University of the Pacific University of the Pacific

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University of the Pacific Theses and Dissertations Graduate School

1972

Birch reduction of benzenesulfonamide, N,N-Birch reduction of benzenesulfonamide, N,N-

dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide, dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide,

and 2-mesitylenesulfonamide and 2-mesitylenesulfonamide

Vishnubhai V. Patel University of the Pacific

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Part of the Chemistry Commons

Recommended Citation Recommended Citation Patel, Vishnubhai V.. (1972). Birch reduction of benzenesulfonamide, N,N-dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide, and 2-mesitylenesulfonamide. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/420

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BIRCH REDUCTION OF BENZENESULFONAMIDE, N,N-DIMETHYLBENZENESULFONAMIDE,

N ,N-DIISOBUTYLBENZENESULFONAMIDE AND 2-MESITYIENESULFONAMIDE.

A Thesis

Presented to

the Faculty of the Graduate School

University of the Pacific

In Partial Fulfillrnent of

the Requirement for the

Degree

Master of Science

by

Vishnubhai V. Patel

June 1972

--j j

ACKNOWLEDGEMENT

The author wishes to express his sincere gratitude to Dr. Charles

A. Matuszak for his unceasing encouragement and help during the course

of-this research.

My grateful thanks to Dr. Herschel G. Frye and Dr. Donald K.

Wedegaertner for their kind suggestions.

I would like to thank Dr. E.G. Cobb, Chainnan of the Chemistry

Department, for his help and facilities.

Finally, rey sincere appreciation to Mrs. Dawn Mallard for an excellent

job of typing.

TABLE OF CONTENTS

INTRODUC'J1ION . • • • .

RESULTS AND DISCUSSION

SUMMARY AND CONCLUSION

EXPERTIVIENTAL • • • • •

A. Summary of General Experimental Procedure

B. Preparation of Benzenesulfonamide

C. Reduction of Benzenesulfonamide

1. First Reduction . 2. ·Second Reduction 3. Third Reduction . 4 . Fourth Reduction 5. Fifth Reduction • 6. Sixth Reduction . 7. Seventh Reduction 8. Eighth Heduction 9. Ninth Reduction .

10. Terith Reduction . 11. Eleventh Reduction 12. Twelfth Reduction • 13. Thirteenth Reduction 14. Fourteenth Reduction 15. Fifteenth Reduction • 16. Sixteenth Reduction . 17. Seventeenth Reduction

D. Preparation of N ,N-D:imethylbenzenesulfonamide

E. Reduction of N ,N-D:imethylbenzenesulfonamide

1. First fuduction . 2. Second Reduction 3. Third Reduction . 4. Fourth Reduction 5. Fifth Reduction . 6. Sixth Reduction . 7. Seventh Reduction .. 8. Eighth Reduction

,PAGE

. I 1

. \u I

. \25

.!27 !

i27

~7 I 28 28

. 29 ~3 33 33 33 33 34 34 34 34 35 35 35 36 36 36

38

38

38 39 39 39 40 lJO 40 40

PAGE

F. Preparation of N,N-Diisobutylbenzenesulfonamide 41

G. Reduction of N,N-Diisobutylbenzenesulfonamide . i, 41

H.

1. First Reduction . . . . . . . . . . . . ~ . . . .' . . . . : 41 2. Second Reduction :. 42 3. Third Reduction 1'. 43 4. Fourth Reduction . 43 5. Fifth Reduction 1• 44 6. Sixth Reduction i• 44

Reduction of 2-Mesitylenesulfonamide (2,4,6-Trimethylbenzenesulfonamide)

1. First Reduction 2. Second Reduction 3. Third Reduction 4 , Fourth Reduction

i • 45 '

• 45 ~ 46

51 52

BIBLIOGRAPHY 53

I ' -,

LIST OF FIGURES

FIGURE NO. PAGE

l. Reduction Products of Toluene, Anisole, Dimethylaniline and Benzoic Acid • • • • . · 4

7 2.

3. 4. 5. 6.

7. 8.

9. 10.

ll.

Reduction Products of p-Toluenesulfonamide

Dimerization of Phenylsulfur Radical to Diphenyldisulfide ll

Reduction Products of Substituted Benzenesulfonamide 13

Reduction Products of 2-Mesitylenesulfonamide • • • . 22

IR Spectrum of Thiophenol from First Reduction Product of Benzenesulfonamide . . • . 30

IR Spectrum of known Thiophenol • • . . • . • .

IR Spectrum of known Mixture of Thiophenol and Diphenyldisulfide •••

IR Spectrum of Mesitylene • • • . . . • . • • .

. . 31

32 47

IR Spectrum of Mesitylene from First Reduction Product of 2-Mesitylenesulfonamide • . • • • . . . . • • • 48

IR Spectrum of 2,4,6-Trimethylthiophenol from First Reduction Product of 2-Mesitylenesulfonamide . . . • • • • . 49

LIST OF SCHEMES

SClJEI'IIE NO. PAGE

I.

II.

III.

IV.

Reaction Mechanism of Birch Reduction . . . . . . . . . . Birch Reduction Cleavage of Supstituted Tosylsulfonamide

Reaction Mechanism for Sulfonamide Cleavage by Arene Anion

Reductive Cleavage of Alkyl Substituted Benzenesulfonamide

2

7

9 12

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LIST OF TABLES

TABLE NO.

I.

II.

III.

rr.

Comparative Yield of Reduced N-Alkylated Benzamides Comparative Acidity Tabulation . . . . . . . . L~quid Ammonia Cleavage of p-Toluenesulfonamide

N-Ethyl-N-Phenyl-p-Toluenesulfonamide Cleavage

V. Birch Reduction of Benzenesulfonamide • • • • •

VI. Birch Reduction of N,N-Dimethylbenzenesulfonamide

VII. Birch Reduction of N,N-Diisobutylbenzenesulfonamide

VIII. Birch Reduction of 2-Mesitylenesulfonamide ••••

PAGE

5 6 8 8

14 19 21 23

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Chapter I

INTRODUariON

The use of active metal-liquid ammonia-alcohol reagents in the

reduction of aromatic compounds dates from 1937, when Wooster (1) showed

that the presence of alcohol in active metal-liquid ammonia allowed the

reduction of benzene to its dihydro derivative, Whereas~ in· the absence

of the alcohol there was no reduction.

He did not examine the reduction product in detail (1). In later

years Arthur J. Birch (2,4,5,7,12) reexamined the method, improved it

and utilized it extensively in the reduction of a variety of aromatic

compounds and this type of reduction often is called "Birch Reduction".

The Birch method (2,4,5) has great synthetiq usefulness because it

proVides a simple route to 19-nor-analogues of steroidal hormones (37

and in peptide chemistry (19,20) to remove tosyl blocking groups. ·.The

extensive modifications of this method by variation of experimental

conditions have proven its versatility.

The original method used an alkali metal, liquid ammonia and an

acid or proton source (1). The most commonly used metal is sodium,

although lithium and potassium have also been used. The proton source

is usually an a~cohol (methyl or ethyl) or an amnonium salt e.g. NH4Cl.

Sometimes cosol vents such as anhydrous tetrahydrofuran and ether are

used when the compounds are not very soluble in liquid anmonia. The

1

primary function of the alcohol is that of a proton donor, but it also

facilitates the process by buffering the reaction mixture, thus preventing

the accU!Illllation of strongly basic li!H2

ion. Thus the base catalysed

rearrangements can be minimized. The acidity of the proton source is

an important factor in determining the nature of the reduction product ( 6).

If the acidity is very high, the proton donor will react readily with the

alkali metal and gaseous hydrogen will be the main product. Alcohols

have optimum pKa for the reduction of aromatic rings.

The mechanism of Birch reduction (2,15,16,17,18,24) as established

for most benzenoid compounds is depicted in Scheme I.

Scheme I

[A]

(?olvated catio'11 a.md <;,olvcded eleci;to'Yl)

CBJ

MQ) e + CNH ')------ e CNH) 3 3 0 " e -e

.. 0-----M~""Y

e(NH~)

( il.+e'l'le "-'1'1 i 01'\ "1'-o.d i ca. I )

2

-j .

!

CCJ

0.. pKc.;: 16-1~

------MEFJ +ROH -~ ( NH~)

• • C NH) e :;

CD]

·•- .. -.

Q H H ...

C.E1

3

H H

+ROMCNH) 3

-,

---~

It can be noted that .ammonia can not furnish proton due to its low

acidity (pKa about 34) . Therefore, more acidic proton sources such as

alcohols (pKa about 16-18) are required. Wilds and Nelson (3) modified

this method by using lithium instead of sodium or potassium and adding

alcohol last. This procedure has improved the yields in many cases and

therefore is widely used.

