Some beta - hydroxypropyl sulfides and their derivatives.

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Title:
Some beta - hydroxypropyl sulfides and their derivatives.
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72 leaves : ; 28 cm.
Language:
English
Creator:
Todsen, Thomas Kamp, 1918-
Publication Date:

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Subjects / Keywords:
Sulfur compounds   ( lcsh )
Organic compounds -- Synthesis   ( lcsh )
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bibliography   ( marcgt )
theses   ( marcgt )
non-fiction   ( marcgt )

Notes

Thesis:
Thesis (Ph. D.)--University of Florida, 1950.
Bibliography:
Bibliography: leaves 69-71.
Statement of Responsibility:
By Thomas Kamp Todsen.
General Note:
Manuscript copy.
General Note:
Biography.

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University of Florida
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All applicable rights reserved by the source institution and holding location.
Resource Identifier:
aleph - 000549690
notis - ACX3986
oclc - 13277432
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AA00003989:00001


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SOME BETA-HYDROXYPROPYL SULFIDES

AND THEIR DERIVATIVES










By
THOMAS KAMP TODSEN


A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF
THE UNIVERSITY OF FLORIDA
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY











UNIVERSITY OF FLORIDA
September, 1950









PREFACE


Since this dissertation is concerned primarily with the

synthesis of compounds new to the literature, the material

relative to the synthesis of these compounds is given in de-

tailed form for all products as an aid to further investi-

gation, even though essentially the same basic procedure may

be followed in the synthesis of compounds of a homologous

series.

All temperatures are based on the centigrade scale and

its symbol is, therefore, omitted.

Melting and boiling points given are corrected values,

the thermometers used in obtaining these values having been

calibrated against a set of thermometers standardized by the

United States Bureau of Standards.

References are given in the manner usual for technical

reports of this sort. Journal abbreviations are those stand-

ardized upon by *Chemical Abstracts".









TABLE OF CONTENTS


Page

I. INTRODUCTION .....*................*... ..**..... 1

II. DISCUSSION AND EXPERIMENTAL .................... 3

A. Synthesis of chlorohydroxypropyl sulfides .. 3

1. Review of the literature ...........**** 3

2. Experimental ........................... 4

a. Synthesis of l-methylthio-3-

chloro-2-propanol ...........,.... 4

b. Synthesis of 1-ethylthio-3-

chloro-2-propanol ................. 5

e. Synthesis of 1-propylthio-3-

chloro-2-propanol .................. 6

d. Synthesis of 1-butylthio-3-

chloro-2-propanol .................. 6

e. Synthesis of 1-pentylthio-3-

chloro-2-propanol .*.......**....... 7

f. Synthesis of 1-hexylthio-3-

chloro-2-propanol ................,, 8

3. Discussion of experimental results ..... 9

4. Summary *............................ 9

B. Synthesis of epoxypropyl sulfides .......... 13

1. Review of the literature ............... 13

2. Experimental ........................... 14


iii







Pare


a. Synthesis of 1-methylthio-2,3-

epoxypropane ....................... 14

b. Synthesis of 1-ethylthio-2,3-

epoxypropane ..................... 15

o. Synthesis of 1-propylthio-2,3-

epoxypropane ....................... 16

d. Synthesis of 1-butylthio-2,3-

epoxypropane *.*.......*............ 17

e. Synthesis of l-pentylthio-2,3-

epoxypropane ....................... 18

f. Synthesis of 1-hexylthio-2,3-

epoxypropane *....*................ 18

3. Discussion of experimental results ..... 19

4. Summary ................................ 24

C. Synthesis of hydroxydisulfides ............. 24

1. Review of the literature ............... 24

2. Experimental ........................... 25

a. Synthesis of 1,3-bis(methylthio)-2-

propanol ........................... 25

b. Synthesis of 1,3-bis(ethylthio)-2-

propanol 25......................... 25

c. Synthesis of 1,3-bls(propylthio)-2-

propanol ........................... 26

d. Synthesis of 1,3-bia(butylthio)-2-

propanol ..............*...........* 27

iv







Page


e. Synthesis of 1,3-bis(pentylthio)-2-

propanol **************.*********

f. Synthesis of 1,3-bis(hezylthio)-2-

propanol .......,,.......,.....

3. Discussion of experimental results .....

4. SuHRary ********************************

D. Synthesis of chlorohydroxypropyl sulfones .

1. Review of the literature ...,...........


2.


3.


Experimental .........................*

a. Synthesis of l-methylsulfonyl-3-

chloro-2-propanol ..............0..*

b. Synthesis of 1-ethylsulfonyl-3-

chloro-2-propanol .................

c. Synthesis of l-propylsulfonyl-3-

chloro-2-propanol .................

4. Synthesis of 1-butylsulfonyl-3-

chloro-2-propanol ..,...*,,,....,*.

e. Synthesis of 1-pentylsulfonyl-3-

chloro-2-propanol ..................

f. Synthesis of 1-hexylsulfonyl-3-

chloro-2-propanol ................

Discussion of experimental results .....


4. Summary eeeeeeee.ee..e.oe..e,...e..e.eeo

E. Synthesis of epoxypropyl sulfones .....*....







Page

1. Review of the literature ............... 39

2. Experimental ..............*....** ...... 39

a. Synthesis of l-methylsulfonyl-2,3-

epoxypropane *...................... 39

b. Synthesis of l-ethylsulfonyl-2,3-

epoxypropane .............*......... 39

a, Synthesis of 1-propylsulfonyl-2,3-

epoxypropane ........... ......... 40

d. Synthesis of l-butylsulfonyl-2,3-

epoxypropane ...........*...*....... 40

e. Synthesis of l-petylsulfonyl-2,3-

epoxypropane 4...................*.* 41

f. Synthesis of 1-hexylsulfonyl-2,3-

epoxypropane ....................** 41

3. Discussion of experimental results ..... 42

4. Summary .............................. 43

F. Synthesis of hydroxydisulfones ............. 43

1. Review of the literature ............... 43

2. Experimental .......... ..........*..*.. 43

a. Synthesis of 1,3-bis(methylsulfonyl)-

2-propanol ......................... 43

b. Synthesis of 1,3-bis(ethylsulfonyl)-

2-propanol ......................... 45

o. Synthesis of 1,3-bis(propylsulfonyl)-

2-propanol ...4..................... 45

vi







Page
d. Synthesis of 1,3-bis(butylsulfonyl)-

2-propanol ,.....,,,,................ 46

oe Synthesis of 1,3-bis(pentylsulfonyl)-

2-propanol ...............*****...... 46

f. Synthesis of 1,3-bis(hexylsulfonyl)-

2-propanol ,*******.,*,.*..,,******** 47

3. Discussion of experimental results ...... 47

4, Summary .8.,,o.*..,...*0.,,.,.,. ,,o.,., 48

G. Synthesis of alkylthioalkoxypropnols .e..... 48

1. Review of the literature ................ 48

2. Experimental *...............,,,,,.,,,,,, 48

a. Synthesis of l-ethylthio-3-methoxy-2-

propanol ........................... 48

b. Synthesis of l-ethylthio-3-ethoxy-2-

propanol *..*......... ............. 50

e. Synthesis of l-ethylthio-3-propoxy-2-

propanol ........................... 51

d. Synthesis of l-ethylthio-3-butoxy-2-

propanol *................*.,***..... 52

e. Synthesis of l-propylthio-3-methoxy-

2-propanol ,*....*,,*............... 53

f. Synthesis of l-propylthio-3-ethoxy-2-

propanol ....**** ................. 54

g. Synthesis of l-propylthio-3-propoxy-

2-propanol *.*,*......*,**........... 54

vii







Page


h. Synthesis of l-propylthio-3-butoxy-

2-propanol .......................

3. Discussion of experimental results .....

4. Summary ..o... 00o... ........o..

III. PROOF OF STRUCTURE .........................

A* Of chlorohydroxypropyl sulfides and epoxy-

propyl sulfides ............................

1, Review of the literature ..o....**......


2,


3.

B. Of

1.

2.


3.


Experimental ...........................

a. The action of chlorohydroxysulfides

on skin tissue......................

b. The formation of formaldehyde from .

(1) 1-ethylthio-3-chloro-2-propanol

(2) l-ethylthio-2,3-epoxypropane ..

Discussion and summary .................

hydroxydisulfides and hydroxydisulfones

Review of the literature ...............

Experimental ...........*...............

a. Identity of bis(butylthio)propanols.

b. Reaction of disulfones with sodium

hydroxide .. ......... .............

Discussion and summary .................


IV. SUMMARY..........o,.................o ........

V. BIBLIOGRAPHY ..........O.......................

VI. ACKNOWLEDGEMENTS ..............*............

viii







Page

VII. BIOGRAPHY ...R ............................... 73

VIII. COMMITTEE REPORT .............................. 74









LIST OF FIGURES


Figure Page


1 Refractive Index vs. Molecular Weight for

Chlorohydroxypropyl Sulfides ................ 10

2 Density vs. Molecular Weight for Chloro-

hydroxypropyl Sulfides ...................... 11

3 Molecular Refraction vs. Molecular Weight

for Chlorohydroxypropyl Sulfides ............ 12

4 Refractive Index vs. Molecular Weight for

Epoxypropyl Sulfides ...................... 21

5 Density vs. Molecular Weight for Epoxy-

propyl Sulfides ............................ 22

6 Moleoular Refraction vs. Molecular Weight

for Epoxypropyl Sulfides .................... 23

7 Refractive Index vs. Molecular Weight for

Hydroxydisulfides ........................... 30

8 Density vs. Molecular Weight for Hydroxy-

disulfides .,................................ 31

9 Molecular Refraction vs. Molecular Weight

for Hydroxydisulfides ...........,,.......... 32

10 Melting Point vs. Molecular Weight for

Chlorohydroxypropyl Sulfones ............... 38









Figure


11 Melting Point vs. Molecular Weight for

Epoxypropyl Sulfones ....................... 44

12 Melting Point vs. Molecular Weight for

Hydroxydisulfones ........**......... .....* 49

13 Refractive Index vs. Molecular Weight for

Alkylthioalkoxypropanols .................... 57

14 Density vs. Molecular Weight for Alkyl-

thioalkoxypropanols ......................... 58

15 Molecular Refraction vs. Molecular Weight

for Alkylthioalkoxypropanols ..........*..*.. 59


Page









INTRODUCTION


Though the preparation of epoxy compounds and the re-

actions of these compounds with substances containing active

hydrogen have been known for nearly one hundred years, only

in relatively recent times have studies been conducted on the

specific reaction between alkene oxides and mercaptans. The

dearth of material on this subject, as well as a desire to

extend the work of Flores-Gallardo (1) on epoxy ethers to

epoxy sulfides, initiated this investigation.

