Part I: the Chemistry of 2-Diazoimidazole and 2H- Imidazolylidene, Part Ii: Rearrangements of 1-(5-Oxazolyl)• 1-Alkylidenes

INFORMATION TO USERS

This was produced from a copy of a document sent to us for microfilming. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the material submitted.

The following explanation of techniques is provided to help you understand markings or notations which may appear on this reproduction.

1. Tlie sign or “ target” for pages apparently lacking from the document photographed is “Missing Page(s)”. If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure you of complete continuity.

2. Wlien an image on the film is obliterated with a round black mark it is an indication that the film inspector noticed either blurred copy because of movement during exposure, or duplicate copy. Unless we meant to delete copyrighted materials that should not have been filmed, you will find a good image of the page in the adjacent frame.

3. When a map, drawing or chart, etc., is part of the material being photo graphed the photographer has followed a definite method in “sectioning” the material. It is customary to begin filming at the upper left hand corner of a large sheet and to continue from left to right in equal sections with small overlaps. If necessary, sectioning is continued again—beginning below the first row and continuing on until complete.

4. For any illustrations that cannot be reproduced satisfactorily by xerography, photographic prints can be purchased at additional cost and tipped into your xerographic copy. Requests can be made to our Dissertations Customer Services Department.

5. Some pages in any document may have indistinct print. In all cases we have filmed the best available copy.

University Microfilms International 30Ü N. ZEEB ROAD, ANN ARBOR, Ml 48106 18 BEDFORD ROW, LONDON WC1R 4EJ, ENGLAND V. h I

8001791 -

NAIR, MRIDULA

PART I: THE CHEMISTRY OF 2-DIAZOIMIDAZOLE AND 2H- IMIDAZOLYLIDENE, PART II: REARRANGEMENTS OF 1-(5-OXAZOLYL)• 1-ALKYLIDENES. PART III: A NEW McFADYEN-STEVENS ALDEHYDE METHOD

The Ohio State University Ph.D. 1979

University Microfilms

I n te r n ât i0 n â I 300 n . Zeeb Road, Ann Arbor, M I 48106 18 Bedford Row, London W C IR 4EJ, England PART I: THE CHEMISTRY OF 2-DIAZOIMIDAZOLE

AND 2H-IMIDAZ0LYLIDENE

PART II: REARRANGEMENTS OF 1-(5-OXAZOLYL)-1-

ALKYLIDENES

PART III: A NEW McFADYEN-STEVENS ALDEHYDE METHOD

DISSERTATION

Presented in Partial Fulfillment of the Requirements for

the Degree Doctor of Philosophy in the Graduate

School of The Ohio State University

Mridula Nair, B. Sc., M. Sc.

*****

The Ohio State University

1979

Reading Committee: Approved By Professor Jack Hine

Professor John A. Secrist III

Professor Harold Shechter

AdvisorIdvisor Department of Chemistry This work is gratefully dedicated to my parents for their selfless love and commitment.

ii ACKNOWLEDGMENTS

I wish to express my debt and my deep sense of gratitude to Professor Harold Shechter for his inspiring guidance and unstinted help. Professor Shechter's constant encouragement, patience, and understanding are truly invaluable and shall never be forgotten.

I would also like to extend my gratitude to The Ohio

State University, the National Science Foundation, and the National Institutes of Health for their financial support. Finally, I gratefully acknowledge the cooperation of Ms. Bobbie Cassity in typing this manuscript.

iii VITA

November 11, 1953 Born - Kerala, India

1973 ...... B.Sc., Madras University, Madras, India

1975 ...... M.Sc., Indian Institute of Technology, Madras, India

1975-1977...... Teaching Associate, Department of Chemistry, The Ohio State University, Columbus, Ohio

1977-1979, Research Associate, Department of Chemistry, The Ohio State University, Columbus, Ohio

PUBLICATIONS

"Vacuum Pyrolysis of Salts of l-Acyl-2-arylsulphonyl- hydraziines; a General McFadyen-Stevens Aldehyde Synthesis." M. Nair and H. Shechter, Chem. Commun., 793 (1978).

"A Convenient Synthesis of 6H-[l]Benzopyrano[4,3-b]- quinolines," K.K. Balasubramanian, G.V. Bindumadhavan, M. Nair, and B. Venugopalan, Synthesis, 511 (1977).

"Thermal Rearrangement of 4-Chloro-3-aryloxymethyl-3- chromenes," K.K. Balasubramanian, M. Nair, C. Devakumar, and B. Venugopalan, Chemistrv and Industry, 611 (1976).

IV TABLE OP CONTENTS Page

DEDICATION...... il

ACKNOWLEDGMENTS...... ill

VITA ...... iv

LIST OF TABLES AND FIGURES...... vii

PART I: THE CHEMISTRY OF 2-DIAZOIMIDAZOLE AND

2H-IMIDAZ0LYLIDENE ...... 1

STATEMENT OF PROBLEM ...... 2

HISTORICAL ...... 3

RESULTS AND DISCUSSION ...... 23

EXPERIMENTAL ...... 81

PART II: REARRANGEMENTS OF 1-(5-OXAZOLYL)-1-

ALKYLIDENES...... 115

STATEMENT OF PROBLEM ...... 116

HISTORICAL ...... 117

RESULTS AND DISCUSSION ...... 125

EXPERIMENTAL...... 139

PART III: A NEW McFADYEN-STEVENS ALDEHYDE METHOD 161

STATEMENT OF PROBLEM ...... 162

HISTORICAL...... 163

RESULTS AND DISCUSSION ...... 167

EXPERIMENTAL ...... 177

V CONTENTS (CONT'D) Page

REFERENCES

Part I ...... 191

Part I I ...... 196

Part I I I ...... 198

VI LIST OF TABLES

Table Page

1 Decompositions of Sodium Salts 33a-c . . . 130

2 Pyrolysis of Sodium Salts 33a-c at 350°C 135

3 Aldehydes by the Present McFadyen-Stevens M e t h o d ...... 170-

4 Decomposition of Sodium and Lithium Salts of l-Acyl-2-p-tosylhydrazides 186.

LIST OF FIGURES

Figure

1 Vacuum Pyrolysis Apparatus ...... 185

vii PART I

The Chemistry of 2-Diazoimidazole

and 2H-Imidazolylidene STATEMENT OP THE PROBLEM

The present study involves investigation of the chemistry of 2-diazoimidazole (^) and 2H-imidazolylidene

(2), the carbene derived from The principal objectives of this research are: (1) to study the thermal and

C > O :

photo lytic reactions of and/or 2 with a variety of substrates such as hydrocarbons, olefins, amines, ethers, alcohols, benzenes, and heterocyclic aromatics; (2) to explore the possibilities of preparing molecules with new and unusual structures that may be of synthetic value; and

(3) to determine the mechanistic features underlying the reactions of 1 and of 2. HISTORICAL

The chemistry of diazocyclopentadiene (3_), its aza- analogS/ and their related car bene s has been of interest because of the fascinating reactions they undergo.

The unusual aspects of some of these transformations have drawn certain attention; however, detailed mechanistic insight with respect to most of these processes is lacking.

In this section which is intended to be illustrative rather than exhaustive, some representative examples of these reactions will be examined.

= 9 ^ = N

3 4

Diazocyclopentadiene (^), first reported in 1953,^ has been important to the theory of organic chemistry because it is a stable 6 Il-electron Hückel system (4).

Cyclopentadienylidene (5_), ,derivable from ^-4 by pyrolysis or photolysis, is a carbene of interest as a singlet (5a)

(1) W. von E. Doering and C.H. DePuy, J. Am. Chem. Soc., 75, 5955 (1953). 0 - - 5a 5b

and as a triplet ( ^ ) . Calculations indicate that ^ is a

stabilized, electrophilic, 611 electron carbene (5^). BSR

studies^ however, establish that 5 is a triplet in its

ground state (5b).

(2) R. Gleiter and R. Hoffmann, J. Am. Chem. Soc., 90, 5457 (1968).

(3) E. Wasserman, L. Barash, A.M. Trozzolo, R.W. Muwayand, and W.A. Yager, J. Am. Chem. Soc., 86, 2304 (1964).

Olefins undergo stereospecific addition of ^ and thus

the reactant is presumed to be the singlet 5a (Eq. 1).^

5 (1)

98%

5 100%

Further, the reactivities of p-substituted styrenes (Eq. 2) to give a linear free energy correlation with a kinetic p 5a + CH=CH, (2)

value of -0.76 and cr substituent constants reveal the

electrophilic character of 5a.^

(4a) R.A. Moss, J. Ora. Chem.. 31, 3296 (1966) ; (b) R.A.Moss and J.R. Przybyla, ibid., 3 3,‘ 38lS^(1968).

(5) H. Durr and F. Werndorf, Angew. Chem. Int. Edn., 13, 483 (1974).

Photolyses of substituted diazocyclopentadienes (6) in benzene and its derivatives give spironorcaradienes (7_) in equilibrium with spirocycloheptatrienes (8).^ Thermal

(6a) H. Durr and H. Kober, Angew. Chem. Int. Edn., 10, 342 (1971); (b) H. Durr and H. Kober, Tetrahddron LettT, 1259 (1972); (c) H. Durr, H. Kober, V. Fuchs, and P. Orter, Chem. Comm.. 973 (1972); (d) M. Jones, Jr., A.M. Harrison, and K.R. Pettig, J. Am. Chem. Soc., 91. 7462 (1969); (e) D. Schonleber, Chem. Ber., 102,"xT89 (1969).

8 rearrangement of 7-8 yields 9, the overall product of aromatic substitution (Scheme 1). Photochemical rearrange ment of the equilibrium mixtures of 7 and 8 results in

I,7-migration or di-IT-methane rearrangement to form and 7 II. Diazocyclopentadienes 12 unsubstituted in their

SCHEME 1

di-II-methane 9 ^

[1,5] 4-positions, irradiate in benzene to give bicyclo[6.3.0]- Q undecapentaenes (^, Eq. 4). The above reactions of ^ and substituted cyclopentadienylidenes with benzene appear

1 hv N 2

12 (4)

R H

13 to involve singlet intermolecular processes rather than intersystem crossing to tripet states.

(7) H. Durr, H. Kober, I. Holberstadt, U. Neu, T.T. Coburn, T. Mitsuhashi, and W.M. Jones, J. Am. Chem. Soc., 95, 3818 (1973).

(8a) H. Durr and G.S. Schoppers, Chem. Ber., 1 ^ , 380 (1970); (b) H. Durr and L. Schrader, ibid., 102, 2026 (1969). 8

The synthesis and reactions of diazocyclopentadiene

(3) have kindled interest in analogous diazoheterocyclic

systems. Although 3-diazo-2/5-diphenylpyrrole (1^) was Q first reported in 1905, the chemistry of diazopyrroles 9b remained essentially unexplored until the late 60's.

/----- \ 1) HNO, ,----- Ù 2

H 14

(9a) P. Angelico, Atti. Acad. Naz. Lincei., 14, II, 167 (1905); (b) R.P. Bartholomew and J.H. Tedder, J. Chem. Soc., (C), 1601 (1968) .

Diazopyrrole has been recently studied in this laboratory

Thermal and photochemical decompositions of result

in 2, 5-diphenyl-3H-pyrrolylidene ( 15) which reacts as a

singlet (15a) and/or a tripet (15b). For example.

(10a) M. Nagarajan, Ph.D. Thesis, The Ohio State University (1978); (b) M. Nagarajan and H. Shechter, J. Am. Chem. Soc., 101, 2198 (1979). photolysis of ^ in cyclohexane results in 3-cyclohexyl-

2,5-diphenylpyrrole (16, 32%) and 2,5-diphenylpyrrole -N, 14 j x c ^6^5 ''6“ 5 "6""56 ^6^5 "6“S 15 15a 15b (17, 25%). The reduction product ^ implies significant

involvement of triplet 15b (Scheme 2).

