Mogratory Abilities of Beta-Heteroatomic Substituents to Divalent Carbon

Home , Hydrazide, Phenylhydrazine, Tosylhydrazone

This dissertation has been microfilmed exactly as received 68-8871

ROBSON, John Howard, 1940- MIGRATORY ABILITIES OF fi -HETEROATOMIC SUBSTITUENTS TO DIVALENT CARBON.

The Ohio State University, Ph.D., 1967 Chemistry, organic

University Microfilms, Inc., Ann Arbor, Michigan MIGRATORY ABILITIES OF p-HETEROATOMIC

SUBSTITUENTS TO DIVALENT CARBON

DISSERTATION

Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University

John Howard Robson, B.S.

******

The Ohio State University 1967

Approved by

Department of Chemistry Dedicated to my wife,

Diane

ii ACKNOWLEDGMENTS

I wish to express my gratitude to Professor Harold

Shechter for his inception of this study and for his masterful help in the preparation of this manuscript. Dr. Shechter*s devotion to chemistry and professional character are qualities that have been most inspiring.

I am grateful to the Chemistry Department of The Ohio

State University, the Department of Navy, the National Institute of Health, and the National Science Poundation for financial assistance.

I wish to thank: my parents, wife, and family for their sacrifices, interest and encouragement which enabled my pur suit of a formal education.

iii VITA

July 26, 194-0 Born - East Liberty, Ohio

1962 ...... B.S., Ohio Northern University Ada, Ohio

1962-1964 ...... Teaching Assistant, Department of Chemistry, The Ohio State University, Columbus, Ohio

1964-1967 ...... research Associate, Department of Chemistry, The Ohio State University, Columbus, Ohio

iv CONTENTS

Page

ACKNOWLEDGMENTS iii

VITA iv

TABLES viii

INTRODUCTION 1

HISTORICAL

DISCUSSION 18

EXPERIMENTAL 51

General Information 51

Melting points Elemental analyses Infrared spectra Nuclear magnetic resonance spectra Mass spectra Gas chromatography Solvents

Intermediates ...... 53

Methoxyacetonitrile 2-Methoxyacetophenone 2-Methoxyacetophenone tosylhydrazone 2-Phenoxyacetophenone 2-Phenoxyacetophenone tosylhydrazone 2-Hydroxyacetophenone 2-Hydroxyacetoohenone tosylhydrazone 2-Dimethylaminoacetophenone 2-Dimethylaminoacetophenone hydrochloride tosylhydrazone 2-Phenylaminoacetophenone 2-Phenylaminoacetophenone tosylhydrazone 2-Phenylmercaptoacetophenone 2-?henylmereaptoacetophenone tosylhydrazone 2-Ethylmercaptoacetophenone 2-Ethylmercaptoacetophenone tosylhydraz one 2-£thylmerc spto-A1 -chloroacetophenone 2-Ethylmercapto-4-,~chloroacetophenone tosylhydrazone CONTENTS (Cont'd)

Page

2-Ethylmercapto-4.,-broEoacetophenone . . 61 2-Ethylm9rcaptO“^*-bromoacetophenone tosylhydrazone 2-Kethyl-l,3-dithiane 2-Lithio-2-methyl-l ,3-dithiane 2-Benzoyl-2-methyl-l ,3-dithiane 2-Benzoyl-2-rnethyl-1,3-dithiane tosylhydrazone 2-ForEyl-2-methyl-l ,3-dithisne 2-Forinyl-2-methyl-l ,3-dithiane tosylhydrazone

Standards ......

2-Methoxy-2-phenylethyl iodide a-Methoxystyrene p-M ethoxystyrene cis- and trans-g-Methoxystyrene p-Phenoxystyrene p-Phenylmercaptostyrene p-Ethylmercaptostyrene

Decomposition of 2-methoxyacetophenone tosylhydrazone ...... 70

Decomposition of 2-phenoxyacetophenone tosylhydrazone...... 74-

Decomposition of 2-hydroxyacetophenone tosylhydrazone...... 76

Decomposition of 2-dimethylaminoacetophenone hydrochloride tosylhydrazone .... 77

Decomposition of 2-phenylaminoacetophenone tosylhydrazone ...... 79

Decomposition of 2-phenylmercaptoacetophenone tosylhydrazone ...... 79

Decomposition of 2-ethylmercaptoacetophenone tosylhydrazone...... 81

Decomposition of 2-ethylmercapto-4-1- chloroacetophenone tosylhydrazone ...... 82

vi CONTENTS (Cont’d) » Page

Decomposition of 2-ethylmercapto-4'- bromoacetophenone tosylhydrazone ...... 83

Base-catalyzed thermolysis of 2-pbenyl- mercaptoacetophenone tosylhydrazone in different environments ...... 84

Decomposition of 2-ethylmercaptoacetophenone tosylhydrazone by various bases in different environments ...... 85

Reaction of 2-ethylmercaptoacetophenone tosylhydrazone with 3 equivalents of n-butyllithium ...... 88

Kinetic study of the thermal decomposition of 1-diazo-l-phenylethane...... 91

Kinetic study of the thermal decomposition of l-diazo-2-ethylmercapto- 1-phenylethane ...... 91

Decomposition of 2-benzoyl-2-methyl-l,3- dithiane tosylhydrazone ...... 92

Decomposition of 2-formyl-2-methyl-l,3- dithiane tosylhydrazone ...... 93

APPENDIX I - Infrared Spectra ...... 95 (Figures 1-9)

APPENDIX II - Nuclear Magnetic Resonance Spectra . . . 99 (Figures IO-15)

APPENDIX III- Kinetic Plots ...... 106 (Figures 16-19)

vii TABLES

Table Page

1. p-Toluenesul fonylhydrazor.es of 2-Substituted Acetophenones ...... 23

2. Base Decomposition of 2-Phenylmercapto- acetophonone Tosylhydrazone...... 86

3. Base-catalyzed Decomposition of 2-Sthyl- mercaptoacetophenone Tosylhydrazone ...... 87

viii INTRODUCTION

In the past two decades there has been renewed interest in the chemistry of divalent carbon (l). Such intermediates are known

(1) Divalent carbon intermediates in this discussion will be denoted by the general term "carbene." The simplest such inter mediate, sCH^ is called methylene; other carbenes are named by adding "-idene" to the name of the corresponding univalent radical. Other members of this homologous series thus are named ethylidene, CH^CH:; benzylidene, PhCH:; etc. [international Union of Pure and Applied Chemistry Report on Nomenclature, J. Am. Chem. Soc.. 82. 5545 (I960)]. as carbenes and contain carbon linked to two adjacent groups by

covalent bonds, and possessing two nonbonding electrons which may have antiparallel spins (singlet state) or parallel spins

(triplet state). The spin states of carbenes will be discussed in more detail later.

The present investigation involves study of intramolecular

rearrangement reactions of carbenic systems which allow possible

participation of substituents containing electron-donor hetero

atoms. The possible participating and rearranging groups of interest

are covalent sulfur, oxygen, and nitrogen in positions beta to the

divalent center (Equation 1).

? ♦ Z - C - C - -- : - C - C (1) I 1 Z = S, 0. and N, 1 2

The purposes of this study are: 1) to evaluate the migratory abilities of the possible participating hetero groups, 2) to study the effects of environment on the paths of decomposition of such diazo compounds, 3) to use hetero atom rearrangement as a synthetic tool, and 4) to compare the reaction patterns of these carbenic systems with those which occur by appropriately modified mechanisms.

The experimental design of this study involves determination of the products of decomposition of selected diazo compounds ob tained pure or generated in situ (Equations 2, 3, and 4) by base- catalyzed thermal decompositions of their respective 2~toluenesulfonylhydrazones, a process known to proceed via a carbenic mechanism (2).

(2) L. Friedman and H. Shechter, J. Am. Chem. Soc., 81, 5512 (1959).

n-nhso2c7 h7 n2 :Z~CR2 - C - R - :Z-CR2 - C - R + 02SC?H7 + BH (2)

N2 i :Z-CR2 - C - R --- * :Z - CR2 - C - R + K2 (3)

:Z - CR2 - C - R --- * :Z - CR* = CR'R + R2C = RC-Z: (4)

For determination of the migratory aptitudes appropriate

2-alkylhetero and 2-arylheteroacetophenone tosylhydrazones were 3 prepared and decomposed carbenically. Analysis of the decomposition products is by gas liquid chromatography.

Base-catalyzed decomposition of the acetophenone tosylhydrazones with sodium methoxide, lithium methoxide, and n-butyllithium (1 .0 to 3*1 equivalents) were investigated in order to ascertain the influence of base strength, stoichiometry and various cations upon the carbenic rearrangement processes. A kinetic study of thermolysis of l-diazo-2-ethylmercapto-l- phenylethane and 1-diazo-l-phenylethane was made in order to

determine the influence of participation in these decomposition

systems. To further extend the study of possible hetero atom

rearrangement to carbenic centers, an investigation of base-

catalyzed thermal decomposition of l,3"dithiane tosylhydrazones was initiated (Equation 5) .

N - NHSOgC^Hy © + N 2 + s o 2 C 7H 7 (5) HISTORICAL

Attempts to prepare the simplest carbene, methylene (l), were

(1) (a) J. B. Dumas, Ann. chlra. phys., [2], ^8, 28 (1865)* (b) H. V. Regnault, Ibid.[21. 71, -427 (1839). (e) A. Penot, Ann., 101, 375 (1857). (d) A. M. Butlerov, ibid.. 120. 356 (1861). made before the quadrivalency of carbon was established. These early synthetic failures were followed in the first decade of the twentieth century by postulation of carbenes as intermediates in many organic reactions. Methylene was suggested as a reaction

intermediate in the photolysis of diazomethane (2) and also in the

(2) T. Curtius, A. Darapsky, and E. Kflller, Chem. Ber., £1, 3168 (1908).

formation of ethylene by hydrogenation of carbon monoxide over

nickel or palladium (3). Early conclusions from work with ketenes

(3) E. I. Orlov, Zh. Russk. Fiz. Khim. Obshch., AO, 1588 (1908).

and diazo compounds suggested that carbenes are transient diradicals

(A), but the observation (5,6) and adequate interpretation (6) of

(A) H. Staudinger, E. Anthes, and F. Pfenniger, Ber. deut. chem. Ges., ££, 1928 (1916).

A (5) H. Murwein, H. Rathjen, and H. Werner, ibid.. 71* 1610 (1942).

(6) W. v. £. Doering, R. G. Buttery, R. G. Laughlin, and N.Chaudhuri, J. Am. Chem. Soc., 78, 3224 (1956). insertion of methylene and other divalent derivatives into carbon— hydrogen bonds made it clear that carbenes are unique intermediates that give reactions not encountered with radicals.

Routes to divalent carbon intermediates have been devised and evidence for the presence of carbenes in numerous reactions has been found. The generation and reactions of carbenes have been extensively reviewed (7-17).

(7) W. Kirmse, Angev. Chem., 71, 537 (1959).

(8) J. Leitich, Osten. Chemiker-Ztg., No. 6. 164 (i960).

(9) W. Kirmse, Angew, Chem., 72, 161 (1961).

(10) P. Miginiac, Bull. soc. chim. France, 2000 (1962).

(11) E. Chinoporas, Chem. Rev., 62, 235 (1963).

(12) J. Hine, "Divalent Carbon," The Ronald Press Company, New York, N. Y., 1964-

(13) H. N. Frey, "Progress in Reaction Kinetics," Vol. II, Chapter 3, The Macmillan Company, New York, N. Y., 1964.

(14) G. M. Kramer and T. J. Wallace, Adv. Petrol. Chem. Refining, % 233 (1964).

(15) W. Kirmse, "Carbene Chemistry," Academic Press, Inc., New York, N. Y., 1964.

(16) A. W. Johnson, Sci. Progr., 22., 127 (1965).

(17) B. J. Herold and P. P. Gaspar, Fortschr. Chem. Forsch., 2, 89 (1965). Discussion of divalent carbon includes consideration of the distribution of its two nonbonded valence electrons. Carbon atoms have four low-energy bonding orbitals. The carbene carbon uses two

orbitals for covalent bonds leaving two for occupation by the two

nonbonding electrons. If the two orbitals are equivalent, the

electrons should, according to Hund’s rules, occupy different 2P

orbitals (I) and have parallel spins; the carbene would therefore

be a triplet. On the other hand, if the two available orbitals are

not degenerate, the two electrons will occupy the lower of the

available orbitals with consequent spin-pairing and therefore be

a singlet. In the singlet state the electrons are considered to

occupy an SP^ orbital leaving a vacant 2P orbital (II).

R C R (E x p

I (Triplet) II (Singlet)

Skell and Woodworth (18,19) have suggested that stereospecific

(18) P. S. Skell and R. C. Woodworth, J. Am. Chem. Soc., 78, -U96 (1956).

(19) R. C, Woodworth and P. S. Skell, ibid., 81, 3383 (1959)

addition to olefins by methylene is evidence for a singlet inter

mediate, whereas the triplet species should not add stereospecifical-

ly. Methylene produced from photolysis of diazomethane is assigned

as a singlet on the basis of its stereospecific addition to cis- and trans-2-butenes. From cis addition to olefins the singlet state is assigned to dibromomethylene (22), dichloromethylene (22), propyli- dene (21), carbethoxymethylene (23), 2-ketopropylidene (21), and

cyclopropylidene (25) as initially generated. The occurrence of nonstereospecific addition is used to assign the triplet state to propargylidene (21), diphenylmethylene (20), fluorenylidene (26),

dicyanomethylene (27), and bis(trisfluoromethyl)methylene (28).

(20) R. M. Etter, H. S. Skovronek, and P. S. Skell, ibid.. 81, 1009 (1959).

(21) P. S. Skell and J. Klebe, ibid.. 82, 247 (i960).

(22) P. S. Skell and A. F. Garner, ibid.. 78, 5430 (1956).

(23) P. S. Skell and R. M. Etter, Chem. and Ind., 624, (1958).

(24) R. W. Murray, A. M. Trozzoli, E. Wasserman, and W. A. Yager, J. Am. Chem. Soc., 8 4, 3213 (1962).

(25) W. M. Jones, M. H. Grasley, and W. S. Brey, Jr., ibid.. 8£, 2754 (1963).

(26) (a) E. Funakubo, I. Moritani, T. Nagi, S. Nishida, and S. Murahashi, Tetrahedron Letters, 1069 (1963). (b) M, Jones, Jr. and K. R. Rettig, J. Am. Chem. Soc., 82, 4013, 4015 (1965).

(27) E. Ciganek, ibid.. 88, 1979 (1966).

(28) D. M. Gale, W. J. Middleton, and C. G. Krespin, ibid., 88, 3617 (1966).

In spite of warnings that all stereospecific additions need not

be due to singlets and that all triplets need not add nonstereo-

specifically (29), the use of the stereochemical outcome of additions 8

(29) (a) W. B. De More and S. W. Benson, Advan. Photochem., 2, 219 (1964). (b) P. P- Gaspar and G. S. Hammond, "Carbene Chemistry," W. Kirmse, Ed., Academic Press, Inc., New York, N. Y., 1964,, p. 235-

of carebenes to olefins as a diagnostic tool for spin states has been widespread. A case in point is that of Murahashi and co- workers (30) who have shown that dibenzo[a,d] cycloheptenylidene (ill)

(30) (a) S. Murahashi, I. Moritani, M. Nishimo, J. Am. Chem. Soc., 89, 1257 (1967). (b) I. Moritani, S. Murahashi, M. Nishimo, Y. Yamamoto, K. Itoh, and N. Mataga, ibid.. 89. 1259 (1967).

and tribenzo[a,c,e]-cycloheptenylidene (IV) add to olefins stereo-

specifically even though hydrogen abstraction products are formed

competitively and these carbenes have triplet ground states. These

results strongly suggest that triplet carbenes might add to olefins

stereospecifically.

Ill IV

A triplet ground state and a close-lying singlet state for

methylene are indicated from quantum mechanical calculations (31-33).

(31) G. A. Gallup, J. Chem. Phys., 26, 716 (1957). 9 (32) A. Padgett and M. Kraus, ibid.. 32, 189 (I960).

(33) J. M. Foster and S. F. Boys, Rev. Mod. Phys., 305 (I960).

Spectroscopic evidence suggests that vapor phase photolysis (34,35)

(34) G. Herzberg and J. Shoosmith, Nature, 183. 1861 (1959).

(35) G. Herzberg, Proc. Roy. Soc. (London!, Ser. A . 262. 291 (1961).

of diazomethane produces singlet methylene which decays to the trip

let in the presence of inert gas at high pressures. Methylene

produced in the presence of argon at high pressures adds nonstereo-

specifically to cis- and trans-2-butenes (36,37); these results

(36) H. M. Frey, J. Am. Chem. Soc., £2, 5947 (i960).

(37) D. B. Richardson, K. C. Simmons, and J. Dvoretsky, ibid.. §2, 1934 (1962).

provide chemical evidence for singlet-triplet decay. Photosensitized

decomposition of diazomethane apparently gives triplet methylene

since nonstereospecific addition occurs to give cis- and trans-2-

butenes (38). Thermolysis of diazomethane produces singlet methylene.

(38) K. R. Kopecky, G. S. Hammond, and P. A. Leermakers, ibid.. Si, 2397 (1961); ibid., £4, 1015 (1962).

From these observations and the fact that methylene is highly

reactive (39), it is reasonable to conclude that thermal or direct

(39) W. von E. Doering, R. G. Buttery, R. G. Laughlin, and N. Chandhuri, ibid.. 78, 3224 (1956). 10 photolytic decomposition of diazomethane in the liquid phase produces excited singlet methylene which undergoes reaction more rapidly than spin inversion to its triplet ground state. This conclusion for carbenes should prevail except when certain structural features

(18-23) either facilitate spin inversion or allow direct formation of the triplet state.

From electron spin resonance studies triplet ground states have been verified for diphenylmethylene (24,40), phenylmethylene

(41), fluorenylidene (41), cyelopentadienylidene (42), indenyli-

dene (42), diazomethylene (43), dicyanomethylene (44), cyanomethylene

(44), propargylidene (45), and various para-substituted diphenyl- methylenes (4 6),

(40) R. W. Brandon, G. L. Closs, and C. A. Hutchison, Jr., J. Chem. Phys., 27, 1878 (1962).