The purpose of the investigation was primarily to:

1. Synthesize chlorohydroxysulfides through the inter-

action of epichlorohydrin and mercaptans;

2. Synthesize epoxysulfides a) from chlorohydroxysul-

fides and sodium hydroxide and/or b) from epichlorohydrin and

alkali mercaptides;

3. Synthesize hydroxydisulfides a) from epoxysulfides

and mercaptans, b) from chlorohydroxysulfides and alkali

mercaptides, and/or e) from epichlorohydrin with an equimolar

alkali mercaptide- mercaptan mixture;

4. Synthesize chlorohydroxysulfones through the oxi-

dation of chlorohydroxysulfides;

5. Synthesize epoxysulfones from chlorohydroxysulfones

and sodium hydroxide;

6. Synthesize hydroxydisulfones by oxidation of








hydroxyd sulfides;
7. Synthesize alkylthiohydroxy ethers from epoxysulfides
and alcohols;
8. Investigate the course of the reactions outlined in
1 and 3 above through proof of the structure of the products
obtained in each.
The reactions through which the above syntheses are
carried out may be diagrammed as follows:


CH C1HCH 20 + RSH zncl2RSCH% CHOHCH 2Cl RS 2CH2CHOHCBHC1

NaOH j NaOH
CH2 CiCHC ,- + RSNa --- RSCH CHCH 0 RSO2CH2CHCi20

RSH R'OH
CH 2C1CCH + RSNa ----RSCH CROUCH SR RSCH CHOHCH OR'
2 2 LRSH 2I 2 2 2

|0)
RSO2CH2CHORCH2802R








DISCUSSION AND EXPERIMENTAL


A. Synthesis of chlorohydroxypropyl sulfides

1, Review of the literature

Studies concerned with the reaction of epoxides with

hydrogen sulfide or mercaptans are met with only in relatively

recent literature, the first being in 1935 when Chichibabin

and Bestuzhev (2) investigated the reaction between ethylene

oxide and hydrogen sulfide. In the same year, Nenitzescu and

Scarlatescu (3) conducted a much more extensive study, in-

volving the reaction of ethylene oxide, cyclohexene oxide,

and epichlorohydrin with hydrogen sulfide, ethyl mercaptan,

propyl mereaptan, thiophenol, and benzyl meroaptan. The re-

action of these mercaptans with epiohlorohydrin, either with

or without an activated charcoal catalyst, produced chloro-

hydroxypropyl sulfides in 90% yields, this being the first

reported preparation of these compounds.

Sjoberg (4) reported the reaction of epiohlorohydrin

with hydrogen sulfide in alkaline solution to give 1-

mereapto-3-chloro-2-propanol. Tseou and Pau (5) investigated

the high temperature interaction of ethylene oxide and

hydrogen sulfide, in the presence of a catalyst. The Shell

Development Company (6) obtained l-pentylthio-3-chloro-2-

propanol by the method of Nenitzesou and Scarlatescu (3).

By treating 1,3-dichloro-2-propanol with sodium ethyl








mercaptide or sodium benzyl mereaptide in aqueous alcohol,

Rothstein (7) synthesized 1-ethylthio-3-ohloro-2-propanol and

1-bensylthio-3-chloro-2-propanol. It is probable that, in

this reaction, the first step is a dehydrohalogenation of the

1,3-dichloro-2-rropanol to epichlorohydrin, which then reacts

with the mercaptan present to give the end product. This

follows from the work of Fairbourne, Gibson, and Stephens (8)

who showed that this is the mode of addition of alcohols to

1,3-dichloro-2-prepanol in the presence of a base.

2. Experimental

a. Synthesis of l-methylthio-3-chloro-2-propanol

One mole (48 g.) of methyl mercaptan, one mole (92 g.)

of epichlorohydrin, one gram of anhydrous zinc chloride, and

150 ml. of dioxane were placed in a 500 ml., three-necked,

round-bottomed flask, equipped with thermometer, stirrer,

and reflux condenser, and refluxed for three hours. Low

boiling material (dioxane and unreacted meroaptan and

epichlorohydrin) was removed under aspirator vacuum at a

maximum temperature of 700, using a water bath as a source

of heat. The residue was then distilled at 1.4 m., 1-

methylthio-3-chloro-2-propanol being collected at 550

B.P. t 550 at 1.4 m.

Yield t 56 g., 0.4 mole, 40%
n25 t 1.5094
2>








dB5 : 1.2250
4
MP : 34.30 (found); 35.03 (calc.)

% C : 34.28 (found); 34.16 (cale.)
% : 6.25 (found); 6.45 (calc.)
b. Synthesis of 1-ethylthio-3-chloro-2-propanol
0.8 mole (50g.) of ethyl mercaptan and 0.5 mole (46 g.)
of epichlorohydrin were placed in a 200 ml., three-necked,
round-bottomed flask, equipped with thermometer, stirrer, and
reflux condenser. The well stirred mixture was heated and on
reaching reflux, one gram of zinc chloride was added through
the condenser. The mixture was heated for an additional five
minutes to initiate the reaction. At this point the heat of
reaction necessitated cooling. After the reaction ceased,
heating was resumed for one hour. The excess ethyl mercaptan
was removed under aspirator vacuum and the residue was dis-
tilled at 1.5 mm, l-ethylthio-3-chloro-2-propanol being
collected at 68-69.

B.P. : 68-69o at 1.5 am.
Yield t 57 g., 0.37 mole, 74%
n25 1.5047
D
d25 1.1651
4

MD : 39.36 (found); 39.66 (oale.)
% C t 38.80 (found); 38.83 (cale.)
% :B 7.53 (found); 7.17 (Calc.)








c. Synthesis of l-propylthio-3-ohloro-2-propanol
0.6 mole (45 g.) of propyl mercaptan and 0.5 mole (46 g.)

of epichlorohydrin were placed in a 200 ml., three-necked,
round-bottomed flask, equipped with stirrer, thermometer, and

reflux condenser. The mixture was heated to reflux and one
gram of zinc chloride was added through the reflux condenser.

After five minutes, a vigorous reaction occurred which was

controlled by strong cooling. After completion of the re-
action, the mixture was heated to the former reflux tempera-

ture (840) for thirty minutes, cooled and distilled at 1.4
mm., l-propylthio-3-chloro-2-propanol being obtained at
79-800
B.P. : 79-80o at 1.4 am.

Yield t 61 g., 0.36 moles, 73%

n25 t 1.4986
25
d 2 1.1286

MD 43.92 (found); 44.28 (cale.)
% C : 42.46 (found); 42.79 (calc.)

% : 7.76 (found); 7.76 (calo.)
d. Synthesis of l-butylthio-3-chloro-2-propanol
0.56 mole (50 g.) of butyl mercaptan and 0.5 mole

(46 g.) of epichlorohydrin were placed in a 200 =l., three-
necked, round-bottomed flask, equipped with stirrer, ther-

mometer, and reflux condenser. The mixture was heated to

reflux with vigorous stirring and one gram of zinc chloride

6








was added through the reflux condenser, After three minutes,
a vigorous exothermic reaction necessitated strong cooling.
The cooled mixture was again heated to the former reflux

temperature for thirty minutes. It was then distilled at 0.5

mm., l-butylthio-3-chloro-2-propanol being collected at 76-
770,
B.P. t 76-770 at 0.5 m,.

Yield : 57 g., 0.32 mole, 64%
n25 : 1.4940
D
d25 t 1.0883
4
M : 48.86 (found); 48.90 (cale.)
% C s 45.74 (found); 46.01 (calc.)
% H : 8.35 (found); 8.28 (calc.)

e. Synthesis of l-pentylthio-3-chloro-2-propanol
0.5 mole (52 g.) of pentyl mercaptan and 0.5 mole

(46 g.) of epichlorohydrin were placed in a 200 ml., three-
necked, round-bottomed flask, equipped with thermometer,
stirrer, and reflux condenser. The stirred mixture was

heated to reflux and one gram of zinc chloride was added

through the condenser. The resulting vigorous reaction

necessitated external cooling, and when this reaction had

subsided the mixture was heated to the former reflux tem-

perature for thirty minutes. It was then distilled at 0.5

mR., 1-pentylthio-3-chloro-2-propanol being collected at 85-

860







B.P. : 85-86 at 0.5 m.
Yield t 45 g., 0.23 mole, 46%
n825 1.400
D
25
d 4 1.0664

MD t 53.34 (found); 53.51 (cale.)
%C t 48.82 (found); 48.84 (cale.)

% R t 8.84 (found); 8.71 (calc.)
f. Synthesis of 1-hexylthio-3-chloro-2-propanol
0.55 mole (85 g.) of hexyl mercaptan and 0.5 mole

(46 g.) of epichlorohydrin were placed in a 200 al., three-
necked, round-bottomed flask, equipped with thermometer,

stirrer, and reflux condenser. The mixture was heated to
reflux with stirring and one gram of zinc chloride was added
through the condenser. After subsidence of the strongly
exothermic reaction, the mixture was reheated to the original
reflux temperature for thirty minutes, then distilled at 0.5
mu., 1-hexylthio-3-chloro-2-propanol being obtained at 96-
97o
B.P. : 96-97 at 0.5 mm.
Yield : 78 g., 0.37 mole, 74%
n25 z 1.4880
d25 z 1.0465
4
MjD 58.02 (found); 58.14 (cale.)
% C 50.92 (found); 51.28 (cale.)
% N t 9.21 (found); 9.09 (eale.)









3. Discussion of experimental results

Figures 1, 2s and 3 show the variation in densities,

refractive indices, and molecular refractions of the

chlorohydroxypropyl sulfides with molecular weights.

In this portion of the investigation, an attempt was

made to synthesize 1-ethylthio- and l-propylthio-3-chloro-

2-propanols by the method of Nenitsescu and Scarlatescu (3).

The results were entirely negative, almost complete recovery

of the initial reactants being effected in each case. Use

of sulfuric acid as a catalyst according to the procedures

of Flores- Gallardo and Pollard (1) and Sworn, Billen, and

Knight (9) resulted in a yield of 44%. Zinc chloride proved

to be the best catalyst, reducing the reaction time from a

minimum of four hours to thirty minutes and providing yields

of about 70%.

The method outlined was satisfactory for the preparation

of all except the methyl derivative, The reaction with

methyl mercaptan leads to a highly viscous polymerized

material, probably through the formation of sulfonium link-

ages which are much more easily formed in methyl sulfides.

It was necessary, in this instance, to carry out the reaction

in an inert solvent.

4. Summary

A new method for the preparation of alkylthiochloro-

propanols is described. Individual syntheses for methyl,





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ethyl, propyl, butyl, amyl, and hexyl derivatives are describ-

ed, of which methyl, butyl, and hexyl are newly reported com-

pounds. The boiling points of the ethyl and propyl derivatives

are the only physical constants previously reported in the

literature.