SCHEME 2

hv 14

c 6 5 15a

V 0 H

CgHg I ^6“5 6 5 6 5 H H

16 or HV 0 , V - H

HI 17 Similarly, reaction of with allylbenzene gives 2,5- — diphenyIpyrrole (1/7) ^ 2, 5-diphenyl-3-(1-phenyl-2-propenyl) pyrrole (^) and 2,5-diphenyl-3-(3-phenyl-2-propenyl)pyrrole 10

(19, Eq. 1), suggesting hydrogen abstraction from

allylbenzene by triplet 15b.

CgHs CH=CH_CgHg '^CH-CH=CH„ \„ 14 2------2 ^ 17 + A or hv =6^5 I ^6“ 5 " 6 “ 5 -( =6^5

iâ 19 (7)

2, 5-Diphenyl-3H-pyrrolylidene ( ^ ) , as generated thermally or photochemically, however, reacts apparently as its singlet (15a) with benzene and the electronegatively substituted benzenes: benzonitrile and nitrobenzene (Eq. 8).

Z 15a + Z

Z= H,CN,NO ^6^5 (=6^5

20 21 (8)

I H - ■z H

CgH T CgHg ° ^ H

22 11

The benzenes undergo ring expansion to give 1,3-diphenyl-

2H-cycloocta[c]pyrroles (2^)/ presumably via 1,5 sigmatropic

rearrangement of spiroeyeloheptatriene intermediates (2^).

The behavior of ^ on triplet photosensitization in benzene

or benzonitrile is different. Ring-expansion products

(22) are not detectable; instead, aromatic substitution

takes place. Aromatic substitution is rationalized as

involving 15b and/or its triplet diazo precursor as in

Eq. 9 in which triplet diradical 23 undergoes intersystem

15b +

Z = H, CN S « 5

crossing to singlet diradical 2£, followed by hydrogen migrations resulting finally in 25.

Reactions of ^ with electron-rich benzenes are

indicative of both singlet (15a) and triplet (15b) 12

participation. Anisole and toluene undergo ortho and/or

para-substitution (2^), presumably via singlet jSa, by

collapse of spi ropyrrolonor car adienes 20 through substituent-

controlled dipolar processes (Scheme 3).

Z SCHEME 3

-N, 14 -> 15a Z=CH3,0CH3 CgHg CgHg CgHs

C.H 26

2,5-Diphenyl-3H-pyrrolylidene, apparently as the triplet

(15b)/ effects hydrogen abstraction to form diphenylpyrrole

(17). In the reaction with toluene, is formed along with

3-benzyl-2/5-diphenylpyrrole by abstraction recombination. 13

2-Diazo-3/5-diphenylpyrrole (27^) has been synthesized

by the action of nitric oxide on 2-nitroso-3,5-diphenyl

pyrrole (Eq. 10).^^ Not much is known, however, about

NO > (10) NO C 6 27

2-diazopyrroles other than that they are less stable than

3-diazopyrroles and that they couple with 2-naphthol.

(11) J.M. Tedder and B. Webster, J. Chem. Soc., 1638 (1962).

Although diazopyrazoles were first synthesized over 12 60 years ago (Eq. 11), their behavior remained unexplored 13 until the early 60's. Recently 3(5)-diazopyrazoles have

A 1) HNO fj\ N-H > 14

(12) E. Meyer, J. Prakt. Chem., 90, 1 (1914).

(13a) D.G. Parnum and P. Yates, Chem. and Ind., 659 (1960); (b) D.G. Parnum and P. Yates, J. Am. Chem. Soc., 84, 1399 (1962); (c) H. Reimlinger, A. von Overstraeter, and H.G. Viehe, Chem. Ber., 94, 1036 (1961); (d) H. Reimlinger and A. von Overstraeter, ibid., 3350 (1966).

14 been investigated at The Ohio State University.

Deconposition of 3-di azo-4-methyl-5-phenyIpyrazole {2^ is particularly interesting in that 2-cyano-2-methyl-5-phenyl-

2H-azirine (^, 60%), acrylonitrile (trace) and benzo nitrile (10%, Scheme 4) result via collapse of 3H-pyrazolylidene 29. Irradiation of 28 in cyclohexane leads to

SCHEME 4

CH CH. CH, ,CN hv or A

-N, C 'N; 29 28 V CH3 CN

^ -- CH--C-CN ^ ^ C^Hc-caN 6 5 H H

^6^5 30 15

capture of carbene 29^ yielding 3(5) -cyclohexyl-4-methyl-

5 (3)-phenylpyrazole (^) along with azirine Photolysis

of 5-phenyl-3-diazopyrazole (32) in ethyl ether results

(14a) W.L. Magee, Ph.D. Thesis, The Ohio State University, 1974; (b) W.L. Magee and H. Shechter, J. Am. Chem. Soc., 99, 633 (1977).

CH hv (12) 28 0 29 31 in cleavage of the ether (Eq. 13) presumably from attack at oxygen by the electrophilic singlet carbene 33.

0—CgHg

n (13)

0-C H 32 33 SCHEME 5 t- c .H,

36 t-C ,H, t-C ,H, +

-N 35

H» 37 a\ 17

Reactions of 3H-pyrazolylidenes with benzenes have

also been studied. Thermal and photolytic decompositions

of 5-t-butyl-3-diazopyrazole (34) in benzene yield 3(5)-t-

butyl-5 (3)-phenylpyrazole 90%) and, in minor amounts,

2-t-bwtylpyrazolo[3,2-a]azocine (^, 10%), possibly through

the intermediacy of singlet carbene ^ (Scheme 5).

Diazopyrazole ^ undergoes cycloaddition to electron-

rich olefins with retention of nitrogen. Thus ethyl vinyl

ether reacts with ^ with elimination of ethanol, to give

7-t-butylpyrazoles [3,2-c]-as-triazine (3^, Eq. 14).

CH„=CH-OC„H 34 t-C t-C H,

38 (14)

Among the other 5-membered ring diazo heterocycles

known are those derived from imidazole. 4-Diazoimidazole-

5-ucarboxamide (^) has antibacterial properties and its 15 derivatives are potent antitumor agents. Decomposition

of ^ with loss of nitrogen leads to 5-carboxamido-4H-

imidazolylidene (^), a highly electrophilic carbene^^ which inserts readily into C-H and 0-H bonds of alcohols.

Thus photolysis of 39 in ethanol yields 18

-N, (15)

5 (4)-(hydroxyalkyl) imidazole-4 (5)-carboxamide 29%) and 5(4)-etboxyimidazole-4(5) -carboxamide (^, 39%) in addition to imidazole-4-carboxamide (^) and acetaldehyde

(Eq. 16) .

(15) Y.F. Shealy, R.F. Struck/ L.B. Holum/ and J.A. Montgomery, J. Ore. Chem., 26, 2396 (1961).

(16) U.G. Kang and H. Shechter, J. Am. Chem. Soc., 100, 651 (1978). ~

CH, 0 H-C - OH 0 CHg- CHg-OH

H„N N-H N=i/

41 42

hv 40 > 4 1 (16) 0-C.H 0

H N H^N + CHjCHO = l / N

43 44 19

2-Diazo-4/ 5-dicyanoimidazole (;^), synthesized by diazotization of 2-amino-4,5-dicyanoimidazole (45), followed by neutralization has been investigated in some 17 detail Decomposition of 46 with loss of nitrogen

CN NC NC 1) HNO, -N V V i 'NH, ."“ 2 2) B a s e ^ ^2 CN H NC NC (17) 45 46 results in 4,5-dicyano-2H-imidazolylidene (£7), a highly electrophilic carbene. Pyrolyses of ^ in halobenzenes

(bromo, chloro, and iodobenzenes, respectively) are of note in that dicyanoimidazole halonium ylides (^) are formed along with 4,5-dicyano-2-halophenylimidazo1es (48) and 4,5-dicyano-2-halo-l-phenylimidazoles (49, Eq. 18).

47 -C.H X = Br,Cl,I

(18) 20

Ylides ^ rearrange to ^ thermally, a,a,o?-Trifluorotoluene reacts with 47 to give the product of C-F insertion and

Q'/Q'-difluorobenzyl migration (53^) along with 4,5-dicyano-2- m-trifluorotolylimidazole (5^), as derived by meta-electrophilic aromatic substitution (Eq. 19).

NC NC, CF 47 + (19)

NC CF 5 52

(17) W.À. Sheppard and O.W. Webster, J. Am. Chem. Soc., 95, 2697 (1973).

2-Diazoimidazole (1), the unsubstituted analog of 18 46, has been prepared from 2-aminoimidazole (5^) as in

Eq. 20 and is unstable above 0°C. Very little is known about 1^. Coupling of 2-naphthol with 1 yields azo

NaNO, 'N © 0 Base N HSO^ NH 2 2 HgSO^ 2

i (20) 53 H 21

derivative 5£ which upon heating cyclizes to naphthoimida-

zolo-as-triazene (55, Eq. 21). 2-Imidazolediazonium

(21) 54 55 fluoroborate ( ^ ) , a derivative of 1, converts to 19 2-fluoroimidazole (^, 30%, Eq. 22) upon irradiation.

H H 56 57

(18a) E. Melendez and J. Vilarrasa, An. Quim., 70, 966 (1974); (b) J. Vilarrasa and R. Grandes, J. Het. Chem., n , 867 (1974).

(19) K.L. Kirk and L.A. Cohen, J. Am. Chem. Soc., 95, 4619 (1973).

20 Diazotriazoles have been prepared but their chemistry is practically unexplored. Diazotetrazole (58) 21 is the first diazoheterocycle of any kind to be synthesized.

An interesting application of 58 is in the production of 22

22 atomic carbon as in Eq. 23. Tetrazolylidene (^) has

not been captured, however, and there is no evidence for

its formation.

C + 3Ng (23)

58 59

(20) J.M. Tedder in Advances in Heterocyclic Chemistry. Vol. 8, Academic Press, New York, 1967, p. 18.

(21) J. Thiele, Ann. Chem., 270, 46 (1892).

(22a) P.B. Shevlin, J. Am. Chem. Soc., 94, 1379 (1972); (b) P.B. Shevlin and S. Kammula, ibid., 99, 2617 (1977); (c) S.P. Dyer and P.B. Shevlin, ibid., 101, 1303 (1979). RESULTS AND DISCUSSION

The present effort involves study of the chemistry

of 2-diazoimidazole (^) and its subsequent carbene,

2-imidazolylidene (2), as derived thermally and photo-

lytically. The choices of 1 and 2^ were made on the basis

of the intrinsic symmetries of these parent molecules

and above all, their potential for unusual and illustrative

chemistry.

2-Diazoimidazole (1) is prepared from S-methyliso-

thiourea sulfate ( 6 0 ) as shown in Scheme 6. The

instability and explosive nature of 1 prompts its

generation shortly before use and careful handling in

(23) B.T. Storey, W.W. Sullivan, and C.L. Mayer, J. Ora. Chem., 29, 3118 (1964).

small quantity (0.5-0.6 g). Dry 1 is highly shock

sensitive and to avoid explosions the preferred procedure

is to transfer 1 in methylene chloride to a reaction vessel and then effect near total removal of the solvent in vacuo.

23 24

SCHEME 6

NH C 2H 5.O H 2SO4 + CH-CHg-NHg CH3-S'A 'NHg C 2H 5-O

HgO, Û

NH n JZ H 2SO4 HgN NH-CHg-CH(00 ^Hg)%

H I -N, e - 1) NaNO_/HBF. ^ NH3HS0 ^ 2) NaHCO.

2-Diazoimidazole (1) reacts rapidly with pyrrolidine in methylene chloride, even at 0°C giving 2-pyrrolylidinyl- azoimidazole (1^, 84%, Eq. 24), a white crystalline solid whose structure is established from its elemental analyses and spectral properties. Formation of 61 results from 25

coupling of the diazo group in 1 and the nucleophilic

nitrogen of pyrrolidine followed by tautomerization as in

Eq. 24.

