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University Microfilms 300 North Zeeb Road Ann Arbor, Michigan 48106 A Xerox Education Company ORPHANIDES, Gus George, 1947- THE CHEMISTRY OF 2- AND 3-THENYLIDENES; CARBENIC AND CATIONIC REACTIONS OF flt-DIAZO THIOLESTERS.

The Ohio State University, Ph.D., 1972 Chemistry, organic

University Microfilms, A XEROX Company, Ann Arbor, Michigan '

THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. THE CHEMISTRY OP 2- AMD 3 -THENYLIDENES; CARBENIC AMD CATIONIC REACTIONS OP a-DIAZO THIOLESTERS

DISSERTATION

Presented In Partial Fulfillment of the Requiremen bs for the Degree Doctor of Philosophy in the Graduat School of The Ohio State University

Gus George Orphanides, B.S. * # # #

The Ohio State University 1972

Approved hy

Advisor Department of Chemistry PLEASE NOTE:

Some pages may have

indistinct print.

Filmed as received.

University Microfilms, A Xerox Education Company DEDICATION

To ray wife, Jeanne-Marie

11 ACKNOWLEDGMENTS

I would like to thank Dr. Harold Shechter for the suggestion of this research problem and his expert guidance in the preparation of this dissertation.

I also wish to extend appreciation to Dr. John Swenton for his guidance in the photochemistry in this research.

I am grateful to the National Institute of Health and the Depart ment of Chemistry of The Ohio State University for financial support.

iii VITA.'

January 27, 19^-7 Born - Kew Gardens, New York

1967 ...... B.S., Hobart College, Geneva, New York

1967-1969 ...... Teaching Assistant, Department of Chemistry, The Ohio State Univer s i t y , Columbus, Ohio

1969-1972 ...... Research Associate, Department of Chemistry, The Ohio State Univer s i t y , Columbus, Ohio TABLE OPcontents

Page

DEDICATION...... '...... i l ACKNOWLEDGMENTS ...... i l l VITA...... iv

SECTION 1 STATEMENT OF THE PROBLEM...... 1

HISTORICAL...... 3

DISCUSSION OP RESUITS...... 16 SUMMARY AND CONCLUSIONS ...... 31

EXPERIMENTAL...... 3& General Procedures and Techniques ...... 38 Preparation of 2-Thiophenecarboxaldehyde p-Tosylhydrazone .. 39 P reparation of the Sodium S alt of 2-Thiophenecarhoxaldehyde p-Tosylhydrazone ...... 39 Decomposition of the Sodium S.alt of 2-Thiqphenecarboxalde- hyde j-Tosylhydrazone in Cyclooctane ...... *t-0 Gas Phase Pyrolysis of Substituted Thienyldiazomethanes Prepared in Si t u ...... *t-l

Gas Phase Pyrolysis of 2-Thienyldiazomethane Generated in S i t u ...... Preparation of 2-Thiophenecarhoxaldehyde Azine ......

Synthesis of l,2-Di(2-thienyl)ethylene ...... UH

v Page

Preparation of 3-Thiophenecarboxaldehyde |>-Tosylhydrazone .. 46

Preparation and Decomposition of the Sodium Salt of 3-Thio phenecarboxaldehyde £-Tosylhydrazone in Cyclooctane 46

Gas Phase Pyrolysis of 3-Thienyldiazomethane Generated In S i t u ...... 4?

Preparation of 3-Thiophenecarboxaldehyde Azine ...... 48

Preparation of 5-Methyl-2-thiophenecarboxaldehyde £-Tosyl- h yd razon e ...... 48

Gas Phase Pyrolysis of 5-Methyl-2-Ihienyldiazomethane Generated in S itu ...... 49

Preparation of Methyl 2-Thienyl Ketone £-Tosylhydrazone .... 50

Gas Phase Pyrolysis of a-Methyl 2-Thienyldiazomethane Generated in S itu ...... 51

Preparation of Methyl 2-Thienyl Ketone A zine ...... 52

Preparation of 2-Thiophenecarhoxaldehyde Hydrazone ...... 53

Preparation of 2-Thienyldiazomethane ...... 53

Preparation of the Cyclic Trlmer of Prppenthial ...... 54

SECTION 2

STATEMENT OF THE PROBLEM...... 56

HISTORICAL...... 59

DISCUSSION OF RESUITS...... 84

EXPERIMENTAL...... 144

General Procedures and Techniques ...... 146 Preparation of Glyoxylic Acid p-Tosylhydrazone ...... 146

Preparation of Ethyl o'-Diazothiolacetate ...... 146

vi Page

Reactions of Ethyl o’-Diazothiolacetate Decomposition in Acidic Methanol ...... llj-8

Methanolysis at 65° ...... 1^8 Photolysis in Methanol ...... 1^9 Decomposition in Glacial Acetic A cid ...... 1^9 Decomposition in Trifluoroacetic Acid at 0 ° ...... 1?0

Decomposition in Silver Nitrate-Acetonitrile-Methanol ... 150

Decomposition in Morpholine ...... 151

Photolysis in 2-Propanol ...... 151 Photosensitization in 2-Propanol ...... 152

Photolysis in t-Butanol ...... 153 Photosensitization in t-Butanol ...... 153 Decomposition in Acidic 2-Propanethiol ...... 15^

Photolysis in 2-Propanethlol ...... 15^

Photosensitization in 2-Propanethlol ...... 155 Photosensitization in Cyclohexane ...... 155

Photosensitization in 1,1-Dimethoxyethylene ...... 156

Photosensitization in Methylenecyclohexane ...... 157 Preparation of Phenylglyoxylic Acid ^-Tosylhydrazone ...... 159 Preparation of Ethyl a-Diazophenylthiolacetate ...... 159

Thermolysis of Ethyl a-Dlazophenylthiolacetate in Hexane ... l6l

Oxidation of (CioHioSO)s ...... 162 Ammonolysis of (CioHioOS)^ ...... 162

Preparation of a-Thioethoxyphenylacetlc Acid ...... 165

vii Page

Preparation of Phenylthioethoxyketene ...... 165 Reactions of Ethyl ctf-Dlazophenylthiolacetate Decomposition in Silver Nitrate - Acetonltrlle and Cuprous Chloride - Acetonitrile ...... 166

Methanolysis at 6 5 0 ...... 168 Decomposition in Acidic Methanol ...... 168

Methanolysis at 25° ...... 169

De coup os it ion in Glacial Acetic A cid ...... 169 Decomposition in Acidic t-B utanol ...... 170

Decomposition in Morpholine ...... 171 Decomposition in Trifluoroacetic A cid ...... 172

Decomposition in Silver Oxide-Methanol ...... 175 Decomposition in Silver Nitrate-Acetonitrile-Methanol ... 175 Decomposition in Cuprous Chloride-Acetonitrile-Methanol . 17^

Photolysis in Methanol ...... 17*1- Photolysis in 2-Propanol ...... 175 Photolysis in 2-Propanol and Methylene Bromide ...... 175

Photosensitization in 2-Propanol ...... 176 Treatment of Ethyl a-Chloropheny 1thiolacetate with Silver Nitrate-Methanol ...... 177 Photosensitization of Ethyl d'-Dlazophenylthiolacetate in Cumene-2-Propanol ...... 178 Preparation of Ethyl jo-Nitrophenylthiolacetate ...... 179 Preparation of Ethyl a-Diazo-jD-nitrophenylthiolacetate 180

Preparation of Methyl £-Nitrophenylthiolacetate ...... 180

viii Page Preparation of Methyl a-Diazo-£-nitrophenylthiolacetate .... l8l Thermolysis of Ethyl a-Diaz o-£-nitrophenylthiolacetate in Hexane ...... 181 Thermolysis of Methyl a-Diazo-£-nItrophenylthiolacetate in H exane...... 182

Oxidation of (CioHgN03s)2 and (CbH7N03S)2 ...... l8 j Reactions of Ethyl o-Diazo-£-nitrophenylthiolacetate Decomposition in Methanol ...... 18U Decomposition in Acidic M ethanol...... 18^

Decomposition in Acetic A cid ...... 185 Decomposition in Trifluoroacetic Acid ...... 186 Photolysis in Methanol ...... 186

APPENDIX

Infrared Spectra ...... 187

ix SECTION 1' Statement of th e Problem

The present study involves investigation of the chemistry of 2- and 5-thenylidenes (l and 2) respectively, as derived by generation and de composition of 2- and 5-th.lenyldiazomethanes (Equations 1 and 2). The principle objectives of this research were to determine (a) if 2- and 3-

R ^\s/^CR'-Na R ^ g ' CR S II R-C-CH“ CH-CHC-R*

.CR' H'

,-cf — .O* — .O

thenylidenes ( l and 2), respectively, maintain their structural integre- ties aB carbenes, (b) if 2-thenylidenes (l) isomerize (Equation l) to 2 a~ and/or p-thiapyranylidenes and It), respectively, (c) if 2- thenylidenes (l) undergo ring opening to of,p-olefinlc-Y» 6-acetylenic thials and thiones (%), and derivatives thereof, and (d) if 5-thenylidenes (2) rearrange to Y- and/or p-thiapyranylidenes (6 and j), re

spectively. a,p and Y-ThiaPyranylidenes jt* and £) are of in" terest as possible 6it electron nucleophilic carhenes. HISTORICAL

One of the most fascinating properties of carbenes, -which are in conjugation vith carbon-carbon double bonds, is that they may reorganize to cycloprqpenes which revert to the initial carbene or rearrange to an isomeric conjugated carbene. Thus vinylcarbene 8 can cyclize reversibly to cyclopropane £ and then give isomeric carbene 10 (Equation 3)* Tor

a C = > = < (5) / C*— a C*—b

8 10 example, 2,3-dimethyl-2-buten-l-ylidene (ll) undergoes ring closure to 1 > 3j 3“trimethylcyclopropene (12); at higher temperatures 12 isomerizes *■>1.2 to 4-methyl-3-penten-2-ylidene (l^) and products thereof (Equation ^).

CH3 ^ ,CH3 © CH3> ch3 C=C Ha C = C CH3^ X C = N -N — Tos ch 3' "c*-H I 0 H 11 (k) CH; CH3 „H CH; c h 3 c - c h 3

H 12 k

(1) G. L. Closs and L. E. Closs, J. Amer. Chem. Soc.. 6 3 , 2015 ( 1961 ). (2) G. L. Closs, L. E. Closs, and W. A. Boll, J. Amer. Chem. Soc,,

85 , 3796 (1963 ).

The conversion of vinylcarbenes to cycloprqpenes is an important method for preparing the strained cycloolef insj the details of reac- b s tion mechanism have "been subjects of considerable study.

Aromatic and heterocyclic carbenes such as 14 are analogs of vinyl

carbenes (8 ). Investigation of the various isomerization reactions of have been recent subjects of intense study in these and in other laboratories. Thus 2-methylbenzylidene (l|) rearranges to benzocyclo-

butene (1$ ) and styrene (7%) when pure diazo( 2-methylphenyl)methane 3 is pyroilyzed &b I 5O0 (Equation 5)«

(3) G. G. Vander Stouw, Ph.D. D isse rta tio n , The Ohio S tate U niversity,

1964. 5

oh = n2 .CH 150° — v -N2 CHa 'CHa

(5)

CH2 0 +

The Intermediacy of fuaed cyclopropane 16 is proposed (Scheme l) to explain the formation of benzocyclobutene and styr.ene. Thus 16 might isomerize to a new fused cyclopropene 1£ or collapse to 2-methyl- cycloheptatrienylidene (l8). Conversion of rf to carhene lg, followed by hydrogen migration affords styrene. Reorganization of 18 to by intramolecular addition, and formation of 20 from 18 by carbon-hydrogen insertion, followed by collapse of strained cyclopropane 20, are alter nate routes to styrene. Benzocyclobutene is formed from carbon-hydrogen in se rtio n of 1£. The results of deuterium labeling at the o-carbon of 1£ support the proposed scheme. P yrolysis (350°) °f 'the sodium s a lt of o?-deuterlo-

2-methylbenzaldehyde j>-tosylhydrazone, generating a-deuterio-2-methylbenzylidene (21), affords 2-deuteriostyrene and 1-deuteriobenzocyclo- 4 , 5 butene in a 1:3 ratio (Equation 6). 6 Scheme 1

addition

in sertio n (4) A. R. Kraska, Ph.D. Dissertation, The Ohio State University, 1971. (5) 0. G. Vander Stouw, A. R. Kraska, and H. Shechter, J . Amer. Chem.

Soc., Jglf, 1655 (1972).

Other investigators have observed similar processes. Thus, thermo ly s is ( 250O) of the sodium salt of benzaldehyde j)-tosylhydrazone yields e heptafulvalene (22, and stilbene (g5, 15^) (Equation 7). Isolation

(6) R. C. Jolnes, A. B. Turner, and W. M. Jones, J. Amer. Chem. Soc., 21, 775^ (1969 ). of heptafulvalene (22) supports the proposed intermediacy of cycloheptatrienylidene. Gas phase pyrolyses of ortho-, para-, and meta- methylphenyldiazo- methanes (24) give mixtures of benzocyclohutene and styrene (Equation 8). For the para and meta diazo compounds, the ra tio of benzocyclohutene

HCN2 (a) CH3 24 to styrene is 0.8; from ortho-methylphenyldiazomethane the ratio is 7 2.8. Baron et al propose that intramolecular rearrangement of benzyli-

(j) W. J. Baron, M. Jones, Jr., and P. P. Gaspar, J . Amer. Chem. Soc.,

52, 4-739 (1970). dene to cycloheptatri&nylidene is reversible (Equation 9). para-ToIyl- carbene 2%. can undergo intramolecular rearrangement to fused cyclopropene 26 which rearranges to cycloheptatrienylidene 27 which then collapses to a new fused cyclopropene 28 and then yields meta-tolylcarbene 2g. The similar ratio of benzocyclohutene to styrene from meta- and para-tolylcarbenes supports the theory of their interconvertibility. meta-Tolylcarbene (2j?) may undergo a Bimilar series of ring expansions 9

ch3

26 SL

iCH (9)

ch3 CH3

and contractions leading to ortho-tolylcarbene, (2-methy lbenzylidene) whose chemistry has been previously described in yielding styrene and 3 - 9 benzocyclohutene.

(8) C. Wentrup and K. Wilczek, Helv. Chim. Acta., 1^59 (19T0). (9) J. A. ttyers, R. C. Joines, and ¥. M. Jones, J. Amer. Chem. Soc., . 22, WO (19T0).

Additional evidence for the proposed Beries of intramolecular rearrangements is provided by l3C labeling. £-[13C]Tolyldiazomethane

(3 0 ) is converted to [l*-13C]benzocyclobutene (^ l) and [U-13C]styrene (52) at TOO o in the gas phase (Equation 10). 1 0 At temperatures in 10

(10) E. Hedaya and M. E. Kent, J. Amer. Chem. Soc., 3283 (l9Tl).

CH=CH2 O 13

5 ° 51 3S excess of 600°, henzylidene undergoes a competitive process of ring contraction leading to fulvenallene (%%) and ethynylcyclopentadiene n (Equation ll). Heptafulvalene (22) and stilbene are also obtained. The

(ll) P. Schissel, M. E. Kent, D. J, McAdoo, and E. Hedaya, J. Amer. Chem, Soc., %2, 21b7 (19T0).

• CH H C=CH o r > 600° &

ch2 II (1 1 ) C=CH 0 & 11 proposed scheme involves reorganization of benzylidene via d ira d ic a l

^ to 5-ethynylcyclopentadiene (%6) which then isomerizes to and (Equation ll). As teniperatures approach 1000° products and pre dominate over heptafulvalene and stilhene. At the elevated temperatures i i ring contraction of benzylidene is thus favored over ring expansion.

2-Pyridylcarbene (j£ 8 ) generated at 500° in the gas phase from vic-trlazolo[l. gajpyridine (%[) yields aniline {Wf), azobenzene ( 77#)» is and 1-cyanocyclopentadiene (^2., minor) (Equation 12).

(12) W. D. Crow and C. Wentrup, Tetrahedron Lett ., 6lk9 (1968).

These products are also obtained in similar yields when phenyl aZide

(i+0) is pyrolyzed in the gas phase between 550 and 700° (Equation

13). 1 3 It has been proposed that 2-pyridylcarbene ( 5 8 ) and phenyl (13) W. D. Crow and C. Wentrup, Tetrahedron L ett.> 1*379 ( 1967 ).

e xn 3 * * a . — c x j o

1*0 1*1 (1 5 ) CM O l * 6

nitren e (1*1 ) interconvert via a mechanism similar to that for tenzyli- dene inter conversions (Equation ll*). 2-Pyridylcarbene ( 3 8 ) can thus 1 5 form a fused cyclopropene 42 which expands to 2-azaheptatrienylidene

(42.)j 42 contracts to azirine 44 which then collapses to phenyl ni-

trene (4l). Aniline is presumed to he formed by phenyl nltrene ab- stracting hydrogen; azobenzene is possibly formed by dimerization of 12, 13 phenyl nitrene. 1-Cyanocyclopentadiene {pj)) purportedly arises

from collapse of azirine .44, (Equation 15).

C5IJ (1 5 )

In this laboratory, a desire to establish further the generality of isomerization of conjugated carbenes was expressed in the study of 14 2-furylldenes (4£). The chemistry of 4j5, as generated by pyrolysis

(l4) R. V. Hoffman and H. Shechter, J. Amer. Chem. Soc., <£5, 5940

(19T1). ..

(25O0) of the sodium salt of the corresponding £-tosylhydrazone, differs from that anticipated. Intramolecular rearrangement via ring opening occurs to give a,p-olefinlc, y,6-acetylenic ketones and aldehydes (46) (Equation l6). Variously substituted (2-furyl)-l-dlazoalkanes (4%) were studied. The results are summarized (Table l). l4

Table 1. Vapor Phase Pyrolysis of (2-Furyl)-l-aiazoalkanes (4£).

47 a , R = Hj R1 t= H W b, R = GH3; R' = H SET, R = H; R' = C q H s Vrq» R = Hj R1 = CH3 Me, R = H] R' = CH2CH3 47

iDiazo 0 ^ H H Compound Yield (?) C-C=C-C^CR* + others R^

47a 66 c is , 81? tra n s , 19 ?

47b 43 c is , 87? tra n s , 13?

4jc 43 cis, 52. 5? trans, 47.5?

4jd 36 c is , 73? tra n s , 27? •O' (3.6?)

4£e 47 cis, 68? CX. trans, 32? —CH3

(3.2?) 15

H H 250° ^ - 1 1 C —C=*C“C2C-R' ✓ (1 6 ) 0.5 mm R

46 i£

No evidence for the intermediacy of a-pyranylidenes (48) formed hy V4 ring expansion of a fused cyclopropene vas found (Equation IT). 1

e — . , £ r <»>

Carhenes such as 48 are predicted to he highly stabilized, 6jt electron nucleophllic carhenes (Equation 18).

(15) R. Gleiter and R. Hoffman, J. Amer, Chem. Soc., %0, 5457 (19^8).

48 48 DISCUSSION 03? EESUI/TS

The present Investigation involves study of the properties of 2-

and 5-thenylidenes (l and 2) as generated by thermolysis of their pre

cursor diazo compounds. The p rin c ip a l In te re s t in 2-thenylldenes (I;

Plow Sheet l) was to determine if they undergo ring opening to <*,£-

olefinic-\> 6-acetylenic thials and thiones {£) or isomerize to ot-

thiapyranylidenes (£) and/or 0-thiapyranylidenes (4). 3-Thenylidenes

(2, Plow Sheet 2) were studied as possible sources of Y-thiapyranyll-

denes (6) and/or p-thiapyranylldenes (£). As has been reviewed, the

possible isomerization reactions of 2- and 3-thenylidenes (l and 2)

and the reaction mechanisms thereof are analogous to those- found pre

viously for phenyl carbenes, pyridyl carbenes, and phenyl nitrenes, 1 Pyrolysis of 2-thienyldiazomethane (4£, Equation 19) as generated

in situ by decomposition of. the sodium salt of 2-thiophenecarboxalde-

hyde j>-tosylhydrazone at 300° (0.1 mm) yields a polymer of 2-penten-

4 -y n e -l-th ia l (jjO, 19%) f trans -1,2-di (2-thienyl) ethylene (51, $2%),

cis-l,2-di(2-thienyl)ethylene (jj2, 21 %), and 2-thlophenecarboxaldehyde

azine 5%), respectively, in an overall material balance from 4^,

of 39 percent. Many pyrolyses of this type were conducted at tempera tures from 250-400° and at different exposure times* the results ob tained, however, are similar to those described (Equation 19).

16 Plow Sheet 1

R* 1

R 1

R s ^ R

R' 0 h % Flow Sheet 2

e 1 9

j§l , tranB

55.

2-Fenten-*(-yne-l-thial (j§4) could nob be obtained as a monomer ■because of Its instability. The thial (^4) could however be Isolated as a liquid polymer (j?0) by column chromatography. Elemental analysis supports the elemental formula (C^H 4S)n for £0. The nmr absorption of jjO reveals a one acetylenic proton doublet at 5*21 ppm (J = 2 cps) 16 allylically coupled with an ethylenic xj**oton, a two ethylenic proton

(l6) R. M. Silverstein and G. C. Bassler, “Spectrometric Identifica

tio n of Organic Compounds,” Chapter k, John Wiley and Sons, New York, 1968.

—CHjj- C=C“ Ha J al3 = 2-3 cps 20 muitlplet at 6.60 ppm, and a one proton doublet (j = lOcps) at 5.37 -S 16,17 ppm ass Ignat le to .CH- C= . The l r spectrum of 50 shows the -S “ - ..

(17) C. A. Reece, J . 0. Rodin, R. G. Brownlee, W. G. Duncan, and R. M. Silverstein, Tetrahedron, 2j^, 42^9 (1968). The nmr ab sorption of i in the region of interest is:

, H_ ^.70 ppm (doublet), ft

J ab = 10cPB

following absorptions for the indicated functional groups: 531° (sharp, 18 eC-H stretch), 208? (-C=G- stretch), and 1605 cm" (-C=C- stre tc h ).

( l 8 ) K. Nalcanlshl, “Infrared Absorption Spectroscopy,w p. 2k, Holden-

Day, San Francisco, 1962 .

The' principal ions displayed by mass spectral analysis of JO are: m/e

(ion) (rel. int.): 256 (CigHiaSa*) (ll), 22^ (Ci5HieS+) (12), 192

(CioHsS/*) (95), 160 (C10HbS+) (kk), 128 (CioHa+) ( 28 ), 97 (C 5H5S+)

(100), 96 (CsH4S+*) (18), 63 (CsH3+) (15). The nmr, i r , and mass spectral properties of JO thus suggest that the thial polymer has the following structure: Product jjO must be stored at -78° to maintain its homogeneity. At room temperature, the yellow liquid turns brown and tarry within one hour. Column chromatography of the pyrolysate is accompanied with darkening which is attributed to alteration of jjO, Chromatography must be completed as quickly as possible in order to isolate the pro duct (^_0). Lengthy chromatographic elutions did not result in sep- 1 9 aration of jjO.

(19) Vapor phase pyrolysis of 2-thienyldiazomethane (prepared by the method of T. Holton, Ph.D. Dissertation, The Ohio State Univer

sity, 1971) by its evaporation through a hot tube at tempera-

tures between 250 and ^25° does not give an Increased yield of

ring opened product In fact, no pyrolysate was ever col

lected in the cold trap (- 78 °). During decomposition a black

polymeric coating buildsj up on the walls of the hot tube. Many pyrolyses were attempted covering a fu ll range of possible con ditions, from the use of glass beads with and without a nitrogen bleed to no glass beads with and without a nitrogen bleed.

The possibility that polymer j?0 is formed by alteration of mono mer 2-penten-4-yne-l-thial (jjj*) during chromatography is unlikely. The 22 nmr spectra of the crude pyrolysate and the chromatographed product j>0 show the same characteristic absorptions at 3,21 ppm and 5*37 ppm previously described (absorptions near 6.60 ppm are submerged by th a t of other components in the pyrolysate), 20 Thials have never been observed as monomers. Thiones can be

(20) M, J. Janssen, "Organosulfur Chemistry,” Chapter 13, Inter science, New York, 19&J.

isolated as monomers, however, they are also unstable and eventually a i polymerize. (Thiones and thials are unstable monomers because ..sul-

(21) R. Mayer, J. Morgenstern, and J. Fabian, Angew. Chem., Intern. Ed. E ngl., 3, 277 (19610.

2a fur does not readily form Prt“Prt bonds with carbon. Overlap of the

(22) The bond energy of C=S is 103 kcal/m ole as compared to 152 kcal/m ole fo r C=0i E. Campaigne, Chem. Rev., 39, 1 (19^6).

2p orbital of carbon with the 3P orbital of sulfur is difficult. Thio- carbonyl groups thus convert readily to carbon-sulfur single bonds by enthiolation, dimerization, trimerization, or polymerization (Equation 20 20 ). 23

(20 )

^ “C-SH

The difficulty in establishing the structure of the product ,§0 de rived from 2-penten-4-yne-l-thial (j>4) as a cyclic dimer or trimer, or

a chain polymer is not surprising in light of the previous chemistry

of thials. Mass spectrometry could not he used to determine the mole

cular weight of j>0 because a parent ion of a multiple of C 5K4S was not seenj an ion of mass CisHigSa was detected however.

There is little mass spectral information on thiocarbonyl dimers and trimers. The .cyclic trimer of cyclohexanethione shows a weak

parent peak at m/e 342 (CiqHsoSs^ ), with other ions at 228 (Ci2BaoS 2+* ), 23 146 (C6H io S2+), Il4 (C6H iq S+*), and 81 (CQHg+, 100?»), respectively.

. (23) C. D jerassl and B. Tursch, J . Org. Chem., 27* 104l ( 1962 ).

24 The trimer of propanethial, as presently studied, displays the follow-

(24) I . B. Douglass and F. T. M artin, J . Org. Chem., 1£, 795 (1950)* 2k lng mass spectral fragmentation pattern: m/e 222 .(CaHieS3+*) ( 26$),

190 (c9HiBs2+) ( i.o ) , 1^8 (c6Hi2sa+‘ ) ( n ) , 116 (c6Hi2s+) (9 . 5), H 5

(CbHhS+‘) (9.6), 106 (c6HiaS+), (C 3H6S+*) (100$), and k l (C^Hs+)>

(1*2), respectively. The cyclic trimers of cyclohexanethione ana pro panethial thuB show significant parent peaks along with dimer and monomer ions. The product j>0 Isolated from 2-penten-4-yne-l-thial (j&) might not he a trimer since there is no mass spectral evidence for such a species. The detailed structure of jjO is thus not known.

Attempts to prove the structure of £0 hy chemical methods failed. Treatment of polymer jjO with 2,l*-dinitrcphenylhydrazine reagent did 22 not yield a derivative. Previous studies have shown that polymers of thioneB and thials do not react with carbonyl reagents unleBS dis sociated in some manner to the monomer thiones and thials, in which case carbonyl derivatives are readily formed. The trimer of prcpane- thial does not give a hydrazone upon treatment with 2,4-dlnitrophenyl- hydrazine reagent. Deblocking of the polymer of 2-penten-l*-yne-l- 1 7 thial hy silver nitrate-ethanol or mercuric chloride-mercuric 2 5 oxide-methanol and hydrolysis to give 2-penten-^-yne-l-al was un successful.

(25) D. Seehach and D. Steinmuller, Angew. Chem., 80, 617 (1968 ).

cis- and trans-1,2-Di(2-thienyl)ethylenes (%2 and J51, respec tively) were Isolated and separated from the pyrolysate of vapor phase decomposition of 2-thlenyldiazomethane (jjg.). Independent synthesis of jjl and ^2 substantiated the structure assignments. The stereochemis tries of jjl and %2 “were assigned on the haBiB of th e ir nmr and i r ab sorption spectra, trans- 1, 2-Di (g-thienyl)ethylene (£l) exhibits a „H ia strong absorption a t 9^5 cm -1 characteristic of ^C=C' . The nmr H" H spectra of J§1 and j>2 exhibit a singlet at 6.98 ppm (H-VC=C^_) fo r the * — trans isomer and a singlet at 6 . 5^ ppm (-C=C-) for the cis Isomer j52. H H

(26) The nmr of trans- and cis-stilbenes in the regions of interest

are: CaH5^ H C = C , 7.10 ppm (singl) and CQH 5 ^CeH5 H CeHs > = C. , H H 6.55 PP® (singl)j “Varlan NMR Spectra Catalog,” spectra 3°5 and

306, National Press ( 1962 ).

