Attempts to synthesize vinyl

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Authors Ciko, Geraldine Ann, 1941-

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Link to Item http://hdl.handle.net/10150/318492 ATTEMPTS TO SYNTHESIZE VINYL THIAZOLES

by

Geraldine Ann Ciko

A Thesis Submitted to the Faculty of the

DEPARTMENT OF CHEMISTRY

In Partial Fulfillment of the Requirements For the Degree of

MASTER OF SCIENCE

In the Graduate College

THE UNIVERSITY OF ARIZONA

19 66 STATEMENT BY AUTHOR

This thesis has been submitted in partial fulfillment of requirements for an advanced degree at The University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library.

Brief quotations from this thesis are allowable without special permission, provided that accurate acknowledgment of source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author.

SIGNED

APPROVAL BY THESIS DIRECTOR

This thesis has been approved on the date shown below:

JAMES E. MULVANEY Associate Professor of Chemistrys ti ACKNOWLEDGMENT

I would like to thank Dr. James Mulvaney for directing this work and for the interest and patience he has shown throughout my two years of graduate study.

I would also like to thank my parents, without whose love, devotion, and encouragement my attainment of this degree would not have been possible. TABLE OF CONTENTS

Page

LIST OF TABLES . vi

ABSTRACT ***•**♦*♦♦*♦♦•*♦*♦*«♦«»♦•»♦»♦♦♦•♦*•#»* yii

INTRODUCTION 1

DISCUSSION OF RESULTS , . , , ...... 7

EXPERIMENTAL 19

Friedel-Crafts Reaction of Chloroacetyl Chloride and Ethylene 19 Methyl Vinyl Ketone and Thioacetamide with Sulfuryl Chloride ...... 20 Methyl Vinyl Ketone and Thioacetamide with Iodine . .... 21 Methyl Vinyl Ketone and Thioacetamide with Thionyl C h lo rid e ...... 21 Acrylonitrile and Hydrogen ...... 21 Acrylamide and in Xylene ..... 22 Acrylamide and Phosphorus Pentasulfide in Chloroform . . 23 Methacrylamide and Phosphorus Pentasulfide in Chloroform ...... 24 Thioacrylamide and Chloroacetaldehyde ...... 24 Thioacrylamide and Chloroacetal in Ethanol ...... 25 Acrylamide, Phosphorus Pentasulfide, and Chloroacetone ...... 25 Thioacrylamide and Chloroacetal in Hydrochloric Acid ...... 26 Thioacrylamide and Chloroacetal with Anhydrous Oxalic Acid ...... 26 Thioacrylamide and (phloroacetal in Ethanol (Acid Catalyzed) ...... 27 Thiomethacrylamide and Chloroacetal with Anhydrous Oxalic Acid ...... 27 Thiomethacrylamide and Chloroacetal in Dimethylformamide, ...... 28 Thioacrylamide and Cyclopentadiene ...... 28 Thiomethacrylamide and Cyclopentadiene ...... 28

iv V

TABLE OF CONTENTS - - (Continued)

Page

Thiomethacry 1-amide with Hydrochloric Acid in E th a n o l ...... 29 Base-Catalyzed Polymerization of Thioacrylam ide ...... 29 Base-Catalyzed Polymerization of Thiomethacrylamide . . . 30

REFERENCES ...... 31 LIST OF TABLES

Table Page

1. Summary of Attempts to Synthesize Vinyl and 2-Isopropenyl Thiazoles ...... 11

vi ABSTRACT

Reaction of acrylamide with phosphorus pentasulfide in chloro­ form yields thioacrylamide (I, 45. 9%). Under the same conditions methacrylamide yields thiomethacrylamide (II, 44%). When reacted with chloroacetaldehyde or chloroacetaldehyde diethyl acetal, both thioamides failed to yield thiazoles.

CH =NH

I II

Polymerization of (II) with potassium t-butoxide yielded pri­ marily simple vinyl polymer. Polymerization of (I) under the same conditions yielded a polymer of undetermined structure. INTRODUCTION

Until recently, the most widely studied vinyl monomers and polymers were those of styrene and its derivatives. These studies have yielded much information concerning the effect of substituents on the double bond on monomer reactivity. The most direct means of determining monomer reactivity is through copolymerization experi­ ments, whereby the tendency of the active chain end, whether it be radical, carbonium ion, or carbanion, to add to its own monomer or the second monomer can be measured.

Assuming the following reactions to take place during a copolymerization 11 -M • + M -M.

+ M2 -m 2- 2T -Mg' + M -M -

-m 2-+ m 2 -M2- and defining M and M9 as monomer 1 and monomer 2, respectively, ku k22 r i aS ” k ------' and Tg as — ----- , the copolymer composition equation 12 21

dMt M l r 1[M1] + [M2]" Im J dM2 M2 r 2[M2 J +

1 provides for the determination of the desired relative reactivities.