^ [p)-N=K.-N^ ---- ^

(24) N = N — 1 G

2-Diazoimidazole (1) is presumably delocalized as in ^ and ^ and thus might undergo 1,3- or 1,4-dipolar additions to appropriate unsaturated reagents. Reaction

1-cyclohexenylazoimidazole (^, 38%, Eq. 25). An 26

N © 1 +

(25) 63 unidentified product/ (^/ 38%) derived from addition of 1 to 6^ with loss of morpholine is also obtained. Adduct a fairly unstable derivative, is apparently formed via nucleophilic attack of the double bond of the enamine. 62 on the terminal nitrogen of 1 followed by proton transfer as in Eq. 25. The unassigned product, (^), is of proper mass and analyses and is presumed to result upon initial dipolar cycloaddition of 1 to 62. As shown in Scheme 7, 1 might react by direct or stepwise 1,4-cycloaddition or a similar 1,3- cycloaddition followed by one of three possible 1,5- rearrangements. These various possibilities lead to the different products: 64a, 64b, and 64c, respectively.

Differentiation of these structural possibilities by IR,

NMR, and MS methods is as yet impossible; however, on the basis of precedent and intuition, 64c is a preferred 27

SCHEME 7

1,5-shift -Ô

1/5-shift

1 +

64b

/=r^ -Û ^ Q r Y

64c 28

structure. Absolute structural assignment of the product

awaits crystallographic analysis or unambiguous degradation

or synthesis.

Study was then directed to 2H-imidazolylidene (^)

as derived from 1. Decomposition of 1 either thermally

or photochemically can give, in principle, the highly

delocalized singlet carbene 2k with 611 electron (aromatic)

stabilization of its imidazole nucleus, and then the

triplet carbene 2b, a species dominated by Hund orbital

0 “. ^ O' #>3 : i i 2|L 2b effects. An ESR study (with Dr. M. Platz) of 2 upon

photolysis at 77°K in hexafluorobenzene shows no evidence

for 2b. The ground state of 2_, therefore, is most likely

a singlet (2a). Contrastingly indeed, cyclopentadi- 3,24 enylidene (5) has a triplet ground state (^). The

(24) P.P. Caspar and G.S. Hammond in Carbenes, Vol. II, J. Wiley and Sons, 1975, p. 207. 29

lower energy of 2a as compared to 2b is possibly due to

the strong electron attraction of the two nitrogens in 2_

leading to enhanced delocalization as in 2a' and 2a". 8 ^ f ;>0 ^ ^ O © 2a 2^ 2a , ' 2a'"

Compensating back-bonding effects as in 2a''* which 2 partially fill and stabilize the empty carbenic sp orbital may also be operational. The predcminant property of 2^ is thus expected to be as a highly electrophilic reagent which will insert into various types of bonds. To explore these predicted possibilities, 1 was decomposed in the presence of various substances.

Photolysis (25°C) or thermolysis (70°C) of 1 in cyclohexane results in 2-cyclohexylimidazole (^, 80% and

78%, respectively). Isolation of ^ is reasonable evidence for the intermediacy of 2H-imidazolylidene (2).

Cyclohexyl derivative could arise either by 1,1 C-H- insertion into cyclohexane to give 6^ followed by (1,5- sigmatropic) rearrangement, or by direct 1,2-insertion 30

SCHEME 8

O'- 2 H H 66

V V

■>

S 65

(Scheme 8). There is no evidence which differentiates

between the mechanistic possibilities, but in subsequent

examples and discussion, the first possibility will only

be considered because of brevity and tradition.

Irradiation of 1 in cyclohexane yields 2-(3-cyclohexenyl) imidazole (67;, 31%) and intractables. The

structure of 6^ is assigned by elemental and spectral

analyses. Product 6^ could arise by direct insertion of H

hv 1 + (26)

67 31

singlet 2a into an allylic C-H bond of cyclohexane/ or via spiro adduct 6^ which undergoes ring opening with

P-hydrogen migration as in Scheme 9. The ring-opened intermediate 69a or 69b might also undergo shift of or-hydrogen to give 2-(1-cyclohexenyl) imidazole (70).

However, no evidence for formation of 7£ was seen.

SCHEME 9

1 + 0 67

hv, -N,

\/ 8-H/ shift 8 69a or a-U, shift V

69b. 70 32

To verify if indeed spiro intermediates (like 6£)

are formed during reactions of 2 with olefins, 1 was

decomposed in 2, 3-dimethyl-2-butene and in 2-methyl-2-

butene. Direct insertion of carbene 2 into the allylic

C-H of these olefins will give 7^ and/or 72. The route

involving spirocyclopropane adducts would yield 73 and/or

•N, r - v CH 1 r / H CH Zi R = H or CH3 2 1 74 and 7^ when R=H, as in Scheme 10. Photolysis of 1 in

2,3-dimethyl-2-butene or 2-methyl-2-butene unfortunately

SCHEME 10

Nnz/ R

CH- H 2 + CH,

R = H or CH. 33

led to no isolable products. As pointed out earlier singlet 2H-imidazolylidene

(2a) is predicted to display marked electrophilic behavior.

To test this hypothesis, 2 was generated in the presence

of compounds bearing non-bonded electron pairs. 2-Diazo-

imidazole (1) was, therefore, decomposed thermally and

photolytically in ethers, alcohols, and aromatic

heterocycles.

Photolysis of 1 in diethyl ether results in production of 2-ethoxyimidazole (77^) in low yield (— 16%)

along with resinous material. C-H insertion products of

diethyl ether are not found and it is likely that there is

considerable destruction of 11^ in the presence of

2-Ethoxyimidazole (77^) is a sensitive compound and is assigned on the basis of its analyses and its IR and NMR spectra. Formation of T7 indicates attack of 2_a on oxygen in diethyl ether and collapse of betaine 7^ as in Eq. 27.

C2H 5 s | ) ‘F 2

1 + CjHj-O-CjHg °-C2%5 + =2*4

H 76 77 34

No effort was made to detect ethylene. The behavior of

2 and diethyl ether is apparently partly similar to

photolysis of ethyl diazoacetate in dimethyl ether to

give ethyl ethoxyacetate and ethylene (Eq. 28) along 25 with insertion products.

H-C-COg-CgHg -----> I ^

, o © ' ~ S l / \ H COg-CgHg (28)

CgHg-O-CHg-COg-CgHg +

(25a) V. Pranzen and L. Fikentschen, Ann. Chem., 617/ 1 (1958); (b) W. Kirmse, Carbene Chemistry/ Academic Press, New York and London, 1971, p. 430.

The reactions of 1 with ethyl vinyl ether were then

investigated. Photolysis of 1 neat in ethyl vinyl ether

at 5-10°C results in extensive polymerization along with

formation of 2-imidazolyl vinyl ether (80^, 10%). Efforts

to improve the conversion to 80_ were unsuccessful.

Reaction of 1 in the dark with ethyl vinyl ether does not 35

lead to products of addition either with retention of the diazo- nitrogen or without (78_) ; 80_ is formed, however.

Vinyl ether 80^ is not a very stable compound but is identifiable from its spectra (IR, NMR) and by analyses.

Formation of 80^ may arise from 2_ by a mechanism (Scheme

11). involving attack on oxygen and elimination similar to that of 2^ and diethyl ether (79) . An alternate interesting possibility involving addition of 2^ to the vinyl group of ethyl vinyl ether (7£) followed by nucleophilic attack by ether-oxygen on the spiro center to give or manifesta tions thereof cannot be excluded.

SCHEME 11.

GH=CH, t y - é p ^ - 0-CH=CH,

H — CH I 88

1 + CgHg-O-CHzzCHg 36

To study further the electrophilic reactivity of

2H-imidazolylidene (2^), 2-diazoimidazole (1) was photo-

lyzed in isopropanol. The products of reaction are

2-isopropoxyimidazole (81, 41.8%), 2-(2-hydroxypropyl)

imidazole (8^, 2%) and acetone (24.4%) as determined by

gas-chromatographic analysis. Products 8^ and 8^ are

assigned by their spectra and combustion analyses.

H ^ H ^ 81 82 ^^^3^2^"°

The mechanism(s) of formation of 81 is(are) not clear. One presumption is that singlet ^ undergoes attack by oxygen of the alcohol to give betaine §2 followed by hydrogen migration (Scheme 12).^^ Another

(26) Diazodiphenylmethane apparently reacts carbenically with alcohols to give ethers via a betaine mechanism; D. Bethell, A.R. Newall, G. Stevens, and D. Whittaker, J. Chem. Soc., B, 749 (1969). 37

SCHEME 12

OCH^I^)^

H ^ t A n 83 2a 81 / (CH3) ^ ^ ^ C H ( C H 3 ) 2

-H ©

84 route might involve protonation of 2a to give a highly energetic cation 84, which is captured by the alcohol to give 81. A still different mechanism may be protonation of 2-diazoimidazole (1) to diazonium ion 8^ which reacts with the alcohol with loss of nitrogen to give 83^

(Eq. 30).

-(CHg >2 CH O © © (CH3)gCH-OH 1 + (CHgjgCH-OH N > 81 2 -Ng,

H (30) 85

Formation of alcohol 8^ is readily explained via

C-H insertion into isopropanol by electrophilic singlet carbene 2 a . Such processes are documented for related 38

carbenic systems as summarized in the Historical, e.g., 1 6 5-carboxamido-4H-imidazolylidene ( ^ ) .

Acetone may be formed by oxidation of isopropanol

by singlet 2a. Abstraction of methine hydrogen from

isopropanol by 2a would lead to 8^ and 2-hydroxy-2-propyl

cation (87). Further reaction as in Eq. 31 accounts for

acetone. Another mechanism for the formation of acetone

2a ------H + (CH,),C-OH(CHL)_C_OH > (CH3) 2C=0 +

(31) 86 87 O I H 88

may involve the diazonium ion 8^ as in Eq. 32. No

evidence so far is seen for formation of imidazole (88)

Perhaps 88 is destroyed in the reaction environment.

r ' N . © (CH ) CHO© 2 (CH3)2CH-0H----- ^ --- > 2 + (€#3)20=0

k ^1+87

85 88 (32) 39

2-Diazoimidazole (1) was then decomposed in the

presence of various aromatic heterocycles. Photolysis of

1 in furan yields cis-l-huten-S-ynyl 2-imidazolyl ether

(89/ 20%) along with intract ables. Ether 89_ is a remark

able product of insertion of 2 involving cleavage of furan.

H H (33) 2 ^ - f T l H I 89 H

The structure of 89^ is assigned from its spectra and

analyses and by comparison with cis-l-methoxv-l-buten-3- 27 yne (90). The terminal acetylenic group in 89 is

K H W '

(27) High Resolution NMR Spectra Catalog, Varian Associates, 1962, Spectrum No. 100. 40

indicated by IR absorption at 3210 and 2110 cm“ ^. The

sharp band at 1645 oti"^ reveals the olefinic linkage and

the strong absorption at 1250 and 1090 cm“ ^, the ether

linkage. Ether 8£ displays a doublet in the NMR at

6 3.10 corresponding to with = 2Hz; a doublet of

doublets at 6 4.96 coming from with = 2Hz and

J, = 7 Hz; a doublet at ô 7.50 due to H with J, = 7Hz; D C C DC a singlet at 6 6.66 resulting from the two imidazole protons at C-6 and C-6 '. The small coupling between H^ and suggests cis-stereochemistry about the olefinic site (J. _(trans) = 12-18 Hz). The downfield shift of H DC ------c (the corresponding proton in 9£ comes at 6 6.35) is attributed to deshielding by the imidazole ring. Further evidence for 89 comes from the characteristic coupling constants for primary acetylenes (250 Hz). A 13 gated C-NMR spectrum of 89 displays a doublet of doublets centered at 82.75 ppm arising from with

„ = 251.4 Hz. Also the values for ^J_ „= 194.3 Hz and

Jq H “ 169.6 Hz are consistent with structure 89.