The nature of substituents in a benzene nucleus profoundly effect

the mode of Birch reduction. Substitution of a benzene nucleus with

electron releasing groups (e.g. alkyl and amino) generally decrease ease

of Birch reduction and give 2,5-dihydroderivatives (6) ~ Electron with­

drawing groups (COOH, amide) give increased ease of reduction and give

1,4-dihydroderivatives as illustrated in Fig. 1.

R. R

0 M r L,[q_ NH3 -ROH 1--1

-N ..- cH, H R = -cH -oc.H . 3 I ~I -.. Gf-3

cooH H cooH

0 M+ Liq NH3 I. :ROH

\-\ \-\

Figure 1

4

-~

d

Kuehne and Lambert (6) reported the reduction of the ring of ben-

zarnide in high yields using :!2_-butanol but not using ethanol. However,

Niem (10), Dickson (27) and Qazi ( 36) found that reduction of the ring

rather than amide group occurred using either ethanol or :!2_-butanol.

The following 1,4-dihydro-3,5-dimethoxybenzarnides (Table I) were

obtained from Birch reduction of 3,5-dimethoxybenzamide, 3,4,5-trimethoxy­

benzarnide or N-alkyl-3,4,5-trimethoxybenzarnides (6).

TABLE I

A B 1\ R2 % yield

OCH3 OCH

3 H H 90*

OCH3

OCH3

H c2~ 90 1\ 13 OCH

3 OCH

3 H CH(CH

3)2 74

H H OCH

3 OCH

3 CH3 CH3

6

OCH3

OCH3

H C(CH3)3 8

* About the same yield of 1,4-dihydro-3,5-dimethoxybenzamide was obtained from 3,5-dimethoxy benzarnide as from 3,4,5-trimethoxybenzarnide.

The yield of the substituted 1,4-dihydro-N-:!2_-butyl-3,4,5-trimethoxy-

benzamide was much lower than that obtained from the other mono-N-substi-

tuted trimethoxybenzamides . Thus, in that compound the amide apparently

behaves as one which can not be stabilized by a negative ion (N,N-dimethyl

compound). Since methyl, ethyl and isopropyl groups have no similar

large effect, the size of the single substituent on the nitrogen may be

:important.

5

l

L

The acidity factor plays a great role in the protection of amide

groups (6~ 10, 27). A comparative tabulation of the acidities of benzoic

acid, benzamide and benzenesulfonamide showed (Table II) that the order

of acidity is ~co2H) ~S02NH2 ) ~CONH2 , (36) •

TABLE II

-K P a

Benzoic acid 4.5

Benzamide 15-16

Benzenesulfonamide 10

Ethanol 18

t-Butanol 19

Benzoic acid is highly acldic, so anionic form of carboxyl group

is protected during Birch reduction. According to Lambert and Kuebne

(6) benzamide is a weak acid so it does not exist in anion form and the

amide group undergoes Birch reduction in presence of ethanol. They found

the use of a weaker proton source (!_-butanol) preferentially led to re-

duction of the ring rather than the amide group.

Benzenesulfonamide is more acidic than benzamide, therefore it is

logical to predict that the ring rather than the sulfonamide group would

be reduced when either !_-butanol or ethanol is used as proton source.

However, it is well known that in the case of p-toluenesulfonamides,

6

the functional group is reduced to thiocresol (19) as shown in Figure 2.

Figure 2.

Rf!N-1~ -o _ Na./NH'. S \ J CH 11 \\ II ~ RoH 0

Kovacs et al (19) reported that during Birch reduction of the sub-

stituted tosylsulfonamide follows two paths. Cleavage of carbon-sulfur

(a) bond gives sulfur dioxide and toluene whereas cleavage of sulfur-

nitrogen bond (b) yields s ulfinic acid which undergoes further reduction

to both p-thiocresol and toluene, as depicted in Scheme II.

Scheme II. j G.. -. b !

b

7

r

The liquid ammonia cleavage of p-toluenesulfonamide gave 70-80%

of sulfite and 10-14% of thiocresol when 3.5 g atoms of sodium was

used (19) Table III.

TABlE III

Coll'q)ound g. a toms of sodium/mole

p-Toluenesulfonamide 3.5

p-Toluenesulfonamide 2.5

% sulfite Iodometric

70, 81

59, 65

% thiocresol

14, 10

traces

Later Closson and his coworkers (21) studied the similar reduction

of N-ethyl-N-phenyl-p-toluenesulfonamide in dimethoxyethane with sodium­

naphthalenide. The stoichiometric data is provided in Table IV.

TABlE r1

The Products from the Cleavage of N-Ethyl-N-Phenyl-p-Toluenesulfon­

amide with Sodium-Naphthalenide in Dimethoxyethane at 25° C*.

Exp. No. Molar ratio of arenide

to sulfonamide

1 9 2 7

* Reaction time = 12 hr

Toluene

85 78

** Yield based on sulfonamide

% yield **

Ethyl- Na2s

aniline

100 20

99 23

29 23

*** Calculated on the basis of sulfur content

8

Na S 0 *** 2 2 3

32 46

1

Closson ( 21) proposed a possible mechanism for N-ethyl-N-phenyl-

p-toluenesulfonamide cleavage by arene anion radical as depicted in

Scheme III.

SCHEME III.

'D i 'YYl et\-, 0 )( 'f e.tho..m e

e e SOi + C1o Hg•

e 2.. s 0 • :1-

'f. '

'Sodiww, No.phth~;lide

e 2.C1oHs

C. a:"-e11e AA'I i crY\ "1'-o.d i co. I )

(Qffll j de, CVYiiO')'))

?.---'>) S 02. + (I o H 8

9

It occurred to Dr. C.A. Matuszak and his coworkers to study arene­

sulfonamide reduction by Birch method var~ing different experimental

parameters. They reported in 1965 ( 10) that benzenesulfonamide can

be reduced using ethanol or t-butyl alcohol as a proton source and found

that the Birch reduction preferentially reduced the sulfonamide group

rather than the arene ring. Thus reduction of sulfonamide does not

resemble the reduction pattern of aromatic amides or acids.

This thesis is a report on the study of the Birch reduction of

benzenesulfonamide and alkyl-substituted sulfonamides. This work was

carried out in order to elucidate the role of steric factors, to ex­

amine the possibility of a large temperature effect (-33° vs ~75° C)

and to see the effect of no acidic hydrogen on the sulfonamide nitrogen.

With this objective the Birch reduction of benzenesulfonamide

N ,N-dimethylbenzenesulfonamide· and N ,N-diisobutylbenzenesulfonemi.de

were performed at -33°C and -75°C as well as 2,4,6-trimethylbenzene­

suJ.foncunide (2-mesitylenesulfonanride) at -33°G.

10

Chapter II

DISCUSSION AND RESULTS

The present study involved the Birch reduction of benzenesulfonam1de,

N,N-dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide and

2-mesitylenesulfonamide.

It has been previously shown (10) that benzenesulfonamide gives

thiophenol and diphenyldisulfide upon Birch reduction. The sulfonamide

.group is easily reduced. Probably the electron deficient sulfur atom

in sulfonamide can accommodate an electron easily.

Diphenyldisulfide could have formed as shown in Figure 3 by dimer­

ization of thiophenyl radicals possibJy formed during reduction or by

direct air oxidation of thiophenol during work-up.

Figure 3.

The reduction follows two competing pathways of reduction (19)

as shown in Scheme DJ. A higher yield of thiophenol would result when

pathway (b) is favored over pathway (a).

ll

Scheme IV.

a.. b

0 : 1? j /R 5--:-N · II : ........... R

. 0 :

No../NH?;, RoH

(a.. (j,)

R H

There were several experimental factors which effect the amount

of thiophenol isolated. ~nall amounts of thiophenol were being handled

in the work-up and millor losses affected the yield appreciably. The

b .p. of thiophenol is 168°C and some loss by evaporation probably oc-

curred during removal· of ether and ethanol using the rotatory evaporator

12

under vacuum with hot water for heating. Any unx'ellloved ether or ethanol

in the san:ple would increase the apparent yield of thiophenol. Mechanical

losses undoubtedly also occurred.

Birch Reduction of'Benzenesulfonamide:

Birch reduction of benzenesulfonamide yielded thiophenol and diphenyl~

disulfide. Benzene formation was assumed but no attempt 1<1as made to

isolate it , The reaction is shown in Figure 4,

o c. •C Li / li(jl NH3 -33 o-'t -'l5

Abso. EtoH /NH4-c.l CASSLI'YYiecl)

+

<(1}-s--6-Q Figure 4

~be reduction was carried out seventeen times under various ex-

perimental conditions, (See Table V.) The range of yields of thiophenol

ran from 10 to 28% (average 18%) but none of the experimental variations

c.aused a :!hange in the yield beyond experimental error. Thiophenol was

identifled by comparison of its ir spectrum with the ir spectrum of

authentic thiophenol .. A small amount of solid was also often present

13

! .