B. Synthesis of epoxypropyl sulfides

1. Review of the literature

Epoxides have been prepared in many ways. Epichlorohydrin

or epibromohydrin were made by Berthelot and Luca (10) as one

of the products of the reaction of phosphorus trichloride or

phosphorus tribromide on glycerol, Dehydrohalogenation of a

1,2 chlorohydrin by alkali hydroxides in various solvents is

an old and well known process for the preparation of these com-

pounds (1), (8), (11), (12), (13), (14), (15). More recently,

oxidation of a double bond, either by perbenzoic acid (16),

(17) or by air in the presence of appropriate catalysts (18),

(19) has come into prominence as a preparative method for

oxiranes.

The synthesis of epoxysulfides has been carried out by

dehydrohalogenation and by a modified Williamson synthesis.

Nenitzescu and Scarlatescu (3) produced l-ethylthio-2,3-

epoxypropane by dehydrohalogenation of l-ethylthio-3-chloro-

2-propanol with aqueous sodium hydroxide and by treatment of

epichlorohydrin with an aqueous solution of sodium ethyl

mereaptide. The Shell Development Company (6) reported the








synthesis of 1-pentylthio-2,3-epoxypropane by dehydrohalogena-

tion. Gilman and Woods (20) treated epichlorohydrin in

anhydrous alcohol with mercaptides of the type (CH3)2NCH2

(CH2) CH2SNa to obtain epoxysulfides.

2. Experimental

a. Synthesis of 1-methylthio-2,3-epoxypropane

Two moles (190 g.) of epichlorohydrin was placed in a

one 1,, three-necked, round-bottomed flask, equipped with

stirrer, reflux condenser, and dropping funnel. The flask

was cooled in an ice-salt mixture and a freshly prepared ice-

cold potassium methyl mercaptide solution (prepared by drop-

vise addition of 2.1 moles (100 g.) of methyl meroaptan to a

cooled stirred solution of 2.1 moles (137 g.) of 85% KOH in

150 ml. of water) was added dropwise with vigorous stirring.

The stirring was continued for two hours after the addition

was completed. The layers that formed were separated and the

aqueous layer extracted twice with ethyl ether. The ethereal

extracts and the non-aqueous layer were combined, dried over

anhydrous calcium sulfate, and distilled at 70 mm. 1-

methylthio-2,3-epoxypropane was obtained at 84.5-850.

B.P. i 84.5-850 at 70 a.

Yield* : 39.5 g., 0.38 mole, 19%

n25 t 1.4817

This preparation yielded both this product
and 1,3-bis(methylthio)-2-propanol.








d : 1.0583
4
M : 28.04 (found); 28.34 (calc.)

% C 45.52 (found); 48.12 (cale.)

%H 8.07 (found); 7.74 (cale.)
b. Synthesis of l-ethylthio-2,3-epoxypropane

(1) A solution of 19 grams of 85% potassium hydroxide
in 40 ml. of water was placed in a 200 ml., three-necked,
round-bottomed flask, equipped with thermometer, stirrer,
and dropping funnel. To the vigorously stirred, cooled

solution was added dropwise 0.11 mole (17 g.) of 1-ethylthio-
3-chloro-2-propanol. After stirring for two hours following
addition of the chlorohydroxysulfide, the mixture was
extracted twice with ethyl ether, the combined extracts dried
over anhydrous calcium sulfate, and the dried ethereal

solution distilled; 7 grams (54%) of l-ethylthio-2,3-epoxy-
propane was obtained.

(2) A solution of two moles (82 g.) of sodium hydroxide
in 300 ml. of water was placed in a one 1., three-necked,

round-bottomed flask, equipped with stirrer, reflux condenser,
and dropping funnel. The flask was cooled in ice slush and

two moles (124 g.) of ethyl mercaptan added dropwise. The
resulting sodium ethyl meroaptide solution was added dropwise

with vigorous stirring to two moles (185 g.) of epichlorohydrin
contained in a similarly equipped flask. After addition of
the mercaptide solution, the mixture was stirred for two hours.







The layers of the mixture were separated, the aqueous layer

extracted twice with ethyl ether, and the extracts and non-

aqueous layer combined and dried over anhydrous potassium

carbonate. The dried solution was distilled, 1-ethylthio-2,

3-epoxypropane being collected at 3.5 m.

B.P. : 41.5-42 at 3.5 mm.

Yield : 163 g., 1.38 moles, 69%
n25 : 1.4757

d254 1.0170

fn i 32.76 (found); 32.96 (calo.)
% C 50.73 (found); 50.81 (calc.)
% s 8.77 (found); 8.53 (cale.)
e. Synthesis of l-propylthio-2,3-epoxypropane

0.33 mole (31 g.) of epichlorohydrin was placed in a
200 ml., three-necked, round-bottomed flask, equipped with

stirrer, reflux condenser, and dropping funnel. To the cool-

ed, vigorously stirred epichlorohydrin was added dropvise a

solution of potassium propyl mercaptide (prepared from 24

grams of 85% potassium hydroxide and 25 grams of propyl mer-

captan). Stirring was continued for two hours after the

addition was completed. The two layers formed were separated,

the aqueous layer extracted twice with ethyl ether, and the

extracts and the non-aqueous layer combined. The resulting
solution was dried over anhydrous calcium sulfate, filtered,
and distilled, l-propylthio-2,3-epoxypropane being collected

at 43-440 at 2 m.








B.P. : 43-440 at 2 mm.
Yield : 25 g., 0.19 mole, 57%
n25 : 1.4730
D
d2 0.9905
4
MD : 37.44 (found); 37.58 (cale.)
SC 5 54.66 (found); 54.50 (cale.)
% : 9.59 (found); 9.15 (calc.)
d. Synthesis of 1-butylthio-2,3-epoxypropane
0.23 mole (43 &,) of 1-butylthio-3-chloro-2-propanol
and 400 ml. of ethyl ether were placed in a one 1., three-

necked, round-bottomed flask, equipped with stirrer and

reflux condenser. 40 grams of powdered sodium hydroxide was
slowly added to the vigorously stirred, cooled solution.
Stirring was continued for twelve hours. The mixture was
then filtered and dried over anhydrous calcium sulfate. The
dried solution was filtered, the ethyl ether removed under

reduced pressure, and the residue distilled at 70 mm.,
l-butylthio-2,3-epoxypropane being obtained at 132-132.50
B.P. : 3132-132.5 at 70 mm.

Yield : 17 g., 0.12 mole, 50%
25
n5 : 1.4723
d25 : 0.9716
4
MD : 42.17 (found); 42.20 (oale.)
% C 57.72 (found); 57.49 (oale.)

SH : 10.14 (found); 9.65 (oalc.)








*. Synthesis of l-pentylthio-2,3-epoxypropane
0.33 mole (31 g.) of epichlorohydrin was placed in a

200 ml., three-necked, round-bottomed flask, equipped with

stirrer, reflux condenser, and dropping funnel. A potassium

pentyl meroaptide solution was prepared by dropwise addition

of 0.33 mole (35 g.) of pentyl mercaptan to a cooled, stirred

solution of 0.33 mole (24 g.) of potassium hydroxide in 100

ml. of 95% ethanol. This mercaptide solution was added drop-

wise to the cooled, stirred epichlorohydrin. Stirring vas

continued for six hours. The resulting mixture was extracted

three times with ethyl ether and the combined extracts dried

over anhydrous potassium carbonate. The dried,filtered

solution was distilled, 1-pentylthio-2,3-epoxypropane being

obtained at 67-68o at 1.6 mm.

B.P. : 67-68 at 1.6 mm.

Yield : 27 g., 0.17 mole, 50%
25
n 2 1.4707
D
d25 : 0.9544
4
MD : 46.90 (found); 46.82 (cale.)
% C 59.92 (found); 59.95 (cale.)

%H : 10.26 (found); 10.06 (cale.)

f. Synthesis of l-hexylthio-2,3-epoxypropane

0.33 mole (31 g.) of epichlorohydrin was placed in a
200 ml., three-necked, round-bottomed flask, equipped with

stirrer, reflux condenser, and dropping funnel. A potass-







lum hexyl mercaptide solution was prepared by dropwise addi-

tion of 0.33 mole (40 g.) of hexyl mercaptan to a cooled,
stirred solution of 0.33 mole (24 g.) of 85% potassium hy-

droxide in 100 ml. of 95% ethanol. The mercaptide solution
was added dropwise to the cooled, stirred epichlorohydrin.

Stirring was continued for six hours. The resulting mixture

was extracted three times with ethyl ether and the combined

extracts dried over anhydrous potassium carbonate. The dried,

filtered solution was distilled, 1-hexylthio-2,3-epoxypropane

being collected at 69.5-70o at 0.7 mm,

B.P. t 69.5-700 at 0.7 mm.

Yield : 17.5 g., 0.11 mole, 32%
n25 : 1.4702
D
d25 : 0.9471
4
MD 51.36 (found); 51.44 (calo.)

% C : 62.00 (found); 62.01 (cale.)
% : 10.64 (found); 10.41 (sale.)
3. Discussion of experimental results

The method of Nenitzescu and Scarlatescu (3) for the
preparation of epoxysulfides from chlorohydroxysulfides was

repeated with fair results. It is felt that dehydroha-
logenatien according to the modification of Flores-Gallardo

and Pollard (1) is somewhat more advantageous since the pro-
duct of the initial reaction with alkali is an essentially

dry, ethereal solution of thie desired epoxysulfide and is
much easier to handle.








The method of Nenitzescu and Soarlatescu (3) which in-

volves the reaction of epichlorohydrin and an aqueous solution

of an alkali mercaptide included the dropwise addition of

epichlorohydrin to the cold sodium mercaptide solution.

Repetition of this preparation led to very poor yields. It

was supposed that, in the presence of the excess of mercaptide,

the epichlorohydrin reacted completely to form bis (alkylthio)

propanols. When the order of addition was reversed, i.e.,

when the mercaptide solution was added dropwise to epichloro-

hydrin, there was an excess of epichlorohydrin present at all

times, so that good yields were obtained.

In the calculation of the molecular refractions of these

epoxysulfides, the value for the atomic refraction of epoxy

oxygen used was 1.890, as determined by Flores-Gallardo and

Pollard (1).

Figures 4, 5, and 6 show the variation in refractive

index, density, and molecular refraction for these compounds

as their molecular weight varies.

It may be seen that, generally, yields were of the same

order, whether a chlorohydroxysulfide was dehydrohalogenated

or a mercaptide was reacted with epiohlorohydrin. Therefore,

on the basis of the mercaptan used directly or to form

intermediates, the mercaptide-epichlorohydrin method gave

better overall yields.




.7''C-~--------------


21

S- Figure 4.


