Reductive Cleavage of N-Substituted Benzenesulfonamides and P-Sulfamylbenzoic Acid

University of the Pacific Scholarly Commons

University of the Pacific Theses and Dissertations Graduate School

1975

Reductive cleavage of N-substituted benzenesulfonamides and p- sulfamylbenzoic acid

Robert E. Davenport University of the Pacific

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Recommended Citation Davenport, Robert E.. (1975). Reductive cleavage of N-substituted benzenesulfonamides and p- sulfamylbenzoic acid. University of the Pacific, Thesis. https://scholarlycommons.pacific.edu/uop_etds/ 1869

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REDUCTIVE CLEAVAGE OF N-SUBS'J,ITOTED -BENZENF-BULFONAMIDES AND p·-SULFAMYLBENZOIC ACID

A Thesis Presented to the Faculty of the Graduate School University of the Pacific

In Partial Pulfillrnent of the Requ:i.rement for the Degree Master of Science

by Robert E. Davenport July 1975 This thesis, written and submitted by

~E.

is approved for recommendation to the Committee on Graduate Studies, University of the Pacific.

Department Chairman or Dean:

Thesis Committee:

P~- a~·. Chairman

Dated__ --'J~_L---::~~---..;./--'2?--,.'""""""/_....9_7=------~-- 7 I ACKNOWLEDGEMENT

~~ rrhe author wishes to express· his sincere gratitude to Dr G'harles

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

My grateful thanks to Dr. Michael J. Minch and Dr. Herschel G. Frye for their helpful suggestions. I would like to thank Dr. Donald K. Wedegaertner, Chairman of the

Chemistry Depe..rtment, and Dr. Enerson G. Cobb, former Chairman of the Chemistry Department, for their help and facilities.

Finally, my sincere appreciation to Mrs. Dawn Mallard for an excellent job of typing. TABLE OF CONTENTS PAGE

INTR.ODUCriON • 0 • • • • • • • • . •• 0 •••••• 1

RESULTS • ·• ...... 12

. NJVffi lNTERPRNI'ATION ...... •· 24

DISCUSSION • • • • • • • • • • & • Q • • ••• 28

SUMMARY AND CONCLUSIONS ••• 0 ••.• . 38 EXPERJJ'.ffiNTAI., • • • • • . • ...... 40 A. Summary of General Experimental Procedures 40 B. Preparation· of Diphenyl Disulfide • 43 C. Reduction of Benzenesu1fonamide • 43 First Reduction • • · 43 Second Reduction ...... 45 Third Reduction · 45 Fourth Reduction . 45 F~fth Reduction 46 Sixth Reduction . . . 1!6 Seventh Reduction 46

D. Preparation of N-Phenylbenzenesulfonamide • ~·7 E. Reduction of N-Pnenylbenzenesulfonamide • • 117 ·First Reduction . • • • • • • • · •. ·• • • · • ~ • • • • 47 Second Reduction • • • . • • • • • • • • • • • • • 49 Third Reduction • • · • 49 Fourth Reduction • • • • • • • • • • • • • • 49 Fifth: Reduction • • • • • • • • • • • • 50 . Si.xth. Reduction • • • • • • • • . . . 50 Seventh Reduction ...... 50 F •. Preparation of N,N-Diphenylbenzenesulfonamide 51 G. Reduction of N,N-Diphehylbenzenesulfonamide • 51 First Reduction • •. • •. • .• 51 Second Reduction • • • • • • 53 Third Reduction • • • • • 54 Fourth Reduction • • • • • • 54 . H. Preparation of N-Methyl-N-phenylbenzenesulfonamide . . . 55

I. Reduction of N-Methyl-N-phehylb~nze~esulfonamide • . . . 55 First Reduction • ...... 55 Second Reduction ...... •. ' ...... 57 Third Reduction • ...... 57 J. Preparation of N,N-Dimethylbenzenesulfonamide 59

K. Reduction of N,N-J)imet.hylbenzenes~lfonarnj_de 59 Fir•st Reduction • • • • •. • •. · •. •. • •. • • • 59 Second Reduction • • • • • • • • 60

M. Reduction of N-Methylbenzenesulfonamide 61 First Reduction • ...... 61 Second Reduction ...... 62 Third Reduction • ...... 63 N. Preparation of N,N-Diisobutylbenzehesulfonarnid.e 64

---~ o. Reduction of N,N-Diisobutylbenzenesulfonarnide 64 First Reduction . . . 64 Second Reduction 66 Third Reduction • . • . • 66 Fourth Reduction 66 Fifth Reduction • . 66 P. Preparation of N-Isobutylbenzenesulfonamide 68 Q. Reduction of N-Isobutylbenzenesulfonamide 68

First Reduction . ~ . 68 Second Reduction 69 Third Reduction . • • • . • . • • • • • • 69 Fourth Reduction 70 Fifth Reduction . . . . . 70 R. Preparation of Lithium SaJt.. of N-Phenylbenzenesulfortamide • . • • • . . • • • • • 71 S. Reduction of Lithium Salt of N-Phenylbenz.enesulfonamide 71 First Reduction • ...... 71 Second,Reduction ...... 72 T. Reduction of p-Sulfareylbenzoic Acid 74

,First Reduction ... .. 74 Second Reduction 75 Third Reduction .. 75 .FourthReduction. 76 BIBLIOGRAPHY • .. 78

APPENDJ.:X • 81 LIST OF TABlES

PAGE 1. Birch Reduction of Benzenesu1fonamide • .13 2. Birch Reduction of N-Pheny1benzenesulfonannde 15 3. Birch Reduction of N,N-Diphenylbenzenesu1fonamide • 16 4. Birch Reduction of N-Methy1-N-pheny1benzenesu1fonamide 17 5. Birch Reduction of N,N-Dimethy1benzenesu1fonamide . 18 6. Birch Reduction of N-Methy1benzenesu1fonamide 18 7. Birch Reduction of N,N-Diisobuty1benzenesu1fonamide 19 8. Birch Reduction of N-Isobutylbenzenesulfonamide. 20 9. Birch Reduction of Lithiwn Salt of N-Phenylbenzenesulfon- arnide 21

10. Birch Reduction of p~Sulfamylbenzoic Acid 22

LIST OF SPECTRA

PAGE

IRl. Thj.ophenol • 83 IR 2. Diphenyl Disulfide 84 IR 3. Thiophenol from Reduction #1 of Benzenesulfonamide. 85

IR 4. Diphenyl Disulfide from Reaction #1 of Benzenesulfonamide 86 IR 5. Diphenylamine .. . ' 87 IR 6. Diphenylamine Recovered from Reaction #1 of N,N-Diphenylbenzenesulfonarnide 88 IR 7. · Partially Reduced Diphenylamine from Reaction #1 of N,N-Diphenylbenzenesulfonamide • 89

IR 8. Partially Reduced Diphenylamine from Reaction #l~ of N,N-Diphenylbenzenesulfonamide . 90

NMR 1. Thiophenol . . . e ~, o 91 NMR 2. Diphenyl Disulfide • 92 NMR 3. Thiophenol (with Diphenyl Disulfide) from Reaction .#1 of Benzenesulfonamide • 93

NMR 4. Partially Reduced Diphenylamine fr~o~m:__R~e~a~c~t'_:l:i~on~------;:T."------(______-Ttu· 4-ef-N-,N=B::i::pherry1b-enzenesul1·onamide . 94 NMR 5. 1,4 Dihydrobenzoic Acid (Student Prepared) • 95 NMR 6. p-Sulfamylbenzoic Acid 96 NMR 7. Product From Reaction #1 of p-Sulfamylbenzoic Acid 97

i' NMR. 8. Product from Reaction #2 of p-Sulfamylbenzoic Acid 98 NMR 9. Product from Reaction #3 of p-Sulfamylbenzoic Acid 99

NMR 10. Product from Reaction #4 of p-Sulf~~lbenzoic Acid . 100 NMR 11. Diphenylamine • 101 ------··------"

INTRODUGriON

.ArnriDnia solutions of alkali metals have long been known to reduce certatn aromatic systems to their dihydro product . In many cases the reduction proceeds even further to more saturated products. 'I'his medium has also served ,to c1ea1le-var-ioui?-rneleeules-.-'------

The first reported use of this reaction was by Lebeau and Picon

(1) in 1914 whereby naphthalene was reduced to tetrahydronaphthalene. During the nineteenth centuvy similar reductions had been done with sodium amalgam and water ( 2) .

Dur:i.ng the several decades following the discovery of these reactions, several reaction mechanisms were proposed (3). The first envolved the reaction of the alkali metal with the ammonia to produce "nascent" hydrogen which then reacted with the hydrocarbon. This is given by equations 1 and 2. This "nascent" hydrogen, (H)*, was

. 4Na + 4NH ~ 4NaNH + 4 (H)* 1 3 2 !i(H)* + ClOH8---? Cl0Hl2 2 rather vaguely referred to as a chemically distinct species of hydrogen which preferentially reduced aromatic hydrocarbons rather thaYl I combined to form hydrogen molecules ( 16).

The second mechanism mvolved addition of the alkali metal to -- "" the naphthalene followed by solvolysis to the reduced hydrocarbon.

This is g1 ven by equations 3 and 4. This particu1ar mechanism was supported by the isolation of 1,1! dilithium naphthalene I (4), .2

c1d1s + 4Na --7 c10H8Na4 3 c H Na + 4NH ~ c H + 4NaNH 4 10 8 4 3 10 12 2 a possible intermed~ate. As further support for thi.s mechanism,·

I is was shown that the tetrahydro product was formed stepwise (5),

· 2N'a + 2NaNH ? 2

2Na Na E-(--

A third theory proposed that the intermediate in the reaction was an anionic species derived from the hydrocarbon ( 5) • For naphthalene the cJianion III was proposed. Whether the electrons added

III 3

directly from the ammonia solution to the naphthalene or whether II formed and then ionized to III was not known. · Since benzene and its simple homologs generally do not add alkali metals, benzene or toluene was often used as a cosolvent for the reduction of large polynuclear aromatic systems of low solubility in ammonia. In 1937 Wooster (6) showed that toluene could also react under these conditions if water were present. Although the products he obtained were not characterized, it was shown_tha.t_wat:er>.______. must be pi>esent for ring reduction and that anhydrous ammonia with ammonium chloride, ethyl bromide, or iron oxides yielded only molecular hydrogen and unreacted toluene. This initiated more interest in the "nascent" hydrogen theory as a possible mechanism for these reactions. Later vlooster improved his methods ('"() for reducing the monobenzenoid systems by using alcohols as proton sources rather than water. This provided the first easy way to reduce monobenzenoid compounds to their dihydro products.

The reaction as reported by Wooster, along with many modifications, is generally referred to as the Birch reduction, stemming from the numerous reports by Birch and his co-workers on this reaction (8-15). Due to the fact that alkali metals do not normally add to monobenzenoid systems, the mechanisms applicable to polynuclear aromatics, i.e. the addition of the metal followed by solvolysis, were considered untenable for these systems. During the first several years of Birch's work with the reaction there were several pl'oposed mechanisms in competition. The idea of the formation of "nascent" hydrogen was still 4

popular, but Birch proposed the addition of electrons to yhe:.,benzenoid ·system as the initiating step of the reaction (9) as given by equation 6. Initially, the argument against a stepwise formation of the products was that any monoanionic radical form would isomerize to con-

jugated systems and be further reduced· ( 8) . It was later theorized

that 'tetrahydro products occured when the basic reaction media abstracts an allylic hydrogen from the 1,4 product causing rearra..'1gement to conjugated systems, which were then further reduced ( 10) . Cor- relation of inductive effects of ring substituents with isolated products gave further evidence to this j_dea. Isolated double bonds had been shown to be generally stable to Birch reduction conditions.

TI~ currently accepted mechanism for this reaction is a multistep process initially involving anion radical formation, although dianion

formation has not been completely excluded in all cases. Birch pre-

sented this mechanism in 1950 (17) and evidence had~been presented before this for the two step process of reduction with anion radical

intermediates (18). ~1e complete·mechanism with reference to the significa11ce of the pKa of the proton source was presented in 1958 ( 19) . I

7 5

Polarographic studies show that the electrolytic reduction of polynuclear-fu""''ma.tic systems at----a-dropping mercury electrode probably follows a mechanism similar to the addition of lithium to polynuclear aromatic systems (20), but attempts to isolate lithium addition

products ~~th monobenzenoid systems have generally not been suc cessful (21). Electron spin resonance studies, however, have shown that both monobenzenoid (22,25) and polynuclear (23,25) systems form

anion radicals in the pres_en.c_e_of_alkali_metals-(-:t"lot-disgol-vsGl.-.tn------ . ammonia). The possibility of more than one mechanism for the reduction of polynuclear compounds is still open to question. Given this mechanism, the initial rate detennining step would be the initial addition of one electron (14) with the overall kinetj.cs of the reaction following equation 8 (24). Others have proposed

fourth order kinetics for benzene as given in 9 (27). Equation 8 might be expected when the first intermediate formed is an anion radical, while equation 9 would support the concerted addition of two electrons to the aromatic system as in equation 6.

-d(ArH)/dt = k(ArH)(Alkali metal)(ROH) 8 2 -d(Benzene)/dt = k(Benzene)(metal) (ROH) 9 The effect of ring substituents on the ease of reduction and on the orientation of the double bonds in the product is consistent with the lmown inductive and resonance effects of substituents on an anionic intermediate. Electron withdrawing substituents enhance the r·eduction by stabi.lizing the intermediate. This effect is most pronounced at ortho and para positions and leads to 1,4 addition (10). 6

Electron donating substituents retard the reaction and lead to 2,5 addition (eq. 11) (14,26,28).

The addition of the second hydrogen to the mesomeric ions Dl and V gives unconjugated products rather than the more thermodynamically stable conjugated products because it is an irreversible kinetically controlled proton addition to the area of greatest charge density. Certainly if dianions were intermediates, para addition would be expected due to the resultant charge separation expected in the dianion. In the presence of a strong base (LiNH2) reversible ab~ stract:i.on of one of the allylic hydrogens may occur. When this occurs

dm~ing reduction the conjugated diene formed i.s easily further reduced to an alkene. Besides the reduction of the aromatic ring systems, the ammonia, i alkali metal, alcohol reaction has been used to reduce or cleave

off a number of other functional groups. Often this reaction is in -- e= competition wlth the reduction of the ring itself, and which re~ duction predominates is a function of the reaction conditions (temp- 7

erattire, pKa of proton source, presence of speeies which tend to decrease the effective reduction power of the solution such as Fe, etc.); One example of this phenomenon is the reduction of benzamide.

De!~nding upon the alcohol used as a proton source, either the ring of the amide group may be reduced (29,30). Recent work by Dickson (44) contradicts that report as he found only the ring was reduced regardless of proton source unless the amide was of a secondary amine, in which case only the amide group was reduced.

The effect of the lack of a proton som·ce can be dramatic. With only ammonia and alkali. metal cyclophane VI is cleaved to VII (28), but when a proton source is present the rings are reduced to

VI. VII

produce VIII (31). Likewise, m-tolyl metr~l ether is demethylated

VIII in the absence of a proton source, but ring reduction occurs in the

presence of alcohol (11). Recent studies have show11, as expected, that the ring of phenyl methyl ether is reduced under Birch conditions, but some phenol is recovered ( 32), indicating possible competition for the reductive cleavage of the methyl group. Perhaps the most important reductive cleavage reaction, with ---~~~-~-- -~

-.respect to synthetic problems in peptides and aminosugars is the

reductive cleavage of sulfonamide protecting groups.

'lhe cleavage of p-toluenesulfonamide protective groups in liquid

cai~IIDnia and alkali metal without a proton source, was used by du Vigneaud

in peptide synthesis (33) in 1937. Removal of this group earlier had been done by use of the more drastic conditions of phosphonium

iodide-hydroiodic acid mixtures, first reported by Fisher ( 3ll) •

------c-';B:i~reh~E-1--9)-reporte-d-the reduction or the sulfonamides to yield thiol as given in equation 13, and others have· also isolated the thiol

product- ( 42).

The interest of practically all experimenters was in obtaining

the am:Lv:te or peptj_de residue jn good yield with no undesirable side

reactions. As a result the fate of the rest of the molecule after cleavage was generally not determined. Usually the excess alkali

. metal present was reacted with ammonium salts to form molecular hydrogen to prevent reduction of aromatic systems.

One of the first examinations in detail of the fate of the

-sulfur from the reduction in arrmonia with alkali metal vms done by Kovacs and Ghatak ( 35) . They used the method of du Vigneaud ( 33) i and the only sources of protons were the amnoma and then ammonium

acetate which was not added until the cleavage was essentially --

~ complete.