The fact that ether 89_ is obtained may seem to indicate attack of electrophilic ^ on oxygen in furan followed by ring collapse as in Eq. 34. However, the 41

H H H-Shift V / l f > o

2a H / 1 89 (34) furan HOMO (highest occupied molecular orbital) has no electron density on oxygen but is of proper symmetry for the empty H orbital of singlet 2a to add to the 2-3 double 28 bond of furan, A route to 89 may thus be visualized to

(28a) W.L. Jorgensen and L. Salem, The Organic Chemists Book of Orbitals, Academic Press, New York, 1973, p. 234; (b) S.F. Dyer and P.B. Shevlin, J. Am. Chem, Soc., 101, 1303 (1979). "

involve attack of ^ on the double bond of furan to give spirocyclopropane ^ which ring-expands to spirointer- mediate 92. 1,2-Elimination about the 4-5 double bond

91 42

of the pyran nucleus in 9 ^ and proton transfer will yield

89. Synchronous elimination will explain the exclusive cis-geometry around the double bond in 89.

2-Diazoimidazole (1) was also photolyzed in

2/5-dimethylfuran in an effort to understand better the reactions of 2^ with fur ans. However / the photolysis yields a large number of compounds none of which can be successfully separated and isolated. 29 Electrophilic carbenes form stable sulfur ylides upon reaction with divalent sulfur compounds such as 30a vinyl sulfides, thiophene (Eg. 36), and dibenzothiophene.

S +N,C(CO,CH^), ----- > L S — C(CO,CH,)^ (36)

Similarly, photolysis of diazocyclopentadiene in a variety of dialkyl sulfides yields sulfonium cyclopentadienylides

93, Eg. 37).^^^'^ Since ^ has so far proved to be an

(29) W. Ando,Acc. Chem. Res., 10, 181 (1977).

(30a) W. Ando, T. Yagihara, S. Tozune, I. Imai, J. Suzuki, T. Toyama, S. Nakaido, and T. Migita, J. Orq. Chem., 3J7/ 1721 (1972); (b) W. Ando, J. Suzuki, Y. Saiki, and T. Migita, Chem. Comm., 365 (1973); (c) W. Ando, Y. Saiki, and T. Migita, Tetrahedron, 29, 3511 (1973). 43

3 92

avid acceptor of nucleophiles, 1 was decomposed in

thiophene. Irradiation of 1 in thiophene gives 2-(2-

thenyl)imidazole (94, 11%) and an isomeric product (95,

11%, mol. form.CyHgNgS). The structure of 94^ is assigned

,HôN2S 0 ». • O ^ ' -,

1 H 51 - (38) on the basis of spectral and elemental analyses, and by

comparision of its spectra with that of other 2-substituted

thiophenes.

The NMR of £2 displays broad absorption at Ô 10.66

indicative of an N-H group. Signals at ô 5.60 and 6.10

reveal the presence of two olefinic protons and resonances

in the 6 6.90 - 7.70 region suggest three olefinic protons

shifted downfield by the adjacent heteroatoms. Product

95 is tentatively assigned as 5H-thiopyrano[3,2-blpyra-

zine and its formation along with 94 can be explained as shown in Scheme 13. Thenylimidazole 9£ may also have been formed by direct electrophilic substitution of thiophene by 2 a . 44

SCHEME 13

O -N,

94 <■

Rhodium (II) acetate catalyzed addition of dimethyl diazomalonate to thiophene has been reported to give thiophenium bismethoxycarbonylmethylide (96) in 31 almost quantitative yield (Eq. 39).

CH-O-C Rhll C=N2 + CH-O-C o COjCHj ' 'i 96 (39)

(31) R.J. Gillespie, J. Murray-Rust,\P. Murray-Rust, and A.E.A. Porter,, Chem. Comm., 83 (1978). 45

2-Diazoimidazole (1) was therefore decomposed at room

temperature in thiophene using rhodium (II) acetate as

catalyst. However, no ylide was obtained. The products

of reaction are 2-(2-thenyl)imidazole (94, 7%) and 9^

(13.3%).

Among other ylides formed by reactions of carbenes

with heteroatoms are those derived from pyridines. For

example, decomposition of diazocyclopentadiene £7 in

pyridine yields pyridiniumtetraphenylcyclopentadienylide, 32 a stable ylide (98^) . Investigations of the reactions of

C 6 (40) -N C

(32) I.B.M. Band, D. Lloyd, M.I.C. Singer, and P.I. Wasson, Chem. Comm., 544 (1966).

2 with various pyridines were thus initiated. Decomposition of 2-diazoimidazole (1) in pyridine at 25°C yields 2- imidazol-2-ylpyridine (99, 8.5%), 3-imidazol-2-ylpyridine 46

(100/ 34.6%) and 2-pyridiniumimidazolylide (101/ 50%) in excellent overall yields. The structures of ^ and 100

100 o (41)

101 are established by their spectral properties and by 51/52 comparison with literature melting points. Ylide 101 is assigned as follows. The NMR spectrum of 101 shows a singlet at 6 7.20 arising from its identical imidazole ring protonS/ a complex pattern at 6 7.50 - 8.20 for three protons of the pyridine ring (at 2, 2 ' and 1), and a doublet at

6 9.73 due to the a-pyridyl protons (at 3 and 3'). The 13 C-NMR of 101 gives further structural insight and is 13 14 particularly interesting because of the C- N couplings for C-3/ C - 3 ' and C-1. The broad-band decoupled ^^C-NMR spectrum of 95_ shows a triplet at 139.5 ppm for C-1 (J^ =

3.4 Hz)/ a triplet at 136.1 ppm (J^_^ = 9.7 Hz) due to C-3/ a singlet at 131.2 ppm from C-4 and C-4'/ and a singlet at 47

33 126.5 ppm due to C-2 and C-2'. Such spin-spin coupling

involving nitrogen is usually hampered by the quadrupole

(33) The assignments made are based on gated and off- resonance l^C-NMR studies.

relaxation of which has a spin of 1. Small

couplings have been observed, however, in symmetrical 34 quaternary ammonium salts. The electric fields at

nitrogen in such compounds and in 101 are obviously highly

symmetrical and lead to long quadrupole relaxation times 14 ’ 14 35 for N and hence to sharp lines with N spin couplings.

(34a) F.J. Weigert and J.D. Roberts, Inorq. Chem., 12, 313 (1973)7 (b) W. McFarlane, J. Chem. Soc., A, 1660 (1967); (c) E. Bullock, D.G. Tuck, and E.J. Woodhouse, J. Chem. Phvs., 2318 (1963) .

(35) J.A. Pople, W.G. Schneider, and H.J. Bernstein, High Resolution Nuclear Magnetic Resonance, McGraw-Hill, New York, 1959, p. 102.

Various mechanisms can be invoked to explain formation

of 9£, 100, and 101. For example, ylide 101 may result

from direct capture of singlet 2a by the nitrogen of the pyridine nucleus or/and by C^=N coordination on pyridine and 48

rearrangement to nitrogen. Ylide 101 is qnite stable in

the absence of oxygen and at low temperatures. Its stabi

lity may be attributed to the extensive delocalization in

each heterocyclic ring and the electrostatic attraction and 36 resonance interactions between both ring systems (Eq. 42) .

O b 101 (42)

(36) A.W. Johnson, Ylid Chemistry, Academic Press, New York and London, 1966, p. 260.

The 2-substituted pyridine 99 is explainable as being formed by rearrangement of ylide 101 (Eq. 43) and/or spirocyclopropane 102»

(43)

Imidazole 100, a 3-substitution product, could arise by several routes. One possibility is direct electrophilic aromatic substitution at the most electron rich carbon 49

0 -carbon) of pyridine by singlet 2a. Another route may involve directed ring opening of spiro-adducts 103 and 104 via dipolar processes to 105 (Scheme 14). A further alternative is directed hemolytic cleavage of 103 and 104 and hydrogen migration in singlet diradical 106.

SCHEME 14

103 100

104

106 50

The reactions of 2 with 4-methylpyridine and with

2/4/6-trimethylpyridine were then studied. Photolysis of

1 in 4-methylpyridine (Eq. 44) yields 3-imidazol-2~yl-4- methylpyridine (107, 5%) and 2r(4-methylpyridinium)imidazolylide (108, » 13%). Substitution product 107 is identi fied from its analyses and spectra. Purification of ylide CH,

C CH 107 108 (44) 108 is very difficult because of the presence of a deep purple impurity and the handling losses lead to the low yield reported. Ylide 108 is assigned from its spectra and 1 3 properties. Of note is that the C-NMR of 108 displays

couplings for the a-carbon atoms of the pyridine ring. The signal for the y-carbon of the pyridine ring in

108 is very weak, apparently because the carbon atom is quaternary.

Photolysis of 1 in 2,4,6-trimethylpyridine gives

3-imidazol-2-yl-2,4,6-trimethylpyridine (109, > 30%) identified by spectral and elemental analyses. Ylide 110 is not obtained, possibly due to steric hindrance to its 51

formation and/or to instability because of steric congestion.

CH VL r = - V N ^ c H

CH 109 110

A major study was then initiated of the reactions of

1 with benzene and its derivatives. A principal objective of this effort is to determine the response of 2a to the inductive, resonance and steric effects of substituents on benzene derivatives during reaction.

Thermolysis of 2-diazoimidazole (1) in benzene at 60°C yields 2-phenylimidazole (111) in 73% yield; 111 is identified by comparison of its spectral properties with that 44 of an authentic sample. Photolysis of 1 in benzene for 3 hr yields 111 in 68% yield along with 112 (24%), a high melting solid (189-191°C), whose molecular weight and formula

(C.qHt^N.) are twice that of 111. Dimer 111, as yet not iO J.O 4 ^ assigned, shows the presence of (1) a phenyl group as in

111, and (2) an imidazole ring with hydrogen on nitrogen or else two olefinic protons with identical environments.

Further summary of the properties of 112 is included in the

Experimental. 52

à or

hv (45) 111

112

Decomposition of diazocyclopentadiene (3)/ 3-diazopyrrole and, to a certain extent 3-diazopyrazole ^

(see Historical), results in ring expansion of benzene via spironorcaradiene intermediates. It therefore might be expected that 2-diazoimidazole (1) behaves as in Scheme 15.

SCHEME 15

-N

hv or A

113 114

H 116 117 115a 53

Spironorcaradiene 113 if formed might rearrange to cyclo-

heptatriene 114 which then undergoes ring expansion to 115

and 116 by [1,7] and [1,5] sigmatropic shifts, respectively.

Isomerization of 115 would lead to 115a. During photolysis, 37 114 could convert to its valence isomer 117, Since 115,

115a, 116 and 117 could not he found in the reaction

(37) Photolysis of bis(trifluoromethyl)diazomethane and benzene gives the valence isomer (analogous to 117) of 7,7-bis(trifluoromethyl)cycloheptatriene; D.M. Gale, W.J. Middleton, and C.G. Krespan, J. Am. Chem. Soc., 87, 657 (1965); ibid., 88, 3617 (1966).

product and since 2-phenylimidazole (111) does not dimerize photolytically, the possibility exists that 112 is a product of photolysis of 115, 116 and/or 117.

In attempts to limit dimer formation the photolysis time for 1 in benzene was reduced to 15 min. However, the reaction still yielded 17% of dimer 112 along with 61% of

111. In a further effort to retard thermal dimerization of intermediates derived from ring expansion of benzene by 2a, photolysis was effected at 10°C for short periods.No monomeric isomer of 112 was detected and the reaction products are essentially identical (69% of 111 and 23.4% of

112) with those formed at higher temperatures. 54

(38) Photolysis of diazocyclopentadiene (^) in benzene at lower temperatures results in increased ring expansion as compared to substitution.