1--' -1="

--~'-

TABLE V

BIRCH P.EDUCTION OF BENZENESULFONAMIDE*

• Reduction

No. Reduction

·Temperature

Product **

% yield

1

2

3 4

5

6

NCJI'E: *

**

-75°C 22.3% (1.155 g)

-75°C 19.9%

-75°C 20.7%

-33°C 21.6%

-33°C 15. 2% some material was lost during work-up;

-33°C 21.0%

In each reduction 7.4 g (0.0471 mole) benzenesulfonawdde, 2.678 g (0.4 mole) lithium, 65 ml absolute ethanol and 21.4 g (0.4 mole) =nium chloride were used

In each case the isolated reduction product was a mixture of mostly thiophenol and small amount of diphenyldisulfide. The yield calculated as if all the product was thiophenol. Benzene is also assumed to fonn.

I

--'·~--, __ ,_ L_ , --·--- --'"' ,

TABlE: V -Continued

BIRCH REDUCTION . OF BENZENESULFONAJVIIDE ***

Reduction Lithium Absolute Reaction Product ** -No. Ethanol Temperature % yield

7 2.768 g 65 ml -33°C 16.8% (0.4 role)

8 2.768 g 65 ml -33°C 15.0% (0.4 mole)

9 5-536 g '65 ml -33°C 15.2% (0.8 mole)

1-' \.YI

10 1.384 g 65 ml -33°C 10.1% (0.2 mole)

ll 11.072 g 105 ml -33°C 12.3% (1.6 mole)

12 5.536 g ,65 ml -33°C ll.O% (0.8 mole) 43.77 g (0.8 mole) some material was lost

ammonium chloride during work-up

13 5-536 g '65 ml -33°C 23.4% (0 .8 mole)

NOTE: ***In each reduction 7.4 g ~0.0471) benzenesulfonamide and 21.4 g (0.4 mole) ammonium chloride were used.

I

In reduction 7 and 8 specially dried ammonia was used (see for detail experimental reduction 7).

I-'

"'

Reduction No.

14 ****

15 ****

16

17

TABLE V - Continued ,

BIRCH REDUCTION OF BENZENESTJLFONAMIDE ***

Lithium

2.768 g (0.4 mole)

2.768 g (0.4 mole)

2.768 g (0.4 mole)

2. 768 g (0.4 mole)

Proton

SoUrce

65 ml absolute ethanol

'

65 ml ab~olute ethanol

20 ml t-butanol

5Q ml t-butanol

Reaction .Temperature

-33°C

-75°C

-33°C

-33°C Diff work-up see exp. reduc.

17

Product ** % Yield

28.2%

21.4%

14.0%

15.5% Thiophenol 2.34% Diphenyldisulfide

NOI'E: **** In reduction 14 and 15, different lithium metal was used (for detail, see experimental reduction 14).

and believed to be diphenyldisulfide. In one case (17th reduction)

the diphenyldisulfide was isolated and had the same melting point as

reported for diphenyldisulfide. The presence of small aiDJunts of diphenyl­

disulfide did not alter the ir spectrum of thiophenol noticeably (see

figure 8 ) .

Reductions 1,2, and 3 were done at -75°C using dry ice and acetone

while 4,5,and 6 were performed at the b.p. of anmonia (-33°C). There

was no significant effect of temperature upon the yield.

In reductions 7 and 8, specially dried am:nonia, prepared by first

refluxing the liquid ammonia with lithium, was used to see if precluding

the possibility of water being a proton source could be important. No

significant effect on the yield of thiophenol occurred.

To examine the effect of moderate changes in the amount of lithium

used, exper·iments 9,10,ll,l2 and 13 wen~ perfor·med. In 9 and 13, double

the usual arnount of lithium was used. In 10, the amount was half, in -

11 the amount was four times and in 12, the amounts of both lithium a'1d

am:noniurn chloride were double. The yields of the products indicated that

within these limits, variations in the amounts of lithium have n:J large

effect. Since 6 equivalents of metal are theoretically needed to reduce

benzenesulfonamide to thiophenol via benzenesulfinic acid, the 4.25

equi v. used i11 experiment 10 does not seem enough to reduce all the

benzenesulfinic acid intermediate. However, since a major part of the

starting material was reduced via path (a) (Scheme IV) to benzene which

requires only 2 equivalents, there is theoretically more than enough.

In experiments 14 and 15,_ the lithium used had been in the department

17

for more than seven years and its origin was unknown. Ne:!m (10) u:sed

this lithium and he reported higher yields of thiophenol and diphenyl­

disulfide than that found in the present investigation. But the present

investigation showed that the use of the same lithium had no large effect

upon the yields of thiophenol.

In reductions 16 and 17 !_-butanol was used instead of absolute

ethanol with no significant effect upon the yield of thiophenol.

Benzenesulfinic acid may be a possible initial product of benzenesul­

fonamide reduction, but no attempts were made to isolate it.

Reduction of N,N-Dimetnylbenzenesulfonamide:

Reduction of N,N-d:!methylbenzenesulfonamide was performed eight

times (see Table V) under different experimental parameters using the

sa.'Jle procedure and work-up as with benzenesulfonamide (see Figure 5).

'Ihe yields of thiophenol were much higher ( 55-73% ,average 67%) , than

from ben~en~sulfonamide itself (10-28%, average 18%). 'l'hus the presence

of the two rr:ethyl groups on nitrogen seems to favor path (b) of Scheme

IV versus path (a), compared to unsubstituted benzenesulfonamide.

The experiments 1 and 2 were done at -33°C, the boiling point of

ammonia whereas 3 and 4 were done at -75°C, the dry ice and acetone

temperature. In experiments 5 and 6 (-33°C) and 7 and 8 (-75°C) specially

dried arrnnonia was used. 'Ihe exper:iinental variables examined did not

cause a change in thiophenol yield outside the exper:!mental error.

18

1--' \D

' --- i ' _j~-- --·"'"'--'--· L - ---~~,~~·~---.:..·--'--~--' _----'..-''---'-·--'---L..LJ-"--";"-----~-

TABlE VI

BIRCH REDUCTION OF N ,N-DTIVJETHYLBENZENES\JLFDNAMIDE * Reduction Reduction A111rnonia Product: % Yield

No.

l ** 2

3 4

5 *** 6

7 8

NOI'E:

Temperature, Calculated as all thiophenol

-33°C Approximately 55.4% Some loss during work-up

-33°C 600 ml of 61.0%

-75°C arihydrous liquid 73.0%

-75°C ammonia 73.16%

-33°C Approximately 69.0%

-33°C 600 rnl of 69.69%

-75°C specially dried 70.65%

-75°C liquid ammonia 68.34%

* In each case 8. 713 g ( 0. OIH mole) of N ,N-dimethylbenzenesulfonami.de, 2.768 g (0.4 mole) of lithium, 20 ml of absolute ethanol, and 21.4 g (0.4 mole) of ammonium chloride were used.

** In 1,2,3 and 4 reductions, 600 rnl of ammonia were used.

*** In 5,6, 7 and 8 reductions, 600 rnl of specially dried ammonia were used. For specially dried ammonia, see exper:!mental.

. ,

J-

Reduction. of N ,N-Diisobutylbenzenesulfonamide:

To examine the steric effect of bulky alkyl substituents on nitro­

gen, six reductions of N,N-dilsobutylbenzenesulfonamide were performed .

(See Table VII).

The products were thiophenol and diphenyldisulfide as shown in Figure 4.

However, the finding that substantial amounts of starting material were

recovered indicates that isobutyl groups retarded the reduction. 1be

yield of thiophenol (36-53%, average 46% based on consumed starting mater­

ial) is somewhat lower than from N ,N-dimethylbenzenesulfonamide ( 55-73%,

average 67%), but much higher than from benzenesulfonamide (10-28%,

average 18%) .

. Experiments 1 and 2 were run at - 33°C and 3 and 4 were run at -75°C.

The recovery .of the starting material was higher at -75°C ( V) 70%) than

at -33°C ( <11 30%).

In reductions 5 and 6 (-33°C) the amounts of lithium and alcohol

were doubled but did not appreciably increase the amount of reduction.

In these reductions excess lithium.probably reacted with alcohol. to

form hydrogen.