In contrast to equation the rrajor sulfur product was . 13 so2 9

~/l'hiocresol was found to be only from ten to twenty percent of the reaction product when 3.5 gram atoms of Na was used per sulfonamide ·

per sulfonamide moiety. Toluenesulfinic acid was also isolated.

They found that cleavage rrnJ.st be primarily at the C-S bond since toluene was the primary product formed. Since reduction of benzene and toluene sulfinic acid gave primarily the thiol~ S-N

to hydrocarbon was not thought to be a major reaction. The result

of their work was summarized by the overall reaction scheme given

in Figure 1.

c-s Cleavage-) CH30 + S02 + H2NR - 0 (Primary) . CH - r~-lffi-R --< 3 (Minor) I OJ 0 ' ~------~ 0 i S-N Cleavage CH3-o-~H + H2NR 0

Fig 1 I I Classen and his co-workers (38,39) cleaved sulfonamides with sodium naphthalide. They found aryl sulfinate anions indicating

cleavage at the S-N bond. They thought that their cleavage mechanism

might parallel that of Kovacs, but with sulfinate anions unable to

be reduced to thiols under their conditions. However, the Kovacs .10

. ·scheme indicates primarily c-s bond cleavage • .Apparently whether S-N or C-S cleavage ls the preferred route

is dependent on both the natur~ of the sulfonamide and the reduction method. Some experimenters have obtained products from cleavages indi-· eating primarily S-N bond rupture, while others have obtained evidence for C-S cleavage. Cottrell and Mann (40) cleaved a number of sulfona- ----.-,.-:Tfm:tdes, generally p--toluenesulfonamides, by electrolysis with almost exclusive production of amide and toluenesulfinate ions, indicating S-N bond cleavage. Sulfonamides with hydrogen on the nitrogen lose

a proton makir~ them less reactive. Polarographic studies of reduction

at a dropping mercur-y electrode by Zuman et ... al. indicate C-S cleavage

(Ill). This work was done only on sulfonamides with W1Substituted rj_trogen (two hydrogens on the nitrogen). Additionally hexmnethyl-

phosphoramide has been used in place of anunonia for Birch reductions ( 36) and cleavage of sulfonamides . Thus Cuvigny and Larcheveque ( 37) reported formation of amine, hydrocarbon, and so2 with only traces of thiol indicating C-S bond cleavage.

As alkali metals in ammonia reductively cleave sulfonamides, it occured to C.A. Matuszak and Vishnubhai Patel to study the cleavage of some sulfonamides by the Birch reduction in which a proton source, i generally alcohol, is also present in the arrnnonia solution along

with the alkali metal ( 43). Benzenesulfonamide "f}.JJ, two nitrogen disubstituted sulfonamides XVII and XVIII, and mesitylenesulfonamide XIX were studied with various ratios of reactants W1der differing conditions. 11

In the case of the disubstituted sulfonamides XVII and XVIII the major product was thiophenol. In the case of the unsubstituted . sulfonamide XVI thiophenol was the minor product and and so2 benzene were assumed to be the major products. Compound XIX gave intermediate amounts of 2,~,6-trirrethylthiophenol and disulfide XX

CH R c 3 3 H3oQ-ss-QoH3 CH H c 3 3 n xx· plus similar quantities of mesitylene. No significant change in the yield of the thiol was obtain~d with changes in temperature, variation in alcohol used as a proton source, moles of lithium used, or dryness of the ammonia. The lowest ratio of moles of lithium to substrate used in the reactions was about 4.25. RESULTS

The objective of the present work was to study fUrther the effect of varying substituents on the nitrogen atom and on the ring of sulfonamides in the Birch reduction of aromatic sulfonamides, especially with respect to the amount_oLt:Riol-~ermed,-±n-are-hope ffiat inforrn.ation concerning the initial cleavage step might be discerned. The procedure of Wilds and Nelson (21), where lithium is added to the reaction solution before the proton source, was used to reduce sulf'onamides XVI-XIX, XXI"-XXVI~ and the salt XXVII. The amounts of lithium and ethanol were generally in excess over that needed to

H w3c' , N 0o~s=o XXI XXII XXIII XXIV I I\~ }{ 0I N Li+ N I I o.lH3 a ~2H a XXVI XXV XXVII ------

-----~-

-cleave the sulfonamide and to further reduce any inte!'Il'Ediate sulfinic :acid to thiol. Tables I-X su.rnrn8rize the results of the reductions of the compounds. In general the amounts of reagents used were not varied. Patel's work indicated that the amounts of thiol produced from the reductions

does not vary significantly with changes in the molar ratio of lithium to substrate from 4. 25 to the more often used 8. 5.

Birch Reduction of Benzenesulfonamide XVI Benzenesulfonamide XVI was reacted seven times with the reaction

pal~ameters kept as constant as possible (Table I). The results were

TABLE I BIRCH REDUGriON OF BENZENESULFONAMIDE xvi* Reduction No. Yield of products**

1 7.4% Thiophenol 5.4% Diphenyl disulfide 2 19.6% 3 20.8% 4 9.4% Thiophenol 5 16.4% 6 5.2% Thiophenol 3.4% Diphenyl disulfide i 7 8.8%

*In each reaction 7.4 g (0.0471 mole) of benzenesulfonamide, 2.768 g (0.399 mole) of lithium, 21.4 g (0.4 mole) of ammonium chloride and 65 ml of absolute ethanol were used. The reaction was completed at -33°C. ** Unless otherwise stated the product was a mixture of thiophenol and diphenyl disulfide and the yield was calculated as if the mixture product were all thiophenol. 14

an average yield of 13.8% thiophenol and diphenyl disulfide with a range of 8. 6% to 20.8%. These yields are comparable althoUf..)1 some what smaller than the yields (10-28%, average 18%) previously reported by Patel (43). For some reactions the diphenyl disulfide was separated f'rom the thiophenol, and the lower total yields may be due

to greater loss of the products in the expanded workup procedure. Even when steps were taken to separate the diphenyl disulfide from ------'----t,he-tP.iGpB.enel--,--a.."'l-Nr·ffi-spectru:ni-o-f--the-tlTiopnenol prodUct indicated -/·, significant quantities of diphenyl disulfide, (NMR #3) undoubtedly due to air oxidation of the thiophenol during workup procedures.

If disulfide formed in the reaction solution, it seems likely that it would in turn be reduced back to thiophenol as the disulfide bond is easily reduced by ammonia solutions of alicali metals ( 48) •

Birch_Beduc~ion of N-Phenylbenzenesulfonamide XXIII i ltrom these reactions only ,a small amount of the thiol or disulfide product could be obtained. The yields varied f'rom 0.9% to 11% with the average 6.2% (Table II). In several cases only the diphenyl disulfide was recovered and it appears that when only a small amount of thiol is formed it is more easily converted to diphenyl disulfide than when there is a larger amount of thiol. This might be due to small but constant quantities of impurities capable of oxidizing the \_,- thiol present during workup. These small constant quantities of impurities then oxidize a proportionally larger fraction of the thiol

~ when the total yield of the thiol is small. The amine function (aniline) was recovered apparently unreduced 15

TABlE II BIRCH REDUCTION OF N~PHENYLBENZENESULFONAMIDE XXIII* Reduction Lithium Yleld of products** No. used '1 2. 768 g 4.4% Thiophenol (0.399 mole) 1;6% Dipher~l disulfide 2 II 0.9% Diphenyl disulfide n 3 II 1L9% 7-6-;-8%-Ani-:i:lne 4 II 6.5% 5 II 4.3% Diphenyl disulfide 6*** 5.536 g 7.7% (0.798 mole) 77.7% Aniline 7 2.768 g 6.0% (0.399 mole) * In each reaction 10.99 g (0.0471 mole) of N-phenyl- ~ benzenesulfonamide, 21.4 g (0.4 mole) of ammonium I chloride and 65 ml of absolute ethanol were used. ~he reaction was completed at -33°C. ** Unless otherwise stated the product was a mixture of thiophenol and diphenyl disulfide and the yield was calculated as if the mixture product were all thiophenol. *** Twice the normal amount of ammonium chloride was used in this reaction. even when the amount of lithium was doubled. In each case examined ·:. a good yield (over 75%) of the aniline was recovered.

-- ~irch Reductj.on of N,N-Diphenylbenzenesulfonamide XXIV "" The average yield of the thiophenol was 66.5% with a l'ange over four reductions from 63.6% to 70.8% (Table III). Generally a good 16

yield of the diphenylamine (IR #6) was obtained when isolation of this species was attempted (an average of 71.3% for two reactions), however, sorre of the diphenylamine underwent ring reduction (NMR #4, IR #7 ,8). The partially reduced amine was separated from the diphenylamine due to its increased solubility in acid compared to diphenylamine.·

l------~------TABIE-III BIRCH REDUcriON OF N ,N-DIPHENYLBENZENESULFONAL'VIIDE ·x:x:IV*

Reduction No. Yield of products

1. 63.6% Thiophenol** 62.6% Diphenylamine 2.71 g of partially reduced diphenylamine I 2 64.9% Thiophenol 80.0% Diphenylamine i 2.49 g of partially reduced diphenylamine

3 67 .1% )I'hiophenol 4 70.8% Thiophenol 1.874 g of partially reduced diphenylamine

* In each reaction 14.55 g (0.0471 mole) of XXIV, 21.4 g ( 0. 4 mole) of' ammonium chloride, and 65 ml of absolute ethanol were used. The reaction was completed at -33°0. i ** All thiophenol samples may contain traces of diphenyl disulfide. 17

Birch. Reduction of N-.Methyl-N-phenylbenzenesulfonamide XXV .The yields of thiophenol were very similar to those of XXIV. . . Tne a~erage yield was 79.7% thiophenol ru1d diphenyl disulfide with .. a range of 74.1% to 84.5% for three reductions (Table IV). From the first reduction unchanged N-methylaniline (23.3%) was recovered.

TABLE IV

BIRCH 'REDUCTION OF N..:.M8TI-fYL-N-PHENYLBENZENESLJLFONAJ\1IDE XXV* Reduction No. Yield of Products

1 67.9% Thiophenol 12.7% Diphenyl disulfide 23.3% recovery of N-methylaniline

2 · 69. 7% Thiophenol 14.8% Diphenyl disulfide

3 66.9% Thiophenol 7.2% Diphenyl disulfide * In each reaction 11.6959 g (0.0473 mole) of XXV, 21.4 g (0. 4 mole) of ammonium chloride and 65 ml of absolute ethanol were used. Tile reaction was completed at -33°C.

Birch Reduction of N,N-Dimethylbenzenesulfonamide XVII For the disubstituted compound XVII the yield of the thiophenol was a 74.4% average of two reductions (Table V), somewhat higher than the 55-73% range, 67% average previously reported by Patel (43). i

Birch Reduction of N-Met~ylbenzenesulfonamide XXI The monosubstituted sulfonamide XXI behaved similarJy to the monosubstituted sulfonamide XXIII and only a small portion of the thiol product was found. . The average yi.eld of three reductions was 6.8% thiophenol with a range of 4.2% to 11.8% (Table VI). ~-~-·- --=~~~-'-'---·=~. . ·~· ·--~~ --

TABlE V BIRCH REDUCTION OF N,N-DIMETHYLBENZENESULFONAMIDE XVII* Reduction No. Yield of Products

1 75;6% Thiophenol**

2 ·73 .1% Thiophenol

* In each reaction 8.7155 g (0.0471 mole) of XVII, 21.4 g ( 0. 4 mole) of arrnnonium chloride and 65 ml of absolute ethanol were used. The reaction was completed at -33°C •. ** Thiophenol samples may contain traces of diphenyl disulfide.

TABLE VI BIRCH REDUCTION OF N-METHYLBENZENESULFONAMIDE XXI* Reduction No. Yield of products

1 7.5% Thiophenol**

2 4.3% Thiophenol

3 11.8% Thiophenol * In each reaction 8.0646 g (0.0471 mole) of XXI, i 21.4 g (0.4 mole) of ammonium chloride and 65 ml of absolute ethanol were used. The reaction was completed at -33°C~

** Thiophenol samples may contain traces of diphenyl disulfide. 19

Birch Reduction of N,N-Diis6butylbenzenesulfonamide XVIII SuJ.fohamide XVIII gave an average yield of 65.8% thiophenol based upon the amount of starting material consumed (Table VII).

Ih this reaction some starting material was always reco~ered, but the amount was cut in half (12.3% from reaction one to 6.1-6.9% for reactions two, four, and five) by pulverizing the starting material to increase the surface area. The yields range from 57.0%

-----te-7-7 .1-%-E-net :i:nci:udtng-rea:et~i--o~three because of accidental loss of rmterial in workup) • This was higher than Patel's ( 43) results (36-53% average 46%).

TABLE VII

BIRCH REDUCTION OF N,N-DIISOBUTYLBENZENESULFON~ITDE XVIII* Reductj_on No. Yield of products**

1 53.7% Thiophenol 12.3% Unreacted XVIII 61.2%***

2 53.5% Thiophenol 6.1% Unreacted XVIII 57.0%*** 3 22.9% rrhiophenol**** 4 63.7% Thioohenol 6.9% Unreacted XVIII 68. ~%***' I 5 71.7% Thiophenol 6.9% Unreacted XVIII 77.1%*** = * ') In each reaction 12. 6888g ( 0. 04 71 mole) of XVIII, 21.1~ g e (0.4 mole) of ammonium chloride and 65 ml of absolute ethanol were used. The reaction was completed at -33°C. ** Thiophenol and unreacted XVIII samples may contain traces of diphenyl disulfide. *** Yield based upon amount of XVIII consumed. **** Loss due to spillage. 20

"Birch. Reduction of N-Isobutylbenzenesulfonarn:i.de. XXII .Five reductions. of XXII gave an average yield of 8.4% thiophenol ···with a range of 3.0%. to 11.2% (Table VIII).

·TABLE VIII

·BIRCH REDUC'"fiON OF N-ISOBUTYLBENZENESUIFON.AJVJIDE XXII* .Reduction No. Yield of Thiophenol**

______· -=1 ______3_ .• _0%'------; 2 11.2% 3 7.5% 4 10.4% 5 9.9%

* In each reaction 10.046 g (0.0471 mole) of XXII, 21.4 g - ( 0. 4 mole) of ammonium chloride and 65 ml of absolute :ethanol were used. The reaction was completed at -33°C. i ** Thiophenol may contain traces of diphenyl disulfide. I

Birch Reduction of Lithium Salt of N-Phenylbenzenesulfonamide XXVII The lithiuni salt of N-phenylbenzenesulfonamide was reduced twice with an average yield of 4 .1% thiophenol and diphenyl disulfide (Table IX). These small samples were difficult to obtain highly pure and it is likely that the actual percentage of thiol is a little less than that given.

Birch Reduction of p-Sulfarnylbenzoic Acid XXVI The products obtained from the reduction of XXVI were not as easily characterized as those from the other reactions. The reactions 21

TABLE IX BIRCH REDUCTION OF Lf+[0-S02.;.N.;.QSJ- XXVII*

Reduction No. Yield of Products

1 2, 1.7% Thiophenol 2.1% Diphenyl disulfide

* In each reaction 12.2119 g (0.0471 mole) of XXVII, 21. 4 g {0. 4 mole) of arrnnonium chloride and 65 ml of absolute ethanol were used. The reaction was'------c.. ------ccump~etea-at -33°C. ** This sample may have contained diphenyl disulfide and other unidentified products.

generally yielded a mixture of benzoic acid, 1,4 dihydrobenzoic acid, tetrahydrobenzoic acid and ethyl esters of these acids (Table X). The yields of the various products were determined from the NMR spectra. The percent molecular composition was obtained directly from the spectral integration by summing up the· areas of the hydrogens for

each component and dividing by the n~er of hydrogens of that species to obtain the molecular ratios. To obtain the weights of each component the molecular weights were multiplied by the molecular percentages and the ratios of these terms compared to the total weight obtained from I the reaction to obtain each component's weight. Although the percent I yields obtained by this method are undoubtedly not as accurate as direct weighing of individual product, it is estimated they are off by only five to ten percent. Several samples of the reaction product were analyzed for sulfur

to see if any thiol product or unreacted starting material was present

c 22

;TABLE X

:BIRCH REDUCTION OF P-SULF.AivTYLBENZOIC .ACID XXVI* Reduction No. Lithium used Sulfur found** Yield of products***

1 2.768 g. -:No Analysis 52% Benzoic acid (0.399 mole) 42% 1,4 Dihydro benzoic acid

2 2.768 g less than 0.1% 26% Benzoic acid (0.399 mole) 59% 1, 4 Dihydro benzoic acid ------~3------~4.1~4-g~------~no~.lrl~%1----~.Mi~·~xt~-~ur~e~o~f~a~b~o~ut~e:q~u~a~l----- ( 0. 06 mole) amounts of at least three different di- or tetra hydro products

4 4.164 g less than 0.1% 6% Benzoic acid (0.6 mole) 49% 1,4 Dihydro benzoic acid 8% Tetrahydro benzoic acid * See Experimental Procedure f'or amounts of reactants and conditions ** Analyzed by Chemalytics, Inc., Tempe, Arizona *** See text for method of calculation of yields.

as their NMR peru{s could easily be obscured by the benzoic acid peaks. The amounts of sulfur were 0.11% or less, indicating virtually none of' these products were present. A value of 0.11% sulfur was found for the product of reaction three, which corresponds to only 0.7% starting material.