(41) A. M. Trozzolo, R. W. Murray, and E. Wasserman, J. Am. Chem. Soc., 84, 4990 (1962).

(42) E. Wasserman, L. Barash, A. M. Trozzolo, and R. W. Tager, ibid., 86, 2304 (1964).

(43) E. Wasserman, L. Barash, and W. A. Yager, ibid.. 87. 2075 (1965).

(44) R* A. Bernheim, R. J. Kempf, P. W. Burner, and P. S. Skell,J. Chem. Phys., £1, 1156 (1964).

(45) R. A. Bernheim, R. J. Kempf, J. V. Gramas, and P. S. Skell, ibid.. 196 (1965).

(46) A. M. Trozzolo and W. A. Gibbons, J. Am. Chem. Soc., §2, 2391(1967). 11

Carbenes undergo several types of bimolecular processes.

Insertion into carbon-hydrogen bonds (4-7-51) is the most character istic reaction of carbenes.

(4.7) Vf. v. E. Doering and L. H. Knox, ibid.. 78. 4-94-7 (1958).

(48) W. v. E. Doering, L. H. Knox, and M. Jones, J. Org. Chem., 2£, 136 (1959).

(49) L. Friedman and H. Shechter, J. Am. Chem. Soc., 82, 1002 (I960).

(50) L. Friedman and H. Shechter, ibid.. 83. 3159 (1961).

(51) C. G. Gutsche, G. L. Backman, and R. S. Coffery, Tetrahedron, 18, 617 (1962).

There is evidence (52) by labelling that insertion into carbon-

(52) W. v. E. Doering and H. Prinzbach, ibid.. 6, 24 (1959). hydrogen bonds proceeds by a "three-center" mechanism without inter vention of a detectable intermediate (Equation 1).

N — C - H + rCHg - C - CH2 - H (1)

From the research of Doering and co-workers(6) it was shown that the various carbon-hydrogen bonds in n-pentane, 2,3-dimethyl- butane, and cyclohexene are attacked indiscriminately by methylene in the liquid phase. However there is some discrimination of these reactions in the gas phase (53). The rates of insertion into 12

(53) H. M. Frey, J. Am. Chem. Soc., 80, 5005 (1958). secondary and tertiary carbon-hydrogen bonds are, respectively, about 20 and 5C$ higher than the rates of insertion into primary bonds. In photolysis of diazomethane in cyclohexane there is no discrimination of insertion into aliphatic and allylic hydrogens; however a slight preference for vinylic hydrogen is indicated (6).

There is an isotope effect of k^/hQ = 1*3 for insertion of methylene into secondary carbon-hydrogen bonds (54).

(54) J. Chesick, ibid.. 84, 2448 (1962).

Carbon-carbon single bonds are inert to methylene. However carbon-carbon double bonds add methylene easily to form cyclopropanes

(Equation 2). This ability of carbenes is the basis for many useful syntheses (55).

(55) For a review of the synthetic applications of carbenes see H. Kloosterziel, Chem. Weekblad, (1963).

= =CH2 _ /c -/cx (2) CH2

When intramolecular stabilization of a carbene is possible, there is only a slight chance for intermolecular reactions. Possible intramolecular reactions are insertion, rearrangement, and fragmenta tion. Insertion of divalent carbon into {i-hydrogen giving olefins 13 involves hydrogen migration (Equation 3); in systems with y -hydrogens, there may be 1,3-insertion to yield cyclopropanes

(Equation 4)•

R'CH - C - R — ~ K-C = CHR (3) 2 2 R R-

R0CH - CR - C - R (4) 2 2 / R

Insertion into 6- and e-carbon-hydrogen bonds occurs readily

in medium-sized rings (50) and transannular (56) carbene insertion

(56) R. S. Shank, Ph.D. dissertation, The Ohio State Uni versity, 1961.

into carbon-hydrogen bonds has also been observed.

Carbon skeleton rearrangement, which is equivalent to intra

molecular insertion across a carbon-carbon single bond, is not a

major process in reactions of carbenes. Carbenes which are members

or are adjacent to small rings are exceptions to this generalization.

Rearrangements are major in thermal decompositions of cyclopropyl-

diazonethane (4-9), diazocyclopropane (50), and diazocyclobutane (4-9).

Migration of alkyl and aryl groups is the basis of the Wolff rearrange

ment of a-diazoketones (57).

(57) W. E. Backmann and W. S. Struve, ’’Organic Reactions," Vol. 1, Ch. 2, John Wiley and Sons, Inc., New York, N. Y., 1942, p. 38. H

Competitive migratory abilities of various groups to divalent carbon have been studied in recent years. Pyrolysis of l-diazo-2- methyl-2-phenylpropane (58) is accompanied primarily by phenyl

(58) H. Philip and J. Keating, Tetrahedron Letters, 1£, 523 (1961).

rearrangement to give 2-methyl-l-phenylpropene (Equation 5)•

CHoi J CK, <3 Ph \ Ph - C - CHN2 — » = CHPh + = CH - CH3 (5)

ch3 ch3 ch3 10 1

In rearrangements of 2-phenylpropylidene and 2,2-diphenylethylidene,

the order of migration is H > 0 > Me (59). Migratory aptitudes

(59) Private communication from G. Kauffman of this labora tory.

for rearrangement in the 2,2,2-triarylethylidene system are:

£-anisyI, 1.37; £-tolyl, 1.23; phenyl, 1.00; p-chlorophenyl,

0.92; p-nitrophenyl, 0.4-5 (60). The migratory aptitudes of base-

(60) C. G. Moseley, Ph.D. dissertation, The Ohio State University, 1967.

catalyzed decomposition of 2,2-diarylpropanal tosylhydrazones are:

£-anisyl, 1.83; £-tolyl, 1.41; phenyl, 1.00; p-chlorophenyl, 0.90;

and £-nitrophenyl, 0.23 (60). These relative rates of migration are 15 in the order expected for rearrangement to an electron deficient center and a reasonable representation of the transition state is V.

CHo I ' — CH

Z V

Carbenic rearrangements involving migration of atoms other than carbon and hydrogen have also been reported. Migration of fluorine occurs in photolysis of 2,2,2-trifluorodiazoethane to trifluoroethylene (Equation 6) (61). In photolysis of

(61) R. Fields and R. N. Haszeldine, J. Chem. Soc., 1881 (1964).

hv CF3CHiN2 CF-jCH — ► CF2 = CHF + CFjCH = CHCF-j

32% 4B% (6) l-diazo-2,2,3,3,4,4,4-heptafluorobutane, migration of a perfluoro- alkyl group rather than of fluorine occurs to yield 1,1,3,3,4,4 ,4* heptafluorc-l-butene (Equation 7) (61).

ViV ■* C3F 7-CHN2 C3F7-C-H — » CF2 = CH-CF2-CF3 + C3F?CH = CHC3F?

31* ' 47$ (7) 16

Diazoacetaldehyde diethylacetal is photolyzed or decomposed catalytically with copper or cuprous chloride to give ketene diethyl acetal derived from hydrogen migration and 1,2-diethoxyethylene by ethoxyl migration (Equation 8) (62). The yields of the products were

(62) W. Kirmse and M. Buschoff, Angew. Chem. Intern. Ed. Engl., 4, 692 (1965).

^ rCH2=C(0C2H5)2

N2CH-CH(0C2H5) 2 ► H-C-CH(0C2Hg)2 (8) 2 V ^C2H50CH = CH0C2H5 not given. Diazoacetaldehyde ethyleneacetal gives upon photolysis

1,4-dioxene via alkoxyl migration and ketene ethyleneacetal by hydrogen migration (Equation 9) (62). Irradiation of l-diazo-2-

/ | 2 N2CH-CH I‘2 + CH2 = C n CH2 (9)

methoxy-2-methylpropane results, apart from intramolecular insertion to 1-methoxy-l-methylcyclopropane, mainly in methyl migration to give 2-methoxy-2-butene; only traces of l-methoxy-2-methylpropene, which is formed by a methoxyl shift, were found (Equation 10) (62). It is reasoned that the p-substituted alkoxyl group is not prone to migrate but rather promotes migration of other p-substituents by stabilization of a partial positive charge in the transition DISCUSSION

The present investigation involves study of carbenic rearrangement reactions of diazo compounds having ether, amine, and thioether substituents in 0-positions (I) (1) and of repre sentative 2-diazomethyI-2-methyl-l ,3**dithianes (II). The

(l) In this work substituents on carbon adjacent to the divalent carbon are referred to as being beta.

«2 n -- ___ 0CH = CHZ - C - ch2z -v gf - c - ch2z 2 = CH? I 0

Z = CMe, 0, OH, NXe2 , NH0, S0, SEt

s. R .. v .C-R_n /— s C - R / C-CH;

\ - f ^ C H 9 * \ _ S ^ C H 3 \ Rv _ ^ CH3 n 5 S R- 0 , H objectives of this investigation are to determine the relative abilities of hetero atom substituents and of hydrogen to migrate to divalent centers, to assess the role of hetero atom participa tion in carbenic processes and to evaluate electronic factors in

18 19 analogous carbonium ion and carbenic rearrangement processes. The method of preparation of the necessary diazo compounds, pure or in situ, entailed initial synthesis of the appropriate tosylbydrazones.

To study the migratory ability of p-hetero atom substituents to divalent carbon, base-catalyzed decomposition of 2-substituted acetophenone p-toluenesulfonylhydrazones in aprotic environments was investigated. This system afforded no major synthetic prob lems to incorporation of the necessary hetero atom substituents.

2-Kethoxyacetophenone (2) was obtained from methoxyacetonitrile (3)

(2) E. B. Moffett and R. L. Shriner, Org. Syn., 21, 79 (1941)• (3) Methoxyacetonitrile was prepared by the procedure of J. A. Scarrow and C. F. K. Allen, Org. Syn., 1J., 56 (1933).

and phenylmagnesium bromide and subsequent hydrolysis (Equation 1).

0 CH,OCH5CN CH O-CH2-C-0 (i) 3 2 2) H30+ 3

2-Phenoxyacetophenone was prepared from phenacyl bromide and phenol

in the presence of potassium carbonate (Equation 2) (A). Hydrolysis

(4) The general procedure used was that of E. Mohlau, Ber., 1£, 2498 (1882).

0 0 0 - C - CH^Br + 0OH K2C03 t 0 - C - CH20jZf (2) of the product of reaction of phenacyl bromide and potassium formate yields 2-hydroxyacetophenone (Equation 3) (5).

(5) This method is a modification of that used for con verting 2-bromopropiophenone to 2-hydroxypropiopbenone; P. L. Julian, E. W. Meyer, A. Magani, and W. Cole, J. Am. Chem. Soc., 62, 1203 (194-5).

0 S 0 - C - CH^r + K02CH ------* 0 - C - CH20H (3)

2-Methoxyacetophenone, 2-phenoxyacetophenone and 2-hydroxyaceto phenone were converted to their corresponding 2,-toluenesulfonylhydrazones by reaction with p-toluenesulfonyl hydrazide (6)

(Equation 4)•

(6) p-Toluenesulfonyl hydrazide was prepared by the method of L. Friedman, R. L, Little, and W. R. Reiehle, Org. Syn., 40, 93 (i960).

o n-nh-so2c7 h7 n . C7H7S02HHNK2 " , RO-CH2-C-0 ------* RO-CH2-C-0 (4)

R = Me, jZf, H

Treatment of 2-chloroacetophenone with dimetbylamine (7)

(7) Caution should be used in transfering dimethylamine.

afforded 2-dimethylaminoacetophenone (Equation 5) (8). Attempts 21

(8) The general procedure used was that of R. L. Letsinger and R. Collat, J. Air. Chem. Soc., 7^, 621 (1952).

0 0 0 - C - CR2C1 + HNMe2 — — — ►’ 0 - C - CH2 - HMe2 (5)

to prepare 2-dimethylaminoacetophenone £-toluenesulfonylhydrazone from 2-dimethylaminoacetophenone and p-toluenesulfonyl hydrazide in refluxing methanol failed. It was necessary to prepare 2-dl- methylaminoacetophenone hydrochloride; the hydrochloride reacts with £-toluenesulfonyl hydrazide to yield 2-dimethylaminoacetophenone hydrochloride 2"toluenesulfonylhydrazone (Equation 6).

0 N- NHS05C7H7 n it 1 ' 0 - C - CH NKe2 1) HC1______0 - C - CHoNHMe2Cl~ (6) * i) c7 h7 so2nhkh2 +

Reaction of 2-bromoacetophenone and two equivalents of aniline in ethanol gave 2-phenylaminoacetophenone (9)• 2-Phenyl-

(9) The method used was based on that of G. Buchmann and R. Lindow, tfiss. Z. Tech. Hochsch. Chem. Leuna-Merseburg, j>, 125 (1963). aminoacetophenone was efficiently converted to its tosylhydrazone

(Equation 7).

0 N-NHS02C7H7 d « a C«K«S05NHNHo , w . 0 - C - CH2NH0 7 7 2 0 - c - CH2NH0 (7) 22 2-Phenylmercaptoacetcphenone (10) (Equation 8) end 2-ethyl-

(10) The procedure used was that of W. J. Kenney, J. A. Welch, and D. A. Davenport, J. Am. Chem. Soc., 82, 4-019 (1961). mercaptoacetophenone (ll) (Equation 9) were prepared by known

(11) The general procedure was that of L. Long, ibid., 6 8. 2159 (1946)-. methods; 2-ethylmercapto-4 '-chloroacetophenone and 2-ethylmercapto-

^-'-bromoacetophenone were synthesized from the corresponding phenacyl halide and ethyl mercaptan in the presence of sodium hydroxide (ll)

(Equation 9)«

8 MeO " , 9 0 - C - CHoCl + 0SH 0 - C - CHpS0 (8) -Meuh

o .0 H HO n 2 - 0 - C - CH-X + EtSH - ■ ■ -« 2 - 0 - c - CtUSSt (9) *H2° 2 X - Cl or Br Z = H, e-CI, 2-Br

The various substituted acetophenone p-toluenesulfonylhydrazones prepared from their corresponding ketones, their melting points, and yields are tabulated in Table 1, p. 23.

A study was then initiated of thermal decomposition of salts of the various tosylhydrazones in aprotic media. Such reactions should lead to intermediate diazo compounds which TABLE 1

£-Toluenesulfonylhydrazones of 2-Substituted Acetophenones

Melting £-Toluenesulfonylhydrazone of point Yield o 1— o

2-Methoxyacetophenone ( 83%

2-Phenoxyacetophenone 125 98

2-Hydroxyacetophenone 142 67

2-Dimethylaminoacetophenone hydrochloride 171 47

2-Phenylarainoacetophenone 128 61

2-Phenylmercaptoacetophenone 98 97

2-Ethylmercaptoacetophenone 124 73

2-Ethylmercapto-4'- chloroacetophenone 104 70

2-Ethylmercapto-4,- bromoacetophenone 119° 81%

subsequently decompose via intramolecular carbenic processes as

illustrated in Equation 10. 2k

The first system in the base-catalyzed thermal decomposition of 2-substituted acetophenone tosylhydrazones to be studied was that of 2-methoxyacetophenone tosylhydrazone. 2-Methoxyacetophenone

tosylhydrazone in tetrahydrofuran was reacted with one equivalent

of n-butyllithium in tetrahydrofuran. The lithium salt of 2-methoxy-

acetophsnone tosylhydrazone was obtained by removal of the solvent

at reduced pressure and pyrolyzed in situ by heating to 160°. The

products of thermolysis are obtained free from lithium jq-toluene-

sulfinate by distillation.

Analysis of the distillate by gas-liquid chromatography

reveals only one major product; the product has the same retention

time as authentic p-methoxystyrene (12). Treatment of a portion

(12) The columns used are 5' x l/8" Carbowax 20 M (15/0 on Chromosorb G and 10' x 1/kn Carbowax 20 M (20%) on Cbromosorb G.

of the distillate with 2,4-dinitrophenylhydrazine reagent gives

phenylacetaldehyde 2,4-dinitrophenylhydrazone.

Of the expected products from carbenic decomposition of

l-dia2o-2-ir9thoxy-l-phenylethane, only hydrogen migration to the

divalent center occurs to give cis-p-methoxvstyrene (k&%) and

trans-S-methoxystvrene (52^); methoxyl migration to give a-methoxy-

styrene (Equation ll) does not occur.

U2 ^ 0CH = CHOMe 0 - C - CH20Ke 0 - c - CH20I'ie (ll)

JC = CHp MeO In order to determine if the lithium cation (13) affects

(13) It has been shown that base-catalyzed decomposition of 3,3-dimethyl-2-butanone tosylhydrazone in diethyl Carbitol con taining lithium cations gives yi% rearranged products. This is in marked contrast to the of rearranged products without lithium cations. It is concluded that there is a lithium cation effect which may well operate through formation of a metalloid carbonium ion complex. G, M. Kaufman, Ph.D. dissertation, The Ohio State University, 1967.

the decomposition path of l-diazo-2-methoxy-l-phenylethane, the

diazo compound was obtained free from lithium £-toluenesulfinate

by pyrolytic distillation (130-14.0°/]. mm.) of the lithium salt

of 2-methoxyacetophenone tosylhydrazone (Equation 12). 1-Diazo- Li N-N-SO2C7 H7 N2 0 - C - CH20Ke -LISO2C7 H7 ^ ^ . c - CH2 - CKe (12)

2-methoxy-l-phenylethane was collected at -78°, and then decomposed

by heating to 150° • Analysis as described previously reveals that

only p-methoxystyrene was formed. Thus thermolysis of l-diazo-2-

methoxy-l-phenylethane Involves selective rearrangement of hydrogen

rather than methoxyl to divalent carbon.

It has been shown that the stoichiometry of the base and

the specific base affect the course of decomposition of tosyl-

hydrazones (.14,15). Thus a study of stoichiometry of various bases

(14) J. A. Smith, H. Shechter, J. Eayless, and L. Fried man, J. Am. Cbem. Soc., 87, 659 (1965). (15) H. H. Shapiro, J. H. Duncan, and J. C. Clopton, ibid.. 8£, 1442 (1967). 26 on the decomposition of 2-methoxyacetophenone p,-toluenesulfonylhydrazone was made. The decompositions were effected in bis(l- methoxyethyl)ether (diglyme) with various amounts of n-butyllithium

(1 .1 and 2 .1 equivalents), sodium methoxide (l.l, 2.1, and 3 .1 equivalents), or lithium methoxide (l.l, 2.1, and 3 .1 equivalents) by slowly beating the mixtures to 130° over ca. 4-5 minute period.