174 -






160






146







132






118






104


1.4740


1.4780


1.4820


25
nD


-' .
--4


Refractive Index vs. Molecular
.-- .. ....... Weight for Epoxypropyj _Sulfildes
of the Type RSGH26HHH2, R being
Methyl through -Heyl







i-


1.4700








r-


SI I .. I ...
-.. 0 .. .. ....1 1..2_0, 0I


S -igure ,.

:. Density vs. Molecular Weight for
-i--;- -~1 ; pbxypr a Sulfides of the Type
S;-- RSCHg H, R being Methyl
-- 14- -- -v--:- -- -gh Hexyl




-- --,-- -- -- ..... ... J ~- | ... -.
I I
e -








--.-..g.,-.----.. .. -- .
-. --. .
I '
















-09800 1.0200 1.0600
:o --- ------ ---











,h_- ... i _.. .- -. .+ ,.
i






-I -- "-- r .

















-'I I, -- -









23
Figure 6.


174--






160






146






1-32






118






104


28 00 36.00 44000 52 00


Molecular Refraction vs. Molecular
Weight for Epocypropy i Sulfides of
the Type RSCH2CHCHO2, R being
-Methyl and Hexyl -


52.00


28.00


36.00


44.00









4. Summary
Syntheses and physical properties were determined for

the six epoxypropyl sulfides, methyl through hexyl. Syn-

thesis of the ethyl and pentyl compounds, together with the

physical properties of the ethyl compound, have been previous-

ly reported (3), (6).

C. Synthesis of hydroxydisulfides

1. Review of the literature

The dialkyl or diarylthiopropanols have been prepared in

the following three ways: treatment of epiohlorohydrin with

an alkaline solution of a mercaptan, treatment of 1,3-dichloro-

2-propanol with a mercaptide solution, and treatment of an

alkylthioohloropropanol with a mercaptide solution.

1,3-bis(ethylthio)-2-propanol was synthesized from 1,3-
dichloro-2-propanol and sodium ethyl mercaptide solution by

Tschugaeff and Kobljanski (21). From, Kappeller, and Taub-

mann (22) treated either epichlorohydrin or l,3-dichloro-2-

propanol with an alcoholic solution of sodium benzyl mercap-

tide to obtain 1,3-bis(benaylthio)-2-propanol. 1-benzylthio-

3-ethylthio-2-propanol was prepared by Rothstein (7) from

l-ethylthio-3-chloro-2-propanol and sodium benzyl mereaptide

solution. The Shell Development Company (8) reported treating

epichlorohydrin with decyl or hydroxyethyl mercaptan, followed

by treating the product with aqueous sodium hydroxide, to
obtain 1,3-bis(decylthio)-2-propanol or 1,3-bis(2-hydroxyethyl)-







2-propanol, respectively.
2. Experimental

a. Synthesis of 1,3-bia(methylthio)-2-propanol
Reference is made to Section II,B,a,"Synthesis of 1-

methylthio-2,3-epoxypropane*, for procedure. 1,3-bis(methyl-

thio)-2-propanol was collected at 159-161' at 50 mm.
B.P. : 159-1610 at 50 mm.

Yield : 27.5 g., 0.35 mole, 17.4%
n2 1.5359
d25 $ 1.1256
4
HD : 42.17 (found); 42.76 (cale.)

% C : 39.63 (found); 39.47 (cale.)

SH : 8.30 (found); 7.95 (calc.)
b. Synthesis of 1,3-bis(ethylthio)-2-propanol

0.5 mole (48 g.) of epichlorohydrin was placed in a 500

ml., three-necked, round-bottomed flask, equipped with stirrer,
reflux condenser, and dropping funnel. A meroaptide-mercaptan
mixture was prepared by dropwise addition of one mole (82 g.)

of ethyl mercaptan to a cooled, stirred solution of 0.5 mole

(33 g.) of 85% potassium hydroxide in 100 ml. of water. The
mercaptide-mercaptan mixture was added dropwise to the cooled,

stirred epichlorohydrin, the resulting mixture being stirred

an additional two hours. The mix was then extracted with

ethyl ether. The extract was dried over anhydrous calcium

sulfate. The dried, filtered, ethereal solution was distilled








at 1 m., 1,3-bis(ethylthio)-2-propanol being obtained at

93.8-94o.
B.P. : 93.8-94o at 1 m.
Yield : 41 g., 0.23 mole, 46%

n25 1.5148
25
d : 1.0528
4
M S 51.63 (found); 51.99 (calc.)
% C : 46.33 (found); 46.62 (cale.)
H : 9.24 (found); 8.95 (cale.)

e. Synthesis of 1,3-bis(propylthio)-2-propanol

0.43 mole (40 g.) of epichlorohydrin was placed in a
500 ml., three-necked, round-bottomed flask, equipped with

stirrer, reflux condenser, and dropping funnel. A mercaptide-
mercaptan mixture was prepared by dropwise addition of 0.86

mole (65 g.) of propyl mercaptan to a cooled, stirred solution

of 28 g. of 5S potassium hydroxide in 100 ml. of water. The

mixture was added dropwise to the cooled, stirred epichloro-

hydrin, the product being stirred an additional four hours.

The mix was extracted with ethyl ether and the extract dried

over anhydrous potassium carbonate. The dried, filtered

solution was distilled, l,3-bis(ethylthio)-2-propanol being

collected at 104-105 under 0.7 m.

B.P. : 104-105 at 0.7 m.
Yield : 56 g., 0.28 mole, 64%

n25 S 1.5063
D







d25 : 1.0144
4
%D 861.06 (found); 61.23 (oslc.)

% C : 51.56 (found); 51.90 (ealo.)
% H 9.77 (found); 9.68 (calc.)
d. Synthesis of 1,3-bis(butylthio)-2-propanol

0.09 mole (13 g.) of 1-butylthio-2,3-epoxypropane and

0.11 mole (10 g.) of butyl mercaptan were placed in a 200 ml.,
three-necked, round-bottomed flask, equipped with thermometer,
stirrer, and reflux condenser. The stirred mixture was heated
to reflux and 0.2 gram of zinc chloride was added through the
condenser. Heating was continued until a sudden clearing of
the milky mixture, accompanied by a rapid rise in temperature,
indicated completion of the reaction. The residue was
distilled at 1 mm., 1,3-bis(butylthio)-2-propanol being

obtained at 133.
B.P. : 1330 at 1 Mm.
Yield : 11.5 g., 0.05 mole, 55%
n25 : 1.5007
D
d25 ~ 0.9867
4
MD 70.55 (found); 70.48 (calc.)

% C : 55.84 (found); 55.88 (cale.)
% : 10.53 (found); 10.23 (cale.)

e. Synthesis of l,3-bis(pentylthio)-2-propanol
0.15 mole (24.5 g.) of l-pentylthio-2,3-epoxypropane
and 0.15 mole (16 g.) of pentyl mercaptan were placed in a








800 ml., three-necked, round-bottomed flask, equipped with

stirrer, thermometer, and reflux condenser. 0.5 gram of

potassium hydroxide was added through the condenser while the

mix was stirred rapidly. After five minutes, the temperature

rose to the boiling point of the mercaptan, necessitating

cooling. After apparent completion of the reaction, the mix

vas stirred an additional four hours. The product was dis-

solved in ether and the solution dried over potassium

carbonate. The ether was removed and the residue distilled

at 0.8 m.a, 1,3-tis(pentylthio)-2-propanol being collected

at 147.5-148.5.

B.P. : 147.5-148.50 at 0.8 m.

Yield : 27 g., 0.10 mole, 67%

n25 : 1.4960
D
d4 0.9692
4
M t 79.71 (found); 79.70 (calo.)

% C t 58.98 (found); 59.03 (calo.)
% H : 10.89 (found); 10.67 (cale.)

f. Synthesis of 1,3-bis(hexylthio)-2-propanol

0.10 mole (17.5 g.) of 1-hexylthio-2,3-epoxypropane and

0.10 mole (12 g.) of hexyl mercaptan were placed in a 200 ml.,

three-necked, round-bottomed flask, equipped with thermometer,

stirrer, and reflux condenser. While the solution was stirred
rapidly, 0.5 gram of potassium hydroxide was added through the

condenser. After five minutes, the temperature rose to reflux,

28









necessitating external cooling. After the reaction subsided,

stirring was continued for four hours. The mix was dissolved

in ether and the ethereal solution dried over potassium

carbonate. Ether was removed and the residue distilled at

1.5 am., 1,3-bis(hexylthio)-2-propanol being obtained at

183-184o

B.P. : 183-1840 at 1.5 mm.

Yield I 18.5 g., 0.06 mole, 63%
n25 : 1.4927
D
d25 : 0.9547
4
M : 89.00 (found); 88.94 (cale.)

% C : 61.21 (found); 61.58 (oale.)

% : 10.54 (found); 11.03 (calc.)

3. Discussion of experimental results

While it would appear from the yields given that the re-

action of mercaptans with epoxysulfides is more advantageous

than the reaction of epiohlorohydrin with an excess of

mereaptide solution for preparation of hydroxydisulfides,

consideration of the time required to prepare the intermediate

epoxysulfides and inclusion of the fact that these epoxy-

sulfides are obtained in 50% yields leads to the conclusion

that the advantage lies with the latter method.

Figures 7, 8 and 9 indicate the variation in physical

properties of the hydroxydisulfides from dimethyl through

dihexyl.




















292








264


286-


,Mol
Wt.


208t


t


180-


-- -52


i': :::: '"
i'
.---,


Methyl through Hexyl
I














--- -
I I















S-- -


















-
. ,





,


1.4900


1.5100


1.5500


n2-5
nD


.- -





50 -

,Figure 7.

Refractive Index vs. Molecular
.. :-Weight for Hydroxyd:isulfides of
S +th Ti ATm RIC1TTTCnHfH-R' R al a


Ileg


.4


i: :
.--~ '





I 1


Figure _8


Density vs. Molecular Weight
-for HTydroxydisulfidea of the
Type RSCHG2HOHCH2SR, R being
Methyl through Hexyl


0 9500 0 9900 1.0300 1. 0700 1.1100


! I


i I


292






264






236







208






180


152


0.9900


1.0300


1.0700


1.1100


0.9500





i--" -:- l .-








-- --- th eyl
I t __ I _.

t ; : -.. : ',- -
" ; !~ .-. .- ,--- : "1 ... .' : "




















---------- -- -
S '
'7t :. :' : --- "^ i '













.. .... ._.. ."































42 00 58.00 7400 90.00
.._ i : -- -
'I
,. .. r. n ...























*.. I T RO, b
-'* :,.., 2 -- -'-'------ -- -, -
---"I- --, .








4. Summary

Syntheses are given for six 1,3 bis(alkylthio) propanols.

Only 1,3-bls(ethylthio)-2-propanol has been reported previous-

ly.