2-Thiophenecarboxaldehyde azine (%%) was isolated from the pyroly sate of the vapor phase decomposition of 2-thienyldiazomethane. Inde pendent synthesis of the azlne substantiated its structure. The carbenic integrity of 2-thenylidene is supported by its inser tion into cyclooctane ( 1^5°) affording 2 -thenylcyclooctane ( 23$ y ield )

(see Experimental). Thermal decomposition of 5-methyl-2-thienylidazomethane (j3£) was studied with the objectives that Its ring-opened products would be more stable and thus their structures more readily assigned than that from

J+2,. Pyrolysis of 5-methyl-2-thienyldiazomethane (_§£, Equation 2l), generated in situ by decomposition of the sodium salt of 5-methyl- 2- thlcphenecarboxaldehyde £-tosylhydrazone at 300° (0 .1 mm), yields a 26 polymer of 3-hexen-l-yne- 5-th ion e 19 $)j tran s- 1, 2-di(5-methyl"

2-thienyl)ethylene (J5£, 2 ^$), and cls-1, 2-dl(g-methyl- 2-th le n y l)-

ethylene 22$) in an overall material balance from jjjj of 3^$.

S II j r \ t [ch3-c-ch=ch-c=c-h] n S'

( 21 )

CH3 CH=CH ch3

£L> ’fcrQ'ns

c lB 20-22 3-Hexen-l-yne-5-thione (jg?) could not he obtained as a monomer;

its transformation products j36 were never isolable from the pyrolysate.

Numerous attempts were made to. isolate 56. Column chromatography was

accompanied with tremendous darkening on the adsorbent. The presence of Jj6

in the crude pyrolysate is ascertained by nmr and ir absorption similar

to that for ^0. The nmr spectrum of the pyrolysate reveals an acety- *

lenic proton doublet at 3.20 ppm ( j = 2cps) allylically coupled with 1 6 an ethylenic proton, and a broad singlet at 1. 8 U ppm assignable to I 1 6 , 1 7 (-C-S-). The ir spectrum of the crude pyrolysate reveals sharp

absorption at 3515 cm -1 (=C-H stretch) and 1600 cm"1 (-C=C- str e tc h ).

cis- and trans-1,2-Dl(5~methyl-2-thienyl)ethylenes (j >8 and J57, respectively) were Isolated and separated from the pyrolysate by chroma tographic methods. Upon standing in light the cis Isomer jj 8 converts 2 7 to the trans Isomer The geometry of the isomers is assigned on the hasis of ir and nmr spectral data, trans-1.2-Di{ 5-methyl-2- , . , , ,N' /H\ 18 thienyl)ethylene (57) displays Btrong absorption at 940 cm"1 '* H The nmr spectrum of trans 57 exhibits a singlet at 6.73 ppm (“^0=0. ); /N A 26 H cis 58 reveals a nmr singlet at 6.37 ppm (

Equation 22), generated in situ b.v decomposition of the sodium salt of methyl 2-thienyl ketone £-tosylhydrazone at 500° (°* 1 mm), affords a polymer of 2-hexen-4-yne-l-thial ( 61, 16$), 2-vinylthiophene ( 62,

16$), trans-2,3-di(2-thienyl)-2-butene ( 65, 12/6), c is -2 ,3 -d i(2 -th ien y l)- 2-butene (6k, h$$)j and methyl 2-thienyl ketone azine (6jjj, 7$) in an overall material balance from 60 of h9%.

O " 0 - C H 3 ------* CH-C-CH=CH-C=C-CH3]n + ( 1 ^ 'S ' M 6 l 60 62

(22) * Q ^ Q B | | S S I ch 3 ch 3 ch 3 ch 3

S b 65 6h, cis 2-Hexen-U-yne-l-thial (66) could not be isolated as a monomer be- 20-32 cause of its instability; its subsequent product 61 was never isolable from the pyrolysate. Column chromatography of the pyrolysate re sulted in major decomposition of the product'6l on the adsorbent during the 28

numerous attem pts to iso la te 6l and its subsequent derivatives. The presence of 6l in the crude pyrolysate was indicated "by nmr absorption

at 1.95 PPM assignable to -C=C-CH 3. Other characteristic peaks for

6l were submerged under other regions of absorption.

2-Vinylthiophene { 62) was separated by gas chromatography and its retention time was identical with that of an authentic sample, cis-

and tra n s -2, 3-Di(2-th ie n y l)- 2-butenes (64 and 63, respectively) were isolated by column chromatography and then separated by gas chromato graphy. The stereochemistry of the cis and trans isomers were assigned

on the basis of nmr and gas chromatographic analyses. £is- 2, 3-Di(2- th ie n y l)- 2-butene (64) exhibits a nmr singlet at 2.20 ppm (-C CH3 ch3 whereas trans-2 , 3-d i(2-th ie n y l)- 2-butene (63,) reveals a singlet at 2.05 \ 27 ppm ( C=CN ). Methyl 2-thienyl ketone azine ( 63) was isolated CH3

(27) The nmr of cis- and trans-2,3-diphenyl-2-butenes in the regions of

interest are CsH5 XC6H5 ^0 = 0. , 2.12 ppm (singl) and CqHs CH 3 ch3 ch3 CH3 CsHs 1.88 ppm (singl). c is- 2,5-Diphenyl-2-butene, purportedly, has

less steric hindrance toward coplanarily than does trans- 2, 3-d i- phenyl- 2-butene j N. Iramota, S. Masuda, Y. Nagai, and 0. Siraa-

mura, J . Chem. S oc., 1433 (19&3)* and identified after independent synthesis, from its melting point and i t s nmr. 2 9 Gas phase thermolysis of 3-thienyldiazomethane (6j , Equation 23), generated in situ from the sodium salt of 3”thiqphenecarboxaldehyde £- tosylhydrazone at 300° (0 .1 mm), yields cis-l, 2-d i( 3-thienyl)ethylene

(68 , 26?5), tr a n s - l,2-d i(3-thienyl)ethylene ( 6^, 61$), and 3-thiophenecarboxaldehyde azine (^ 0 , 9%) in an overall material balance from of 2 7 No products were ever isolated containing the y- or p-thia- 28 pyran moiety.

,___ ^ C“H . CH=CH . 0 — 0 0

67. 68 , cis 63, trans (23) , CM-N=CH

0 0S'

(28 ) The carbenic integrity of 3-thenylidene is supported by its in sertion into cyclooctane (1^5°) giving 3-thenylcyclooctane (6C$ yield). Thermolysis of 3“thienyldiazomethane, generated in situ

by decomposition of the sodium salt of 3-thiophenecarboxaldehyde

jj-tosylhydrazone, in dibenzyl ether ( 260°) and trlbenzylamine

(26O0) resu lted in ta rry , non-homogeneous products. When the

residues were treated with 2,lf-dinitrophenyIhydrazine reagent

[in search for the Y-thiapyranylidene moiety present as a product 50

of solvent insertion (Equation l)], no hydrazone derivative waB

formed.

2,4-DNPH ft SCX 2,4DNP1WP v (i) 0

Y-Thiapyran and Y-pyran, when treated with 2 ,4-dinitrophenyl- hydrazine reagent, hoth give the 2,4-ainitrophenylhydrazone of

glutaraldehyde [j. Stratlng, J. H. Keljer, E. Molenaar, and L.

Brandsma, Angew. Chem., In tern . Ed. E ngl., 1, 599 ( 1962 )].

Column chromatography allowed separation of cis and trans ethylenes

68 and 6£. The stereochemistry of the cis and trans isomers was assigned on the basis of ir and nmr spectral properties. trans-l,2-Dl(5-thienyl)-

ethylene ( 6%) exhibits a Btrong ir peak at 960 cm"1 assignable to v . 1 8 C — C . The nmr spectra of cis 68 reveals a singlet at 6.45 ppm h ; / s j a® J C —C )t tran s 69 exhibits a singlet at 7.00 ppm ( .C-C' ). 5 - H' S H Thlqphenecarboxaldehyde azine was Isolated from the pyrolysate by column chromatography. Its structure was assigned by comparing its

physical properties with those of an authentic sample. SUMMARY AND CONCLUSIONS'

The results of the present study of decomposition of 60, and 6£ are summarized in Table 2. There is as yet no evidence for transformation of the thenylidenes to the 6jr electron nucleophilic car benes k, 6, and X* ^ is now evident that 2-thenylidenes (l) under go ring opening to a lesser extent than do 2-furylldenes (4£). It has been previously fovind that 2-furylidenes (k%) undergo ring reorganiza tion to ar,fl-olefinic-Y, 6-acetylenic ketones and aldehydes (46) with 14 ease (Equation 24). 1,2-Di(2-furyl)ethylenes (71) were not observed Table Table 2 (Continued)

S (H-C-OM-CSC-CH3)n + + (3c=cO CH3 CH3

61 (16*) 62 (l6?>) c is , J& (4996) trans, 0+ (12^)

+ O-—XSX I I -O XSX 03^3 0 0 3

§5. (7*)

C M -H = C H TsalJ 0 0*0 0 c i s , 68 (2&f>) j o (<#) tra n s, 69 . (64#) as products. In the decomposition of 2-thienyldiazoalkanes, however, the major products are those of formal dimerization of 2-thenylidenes

to the appropriately substituted l,2-di(2-thienyl)ethylenes. Ring open ing to o?,p-olefinic-y,fi-acetylenic thiones and thials is a minor process. The greater ease of isomerization of 2-furylidenes as compared to 2-thenylidenes is explainable in part on the baBis that the resonance energy of the thiophene ring is greater (~ 13 kcal/mole) than that for the furan ring. 2-Furylidene is a higher energy carbene than iB 2-

(29 ) G. W. Wheland, "Resonance in Organic Chemistry,” p. 99, John Wiley

and Sons, New York, 1955. thenylldene on the basis of the aromatic character of the ring systems.

Reorganization of 2-thenylidenes to a,p-olefinic-Y, 6-acetylenic thiones

and th ia ls would require I o s b of an extra 13 kcal/mole of resonance energy as compared to 2-furylidenes. A further fact for interpretation

iB that the transition states for ring opening will have some of the

stru c tu ra l character of the products. Thus J2 and £5. resemble the transition states for ring destruction of and b respectively. The

H H 35 representations of the transition stateB show partial formation of a 22 Prt-Prt bond between carbon and oxygen (153 kcal/m ole) in j[ 2 , and be- 22 tween carbon and sulfur (103 kcal/mole) in £5. Bond breaking of a 30 carbon-oxygen bond 78 kcal/mole) in 72, and of a carbon-sulfur bond

(3 0 ) J. Hine, Physical Organic Chemistry,” p. Jk, McGraw-Hill, New

York, 1936 .

30 57 kcal/mole) In j£3 is also involved. On the basis of all of the above thermodynamic considerations, ring reorganization of is much more favorable than is that for 1 . The mechanisms of formation of the l,2-di(thienyl)ethylenes from their parent diazo compounds are not known. Perhaps the simplest route for formation of the ethylenes involves reaction of a thenylidene with 31 a thienyldiazomethane as indicated in Equation 25. An alternate

(25) 36

(51) An extension of a prior proposal by R. Hulgsen, Angew. Chem.,

67, ^39 (1955). possibility is addition of the diazo compound to the azine and collapse as Indicated in Equation 26. The third possibility is pairing of

Ar-CH=N-N=CH-Ar 0 ArCH - N= N - CH — Ar

6© 60 A r-C H -N ^ ArCH (26)

-*• ArCH^CHAr

+ ArCH~ N2

thenylidenes which maintain their integrity as carbenes long enough to collide and dimerize (Equation 27). ■ (X — • 0 — 0 ->

Possible mechanisms for formation of thlophenecarboxaldehyde azines

. 32 are summarized in Equations 26, 29, and 30.

(32) W. Kirmse, "Carbene Chemistry,” Academic P ress, New York, 1971. 37

(28 )

:c= n - n = c

+ N2

S © .C-N-N N==N \ /O * X / © t ■> c L c v © f © / \* ^ \ / X U N=N-CC" N —IT

(29) ^ C = N -W = C ^

+ N2

\ / N <@ -> ^C“N-N=C^ (30) EXPERIMENTAL

General Procedures and Techniques

Melting p o in ts. Melting points were determined with a Thomas Hoover Capillary Melting Point Apparatus. All melting points are uncor rected.

Boiling points. Boiling polntB were obtained at atmospheric pressure unlesB otherwise noted. Thermometer corrections were not made.

Elemental analyses. Elemental analyses were performed by Chemalytics, Inc., Tempe, Arizona, and by Micro-Analyses Inc., Wilmington, Delaware

Infrared spectra. Infrared spectra were obtained on a Perkin Elmer Infracord Spectrophotometer. The spectra of solid compounds were ob tained from potassium bromide wafers, and the spectra of liquid com pounds were obtained from liquid films.

Nuclear magnetic resonance spectra. Nuclear magnetic resonance spec tra were obtained on a Varian A-60 Analytical NMR Spectrophotometer.

38 EXPERIMENTAL

Preparation of 2-Thiophenecarboxaldehyde p-Tosylhydrazone <~i —i n j— j—i ■—i j—i a—i <—11— i— i— — r~m~ i-~ «— r~ — — — ^ ------— — —■ 2-Thiophenecarboxaldebyde (l8.7 Br 0.17 mole) Aldrich Chem. Co.) was added drqpwise with stirring to £-tosylhydrazide [jl.l g, 0.17 mole) prepared hy th e method described in Org. Syn., 40, 93 (i960)] dissolved in a minimum of absolute methanol. Heat was evolved, and a white solid precipitated shortly after addition. The reaction con tents were stirred 2 hours, after which the mixture was concentrated

in vacuo, and the white solid was collected. The 2-thiophenecarboxaldehyde £-tosylhydrazone weighed 25 g (60$ yield) after recrystalliza tion as white prisms from benzene-hexane, mp 1^2-145.5°• Other proper ties of the tosylhydrazone are: ir, vmax (cm’1): 3190 , 1600, I3U0,

II 65.

Anal. Calcd fo r C12H12N2S2O2 : N, 10.00.

Pound: N, 10. 15.

Preparation of the Sodium Salt £-^°syl~ hydrazone A 57# mineral o il dispersion of sodium hydride (0.30 g, 0.0072 mole) was added quickly to a stirred solution of 2-thiophenecarboxalde hyde ^-tosylhydrazone ( 2,00 g, 0.0072 mole) in methylene chloride (50 ml) in a 125 ml Erlenmeyer flask. A drying tube was connected to the

39 4° flask and the reaction mixture was stirred at room temperature for 2 hours. The white precipitate of the sodium salt of 2-thiophenecarboxaldehyde £-tosylhydrazone, which separated immediately, was filtered under nitrogen and washed several times with dry diethyl ether. The filter cake, after transfer to a crystallizing dish and drying in a vacuum desiccator for 3 hours, gave the sodium salt ( 2.05 g, 92 ? yield) as a white solid.

Decomposit ion of the Sodium Salt of 2-Thiophene carboxaldehyde p-Tosyl- hydrazone in Cyclooctane Cyclooctane (50 ml), which had heen dried over sodium and distilled under nitrogen at l49-150o/T60 mm, -was refluxed lh a 250 ml 3~necked round bottom flask, equipped with a Friederich condenser, a mechanical stirrer, and an addition funnel for solids. The sodium salt of 2-thiophenecarboxaldehyde £-tosylhydrazone ( 2.20 g) was added cautiously from the addition funnel to the refluxing cyclooctane. Decomposition was instantaneous with violent gas evolution. The tan reaction mixture was cooled and the sodium p-toluenesulfinate filtered. The tan fil trate was stripped on a rotary evaporator to a brown liquid ( 1.05 g) which was gas chromatographically analyzed on a 20? SE30 chromasorb P column ( 6 1 x 4")* With the column temperature at 222° and the flow ra te a t 50 ml/minute, a water white compound, 2-thenylcyclooctane, with a retention time of 6 .9 minutes, was preparatively collected ( 23? overall yield). Other properties are: ir, (cm-1): 29 50, 695

(broad)j nmr (CDCI 3 ): 1.55 & (broad sin g le t, 15H), 2.6T 6 (doublet,

2H), 6.82 6 (mult, 3H). Ul

Anal. Calcd for C13H20S: C, 7 ^ .9 ^ H, 9.68. Found: C, 75.21j H, 9.6^.

Gas Phase Pyrolysis of Substituted Thienyldlazomethanes Prepared In S itu

The apparatus used for pyrolyses of all of the ^-tosylhydrazone salts of the present study Is described below:

glass wool plug

s a lt s a lt bath -78'

An external s a lt bath waB used to decompose the tosylhydrazone s a lts } dry Ice-Isopropanol served as the trap coolant. Many experi ments were run to find advantageous conditions for decomposition. Tem peratures from 250° to as high as IfOO0 were employed. Between 350° and

400° pyrolysis was very messy, giving poor yields and undesirable pro

ducts arising from decomposition of sodium |>-toluenesulf inate. Best results and yields were obtained when the tosylhydrazone salt was im mersed in a salt bath between 300 and 325°. k2

A typical experiment is as follows: The sodium salt of a tosyl hydrazone (2. IT g, dried under vacuum) was placed in the s till pot of the above described apparatus. With the apparatus at a vacuum of 0.1 mm and the bath trap at -78°, a salt bath at JOO 0 was jacked up to the s till pot. Decomposition within the completely immersed flask occurred within 5 seconds, and a red liquid was distilled into the cold trap. The heat source was removed, nitrogen was admitted into the system, and the apparatus was disassembled. The trap was warmed to room temperature and its contents were washed with anhydrous ether.

Upon removal of the ether in vacuo, a crude pyrolysate, usually red- brown in color, was obtained. Material balances based on the diazo compound ranged from 2J% to 50%. Vapor phase and column chromatogra phy were used far product separation.

Gas Phase Pyrolysis of 2-Thienyldiazomethane Generated In Situ

Material balances based on 2-thienyldiazomethane averaged 59% • Column chromatography of the crude pyrolysate on silica gel: petroleum ether (200:1; absorbent:sample) separated trans -(52 mole % of products based on the NMR of the crude pyrolysate) and cis-(21 mole % of pro ducts ) - l , 2-d i (2-thienyl) ethylenes.

c ls - 1, 2-Di(2-thienyl)ethylene, an oil, has the following proper tie s : ir , vjjjgx (cm"1): 853 , 839 , 695 (broad); nmr (CDC13): 7.03 6

(mult, 3H) and 6.5^ 6 (singl, 1H); mass spectrum, m/e (rel. int.): 192 (100) P*. trans-1,2-Di(2-thienyl)ethylene, mp 129-131°> has the following pro p erties: i r vm x (cm"1): 1370, 9^5> 850 , 82^, 695 (broad); nmr (CCl^): 7*20 8 (mult) and 6 .98 6 (singl), overlapping absorption.

Further elution separated a yellow liquid ( 8 $ by weight, based ■ \ . on the crude pyrolysate). Preliminary nmr analysis of the crude product showed this compound to be present in 19 mole % yield. The column darkened as elution continued. The color change may be a ttri buted to alteration of this component; it was necessary to store this material at -78° to maintain its homogeneity. The properties of this material are; ir, y^y (cm"1): 5310 (sharp), 208?, 1605, I 35O, 978 ; nmr. (CCI4 ): ca. 6 . 60 6 (mult, 2H), 5.37 6 (doublet, J = 10 cps, m),

5.21 6 (doublet, J = 2 cps, 1H)j mass spectrum, 15O0 source and inlet, m/e (rel. int.): 256 ( l l ) , 22^ (12), 223 (10), 192 (9 5 ), 160 (M ),

128 (12), 97 (100), 96 (18 ), 63 (15).

Anal. Calcd for (CsH4S)x: C, 62.^5; H, lf.19. Found: C, 62.31; H, ^.32. Evidence will be presented which Indicates that this material is a polymer of 2-penten-4-yne-l-thial. Continued elution resulted in separation of a yellow solid, 2- thiophenecarboxaldehyde azine (5 mole # of products), mp 158-159° ( l i t . mp 157. 5- 158 . 50); mixed mp with an authentic sample, 157-159°* Addi tional properties of the azine are: ir, Vmny (cm"1): 1600, 1^10,

1070, 760, 715, 698 ; nmr (DMS0-d6): 8.89 6 (Bingl, m), 7*72 5 (mult,

2H), T .21 6 (m ult, m ).

Preparation of 2-ThiophenecEyboxaldehyde Azine Anhydrous hydrazine (0.61+ g, 0.01 mole) was added to 2-thicphene- i carboxaldehyde (2.2U g, 0.02 mole) in ethanol (50 ml). The mixture 44 was s tirre d a t room tem perature overnight. Removal of solvent yielded yellow needles of 2-thiophenecarboxaldehyde azine, mp from nethanol, 33 ** 158-159° (lit. mp 157.5-158.5°).

(53) R. Gaertner, J . Amer. Chem. Soc., J 3934 (1951 ).

Synthesis of 1,2- Di( 2-thienyl )ethylene

( 3J4) R. E. M iller and F. F. Nord, J . Or^. Chem., 16, 1720 (1951).

Pr eparation^ of 2-Thienyla.cetic Acid

A mixture of 9°% 2-thienylacetonitrile (20.0 g, 0.146 mole; Al drich Chem. Co.) and 20% aqueous sodium hydroxide solution (11.7 g of

NaOH in 47 ml of H2O) was refluxed overnight. The reaction mixture was "brought to pH 6 with 20% sulfuric acid. The precipitate of crude 34 _ 2-thienylacetic acid was collected; mp 72-74 (lit. mp 75-76 , 5.4

g, 28% overall yield). Purification of the acid was not attempted.

34 Condensation of 2-Thienylacetic Acid with 2-Thiophenecarboxaldehyde

A mixture of crude 2-thienylacetic acid (5-4 gj O.O38 mole), 2-

thiophenecarboxaldehyde (4.2 g, O.O 38 mole), acetic anhydride (12 g),

and lead oxide ( 5.63 g, 0.025 mole) was refluxed for 5 hours, cooled,

and treated with absolute ethanol (5 ml). The tan p re c ip ita te which formed was recrystallized from benzene. Tan prisms of 2,3-di(2-thienyl)acrylic acid (1.03 g, 14$ yield, mp 236- 258 °) were recovered. The

material has. the following properties: ir, (cm"1): 3100-2500

(broad), I 67O, 1600, 1270, 695 (broad); mass spectrum, m/e: 238 P* \ fo r CixHaSOa.

35 Decarboxylation of 2,3-di(2-thlenyl)acrylic acid

(35) L* Fieser, "Organic Experiments,” p. 228, Raytheon Education

Co., Lexington, Mass., 1968 .

A mixture of 2,3-di(2-thienyl)acrylic acid (l g), copper bronze

(0 ,1 g), and quinoline (2 ml) was refluxed 15 minutes, then cooled, taken up into water and extracted with ether. After concentrating the ether solution, a tan oil (0.4 g) remained which on TLC (silica gel - petroleum ether) showed one spot. The product is assigned the struc ture cis-l, 2- d i( 2-thienyl)ethylene (49$ yield) based on the following

spectral properties: ir, Vmax (cm“1),: 833 , 839 , 693 (broad); nmr

(CCI3D): 7-03 & (mult, 3H), 6.54 6 (sin g l, m ); mass spectrum, m/e (rel, int.): 192 (l00) P*.

Upon standing in light, cis-1,2-di(2-thienyl)ethylene was con- 34 verted to trans-l, 2-d i( 2-thienyl)ethylene, mp 129 - 131° (lit. mp 130-

131°), with the following properties: ir, y,ntlY (cm-1); 1370, 9 ^5# 830

824, 693 (broad); nmr (CCI4): 7-20 6 (m ult), 6.98 8 (sihgl), overlapping absorption; mass spectrum, m/e (re l. i n t.) : 192 (100) P*. The properties of the els- and trans-ethylenes presently obtained agree with those presented earlier for cis- and trans-l, 2-d i( 2-th ien y l) 46 ethylene s, isolated from pyrolysis of 2-thienyldlazomethane.

Preparation of 3-Thiophenecarboxaldehyde p-Tosylhydrazone

A solution of 3-thiophenecarboxaldehyde ( 9 6/5, 17.7 g, 0.152 mole) (prepared according to the method described in Org. Syn., Gol l .jyol^

4, 921 , 918 ) and |>-tosylhydrazide ( 27.65 g, 0.149 mole) in methanol (100 ml) was stirred for 2 hours at room temperature. After removal of the solvent in vacuo, white crystals or 3-thiophenecarboxaldehyde p-tosylhydrazone (34 g, 82$ yield) were collected and recrystallized from methanol, mp 157. 5- 159 0* The tosylhydrazone has the following properties: ir, (cm"1): 3190, 1605. Anal. Calcd fo r Cj.pHiqUpOfoS^: W, 10,00.

Pound; N, 10. 25.

Preparation of the Sodium Salt of 3~Thiophenecarboxaldehyd^^-^osyl- hydrazone

The method of preparation was the same as that described earlier for the sodium salt of 2-thiophenecarboxaldehyde ^-tosylhydrazone.

O verall y ield s averaged 94$. The sodium s a lt was obtained as a white solid and dried in a vacuum desiccator for 3 hours before use.

Decomposition of the Sodium Salt of 3-Thi qphene corboxaldehyde p-Tosyl- hydrazone in Cyclooctane

The procedure and apparatus used was the same as that previously described for the decomposition of the sodium salt of 2-thlophenecarboxaldehyde ^-tosylhydrazone. Upon addition of the sodium salt (2.23 g) to refluxing cyclooctane (50 ml), decomposition occurred within sec onds. The reaction mixture turned pink, then white. The white reac tion mixture was cooled and the sodium £-toluenesulfinate filtered. The filtrate was stripped on a rotary evaporator to a brown liquid (l,l8 g) which was gas chroraatographically analyzed on a 20$ SE 30 chromosorb P column (6' x ^ ). With the column temperature a t 232° and the flow rate at 20 ml/minute, a water white compound, 3-thenylcyclooctane, with a retention time of 8.85 minutes was preparatively collected (60$ overall yield). The material has the additional proper ties; ir, Vinnv (cm"1); 2950, 770 (broad); nmr (CQDQ): 6.80 6 (mult,

3H), 2.1*7 6 (doublet, 2H), 1.52 6 (broad sin g l, 15H).

Anal. Calcd for C13H20S: C, 7i*.91*; H, 9.68.

Found: 0, 7^.77; H, 9 . 63.

Gas Phase Pyrolysis of 3~Thienyldiazomethane Generated In Situ Material balances based on 3-thienyldiazomethane averaged 27$. Column chromatography of the crude pyrolysate on silica gel:petroleum eth er (200; 1; adsorbent:sample) separated trans (61* mole $ of products based on the nmr cf the crude pyrolysate) and cis (26 mole $) 1, 2-d i-

(3-thienyl)ethylenes, cis - 1, 2-D1 (5-thienyl)ethylene. an oil which isomerizes to trans-l, 2 -d i( 3-thienyl)ethylene in light, has the following properties: ir, \>SDBX (cm-1 ): 81*0, 815 ,.75^ (broad); nmr (CCI 4 ): 7.11 6 (mult, 3H); 6.1*3 6 (singl, IH); mass spectrum, m/e: 192, M*.

trans-l,2-Dl(3-thienyl)ethylene, white needles, mp 11*8 - 150°, has th e following p ro p erties: i r , (cm"1): 9&0, 905 , 775 (broad); 48 nmr (CCI4 ): 7.28 6 (mult, 3H), 7*00 6 (singl, IH).

Anal, Calcd fo r CibHaSs: C, 62,4-5; H, 4.19.

Found: C, 62. 65? H, 5.95. Further elution separated 3“thiophene c arboxaldehyde azine (9 mole $ of products), mp 147-149°; mixed mp with an authentic sample, 147- 149°. Additional properties of the azine are: ir, y^y (cm-1): 1600? nmr (CCI4 ): 8.72 6 (singl, IH), 8.13 6 (mult, IH), 7.62 6 (mult, 2H).

Anal. Calcd for CioHsS 2N2: E, 12.72. Found: N, 12.86,

Preparation of 3 - Thiophenecarboxaldehyde Azine

Anhydrous hydrazine (O .32 g, O.OO5 mole) was added to 3-thiophenecarhoxaldehyde (1.12 g, 0,01 mole) in ethanol (30 ml). The mixture was stirred at room temperature overnight. Removal of solvent yielded yellow crystals of 3-thiophenecarboxaldehyde azine? mp 148-149° from methanol.

Preparation of 5-Methyl-2-thiophenecarboxaldehyde ^-Tosylhydrazone • A solution of 5-Jnebhyl-2-thiophenecarboxaldehyde (25.2 g, 0.2 mole;

Aldrich Chem. Co.) and £-1osylhydrazide (37*2 g, 0.2 mole) in methanol (100 ml) was stirred for 2 hours at room temperature. After removal of the solvent jLn vacuo, white crystals of 5-Jneth y l- 2-thlophenecarbox aldehyde ^-tosylhydrazone (43 g, 0.146 mole) were collected and recry stallized from ethyl acetate. The tosylhydrazone, -rap 157-158°j has the following properties: ir, vmax (cm-1): 3190 ; 1600.

Anal. Calcd for Ci 3Hi4N2S202: N, 9*51. Found: N, 9.60, 49

Preparation of the Sodium Salt of JHfethyl-2-Th^

£-Tosylhydrazone The method of preparation was the same as that described earlier for the Bodium salt of 2-thiophenecarboxaldehyde £-tosylhydrazone.

Overall yields were between 90-95$ • T*16 sodium salt was obtained as a white solid and dried in a vacuum desiccator for 3 hours before uBe.