Reduction of 2-Mesitylenesulfonamide:

It is well known that benzoic acid (32) can be easily esterified

with alcohol in the presence of acid, whereas mesi toic acid ( 2, 4, 6-

trimethylbenzoic acid) does not undergo this type of esterification due

to the steric effect of the two ortho methyl groups. It interested us

to subject 2-mesitylenesulfonamide (2,4,6-trimethylbenzenesulfonamide)

20

___ l ,,. ___ . ____ !_ -~~-

I TABlE VII

BffiCH REDUCTION OF N1,N-DIISOBUTYI.BENZENESULFONAMIDE *

Reduction Lithium Absolute Reduction Ammonium Product * No. Ethanol Temperature Chloride % Yield

1 2.768 g 20 ml -33°C 21.4 g 32. 8% starting material (0.4 mole) (0.4 mole) (a) 27.8% Thiophenol

(b) 41.2% Thiophenol

2 2.768 g 20 ml -33°C 21.4 g 28. O% starting material (0.4 mole) (0.4 mole) (a) 26.0% Thiophenol

(b) 35.7% Thiophenol

3 2.768 g 30 ml -7~C 21.4 g 74.8% starting material

"' (0.4 mole) (0.4 mole) (a) 11.0% Thiophenol f-' (b) 41.9% Thiophenol

4 2.768 g 30 ml -75°C 21.4 g 67.6% starting material (0.4 mole) (0.4 mole) ·(a) 17.1% Thiophenol

(b) 53.0% Thiophenol

5 5.536 45 ml -33°C 42.8 g 24.2% starting material (0.8 mole) (0.8 mole) (a) 39.2% Thiophenol

(b) 52.0% Thiophenol

6 5-536 45 ml -33°C 42.8 g 24. 5% starting material (0.8 mole) (0.8 mole) (a) 39.0% Thiophenol

I (b) 51.5% Thiophenol

NO.I'E: * In each case, 12.688 g (0.0471 moleD of N,N-diisobutylbenzenesulfonamide was used. The % yield of thiophenol was calcu1Lated (a) in relation to all 12.688 g of starting material and (b) in relation to material consumed ( 12. 688 g minus the am:>unt recovered) •

I

to the Birch reduction in order to find out if .there is a similar retarding

steric effect of the ortho methyl groups on this reduction.

2-Mesitylenesulfonamide was subjected to four reductions (See

Table VIII) and yielded mesitylene, 2,4,6-trimethylthiophenol and mesityl-

disulfide as shown in Figure 5, The later two were formed in combined

yield (13-37%, average 27%) about the same or slightly more than from

benzenesulfonamide. The mesitylene was characterized by comparison

with ir spectrum and glc of known sample of mesitylene.

so2_NH2.

""'.:::::: CHJ L.i (li<f.NH3 "\c .::0. Aloso.J=toH / NH4-cl

CH3

r-----< c,\-13

··if ··~······ s ; ~---· -_···-;;.... ~ c

Figure 5.

22

·'·

cCC- _1, , '""-~~~- - __ j

;TABLE: VIII

' BIRCH REDUCTION ,OF 2-~'IESITl.wENESULFONJ\ll'liDE *

Reduction LithiUm Absolute A'llDlonimn T:iJll.e Interval Product No. Ethanol Chloride between reduc- % Yield

and tion and work-up Reaction Temperature

l 2.768 g 20 rrJ. 21.4 g about 4 hrs. 33.33% Mesitylene (0.4 mole) ~33°C (0.4 mcle) (some material used for IR)

20:27% 2,4,6-Trirnethyl-thiophenol

1\) 2 2.768 g 20 ml 21.4 g about 16 hrs. 21.27% Mesitylene w (0.4 mole) -33°C (0.4 mole) 2.13% 2,4,6-Trimethyl-

thiophenol ·21. O% Mesityldisulfide

3 2.768 g 20 ml 21.4 g about 16 hrs .-: 23. O% r1esitylene (0.4 mole) -33°C (0.4 mcle) (some material was lost

during work-up) 10.69% 2,4,6-Irimethyl-

thiophenol 20.00.% J'fJesityldisUlfide

4 2.768 g 20 ml 21.4 g about 4 hrs. 41.71% !1esitylene (0.4 mole) '-'33°C (0.4 mole) 28.30% 2,4,6-Trimethyl-

thiophenol

i

NOI'E: * In each reduction 9.385 g (0.0471 mel~) of 2-mesitylenesulfonamide and approximately 600 ml of dry liquid ammonia were used.

J -­f

In reductions 1 and 4 the time interval between the reduction and

work-up was about 4 hours whereas in 2 and 3 it was 16 hours. The yield

of mesityldisulfide versus 2,4,6-trimethylthiophenol was greatly in­

creased in reductions 2 and 3. This indicates that 2,4,6-trimethylthio­

phenol air oxidized more easily than did thiophenol. This might be due

to increased stability of the thiol radical intermed:iate due to the electron

donating ability of methyl group as shown in Figure 5.

Thus di-ortho alkyl substitution in the arene ring did not slow

down the reduction or change the nature of the reduction products.

However, there could be differences in the ease of the reduction of 2-

mesitylenesulfonamide compared to benzenesulfonamide that these experiments

were not sensitive enough to detect.

24

SUMMARY AND CONCLUSION

1. Birch reduction of benzenesulfonarnide using lithium and absolute

ethanol or t-butanol yielded thiophenol (10-28%, avera§e 18.3%, 17

exper:illlents) and small amounts of diphenyldisulfide. Benzene is assumed

to also form. Variation in temperature (-33°C vs -75°C), variation in

the amounts of lithium from four times to half the usual amount and the

use of specially dried ammonia vs undried ammonia did not effect the

yield within experimental error.

2 . Reduction of N ,N-dimethylbenzenesulfonarnide also yielded thiophenol

plus small amounts of diphenyldisulfide but in much higher yield ( 55-73%,

average 67%, 8 experiments) than benzenesulfonarnide, The use of' -33°C

vs -75°C or specially dried aJm.onia vs undried ammonia did riot effect the

yield within experimental error.

3, The reduction of N,N-diisobutylbenzenesulfonarnide resulted in

recovery of starting material with more recovered using -75°C than

-33°C. This indicated that bulky alkyl substitution in sulfonamide

group did retard the reduction. The yield of' diphenyldisulfide and

thiophenol ( 36-53%, average 46%, 6 experiments) based on consumed

starting material, was not affected by temperature (-33°C vs -·75°C)

within experimental error but seems to be somewhat less than the yield

from N,N-dimethylbenzenesulfonarnide but substantially is larger than

from benzenesulfonarnide.

25

i I

'

4. 'lhe reduction of 2-mesitylenesulfonamide at -33°C gave 2,11,6-trimethyl­

thiophenol (20-37%, average 27%, 4 experiments) and mesitylene (21-42%,

average 26%) leaving no starting material. Mesitylene was identified

by corrparison by :i.r and glc with known mesitylene. Thus di-ortho methyl

substitut.i.on did not cause an observable change in reduction within the

limits of the experiments perfonred. The 2,4,6-trimethylthiophenol

was more readily air oxidized to mesityldisulfide than was thiophenol

itself.

26

SUMMARY OF GENERAL EXPERIMENTAL PROCEDURES

In all of the reducUons the arru:nonia was distilled from the gas

cylinder and condensed into the reaction flask by a dry ice-acetone

condenser but was not dried \mless so indicated.

'!he lithium (Foot Mineral Co.) used was cut from llDiform thickness

lithium ribbon that was protected by petrolatum. '!he petrolatum was

removed by washing the lithium ribbon in a series of baths of low-boiling

petrolemn ether and cut into small pieces just before use.

A rotatory evaporator with partial vacuum from a water aspirator

··- and a hot v<ater bath for heating was used for evaporation of •5r·ganic

solvents and for concentration of solutions.

All melting points were determined with a 'Ihomas Hoover capillary

melting point apparatus and: are \lDcorrected. ·

Ir spectra were obtained utilizing a Perkin-Elmer Model 137 spectro­

photometer.

Benzenesulfonanlide, N,N-dimethylbenzenesulfonamide and N,N-diiso­

butylbenzenesulfonamide were prepared as indicated in experimental section

while 2-mesitylenesulfonamide was purchased from Aldrich Chemical.

Organic solvents used were, in general, not distilled prior to use.

Reductions were performed at either refluxing arru:nonia (-33°C) or at

about -75° C using dry ice-acetone bath and Wilds and Nelson's ( 3) pro­

cedure of adding the alcohol last .

27

--~

EXPERIMENTAL

Preparation of Benzenesulfonamide:

To 800 ml of concentrated ammonium hydroxide, 314 g (2.00 mole)

of benzenesulfonylchloride was slowly added over a period of 20 minutes

wlth constant stirring. An additional 400 ml of concentrated ammonium

hydroxide was slowly added into the mixture and the mixture was allowed

· to stand for four hours. The excess ammonium hydroxide was decanted from

the sol:l.d benzenesulfonsmide which was then washed with three 200 ml

portions of distilled water. The benzenesulfonamide was recrystallized

from water, yielding 240 g (1.53 mole, 76% yield), melting point

1511·-155°C (lit. (10) rn.p. 155ac) and·had an ir spectrum identical to

a known sanple of' benzenesulf'onamide.

REDUC'l'ION OF BE:NZmESULFONAMIDE:

Fi:rst Reduction of' Benzenesulfonamide (-75°C).

Benzenesulfonamide, 7.4 g (0.0471 mole) was added to 600 rru of dry

Hquid ammonia in a two liter, three-necked flask equipped with a mechan­

ical stirrer, a dropping furmel and a dry ice condenser.

