight of dibromide hydrolyzed, 0.0730 g.
Weight of precipitate,
0.1895 g.
Calculated weight for 2
equivalent moles p-nitrophenylosazone of glyoxal, 0.1829 g.
Calculated weight, assuming product to be p-nitrophenylhydrazone
of diglycolaldehyde,
8.
0.1108 g.
Synthesis of the diacetate from 2,5-dibromodioxane and
identity with glycolaldehyde dimer diacetate.
A mixture of S g. (0*012 mole)
of 2,5-dibromodioxane,
80 ml* of dry toluene, and 5 g. of silver acetate was
for twelve hours.
shaken
The mixture was filtered and the solid
washed with 20 ml. of dry toluene.
The combined filtrate was
evaporated under reduced pressure at 40°.
The residue was
recrystallized from absolute ethyl alcohol yielding white
crystals melting at 151-4°.
The crystals were recrystallized
several times from absolute ethyl alcohol and finally melted!
at 157-8°•
Glycolaldehyde dimer diacetate melted at 157-8°.
A mixed melting point showed no depression.
9*
Preparation of 2.5-dihydrofuran.
The method followed was essentially that of Henninger.114
Two hundred grams of erythritol and 500 g. of formic acid
1*185) were refluxed for four hours with continual stirrin
The excess water and formic acid was distilled off and the
bath temperature raised to 200°.
The liquid residue started
to decompose and a gas began coming off.
The gas was trapped
in a water cooled spiral condenser and the excess passing
through was further condensed after being washed by a concen­
trated potassium hydroxide solution.
Any further gas escaping
was bubbled through an ether trap at 0°.
All distillates were combined after the bath temperature
bad reached 310°.
The total distillate was fractionated and
the fraction distilling below 90° at atmospheric pressure was
dried over potassium carbonate.
The dried fraction was
redistilled and the portion coming over at 64-70° was dried
over metallic sodium for one day.
The liquid was redistilled
through a 30 cm. Podbielniak column, yielding 12.9 g. of
2,5-dihydrofuran.
This represents a 11.3# yield.
Solubility
In water at 20°, 36.18 g./lOO g. water.
10.
Attempted synthesis of p-nitrophenylhydrazone of
diglycolaldehyde.
a.
A solution of 1.1 g. of 2,5-dihydrofuran in 25 cc.
glacial acetic acid was ozonized for twelve hours.
( 114)
Henninger, Ann. de Chim. et de Phys.,
At the end
[ 6 j 7, 211 (1886)
of that time, a sample of the solution did not decolorize a
solution of bromine in acetic acid.
The acetic acid solution
of the ozonide was diluted with an equal volume of water and
10 g. zinc dust was added.
Traces of silver nitrate and
hydroquinone were also added.
The mixture was then refluxed
over a steam bath for four hours.
A solution of 5.5 g.
p-nitrophenylhydrazine hydrochloride in 100 cc.
25^ acetic
acid was prepared.
The hydrolyzed solution was filtered free of zinc dust
and zinc acetate, and the filtrate diluted with an equal
volume of water, thus making it approximately a 25^ acetic
acid solution.
To this solution was then added the p-nitro-
phenylhydrazine solution.
An immediate precipitation of a
red, flocculent solid occurred.
The mixture was digested
on the steam bath for two hours, cooled to room temperature,
and filtered.
The solid was then washed successively with
water, alcohol, acetone,
1.3 g.
and ether.
Yield of the solid was
After successive recrystallizations from alcohol
and pyridine,
the small red needles melted at 304-6° (uncorr.) •
An alcoholic sodium hydroxide solution of the substance gave
a blue color.
The same color test is given by p-nitrophen-
ylosazone of glyoxal "which melts at 306°.
b.
The ozonolysis and subsequent hydrolysis of 2.2 g.
2,5-dihydrofuran was repeated exactly as described above.
A solution of 11 g* of p-nitrophenylhydrazine hydrochloride
in 300 cc. 25^ acetic acid was prepared.
To the cold, hydrolyzed
solution was added the cold solution of p-nitrophenylhydrazine
hydrochloride•
There resulted an immediate precipitation
of a yellow solid*
It was filtered and recrystallized from
50% ethyl alcohol, yielding 7 g. orange-red needles melting
at 156°.