Gas Phase Pyrolysis of ^-Methyl-2-Thienyldlazomethane Generated In S itu

Material balances based on 5-methyl-2-thienyldiazomethane averaged 34$. Column chromatography of the crude pyrolysate on silica gel:petro

leum ether (200: 1; adsorbent:sample) separated trans- (42 mole ?> of pro

ducts based on the nmr of the crude pyrolysate) and els- (22 mole $)

1, 2- d i( 5-m ethyl- 2-thienyl)ethylenes.

c is - l 12-Dl(3-methyl-2-thlenyl)ethylene is a yellow oil and isomerizes to the trans isomer upon standing in light. The cis isomer has

the additional properties: ir, %ax (cnT1); 800 (broad); nmr (CCI 4 ):

6.60 6 (mult, 2H), 6,37 6 (singl, IH), 2,46 6 (sin g l, 3H); mass spec

trum, m/e: 220 M*.

tra n s - 1, 2-D i(3-methyl- 2-thienyl)ethylene, white needles, mp 92 -93 °* has the following properties: ir, Vmax (cm-1): 940, 800 (broad); nmr

(CCI4 ): 6,73 6 (singl) and 6.60 6 (mult) total 3H; 2.46 6 (sin g l, 3H),

Anal. Calcd for C12H12S2 : C, 63.48; H, 5>49.

Pound: C, 65. 69 ; H, 5.59. As elu tio n continued, the column darkened. The column darkening may be attributed to alteration of a polymer of 3-hexen-l-yne- 5-thione, aince no homogeneous component was iso la te d in these experiments. The crude pyrolysate, however, showed spectral evidence for the presence of

a polymer of 3-hexen-l-yne- 5-thione; its ir and nmr spectral proper ties are: ir, vTnqx (cm"1): 3315 (sharp, C^C-H stretch), 1600 (sharp);

nmr (CCI4 ): 3*20 6 (doublet, C^C-H, J = 2 cps, IH), 1.8k 6 (sin g l,

3H); (olefinic protons were camouflaged by the thiophene ring protons of cis- and trans-l,2-di(5-methyl-2-thienyl)ethylenes). Integration

of these areas of absorption showed that a derivative of 3-hexen-l-yne-

5-thlone was 19 /S of the products.

No 5"methyl-2-thiophenecarboxaldehyde azine was ever isolated by further chromatographic elution; also, the nmr spectrum of the crude . pyrolysate did not reveal the presence of the azine.

Preparation of Methyl 2-Thienyl ICetone ^-Tosylhydrazone

A stirred solution of 2-acetylthiophene ( 25.2 g, 0.2 mole; Al

drich Chem. Co.) and £-tosylhydrazide (37.2 g, 0.2 mole) in methanol (100 ml) was refluxed for 2 hours. Removal of solvent, in vacuo, yielded white needles of methyl 2-thienyl ketone ^-tosylhydrazone (52 g t 91 $ yield), which was recrystallized from ethanol-benzene, mp 207- 208.5°. The tosylhydrazone has the following properties: ir,

(cm"1): 3190, 1605.

Anal. Calcd for Ca,3Hi4N2S202: N, 9*51.

Pound: N, 9.51. 51

Preparation of the Sodium Salt of Methyl 2-Thienyl Ketone £-Tosylhydra-

zone

The method of preparation was identical to that described earlier

for the sodium salt of 2-thiophenecarboxaldehyde ^-tosylhydrazone. Overall yields ranged between 90-95$. The sodium sa lt was obtained as a white solid and dried in a vacuum desiccator for 3 hours before being used.

Gas Phase Pyrolysis of o-Methyl 2-Thienyldiazomethane, Generated In Situ

Material balances of products based on or-methyl 2-thlenyldiazome-

thane averaged 49$. Vapor phase chromatography on a 20$ SE 3°

chromosorb P column (6* x 4") at 129° identified 2-vlnylthiophene (l 6 mole $ of products) by comparison of its retention time with an authen tic sample (Pfaltz and Bauer Co.). Column chromatography of the crude pyrolysate on silica gel:petroleum ether ( 200: 1; adsorbent:sample) sep

arated els- and trans- 2 , 3- d i( 2-th ie n y l)- 2-butenes (62$ of the product based on the nmr of the crude pyrolysate) as a mixture. The two isomers were separated by vapor phase chromatography on a 20$ SE 30 chromosorb

P column ( 6 * x ^")* With the column temperature at 107° and the flow r a te a t 72 ml/minute, the retention time of cls- 2 , 3-

(2-th le n y l)- 2-butene was 5.8 minutes ( 19 $). The nmr sp e ctral data of this mixture corroborated the ratio of els to trans isomers. Prepara tive vapor phase chromatography was not successful in separating the two isomers. The following properties are exhibited by this cis-trans mix tu re . I r , Vppqy (cm"1): 690 (broad); nmr (CCI 4 ): ca. 7.00 6 (mult, 3H), 52

cis 2 .2 0 6 (sin g l), 8 l$ j 5H tra n s 2 .0J5 6 (sin g l), 19 $

Anal. Calcd for Ci 2Hi 2S2: C, 65.48; H, 5.49.

Found: C, 65.71; H, 5. 56. As column chromatography continued the column darkened. This may he attributed to alteration of a polymer of 2-hexen-4-yne-l-thial. . No homogeneous component was iso late d . The sp e c tra l data of the crude

pyrolysate provide evidence for the presence of a polymer of 2-hexen-

4-yne-l-thial ( 16$ of products baBed on the nmr); nmr (CCI 4 ): 1.95 6

(2 peaks) assigned to CH 3-C=C-. Oleflnic and allylic proton absorptions are camouflaged by absorptions of other components. Further elution separated methyl 2-thienyl ketone azine (7$)j mp 89-91°; mixed rap with an authentic sample 87-91° . Additional properties ) of the azine are: ir, v (cm-1): 1590; nmr (CDC13): 7 .3 8 8 (mult, UlclX 2H), 7.04 6 (mult, IH), 2.4l 8 (singl, 3H).

Anal. Calcd for Ci 2Hi2S2N2: N, 11.28. Found: N, 11.31.

Preparation of Methyl 2-Thlanyl Ket one Azine Anhydrous hydrazine (0.64 g, 0,0-1-mole) was added to 2-acetylthiophene (2.54 g, 0.02 mole) in ethanol (20 ml). The mixture was refluxed overnight. Removal of solvent in vacuo yielded orange prisms 'of methyl

2-thienyl ketone azine; mp 90 -91 ° (recrystallized from 95 $ ethanol). 55 30 ,3 7 Preparation of 2-Thlophenecarboxaldehyde Hydrazone

( 36) T. Holton, Ph.D. Dissertation, The Ohio State University, 1971.

2-Thlophenecarboxaldehyde (4.48 g, 0.04 mole) was added dropwise to anhydrous hydrazine ( 18.3 g# .60 mole) a t 70° in 10 minutes. The reaction mixture stirred for 1 hour at 70°. After cooling the reaction mixture, saturated sodium chloride solution (75 ®l) was added; the re sulting aqueous solution vas extracted with methylene chloride (three 25 ml portions). The methylene chloride fractions were combined and "back extracted with saturated sodium chloride solution, and then dried over potassium carbonate (anhydrous). Solvent removal in vacuo yielded

2-1hiophe ne carb oxaldehyde hydrazone, white crystals (4.57 St 9®% y ie ld ), mp 60-62°. Storage of the hydrazone at -20° prevented its conversion to its azine. The hydrazone has the following spectral properties:

(37) J. B. F. N. Engberts, G. Von Brugger, J. Strating, and H. Wyriberg,

Rec. Tray. Chim. , 84, 1610 (1965). ir, v (cm-1): 3360, 3275, 3180, 3100, 1635 (broad), 1600, 1563, Hl&X 1442, 1385, 910, 700 (broad).

30 Preparation of 2-Thien^ld.iazomethane 2-Thiophenecarboxaldehyde hydrazone (1.15 g> 0.0089 mole) was diS' solved in dry diethyl ether (50 ml) in an Erlenmeyer flask (250 ml). The flask contents •were "brought to 0°, and an ether solution (20 ml)

of lead tetravalerate ( 5A Bt O.OO89 molej prepared by T. Holton) was added dropwise in 15 minutes. The reaction mixture was then cooled to

-78° and dry ice ( 5° s) "wa13 added. The red supernatant liq u id was

decanted and filtered through a sintered glass funnel at -78°. The

red filtrate was treated with dry ice (25 g) and filtered a second time through a sintered glass funnel at -78°. The red filtrate was then

stripped of solvent•on a rotary evaporator yielding 2-thienyldlazome-

thane, a red liquid (0,95 Bt 8 *$ yield). The 2-thienyldiazomethane,

stored a t -780 to prevent alteration, has the following spectral pro

p e rtie s: i r , Vmax (cm-1): 2068 , 697 (broad).

2 4 Preparation of the Cyclic Trimer of Propanethial Propionaldehyde (10 g, 0.175 mole; Eastman Kodak Co.) was dis

solved in ethanol (50 ml). Gaseous hydrochloric acid was bubbled into

the ethanolic propionaldehyde solution at 0° fo r 1 .5 hoursj hydrogen sulfide was then passed into the mixture at 0° for 2 hours. A dark

viscous liquid separated when water (50 ml) was added. The aqueous

layer was discarded, and the viscous liquid was taken up into diethyl • ether. The ether solution was extracted with water, saturated sodium bicarbonate solution, and dried over calcium sulfate. Solvent removal

in vacuo yielded a brown viscous liquid, which was distilled. Collec tion of the fraction boiling at 91 - 95 °/°* 5 ®m yielded the cyclic trimer 24 of propanethial ( 2 .1 g, 16^ yield, lit. bp lt 5°/l° mm) having the

following mass spectral properties: mass spectrum, 150° source and Filmed as received without page(s ) 55 *

UNIVERSITY MICROFILMS. SECTION 2'

Statement of the Problem

The present study involves investigation of carbenic and cationic decomposition of a-diazo thiolesters (l, Equation l). The principle

N2 0 0 II II . . II r - c - c - s - c h 2ch3 r - c - c - s c h 2ch3

(1 ) 0 H + II r - c - c - s c h 2ch3 -n2 H 5

R = H o 2n < § > - ~ © ~

objectives of this research were to determine fa) the differences in the reaction paths and the products'of decomposition of a-diazo thiol esters (l) by cationic and carbenic mechanisms, (b) if of-carbothio-

56 57

0 .. II R~C -C -SCH 2CH3 ------> R - c = C = 0

I • SCH2CH3 (2)

alkoxy carbenes ( 2 ) undergo Wolff rearrangement to thioalkoxy ketenes (kt Equation 2), and (c) if a new class of compounds 2-thiacyclqpro- penones (j>) are isolable as discrete products of intramolecular migra tion of divalent sulfur to divalent carbon (Equation 3). 2-Thlacyclo-

0 |l © / 0 R-*C -C-SCH2CH3 ------R-C ----C ' (3)

2 I ~ CH2CH3

• 1 propenones {%) are of interest as cyclic 2jt electron analogs of cyclo- propenones ( 6 , Equations k and 5)» Thioalkoxy ketenes (j+) are of possible utility in synthetic organic chemistry.

R R

6 58

. 0 0©

•*------(5) S. R R ^ R R

1 HISTORICAL

Wolff rearrangement of a-diazocarbonyl compounds is important synthetically and has received much mechanistic attention. Thus, ther molysis and photolysis of a-diazo ketones in protic solvents result in carboxylic acid derivatives by rearrangement of the carbon skeleton and reaction with the proton donor solvents (Equation 6 ). Ketenes (X) have been proposed as reaction intermediates in these systems.

Ng 0 0

R-C-C-R’ . ► R-C~C»0 RM~ 0H1 R-CH-C-OR" I I R' R1

(6)

( l) W. Kirmse, “Carbene Chemistry, ” Academic Press, Hew York, 1971.

In aprotic environments ketenes are often obtainable in preparative l quantities. Many studies have attempted to determine whether migration and loss of nitrogen from a-diazo ketones occur simultaneously, or whether loss of nitrogen precedes migration to give an intermediate o-ketocarbene ( 8 ) and/or itB subsequent oxirene (

59 6 0

0n /\0 R-C-C-R’11 R > C=CN R'.

8 9

details of mechanism of the Wolff rearrangement are s till somewhat uncertain, the intramolecular reaction has found considerable synthetic utility. For example, a valuable method of homologating a carboxylic acid is the Arndt-Eistert Synthesis (Equation 7). Thus an acid chloride upon treatment with diazomethane affords an a-diazo ketone ( 10) which can be photolyzed or thermolyzed in aqueous solution to give a higher x carboxylic acid, via a ketene intermediate (ll).

0 O ' 0 N2 _ !* „ 1* 2 CHpNp „ !! L A . R - C “ OH ------*• R—C -C l ------> R -C — CH ' -CH3C1, N2 or 10

(T) 0

R—C~C»0 ■ K- 2 0 -- > R-CH2- C11 -OH I H

Wolff rearrangement of a-diazo esters (12) (Equation 8 ), to al- koxyketenes (lj), and products thereof, was first reported upon study s of photolysis of diazoacetyl enzymes (Equation 9)* Azaserine (l4) 6 1

Na 0 R — C — C - 0 —R1 hv---- * R —C = C =0 > products ( 8 ) I OR'

12 22

(2) P. H. Westheimer, J . Shafer, P. Baronowsky, R. Laursen, and F, \ Finn, J . B iol. Chem., 2_4_1, 421 ( 1966 ). thus gives amino acid uP°n photolysis in water. Ethyl diazoacetate

N2 0 0 11 11 <=> hvj 11 (=1 HC - C - 0 - CH2- CH - C02 — —— * HOC - CH20 - CH2CH- C02 (9) 1 © * 0 1 ©

2k 2&

( l 6 ), phenyl diazoacetate (l£), and N-methyldiazoacetamide ( 18 ) also yield products from Wolff rearrangement when photolyzed in protic sol- 3 vents (Equations 10, 11, and 12). The major competing reaction is

insertion into the 0-H bond of the solvent. In the only report of

Na 0 0 II H ch 0H II HC-C-OCH2CH3 ■ n ■> C2H50-CH2-C -0C H 3 20-25# h\> 16 ~ + (10) 0 II ch3o - ch 2 - c - oc 2h5 T5_ 6 2

Na 0 0 II II CHaOH II h c - c - o - c 6hs C0H5O-CH2“ C-OCH3 45-6056 hv i t (11 ) 0 II CH3O- ch2 - c - o - c 6h5 40- 55#

Ka 0 0 II II hy II HC-C- KHCH3 ch3nh-ch2-c —oh 5056 Ha0 18 (1 2 ) 0 II HOCHa-C-HHCHa 70#

photolysis of an a-diazo thiolester protein derivative ( 1£) in water and 3 hydrolysis gives the single product 20 (Equation 13) as derived hy

Na 0 0 II II II h c - c - s c h 2ch -cn h 1. hy, HaO II 0 I } protein HOC - CHaSCHa-CH C02 HKC- 2. HC1, H20 II hh 3® 0 20 & (15)

(3 ) P. H. Westheimer, H. Chamovich, and R. J . Vaughn, J . Amer. Chem. SocL, JgO, 4088 (1968). 63

Wolff rearrangement of the thioalkyl moiety.

Other laboratories have studied Wolff rearrangement of a-diazo esters. Methyl diazoacetate (2l) upon photolysis in benzene affords 4 tvo isomers, 22 and 2£ (55$ overall) (Equation 14). The isomeric

Ns 0 H3C O^CHCCfeCHa II II . HC-C-OCH3 hy benzene CHaCfeCHC^o^Hs 21 22

(l4)

CH302CHC ^ chco 2ch3

CH3 ^ v 0 ^ C H 3

Z l

(4) G. 0. Schenck and A. Ritter, Tetrahedron Lett., 3189 (1968).

tetramers, 22 and 23, apparently arise from dimerization of cyclqpropa- none 26 formed by addition of methyoxyketene (24) (the Wolff rearrange ment product) to carbomethoscycarbene ( 2|?) or to methyl diazoacetate ( 21)

(Equation 15). 64

1 1 -s C = c = 0 + 21 CHaO^ \ - N 2 24 21 CH30-C"? A------vOCH3 0 II 26 ‘CH-C-OCHa + 24 (15) 2^

To date, the most thorough study of Wolff rearrangement of a-diazo 5-10 esters has been conducted "by Strausz and coworkers. Photolysis of ethyl diazoacetate (l 6 ) in 2-propanol affords 2£ (9 $)> 28 (29 $), 2^ 5 • (25$), and £0 (12$) (Equation 16). Ethoxyl ether 28 results from

(5) 0. P. Strausz, T. DoMinh, and H. E. Gunning, J. Amer. Chem. Soc., 1 5 0 , 1660 (1968 )..

ethoxyl migration (Wolff rearrangement) to form ethoxyketene which is trapped hy 2-propanol. p-Hydroxy ester 2£ stems from C-H insertion

into the solvent; ether 2J? arises from 0-H insertion as does %Q which 6 is also a product of transesterification. The intermediacy of a car-

(6 ) 0. P. Strausz, T. DoMinh, and H. E. Gunning, J . Amer. Chem. Soc.,

£1, 1261 (1969 ). 6 5

OH 0 I II* (c h 3 )2c - c h 2 - c - o - c2h s

0 II c 2h 5o - ch2 - c - o c h ( c h 3 )2

1& — > (16) -N2 0 II (ch3 )2c h - o -ch 2 - c - OC2Hs

0 II (CH3)2C H - 0 - C H s -G-0-CH(CH3)2

bonium ion is discounted in the various processes involved in photo lysis of ethyl diazoacetate in 2-propanol. Lithium bromide in the photolysis mixture does not change the product distribution and does not result in formation of ethyl of-bromoacetate. Photolysis in the presence of trlethylamine also does not alter the percentages of pro ducts. In 2-propanol saturated with gaseous hydrogen chloride, how- „ ever, ethyl dlazoacetate (l 6 ) decomposes to 2^ (2U?6) and ethyl oi-

chloroacetate ( 75$)J these products are attributed to carbonium ion 5 j£L (Equation 17) which doeB not undergo rearrangement.

16 £ ------► h - ® - o - o o 2h5 ....(°H3 ) a ? - 0K- > -n 2 i cr3 H & (17) Cl 0 I II 2£ + H2C -C - OC2H5

The details of the mechanism of Wolff rearrangement of a-diazo ke- 7"10 13 tones and esters in the gas phaBe have been studied by C

(7) 0. P. Strausz, J. Font, and I. G. Csizmadia, J. Amer. Chem. Soc., 20, 7360 (1968).

(8 ) 0. P. Strausz, D. E. Thornton, and R. K. Gasavi, J . Amer. Chem. Soc., 22, 1768 (1970).

(9) 0. P. Strausz and G. Frater, J. Amer. Chem. Soc., ^2, 665^ (1970).

(10) 0. P. Strausz and T. DoMinh, J . Amer. Chem. Soc., $2, 1766 (1970).

labeling of diazo derivatives 2. By mass spectrometry it was observed that some l3C is incorporated into the carbon skeleton as well as in the carbon monoxide (Equation 18). The re su lts are a ttrib u te d to formation n2 0 hv R-C11 -C-R’ 1311 R - C = C= 0 R- C = C = 0 gas phase I I 2 & R' R'

2 2 2 *t

32a, R CH3; R* = CH3 I I (1 8 ) 32b, R H; R' = CH3 13C0 + °?. + ^2c, R Hi R* = OC2H5 R-C-R' R- 13C-R’ m r Hi R' = OCH3 Lproducts Lproducts of two different ketenes, JQ and whose contribution to product for mation is based on the extent to which an oxirene intermediate is in volved (Equation 19). Thus, initial carbene %6 may undergo Wolff rear-

± R-C—13C-0 13CO + products

R-C-13C-R» (19 ) 2 l II 13* • ...A~ =. R-C- C-R' 22 2 1

co i + laproducts 4- r - 13c- c = o I R* at 6 8 rangement to or reversibly form which yields new carbene %Jj that Wolff rearranges to ketene i From the 1 C 3 in the carbon mon oxide and the carbon skeleton fragmentation products, and correcting To for incomplete C labeling, the extent of oxirene formed in decompo s itio n of £2 in the following compounds is:

ft oxiirene formation

0 II H CH3-C-C-CH 3 100

n2 0 II II HC-G — CH3 16

N2 0 II II HC— C-0C2H5 32

n2 0 II II H -c — C-OCH3 28

7 An oxirene is predicted to be a ground state singlet of low stability.

Strausz*s results for o-diazo ketones conflict with earlier work IX by Franzen. The Franzen study Involves solution photolysis and ther-

(ll) V. Franzen, Ann., 6l4, 31 (1958).

molysis of [ 14C] azibenzil (3 8 ) in dioxane-water-trlethylamine and dioxane-water. Upon degradation of the diphenylacetic acid, all of 69 the radioactivity was in the carbon dioxide and none in the benzophe- none (Equation 20). These results do not indicate the intermediacy

Na 0 -J f e - flJ-C-=14C = 0 ---- ^ ---- > I 58 f (2 0 ) 0

(z~~ CHg- C - OH — > 02c= o + 14co 2

of oxirene 2%.

0 0 38 > 0 - c - 14c-0H ■■■// » 0 -G / ==^c X 22

9 Strausz has repeated the work of Franzen. [13C] Azibenzil photolyzed in cyclopentane reveals formation of oxirene (measurement of carbon monoxide) and in dioxane-vater k&fi oxirene (measurement of *1* the +COOH and 3COOH fragment Intensities) using mass spectral tech niques. The disagreement in two studies concerning formation of ox irene is obvious. Photolysis of [13C] 3“dlazo-2-butanone in cyclopen tane and in dioxane-water involves 60$ oxirene formation.

Solution photolyses of methyl and ethyl diazoacetates did not re- s veal formation of oxirene (Equation 21). Formation of oxirene k l *• ^C = c ~ 0 OC2H5 thus involves a greater energy barrier than does formation of ketene. In the gas phase some carbethoxycarbene (UO) possesses sufficient energy to overcome this barrier, but in the condensed phase only a small fraction of 40, has sufficient energy to rearrange.

Thermally-induced Wolff rearrangement of or-diazo esters in solu- s , 12 0 tlon has as yet not been observed. Ethyl diazoacetate at 1^0 in

(12) (a) W. Ju^elt and D. Schmidt, Tetrahedron, j2£, 9^9 (1969); (b)

R. W. Hoffman and J . Gehlaus, Tetrahedron, 2 6 , 5901 (1970). olefins yields only products of addition of carboalkoxycarbene to the ’ 6 o olefins. Thermolysis of tosylhydrazone salt J+2 in mineral oil at 140 does not give products of Wolff rearrangement of methoxycarbomethoxycarbene i a The products are fumarate hk and maleate ^5, both derived from dimerization of and dimethyloxalate resulting from oxidation of (Equation 22). Tosylhydrazone k2 also does not give 71

0 n ' 0 - II i 4o° II ** CH30 -C -C -0 C H 3------—— ---> CH3O-C-C-OCH3 42 43

(22)

CH3Q2C ^ . 0CH3 H3CO£CL .COaCH3 •> c=cC + c-c, ch3o ^ v co 2ch3 ch3o x ^ och 3

hl%

0 0 II II + CH30 “ C-C-0CH3

38 ^ products of Wolff rearrangement when photolyzed in tetrahydrofuran.' 12 The products are a mixture of 44 and 4jj (36$) and sulfone 46 (21$).

C7H7S0a -CH-CCi2CH3 I OCH3 46

The stability of methoxycarbomethoxycarbene (4^) is presumed to result 12,13,14 from donor and acceptor effects in the carbene. The empty orbital 72

(13) R. Hoffman, J . Amer. Chem. Soc., JgO, 51+57 (1968 ).

(li+) J. Hine, “Divalent Carbon, ” p. 169 , Ronald Press, New York, I 96 I+.

of d ivalent carbon in J+£ aooeptS eleotrons from the methoxy groupj the filled orbital of the divalent center delooalizes its electron pair into the carbonyl group, as represented below:

0 cP II © 1 0 CH3O -C C — 0CH3 <------*• CH3O-C =■ C — 0CH3 0

!& &

The “added stability” in Uj is believed to prevent rearrangement of the carbene. Thermal Wolff rearrangement of dicarbomethoxycarbene (3.2) occurs is in the gas phase. Methyl diazomalonate (j£X), upon decomposition at

(15) M. Jones, D. C. Richardson, and M. E. Hendrick, J. Amer. Chem.

Soc., 2 2 , 3790 (1971).

temperatures between 280 ° and gives the following products ^ 15 (Table l ) : 73 Table 1; Product Variation {%) in Pyrolysis of Methyl Diazomalonate' at Different Temperatures.

methyl Temp. methyl methyl methyl vinyl acrylate pyruvate acetate ether ______(fe)______CfeT______(g>) ______•(§!)

280 92 0 3 3

330 72 6 12 31

420-540 32 7 8 52

A scheme fo r formation of the various products from jj 2 is summarized in Equation 23. At lower temperatures C-H insertion of bis(carbomethoxy)- carbene (j>2) predominates leading to methyl acrylate (48). At higher temperatures Wolff rearrangement of £2 to ketene £3. becomes com petitive.

Decarbonylation of $2. affords methosycarbomethoxycarbene (4^) 'which undergoes (a) intramolecular C-H insertion to a p-lactone that decar- boxy lates to methyl vinyl ether (£l), (b) Wolff rearrangement to dime- thoxyketene (34 )j which after decarbonylation and methyl migration, gives methyl acetate ( 50 )» and (c) methyl migration to yield methyl pyruvate (49,). 1 6 , 1 7 The photochemistry of a-diazoamides has been studied. N,W-

( l 6 ) R. R. Rando, J . Amer. Chem. Soc., $2, 6JO6 (1970).

(l? ) R. R. Rando, J . Amer. Chem. Soc., Jg4, 1629 (1972). , CH3 Q2 C -co2 > CH30sC “* OH ~~ CH5

k S

0 II CH3Q2C * C “ C -OCH3 CH302 C—COCHo

JS ia \ (25) ch3 o2 c x ch 3 o 2 c , C=C: C: ~C.QS->. CH3OCH=CHa ch3o '

S i

w. eN ^ (ca 3 0 )so=o=o -=S1*' OCH3 & 0 II CH3O-C-CH 3

J8 . 75 Diethyl diazoaoetamide ( 5 5 ) photolyzes in dioxane to give product lac

tams (57?) and (^3?) (Equation 2l+)..

N2 0 II II ,ch2ch3 H C - C — N, hv ‘CH2CH3 dioxane CH3' ‘CH2CH3 55

N-CHaCH.

Photolysis of 55. methanol, however, affords amide 58 (3^?) and ester 1 52 (18?) along with lactams 58 (^3?) and 51 (5?) (Equation 25).

h'j 5k + 5L lie OH

0 - II + CH30“ CH2'“-C “ N(C2Hg )2

58 ( 25) 0 . II + ( C2H5 >2W "CH2 — COCH3

52. Amide j>8 results from solvent insertion; ester a product of

Wolff rearrangement.

Wolff rearrangement of cv-diazo ketones may be initiated by silver 1 >1B»10 ion. Thus diazo ketone 60, heated in a suspension of silver IB oxide in methanol, affords esters 6l (53$) and 62 (23$) (Equation 26).

0 CH3 CH3 0 II II I I II HC-C — C C-CH3 Ag20 CH3-C-CH 2 -C -0C H 3 I CH3OH I ch3 CHS

60 61

(26)

CH3 0 I II CHs-C-CH-COCHs I ch3

(18 ) E. Werikert, B. L. Mylarl, and L. L. Davis, J. Amer. Chem. Soc.,

jgO, 3870 (1968).

(19) 0. Stork and J. W. Schuleriberg, J. Amer. Chem. Soc. f 8k, 281f (1962 ).

Copper ion is used to initiate Wolff rearrangement of a-diazo ke- 30,21 tones in certain cases; however, in general intramolecular C-H insertion and intermolecular solvent insertion are the prevalent pro v e s cesses. To date initiation of Wolff rearrangement of n-diazo

( 2 0 ) P. Yates and J. Fugger, Chem. Ind ., 1 5 1 1 (1957).

( 2 1 ) M. F. Dull and P. G. Abend, J. Amer. Chem. Soc., —8 l, 2588 (1959). ^ (2 2 ) (a) D. S. Wulfman, B. W. Peace, and E. K. Steffen, Chem. Commun., 1 5 6 0 (1972); (b) P. S. Skell and P. M. Elter, Chem. Ind., 62k

(1958); (c) H. Erlenmeyer and M. Aeberli, Helv. Chlm. Acta., JgL,

23 (19^8); (d) R. Cassanova and T. Reichstein, Helv. Chim. Acta.,

a k i r ( 1950 ).

esters by metal ions has not been reported.