'lhen 2.768 g (0.400 mole) of lithium ribbon, after being cleaned

of 1.ts protective coating of petrolatum in a series of baths of low

boiling petroleum ether, was added in small pieces over a period of 15

minutes with stirring, to the mixture of benzenesulfonsmide and liquid

28

amnonia. While the solution was stirred, 65 ml of absolute ethanol was

added over a period of 30 minutes. The reaction was held at -75°C, the

temperature of dry ice and acetone. After the blue color of the rrd,xture

had disappeared, 21.4 g (0.4 mole) of amnonium chloride was added very

slowly to reduce the basicity, and the Jlli.xture was stirred an additional

hour. The amnonia was allowed to evaporate overnight at ambient temperature

and pressure.

The residual material was dissolved in 200 ml of ice cold distilled

water. After acidification with 10% hydrochloric acid to pH 1 to 2,

the solution was extracted with four 100 ml portions of ether. The com-

bined ether solution was dried over 3 g of anhydrous magnesium sulfate.

The ether and ethanol was removed by using a rotatory evaporator under

reduced pressure. The remaining light yellow liquid weighed 1.155 g

(22. 3% yield). The ir spectrum of the reduction product (Figure 6)

was identical to the spectrum of known thiophenol (Figure 7). The --- - - --- ---

ir spectrum of known thiophenol was not affected appreciably by the

addition of .small amounts of diphenyldisulfide (Figure 8).

Second Reduction of Benzenesulfonaw~de (-75°C).

Tne experimental conditions (equipment, quantities of reagents

and reaction temperature) were the same as the first reduction of ben-

zenesulfonsmide. The isolated light yellow liquid weighed l. 032 g

(19.9% yield) and its ir spectrum was the same as the .ir spectrum of

thiophenol.

29

I ,

I 4000 3000

.10

J.J J 20r• z· <( "' ~'i-· i [! """' 30 __ ,_,~ -, ::!:: • H .. L _

::> ~.40

2000

, --·--· ' - --'---- '- ---~ '· ·--·~--- .. L __ , ___ ,.. -~~-----'-,___.,___ -- __.____1____ _ ________ ~-_ ___ ,, ------- _, ~----~~-- _, -·'"----'--'-'-"--'--~"----~-- .. ·-·---

1500 . cM-l 1000 900 800 700 .0

.lO•

-= "0 ; •.L

~.50 .60f::i_ .70-

.30

'.40 -·50'

. '• ; i\ i -, --- ~- --rr ~~ T - -. ~-- .. __ __ _ _ • i

1 0=· " ' -~- ~ ~ 60 . ki~~9J!s_, ... 1 1 L ~- ~~ __ , ~ +- _ _ .. -~. . .: eg&JT ,, '-" · ~ · ,_, - 70 = ' " c <fi 1 ' " " • , i 'i " i 1 , ' i i ,

I - I

3

w 0

4

I ! II ' I 1 1 0 ' _j_"-[bY , H+!- • I I ·i=±±t-' -I I I - ., _______._,_.

: I ! I ! I I I I ~ I ·= 5 6 7 B 9 10 11 12 13 14 15

WAVELENGTH (MICRONS)

Ir Spectrum of Thiophenol from First Reduction Product of Benzenesulfonarnide (Neat)

Figure 6

I 4000 3000 2000

I' I _j

0.0

' In

.10~

-·'-J..._J_ I . ~~~~~~~~~~~~+ - J=i:cffcffl

1500

lu !I-I--·

il!

IJF ·1'-.. ·.'t} ~f:fi rl 1 '.'

X, ~c· •.

'-~--~--"· --·· .. J

CM·1 1000 -&rti::

+

i l I !

r::c.l

900 800

··I

700 I

. ±' c[c·'f't ..

.10 I

-~ . =~=t=t" + .. ·- e: "': - cc=Rcl=i= . · + · .. _ = .. o;c+• -i'it~:·ooc-lc 1 ft 1- 11 I · I

1 • ~~-~ '"'t.c.cLcL· • -• ·•-1-•- 1 ; I 1 I 1-\-- • I I i I I • I loll

11

1 00 • ~ -+- . i I '

-Lf.4'

00 _[I i I I I i I . '· II ! I 15 3

LV 1-'

4 5 6 7 8 9 10 11 W AVE~ENGTH (MICRONS)

Ir Spectrum of known Thiophenol (Neat) (Eastman Kodak)

' Ffca:ure 7

12 13 14

I

4000 3000

.10

;_u

~.20 <(

~.30 0 fj) 40R-ca· r <( H,

.50

.60 --

, ______ ---- ___ ____,______.., _______ ,, ___ ,_---'-..,.C .. _ -.LC...J•~·-"·''""---'-~- ····------

2000 1500 I cM-1 1000 900 800 ;700

.7 Q -::- r:-,.::··· _:;::_--'~ _ .--:.-. .•. -· __ ,- ·== ·1=1- =1-1=-" ,_ 1 1·- :.J=.:l=l :::r: ·:t::;:::t:.: ~ - ·-,:::c:-· - =t= - ;::;r___:;);::=-t- ·:::::r_:::.. ·· :--:·=r-. 8=E: .. : _-,-1 -l---- . -- ·~..:..:7::r: •.tJ: __ :-::.;-_.:::_

' I i ! I 1 I I I I I I ! I

10

a

'.30

10 "' ! i ,,, 1( • I I , •

00 I I I 00

3

w 1\)

4 5 6 7 8 9 10 11 12 WAVELENGTH (MICRONS)

Ir Spectrum of !mown mixture of Thiophenol and Diphenyldisulfide. (98% Thiophenbl and 2% Diphenyldisulfide) (Neat)

Figure 8

13 4 15

i l

Third Reduction of Benzenesulfonamide.

The factors were the same as the first reduction (-75°C). 'rhe

isolated yellow liquid weighed 1.07 g (20.7% yield). Their spectrum

was identical with the spectra of the first and second reduction product.

Fourth Reduction of Benzenesulfonamide.

The exper:ilnental conditions, equipment, quantities of reagents

and wor·k-up were the same as in the first reduction except that the

reaction temperature was -33°C.

The isolated light yellow liquid weighed 1.2 g (21.6% yield).

Fifth Reduction of Benzenesulfonamide.

The conditions were the same as the fourth reduction (-33°C). There

was an accidental loss of some compound during I'Otatory evaporation

to remove the ether. The isolated light yellow liquid weighed 0. 787 g

( 15. 2% yield) .

Sixth. Reduction of Benzenesulfonamide.

'l'he set-up, exper:ilnental conditions, ·quantities of reagents and

work-up were the same as the fourth reduction of benzenesulfonanrl.de

(-33°C). The isolated light yellow liquid weighed 1.09 g (2l.O%_yield).

Seventh Reduction of Benzenesulfonamide.

The procedure was the same as the first reduction except for the

arrnnonia used and the reaction temperature. The liquid ammonia was first

33

dried by being refluxed for two hours with 5 g of lithium in a two­

liter, three-necked flask with stirring. It was then distilled into

another two-liter, three-necked flask for the reduction. 'Ihe reduction

reaction temperature was -33°C, the boiling point of arrnnonia. 'Ihe

light yellow liquid weighed 0.868 g (16.8% yield).

Eighth Reduction of Benzenesulfonamide.

'Ihe same experimental conditions, quantities of reagents and work-,

up were used as ih the.sevehth reduction (-33°C). TI1e isolated light

yellow liquid weighed 0.797 g (15.0% yield).

Nineth Reduction of Benzenesulfonamide.

'Ihe factors were the same as the fourth reduction (-33°C) except

that double the aT!JOunt (5.536 g, 0.8 mole) of lithium was used. 'Ihe

isolated light yellow crude liquid 0.789 g (15.2% yield).

Tenth Reduction of Benzenesulfonamide.

Here the procedure, the reagents and the reaction were the same

as the fourth reduction (-33°C) except that one half the amount (1.384

g, 0.2 mole) of lithium was used. 'Ihe extracted li@1t yellow crude

liquid weighed 0.526 g (10.1% yield).

Eleventh Reduction of Benzenesulfonamide.

'Ihe parameters were the same as the fourth reduction (-33°C) except

that four times the amount (11.07 g, 1.6 moles) of lithium and 105 ml

34

of absolute ethanol were used. The isolated light yellow liquid weighed

0.636 g (12.3% yield).

Twelfth Reduction of Benzenesulfonamide.

Everything was the same as in the fourth reduction (-33°C) except

that double the amount ( 5 . 536 g, 0. 8 mole) of lithium and 4 3. 77 g ( 0. 85

mole) of ammonium chloride were used, yielding 0.568 g (11.0% yield)

light yellow liquid product; the ir spectrum was identical to the ir

spectrum of the previous reduction products.

Thirteenth Reduction of Benzenesulfonamide.

The factors·(-75°C) were the same as in the first reduction except

that double the amount (5.536 g, 0.8 mole) of lithium was used, yielding

1.212 g (23.4% yleld) of light yellow liquid.