2-Phenylimidazole (111) is an acid (pK^ 13.32)^^ whose strength might be considerable upon photolytic excitation. Photolysis of 1 in benzene was thus carried out in the presence of sodium hydride at 10-15°C in an attempt to limit formation of 112 by any dimerization pro cess as catalyzed by 111. The overall character of the system was not altered in that 111 and 112 are formed in

53% and 19% yields, respectively.

(39) H. Walba and R.W. Isensee, J. Orq. Chem., 26, 2789 (1961). "

Further, cuprous salts are known to favor ring- expansions of benzenes in reactions with diazo compounds.

In the present system, however, thermolysis of 1 in benzene in the presence of copper (I) bromide yields only 111 (46%) as an assignable product. Elucidation of 112 thus remains at present an important crystallographic problem.

(40) D.S. Wulfman, G. Linstrumelle, and C.F. Cooper, The Chemistry of Diazo and Diazonium Groups, Part 2, J. Wiley & Sons, 1978, p. 935. 55

Reactions of 1 were then extended to alkylhenzenes.

Photolysis of 1 in isopropylbenzene results in 2-(2-

isopropylphenyl) imidazole (118, 31%) and 2-(4-isopropyl-

phenyl) imidazole (119, 26%) along with 2,3-dimethy1-2,3- 41 diphenylbutane (120, 6%) The extensive ortho-substitution

of isopropylbenzene is impressive; of further note is that

products of meta-substitution and methyne C-H insertion are

not found. Ç ^ h Q-<=H(CH3)3

H 118 119 hv 1 (46)

C C

CH3 CH3

120

(41a) The assignments of the benzene substitution products as ortho, meta, or para-substituted phenylimidazoles were made by (1) comparison with literature physical constants and/or (2) by analyses of their 650-1000 cm-1 infrared absorptions. Strong bands for benzene derivatives in the 650-1000 cm“l region are due to out-of-plane deformation vibrations of hydrogen atoms. The specific absorptions for substituted phenylimidazoles (see Experimental) allow reliable recognition of the type of substitution, except when the benzene ring is heavily substituted with highly polar groups such as nitro or fluoro. (b) L.J. Bellamy, The Infrared Spectra of Complex Molecules, Chapman and 56

Hall, London, 1975; (c) all jg-substituted phenyl imidazole derivatives of the present study other than 2-(4-nitrophenyl)imidazole exhibit characteristic aromatic A.BgNMR patterns.

Photolysis and thermolysis (80 C) of 1 in 2,4,6-

trimethylbenzene also results in efficient aromatic C-H

substitution (Eq. 47); 2-(2,4,6-trimethylphenyl)imidazole

(121; 73 and 71%, respectively) is produced as identified by spectral and elemental analyses. Insertion of 2 into

a methyl group of 2,4,6-trimethylbenzene is not detected.

The ability of 2 to substitute into ortho positions of

CH. CH hv or CH (47)

CH H 3 isopropylbenzene and 2,4,6-trimethylbenzene is thus impressive and implies that the singlet transition states for aromatic substitution by 2_ are not subj ect to severe steric hindrance and are thus close to reactants in structure.

Anisole undergoes ortho and par a-substitution and

O-CHg cleavage upon reaction with 2. Thus irradiation of 57

1 in anisole results (Eq. 48) in 2-(2-methoxyphenyl)-

imidazole (122/ 25%) and 2-(4-methoxyphenyl)imidazole

(123/ 24%) along with 2-phenoxyimidazole (125/ 10%). Both

122 and 123 are assigned upon comparison with reported

properties;the meta-substitution product/ 2-(3-methoxy-

phenyl) imidazole is not detected. Ether cleavage product

125 involves formal loss of a methylene (-CHg-) unit

OCH OCH OCH hv 1 122 123 (48)

I H 124 125

during photolysis. A reasonable process for the anisole

cleavage involves ylide 124 which effects méthylation of

its environment.Efforts to detect N-methylimidazole

and/or methyl anisoles are as yet unsuccessful. The mechanisms of formation of 122 and 123 are to be discussed

later. 58

(42) A similar dimethylation reaction occurs during decomposition of 3-diazopyrrole ^ in N,N-dimethylaniline and is believed to involve a nitrogen ylide.

N,N-Dimethylaniline also undergoes ortho and para-

substitution (Eq. 49) upon photolysis of 1. In spite of possible steric hindrance to ortho-substitution/ 2-[2-(N/N- dimethylamino)phenyl]imidazole (126/ 42.5%) and 2-[4-(N/N- dimethylaminophenyl)imidazole (127/ 23%) are produced in essentially statistical (2:1) ratio. Identification of

126 is confirmed upon comparison of its properties with 55 literature values whereas 127 is assigned from its analyses and its spectral properties. Products derived by

CH ^ N(CHo)o

(49)

H 126 127 déméthylation of N/N-dimethylanilineupon irradiation of

1 are not found. 59

The principal features observed for reactions of 2

with isopropylbenzene/ 2/4,6-trimethylbenzene/ anisole/

and N/N-dimethylaniline are thus that 2 (1) is a highly

discriminating electrophilic reactant (£a) / (2) effects

ortho- and para-substitution with exclusion of meta-

substitution/ and (3) steric factors are minimal. One

interpretation of these results is that benzenes undergo

reaction by simple aromatic substitution processes as in

Eq. 50. For there to be the high positional selectivity

128 2a + (50) N

129 which reflects electron-donation by the substituents/ the transition states are expected to resemble dipolar inter mediates 128 and 129. Such mechanistic routes lead/ however/ to anticipation of some meta-substitution and to 60

significant steric retardation to ortho-attack. Since the

latter results are not observed, such simple mechanistic processes are suspect. Further, on the basis that free radical substitution of benzene derivatives proceeds with little site selectivity with respect to the relative positions of attack and the substituents, and the observation that ^ is not converted readily to triplet

2b, direct hemolytic substitutions of the benzenes by 2b also appear to be unlikely processes.

An alternative mechanistic sequence, analogous to that proposed for substituted benzenes with 3,5-dichloro- 43 14 benzene-1,4-diazooxide and with 3H-pyrazolylidenes, is

(43) M.J.S. Dewar and K. Narayanaswami, Am. Chem. Soc. 86, 2422 (1964).

that singlet 2H-imidazolylidene (2a) attacks the benzenes by exothermic processes (Scheme 16) to give spironorcara-• dienes 130 which undergo ring opening to dipolar ions

(131) that then isomerize to products (132). An important aspect of such possible processes is that the rate determining step for the overall sequence is formation of 61

SCHEME 16

2a • X

'N,

H 131 132 spironorcaradienes 130 in which transition states are close in structure to reactants. Since either bond a or bond b in 130 can break, the substituent X might be expected to dictate the openings so as to afford maximum stabilities to the dipolar species 131.

In generation of spironorcaradienes 130, there are three isomeric possibilities: 133, 134, and 135. If in formation of the adducts steric and electrical effects are small, spironorcaradienes 133 - 135 will be produced in near statistical quantities. On the basis that collapse of 133 - 135 is controlled by electron-donating substituents, the ring openings will occur preferentially such that the 62

(51a)

(51b)

134

(51c) X b

X 135

vacant orbitals of the benzenonium moieties will most effectively conjugate with the substituents X. Spiro norcaradienes 133 and 134 will then give (ortho-substituted phenyl)imidazoles and 135 will convert to (para-substituted phenyl)imidazoles. The results for the reactions of 2a 63

with benzenes substituted by electron-donors are thus

rationalizable. (Formation of 2,3-dimethyl-2,3-diphenyl-

butane (120) from photolysis of 1 in isopropylbenzene is

not readily explainable, however, from the sequences of

Scheme 16.) Extension of such mechanisms lead thus to

the prediction that reactions of 2a with benzenes substituted

by overall electron-withdrawing groups should cause 133,

134, and 135 to yield mainly ortho- and meta-substituted

products. Study was thus extended to the various reactions

of 1 with halobenzenes, and electron-poor benzenes.

Photolysis of 1 in fluorobenzene occurs efficiently

to form 2-(2-fluorophenyl)imidazole (136, 43.6%) and

2-(4-fluorophenyl)imidazole (137, 29%). The ratio of

F 1 + 6 + F (52) 136 137

ortho; para substitution is 1.5:1; meta-substitution is not observed. Para derivative 134 is identified by comparing 57b its properties with literature values. Ortho derivative 64

57a 136 has been previously reported. However, the melting

point given for 136 is 30°C higher than that presently

observed for 136. Unambiguous synthesis of 136 from 44 2-fluorobenzaldehyde by a modified Radziszewski method

confirms the lower melting point and thus the present

assignment.

(44) L.E. Hinkel, G.O. Richards, and 0. Thomas, J. Chem. Soc., 1437 (1937) .

Deccmposition of ^ by photolysis in bromobenzene

(Eq. 53) results in the ortho and the para-substituted products: 2-(2-bromophenyl)imidazole (138, 17.5%) and

2-(4-bromophenyl)imidazole (139, 19%). The system is of further interest in that met a-substi tution does not occur and particularly in that 2-bromo-1-phenylimidazole (141,

12%) is formed (Eq. 53) along with intractables. Products

-N, -N.

H Br hv (53) 1 + 138

140 Br 141 65

138/ 139/ and 141 are identified from their elemental

analyses and their spectral properties. Although the

overall yields are not good/ formation of 138 and 139

follows the patterns exhibited previously by substituted

benzenes with 2a. Of mechanistic import is that 141

possibly arises by rearrangement of the intermediate

bromonium ylide 140 (Eq. 53); a related process has indeed 17 been observed for phenylbromonium-4/5-dicyanoimidazolylidet

Thermolysis and photolysis of 1 in iodobenzene are

revealing in that ortho- and para-substitution products/

2-(2-iodophenyl)imidazole (142; 11 and 1%, respectively)

and 2-(4-iodophenyl)imidazole (143; 24 and 9% respectively) are formed/ along with phenyliodoniumimidazolylide (144;

4 and 7.5%/ respectively)/ a high melting/.unstable product.

■N

'l I H 142 H 143 6 or (54) hv

*-^7© 0 \=/

144 66

Elemental analyses and spectral methods lead to definitive

assignments for 142 and 143. Although iodonium ylide 144

is difficult to isolate in analytical purity, its structure

can be assigned from its NMR, IR, and mass spectra (see

Experimental) and its obvious origins: capture of electro philic singlet 2^ by iodine in iodobenzene. Formation of

144 as an isolable product parallels the previous behavior observed for 4,5-dicyanoimidazolylidene and halobenzenes 17 (X = Cl, Br, I) and that postulated for 2^ and bromo benzene (Eq. 53) to yield 141.

The reactions of 2a with bromobenzene and iodobenzene merit further study, possibly at lower temperatures and even higher ratios of the halobenzenes to 2a. The facts that the halobenzenes undergo ortho- and para-substitution and ylidic coordination at halogen are important, however, to the objectives of the present research effort.

Attention was then directed to the reactions of 1 with benzenes substituted by strong electron-withdrawing

(meta-directing) substituents. Irradiation of 1 in a,a,a- trifluorotoluene leads to 2-(3-trifluoromethylphenyl)- imidazole (145, Eq. 55, > 86%) as identified by comparison

CP 3 hv (55) -^2 C 145 67

with reported properties.Decomposition of 1 in methyl

benzoate either by photolysis or thermolysis gives

2-(3-carbomethoxyphenyl)imidazole (146, 56 and 54%

respectively) as in Eq. 56. Neither ortho- nor meta-

substituted derivatives were found in these experiments.

COOCH^ 3 COOCHg hv or à (56) -N

G 146

Further, thermal or photochemical decomposition of 1 in acetophenone results in 2-(3-acetylphenyl)imidazole (147,

11%) as identified by its spectral properties and analyses,

COCH^ hv or A (57)

147

A prominent feature of the aforementioned results is the high order of selectivity: the absence of ortho and para- isomers in the products from a,a,or-trifluoro- tolüene, methyl benzoate, and acetophenone, and the absence of meta^isomers in the products from halobenzenes 68 and electron-rich benzenes. These very high selectivities in choosing between the positions for substitution of highly electronegatively-substituted benzenes seem consistent once again with the mechanisms of Scheme 16 in which intermediate spironorcaradienes undergo dipolar collapse with hydrogen migration.