The ability of divalent sulfur to rearrange to divalent carbon 2 3 has been observed in this laboratory. Thus thermal decomposition of

(2 3 ) H. S h ech ter and J . H. Robson, J . Amer. Chem. S o c ., 89, 7 H 2

(1967).

sodium or lithium salts of 2-ethylmercaptoacetcphenone £-tosylhydrazone

(6 3 ) leads to cis- and trans- 0 -thioethoxystyrenes (6J+, 9 “ 15$ )„ and a- thioethoxystyrene ( 6%, 91-85$) (Equation 27). Carbenic migration of an o'-thioethoxyl group predominates over that of cr-hydrogen. When sulfur is replaced with oxygen, as in 66 (Equation 28), and nitrogen, as in

67 (Equation 2 9 ), only products from migration of

L3® or Tos < V H II CqHs *—C — CH2- SC 2Hs CsH5“ CH=CHSC2Hs 65 cis and trans St (27) CqHs-CH—Cife

SC2H5 S i

Na© Tos

Wy II C6H5 — C — CHaOCH3 CeHs- CH = CHOCH3 cis and trans $0$ 66 (2 8 )

CqH5-CH=CH2 OMe

NeP & Tos N H II CeHs— C — CH22T(CH3 )2 CeH5-CH = CHN(CH3 )2

S i cis and trans (29)

CqHsCH —CH2 I n ( ch 3 )2 79 It has heen rationalized that divalent sulfur's ability to mi- 2 4 ,2 5 grate to carbenic sites is related to its nucleophllicity via d- 23 orbital effects.

(24) S. Winstein and-E. Grunwald, J. Amer. Chem. Soc., JO, 828

(1948).

(2 5 ) P. D. Bartlett, S. D. Ross, and C. G. Swain, J. Amer. Chem.

Soc., J l , 1415 (1949).

Intramolecular sulfur participation at carbenic siteB in a and (3 positions has been reported. Tosylhydrazone salt 68 photolyzes at

10° in glyme to 6£ (25$), JO (33$), and J l (4l$) (Equation 30). Thietan

68 &

CeHs

+ 80

(26) K. Kondo and I . Ojima, Chem. Commun. , 62/ 6 h (1972).

6g arises from {3-sulfur participation giving intermediate J2, which undergoes allylic rearrangement to 6^ (Equation 3l). Thioether is

.Cells

(31)

derived from insertion into an allylic carbon-hydrogen bond, whereas thioether £1 results from migration of or-hydrogen to divalent carbon.

Tosylhydrazone salt Jp, upon irradiation at -78°, yields 7jv ( 89 ^) and

£5 (ll^S) (Equation 32).

1 1 ik ( 32)

/«?rsV / S \ ^ ■Cq H5

1 1 81

Thioether ^ is proposed to result from collapse of ylide j 6 , formed by participation of a-divalent sulfur at the carbenic center (Equation 33)*

cqh 5 * lit s ©

(55)

Sulfide seises from migration of an a-hydrogen to the divalent center. Ylide-like intermediates, analogous to 7^6, have been previously proposed S3 for migration of divalent sulfur to divalent carbon. Intermolecular reactions of divalent sulfur with carbenes have 27,28,29 also been reported. Deuterated diallyl sulfide and diazomethane in the presence of cuprous salts yield the insertion products, t 27 78 (83%) and 72 (17#) (Equation 3b).

D 82

(27) W. Kirmse and M. Krepps, Chem. Ber., 101, 994, 1004 ( 1968 ).

It has teen proposed that £ 8 arises from collapse of ylide 80j

(Equation 35)t conversion of ,77 'fc0 cyclopropane 7£ is a typical addi tion reaction of diazomethane. ^>rD II I d (3 5 )

O *

80 l a

Diazocarbonyl compounds 81, 82, and 85 ^ react with dimethyl sul fide when irradiated to form stable, isolable aulfonlum ylides 84 ( 88 %), as 85 (87 $), and 86 (52%), respectively (Equation 3 6 ). ‘ v \

R. R. © © hv j;C - S(CH3)a (36) R‘ (CH3)2S R

81, R = C0 2CH3 84, R = C0 2CH3 82, R = COaCaHs ££, R = COaCgHs

8 J, R = C0CH3 8 6 , R = COCH3 83

(28) W. Ando, T. Yagihara, S. Tazune, and I . Migita, J. Amer. Chem.

Soc., 21, 2786 (1969).

It haB teen proposed that sulfonium ylides 8J+, JJjj, i*01111 from reactions or singlet carbenes -with dimethyl sulfide. Diazocar- honyl compounds 8l, 82, and 8£, when photolyzed in dimethylsulf ide in the presence of tenzcphenone (a triplet sensitizer), do not yield 20 sulfonium ylides 8k, &£, and 86, respectively.

Sulfonium ylides have also teen prepared ty photolysis of tis- 2 9 (phenylsulfonyl)diazomethane (&£) in the presence of sulfides.

(jZSS9a)2C = N2

(29) J . Diekmann, J . Qrg. Chem., ;50, 2272 ( 1965 ).

4 DISCUSSION OP THE RESULTS

The present study involves investigation of various cationic and carhenic reactions of ethyl a-dlazothiolacetate ( 8 8 ), ethyl ff-diazophenylthiolacetate (S^), and ethyl ar-diazo-jg-nitrophenylthiolacetate

(^O), respectively. Na 0 (I li R-C-C-SCsHs

R = H, 88

R = CsH5, - 8 £

R = E-02N-C6H4 , 20

Ethyl jy-diazothiolacetate ( 8 8 ) was prepared from glyoxylic acid tosylhydrazone by reaction with thionyl chloride and then ethanethiol and triethylamine (Equation 37); the synthetic method is an extension 30 of that of House and Blankley. Thlolacetate 88 exhibits character-

(30) H. 0. House and C. J. Blankley, J . Org. Chem., j£ , 53 ( 1968 ).

istic infrared absorption at 2110 cm"1 for its diazo group ( 3 C=Na) and 11 31 a t 1630 cm-1 for a thiolester (-C-S-). ; The nmr and uv absorption

81f 85

0 0 N2 0 II II l) TosNHEH2 I! II H-C-C-OH h - c - c - s c 2h5 (57) 2) SOClg 5) C2H5SH, 2 Et3N 88

(51) K. Nakanishi, "infrared Absorption Spectroscopy," Holden-Day, San Prancisco, 1962.

spectra (see Experimental) of 88 support the structural assignment.

Proper elemental analysis for 88 was not obtained because it contained an impurity, diethyl disulfide ( 10^ by weight), which could not be re moved readily by distillation. Ethyl cn-diazothiolacetate ( 8 8 ) is a yellow liquid which is stable at room temperature for long periods.

In the present work however, 88 was stored at - 78 ° in the dark for pre cautionary purposes.

A study was initiated of decomposition of 88 as catalyzed by pro tonic acids. The results of this study are summarized in (Equations

58 -^3 ). Diazo thiolester 88 does not react in methanol at 23° in the dark in U8 hours (Equation 3 8 ). When catalytic quantities of concentrated sulfuric acid are added to a methanol solution of 88 a t

25°, nitrogen evolution is spontaneous and within one hour the reaction mixture is colorless giving ethyl a-methoxythiolacetate (jgl, 32 \ 93$) (Equation 39) as the sole product. The structure of £1 is assigned on the basis of the ranr and lr spectra of a preparative gas MeOE______> H.R. (38) 2 5°f dark

0 Me OH______II CH3O *— ch2— c ~ sc 2h3 (5 9 ) E+, 25°

0 0 CH3C02H 11 11 CH3C -O-CHa-C-SC 2H5 (Uo) H2 0 25’' I I I I 2 2 H-C-C-SCgHs

88 CF3C02H fl1 y % CP3G “ 0 ^ CHa “ C -SC3 H5 (4 l) 0° 2 1

(ch 3)2ch - sh > N.R. (^2) 25°, dark

0 (ch 3)2ch - sh II (CH3)2CH-S *-CH 2 -C-SC 2H5 m ' H+, 25° CD 9b 87

(32) Y. Yamamoto and I. Moritanl, Tetrahedron L ett., 308? (1969) re port that decomposition of diethyl diazosuccinate in cyclohex-

anol-di occurs almost completely ( 92 $) by a carbenic process.

In acetic acid-di and in DCl-DaO decompositions of the diazo

ester by cationic processes become of increasing importance

(3b and 100$, respectively).

chromatographic sample. Infrared absorption in ^1 at 1685 cm"1 in d i ct 33* cates that the reaction product is a thiolacetate (-C-S-). The chemical point of interest in the present experiment is that cationic decomposition of 88 in methanol does not result in migration of the

S-ethyl group.

An investigation of acid-catalyzed decomposition of 88 in environ ments less nucleophilic than methanol was initiated. Treatment of 88 with glacial acetic acid at 23-30° (Equation ij-0) yields ethyl n-acetoxy thiolacetate (£2, 91$) as the only product. The overall processes for acid-catalyzed decomposition of 88 in methanol and acetic acid are id e n tic a l. IR absorptions in §2 a t 1750 and 1690 cm"1 are assignable to its acetoxy (_q^C= 0 ) and its thiolacetate (_S^.C=0 ) groups, respec- 31 tlvely. Preparative gas chromatography gave an analytical sample of

%2 having proper ir and nmr properties. Trifluoroacetic acid, a reagent less nucleophilic than methanol or acetic acid, reacts vigorously with 88 a t 0° to give ethyl o'-acetoxy- thlolacetate (9,5, Equation 4l) exclusively. Purification of was not 8 8 attempted. The structure of is assigned on the basis of its nmr and mass spectral properties (the parent ion of has a m/e of 216 with a relative intensity of 12 percent).

Decomposition of 88 was then studied in nucleophilic environments containing sulfur rather than oxygen. A solution of diazo thiolester

88 in 2-propanethiol does not react at 25° in 4 hours (Equation 42). Addition of trace amounts of concentrated sulfuric acid results in rapid evolution of nitrogen; the solution becomes colorless rapidly affording ethyl o'-thioisopropoxythiolacetate (£4/ 84$) as the sole product (Equation 43). The structure of 94 is assignable on the basis of the nmr spectrum of a preparative gas chromatographic sample.

The cationic reactions of 88 and the products therefrom are ex plainable by any/or all of the mechanisms outlined in Scheme 1. The cationic processes of 88 do not result in products in which the thioethoxyl group has migrated. The initial step in these reactions is protonation of diazo thiolester 88 to give diazonium ion £§, which may (a) expel nitrogen in a nucleophilic process in which solvent partici pates, (b) expel nitrogen forming the carbothioethoxycarbonium ion

(g 6 ) that reacts with solvent at its cationic site, or (c) lose nitro gen by an intramolecular process in which sulfur participates affording sulfonium ion that reacts with solvent at tetrahedral carbon. The 5 present results are analogous to prior observations in which acid- catalyzed decomposition of ethyl fy-diazoacetate (l 6 ) yields products of reaction in which the ethoxyl group does not migrate (Equation 44). 89

Scheme 1

0 R'OH , H ------» roch2- C-SC2H5 * -n2

R'OH -i@

©N2 0 0 I II ■Na © II R'OH 88 H-C — C-SC2H5 -» h2c - c - s c 2h5 -#> I H &

-U2 H 2C p

C 2H 5

2 1 90

Na 0 0 II II II h c - c - o c 2h5 — is------* R' 0 - CH2- C - C02C2H5 (^ ) R'-OH 16

Participation of carboxylate anion in methanolysis of optically 33, 34 active a-bromopropionate in dilute alkaline solution has been proposed to explain displacement of bromide by methoxyl vith overall retention of configuration (Equation h$) to form 2-methoxyprqplonate. Methanoly- sis of methyl

(33) W. A. Cowdrey, E. D. Hughes, and C. K. Ingold, J . Chem. Soe .,

1208 (193T).

(3^) S. Winstein and H. J. Lucas, J. Amer. Chem. Soc., 6l , 1576

(1939)I S. Winstein, J. Amer. Chem. Soc., 6l , 1635 (1939)*

Br 0 OCH3 * CH3- CH-C^ \ / ^ 0 (a) (a) <*«?)*

figuration (Equation k6 ) rather than retention. A carboxylate group is apparently sufficiently nucleophilic to participate at o'-carbon, whereas alkoxyl is not. By analogy, thloethoxyl may be sufficiently 91

Br 0 0 I II CH3OH CH3-CH-C-OCH3 > CH3-CH-C-OCH3 (46) I OCH3

(d) (l) nucleophilic to participate in a carbonium ion process as in Equation

45. A study has been made of thermal, photochemical, and photosensi tized decomposition of ethyl cvdiazothiolacetate ( 8 8 ) in various envi ronments. The results of these varied carbenic reactions of 88 are sum marized in Equations 47-58.

Diazo ester 88 decomposes in refluxlng methanol (7 hr) to yield methyl a-thioethoxyacetate (

88 in various experiments. The objective of this effort was to deter- cs3oh li C2H5-SCH2— C “OCH3 65 2 8

c2h5s - ch2 - c11 0 65c 21 0 II II H — C — C — SC2H5 ■

88 CH3OH 2 1 lav

0 (CH3)2C5H-QH II ■ 1 ■ 11 1 “ C2H5S — CH2 — C — OCH(CH3)a

100 (9 6 . 5^)

0 II + CH3 — C — SC2H3 (CH3 )3 C“OH caH5scBh - c - oc(ca 3)3

102

0 (CH3)2Ca-SH T II C”*SCH(CH3 )2 hv 105 (98?) ft U2 0 0 fl H II H — C — C — SC2H5 ( CH3 )2 CHS-CH2 - C - s c 2h5

88 (196) 0 II CH3 ~ C *“ SC2Hs

101 (trace) \_ (C53 )CH-QS 100 (199 G) + 101 (8196 ) hv? Michler' s ketone

(CH3)3CQH 102 (1296 overall) hvj Michler’s ketone (CHs)aCH-SH ---- :----=^=------> 103 (W) + (3k%) + (a!tf) (55) hv, Michler's ketone

0 0 / — \ I* M ® . . ( V-CH2-C-SC2H5 + CH3-C-SC2H5 (56) hv, MichlerTs 105 ( 10# 101 (12# overall) ketone overall)

CH3OV 0 0 CH3O' ch3oc-ch2CH2H ^0-SC2H5 t v(l7T)5t ; tv? Michler's ketone 106

II O C-SC2H5 + 101 (trace) (5 8 ) hv? M ichler' s ketone 2SL ^ 95 mine If there are any differences In the thermal and the photochemical

■behavior of 88 in different solvents. Irradiation of 88 in methanol in Pyrex (JO min) affords methyl a-thioethoxyacetate (

(Equation 49). The products of thermal and photolytic decomposition of 88 are identical and are presumably formed via a carbenic rearrange ment p rocess.

Direct photolysis of thiolacetate 88 in 2-propanol (Equation 5 0 ) through Pyrex results in near-quantitative conversion to a mixture of iBoprppyl a-thloethoxyacetate ( lOO, 96 . 5 mole $) and e th y l th io la c e tate (10lj 5-5 mole ^). Ester 100 is a product of rearrangement and solvent incorporation ester 101 is a reduction product of 88. Ester

100 was separated by preparative vapor phase chromatography and its structure is established by elemental analysis and ir and nrar spec trometry. Reduction product 101 is assigned by comparing its reten tion times on gas chromatography with that of an authentic sample.

Direct photolysis of 88 in t-butanol (Equation 51) affords t- butyl a-thioethoxyacetate (102) ~ quant) in JO minutes. Ester 102 is a product from Wolff rearrangement whose structure is assigned on the basis of ir and nmr analyses of a preparative gas chromatographic sample. Photolysis of 88 in the more nucleophilic solvent 2-prcpane- thlol (Equation 52) yields isopropyl a-thioethoxythiolacetate (lOJj

98 mole %), ethyl n-thioisopropoxybhiolacetate (§4, 1 mole °f>), and ethyl thiolacetate (101, trace) in an overall material balance from

88 of 95^5. Thiolester 10J, the product of rearrangement and addition, was separated by preparatiye vapor phase chromatography. Ester a 96 product of solvent insertion, and ester 101, a product of reduction, were id en tified ‘by reten tio n time comparisons with authentic Baraples.

Photolysis of diazo thiolester 88 was then Investigated in the presence of photosensitizers with the objective of effecting triplet paths for decomposition of 88 in which the chemistry might be differ ent from the Binglet processes presumably involved in thermolysis and direct photolysis of 88 . Sensitized decomposition of 88 in 2-propanol, a good hydrogen-atom donor solvent, by Michler*s ketone [bis(^-dimethylaminophenyl) ketone] (Equation 5?) gives a mixture of ethyl thiolace ta te (101, a reduction product, 8 l mole $) and isopropyl a-thioethoxyacetate (100, a rearrangement product, 19 mole $) in an overall material balance from 88 of 62$. Overall and relative yields were determined from gaB chromatography by use of an internal standard. The light, from a 45° watt Hanovia lamp, was filtered through Pyrex. The solvent had been purged with nitrogen prior to reaction; during photolysis an inert atmosphere was maintained by bubbling nitrogen through the stirred reaction mixture. The incident irradiation at 366 np. is captured (> 35,38,37 99$) by the sensitizer, Michler 1 s ketone. The increased yield

(35) Michler1 s ketone exhibits a maximum absorption at 366 ny (e = 28,500) in ethanol. Ethyl o'-dlazothiolacetate shows absorption

a t 366 ( e = 15). By use of Equation i the percent light cap

ture by the senBitizer is calculated to be greater than 99$*

el is the extinction coefficient at wavelength 1 and 0 is the

concentration. 97

y . ®^sencsen x 100 / v t> light capture = —------—— ...... — (1 ) ' e^Bencsen + e^diazocdiazo ♦ .»

2 8 ,5 0 0 (0 .1 5 molar) x 100 2 8 ,5 0 0 (0 .1 5 molar) + 15 (.115 molar)

“ 99 (5 6 ) M. S. Newman, “An Advanced Organic Laboratory Course,” Chapter

9, MacMillan, New York, 1972. (37) Neither ethyl thiolacetate (lOl) nor isopropyl o'-thioethoxyace tate (lOO) react under the reaction conditions for photosensiti

zation. Ethyl cv-dlazothiolacetate ( 8 8 ) does not react in 2-pro panol in the presence of Michler's ketone at 25° in the dark in 4 hours.

of reduced product, ester 101, upon use of 2-propanol rather than me thanol is proposed to result from abstraction of hydrogen from the sol vent by triplet intermediates. Photosensitization of 88 in the poor hydrogen-atom donor medium t-butanol (Equation 5^) affords e ste r 102

(125G overall), a product of Wolff rearrangement and solvent incorpora tion; no ethyl thiolacetate (lOl), a reduction product, is formed. Great care was given to use of proper photosensitization techniques in these 35, 36 experiments, as outlined previously.

On the other hand, photosensitization of dlazo thiolester 88 in an excellent hydrogen-atom donating solvent such as 2-prqpanethiol (dis tilled and purged with nitrogen before use) (Equation 55) yields iso 98 propyl cy-thioethoxythiolacetate (lOJ, kO mole $ ), ethyl a-thioisopropoxythiolacetate (9k, Jk mole $), ethyl thiolacetate ( 101, 2k mole $), and 2-propyl d isu lfid e (lOU, 3$ hy weight) in an overall material "bal ance from _88 of Vf$ (3 hr). Overall and relative yields were deter mined from vapor phase chromatography "by use of internal standards. Products 1 0 %kf 1 0 1 , and 10k are identified "by comparisons of gaB chromatography retention times with authentic samples. Ester 103, is a product of Wolff rearrangement whereas thiolesters %k and 101 are apparently products of H-abstract ion and then radical recombination with solvent, and H-abstraction, respectively. The formation of pro duct j i g , will be discussed shortly.

Photosensitized decomposition of of-diazothiolacetate 88 was then investigated in cyclohexane. The purpose of this study was to deter mine if cyclohexane undergoes efficient hydrogen abstraction and carbon- hydrogen insertion in the photosensitized process. In the presence of

Michler's ketone (Equation 56) irradiation of 88 in neat hexane for 3 hours gives ethyl cyclohexylthiolacetate ( 105* 10$ overall yield), a product of C-H Insertion, and ethyl thiolacetate (1 0 1 , 11$ o v erall yield), a reduction product derived from transfer of two hydrogen atoms from the environment. Cyclohexylcyclohexane, a product of apparent dimerization of eyclohexyl radicals, was also obtained in low yield

( 5 . 3$). It was not possible however to obtain satisfactory material balances or establish the products or the course of the major processes by which 88 decomposes in these experiments. Comparisons of the chromatographic retention times of 105. and 31)1 with authentic samples verify the structures of these products. Cyclohexylcyclohexane was identified "by gas chromatography-mass spectrometry.

Photolytic and photosensitized decompositions of 88 were then studied in olefinic solvents to determine if the carbenic processes 38 allow addition to carbon-carbon double bonds. Ethyl o'-diazothiolace-

(3 8 ) M, Jones, A. Kulczycki, and K. E. Hummel, Tetrahedron Lett ., 183

(1967 ); M. Jones, W. Ando, and A. Kulczycki, Tetrahedron L ett.,

1391 (1967 ) report stereospecific addition of singlet bis(carbomethoxy)carbene to olefins, and non-stereospecific addition of

trip let bis(carbomethoxy)carbene.

ta te (8 8 ) and 1, 1-dimethoxyethylene do not react in the dark at 25° in

24 hours. Direct photolysis of 88 in 1,1-dimethoxyethylene results in formation of ethyl 3 -carbomethoxythiolproplonate ( 106) in trace amounts. Under these conditions 1,1-dimethoxyethylene does not function as an effective capture agent; apparently Wolff rearrangement of 88 to th io - ethoxyketene ( 110) and products thereof occurs almost completely.

Photosensitized decomposition of 88 in 1,1-dimethoxyethylene in the presence of Michler1s ketone (3 hr; 99% of the light was captured by the photosensitizer; oxygen was excluded from the reaction mixture) results however in effective addition to the electron rich olefin to y ield e ste r 106 ( 38 $ overall yield) (Equation 57)* An analytical sample of 106 , obtained by preparative vapor phase chromatography, was identi fied by ir (ester and thiolester absorptions at 1735 and 1690 cm"1 re- spectlvely), 3 1 nmr, and mass spectrometry. Ester 106 is proposed to result from in itial formation of a, cyclopropane which may undergo ring cleavage as indicated in Equation 59- What is of significance

.0CH3 CH3O OCH3 N2 0 / \ / 0 n II h2 c = c < / „ H-C-C-S-C2H5 ------| CH-C-S-C2Hs -£-»■ PS* HaC""

CH3O OCH3 \ / OH 0 cN 1 e 11 | CH— C—S - C2Hs ------► CH3O-C - CH2- CH2 -C —S - C2H5 (59 ) HaC' © I OCH3

0 0 HaO I I I I > CH3O - C - OH2- CHs- C - S - CaHs

in this system is that by an apparent triplet rather than a singlet process 88 undergoes loss of nitrogen and capture by 1, 1-dimethoxy- ethylenej capture of diazo compounds and/or carbenes by 1., 1-dimethoxy- olefins may also be of synthetic value for preparing n-substituted carboxylic esters.

The behavior of 88 toward methylenecyclohexane is analogous to that with 1,1-dimethoxyethylene. Thiolester 88 and methylenecyclo- 101 hexane do not react in the dark at 25° in 2k hours. Direct photolysis of 88 in methylene cyclohexane does not allow capture by or hydrogen transfer from the solvent. Photosensitized decomposition of 88 in the presence of methylenecyclohexane and Michler1s ketone however (Equation

58 ) yields the adduct, 1-carbcthioethoxyspiro[ 2 . 5] octane ( l 0£, 51$ 30 overall yield) and the reduction product, ethyl thiolacetate ( 101* tra c e ).

(39) Spiro compound 10£ was isolated "by preparative gas chromatography and its structure established by analysis and by ir and nmr 40 methodB. The cyclopropyl protons of 10J absorb at 0.8J ppm.

(40) R, M. Silverstein and G. C. Bassler, "Spectrometric Identifica tio n of Organic Compounds,” Chapter k, John Wiley and Sons, New

York, 1967 .

Carbenic decomposition of ethyl or-diazothiolacetate ( 8 8 ) may occur by singlet and/or triplet mechanisms. If discrete carb.enes are

OU) (a) a-Diazoesters and o'-diazoketones photolyze and thermolyze b-d , . primarily via carbenic processes in alcohols. (b) E. Wolff, Z. Phys. Chem. A bt., BIT, k6 (1932); (c) W. Kirmse and L. Horner, Ann., 62£, $k (1959); (d) U. Mazzucato, D. Cauzzo, and A. Fol-

fanl, Tetrahedron L ett., 1525 ( 1963 ). 1 0 2 actually, involved as reaction intermediates from 88 , there are thus two structural possibilities, singlet (108) and triplet (lOg.) carbo- thioethoxycarbenes. For thermal (Equations 4-7 and 48) and photochemi cal (Equations 4-9-52) decompositions of 88 which result in Wolff rear rangement, it is likely that the reaction process is of the singlet

0 0 © II . II H-C-C-S-C 2H5 H-C-C-S-C 2H5 © 108

1 , 5 - 1 0 , 1 5 type possibly as Indicated in Scheme 2. Thus 88 may decompose to singlet carbene 108 which undergoes intramolecular attack by diva lent sulfur to give S-ethylthiacyclcprqpenone (ill) and/or thioethoxy- ketene (110). Reactions of 110 and/or 111 with nucleophilic solvents w ill thus lead to derivatives of thioethoxyacetlc acid as is observed. An alternate mechanism for Wolff rearrangement which cannot be excluded is participative attack of divalent sulfur at the or-carbon of 88 in which there is nucleophilic elimination of nitrogen giving 110 and/or 1 1 1 . The important feature in the present system leading to rearrange ment is the ability of divalent sulfur to express nueleophilicity and possibly utilize itB d-orbitals in reaction at singlet divalent car- 23, 2 0 - 2 9 , 4 2 bon. Singlet carbenic decomposition of 88 doeB not give pro ducts of solvent capture and insertion because the intramolecular rear rangement process(es) are so much more rapid. Scheme 2

0 II H-C=C=0 3*03 ^ C2HsS-CHaC-GR* I SC2H5

- ] f e J (42) C. C. Price and S. Oae, "Sulfur Bonding/’ Ronald Press, New York,

1962 .

Photosensitized decomposition differs from thermal or photolytic

decomposition of 88 in that rearrangement is suppressed and products 43 derived from radical-like abstraction and insertion are obtained.

(43) A. Padwa and R. Layton, Tetrahedron Lett., 2167 (1965 ) report that

photosensitized decomposition of a-diazoacetophenone in 2-pro-

panol results in a decrease in yield of Wolff rearrangement pro

duct 112 and an increase in reduced product 11% as compared to direct photolysis.

0 Na 0 II II hv II Cq H s-C-C-H CsH5CH2C02 CH(CH3)2 + c6h5-c-ch3 2-propanol 112 113

d ire c t photosensitized 2.5 0 .0 0 3

Photosensitized decomposition of diazothiolacetate 88 is a triplet process and the various reactions of triplet ethyl a-diazothiolacetate (114) and/or trip let carbene 10£ are summarized in Scheme 3* Although

the triplet processes for 88 have not been completely defined, it is clear that divalent sulfur is much less involved in triplet than in Scheme 3

o II CH3-C-SC2Hs

E-abstraction

3 E2 0 0 0 II II H • II E-H H-C-C - SCgHg H- G — C — SCsHs R—CH2 -C-SC2H5

n h m

Infcersystem Crossing

C-SCaHs II 106 28 ,29 singlet carbenic processes. It is also apparent that there can he only minor intersystem crossing in photosensitized decomposition 4 4 - of diazo thiolester 88 . Nevertheless, Wolff rearrangement products

(41*) N. J. Turro, “Molecular Photochemistry,” p. 50, W. A. Benjamin,

New York, 19&5*

(lOO, 1 2 $ , Equation 55; 102, 1 2 $ , Equation ^b; 1 0 £ , 1 8 $ , Equation 55) are formed in photosensitized decompositions of 8 8 , Singlet carbothioethoxycarbene (l 0 8 ), formed from triplet lffi hy intersystem cross ing, may lead to Wolff rearrangement in the photosensitized processes since rearrangement of triplet carbothloethoxyearbene ( 10^) is pre- 7 -1 0 sumahly forbidden. Prior investigations have proposed rearrangement of triplet of-carbonylcarbenes to ground state ketene is spin forbidden (Equation 60), and isomerization of triplet carbenes to the lowest excited triplet ketene is energetically unfavorable (Equation 6l ) .