Much interest has been shown in monomers related to styrene, that is, in monomers containing ring structures which can exhibit aromatic character similar to benzene. In an extensive study of such compounds, Koton* found that the introduction of a heteroatom into the ring usually causes a marked increase in monomer reactivity. Re­ activity is further enhanced if a condensed ring structure is present.

Co polymerizing 2-vinyl pyridine (I), 2 -vinylthiophene (II), 2-vinyl- furan (III), 2-vinyl quinoline (IV), 2-vinyl benzofuran (V),

2-vinyldibenzothiophene (VI), and 2 -vinyldibenzofuran (VII) with styrene as Mg, he found the heterocyclic monomer to be more reactive than styrene itself in all cases except 2-vinylfuran, as indicated by r^ values greater than one, and r^ values less than one.

CH = CH, -CH = CHr CH = CHr S O' I II III

CH = CHr CH = CH IV

CH = CH CH = CH, In addition, Koton found that monomers containing condensed ring

structures were more reactive than those containing only one ring. 2 Koton's results substantiate those reported earlier by Walling on

vinyl pyridine and vinyl thiophene.

While the trend toward increased reactivity of heterocyclic

monomers is not confined to copolymerization with styrene, the use

of other monomers as yields results not quite as consistent. 3 4 Frank ’ showed that while 2-, 3-, and 4-vinyl pyridine and several

alkylated derivatives of these copolymerize faster with butadiene than

does styrene, 2-vinylfuran, and 2-vinylthiophene copolymerize slower 5 than styrene with the same comonomer, and Kamenar found.that the

copolymerization of 2-vinylfuran with vinylidene chloride proceeded at a slower rate than did the ho mo polymerization of either monomer. In the case of the 2-vinylthiophene-butadiene system, however, Meehan^

showed that, while the copolymerization proceeded at a slower rate than did the styrene -butadiene system,. 2 - vinyl thiophene enters the

chain at a faster rate than , does styrene, since butadiene - styrene

(75:25) copolymers at 70-80% conversion have styrene constants of

20.3-21.2%, while 2-vinyl thiophene enters the copolymer at a rate approxim.ately proportional to its concentration, in the monomer mix­ ture (25%).

The furan ring apparently deactivates the vinyl group in 7 copolymerization reactions. Borrows studied the effect of furan analogs of einnamonitrile on the polymerization of styrene, and found that these compounds inhibit the polymerization in the presence of air

and retard in the absence of air. Koton* also found that the properties of vinyl furan homopolymers are dependent on the availability of molecular oxygen. In the presence of oxygen, a soft, low melting polymer was obtained, while in the absence of oxygen, free radical initiation.yielded a hard, infusible polymer., Koton proposed that, in this case, the double bonds in the furan also polymerize, forming a three-dimensional, highly cross-linked polymer.

The addition of a second or third heteroatom further enhances activity, as has been shown by the copolymerization of styrene with

2, 4-dimethyl-6-vinyl-s-triazine and 2 - dim ethyl amino- 4 -vinylpy rim i - 8 dine.

Another area of interest in the study of vinyl heterocycles, is that of biological activity. Although there are a great many naturally- occurring polymers which exhibit biological activity, notably the proteins and nucleic acids, these are classified as condensation poly­

mers, and vinyl polymers exhibiting similar activity are rare, if indeed, existent at all.

Some synthetic vinyl polymers, however, do show biological

activity. Polyvinyl pyrrolidone (VIII) has been used in the preparation g . of synthetic blood plasma , although the reasons for its effectiveness 5 are incompletely understood.

VIII

There exists the possibility, however, that if vinyl polymers could be prepared containing substituent groups sim ilar to those consi­ dered to be the active site in biologically active compounds, the polymers themselves might show biological activity. But it has been shown that similarity in structure does not in itself guarantee the desired activity. For example, Overberger"*-^ studied the polymeriza­ tion of 4-vinylpyrimidine (IX) and 2-N, N, -dimethylamino-4- vinyl- pyrimidine (X). The pyrimidine bases are primary constituents of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), and it was hoped that the polymers under investigation would exhibit antibiotic activity. Although the monomers polymerized readily, the resulting polymers showed no outstanding biological activity.

i CH=CH, CH—CH,

rx X The interest in thiazoles arose from the fact that the ring system is part of the basic nucleus of thiamine (Vitamin B^) (XI).

TNK + _ .CH2 CH2OH H3C" y-NHgCl + N. -CH2 .N CT - CH3 XI 11 Buchman , in a study of the effect of attached group -R on therapeutic activity, synthesized a series of 4-methylthiazole analogs

(XII), and found that none of these

R = -H, -C 2H5, -CH=CH2, H3C- ‘N R- - c h o h c h3, - c h 2 c h 2c h 2o h , - S - XII -CH2 CHOHCH3, -CHgOH compounds exhibited vitamin B^ potency. From this he concluded that even a small change in the substituents on the ring results in loss of activity. DISCUSSION

Although the synthesis of vinyl thiazoles and 2-isopropenyl thiazoles is reported in the literature, * * * ^ these methods involve as the final step the dehydration of alcohols, the dehydrohalogenation of halogenated derivatives, or the pyrolysis of esters. This work deals with attempts to prepare vinyl thiazoles and 2-isopropenyl thiazole from compounds already containing the vinylic bond, and, finally, the polymerization of these compounds.