D. Synthesis of ehlorohydroxypropyl sulfones

1. Review of literature

Sulfones have been prepared by oxidation of sulfides and

sulfoxides with potassium permanganate, chromic anhydride,

sodium dichromate, nitric acid, sodium hypochlorite, chlorine,

hydrogen peroxide, and various organic peroxides and peracids

in a variety of solvents. In addition, the action of metal

sulfinates on organic halides and the action of metal alkyls

on sulfonyl halides have been used as means for the preparation

of sulfones. Suter (23) lists over 500 references dealing with

these compounds.

Chlorohydroxypropyl sulfones have been prepared by

oxidation of the corresponding chlorohydroxypropyl sulfides.

Nenitzescu and Scarlatesou (3) oxidized l-phenylthio-3-chloro-

2-propanol to 1-phenylsulfonyl-3-chloro-2-propanol with

potassium permanganate. Rothstein (7) obtained 1-ethylsulfonyl-

3-chloro-2-propanol and 1-benzylsulfonyl-3-chloro-2-propanol

by oxidation of the sulfides in acetic acid solution with 30%

hydrogen peroxide.

2. Experimental

a. Synthesis of 1-methylsulfonyl-3-chloro-2-propanol

Fourteen grams of 1-methyl thio-3-chloro-2-propanol and

33








50 ml. of glacial acetic acid were placed in a 250 ml. beaker.
To this solution 30 ml, of 30% hydrogen peroxide was added
dropwise with stirring, at such a rate that ebullition did
not become too violent. Acetic acid, water and excess hydro-
gen peroxide were removed under aspirator vacuum while heat-
ing on the steam bath. The residue slowly crystallized over
two days and was recrystallized from ethyl ether.
M.P. I 58.7-59.00
Yield t 13 g., 76.5%
% C 27.42 (found); 27.83 (calc.)
% H : 5.16 (found); 5.26 (calc.)
b. Synthesis of l-ethylsulfonyl-3-chloro-2-propanol
Ten grams of l-ethylthio-3-chloro-2-propanol and 50 ml.
of glacial acetic acid were placed in a 250 ml. beaker. 30
ml. of 30% hydrogen peroxide was added dropwise with stirring,
at such a rate as to maintain gentle ebullition. Acetic acid,
water, and excess hydrogen peroxide were removed by evaporation
on the steam bath. The highly viscous residue crystallized
very slowly in the ice-box. The solidified material was re-
crystallized from ethyl ether. (The hygroscopic character of
this and the preceding compound made recrystallixation very
difficult).
M.P. t 47.5-48.50
Yield : 10 g., 83w
% C 31.78 (found); 32.17 (calc.)
% H 6.02 (found); 5.94 (ealc.)
34








e. Synthesis of l-propylsulfonyl-3-chloro-2-propanol

In a 250 ml. beaker were placed ten grams of 1-propyl-

thio-3-chloro-2-propanol and 50 ml. of glacial acetic acid.

30 ml. of 30% hydrogen peroxide was added dropwise with

stirring, at such a rate as to maintain gentle ebullition.

The resulting mixture was evaporated to a thick syrup on the

steam bath and set in the icebox to crystallize. The

solidified material was recrystallized from ethyl ether.
M.P. : 48-49

Yield : 8 g., 67P

% C : 35.92 (found); 35.91 (calc.)

%H : 6.55 (found); 6.53 (calc.)

d. Synthesis of l-butylsulfonyl-3-chloro-2-propanol

In a 100 ml. beaker were placed ten grams of 1-butylthio-

3-chloro-2-propanol and 30 ml. of glacial acetic acid. 25 ml.

of 300 hydrogen peroxide was added dropwise with stirring, at

such a rate that gentle ebullition was maintained. The result-

ing solution was evaporated on a steam bath to a thick syrup

which crystallized on standing. The solid product was re-

crystallized from acetone and from 95% ethanol.

M.P. : 57-57.30

Yield : 10 g., 85%

% C : 38.98 (found); 39.16 (cale.)
% H : 7.28 (found); 7.04 (cale.)








e. Synthesis of l-pentylsulfonyl-3-ohloro-2-propanol
In a 100 al. beaker were placed five grams of 1-pentylthio-
3-chloro-2-propanol and 15 ml. of glacial acetic acid. 10 ml.

of 30% hydrogen peroxide was added dropwise with stirring.
After the vigorous reaction was completed, the resulting mix-

ture was evaporated to a thick syrup on the steam bath. The
syrup crystallized on standing, the solid being recrystallized
from 95% ethanol and from acetone.
M.P, : 58.4-58.7
Yield t 5.3 g., 90%

% C 42.02 (found); 42.00 (cale.)
H : 7.69 (found); 7.49 (calc.)
f. Synthesis of l-hexylsulfonyl-3-chloro-2-propanol
In a 250 al. beaker were placed ten grams of 1- hexylthio-
3-chloro-2-propanol and 50 ml. of glacial acetic acid. 30 ml.

of 30% hydrogen peroxide was added dropwise with stirring.
After the vigorous reaction had ceased, the remaining solution

was evaporated to a syrup on the steam bath. The syrup

solidified on standing, the solid being recrystallized from

ethyl ether, acetone and 95% ethanol.
M.P. : 59.5-59.8
Yield : 4.5 g., 40%

% : 44.19 (found); 44.52 (cale.)
% 8.22 (found); 7.89 (cale.)
3. Discussion of experimental results










Hydrogen peroxide was chosen as the oxidizing agent in

these syntheses because its use does not ordinarily lead to

undesirable side reactions and the water, acetic acid, and

excess peroxide are easily removed, leaving the desired pro-

duct in a relatively pure state as a residue.

It is probable that distillation would be a better means

of purification of the first three members of this series

than is crystallization, due to their low melting points,

their hygroscopic character and their marked tendency to

supercool. Distillation of the ethyl compound at 0.5 mm. was

attempted, with decomposition resulting. Rothstein (7) was

able to distil the latter substance at 1410 at 0.1 mm.

After two recrystallizations, the last three compounds

of the series all melted in the range, 57-58. As many as

ten recrystallizations were necessary to obtain the points

given.

Figure 10 shows the change in melting point of these

substances as their molecular weight increases. It is

remarkable that there is such slight variation in this pro-

perty.

4. Summary

Syntheses have been presented for six chlorohydroxypropyl

sulfones, one of which, ethylsulfonylchloropropanol, has been

previously reported (7), the others being new to the litera-

ture.







'.--- i : ::-'- 1 .I I- .
------ : -" -------- --- --- -- .... 7.. .


- --28-


- -748




AI

i~ "
!..t .-


j0


52


Melting Point


Mol.
wt ;-



200






...- 186-s


560


600


i__ .


---~----


.......Figure 10.

Melting Point vs. Molecular Weight
--'-f-- t'oit Chlorohydroxypropyl Sulfones of
the Type RPO2GH2CHOHCH2C1, R
-----being ---ethyl through Hexyl




-

















-


-r: 1









E. Synthesis of epoxypropyl sulfones

1. Review of the literature

Reference is made to Section II,B,1 and Section II,D,1

of this report for reviews of the preparation of epoxides

and sulfones, respectively.

Epoxypropyl sulfones appear to be a new class of com-

pounds, there being no reference to them in the literature.
2. Experimental

a. Synthesis of l-methylsulfonyl-2,3-epoxypropane

In a 100 ml. beaker was placed a solution of five grams

of 1-methylsulfonyl-3-chloro-2-propanol in 10 ml. of water.

To this cooled, stirred solution was added dropwise an ice-

cold solution of ten grams of 85% potassium hydroxide in 10

ml. of water. Stirring was continued for two hours. The

resulting mixture was diluted with 20 ml. of water and the

solid material collected by filtration. Purification was

effected by successive washing with water, ethanol, and

acetone, since the product appeared insoluble in any solvent

other than a strong mineral acid.

M.P. : 260-2610d.

Yield : 3 g., 75%

% C 35.54 (found); 35.28 (cale.)

% H : 6.32 (found); 5.92 (cale.)
b. Synthesis of 1-ethylsulfonyl-2,3-epoxypropane

In a 25 ml. beaker was placed a solution of 0.6 gram of

39








1-ethylsulfonyl-3-chloro-2-propanol in 5 ml. of water. To
this cooled, stirred solution was slowly added one gram of
powdered 98% sodium hydroxide. After fifteen minutes, the
solid formed was taken up in acetone and recrystallized from
the same solvent.

M.P. : 225-226
Yield : 0.15 g., 31%

% C 39.81 (found); 39.98 (calc.)
% t 6.96 (found); 6.71 (calc.)
c. Synthesis of l-propylsulfonyl-2,3-epoxypropane
In a 25 ml. beaker was placed a solution of one gram of

1-propylsulfonyl-3-chloro-2-propanol in 5 ml. of water. To
this cooled, stirred solution was slowly added two grams of

powdered 98% sodium hydroxide. After fifteen minutes, the
solid formed was taken up in acetone and recrystallized from

the same solvent.

H.P. : 193-1940
Yield : 0.5 g., 61%

% C 44.00 (found); 43.88 (calc.)

% H 7.42 (found); 7.37 (cala.)
d. Synthesis of l-butylsulfonyl-2,3-epoxypropane
In a 25 ml. beaker was placed a suspension of one gram
of l-butylsulfonyl-3-chloro-2-propanol in 5 al. of water.
To this cooled, stirred suspension was added, slowly, two
grams of powdered 98% sodium hydroxide. After 15 minutes

40








the solid formed was taken up in acetone and recrystallized
from the same solvent.

M. P. : 169-170o
Yield 0 0.75 g., 90%
% C t 47.45 (found); 47.17 (calc.)

%H : 8.35 (found); 7.93 (oalc.)

Mol.Wt. t 179 (found); 176 (cale.)
e. Synthesis of l-pentylsulfonyl-2,3-epoxypropane
In a 100 ml. beaker was placed a suspension of 1.28
grams of l-pentylsulfonyl-3-chloro-2-propanol in 25 ml. of

water. To this was added a solution of two grams of sodium

hydroxide in 25 ml. of water. The mixture was warmed to 700
with stirring, cooled, and the impure l-pentylsulfonyl-2,3-

epoxypropane filtered off. The material was recrystallized
from acetone.

M.P. : 160-161o

Yield : 0.70 g., 65%

% C : 49.92 (found); 49.97 (calo.)
% H 8.71 (found); 8.39 (calc.)

f. Synthesis of l-hexylsulfonyl-2,3-epoxypropane
In a 100 ml. beaker was placed a solution of two grams

of l-hexylsulfonyl-3-chloro-2-propanol in 25 ml. of 50%

aqueous ethanol. To this cooled, stirred solution was added
dropwise a solution of five grams of potassium hydroxide in

25 ml. of 50% ethanol. The mixture was stirred for one hour,
41








diluted with an equal volume of water and filtered to remove

the crude l-hexylsulfonyl-2,3-epoxypropane. The material was

recrystallized from acetone.