0 . II H- c-C-R H-C=C=0 (6 0 ) I R

0 ■I* < 1 H-C-C-R 0—> H—C—C=0 — H—C=C—0 I inversion I (6 1 ) R R 107

Triplet carbothioethoxycarbene (109.) rather than triple* carb- 7 ethoxycarbene (ll£), however, may he able to undergo Wolff rearrange ment to the lowest excited trip let of thloethoxyketene ( 117 ) in a more

energetically favorable process (Equation 6 2 ). Diradical 116 may re-

0 . I! H — CJ—C—SCpHs H“ C C H— C- C = 0 \ / t S* SCa H5 I C2H5 116

(6 2 ) s p in H -C =C =0 in v e r s io n t SC2H5

110

present a transition state or an intermediate in which sulfur partici- 42 pates by expansion of its octet using a vacant 3d orbital. Triplet lOff is radical-like and sulfur has been reported to stabilize distant 45*49 radicals. Thus, t-butyl ortho-thiosubstituted perbenzoates (ll 8 ) decompose 10 4 times faster than t-butyl ortho-iodoperbenzoates (Equa- 45 42 t i o n 6 3 )* Formation of radical lift in which sulfur expands its octet 4 5 ,4 6 has been proposed to account for the rate acceleration. Similarly, photolysis of 2- io d o - 2 '-(raethylthio)biphenyl ( 120) to give dibenzothio- 108

CH3 I s ^ o - o - c ( c h 3 ) 3 (63) Os. ■oc(ch 3 ) 3

118 233.

(4 ?) J» C. Martin and W. G. Bentrude, J . Amer. Chem. Soc., 84 , 1561 (1962 ).

(46) M. C. Caserio, R. E. Pratt, and R. J. Holland, J, Amer. Chem.

S o c ., 88 , 57^7 (1967).

p h en e ( 100$) has "been proposed to involve a radical path in which sul 47 fur participates at the radical site (Equation 64).

CH3S hv -CHsI

120 (64)

(47) J. A. Karapmeier and T. R. Evans, J. Amer. Chem. Soc., 88 , 4096 (1966 ).

(48) W. A. Pryor and K. Smith, J. Amer. Chem. Soc., £2, 2731 (197°). (49) E. S. Huyser, “Methods in Free-Radical Chemistry," Volume 2,

Chapter 1, Marcel Dekker, New York, 19 69 .

Among the more interesting observations of the present study is that decomposition of thiolacetate 88 as catalyzed hy silver or cuprous

ion results in exclusive formation of products of Wolff rearrangement with incorporation of solvent (Equation 6 5 ). Metal ion catalyzed de composition of o-diazocarboxyllc esters has been observed to give sol-

AgNOa CH3CH, CH30H 0 If ♦ C2Hs - S - CH2 - C — och 3 (6 5 )

CuCl 28 CH3CN, CH3OH

vent and intramolecular insertion products, whereas, Wolff rearrange- 1, iB-22 ment processes have never been reported. In the present system

ethyl o-diazothiolacetate ( 8 8 ) may react however with silver or copper

ionB by the proposed simplistic mechanistic paths to give products of

rearrangement (Schema 4). The metal ion may thus coordinate with 88 to form m etallo diazonium ion 121 (Scheme 4) which (a) loses nitrogen

and the metal ion to give carbothioethoxycarbene ( 1 08 ) which reacts via the reaction paths described in Scheme 2, or (b) expels nitrogen to yield organoraetallo cation 122 which undergoes rearrangement and Scheme h

0 -B a h - o - o - s c 2h5 J S S S L i . -M© 108

1 MO HsC------C

-Ba I H \ / h - c - c - sc2h 5 ——42— » s © © I 122 CaHs

M 0 _ 0 | II h 11 RQH H -C -C -O R ------z*—* C 2H5S-CH^-C0R | -M ^ SC2H5 110 I l l

subsequent reaction with nucleophilic solvents.

The f i r s t of the two mechanisms is the simpler process and has th e advantage that a carbene is produced whose properties are identical to that presumably involved in thermolysis and in photolysis of 8 8 . Re arrangement of metallo cation 122 as in Scheme 4 is analogous, however, IB to the mechanism proposed by Wenkert et al for Wolff rearrangement

of or-diazo ketones. If indeed argento and cupro cations of 121 and/or 122 do lead directly to Wolff rearrangement processes, as in Scheme k, the behavior of 121 and/or 122 is decidedly different from that of pro vocation analog 9,5 and/or g 6 as presumably involved in Scheme 1. It

is noted however that the behavior of 121 and/or r122 can be different than that of provocation analog and/or. 96 i f 121 and/or 122 under go sulfur participative attack in which bond breaking involving the metal is highly or completely developed (Equation 6 6 ). Such a mechan istic process then is a variant of mechanism waw as outlined in Scheme

M 0 0 I II -M II H-C-C-SC 2Hs H-C ------C'‘ ROH C2H5SCH2-COR © V 122 I (66) C2Hs

Other BUbtle differences may be envisaged which might result in the difference in behavior of 1 2 1 and/or 1 2 2 and their provocation

analogB. 112

Cationic and carbenic reactions of ethyl a-diazophenylthiolace-

tate (82.) have also "been studied. The experimental plan for investi

gation of 8 2 is analogous to that followed for 8 8 .

» Ethyl a-diazophenylthlolacetate (82) is obtained from phenylglyoxylic acid jo-tosylhydrazone by reaction with thionyl chloride and then

ethanethiol and triethylamine (Equation 6 7 ). The synthesis is a fur- 30 ther extension of that of House and Blankley. Diazo thiolester 82

0 0 Na 0 || || 1. TosEHMIs 11 11 C6H5- C - C - O H g* 80Cla CqH5-C-C-SC 2 H5 \°J) 3. C£H 5SH, 2 82 ,

is an orange liquid which exhibits infrared absorption at 208 l ( C=N2), i? 33- 1645 (-C -S-), and 1615 cm”1 (-C=N-). The nmr and uv absorption

spectra (see Experimental) of 82 support its assigned structure, Thiol

e s te r 8 2 is fairly unstable and thus its quantitative elemental analy ses differ slightly from that of theory. Use of tertiary amines to

minimize decomposition of 8 2 is of limited advantage. Diazo ester 8 2

decomposes in pyridine-d 5 a t 25° in the dark. UMR analysis of a pyri

dine solution of 8 2 reveals steady disappearance of absorption at 2.93

ppm (quartet) and appearance of absorption at 2 .6 7 ppm (quartet). After 48 and 72 hours, respectively, at 25°, 82 is 42 and 60$ altered. Ester 82 is satisfactorily storable however at -78° in darkness. The study of cationic reactions of ethyl of-diazophenylthlolace-

ta te (8 2 ) is summarized in Equations 68-72. In darkness and in the CH30H >■

25° i SC2H5 (69^5) 0 CH3OH II „ ------I --► CgHs C5 — C—SC2H5 25°, H I 0C53 12lf

N2 0 0 II II ch3co2h II CeHs-C-C-SCsHg CsHs-CH—C-SC2H5 251 OCOCH3 J& 125

0 0 (053)3005 II II CsSs- CH-C-SC2H5 + CsH5- OS-C - SC0H5 H+, 25° * OH 0- 0 (053)3 126 (k5%) 127 (55%)

0 II CF3C02S c6h5 - c h - c - s c 2h5 I ~ * 0 -COCF3 1 2 Q 114 absence of additional acid, dlazothiolacetate 82, reacts with methanol (Equation 68) in 48 hours to give methyl a-thioethoxyphenylacetate

(125, 69 $) and unchanged 82 (31$)• V7hen 82 in methanol is treated, however, with sulfuric'acid in catalytic quantity, gas evolution is rapid and within one hour ethyl o-methoxyphenylthiolacetate (124, 85 $;

"by nmr, gas chromatography, and isolation) is produced (Equation 6 9 ). Reactions of ,§2 with methanol and with methanol-sulfuric acid differ in that in the acid-catalyzed process the thioethoxyl group does not migrate, Ihe behavior of 82 in methanol-sulfuric acid is analogous to that found for dlazothiolacetate 88 (Scheme l) and is described in 5 Scheme 5* Acid catalyzed decomposition of thlolester 82 in less nucleophilic solvents than methanol such as glacial acetic acid at 25° (Equation 70), acidic t-butanol at 25° (Equation 71), and trifluoroacetic acid at 0° (Equation 72) yields products derived from processes in which the t. S-ethyl group does not migrate. Products 125 (Equation 70), 126 and ~~ V .127 (Equation 71), and 128 (Equation 72) arise from solvent Insertion via cationic mechanistic pathways as proposed in Scheme 5* Identifi cations of • 125i"12 jTi were made, after their separation by gas chromato- / graphy, from their elemental analyses and their ir and nmr spectra.

E ster 328 was id e n tifie d by nmr and mass spectrometry.

An alternate method of generating cation 129 (Scheme 5 )# 8y reac tion of ethyl a-chlorophenylthiolacetate ( 1 5 0 ) with an equivalent of silver nitrate (Equation 7 3 ) in methanol, re s u lts in ethyl or-methoxy- Scheme 5

OR 0 ROH I H “*• C5H5 ■*** CH ~~ C — SC 2H5 ^ -N2

ROH -rfD

® R2 0 I II © II H - f e & CgHg” C C —SC 2H5 » CsH5CH-C-SC2H5 I H 129

-Ha > C6H5- CH----- Ye CgHg 1 1 6

C l 0 OCH3 0 1 , r AMD* "l 11 C6H5 ~ CH - C - SC2H5 > Cq H5- CH------C - S C 2H5 Me OH 130 124 (rflG)

(73) Cl 0 I II Cq H s -CH-C-OCH s + 1^0

' ------V------'

83^

phenylthiolacetate (124, 17$ overall), and starting ester 12& and methyl a-chlorophenylacetate 1^1 (a product of transesterification) to ta llin g 8 yield. No product was observed resulting from thioethoxyl i migration. NMR and vapor phase chromatography were used to identify the products.

The carbenic properties of ethyl

(123, 67$) and ethyl of-methoxyphenylthiolacetate (IS4, 33

♦y »-. - collected by gas chromatography and the relative yields were obtained , 50 from the nmr integration of the respective absorptions of 12% and 124.

(50) Acetate 12% exhibits nmr absorption at 4.49 ppm (CaHs-S-CH, slngl)

and 3 .6 7 ppm (-CO2-CH3, singl); thiolester 124 absorbs at 4.60 0 0 GH3 0 H II II C©H5—CH—C -OCH3 + CsH5—CH - C - SC£H5 (711.) 65° I I SC2H5 OCH3

123 (67%) 3 * (33%)

r ~ ^ Ife 0 m p 0 li II II f - \ CqH5"“ C— C—SC2H3 CqH5 — CH — C - U 0 (7 5 ) 65 I \ ----/ 82 SC2H5

222

0 H CB3OH CgEg CH “ C — OCH3 (76) 25°, hv ! SC2H5 . ’ 123 E 0 0 (CE^)aCH-OH 11 11 > CeHs— C H - C - 0 CH(CH3 )2 + CsHsCHs-C-SC2H5 (77) , hv I SC2Hs

13k (9990 135 (trace)

( CM3 ) 2CH- OH 13^ (9996 ) + 135 (trace) (7 8 ) li\)^ CH2Br2

Xfe 0 (I il CgH5 ~■ C *“ C — SC2Ife-

(CH3)2CH-OH 13^ (8l95 overall) + 135- (trace) (79) hv, Michler*s ketone

CH(CE3)a I 3jj- (5796 overall) + Xpp (1.790 (8 0 ) ( CH3 )2 CH- OH, h.v Michler*s ketone £CD 119

ppm (CH3O-C-H, sin g l), and 3.^° ppm (R 2 CH-OCH3 ).

Independent synthesis of methyl a-thioethoxypherylacetate supports the structural assignment of lg3. Formation of methyl n-thioethoxyphenylacetate (3.2^) from 8 £ and warm methanol involves Wolff rearrangement of the thioethoxyl group and subsequent addition of methanol. This process for 8 g, is analogous to that observed for 08 and appears to involve formation of thioethoxyphenylketene ( 132) hy a carbenic process and solvent incorporation. Ethyl a'-methoxyphenylthiolacetate QS4) may be formed by cationic reaction with methanol, or, less likely, by carbenic insertion into methanol rather than rearrangement. The reason for the latter opinion will be indicated shortly.

Carbenic decomposition of diazo thiolester 89 was then investi gated in a nucleophilic solvent that is ..much less acidic than methanol.

Thermolysis ( 65°) of 8 £ in the jpresence of one equivalent of morpholine

(Equation 75) yields k(o'-thioethoxyphenylacetyl)morpholine (133, 67$ overall), the product of Wolff rearrangement and subsequent addition of morpholine. There are no products derived from insertion or addition of the solvent at the diazo center of 8 g, and thus it may be presumed that the previous thermal reaction of methanol (Equation 7^) to give 12jl involves a cationic mechanism. Amide 133 ‘was separated by column chromatography and its structure is assigned on the basis of its ele- f l , 3 1 mental analysis and its ir absorption at l 6h$ (-C-Nx ). 1 2 0

Direct photolysis of 8 ^ in methanol (Equation 76), through Pyrex * a t 25° (30 min), gives methyl ester 12^ the product of thloethoxyl migration and methanol addition, in near quantitative yield. It seems

convincing that photolysis of 8 g, in methanol involves a carbenic pro cess and that thermal reaction of in methanol to give 12 ^ occurs via a cationic rather than a carbenic mechanism. Furthermore, decom position of by incident Irradiation at 25° in 2-prqpanol (Equation

7 7 ) results in isopropyl

(5l) Ester was preparatively collected by vapor phase chromatogra phy and its structure determined from analytical, ir, and nmr

data. Thiolacetate 135 -was identified by comparison of its re

tention time upon vapor phase chromatography with that of an authentic sample.

photolysis of 8 *? in 2-prqpanol containing methylene bromide yields products (Equation 78 ) essentially identical with those outlined in

• the absence of methylene bromide. Photolytic .formation of 134 from

89 , and 2-propanol thus appears to occur by a singlet carbenic pathway as outlined In Scheme 2 , and heavy atoms from methylene bromide do not cause intersystem crossing to a triplet, mechanism,.

Photosensitized decomposition of 8 £ in 2-propanol, in the pre sence of Michler1s ketone (Equation 79), for 3 hours, yields isoprqpyl e s te r .134 (81^ overall), a product of Wolff rearrangement and subse- 1 2 1 quent solvent incorporation, and thiolester 135 (trace). There is no essential change in products when 89 is decomposed "by incident irra - diatlon or by photosensitigation (Equations 77-80). Photosensitized \ decomposition of 8jj? was carried out in oxygen-free 2-propanol under nitrogen at 25°. A uranium glass filte r (Corning Glass Co. #3178)# w ith a 530 np cutoff was used to remove incident lig h t th a t might cause direct photolysis of diazo thiolester 89 . The concentrations of thiol ester 89 and sensitizer are such that the Michler's ketone absorbs 35,36 better than 99$ of the light at 3 66 ny. [Ethyl o-diazophenyl- \ thiolacetate ( 8 9 ) exhibits absorption at $66 ny (e - 6 0 ).] The photo sensitized reaction was repeated four times; the results are repro ducible. Photosensitization of 89 in a better hydrogen-atom donating solvent, such as cumene/ 2-propanol, affords no essential change in products (Equation 80 ).

The difference in behavior of ethyl a-dlazothiolacetate ( 8 8 ) when decomposed by direct light and by photosensitization has been previously described (Equations ^9-58). Ethyl a-diazophenylthiolacetate ( 89 ), however, ex h ib its no change in i t s chemistry when decomposed by in c i dent irradiation or by sensitization (Equations 77-80),

Direct photolysis of 89 (Equations 76-78) is expected to involve the excited singlet diazo compound (136) and/or singlet carbene 137 and/or the corresponding B-ethylthiacyclcpropenone;.photosensitization . of 89 should result in triplet dlazothiolacetate 13.8 and/or triplet 8 -1 0 carbene 1^9. Strausz et al have reported that Wolff rearrangement of triplet carbethoxycarbene (ll^) does not occur. The chemical results 1 2 2

'Na 0 0 3jfe 0 II H 0 II It II CqHs-C-C-SC 2H5 C0H5 -C-C--SC 2HS C6H5 -C-C-SC 2Hs © 13g 137 3g8

0 . II CeHs-C-C-SCaHs

for photolysis and photosensitization of* 8 %, however, are identical and involve Wolff rearrangement with incorporation of solvent. A possible explanation for the results of photosensitized decom position of diazo thiolester jBg, is that rearrangement might actually

* involve a singlet process. One such possibility is that the ground state multiplicity of carbene 1J5J is singlet. Therefore, if triplet carbene 13% is generated, intersystem crossing to singlet l^X w ill be energetically favorable (Equation 8 l). Furthermore, if this iB the case and intermolecular reactions of triplet 13% are slower than spin

0 0 . 1 1 0 II CeHg-C-C-S-C 2H5 3£S___> CqH5 - C - C - S - C s H 5 (8 l) ©

m m l inversion to singlet 23L> only singlet processes (Wolff rearrange ment) w ill be observed. 125 Carbene Z5J may be a ground state singlet if its phenyl group do nates electrons sufficiently to the vacant orbital while carbonyl withdraws electrons from the filled orbital (l4o) of divalent carbon.

gVVc=<° SC2H5

140

Carbene 1%% may also be stabilized as a singlet by sulfur participa- 4 2 tion at the vacant orbital of the carbene involving 3p- 2p bonding and by sulfur expanding its octet via d-orbltal overlap (Equation 82) with the filled orbital of the carbene moiety. Within such a system, the

v ^ ^ t m I I I c2h5 c2h5 c2h5

phenyl ring and the carbonyl function can also delocalize the filled orbital of the carbene. A third possibility for stabilization of ljgfc as a singlet Involves donation by phenyl to the vacant carbene orbital while sulfur expands its octet (lbl). v I C2H5 1U1 . It Is not necessary for carbene 3J££ to be a ground state Binglet In order for the chemistry of direct and for photosensitized decompo sition of thiolester to be identical. If is a ground state triplet but yet is substantially populated as a singlet and if Wolff rearrangement of the singlet 1b faster than for its triplet, then only singlet chemistry will be observed. The resultant depletion in population of the singlet would lead to repopulation by intersystem crossing from the triplet and thus a triplet process might never be observable. A further modification of interpretation is that the energy levels of the singlet and triplet states of 3j?7 and re spectively, are very close and thus the chemistry of the two states is essentially identical and Wolff rearrangement may come from singlet and triplet processes.

The behavior of th io la c e ta te 8 ^ in methanol containing silver or cuprous ions became of interest to determine if the reaction paths are analogous to that for carbenic or cationic decomposition of 8 9 . S ilver n itra te or cuprous chloride rap id ly decomposes 8 £ (25°, one hour) to methyl

(91$ yield)], the product of Wolff rearrangement and addition of me thanol. Similarly decomposition of 8 g_ by silver oxide in refluxing methanol yields (Equation 85 ) ester 123, (67$) along with methyl phenyl- 5 2 glyoxylate (142, 26$) and methyl or-methoxyphenylacetate (l{£j 5, 7$).

Metal ion catalyzed decomposition of thiolacetate 8 g. in .methanol is thus analogous to thermal, photolytlc, and photosensitized decomposition of 1 2 5

(85)

Ha 0 0 II II II CaHsC — C-SC2H5 CeH5 -CH— C -OCH3 I sc2h 5 & s!a a . CuCl (8t)

N2 0 0 0 11 11 t e » 0 11 11 CsH5C — C -SC2H5 _£§£- —». 123 + CeHsC-C-OCHa CH3OH & (85) 0 II CeHg-CH- COCH3 I OCH3

1^3

8 £. The "behavior of Sg with metal ions is also identical to that of

(52) Methyl phenylglyoxylate (1^2), identified "by nrar and gas chroma

tography, is derivable from 8 £ "by oxidation and transesterifica-

tion, or transesterificatlon and oxidation. Methyl o'-methoxyphenylacetate (14^), also identified "by nmr and gas chromatogra

phy, may have "been formed hy transesterificatlon of 8 *? and ca- 1 2 6

tlonic methanolysiB, or cationic decomposition of jBg, and trans-

esteriflcation.

thiolester 68 (Scheme *0, thus Indicating that metal ion catalyzed 1, 10-22 Wolff rearrangements of o-diazo thlolesters will be general. Cationic and carbenic decomposition of ethyl o-diazo-£-nitrophenylthiolacetate (go) was then studied. Thiolacetate ^0 was synthe sized by reaction of ethyl £-nitrophenylthiolacetate with N-methylmorpholine and j>-tosyl azide (Equation 8 6 ). The synthetic method is an extension of that of Regitz. 5 3 Diazo thiolester ^0 is a solid (mp 8 l -

82 °) that can be stored Indefinitely at room temperature taking normal

0 N2 0

P-02N-CsH4-CH2-C-S-C2H5 -9^^ £-02N-C6H4-C-C-SC2Hs (8 6 ) CVH7S02N3 \

. 2 0

(53) M. Regitz, Angew. Chem., J 8 ,6 8 4 ( 1966 ). precautions for light exclusion. The ester exhibits lr absorption at

2090 (^C=N2)j l6k0 (-G-S-), and 1582 cm" (XC=K<-). The stru ctu re assignment for JgO is also in agreement with its quantitative analysis and its uv and nmr absorption. . ... Study of decomposition of thiolester £0 by protonic acids was effec ted (Equations 87 - 9 1 ). Thiolester £0 does not react with methanol o H 127 & » ■ ' ON ON

0 — 0 i to o = o w 0=0 w* 0 = 0 fcd ‘ < S * — to f t H CV1 04 si 1 *1 Si ft I

£ $ d CO to n 0 = 0 n o = o is ^ | f t 0 — 0 IA ii-8 f CO I h O O \k> 5 03 2> f t pj ft P4

lf\ VO

t? CQ9 I o = O I 3OI 81 hi 1 2 0

at 25° in the dark in 1*8 houPB (Equation 87). When catalytic quanti

ties of concentrated sulfuric acid are added to £0 in methanol at 25°*

(Equation 8 8 ) nitrogen is evolved and within 3 hours the color of the

reaction mixture is pale yellow. NMR analysis of the product reveals it to he a mixture of ethyl a'-methoxy-jj-nitrophenylthiolacetate (144, 54 85?*) and methyl o'-thioe thoxy nltrophenylacetate (l45, 15^). In this acidic system the major product (j44) is apparently farmed via a ca-

( 34) Thiolacetate 144 has a nmr singlet at 4.75 PPm for methine Ha P-O2NC0H4 0 I tl (CH3O-C — C-) and a singlet at 3*52 ppm for methoxyl protons. I Ha Phenylacetate 143 exhibits a nmr singlet at 4.58 ppm for methine 0 SC2H5 II I Hb (CH3 0 -C-C-C6H4N02) and a singlet at 3*72 ppm for methoxyl — I Hb protons.

tionic process in which there is no thioethoxyl migration. It is noted, { however, that acetate ,14§ is formed in significant quantity, and it is * a product derived from migration of the S-ethyl group.

Decomposition of jgO in acetic acid was then examined. Glacial acetic acid at 25° in the dark does not alter jgO in 24 hours (Equation •

89). At 650 however jgO is converted in one hour to a mixture of ethyl

a-acetoxy-£-nitrophenylthiolacetate (146, 60$) and acetic of-thioethoxy- 55 j>-nitrophenylacetic anhydride (147, 40^) (Equation 90). 229

(55) Products 1 ^ and lV£ were identified by nmr methods. Ester 3-^7

exhibits a singlet absorption at 6 .2 0 ppm for methine H I Cj (CH3CQ2 — C—, -H) and a quartet a t 2.81 ppm (-C-S-CHp) — . Anhydride 1^7 shews a sin g le t a t 55 ppm for methine H^-C-Ha) and a SC2H5 quartet at 2.60 ppm for methylene protons adjacent to sulfur.

Formation of thiolester 1 k6 as the principle product thus occurs with out thioethoxyl migration and is consistent with the previous patterns

for cationic decomposition of u-diazo thlolesters. Conversion of 2_0 by acetic acid to anhydride lV£ involves migration of S-ethyl how

ever, and the process is near competitive with that leading to 3A6. Trifluoroacetic acid converts jgO at 0° (Equation 91) to ethyl o-

trifluoroacetoxy-j>-nitrophenylthiolacetate (lU 8 , 72%) and u-thioethoxy-

nitrophenylacetic trifluoroacetic anhydride (Jjj&t> 28%). N 5 6The major action of trifluoroacetic acid thus results in cationic alteration of

(56) Ester 0*8 displays a sm yinglst at 6.32 ppa (® 3-C

a quartet at 2.81 ppm (-C-S-CHg-). Anhydride lUg. shows a nmr

singlet at 4.57 ppm (C2H5-S-C-H) and a quartet at 2,59 ppm

(-C H a -S ).

£0 without S-ethyl migration. This acid-catalyzed process is

accompanied however by thioethoxyl migration and solvent addition upon

formation of from 2 2 .. 330 I The conversions of Jgfi by acidic methanol, acetic acid, and tr i fluoroacetic add to thlolacetates JAjfc 3A6. and 3.48 are apparently cationic reactions (Scheme 6 ) ^analogous to that described for 88 and

8 ft (Schemes 1 and 5). The transform ations of _§0 by acidic methanol, ace tic add, and trifluoroacetic acid to products deriyed via thioethoxyl migration and solvent Incorporation (3A-5, l^T, and ±}\p) are of note however in that they are formally analogous to prior carbenic pro cesses exhibited by 88 and 8 £. It is likely however that In formation of l kj?, and even from $0 the mechanistic routes are of the cationic rather than the carbenic type. Cationic behavior of .ftp leading to S-ethyl migration may srlee as a result of generation of of the high energy cation 150* Cation 150, destabilized by the conju- gative and inductive effects of its nitro group, may react intramole- cularly with thioethoxyl and undergo- ring opening in competition with reaction with nucleophllic solvents (Equation 92).

0 © II £-0eN-C6H4-CH-C-SCaH5 £-0aN-C6H4-C

(92)

> £-02H-CeH4-CH-C-0R

SC2H5 Scheme 6

OR 0 -Ha, I II £-Q2RC0H4 - CH- C - SC2H5 4- ROH

-H' HOR

®lTa 0 0 H+ 1 II -ira © II JgO r- ^-QaUCsEi “ C~ C -S C a a s ■ E “QaN—CqH^— C — C— SC2 Hs I H H 150

■Na

j CL CqHi — CHY QaHs 1 3 2 The studies of carbenic reactions of ethyl oe-dlazo-jD-nitrophenylthiolacetate (90) are summarized in Equations 9? and 9*1- Diazo thiol

acetate jgO in refluxing methanol for 12 hourB y ield s methyl e s te r l fe% (91 %) as the sole product (Equation 93).. Direct photolysis of ^0 in \ \

90 M*03- p -0 2N- CsH4- CH—C -0CH3 (93) A 1 SC2H5

20 1U5 (9 *1-)

methanol at 23° also gives methyl ester lj+Jj quantitatively. Ester 1^5

is proposed to arise via mechanistic paths as outlined in Scheme 2 for 88 . Photosensitization of diazo thiolester %0 was not attempted be

cause its uv spectrum reveals very large absorption maxima at 236 up (e = 9,000) and 3^5 njt (e - 10,500). Absorptions in these regions can

“* result in ineffective photosensitization of JgO by Michler’s ketone. Diazo compound 2Q, a poor nucleophile, does not decompose in me

thanol a t 25- 30° in the presence of silver or cuprous ionB. \ Interpretation of the carbenic reactions of diazo esters 8 8 , 89 ,

and 3 0 invoke S-substituted 2-thiacycloprcpenones and"'ttiioalkoxyke- 1 tenes as Intermediates which add to solvent to give products of Wolff \ rearrangement. A further objective of this study then has been to determine whether a new cI sbs of compounds, S -su b stitu ted 2-thiacyclopropenones (%), are isolable as discrete products of intramolecular migration of divalent sulfur to divalent carbon In

(57) R. Breslow, R. Haynie, and J. Mira, J. Amer. Chem. Soc.. 8l,

247 ( i 960 ).

Thermolysis and photolysis of diazo thiolester 83 , in hexane were effected in efforts to prepare S-ethyl-3 -phenylthiacyclopropenone

(1 5 1 ). Thermolysis of 8£ in hexane ( 50- 65°* 5-12 hr) giveB a yellow a solid after fractional crystallization, rap IO 5-IO6 (36% y ie ld ), analyzing for C 10H10OS (1^2. see Experimental). Product 1§2 undergoes alteration upon standing several days in a capped bottle. The yellow solid turns straw-like and has a mp 180-184° (dec,). The physical and spectral data described are on a freshly prepared sample of 132.

The in frared spectrum shows a sharp peak a t 1734 cm -1 assignable to a carbonyl group ( C=0). \ 3 1 The aromatic protons in the nmr absorb at r * 7.75 ppm (2H) and 7.42 ppm (3H); the nmr shows a quartet at 2.62 ppm

(-S-CIJ2-) and a triplet at 1,01 ppm (-CH 3 ) indicating that the ethyl groups are symmetrical. Ultraviolet absorption maximum of 152 in cyclohexane occurs at 202 nji (e = 44, 000), with shoulders at 221 (e a lB ,6 0 0 ) and 262 (e = 4,040). These UV data imply that the 1^2 does 1 5 ^ not possess extensive conjugation. Molecular weight determination

(367) "by osmometry ("benzene) indicates th a t 152 is a dimer (MW = 356) of the formula (CioHioOS^. Mass spectrometry supports a dimeric product w ith a weak parent peek of m/e 356# and a prominent monomer peak of m/e 178 (<&$). I t appears th a t dimer 1§2 d isso ciates in the mass spectrometer to a monomeric species.