In the first two reductions the materials recovered were mostly

benzoic acid and 1,4 dihydrobenzoic acid in relatively good yields.

In one of the first two reactions the benzoic acid was a major product. In the other reaction about twice as much dihydro product was ~---""'~~--·-·-·--·--~ 23

formed. The ratio of moles of lithium to moles of substrate was 8.5 for both of these· reactions. In the· second two reductions the molar ratio of lithium to substrate· was increased to 12~ 75 with. the expected result that nnre ring reduction occured. The first time the reaction was done with the greater amount of lithium, the reaction residue was allowed to remain standjng in the reaction flask about twelve hours after nnst of the occured. This was probably due to isomerization and polymerization of. the initially formed products most likely dihydro and tetrahydro benzoic acids in the basic media. Other compounds have been reported to do this (10). The fourth reduction of XXVI was worked up shortly after the amnonia had evaporated. This yielded primarily 1,4 dihydrobenzoic acid with smaller amounts of benzoic acid and tetrahydrobenzoic acid. Some of the acids became esterified during workup. NMR spectra (spectra 7-10) were taken of all the reduction products of XXVI and their interpretation is given in the next section. i ·:.NMR INTERPRETATION

Tetrahydrodiphe11yl~.ne

From the NMR spectra (#4) the following assignments are made: Five aromatic hydrogens at 6. 7 and 7.2 8; two vinyl hydrogens at 5. 7 S; and eight other hydrogens less easily assigned. One of the eight is the amine hydrogen and it is probably at 3. 6 8 as is one other hydrogen, probably the rnethine hydrogen alpha (Ha) to the nitrogen atom. The remaining six hydrogens of the reduced ring produce the eomplex pattern from 1. 4-2. 6 S .

o:-o-a I ·: o:zQ XXVIII XXIX XXX Structures XXVIII and XXIX are the best possibilities. Compound

XXX is ruled out because it has only one rather than two vinyl hydrogens.

Also the chemical shift of the vinyl is calculated to be much higher

(7. 02) than observed. The 0 values are calculated according to Siverstein, Bassler and Morrill (49). It has also been shown that XXX tautomerizes to the imine (56) with the equilibrium favoring I the imine.

Birch gave the pathway for the reduction of aniline to the tetrahydro product as that of equation 14 (50). Simple extrapolation of this route to diphenylamine gives structure XXIX as likely the tetrahydro amine product from the reduction of XXIV. The calculated 25

value of 5. 8 S for the vinyl hydrogens of such a structure agrees with. the observed spectra. The vinyl hydrogens for structure XXVIII . . are calculated at 5. 64 8 and 5. 76 8 ,' rather than one value.

Possibly there is a mixture of products, but the sharp single

L-----~viny~_peak-a-qQ.-eJ:ese-agreemenr-of-tne ir spectra ( IR #7, 8) from different reaction products would tend to dispute this. Gas chromatography was inconclusive as temperatures high enough to volatilize the material also caused decomposition.

Reduced Benzoic Ac~Lds The materials from the first two reductions of XXVI gave easily

interpreted spectra (NMR #7 ,8). An NlVJR of lmown 1/1 dihydrobenzoic acid (NMR #5) indicates the peaks at 2. 6, 3. 7 , and 5. 9 S are due to the absorption of the 1,4 dihydrobenzoic acid. The peaks at 7.5 and 8 .1 S agree with benzoic acid. The NMR absorptions at 1. 25

and lt. 2 8 were at first assumed to be from diethyl ether or ethanol still present in the mixture, but closer analysis indicates ethyl esters. The quartet at 4.2 8 agrees quite well with the ar of ethyl I 2 benzoate, being too high for an ether or ethanol. The ester seems a likely byproduct of the workup of the reactions as ethanol and the acids are both present in an acid solution of pH 1-2. Therefore

in determining the masses of the products, the CH cH group was 2 3 26

-treated as an entity in itself and only the protons of the ring were

considered in determining the yields of reduced and unreduced ring. The spectra of the-') products. of the second two reductions are not as simple as the first two. · There appears to be at least three different types of vinyl hydrogens from the NMR spectra of third reaction

product (NMR #9). A number of vinyl hydrogens are shown with calculated S values. Also listed are observed values from NMR #9 . ------.;TflePe-are-a-nunll:rer·-of-pussiole

should absorb from 6.75-6.95 Sand no absorption is observed in this

H COOH H' cOOH' H· H ;====\ F\ (\ ~ F) I ~ Calculated 7-31 6.44 6.0 5.8 ~ ;;. Observed 7.14 6.42 5.8-6.05 5·8-6.05 (NMR tf9), ~--

range. Compounds XXXII and XXXIII are the most likely candidates for the tetrahydro products based upon the spectrum, but the ratio of alkyl hydrogens to vinyl hydrogens from the spectral integration

OOOH OOOH COOH COOH I- 0 0 0 0 - XXXI XXXII XXXIII XXXIV

COO!L 0I ' OH c XXXV XXXVI 27

indicate that some clihydro product, possibly XXX:V or XXXI must be

;present. No conclusion is made as to which compoiinds cofnprise the tetrahydro mixture or what the percentage present of each compound r.might be, but there appears to be a mixture of at least three clif- 'ferent products . Benzoic acid appears to be present only to a small

-extent and the absorptions at 3. 7 and 1.2 care attrib~uted to diethyl ether. or ethanol.

------~··'111~-spe~ct~rum from tne f'ourth reduction ( #10) ·is somewhat more

easily interpreted. There is a small amount of benzoic acid (7 .6 and 8.2 S ) , rather large amounts of ethyl ether (1.2 and 3.5 8) and ethyl ester (1.2 and 4.2 8), large amounts of 1,4 dihydrobenzoic acid (2.7, 3.75, and 5.9 S)and some tetrahydro products (2.3, 6.4, and 7.1 S) . The percentage of tetrahydro product was calculated I -assumlng the peak at 2.3 resulted from 7 -CH - or -CH- ring hydrogens. 8 2

I DISCUSSION

The· original goal of this work was to see-how various substit-

.uents on the nitrogen of sulfonamides affect the reductive cleavage to thiophenol. Kovacs and Ghc:ttak (35) had reported in the sodium

.liquid ammonia reduction of p-toluenesulfonamide that the_pr.i.rp.a~J'------~, - cleavage occured at the c-s bond to yield toluene with srnaller amounts -of thiocresol.

From the results of this work and that of Patel it is clear that

.Kovac 1 s scheme should be modified to take into cons:i.deration the nu.lTJber of hydrogens on the nitrogen atom. vJhen the sulfonamide is of a secondary amine , the cleavage takes place prirr.arily at the S-N bond wlth a large yield of thiophenol. When the sulfonamide is of a primary amine, C-8 bond cleavage seems to be favored with S-N cleavage, eventually forming thiophenol, the minor path. Kovacs and Ghatak .

assumed all sulfonamides cleaved primarily at the C-S bond, but they

studied only sulfonamides of primary amines and peptides where there

-was one -hydrogen on the nitrogen. The overall mOdified reaction scheme is then given by Fig. 2. Although in the current investigation I no attempt was made to isolate benzene, it is assumed that some

cleavage does occur at the C-S bond to yield benzene.

It is interesting to note that Kovacs obtained only a little -

~ over 50% thiol from the direct reduction of sulfiDic acids. Since 29

yields of up to 75% thiophenol were obtained in this work, Birch reduction may enhance the formation of thibls from sulfinic acid intermediates (no alcohols were used as proton sources in Kovac's work).

< Minor (

+ I NHr -R ~ 2 J.iajor or . Nli::..R 2

Birch. (29) suggested the following reaction scheme for the reductive cleavage of a generalized molecule A-B. In this scheme a number of possible species can form by the cleavage of one molecule. I 30

For sulfonarnides use of A-so2-B, where A equals benzene and B equals NR2, for the.· generalized molecUle is more appropriate. The number of possible pathways tO.. the various products. (benzene, thiophenol, diphenyl disulfide, amine, etc.) is much larger due to two possible . c cleavage sites. Likewise, if one includes the possibility of proton- ation of the anion radical intermediate before cleavage or second electron addition, the number of pathw·ays dramatically increases .

_____Some-of.-tiC1e-}3es-s-ib-l-e-pathways-are-included m the appendix. The essential question is, why do tr1e monosubstituted sulfonamides

give products that indicate C-S cleavage a.s the primary route, while disubstituted sulfonamides undergo S-N cleavage. If the sulfonamide

loses a proton from the nitrogen to fonn an anion A-S02-B- then sub sequent addition of an electron would seem to be favored at some distance from the nitrogen bearing the negative charge. It is not likely that the weak base annnonia would abstract H+ from the sulfonamide, but the lithium metal easily can. Addition of an electron to an anion would produce a dianion radical, a species not proposed as an intermediate in the cleavage of sulfonamides by other experimenters. However, this type of species

may be important in other Birch reductions such as the reduction of benzoic acid and benzamide. Dickson found that benzamides with at least one hydrogen on the nitrogen gave only ring reduction. Resonance

c of the dianionic radical, shown below, of this species and also of benzoic acid seems to account for enhanced ring reduction due to

stabilization of the charge of the ring (17, 51, 52). 31

'-·'

.. •.

Since cleavage of sulfonamides occurs rather than ring reduction / \ ~-:;w-"-R V 0II 'H. XXXVII to XXXVII, the situation is not completely analagous, but in both benzamides and sulfonamides the presence or absence of hydrogen on nitrogen profoundly influences the course of the reaction. Since the ability of benzamide and benzoic acid to form anions tends to protect the functional group from reduction and to enhance reduction of the ring, it does not seem surprising that sulfonamides capable of losing a proton are cleaved between the ring and the functional group (C-S) rather than between heteroatoms of the functional group itself (S-N). In the reduction of compounds XXVI and XXIV the aromatic r:i.ng .systems were very likely reduced after the· cleavage of the sulfon- I anrl.de function. If this were not the case, one should be able to reduce the amounts of reductant and obtain the sulfonamide with the reduced ring systems. Evidence for any such compounds was not found in these reductions, although the excess lithium and ethanol used probably would have cleaved the sulfonamide even if prior ring re- 32

duction occured. In the case of XVII, recovery of unreduced starting material is probably due to its low solubility·.· Difficulty of reduction of sulfonamides with a hydrogen on nitrogen has been encountered in other reduction media. Anionic

reducing agents, such as LiAIH4, do not cleave these sulfonamides, but some N,N-disubsti tuted sulfonamides are cleaved. When sodium and alcohols are used (without ammonia) N-phenyl-p-toluenesulfonamide . ------==~ ,-:-:-:-~~~,---::-:,-'-::-:~:-:L:i;::-::::;:;__:_~::-:::::ll-~-=~:-::::::-----:---.. -----grve-s-rro~odi:um p-toluenesulfonate, but when methyl, ethy , or another - phenyl group is also substituted with phenyl on the nitrogen, about 70% yield of the toluenesulfonate is obtained (53,· 54). Most of the examples of sulfonamide cleavage in the introduction give C-S cleavage, or no cleavage at all, when there is hydrogen on the nitrogen. Factors other than whether there is a hydrogen on the nitrogen probably also play an important role in deterrnin:i.ng the course of the reaction. In Classen's (38, 39) work it v.ra.s,shown that methanesul- fonamides only cleaved by sodium naphthalide if the nitrogen was disubstituted and at least one substituent was aromatic. Additionally it has been shown that the related cleavage of sodium salts of sulfonic acids by sodium in ammonia depend on whether or not the sulfonic acid group is alpha to an. unsaturated system. Compoun0. XXXVIII was not cleaved whereas the others shown were cleaved (55). I

QcH2G112so3Na

XXXVIII ,, 33

Although the cleavage mechanism for the sulfonic acid salts is . probably quite different from sulfonamides, the presence of a pi system of electrons, which_may be capable of accepting an electron from the reductant, riear the· group cleaved is indicated as a necess1ty in both cases • In view of the above it appears that the initial step in the reductive cleavage of sulfonamides is the addition of an electron to _____t,he-b@nzene-r>ing-882-pi-erect--r·on system. Then cleavage may occur . . . . . + . . or the system may add either another electron or H before cleavage. These three p9ssibilities are illustrated in Figs. 3A and 3B for disubstituted and monosubstituted sulfonamides.

Rv R 0o=-s=o

R R R R \ I R R ' I minor N \ "' major N I . o=s-=oI O=S=O 00SH + so i 2

Fig 3A

+ R-N-R -·or~ 34

•. or - Fig JB 0

= or -:

Assuming that the so2-benzene ring pi. electron systems overlap sufficiently to delocalize the electron added to the molecule, a negative charge on the nitrogen would cause the electron density in i the ring (from the added electron) to be increased relative to the sulfur-oxygen system, due to repulsion of one charge by another. ,---- This would faciliteat C-S bond cleavage and formation of benzene, as is found for monosubstituted sulfonamides, rather than thiophenol - formation, especially if H+ attack occurs at the ring before cleavage. 35

Further argwnent against S-N cleavage when nitrogen has a negative . charge is that such a cleavage would produce species with either two negative charges on the nitrogen or a negative charge plus an ,cunpaired electron. Such ·a leaVing group does not seem likely.

Therefore, the leaving group contains the sulfur, capable of assuming

vai,ious oxidation states with its unfilled d orbitals. With no

,charge on the nitrogen before cleavage, S-N cleavage could easily

~-==----=--~--.------~-- UC<:..'Ut--t-o~-roG.uce NK as a leaving group. 2 Further it would seem that if S-N cleavage did occur with a

double negative charge on the nitrogen or a negative charge plus an

unpaired electron, an electron withdrawing aromatic group on the

nitrogen would greatly facilitate such cleavage compared to an electror1

donating alkyl group. This would result ultimately in more thiophenol

for the former. However no such increase in the thiophenol was ob-

served for N-phenylbenzenesulfonamide compared to N-lnethylbenzene-

sulfonamide and N-isobutylbenzenesulfonamide.

However, since some thiophenol was formed for sulfonamides of the

primary amines, some cleavage of S-N occurs, either vdth the nitrogen

leaving with a double charge or as an anion radical, or the cleavage

at S'-N occurs to that portion of the sulfonamide that still has the hydrogen on the nitrogen. i Substituents of the ring should affect the product fonnation,

i.e. the pathway of the cleavage, by stabilization or destabilization

of intermediates formed. This being the case, the r~1g ion intermediate

of Fig. 4, which could be formed in the cleavage, would be stabilized by 36

• so Nii 2 2

X0 .. or or ) + ---7 products • ~

NH -so2 2 X 0 stabilized by electron 1·rith dral"1ing groups ~------~-- Fig 4

electron withdrawing substituents yielding almost exclusively C-S

cleava@e products. The oposite effect should be seen for electron

. donating substituents. Stabilization of the ring radical of Fig. 4

by substituents might be arguable, but it is doubtful that much of

this intermediate is present as it should dimerize appreciably and

no biphenyl analogs were found. Also, Rossi and Bunnett reported

phenyl anion was formed on the potassillnl, liquid ammonia cleavage

of so, so , ¢so cH , and ¢so3 (57). ¢2 ¢2 2 2 3 1I H' ' NI • greater electron donating @ effect, more thiol I X

greater electron lri thdravring effect, less thiol

Fig 5 37

'lb.e inductive effect of the substituents on the rings would also influence the acidity of the inolecules ·• Less. acidic molecules would yield more thiol from the cleavage of the· Unionized molecule at the· S-N bond. Electron withdrawing groups would tend to. make the molecule more acidic and the cleavage would be· favored at C-S, as

s.:.N cleavage would produce unstable nitrogen leaving gpoups. Fig. 5 summarizes the substituent effects.

------':'Ihe-reducti-orrs--of--,-XIX-C4]~) , XVI and XXVI support this scheme.

The ,2 ....mesitylenesulfonamide with electron donating groups ortho and para to the sulfaxeyl group gave an average of 27% ;2 ,:4 ,'6-trimethyl- thiophenol, while p-sulfamylbenzoic acid with the electron withdrawing group COOH at the para position gave little or no p-thiosalicylic acid. As would be expected theunsubstltuted benzenesulfonamide is intermediate at 13.8% thiophenol.