At approximately 110° the mixture became cloudy red and nitrogen

evolution began. The decomposition mixtures were analyzed by gas- liquid chromatography. The results of the decompositions showed that only p-methoxystyrene, as derived by hydrogen migration, is

formed. Due to the feet that p-methoxystyrene is the only intra

molecular products in these experiments, it is concluded that the

bases, in the stoichiometries studied, do not affect the decomposi

tion of l-dinzo-2-methoxy-l-phenylethane in diglyme.

To extend the study of possible rearranging oxygen hetero

atom substituents investigation was made of 2-phenoxy-l-phenyl-

ethylidene. The objective of this research was to compare the

migratory ability of phenoxy versus hydrogen to the divalent carbon.

2-Phenoxyacetophenons p-toluenesulfonylhydrazone in ether

was converted to its lithium salt upon addition of an equivalent

of n-butyllithium at 25-30°. After removal of the solvent, thermal

decomposition of the dry lithium salt at 14.0° gave p-phenoxystyrene

(Equation 13) as the only intramolecular rearrangement

(13) 27 product. The product was identified by comparison of its retention time with that of an authentic sample of p-phenoxystyrene (i6) and

(16) The columns used were 5' x l/8" FFAP (5;£) on Chromosorb G and 5' x 1/8" FFA? {15%) on Chromosorb G. by its hydrolysis to phenylaaetaldehyde with 70% perchloric acid.

A series of experiments was then conducted of decomposition of 2-phenoxyacetophenone tosylhydrazone with various bases in an

aprotic solvent in order to establish if the base or the equivalents

of base altered the process. The base-catalyzed thermal decomposi

tions of 2-phenoxyacetophenone tosylhydrazone in diglyme with n-

butyllithium (l.l and 2.1 equivalents), sodium methoxide (l.l, 2 .1 ,

and 3*1 equivalents) or lithium methoxide (l.l, 2 .1 , and 3*1 equi

valents) proceed only with formation of jl-phenoxystyrene.

As observed in the Eethoxy analog, thermolysis of l-diazo-2-

phenoxy-l-phenylethane results in rearrangement of fj-hydrogen

rather than the phenoxy group. It is apparent from these results

that in carbenic rearrangement of 2-methoxy-l-phenylethylidene and

2-phenoxy-l-phenylethylidene, hydrogen migrates much more readily

than do phenoxy or methoxy groups (17).

(17) A preliminary study of the base-catalyzed decomposition of 2-hydroxyacetophenone tosylhydrazone with two equivalents of n- butyllithium was made, analysis of the thermolysis mixture shows that acetophenone, phenylacetaldehyde, or styrene oxide are not present. Further study needs to be made in this system. 28

An investigation of thermolysis of l-diazo-2-dimethylamino-

1-phenylethane was then initiated. The objective of this study was to determine if the dimethylamino substituent would migrate to the divalent center. It was thought that a dimethylamino group would shift to a carbenic center more readily than do methoxy or phenoxy groups. This result might be expected on the basis that nitrogen- containing nucleophiles are more nucleophilic than the corresponding oxygen species (18). In general neighboring group participation in

(18) S. Streitwieser, Chem. Revs., £6 , 573 (1956).

carbonium ion processes occurs more effectively with nitrogen-con

taining than with analogous oxygen-containing functions.

In order to effect base-catalyzed decomposition of 2-dimethyl-

eminoacetophenone hydrochloride tosylhydrazone, two equivalents of

base were necessary (Equation 14). Pyrolysis of the lithium salt of

N-NHS0oCr7H9 n-»so2o7h7 + n * t f h e2h H-CH2-C-$ ► Ke2N-CH2-C-0 (14) Cl“ -2BH

2-dimethylaminoacetophenone tosylhydrazone in diglyme gave with

loss of nitrogen one volatile product, p-dimethylaminostyrene,(19)

(19) Analysis was by gas chromatography with 5' x l/8" Carbo wax 2QM (15^) on Chromosorb G and 5' x 1/8" 3C-3Q (5*) on Chromosorb W columns. 29 which on hydrolysis with hydrochloric acid yielded phenylacetaldehyde. Treatment of p-dimethylaminostyrene with 2 ,4-dinitrophenylhydrazine reagent afforded phenylacetaldehyde 2 ,4-dinitrophenyl- hydra2one.

To ensure that the decomposition of l-diazo-2-dimethylamino-

1-phenylethane occurred via a carbenic process reaction of 2-dimethyl

aminoacetophenone hydrochloride tosylhydrazone with excess base was

investigated. l-Diazo-2-dimethylamino-l-phenylethane, prepared

in situ from 2-dimethyleminoacetophenone hydrochloride tosyl

hydrazone and sodium methoxide (2 .1 , -4*1 , and 6.1 equivalents)

or n-butyllithium (a.I equivalents) decomposes in diglyme to give

only {1-dimethylaminostyrene (equation 15) . The {S-dimethylamino

0CH = CHNKe2

(15)

group does not undergo carbenic rearrangement in competition with

hydrogen in 2-dimethylamino-l-phenylethylidene. There are no

apparent base and cationic effects in carbenic decomposition of

l-diazo-2-dimethylamino-l-phenylethane (20).

(20) 2-Phenylaminoacetophenone tosylhydrazone was converted to its lithium salt with n-butyllithium. Thermolysis of the dry salt gave a dark intractable oil, which on treatment with 2 ,4- dinitrophenylhyarazine reagent afforded no precipitate. This system was not further investigated.

To extend the study of possible participative rearrangement

of jJ-hetero substituents to divalent carbon, a series of beta 30 thioether tosylhydrazones was investigated, 2-Phenylmercaptoaceto- phenone tosylhydrazone was the first to be examined in this series.

N-Lithio-2-phenylmercaptophenone tosylhydrazone was prepared by reaction of 2-phenylmercaptoacetophenone tosylhydrazone and one equivalent of n-butyllithium in anhydrous tetrahydrofuran

(Equation 16). Thermolysis of the dry lithium salt gives a light

Li N-NHSOpCrjHr, K-N-S0»C„H„ n *• t t n <■ i 7 0-C-CH2S0 „ BuLi 0-C-CH2S0 (16) -BuH yellow product which on gas chromatographic analysis (21) separated

(21) The columns used were 5' x 1/8" FFAP (5>) on Chromosorb G, V X 1/4" FFAP (3t) on Chromosorb G, and 5' x l/8" FFAP (15%) on Chromosorb G. into two components. The minor peak (8 S) was identified as fi-phenyl- m9rcaptostyrene by comparison of its retention time with an authentic sample. The major peak (92%) was shown to be a-phenylmercaptostyrene by its KKE spectrum (singlet at 4*75 I and 4«50 T arising from the terminal methylene protons and a multiplet at 2.8 T resulting from the aromatic protons) and its conversion to acetophenone 2 ,4-dinitrophenylhydrazone. Other supporting evidence is its mass spectral molecular ion at 212. Carbenic decomposition of l-diazo-l-phenvl-2-thiophenoxvethane thus Involves ma'.or rearrangement of the thiophenoxy group rather than hydrogen (Equation 17).

N2 0CK = CH30 ft S minor 0-C-CH2S0 (17)

0 major

k saries of experiments was then conducted of decomposition of 2-phenylmercaptoacetophenone tosylhydrazone with various bases in an aprotic medium. The objective of this investigation was to ensure carbenic decomposition of the intermediate 1-diazo-l-phenyl-

2-pbenylmercaptoethane and to check on a possible lithium cation effect. Base-catalyzed thermal decomposition of 2-phenylmercaptoacetophenone tosylhydrazone with 1 .1 , 2 .1 , and 3.1 equivalents of

sodium methoxide or lithium methoxide in decalin or diglyme proceeds with sulfur migration to give a-phenylnercaptostyrene (82-100^) and hydrogen migration to give p-phenylmercaptostyrene (18-CK).

Thus, from this study, it can be concluded that there is no

major cation effect and that carbenic decomposition of 1-diazo-l-

phenyl-2-phenylmercaptoethane in aprotic solvents involves major

rearrangement of the thiophenoxy group rather than hydrogen to the

divalent carbon.

In order to determine if thiophenoxy rearrangement in 1-diezo-

l-phenyl-2-thiophenoxyethane is atypical or part of a general scheme

for p-thioalkyl substituents, additional thioethei’ sulfonyl hydrazones

were investigated. A second example of thioalkyl migration to a carbenic center was found in thermolysis of l-diazo-l-phenyl-2- thioethoxyethane generated in situ by pyrolysis of N-lithio-2- ethylmercaptoacetophenone tosylhydrazone. The lithium salt was prepared by reaction of 2-ethylmercaptoacetophenone tosylhydrazone with n-butyllithium in ether and isolated after removal of the solvent at reduced pressure. Analysis of the decomposition mixture by gas chromatography (22) reveals a minor peak (10'£) identified by its

(22) The columns used were 51 x l/8" FFAP (l5/£) on Chromo sorb G and 10’ x l/4" FFAP (5/^) on Chromosorb G. retention time as p-ethylmercaptostyrene arising from hydrogen migration. The major gas chromatographic product (90/') was shown to be a-ethylmercaptostyrene from its conversion to acetophenone

2 ,4-“dinitrophenylhydrazone and by its mass spectral parent ion at

164 (the calculated molecular weight for a-ethylmercaptostyrene). fcajor rearrangement of the thioethoxy group on pyrolysis of 1-diazo-l- phenyl-2-thioethoxyethane provides a second example of the greater

ability of p-thioalkyl groups than of hydrogen to migrate to a di valent center (equation 18).

0CH=CHSiSt S minor (18)

;c = ch2 EtS major

To expand the investigation of base-catalyzed decomposition

of 2-ethylmercaptoacetophenone tosylhydrazone with various bases in 33 aprotic solvents, a study, as in the thiophenoxy case, was initiated to check on a possible lithium cation effect and to promote carbenic decomposition of l-diazo-2-ethylmercapto-l-phenylethane.

2-Ethylmercaptoacetophenone tosylhydrazone in decalin or diglyme was reacted with 1 .1 , 2.1 , and 3*1 equivalents of sodium methoxide or lithium methoxide. Pyrolysis of the resulting salt proceeds through coloration of the solution followed by nitrogen

evolution. Gas chromatic analysis of the decomposition mixtures

shows a-ethylmercaptostyrene (86-91$) by sulfur migration and

p-ethylmercaptostyrene (14-9$) by hydrogen rearrangement. Conclusions

from this study are: there is no base effect over the stoichiometric

range studied, lithium cation does not alter the product ratios, and

carbenic decomposition of l-diazo-2-ethylmercapto-l-phenylethane

proceeds with selective rearrangement of the thioethoxy group (~90$)

in competition with hydrogen (~10$).

Additional examples of migration of p-thioethoxy groups to

divalent carbon were realized upon base-catalyzed thermolyses of

2-ethylmercapto-4 '-chloroaoetophenone tosylhydrazone and 2-ethyl-

mercapto-4*“bromoacetophenone tosylhydrazone, Thermolysis of dry

N-lithio-2-ethylmercapto-4,_chloroaoetophenone tosylhydrazone under

vacuum (2 mm.) and at 140° yielded 89$ a-ethylmercapto-4'-chlorostyrene.

Pyrolysis of dry H-lithio-2-ethylmercapto-4! -bromoacetophenone gave

similarly 93$ a-ethylmercapto-4' -broiaostyrene (Equation 19) (23).

(23) The products were converted to 4*-chloroaoetophenone end 4 '-bromoacetophenone 2 ,4~dinitrophenylhydrazones efficiently by 2 ,4-dinitrophenylhydrazine reagent. 34

S 2 .. 2113 X-^-C-CH23Zt — 5^*- X-0-C-CH2SEt— » = CH2 (19) X-0

X = £-Cl, p-3r

From carbenic decomposition of l-diazo-2-methoxy-l-phenylethane,

1-diazo-2-phenoxy-l-phenylethane and l-dia.zo-2-dimethylamino-l- phenylethane it was observed that hydrogen migrates to the divalent carbon selectively. There is no observable rearrangement of methoxy, phenoxy, or dimethylamino groups. This is in contrast to thermolysis of l-diazo-l-phenyl-2-phenylmercaptoethene, 1-diazo-

2-ethylmercapto-l-phenylethane, l-diazo-2-ethylmercapto-l-(4’- chlorpphenyl) ethane and l-diazo-2-ethylmercapto-l-(4 ,~hi,omophenyl) ethane all of which undergo major thiophenoxy and tbioethoxy rearrange ment and only minor migration of hydrogen to the carbene. The much greater tendency of thiophenoxy and thioethoxy than of phenoxy, methoxy or dimethylamino substituents to rearrange may be rationalized

in terms of the greater participative ability of sulfur than of oxygen

or nitrogen (24). In carbenic rearrangement of l-diazo-l-phenyl-2-

(24) For discussion of participation of oxygen, nitrogen, and sulfur-containing substituents in intramolecular nucleophilic processes see S. /iinstein and E. Grunwald, J. Am. Chem. Soc., 70, 628 (1943) and ?. D. Bartlett, 3. D. Ross, and C. G. Swain, ibid.. 71, 1415 (1949).

thiophenoxyethane and l-diazo-l-phenyl-2-thioethoxyethane, it is

also possibly significant that 3d orbital delocalization involving

the rearranging sulfur group leads to an ylid-like transition State (ill) which is not readily available to the oxygen (IV) or nitrogen (7) analogs (25).

(25) Sulfoniom alkylides which are related structurally to III are described by R. J. Corey and K. Jautelet, ibid.. 89. 3912 (1967) and references cited therein.

0 - C CH. 0 - C :h , V/ f 1 R R Ilia Illb

R = Et, 0

i - c 0-0 CH' V h T R, R

R = M e , 0 R = Me

As previously discussed neither excess sodium methoxide nor lithium methoxide effect appreciable change in the reaction mechan ism or the product composition of base-catalyzed decomposition of

2-phenylmercaptoacetophenone tosylhydrazone in diglyme or decalin.

Since sodium methoxide end lithium methoxide are only fairly strong bases and their conjugate acids are possible proton donors, it be came of interest to study the actions of very strong bases in decomposition of 2-phenylmercaptoacetophenone tosylhydrazone. n-

Butyllithium was chosen for this investigation because of its strength,

its availability, its convenience of handling, and its conjugate

acid is butane.

Reaction of 2-phenylmercaptoacetophenone was first effected

with 1.1 equivalents of n-butyllithium in decalin. Thermolysis of the resulting lithium salt in situ results in nitrogen evolution

and formation of a mixture of c-phenylmercaptostyrene (94-^) and

p-phenylmercaptostyrene (6^-). Decomposition of 2-phenylmercapto-

acetophenone tosylhydrazone with 1.1 equivalents of butyllithium

thus results primarily in rearrangement of the thiophenoxy group

and the overall process is similar to that for decomposition of the

tosylhydrazone with excess sodium or lithium methoxides. Increasing

the n-butyllithium to 2.1 equivalents affects the path of decomposi

tion in decalin in that the product mixture consists of 21* fJ-phenyl-

merc&ptostyrene end 79^ a-phenylmercaptostyrene. Use of 3.1

equivalents of n-butyllithium for decomposition of the tosylhydrazone

gives B-nhenvlr.ercaptostvrene as the only intramolecular product;

there is complete exclusion of a-phenylmercaptostyrene, the product

of thiophenoxy rearrangement. A similar effect occurs with excess

n-butyllithium in diglyme but it is not as pronounced because the

strong base is destroyed in part by reaction with the solvent.

A possible mechanism to explain the increased formation of

p-phenylmercaptostyrene from 2-phenylmercaptoacetophenone tosyl

hydrazone upon increasing the equivalents of n-butyllithium is 37 outlined in Equation 20. The significant point in this mechanism

N-NH302C7H7 N-2fS02C7H7 0-C-CH2S0 0-C-CHoS0nl n m : or/ BuLi -BuH -BuH

Li N-N302C?K7 N2tt*- ■LiE02C7H7 0-C-CHS0 r 0 -C-CHS0 (20) Li Li

NoLi f 0-C = CHS0 ] 0-0*= CHS0 H~S j 0CH = CHS0 -Li-3 '

is attack of n-butyllithium on the p-hydrogen of the lithium salt of 2-phenylmercaptoacetophenone tosylhydrazone to form the indicated dilithium salt. Decomposition of the dilithium salt by loss of lithium jo-toluenesulfinate and nitrogen yields a-litbio p-thiophenoxystyrene. The driving force for such a process could arise from delocalization of the carbanionic electron pair with the adjacent vacant 2? orbital. Exchange of a-lithio p-thiophenoxystyrene with the reaction solvent allows generation of p-thiophenoxystyrene.

If this mechanism is correct, it might be possible to prepare the dilithio salt of the tosylhydrazone without effecting its

decomposition; reaction of such a salt with a deuterium donor acid should result in deuterium incorporation into p-carbon protium bonds of the tosylhydrazone. This led to the treatment of 2-phenylmercaptoacetophenone tosylhydrazone with 3 equivalents of n-butyllithium in tetrahydrofuran. The resulting red solution was stirred at 0° for 60 minutes, and then neutralized with exactly 3 equivalents of deuterotrifluoroacetic acid (26). Concentrating the solution

(26) The deuterotrifluoroacetic acid was prepared upon mixing equal moles of deuterium oxide and trifluoracetic anhydride. afforded N,2-dideutero-2-phenylmercaptoacetophenone tosylhydrazone

(Equation 21). Isotopic analysis and assignment of the deuterium

Li n-n-so2c?h7 n-hd-so2c7h7 ^ " u 2CFoC0~D , " 0-C-CH-30 2 , 0-C-CHD-30 (21) Li to the 2-position was possible from the NltR spectrum of the product

The spectrum exhibits a singlet at 6.08 T which integrates to one

hydrogen. la is therefore concluded that Equation 20 is represents

tive at least of the initial processes in decomposition of 2-phenyl

mercaptoacetophenone tosylhydrazone with excess n-butyllithium.