Dimer 132 does not form a 2 ,4-dinitrophenylhydrazone when treated with 2,4-dinltrophenylhydrazine.or react with "bromine - carbon tetra chloride in the dark. Oxidation of 152 by potassium permanganate - pyridine gives benzoic add. in near theoretical material balance. Ammonolysis of 1%2 in benzene yield s a white so lid (55$ y ield a f te r recrystallization), nip 139 -lUl0, whose elemental and spectral (see

Experimental) analyses are consistent with the structure 1%5.

(58 ) J . L. E. Erickson and G. C. Kitchens, J . Org. Chem., 2J, lf60

(1962 ) report that 2, 2 , k,^-tetraphenylcyclobutanedione is re

duced by potassium borohydride to syn- and antl- 2 . 2 ,4 ,4- te tr a -

phenylcyclobutanediols in high yield. Attempted reduction of

152 by sodium borohydride gives a white solid V?h (mp 185 - 190 °#

dec. j 52$ yield) exhibiting ir absorption at 1660 cm"x (^C=0 ) 31 and no hydroxyl absorption. Mass spectrometry of 1%_4 shows

what is probably the parent ion at 470 (l 5$)i the mass spectrum and elemental analysis show that sulfur and the ethyl group are

not present in 1§4. 355

0 GoH5 0 C®H5 II I II I • S jjN -C -C C—CH-SC2H5 I SC2H5

152.

The structure of thermolysis product ,122 was not ascertainable by the instrumental and chemical methods outlined above. It was therefore desirable to determine if dimer 1^2 could be prepared by another route* Phenylthioethoxyketene ( 132), a proposed product of

Wolff rearrangement of diazo thiolester 8 *? was prepared in situ from

(y-thioethoxyphenylacetyl chloride and triethylamine at 25° (Equation 59 95)* Workup of the ketene reaction mixture yields 1 5J2 (k2$). The

CeHs-CH-C-Cl------€ ---- * 1^2 + l§g (9 5 ) I -E ta®NH SC2H5 q]©

(59) The presence of ketene 1,2,2 was substantiated by l r absorption

physical and spectral properties of 1£2 correspond exactly with that of the product of thermolysis of diazo thiolester 8 £.It Is thus possible that 152 results from dimerization of phenylthi oethoxyket ene

C a s )• 136

Ketoketenes usually dimer lze to 1 , 3-cyclobutanedlones upon stand- eo-e3 no2 lug (Equation 96). Woodward argues that dimerizatlon of keto-

2 R^C -C *0 ► H2< 'yKs (9 6)

(60) H. Ulrich, “Cycloaddition Reactions of Heterocumulenes,” Aca

demic Press, New York, 1 9 6 7 .

(61) S. Patai, “The Chemistry of Alkenes,” Chapter 14, Interscience,

New York, 1964.

(6 2 ) R. B. Woodward and G. Smith, J. Amer. Chem. Soc.« JJ2, 1297 (.1950)•

(6 3 ) R. B. Woodward and R. Hoffmann, ‘*The Conservation of Orbital

Symmetry,” p. 168, Verlag Chemie, Weinheim, Germany, 1970*

ketenes to 1,3-cyclobutanediones proceeds in the least hindered direc tion at right angles to the planes of both molecules in a concerted fashion (Equation 97) If concerted, dimerizatlon of ketoketenes

R'"„ 1, c — c = 0 0

Ba (97) ss* o= c= c^' 0 R follows the rules of conservation of orbital symmetry. Dimerizatlon of ketoketenes to p-lactones Is extremely rare and apparently requires ©4 65 _ 61,66 acid or base catalysis (Equation 98).

Ra 2 R2C= C=0 AlCla (98) or NaOMe Ra

(64) R. H. Hasek, R. D. Clark, E. V. Elam, and J . C. Martin, J . Org. Y Chem.. ££, 60 (1962).

(6 5 ) R. Anet, Chem. In d .. 1313 (1961).

(6 6 ) D. G. Parnum, J. R. Johnson, R. E. Hess, T. B. Marshall, and B.

Webster, J . Aroer. Chem. Soc., 8 £> 5191 ( 1965 )*

Possible ketene dimer structures for dimer 15^2 are shown below:

CeHj CqHs /X/ ° e H5

ozn5s r \ y c2h 5s ' \ o / b c 2h5 « Cq H s X SCsH5 358 Structure JL56 can be eliminated since S-lactones exhibit characteris- 31 tic ir absorptions near 5 Structures analogous to 2£Z have never been reported for ketene dimers j Igfc can be eliminated on the basis of the nmr spectrum of lg 2 which shows symmetric ethyl groups, and on the UV spectrum which does not indicate extensive conjugation In the molecule. Other possible structures for CsoHgoOaSs are:

CqHs C6H5 \ * 0 \ CaHgS— C — C OaHgS-O— 0 / \ / \ 0=C^ ^S-C2H5 CaHs-S^ ^0 = 0 ? ? CeH5 CeHs

is § m

160

Structures 158 and l g ? would re s u lt from 1,3-cycloaddltion of th ia - cyclopropenone lgl to ketene 152, and can be eliminated on the basis of the nmr and uv properties of product lg 2 which reveal identical 1 3 9 3-ethyl groups and the absence of significant conjugation. Thia- benzoquinone l6 0 is symmetric and could be formed by dimerlzation of

151. The uv and ir absorption spectra of the dimer 15,2 do not sup port, however, assignment of its structure as l60. A tentative con clusion is that dimer 1 § 2 possesses structure 1 %% of one isomeric form; a priori, the Isomer in which the pheryl groups are trans would be predicted. Spectral evidence is in agreement with 15J?t however, dimer 1 5,2 does not react as a typical dione to give 2 ,^-dinitrqphenyl- 59 hydrazone derivatives or reduce to a diol by sodium borohydrlde.

Dimer 3J§2 also does not revert to ketene 15,2 when refluxed in cyclo- 67 hexane for 5 hours. Dimer 1^2 is recovered unchanged. The struc-

(6 7 ) C. M, Hill, G. W. Senter, and M. E. Hill, J. Arner. Chem. Soc.,

2 2 8 6 (1 9 5 0 ) report that phenoxyketene (mp 9 1 -9 2 °) is a

stable monomer.

ture of amide 1 %£, the product of ammonolysis of dimer 1 ^2 , supports the tentative assignment of dione _lgj> as the structure of lg2 .

Photolysis of diazo thiolacetate 8 £ in hexane gives intractable products. The IR absorption of the crude photolysis product shows complex absorption in the carbonyl absorption region (1 7 6 0 - 1 7 0 0 cm**1 ).

In an effort to prepare thiacyclopropenone 1%1 under milder con ditions, diazo thlolester 8 £ was decomposed in acetonitrile in the . presence of an equivalent of silver nitrate or cuprous chloride. Gas evolution was accompanied by a color change from orange to yellow. ■ 1U0

Workup of the reaction mixture gives a syrupy product (3,61) having an

ir hand at 1 7 8 5 cm"1 vith a shoulder at 1770 cm"1. No absorption in 3 1 the region of 2100 cm"1 vas observed (ketene absorption area).

Product l6l has different ir and nmr properties than does 1£2.

The nmr spectrum of l6l displays complex absorption in the aromatic

region (5H), a multiplet at 2.7 ppm (2H), and a multiplet at 1.2 ppm

(JH). Product l6l does not give a 2*4-dinitrophenylhydrazone nor

does it afford ketene 132 upon thermolysis in benzene. Whereas* a

refluxed solution (12 hr) of _l6l in methanol yields methyl o-thio-

ethoxyphenylacetate CL2%, h5%), the product of Wolff rearrangement and

solvent incorporation of. diazo thiolester 8£. The structure of l6l

cannot be assigned as yet.

Thermolysis and photolysis of diazo thiolester 90 in hexane were

effected in efforts to prepare S-ethyl-3-j>-nitrqphenylthiacycloprope-

none (l_62). Thermolysis of 90 in hexane (65°j 24-48 hr) gives a yellow

I C 2 H 5 162 product (mp 210- 215°* dec. % €0>) which analyzes for CX0 H 9 NO3 S (163.

see Experimental). Product 163 has a long shelf life when normal pre

cautions against light are taken. The ir of 1 6 3 shows a. sharp car bonyl absorption peak at 1734 cm"1, identical to that of dimer 1 5 2 .

Product 163 displays a nmr multiplet at 8.28 ppm (4h* aromatic)* a l b l

quartet at 2.70 ppm (2H, -S-CH2-)# and a triplet at 1.25 ppm (3H,

-CH3). The nmr Indicates symmetric ethyl groups. UV absorption max

ima In 1 6 5 In ethanol occur at 2 2 5 ty* (shoulder, c = 1 6 ,2 0 0 } and 2 7 5 W

(e = 21,400), with gradual tailing off. The UV data imply that 16%

does not possess extended conjugation 'with chromophores other than

its phenyl groups. Molecular weights of 16% as determined by osmo

metry are 454 (benzene), 476 (chloroform), 2 7 6 (acetone)* 5 0 0 (acetone,

Galbraith Laboratory), and 219 (dimethylformamide, Galbraith Labora

tory); freezing point depression in nitrobenzene gives the molecular weight of 16% as 406, Thus, the molecular weight of 16% appears to be solvent dependent. Mass spectrometry of 1 6 % shows no dimer ion at m/e 446, but there is a significant monomer ion at m/e 22%. From what

is known about 1 § 2 it is likely that 1 6 3 is a dimer that dissociates

in a mass spectrometer and in solvents such as dimethylformamide and perhaps acetone. As for 1%2, 1 6 % does not give a 2,4-dinitrophenyl-

hydrazone nor does it react with bromine - carbon tetrachloride in the

dark. Oxidation of 1 6 % by potassium permanganate gives a near theo

retical yield of ja-nitrobenzolc acid. Attempted degradations of 165 by acid or base hydrolysis and ammonolysis give intractable products.

The structural possibilities considered for 1%2 are also appli

cable to l6 % . Structures analogous to 1%6, 1%7» _1%8, 15g, and 160 are

inconsistent with the uv and nmr properties of dimer 1 6 %. 1 ,3 -Cyelo- butanedione 164, with anti stereochemistry, best fits the instrumental data. ik z

164

Photolysis of diazo thiolester jgO in hexane gives intractable products. IR absorptions of the crude product shows complex absorp tion in the carbonyl region (I7 6 O-I7 OO cm"1 ).

It must be added; that assignment of structures ljjfj and l6k to dimers 15,2 and 1 6 5 . respectively; is merely tentative. The question of whether or not S-substituted 2-thiacyclopropenones are isolable as discrete products remains open.

Thermolysis of methyl -nitrophenylthiolacetate (l64) in hexane also yields a yellow solid (up 1 8 0 -1 8 1 °. dec.j 5 5 ?> yield).

This product precipitates from hexane during reaction; and analyzes for C9H7NO3S (1 8 5 . see Experimental). Product JL65« like dimer 163, has a long shelf life; and exhibits a sharp ir peak at 1 7 3 ^ cm" 1 (as in dimer lg2 and dimer 1 6 %). Prom its mass spectrum and its molecular weight in solution; it is concluded that 1 6 % is a dimer, CiaHj^lfeOeSa, that dissociates into its monomer during mass spectral analysis. The properties of 1 6 5 and _l6>3 imply that they are of similar structure. t Proof of structure by chemical means was not attempted. t In conclusion, It appears that S-substituted 2-th lacy cloprope-

nones are not isoluble under the conditions presently employed far their preparation. Perhaps, S-substituted 2-thiacyclcprcpenones may be prepared under milder conditions. EXPERIMENTAL

General Procedures and Techniques

Melting -points. Melting points were determined with a Thomas Hoover

Capillary Melting Point Apparatus. All melting points are uncorrected.

Boiling points. Bolling points were obtained at atmospheric pressure

unless otherwise noted. Thermometer corrections were not made.

Elemental analyses. Elemental analyses were performed by Chemalytlcs,

Inc., Tempe, Arizona, and by Micro-Analysis, Inc., Wilmington, Delaware.

Infrared spectra. Infrared spectra were obtained on a Perkin Elmer

Infracord Spectrophotometer. The spectra of solid compounds were ob

tained from potassium bromide wafers, and the spectra of liquid com pounds were obtained from liquid films.

Nuclear magnetic resonance spectra. Nuclear magnetic resonance spectra were obtained on a Varian A-60 Analytical NMR Spectrophotometer.

Ultraviolet spectra. Ultraviolet spectra were obtained on a Cary lU

Recording Spectrophotometer and a Perkin Elmer 202 Spectrophotometer.

Molecular weight determinations. Molecular weights were obtained on a

. * F & M Vapor Pressure Osmometer, Model 302, unless otherwise noted.

Ikk 1&5

Mass spectra. Mass spectra were obtained on a MS-9 Mass Spectrometer.

Gas chromatography. Gas chromatography analyses were determined on an

Aerograph, Model A90-P3 Gas Chromatograph, equipped with a thermal conductivity detector and connected to a 2 . 5 millivolt full-scale de- • flection Brown Electronik recorder.

The different columns and conditions employed in the separation and identification of products are described with the various experi ments.

Quantitative measurements were made by comparison of peak areas of products to the peak areaB of measured standards. Relative peak areas were obtained using the method of multiplying the peak height times the width at half-height.

Photolyses. Photolyses were carried out using a ^50 watt high pressure

Hanovia lamp, 679A$ 6.

\ EXPERIMENTAL

60 Preparation of Glyoxylic Acid p-Tosylhydrazone

(6 8 ) H. 0. House, Qrg. Syn., 4ft, 22 (1969).

A warm solution of 98^ glyoxylic a d d hydrate (23 Et 0.23 mole;

Aldrich Chem. Co.) in water (230 ml) was treated with a warm solution of ^-tosylhydrazide (46.3 Er 0.23 mole) in aqueous hydrochloric acid

(250 ml; 2.5 M). The white precipitate of glyoxylic acid £-tosylhydrazone that had formed overnight was filtered and air dried. Recry stallization from ethyl acetate ( 1 0 0 ml) and carbon tetrachloride ( 2 0 0 ml) yielded white needles of the tosylhydrazone (5 0 . 7 g)j mp 14-5-150 88 A (lit. rap 148-154 ).

Preparation of J^t^l o^Dlazothiola,cetate

A suspension of glyoxylic acid p-tosylbydrazone (25,1 g, 0.11 mole) in "benzene ( 1 2 5 ml) and thionyl chloride (24.8 g, 0 . 2 2 mole) was refluxed for 1.5 hours. The reaction mixture at this point was cloudy and orange in color. The contents were cooled and filtered through a celite pad. The filtrate was stripped of solvent in vacuo, yielding crude glyoxylic acid chloride £-tosylhydrazone. Recrystalli zation from henzene-petroleum ether afforded white crystals of the acid ee q chloride (2 0 . 8 g, 7 2 ?G yield), rap 1 0 0 -1 1 2 ° (lit. rap 1 0 1 - 1 1 2 ).

146 147

Glyoxylic acid chloride ^-tosylhydrazone (20.8 g, 0.079 mole) was dissolved in dry methylene chloride ( 2 0 0 ml) ln_a 5 0 0 ml 2 -necked round bottom flask, fitted with a condenser and an addition funnel. The con tents were brought to 0 °, ethyl mercaptan (4.9 g, 0 . 0 7 9 mole) was added, and the reaction mixture stirred at 0° for 45 minutes. A solution of distilled trlethylamine (l6.0 g, O . 1 5 8 mole) in methylene chloride ( 5 0 ml) was then added dropwise over a 25 minute period. The reaction con tents stirred at 0° for an additional hour, and turned red. The Bolvent was carefully stripped, in vacuo. The red syrupy residue from the reac tion mixture was dissolved in benzene (400 ml) thoroughly mixed with

Florisil (60-100 mesh, 200 g) and filtered. The Florisil was washed with additional benzene ( 5 0 0 ml)> the yellow washings and the yellow filtrate were combined and stripped of solvent in vacuo. An orange- yellow viscous liquid remained from which ethyl ar-dlazothiolacetate, a yellow liquid, was distilled via trap to trap at 25%>.3 mm. Ethyl o-dlazothiolacetate (4.2 g, 4l$ from the acid chloride) has the follow- Efc GH ing properties: ir, vm x (cm-1); 2110, 1 6 3 0 , 1330, 862| UV, (c):

248 mi (8,300), 280 mi (11,000), 375 nji (15)* nmr (CCI4 ): 5.33 « (singl,

IB), 2.97 6 (quart, 2H), I . 3 0 6 (trip, 3H). .

Ethyl disulfide is an impurity in the preparation (~ 10^ by weight) and could not be removed by distillation...... 3*8

Decomposition of Ethyl o-Diazothiolacetate in Acidic Methanol at 25°

Concentrated sulfuric acid (* drops) was added to a stirred solu

tion of ethyl of-diazothlolacetate ( 0 .6 g, 0 . 00*6 mole) in methanol (20 ml) at 25°. Gas evolution vas instantaneous. After one hour the clear,

colorless reaction mixture vas stripped of solvent; the residue vas taken up into ether, washed with water, and saturated sodium chloride solution, and then dried over calcium sulfate. The ether phase after

solvent removal yielded a nearly colorless residue, whose nmr spectrum revealed ethyl o^methoxythiolacetate ( 93 ?> overall) as the only product.

Preparative gas chromatography on a 10^ SF $6 column ( 6 ' x VO at 130°

and 80 ml/minute separated an analytical sanple (retention time is 2.16 minutes). Other properties are: ir, vmov (cm"1): 1685; nmr (CCl*):

3.98 6 (singl, 2H), 3.*5 « (singl, 3H), 2.86 6 (quart, 2H), 1.25 6 ( tr ip , 3H).

Anal. Calcd for CsHioOaS: C, **.75; H, 7*51. Pound: C, **.62; H, 7.57.

Methanolysis of Ethyl c-Diaz^hloIacetate at 65°

A stirred solution of ethyl of-diazothiolacetate ( 0 .5 g, O.OO39 mole)

in methanol (20 ml) was refluxed fo r 7 hours. The colorless reaction mixture was stripped of solvent, in vacuo, to a colorless liquid (O .51 g). Gas chromatography and nmr analysis shoved methyl o-thioethoxyace- 69 tate (9*$ by weight) to he the product. The ester has the following physical properties; ir, \>mav (cm“ ): 1738 ; nmr (CCli): 3-70 S (singl,

3H), 3.13 6 (sin g l, 2H), 2.65 6 (quart, 2H), 1.28 6 ( tr ip , 3H). 11*9 Retention time of 2.16 minutes on a 10$ SF $6 column ( 6 ' x J") at

130° and 80 ml/minute.

(69 ) L. Ramberg, Ber.. 1*6, 3889 (1913).

Ethyl o-diazothiolacetate does not react In methanol in the dark

a t 23° in 2 days; the diazo compound is recovered completely.

Photolysis of Ethyl of-Dlazofrhiolacetate in ^thanol at 23°

A stirred solution of ethyl of-diazothiolacetate (0.28 g, 0.00215

mole) in methanol (10 ml) purged with nitrogen was photolyzed through

Pyrex with a 1*50 watt Hanovla lamp. After 0 ,5 hour a colorless solution

was observed, which was stripped of solvent to a colorless residue ( 0.29 g). Gas chromatography and nmr analysis showed the product to be methyl

Of-thioethoxyacetate ('- quant).

Decomposition of Etjyl o-Dlazothiol^ in Glacial Acetic Acid at 25° A solution of ethyl o-diazothiolacetate (0.25 g) in glacial acetic acid (20 ml) was stirred at 25° overnight. The solvent was removed in

vacuo. P reparative gas chromatography on a 25$ SE 30 column ( 6 1 x £")

a t I 5O0 and 110 ml/minute separated ethyl a-acetoxythiolacetate ( 91 $

yield by weight)* the retention time of the ester 1b 3.33 minutes. The product has the following additional properties: ir, Vpay (cm"1): 1750,

1690 , nmr (CCI4 ): l*. 6l & (sin g l, 2H), 2.88 6 (quart, 2H),. 2.13 6 (sin g l,

3H), 1.27 « (trip, 3H). 150

Anal* Calcd for C 0H1OO3S: C, M*.l*3; H# 6.21. Pound: C, kk.kOf H, 6.11.

Decomposition of Ethyl a-Diazothiolacetate in Trlfluoroacetlc Acid at 0°

Ethyl of-dlazothlolacetate (0.2 g) was cautiously added to stirred trlfluoroacetlc acid (10 ml) at 0°. Evolution of nitrogen was not vio lent; the reaction mixture vaB orange. Solvent removal, after 0.5 hour reaction time, yielded an orange-red liquid (O .33 g), ethyl o-trlfluoro- acetoxythiolacetate, having the following nmr spectral properties: nmr

(CCI4 ): 5.00 6 (singl, 2H), 2.71 6 (quart, 2H), 1.32 (trip, 3H).

Mass Spectrum, m/e (rel. Int.): 216, p^ (12), 155 (^* 8 ), 127 (19)# 89

(62), 61* ( 88 ), 1*5 (7 9 )# ^5 (100).

Itecomposltion of Erthyl cy-Dlazothlolflcetate in S llv ^ Nitrate-A.cetonitrile

In Methanol

A stirred solution of silver nitrate (0.62 g, O.OO 36 mole) aceto- n itr il e (15 ml),, and methanol (5 ml) was treated with ethyl of-diazothiolacetate (0.1*7 g, O.OO 36 mole) at 25°. Gas evolution and a color change from orange to yellow was observed. After one hour, the solvent was stripped, in vacuo; the residue was taken up into ether and washed with distilled water. The ether phase yielded a yellow liquid (0.1*1 g), methyl a-thioethoxyacetate ( 87 # yield). Gas chromatography and nmr analysis confirmed the structural assignment. ^ . When cuprous chloride is substituted for silver nitrate, methyl af- thioethoxyacetate is produced in 83 ?> y ie ld . 1 5 1

Decomposition of Ethyl a-Dlazothlolacetate in the Presence of Morphollne

A solution of ethyl a-diazothlolacetate (l._3 g> 0.01 mole) and mor-

pholine ( 0 .9 g> 0.0102 mole) in benzene vas stirred at 65° fo r 6 hours. The solution was stripped of solvent, in vacuo, to an orange-brown resi due. Preliminary nmr and ir analyses of the crude revealed 4-(a-thio-

ethoxyacetyl)morpholine, a pale yellow liquid as the product. The pro duct vas purified by column chromatography on silica geljbenzene and ob

tained in 78 percent overall yield. Other properties of the amide are:

i r , Vmnv (cm"1): l645> 1105i mnr (CCI4 ): 3.55 6 (structured singl, 8 h ),

3.19 « (singl, 2H), 2.61 fi (quart, 2H), 1.29 6 (trip, 3H).

Anal. Calcd fo r CeHisNOaS: C, 50.75* H, T.93.

Found: C, 50. 56; H, 7.77.

Photolysis of Ethyl of-Diazothiolacetate in 2-Propanol at 25°

A stirred solution of ethyl a-diazothiolacetate ( 0 .5 g, O.OO385 mole) in 2-propanol (20 ml), purged with nitrogen, was photolyzed through

Pyrex with a 450 watt Hanovia lamp at 25°. After 0 .5 hour a colorless so lu tio n vas observed. Gas chromatography on a 25$ FFAP column (8.5* x ) i*) showed the product to be the following mixture (~ quant, material balance): ethyl thiolacetate ( 3*5 mole $ ), reten tio n time is 7.63 min- V u tes a t 870 and 80 ml/minute; and isopropyl of-thioethoxyacetate ( 96.5 mole $), retention time is 5.58 minutes at 178° and 60 ml/minute. Iso propyl of-thioethoxyacetate has the additional properties: ir,

(cm"1): 1738; nmr (CDC13): 5*07 6 (heptuplet, 3H)., 3*20 8 (sin g l, 2H),

2.68 6 (qu art, 2H), 1.27 8 (doublet and triplet overlap, 9H). 152 Anal. Calcd for C^Hi^OaS: C, 51.82; H, 8.70.

Pound: C, 51.77; H, 8.64. An authentic sample of ethyl thiolacetate was prepared from acetyl 7 0 chloride and ethyl mercaptan. Ethyl thiolacetate has a hp 116-117 / 760 mm..

(7 0 ) R. B. Baker and E. E. Reid, J . Amer. Chem. Soc.. 51, 1568 (1929).

Photolysis of Ethyl tt-Diazoethiolacetate in 2-Propanol in the Presence of * ■ ^ — j—|—- |— |— ri_ri_rifirij^j._r J- j- J-| f- j - ^ J— j-u-j- j-Lrnijn/ij- r . u uuu Michler's Ketone at 25°

A stirred solution of ethyl of-diazothiolacetate (0.3 g, 0.0023 mole) Mlchler'B ketone [b i s (£-dimethylaminopheny1)ketone] (0.08 g, 0.003 mole),

in 2-propanol (20 ml), previously purged with nitrogen, was photolyzed through Pyrex by a 450 watt Hanovia lamp, at 25° under nitrogen. The photosensitizer absorbed better than 99^ of the light at 366 ny. The photolysis tim e was 3 hours. Gas chromatography on a 25/C FF.AP column

(8.5* x i " ) showed th e follow ing product mixture ( 62# overall yield by weight): ethyl thiolacetate (81 mole ?>)j and isopropyl of-thioethoxy- a c eta te (19 mole ^ ).

The use of a uranium glass filter (Corning Glass Co. # 3178 ) did not change the product ratio or the overall yield. The products were not altered under the reaction conditions. Three additional experiments under the same conditions gave reproducible results. 155 Photolysis of Ethyl a-Diazothiolacetate In t-Butanol at 25°

A stirred solution of ethyl df-diazothiolacetate (0.5 g, O.OO 385 * . .«• mole) in t-butanol (20 ml), purged with nitrogen, was photolyzed through Pyrex with a 450 watt Hanovia lamp, at 25°* A colorless solution was observed after 0.5 hour. Gas chromatography on a 25$ FFAP column (8.5' 7 1 x J*) a t 1550 and 70 ml/minute separated t-butyl o-thioethoxyacetate (~ quantitative yield by weight)j the retention time of the product is 10.75 minutes. The ester has the additional properties: ir, (cm*1):

1748; nmr (CCl*): 3.02 6 (sin g l, 2H), 2.65 S (quart, 2H), 1.45 6 (sin g l,

9H), 1.27 6 ( tr ip , 3H).

(71) J. R. Nooi and J. P. Arens, Rec. Trav. Ohlm.. 80, 294 ( 1961 ). The

recorded boiling point of t-butyl o-thioethoxyacetate is 78 -79 ° /

9 mm.

Photolysis of Ethyl g-Dlazothlolacetate in t-Butanol in the Presence of Mlchler1s Ketone at_ 25°

A stirred solution of ethyl a-diazothlolacetate ( 0 .3 g, 0.0025 mole) Mlchler*s ketone [bis(£-dimethylamlnophenyl)ketone] (0.08 g, 0.005 mole), in t-butanol (20 ml), previously purged with nitrogen, was photolyzed far 3 hours through Pyrex with a 450 watt Hanovia lamp, at 25° under nitrogen. The photosensitizer absorbed better than 99$ of the llg it at

386 nn. GaB chromatography on a 25$ PFAP column ( 8 . 5 * x showed th a t t-butyl of-thioethoxyacetate ( 12$ overall yield).was a reaction product. A second experiment under the same conditions gave reproducible results. 15^ Decomposition of Ethyl tv-Dlaaothlolacetate In Acidic 2-Propanethlol

A stirred solution or ethyl a-diazothlolacetate (0.4 g, 0.0031 mole) In 2 -propanethlol ( 1 0 ml) vas treated vlth concentrated sulfuric a d d (4 drops). After one hour, the reaction solution vas colorless. The solvent vas removed by evaporation under nitrogen. The residue vas taken up into ether, washed vlth water, dried over calcium sulfate, and then stripped of solvent to a colorless liquid, ethyl of-thioisopropoxythiolacetate (84% overall). Preparative gas chromatography on a

25% FFAP column (8 .5 ' x i M) l 68 ° and 40 ml/minute provided a pure sample of ethyl a-thioisopropoxythiolacetate (the retention time is 24.6 minutes) having the following properties; nmr (CDC13): 3.43 A (singl,

2H), 3*00 6 (heptuplet) and 2.90 A (quart) overlapping, 3H; 1.27 A (doublet) and 1.24 A (trip), overlapping 9H.

Anal. Calcd for 0^ 1* 062: C, 47.15; H, 7*91.

Found; C, 47.27; H, 7.87.