Both 1~substituted and monosubstituted sulfonamides favor C-S cleavage. The similarity is probably due to the ability of the unsubstituted sulfonamide to form an anion also.

An interesting series of compounds for further study to correlate the ring substituent effects and the hydrogen on nitrogen effect would be the compounds listed below. Yields of thiol would be predicted i to range from zero for XXXX to nearly quantitative for XXXIX with the other two being intermediate.

HR HR R R R R • I ' . ' NI ' ' N N I 1l o::.s::oI I o=s=o H3COtH3 n3oocH3 a aCOOH CH coon OH 3 3 xx.xx XXIX SUMMARY AND CONCLUSIONS

1. The disubstituted sulfonamides N,N-d:imethylbenzehesulfonamide, N,N-diisobutylbenzenesulfonamide, N,N-diphenylbenzenesulfonamide; and N-methyl,N~phenylbenzenesulfonamide were reduced with primarily the fonnation of thiophenol (low of 5}_._Q~Land_higb_oL81L~%-1'rith------~ - average of 70.6% for 13 reactions) . ·

2~' The monosubstituted sulfonamides N-methylbenzenesulfonamide, N-isobutylbenzenesulfonamide, and N-phenylbenzenesulfonamide were reduced with little thiophenol formation (low of 0.9% and high of 11. 9% with average 7. 2% for 15 reactions) .

3. Benzenesulfonrurdde was reduced yielding a modest amount of thiophenol (low of 8.6% and high of 20.8% with average of 13.8% for 7 reactions).

It. The lithium salt of N-phenylbenzenesulfonamide was reduced with results similar. to that of the free sulfonamide (average of lt~l% for two reactions).

5. p-Sulfamylbenzoic acid was reduced with the formation of benzoic acid, l,lt dihydrobenzoic acid, and various other dihydro m1d tetrahydrobenzoic acids. The· more moles of reactant us.ed, the more the reduction of the benzene ring. Little or no thiol was produced. 39

6.· Partially reduced diphenylamine was recovered from the reduction of N,N-diphenylbenzenesulfonamide.

The clea~age path. for sulfonamides is primarily determined by whether or not there is a hydrogen on the nitrogen atom. When a hydrogen is present cleavage primarily occurs at the c-s bond yielding small amounts of thiol, while disubstituted sulfonamides give high

[email protected]:i:i"lElicat-ing-p-rimar21y S-N cleavage . Substituents on the ring further affect the cleavage. Electron withdrawing groups enhancing c-s bond cleavage while electron donating groups enhance C-N cleavage. Reduced ring products are formed when excess reductant is present to reduce rings after cleavage.

-ii:---=--= EXPERIMENTAL

General Experimental h~ocedures

F,- All of the reductions were performed in essentially the same manner. A three neck, two liter, round bottom flask was equipped with a dry ice condensor, a glass mechanical stirrer with variable speed control and a dropping funnel. The substrate (0.0471 moles) was introduced into the flask and approximately 600 m1 of anhydrous ammonia was distilled from its tank and condensed into the reaction flask without any additional measures to further dry the ammonia. The substrate was generally pulverized if it did not readily dissolve in the anrrnonia. T'ne lithium (Foote Mineral Co.) was cut from uniform thickness ribbon and the Vleights used determined by measuring the lengths of the pieces and applying the factor 0.089 g/cm quoted by the supplier. The lithium was cut into small pieces and the protective coating of petrolatum was removed by a series of five baths of low boiling petroleum ether (30-60°C). In the manner of Wilds and Nelson (21), the ethanol was added last after the addition of the lithium to the ammonia solution. The ethanol was absolute and was only added I after all of the lithium metal had dissolved and the temperature of the reaction solution had reached -33°C and the ammonia was refluxing.

Generally all 65 Inl of the ethanol was added even though the reaction was often completed, as indicated by the fading of the dark blue color, .,£l.f'ter the addition of less than half of this amount. A molar amount ,of NH4Cl equivalent to the moles of lithium used was then added and i the solution stirred an additional 30 to 60 minutes. The arrnnonia F"

was allowed to evaporate at ambient temperature and pressure. The reactions were worl<:ed up from 8 to 30 hours after the com-

.pletion of the reaction. In general four 100 m1 ether extractions

-were done. T'ne combined ether extracts were washed with water and

-----i3-

reduced pressure with heating from a water bath at 40-50°C. The weights

of Birch reduction products were obtained by weighing the tared round bottom flasks after solvents had been evaporated. In most of the re- - - actions the product obtained was a mixture of thiophenol and diphenyl I ill disulfide. Except where otherwise indicated the percent yield cal ~ culations were as if the total product were thiophenol.

Deionized water was used without further purification. Melting

points were obtained on a Thomas-Hoover capillary melting point appar-

atus and are not corrected. Infrared spectra were run on a Perkin-

Elmer 137 Infracord and Proton Magnetic Resonance spectra were run

on a JOEL Minimar 100. Gas chromatography was run on a Varian H350

Ae:rograph with colurm "A" 6 1 by 0. 25" aluminum packed with 20% SF-96 I

on 60-80 mesh firebrick and colurm "B" 6 1 by 0. 25" aluminum packed

with 10% apiezon on 60-80 mesh firebrick. Weights, when expressed

in milligrams or one tenth milligram, were obtained on an Ainsworth lON

analytical balance. Other weights were obtained on an Ohaus Dial-0-Gram

pan balance . 42

The following reagents were used for the production of the sulfonamides and diphenyl disulfide: Methylamine hydrochloride, J. T. Baker unspecified quality; N-methylaniline,J.T. Baker.practical grade;

. . · diphenylamine, Eastman Organic Chemical practical grade; isobutylamipe,

J. T. Baker unspecified grade; dimethylamine hydrochloride, J. T. Baker "Baker Grade"; benzenesulfonyl chloride, Matheson, Coleman and Bell unspecified grade; thiophenol, Matheson, Coleman and Bell unspecified

grade. Unless otherwise indicated all other chemicals used were shelf stock of unknown origin and purity.

I 43

Preparation of Diphenyl Disulfide XXI: Diphenyl disulfide was prepared by the method of Field_and

Lawson (45). To a 500 ml flask 300 ml of dry benzene and 24.4 g (0.055 mole) of Pb(C H ) , anhydrous, were added. Then 11.02 g 2 3o2 4 (0.1 mole) of thiophenol was mixed with 10 ml of dry benzene and added slowly to the lead tetraacetate solution with swirling. When the thiophenol was added to the solution, the color changed to brown with ------:a-yei.-:tow-orange preclpltate. Upon standing for 30 minutes, after all the thiophenol had been added, the solution turned dark brown and the precipitate became lighter. The solution was filtered and the filtrate evaporated in·a rotatory evaporator under reduced pressure

yielding a brown solid. The solid was mixed with 200 ml of diethyl

---- ether and filtered. The ether was evaporated at ambient temperature 1 ~ and pressure. The resultant solid was recrystallized from methyl alcohol ll:!l l!;l until a constant melting point was obtained. This yielded 5.2817 g (0.0242 mole, 48.4%) of diphenyl disulfide, long, near white needles, melting point 60-61°C (lit. m.p. 60-61°)(46).

REDUCTION OF BENZENESULFONAMIDE: First Reduction of Benzenesulfonamide XVI: Benzenesulfonamide (prepared by Patel and labeled VVP-50-1 I m.p. 151-152)(43), 7.4 g (0.0471 mole) was added to a two liter, three-neck fla..sk equipped with a rrechanical stirrer, dry ice condenser >.---- "=== and dropping furmel. Then 600 ml of anhydrous ammonia was condensed into the flask. As the ammonia was allowed to reflux at -33° C, the sulfonamide dissolved. Next 2.768 g (0.399 mole) of lithium metal,

( --- -·----~ ____ .:...·----~-·.-·· --· ·---·. -·-':

411

cleansed of protective petrolatum in a series of five baths of low

d h- boiling petroleum ether, was dissolved in the ammonia solution. rlhe = ~ .. E resultant solution is dark blue. F From the dropping funnel 65 ml of absolute alcohol was added. After about half of the ethanol had been added the solution began to change in color from blue to green to yellow. After the addition of all the ethanol the color faded completely. Then 21.4 g (0.4 mole) of ammonium chloride was cautiously added and the solution stirred for an hour. The ammonia was allowed to evaporate overnight at ambient temperature and pressure. To the residue of the reaction 200 ml of cool deionized water was added with the formation of clear solution with small amounts ---- ~ of preclpitate. With 10% HCl the mixture was brought to a pH of 1-2

~ with the resulting formation of a cloudy light pink suspension.

That was extracted with four 100 ml portions·of diethyl ether and the combined ether extractions dried over 5 g of anhydrous Mgso4. Upon the addition of the first ether portion to the acid solution the pink color disappeared, but it was noted that there was a fiJm at the interface of the two layers that was reddish. This was probably due to small amounts of polymers forming or inadvertant introduction I of indicator to the reaction mixture from pH papers. TI1e ether was evaporated with a rotatory evaporator under reduced pressure with heating yieldlng a light yellow oil containing some solid. The oil was decanted off yielding 0.38 g (0.00345 mole, 7.4%) of a thiophenol solution of diphenyl disulfide whose ir spectrum (IR 113) compared favorab]y with that of known thiophenol (IR til). The solid

'Was 0.28 g (0.00128 mole, 5.4%) of diphenyl disulfide identified by ir (IR #4) spectrum comparison with that of prepared diphenyl

,disulfide (IR #2). NMR spectrum (NMR #3) of the liquid showed it

·to be a solution of about 25% mole/mole of diphenyl disulfide in thio-

.phenol.

Second Reduction of Benzenesulfonamide XVI:

The a.rrounts of reactants, experimental conditions, procedures, and equipment used for the second reduction of XVI were the same as the first reduction. The reaction yielded 1.02 g (0.00926 mole, 19.6%)

.of a light Yellow liquid that was assumed to be thiophenol.

Third Reduction of Benzenesulfonamide XVI:

The amounts of reactants, experimental conditions, procedures, and equipment used for the third reduction of XVI were the same as the first reduction. The reaction yielded 1.08 g (0.0098 mole, 20.8%) of·a light yellow liquid with some precipitate in the form of long needles assumed to be diphenyl disulfide. 'lhe liquid was identified

as thiophenol by ir spectrum comparison with that of known thiophenol. Fourth Reduction of Benzenesulfonamide XVI: I The amounts of reactants, experimental conditions, procedures,

and equipment used for the fourth reduction of XVI were the same

as for the first reduction with one exception. After the reaction

~xture was acidified to pH 1-2 with 10% HCl the solution was filtered

in order to remove any diphenyl disulfide. 'lhe solution was then -46

worked up as bef'ore. This yielded 0.49 g (0.0045 mole, 9._4%) of a lig1lt yellow liquid identified as thiophenol by ir spectrum ( ,con:parison with that of' known thiophenol.

Firth Reduction of Benzenesulfonamide XVI:

The amount of' reactants, experimental conditions, procedures, and equiprrent used f'or the fifth reduction of' XVI w·ere the same as for the f'irst reduction. The reaction yiP lded-0-.-8§-g~tG-.08-'7-7-l~me:d~e-,-,------,~

16.4%) of a light yellow liquid identified as thiophenol by ir spect1~ comparison with that of' known thiophol.

Sixth Reduction of Benzenesulfonamide XVI:

The amounts of reactants, experimental conditions, procedures, and equipment used for the sixth reduction of XVI were the same as f'or the fourth reduction. The precipitate collected weighed 0.1733 g (0.00079 mole, 3.4%), melted at 59-60°C and was assumed to be di phenyl disulfide. The light yellow liquid weighed 0.1733 g (0.00157 mole, 5. 2%) and was assumed to be thiophenol.

Seventh Reduction of Benzenesulfonamide XVI:

The amounts of reactants, experimental conditions, procedures, and equipment used for the seventh reduction of XVI \'/'ere the same as I for the first reduction. The reaction yielded 0.460 g (0.00417 mole,

8.8%) of the yellow liquid assumed to be thiophenol with traces of diphenyl disulfide. 47

Preparation of N-Phenylbenzenesulfonamide XXIII: To 500 ml of 10% NaOH solution in a one liter beaker was added i ~ 93.1 g (1 mole) of aniline. Benzenesulfonylchloride, 175.6 g (0•99 i1

mole) , was added dropwise to the solution vJhich was stirred by a mag

netic bar stirrer for eight hours . At the end of that time there was

some precipitate at the bottom of the beaker. The solution was acid-

ified with 20% HCl and more precipitate was formed. 'Ihis was collect ------t=o-d-cy--ri-rtra'E1on and recrystallized from ethanol/water mixtures until

constant melting point was obtained upon air drying. This yielded

162.2 g (0.695 mole, 69.5%) of XXIII, white crystals, m.p. 110-111° (lit. m.p. 112°) (47).

REDUC'l'ION OF N-PHENYLBENZENESULFONAMIDE:

!t'irst; Eeduction of N-Phenylbenzenesulfonamide XXIII:

N-Phenylbenzenesulfonamide, 10.99 g (0.0471 mole) was added to

a three-neck, two liter flask equipped vd.th a mechanical. stirrer,

dry ice condenser, and dropping funnel. Then 600 ml of anhydrous

ammonia was condensed into the flask and as the ammonia refluxed at

- 33°C, the N-phenylbenzenesulfonamide readily dissolved. Then 2. '{68 g (0.399 mole) of lithium metal, cleansed of protective petrolatum coating I with a series of five baths of low boiling petroleum ether and cut into

small pieces, was dissolved in the amnonia solution. The color of the

solution progressed from clear to yellow to green to blue as the lithium

was added.

From the dropping funnel 65 ml of absolute alcohol was added dropwise. After about 20 ml of the alcohol had been added the sol-

ution turned to a deep yellow, which lightened upon the addition of _" . 48

the remainder of the alcohol. A brown solid began to form at the edges of the reaction flask at that time. TI1eh 21.4 g (0.4 mole) of

NH4Cl was cautiously added and the solution stirred for about an hour. The ammonia was allowed to evaporate overnight. at ambient temperature ~- and pressure, yielding a light· yellow'-brown paste. To the residue of the reaction was added 200 ml of cool deionized water and a clear, faintly colored solution resulted. With 10% HCl

----~the-so-J.:ut±on--wa:s-brougi1t to a pffOf 1-2 with_ the formation of a white

suspension. TI1e acid solution was extracted four times with 100 ml portions of diethyl ether. The combined extracts were labeled "A"

and were extracted four times with 100 ml portions of 10% NaOH, then

washed, dried over anhydrous M§S04, filtered and allowed to evaporate at ambient temperature and pressure. After the ether had evaporated from "A" 0.08 g (0.0037 mole, 1.6%) of a solid was obtained and identified as diphenyl disulfide by ir spectrum comparison with that of prepared diphenyl disulfide. The combined NaOH solutions were acidified to pH 1-2 with 10%

· HCl and extracted four times with. 100 ml portions of diethyl ether. 'Ihe combined ether extractions were labeled ether solution "B".

Solution "B" was washed, dried over anhydrous MgS04 and the ether removed with a rotatory evaporator under reduced pressure with heating i yielding 0.23 g (0.0021 mole, 4.4%) of a li@1t yellow liquid identified as thiophenol by ir spectrum comparison with that of known thiophenol. There was no indication of XXIII starting material in the products obtained from either solution. 49

Se~9nd Reduction of N-Phenylbenzenesulfonamide XXIII: The amounts of reactants, experimental conditions, procedures, and equipment used for the second reduction of XXIII were the same as the first reduction except ether solution "A" was not further extracted with 10% NaOH. The reaction yielded 0.0442 g (0.0002 mole, 0.9%) of only diphenyl disulfide, m.p. 57-59°, identified by ir spectrum comparison with that. of prepared diphenyl disulfide.

Third Reduction of N-Phenylbenzenesulfonamide XXIII: 'Ihe amounts of reactants, experimental conditions, procedures, and equipment used for the th::i.n:l reduction of XXIII were the same as the second reduction except that the aniline produced in the reaction was recovered. The acidic solution of the reaction residue, after extraction with ether to produce ether solution "A", was brought to pH greater than 11 by the addition of 10% NaOH. That was extracted four times witr1 100 ml portions of diethyl ether and the combined ether solutions washed and dried over anhydrous Mgso4• The ether was removed with a rotatory evaporator under reduced pressure with heating. That yielded 3. 37 g ( 0. 036 mole, 76 .8%) aniline identified by ir spectrum comparison with that of known aniline. I Ether solution "A" yielded 0.72 g (0.0065 mole, 11.9%) of a yellow liquid identified as thiophenol by ir spectrum comparison of lmown thiophenol. ·..-=---- ~ ~

Fourth Reduction of N-Phenylbenzenesulfonamid.e XXIII:

The amounts of reactants, exper~nental conditions, procedures, 50

and equipment used for the fourth reduction of XXIII were the same as the second reduction. 'lhat yielded 0.34 g co·.o031 mole, 6.5%) of a light yellov: liquid identified as thiophehol and diphenyl disulfide by ir spectra comparisons with that of lmown compounds.