The most generally applicable method of thiazole synthesis is 14 the reaction of thioamides with u-halo carbonyl compounds. The mechanism appears to be as follows:

where -R, -R , and -R may be H, alkyl, aryl, etc. By the use of the proper thioamides and carbonyl compounds, it is possible to obtain an unlimited number of substituted or unsubstituted thiazoles.

7 Thioformamide is reported in the literature^, and yields

thiazoles unsubstituted in the 2-position. It was hoped that treatment

of thioformamide with chloromethyl vinyl ketone would yield 4-vinyl

thiazole (XIII). CH=CH N 2

XIII

McMahon reports the synthesis of ethyl vinyl ketone by a

Friedel-Crafts reaction of propionyl chloride and ethylene, followed by 16 the dehydrochlorination of the obtained ethyl /3-chloroethyl ketone

Application of this method using chloroacetyl chloride to the preparation

of chloromethylyvinyl ketone, however, resulted in a black infusible,

insoluble material, presumably some sort of cross-linked polymer

(see experimental). Since methyl vinyl ketone is one of the most reactive 17 monomers known , it is possible that polymerization occurred under

the reaction conditions employed.

Dodson and King developed a method whereby a thioamide and a ketone are heated with a halogen, thereby avoiding the necessity of 18 isolating the a-halo carbonyl , or, alternately, dispensing with the halogen entirely, and substituting a strong oxidizing agent, such as 19 thionyl chloride, sulfuric acid, sulfuryl chloride, etc. Both these methods were attempted with methyl vinyl ketone and thioacetamide, using iodine, thionyl chloride, and sulfuryl chloride. All three reactions 9 resulted only in unworkable tars. Presumably, the reactivity of methyl vinyl ketone makes it unsuitable for such reactions.

Attempts to synthesize thioacrylamide by the procedures reported in the literature failed to yield the desired product. The method of Fairfield, involving the addition of to 20 nitriles , when applied to acrylonitrile, yielded a saturated compound which may be NC-CHgCH^SCHgCHg-CN. This compound contained and , but the n. m. r. spectrum showed a complex multi­ ple! at 7. 1‘T', and the infrared spectrum showed strong nitrile -1 -1 absorption at 2250 cm and peaks in the region 730-780 cm , strongly 21 suggestive of the -CHg-S-CHg- linkage . Presumably, cyanoethylation of hydrogen sulfide took precedence

CH2 = CH-CN + H2S ----^ NCCHgCHgSCHgCHgCN over thioamide formation. An attempt to prepare thioacrylamide by 15 Erlenmeyer's procedure for thioformamide resulted in an almost quantitative recovery of starting material.

The desired thioacrylamide and thiomethacrylamide were finally acquired by a modification of this procedure (see experimental).

50-60 CH CH2= C-C -NH2 CHC1 50-60° 10

The n.m .r. spectrum of thioacrylamide showed vinyl absorption at

4. 25 T and 3. TS'tf, as w ell as a sh arp singlet at 7. 84 'C', which was assigned to the -SH proton on the basis of comparison with the spec­ trum of thioacetamide. The n.m .r. spectrum of thiomethacrylamide showed vinyl absorption at 4. 5 2 and 4 .157f, the -SH singlet at 7. 84 nf, and a methyl peak, split into a doublet, at 8. 01T. The infrared spectra of both compounds showed the disappearance of the carbonyl bands. Both compounds had correct elemental analyses. Thioacryla­ mide yielded a Diels-Alder adduct when treated with cyclopentadiene in refluxing ethanol, but thiomethacrylamide failed to react with cyclopentadiene in anhydrous ethyl ether at room temperature or in refluxing chloroform or ethanol (see experimental).

In order to obtain a vinyl thiazole unsubstituted in both the

4- and 5- positions, it would be necessary to use a haloacetaldehyde.

Wiley and England state that it is preferable to use some more stable 22 derivative of these. There are numerous accounts in the literature of the use of acetals. ^ ^ In this work, chloroacetaldehyde diethyla- cetal as well as chloroacetaldehyde was used.