Photolysis of Ethyl a-Diazothiolacetate in 2-Propanethiol at 25° A stirred solution of ethyl a-dlazothiolacetate (0.43 B> 0.00343 mole) in 2-propanethiol (20 ml; distilled under and purged vith nitrogen) vas photolyzed through Pyrex with a 430 watt Hanovia lamp at 25°. After 30 minutes the solution vas colorless. Gas chromatography on a 23% FFAP column ( 8 . 5 * x 4") showed the product to be the following mixture ( 95 % material balance): ethyl thiolacetate (trace); isoprppyl a-thioethoxythiolacetate (98 mole %), retention time is 23.3 minutes at 168 ° and 40 ml/minute; and ethyl a-thiolsopropoxythiolacetate (l mole %), retention time is 24.6 minutes at 168 ° and 40 ml/minute. 1 5 5 Isopropyl o?-thioethoxythiolacetate has the additional properties: nmr (CDC13 ): 3.68 fi (heptuplet, 1H), 3..38 6 (singl, 2H), 2.6T $ (quart,

2H), 1 , 3 1 6 (doublet) and 1.24 6 (trip) overlapping 9H.

Anal. Calcd for {VHi4 0Ss: C, 47.15* H, 7*91.

Pound: C, 46.91* H, 7.90.

Photolysis of Ffchyl o-Diazothiolacetate in 2-Propanethiol in the Pre- sence of Mlchler’s Ketone at 25°

A stirred solution of ethyl a-diazothiolacetate (0.3 g, 0.0023 mole),

Mlchler's ketone [bis(£- dimethylaminophenyl)ketone] (0.08 g, 0.003 mole), and 2 -propanethiol ( 2 0 ml), previously purged with nitrogen, was photo lyzed 3 hours through Pyrex by a 450 watt Hanovia lamp, at 25° under nitrogen. The photosensitizer absorbed better than 99$ of the light at

3 6 6 ny. Gas chromatography on a 2 5 $ EPAP column (8 .5 1 "X i") showed the product to be the following mixture (47$ overall): ethyl thiolacetate (24 mole $)* Isopropyl o-thioethoxythlolacetate (40 mole $); ethyl Qf-thioisopropoxythiolacetate ( 3 4 mole $)* and 2 -propanedisulfide (3 $ overall by weight).

Photolysis of Ethyl o-plazothiolacetate in Cyclohexane in the Presence of

Mlchler's Ketone at 25°

A stirred solution of ethyl'of-dlazothiolacetate (0.3 g, 0.0023 mole),

Mlchler1s ketone [bis(£-dimethylaminophenyl)ketone] (0.08 g, 0.00Q3 mole), and cyclohexane:benzene ( 2 0 ml; 5 0 : 5 0 hy volume), previously purged with nitrogen, was photolyzed 3 hours through Pyrex with a 450. watt Hanovia lamp, at 25° under nitrogen. The photosensitizer absorbed better than

99$ of the light at 3 8 6 ny. Gas chromatography-mass spectrometry on a 25$ 156

FFAP column identified the following products (2 2 *JG overall): ethyl thiolacetate ( 5 3 mole %)i ethyl cyclohexylthlolacetate (U? mole #)j and * cyclohexylcyclohexane (5 .3 5 6 by weight).

An authentic sample of ethyl cyclohexylthiolacetate was prepared as follows:

A solution of ethyl mercaptan (2.0 g, O.O3 2 5 mole) and cyclohexyl- acetyl chloride (1.60 g, 0.01 mole; Aldrich Chem. Co.) was stored in a closed flask overnight. Volatiles were removed in vacuo. Preparative gas chromatography on a 20^ QF-1 column separated ethyl cyclohexylthiol acetate, a colorless liquid having the following properties: Retention time is 5 . ^ 6 minutes on a 1 <# FFAP column (1 0 ' x Vsw) at 125° and 9 ml/ minute. IR, \^gv (cm*1); 1 6 8 5 .

Anal. Calcd for CioHia0S: C, 6k,k6f H, 9.7^.

Found: C, 64.18} H, 9*74.

Cyclohexylcyclohexane has the following mass spectral properties

(m /e): 166 (P1*), 83 , 82. 71, 52 (100*).

Photolysis of Ethyl u-Dlaz^hlolacetate in l,l-Dimetho^ethylener in the

Presence of Mlchler f s Ketone a.t 25°

A stirred solution or ethyl a-diazothiolacetate (0.3 g, 0.0023 mole), Mlchler' s ketone [bis(jj-dimethylaminopheny 1 )ketone], (0.08 g,

0.0003 mole),, 1,1-dimethoxyethylene (l.5 g, 0.017 mole} Chemical Sam ples Co.), and benzene (10 mlj previously purged with nitrogen) was photolyzed through Pyrex by a 1*5° watt Hanovia lamp, at'25° under nitro gen. The photosensltlzer absorbed better than 99^ of the light at 3 6 6 157 ny. Photolysis tine vas 5 hours. Gas chromatography on a 2555 FFAP column ( 8 . 5 ' x V;) a t 166° and 66 ml/minute separated ethyl 3 -carbomethoxythiolpropionate (3855 overall) a colorless liquid; retention tine is 32.1 minutes. Other properties of the compound are: ir,

(cm*i): 1735* 1690; nmr (CCI 3D): 3*72 6 (sin g l, 3H), 2.80 6 (conplex,

6h ), 1.25 6(trip, 3H). Mass Spectrum, 150° inlet and source, m/e (# rel. int.): 176 (O .l), 145 (13), 115 (100), 86 (28), 84 (44), 59 (20), 55 (45), 43 (20).

Anal. Calcd fo r C7H12O2S: C, 47.68; H, 6 . 86 .

Found: C, 48.05; H, 6.94. The reaction was repeated and gas chromatography on a 2055 QF-1 column (10* x VO and a 15^ SE 30 column ( 6. 51 x VO separated ethyl 3- cartomethoxythiolpropionate ( 39 ?! overall).

Direct photolysis of ethyl a-diazothlolacetate in 1, 1-dimethoxyethylene, under the same conditions as described above, without Michler's ketone,' yielded ethyl 3-carbomethoxythiolpropionate (trace). Other products were not identified. The gas chromatographic trace revealed several products; the ir spectrum of the residue after solvent removal revealed a complex carbonyl region. NMR analysis revealed that ethyl a-diazothiolacetate does not react in 1, 1-dimethoxyethylene in the dark at 25° in 24 hours

ne cyc lohexane in the Presence of Michler/s Ketoneat 25°

A stirred solution of ethyl a-diazothiolacetate (0.3 g, 0.0023 mole), Michler's ketone [bis(£-dimethylaminophenyl)ketone] (0.08 g, 0.0003 mole), 1 5 8 methylenecyclohexane (1.5 g t 0.016 mole) Chemical Samples Co.), and ben zene (10 ml) previously purged with nitrogen) was photolyzed 5 hours through Pyrex hy a If50 watt Hanovia lamp, at 25° under nitrogen. The photosensitizer absorbed better than 99$ of the light at 366 np. Gas chromatography on a 25$ FFAP column (8.5* x i ff) at 90° and 60 ml/minute separated ethyl thiolacetate (trace). Gas chromatography on a 20$ QF-1 column (lO 1 x £") a t 197 ° and 60 ml/minute separated a colorless liquid, l-carbothioethoxyspiro[2. 51octane (51$ overall)) retention time is

16.UO minutes. Other properties of the compound are: ir, v^bx (c®-1 ):

3010, 1680, 1028, 1015) nmr (CCI 4 ): 2.83 8 (q u art, 2H)) ca. I .50 6

(complex) and 1.25 8 (triplet) overlapping lk-H; 0,83 6 (mult, 2H).

Anal. Calcd for CnHie0S: C, 66.62) H, 9.15.

Found: C, 66. 36) H, 9.01.

NMR analysis revealed that ethyl or-diazoethiolacetate does not react in methylenecyclohexane, in the dark, at 25° in 2k hours.

Direct photolysis of ethyl a-diazothiolacetate in methylenecyclo hexane, under the same conditions as described above, without Michler's 1 ketone, did not yield l-carbothioethoxyspiro[2.5]octane. 159 es Preparation of Phenylglyoxyltc Acid £-ToBylhydrazone

A solution of phenylglyoxylic acid (30 g, 0.2 mole; Aldrich Chemical Co.) in water (230 ml) vas wanned to 60°. A warm solution of £-tosylhydrazlde (37 g, 0 .2 mole) in aqueous hydrochloric acid

(230 ml, 2.3 M) vas then added. The white precipitate of phenyl glyoxylic acid £ -1 o ByIhydra zone that formed overnight vas filtered and air dried. Re crystallization from ethyl acetate (100 ml) and carbon tetrachloride (200 ml) yielded white needles (38 St 91 $ y ie ld ), up 175- 176°, having the following properties: ir, vmax (cm"x): 3^50,

3230, 1750, 1330, 1170.

Anal. Calcd for C12H14N2O4S: N, 8.80.

Pound: N, 8 , 85 .

ea Preparation of Ethyl o-Diaz ophenylth iolacetate

A suspension of phenylglyoxylic acid £-tosylhydra 2one (22 . k g,

0 .0 7 mole) in benzene (85 ml) and thlonyl chloride (l6.4 g, 0 . 1*1 mole) vas refluxed for 1.3 hours. The reaction mixture at this point vas cloudy and yellow-orange in color. The contents were cooled and fil tered through a cellte pad. The filtrate vas stripped of solvent in vacuo, yielding crude phenylglyoxylic acid chloride £-tosylhydrazone

(20 g). The crude acid chloride vas washed with petroleum ether, dried in vacuo, and used in the subsequent steps. Crude phenylglyoxylic acid chloride £-tosylhydrazone (20 g, 0.06 mole) vas dissolved in dry methylene chloride (210 mil) In a 3°° ml

2-necked round bottom flask, fitted with a condenser and an addition funnel. The contents were brought to 0°, ethyl mercaptan (3*7 g t 160

0.06 mole) vas added, and the reaction mixture stirred at 0° fo r 45 minutes. DropwiBe addition (25 min) of a solution of distilled triethylamine ( 12.0 g, 0 .1 2 mole) In methylene chloride (50 ml) f o l lowed. The reaction mixture stirred at 0° for one additional hour, and turned red. The solvent vas carefully stripped In vacuo yielding a crude red-brown syrup containing a yellow solid. This crude resi due vas dissolved in benzene (400 ml) and thoroughly mixed vlth Florisil (200 g, 60-100 mesh) and filtered. The Florisil filter cake vas washed with additional benzene (500 ml). The coniblned orange benzene washings were stripped of solvent In vacuo at 25°• An orange- red viscous residue resulted which vas taken up Into petroleum ether.

The clear orange supernatant liquid vas decanted. This extraction vas performed several times; the combined extracts were thoroughly mixed with Florisil (10 g) and filtered. The clear orange filtrate vas stripped of solvent In vacuo yielding ethyl Cf-dlazophenylthiolacetate (5 .6 g, 45^> yield) a red-orange liquid. Storage at -78° was necessary to prevent alteration. The material has the following pro perties: ir, (cm-1): 2081 , 1645, 1615, 1215; nmr (CCI4): 7.55 •tU -Q T T fi (mult, 5H), 2.96 6 (quart, 2H), 1.25 « (trip, 5H); UV> (e):

215 nn (9 , 000), 255 (11,400), 287 (5, 800 ).

Anal. Calcd for Ci6HiON20S: C, 58.23; H, 4.89; N, 13.58; S, 15.54.,

Found: C, 59.94; H, 4.87; N, 11.26; S, 17.15. The analysis vas performed one day after preparation and Isola tio n . l 6 l

Ethyl af-diazophenylthiolacetate undergoes alteration upon stand

ing In pyridine-d 5 at 25° in the dark. NMR analysis following the decrease of absorption at 2.98 A (quart) and the increase of absorp tion at 2.67 A (quart) revealed that after 48 hours there was 42$ alteration) after 72 hours there vas 6Qf alteration.

^ e rmolysls of Etlyl c^Dlazcpheny^ in Hexane

A solution of ethyl of-diazophenylthiolacetate (2.0 g, O.OO97 mole) in hexane (300 ml), purged vlth nitrogen, vas heated at 30° for 12 hours, under nitrogen. The clear, yellow reaction mixture vas stripped of solvent in vacuo, yielding a yellow syrupy residue (1.6 g) which later crystallized. Recrystallization from ether-hexane at 0° afforded yellow prisms (0.45 St 36$ yield), mp IO5-IO60. The product has the following properties when freshly prepared: ir, v^y (em“x): 1734 v (sharp), 1485, 1440, 1105, 767, 724, 693* nmr (CDC13): 7.75 A (mult,

2H), 7.42 6 (mult, 3H), 2.62 A (quart, 2H), 1.01 A (trip, 3H)* UV, ^cyclohexane ( 6 for MW of 356): 202 ny (44,000), 221 ny (l8,600), 262 ny max (shoulder, 4,040)* mass spectrum, 150° source and in le t, m/e ($ r e l. i n t .) : 356 (< 0 . 1 ), 328 (0 . 7 ), 296 ( 2. 8 ), 267 (1 . 9 ), 266 (2. 0 ), 233

(2 .9 ), 211 (2 . 8 ), 210 (2 . 8 ), 178 (64), 151 (9 .0 ), 150 (2 . 5), 122 (57),

121 (100), 105 (4 .3 ), 9 ^ (29), 77 (11), 66 (36). 2,4-dinitrophenylhydrazone: negative, accompanied with alteration. Bromine, Carbon Tetrachloride: negative. Soluble: benzene, ether, hexane. Molecular weight by osmometry: 367 (benzene). * ■ V

Anal. Calcd for CioHioSO: (sample was analyzed 3 days after pre paration) C, 67.38; H,”5 . 66; S, 17.99* 0,8*97.

Pound: C, 67.57* H, 5.58* s, 15.88* 0, 11.21. 162

This product upon standing several days in a capped "bottle under goes a lte ra tio n . The clear yellow prisms tu rn straw -like and become

cloudy, mp 180 - 181*-0 (dec.), and have the following properties: ir,

(cm-1): 1760 (sharp), 1485, 1^ 0 , 1125 (broad medium), 715, 6931 mass spectrum, 150° source and inlet, m/e ($ rel. int.): 178 (1 .7 ),

151 (100), 123 (17), 122 (45), 121 (18), 118 (18 ), 107 (16), 105 (8 . 0 ),

94 (27), 77 (10), 66 (35)* Insoluble: benzene, ether, hexane.

Oxidation of (C i6H io 30)a by Potassium Permanganate-Pyrldine Freshly prepared (CioHioSO)a (0.25 g) dissolved in pyridine (4 ml) and water (2 ml), was treated with potassium permanganate (0,6^ g). A brown precipitate of manganese dioxide was formed shortly after addi tion. The reaction mixture, after standing overnight, was filtered! the filter cake was washed with warm water. The clear colorless fil trate was acidified with concentrated aqueous hydrochloric acid and extracted with several portions of ether. The ether fractions were combined! th e solvent was removed in vacuo yielding white cry sta ls of benzoic acid ( 0 .1 6 g), mp 118-121 , mixed mp with an authentic sample

. is 118-122°. The ir spectrum of the product was superimposable over that of an authentic sample of benzoic acid.

Ammonolysis of (CioHioS 0 )2 in Benzene Freshly prepared (CioHioSO)^ (0.2 g) dissolved in benzene (10 ml) was purged with gaseous ammonia for 2 hours. Solvent removal yielded * • i* * an off-white solid! recrystallization from ethanol-water afforded white prism s, ( 0 .1 1 g) up 139 - 1^1°, having the following properties: Ir, w 163

(cm-1): 3440, 3200, 1700, 1680, 158 O, 1550) nmr (CDC13): 7.55 6

(mult, 10H), 7.10 6 (broad, 2H), 4.88 fi (sin g l, 1H), 2.15 6 (quart,

4h), O.98 6 ( tr ip , 6h )j mass spectrum, 150° source and inlet, V e ($ r e l. i n t .) : 375 (4 .0 ), 350 (lf.O), 269 (4 .0 ), 195 (22), 151 (100),

179 (5 .1 ), 178 (9 .2 ), 125 (7 .1 ), 121 (11), 45 (17).

Anal. Calcd for C20H23KO2S2 : 0, 64.31) H, 6 .21) IT, 5*76) S, 17.17*

Pound: C, 64.16) H, 6.16; N, 4 .l6 j S, 17. 36.

ThlB product is assigned the structure:

0606 H I II I H2N -C -C -C -C H - SEt \ SEt

Upon further ammonia purging, no alteration of this product is observed.

7 2 Preparation of or-Thloethoxyphenylacetic Acid

(72) K. Fuchs, Monatsh.. ^/^4, 44l (1929).

A suspension of sodium thloethoxide (8.4 g, 0.1 mole) in ether (50 ml) vas dissolved in minimal methanol, and treated with a solution of the potassium salt of a-bromophenylacetio acid (2.16 g, 0 .1 mole) Al drich Chemical Co.) in tetrahydrofuran-methanol. The reaction mixture * * • stirred at room temperature overnight. The resulting white precipitate of sodium bromide was filtered; the filtrate was stripped of solvent in vacuo, taken up into water, and acidified with concentrated aqueous 164 hydrochloric add. The aqueous solution was extracted with several portions of ether) these ether fractions were combined and stripped of solvent to a yellow syrup. Column chromatography on Florlsil (30:1, adsorbent: sample) separated a yellow syrup of o-thioethoxyphenylacetic acid (ll.O g, 5556 yield), which failed to crystallize. The acid has the following spectral properties: ir, V y (cm"1): 3200-2500 (broad),

1705.

She corresponding amide derivative, Of-thioethoxyphenylacet amide, was prepared to corroborate the structure of the CKthioethoxyphenyl- acetic acid.

Of-Thioethoxyphenylacetyl chloride (2.14 g, 0 .0 1 mole), prepared by refluxing

685; nrrc* (CDC13): 7.35 ® (structured singl, 5H), ca. 6 .6 6 (broad,

2H), ll-,56 6 (singl, 1H), 2.60 6 (quart, 2H), 1.26 6 ( tr ip , 3H)) mass spectrum, 150° source and inlet, m/e ($ rel» int.): 195 (< 1.0 ), 177

(< 1 . 0 ), 151 (92 ), 135 (100), 123 (28 ), 121 (8 . 0 ), 106 (3 . 5), 91 (20),

77 (8 .5 ), 62 (4 .0 ), 45 (44).

Anal. Calcd for CioH 13N0S: C, 6I. 5O) H, 6.71) tf, 7.17) S, 16.42.

Pound: C, 61.39; H, 6.79) -N,. 7% 05) s , 15.95. 165 73 Preparation of Fhenylthloethoxyketene

(-73) H. Staudinger, Ber., 44, 1620 (l91l).

df-Thioethoxyphenylacetlc acid ( 1 .96 g, 0 .0 1 mole), carbon tetra

chloride (15 ml), and thionyl chloride ( 3 .0 g, 0.025 mole) 'was re

fluxed for 2 hours. The solvent was stripped in vacuo yielding a yellow liquid, which was dlBsolved-in benzene and filtered through Florisil. The filtrate upon removal of solvent yielded c-thioethoxy-

phenylacetyl chloride, a yellow oil ( 1 .8 g, 85 $.yield), having the

spectral properties: lr, \^aV (cm-1): 1795 * The acid chloride (1.8 g) thus prepared was dissolved in hexane

(75 m l), previously purged w ith nitrogen. The solution was added to a 250 ml 3-necked round bottom flask, equipped with a nitrogen gas inlet, an addition funnel, and a condenser with a drying tube. To the vigorously stirred solution, at 25°, was added in 15 minutes distilled

dry trlethylamine ( 0 .9 g, 0.011 mole) in hexane (30 ml), under nitrogen.

The yellow reaction mixture, while stirring at 25° for 1.5 hours, deposited a white precipitate of trlethylamine hydrochloride. Filtra tion under nitrogen separated a clear yellow filtrate, which was stripped of solvent In vacuo at 25°. A yellow syrup (1.47 e) resu lted , from which crystals appeared. Fractional crystallization from ether - hexane separated yellow prisms (O .65 g) of a product whose physical

(mp IO5-IO60) and spectral properties were identical to those of the

thermolysis product of ethyl cr-diazophenylthlolacetate. 166

The ether-benzene filtrate from above was stripped of solvent to a yellow-orange residue, whose IR spectrum showed strong absorption

a t 2100 cm-1 (>C=C=0) and weaker absorption at TfUO cm"1. After stand

ing neat for 0 .5 hour a t 25° under nitrogen, the orange-brown residue

exhibited complex IR absorption in the carbonyl region and the char* acteristic ketene band at 2100 cm”1, had disappeared. Column chroma-

i grapby on s ilic a -g e l: cyclohexane did not separate any homogeneous com ponent.

Reactions of Ethyl tozophenylthiolacetate with Silver Nitrate/

Acetonltrile and with Cuprous Chlorlde/Acetonltrlle In the Absence of tfethanol To a stirred solution of silver nitrate (O.UU g, 0.0026 mole) In

acetonltrile (50 ml) was added ethyl o-diazophenylthiolacetate ( 0 « g,

0.0026 mole). Gas evolution was observed along with a color change from orange to yellow. After one horn1, the reaction appeared to be complete. Solvent removal in vacuo at 25° yielded a brown syrup which

was taken up Into benzene. The yellow supernatant liquid was decanted

and reduced in volume to an orange syrup (0.29 g). This residue has

the following properties: lr, vmPV (cm-1): no band at 2100, 1785 ,

1770 (shoulder), 1030 (broad), 950, 920 ; nmr (CDC13): 7.35 6 (mult,

5H), ca. 2.70 6 (complex, 2H), ca. 1.10 6 (complex, 3H).

Treatment with 2|U-Dlnitrophenylhydrazlne Reagent

An ethanol solution of this crude product (0.1 g) was treated with 2,4-dinitrcphenyIhydrazlne reagent. Crystallization of a deriva- 167

tive did not occur. After standing overnight the mixture was dark hrown, and no derivative had precipitated.

Treatment with Methanol The crude residue was recovered unchanged from a methanol solu tion at 25°, after standing 15 minutes. The IR spectra of the residue

"before and after treatment with methanol were superimposable.

The crude residue (0.29 g) was refluxed in methanol (10 ml) for 2 hours and then kept at room temperature overnight. A gray precipi tate was filtered, and the filtrate stripped of solvent in vacuo yielding a yellow-orange liquid (0.2T g). Column chromatography on silica gel:"benzene separated methyl o-thioethoxvuhenylacetate (0.13 St k5 by weight), whose structure was verified by comparing its NMR and gas chromatographic properties with an authentic sample.

Thermolysis ln Benzene The crude product (0.2 g) was refluxed in benzene (20 ml) over night. Solvent removal in vacuo yielded a residue (0.2 g) whose IR spectrum showed no band a t 2100 cm"1, medium absorption a t 1780 cm"1, and a strong absorption complex between 175° to 1660 cm"1. Column chromatography did not separate any homogeneous components. A stirred solution of cuprous chloride (0.2^ g, 0.002^ mole) and acetonltrile (30 ml) was treated with ethyl o-diazophenylthiolacetate (0,30 g). Work up as described above yielded a crude product whose IR and NMR spectra are superimposable with those presented ear li e r . l£ 8 Methanolysls of Ethyl Q’-Plazophenylthlolacetate at 65°

Ethyl or-diazophenylthiolacetate (1 .65 g, 0.008 mole) In methanol

(?0 ml) was refluxed fo r 1 hour. The color of th e clear reactio n mixture was yellow. Solvent removal In vacuo yielded a yellow liquid

(.1.67 g). NMR analysis of this crude product showed it to he a mix ture of methyl ar-thioetho3Qrphenylacetate ( 67$) and eth y l or-methoxy- » phenylthiolacetate (33$)-(93$ overall). Preparative gas chromatogra phy on a 10$ SF 96 column (6’ x £") at 200° and 60 ml/minute allowed isolation of the two products as a mixture. Independent synthesis of the two components substantiated their structures.

Preparation of Methyl or-Thloethoxyphenylacetate

Crude a-thioethoxyphenylacetyl chloride (0.43 St 0.002 mole) was refluxed in methanol (15 ml) for 2 hours. Solvent removal in vacuo yielded crude methyl or-thioethoxyphenylacetate (0.4l g). Preparative gas chromatography on a 10$ SF 96 column ( 6 * x %**) at 200° and 80 ml/ minute was used for purification (retention time, 2.93 minutes). The ester has the following properties: ir, vmPV (cm"1): 1740, H 30) nmr (CCI4 ): 7.3 « (mult, 5H), 4.49 « (singl, 1H), 3 .6 7 & (sin g l, 3H),

2.48 6 (quart, 2H), 1.23 6 (trip, 3H).

Anal. Calcd for CnH^OaS: C, 62.831 H, 6.71) S, 15.24.

Found: C, 62.84) H, 6 . 6l) S, 14.94.

Decomposition of Ethyl a-Diazophenylthlolacetate in Acidic Methanol a t 25° A stirred solution of ethyl or-diazopheny 1thiolacetate (1.4 g,

0.0068 mole) in methanol (30 ml) was treated with concentrated sulfuric acid (4 drops). Gas evolution was Instantaneous. After one hour the yellow, clear reaction mixture vas stripped of solvent, taken up

Into ether, and extracted with water. The ether extract was dried over calcium sulfate and after solvent removal yielded a yellow liquid (1 . 2 g, 8 5 $ yield), ethyl o-methoxyphenylthiolacetate. Pre parative gas chromatography on a 10$ SF 9 6 column (6* x ^w) at 200° and 80 ml/minute separated an analytical sample (retention time,

2 . 9 3 minutes) having the following properties: ir, Vm^y (cm-1): l6801 nmr (CCl*): 7.30 6 (mult, 5H), 1).6o 6 (singl, IE), 3 . ^ 0 6 \ (singl, 3H), 2.78 6 (quart, 2H), 1.18 6 (trip, 3H).

Anal. Calcd for CxiHi4 0aS: C, 6 2 .8 3 * H, 6,71* S, 15.21).

Found: C, 6 3 .0 6 * H, 6 ,6 l* S, 13*32.

Methanolysls of Ethyl o-Dlazophenylthiolacetate at 23°

A solution of ethyl a-diazophenylthlolacetate (0.3 g, 0.00214- mole) in methanol ( 1 3 ml) was stirred at 2 3 ° for 2 days in the dark.

Solvent removal yielded a yellow-orange liquid residue (0.3 g) con taining methyl o'-thioethoxyphenylacetate (6 9 $: based on the NMR of the residue) and ethyl of-diazophenylthlolacetate (31$*) based on the NMR of the residue).

Decomposition of Ethyl o-Diazophenylthiolacetate in Glacial Acetic

Acid at 23°

A solution of ethyl o-diazophenylthiolacetate (l.l) g, 0.0068 mole) in glacial acetic acid (1)3 ml) was stirred at 2 3 ° for 2 hours,.

The clear, yellow solution was stripped of solvent in vacuo to a 1 7 0 yellow liquid (1.6 g). Column chromatography on silica gel:petroleum ether separated ethyl cy-acetoxyphenylthlolacetate (82$ overall yield).

Preparative gas chromatography on a 10$ SF $6 column (6* x ) at

2 0 7 ° and 100. ml/minu±e gave an analytical sample (retention time,

3.60 minutes) having the following properties: ir, Vma* (cm*1): 1750,

1 6 9 O 1 nmr (CCI4 ): 7.41 6 (mult, 5H), 6.01 6 (singl, 1H), 2.80 6

(quart, 2H), 2.12 6 (singl, 3H), 1.15 « (trip, 3H).

Anal. Caled for C^H^OsS: C, 60.48j H, 5.92* S, 13.45.

Found: C, 60.45, H, 5.80, S, 1 3 .6 6 .

Decomposition of Ethyl

A stirred solution of ethyl o-dlazophenylthlolacetate (1.4 g,

0.0068 mole) In t-butanol ( 3 0 ml) was treated with concentrated sul furic a d d (4- drops) at 25°. Gas evolution and a color change from orange to yellow were observed. After 30 minutes of reaction time, the solvent was removed in vacuo, the residue was taken up Into ether and extracted with water. The ether phase after drying and solvent removal gave a yellow liquid (1.17 g). Column chromatography on silica gel:petroleum ether separated ethyl a?-t-butoxyphenylthiolacetate (55$ of the products by weight) and ethyl CK-hydroxyphenylthiolacetate (45$ of the products by weight) accounting for 55$ overall yield of products. Preparative gas chromatography on a 10$ SF 96 column (6' x i" ) at 2 0 7 ° and 100 ml/minute provided analytical samples of ethyl a-t-butoxyphenylthiolacetate (retention time 3*44 minutes) and ethyl a-hydroxyphenylthiolacetate (retention time 0.60 minutes). 1 7 1 Ethyl Of-£-buio^henylthlolacetate has the following properties: ir,

Vmnv (cm-1): 1685; nmr (CCl*): 7 . 3 0 6 (mult, 5H), 4.97 ft (singl, 3H), \ 2.72 6 (quart, 2H), 1.27 & (singl) ana 1,15 6 (trip) totaling 12H.

Anal. Calcd far C 14 H 2 0 Q2 S: 66. 65; H, 7.99*

Found: C, 66.6l; H, 7*82.

Ethyl a-hydroxyphenylthiolacetate has the following properties: lr, 1 vna* (cm-1): 5^70, I 69 O; nmr (CCl*): 7.30 5 (singl, 5H), 5.05 ft

(singl, IE), 3.95 ft (broad, OH), 2 .7 8 6 (quart, 2H), 1.17 ft (trip, 5H).