The substance was indicated to be p-nitrophenyl­
hydrazine by reacting it with benzaldehyde to give the hydrazone
m . p . 190°•
p-NitrophenylhydrazIne melts at 157°, and the
p-nitrophenylhydrazone of benzaldehyde melts at 191°.
c.
The following experiment was carried out with the
hope of isolating the free dialdehyde.
A solution of 2.2g.
(0.031 mole) of 2,5-dihydrofuran in 50 cc. dry carbon
tetrachloride was ozonized for twelve hours.
Hydrolysis
7
was carried out according to the method of Hurd and Filachione.
To the solution of the ozonide were added 50 cc. of a 20$
pyruvic acid solution.
off at 70-80° •
on a steam bath*
The carbon tetrachloride was distilled
The mixture was then slowly heated to 100°
It was thus heated until the evolution of
carbon dioxide ceased.
The cold solution was extracted with
100 cc. of ether and the ether solution washed free of acid
with sodium bicarbonate solution.
The ether extract was
dried over sodium sulfate and the ether removed by distillation.
There was practically no residue.
a
11.
Synthesis of 4-pentene-l-ol.
A solution of allylmagnesium bromide was prepared from
(a)
checked by Dr. R. R. Umhoefer.
278 g*
(2*5 moles) allyl bromide, 750 cc* dry ethyl ether
116*116
and 60 g* magnesium turnings*
To the filtered
Grignard reagent was added dropwise a solution of 88 g*
(2 moles)
of ethylene oxide in 500 cc. dry cold benzene*
The benzene solution was kept at 0° during its dropwise
addition with efficient stirring.
The mixture was gently
refluxed for two hours and the excess ether distilled off
until the temperature of distillate had reached 65° •
It
was then refluxed for two hours and hydrolyzed with iced
dilute hydrochloric acid*
Five hundred cc* ether were
shaken with the hydrolyzed mixture*
The ether-benzene layer
was separated, dried over sodium sulfate and distilled*
fraction was obtained at 139-143°, weighing 98 g*
A
This is a
61*2% yield of pentene-4-ol-l based on the ethylene oxide
a,b
<3o
a
so
a,b
used*
B.P* 140°/746 mm*
; d 4 0.8461 ; n 4 1*4346.
12*
a*
Preparation of dioxene*
At room temperature*
The directions followed in this preparation were those
46
outlined by Summerbell and Umhoefer*
In a three—necked,
two-liter flask equipped with a dropping funnel, bulbed
(iX6j
(lie)
oilman and McGlumphy, Bull. soc. chim., 43 1322 (1928)
Young, Prater, and Winstein, J* Am* Chem* Soc*, 55
4908 (1933)
(a)
Paul, ref* 103, reported: disO.848; n ^ s1.4305; b*p. 142°.
(b)
Robinson, ref* 104, reported:
750 mm*
n^
1*4312; b.p* 136
at
condenser fitted with a calcium chloride tube, and a mercurysealed stirrer, were placed 900 cc. dry ether and 62 g.
(2.55 moles) of magnesium turnings.
With constant stirring,
68.7 g* (0.3 mole) of iodine were added in small portions*
When the mixture became colorless, 233.5 g. (1.5 moles) of
2,3—dichlorodioxane in 200 cc* dry ether were added dropwise
at such a rate that the color of the mixture due to the free
iodine was never darker than amber.
At the end of eight hours
the entire amount of dichlorodioxane had been added and stirring
was continued until the mixture became colorless*
It was then
poured onto cracked Ice and the ether layer separated and
dried over sodium sulfate.
distillation,
After removal of the ether by
the residue was fractionated.
A fraction
distilling at 91-93°/747 mm. weighed 50*6 g.
This Is a
39.8$ yield of dioxene based on the 2,3-dichlorodioxane*
b*
At the temperature of 140°.
This attempt to improve the yield of dioxene was based
on the synthesis of dioxadiene in high yields*
Conditions
in the dioxadiene preparation were simulated as far as
possible*
To 1200 cc. of dry n-butyl -ether in a five-liter, three­
necked flask equipped as described under the dioxadiene
synthesis,
there were added 82.6 g. (3*4 moles) of magnesium
turnings*
Over the period of one and one-half hours 91.5 g.
(0*4 moles)
of iodine were added in small portions*
Tv/o moles
of dichlorodioxane (314 g.), diluted with an equal volume of
n-butyl ether, were added dropwise to the stirring mixture,
an oil bath temperature being maintained at 140°.