Fifth Reduction of N~Phenylbenzenesulfonamide XXIII: The amounts of reactants, experimental conditions, procedures, the second reduction. The reaction yielded 0.22 g (0.001 mole, 4.3%) of a solid consisting of long, pale yellow needles assillned to be diphenyl disulfide.

Sixth Reduct~ on of N-Phenylbenzenesulfonarrd.de XXIII: The amounts of reactants, experimental conditions, procedures, and eqLLi.pment used for the sixth reduction of XXIII were the same as the third reduction except that the amounts of lithiwn and NH4Cl were doubled (5.536 g, 0.798 mole and 42.8 g, 0.8 mole). The reaction yielded 0.40 g (0.0036 mole, 7.7%) of thibphenol and diphenyl disul fide and 3.41 g (0.0366 mole, 77.7%) of aniline, all identified by ir spectra comparisons with that of known compound samples.

Seventh Reduction of N~Phenylbertzertesulfonamide XXIII: I The amounts of reactants, experimental conditions, procedures, and equipment for the seventh reduction of XXIII were the same as the second reduction. The reaction yielded 0.3129 g (0.00284 mole, 6.0%) of thiophenol identified by ir spectrum comparison with that of known thiophenol. 51

Preparation of N,N-Diphenylbenzenesulfonamide XXIV:

In a one liter beaker 84.5 g (0.499 mole) of diphenylamine was dissolved in. 250 ml of pyridine. . Benzeriesulfonylchloride, 87. 8 g

{0.1!97 mole), was added dropwise accompanied by stirring with a mag-

.,netic bar stirrer. The solution was stirred for 14 hours. At the

.end of that time there was much precipitate present. About 100 ml

of water was added to the mixture and the resultant precipitate

col"lected by filtration. This was recrystallized f'rom ethanol twice and dried in an oven at 75°C. This yielded 29.4 g (0.095 mole, 19.1%)

-of N,N-diphenylbenzenesulfonamide, long white needles, m.p. 125°C

(lit. m.p. 124°) ( 47).

A second preparation of XXIV was dqne with similar procedures

as the first preparation with the exceptions that the reaction solu

tion was stirred for 18 hours with heating at 75°C. The sulfonamide

was recrystallized four times from ethanol yielding 54.9 g (0.177 mole,

35.5%)of XXIV, m.p. 124-125°C.

REDUCTION OF N,N-DIPHENYLBENZENESULFONAMIDE XXIV:

First Reduction of N,N-Diphenylbenzenesulfonamide XXIV:

;N ;N-Diphenylbenzenesulfonamide, 14 . 55 g ( 0. 04 71 mole) , was added to a two liter, three-neck flask equipped with a mechanical stirrer, I

dry ice condenser, and dropping funnel. First 600 ml of anhydrous

ammonia was condensed into the reaction flask and then was allowed to reflux at -33°C, but very little of the sulfonamide dissolved. -- Next 2.768 g (0.399 mole) of lithium metal, cleansed of protec- l_ 52

tive petrolatum coating in a series of five baths of low boiling pet roleum ether, was dissolved in the arnmonia. With the addition of the first piece of lithium a deep yellow color developed, but eventually the solution turned deep blue with the addition of all of the lithium.

All of the lithium dissolved in fifteen minutes, but much o~ the starting material XXIV appeared still to be undissolved.

Next 65 ml of absolute ethanol was added dropwise. After the addition of approximately 15 ml of the ethanol the blue color turned to bright yellow. The rest of the ethanol was added and further cnange in color to white occured. Then 21.4 g (0.4 mole) of NH4Cl was cau tiously added with subsequent stirring for one hour. The ammonia was allowed to evaporate overnight at ambient temp-

----- erature and pressure. The residue of the reaction was dissolved in !1 200 ml of deionized water vdth the formation of a cloudy white solution ~ ~ with a brown oily layer. The pH was lowered to 1-2 with 10% HCl, but the oil did not dissolve (diphenylamine is insoluble in 10% HCl at room temperature), and the solution became more cloudy. That solution was extracted with four portions of 100 ml of diethyl ether. The brown oil dissolved in the ether layer. The combined ether extractions were extracted with four 75 ml portions of 10% NaOH. The ether phase was washed and dried over 5. g of' anhydrous MgSo and labeled ether I 4 solution nA". The combined NaOH solutions were brought to pH 1-2 with 10% HCl and extracted with four 100 m1 portions of diethyl ether. This ether

extraction was combined, washed and dried over 5 g of anhydrous ~so 4 , and labeled ether solution "B". 53

The ether was removed from both solutions with a rotatory evap -orator under reduced pressure with heating. From solution "A" 4. 99 g {0.029 mole, 62.6%) of a brown solid was obtained· and identified as

,diphenylamine by ir spectrum comparison with that of known diphenyl~ -am.ine. There was no evidence of the presence of any of the starting material XXIV. The brown color is apparantly due to small amounts of impurities. From solution 11B11 3.30 g (0.0299 mole, 63.6%) of a light yellow liquid was obtained and identified as thiophenol by comparison .of ir spectrum with that of known thiophenol. The acidified mother liquor of the reaction was brought to over pH 12 with 10% NaOH solution and a dark brown oil separated. The solution was extracted with four lOO ml portions of diethyl ether

- .. and the combined ether extractions washed and dried over 5 g of MgSo4. I ~ The ether was evaporated with a rotatory evaporator under reduced II- pressure •#fth heating yielding 2.71 g of a brown thick oil. Ir spectra (IR spectra #6) indicated the presence of the amine functional group, but the spectra differed from that of diphenylamine greatly.

Nf\'IR spectra (N\VJR #4) indicated the formation of a tetrahydro product v (see discussion section for further analysis).

Second Reduction of N,N-Diphenylbenzenesulfonamide XXIV: I The amounts of reactants, experimental conditions, procedures, and equipment used for the second reduction of XXIV were the same as for the first reduction. The reaction yielded 3.37 g (0.031 mole, 64.9%) of thiophenol, 6.38 g (0.038 mole, 80.0%) of diphenylamine, ·and 2.49 g of the 10% HCl soluble 'amine. Th:\.ophenol and diphenyl-:- amine were identified by comparison of ir spectra with those of

known compounds. ~-

Third Reduction of N,N-Diphenylbenzenesulfonamide XXIV: The amounts of reactants, experimental conditions, procedures, and equipment used for the third reduction of XXIV were the same as for tpe first reduction except that only thiophenol was isolated. No attempt was made to isolate to· the. other species. The reactiont______yielded 3.4817 g (0.0316 mole, 67.1%) of thiophenol identified by ir spectrum comparison with that of known thiophenol.

Fourth Reduction·of N,N-Diphenylbenzenesulfonamide x:xry: The amount of reactants, experimental conditions, procedures, and equipment used for the fourth reduction of XXIV were the same as for the first reduction except that no attempt is made to recover the diphenylamine. The reaction yielded 3.6759 g (0.0333 mole, 70.8%) of thiophenol identified by ir spectrum comparison with that of known thiophenol. The 10%. HCl soluble amine was recovered (1.8740 g) and its ir spectrum (IR #7) compared favorably with the material recovered

from the first reduction of XXIV. An NMR. spectrum was run (NMR. #4) and the spectrum indicated reduction of one of the rings of the amine moiety to tetrahydrodiphenylamine (further analysis is in the dis- I cussion section) . An attempt was made to determine the number of · isomers present with gas chromatography at temperatures from 50 to 250°C, but apparantly at the lower temperature the amines were not volatile and at higher temperatures they decomposed or polymerized.

Column packings are listed in general experimental section.

(_, r 55

Preparation of N-Methyl-N-phenylbenzenesulfonamide Y:XV_:

N-Methylanillne, 80.4 g (0.75 mole), was dissolved in 250 ml a= of pyridine in a one liter beaker. Then 133.3 g (0.75 mole) of F== benzenesulfonylchloride was added· dropwise accompanied wj_th stirring from a magnetic stirring bar. The solution was stirred for a total of six hours. Precipitate had formed at the end of that time and

more formed wheh 100 ml of water was added to the· mixture. r:Llfle

------~------~------~------~------~- precipitate was collected by filtration and recrystallized from ethanol until constant melting point was obtained. That yielded 146 g (0.59 mole, 78.7%) N-methyl,N-phenylbenzenesulfonamide, white crystals, m.p. 77-79°C (lit. m.p. 79°C) (47).

-- REDUCTION OF N-METHYL -N-PHENYIBENZENESULFDNAMIDE XXV: 1 First Reduction of N-Methyl-N-phenylbenzenesulfonamide XXV: ~ Ill- N-Methyl, N-phenylbenzenesulfonamide, 11.6959 g (0.0473 mole)

was added to a two liter, three~neck flask equipped with a mechanical

stirrer, dry ice condenser, and dropping funnel. Then 600 ml of anhydrous amnonia was condensed into the flask. At the refluxing tem perature of -33°C not all of the sulfonamide was dissolved. Next 2.768 g (0.0399 mole) of lithium, cleansed of its protective coating of petrolatum by a series of five baths of low boiling petro- i leum ether, was dissolved in the ammonia. After several minutes of stirring the lithium began to dissolve with the formation of a yellow solution which finally turned dark blue after the addition of all of the lithium. It was not known whether all of the sulfonamide was dissolved by that time. 56

ml Next 65c) of absolute alcohol was added dropwise. After the addition of approximately 15 to 20 ml of the alcohol the solution turned white. rrhe rest of the ethanol was added and, followed by the cautious addition of 21.4 g (0.4 mole) of NH4Cl, the solution was stirred for one hour. The. ammonia was allowed to evaporate overnight at ambient temperature and pressure. The residue of the reaction was dissolved in zOO m1 of cool aeionlzed water. That solution was brought to pH of 1-2 with the addition of 10% HCl resulting in the formation of a suspension of oily droplets.

The solution was then extracted four times with 100 ml portions of diethyl ether. The combined ether extractions were then extracted with four 100 ml portions of 10% NaOH. The ether solution vas then washed and dried over anhydrous MgSo4 and labeled ether solution "A". The combined NaOH solutions were then brought to pH 1-2 with 10% HCl and extracted with four portions of 100 ml of diethyl ether.

The combined ether extractions were washed and dried with ~1Ydrous

MgSo4 and labeled ether solution "B". The ether was removed from "B" with a rotatory evaporator under reduced pressure with heating. That yielded 3.5420 g (0.0321 mole, 67. 9%) of thiophenol identified by ir spectrum comparison with that I of known thiophenol. The ether from solution "A" was allowed to evap orate at ambient temperature and pressure. Obtained was 0.6513 g (0.00298 mole, 12.7%)of a pale yellow crystalline solid identified as diphenyl disulfide by ir spectrum comparison with that of prepared 57

diphenyl disulfide. No evidence of starting material XXV could be seen from the spectra, but the melting point of the solid (55-58°C) was depressed several degrees below that of pure diphenyl disulfide {60-61°C). The acidified mother liquor of the reaction was brought to above pH 11 by the addition of 10% NaOH and oil droplets separated from the

solution. They were extracted out with four 100 ml portions of diethyl r ·::-- ~~~~~~~~~~~~~-~~~~~~~ ether and the combined ether solutionwas washed and dried over anhy-

drous Mg-;304• The ether was allowed to evaporate at ambient temperature and pressure until a small volume of brown oil remained. That was

placed in a rotatory evaporator to remove the last remnants of solvent. That yielded 1.1793 g (0.011 mole, 23.3%) of an oily liquid identified as N-methylaniUne by ir spectrum comparison with that of Jmown

N-methylan:i.l ine.

Second Reduction of N-Methyl- N-phenylbenzenesulfonamide XXV:

rlhe amounts of reactants, experimental conditions, procedures,

and equipment used for the second reduction of XXV were the same as

for the first reduction except that no attempt was made to recover the N-methylaniline. The reaction yielded 3.6324 g (0.329 mole, 69.7%) of thiophenol and 0.7619 g (0.00349 mole, 14.8%) of diphenyl disulfide, i both identified by ir spectra comparisons with that of known compounds.

1lhird Reduction of N-Methyl- N-phenylbenzenesulfonamide XXV:

The amounts of reactants, experimental conditions, procedures,

and equipment for the third reduction of XXV· were the same as for 58

the second reduction. The reaction yielded 3.4747 g (0.0315 mole, 66.9%) of thiophenol and 0.3678 g(0.00168 mole, 7.2%) of diphenyl disulfide, both identified by ir spectra comparisons with that of

E1- ~ known compounds. r;--- ~----

I"===== 59

Preparation of N,N-Dimethylbenzenesulfonamide XVII: In a 600 ml beaker 100 g of NaOH was dissolved in 100 ml of water and cooled. rlhen 100 g (1.·1 mole) of dimethylamine hydrochloride was slowly dissolved followed by the addition of 200 nu of diethyl ether. Next 80.0 g (0.453 mole) of benzenesulfonylchloride was added dropwise, accompanied by stirring from a magnetic stirring bar. After the reaction was completed the ether layer was removed and evaporated at ambient temperature and pressure. The resulting white solid was recrystallized from ethanol yielding 79.5 g (0.429 mole, 94.7%) of N,N-dimethylbenzenesulfonWRide, white needles, m.p. 47-47.5°C (lit.

REDUCTION OF N,N-Dil\'IETHYLBENZEJ\lESULFONAMIDE XVII : F'irst Reg.uction of N.lN-Djmethylbenzenesulfonamide: N,N-Dimethylbenzenesulfonamide, 8.7155 g (0.0471 mole), was added to a tvvo liter, three-neck flask equipped with a mechanical stirrer, dry ice condensor, and dropping funnel. Then 600 ml of anhydrous ammonia was condensed into the flask. As the amnonia refluxed at -33°C, all of the sulfonamide dissolved. Next 2.r{68 g (0.399 mole) of lithium metal, cleansed of protective I petrolatum coating with a series of five baths of low boiling petroleum ether, was dissolved in the ammonia solution. After much of the ammonia dissolved, the solution turned dark blue. Then 65 ml of absolute ethanol was added dropwise. After the addition of approximately 15 to 20 nu of the alcohol, the reaction 60

solution turned white. After all of the ethanol was added 21.4 g of M14c1 (0.4 mole) was cautiously added and the solution stirred for one hour. The anmonia was allowed to evaporate overnight at ambient temperature and pressure. The residue of the reaction was dissolved in

200 ml of cool deionized water and the solution brought to pH 1-2 with 10% HCl. The solution was then extracted four times with 100 ml portions of diethyl ether. The combined ether extractions were then washed and dried over 5 g of anhydrous MgSo 4. The ether was removed with a rotatory evaporator under reduced pressure with heating. That yielded 3.9269 g (0.0356 mole, 75.6%) of a light yellow l:i.quid identified as thiophenol by ir spectrum compru..... ison with that of known thiophenol.

Second Reduction of N,N-Dimethylbenzenesulfonamide XVII: The amounts of reactants, experimental conditions, procedures, and equipment used for the second reduction of XVII were the same as for the first reduction. The reaction yielded 3.7898 g (0.0344 mole, 73.1%) of thiophenol identified by ir spectrum comparison with that of known thiophenol. I 61

Preparation of N-Methylbenzenesulfonamide XXI:

In a 600 ml beaker 100 g of NaOH was dissolved in 200 ml of water and the solution cooled. Then 80.0 g (1.19 mole) of methylamine hydrochloride was dissolved in the solution followed by t~e addition of 200 ml of diethyl ether. Then 119. 8 g ( 0. 678 mole) of benzenesulfonyl·- chloride was added dropwise as the solution was stirred with a magnetic stirring bar. There was a vigorous reaction and the rate of addition of benzenesulfonylchloride was reduced to about one drop per second.

Af~er the reaction was completed the layer was decanted off and the ether allowed to evaporate at ambient temperature and pressure. That yielded a viscous oil which solidified after cooling at -20°C for several days. This was recrystallized from CH2Cl2 at -20°C and dried ~ in a vacuum dessicator at room temperature, yielding 21.2 g ( 0 .123 i!]!! mole, 18. 2%) of N-methylbenzenesulfonainide, large clear crystals, i m.p. 30-31°C (lit.- 30°C) (47). Another preparation using a stock water so1ution of methylamine gave a slightly higher yield of sulfonamide.