M.P, i 178-1790

Yield : 1.5 g., 86%

% C : 52.35 (found); 52.39 (calc.)

% H t 9.04 (found); 8.79 (cale.)

3. Discussion of experimental results

In view of the unexpectedly high melting points of this

series of compounds, it was thought that there was a possibility

of the compounds existing as dimers or even higher polymers of

the simple epoxypropyl sulfones. To further investigate this

possibility, the molecular weight of the supposed butylsulfonyl-

epoxypropane was determined by the Rast camphor method (24).

Since the determined value checked the calculated value for the

monomer, it may be assumed that these are truly epoxypropyl

sulfones, rather than bis(jalkyl sulfonyj7methyl)dioxanes, for

example.

Generally, optimum yields were attained for this series

when the reaction temperature was below 10. The anomalous

preparation of the pentyl derivative, using elevated tempera-

tures, has not been explained.

The compounds appear to be decomposed slowly upon long
heating with aqueous acid or base, probably through rupture

of, and addition of water to, the epoxide ring.

42









Figure 11 shows the variation in the melting points of

the series as the molecular weight increases.

4. Summary

Syntheses for six members of a new series of compounds,

the epoxypropyl sulfones, have been proposed.

F. Synthesis of hydroxydisulfones

1. Review of the literature

The formation of sulfones was summarized in Section II,

D, 1 of this investigation.

Hydroxydisulfones have been prepared by oxidation of

the corresponding disulfides. Fromm, Kappeller, and Taub-

mann (22) oxidized l,3-bis(benzylthio)-2-propanol with potass-

ium permanganate to obtain 1,3-bis(benzylsulfonyl)-2-propanol.

Rothstein (7) synthesized 1,3-bis(ethylsulfonyl)-2-propanol

and 1-benzylsulfonyl-3-ethylsulfonyl-2-propanol from the

corresponding sulfides by oxidation in acetic acid solution

with 30% hydrogen peroxide.

2. Experimental

a. Synthesis of 1,3-bis(methylsulfonyl)-2-propanol

In a 100 ml. beaker was placed three grams of 1,3-bis

(methylthio)-2-propanol and 15 ml. of glacial acetic acid.

To this solution was added dropwise, with stirring, 12 ml.

of 30% hydrogen peroxide. After the reaction subsided, most

of the water and acetic acid was evaporated on a steam bath,

the residue cooled, and the crude bis(methylsulfonyl) propanol

43








" i'i .. ':
; 1.. .. I *


-- -;- -
:



-


I 1


44-

-- Figre 11.

Melting Point vs. Molecular Weight
for Epoxyptopyl Sulfones of the
Type RSOgGH2OHCH26, R being Methyl
-to ugh- eyl
ii


--












.. -
I i I .







--- ---
i I







I_. : .. ... .. -.. j.-.. ..


1600 :


1920


2240


2560


Melting Point


- i *1 .tPZ L


-198


Mol,.
Wt.


164


150








156


___: ~


-


I I









filtered off and recrystallized from 95% ethanol.
M.P. : 138-137o
Yield : 3.9 g,, 93%

% C t 27.28 (found); 27.77 (cale.)
% H 5 5.92 (found); 5.59 (cale.)
b, Synthesis of 1,3-bis(ethylsulfonyl)-2-propanol
In a 100 ml. beaker were placed two grams of 1,3-bis
(ethylthio)-2-propanol and 15 ml. of glacial acetic acid.
12 al. of 30% hydrogen peroxide was added dropwise, with
stirring. After the reaction subsided, the solution was
evaporated on a steam bath to a small volume. Crude 1,3-bis
(ethylsulfonyl)-2-propanol separated on cooling, was filtered
off, and recrystallized from 95% ethanol.
M.P. : 113-114
Yield : 1.5 g., 702
% C t 34.45 (found); 34.41 (calc.)
% H t 6.70 (found); 8.60 (calc.)

c. Synthesis of 1,3-bis(propylsulfonyl)-2-propanol
In a 100 al. beaker were placed five grams of 1,3-bis

(propylthio)-2-propanol and 20 ml. of glacial acetic acid.
15 ml. of 30o hydrogen peroxide was added slowly with stir-
ring. The mixture was allowed to stand overnight, then evap-
orated to incipient crystallization on a steam bath. 20 ml.
of water was added and the crude 1,3-bis(propylsulfonyl)-2-
propanol filtered off and recrystallized from 95% ethanol.
45








M.P. : 155-156o
Yield : 5.5 g., 84%
SC z 39.99 (found); 39.68 (calc.)
% H : 7.56 (found); 7.40 (oale.)
d. Synthesis of 1,3-bis(butylsulfonyl)-2-propanol
In a 100 ml. beaker were placed five grams of 1,3-bis
(butylthio)-2-propanol and 20 ml. of glacial acetic acid.
12 ml. of 30o hydrogen peroxide was added slowly, with stir-
ring. After the vigorous reaction had subsided, the solution
was evaporated on a steam bath to incipient crystallization,
20 ml. of water was added and the crude product filtered off.
Recrystallization was from 95% ethanol.
M.P. : 135-136
Yield : 4.5 g., 71%

% C 43.92 (found); 43.97 (calc.)
f% : 8.19 (found); 8.05 (cale.)
e. Synthesis of 1,3-bis(pentylsulfonyl)-2-propanol
In a 250 ml. beaker were placed thirteen grams of 1,3-
bis(pentylthio)-2-propanol and 50 ml. of glacial acetic acid.
35 ml. of 30% hydrogen peroxide was added slowly, with stir-
ring. The solution was allowed to stand overnight. The
crude product was filtered off and recrystallized from 95%
ethanol.
M.P. : 143-1440
Yield : 10 g., 60%









% C : 47.69 (found); 47.53 (calo.)
% II 9,03 (found); 8.59 (Cale.)
f. Synthesis of 1,3-bis(hexylaulfonyl)-2-propanol
In a 250 ml. beaker were placed eighteen grams of crude

1,3-bis(hexylthio)-2-propanol and 50 ml. of glacial acetic
acid. 35 ml. of 30% hydrogen peroxide was added slowly, with

stirring. The solution was allowed to stand overnight. The
crude product was filtered off and recrystallized from 95%
ethanol.
M.P. : 149-1500
Yield 11.5 g., 53%

% C : 50.59 (found); 50.52 (cale.)
% I : 9.29 foundid; 9.05 (eale.)
3. Discussion of experimental results
Though Fromm, Kappeller, and TaItbmann (22) found that

bis(benzylsulfonyl)propanol crystallized from aqueous alcohol
with a molecule of water, this phenomenon was not observed
with the compounds of the series herein reported.
It is noteworthy that the melting point of the propyl
derivative is anomalous, in that it is unexpectedly high.
However, the same compound was obtained from the disulfide
synthesized by different methods.

Generally, the compounds were colorless (white), waxy

platelets, readily prepared in good yields by the methods
described.








Figure 12 indicates the variation in the melting points

of the compounds as the molecular weight increases.

4. Summary

Syntheses of six bis(allcylsulfonyl)propanols, methyl

through hexyl, are described. The ethyl derivative has been

previously reported (7).

G. Synthesis of alkylthioalkoxypropanols

I. Review of the literature

Mixed sulfur-oxygen ethers have been the subject of

very little study. Clarke (25) obtained l-methylthio-2-

methoxyethane from the action of sodium ethyl mercaptide on

l-iodo-2-methoxyethane in methanol. One investigator (26),

used a modified Villiamson synthesis to obtain mixed ethers

from the interaction of zinc, alcohols, and mustard gas.

Formation of hydroxy ethers by treatment of epoxides

with alcohols in the presence of various catalysts has been

reported by many investigators (1), (8), (9), (27), (28),

(29), (30), (31).
No mixed ethers of the type herein reported (derived

from thioglycerol) appear in the literature.

2. Experimental

a. Synthesis of l-ethylthio-3-methoxy-2-propanol

A solution of 1.6 grams of metallic sodium in 2.5 moles

(80 g.) of methanol was placed in a 500 ml., three-necked,

round-bottomed flask, equipped with thermometer, stirrer, and

48









reflux condenser. To this stirred solution vas added, drop-

wise, through the condenser, 0.25 mole (30 g.) of 1-ethylthio-

2,3-epoxypropane. No temperature rise was noted. The solution
was then refluxed for three hours, Most of the methanol was

removed at atmospheric pressure, the sodium methylate present

neutralized with 6N sulfuric acid, and the distillation con-

tinued at 9 mm. l-ethylthio-3-methoxy-2-propanol was obtained

at 92.5-92.8*.

B.P. : 92.5-92.80 at 9 am.
Yield : 23.5 g., 0.15 mole, 62%
25
n : 1.4734
d2 1.0322
4
MD : 40.86 (found); 41.05 (sale.)

% C : 48.24 (found); 47.97 (calc.)

% H : 9.52 (found); 9.39 (cale.)
b. Synthesis of l-ethylthio-3-ethoxy-2-propanol

A solution of one mole (66 g.) of 85% potassium hydroxide

in five moles (240 g.) of 95% ethanol vas placed in a 500 al.,

three-necked, round-bottomed flask, equipped with stirrer,

reflux condenser, and dropping funnel. To this cooled, stirred

solution was added dropwise one mole (62 g.) of ethyl meroaptan.

In a similarly equipped one liter flask was placed one mole

(92 g.) of epichlorohydrin. The ethanol solution of potassium
ethyl mercaptide was added dropwise to the cooled stirred

epichlorohydrin. After all of the solution had been added,

50






jI
::' ,. : : -. t :- ..... ... ............ ; .. .. .. .. ... '- 1

.'' .. .. .'



SFigu '

Me*tinrg Point vs. Molecular Weight
Sto ydroxydisulfoliep of the Type
ftso2CHgCHOHGH2SOgR, R 'ei
S56- metyl through -Hexyl-'


328f


501


Mol,
lWt.


272






244-


I 1-


-


4 -- --


--- 16 -------. ._





1100 1.o .

.Melting Po


.4' ..


Int
tnt


142o


1580


'









the cooling bath was removed and the temperature rose to 600.

Stirring was continued for four hours. The product was

filtered and dried overnight with anhydrous potassium car-

bonate. Excess ethanol was removed from the dried solution

at atmospheric pressure, the residue being distilled at 40

am. 1-ethylthio-3-ethoxy-2-propanol was collected at 136-

137.

B,P. : 136-1370 at 40 am.

Yield : 56.5 g., 0.34 mole, 34%
n25 : 1.4679
D
25
d2 : 1.0037

MD : 45.49 (found); 45.66 (cale.)

% C : 50.78 (found); 51.16 (cale.)