As suggested earlier, 2^ presumably reacts with an aromatic substrate by highly exothermic, low activation energy processes to form intermediate spironorcaradienes

130. The energies of isomerization of 130 to benzeno- niumimidazolyl dipolar ions (Eq. 51 a-c) will then depend in part on the nature of the substituent X in stabilizing or destabilizing the transition states leading to the dipolar intermediates and thus will differ with X. If the activation energies for isomerization of the norcaradienes are appreciable and there are large substituent effects, there could very well be significant rate differences for the conversions of 133-135 into the various possible dipolar ions. Exothermic formation of spironorcaradiene(s)

130 may still be the rate-determining step(s) of the over all process(es) even though isomerization of 130 to 131

(Scheme 16) has a large activation energy. Such a situation can give rise to large differences in the rates 69

of formation of the various products from a given

substrate (Eq. 51a-c) on the basis that the subsequent

hydrogen migrations are not very energy demanding.

A number of questions still remain to be resolved.

It was mentioned earlier that in keeping with the

mechanism of Scheme 16, benzenes substituted by meta-

directing groups should cause 133-135 to yield both meta-

and ortho-substituted products. However, the results

from O ', O ', a-trifluorotoluene, methyl benzoate and aceto phenone indicate that only the met a-i somer s are obtained.

It may be argued that in these systems spironorcaradiene

133 is not formed at all. In other words, carbene 2a is a more selective electrophile than originally predicted and therefore adds to the Cg-C^ and C^-C^ double bonds rather

135 than to the relatively electron poor C^-Cg double bond of these benzene substrates. Furthermore, based on structural factors, it may be predicted that 133 is less stable than the more highly conjugated isomers 134 and 135. The spironorcaradienes 134 and 135 could subsequently undergo 70

ring opening to give their meta-substituted benzene

derivatives as in Eq. 51b-c.

Another explanation for the absence of the ortho isomer may be that, for these deactivated benzene sub strates, if spironorcaradiene 133 is formed, then its isomerization to the corresponding dipolar ion (Eq. 51a) may not be a very feasible process due to the destabilizing effect of X on the adjacent carbonium ion center.

Intermediate 133 may instead undergo a degenerate

133 134 ^ 135 (58) norcaradiene rearrangement involving a C(l)-C(7)/C(6)-C(5)

process (Eq. 58) to 134 and/or 135

which in turn could ring open to the

N' X'l meta-substituted benzene. Such

norcaradiene rearrangements are indeed 45 well documented. For instance 2,7-dimethylnorcaradiene-

7-carboxylate (148) when thermolyzed in benzene leads to an equilibrium mixture of norcaradiene isomers 148-150 in the ratio 48.7:39.8:3.1 (Eq. 59).^^^ It is noted that

CH CH, (59) CH

148 149 150 71

isomer 15J)^ is present in negligible amounts as compared

to 148 and 149 in the equilibrium mixture. In a similar

manner the various methyl-7,7-dicyanonorcaradienes 45 c interconvert readily upon warming.

(45a) J.A. Berson, Acc. Chem. Res., 1, 152 (1968); (b) F.G. Klaner, Angew. Chem. Int. Edn., 13, 268 (1974); (c) J.A. Berson, P.W. Grubb, R.A. Clark, D.R. Harter, and M.R. Willcott, III, J. Am. Chem. Soc., 89, 4076 (1967).

Reexamining the reactions of 2a with electron rich benzenes and halobenzenes mentioned earlier in this

research, such spironorcaradiene interconversions between

133, 134, and 135 may possibly be taking place in those

systems too. However, regardless of whether such inter conversions occur or not the products obtained by dipolar collapse of the norcaradienes would still be the ortho- and para-isomers. It is only the ratios of these isomers that would change with the positions of the equilibria between 133, 134, and 135.

Study of the reactions of 1 with substituted benzenes was next extended to benzonitrile and nitrobenzene.

Irradiation of 1 in benzonitrile leads to (Eq. 60) 2-(2- cyanophenyl)imidazole (151, > 15%) and 2-(4-cyanophenyl)- imidazole (152, > 31%), products of ortho- and para- substitution of benzonitrile, identified by their spectral 72

CN hv

-^2 ^ H a 151 152

properties and elemental analyses. The isomer derived

from met a-substitution was diligently sought but could not be detected. It is clear then that the explanations forwarded earlier for substitution of electron-deficient benzenes by 2a, cannot be extended to the reactions with benzonitrile. Curiously enough, the carbenes derived from

3,5-dichlorobenzene-l, 4-diazoxide^^ and from 3-diazo-3H- pyrazoles^^ also effect considerable ortho- and para- substitutions of benzonitrile.

Photolysis and thermolysis of 1 in nitrobenzene yield the para-derivative (Eq. 61), 2-(4-nitrophenyl)- imidazole (153, 7%) as the only substitution product. The structure of 153 is assigned upon comparison with reported properties.^® The ortho- and meta-substituted derivatives are not found in the reaction product. Of additional significance is that the principal product of the photolysis and the thermolysis is nitrosobenzene (82 and 90-100%, respectively, by gas chromatographic methods). A cry stalline derivative C^gH^gN^O (154, mp 297-300°C, 4.5%) is also obtained from decomposition of 1 in nitrobenzene at 60°C.4G 73

hv NO or A'

153 1 + (61)

154

(46) The structure of 154 is as yet unclear. The IR spectrum of 154 has no well defined bands and the NMR spectrum shows only the presence of aromatic protons and/or imidazole protons.

Oxygen abstraction from nitrobenzene by, ^ to yield nitrosobenzene is formally analogous to the recent obser- 47 vation that 5-phenyl-3H-l/2,4-triazolylidene as derived thermally and photolytically from 3(5)-diazo-5(3)-phenyl-

1, 2, 4-triazole reacts with nitrobenzene to give 3(5)-(3- nitrophenyl)-5(3)-phenyl-1, 2,4-triazole (155, 17%) along with nitrosobenzene (77 and 45%, respectively) and benzo nitrile (84 and 48%, respectively) apparently as in Eq. 62.

In the present experiments oxygen transfer from NO

(62) +

^ CgHgCSN + CO + N A C 74

(47) J. Glinka, The Ohio State University, unpublished results.

nitrobenzene to 2a would give 2H-imidazolone (156, Eq. 63)

an unlcnown heterocyclic system which may be anti-aromatic.

Detection or trapping of 156 has as yet been unsuccessful;

2a (63)

156 collapse of 156 to hydrogen cyanide and carbon monoxide and/or to acetylene, nitrogen and carbon monoxide (Eq. 64) have not been proved. Generation and elaboration of the

2H-C = N + CO 156 (64) H-C=C-H + CO + N, chemistry of 2H-imidazolones are future major research commitments of possible high-order significance. Further more, such oxygen-abstraction reactions of carbenes appear promising for synthesis of nitroso compounds.

The facts that benzonitrile undergoes ortho- and para-substitution by 2_a must mean that different mechanisms operate in these reactions as compared to those for 2a. with 75 other substituted benzenes. An interesting interpretation of these results is that the highly electronegative cyano and nitro substituents may cause spironorcaradiene 130 to undergo hemolytic rather than dipolar collapse as in

Eq. 65a-c. Electronically these substituents should retard dipolar but accelerate hemolytic ring openings of 133-135.

(55a)

157

(65b)

134 X 158

X (65c) X 135 159

On the basis of direct resonance and electronic effects hemolytic ring openings of 133-135 should lead to ortho-

(Eq. 65a) and para- (Eq. 65c) rather than meta-substituted products if the transition states for the ring-opening are close to the diradical intermediates in structure. Thus 76

radical stabilization by the a-cyano and by of-nitro groups

will favor 157 (Eq. 65a) and 159 (Eq. 65c) over 158. Of

further note is that if there is isomerization of 133, 134,

and 135, as in Eq. 58, subsequent diradical ring opening

(Eq. 65a-c) will still yield ortho- and para-derivatives

157 and 159 although in different ratios.

One of the alternate explanations for the ortho- and

and/or para-substitutions of benzonitrile and nitrobenzene

is that carbene 2a complexes with the functional group of benzonitrile or nitrobenzene to give ylids 160 and 161

(Scheme 17) rather than spironorcaradiene(s) 130 (Scheme

16). Such coordination is similar to the observation that

4,5-dicyanoimidazolylidene (£7) yields a stable ylid with

Scheme 17

151 + 152

160

- > 153 © C6H5NO2 161

(48) O.W. Webster, private communication.

48 benzonitrile. Formation of intermediates such as 160 and 161 could transform electrophilic carbene 2a into a 77

nucleophilic reagent. Nucleophilic attack of 160 on

benzonitrile as in Eq. 66 would then give ortho- and para-

substituted products 151 and 152. Similarly, reaction of

151 \ (66) (? 152

161 at the para-position of nitrobenzene will lead to 153.

It may well be that the isomer from ortho-substitution of nitrobenzene, 2-(3-nitrophenyl)imidazole, escaped detection because of its low yield and the occurrence of oxygen abstraction as a major process.

There is yet another serious alternative for the unusual substitution of benzonitrile and nitrobenzene.

These substrates may be sufficiently electron-deficient to allow nucleophilic attack by 2-diazoimidazole (1) itself as in Eq. 67. Such nucleophilic reactions either by ylidic intermediates 160, 161 or 2-diazoimidazole (la) can also account for the absence of the meta-isomers in the products from benzonitrile and nitrobenzene. 78

(67) la +

H Reaction of 1 was extended to hexafluorobenzene with

the expectation that carbon-fluorine insertion would not

occur and that aromatic ring-expansion will result.

Thermolysis of 1 at 80°C in hexafluorobenzene does give a

ring-expanded product (Scheme 18) in good yield (> 72%)

assigned as llH-hexafluorocyclohepta[b]pyrazine (163;

white, mp 35-36°C) from its analysis and spectral

properties, and by mechanistic principles. Of major

significance to the structural assignment is that the 19 P-NMR (in ppm downfield from hexafluorobenzene) of the

product displays signals for six different fluorines. All

resonances except one at 67.57 are coupled to neighboring

fluorines and thus structure 164 is excluded. In 163,

is near orthogonal to F^ and the angle between C-F^ and

C-Fg is almost 90°. Coupling of F^ and F^ in 163 is 19 unlikely and thus F^ displays a F-NMR singlet. 79

Formation of 163 is described in Scheme 18 and

apparently involves ring expansion of the imidazole moiety

in 162a or 162b to give 163 rather than 1,5 sigmatropic

ring expansion of the perfluorocycloheptatriene system to

yield 164. The behavior proposed for hexafluorobenzene

and 2a in giving a [6,7] (163) rather than a [8,5] (164)

derivative is thus different from that reported for hexafluorobenzene with cyclopentadienylidene^^^ and with

3H-pyrazolylidene^^^ in which formation of [8,5]benzene ring-expansion products is presumed.

(49a) M. Jones, J. Org. Chem., 32, 2538 (1968); (b) W.L. Magee, The Ohio State University, private communication. 80

SCHEME 18

F 1 + F -N, F F F 162a

163 F F

16 2b ■>

F F 164 EXPERIMENTAL

Melting Points. Melting points were determined

using a Thomas Hoover capillary point apparatus or a

Fisher melting point block and are uncorrected.

Elemental Analyses. Elemental analyses were performed

by the Scandinavian Microanalytical Laboratory, Herlev,

Denmark.

Infrared Spectra. Infrared spectra were obtained on

a Perkin-Elmer Model 457 Grating Infrared Spectrophotometer.