Anal. Calcd far CinHigQoS: C, 61.21; H, 6 . l 6 .

Found: C, 61.07; H, 5.98.

Decomposition of Ethyl of-Dlazophenylthiolacetate in the Presence of

Morpholine

A stirred solution of morpholine (O.8 7 g, 0.01 mole) in benzene

(25 ml) at 65° was treated with ethyl af-dlazophenylthiolacetate (2.08

g, 0,01 mole) in benzene (5 ml). Gas evolution was spontaneous.

After one hour, the reaction contents were stripped of solvent in vacuo. The crude residue was taken up into ether, washed with water, and dried over calcium sulfate. The ether phase after solvent removal yielded a yellow viscous liquid (2.1 g). Column chromatography on

silica gel:cyclohexane separated 4- (a-thioethoxyphenylacetyl)morphol-

ine (6 7 # overall yield by weight).

The material never crystallized and was not suitable for prepara tive gas chromatography. An analytical sample, obtained by additional

column chromatography, has the following properties: lr, \)aax (cm-1 ):

1645, 1110; nmr (CCl*): 7-3 ft (mult, 5H), 4.82 6 (singl, 1H), 3.40 6 1 7 2

(singl, 8 H), 2.1*3 6 (quart, 2H), 1.15 6 (trip, 3H).

Anal. Calcd for C 1 4 H 1 9 HO2 S: C, 6 3 .3 6 ) H, 7.22.

Found: C, 6 3 .2 8 ) H, 7.08.

Decomposition of Ethyl o-Diazophenylthlolacetate in Trifluoroacetic

Ethyl a-diazophenylthiolacetate (0. 5 g) was cautiously added to stirred trifluoroacetic acid at 25°. The reaction was violently exothermic) the contents turned red-hrown. After 0.5 hour, the sol vent was removed yielding a red-hrown liquid (0 . 7 g), whose HMR spec trum showed the mixture to he ethyl of-trlfluoroacetoxyphenylthiolace- tate (8 8 $) methine H, If. 7 0 6 ) and of-thioethoxyphenylacetic acid tri fluoroacetic acid anhydride (12$) methine H, 6.28 fl).

At 0°

The experiment was repeated) however, the trifluoroacetic acid was cooled to 0 ° before and during the addition of ethyl a-diazophenylthiolacetate. The reaction wan not violent) the contents were orange- red. Solvent was removed after 0.5 hour yielding an orange-red liquid, whose NMR spectrum showed only ethyl c-trifluoroacetoxyphenylthiolace- tate (100$) to he present. The NMR spectrum has the following absorp tion: nmr (CF3 CO2 H): 7.5 ® (structured singl, 5H), 6.45 6 (singl,

1H), 3.02 6 (quart, 2H), 1.28 6 (trip, 3H). Mass Spectrum, a/e (rel. int.): 2 9 2 , p * (1 .2 ), 264 (2.4), 203 (19), 175 (3.7), 1§1 (8.7), 1 2 2

(6 .2 ), 1 0 5 (13), 8 9 (2 6 ), 6 9 (8 3 ), 45 (1 0 0 ). 175 jtegffiosltion of Ethyl o^lazc^hery^ In Silver Oxide -

Methanol

A stirred suspension of silver oxide (freshly prepared> 1.4 g,

0 . 0 0 6 mole) in methanol ( 2 0 ml) was treated with ethyl o-diazophenylthiolacetate (O.JO g, 0.0025 mole) and refluxed for one hour. The chocolate-like precipitate was filtered and washed with ether. The combined filtrate and ether washings yielded a yellow liquid (0 . 4 g) after solvent removal. Gas chromatography and NMR analysis showed the product to he methyl a-thloethoxyphenylacetate (67% by weight), methyl phenylglyoxylate (2&f> by weight), and methyl

Itecocposltlon of Ethyl o^Diaz<«ffi In Silver Nitrate-

Acetonltri^

A stirred solution of silver nitrate (0.62 g, O.OO3 6 mole), acetonltrile ( 1 5 ml), and methanol ( 5 ml) was treated with ethyl o- dlazqphenylthiolacetate (0 . 5 g, 0.0024 mole) at 25°. Gas evolution and a color change from orange to yellow were observed. After one hour, the solvent was stripped in vacuoi the residue was taken up into ether and washed with distilled water. The ether phase yielded a yellow liquid (0.42 g) after solvent removal. Gas chromatography and

NMR analysis confirmed that the only product present was methyl of- thloethoxyphenylacetate (84^ overall). lTfc Decomposition of Ethyl

Acetonltrlle-Methanol

The treatment of ethyl o-diazophenylthlolacetate vlth cuprous

chloride (purified hy the method described In Inorg. Syn., II, 2

(1946)), acetonltrile and methanol was Identical to that described for

silver nitrate, acetonltrile, and methanol. Gas chromatography and

» NMR analysis revealed that the only product formed was methyl o-thioethoxyphenylacetate (9 1 $ overall).

Photolysis of Ethyl y Diag cphen^^ e in Iffihanol at 25°

A stirred solution of ethyl o-diazophenylthiolacetate (0 . 5 0 g,

0»;0024 mole) in methanol ( 2 0 ml), previously purged with nitrogen, was photolyzed through Pyrex with a 450 watt Hanovia high pressure lamp.

After 0.5 hour the.dear solution was nearly colorless. Solvent re moval afforded a yellow liquid (0 . 5 0 g). Gas chromatography and NMR analysis confirmed that methyl a-thioethoxyphenylacetat e was formed in near quantitative yield. 1 7 5 Photolysis of Ethyl a-Diazophenylthiolacetate in 2-Prcpanol at 25-o

A stirred solution of ethyl a-diazophenylthiolacetate (0. 5 g,

0.0024 mole) In 2-propanol (20 ml), previously purged with nitrogen, was photolyzed through Pyrex with a 450 watt Hanovia high pressure lamp.

The reaction mixture was colorless after 0 . 5 hour. Solvent removal yielded a yellow liquid (0 . 5 6 g) which upon chromatographic analysis on a 20$ SE 50 column (6* x Jw) at 190° and 110 ml/minute contained the following products: ethyl phenylthlolacetate (retention time 5*76 minutes) (trace) and lscpropyl a-thloethoxyphenylacetate (retention time 7.55 minutes) (99^ by weight). Isopropyl of-thioethaxyphenylace- tate has the following properties: lr, vmax (cm-x): 1740j nmr (CCI4 ):

7.30 6 (mult, 5H), 4.96 6 (heptuplet, 1H), 4.55 * (singl, OB), 2.45 6

(quart, 2H), 1.22 6 (doublet and triplet overlap, 9H).

Anal. Calcd for CisHieO^S: C, 65*50; H, 7*61; S, 13*45*

Pound: C, 65*a5; H, 7*46; S, 13*40.

Photolysis of Ethyl o-Diazophenylthiolacetate in 2-Fropanol in the

Presence of Methylene Dibromide at 25°

A stirred solution of ethyl o-diazophenylthiolacetate (0.2 g,

0 . 0 0 0 9 7 mole), 2-propanol (7*5 &> 0 , 1 2 5 mole), and methylene bromide

(10 g, 0.0575 mole) was photolyzed through Pyrex by a 450 watt Hanovia high pressure lamp. (The solution of 2-propanol and methylene bromide was previously purged with nitrogen.) Solvent removal, after 0.5 hour reaction time, yielded a yellow liquid (0 . 2 3 g)* * Gas chromatographic analysis on a 20$ SE 30 column (6* x *M) at 190° and 110 ml/minute showed the following mixture of products: ethyl phenylthlolacetate 1 7 6

(trace) and lsopropyl a-thioethoxyphenylacetate (9 9 $ by weight).

Photolysis of Ethyl a-Dlazophenylthiolacetate in 2-Prcpanol in the

Presence of Mlchler ’ b Ketone at 25°

A stirred solution of ethyl or-dlazophenylthlolacetate (0.23 g,

0 . 0 0 1 1 2 mole), 2 -propanol ( 2 5 ml* previously purged with nitrogen), and Mlchler' s ketone [bis(£-dimethylaminophenyl)ketone] (0.50 g,

O.OOI 8 7 mole) was photolyzed through a uranium glass filter (Corning

Glass Co., #5 1 7 8 ) by a U 5 0 watt Hanovia lamp. An atmosphere of nitro gen was maintained; the temperature was 25°. Based on the molar ex tinction coefficients of the photOBensltlzer and the dlazo compound at 5 6 6 ny, the photosensitizer was absorbing better than 9 9 $ of the light. Photolysis time was 2.5 hours. Gas chromatography on a 15$

SE 30 column (6.5* x V O showed the following mixture of products: ethyl phenylthlolacetate (trace) and iscprcpyl of-thioethoxyphenylacetate (8 l$ by weight).

This experiment was repeated four times; each time the results were reproducible.

Ethyl o-dlazcphenylthiolacetate did not react in the dark with 2- prcpanol, in the presence of Mlchler’s ketone at 25° in 4- hours.

Preparation of Ethyl of-Chlorqphenylthiolacetate

A solution of o-chlor ophenylacetyl chloride (9*5 g> 0.05 mole;

Aldrich Chemical Co.), ethyl mercaptan (3 . 3 g, O.O 5 1 mole), and ether * • ■ «• * (75 ml) stirred at 25° overnight. The solution was washed with water, aqueous saturated sodium bicarbonate, and aqueous saturated sodium chloride. The ether phase was stripped of solvent, and the crude resi due was filtered through Florisil (25 g) by benzene. The filtrate yielded ethyl o-chlorophenylthiolacetate ( 9 g> 8 7 $ yield). Preparative gas Chromatography on a 10$ SF $6 column (61 x V ) at 202° and 100 ml/ minute (retention time 2 . 5 8 minutes), separated an analytical sample having the following properties: lr, vmax (cm**1): 1685j nmr (CCI4 ):

7.56 6 (mult, 5H),( 5 M 6 (singl, IB), 2.71 fi (quart, 2H), 1.02 6

(trip, 5H).

Anal. Calcd for CioHnClOS: S, <5.70.

Found: S, 6 .9 3 .

Treatment of Ethyl a-Chlorophenylthiolacetate with Silver Nitrate in

Methanol

A stirred solution of ethyl a-chlorophenylthiolacetate (2.15 g,

0.01 mole) and silver nitrate (1.7 g, 0.01 mole) in methanol (100 ml) was refluxed for one day. The white precipitate formed was filtered and the filtrate stripped of solvent in vacuo. The liquid residue was taken up into ether, washed 'with distilled water, and dried over calcium sulfate. The ether phase yielded a colorless liquid (1.7 g) after solvent removal. Gas chromatography on a 20$ SE 30 column

(6T x V') showed a complex mixture containing ethyl ar-methoxyphenyl- thlolacetate (17$ by weight), and methyl cf-chlorophenylacetate and . ethyl o-Chlorcphenylthlolaeetate (8 3 $ by weight). 1 7 8 Photolysis of Ethyl o-Diazophenylthiolacetate In Cumene/2-Propanol in

A stirred' solution of ethyl o-dlazophenylthiolacetate (0 . 2 0 g, , i

0 . 0 0 0 9 7 mole), cumene ( 1 5 ml, previously purged with nitrogen), 2 -propanol ( 2 ml, previously purged with .nitrogen), henzene ( 3 ml, previously purged with nitrogen), and Mlchler's ketone [t>is(p -dimethy laminophenyl)- t f ketone] (O.l* g, 0.00162 mole) was photolyzed through a uranium glass filter (Corning Glass Co., #3178) by a ^50 watt Hanovia lamp. An atmosphere of nitrogen was maintained! the temperature was 23°. Based on the molar extinction coefficients, of the photosensitlzer and the diazo compound at 3 6 6 npi, the photosensitlzer was absorbing bett.er than

99$ of the light. Photolysis time was 2.3 hours. Gas chromatography on a 15$ SE 30 column (6.5* x £") showed the following mixture of pro- 7 4 duets: ethyl phenylthlolacetate ( 3 mole $) and isopropyl a^thioethoxyphenylacetate ( 9 7 mole $) (3 9 $ material balance).

(7 U) S. Kushner, H. Dalallan, P. L. Bach, 2). Centola, J. L. Sanjurjo,

and J. H. Williams, J. Amer. Chem. Soc., 77, 1152 (1955)* Ethyl

phenylthlolacetate has a reported bp 102-h°/3 mm. An authentic

sample was prepared from ethyl mercaptan and phenylacetyl chloride,

bp 8l-83°/0.h mm. 1 7 9

Preparation of Ethyl £- Itttr ophenylthiolacetate

A solution of p-nitrophenylacetic acid (90 g, 0 . 5 molej Matheson,

Coleman, and Bell) and phosphorous trichloride (22.? g, 0.2 mole) in henzene ( 1 5 0 ml) was refluxed overnight. The yellow supernatant liquid was decanted and stripped of solvent on a rotary evaporator to yellow needles of p-nitrophenylacetyl chloride, mp 43-47 o (lit. 7 5 mp 45.8-

(75) P. D. Bartlett and C. Ruchardt. J. Amer. Chem. Soc., 82, 1758 (I960).

i . ,

46.8°) (885 G yield).

The crude p-nitrophenylacetyl chloride was dissolved in diethyl ether (100 ml) and treated with ethyl mercaptan (31 g, 0.5 mole). The reaction mixture stirred at reflux overnight. The clear, orange solu tion was reduced to half its volume and washed with saturated sodium

Bicarbonate solution, saturated sodium chloride solution, and dried over calcium sulfate. The resulting ether solution was reduced in vacuo to a viscous liquid and distilled. The fraction boiling at 88-

94°/3 mm, ethyl ^-nitrpphenylthiolacetate (4? 'g,’ 51?> yield from nitrophenylacet ic acid), was collected. The red product (color due to alteration during distillation) has the following properties: lr,

W (cm'1 ): 1 6 8 5 , 1515* 1340j nmr (neat): 7.88 fl (AaBa, 4h), 4.02 6

(singl, 2H), 2.90 fi (quart, 2H), 1.21 6 (trip, 3H). .

Anal. Calcd for C10H11NO3S: S, 14.23.

Found: S, 14.22. 180

Preparation of Ethyl of-Dlazo-g-nltrophenylthiolacetate

(76) M. Regitzt Tetrahedron Lett. , 1403 (1964);,M. Regitz, Angew.

Chem., JQ, 684 ( 1966 ).

*s> Ethyl £-nitrophenylthiolacetate ( 9 .0 g, 0.04 mole) was dissolved in pyridine (40 ml, dried over potassium hydroxide). The solution was

cooled to 0 ° and treated with N-methylmorpholine (4.5 ml# 0.04 molei

distilled over "barium carbonate; Union Carbide Corp.), followed imme

diately by £-tosylazide [ 7 .7 8 g, 0.04 mole; prepared by the method of

Von Doerlng and DeiPuy, J . Amer. Chem. Soc., 5955 (1953)]. red

reaction mixture was stirred at 0° fo r 0 .5 hour and then at 25° fo r

1.5 hours. The deep red solution was treated with water (150 ml) .’caus

ing the precipitation of orange needles of ethyl o-diazo-£-nitr opheny 1 - thiolacetate. Recrystallization from methanol yielded orange needles

( 5 .1 g, 51$ yield), mp 81 - 82 ° having the following properties: ir,

(cm"1): 2090 , 1640, 1582 , 1505, 1330; runr (EMS0-de ): 8 .1 3 S

(AeBia, 4H), 3.09 6 (quart, 2H), 1.28 6 (trip, 3H); UV, («): 236 IV (9,000), 3^5 iV (10,500). > . Anal. Calcd for C10H9N3O3S: C, 47.90; H, 3.62; N, 16. 7 8 ; S, 12.76.

Pound: C, 48.05; H, 3.53; N, 16. 56; S, 12.49.

Preparation of Methyl £-Nitrophenylthiolacetate Methyl mercaptan was bubbled into a solution* of £-nit r ophenylacetyl chloride (9 8 g, 0 .5 mole; previously described), in chloroform (the mini- 181 mal quantity for solution), until hydrogen.chloride was no longer - evolved. The solvent was removed in vacuo yielding a red syrup which

crystallized. Recrystalllzatlon from 95 $ ethanol afforded methyl £- nitrophenylthlolacetate, white needles, mp 58-39° (85$ yield). The

material has the following properties: ir, Vmv (cm-1): 1(585, 1515# 1340.

Anal. Calcd for CeHgN0 3S: s, 15*17* Found: S, 15.28.

Preparation of Methyl of-Dlazo-£-nitrophenylthlolacetate The preparative method was the same as that described for ethyl o-diazo-£-nitrophenylthiolacetate. Yellow-orange threads of methyl

of-diazo-£-nltrophenylthiolacetate, mp 139-140° (dec.), from methanol, were obtained in 60$ yield having the following properties: ir, v^y

(cm-1 ): 2090, 1640, 1580 , 1505, 1330; nmr (CDCI3 ): 8.18 fi (AaBa, 4h),

2.67 6 (singl, 3H).

Anal. Calcd for C9 H7K303S: C, 4 5 . 56; H, 2.97; N, 17*72; S, 13*51*

Found: C, 45*55; H, 2.85; N, 17*65; S, 13*39*

Thermolysis of Ethyl or-Diazo-£-nitrophenylthiolacetate in Hexane A solution of ethyl a- d ia z o-£-nitropheny 1thiolacetate (2.0 g, 0.008 mole) In hexane (400 ml), which had been previously purged with nitrogen, was refluxed fo r 36 hours in a nitrogen atmosphere. A yellow precipi tate which had coated the reaction flask was collected. Filtration under nitrogen and recrystallization from benzene-hexane yielded pale 1B2

yellow needles ( 1 .2 5 8, 62# yield by weight), op 210- 215° (d ec.). The

product has the following properties: ir, (cm’1); 1731*, 1500,

13to, lllOj nmr (EM30-de): 8.28 fl (mult, kE), 2.70 6 (quart, 2H), 1.25

6 (trip, 3H)j 07, \ oax (* MW of M* 6 ): 225 W (shoulder, 1 6 , 200),

2 7 5 \(21,^00). Mass spectra: (a) 150° inlet and source, 70 evi m/e

(?6 rel. int.): 223 (1 3 ), 166 (3 7 ), 122 (1 0 0 ), 120 ( 17), 9 U (6 3 ), 66

(7*0 . (0 ) 150° inlet and source, 1 5 .5 evj m/e (# rel. int.): 223 (2 1 ),

166 (35), 122 (lOO), 120 (12), 9^ (^9), 66 (37). Molecular weight by

osmometry (so lv en t): 1*5 ** (benzene), kj6 (chloroform), 276 (acetone), 300 (acetone, Galbraith Laboratory), 219 (dimethylformamide, Galbraith Laboratory); by freezing point depression; 1*06 (nitrobenzene). 2,1*- Dinitrophenylhydrazone: negative, accompanied with alteration. Bromine,

Carbon Tetrachloride (dark): negative.

Anal. Calcd fo r C10H9 NO3S* C, 53*79j H, 1*.06; N, 6.29) S, ll*.35. Found: C, 53.85) H, 3.80; N, 6.15; S, ik M -

Thermolysis of Methyl or-Diazo-£-nitraphenylthiolacetate in Hexane

A solution of methyl a-diazo-£-nitrophenylthiolacetate ( 2 .0 0 g,

O.OO85 mole) in hexane (1*00 ml), which had been previously purged with

nitrogen, was refluxed fo r 36 hours under nitrogen. A yellow solid, coating the flask, was collected. Filtration under nitrogen §md recry- " 1 v • • •••, • stalllzation from benzene-hexane yielded pale yellow needles ( 1 .1 7 g, 55# yield by weight), mp l80-l8l° (dec.). The product has the following properties: lr, Vjnax (cm-1): 173^, 1505, 13^0, HlO)‘the spectrum is nearly superimposable with that of the thermolysis product of ethyl a~ 183

dlazo-£-nitrophenylthiolacetate* nmr (DJBO-de): 8.28 6 (mult, 4h)j

2 .k l 6 (singl, 3H). Mass Spectra: (a).150° inlet and source, 70 ev*

m/e (* r e l. in t.) : k l 8 (< 1 .0 ), 209 (3 9 ), 166 (6 l ) , 120 (2 2 ), 9 k (100),

79 ( 50). (b) 150° in le t and source, 18 ev* m/e (% r e l. in t.) : 209 ( 57),

166 (35), 120 (13), 9^ (lOO), 79 (2 5 ). Molecular Weight* by osmometry (solvent): k29 (tetrahydrofuran, Galbraith Laboratory), k31 (chloroform), 218 (aimethylformamide, Galbraith Laboratory). 2,k-DinitrophenyIhydra-

zone: negative, accompanied vith alteration. Bromine, Carbon Tetra chloride (dark): negative.

Anal. Calcd for CeH7 N03S: C, 51.67* H, 3-37* N, 6.70* S, 15*32.

Pound: C, 51.k5* H, 3*31* N, 6 . 50* S, 15-35.

Oxidation of (CibHgN0 3S)a and (C9 H7M03S )s by Potassium Permanganate - 77 Pyridine

(7 7 ) T. P. Corbin, Ph.D. Dissertation, The Ohio State University, 1956.

A solution of CioHgN03S (0.25 g) in pyridine (k ml) and voter (2 ml) was treated vith potassium permanganate (0.6k g). Shortly after addition, a brown deposit of manganese dioxide was formed. The reaction mixture, after sitting overnight, was filtered and the brown filter cake was rinsed vith warm water. The filtrate was acidified vith concentrated aqueous hydrochloric acid. White needles of £-nitrobenzoic acid (0.16 * * * g) precipitated, mp 235- 237°* the mixed mp v ith an authentic sample vas

235-238 °. IR spectral comparison with an authentic sample substantiated 1B4 the structure assignment.

When a similar oxidation vas effected on C 8 H7NO3S (0.2? g) j>-nitrobenzolc acid ( 0 . 1? g) -was obtained as product.

Methanolysls of Ethyl a-Dlazo-jJ-nltrophenylthlolacetate

An orange solution of ethyl a-diazo-£-nitrophenylthiolacetate (l.O g, 0.004 mole) In absolute methanol (20 ml) vas refluxed fo r 12 hours.

The yellow solution was stripped of solvent In vacuo yielding a yellow viscous residue (1.0 g). HMR analysis of the residue revealed methyl a- thioethoxy-£-nitrophenylacetate as the only product. Purification on a s ilic a gel: cyclohexane column yielded methyl a- 1hioethoxy-£-nit r ophenyl- acetate (0 .9 1 g, 91$) having a retention time of 9*24 minutes on a 10$ SE 96 column (6* x %") at 207° and 100 ml/minute. Other properties of the thiolacetate are: ir, v^ay (cm*1): 174?$ nmr (CCI 4 ): 8.00 6 (AsB2,

4h)> 4.60 6 (sin g l, 1H), 3*71 6 (sin g l, 3H), 2.?3 6 (quart, 2H), 1.72 fl

(trip, 3H).

Anal. Calcd for C11H13NO3S: C, ?1.75i H, ?.l4$ S, 12.??.

Found: C, ?1.92$ H, ?.33$ S, 12.26. Ethyl a-diazo-£-nitr opheny lthiolacetate did not react with methanol a t 2 ?° in 48 hours.

Decomposition of Ethyl a-Diazo-£-nitrophenylthiolacetate in acidic

Methanol at 2?° Concentrated sulfuric acid (4 drops) was added to a solution of ethyl

for 3 hours. The solution changed from an orange to yellow color. Sol vent removal In vacuo yielded a yellow residue that vas taken up into

ether and then extracted with water. The ether solution was stripped of

solvent in vacuo yielding a yellow liquid ( 0 .3 7 g)> whose nmr spectrum

(CCI4 ) showed it to he a mixture of methyl af-thioethoxy-£-nitrophenyl-

acetate (15%) [7.85 6 (AaBa, 4H), 4.58 6 (sin g l, 1H), 3*72 fi (singl, 3H),

2.59 6 (quart, 2H), 1,20 6 (trip, 3H)] and ethyl o-methoxy-ji-nitropheny1- thlolacetate ( 85 %); [7.85 6 (AaBa, 4h), 4.75 fi (sin g l, 1H), 3-52 6 (sin g l,

• 3H), 2,79 fi (quart, 2H), 1.20 6 (trip, 3H)]. i No separation was attempted.

Decomposition of Ethyl g-Plazo-£-nltrophenylthiolacetate in Glacial Ace

tic Acid at 65° Ethyl a-diazo-^-nitropheny lthiolacetate (0.4 g) did not react with

glacial acetic acid (20 ml) standing overnight at 25°. The initial dlazo compound was recovered. A solution of ethyl a-dlazo-£-nitropheny lthiolacetate (0.4 g) in

glacial acetic acid (20 ml) was heated at 65° for one hour. Gas evolu

tion and a color change from orange to yellow was observed. Solvent re

moval in vacuo yielded-a yellow liquid (0.45 g) whose nmr spectrum (CCI 4 )

showed to be a mixture of ethyl o-acetoxy-£-nitrophenyIthiolacetate ( 60%)

[jja. 7.90 6 (AaB2, 4h), 6.20 6 (singl, 1H), 2.8l 6 (quart, 2H), 2.12 6

(singl, 3H), 1.24 6 (trip, 3H)], and a-thioethoxy-£-nitrophenylacetic

acid acetic acid anhydride (40%) [ca. 7*90 & (A2B2, 4h), 4.55 A (singl,

1H), 2.60 6 (qu art, 2H), 2.12 6 (singl, 3H), 1.24 fl (trip, 3H)]. Separation was not attempted. 166 Decomposition of Ethyl a-Diazo-£-nitropheny lthiolacetate in Trifluoro acetic Acid at 0° A solution of ethyl o-diazo-£-nitrophenylthiolacetate (O.lf g) in acetonltrile (3 ml) vas carefully added to trifluoroacetic acid (20 ml) at 0°. The color of the resulting mixture vas red-orange. After the mixture had heen standing at 0° fo r 15 minutes the solvent vas removed in vacuo yielding a red-orange liquid ( 0 .5 3 g ), whose nmr spectrum

(CCI4 ) showed it to he a mixture of ethyl o-trifluoroacetoxy-£-nitrophenylthiolacetate ( 72#) [ca. 7*90 8 (AgBej ^H), 6 .3 2 ft (singl, Hi),

2 .8 1 6 (quart, 2H), I .2 5 fi (trip, 3H)] and of-thloethoxy-£-nltrophenyl- acetic acid trifluoroacetic acid anhydride ( 28 #) [ca. 7 .9 0 6 (A2B2 , 4h),

4.57 8 (singl, IB), 2.59 8 (quart, 2H>, 1.25 8 (trip, 3H)].

Photolysis of Ethyl Of-Diazo-j>-nitrophenylthiolacetate in Methanol at 25° A solution of ethyl o-diazo-£-nitr opheny lthiolacetate (0.3 St 0.0012 mole) in absolute methanol (15 ml) vas photolyzed 30 minutes, through pyrex, vith a h$0 watt Hanovia high pressure lamp. Solvent removal, in vacuo, from the near colorless reaction mixture yielded a yellow liquid

(O.3 4 g), methyl of-thloethoxy-£-nltrophenylacetate (~ quant) whose ir, nmr, and gas chromatographic properties correspond vith those of an authentic saiqple. APPENDIX

Infrared Spectra

187 WAVELENGTH (MICRONS)

n 2 o II II H-C-C-SCgHs

Figure 1 J

' 4 0 0 0 3000

7 8 9 10 WAVELENGTH (MICRONS)

lfe 0 II II GaHs-C—C-Sq^s

Figure 2

i 4000 3000 iqoo 990 890 iimiiil

—1— r—i— T— 1— r— 1— 1— 1— 1— 1— 1— r— 1— 1 — 1— 1— r— • B * WAVEl^NGTH (MICRcSlS) T . .

Ife 0 It II CflRi- C— C-SC2H5

Figure 3 4 0 0 0 3000

¥ t

ffl

7 0 9 10 WAVELENGTH (MICRONS)

(Cig H io OS)2

Figure U 4 0 0- 0 3000 2000 spo CM*' KUO 11 i h i*i 1*1 i'i * Ill A III, i I..I ■ I I M.Jl || I I | I | |. J I I I I I I I) ° 79°. tr.iooi Vr+l f, ■>, X, < i .i. t f f f^ !*■*! 1 1I*.29° Li f l "j, l M f . 1. r * 3 uitiniiiiiiiiiiiiiiiiiiiiiiiiuniiuiiiiniiiiiiiHiiiiiiiiii70^289 iiiiuiHUiiiitinuii 100 82

in : im

7 9 10 WAVELENGTH (MICRONS)

(CxoHaKgS )z

Figure 5 4 0 0 0 3000

; t4o m m ii * 1 : • 11 i:;- L;-LLLi U.

a i UMJu-il! ini m i l WAVELENGTH (MICRONS)

( CjgfyllOsS )s

Figure 6 CM** 40003000 2 0 0 0 1500 icp o 9 9 0 8 9 0 700 100- I...... I . . « 0.0

80 u j ^ 6 0

WAVEI

CH=CH-C=C -H Figure 7