Distillation
occurred as soon as the dichlorodioxane hit the surface of
the solution*
At the end of one—half hour appreciable
tarring was noted*
The addition required four hours*
To
replace the ether lost by distillation, 400 cc. of n-butyl
ether were added during the course of the reaction.
distillate,
The total
after the bath temperature had been raised to
165°, was 850 cc*
Fractionation through an efficient column
yielded no dioxene*
c*
By means of a zinc reagent*
A one—liter, three—necked flask was fitted with a dropping
funnel, a mercury-sealed stirrer, and a bent tube of large
diameter connected to a condenser set for distillation*
Three hundred grams
(5.1 moles) of acetamide were placed in
the flask and the flask placed in an oil bath at 125° •
To
the melted acetamide were added 140 g. of zinc dust (2*1 moles),
106 g*
(1 mole)
sodium iodide*
of sodium carbonate, and 30 g.
(0*2 mole) of
The mixture was kept at 125°, through the
course of the reaction*
With vigorous stirring, 157 g* (1 mole)
of dichlorodioxane were added dropwise to the mixture over
a period of three hours*
Distillation of the dioxene occurred
as soon as the dichlorodioxane hit the surface of the reacting
substances.
Addition was so controlled that the color of
the reaction due to the liberated iodine was never darker
than light brown*
sulfate.
The distillate was dried over sodium
Fractionation of the dried liquid yielded 14.6 g.
of* dioxene distilling at 90-91* 5° *
Tiiis represents a
V7% yield*
Solubilities *
The solubilities of dioxene and of the subsequently
described 2 , 5-dlhydrofuran in water were determined by a
XX7
method outlined by Sobottka and ^ohn
•
To a measured
quantity of distilled water at 20°C*, containing a very
small amount of a lipoid soluble dye, there is added through
a microburette the organic liquid utiose solubility is to be
deteimined*
The dye used for this was Sudan IV*
At the
saturation point one drop of the organic liquid will take
up the floating dye, resulting in floating, dark, trans­
parent droplets on the surface of the liquid*
In the case
of dioxene saturation was reached when 5*1 cc* of dioxene
had been .added to 100 cc* water at 20°C*
Solubility
of dioxene is therefore 5*53 g* per 100 g* water.
One cc*
of water required 0*38 cc* of 2 , 5-dihydrofuran for saturation
at 20°C* or a solubility of 36.18 g* per 100 g. water*
13*
Synthesis of 5-hydroxy-5-oxapentanal p-nitrophenylhy-
drazone*
A mixture of 2 g. (0.023 mole) of dioxene, 2 drops
concentrated hydrochloric acid, and 25 cc. water were re­
fluxed over a steam bath for one hour.
(117)
To the cooled solution
Sobottka and Kohn, J. Am* Chem. Soc*, J53, 2935 (1931)
was added a cold solution of 2.6 g# p-nitrophenylhydrazine
hydro chloride in 100 cc# water#
The resulting orange solid
was filtered and recrystallized from 50^ ethyl alcohol*
product consists of orange needles melting at 142°•
was 3.1 g# of the hydrazone or 56#b% of theoretical*
The
Yield
Analysis
indicated the possibility of the hydrazone being a dihydrate#
Of the theoretical 13#01$ water in the dihydrate, only 8.65^
could be removed by drying under 15 mm# pressure at 134° •
Anal# Calculated for CloH 1304feU s #2HJ30; N, 15#26.
Found,
15*05, 15#19, 14.91#a
14#
Oxidation of 5-hydroxy-5-oxapentanal p-nitrophenylhydrazone.
A mixture of 0.1821 g# (0.00076 mole) of the above hydrazone,
0.3814 g*
(0*0018 mole) of p-nitrophenylhydrazine hydrochloride,
and 100 cc# of a 25^ acetic acid solution were refluxed for
5 hours.
The mixture turned from the original yellow orange
to red in thirty minutes.
quantitatively#
The mixture was cooled and filtered
After being washed with 95^ ethyl alcohol,
the red residue was air dried and weighed.
Wt., 0.1561 g.
Theoretical weight of the glyoxal osazone was 0.2205 g*
The
red solid was twice recrystallized from pyridine, yielding
short red needles, m.p. 310° (uncorr.).
The substance gave
a blue color with alcoholic sodium hydroxide, a typical re­
action of p-nitrophenylosazone of glyoxal.