% : 10.06 (found); 9.81 (cale.)
c. Synthesis of l-ethylthio-3-propoxy-2-propanol

A solution of 1.6 grams of metallic sodium in 2.0 moles

(120 g.) of propanol-1 was placed in a 500 ml., three-necked,

round-bottomed flask, equipped with thermometer, stirrer, and

reflux condenser. 0.25 mole (30 g.) of 1-ethylthio-2,3-

epoxypropane was added dropwise to the stirred solution

through the condenser. No temperature change was observed

during one hour. The stirred mix was then heated to reflux

for five hours. The cooled product was neutralized with WN

sulfuric acid, five grams of potassium carbonate added, and

the mixture allowed to stand overnight. The solid was fil-

51








tered off and the filtrate distilled, l-ethylthio-3-propoxy-
2-propanol being obtained at 78-78.5* at 2 m.
B.P. t 78-78.5 at 2 mm.

Yield : 29 g., 0.16 mole, 65%
n25 1.4661
D
2 0.9837

MD t 50.20 (found); 50.28 (cale.)
% C 53.97 (found); 53.89 (calc.)
% H 10.62 (found); 10.18 (cale.)

d. Synthesis of l-ethylthio-3-butoxy-2-propanol

1.34 moles (100 g.) of butanol-1 and 1.6 grams of

metallic sodium was placed in a 500 ml., three-necked, round-
bottomed flask, equipped with a stirrer, thermometer and re-

flux condenser. To this stirred solution was added, dropwise,
0.25 mole (30 g.) of l-ethylthio-2,3-epoxypropane. After be-

ing stirred for two hours without a rise in temperature, the
mix was heated to 75-80o during six hours. The cooled pro-

duct was neutralized with 1:1 hydrochloric acid, 100 ml. of

water added, and the mixture extracted twice with ethyl

ether. The combined extracts were dried over anhydrous

potassium carbonate. Ethyl ether and excess butanol were
distilled off at atmospheric pressure. The residue was

distilled at 2 mm., 1-ethylthio-3-butozy-2-propanol being
collected at 85.5-86.5.









B.P. : 85.5-86.50 at 2 mm.

Yield : 33.5 g., 0.17 mole, 69.5%
n25 1.4652
d 25 0.9695
4
MD : 54.91 (found); 54.90 (calc.)
% C : 55.91 (found); 56.20 (calc.)

% H : 10.47 (found); 10.48 (cale.)
e. Synthesis of 1-propylthio-3-methoxy-2-propanol
A solution of 1.6 grams of metallic sodium in 2.5
moles (80 g.) of methanol was placed in a 500 ml., three-
necked, round-bottomed flask, equipped with thermometer,

stirrer, and reflux condenser. To this stirred solution was
added, dropwise, through the condenser, 0.25 mole (33 g.) of

1-propylthio-2,3-epoxypropane. The mixture was refluxed for
three hours, cooled, and neutralized with 6N sulfuric acid.
The neutralized mixture was dried over anhydrous potassium

carbonate and distilled. l-propylthio-3-methoxy-2-propanol
was collected at 65-660 at 2 mm.

B.P. : 65-660 at 2 mm.
Yield : 20 g., 0.12 mole, 49%
n25 : 1.4719
25
d 25 1.0095
4
MD : 45.55 (found); 45.66 (tale.)

% C : 50.98 (found); 51.18 (calc.)

% H : 10.14 (found); 9.82 (calc.)
53








f. Synthesis of 1-propylthio-3-ethoxy-2-propanol

1.3 grams of metallic sodium and 2.2 moles (100 g.) of

ethanol were placed in a 500 ml., three-necked, round-

bottomed flask, equipped with thermometer, stirrer, and

reflux condenser. 0.2 mole (26.5 g.) of 1-propylthio-2,3-

epoxypropane was added through the condenser to the stirred

solution. There was no temperature change during one hour's

stirring. The stirred mix was then heated to reflux for

three hours, cooled, neutralized with 6N sulfuric acid, and

five grams of potassium carbonate added. The mixture was

left in the icebox overnight, the solid filtered off, and

the filtrate distilled. l-propylthio-3-ethoxy-2-propanol

was collected at 69.5-700 under 1.5 mm. pressure.

B.P. : 69.5-70 at 1.5 mm.

Yield : 22.5 g., 0.126 mole, 63%
25
n 2 1.4670
d2 t 0.9850
4
M : 50.22 (found); 50.28 (cale.)

% C : 53.41 (round); 53.89 (cale.)

% H : 10.49 (found); 10.18 (cale.)

g. Synthesis of 1-propyltliio-3-propoxy-2-propanol
1.3 grams of metallic sodium and two moles (120 g.) of

propanol-1 were placed in a 500 ml., three-necked, round-

bottomed flask, equipped with thermometer, stirrer, and

reflux condenser. 0.2 mole (26.5 g.) of l-propylthio-2,3-

54









epoxypropane was added dropvise through the condenser and the

solution stirred for one hour. It was then refluxed with

stirring for three hours, cooled, and neutralized with 6N

sulfuric acid. Five grams of potassium carbonate was added

and the mixture allowed to stand four hours. It was then

filtered and the filtrate distilled at 1.5 mm., 1-propylthio-

3-propoxy-2-propanol being obtained at 81-81.5.

B.P. : 81-81.50 at 1.5 mm.

Yield : 12 g., 0.06 mole, 31%
n : 1.4641
25
d : 0.9676

MD : 54.85 (found); 54.90 (cale.)

% C 56.22 (found); 56.21 (calc.)

% H : 10.68 (found); 10.48 (calo.)
h. Synthesis of l-propylthio-3-butoxy-2-propanol

1.3 grams of metallic sodium and 1.3 moles (100 g.) of

butanol-1 were placed in a 500 ml., three-necked, round-

bottomed flask, equipped with stirrer, thermometer, and

reflux condenser. 0.2 mole (26.5 g.) of l-propylthio-2,3-

epoxypropane was added dropwise through the condenser and

the solution stirred for one hour. It was then heated with

stirring to 800 during five hours, cooled, and neutralized

with 6N sulfuric acid. 100 ml. of water was added and the

mixture extracted twice with ethyl ether. The combined

extracts were dried over potassium carbonate, filtered and

55








distilled, 1-propylthio-3-butoxy-2-propanol being collected
at 90.5-91 under 1.5 -m. pressure.
B.P. : 90.5-91 at 1.5 mm.

Yield t 27,5 &., 0.13 mole, 67%

n25 1.4639
25
d 25 0.9578

MD : 59.44 (found); 59.52 (calo.)
% C t 58.35 (found); 58.21 (cale.)
% R t 11.04 (found); 10.75 (calc.)
3. Discussion of experimental results

The methods described herein were modifications of the

method of Swern, Billen, and Knight (9), using a basic

catalyst to assure formation of a secondary alcohol. The
yields obtained correspond to the yields obtained by the

aforementioned investigators.

Figures 13, 14, and 15 indicate the variation in the

refractive indices, densities, and molecular refractions of

the compounds as their molecular weight varies.

4. Summary
Eight new alkylthioalkoxypropanols were synthesized
and characterized.





Refracti
for AlTcy:
Type R'S'
or Propy
Butyl


ve Index vs. Molecular Weight
1thMoalkoxypropa&obls of the
CH2gUHOCH20R, R' being Ethyl
I and R being Methyl through

C.. SC CHOHCH2OR ----

CG57SCH2CHO0HGH2R


No


1.4660


1.4700


1.4740


25
nD


206








192


178


Wt.


1641


150


1.4620


Figure 13,


----- ------- --- -r--


__ __~____ __._ __ ._. _..._.










-.-. .-9:: $C 2:-.HOHCH2 R being Ethyl or '
.. i he-.








S2 : 3H7SCH.2C ORC 2O
.. .. .: .... ... -.....1 ,- .....J. ur e 14 .

'De1 ty vs. Molecular Weight for
-': i ..... At tllteOalkoxypropanols of the Type
...,,-- ..... !-- ---'CHgpOHOEHgOB, R' being Ethyl or
--4--r- -.0--..- ---i 1 d ..... ,- R- being Methyl through

. ?,V [ .. i O H -SCH GHOHGH, bR ... .







i I ; .




S I
-7 -








ol.












1-5.
.. .... ; ... _.i


os 0.9 00 0.9780

5 -


,-: .. .- .. .. .... _- __. .. .... ^..


1.0060


1.0340


i : *-


___


_ ______ _~_


*~~ 1







.. .. .... ... .. .. ._



Figure 15.

Molec-lar Refraction vs. Molecular Weight
Sfor Alkylthloalkoxypropariols of the Type
R'SCH2CHOHCH2OR, R' being Ethyl or Propyl
206 -- and R being Methyl through Butyl

C2H5SCHgCHOHCH20R

Cg3H7SCH20HOHCH20R




192







Mol.
178
Wt.







164








150


40.00 46.00 52.00 58.00









PROOF OF STRUCTURE


A. Of beta-hydroxypropyl sulfides and epoxypropyl
sulfides

1. Review of the literature

The method of addition of compounds containing active

hydrogen to unsymietrical epoxides has long been a point of

conjecture and study. It will be seen that the reaction may

proceed, theoretically, in either of two directions, as

illustrated by the following equations
RH + R'CHCH 0 R-- R'CH(OH)CH R
2 2
RH R'HCHR----- -RCH(R)CH2OH

Krasuskii (32) showed that, when ammonia or amines re-

acted with unsymmetrical epoxides, the reaction conformed

with the first equation. Castro and Koller (33) confirmed

this observation. It has been reported by a number of in-

vestigators, working on the addition of various compounds to

epoxides, that the ozirane ring was cleaved to give secondary

alcohols in the presence of basic catalysts and primary

alcohols in the presence of acidic catalysts (8), (9), (27),

(28), (29), (30). That this is not invariably the case was
shown by Swern, Billen, and Knight (9), whose work indicated

that the addition of allyl alcohol to styrene oxide was just

the reverse of the above generalization, the same investi-

gators proved that the reaction of allyl alcohol with

60








epichlorohydrin proceeded to the secondary alcohol, regard-
less of catalyst.
Nenitzescu and Scarlateacu (3) reported the formation
of l-ethylthio-3-chloro-2-propanol from ethyl mercaptan and
epichlorohydrin. They then prepared 1-ethylthio-2,3-
epoxypropane, both by dehydrohalogenation of the ethylthio-
chloropropanol and by reaction of sodium ethyl mercaptide
directly with epichlorohydrin, the reactions proceeding ac-
cording to the equations:
C H SH -t-OCR CHCHCCl -- C HSCH CH(OH)CH Cl

C2HSCH2 CH2

C2%5SNa OCCH2 HCH C1 C2H 5SCH 2CH2CHH2

Fairbourne, Gibson, and Stephens (8), working on the
reaction of 1,3-dichloro-2-propanol with an alcohol in the
presence of base, found that the reaction proceeds in four
steps, as follows:
(1) C1CH CH(OH)CH C1 ClCH nHCH6

(2) CICH CH2 4- ROH ---- CICH 2C(OH)CH2OR

(3) cCI CH(OH))cHOR C66 HCH OR20

(4) 6CH HC6H2R + ROH--RROCH cH(OH)cH OR

It is reasonable to assume that Nenitzescu and Scarlatescu's
second reaction proceeded according to reactions (2) and (3)
and was, therefore, no proof of the structure of the epoxy-
61








propyl sulfide.
Gilman and Fullhart (35) have shown that sodium methyl

meroaptide reacted with styrene oxide to give C6H5CB(OH)CH2SCH3

by proving the latter's identity with the same compound syn-

thesized by reduction of C6H5COCH2SCH3 through identity of the

sulfonium iodides.