All spectra were calibrated against polystyrene absorption

at 1601 cm“^. The spectra of all compounds were obtained from KBr wafers unless otherwise stated.

Nuclear Magnetic Resonance Spectra. Proton magnetic resonance spectra were determined on Varian A-6QA or 13 EM-360L, or Bruker HX-90, spectrometers. Carbon magnetic resonance spectra were run on a Bruker WP-80 instrument. ^%luorine magnetic resonance spectra were obtained using Varian EM-360L and Bruker HX-90 spectro meters .

Ultraviolet Spectra. Ultraviolet spectra were determined using a Cary Model 14 recording spectrophoto meter.

81 82

Mass Spectra. Mass spectra were determined by

Mr. C.R. Weisenberger on an AEI-MS-9 mass spectrometer.

Column Chromatography. Column chromatography was

effected on MN Laboratories' "Silica Gel for Column

Chromatography" (70-270 mesh), or MC & B's Silica Gel

(100-200 mesh), or EM Laboratories' Silica Gel 60 for

column chromatography (230-400 mesh).

Solvents. All solvents were dried, distilled and deoxygenated prior to use in decomposition experiments.

Decompositions. The decompositions (both thermal and photochemical) of diazoimidazole 1 were carried out under nitrogen. All photolyses were performed with a

Hanovia 450 watt medium pressure mercury lamp which was placed in a Pyrex immersion well. The well itself was fitted with a photochemical reactor containing the solution to be irradiated.

S-Methvlisothiourea Sulfate (60). To thiourea (152 g,

2 m) in water (70 cc) was added dimethylsulfate (138 g,

1.1 m), followed by cooling of the mixture to control the initial vigorous reaction. The mixture was then refluxed for 1 hr, cooled and treated with 95% ethanol (200 ml).

The white crystals formed, S-methylisothiourea sulfate 83

(60) were filtered, washed twice with 95% ethanol (100ml

portions) and allowed to air dry (225 g, 80.7%; mp 235°C,

lit.50 235°C).

(50) Ora. Svn.. Coll. Vol. II, 411.

2-Aminoimidazolium Sulfate. A mixture of amino-

acetaldehyde diethyl acetal (25 g, 0.187 m), water (40 ml), and S-methylisothiourea sulfate (^, 25 g, 0.18 m) were heated at 90°C for 1 hr. Removal of water gave an oil which was dissolved in methanol; precipitation with acetone yielded N-(2,2-diethoxyethyl)guanidine sulfate

(30 g, 75%, mp 148-152°C, lit.^^ mp 148-152°C).

N-(2,2-Diethoxyethyl)guanidine sulfate (10 g, 0.045 m) in concentrated hydrochloric acid (6 ml) was warmed on a steam bath for 15 min, water (30ml) was added, and the solution was evaporated to a syrup. More water (30 ml) was added, and the solution was evaporated to dryness.

The syrup on trituration with absolute methanol gave 2- aminoimidazolium sulfate (3.2 g, 54%, mp 275-278°C, lit.^^

275-278°C. 84

2-Diazolmidazole (1). To a solution of 2-amino-

imidazolium sulfate (1.32 g, 0.007 m) in 50% tetra-

fluoroboric acid (13 ml) at -10°C was added sodium nitrite

(0.75 g, 0.01 m) in water (1 ml). The mixture was stirred until precipitation of the diazonium salt occurred, and then neutralized carefully with sodium bicarbonate solution, followed by extraction with methylene chloride.

Concentration of the extract at 0°C and reduced pressure gave 2-diazoimidazole^®^ (1, 0.5336 g, 77.8%); IR (CCl^):

— 1 2125 cm” (s, diazo group); UV; 312 nm. Diazo imidazole 1 is unstable above 0°C and when exposed to direct light. When dry, 1 is highly shock sensitive. To avoid explosions, therefore, 1 is transferred in methylene chloride to the reaction vessel and then near total removal of the solvent in vacuo is effected.

Reaction in Pvrrolidine. To a methylene chloride solution (25 ml) of 2-diazoimidazole (1, 0.5 g, 0.005 m) was added pyrrolidine (0.5 g, 0.007 m) at 0°C, upon which

2-pyrrolidinylazoimidazole (6^, 0.71 g, 83.5%; mp

(iaopropanol) 188-190°C) precipitated out as a white solid;

IR: 3150(N-H), 2970 and 2880 cm”^ aliphatic (C-H); NMR

(CDgOD): 6 2.00(complex, 4, -, 3.73(complex, 4,

2 CHg)/ 6.83(s, 2, imidazole H ) ; exact mass: calcd.

165.10143; obsvd. 165.10180. 85

Anal. Calcd. for C, 50.89; H, 6.71; N, 42.39.

Found: C, 50.67; H, 6.71; N, 42.67.

Reaction with N-Morpholino-l-cyclohexene ( ^ ) . A

solution of 2-diazoimidazole (^, 0.5 g, 0.005 m) in

methylene chloride (50 cc) at 0°C was added in drops to

N-morpholino-l-cyclohexene (62, 1.67 g, 0.01 m) in methylene chloride (15 ml) keeping the temperature at

-55°C throughout addition (1 hr). The resulting red

solution warmed to room temperature overnight. The white solid which formed was filtered and washed several times with methylene chloride (0.3297 g, 38%). Recrystal lization from ethyl acetate yielded corrpound ^ (mp 169-

170°C with dec.); IR: 1590 cm"^ (C=C, C=N); NMR(CDCl^/

CDgOD): 6 1.60(complex, 4, cyclohexene H), 2.30(complex,

4, allylic cyclohexene H), 6.50(d, 1, olefinic H), 6.63

(d, 1, olefinic H); exact mass: calcd. 174.09054; obsvd. 174.09093.

Anal. Calcd. for CgH^^N^: C, 62.05%; H, 5.78%; N, 32.16%.

Found: C, 62.65%; H, 6.22%; N, 32.61%.

Concentration of the filtrate yielded a pale orange solid (0.3301 g, 38%) which was contaminated with 64. 86

Purification of the solid by repeated recrystallization

from benzene yielded N-morpholino-l-cyclohexenylazo-

imidazole (^; rap 157-158°C) ; IR: 1600 cra"^(C=C); NMR

(CDClg): 6 1.70(complex, 4, cyclohexene H), 2.33(complex,

4, allylic cyclohexene H), 2.80(complex, 4, morpholine H),

3.70(complex, 4, morpholine H), 6.63(s, 2, imidazole H); exact mass: calcd. 261.15895; obsvd. 261.15940.

Anal. Calcd. for" C^^H^gNgO: C, 59.75; H, 7.33; N, 26.80.

Pound: C, 59.47; H, 7.41; N, 26.34.

Photolysis in Cyclohexane. A solution of 1 (0.53 g,

0.0056 m) in cyclohexane (220 ml) was irradiated for 3 hr.

Vacuum concentration of the mixture gave a yellow residue which was chromatographed on silica gel. Elution with

1:1 benzene : ethyl acetate gave 2-cyclohexylimidazole (65,

0.67 g, 80%; mp (benzene) 175-176°C); IR: 3160(N-H),

2940 and 2860 cm"^ (aliphatic C-H); NMR (CDClg/DMSO-dg):

Ô 1.00-2.33 (complex, 10, H ) , 2.66 (complex, 1,

'), 6.83(s, 2, imidazole H ) ; exact mass: calcd.

150.11569; obsvd. 150.11618.

Anal. Calcd. for CgH^^N^: C, 71.95; H, 9.39; N, 18.64.

Found: C, 71.99; H, 9.24; N, 19.01. 87

Thermolysis in Cyclohexane. 2-Diazoimidazole (1,

0.53 g# 0.0056 m) was thermolyzed in cyclohexane (100 ml)

at 80°C for 3 hr. Concentration of the resultant solution

and chromatography on silica gel using 1:1 benzene: ethyl

acetate as eluent gave 2-cyclohexylimidazole (6^, 0.65 g,

78%), identified from its spectral characteristics (see

previous experiment).

Photolysis in Cyclohexene. A cyclohexene solution

(220 ml) of 1 (0.50 g, 0.005 m) was photolyzed for 3 hr.

Concentration of the resulting solution under vacuum gave

an oil- Chromatography on silica gel using ethyl acetate

gave 2-(3-cyclohexenyl)imidazole as a white solid (67,

0.23 g, 31%; mp(benzene) 150-153°C sublimes); IR: 3150

(N-H), 3030 (olefinic C-H) and 2930 cm“^(aliphatic C-H);

NMR (CDCl^): 6 1.50-2.50(complex, 7, ^ ^ H), 5.70 and

5.83(br, s, 1 each, olefinic H), 6.96(s, 2, imidazole H),

10.83(s, 1, NH); exact mass: calcd. 148.10004; obsvd.

148.10035.

Anal. Calcd. for C, 72.94; H, 8.16; N, 18.90.

Found: C, 72.54; H, 8.16; N, 18.53.

Photolysis in Diethyl Ether. 2-Diazoimidazole (1,

0.5 g, 0.005 m) was dissolved in ether and photolyzed 88

for 2.5 hr. The resulting red solution was concentrated

and chromatographed on silica gel using 1:4 ether:ethyl

acetate as the eluent. 2-Ethoxyimidazole was obtained as

a white crystalline solid (77, 0.1131 g, 16%; mp (1:1

hexane:benzene) 92-93°C); IR: 1300 and 1060 cm"^(C-0); NMR

(CDCl^): Ô 1.33(t, 3, 4.36(q, 2, 6.60(s, 2,

imidazole H), 9.16(s, 1, NH) ; exact mass: calcd. 112.06365,

obsvd. 112.06393.

Anal. Calcd. for CgHgNgO: C, 53.55; H, 7.19; N, 24.98.

Found: C, 53.37; H, 7.13; N, 24.91.

Reaction with Ethyl Vinyl Ether. 2-Diazoimidazole

(1, 0.53 g, 0.0056 m) in ethyl vinyl ether (50 ml) was

stirred at 0°C for 0.5 hr, and then at 25°C for 3 hr. A

red-black solution and some insoluble matter were obtained.

The residue appeared to be polymeric. The filtrate was

concentrated and then chromatographed using 1:4 ethyl

acetate:benzene, on silica gel. 2-Imidazolyl vinyl ether was obtained as a white solid (80_, 0.02 g, 4%; mp (1:1 hexane:benzene) 75-78°C); IR: 1305 and 1160 cm” ^(C-0); NMR H (CDCl ): 6 4.55 (d of d, 1, > = < )/ 4.75(d of d, 1, H H r / ^0- H H /— / ), 6.06(s, 2, imidazole H), 7.13 (m, 1, V = < f \ H 0- e ' 0-^ 89

9.5(s, 1/ NH) 7 exact mass: calcd. 110.048007 obsvd.

110.04826.

Anal. Calcd. for CgH^NgO:C, 54.547 H, 5.497 N, 25.44.

Found: C, 54.377 H, 5 .I87 N, 25.34.

Photolysis in Ethyl Vinyl Ether. 2-Diazoimidazole

(1, 0.5 g, 0.005 m) was dissolved in ethyl vinyl ether

(220 ml) and photolyzed for 2 hr. Concentration in vacuo

gave a red oil, which was chromatographed on silica gel

and eluted with 1:4 ethyl acetate:benzene. The only

product isolated was 2-imidazolyl vinyl ether (80, 0.05 g,

10%) which was identified by its spectral characteristics

as described in the previous experiment.

Photolysis in Isopropanol. A solution of 1 (0.5 g,

0.005 m) in isopropanol (120 ml) was photolyzed for 1 hr.

The resulting red solution on analysis by gas-chromatography

(10% Carbowax 20M on Chrom W, 17^' x h " , 70°C) showed

acetone to be present. The acetone was quantitatively

estimated using n-butanol as an internal standard (0.0753 g,

24.4%) .