A mixed melting
point with the known osazone showed no depression.
(a) Analysis by Mr. E*. L. Washburn.
15#
Chlorination of Dioxane#
a#
Isolation of 2,5—dichlorodioxane#
A solution of 6 g# iodine in 3#1 kilograms of dry dioxane
was heated to 95° and chlorinated for twenty hours#
Excess
hydrogen chloride gas was removed by passing dry air through
the solution for five hours#
It was then distilled under
reduced pressure to yield approximately 2 liters of distillate
below 40° at 30 mm.
This large amount of low boiling distillate
indicated a very incomplete chlorination*
The residue and dis­
tillate were recombined and chlorination continued for twenty
more hours at the same temperature*
At the end of this time
the source of heat was removed and the chlorine passed through
the solution at a very rapid rate for six more hours with
rapid stirring#
hour
The temperature of the bath during this six
period remained at 46°•
At the completion of the chlorination, it was noticed that
the inside of the condenser was coated with a brown solid*
This was removed and dry air passed through the solution for
fifteen hours
to remove the excess hydrogen chloride#
Fractionation of the liquid under vacuum yielded 2.8 kilograms
of 2,3-dichlorodioxane*
The solid found in the condenser was recrystallized three
times from petroleum ether#
needles melting at 118-119°•
The yield was 0.23 g# of long white
These needles were subsequently
shown to be 2,5-dichlorodioxane*
The crystals melt at 119°
when pure and decompose slightly when exposed to air at room
temperature*
Anal# Calculated for C4H 602C12 ; Cl, 45*22*
Found, 44.63#
Thirty ml# of distilled water were added to 0.0421 g* of
2, 5-dich.lorodioxane and the mixture hydrolyzed over a steam
bath for one and one-half hours*
To the solution was added a
solution of 0.35 g* of p-nitrophenylhydrazine hydrochloride
In 50 cc* of 2b% acetic acid*
The mixture was heated on a
steam bath for one hour and the red precipitate filtered
quantitatively*
After being successively washed with water,
alcohol, and ether, it was dried at 110° for three hours to
constant weight#
Weight,
0*1628 g#
Calculated weight, for
2 equivalent moles of p-nitrophenylosazone of glyoxal, 0*1772 g#
Calculated weight, for one equivalent mole of the osazone,
0*0886 g#
Calculated weight, assuming product to be
p-nitrophenylhydrazone of diglycollicaldehyde, 0*1005 g#
The red powder was recrystallized from pyridine to yield
short red needles, melting at 304-306°*
The characteristic
blue color with the glyoxal osazone was obtained when the red
needles were treated with alcoholic sodium hydroxide.
b#
With sulfuryl chloride in the presence of peroxides*
(1) Excess sulfuryl chloride#
A mixture of 2 2 g* (0#25 mole) of dioxane and 202*5 g.
(1.5 moles)
of sulfuryl chloride was placed in a 200 cc.
round bottom flask equipped with an efficient condenser.
As
soon as 0#5 g# benzoyl peroxide was added an Immediate reaction
took place with evolution of heat and gases (sulfur dioxide
and hydrogen chloride).
The mixture was refluxed for seven­
teen hours until the reaction appeared to be complete as
-89r*
1y
9 1r -
U»rAr>
evidenced b y the cessation of gas formation.
The liquid was
fractionated under vacuum#
I.
up to 102°
II.
at
102-108°
III.
92-105°
IV.
105°
36
36 mm.
mm.
1.1 g.
36 mm*
9.0 g.
25-32 mm.
27.0 g.
32 mm.
4.8 g.
at
Fraction IV partially solidified In tlie refrigerator to yield
0.6 g. of rectangular crystals melting at 100°.
These crystals
were symmetrical tetrachlorodioxane.
(2) Excess dioxane.
One mole (88 g.) of dioxane was mixed with 68 g. (0.5
mole)
of sulfuryl chloride in a 500 cc. round-bottom flask
equipped with an efficient reflux condenser.
benzoyl peroxide were added,
As soon as 0.5 g.
a violent reaction occurred and
It was necessary to cool the reaction mixture with an ice
bath.
The reaction was over in thirty minutes, leaving a
clear, colorless solution.
This liquid was fractionated
under reduced pressure, yielding 24 g. of a distallate at
88-90° under 23 mm.