Thioacrylamide and chloroacetal were heated with ethanol until the ethanol evaporated. Dissolving the residue in water, treat­ ment with sodium hydroxide, extraction with ether, and distillation resulted in a nearly quantitative recovery of chloroacetal. Since it is necessary for the acetal to break down to the aldehyde before reaction 11

TABLE I

SUMMARY OF ATTEMPTS TO SYNTHESIZE VINYL AND 2-ISOPROPENYL THIAZOLES

Thioam ide Carbonyl or D erivative Solvent Catalyst Result

Thioacet- Methyl vinyl None T ar amide ketone

• M SOCL

S02C12

T hioacryl- Chloroacetal Ethanol None 99% recovered am ide chloroacetal

it Dimethyl- " U nidenti­ form am ide fied solid

None Anhyd, U nidenti­ oxalic fied sludge acid

6N HC1 U ndistil- able amount oil

E thanol HC1 75% ch lo ro ­ acetal + chloroacet- aldehyde

Chloroacet- Ethanol None ■ Unidenti­ aldehyde fied carbonyl compound

Thiomethacryl- Chloroacetal , None Anhyd. U ndistil- am ide oxalic able amount acid oil " D im ettiyl- None T ar form am ide 12 can occur, it is probable that such decomposition did not occur under under the reaction conditions. The failure to recover any thioacryla- mide can. be explained by the fact that this compound, is readily soluble in water and. is, therefore, lost in the workup.

An attempted reaction of the same two compounds, in refluxing dimethyIformamide yielded a white crystalline solid melting at 179-

180°. This compound contained chlorine, but neither nitrogen nor sulfur. The n. m. r. spectrum failed to indicate any vinylic protons, and this compound was not characterized further. 23 The method of Hantzsch utilizes anhydrous oxalic acid, pre­ sumably to facilitate the decomposition of chloroacetal to chloroacetal- dehyde. The product obtained in this case was a brown sludge, which could not be recrystallized or identified.

When 6N hydrochloric acid was employed as solvent, the residual oil after removal of the ether was present in such small amounts that distillation was not possible. It is possible, but not proven, that such a high acid concentration did completely decompose the acetal, but that the aldehyde was lost in the workup. The failure of thiazole formation to occur could not be explained at this point.

A. sim ilar reaction of the thioamide and chloroacetal in refluxing ethanol with a trace of acid resulted in 75% recovery of unreacted chloroacetal, However, a small amount of chloroacetaldehyde was obtained, indicating that some hydrolysis did occur. The fact that no 13 vinyl thiazole was obtained seemed.to suggest the possibility of a competitive reaction occurring which would essentially remove thp thioamide from the reaction. The obvious conjecture, of course, was that the thioamide was reacting with, itself in some way, A. study of thiomethacrylamide showed what the nature of this reaction was (see below).

A modification of the reaction, introduced by Hrom atka^^' ^ / avoids isolation of the thioamide, and consists of heating a mixture of the amide, phosphorus pentasulfide, and the a-halocarbonyl compound. 27 A reaction following the method described by Schwarz for 2,4-di­ methyl thiazole, using aerylamide, phosphorus pentasulfide, and chloroacetone, failed to yield the desired product (2 - vinyl - 4 - methyl - thiazole). However, this reference mentions the possibility of obtaining a substituted oxazole in this reaction. This eliminates hydrolysis of the thioamide as a reason for the failure of the previously described reactions, since, even were hydrolysis to occur, some

2-vinyl oxazole should be isolated, which was not the case.

Reactions of thiomethacrylamide and chloroacetal met with no more success than did those with thioaerylamide. In all cases, tars, recovered starting material, or fractions too small to purify were the result (see experimental).

To determine the nature of a possible competitive reaction, thiomethacrylamide was refluxed.in ethanol with a trace of hydrochloric 14

acid in the absence of chloroacetal. Removal of the solvent yielded a

polymeric white solid, m.p. > 250°, which was insoluble in chloro-

form, carbon tetrachloride, acetone, and dioxane, but soluble in water,

methanol, ethanol, and dimethyIsulfoxide. This material had an

inherent viscosity of 0.117 in dimethylsulfoxide. If this reaction takes

place rapidly enough under the reaction conditions, it would explain the

failure to obtain the desired thiazoles, since the thioamide is thus

essentially removed from the reaction mixture. Its solubility in water

would cause it to be lost in the reaction workup, explaining the recovery

of only chloroacetal.

Since it now appeared unfeasible to use these thioamides in the

synthesis of vinyl thiazoles, attention was turned to the possibility of

polymerizing a, /3 -unsaturated thioamides.

Free radical polymerization would not be expected to yield high

molecular weight polymers, since the -SH group would act as a chain transfer agent.

Studying the base-catalyzed polymerization of acrylamide, 28 Breslow found that he obtained, not the expected simple vinyl polmer, but one which arose from a proton transfer mechanism:

OCH 3

CH2 = CH-C-NH-CH2-CH-C-NH > CH2 = CH-C-NH-CH2-CH -C-NH 15

Marvel and Yoda obtained sim ilar results with jD-styrenesulfona- 29 mide. The polymer resulting from the base-initiated polymerization of this monomer proved to be one with mixed recurring units, some arising from simple vinyl polymerization and others from the proton transfer reaction, which would yield a structure (XIV). They assumed that the

SO N H—

XIV proton-transfer reaction was occurring because of the decrease in the

-NH- stretching band at 3310 and 1615 cm *.

Thioacrylamide and thiomethacrylamide were polymerized with potassium t-butoxide according to Marvel's procedure. They both yielded white, powdery solids, melting above 275°. The polymer obtained from thioacrylamide had an inherent viscosity of 0. 055, while that of the thiomethacrylamide polymer was somewhat higher, 0.171.