Extension of the strong base effect was sought in the

decomposition of 2-ethylmercaptoacetophenone tosylhydrazone in

aprotic solvents. If this is a general phenomenon, one would pre

dict that as the equivalents of base are increased, there would be

a corresponding decrease in thioethoxy migration giving c-ethyl-

mercaptostyrene with a corresponding increase of J3-ethylmercapto-

styrene. The base-catalyzed decomposition of 2-ethylmercaptoaceto-

phenone tosylhydrazone with 1.1 equivalents of n-butyllithium

proceeds with formation of a-ethylmercaptostyrene (84-^) via 39 thioethoxy migration and p-ethylmercaptostyrene (l6^) by hydrogen rearrangement. This result is similar to that for decomposition of the tosylhydrazone with excess sodium or lithium methoxide.

However, repeating the experiment with 2.1 equivalents of butyllithium yields 53^ a-ethylmercaptostyrene and p-ethylmercaptostyrene. When 3*1 equivalents of n-butyllithium are used for the decomposition of 2-ethylmercaptoacetophenone tosylhydrazone in decalin, the only observed product is {U-ethylmercaptostyrene with exclusion of a-ethylmercaptostyrene. The effect of n-butyllithium in diglyme on the base-catalyzed decomposition of 2-ethylmercapto acetophenone was not as evident due to attack of the base on the solvent (27). This diglyme solvent effect would be further amplified

(27) The loss of n-butyllithium by cleavage of diethyl Carbi- tol (which is similar to diglyme) was observed, Ref. 13* if the dilithio salt of 2-ethylmercaptoacetophenone tosylhydrazone is prepared independent of the solvent in which the salt is decomposed.

After treatment of the tosylhydrazone with 3 equivalents n-butyllithium in tetrahydrofuran the salt was obtained by removal of the solvent at reduced pressure. Thermolysis of the salt in diglyme yields c-ethylmercaptostyrene (^5%) and {S-ethylmercaptostyrene (55%). Upon pyrolysis of the salt in decalin, the only intramolecular product is

{5-ethylmercaptostyrene.

Excess n-butyllithium probably reacts, as previously discussed with 2-phenylmercaptoacetophenone tosylhydrazone, with 2-ethylmercahto- phenone tosylhydrazone by the sequence indicated in Equation 22. AO Li N-NH302CoH7 N-N-SO2C7H7 11 A ' ' n 0-C-CK2SSt 2BaL1 , 0-C-CH-SIit -2BuH Li (22)

N Li -LiS02C7H? ,,2 N2 I *■ 0-C-CH-32t----— ----- » 0-C=CII32t Li Li - No , » H - S =---► 0-C-CH-SEt ► jUCH = CHSEt -Li -S

Evidence for the dilithio intermediate is obtained on neutralization of a mixture of 3 equivalents of n-butyllithium and 2-ethylmercapto acetophenone tosylhydrazone in tetrahydrofuran with deuterotrifluoro acetic acid (exactly 3 equivalents) to give N,2-dideutero-2-ethylmercaptoacetophenone tosylhydrazone (Equation 23). Incorporation of

Li N-N-S02C7H7 H-ND302C7H7 tf-C-CHSEt 2C/3C02D gf-C-CHDSEt (23) Li

deuterium into the 2-position is evident from the NKH spectrum of

the tosylhydrazone which exhibits a singlet at 6.32 T which

integrates for one hydrogen. It is therefore concluded that Equation

22 is representative at least of the initial processes in decompo

sition of 2-ethylmercaptoacetophenone tosylhydrazone with excess

n-butyllithium (2b).

(28) The existence of similar dianions have been observed on treatment of acetophenone phenylhydrazone with two equivalents potassium amide. ?. 2. Henock, K. G. Hampton, and C. H. Hauser, J. Am. Chem. Soc., 82, 4-63 (1967). 4i

It has been observed that decomposition of salts of tosylhydrazones in effective protonic environments lead to products derived from cationic mechanisms. An example of this phenomenon is observed in the decomposition of the salt of 2 ,2-dimethylpropanal tosylhydrazone in a proton donor environment (13) to give 2-methyl-l- butene (56^) and 2-methyl-2-butene (39%) which are probably formed via carbonium-ion processes (Equation 24), whereas decomposition

c k 3 n 2 ch3 n2 + GH3 ' " + I t , + H3C-C - C-K -iL*. H3C-C - C-H — H3G-C - CH2 (24)

ch3 ch 3 h c h 3

c h 3

——-H--- + > H.C-CHp - C = CH- + H-C-CH = ^PH3 * * 3 ch3

in an aprotic media produces 1 ,1-dimethylcyclopropane (96^) with

near exclusion of the rearrangement products. The carbenic

mechanism is illustrated in Equation 25.

CH. Np CH. H.C CH3 t J II -k2 t 3 V H3C-C- C-H -----^K3C-C - C-H ---- — ► A (25) CH3 cr3

With this background it became of interest to study the

decomposition of 2-phenylmercaptoacetophenone tosylhydrazone in

ethylene glycol with various bases. The objective of this investi

gation was to determine the products of decomposition of 1-diazo-l-

phenyl-2-phenylmerceptoethane in an excellent proton-donor solvent

find to compare them* with the products derived from carbenic decompo

sition. Reaction of 2-phenylmercaptoacetophenone tosylhydrazone with

1.1, 2.1, and 3.1 equivalents of sodium methoxide in ethylene glycol gives a-phenylmercaptostyrene (89-36;$) and p-phenylmercaptostyrene

(11-14$).

In order to determine if the effect can be attributed to the sodium methoxide in base-catalyzed decomposition of 2-phenyl mercaptoacetophenone tosylhydrazone in ethylene glycol, similar experiments were conducted using n-butyllithium. Reaction of

2-phenylmercaptoacetophenone tosylhydrazone in ethylene glycol with

1, 2.1, and 3.1 equivalents of n-butyllithium followed by pyrolysis of the resulting salt in solution gives a-phenylmercaptostyrene

(83-90;$) and p-phenylmercaptostyrene (17-10,$) which is in close agreement to the data obtained from sodium methoxide. Thus it can be concluded that there is no apparent base effect.

Decomposition of the intermediate l-diazo-l-phenyl-2-phenylmercaptoethane in this proton-donor solvent probably proceeds through a carbonium ion process with high selectivity for rearrange ment of the thiophenoxy group. There are two possible mechanisms for the proposed cationic process; one with proton attack on the nitrogen (Equation 26), the other involves protonation at carbon U 3 of the diazo function (Equation 27). As yet the two mechanisms cannot be distinguished.

m 2 H 0-C - 0H2 _ H _ 0-C - CH2 H - ' c - CB,

* H 20 + S* (27)

(l-C• — CK, -Ht ,+ "• .C = CH, \ + / 2 ds i I*

The fact that the product ratios from decomposition of l-dia2o~l-phenyl-2-phenylmerc8ptoethane in aprotic and protic

solvents are similar, ca. 9il of a-phenylmercaptostyrene to p-phenylmercaptostyrene, is of note. This can be rationalized on the basis that participation of a thiophenoxy group is so great,

that there is little discrimination in rearrangement to either a

carbenic or an energetic cationic center.

Extending the study of proton-donor effects to decomposition

of l-diazo-2-ethylmercapto-l-phenylethane in ethylene glycol lead

to a series of experiments which were to determine the general

applicability of thioslkyl and thioaryl rearrangement. Thermolysis

of the sodium salt of 2-ethylmercsptoacetophenone tosylhydrazone

from reaction of the tosylhydrazone and 1.1, 2.1, and 3.1 equiva

lents of sodium methoxide in ethylene glycol yields a-ethylmercapto-

styrene (65—53 -) and p-ethylmercaptostyrene (35-4-7^) . If similar

experiments are repeated using n-butyllithium (l.l, 2.1, and 3.1

equivalents) , the decomposition products are a-ethylmercaptostyrene (60-53 ^) end fj-ethylmercaptostyrene (l+O-Llt) . From the result of base-catalyzed decomposition of 2-ethylmercaptoacetophenone tosyl hydrazone with sodium methoxide and with n-butyllithium in ethylene glycol there is no apparent cationic effect.

The possible mechanisms for the protic decomposition of l-diazo-2-ethylmercapto-l-phenylethane are initial proton attack on the nitrogen (Equation 28)

^C=Ch'2 + 0CIi=CHSGt (28) or protonation at carbon of the diazo function (equation 29),

(29)

♦ efCH = CHSZt + C = CHo

The greater ability of the thiophenoxy group (~85 ;) than the thioethoxy group (~60i) to rearrange might well be due to the possible resonance stabilization of the transition state (VI) which is not available to the thioethoxy group. Y Y During the course of this reseerch it became essential to prepare pure l-diazo-2-ethylmercapto-l-phenylethane. The general procedure of Farnum (29) gave a 40^ yield of product which vies

(29) D. G. Farnum, J. Org. Chem., 23, 870 (1963).

only 51.5/> diazo compound. Vacuum pyrolysis of the dry lithium salt

of 2-ethylmercaptoacetophenone tosylhydrazone yields a red product

in 66£ yield -which analyzes to be 46,t l-diazo-2-ethylmercapto-l-

phenylethane.

The need for preparing the pure diazo compound led to a

procedure in which piperidine is the base and also the solvent for

decomposing 2-ethylmercaptoacetophenone tosylhydrazone. By this

method l-diazo-2-ethylmercapto-l-phenylethene was prepared in 54;^

yield and in 94'S purity (aquation 30).

N-NH302C7H7 n -n -so2c7h 7 n 0-C - CH2Sbt

(30)

* szf-c - CK2 -S4t

Due to the ease of handling and the relative good yield of

l-diazo-2-ethylmercapto-l-phenyletbane, this procedure may be of

general importance. The method is not restricted to piperidine as

the base-solvent. Other amines may be better suited to conversion

of various tosylbydrazones to their corresponding diazo compounds. It then became of interest to determine in decomposition of

2-ethylmercaptoacetophenone tosylhydrazone ’whether there is participation of the rearranging thioethoxy group before, during, or after nitrogen evolution from l-diazo-2-ethylmercapto-l-phenylethane (equations 31 and 32). A study of the kinetics of thermolysis

N2 N2' a J » ' -N3 0-C - CHpSdt --- ► 0-C— C t U C = CH_ (31) \ + / EtS 2 ? Et

h2 n No , - , - 0-C - CEgSEt 0-C-CH2SSt ►tf-C CK2 .C = CHp \ + / EtS t (32) Et

of l-diazo-2-ethylmercapto-l-phenylethane and of 1-diazo-l-phenylethane was thus initiated. l-Diszo-2-ethylmercapto-l-phenylethane and 1-diazo-l-phenylethane, prepared by decomposition of the piperi dine salts of their corresponding tosylhydrazones were thermolyzed in anhydrous diglyme at 85°* The decompositions were followed by monitoring the rates of evolution of nitrogen by volumetric methods.

The processes obeyed satisfactory first order kinetics in that plots of log1Q(diazo) versus time are satisfactorily linear up to 70^ reaction. The rate constants for decomposition of 1-diazo-l- phenylethane to styrene (k = 1.51 x 10“^ sec-1) and l-diazo-2- ethylmercapto-l-phenylethane (k = 1.44 x 10"^ sec"1) to un c-ethylmercaptostyrene at 85° are very similar. It thus appears

that the rate-determining step for decomposition of the diazo com pounds involves thermolysis to their intermediate carbenes;

subsequent rearrangement of hydrogen in 1-phenylethylidene end of

the thioethoxy group in 2-ethylcercapto-l-phenylethylidene occurs

relatively rapidly. If there was significant concerted participa

tion of the thioethoxy group in decomposition of l-diazo-2-ethyl-

mercapto-l-phenylethane it Is to be expected that the rate constant

for thermolysis of the diazo compound would be larger, perhaps much

larger, than that for 1-diazo-l-pbenyiethane.

Carbenic decomposition of 2-benzoyl-2-netbyl-l,3-dithiane

tosylhydrazone (VII) and 2-formyl-2-methyl-1,3-dithiane tosyl

hydrazone ('/III) has also been investigated. The objectives of

this study were to determine if rearrangement of beta sulfur groups

to divalent carbon would be observed, to compere methyl versus sulfur

migration and check if two beta thioalkoxy groups affect the carbenic

processes.

n -n h s o 2c7k7 11 It

VII VIII

2~Benzoyl-2-nethyl-l,3-dithiane tosylhydrazone was prepared

in 52b yield from p-toluenesulfonyl hydrazide and 2-benzoyl-2-

methyl-1,3-dithiane (30)• deaction of 2-formyl-2-methyl-l,3-dithisne (31) and p-toluenesulfonyl hydrazide gave 2-formyl-2-methyl-1,3- dithiane tosylhydrazone in 1\% yield.

(30) 2-3enzoyl-2-methyl-l,3-dithiane vas obtained from 2- lithio-2-methyl-l,3-dithiane and benzonitrile and subsequent hydrolysis by the general procedure of 3. J. Corey and D. Seebach, Angew. Cbem. Internat. Edit., 1075 (1965).

(31) 2-Lithio-2-methyl-l,3-dithiane reacts with N,N-dimethylformamide to give 2-formyl-2-methyl-l,3-dithiane. The procedure vas essentially that of E. J. Corey and D. Seebach, ibid., 1077 (1965).

Reaction of 2-benzoyl-2-methyl-l,3-dithiane tosylhydrazone with one equivalent of butyllithium in tetranydrofuran and decomposi tion of the subsequent dry lithium salt results in formation of

6,7-dihydro-2-methyl-3-phenyl-5S-l,4-dithiepin rather than 2-(c- methyl-benzylidene)-meta-dithiane (Equation 33).

S S

(33) 49

The NXR spectrum of the intramolecular reaction product shows a singlet at 8.25 T (relative area 3» C = C-CRj) , a uiultiplet at

7.91 T (relative area 2,-CH^-CH^-CH^-). two superimposed triplets at 6.50 T (relative area 4, -S-CKq-CHq-CI^-S), and a singlet at

2.77 ^ (relative area 5, ^-C) which is consistent with either sulfur or methyl migration products. The structure of 6,7-dihydro-2- methyl-3-phenyl-5H-1,4-dithiepin was established upon its reduction with Aaney nickel (32) to n-propylbenzene (Equation 34).

(32) The procedure used was based on that of M. Z. Nazer and C. H. Issidorides, J. Org. Chem., 26, 839 (1961).

h^C \ ^ CH -CH -Cr' -0 (34) Ni 3 2 2

The intramolecular rearrangement product, 6,7-dihydro-2-

methyl-3-phenyl-5H-l,4-dithiepin, gives support to the generality

of sulfur migration to a carbenic center. There is no observable

effect from the stationary sulfur group promoting methyl migration.

The dithiane investigation was expanded to the base-catalyzed

decomposition of 2-formyl-2-methyl-l,3-dithiane tosylhydrazone. The

aims of this study were to extend the general applicability of sulfur

migration s.s a synthetic tool for preparation of 6,7-dihydro-5*1-1,4“

dithiepins and to determine if replacing a phenyl group by a hydrogen

alters the carbenic processes. 5° Reaction of 2-formyl-2-methyl-l,3-dithiane tosylhydrazone with one equivalent of n-butyllithium in tetrahydrofuran followed by thermolysis of the subsequent dry lithium salt results in forma

tion of 6 ,7-dihydro-2-methyl-5H-1,4-dithiepin rather than 2-ethylidene-

meta-dithiane (dquetion 35). The structure of the intramolecular

rearrangement product is assigned from its M'd spectrum which shows H CH a doublet at 8.15 T (J~l, relative area 3, C = C — “^) » a broad

jnultiplet at 7.85 T (relative peak area 2, -S-CHq-CKq-CHq-S-) .

two superimposed tripletst at 6.58 T (relative peak area 4,

-S-CHp-CHq-CKo-S-) and a quartet at 4.32 T (J~l, relative peak area H ,CH,. one, c = C J)• The product assignment is based upon the smell

coupling constant (Jsl) between the vinyl methyl and vinyl hydrogen.

If the product had been 2-ethylidene-meta-dithiane, one would

predict the coupling constant to be ca. £ cps.

Thus from the fact that 6,7-dihydro-2-methyl-5H-l,4-

dithiepin is the decomposition product of N-lithio-2-formyl-2-

methyl-1,3-dithiane tosylhydrazone it appears that the a-hydrogen

does not alter the previously discussed carbenic process. EXPERIMENTAL

General Information

Melting points.— Melting points were determined on a melting point block manufactured by the Fisher Scientific Company. All melting points are uncorrected.

Elemental analyses.— Elemental analyses were performed by

Micro-Analysis, Inc., Wilmington, Delaware.

Infrared spectra.— The infrared spectra of compounds prepared in this research were obtained with a Perkin-Elmer Infracord Spectro photometer. Spectra of solid samples were obtained from potassium bromide wafers and those of liquid samples from liquid films. The reported absorptions are within t 10 cm-^.

Bolling points.— Boiling points were obtained as the compounds distilled. Thermometer corrections were not made.

Nuclear magnetic resonance spectra.— Nuclear magnetic reson ance spectra were determined in deuterochloroform with a Varian

Associates A-60 Instrument using tetramethylsilane as internal standard.

Mass spectra.— Mass spectra were obtained on an Associated

Electrical Industries MS-9 high resolution mass spectrometer.

Gas chromatography.— An F & M Scientific 720 dual column programmed temperature gas chromatograph equipped with thermal

51 conductivity cell detectors (helium carrier gas) and connected to a Honeywell Electronic 15 strip chart recorder, an A-90 Aero graph gas chromatograph equipped with thermal conductivity cell detectors (helium carrier gas) and connected to a one-millivolt

Sargent recorder with disc integrator and a model 600D Aerograph gas chromatograph equipped with a flame detector (nitrogen carrier gas) and connected to a one-millivolt full-scale deflection Brown recorder were used in this work. All stationary phases and solid supports used in this research were purchased from Varian Aerograph,

Walnut Creek, California.