-- -- --

Fourteenth Reduction of Benzenesulfon8inide. ··

In this reduction the major change was that the 2. 768 g ( 0. 40 mole)

of lithium used was in large pieces which had been in the department for

years and whose origin is unlmown and which Neim (10) used. It was

cleaned using low boiling petroleum ether, flattened, and cut into small

pieces. The amounts of benzenesulfonamide, absolute ethanol and arrmonium

chloride, the reaction temperature (-33°C) and the isolation procedure

were the same as the fourth reduction. The light yellow liquid weighed

1.46 g (28.2% yield).

35

.,

Fifteenth Reduction of Benzenesulfonamide.

Everything was the same as the fourteenth reduction except that

the reaction temperature was -·75°C. The light yellow liquid weighed

1.11 g (21.4% yield).

Sixteenth Reduction of Benzenesulfoncurrl.de.

The set-up, work-up, quantities of reagents and experimental con­

ditions were the same as the fourth reduction (-33°C) except that 40 rol

of t-butanol was used instead of absolute ethanol. The isolated liquid

weighed 0.726 g (14.0% yield). The product's ir spectrum was not sig­

nificantly different from the ir spectrum of the products of the previous

reductions.

Seventeenth Reduction of Benzenesulfonamide.

Ir1 this_re(j_uctlon the major ch§Ilge .was the work-up. 'I'he quantities

of reagents, reaction temperature and procedure were the same as in the six­

teenth reduction ( -33°C).

The residual material was dissolved in 200 ml of ice cold distilled

water and acidified with 10% hydrochloric acid to pH l to 2; the solution

was extracted wlth four 100 ml portions of ether. The ether extract

was again extracted with four 100 ml portions of 10% sodium hydroxide.

The ether solution was dried over 3 g of anhydrous magnesium sulfate

and was concentrated using the rotatory evaporator. The remaining di­

phenyldisulfide weighed 0.12 g (2. 34% yield), m.p. 66-68°C [lit. (3'7)

m.p. 68°C].

36

The above basic solution was acidified with .10% hydrochloric acid

to pH 1 to 2 and was extracted with four lOO rnl portions of ether. The

ether solutions were combined and dried over anhydrous magnesium sulfate.

The ether and ethanol were removed using a vacuum rotatory evaporator.

The remaining light yellow liquid weighed 0 .804 g (15. 5% yield), n~5

l. 5260, [lit. (37), n65 l. 5893] and was identified from its ir spectrum

as thiophenol by comparison with ir spectrum of an authentic sample.

The refractive index is lower than the literature value. This is probably

due to presence of some diphenyldisulfide and/or solvent.

37

. i j

'

Preparation of N,N-Dimethylbenzenesulfonamide:

One hundred grams ( 2. 5 mole) of sodium hydroxide was dissolved in

200 ml of distilled water, and the solution was allowed to cool. Then

100 g (1.1 mole) of dimethylamine hydrochloride was slowly added followed

by 200 ml of ether. The solution was constantly stirred by a magnetic

stirrer for 30 minutes, while 80 g (0.46 mole) of benzenesulfonylchloride

was slowly added. The ether layer was decanted and evaporated at room

temperature yielding 85 g (0.40 mole~ 80% yield) of solid N,N-dimethyl­

benzenesulfonamide white needle crystals, m.p. 47-48°C [lit. (ll) m.p. 48°C].

REDUCTION OF N ,N-DIMETHYLBENZENESULFONAMIDE.

First Reduction of N,N-Dimethylbenzenesulfonamide (-33°C).

In a three-necked, round-bottomed, two liter flask, equipped with

a mechanical stirrer and dry ice condenser, was placed 8. 7155 g ( 0. 04'(1

mole) of N,N-dimethylbenzenesulfonamide and approximately 600 ml of

anhydrous liquid ammonia.

Then 2.768 g (0.4 mole) of lithium ribbon was cleaned of its pro~

tective coating of petrolatum in a series of baths of low boiling petro-

leum ether and was added in small pieces over a ·period of 15 minutes

with stirring at -33°C (boiling point of amnonta). While the soluUon

was sti.rred, 20 ml of absolute ethanol was added over a period of 30 minutes.

After the blue color of the mixture had disappeared, 21.4 g (0.4 mole)

of amrr.on:tum chloride was added very slowly to reduce the basicity. and

the mixture was stirred an additional hour. The amnon:ta was allowed

to evaporate overnight at ambient temperature and pressure •

38

i

I

The residual material was dissolved in 200 ml of ice cold distilled

·water. After acidification with 10% hydrochloric acid to pH 1 to 2,

the solution was extracted with four 100 ml portions of ether. The.

combined ether extracts were dried over 3 g of anhydrous magnesium sulfate

and the ether and ethanol were removed using a rotatory evaporator under

vacuum. The remaining light yellow liquid weighed 2. 87 g (55. 4% yield) •

Second Reduction of N,N-Dimethylbenzenesulfonamide,

The experimental conditions, equipment, quantities of reagents,

reaction temperature (-33°C) and work-up were the same· as in the first

reduction of N,N-dimethylbenzenesulfonamide. The extracted light yellow

liquid weighed 3.16 g (61.0% yield).

Third Reduction of N~-Dimethylbenzenesulfonamide.

The factors were the same as in the first reduction of N,N-dimethyl-

benzenesulfonamide except that the reaction temperature was -75°C.

Reaction work-up yielded 3.79 g (73.0% yield) of light yellow liquid

whose ir spectrum was identical to the spectrum of the product of the

first reduction.

Fourth Reduction of N,N-Dimeth.ylbenzenesulfonamide,

'Ihis reduction was the same as the third (-75°C), yielding 3. 79 g

(73.16% yield) of product.

39

Fifth Reduction of N,N-Dimethylbenzenesulfonamide.

The parameters were the same as the first reduction of N,N-dimethyl­

benzenesulfonamide (-33°C). The major change being that the arrmonia was

dried prior to use in the reduction by refluxing with 5 g of lithium

for an hour in a two liter, three-necked flask with stirring. It was

then distilled into another two liter, three-necked, round-bottorr.ed

flask for the reduction. The isolated light yellow liquid weighed

3.73 g (69.0% yield).

Sixth Redu~tion of N,N-Dimethylbenzenesulfonamide.

The parameters were the same as the fifth reduction (-33°C), yielding

3.61 g (69.69% yield) of light yellow liquid.

Seventh Reduction of N 1N--Dimethylbenzenesulfonamide.

The set-up, work-up and quantities of reagents were the same as the-- - --

fifth reduction except that the reaction temperature was -75°C. The

isolated light yellow liquid weighed 3.66 g (70.65% yield).

Eighth Reduction of N ,N-Dimethylbenzenesulfonanrl.de.

The factors were the same as the seventh reduction (-75°C). The

isolated lig.ht yellow liquid weighed 3.54 g (68.34% yield).

40

Preparation of N,N-Diisobutylbenzenesulfonamide:

To a solution of 40 g of sodium hydroxide in 300 ml of distilled

water, 100 g (0.7 mole) of diisobutylamine was slowly added followed

by adQition of 85 g (0.49 mole) of benzenesulfonylchloride. While the

solution was stirred with a magnetic stirrer for 15 minutes, 200 ml of

ether was added. The ether portion was decanted and evaporated at am­

bient temperature and pressure .. The N,N-diisobutylbenzenesulfonamide was

recrystallized in low boiling petroleum ether giving 95 g (0.35 mole,

70% yield), m.p. 54-55°0 {lit. (8) m.p. 55°C).

REDUCTION OF N,N-DIISOBUTYLBENZENESULFONAMIDE.

First Attempt of R~duction of N,N~Diisobutylbenzenesulfonamide.

To a three-necked, round-"bottom flask equipped with a dry ice

condenser ~"ld mechanical stirrer was added 12.6888 g (O,Oij7l mole) of

N,N-diisobutylbenzenesulfonamide and approximately 600 ml of .anhydrous - - --

liquid ammonia.

Then 2.768 g (0.4 mole) of lithium ribbon (after being cleaned of

its protective coating of petrolatum in a series of baths of low boiling

petroleum ether) was added in small pieces to the reaction Jrj_xture over

a period of 15 minutes with stirring at the boiling polnt of a'lllllonia

(-33°C). While the solution was being stirred, 20 ml of absolute ethanol

was added over a period. of 30 minutes . After the 15lue color of the

mixture had disappeared, 21. lj g ( 0. 4 mole) of ammonium chloride was

added very slowly to reduce basicity and the mixture was stirred an

additional hour. The ammo11ia M>s allowed to evaporate overnight at

41

ambient teJlllerature and pressure.

The residual material was dissolved in 200 ml of ice cold distilled

water. After acidification with 10% hydrochloric acid to pH 1 to 2,

the solution was extracted with four 100 ml portions of ether. Then the

combined ether extracts were extracted with four 100 ml portions of

10% sodium hydroxide. The ether was dried with 3 g of anhydrous mag-

nesium sulfate and was allowed to evaporate at ambient temperature and

pressure. The remaining solid material weighed 4.16 g ( 32.8% recovery) .