REDUCTION OF N-METHYLBENZENESULFONAMIDE XXI: First Reduction of N-Methylbenzenesulfonamide XXI: N-Methylbenzenesulfonamide, 8.0646 g (0.0471 mole), was added to I:== a two liter, three-neck flask equipped with a mechanical stirrer, dry ice condensor, and dropping funnel. Then 600 ml of anhydrous ammonia was condensed into the flask. At the temperature of refluxing ammonia, -33°C, all of the sulfonamide easily dissolved. Next 2.768 g (0.399 mole) of lithium metal, cleansed of its ., 62

protective petrolatum coating with a series of five baths of low

boiling petroleum ether, was dissolved in the arrnnonia solution.

After the first few pieces dissolved there was a very faint yellow

color which turned dark blue upon the addition of the remainder of

the lithium.

Then 65 ml of absolute ethanol was added dropwise. After the

addition of approximately 20 to 25 ml of the alcohol the color dissipated .

.A!~er all of the alcohol was added 21.4 g (0.4 mole) of NH4Cl was

.cautiously added a~d the solution stirred for an hour.

llie ammonia was allov1ed to evaporate overnight at ambient te~-

era.ture and pressure. The residue was dissolved in 200 ml of cool deionized water and the solution brought to pH 1-2 with 10% HCl. The solution vias th2n extracted four ti.rlles ·with 100 ml portions of

dj.ethyl ether. The combined ether extractions were washed and dried

over 5 g of anr.:ydrous MgSO 4• The ether was removed by a rotatory evaporator under reduced

pressure with heating. That yielded a small portion of yellow liquid

with water droplets. After the water droplets coalesced into one drop

it was carefully removed with a pipet. This left 0.3868 g (0.00351

mole, 7.5%) of a light yellow liquid identified as wet thiophenol

from ir spectrum comparison with that of known thiophenol. I==

Second Reduction of N-Methylbenzenesulfonamide XXI:

The annunts of reactants, experimental conditions, procedures,

and equ:i.pment used for the second reduction of XXI were the same as

for the first reduction except more MgSo4 was used to facilitate { . 63

better drying. The reaction yielded 0.2159 g (0.00196 mole, 4.2%) of t!Ltophenol identified by ir spectrum comparison with that of known thiophenol.

Third Reduction of N-Methylbenzenesulfonamide XXI: The amounts of reactants, experimental conditions, procedures, and equipment used for the third reduction of XXI were the same as for the second reduction. The reaction y:ielded_0_._6ng_g_(_Q_,_QO;J;J;J-m1e-~,----- 11.8%) of thiophenol identified by ir spectrum comparison with known thiophenol.

\_ ,64

· ·Prepa.ratlon of N,N-Diisobutylbenzenesulfonamide XVIII:

;-:;- In a 600 ml beaker 100 g (0. 7 mole) of diisobutylam:ine was dis

solved in 300 ml of 12% NaOH. Then 85 g (0.49 mole) of benzenesul-

ronylchloride was added dropwise accompanied with stirring from a

,magnetic stirring bar. Then 200 ml of diethyl ether was added and,

after the reaction was completed; decanted and evaporated at ambient

temperature and pressure. The white solld was recrystallized from

ethanol-to a constant melting point. This yielded.l00.8 g (0.371

mole, 75.8%) of N,N-diisobutylbenzenesulfonamide, m.p. 54-55°C (lit.

REDUCTION OF N,N-DIISOBUTYLBENZENESULFONAMIDE XVIII:

First Reduction ?f N,N-·Diisobutylbenzenesulfonamide XVIII:

N,N-D1isobutylbenzenesulfonarnide, 12,6888 g (0. 04 71 mole) , . was

placed in a three-neck, two liter flask equipped with a dry ice con

denser, mechanical stirrer, and dropping funnel. Then 600 ml of a'1-

hydrous ammonia was condensed into the flask. Very little of the

sulfonamide appeared to dissolve in the refluxing ammonia (-33°C).

Next 2.768 g (0.399 mole) of lithium Jnetal, cleansed of protec-

tive petrolatum coating in a series of five baths of low boiling

petroleum ether, was dissolved in the ammonia. After about one third

of the lit:qium was added the solution turned dark blue.

·_,,- Then 65 ml of absolute ethanol was added dropwise. After less =:----

than 20 ml of alcohol was added the color changed to dull white.

After all of the alcohol was added 21.4 g (0.4 mole) of NH Cl was 4 added and the solution stirred for about an hour. 65

The ammonia was allowed to evaporate at ambient temperature and pressure overnight. The residue of the reaction was dissolved in

200 m1 of cool deionized water. Tt1is yielded a cloudy solution with some precipitate. The solution was brought to pH 1-2 with 10% HCl and extracted four times with 100 m1 portions of diethyl ether. The combined ether extractions were extracted four times with 100 m1 portions of 10% NaOH. The ether solution was then washed and dried over 5 g of anhycl:Pous MgSo and labeled ether solution "A". 4 The combined NaOH extr~ctions were brought to pH 1-2 with 10% HCl. This resulted in some oil formation. The solution wa.s then extracted four times with 100 m1 portions of diethyl ether. The combined ether extractions were washed, dried over MgS04 and labeled ether solution "B". The ether was removed from ether solution "B" with a rotatory ev~porator under reduced pressure. That yielded 2.7867 g (0.0253 mole, 53.7%) of a light yellow liquid identified as thiophenol by ir spectrum comparison with that of known thiophenol. r.fue ether solution "A" was allowed to evaporate at ambient temperature and pressure. ~bat resulted in the formation of white needle crystals, m.p. 52-54°C, and small, amorphous, slightly colored I== lumps, m.p. 40-45°C, where the last remnants of solvent had evaporated. Both materials were identified as unreacted XVIII by ir spectra comparison with that of starting material. The amorphous mass probably contained a significant amount of diphenyl disulfide. The:i.r combined '*'=-.-.- weight was 1.5626 g (0.0058 nnle, 12.8% recovery of starting material). The yield of thiophenol based upon the consumed sulfonamide was then 61. 2%. 66

§econd Reduction of' N,N-Diisobutylbenzenesulfonamide XVIII:

·The arnooots of' reactants, experimental conditions, procedures,

-m!d equipment used f'or the second reduction of XVIII were the same

- as the first reduction except that the sulfonamide was finely pul-

-verized before addition to the flask in an attempt to get rrore of'

the sulfonamide in solution. The reaction yielded 2.7787 g (0.0252

mole, 52.5%) of' thiophenol identified by ir spectru~ and 0.7797 g ------:l{o---;o-o-289 mole, 6.1%) of' a solid assumed to be starting material with

traces of' diphenyl disulfide. The yield of the thiophenol based upon

consumed sulfonamide was then 57%.

Thl.rd Reduction of' N,N-DiisobutY.lbenzenesulfonamide X\TIII:

The am::>unts of' reactants, exper:imental conditions, procedures,

and equipment used for the third reduction of XVIII were the same as

second reduction, ho1.vever much of' the material was lost due to spillage.

All that was recovered was 1.1897 g (0.0108 mole, 22.9%) thiophenol.

Fourth Reduction of N,N-Diisobutylbenzenesulfonamide XVIII:

The amooots of' reactants, experimental conditions, procedures,

and equipment f'or the fourth reduction of XVIII were the same as the

second reduction. The reduction yielded 3.3063 g (0.030 mole, 63.7%) of thiophenol, identified by ir spectrum, and 0.8222 g (0.003 mole, I== 6. 2%) of a solid assumed to be mainly starting material. The yield of' thiophenol based on consumed starting material was then 68.2%. = Fifth Reduction of N,N-Diisobutylbenzenesulfonamide XVIII:

The amow1ts of reactants, experimental conditions, procedures,

ru1d equipment for the fifth reduction of XVIII were the same as the 67

second reduction. 'Ihe reaction yielded 3.7221g (0.0338 mole, 71.7%) of thiophenol, identified by ir spectrum, and 0.8766 g (0.0033 mole, 6.9%) of a solid assumed to XVIII. The yield of thiophenol based upon consumed sulfonamide was then 77.1%.

E Ill ~ Ill 68

·Preparation of N-Isobutylbenzenesulfonamide XXII:.

In a 600 ml beaker 80.5 g ( 1.1 mole) of isobutylamine was dis

solved in 200 ml of 20% NaOH. 'Ihen J:76.5 g (0.994 mole) of benzene-

sulfonylchloride was added dropwise to the solution with vigorous

reaction. 'Ihe reaction solution was so warm it was feared that

sore isobutylamine might have evaporated (b.p. 69°C;), so 20 ml more

of isobutylamine was added. The solution was stirred f'or six hours

and some precipitate formed. The solution was then extracted with

250 ml of citethy 1 ether and then the ether evaporated in a warm water

bath. The oil that was left solidified on cooling. 'Ihe solid was

recrystallized from ethanol/water mixtures until a constant melting

point v:as obtained upon air drying. This yielded 156.8 g (73.9%)

of N-isobuty1benzenesulfonamide, m.p. 51-53°C (lit. 53°C) (47). ~ •i REDUCTION OF N-ISOBUrYLBENZ&\~SULFONAMIDE XXII:

First Reduction of N-Isobutylbenzenesulfonamide XXII:

Into a three-neck, two liter flask equipped with a dry ice con-

densor, mechanical stirrer, and dropping funnel 10.0460 g (0.0471

mole) of N--isobutylbenzenesulfonamide was added. 'Iheh 600 ml of an-

hydrous ammonia was condensed into the flask. As the amnonia was I== refluxing at -33°C, all the sulfonamide readily dissolved.

Next 2.768 g (0.399 mole) of cleaned lithium metal was dissolved

in the solution. When the first portion of lithium began to dissolve, = the solution began to foam vigorously. Only with careful stirring

and slow addition of the lithiwn was the foam contained within the 69

reaction vessel. This behavior was observed :for all o:f the reductions

~ o:f XXII. The color o:f the solution at that time was yellow-orange. After about one third of the lithium had been added, enough to sustain the deep blue color, the :foaming stopped and the lithiUm was added without any further difficulty.

Next 65 ml of absolute ethanol was added dropwise. After about

20 to 25 ml of the ethanol was added the color lightened to blue- green, then to yellow, and :finally to white after all the ethanol had been added. Finally 21.4 g (0.4 mole) of NH4Cl was added and the solution stirred :for an hour. The ammonia was allowed to evaporate overnight at ambient temp erature and pressure. The residue was dissolved in 200 ml o:f cool deionized water and brought to pH 1-2 with 10% HCl. That solution was extracted four times with 100 ml portion of diethyl ether. The combined ether extractions were washed and dried over 5 g of ~~0 4 . The ether was removed by a rotatory evaporator under reduced pressure with heating. That yielded 0.1572 g (0.0014 mole, 3.0%) of a light yellow liquid which was asswned to be thiophenol.

Second.Reduction of N-Isobutylbenzenesulfonamide XXII: The·amounts of reactants, experimental conditions, procedures, I:c__ and equipment used for the second reduction of XXII were the same as the first .reduction. The reaction yielded 0.5815 g (0.0053 mole, 11.2%) of a light yellow liquid assumed to be thiophenol.

Third Reduc~ion of N~Isobutylbenzenesulfortamide XXII: The amounts of reactants, experimental conditions, procedures, 70

.. and equipment used for the third reduction of XXII were the same as

for the first reduction except. that the reaction flask was cooled

with dry ice (-75°C) while the lithium was being added to reduce the

~ foaming. The solution was allowed to warm to reflux temperature G- ~- (-33°C) before the ethanol was added. That yielded 0.3890 g (0.0035

mole, 7. 5%) of a light yellow liquid assumed to be thiophenol. Upon

standing for 24 hours the liquid solidified to diphenyl disulfide.

Fourth Reduction of N-Isobuty1benzenesulfonamide XXII:

The amou11ts of reactants , experimental conditions, procedures,

and equipment used for the fourth reduction of XXII were the same as

for the second. The reaction yielded 0.5383 g (0.00489 mole, 10.4%)

of a Jj_ght yellow liqu:i.d identified as thiophenol by ir spectrum com-

parison with that of known thiophenol.

Fifth Reduction of N-Isobutylbenzenesulfonarn:ide XXII:

The amounts of reactants, experimental conditions, procedures,

and equipment used for the fifth reduction of XXII were the same as

for the third reduction. The reaction yielded 0.5140 g (0.00467 mole,

9.9%) of a light yellow liquid identified as thiophenol by ir com-

parison with that of known thiophenol. ------71

PreEaratj_on of Lithium Salt of 'N-Phenylbenzenesulfortarilide XXVII: r.J.be lithium salt of N-phenylbenzenesulfonamide was prepared by reacting the 'sulfonamide with a solution of LiOH. First 6.9L1 g (1.0 mole) of lithium, after being washed of petrolatum in a series of five baths of low boiling petroleum ether, was allowed to react with several hundred m;Hliliters of water. The· solution was transferred to a o~e liter volumetric flask ru1d filled to the mark. Then 23.329 g (0.1000 mole) of XXIII was placed in an Erlenmeyer flask. Next 110 m1 of the 1.0 N LiOH solution was added to the flask. The sulfonamide readily dissolved in this solution with heating. The solution was heated to concentrate the salt. 1N.hen the salt began to precipitate out of the solution, the solution was cooled and filtered. The salt was washed with cool water and dried at 100°C under a vacuum for several hours. Tl1e· white powder showed no sJgns of melting when heated to 270°C. This was collected as the lithium salt of XXIII, 23.9671 g (0.10 mole, 100%). The unusually high apparent yield was attributed to be from traces of the excess LiOH used in the reaction not being completely washed from the product.

REDUCTION OF THE LITHIUM SALT OF N-PHENYLBENZENESULFONAMIDE XXVII: I=-- First Reduction of Lithium Salt of N-Phenylbenzenesulfonamide XXVII: The lithium salt XXVII> 12 . 2119 g ( 0 . 04 71 mole) , was added to a three-neck, two liter flask equipped with a mechanical stirrer, dry ice condenser, and a dropping funnel. Then 600 ml of rumydrous ammonia was condensed into the reaction flask. · The refluxing ammonia readily dissolves the salt. 72

Next 2.768 g (0.399 mole) of lithium metal, cleaned of protective petrolatum coating by low boil~ng petroleum ether, was dissolved in the ammonia. · A small amount of white precipitate was detected in the deep blue solution.

Next 65 ~ of absolute ethanol was added to the solution drop

'·wise. Aft~r- addition of 15 to 20 ml of the ethanol the color changed to orange and rem..ained that color after all of the ethanol was added.

After 21.4 g (0.4 mole) of M14Cl was added cautiously the color of the -solution was white and the solution was stirred for 45 minutes. The ammonia was allowed to evaporate at ambient temperature and pressure. The residue of the reaction was dissolved in 200 ml of cool deionized water and brought to pH 1-2 with 10% HCl. When the solution was acidif:i.ed there was very little visible evidence of change, but the solution did have the characteristic thiol odor. The solution was extracted four times with 100 ml portions of diethyl ether and the combined ether extractions were waShed and dried over

The ether was removed with. a rotatory evaporator under reduced pressure. Tnat yielded 0.2339 g (0.002 mole, 4.5%) of a yellow liquid with traces of a yellow precipitate. The liquid was identified as I=-- thiophehol with small amounts of other impurities by ir spectrum.