Peak areas, calculated by multiplying the peak height by the

peak width at half-height, were used to determine product composition

Near-quantitative measurements of the compositions of many mixtures

of organic compounds can be made by using the peak areas resulting

from chromatographic analyses (1). No corrections were made for

(1) E. M. Fredericks and F. R. Brooks, Anal. Chem., 28, 297 (1956).

differences in thermal conductivities of the compounds involved (2).

(2) Studies of a representative mixture containing aromatic, cyclic, and aliphatic hydrocarbons, acetone, acetaldehyde, and methyl and ethyl alcohols indicate that the maximum error resulting from the assumption that all the compounds possess the same thermal conductivity is 3.5^. [M. Dimbat, P. E. Porter,and F. H. Stross, ibid.. 28, 290 (1956)].

The 600D Aerograph gas chromatograph equipped with flame detector was checked with known composition mixture and corrections made if needed. Solvents.— Ether and tetrahydrofuran were distilled from lithium aluminum hydride. Diglyme[bis(2-methoxyethyl)ether] was predried over calcium hydride and distilled under reduced pressure from lithium aluminum hydride. Ethylene glycol was purified by distillation from sodium. Reagent grade pentane was eluted through basic alumina and used without further purification.

Pyridine was predried over sodium hydroxide pellets and distilled from barium oxide. Pure decalin was furnished by Chemical Samples

Company. Reagent grade benzene was dried by distillation of 2 % of the material.

Intermediates

Methoxvacetonitrile.— To a cooled, stirred solution (3) of

(3) General procedure of J. A. Scarrow and C. F. H. Allen, Org. Syn., 12., 56 (1933). pulverized sodium cyanide (98 g., 2 moles) in water (200 ml.) was

added paraformaldehyde (60 g., 2 moles) in small quantities so that

the temperature remained between 20-25°. The solution was then

cooled to 13° and dimethyl sulfate (200 ml., 270 g., 2.1 moles)

was admitted at such a rate so as to keep the temperature at 12-15°.

After the reaction mixture was stirred for 4.0 minutes, the stirrer

was stopped and the oily upper layer was separated at once, dried over sodium sulfate and distilled at 15 mm. The portion boiling below 70° at 15 mm. was mainly methoxyacetonitrile. This crude fraction was distilled at atmospheric pressure to give methoxyaceto nitrile [89.5 g*, 1.26 moles, 63/6 yield, b.p. 118-120°/74S mm., lit. (4) b.p. 120-121°/759 mm.].

(4) H. R. Henze and M. E. Rigler, J. Am. Chem. Soc., $6, 1350 (1934).

2-Methoxvacetophenone.--A mixture of methoxyacetonitrile

(21.3 g«, 0.3 mole) and anhydrous ether (50 ml.) was slowly added to a stirred 3 W solution of phenylmagnesium bromide in ether

(120 ml., 0.36 mole) (Arapahoe Chemicals, Inc.) cooled in an ice- salt bath. A colorless adduct separated at once. After standing at ambient temperature for two hours, the mixture was again cooled

and then decomposed with water and cracked ice (500 ml.) and then

cold dilute sulfuric acid (100 ml.) (one volume of concentrated

sulfuric acid to two volumes of water). The ether layer was separated

and the aqueous layer extracted with ether (2 x 50 ml.). The combined

organic portions were washed successively with 5% sodium carbonate

solution (50 ml.) and water (2 x 50 ml.), dried over sodium sulfate,

filtered, and concentrated. The residue was distilled to give 2-

methoxyacetophenone [33.1 g., 0.22 mole, 73% yield, b.p. 118-120°/

15 mm., lit. (5) b.p. 118-120°/l5 mm.

(5) D.D. Pratt and R. Robinson, J. Chem. Soc., 123. 745 (1923). 55

2-Methoxvacetophenone tosylhydrazone. — To a vanned, stirred solution of £-toluenesulfonyl hydrazide (28.65 g*, 0.154 mole) in anhydrous methanol (100 ml.) vas added a solution of 2-methoxy-

acetophenone (23*16 g., 0.154 mole) in anhydrous methanol (100 ml.}.

The stirred mixture vas refluxed for tvo hours. The methanol solu

tion vas concentrated at reduced pressure to half its volume and

cooled in an ice bath; the resulting off-vhite precipitate vas fil

tered. Recrystallization from methanol gave 2-methoxyacetophenone

tosylhydrazone (40.6 g., 0.128 mole, yield 83%» m.p. 104-105°)

white crystals.

Anal. Calcd. for C ^ ^ O S: C, 60.36; H, 5.70; N, 8.80

Found: C, 60.64; H, 5.80; N, 9*01.

2-Phenoxyacetophenone.--A stirred mixture of 2-bromoaceto-

phenone (19*9 g*> 0.1 mole), phenol (9*4 g*» 0.1 mole), potassium

carbonate (18.5 g«, 0.125 mole) and anhydrous acetone (150 ml.)

vas refluxed for 7 hours. The mixture vas cooled, diluted with water

(150 ml.), and then extracted with ether (3 x 100 ml.). The ether

extract, after having been washed with 10% sodium hydroxide

(2 x 100 ml.) and water (2 x 50 ml.), was dried over sodium sulfate,

filtered and concentrated. Recrystallization of the residual preci

pitate from ethanol gave 2-phenoxyacetophenone [14*2 g., 0.067 mole,

67% yield, m.p. 71-72°, lit. (6) 72°].

(6) R. Xohlan, Ber., 1£, 2498 (1882). 2-Phenoxvacetophenone tosylhydrazone.— To a solution of j>-toluenesulfonyl hydrazide (7.44- g., 0.04- mole) in absolute methanol (60 ml.) was added 2-phenoxyacetophenone (8.48 g., 0.04. mole). After the stirred solution had been refluxed for one hour it was cooled in ice. The white crystals of 2-phenoxyacetophenone tosylhydrazone (14«9 g., 0.034 mole, yield 98%, m.p. 123-125°) were

filtered and washed thoroughly with cold methanol.

Anal. Calcd. for C, 66.29; H, 5.30; N, 7-36

Found: C, 66.51; H, 5-39; N, 7.46.

2-Hydroxyacetophenone.— Sodium formate (6.8 g., 0.1 mole)

and 2-bromoacetophenone (19-9 g., 0.1 mole) were dissolved in

anhydrous methanol (60 ml.), and then refluxed for 5 hours. The

mixture was then diluted with water (100 ml.) and extracted with

ether (3 x 50 ml.). The ethereal solution, after washing with

water (2 x 25 ml.) and drying over sodium sulfate, was concentrated

in vacuo to give a precipitate which was filtered. The aqueous

portion and the aqueous washings were combined and then concentrated

in vacuo to yield additional product. Recrystallization of the com

bined precipitates from water gave 2-hydroxyacetophenone [11.3 g«,

0.083 mole, 83% yield, m.p. 84-85°, lit. (7) m.p. 85-86°].

(7) W. L. Evans, Amer. Chem. J., 3L£> H 5 (1906).

2-Hvdroxyacetophenone tosylhydrazone. 2-Hydroxyacetophenone

(1.36 g., 0.01 mole) was added to a solution of £-toluenesulfonyl hydrazide (1.86 g., 0.01 mole) in absolute methanol (15 ml.). The mixture was refluxed for one hour. Cooling the solution to 0

afforded a precipitate which was recrystallized from methanol to

give white crystals of 2-hydroxyacetophenone tosylhydrasone [2.05 g.,

0.0067 mole, 67% yield, m.p. 14-0-142° (d)].

Anal. Calcd. for C ^ H ^ q^O^S: C, 59*20; H, 5-30

Found: C, 58.99; H, 5-10.

2-Dlmethvlaninoacetophenone.— To a cooled solution of di-

methylamine (4.0.5 g., 0.9 mole) in anhydrous ether (100 ml.) was

admitted dropwise 2-chloroacetophenone (15.4-5 g., 0.1-mole) in

anhydrous ether (100 ml.). After the mixture had been stirred for

2 hours, it was then cooled at -15° for 10 hours. After the dimethyl

amine hydrochloride had been filtered, the ether solution was evapo

rated under a stream of nitrogen to yield a residue (14-.8 g.) which

on distillation gave 2-dimethylaminoacetophenone [14-.0 g., 0.086

mole, 86% yield, b.p. 123-126°/l5 mm., lit.(8) b.p. 126-128°/l8 mm.].

(8) J. v. Braun and K, Weisbach, Ber., 62, 24-16 (1929).

2-Dinethylaninoacetophenone hydrochloride tosylhydrazone.—

£-Toluenesulfonyl hydrazide (1.86 g., 0.01 mole), concentrated hydro

chloric acid (1.06 g., 0.011 mole) and 2-dimethylaninoacetophenone

(1.63 g., 0.01 mole) were dissolved in anhydrous methanol (20 ml.).

The reaction mixture was refluxed for 5 hours after which it was

cooled at -15° to allow precipitation. 2-Dimethylaminoacetophenone

hydrochloride tosylhydrazone [1.71 g., 0.004,6 mole, 46.5% yield, m.p. 170-171° (d)], a white crystalline material, was collected by filtration.

Anal. Calcd. for C ^ H ^ C I N ^ S : C, 55.50; H, 6.03; N, 11.42 Found: C, 55*69; H, 6.16; N, 11.76*

2-Phenvlandnoacetonhenone.— Aniline (48*4 g., 0.52 mole) was added to a stirred solution of 2-bromoacetophenone (49.8 g.,

0 25 mole) in 95% ethanol (200 ml.). After the reaction mixture

had been stirred at ambient temperature for 30 minutes, it was

then cooled and filtered. Recrystallization of the crude product

-from 95% ethanol yielded 2-phenylaminoacetophenone [30.0 g., 0.142

mole, 54% yield, m.p. 95-96°, lit. (9) 98-99°].

(9) G. Bachmann and R. Lindown, Wiss. Z. Tech. Hochsch. Chem. Leuna-Merseburg, 125 (1963).

2-Phenylaminoacetophenone tosylhydrazone.— 2-Phenylamino-

acetophenone (3*33 g*, 0.016 mole) was added in one portion to p-

toluenesulfonyl hydrazide (2.94 g«, 0.0158 mole) in anhydrous

methanol (50 ml.). The stirred solution vas refluxed for 30 minutes

and then kept at 0°. The resulting precipitate was filtered and

washed with cold methanol. Recrystallization from methanol gave

2-phenylaminoacetophenone tosylhydrazone (3.66 g., 0.0096 mole,

61% yield, m.p. 127-128°) as white crystals.

Anal. Calcd. for C2iH2iN3°2Sl c > 66.46; H, 5-58; N, 11.07

Found: C, 66.42; H, 5.82; N, 10.85. 59

2-Phepylreercaotoacetophenone.--To sodium methoxide (5-4 g.,

0.1 mole) and thiophenol (11.0 g., 0.1 mole) (Matheson Chemical

Corporation) in absolute ethanol (50 ml.) was added 2-chloroacetophenone (15*4- g», 0.1 mole) (Eastman Organic Chemicals). The stirred solution was refluxed for 2 hours after which the mixture was stored at 25-30° for 12 hours. After the solvent had been removed the crystalline residue was filtered and washed free of sodium bromide with cold water. Recrystallization from ethanol gave 2-phenylmercapto acetophenone [13.0 g., 0.057 mole, yield 5756, m.p. 53-54°, lit. (10)

52-53°].

(10) A. Delisle, Ber., 22, 309 (1899).

2-Phenylmercaptoacetophenone tosylhydrazone.— To a solution of 2-phenylmercaptoacetophenone (28.5 g., 0.125 mole) in anhydrous methanol (75 ml.) was added jc-toluenesulfonyl hydrazide (23.25 g.,

0.125 mole) in anhydrous methanol (75 ml.). The stirred mixture was refluxed for 2 hours after which approximately 75 ml. of methanol was removed, at reduced pressure. Cooling the concentrated solution to 15° for 12 hours allowed precipitation. The product was filtered and washed thoroughly with cold methanol to give 2-phenylmercapto acetophenone tosylhydrazone (48.0 g., 0.121 mole, yield 98$, m.p.

96-98°) as white crystals.

Anal. Calcd. for C21H20N202S2 : G’ 63*61’ H * 5*o8J N > 7*07 Found: C, 63.61; H, 4.98; N, 7.24. 60

2-Ethrlmercaptoacetophenone.--To a cooled, stirred solution of sodium hydroxide (20.0 g.f 0.05 mole) in 50^5 ethanol (4-00 ml.) vas added slowly ethanethiol (31.1 g*, 0.5 mole). 2-Chlorosceto-

phenone (77.0 g., 0.05 mole) vas then poured into the above solution.

The mixture was stirred and refluxed for 45 minutes, cooled and di

luted with water (800 ml.). After extraction of the aqueous solution

with ether (2 x 100 ml.), the ether extracts were combined, washed

successively with 5% hydrochloric acid (25 ml.) and water (2 x 25 ml.),

dried over sodium sulfate, filtered and concentrated. Fractionation

of the residue gave 2-ethylmercaptoacetophenone [83.9 g., 0.466

mole, yield 93%, b.p. 115-118°/3 mm., lit. (11) 106°/ 2 mm].

(11) L. Long, J. Am. Chem. Soc., 68, 2159 (1946).

2-Ethylmercaptoaeetophenone tosylhydrazone.--A mixture of

£-toluenesulfonyl hydrazide (18.6 g., 0.1 mole) and 2-ethylmercapto

acetophenone (18.0 g., 0.1 mole) in absolute methanol was refluxed

for one hour. The solution was cooled at 0° and the white precipi

tate of 2-ethylmercaptoacetophenone tosylhydrazone (25.5 g., 0.073

mole, yield 13 >3%, m.p. 122-124°) was filtered end thoroughly

washed with cold methanol.

Anal. Calcd. for C17H2oN202S2: C, 58.59; H, 5.78; N, 8.04

Found : C, 59.01; H, 5.46; N, 8.27.

2-Ethylmercapto-41-chloroacetophenone.--To a stirred solution

of sodium hydroxide (2.0 g., 0.05 mole) in 50* ethanol (40 ml.) at

0-5° was added slowly ethanethiol (3*11 g», 0.05 mole) and then 2-

bromo-4'-chloroacetophenone (11.68 g., 0.05 mole) (Eastman Organic 61

Chemicals) in one portion. The mixture vas refluxed for 45 minutes, cooled and diluted with water (80 ml.). The aqueous solution vas extracted with ether (3 x $0 ml.) and the combined extracts were washed with water (2 x 25 ml.) and dried over sodium sulfate. After filtration and removal of the ether under vacuum, fractionation of the residue yielded 2-ethylmercapto-4'-chloroacetophenone (7.12 g.,

0.033 mole, yield 66.4/6, b.p. 133-135°/l mm.) (12).

(12) The infrared spectrum of the product exhibited carbonyl (1680 cm"l) and C^-S (1420 cm'l) absorption (Figure 1).

2-Ethvlmercaoto-41-chloroacetophenone tosylhydrazone.— 2-Ethyl- mercapto-4'-chloroacetophenone (4-29 g., 0.02 mole) and £-toluenesulfonyl hydrazide (3.72 g., 0.02 mole) in absolute methanol (25 ml.) were refluxed for one hour and then cooled in an ice bath to allow precipitation. The product was filtered and recrystallized from methanol to give white crystals of 2-ethylnercapto-4l-chloroaceto phenone tosylhydrazone (5.35 g-, 0.014 mole, yield 70%, m.p. 103-104°).

Anal. Calcd. for C17H19C1N202S2 : C, 53-32; H, 5.00; N, 7.32

Found: C, 53.58; H, 4.93; N, 7.54.

2-Ethylmercaoto-4l-bromoacetophenone.--Ethanethiol (3.11 g..

0.05 mole) was added slowly with stirring to a cooled solution of sodium hydroxide (2.0 g., 0.05 mole) in 50^ ethanol (40 ml.). , In one portion 2,4'-dibronoacetophenone (13.9 g., 0.05 mole) (Eastman

Organic Chemicals) vas added to the resulting solution and the mix ture was refluxed 45 minutes, cooled and diluted with water (80 ml.).

The aqueous solution was extracted with ether (3 x50 ml.). 62

The ether extract was washed with water (2 x 25 ml.), dried over sodium sulfate, filtered and concentrated. The solid residue, on recrystallization from ether, gave 2-ethylmercapto-4**bromoacetophenone (11.4 g., 0.042 mole, yield 88%, m.p. 38-39°) (13).

(13) The infrared spectrum of the product exhibited car bonyl (1680 cm"1) and I^C-S (1415 cm"1) absorption (Figure 2).

2-Ethvlmercapto-4l-bromoacetophenone tosylhydrazone.— 2-Ethyl- mercapto-4'-bromoacetophenone (10.0 g., 0.039 mole) was added to

E-toluenesulfonyl hydrazide (7.25 g., 0.039 mole) dissolved in anhydrous methanol (25 ml.). The stirred solution was refluxed for one hour, then cooled in an ice bath and the crystals collected.

Recrystallization from methanol gave 2-ethylmercapto-4,-bromoacetophenone tosylhydrazone (13*5 g*, 0.0316 mole, yield 81%, m.p. 118-

119°) as white crystals.

Anal. Calcd. for c17H19BrN202S2 : C, 47.77; H, 4*48; N, 6.56

Found: C, 47.89; H, 4*49; N, 6.69.

2-Methvl-l.3-dithiane.— To a mixture (14) of acetaldehyde

(14) General procedure of R. M. Roberts and Ch.-Ch. Chang, J. Org. Chem., 2£, 963 (1958).

(8.8 g., 0.2 mole), 1,3-propanedithiol (21.6 g., 0.2 mole) (Columbia

Organic Chemicals Co.) and anhydrousbenzene (60 ml.) was added

3 drops of concentrated hydrochloric acid. An exothermic reaction ensued, and the flask was immersed in ice water with continuous stirring. After 15 minutes the exothermic reaction subsided and the mixture was heated on a steam bath for 10 minutes (water separated from the reaction mixture during this time). The mixture was poured into water (200 ml.) and then extracted with chloroform

(3 x 50 ml.). The combined extracts were washed with 1055 sodium hydroxide solution (2 x 25 ml.) and water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Distil lation yielded 2-methyl-l,3-dithiane [12.4. g., 0.091 mole, yield

46/6, b.p. 79-82°/l5 mm., lit. (15) b.p. 66°/5 mm.].