There were no higher or lower boiling
fractions under these conditions after the excess dioxane had
been removed.
tionation.
The mixture tarred considerably during frac­
The distillate dolidifled in the refrigerator and
melted at 14°•
Refractionation and solidification gave
the same melting point.
A mixture of 1.4 g. of the liquid and 25 cc. water was
refluxed over a steam bath for one hour.
One-half of the
cooled solution was made alkaline with dilute sodium hydroxide
and an equivalent amount of benzoyl chloride was added*
The mixture was shaken and permitted to stand for two hours*
It was then extracted with ether, and the ether evaporated
on the steam bath*
The residue was reGrystallized from
50# alcohol to yield a white crystalline solid melting at
72° •
Glycol dibenzoate melts at 73°.
Evidently, ethylene
glycol was one of the hydrolytic products*
To the other half of the hydrolyzed solution was added
an equivalent of phenylhydrazine hydrochloride in water*
The resulting yellow precipitate was recrystallized from
50# alcohol to yield a solid melting at 169-170°•
The
melting point of the phenylosazone of glyoxal is 169-170°•
One of the products of hydrolysis must have been glyoxal*
The liquid (1*4653 g*i believed to be 2,3-dichlorodioxane,
was hydrolyzed with 50 ml* water*
To the hydrolyzed solution
was added a water solution of 4 g* of p-nitrophenylhydrazine
hydrochloride*
The resulting red solid was filtered and washed
successively with water,
alcohol, and ether*
dried to constant weight at 110°*
It was then
Weight, 2*987 g*
On
hydrolysis of 1*4653 g. of 2,3-dichlorodioxane, the resulting
glyoxal would have yielded 3*066 g* of the glyoxal p—
nitrophenylasozone •
The substance melting at 14° and distilling
at 88— 90°/23 mm* was 2,3-dichlorodioxane.
16 0
Chlorina t ion of 2,3-dichlorodioxane#
a#
Preparation of 2,3,5,6-tetrachlorodioxane#
A very rapid stream of chlorine was passed through 100 g
of 2,3—dichlorodioxane at 125—130°•
Stirring was rapid
enough to cause the formation of a foam above the liquid#
Dry air was passed into the solution for one day and the
liquid, fractionated under reduced pressure#
I -
110-114°
at
II -
114-120°
at
III-
120-125°
at
IV -
125-130°
at
it
130° —
at
ft
V -
18mm#
61 g#
ti
49 g#
i»
4 g#
6 g#
-9 g#
10 g#
Residue
All fractions solidified on standing in the refrigerator#
room temperature, part of each fraction liquified.
At
From
fractions I and II were Isolated 16 g. of symmetrical
tetrachlorodioxane, m*p# 59-60°•
From fractions III, IV,
and V were isolated 7 g# of symmetrical tetrachlorodioxane,
m.p# 143°•
The filtrates from these fractions were again
placed in the refrigerator to yield 4 g. crystals, m.p. 59-60
and 2 g#, m.p# 143°#
The total yield of symmetrical
tetrachlorodioxane was 29 g. or a yield of 11#8$.
b#
W ith sulfuryl chloride in presence of peroxides.
A mixture of 45 g. (0.285 mole)
118 g.
(0#57 mole)
of dichlorodioxane,
sulfuryl chloride, and 0.5 g. benzoylpero-
xide were placed in a 200 cc. round-bottom flask equipped
-
with an efficient condenser.
92 -
Very little reaction occurred
until the mixture was refluxed*
Refluxing was continued
for twenty—five hours, after which time gas evolution had
ceased.
I -
The mixture was distilled under reduced pressure.
up to 106° at 23 mm.
6.5
II -
106-112°
«
24.0 g.
Ill-
112-116°
"
20.0 g.
IV -
116-121°
f*
6.1 g.
121°—
”
6.3 g.
V -
g.
The last two fractions solidified partially on
standing in the refrigerator for several days.
The solid was
filtered and recrystallized from methyl alcohol to yield
5.1 g. of symmetrical tetrachloridioxane, m.p. 101°•
IV. SUMMARY
A general method for the preparation of dioxane homologs
hy means of the correctly substituted ( 3 , (? t-dihalogen #bh©rs
has been further developed and studied.
The above procedure has been employed to synthesize a
series of 2,6-dialkyldioxanes for the first time.
The
density, boiling point and refractive index vary in a
uniform manner with increasing size of substituent.