2. Experimental

a. The action of chlorohydroxysulfides on skin tissue

One drop each of the methyl, ethyl, propyl, butyl, amyl,

and hexyl thiochloropropanols, prepared as shown in Section

II, A, were placed on the forearm of the investigator, cover-

ed to prevent inadvertent removal, and allowed to remain

overnight. Examination revealed no action whatsoever upon

the skin.

b. Formation of formaldehyde from

(1) l-ethylthio-3-chloro-2-propanol

9.5 grams of l-ethylthio-3-chloro-2-propanol and a

solution of five grams of 85% potassium hydroxide dissolved

in 90 ml. of water were refluxed together for two hours.

The resulting solution was made slightly acid with 6N

sulfuric acid. The solution was cooled in an ice bath and

five grams of potassium metaperiodate was added with vigorous

stirring. After thirty minutes, the solution was filtered to

remove potassium iodate and periodate, and ten ml. of the

solution was distilled into 95% ethanol. The dinitrophenyl-

62









hydrazone of formaldehyde (m.p. 164-1650) was obtained on

treatment of the alcoholic solution according to the pro-
oedure given in Shriner and Puson (24).
(2) 1-ethylthio-2,3-epoxypropane

8.0 grams of l-ethylthio-2,3-epoxypropane and a solution
of one ml. of 98% sulfuric acid in 55 ml. of water were
refluxed together for four hours. The mixture was filtered
and the solution made up to 100 ml. A 50 ml. aliquot was
treated with 50 ml. of 0.7337 M periodic acid solution,
according to the method of Hatch and Nesbitt (37). After

the chilled reaction mixture had been stirred for two hours,

it was neutralized to methyl red with dilute potassium hydr-
oxide solution, treated with a slight excess of barium chlor-
ide solution (saturated), and the precipitate of barium sul-
fate and barium iodate filtered off. The filtrate was made

up to 250 ml. Ten ml. of this solution was analyzed for
formaldehyde according to the method suggested by Walker (36).
0.2224 gram of methylene dimethone (m.p. 188-1890) was ob-

tained, corresponding to a 60% yield of formaldehyde.

3. Discussion and summary
RSH CIH.HC2b- ---- RSCH2CH(OH)CHCl(I)

-'HOcCH2CH(SR)CH2 Cl(I)

It has been shown by a number of investigators, (41),

(42), (43), (44) that compounds containing chlorine beta to








a sulfide linkage, corresponding to product II above, usually
exhibit a marked irritant effect on skin tissue. Since no

such effect was observed in these experiments, it was deduced

that the compounds tested were of type I.

I 4 HOB---RSCH2CH(OH)CH2OH<-

II + HOH---HOCHSCH(SR)CH2OH

I HC1--RSCH2dHCB26 + HOH-

II Cl--6H 2CH(SR)CH2 + HOH--

The preceding equations ahow that a 1,2 glycol is form-

ed from the hydrolysis of the chlorohydroxysulfide or

epoxysulfide derived from the reaction of a mercaptan with
epichlorohydrin if the reaction proceeds according to equa-

tion I, and that a 1,3 glycol results if the reaction pro-

ceeds according to equation II. It has long been known that

1,2 glycols are split to aldehydes by a solution of periodic
acid while 1,3 glycols are unaffected. The reaction is

discussed at length by Jackson (38). Since the hydrolysis

product was split by periodic acid to give a 60o yield of

formaldehyde according to the equation below, it was shown

that the initial reaction between mercaptans and epichloro-

RSCH CH(OH)CH 20 4- (0)-- RSCH CHO + CHO-+HOH
hydrin proceeded according to equation I.

B. Of hydroxydisulfides and hydroxydisulfones

1. Review of the literature









While it has been assumed that the reaction of epi-

chlorohydrin with mercaptans in the presence of an excess of

base leads to 1,3 disubstituted propanols (21), (22), actual

proof seems entirely lacking.

2. Experimental

a. Identity of bis(butylthio)propanols

Bis(butylthio)propanol, prepared according to the pro-

cedure in Section II,C,2,d, and another bis(butylthio)pro-

panol, prepared similarly except that potassium hydroxide

rather than the acidic zine chloride was used as a catalyst,

were oxidized to disulfones with 30% hydrogen peroxide in

acetic acid. The melting points of the two products and

their mixed melting point were 135-1360

b. Reaction of disulfones with sodium hydroxide

0.2501 gram of bis(ethylsulfonyl)propanol was digested

with 25.00 ml. of 0.1038 N sodium hydroxide for eight hours

at 80-900. Titration of the cooled solution required 21.39

ml. of 0.1134 N hydrochloric acid. This corresponds to a

16% decomposition according to the equation,
RSO2CH2CH(OH)CH2SOR 4- NaOH

RSO HCHC(H)CH 2OH NaSO R

0.2456 gram of bis(hexylsulfonyl)propanol was treated

in similar fashion with 25.00 ml. of sodium hydroxide

solution. In this instance, 22.89 ml. of hydrochloric acid

was required for neutralization. This indicates no decom-
65








position according to the above equation.
3. Discussion and summary
It was shown in part A of this section that the initial
reaction products of mercaptans with epichlorohydrin were
compounds of the types RSCH2CH(OH)CH2C1 and RSCH26HCHg6.

The subsequent reaction of these substances with additional
mercaptan may proceed in two directions as illustrated by the
following equations

RSCH2 cC62 + RSH--- RSCHU2C(OH)CH2SR

RSCH2CH(SR)CH2OH

It was demonstrated in part 2a above that identical products
were obtained with either an acidic or a basic catalyst. Ox-
idation of the two possible disulfides would lead to disul-
fones according to the equations
RSCCH2C(OH)CH2SR RSO2CH2CH(OH)CH2SO2R

RSCH2CH(SR)CH2 OH RSO CH2CH(SO2R)CH20H

It will be noted that the product in the first equation is a
delta-disulfone while that in the second equation is a gamma-
disulfone. It was found by StAffer (39) that gamma-disulfones
were readily decomposed by heating with dilute alkali, while
beta- or delta-disulfones were unaffected. Subsequently,
Otto and Trfger (40) found that an additional reaction occurred.
These two reactions are outlined by the following equations:









RSO2CH2CH2SO2R -- NaOH---RSO2CCH2CH0H + NaSO2R

RSO2CH2CH2OH -+- RSO2CHBCH2SOOR NaOH

RSO2CH2CH2OCH2CH2SO2R + NaSO2R -+ 120

The conditions for the decomposition as used in part 2b above

were those of Stiffer. Little or no reaction was observed
where StAffer reported complete decomposition under these

conditions. It was thus proved that the sulfones synthesized
were delta-disulfones rather than gamma-disulfones.

The small amount of decomposition of the diethyl

disulfone may possibly be accounted for by the etherification

reaction of Otto and Troger since the required hydroxy group

was present in the initial compound.

Thus, it has been shown that a delta-disulfide (or a

secondary alcohol) rather than a gamma-dieulfide (or a

primary alcohol) was formed when an epoxypropyl sulfide re-

acted with a mercaptan.








SUMMARY


The condensation of epihlorohydrin (l-ohloro-2,3-

epoxypropane) with normal mercaptans, methyl through hexyl,
to form chlorohydroxypropyl sulfides (RSCH2CHOHCBC C1) was

investigated.

The chlorohydroxy propyl sulfides were oxidized to

sulfones (RSO2CH2CHOHCH2Cl).

By dehydrohalogenation, corresponding series of

epoxypropyl sulfides and epoxypropyl sulfones were formed
from the chlorohydroxypropyl sulfides and ohlorohydroxypro-

pyl sulfones, respectively. The epoxypropyl sulfones are a

new class of compounds.

Six bis(alkylthio)propanols (RSCH2CHOHCH2SR) where R

was methyl through hexyl, resulted from the addition of

mercaptans to epoxysulfides or epichlorohydrin. These om-

pounds were oxidized to a series of bis(alkylsulfonyl)pro-

panols (RSO2CH2CHOHCegSOgR).

Eight new alkylthioalkoxypropanols were obtained

through the combination of epoxypropyl sulfides with alco-

hols.

The structures of the chlorohydroxypropyl sulfides,

the epoxypropyl sulfides, and the bis(alkylthio)propanols

were proven by several methods.








BIBLIOGRAPHY


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70










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ACKNOWLEDGKMKNMTS


The author wishes to express his deep appreciation to

Dr. E. G. Riets, who directed this investigation. Without

Dr. Riets's patient guidance, untiring assistance, and un-

flagging inspiration, the work could not have been complet-

ed.

It is desired, also, to acknowledge the aid and

encouragement rendered, knowingly or unknowingly, toward

the successful pursuit of this investigation by the staff

and the graduate students of the Department of Chemistry of

the University of Florida.










BIOGRAPHY


Thomas K. Todsen was born in Pittsfield, Massachusetts,

on October 21, 1918, but moved to St. Petersburg, Florida at

an early age.

In due time, he took up his undergraduate studies at the

University of Florida, being granted the Bachelor of Science

degree in May 1939.

He was awarded the degree, Master of Science, with a

major in sanitary chemistry, by the same institution in

January 1942 and, shortly thereafter, entered the Chemical

Warfare Service of the United States Army.

After his return to inactive duty, in August 1947, he

reentered the University of Florida to pursue his graduate

studies further.

During his graduate career, Todsen has held the

Tennessee Corporation Research Fellowship and the Dudley

Beaumont Memorial Fellowship. He has also served as teach-

ing assistant and interim instructor (part-time) in chemistry.







COMMITTEE REPORT


This dissertation was prepared under the direction of
the Chairman of the candidate's Supervisory Committee and
has been approved by all members of the Committee. It was
submitted to the Graduate Council and was approved as partial
fulfillment of the requirements of the degree of Doctor of
Philosophy.


Date 2'V 1. 50



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Chairman






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UNIVERSITY OF FLORIDA

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