(15) E. E. Campaigne and G. F. Schaefer, Bol. col. quim. Puerto Rico, 25 (1952).

2-Lithio-2-riethvl-l.3-dithiane.— n-Butyllitbium (1.627 N in hexane, 47 ml., 0.075 mole) (16) was added,at the rate of 3*5 ml.

(16) n-Butyllithium (Foote Mineral Co., solution in hexane) was standardized by titration with hydrochloric acid using phenolphthalein as an indicator. per minute, to a stirred solution of 2-methyl-l,3-dithiane (10.11 g.,

0.075 mole) in anhydrous tetrahydrofuran (180 ml.) at -30° under nitrogen (17). The mixture was stirred at -30 to -20° for 90 minutes

(17) The procedure used was essentially that of E. J. Corey and D. Seebach, Angew. Chem. Internet. Ed., 1075 (1965). to give a solution of 2-lithio-2-methyl-l,3-dithiane. u

2-Benzoyl-2-methyl-l,3-dithiane.— To a stirred solution of

2-lithio-2-methyl-1,3-dithiane (0.075 mole) in anhydrous tetrahydrofuran (180 ml.) at -78° was added benzonitrile (7.7 g.,

0.075 mole) (Eastman Organic Chemicals). The resulting bright

orange mixture was kept at -78° for 40 minutes after which the Dry

Ice— acetone bath was removed and stirring was continued for an

other 40 minutes. The reaction mixture was then poured into ice

(300 g.) and extracted with ether (3 x 50 ml.). The combined ex

tracts were washed with 5% sodium hydroxide (2 x 25 ml.) and water

(25 ml.), and concentrated under a stream of nitrogen to give the

crude inline which was stirred with I& hydrochloric acid (800 ml.) o at 70 for 45 minutes. During the hydrolysis colorless crystals

separated from the medium. The product was dissolved in ether and

the aqueous solution was extracted with ether (3 x 100 ml.). The

combined ether extracts were washed with water (2 x 50 ml.), dried

over sodium sulfate, filtered, and concentrated; recrystallization

from methanol gave 2-benzoyl-2-methyl-l,3-dithiane [16-3 g-, 0.0685

mole, yield 91%, m.p. 99-100°, lit. (18) m.p. 98.4-98.8°].

(18) E. J. Corey and D. Seebach, ibid.. 4, 1077 (1965).

2-Benzovl-2-rethvl-1.3-dithiane tosylhydrazone.--2-Benzoyl-

2-methyl-l,3-dithiane (2.83 g., 0.01 mole) and 2 drops of concentrated

hydrochloric acid were added to j>-toluenesulfonyl hydrazide (1.86 g.,

0.01 mole) in absolute methanol (50 ml.). The stirred mixture was re-

fluxed for 24 hours. After cooling the mixture a precipitate formed which was filtered. Recrystallization from methanol afforded white crystals of 2-benzoyl-2-methyl-l,3-dithiane tosylhydrazone [2.11 g

0.0052 mole, 52^ yield, m.p. 143-145°].

Anal. Calcd. for ^ 56.13; H, 5*45; N, 6.89

Found: C, 56.33; H, 5-56; N, 7.07.

2-Forxnvl-2-tnethvl-l.3-dithiane.— To a cold (-10°) solution of 2-lithio-2-methyl-l,3-dithiane (0.04 mole) in anhydrous tetrahydrofuran (120 ml.) was added with stirring N,N-dimethylformamide

(2.92 g., 0.04 mole) (19). The resulting mixture was kept at -10°

(19) N,N-Dimethylformamide was purified by distillation from calcium hydride. for 40 minutes after which the bath was removed and stirring was continued for 40 minutes. The reaction mixture was then poured into ice (150 g.) and extracted with ether (3 x 50 ml.). The com bined ether extracts were washed successively with 5% sodium hydroxide (2 x 25 ml.) and water (25 ml.), dried over sodium sulfate, filtered and concentrated under reduced pressure. Distil lation gave 2-forcyl-2-methyl-l,3-dithiane [5-35 0.0866 mole, yield 8255, b.p. 110-115°A o mm.] (20).

(20) 2-Formyl-2-methyl-l,3-dithiane was reported in Ref. 18 but no physical data were given. The infrared spectrum of the product exhibited carbonyl (1710 cn“l) and aldehyde C-H absorption (2700 cm'l and 2800 cm“l) (Figure 3).

2-Formvl-2-methvl-l.3-dithiane tosylhydrazone.— A stirred mixture of 2-formyl-2-methyl-l,3-dithiane (5-35 g.t 0.033 mole) and £-toluenesulfonyl hydrazide (6.14 g., 0.033 mole) in anhydrous 66 methanol (50 ml.) was refluxed for 3 hours. Cooling the mixture afforded a precipitate which was collected by filtration. Recrystal lization from methanol gave 2-formyl-2-methyl-l,3-dithiane tosyl hydrazone (7.78 g., 0.0235 mole, 71^ yield, m.p. 121-123°) as white crystals.

Anal. Calcd. for : 47.24; H, 5.49; N, 8.47

Found: C, 47.67; H, 5.75; N, 8.54*

Standards

2-Methoxy-2-phenylethyl iodide.--Styrene (104 g., 0.1 mole)

in anhydrous methanol (400 ml.) was added to iodine (139-7 g.,

0-55 mole) and mercuric oxide (162.8 g., 0.75 mole) in anhydrous

methanol (400 ml.). The mixture was stirred for 4 hours end then

filtered, concentrated and distilled to give 2-methoxy-2-phenyl-

ethyl iodide [70.0 g., 0.267 mole, 48.6% yield, b.p. 107-108°/5 mm.,

lit. (21) b.p. 135-138%4 mm.].

(21) K. Tiffeneau, Compt.. rend., 145. 811 (1901).

q-Methoxystvrene.— Sodiun (2.3 g., 0.1 g. atom) was dissolved

in anhydrous methanol (50 ml.) and 2-methoxy-2-phenylethyl iodide

(13.1 g-, 0.05 mole) was added to the resulting basic mixture in

one portion. The solution was refluxed for an hour, poured into

water (50 ml.) and extracted with ether (3 x 25 ml.). The ethereal

solution was dried over potassium carbonate, concentrated and

distilled to give a-methoxystyrene [5.76 g., 0.043 mole, 86* yield,

b.p. 97-98°/24 mm., lit. (22) b.p. 9 0 . 5 % 8 mm.]. 67

(22) K. Auwers, Ber., 3514 (19H).

B-Methoxvstvrene.— Phenylacetylene (10 g., 0.098 mole) was added to sodium (10 g., 0.4.3 mole) dissolved in absolute methanol

(100 ml.). The mixture was refluxed for 72 hours, cooled, added to ice water (150 ml.) and then extracted with ether (3 x 50 ml.).

The combined ether extracts were washed with water (50 ml.), dried over magnesium sulfate and concentrated. Fractionation of the

residue yielded p-methoxystyrene (23) [5*86 g., 0.044 mole,

(23) This appears to be mainly the cis isomer from its infrared spectrum which exhibited the characteristic cis out- of-plane band (726 cm"^-) (Figure 4) •

yield 45/6, b.p. 110-lll°/25 mm., lit. (22) b.p. 210-213°/atmosphere].

cis- and trans-B-Methoxvstyrene (24).— Acetyl chloride (50 ml.)

(24) The procedure was essentially that of S. I. Miller, J. Am. Chem. Soc., 78, 6091 (1956).

in ether (25 ml.) was added dropwise to a cooled, stirred solution

of pyridine (50 ml.) in ether (25 ml.). To the resulting white

solid was added phenylacetaldehyde dimethylacetal (43.0 g., 0.26

mole) (Aldrich Chemical Co.). The mixture was heated 15 minutes

without a condenser on a steam-bath, then in an oil-bath at 170°

for 15 minutes. The dark liquid was poured on ice (200 g.), ex

tracted with ether (3 x 100 ml.), dried over potassium hydroxide, 68 filtered and concentrated. The residue on fractionation gave a mixture of cis- and trans-B-methoxystyrene (25) [24.4.0 g., 0.183

(25) The infrared spectrum exhibited cis and trans out- of-plane vibration band (726 cm*^ and 937 cm' ) (Figure 4) • mole, 71? yield, b.p. lll-112°/30 mm., lit. (24) b.p. 205°/atmosphere].

ft-Phennxvstvrene (26).--To a glass-lined autoclave was added

(26) The general procedure used was that of A. V. Kalabina, A. S. Brykina, L. V. Tomilova, V. D. Kudryavtseva, and T. T. Mina- kova, Ivest. Fiz. Khim. Nauk. Issledovatel. Inst. pri. Irkutskom Univ., #2. Ill (1959). This procedure was reported for the synthesis of a-phenoxystyrene. The product obtained in the present work has a nuclear magnetic resonance spectrum (Figure 10) which exhibits a doublet at 4-58 f (J=7), a doublet at 3.67 T (J=7) and a multiplet at 2.72 7. The doublets are attributed to cis vinylic protons and the multiplet to aromatic protons. Also the infrared spectrum (Figure 6) shows a band at 715 cm“l which is assigned to the cis out-of-plane vibration band. These data suggest trans addition of phenoxide to give the cis-B-ohenoxystvrene, Hydrolysis of the product with 70? perchloric acid gives phenylacetaldehyde. phenylacetylene (22.4 g., 0.22 mole), phenol (22.5 g., 0.24 mole), potassium hydroxide (3*0 g., 0.0535 mole) and water (3 ml.). The stirred mixture was heated for 5 hours at 250-270°, cooled, taken up in ether, washed with water (2 x 25 ml.), dried over sodium sulfate, filtered and concentrated. The residue (37.2 g.) was distilled into 2 fractions. Fraction 1 was phenol and phenyl acetylene. Fraction 2 on redistillation gave p-phenoxystyrene

[11.3 g-, 0.058 mole, yield 26?, b.p. 119-120°/l mm., lit.(27) b.p. 113-114°/o.6 mm.]. 69

(27) G. Vfitteg, W. Eoell, snd K. Heinrich, Ber., 2514 (1962).

p-Phenylmercaptostyrene.— Bensenethiol (27.5 g., 0.25 mole)

(28) was added in one portion to phenylacetylene (25.5 g., 0.25

(28) General procedure of W. E. Trace, H. E. Hill, and M. M. Boudakian, J. Ain. Chem. Soc., 78, 2760 (1956). mole) at 0-5°* After the mixture had been stored for 12 hours at

ambient temperature, it was distilled to give p-phenylmercapto-

styrene [43-5 g-, 0.205 mole, 82% yield, b.p. 142-145°/0.9 mm., lit. (29) 146-147%

(29) L. I. Smith and H. R. Davis, Jr., J. Org. Chem., 2J5, 824 (1950).

B-Bthylmercaptostyrene.— To a solution of 63$ sodium

methoxide (IS.3 g.> 0.22 mole) in absolute methanol (150 ml.)

was added ethanethiol (13«6 g., 0.22 mole) and then phenylacetylene

(20.4 g., 0.20 mole). The stirred mixture was refluxed for 25 hours.

Most of the methanol was remove;! from the mixture at reduced pres

sure. The residue was then poured into water (100 ml.) and

extracted with ether (3 x 50 ml,). The combined ether extracts

were washed with water (2 x 25 ml.), dried over sodium sulfate,

filtered, and concentrated. The residue on fractionation gave

p-ethylmerc&ptostyrene [15.9 g., 0.097 mole, 49$ yield, b.p. 119-

120°/5 mm., lit. (30) b.p. 85-86°/l mm.j. 70

(30) A. A. Oswald, K. Friesbaum, B. E. Hudson, Jr., and J. M. Bergman, J. Am. Chem. Soc., 86, 2881 (1964.)*

Decomposition of 2-methoxyacetoohenone tosylhydrazone.

Experiment I«— n-Butyllithium (1.40 N in hexane, 7.2 ml., 0.0101 mole) was syringed slowly into a solution of 2-niethoxyaceto- phenone tosylhydrazone (3*18 g., 0.01 mole) at 0° in anhydrous tetrahydrofuran (50 ml.). After addition was complete the mixture was stirred for 2 hours at room temperature. A white precipitate formed during this period. The solvent was removed at reduced pressure and the off-white solid was dried under vacuum (l mm.) for 5 hours. The dry lithium salt of 2-methoxyacetophenone tosyl hydrazone was decomposed by heating at atmospheric pressure to 160° over a 45-minute period. The yield of nitrogen corrected to STP was 212 ml. (95%)- Purification of the decomposition product by distillation gave one fraction (b.p. 88-89°/7 mm.).

Analysis of the distillate by gas-liquid chromatography (31)

(31) The columns employed for analysis of the decomposition products of 2-methoxyacetophenone tosylhydrazone are 10’ x 1/4” Carbovax 2 CM (2C%) on Chromosorb G and 5' x l/8” Csrbowax 2CM {15%) on Chromosorb G. exhibits only one major peak which has the same retention time as an authentic sample of fS-metnoxystyrene. The peak when analyzed at lower oven temperature shows ci s-B-methoxvstvrene (48%) and trans-B-methoxvstvrene (52*). 71

The infrared spectrum (Figure 7) of the distillate exhibited cis and trans ethylenic (HC=CH) absorption at 726 cm"l and 935 cm

Treatment of a portion of the distillate (0.03 g., 0.000224- mole) with a 2 ,4-dinitrophenylhydrazine reagent (32) gave a yellow

(32) R. L. Shriner and R. C. Fuson, "The Systematic Identi fication of Organic Compounds," Third Edition, John Wiley and Sons, Inc., New York, N. Y., 194-8, p. 97. precipitate which was filtered. Recrystallization from ethanol afforded phenylacetaldehyde 2 ,4*dinitrophenylhydrazone [0.055 g.,

0.000183 mole, 82$ yield, m.p. 118-19°, lit. (33) m.p. 110°].

(33) 0. L. Brady, J. Chem. Soc., 757 (1931).

The melting point of the derivative was undepressed by an authentic sample of the phenylacetaldehyde 2 ,4-dinitrophenylhydrazone.

Experiment II. To the heterogeneous solution of 2-methoxy acetophenone tosylhydrazone (3*18 g., 0.01 mole) in anhydrous ether (30 ml.) was syringed In slowly n-butyllithium (1.744 N in hexane, 5*75 ml., 0.01 mole). The solvent was removed at reduced pressure and the lithium salt was dried for one hour under vacuum

(l mm.). The dry salt was heated to 140° under vacuum (l mm.) and the volatile product was collected in a Dry Ice trap to give a red liquid (1.3 g*, 8C$ yield based on C^H^qNjO). The infrared spectrum showed the characteristic diazo band at 2080 cm”^ (Fig ure 8) - The red liquid was decomposed by heating to 150°* The re sulting slightly yellow liquid, analyzed as in Experiment I, shows only p-methoxystyrene as the migration product.

Experiment III. Lithium methoxide (0.2090 g., 0.0055 mole) was added to a solution of 2-methoxyacetophenone tosylhydrazone

(1.59 g-, 0.005 mole) in anhydrous diglyme (20 ml.). The resulting

solution was stirred for 45 minutes then heated from 30° to 135°

over a 30-minute period. At ca. 105° the solution started to

turn pink and .ca. 117° nitrogen evolution was apparent. The

evolved nitrogen (107 ml., 96%) was collected and corrected to

STP.

The decomposition solution was analyzed by gas-liquid chroma'

tography (31)■ The product of reaction was only that from hydrogen

migration, p-raethoxystyrene.

Experiments IV and V . Experiment III was repeated using 2.1

and 3.1 equivalents of lithium methoxide. Analysis (31) exhibits

only hydrogen rearrangement product, p-methoxystyrene, in both

Experiments IV and V.

Experiment VI. Sodium methoxide (34) (97.5* pure, 0.3044 g.

(34) Sodium methoxide (Matheson, Coleman, and Bell) was standardized by titration with standard hydrochloric acid using phenolphthalein indicator. It was stored under nitrogen and sealed with paraffin wax.

0.0055 mole) was stirred with 2-methoxyacetophenone tosylhydra

zone (1.59 g., 0.005 mole) in dry diglyme (20 ml.) for 45 minutes,

and then heated to 130°. The mixture turned red. and nitrogen evolution began at approximately 110°. The heating process re quired 45 minutes, and the nitrogen (110 ml., 98^ yield) was collected and corrected to STP. The diglyme solution was diluted with ether (25 ml.) and then washed with water (2 x 15 ml.), dried over sodium sulfate, filtered and concentrated under a

stream of nitrogen.

Gas chromatographic analysis (31) shows only the product

from hydrogen migration, p-methoxystyrene.

Experiments VII and VIII. Experiment VI was repeated

using 2.1 and 3*1 equivalents of sodium methoxide. Analysis as

before exhibited only p-methoxystyrene.

Experiment IX. To a solution of 2-methoxyacetophenone

tosylhydrazone (1.59 g., 0.005 mole) in dry diglyme (20 ml.)

slowly was syringed n-butyllithium (1.74- N in hexane, 3.16 ml.,

0.0055 mole). The mixture was stirred for 45 minutes and then

heated to 130° over a 45-minute period. The evolved nitrogen

(96 ml., 84^) was collected and corrected to STP. The diglyme

mixture was diluted with ether (25 ml.) and it was then washed

with water (2 x 15 ml.). The ethereal solution was dried over

sodium sulfate, filtered and concentrated under a stream of nitro

gen. The resulting liquid was analyzed as in Experiment III.

Only residual diglyme and p-methoxystyrene were present.

Experiment X. n-Butyllithiun (1.74 N in hexane. 6.05 ml.,

0.0105 mole) was syringed slowly into a solution of 2-methoxy-

acetophenone tosylhydrazone (1-59 g., 0.005 mole) in dry diglyme

(20 ml). As the n-butyllithiura is added to the stirred diglyme n solution a red color appears but then disappears quickly; in the presence of excess n-butyllithium the red color persists. After the mixture had been stirred for 30 minutes the diglyme solution was brown and hard to stir. The solution was heated to 130° and the nitrogen evolved (51 ml., yield) was collected and cor rected to STP. The work-up was the same as in Experiment IX; analysis showed that only p-methoxystyrene was present.

Decomposition of 2-phenoxyacetophenone tosylhydrazone.