The -NH- stretch in the infrared spectrum of polythioacrylamide appears at the same wavelength as it does in the monomer, 3325 and -1 3175 cm , while the polymer obtained from thiomethacrylamide shows the -NH- stretch at somewhat higher wavelengths than does the monomer, -1 -1 3430 and 3180 cm as opposed to 3380 and 3175 cm 16

Two obvious structures are possible for the polymer

n SH

A B

Because of the deshielding effect of —C— and —NH— the protons bound to carbon in structure B would be expected to appear at considerably lower fields than carbon bound protons in A.

The n. m. r. spectrum of the thiomethacrylamide polymer, while poorly resolved, shows no absorption at lower fields which would indi­ cate proton transfer. Two broad peaks, at 8. 75'X and 8. OSTf, having relative peak areas of 3:2, seem to indicate that polymerization in this case occurs primarily, if not exclusively, through a simple vinyl mechanism, and that the polymer has structure A(R=CH^).

The n. m. r. spectrum of the thioacrylamide polymer, presents a more complex picture. The absence of peaks in the region lO'X to

8. 5 would seem to indicate that, in this case, no significant amount of vinyl polymer is formed. The spectrum shows peaks at 7. OS't,

7. 21+t , 6. 9 0 f, and 6. 75 . It is possible that the polymer contains several types of recurring units. These can be postulated readily from the mechanistic view, but are difficult to assign to the spectrum without broad generalizations. 17

One of these units, of course, is the one arising from proton transfer, which would yield a polymer of structure (XV).

4-CHg-CHg-NH-f

(XV)

The problem with assigning this structure is that the methylene signals would be expected to appear as multiplets, whereas the observed signals are apparently singlets. Although the evidence is far from 32 exhaustive, there is a possibility that protons a to C=S and £to —NH— fall in roughly the same area of the spectrum as those in the reverse case. The probability of the two sets of protons having the same chemical shift, and appearing as a singlet is too unlikely to consider seriously at this time. -1 The fact that the polymer shows imine absorption at 1650 cm in the infrared, which cannot be assigned to —C=NH as it could were SH vinyl polymer present, makes possible another postulation concerning the structure of the polymer, namely

-K:h2^h24^-6-^ c

This structure could also arise by the proton transfer mechanism, but involves a different attacking species than that required for B.

Assuming —SH to be the most acidic species in the monomer, this mechanism could be as follows: 18 H =NH ___ CH =6-C=NH -> c h = 6- c = n h * & t-BuO NH NH NH C-S-CH--CH-CA - ^C x sh c n f h CH _ H EXPERIMENTAL

Melting points are unconnected. Infrared spectra were determined on a Perkin-Elmer Infracord, calibrated against polystyrene; n. m. r. spectra were determined on a Varian Model

A-60 (60 Me. )spectrometer using tetramethylsilane as internal or external standard, Microanalyses were performed by tbe Micro-

Tech Laboratories, Skokie, Illinois. Solvents used were all reagent grade and not redistilled, with the exception of benzenp, which was dried over calcium chloride and distilled, and dimethylformamide, which was dried and distilled over calcium hydride. Liquid reagents were distilled and solid reagents re crystallized prior to use wherever possible. Anhydrous oxalic acid was obtained by sublimation from the dihydrate. Hydroquinone was added to all reactions in which potentially polymerizable compounds were used,

A. Friedel-Crafts Reaction of Chloroaoetyl Chloride and 16 Ethylene

Chloroacetyl chloride was prepared from chloroacetic acid and 30 thionyl chloride by the method of McMaster and Ahwann. ' This

compound, boiling at 96-98°, showed carbonyl absorption at 1790 _ 1 ^ cm in the infrared, indicative of an acid chlpride.

19 Chloroacetyl chloride (4Qd g„, 3. 54 mole) was added slowly to

a stirred mixture of 2000 ml. of carbon disdlfide and 575 g. (4„ 3 mole)

of anhydrous aluminum chloride. The mixture was cooled to 0° with

stirring and dry ethylene passed into it for 7 hours, The mixture

was heated on a steam bath at 40-45° until brisk evolution of HCl

diminished and was then allowed to stand at room temperature

overnight. The residue was poured onto ice to decompose the

aluminum chloride complex, resulting in a two phase system. The

organic layer was washed with dilute hydrochloric acid, water, and

dilute sodium bfcarbpnate until an alkaline reaction was obtained. .

The resulting slightly tarry solution was distilled at atmospheric pressure to remove the solvent. The residue in the distilling flask was a black, infusible, insoluble solid, which was not identified.