Second Reduction of Lithium Salt of N-Phenylbenzenesulfonamide XXVII: 'lbe amounts of reactants, experimental conditions, procedures, and equipment for the second reduction of XXVII were the same as for the first reduction except for the recovery of the products. 73

The combined ether extraction of the reaction mixture was extract-

ed with four 100 m1 portions of NaOH. ~be ether solution was washed

and dried over anhydrous Mgf)04 and labeled ether solution "A". The combined NaOH extractions were acidified to pH 1-2 with 10% HCl and

extracted four times with 100 m1 portions of diethyl ether. The'

combined eth~r extractions were washed, dried with anhydrous MgS04 and labeled ether solution "B".

~~~~~~-r.rhe-ether from solution 11B" was removed with a rotatory evaporator

under reduced pressure with heating. That yielded 0. 0893 g ( 0. 00081

mole, 1.7%) of a light yellow liquid identified as thiophenol by ir spectrum comparison with. that of known thiophenol. Tne ether from solution "A" was allowed to evaporate at ambient

temperature and pressure. That yielded 0.1066 g of pale yellow,

needle--like ct>';stals assumed to be diphenyl disulfide ( 0 .·00049 mole, 2.1%).

I=-- --'-'-"------' =oo_::..--~~~-~ ~ ~-~-

>'REDUGriON OF P-SULFAMYLBENZOIC ACID XXVI:: First Reduction of p..:..Sulfanwlbenzoic Acid XXVT:

into a three-neck two· liter flask, equipped with a dry ice .condenser, mechanical stirrer and dropping funnel, 9.5768 g (0.0476

mole) of p-sulfarnylbenzoic acid (K&K unspecified grade, d260-270°C)

was placed. Next 600 ml of anhydrous ammonia was condensed and the .acid dissolved with the formation of a very light brown solution. ------~~~-'--''lhe-aTunolna-was-r•efluxing at -33°-C. Then 2.768 g (0.399 mole) of lithium rretal, cleansed of petrolatum protective coating in a series of five baths of low boiling petrolewn

,) ether, was dissolved in the mrunonia solution. The color of the solution was bright yellow after the addition of the first piece of lithium.

As more lithium was added the color became bright orange and eventually ~ II ~

dark blue after about one third of the lithium was added. ~ II;:::; ---- Next 65 ml of absolute ethanol was added dropw:i.se. After about

15 to 20 ml of the alcohol was added the solution again became bright yellow and retained that color after all of the ethanol and the 21. 4 g

(0.4 mole) of NH4Cl were added. The ammonia was allowed to evapora~e overnight at ambient temperature

and pressure. The residue was disso1ved in 200 m1 of cool deionized

water producing a pale yellow-green so1ution. The so1ution was I~ acidified to pH 1-2 with 10% HCl yielding a nearly colorless, clear

solution. The solution was then extracted four times with 100 m1 portions of diethyl ether and the combined ether extractions were

washed and dried over 5 g of anhydrous M§SO 4. 75

The ether was allowed to evaporate at ambient temperature and pressure. This left a light yellow oil and white solid mixture. The yellow oil was decanted from the solid and placed_jn a rotatory evaporator to remove the· last traces of solvent. This yielded 1.6577 g . . of product. The· solid material was collected and weighed 4. 8821 g.

An NMR spectra (NJVIR #7) was taken of the solid material. A mixture of benzoic acid, 1,4 dihydrobenzoic acid and other products was indicated (see discussion for further analysis). Upon setting for several days much of the solid had turned to oil and some of the light yellow oil had solidified and it was assumed

both. were mixtures of only slightly different composition. An attempt

to· remove all traces of solvent in the smaller sample by rotatory evaporation at 100°C decomposed and polymerized the material.

Second Reduction of p-SulfamylbP:_nzoic Acid XXVI: The amounts of reactants, equipment, procedures and experimental conditions of the second reduction of X:XVT were the same as the first reduction except that 9.4768 g (0.0471 mole) of XXVT was used and the

ether was removed with a rotato1~ evaporator under reduced pressure at moderate temperatures (40-50°C). This yielded 5.2479 g of a light yellow liquid which solidified on cooling. An NMR spectra (NMR #8) I was run and it indicated similar results as the first reaction, but v withdifferent percentages of products (see discussion for further analysis). =

Third Reduction of p~SulfruAylbenzoic Acid XXVI: The amounts of reactants, procedures, experimental conditions, '(6

.··~and equ:lpment used for the third reduction of XXVI. were the same as

for the second except the amounts of lithium and Mf4Cl were increased 50% to lJ.l64 g ( 0. 6 mole) and 32 .1 g ( 0. 6 mole) • After the ammonia had evaporated from the reaction flask it was

~---- ~ noted that the color of the residue was light yellow, as in the previous reactions. The reaction was not worked up until 12 hours later, however, and at that time the reaction residue had turned dark brown.

------~·we ·acielTfieCJ. solution of the reaction res]due was inadvertantly extracted twlce with low boiling petroleum ether before it was extracted normally with diethyl ether. Both ether solutions were combined and worked up as in previous reactions. The :f"lnal result was 3. 4753 g of a reddish liquid that solidified on cooling, but partially remelted at room temperature. T\1MR spectra.

(NMR #9) showed somewhat different results from the previous two reactions (see mscussion). The presence of more highly saturated material was indicated. After several weeks the material polymerized into a glassy solid.

Folll~th Reduction of p-Sulfamylbenzoic Acid XXVI: The anom1ts of reactants, procedures, experimental conditions, and equipment used for the fourth reduction of XXVI were the same I======as the third (except no petroleum ether was inadvertantly used to extract the solutior1), but was worked up shortly after the ammonia. had evaporated leaving the residue light yellow. NMR spectra. (NMR #10) = indicated primar:lly 1,4. dihydrobenzoic acid and traces of other products (see discussion for further analysis). 77

Gas chromatography ( colUIIDs listed in general experimental) at temperatures from 200 to 250°C indicate the presence of several products. Analysis of a known sample of 1,4 dihydrobenzo~c acid

(student prepared, which NMR f/.5:. showed was about 95% pure with benzoic acid and ethyl esters as the impurities) gave at least four peaks. One minor peak from both samples can probably be attributed to ethyl ether, but it appeared that the 1,4 dihydrobenzoic acid was isomerizing in the· columns. BIBLIOGRAPHY

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= 82

.. SOME PATHVIAYS FOR· THE CLEAVAGE OF SULI~'ONAM!DJES

~~- G___ _ = -

AH + BH I2H f - -·1' A + B + so 2

ASH ~<--- AS0 • + BH 2 i I 83

,-... ~ d A• ~"" ......

,-...... ::! ...::! ra A ?. .. ~ ~.,.., ~ :§ 0 0 ... r-1 ~·(-< ~ 0 r.t..: .::1 ..::J p:: ,... ~ >'-< (-! 8 0 ~ ~"~ ...._.. t'2

~ H ...::! 0 ?: ~ "-< 0 H...... ,.,.. 8 I

0 __ 0- 0 M I 4000 3000 700 (,,,,,,I It! I o 20~o , . , . , Jspo , , c~-~~ ., . JO.E_.ili.w~~~L so?. . , . ~· , . ··o.o

00 ~ · . , , . 1.. , 1 I• .' ••.•. L •••. l ...... j ... \:r:.·· !· ··------~ · 1:>:!::~:; ·· ··---~------~-- ··-;---"-'~-H="~i·:------~--··;--:_-l--•i: .:.:1.:--~:·(-·j:·---·j·-4· --4· -.·1 .. ---1--i±-- I ------:- · 1 1

< pp.::l ;.: :::!:-!-!': :! . .-'-·:-:!=-=·:-= ·= 4-- : --LI--;_,., -1 ...... __:_·tf:3o co 30 .. :_:._ ·:·-1:::=·=--=~1: --:--· . ~-1.-:-- I--- .... •.. Ir~ ... , .. I ' 1.. T .. ;.... ·I·J.. . v· . · :__ . :· ~. . i ...... t ...... :! ::. :. - I ' .. ' ... ' I I ... ' ' .. J I .. f.. I. .. ' .. l .. · ·• · r i . .·I •· --i ... : .. lli I 1 I ., ,. I : 0 . ! ''l . I ' : i 1_'' ·: ., ., • :! ... _j ___..:J ______~ .....-!.-:...... L-:J ____ !______.... ·-·--- 40 I../) Ao-~--1------.. ------' ·-----]· --~- .-:;7--:-----•· :-•·-- I • . ' .. ,. j ! ; .. ,.. . . . • co-~ i , · · I . ' .. : ·. . r . • · • · I · · 1 I ··I : • , • 1 ::. • ... ·. • •

. . . .

3 4 5 6 7 8 9 "!0 l1 112 13 14 . 15 WAVELENGTH (MICRONS)

DIPHE1"YL DISULFIDE (KBr Nafer)

· IR 3?J~CTRA # 2 co ~

I :1.:1 :::1. 1- I ·: ,, ":lll~~llrnlll' ' ·"'I II i: 11. llllliHrlllll'll'lllJ II. lll'ii.llll rr '---,

I 40 0 10 P.?,??P.~,~I 1, ~~ R~,It_l_t_l_~,~o~!, I ,(~\A-l' I r ?~"'"~9?.1,1,,.,~9~~ 1, I,, 1~9° 00 " ',,, 1 '!'''' ""T'1 Lt Itt!-t-l, rlj'll! t I fl··nl·lt-1 i j! j i Ut'i+l ;-u i; :1·_,;. ;1: ~ l::: ::::; !·tPl~ t H-r 1 ---~-j= '!·nJ+l,·r1~jf·[·r·-1 L~-· jlj-L-!~i-l:*h; ;::~ ;~r: .·-. '~,o.o --~-:---:-:-:-:--1, ~; .:·:J~~;.j·: ~!- : u lJ_·_rt·-:t·it·~ +1R- r~1 +-i+~Lt-lLHi·: JiB i-1-··li'--~m;:,J lL;l-1 :r,j·,:;: ~::1111;T -ru\ -~:; :1tti . . . . . • ~-· • t f ~ , 11 -t-!- ll +-i-- :.. !-· _ ~ ~l' I,·~ l, l l. l jT '[m -- .. -...... _ ;-~- ~... . . ___ , t •• .1ok~~:::: :~ :ft;.,:;·\~~~;-·:;rr:~~-::r-r:+1 1 :rl-+v.t-·11 r1 ~Hl- i-J-i:l-1--l+tt~i~ii.!::fhtH:f1 1 jJd iJI;ti~\lj!i~~- :ir~=t~-t: :;~t::=:-:J 1 .:~~- (.::\: .':r-HrjTI~)ViV)1 ki 1\[f f:VIh~·>v-Y;\{Ii''lli·-~·--· ~; 1 ~.h ~ ... ;.. ,_., ···: ..... , .. ,±t.:.- ---·-,--"-:--: 10 1 1 w ~d~- ~::: :~·!=:~~Ft"~.- ~-:;}tHT:L.t..!. ~: +---r:~ l~""··n:i_ L!~J-qiA!J\!1 1 ~w~:TG;~(\f' ,lt{fli~Jlft: 1-~}i-iJ~E\I~~ ~~-~-J~~~ i u 20 .:;:j· :::: 1:::! 1-r.f ;;:; Ill :i i : iT l i l{ ! ·. l'::ti r·l· .- .!1:.: . I • . . I ' ' '1 ;__ f-!- .' • " ' I ill:Hl'·l'!I I :\i' I '~lllI' I ' I .tl.:i. l .. :~-:!t-l~t-~+_f-:-ix~:-~~"7-'li I' ' :. :.:t-1 .. \ .. ~--.,... -: '--..:J:=~.:~--·.,-· 1. 1 Z . :: _._._.. :i:: ;\tr i!:i :l_~l~! 1:- I':· ~~ 1 1t: 1 11 1'!' :···l' 11 !LilliJ,• 1 · ·; :1::·: :·:: ·:·:· .(-- ., .. :-:. .--:.::.·:::: 20 ~ ·:: :- - --!:tt 1~rH- tci-t- +I ;-r i- · 11: ~ -r' ~: I - ~ -H- -W- ' .; : ! r m ~ · 1.1 L~~w-; -~: ~: i 1 ! : dj 1 j-!; ~ ~; i ~ t ~ ~ u ~ 30 · · · · · ' · t \ 1 ! , : · I l ' ! It - I I lffijt1 j- · : 1-i jl 1 I r! \ ; I i 'i I I i 1 : : ! : . · · : : ::: · ·...... ,s 1 o· ~:::-: .;:::. :::1 1:; 1 il:l Ti11 I:: ·;il'i I lil'i' 11: :-~~~fi · : IJ·_,; jii1 ~iii Iii;:::;;;::~: : ;';~; ":;; ::7·A;3o ++-f'..Ll,W:llJ I ' i I j I jljll j,:; I t/)40r--·-t--·---:-··-·-·4' _·...;·...;.1 1 1 !Iii l :I I lJI'iii'): .., !;;: :. : il}:J.\::1 .. c:.o • ' ' . ' ' . : • i ! I ! TI ' !T T,l- ·;-· T' ··-~p-- u -- I ' ' l I I I • : ' I I • : • I I ' /I I 0 1 1 4:.so ·••• :. .!. I ::! !! : I ~: I i_.l . !11 1 11 lul .: llll!lll!!l !II! ill! ti , J ~U! T.t:~ .60 .. --::::::: ::: :: i: ; ~ ! I, ~ i_ :m:-~: ,_; il , , i d_: l , ! i~ ~, ~:: i P1 ~ ,~ 1~~ _! j ~~ i, ; ! l; :! i :j! :::_ __. j .. l =, t. ;.)Q 70 ::: ::: ~:::: :! : i;; 1 1 : i j iT I i j j: i 'illl I I j I i II! i! II l i j I,,;,· j I;! ; j I; :; I; ; ; ; : ;; ; ; :. ; ~: .1'~:::: .60 • • :: . : ·.::. • • • • • t l:. : ; ! I i 'I .. ' '.' ' " I ' ' ' ;_j - 'I. _, __ I; . :! I :: ... ·-·.. .. . ' .. . - . . . - , - , , , , . , • , , , , : i . , : r : 1 ,_ · · - : .J ! 1 • 1 : 1 , 1 1 1 1 1 : ! 1 i r 1 ; 1 1 1 ~ 1 , I ~ 1 ~ - , , 1 : , , • • • : 1 : r :-.: : : . -·1 - ' · · 7 o 1.0 . . ! i ;; ; ; , ;l , ... :: I:: ' ! i i; ' ' . ; iT ; _ ' i : · l :~] f': ;;" :!:: : :: :: >i: i' <' >1 [:: ]' ::::·:: ::: t-l!i!: ll ,,,, Jili r-r:l·l-fl: Jljll llil !ljl I I )jl) il- :l j!'[-J .i'L iLl .. : -y--7-1· ···'···· i.O . ' ' I ' ' I :- I j t : ! I I : I ! t ' • • • ; •• : ; ' '-:;-'.:.....,:..J,...;..;.J,.'~ li..LI.L.Ll. I_;_' L'--':'~' l_w.J...!_I u'-:;-1 I!J...L:WT.i.' :' ~:u: lj_l.J' .r:l ~II!u' :0!~1~::::::1 Dt u!J!~ ~: ':t::' -~' !tttr:!:'j' ::t::.:~ ~:l±.t' :=:=: tl =: =:r!:. =::±1: 00 co """ 3 4 5 6 7 8 9 10 11 12 13 14 15 WAVELENGTH (MICRONS)