Experiment I .--n-Butyllithium (1.74 N in hexane, 5.75 ml., 0.01 mole) was syringed slowly into a solution of 2-phenoxyacetophenone tosylhydrazone (3-80 g., 0.01 mole) in anhydrous ether (25 ml.).

The mixture was magnetically stirred for 15 minutes; concentration

i gave the lithium salt which was decomposed in situ at 140°. The

mixture was cooled, diluted with water (50 ml.) and extracted with

ether (3 x 25 ml.). The combined extracts were washed with water

(25 ml.), dried over sodium sulfate, filtered and concentrated.

The oil (1.8 g., 91.9?) was analyzed by gas-liquid chroma

tography on 5% and 15? FFAP columns. The major peak had the same

retention time as authentic p-phenoxystyrene; phenol was also

present in trace amount.

The decomposition residue was treated with a saturated solu

tion of 70? perchloric acid in ether (35) for 15 minutes at 30°.

(35) General procedure of G. Wittig, W. Boell, and K. Hein rich, Ref. 27.

Analysis of the hydrolyzed solution by gas-liquid chromatography on a 15% FFAP column and 5% Si-30 silicone column showed that the p-phenoxystyrene peak disappeared and that phenylacetaldehyde ap peared.

Experiment II. Experiment I was repeated using 1.1 equiva lents of n-butyllithium. Analysis as above showed that the only migration product was p-phenoxystyrene.

Experiment III. n-Butyllithium (1.66 N in hexane, 0.13 ml.,

0.00022 mole) was syringed into a solution of 2-phenoxyaceto phenone tosylhydrazone {0.0761 g., 0.0002 mole) in dry diglyme

(1 ml.). After addition was complete, the mixture was allowed to stand one hour with occasional shaking. Decomposition was effected by heating the diglyme solution to 130° over a 30-minute period.

After cooling the solution was diluted with water (1 ml.) and ether (1 ml.). Analysis of the organic layer as in Experiment I revealed that p-phenoxystyrene was the only rearrangement product.

Experiment IV. Experiment III was repeated using 2.1 equivalents of n-butyllithium. p-Phenoxystyrene was the only intramolecular rearrangement product.

Experiment V . Dry diglyme (2 ml.) was syringed into a mixture of 2-phenoxyacetophenone tosylhydrazone (0.0761 g., 0.0002 mole) and sodium methoxide (93^, 0.0121 g., 0.00021 mole). After the mixture had been stirred at room temperature for 30 minutes a homogeneous solution was obtained. The solution was heated to 130° over a 30-minute period, cooled, and diluted with ether (l ml.) and water (l ml.). Analysis as in Experiment I shows that p-phenoxy styrene is formed during decomposition. Experiments VI and VII. Experiment V was repeated using

2.1 and 3*1 equivalents of sodium methoxide. Analysis of the reac tion products shows that p-phenoxystyrene is the only rearrangement product.

Experiment VIII. Dry diglyme (2 ml.) was syringed into a mixture of 2-phenoxyacetophenone tosylhydrazone (0.0761 g.,

0.0002 mole) and lithium methoxide (0.008 g., 0.00021 mole).

After stirring at room temperature for 30 minutes, the solution was heated to 130° over a 30-minute period, cooled, and diluted with ether (1 ml.) and water (l ml.). p-Phenoxystyrene is the

only rearrangement product.

Experiments IX and X . Repeating Experiment VIII using

2.1 and 3*1 equivalents lithium methoxide, one obtains p-phenoxy-

styrene from hydrogen migration in both cases.

Decomposition of 2-hvdroxvacetophenone tosylhydrazone.--A

solution of 2-hydroxyacetophenone tosylhydrazone (0.61 g., 0.002

mole) in anhydrous tetrahydrofuran (15 ml.) was treated with

n-butyllithium (1.66 N in hexane, 2.5 ml., 0.00^2 mole). After

3 hours of stirring at room temperature the lithium salt was con

centrated under vacuum (1 mm.) and then dried for 3 hours at 0-5 mm.

The salt was decomposed in situ upon heating to 165° over a 4-5“

minute period. The evolved nitrogen (3*2 ml., 11%) was collected

and corrected to ST?. Water (25 ml.), then ether (25 ml.) were

added to the decomposition mixture and the layers were separated.

The aqueous layer was extracted with ether (2 x 15 ml.) then

neutralized with 1C% sulfuric acid and again extracted with ether (15 ml*). The combined organic portions were washed with water

(20 ml.), dried over sodium sulfate, filtered, and concentrated.

The dark oil (0.24 g., 100$ based on CgHgO) was analyzed by gas- liquid chromatography on a 5% SE-30 column. From the retention times it was observed that none of the predicted products, phenyl acetaldehyde, acetophenone, or styrene oxide, were formed.

Decomposition of 2-dimethvlaminoacetophenone hydrochloride, tosylhydrazone. Experiment I.--n-Butvllithium (1.74 N in hexane,

1.25 ml., 0.0022 mole) was syringed slowly into a solution of 2- dimethylaminoacetophenone hydrochloride tosylhydrazone (0.37 g.,

0.001 mole) in dry diglyme (20 ml.). After the addition was com plete, the homogeneous solution was stirred for 30 minutes at 25° and then slowly heated to 135°. The mixture turned red at approxi- o mately 90 , and nitrogen evolution began at ca. 100 . The entire heating process required 30 minutes, and the nitrogen (19.8 ml.,

88.5^ yield) was collected and corrected to STP. The precipitate was filtered and the filtrate was analyzed by gas-liquid chroma tography on a Carbowax 2CM column and a FFAP column. The decompo sition mixture showed only one peak. After treatment of the product with hydrochloric acid, analysis on an SE-30 column showed that phenylacetaldehyde was the only hydrolysis product.

Treatment of the hydrolysis solution with 2,4-dinitrophenylhydrazine reagent gave a precipitate which after recrystal lization from ethanol was identified as phenylacetaldehyde 2.4- dinitrophenylhydrazone (m.p. 120°, lit. (32) m.p. 110°). The mixed melting point with an authentic sample of phenylacetaldehyde

2,4-dinitrophenylhydrazone was undepressed. 78

Experiment II. Experiment I was rerun with 2-dimethylaminoacetophenone hydrochloride tosylhydrazone (0.0736 g., 0.0002 mole), n-butyllithium (1.66 N in hexane, 0-4-8 ml., 0-0008 mole), and dry diglyme (1 ml.). The decomposition mixture was analyzed as above and the results were the same as in Experiment I.

Experiment III. Anhydrous diglyme (l ml.) was added to a mixture of 2-dimethylaminoacetophenone hydrochloride tosyl hydrazone (0.0736 g., 0.0002 mole) and sodium methoxide (93% pure,

0.0256 g., 0.00044- mole). The mixture was stored for 16 hours at room temperature with protection from light. The solution was then heated from 25° to 130° in approximately 30 minutes. Just before nitrogen was evolved at ca. 120° the solution turned red; at 130° the solution was light yellow and contained a white pre cipitate. The decomposition mixture was cooled and ether (1 ml.) and water (l ml.) were added. The precipitate dissolved in the aqueous layer.

The ether layer, on analysis by gas-liquid chromatography on a Carbowax 20M column, showed a minor and a major peak. Treat ment of the ethereal solution with concentrated hydrochloric acid gave a mixture which when analyzed on a Carbowax 20X column exhibited only one peak. This peak had the same retention time as that of the previously described minor peak. Analysis of the hydrolyzed solu tion on an SE-30 column showed only phenylacetaldehyde and no acetophenone. Experiment IV. Experiment III was rerun with 2-dimethylaminoacetophenone hydrochloride tosylhydrazone (0.0736 g., 0.0002 mole) sodium methoxide (93^ pure, 0.0484- £■> 0.00066 mole) and dry diglyme (1 ml.). The results were the same as in Experiment III.

Experiment V. 2-Dimethylaminoacetophenone hydrochloride tosylhydrazone (0.0736 g., 0.0002 mole) and sodium methoxide

(9356 pure, 0.0640 g., 0.0011 mole) in dry diglyme (1 ml.) were reacted as described in Experiment III. fJ-Dimethylaminostyrene

Is shown to be the only rearrangement product.

Decomposition of 2-phenvlaminoacetophenone tosylhydrazone.—

To a solution of 2-phenylaminoacetophenone tosylhydrazone (0.76 g.,

0.002 mole) in dry pentane (10 ml.) was syringed in n-butyllithium

(1.66 N in hexane, 1.3 ml., 0.0021 mole). After the mixture had been stirred 30 minutes, the solvent was removed at reduced pres sure. The residual salt was heated in situ to 160° in one hour.

The decomposition product was taken up in ether (100 ml.) and concentrated. The dark brown intractable oil (0.40 g., 100^ based on was treated with 2 ,4-dinitrophenylhydrazine solution without formation of a precipitate.

Decomposition of 2-Dhenvlnercaptoaceophenone tosylhydrazone.

Experiment I.-- To a cooled solution of 2-phenylmercaptoeceto- phenone tosylhydrazone (3*96 g., 0.01 mole) in anhydrous tetrahydrofuran (50 ml.) was added slowly n-butyllithium (1.40 N in hexane, 7.9 ml., 0.01 mole). After the mixture was stirred for

3 hours, the solvent was removed under vacuum. The deposited lithium salt was heated in situ to 125°. The evolved nitrogen 80

(201 ml.. 90$ yield) was collected and corrected to STP. Distil lation of the volatile decomposition material from the reaction flask yielded a light yellow oil (1.6 g., 76$ yield based on c M h 12s » 126-129°/! mm.).

A portion of the distillate was treated with 2,4.-dinitrophenylhydrazine reagent. The red precipitate after filtration and recrystallization from ethanol, was identified as acetophenone

2,4“dinitrophenylhydrazone (m.p. 14.0-141°, lit. (36), m.p. 237°).

(36) C. F. H. Allen, J. Am. Chem. Soc., £2, 2957 (1930).

The mixed melting point with an authentic sample of acetophenone

2,4-dinitrophenylhydrazone was not depressed.

The nuclear magnetic resonance spectrum of the distillate exhibited singlets at 4-*75 ~ and 4-* 50 “ which are assigned to the terminal methylene protons and a multiplet at 2.8 T which is assigned to the aromatic protons (Figure 11).

Experiment II. n-Butyllithium (1.63 N in hexane, 6.2 ml.,

0.01 mole) was syringed slowly into a cooled solution of 2-phenylmercaptoacetophenone tosylhydrazone (3.96 g., 0.01 mole) in

anhydrous ether (50 ml.). The reaction mixture was stirred for

one hour and then concentrated at 1 mm. Vacuum pyrolysis of the

dry salt at 1 mm. gave a liquid (1.7 g., yield, 80$ based on

C^Hi^S) which was collected in a Dry Ice— acetone bath.

Analysis of the product by gas-liquid chromatography on a

5* x 1/8” FFAP (550 on Chromosorb G column showed a major peak (92$) and 81 a minor peak (8%). The retention time of the minor peak was identi cal to that of authentic (i-phenylraercaptostyrene.

The mass spectrum of the major peak showed a parent ion at

212; the calculated molecular weight for is 212. Treatment of the decomposition product with 2 ,4-dinitrophenylhydrazide solu tion gave a red precipitate which was filtered and recrystallized from ethanol [m.p. 242-24/°, lit. (36), m.p. 237°]. The melting point of the derivative was not depressed upon admixture with an authentic sample of acetophenone 2 ,4-dinitrophenylhydrazone.

Decomposition of 2-ethylmercaptoacetophenone tosylhydrazone.

Experiment I .— To a solution of 2-ethylmercaptoacetophenone tosyl hydrazone (3-4.8 g., 0.01 mole) in anhydrous ether (50 ml.) was syringed n-butyllithium (1.70 N in hexane, 5-9 ml., 0.01 mole).

The solution was stirred for 30 minutes and then concentrated at reduced pressure. The lithium salt was pyrolyzed under vacuum (l mm.) at 140°. The red product (1.7 g., 88.5$ based on C^QH^pNpS) which had been collected in a Dry Ice trap, exhibited characteristic diazo absorption at 2080 cm (Figure 9)• Heating the red liquid to 130° caused gas evolution and a change in color from deep red to light yellow.

Analysis of the yellow product by gas-liquid chromatography on a 5' x 1/8” FFAP (15$) on Chromosorb G column gave a chromatogram with a major (9C$) and a minor (10$) peak. The minor peak had the same retention time as authentic p-ethylmercaptostyrene. The mass spectra of the major (90$) and the minor (10$) peaks gave parent 82 ions at 164- respectively. The calculated molecular weight for

^10^12^ 164*

When the pyrolyzed material was treated with 2,4-dinitrophenylhydrazine solution, a red precipitate formed. Recrystalliza tion from ethanol yielded acetophenone 2,4-dinitrophenylhydrazone

[m.p. 24-3-245°, lit. (36) m.p. 237°]; its melting point was un depressed by an authentic sample.

Experiment II. n-Butyllithium (1.70 N in hexane, 2.95 ml.,

0.005 mole) was added to an anhydrous diglyme (20 ml.) solution of

2-ethylmercaptoacetophenone tosylhydrazone (1.74 6*. 0.005 mole).

After the mixture had been stirred 15 minutes it was heated to

130°. At ca. 45° the solution thickened and began to turn red; by the end of the heating period the solution was an off-yellow color and contained a white precipitate. The entire heating process required 30 minutes. The nitrogen evolved (100 ml., 90% yield) was collected and corrected to STP.

The decomposition mixture was diluted with ether (25 ml.) and washed with water (2 x 25 ml.). The organic portion was dried over sodium sulfate, filtered, and concentrated under a stream of nitrogen. The residual oil, on analysis by gas-liquid chromatog raphy on an FFAP column, contained a-ethylmercaptostyrene (94%) and p-ethylmercaptostyrene (6%).

Decomposition of 2-ethylmercapto-4l-chloroacetophenone tosylhydrazone.--2-gthylmercapto-4T-chloroacetophenone tosyl hydrazone (1.91 g., 0.005 mole) in anhydrous ether (25 ml.) was stirred with n-butyllithium (1.70 N in hexane. 2.95 ml., 0.005 83 mole). After 15 minutes, the solvent was evaporated under a stream of nitrogen and the salt was vacuum-dried. The residual lithium salt was pyrolyzed at 1^0° under vacuum; with observed diazo de composition in the distilling flask. The oily, volatile product was collected in a Dry Ice trap (1.0 g., 100^ based on ^^H^CIS) •

Treatment of a portion of the product with 2 ,4-dinitrophenylhydrazine reagent yielded L '-chloroacetophenone 2,4-dinitrophenylhydrazone [m.p. 229-231°, lit. (37) 235-236°] after recrystal-

(37) A. Jones and C. K. Hancock, J. Org. Chem., 2£. 230 (I960). lization from ethanol. A mixed melting point with an authentic sample was undepressed.

Analysis of the liquid product by gas-liquid chromatography on an FFAP column showed that a-ethylmercapto-A'-chlorostyrene

(89/0 and p-ethylmercapto-4.'-chlorostyrene (ll%) were present.

Decomposition of 2-ethylmercapto-/.l-bromoacetoohenone tosylhydrazone.--An anhydrous ether (25 ml.) solution of 2-ethylmercapto-4.'-bromoacetophenone tosylhydrazone (2.1^ g., 0.005 mole) was stirred with n-butyllithium (1.70 N in hexane, 2.95 ml., 0.005 mole). After 30 minutes at room temperature, the solvent was evaporated under a stream of nitrogen and the resulting precipi tate was dried under vacuum (2 mm.). The lithium salt was thermolyzed in situ under vacuum (2 mm.). The decomposition product was collected (0.8 g., 65^ yield based on cio-HiiB r S > in a Dry Ice trap. 8A

A portion of the product was treated with 2 ,4-dinitrophenylhydrazide reagent. The precipitate found was recrystallied from ethanol to give L x -bromoacetophenone 2,4--dinitrophenylhydrazone

[m.p. 228-230°, lit. (38) m.p. 235-237°].

(38) L. I. Smith and E. D. Holly, J. Am. Chem. Soc., 78. H 7 5 (1956).

Analysis of the volatile decomposition product by gas-

liquid chromatography on an FFAP column showed that it contained

a-ethylmercapto-^'-bromostyrene (93%) and JS-ethylroercapto-4'-

bromostyrene (l%).

Base-catalvzed thermolysis of 2-phenylmercaotoacetonhenone

tosylhydrazone in different environments.--The same general pro

cedure was used in all of the subsequent decomposition experiments.

Base (sodium methoxide, lithium methoxide, or n-butyllithium),

2-phenylmercaptoacetophenone tosylhydrazone and anhydrous solvent

(decalin, diglyme, or ethylene glycol) were mixed at room tempera

ture. Sodium methoxide or lithium methoxide and 2-phenylmercapto

acetophenone tosylhydrazone were weighed into a dried reaction

flask in anenvironment of low relative humidity (~2C&) and the

Solvent was, quickly syringed into the flask. n-Butyllithium was

added slowly by syringe to a solution of the 2-phenylmercapto

acetophenone tosylhydrazone in the appropriate solvent. The reac

tion mixture was stirred and then heated slowly to ca. 130°. The

entire heating process required approximately 30 minutes. The 85 decomposition mixture was cooled and diluted with equal volumes of water and ether. The ethereal solution was analyzed by gas-liquid chromatography (39) to find the percent yield of each isomer. The

(39) The columns used were 5' x l/8" FFAP (5^) on Chromosorb G and 3' x 1/4" FFAP (3^) on Chromosorb G. results of the decompositions are listed in Table 2.

Decomposition of 2-ethylnercaptoacetophenone tosylhydrazone by various bases in different environments.--The procedure used in the subsequent experiments was identical. At room temperature the appropriate base (sodium methoxide, lithium methoxide or n- butyllithium) was mixed with 2-ethylmercaptoacetophenone tosyl hydrazone in an anhydrous solvent (decalin. diglyme, or ethylene glycol). When the relative humidity of the environment was suffi ciently low (*“20?’) sodium methoxide or lithium methoxide and

2-ethylmercaptoacetophenone tosylhydrazone were weighed into a dried reaction flask to which the solvent was then quickly syringed.