B. Methyl Vinyl Ketone and Thioacetamide with Sulfuryl 19 C hloride

Thioacetamide (36 g ., 0. 48 mole) was dissolved in 14 g. (0.2 mole) of methyl vinyl ketone and the mixture cooled in an ice-salt bath. Sulfuryl chloride (27 g ., 0. 2 mole) was added slowly enough to keep the exothermic reaction to a minimum. When addition was

complete, the tarry mixture was heated on a steam bath for 15 minutes. The resultant tar was extracted with ether, but evapora­ tion of the ether yielded only a: film on the inside of the flask. 21

C, Methyl Vinyl Ketone and Thioacetamide with Iodine'*'^

Thioacetamide (30 g„, 0„ 4 mole) was dissolved in 14 g„ (0. 2 mole) of

methyl vinyl ketone and 50. 8 g. (0. 2 mole) of iodine added portionwise

through a reflux condenser. The reaction was highly exothermic, and

gave off dense white fumes. When addition was complete and the re­

action subsided, the mixture was refluxed gently for 2 hours. The

resulting black tar was diluted, with water and heated until maximum

solution occurred. The aqueous solution was made basic with con­

centrated ammonium hydroxide and extracted with anhydrous ether.

The combined ethereal extracts were dried oversight over solid

sodium hydroxide, and the ether removed under vacuum. Attempts to distill the residual oil resulted in the formation of a black solid in

the distilling flask.

D. Methyl Vinyl Ketone and Thioacetamide with Thionyl

C h lo rid e'*' ^

Thioacetamide (30g., 0. 4 mole) and 14 g. (0. 2 mole) of methyl

vinyl ketone in a Dry Ice - acetone bath were treated 11.9 g. (0.1

mole) of thionyl chloride. The resulting black tar was worked up

in the manner described above (see C) with the same result.

20 E. Acrylpnitrile and Hydrogen Sulfide

Acrylonitrile (222 g. , 4. 2 mole) was dissolved in 232 ml. of

pyridine and 101 g. (1. 0 mole) of triethylamine was added. Hydrogen 22 sulfide was bubbled through the mixture in a steady stream for 3. 5 hours. The mixture was poured into distilled water and the organic layer removed. The aqueous layer was extracted with ether. The combined organic fractions were distilled to remove solvents, and the residual vile-smelling red oil cooled in a Dry Ice -acetone bath in an effort to precipitate the suspended crystals. Filtration and recrystallization from ethyl acetate yielded 4. 0 g. of a pale yellow solid, m. p. 35-36°. The infrared spectrum of this solid showed -1 strong nitrile absorption at 2250 cm and peaks in the region 730 -

-1 21 780 cm , strongly suggestive of the -CH^-S-CHg- linkage.

Furthermore, the n. m. r. spectrum showed no vinyl protons, a com­ plex multiple! at 7. 1 T , and singlets at 8. 0 and 9. 55MT , both of which are probably caused by impurities. This compound was assumed to be NCCH^CH^SCH^CH^CN, arising from the cyanoethy- lation of hydrogen sulfide.

15 F. Acrylamide and Phosphorus Pentasulfide in Xylene

To 71 g. (1 mole) of acrylamide suspended in xylene in an ice- salt bath was added 35 g. (0. 16 mole) of phosphorus pentasulfide with vigorous stirring over a period of two hours. The mixture was then left overnight with stirring. The xylene was separated from the residual solid and the solid extracted with ether. Concentration of the combined organic layers and the addition of petroleum ether 23

(30-60°) resulted in the precipitation of a white solid, which, after recrystallization from ethyl acetate, was shown to be unreacted starting material on the basis of infrared spectrum and mixed melting point. Total yield of unreacted starting material - 65 g.

(93%).

G. Acrylamide and Phosphorus Pentasulfide in Chloroform

Acrylamide (200 g. , 2. 82 mole) was dissolved in 400 ml. of chloroform and 100 g. (0. 45 mole) of phosphorus pentasulfide added with stirring at 50-60° over a period of 2 hours. The mixture was stirred without heating overnight and then allowed to stand without stirring for 48 hours. The resulting two-layer system was extracted with anhydrous ether and the ether concentrated on a steam bath under aspirator vacuum. On the addition of petroleum ether (30-60°) a white solid precipitated. Two recrystallizations from ethyl acetate yielded 6 g. (15.3%), m. p. 67-68°. (Repetition of the procedure eventually increased the yield to 18 g. (45. 9%) ). The n. m. r. spec­ trum showed vinyl absorption at 4. 25 ~C and 3. 75‘C and a sharp singlet at 7. 84 ■T which was assigned to -SH on the basis of com­ parison with the spectrum of thioacetamide. The infrared spectrum showed the disappearance of the carbonyl band.

Anal. Calcd. for C^H^NS: C, 41. 34; H, 5. 78; N, 16.07.

Found: C, 41. 38; H 5. 97: N, 15. 95 24

EL Methacrylamide and Phosphorus Pentasulfide in Chloroform

Methacrylamide (200 g„, 2. 38 mole) was dissolved in 400 ml. of chloroform (gentle heating) and was 'treated with 100 g. (.0. 45 mole) of phosphorus pentasulfide in the manner described in (Gr). Workup was the satne except that the reaction mixture did not stand, for 48 hours after overnight stirring. The yield of white, powdery solid, m. p.