THIOPMl'iOL FROM REACTION 1-TUI

IR :--;:t:·l~CTRA !/ 3

co ''-''!1

1.: '"·:I. . 1::1 ;j ,[ .:I I 1 I ! i I 1· 11111llHi~IIIII'II'IIIHI' liii IIIIIID~~~~~ Ti i' i 1 :m1~1•11l' , _)

i 4000 3000

I olt' I ' I . I I'; I

CO - ---- ' • ' I I -, 3 4 5 6 7 8 9 . 10 11 12 13 14 WAVELENGTH (MlCRONS)

DIPHENYL DISULFIDE FROJI:f HEACTIO:N" I'HJiviBER ONE BENZENESU:LFOl'lA!HDE · (KBr Wa:fer) •; IR ·sPECTRA fl 4

00 0\

•t: 1 ;.1: 1.. i! 1111llrmliilr!l"ilnrr· llli!•lr1•m~1m 1'~'- I' ·r ,:m1~1•11r" , - I I 4000 3000 2000 1500 CM-1 1000 900 800

w ~.20

<{ . . . . ., . T • . . " I " . - " l " " --· . ... f ~.30! .. . l Ar I 1 0 4

~.-

1. 0 1.----r--·

o::::l , I I 3 4 5 . 6 7 8 9 10 11 W A VELEt--lGTH (MICRONS)

j DIPHEI'JYLAftTIHE (EA::3TII'IJUT ORGANIC CHEIO:CALS) (~:Br tiaf'er) IR ;~.PlGCTRA # 5

co -..J

·, I' . ~ !· : .... 1i i. 1.,1 ···II

1 .. ·.I :I ~ ·:.mm~;~1•r• .. I I I 1: ]11\lllrHHIII!fl'llllll' llll,:-~11~1 T' 4000 3000 2000 1500 CM-1 1000 900 800 700 0. OL:::::;-·. i_ ••

w U.20z /...... ~.30!-

3 14 15

. ··- --· ------·;-.- ·. - DIPHENYLAT'HiifE FROM RK4.CTION NID1BER ( KBr i·l<:.f' er) IR SPECTRA # 6

co co

]'~· · I '1, "r " '1111~1·1] I I i' I' "rllll'rlllmrlr'rlr:r,,rll'lll' Tll'r':~lllll~~~~~ r , I I '

40E2c_:w'?o ~ , ,20f~, 1 , ._..,, 1,spo . ,. c~v''. 1 , ~oGo. ,, ,. ~?? . .\, 1 .,, .~90, • , ! , , 79~ , ,(' 1 1 1 :;::~--- i- ,.-··-~!-:=~~~-- -~- ;.t!:1.•IT:~.~~--··~".•! =· i_i rH=·t--~--+-J[~f~-·.•.· !~--~- !i_;(~:

·j· · ····• · · ·· ·j ···· i· ··:: I· ·· ·' ··· ·g~· ! · ·· .J ___ .. ;.. -···1·-----·--·- W, .·.;.:-:::: .. ::: :: ::::·:.:~::·:··! ::~~--·-··:· ·~· ::.; ::~ .· ; .... ,;· · ··l1··;· · ::~: l ;~~~~-:-~:! ~~-~:~~~~ u 20 I ' ....,--·---: _,J_ --- ··- --.. .. --·-· .. ------+-·-·· j20 • • :·. '. .. ; ;: , . : ~I , .. ! ! ; . !.: : · r _.:::.: • ~ ___ J ...: __ :...:.:.: -t·· :.. ;_:::.. -~: :. --· . . .:....:. ~- --w~- J ••! . . - - - . --- . --~-j- .. gL. J ---- ·.. :_-. -· __ ..:..!:.::... ·--. - - - ... l C"'- 30 - .. !' . ::;:·:;:,...----- ·:--:.!:...... ·-. ... :···-- . : .. -: --- ,...... ______: . .. __ -~-. -:--r·· -I i . :. - ' :··:·;. -,:·: <~~<-=· .30 ~. . . I ... ' I . . I • . ... : . ' ' I I '. ! '...... ; ... ---. I . I.' . i '. I ' : ' I I . t.' .•. 0 i • " : ' ' • ' • ' : I . I . I : ; : : : ' I u; _, ______. ____ - -·--·! .. -· . ·-·- ·-. j...... \ ···- ----·--· - --! . __,...,.._, 40 40L.--~, ...... ~ .. , . _: _ r : . l -~------·-·-··-·--··t • • 1 f • • -~• ! _ . , . , :· : : .. ! . ~ I . i · ,. _ _.._..j_ :--.-- .. .. 1 . : ;_; ;-: --·----~~~ ------:.•'R .... I . . ! ____L 3 4 5 6 7 8 9 10 11 12 13 14 15 WAVELENGTH (MICRONS)

PARTIALLY REDUCED DIPIIElliYLAMINE FRO}I REACTION NUMBER ON"E N",N-DIPHE1;ryLBENZENESULFONUIIDE (Neat)

1 IR SPECTRA :fl 7

co \.0 ,,

I ,, -.1', I. j].),jj 11 :.i ·:·t , I 'il II,· '1111111 .. I I I : ! I 1: T!. 111 'II lri m,,1\llr~"l11l11, ,1 lll:l~l~~r v~· · 1 4000 30.00 2000 1500 Cfl\" 1000 900 I 800 700

f,, I I I .I '' ''' . ·'' ' ' ' ' ''· ': I .. ·' '; ·' '. : 'I ' l l.,-1;-h, ' .•.. ! . . . '· ''. 1 I . 0 0 0 O ( :' ( f ! ' I. t I . I • ' I '! ! ' I I i. I ' •• I. 11'' I ': I. . :. I . I'. • I I o [ ...... : ''j)·-'-•·• ··.· j'--111! II··~!•· 'lj'j··'l !I·~-~ I !11!-11. 1+··-·j+··· l··lj- .,.l, '·1··~·-f-t·ijl ., ._,.,. ,., .. l.n• .;:, .!...... , o . , . . . . . : ~ : ~ ' i l i \ ! \. l ! j fi I· I 1' I ~ j ; i ! ·!·-!· I I . . ~ ~ I I ! I !I· I I ~ ; ; I ~ \ ; i ! ! t -l t ~ ; .• ; : : ~ ~ ~-+ ...... :·!~I· t!: 1:· ... . I ·tl . ····· I .... t•···· I I. ' I .,. f•' ...... , '! 1·:1 :::· '!!'!' :··~ :·;•-: I ...... I .... '1 t ,J. . -I -1-dJ. ~~ . l:.j -il ~L .j.l U-H'IFI:~ +f· +J !I J. ---~~~--~~·+-··t.L·1 .. '. -· -·- ... -+- ·~··· . ··.-- •...,. ... ·:-·:;+:-, .. ;: .. :~ ··:rY.:-:, .. , :-: .. ~ ~:--LLit~:- +H- -l--h-1· .' ... li-·i--'t--·+++1 -Hj-I·H- -ii-+-L-- :j:J !II J;;_;rii ;_;,.~ :~i~- ';.;: ;~-~L!i j j: \/ ·H .. ! .t. l'..jT.. --l·t+l-11 'r·! I: i: !-:. t ...... , Ill.. I• jV:!". ~~1-l:."1(; '"! ...... ( II ·j··-~-t+ -lr-~rr·.:_t--. . I 1"1'1'·IT'' . T·j Tr::r:l .. 'I',,~* ....1·-·i'l·. , ··I·'I''' - ...... l :; ·.. , ... , ...... tH; . ' ..~. •·'·:·;_~--- .. l\1\..r' II' ·· ... ,,l1•lf, · : li I i'·i i11.. · · .. + ,; · ··11· ,+·--H- -jy,,. :J · ·· 1 i 1 1 !• · :>:. ,;.; ::;:.... : ..... ,;.. ;. "-ci·•·t Q O ,_r·i 1-r-PI .. , l •. .1 ' :· ...... ::·; ,, !ljj-·'i" 1._,_,, jl: !!:: ·~~-~I·'~~~~ j I·,~-~~--~~ill:,- fij---i· t· ti·- 1-jl·-·.11-jJ!I. lj: j·J. I :-lj: ).!'\ flil!~: '!:l; ~_,_l·.·r /.;:l'\'' ~r:·1~-~··~-f-j·"_'_;+·rt..,.,;! :! : ;.·~. :;;;: j.;..IJ ;;;;....._: ...... t-:_;! -r,o1 . ·'! ,,, ·.•1 ilit 1 :'II' · -··1 ,!, ,,., -!·I 1-r.' ,,,, , ;· . 1 ··• ;:·: •• • ..,. :. ·1-'·j:-H·.J--:. :..... , .;. •. 1-: 1 -~-- · · • - .. T ___,... ~ .... ·-4--..· .. - •• .t. •· · '---r-t •.,.--.. ·- . ...,..,. ..•.. -- ~ ···• ,.,. -+-. •···· .... · ... · - ...... ,. r- · ·-t----+~ ...... , .H-HtJ-\ .....11 ~ .,,.~rdj .. nL,··-t--.·-,n· ... ,_f·. .. --,:y.. ··ru··...... ,.. ,,/jr.,. ·. JL .... ;1,,. ..--ili .. , ... __ UJ ·:; ·:;:;·;; 1~!:.:.:~: 1 .. -L i''j ~-~~ijl: 1:\'\r-::·:···.:r !, . I-~·.:.:1 1:::r:1 I i! .-ji. :;·j/ ;: :,t:!~; .::iT:f:::.j.l'.:T't:T;:::: --:_:.:..·,...... :1_: U 20 ...... : ... , .,:.:j..,. ··•. ·l·t·l·:lJt.11 · ··i -: ·"1- .. ··.-· • _· ·-'· H·.' ·' ,;.1 :; -~ ·' ,,.::. ·':·.i··-·--- •-·-~--'---- .. 1,...... · ---·120 0 : :; ; ; , j I i. li :, : i I Uil , , i! :, ..• ,. b4''- u· .~i i j ;I·~ !'il. It, I i ..• , , :; 1::: :, ::I,::: , : ;; : ~;.:: I I • f, i ' . ' : I. . ' ; ! . ' I ,. ! I : . • '· ,.. • : :r·; . ::; . ; . z .. . "• .. :' '• :• .• • I• 'I .j :• i I I' I . '·'I • . I • • ; I . . I .• . • . I I I I " I . f. ;I . ;' ..• t ... • •' ;;I • • t . • ••• ~ • . • • • •'!:: • ... ..~ • < --- ·::-:--;-:-·-::~-r- i .; .-~,+r,- , -:: +·:-; .· "tlf\. · ,; · r-,-.: :· 1+,-i :tr-r.~+t+Tt·h .-. ,-:-:t-t-r-r-:-:-: .. ;; .-.~-1- : ~: •. 1 1 1 1 1 a; 30 : : ; 1 I! ! ~ ' ! : : !: I . : I 1 1 f : :! 1 ! : i : !;·. . . : ! ; . .)!. I ! : ) I ! !i i : I't ! t i: :l ~ .\ ;1 ; ! ! ! : ! ; : ::: : ~ i! : ::. ::! ~=:: f 30 ··_·'•II, I e::;:. · ..,,· i · ::!, .. ; r'•',: I! I:"'ll•jl II i ''·IIr: • · ·! 1'! 1 ! I''!r :I,,1_, !'i j'l'j•i ,.,,,r · 1''1.t IJ•Ill .. ' 1':,i it 'I"'.,,,/'"j 'J j : fi' ,.; ....., ' 1..... · , -~··~'-r'l' ,!. 0 ' .. : ; .. I II ,. ; ' : : ll J l . I I . . I i I I i : ; l i I ' ; I . I' l ' : I II I i' i ' I ! I I ; . ' ' ; I t' ' : I : . : ii· . . : : J-;i . tf) 40 . . ! . : '':: i l I ! . I I ! ' I! . I': li'JJ.' ' ! I . i I; . ' I ' . iII I i i I; I I'! ; ; ' ' I;: ... t1 . . I f \ '40 . r-:--· --· .•. jil.l I''' , ~,,.,,. i;lt->-;·:: .iTfT,,.. , r-1·-:TI .,f, ,~ .. ,,,~,,- ,,, 'l'i' .. · .,., uw.·· ~~- ,~. I w···_ (!) .. .. ; ; : I ! i I I I ' I I . I I .Rf .....I I : ! ··~ ! t I I ! : ! ' I I i ' ! I 1 ! i ! ' ' ' : I . . . ' . ,f ~ . . . . • • I • t • t t·l ' i I ' I I II I I .I '. I . . . I I II· .: . ' !il I I ' • • i . I ' i I I I I I ' ' ' .. ' I •• ' .. I I . .. . " .. I ""' 50 ' . ; . : ' ' . . I t : ' : • i I ' . ' : ' . i I ' I ' : ~· ..i...Ll..I : I ! I • ' ' • ' ' ' : • : ' • ' • ; ' • ' • • • ' . . 50 0 • : -- .. ;;::!iii: ~1::rr:!-r :::- ·Hti -r, ,-,T'' 'I!' i'·l· ·· :i ·11 1'1! :i:, :lr!: ::: :::: ~.::1 :::j·~--:-:~·- .. : . • : : . • .. I I I I i I· I I I I ,. ' ' ! ~ I I I ~ . ! ! I ' ' ' ·f .1 ' i .I 1 ' I !·i ·! I : I I 'I' ' . ; : . . ' .. J ... ' ...... 1 1 1 60 : : : : : : : : I ~ :·~ ~ t : . : : ' ' : • H-1 .. 7-:- :-+-f++-t-:-- '~ fi_;_-t-L-: I ·; : ' +··I-· ,··. ; ' -1-·~·; '· . . : '-: ; '. : : : : : : ~ .: ~ : .: : : ·: : : :.~ : : : . • · : ~ : 6 0 o • • ...... ,,,,.+~·! · 1 t·1-'f' 'I ., ~-.Ill,!, Jl•j •--il'J'] ~o]•-t l!jl '"· ·I·•· "' •·• ...... j ..... 0 .70 ··• ::· :::::m: ·::;:·:: 1i; ~!~~r)J~~u~ 4D~n:~: ·:.: ~/:: :r : :~ ::~rJ. '( j , . . , , I 1 1 , , 1 .••. 1.0 ...... 1, , . 1 , , ~ . .. , +H-+ q , .. . 1 r'' 1 ·~· .•. 1 ,v· .... 1 V... _j)·O 11 i I. ,ffi 'l•l" j'·· :: .. ·:::i-; ::::jf···l11 ! l·· I ' ,, 1 i;·llli,·l,.1 1 1 !1\· I 1 .~ .1:. !i·t: :. ::: :: !::·: :·:.\:::: ...... I . . I : .J1 .. . ' i 'I 11 • ' ' 1i ' i I i I • ' ' I ' ' ' I • ' . I . . ' • • . • ' . ' ' .•.. J.. ' .... ' ... co i : : I i ' I i ! : ' ; 1 ; ' i ; ' I I ' : I I ' I : ij_ i I I ! I : I i I : ' ' I i I I l I ; ; : : I ; :· ' ' . i : : . 6o 3 4 5 6 7 8 9 10 11 12 13 14 15 WAVELENGTH (MICRONS)

I --- :<: PARTIALLY REDUCED DIPHENYLAr

f, ... .l 1.. I.. II :·: :::;: .1:1 r: 11 111 11' lrHilliiWil'1111' 11 · · rrri~•1rr•m~1m· r:· • r· • 1· i ~: 'illl~l•rm " · i I 9i

...--.. tv) -o---r-1 R 0 ~00 ...._.,r-l

+ R ~

I~=- =- ')

-·-

~- - -;,..; __- ; _...:... tn ~~ --- ~ = zd ------~ - - •• 1 .. 1,,. 1 1 1 1 1: 1 1 1 .I 1 1 1 1 1 1 1 1 1 1 r,~,-r-,,-rr-r-,-r-r-r·r-~-~-T-,T~,, 1 1: 1, 1 'l ' . I

~ lr j iji I ( ) . }J. 1 . ~}·l h /r~.II, \ II Jit . . - ~ f:i ~~ ·i . ltii"•~IM<~~\~'1->~~JI.. 1(. ~~~"'J- . . . I I I ' • ' ' -----. + • ' 'I"

I. :. ' . I. ' i. : :t I I . l . I j I I I' I . i ..I l \ • I l I l I ' I l I ' I, I l I I I I I I I, I l I . I I I l I l I l I ' I I I I I l I I I l I l I ' I l I l I l I . I ' I I ' i . ' ; ; I l

CHAATHG. TPJ-4HC DIPHENYL.' :or. suLFIDE (,-., o"blQ c:oc1_ ) 4CKAAG-tpf~- .tiH!Jd _ - __ .._,...,.._-~-... ___ 3 NMR SPECTRA if 2 '-0 N

I .. I ...1 -r.. --I. ILl 1.1 :1 ,;::1 1 .- 'i' ', ·''i !'""'· 'i.llllllll.'ll\ll_'1111lml'i11.· :.:;c: :· I II 1 •, lllillnttllllltlm •tltttl r Till 11· 1n~l11\'il\'ifii1JII' '1111·-~lmn· 1"·~' :l

\,. , I I ' I I ! I I l I l I I I I l I I I I I l I I I I I I I I .j I I I I I I I I I I II c.:.r.

' '. ··:~ I :, ~ ,----:------

~. ll! 1111 -··'

t.-·~-·~r

I I II 0 :s I 2 1 --Cii"PM , I ·- , . I . I .. I I I ~T~ ~~~ . I I I . I I I I I I I I I ' I ' II I I I I I I I I I ; I I I I I I I I I I I I I I I I I I I I I I I I I I l; I_ I I I I I I I I I I I' I ' I I I I I I I I I ' 1 I I . I ' l . I . I i

' --illkWJ-....c;;~"""'Q I •-ota~ .....-~·- urrw,_ _ _...... THIOPHENOL. (HITH DISSOLVED DIPHE1"YL DISULFIDE) FRO!oi RE~Qrr'ON ONE BENZENESULFON..UUDE ( 5% CDC13) w\.0 NMR SPECTRA # 3 ' . I

l. I li J il ,1 J[ 1 1 1 · 1 r· !l ,, :.111~~~~•1111 ·· · · - I I !, I 1Tlllllll iiilllill":liln 11 · I 111 1 •~•~~~ r:· 1 : : 1 , 1 • 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ,---. -r---.---T -~ .-T---r- 1 1 1 1 1-.--r---~1 1 1 1 1 1 1 1 1 1 , , 1 • : j • ; ••

......

I ~~ . --·~·-~ -· .. J~I

6 5 ... 3 OPPM

I ! ' . i . I . \ l . : . i . I . I' l I I I I ' I I I I j ' I I I I I I l I I ; I I I I I I I \. .-'I I I I I I I l I I I I I I I I I ! ' ! I I I I I I I I ' ! ' ! I ! \1 I \ I I I I I I ! ' I . I I I I . ' . I ! l

~·-~-__.,,- TP- • • • -~~~~~~•A..:O"'AIID ·~ .IIIOIQI .....,.._,.. wrNMW6 ___ . . . . I' \0 PARTAILLY REDUCED DIP1IENYLAMI1i'"E FROM REACTiqN FOUR .. N,N'-DIPHElfYLBENZElffiSULFON.AMIDE (1~ C.DC1 ) :'..:· 3 - NMR SPECTRA # 4 ·. . I

i 1 I. I 1: J.il,

1 . I i, ·: ''ill!~IBill , . I 1 r r 111 1 1r~ m1Iill'!l'illll 1· 'I HI·•~•~~· ·r,· 95

H ,-: r;==' ~ ~J~ n_ ~ ~ F I o:::! I ~-~-

~ il -- tl c=l

~ - "'~ 'I ' I l •

... ,

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