2.3-Diethyldioxane
been prepared.
and 2-ethyl-3-methyldloxane have also
The latter,
a new substance,
is the first
example of an unsymmetrical 2,3-dialkyldioxane .
The unusual situation with respect to refractivity inter­
cept discovered by TJmhoefer in the study of ruonoalkyldioxanes was also found to be characteristic of the new
dioxane series.
Constants with possible future useful­
ness in identifying new members of these homologous
series have been evaluated.
Physical data indicate that cis and trans isomers of the
2.3-dialkyldioxanes may exist.
It has been suggested
that these different isomers might arise through different
methods of synthesis.
Incidental to the preparation of the dialkyldioxanes,
the
following halogenated ethers have been prepared for the
f Ir s t t Ime :
a.
«<-clilorobutyl /9 — chloroethyl ether.
94-
b.
4 -chloroethyl
c.
4 , R -dibromobutyl ( 3 -chloroethyl ether.
d.
4 , (3 —dibromoethyl
e.
4 -ethyl- ( 3 -bromobutyl /^-chloroethyl ether.
f.
6*
b.
6*
-chlorolsopropyl ether.
/?—chlorolsopropyl ether.
4 -methyl- (3 -bromobutyl /?-chloroethyl ether.
•©thy 1-
(3 -bromoethyl
o( —me thy 1— /? —bromo ethyl
A m e w and more convenient
/^-chlorolsopropyl ether.
(3 —chlorolsopropyl ether.
synthesis of 4-pentene-l-ol has
been devised.
7.
The yield of dioxadiene from symmetrical tetrachlorodioxane
has been increased to
by increasing the ratio of
iodine to tetrachlorodioxane.
The isolation of dioxadiene
when liquid chlorinated dioxanes are employed in its
synthesis, indicates the existence of one or more 2,3,5,6tetrachlorodioxanes in these high boiling fractions.
8
.A
9.
n e w synthesis of dioxene has been developed.
A n e w compound, 2,5-dich loro dioxane, has been isolated
as a product of the chlorination of dioxane.
Further
study of the factors in the chlorination of dioxane which
affect the yield of the symmetrical tetrachlorodioxane
has been undertaken.
It has been confirmed that at
chlorination temperatures below 80°, the 100° melting
Isomer of symmetrical tetrachlorodioxane Is the only one found.
10. Attempts to prepare diglycolaldehyde p-nitrophenylhydrazone
were unsuccessful under the conditions studied.
-So­
11.
Hydrolysis of dioxane results in the formation of an
aldehyde, probably 5-hydroxy-3-oxapentanal,
of which
the p-nitrophenylhydrazone has been prepared.
12.
It has been indicated that ether bonds beta to a
functional group may be split by comparatively mild
reagents.
Thus,
the treatment of the supposed 5-
hydroxy-3-oxapentanal p-nitrophenylhydrazone with
excess p-nitrophenylhydrazine in 25/o acetic acid re­
sulted in the formation of glyoxal p-nitrophenylosazone.
13.
The dioxane structure for dimeric glycolaldehyde and
related compounds have hitherto lacked synthetic
experimental confirmation.
of definite structure,
Using dioxadiene,
a compound
It has been possible to synthe­
size 2,5-dibromodioxane whose structure was indicated
by the hydrolysis products.
295-Diacetoxydioxane was
then synthesized from 2,5-dibromodioxane.
14.
The 2,5-dibromodioxane and 2,5-diacetoxydioxane are
identical in melting point and other properties to the
corresponding compounds which are two of the Fischer
series of glycolaldehyde derivatives.
The dioxane
structure for this series is thus definitely placed
upon an experimental basis*
V,
)
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VI. VITA
Name:
Leo Kant Rochen
Born:
New York,
New York; October 9, 1913
Educ at ion:
Public Schools of Newark, New Jersey,
City, 1920-1929
and New York
College of the City of New York, 1929-1933
Columbia University, 1933-1934
Northwestern University, 1936-1940
Positions:
Research Assistant, Northwestern University, 1938-1940
Public ations:
nThe Structure of C-lycolaldehyde Dimer1', with
R* K. Summerbell, presented before the
Organic Division of Auerican Chemical Society
at the Spring, 1939 meeting in Baltimore, Lid.
Affiliations:
Sigma XI
Phi Lambda Upsilon
American Chemical Society
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