101-102° after recrystallization from ethyl acetate was 20 g. (44%).

A nal: Calcd. for C ^ N S : C, 4-7. 50; H, 6. 83; N, 13.85.

Found: C, 48.01; H, 7. 15;N, 13. 73. 22 I. Thioacrylamide and Chloroacetaldehyde

Thioacrylamide (5 g ., ,0. 057 mole) was dissolved in 75 ml. 95% ethanol and 4. 5 g. (0. 057 mole) chloroacetaldehyde added. The mixture was then refluxed for 8. 5 hours, after which it was poured into water, made basic with sodium hydroxide, and extracted with anhydrous ether.

The ether extracts were dried, and the ether removed under vacuum.

Distillation of the residual reddish brown oil yielded 2 ml, of a clear, colorless liquid, b. p. 25° (0. 5mm.). The n. m. r. spectrum showed no vinyl protons, and the infrared spectrum showed a strong carbonyl -1 band at 1750 cm . The product contained no sulfur or nitrogen, but did contain chlorine. This product was not further identified. 25

J, Thioacrylamide and CMoroacetal in Ethanol

Thioacrylamide (34. 8 g. t 0. 4 mole) and 61. 04 g. (0. 4 mole) of chloroacetal were heated on a steam bath in 175 ml. 95% ethanol until the ethanol evaporated. The residue was worked up in the usual manner (see I..). Distillation of the residual liquid yielded 50 g. of a clear, colorless liquid, b. p. 44-47° ( 5. 5mm) which contained no sulfur or nitrogen, but did contain chlorine; The infrared spectrum of this material was superimposable on that of chloroacetal.

27 K. Acrylamide, Phosphorus Pentasulfide, and Chloroacetone

A mixture of 150 g. (2. 11 mole) and 100 g. (0. 45 mole) of phor- phorus pentasulfide was added to 100 ml. of dry benzene. To this was added 20 ml. of a mixture of 200 ml. of chloroacetone in 75 ml, of dry benzene. The flask was heated on a water bath to initiate the reaction, after which the bath was removed and the remainder of the chloroacetone-benzene added portionwise through a reflux condenser.

After about one-third of the mixture had been added, a solid formed in the flask, making stirring impossible and necessitating shaking the flask after each addition in order to obtain at least partial mixing.

When all of the chloroacetone-benzene mixture had been added, the flask, was heated on a steam bath for 1/2 hour and.375 ml. of water was added. The reaction mixture was then allowed to stand at room temperature for 2 hours. After this time, the two-phase system was 26 separated. The lower layer, a deep red oil, was made.basic-with potassium hydroxide and extracted with ether. The ether extracts were dried, filtered, and the ether removed. Distillation yielded

5 g. of a slightly viscous orange liquid, b„ p. 76-83° (2-2. 5mm), the. infrared spectrum of which showed strong carbonyl absorption at -1 1720 cm and whose n. m. r. spectrum indicated the absence of aromatic protons.

2 5 L. Thioacrylamide and Chloroacetal in Hydrochloric Acid

Thioacrylamide (17. 8 g ., 0. 204 mole) and 30. 8 g. (0. 204 mole) of chloroacetal were refluxed Under nitrogen in 100 ml, 6N hydro - chloric acid for 1 hour. The dark, viscous mixture was worked up in the usual manner (see I.), and, after evaporation of the ether, there remained only a.few drops Of a brown oil - not enough to distill.

23 M. Thioacrylamide and Chloroacetal with Anhydrous Oxalic Acid

A mixture of 19. 4 g. (0. 127 mole) of chloroacetal and 11.4 g.

(0.127 mole) of anhydrous oxalic acid was heated under a reflux o condenser in an oil bath at 140 until gas evolution ceased. To the solution was then added 11.0 g; (0. 127 mole) of thioacrylamide.

Gentle heating initiated a brisk reaction, whereupon heat was removed and the reaction allowed to proceed until it subsided (about 1/2 hour), o The dark mixture was then heated for an additional hour at 100 , allowed to cool, and diluted with 100 ml. of dilute hydrochloric acid 27 and 100 ml. of water. Filtration removed the precipitated solids, and the clear, dark filtrate was made basic with 5N potassium hydroxide and extracted with ether. An attempt to distill the resi­ dual dark oil under vacuum after removal of the ether resulted in the formation pf a solid in the distillation flask (bath temperature

<100°). This solid, difficulty soluble in most organic solvents, could not be recrystallized, remaining a brown sludge after all attem pts.