After recrystallization in petroleum ether it had m.p. 54-55°C and was

identified as starting material, N ,N-diisobutylbenzenesulfonamide, from

its ir spectrum.

The basic portion.was acidified with 10% hydrochloric acid to pH

l to 2 . The solution was extracted with four 100 ml portions of ether.

The cornbined ether extracts were dried with 3 g of anhydrous magnesium.

su~fate, and the ether solution was concentrated by distillation under -- ----- -- -- ----

vacuum to- :remove -etner-and tEe ethanoL 'ihe r6naining pale yellow

liquid weighed 1.44 .g (27.8% y~eld). It was identified as thiophenol

from the ir spectrum which was identical to the ir spectrum of known

thiophenol.

Second Reduction of N,N-Diisobutylbenzenesulfonamide.

The experimental conditions, equipment, .quantities of reagents,,

reaction temperature (-33°C), and work-up were the same as in the first

reduction of N,N-diisobutylbenzenesulfonamide. The extracted solid

material weighed 3.61 g (28.5% recovery). It was identified as the

42

l !

starting material, N ,N-diisobutylbenzenesulfonamide. The extracted light

yellow liquid weighed 1.39 g (26.83% yield) and was identified as thio-

phenol from its ir spectrum, which was identical to the spectrum of

known thiophenol.

Third Reduction of N,N-Diisobutylbenzenesulfonamide.

The set-up, quantities of reagents and work-up were the same as the

first reduction except that 30 ml of absolute ethanol was used and the

reaction temperature was -75°C. The isolated solid material weighed

9.49 g (74.8% recovery) and the liquid 0.54 g (10.9% yield),

The solid material was identified as starting material (m.p. 53-55°C),

N,N-diisobutylbenzenesulfonamide,from its ir spectrum. The light yellow

liquid was identified as thiophenol from its ir spectrum which was identical

to the ir spectrum of known thiophenol.

-Fourth- Reduction-er-N ,N-'Diisobutyltrenzenesulfonamide ;- -

The factors were the same as in the third reaction (-75°C). The

isolated solid rraterial weighed 8.58 g (67.62% recovery) and liquid

0. 89 g (17 .18% yield) . The solid material was identified as starting

material (m.p. 53-55°Ch N,N-diisobutylbenzenesulfonamid~ w~th small

amounts of diphenyldisulfide from ir spectrum. The light yellow liquid

was identified as thiophenol from its ir spectrum which was identical to

the spectrum of known thiophenol.

Fifth Reduction of N,N-Diisobutylbenzenesulfonamide.

'Ihe experimental apparatus, conditions and reaction temperature

were the same as in the first reduction of N ,N-diisobutylbenzenesulfonamide

(-33°C) except that double the amount (5.536 g, 0.8 mole) of lithium

ribbon was used followed by 45 ml of absolute ethanol and 42.8 g (0.8 mole)

of arrnmnium chloride , 'Ihe isolated solid and liquid material weighed

3.07 g (24.2% recovery) and 2.04 g (39.0% yield) respectively.

The solid material was identified as the starting material (m.p.

52-55°C),N,N-diisobutylbenzenesulfonamide,with small amounts of di­

phenyldisulfide from iT spectrum.

The liquid was identified as thiophenol from its ir spectrum which

was identical to the spectrum of known thiopheno1.

Sixth Reduction of N ,N-Diisobutylbenzenesulfonamide.

'Ihe factors were the same as the fifth reduction (-33°C) of N,N-

- diisooutylbehzenesulTonalnide. The -isolated solid-and-liqUid material weigheo

3.108 g (24.,5% recovery) and 2,02 g (39.0% yield) respectively.

The solid material was identified as the starting material (m.p.

53-55°C),N,N-diisobutylbenzenesulfonamide,with small amounts of di-

phenylsulfide from ir spectrum. 'Ihe light yellow liquid was identified

as thiophenol from its ir spect1~ which was identical with the ir spectrum

of known thiophenol.

44

REDUCTION OF 2-MESITYLENESULFONAMIDE.

First Reduction of 2..;.Mesi tylenesulforuimide. ( 2 , 4 , 6..;.Tr:i.Jilethylberizene­

sulfonamide) :

2-Mesitylenesulfonamide (Aldrich Chemical Co.)(9.3856 g, 0.0471 mole)

was added to 600 ml of dry liquid ammonia in a two liter, three-necked

flask equipped with a mechanical stirrer, a dropping funnel and a dry

ice condenser.

Then 2.768 g (0.4 mole) of lithium ribbon, after being cleaned of

its protective coating of petrolatum in a series of baths of low boiling

petroleum ether, was added in small pieces over a period of 15 minutes

with stirring to the mixture at the boiling point of ammonia (-33°C). ·

While the solution was stirred,· 20 ml absolute ethanol was added over

a period of 20 minutes. After the blue color of the mixture had dis-

appeared, 21.4 g (0.4 mole) of anmonium chloride was added very slowly

to reduce the basicity, and the mixture was stirred an additional hour.

Then the anmonia was allowed to evaporate over a warm water bath for four

hours.

When the ammonia evaporated, the residual material was dissolved

in 200. ml of ice cold distilled water. After acidification with 10%

hydrochloric acid to pH 1 to 2, the solution was extracted with four

100 ml portions of ether. The combined ether extracts were extracted with

four 100 ml portions of 10% sodium hydroxide. Thus an ether solution

(A) and a basic solution (B) were obtained. The ether portion (A) was

dried over 3 g of anhydrous magnesium sulfate. The ether and ethanol

were removed using a vacuum rotatory .evaporator. The remaining light

45

J --

yellow liquid weighed 1.88 g (33.33% yield), ~5 1.5135, [lit.(37), ~5

l. 5155]. This was identified as mesitylene by corrlJarison with known

mesitylene by glc and ir (Figure 9 and 10). The g_lc analysis was done

by comparison of retention time of the reduction product with known

samples of mesitylene. The analysis wa'3 performed on Carle Instrument

Model 6500, 5 ft. x 1/8 .inch columns, l38°C. On a Polar Colurrm (8%

CaT'bowax 15liO on 90-100 mesh anala'om ABC) the retention time was 1.5

minutes. On a nonj:Jolar column (8% di-n-nonyl phthalate on 90-100 mesh

anakron ABC) the retention time was 0. 5 minutes.

The basic portion (B) was acidined with 10% hydrochloric acid

to pH l to 2 and extracted with four 100 ml portions of ether. The

combined ether extract was dried over 3 g of anhydrou'3 magnesiurr1 sulfate.

'I'he ether and ethanol were removed using a rotatory evaporator;· The

rer:].aining crt.::.de matsr:tal was mostly liquid with a s;naJ.l arrnunt of solid,

wej£Shed 1.5 g (2ci .27%yie1d), n~5 1.565~, and was assLl!lled to be mostly .

2,4,6-trimethylthiophenol (major product) and small amount of mesityl­

d~sulfide. (For ir spectrum see Figure 11).

Second Reduction of 2-Mesitylenesulfonamide.

The experimental conditions (equipment, quantities of reagents

and reaction temperature (-33°C) were the same as the first reduction

of' 2..:.mesitylenesulfo[lamide, except that after the reaction, the ammonia

was allowed to evaporate overnight (approximately 15 hours) at ambient

terr~erature and pressure.

'l'he residual material was dissolved in 200. ml ice cold distilled

46

I 4000 3000

~,,,1

00 . ~,,~1'

--·-1

,--~,

r"'" .10[ifl:q~m i--L-·

'+

'J tt t:!: . l: = J 1 I __._L_.j_ ••

.J.20H-i- ; ·i t.:l @t:U:tJ:t:t 7 :!=!=, : ~ l:£i :tl ""' lt++' -~n:J -m

2000 ' ''

lr-HH -r't'l

.•... :.

~t-

·ii!ft~~· U!1'

-~. :t·

'"" 8?=tt- ·:t- ~:-r-I ~~ t=t=~ ~.30f+t-~g··~lf ww --~--·--~--·-

) rTf ~ ~-~ 1-H·rf , -n 40 ,,. , .. , · n · rill r : ':± ±l ~ .. t::+~ ::[. 50 ·. ~r t:i R= • ~'::!:±:""'f=E· :·±ti·7·t 60 '~+;-~~- 't:p~ - ·-~

)o~~fl 1C: '~~~i~,fao I I I! 'I I :I I I :I I I I

0 ' ! I ' I'" 1. ~

-}-rr--r

-'-+-;.=t

nxtJJ

r

__,.. 00 ULL_j__l II

3 4 5 6

1500

n

-f.-Ul.

;---~ c:r •.

111--::. :I= I

CM·1

LLt' t--1--1~~' r-L ..

["'.-"

tt_ ,-n-i r

'-~l=r! I! I I I , n ' . 1+++-fl·:iS-!__,.