When n-butyllithiun was used it was syringed slowly into a solution of 2-ethylmercaptoacetophenone tosylhydrazone in the desired sol vent. After the reaction mixture had been stirred at ambient temperature, it was heated slowly to ca. 130°. The entire heating process required approximately 30 minutes. After the reaction mixture had been cooled and diluted with equal volumes of water and ether, the ethereal extract was analyzed by gas-liquid chroma tography (40) to determine the percent yield of each isomer. The results of the decompositions are listed in Table 3. 86

TABLE 2

Base Decomposition of 2-Phenylmercapto- acetophenone Tosylhydrazone

Products a-phenylmercapto" p-phenylnercapto- Solvent Equivalent base styrene styrene

Decalin 1.1 eq. BuLi 94 6 2.1 eq. it 79 21 2.1 eq. rt 76 24 3-1 eq. ii trace 100 1.1 eq. KeOMe 97 3 2.1 eq. it 98 2 3-1 eq. ii 98 2 1.1 eq. LiOMe 98 2 2.1 eq. ti 98 2 3-1 eq. it 98 2

Diglyme 1 eq. BuLi only product 1.1 eq. n 94 6 2.1 eq. ii 84 16 3-1 eq. n 83 17 3.1 eq. n 78 22 1.1 eq. HaOKe 100 trace 2.1 eq. ii 85 15 3.1 eq. ii 82 18 1.1 eq. LiOMe 100 trace 2.1 eq. ir 100 trace 3.1 eq. ii 100 trace

Ethylene glycol 1 eq. Buli 89 11 1.1 eq. ti 90 10 2.1 eq. n 84 16 3.1 eq. ii 83 17 1.1 eq. NaO'-ie 89 11 2.1 eq. ii 87 13 it 3.1 eq. 8 6 14 87

TABLE 3

Base-catalyzed Decomposition of 2-Ethylmercapto- acetophenone Tosylhydrazone

Products a-ethylmercapto- {J-ethylmercapto- Solvent Equivalent base styrene styrene

Decalin 1.1 eq. BuLi 84 16 1.2 eq. n 84 16 2.1 eq. it 53 47 2.1 eq. li 72 28 3.1 eq. II none only 1.0 eq. NaOMe 91 9 2.1 eq. ii 89 11 3.1 eq. •i 86 14 1.1 eq. LiOMe 90 10 2.1 eq. it 89 14 3.1 eq. n 87 13

Diglyme 1.0 eq. BuLi 94 6 1.1 eq. ii 88 12 1.2 eq. ti 86 14 2.1 eq. n 85 15 3.1 eq. n 78 22 3.1 eq. n a 45 « 55 £ 1.0 eq. NaOMe 91 9 2.1 eq. ii 89 11 3.1 eq. n 86 14 1.1 eq. LiOMe 89 11 2.1 eq. ti 89 11 3.1 eq. ti 88 12

Ethylene glycol 1.0 eq. BuLi 56 44 1.1 eq. ti 60 40 2.1 eq. it 52 48 3.1 eq. it 53 47 1.1 eq. NaOMe 65 35 2.1 eq. it 55 45 3.1 eq. ti 53 47

® Salt was ]prepared in tetrahydrofuran and then diglyme was added. 8 8

(4-0) The columns used were 5' x 1/8" FFAP {15%) on Chromo sorb G and 10' x 1/4" {5%) on Chromosorb G.

Reaction of 2-ethylmercaptoacetophenone tosylhydrazone

with 3 equivalents n-butyllithium.— n-Eutyllithium (1.60N in

hexane. 7.5 ml.. 0.012 mole) was syringed into a solution of 2-

ethylmercaptoacetophenone tosylhydrazone (1.3940 g., 0.004- mole)

in anhydrous tetrahydrofuran (15 ml.) at 0°. The red solution

was stirred for an hour, thai neutralized by rapid addition of

deuterotrifluoroacetic acid (1.38 g., 0.012 mole) (4-1). Upon

(41) Deuterotrifluoroacetic acid was prepared by mixing trifluoroacetic anhydride (10.50 g., 0.05 mole) with deuterium oxide (1.00 g., 0.05 mole).

acidification of the mixture the red color disappeared giving a

light yellow solution. After evaporation of the solvent under a

stream of nitrogen, a precipitate was obtained which was filtered

and washed well with pentane and ether to give N,2-dideutero-2-

ethylmercaptoacetophenone tosylhydrazone (0.71 g., 0.00202 mole,

51^ yield, m.p. 122-123°).

The nuclear magnetic resonance spectrum (Figure 12) of the

recovered tosylhydrazone exhibits a triplet at 8.87 T (CH^-CH^S),

a singlet at 7.61 T (CH^-tf-) and a quartet at 7.59 T (CH -CT^-S). N n _ a broad singlet at 6-32 T (-C-CHD-S-) and a multiplet at 2.48 T

(aromatic protons). Integration shows the singlet at 6.32 T to

be only one hydrogen. 89

Reaction of 2-ohenylir.ercaptoacetophenone tosvlhvdrezone with 3 equivalents n-butvllithium.--n-Butyl]ithium (1.60 N in hexane, 7.5 ml., 0.012 mole) was syringed into 2-phenylmercapto acetophenone tosylhydrazone in anhydrous tetrahydrofuran (15 ml.) at 0°. The resulting red solution was stirred for one hour.

Neutralization with deuterotrifluoroacetic acid (1.38 g., 0.012 mole) (4 1 ) gave a light yellow solution. The solvent was evaporated

under a stream of nitrogen to give a precipitate which was filtered

and washed well with pentsne and ether to yield N,2-dideutero-

2-phenylmercaptoacetophenone tosylhydrazone (l.OO g., 0.0025 mole,

63% yield, m.p. 98-99°).

The nuclear magnetic resonance spectrum (Figure 13) shows

e singlet at 7.61 T (CH^-gf-) , a broad singlet at 6.08 T N n (-C-CHD-S-) and a multiplet at 2.51 7 (aromatic hydrogens).

Integration shows the singlet at 6.06 7 to be one hydrogen.

Preparation of l-diazo-2-ethvlaercepto-l-phenylethane.

Experiment I. — A stirred solution (42) of 2-othylmercaptoaceto-

(42) The general procedure used was that for preparation of 1-diazo-l-phenylethane by D. G. Farnum, -J. Org. Chem., 28, 870 (1963).

phenone tosylhydrazone (3.48 g., 0.01 mole) and sodium methoxide

(97.5/5 pure, 0.56 g., 0.01 mole) in dry pyridine (30 ml.) wes

heated at 65-70° for 35 minutes. The mixture was then poured

into ice water (150 ml.) and extracted with pentane (3 x 20 ml.). 90

The combined extracts were washed with water (4 x 25 ml.) and saturated sodium chloride (30 ml.), dried over magnesium sulfate at 5°, filtered, and concentrated at reduced pressure. The red oil (0.77 g., 0.004 mole, 40# yield based on C10H12H2 S) when

heated at 130° evolved nitrogen (4-6.5 ml.. 51-5% of theoretical).

Experiment II.--n-Butyllithium (1.53 N in pentane, 6.9 ml..

0.0105 mole) was added to a stirred solution of 2-ethylmercapto

acetophenone tosylhydrazone (3.46 g., 0.01 mole) in dry pentane.

After the mixture was stirred for 30 minutes, the pentane was

evaporated at reduced pressure and the residual salt filtered,

washed with pentane. (2 x 10 ml.) and dried for 5 hours at

0.01 mm. From vacuum pyrolysis of the N-lithio-2-ethylmercapto-

acetophenone tosylhydrazone at 110° and 0.01 mm. (43) was collected

(43) Due to decomposition of the diazo compound, it was impossible to maintain 0.01 mm. vacuum.

at-80° a red liquid (1.27 g., 66°^ yield based on C^qH-^^S) which

was shown to be 46^ pure l-diazo-2-ethylmercapto-l-phenylethane by

nitrogen evolution (63 ml.).

Experiment III.--A solution of 2-ethylmercaptoaceto

phenone tosylhydrazone (1.74 g., 0.005 mole) in piperidine (20 ml.)

was heated at 75° for 45 minutes. The solution was poured into a

mixture of pentane (50 ml.) and ice (100 g.). The organic layer

was separated from the aqueous layer, washed with ice water

(3 x 15 ml.), dried over calcium oxide at 0°. filtered, and 91 concentrated under a stream of nitrogen to give l-diazo-2-ethylmercapto-l-phenylethane (0.5198 g., 0.0027 mole, 54$ yield).

The diazo compound was diluted with anhydrous benzene (8 ml.).

Acetic acid decomposition showed the material to be 94$ pure l-diazo-2-ethylmercapto-l-phenylethane by nitrogen evolution.

Kinetic study of the thermal decomposition of 1-dlazo-l- phenylethane. Experiment I .— A eolution of 1-diazo-l-phenylethane

(0.0114 g., 0.00086 mole) (44) in anhydrous diglyme (l6 ml.) was

(44) The diazo compounds were prepared by the piperidine method and their yields were determined by total nitrogen evolution. thermolyzed in a constant temperature bath at 85°. In order to

determine the rate of decomposition of the diazo compound, its nitrogen evolution was followed using a gas buret and manometer

to which was attached a leveling bulb. The time was followed by

stop watch.

Experiment II.— Experiment I was repeated with 1-diazo-l-

phenylethane (0.0109 g*, 0.00083 mole) in anhydrous diglyme (20 ml.)

The rate constants for Experiments I and II were determined graphi

cally by plotting log (diazo) against time as shown in Figures 10 t 16 and 17.

Kinetic study of the thermal decomposition of 1-diazo-

2-ethylmercapto-l-ohenvlethane. Experiment I.--A solution of

l-diazo-2-ethylmercapto-l-phenylethane (0.2299 g., 0.0012 mole)

(44) in anhydrous diglyme (20 ml.) was thermolyzed in a constant 92 temperature bath at 85°. Thermolysis of the diazo compound was

folloued as outlined for decomposition of 1-diazo-l-phenylethane.

Experiment II.— Experiment I was repeated with l-diazo-2-

ethylmercapto-l-phenylethane(0.300? g., 0.00156 mole) in anhydrous

diglyme (20 ml.). The rate constants for Experiments I and II

were determined graphically by plotting log^fdiazo)^ against

time as illustrated in Figures 18 and 19.

Decomposition of 2-benzo.vl-2-methyl-lr3-dithiane tosyl-

hvdrazone.--To 2-benzoyl-2-methyl-l,3-dithiene tosylhydrazone

(2.03 g., 0.005 mole) in anhydrous tetrahydrcfuran (25 ml.) was

added n-butyllithium (1.627 N in hexane, 3*1 ml., 0.005 mole).

The resulting solution was stirred for one hour after which the

solvent was removed at reduced pressure; the residue was dried

under vacuum (l mm.) for 6 hours. The obtained lithium salt of

2-benzoyl-2-methyl-l,3-dithiane tosylhydrazone was decomposed by

heating to 165°. Nitrogen evolution began at approximately 85°.

The entire heating process required 4-5 minutes, and the nitrogen

(119 ml., 106* yield) was collected and corrected to STP. To

the decomposition mixture was added water (50 ml.) end ether

(100 ml.). The layers were separated; the aqueous layer was ex

tracted with ether (2 x 15 ml.) and the combined ether portions

were washed with water (2 x 25 ml)., dried over sodium sulfate,

and concentrated. The oily residue (0.9 g., 76^ yield based on

^12^14^2)» vaS purified by a short path vacuum distillation (45).

(45) When small quantities of liquids were purified in this work they were distilled in a molecular still of the vertical type. 93

The nuclear magnetic resonance spectrum (Figure 14) cf the distillate shows a singlet at 8.25 7 (relative area three, =C-CH^). a multiplet at 7.91 ^ (relative area two. - C ^ - CH^-CHp) . a triplet

at 6.50 t (relative area four, -S-CH?-CHp-CHg-S-), and a singlet

at 2.77 7 (relative area five, ^-C) .

The distillate was dissolved in methanol (50 ml.) and added

to a slurry of active Raney nickel (25 g.) (Grace)-in methanol (50 ml.).

The reaction mixture was stirred and relluxed for 3 days. The hot

reaction mixture was filtered and the nickel washed with warm

methanol (2 x 50 ml.). Analysis of the filtrate by gas-liquid

chromatography on a 15^ FFAP column showed only one peak which,

when compared with the retention times of n-propylbenzene and iso-

propylbenzenej proved to have the same retention time as n-propyl

benzene (46).

(4 6 ) The author wishes to thank Dr. K. V. Greenlee for the pure samples of n-propylbenzene and isopropylbenzene.

Decomposition of 2-formvl-2-methyl-l.3-dithiane tosylhydrazone. —

Butyllithium (1.627 N in hexane, 3*1 ml., 0.005 mole) was slowly

syringed into a solution of 2-formyl-2-met’nyl-l,3~dithiane tosyl

hydrazone (1.65 g.. 0.005 mole) in anhydrous tetrahydrofuran

(50 ml.). The resulting solution was stirred at ambient tempera

ture for one hour after which the solvent was removed at reduced

pressure and dried under vacuum (l mm.) for 6 hours to give the

lithium salt of 2-formyl-2-methyl-l,3“dithiane tosylhydrazone. The lithium salt was pyrolyzed by heating it to 165°* o Nitrogen evolution began at approximately 70 . The entire heating process required 45 minutes, and the nitrogen (68.7 ml.,

61 .4$) was collected and corrected to STP. To the decomposition mixture was added water (50 ml.) and ether (100 ml.). The layers were separated; the aqueous layer was extracted with ether

(2 x 15 ml.); the combined ether portions were washed with water

(2 x 25 ml.), dried over sodium sulfate, and concentrated to give an oil (0.52 g.. 71$ yield based on C^H^q S^). The residue was purified by a short path vacuum distillation (45).

The nuclear magnetic resonance spectrum (Figure 15) of the distillate showed a singlet (slightly split) at 8.15 T (relative area three, C-C ■*) , a broad multiplet at 7.85 "T (relative peak area two, -S-CH^-CIlg^H^S-) . two superimposed triplets at

6.58 T (relative peak area four, -S-CJ^-C^-Cfhj-S-) and a singlet with long range coupling at 4*32 T (relative peak area one, C=C J ). APPENDIX I

Infrared Spectra

Figures 1-9

95 96 CM 4 0 0 0 3 0 0 0 2000 1 5 0 0 7 0 0 tool — 00

8 0

-203co O -3S

O h *SEt

WAVELENGTH (MICRONS) Figure I.

4 0 0 0 3 0 0 0 2000 1 5 0 0 looo 990 890 7 0 0 KX) .. > 00

8 0

2 a O h - :to SEt

WAVELENGTH (MICRONS) Figure 2.

C M ’1 4 0 0 0 3 0 0 0 2000 1 5 0 0 1000 990 890 7 0 0 ■ i 100 L “ 00

8 0

2 cc/j o

|40- [ 32

2 a :io

WAVELENGTH (MICRONS) Figure 3. 97 CM 4 0 0 0 3 0 0 0 2000 1500 7 0 0 100 ■ ■ ■ 00

8 0

■60 i40

20 .C = C, OMe

WAVELENGTH (MICRONS) Figure 4.

C M ' 1 4 0 0 0 3 0 0 0 2000 1500 7 0 0 100 .. 00

8 0

- 2tocd '60 o ■32

0-CH = CHOMe cis - trans

WAVELENGTH (MICRONS) Figure 5. CM-' 4 0 0 0 3 0 0 0 2000 1500 1000 900 8 0 0 7 0 0 ioo h .... 00

8 0

'60 -.32

c = c

WAVELENGTH (MICRONS) Figure 6. CM-' 4 0 0 0 3 0 0 0 2000 (500 7 0 0 I ■ . . 00

s o

LJ ■60

,40

jfCH - CHOMe cis irons

WAVELENGTH (MICRONS) Figure 7. CM-* 4 0 0 0 3 0 0 0 2000 1500 700 t o o — 00

6 0

20 -C-CHpI 0M«

WAVELENGTH (MICRONS) Figure 8.

C M ' 1 4 0 0 0 3 0 0 0 2000 1 500 0 0 9 0 0 7 0 010 (001. 00

8 0

-3S

WAVELENGTH (MICRONS) Figure 9. APPENDIX II

Nuclear Magnetic Resonance Spectra

Figures 10-15

9 9 c— c 0-<

TMS

*1 Vu**1^ ‘i'“ >Mlt|' •“* *** *

2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.01 Figure 10. 100 101

; ■ 2.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 Fi 0 ure ure II. 0 Fi N - ND - SO9C7H7 II jar- c - chd - s cpHc TMS

2.0 3.0 4.0 5 .0 6.0 7.0 8.0 9 .0 lO.Of Figur* 12. N-ND-S0 2 C7 H7 0 —C- CHD-S - 0 TMS

2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 Figure (3. TMS

2.0 3 .0 4.0 5 .0 6.0 7.0 8.0 9 .0 10.0 t F igu re 14.

O 2.0 3.0 4.0 5 .0 6.0 F igu re 15. APPENDIX III

Kinetic Plots

Figures 16-19

1 0 6 t .40

1.30

1.20

1.10

•— 11.00

0 8 0

0.70 k = - 4 sec.

0.60J 20 30 4050 60 70 80 90 100 120 T i m e (mi n.) 107 Figure 16. f',raPh of Kinetic Date for 1-Diezo-l-phenylethane in Diplyme at 8‘j° o N o o o» o

0.9

0 8

0.7 2030 40 50 60 70 80 90 100 110 120 Time (min.) Figure 17.—A Graph of Kinetic Data for 1-Dlazo-l-phenylethane In Diplynie at 85° 108 0.9 log [Diazo] 1.0 1.4 gur 18. re u ig F -- a 0 2 Graph of Xinatic Data for l-Dlaao-2-athyl»arcapto-l-phanyl«thanain Diglyaa at 85° 3x 0 sec.' 4 10x 43 30 40 50 ie (min.) Time 60 70 80 90 100 110

120 109 1.90

1.40 p 1.30

1.20

1.10 1.44 " 4 sac.

0 10 20 3040 50 6 0 70 80 90 100 MO 120 Tima (min.) Fi gu r a 19.—A Graph of Klnatic Data for l-Diaao-2-atbylaarcapto-l-pbenorlethana in Diglyaa at 85°