N. Thioacrylamide and Chloroacetal in Ethanol (Acid Catalyzed)

A mixture of 8. 7g. (0. 1 mole) of thioacrylamide, 15. 3 g. (0, 1 mole) of chloroacetal, and 3 ml. of concentrated hydrochloric acid was refluxed in.95% ethanol fpr 12 hours. The dark mixture was allowed to cool and worked up in the usual manner (see I,). Distil­ lation of the residual dark liquid under aspirator vacuum yielded

3. 5 g. of chloroacetaldehyde and 11. 5 g. of chloroacetal (identified by its infrared spectrum),

O. . Thiomethacrylamide and Chloroacetal with Anhydrous

Oxalic Acid

The procedure described in (M.) was followed, using 10,1 g,

(0.1 mole) of thiomethacrylamide, 15. 3 g. (.0.1 mole) of chloroacetal, and 9. 0 g. (0. 1 mole) of anhydrous oxalic acid. The residue remain­ ing after removal of the ether was not enough to distill, .even" in micro-apparatus. 28

P. ThiomethacryXamide and Chloracetal in Dimethylformamide

Thiomethacrylamide (10. 1 g ., 0. 1 mole) and 15. 3 g„ (0. 1 mole)

of chloroacetal in 50 ml. of dimethylform amide were heated with o stirring in a water bath at 95 for 4 hours. When the heating was

completed, the dark brown mixture was worked up as described

above (see I. ), Attempt to distill the residual oil resulted in the

formation Of an undistillable tar in the distillation flask.

Q. Thioacrylamide and Cyclopentadiene

A mixture of 8. 7 g. (.0. 1 mole) of thioacrylamide and 6. 6 g.

(0. 1 mole) of cyclopentadiene (distilled immediately before use

through a 12-inch column packed with glass helices and caught in a

Dry Ice-cooled receiving, flask) was refluxed in 100% ethanol for 6

hours. Removal of the solvent yielded 7. 4 g. of a white solid, m, p.

198-199°. Its low solubility in most organic solvents made charac­ terization difficult, but the n. m. r. spectrum showed the disappearance

of the vinyl protons of thioacrylamide, and the appearance of higher 33 field peaks characteristic of the bicycloheptene system , although

the low field peaks appear to be absent.

R. Thiomethacrylamide and Cyclopentadiene

Mixtures of 12, 1 g. (0. 12 mole) of thiomethacrylamide and 7. 92 g.

(0, 12 mole) of freshly distilled cyclopentadiene were treated as follows:

1, In anhydrous ether at room temperature for 12 hours. 29

2. In refluxing chloroform for 8 hours.

3. In refluxing absolute ethanol for 18 hours.

All reactions resulted in an essentially quantitative recovery of starting material, as determined by spectra and mixed melting point.

S. Thiomethacrylamide with Hydrochloric Acid in Ethanol

A mixture of 5.0 g. (0.05 mole) of thiomethacrylamide, 2 ml. of concentrated hydrochloric acid, and 50 ml. of 95% ethanol was re- fluxed for 6 hours. Removal of the greater part of the solvent on a rotary evaporator yielded 3. 8 g. of a white solid. The crude material, m. p. > 250°, was insoluble in chloroform, carbon tetra­ chloride, acetone, and dioxane, and soluble in water, methanol, ethanol, and dimethylsulfoxide. The solid was dissolved in dimethyl- sulfoxide and poured into chloroform, resulting in the precipitation of a fine, white powder, which was filtered and dried in vacuo at 70° for 12 hours. rCj (0. 5% in DMSO) 1. 06; ^ 0. 117.

29 T. Base-Catalyzed Polymerization of Thioacrylamide

Potassium t-butoxide was prepared by adding 39 g. of freshly cut potassium to 74. 1 g. of dry t-butyl alcohol (dried and distilled over sodium) and refluxing the mixture for 15 hours. The excess t-butyl alcohol was distilled under reduced pressure, and the product was obtained as a white powder free from the alcohol. 30

A solution of 3. 87 g. of thioacrylamide in 20 ml. of dry dimethyl- formamide in a 100-ml 3-necked flask equipped with a magnetic stirrer and reflux condenser was heated with 0. 00 54 g. of phenyl- (3 -naphthala- mine at 135° under nitrogen for 1 hour. To this mixture was then quickly added 0.0598 g. of potassium t-butoxide, and the mixture stirred at the same temperature for 30 hours. Solid material was noted in the flask after about 10 hours.

The reaction was quenched by pouring into water containing 10% ethanol and a trace of hydrochloric acid. Much of the solid material dissolved, so the aqueous mixture was poured into methanol, result­ ing in a more copious precipitate. The solid was filtered and dried in vacuo at 70° for 12 hours, yielding 2. 5 g. of a white powder, m. p. o > 275 (0. 05% in DMSO) re l

U. Base-Catalyzed Polymerization of Thiomethacrylamide

The same method described above, using 4. 38 g. of thiomethacry­ lamide, 0.0027 g. of phenyl-j3 -naphthalamine, and 0.0293 g. of potassium t-butoxide. The reaction mixture was heated under helium for 36 hours, solid being noted after about 8 hours.

Extraction of the filtrate with ether and evaporation yielded 0. 8 g. of unreacted thiomethacrylamide. Total yield of polymer after drying:

3. 0 g. of white powder, m. p. > 275°. rn r e ^ (0. 0 5% in DMSO) 1. 009; REFERENCES

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