"

[:£ ~ :.!

9~ .. ·~r.~ ..

b-:t~ -~-:t-·

II I I I I! iIi I! i

!fTTT[

1000

-LY+

-~·Hi

'--~-T ·, _ __,__,_"_

7 8 9 10 WAVEL.ENGTH (MICRONS)

900 800

1-

+-t-' it-EEIHH,"

11

-~1-:..i l_V

:1 I i'Tl

.i \tic[ I ft=fi=f-

~n~~ j! r.~.!=!::-

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c!.cj 'I ''·t-! .. co :t.:r. -::::r=l=l--·~='F£b I j·H·! tt --~-~~::t::~::£_; t- j: fl· _::f::EF::Et::::t:c

I II

12 [_L

13

Ir Spectrum of lm~ Mesi tylene (Eastman Kodak) (Neat)

-1=" Figure 9 -'I

_[

II

700 I i i

..J l++t±

=t±+~1 tw_::o: ~_1.0 IJ.UJoo

14 15

! 4000 3000

.10

u ~.20 ;(

2000 1500

--~--'--' . :"'-- - ---'~---"-·--~---· -"--- ----- - "-~-- -----. -------- __ ., _______ _

·cM-1 1000 900 800 700 0.0

.10

.20

fl i~f+lf1l~TI ctfff'tffff+r+fj-fffff-t¥FlJ4Ij1ffltlffRifH'fffFFFFFft1frtfl4'ffffilf/fffffffimtfFffffWtH1Tftf¥tt-'=fH=r_ttfff'T!il WWl. 3 0 ~.30 _____ II.,m o f __ 1111 _.II II I I I _ I. t _ I. I J~J Ci 1J1J .lLLL

) l) 40 -t+t+ 1\ r-t i-ti , ,-1-+t+ •lj- - I --- -+I -- - - - - t-H · +-· -t-+ -• >+ t-f-j- 4Q :a· -n_'';'-+--:f-J':_r_tH- - , - 1'-' . __j '--- ---- --- -H+_ --_~--+'-t_· ,.,. =-+ :p 1 ctlt :J , -- t= ", - +tf - +> ""' t::..Q - _ · '•·-+H+ . --H- 50

• .., ~t-+=1=$ :-' : -- H ~ti:: • ' 60 . . • -·=! • . -+ +:tct.- •t+= A()

:7og~-~:~g~~~~~:,~=t=~-~ >- .J .:: ___ ~. -~

- " -- - -~~: -~-

I I I I I ,\ I I I '

10 ,1 ' ' !I 'I li_+ • I ! I ~ *

' ~ ,__. - :r, I I I I' I' t I I I I I I I I I I 00 I 1!-' II 11 11 11 ~~~~~~~~~· 00

3 4 5 6 7 8 9 10 11 12 13 14 15

..

-"'" 00

W AVHENGTH (N\ICRONS) I

Ir Spectrum of Mesitylene from First Reduction Product

of 2-M<:isitylenesulfonamide (Neat)

Figure 10

i 4000 3000

.10

J..J

{20 <{ ~.30· ) :2.40 <{.50

.6olf.

2000 1500

- --•--'---' '- ~~ ·-·'--'~---- - "~~----·"-"'""-''

I (ll/\-1 1000 900 800 700

.10

0

30

40 50 60 70 .70~~ .____,._.- _-;-:-:r_~ ~·~·...:"'1:: ..... +=---~·_,_··---= --.-:..T;:;~:::t.- >= ,_r-··:~·:::r:> ~:J;:::f:::-·:. .. ,· · .. :::1~-Tnz-·~..":l-- ···::: -~-- ~:- -~ = ...:;.;. ):_..' ___,__ -"-ct.-

i! i Ill hi I i II ii Ill I 1. I i I i II

1 0 1 · . I I I I 0,,...., I I . I I 1 I I I ' 1 I· 1 1 • . r •. , ~ II l++ . -r .- ::.-H- • 0 - .

CO I I I I i II

3

.I= \!)

4 5 6 7 8 9 10 11 12 W A YELENGTH (MICRONS)

Ir Spectrum of 2,4,6-Trimethylthiophenol from First Reduction Product

of 2-l"!~sitylenesulfonamide (Neat)

Figw:>e 11

13 14 HTI=

15

water and extracted with four 100 ml portions of ether. The combined

ether extracts were extracted with four 100 ml portions of 10% NaOH.

Thus an ether portion (A) and a basic portion (B) were obtained. The

ether portion (A) was dried over 3 g anhydrous magnesium sulfate. The

ether and ethanol were removed using a rotatory evaporator. The light

yellow residual material (mostly solid) weighed 4. 22 g (59. 67% yield

calculated as if all mesityldisulfide; 76% yield calculated as if all

mesitylene). This was washed with low boiling petroleum ether and

filtered. The mesityldisulfide was recrystallized from petroleum ether

and weighed 1.5 g (21.0% yield) m.p. 124-l25°C [lit, (8) m.p. l25°C].

The above petroleum ether filtrate was concentrated using a rota-

tory evaporator. The residual crude liquid was decanted and weighed

l. 2 g (.21. 27% yield) . Its ir spectrum was the same as the ir spectrum

of the product of the first reduction and appears to be mostly mesitylene

and a small amount of mesityldisulfide. -- -- -

The basic portion (B) was acidified with -10% hydrochloric aCid and

extracted with four 100 ml portions of ether. The combined ether solution

was dried over 3 g of anhydrous magnesium sulfate. The ether and ethanol

were removed using a rotatory evaporator. The light yellow liquid

weighed 0.158 g (2.13% yield) and was considered to be 2,4,6-trimethyl-

thiopehnol. Its ir spectrum was consistent with that assignment and

it easily air oxidized to material with the same m.p. as that reported

for mesityldisulfide (8).

50

·'·

Third Reduction of 2-Mesitylenesulfonamide.

The conditions were the same as the second reduction including

evaporation of armnonia over 15 hours. The residual material was dis-

solved in 200 rnl ice cold distilled water . After acidification, the

solution was extracted with four 100 rnl portions of ether. The com­

bined ether extracts were extracted with four 100 rnl portions of 10%

NaOH. Thus an ether portion (!\) and a basic portion (B) were obtained.

The ether portion (A) was dried over 3 g of anhydrous magpesium

sulfate. The ether and ethanol were removed using the rotatory evap-,

orator. The residual crude material (A) was a mixture of liquid and

solid and weighed 4.766 g (67.22% yield, calculated as if all mesityl­

disulfide; 78% yield calculated as if all mesitylene). The liquid was

decanted from the solid. The solid was washed with small amount of

low boiling petroleum ether to give 1.47 g (20% yield) of mesity1disulfide,

m.p. 124-125°C [lit. (8) m.p. 125°C). The liquid weighed 1.1 g (23%

yield) and was identified from its ir spectrum as mesitylene.

The basic portion (B) was acidified and extracted with four 100 ral

portions of ether. The combined ether solution was dried over 3 g of

anhydrous magpesium sulfate. The ether and ethanol were removed using

the rotatory evaporator. The light yellow liquid weighed 0.79 g (10.69%

yield) and assumed to be a mixture of 2,4 ,6-trimethylthiophenol· with':.

trace amounts of mesityldisulfide.

Fourth Reduction of 2-Mesitylenesulfonamide.

Everything was the same as in the first reduction of 2-mesitylene-

51

sulfonamide (-33°C) including evaporation of ammonia over a period of

4 hours. The residual material was dissolved in 200 ml ice cold dis­

tilled water. After acidification with 10% HCl, the solution was ex­

tracted with four 100 ml portions of ether. The combined ehter extracts

were extracted with four 100 ml portions of 10% NaOH. Thus an ether

portion (A) and a basic portion (B) were obtained.

After removal of ether and alcohol from ether portion (A) , 'there

was obtained 2.36 g (41.71% yield) of a ligpt yellow liquid, n65 1.5020.

This was identified as mesitylene with trace amounts of mesityldisulfide

by comparison of ir spectrum with the ir spectrum of !mown mesitylene.

The basic portion (B) was acidified and extracted with four 100 ml

portions of ether. The combined ether extracts were dried over anhydrous

magnesium sulfate. The ether and alcohol were removed using the rotatory

evaporator. The ligpt.yellow liquid weigped 2.09 g (28.30% yield) and

was assumed to be 2,4 ,6-trimethylthiophenol with small amount of rnesityl­

disulfide. The ir spectrum was the same as the first reduction product •

52

l ---

'f 1.

>( 2.

L 3.

'{ 4.

V5.

i . 6.

;(7.

8.

'! 9.

10.

111.

·:/12.

/13.

)(1.4.

\15.

(16.

/17.

,./ 18.

BIBLIOGRAPHY

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22. H. Smith, Organic React:ton ill Liquid .Ammoma,. John WHey and Sons, Inc., New York, NY, 1963, p. 253.

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54

..