Removal of excess isopropanol and chromatography of

the residue on silica gel using 1:1 ethyl acetate: petroleum ether as eluent gave 2-isopropoxyimidazole (81, 90

0,2807 g, 41.8%, mp(benzene/hexane) 109-110°C); IR; 2980 CH3 X ), 1 CH3 1115 and 1030 cmT^(C-O); NMR(CDCl^): 6 1.30(s, 3, CH^),

1.40(s, 3, ÇH^), 5.10(septet, 1, CH), 6.65(s, 2, imida

zole H), 10.66(s, 1, NH); exact mass: calcd. 126.07930;

obsvd. 126.07965.

Anal. Calcd. for CgH^gNgO: C, 57.12; H, 7.99; N, 22.20.

Found: C, 57.15; H, 8.01; N, 22.15.

Further elution with acetone yielded 2-(2-hydroxy-

propyl)imidazole (8^, 0.015 g, 2%; mp(benzene/chloroform)

199-200°c); IR:, 3180 (br, O-H), 1380, 1370, 1195 and 965 V /CH3 _ ( )/ 1140 and 1100 cm (C-0 and O-H deformation); / ^ C H 3 NMRfCDClg/CDgOD): 6 1.48(s, 6, 2CH^), 6.80(s, 2, imidazole

H); exact mass: calcd. 126.07930, obsvd. 126.07965.

Anal. Calcd. For CgH^gNgO: C, 57.12; H, 7.99; N, 22.20.

Found: C, 57.56; H, 8.15; N, 22.53.

Photolvsis in Furan. 2-Diazoimidazole (1, 0.52 g,

0.0055 m) was dissolved in furan (220 ml) and photolyzed for 3 hr. The resulting red solution was concentrated and chromatographed on silica gel. Elution with 1:4 91

ethyl acetate:benzene gave l-buten-3-ynyl imidazolyl ether

(89, 0.150 g, 20%; mp(chloroform) 124-125°C); IR: 3210(s,

acetylenic C-H), 3120(N-H), 2110(C C), 1645(C=C), 1250 \ yOaC-g and 1090 cmT^(C-O); NMR(CDCl3): 6 3.10(d, 1, ^ C S O - H % = 2 Hz), 4.96(d of d, 1, = 2 Hz,

= 7Hz), 6.66(s, 2, imidazole H), ?T§0 (d, 1, V yCSC-H 3 = 7Hz), 9.03(br, 1, NH) ; ■^'^C-NMR (in

ppm downfield from TMS; TMS = 0): 150.38(C-5), 149.06

(Ç-4), 118.28(C-6, Ç-6 '), 90.20(Ç-3), 82.75(C_1), 76.75

H\^^ ^ y H (Ç-2) 7 exact mass: calcd.

134.04800; obsvd. 134.04831.

Anal. Calcd. for C^H^NgO: C, 62.68; H, 4.51; N, 20.88.

Found: C, 62.09; H, 4.53; N, 20.88.

Photolvsis in Thiophene. 2-Diazoimidazole (1, 0.5 g,

0.005 m) was photolyzed in thiophene (220 ml) for 2 hr.

The resulting red solution was concentrated and then chromatographed on silica gel. Elution with 1:4 ethyl acetate:chloroform yielded 2-(2-thenyl)imidazole (94,

0.082 g, 11%; mp(ethyl acetate) 194-196°C); IR: 1590 92

(C=N, C=C), 1520, 1385, and 1240 cm“ ^ (thiophene ring);

NMR (CDClg/CDgOD): 6 7.00(s, 2, imidazole H), 6.90-7.46

(complex, 3, thiophene H); exact mass: calcd. 150.02516, obsvd. 150.02554.

Anal. Calcd. for C^HgN^S: C, 55.97; H, 4.02; N, 18.65;

S, 21.34.

Found: C, 55.68; H, 4.01; N, 18.67;

S, 21.23.

Elution with ethyl acetate gave 5H-thiopyrano[3,2-b]- pyrazine (9^, 0.08 g, 11%; mp (ethyl acetate) 221-222°C);

IR: 1590 (C=C, C=N); NMR(CDCl^): 6 5.60(complex, 1, olefinic H), 6.10(complex, 1, olefinic H), 6.90-7.70

(complex, 3, -N-C= and -S-C=), 10.66 (br, 1, NH); exact à k mass: calcd. 150.02516; obsvd. 150.02567.

Reaction with Thiophene using Rhodium(II) Acetate as

Catalvst. Diazo compound 1 (0.5 g, 0.005 m) was stirred overnight at room temperature with anhydrous rhodium(II) acetate (3-5 mg) in thiophene (100 ml). The resultant solution was filtered after diluting with chloroform.

The filtrate was concentrated and then chromatographed on 93

silica gel. Elution with 1:4 ethyl acetate yielded 2-(2-

thenyl)imidazole (9^, 0.05 g, 1%) and further elution with

ethyl acetate gave 5H-thiopyrano[3,2-b]pyrazine (95,

0.1 g, 13.3%). Both ^ and 9^ were identified by their

spectral properties.

Photolysis in Pyridine. A pyridine (220 ml) solution

of 1 (0.5 g, 0.005 m) was photolyzed for 2.5 hr. The red

solution was concentrated under vacuum and chromatographed

rapidly on silica gel. Elution with ethyl acetate gave

an oil that was sublimed (70°C, 1 mm) to give a white

solid identified as 2-imidazol-2-ylpyridine (9^, 0.062 g,

8.5%; mp 132-135°C, lit.^^ 135-136°C); exact mass:

calcd. 145-06399; obsvd. 145.06421.

(51) W.J. Eilbeck and F. Holmes, J. Chem. Soc. A, 1777 (1967).

Further elution with isopropanol gave 3-imidazol-

2-ylpyridine (100, 0.2749 g, 34.6%;, m p (ethyl acetate)

195-196°C, lit.^^ mp 196-198°C); exact mass: calcd.

145.06399; obsvd. 145.06435.

(52) K. Fromherz and H. Spiegelberg, Helv. Physiol, et Pharmacol. Acta, 6, 42 (1948). 94

Elution with methanol, followed by decolorization

with Norit-A yielded a yellow solid (0.36 g, 50%), which

was recrystallized rapidly from carbon tetrachloride to

give 2-pyridiniumimidazolylide (101; mp 147°C); IR(CHClg)

3100(C-H), and 1575(C=C); NMR(CDCl^): 6 7.20(s, 2,

imidazole H), 7.50-8.20(complex, 3, pyridinium H), 9.73 1 3 (2, a, pyridinium H) ; C-NMR (in ppm downfield from TMS;

TMS = 0): 139.57(t, Ç-1), 136.13(t, Ç-3, Ç-3 ' ), 131.20

2 3 ^ ^ (Ç-4, Ç-4'), 126.56(C-2, Ç-2');

^ \ _ exact mass: calcd. 145.06399;

2' ^ obsvd. 145.06420..

Anal. Calcd. for CgH^Ng: C, 66.19; H, 4.86; N, 28.94.

Found: C, 65.54; H, 5.21; N, 27.97.

Photolvsis in 4-Methylpyridine. 2-Diazoimidazole

(1, 0.5 g, 0.005 m) was dissolved in 4-methylpyridine

(125 ml) and photolyzed for 1.5 hr. The resulting purple

solution was concentrated in vacuo and chromatographed on silica. Elution with ethyl acetate gave 3-imidazol-2- yl-4-methylpyridine as a yellow oil (107, 0.04 g, 5%).

Sublimation (80°C, 0.1 mm) and recrystallization from 95

carbon tetrachloride led to white crystals of 107 (mp

157-158°c); IR: 1610, 1555 and 1415 cm"^ (pyridine

ring); NMR (CDCl^) : 6 2.40(s, 3, 7.17(s, 2, imidazole

H), 7.21(d, 1, pyridine H), 8.03(s, 1, pyridine H), 8,35

(d, 1, pyridine H, J = 4.7Hz); exact mass: calcd.

159.07964, obsvd. 159.07997.

Anal. Calcd. for CgHgN^: C, 67.90; H, 5.69; N, 26.39.

Found: C, 67.79, H, 5.67; N, 26.13.

Further elution with methanol gave a purple colored oil. The product was dissolved in dilute hydrochloric acid, neutralized with sodium hydroxide to pH 7, and then extracted with chloroform to give a green-yellow solid identified as 2-(4-methylpyridinium)imidazolylide (108,

0.100 g, 12.6%; mp -180°C); IR: 3100 cm“ ^(C-H); NMR

(CDCl^): 6 2.56(s, 3, Œ ^ ) , 7.03(s, 2, imidazole H), 7.50

(d, 2, pyridinium H, J = 6Hz), 9.38(d, 2, pyridinium H,

J = 6Hz); ^^C-NMR (in ppm downfield from TMS; TMS = 0):

135.74(t, Ç-3, £-3'), 130.64

CH _// , (Ç-4, C-4'), 127.15 (Ç-2, Ç-2 • ) , " ~ • 21.75(C-1); exact mass: calcd.

159.07964; obsvd. 159.08010. 96

Photolvsis in 2,4,6-Trimethvlpvridine. 2-Diazo

imidazole (1/ 0.51 g, 0,0054 m) in 2,4,6-trimethylpyridine

(220 ml) was irradiated for 2 hr. The red solution was

concentrated under vacuum and chromatographed on silica

gel. Elution with 1:2 methanol:ethyl acetate followed by decolorization with Norit-A gave 3-imidazol-2-yl-2,4,6-

trimethyIpyridine (109, 0.3 g, 30%; mp(carbon tetrachloride)

210-212°C); IR: 3090(C-H), and 1600 cm”^(pyridine ring);

NMR(CDCl^): 6 1.96(s, 3, ÇH3), 2.11(s, 3, CH3), 2.40(s,

3, Ç H 3), 6.20(br, 1, NH), 6.80(s, 1, pyridine H), 7.00

(s, 2, imidazole H), exact mass: calcd. 187.11094; obsvd.

187.11135.

Anal. Calcd. for C^^H^3N 3: C, 70.56; H, 6.99; N, 22.44.

Found: C, 70.22; H, 6 .86; N, 22.55.

Thermolvsis in Benzene. 2-Diazoimidazole (1, 0.55 g,

0.0058 m) was thermolyzed in benzene (150 ml) for 3 hr at 80°C. Subsequent concentration of the solution and chromatography on 1:1 ethyl acetate :petroleum ether resulted in 2-phenylimidazole (111, 0.6144 g, 73%; mp

(benzene) 148-149°C, lit.^^ mp 148-149°C); exact mass: calcd. 144.06874; obsvd. 144.06907. 97.

Photolvsis in Benzene (a). A benzene solution (220 ml) of ^ (0.5 g, 0.0053 m) was photolyzed for 3 hr. After

removal of benzene under reduced pressure, the residue was chromatographed on silica gel. Elution with 1:1 ethyl

acetate:petroleum ether gave 2-phenylimidazole^^ (111,

0.5226 g, 68.2%) which was characterized by its spectral analyses and melting point. Elution with pure ethyl acetate yielded compound 112 (0.1844 g, 24.1%; mp(acetone)

189-191°C); IR: 3040(aromatic C-H), 1580(w), 1470(m), 855

(m) and 700 cm“ ^(m); NMR(CDClg): ô 4.09-4.20(complex, 2),

4.31-4.40(complex, 2), 5.95(t, 3), 7.00(s,2), 7.42-7.50

(complex, 3), 7.79-7.90(complex, 2); exact mass: calcd.

288.13748; obsvd. 288.13822.

(b) A solution of ^ (0.5 g, 0.005 m) in benzene

(220 ml) was photolyzed for 15 min. Removal of benzene and chromatography on silica gel yielded 111 (0.437 g,

60.6%) and 11^ (0.12 g, 16.6%).

Photolvsis in Benzene at 10°C. A benzene solution

(220 ml) of ^ (0.5 g, 0.005 m) was photolyzed at 10°C for 45 min. Chromatographic separation on silica gel yielded 111 (0.496 g, 69%) and 112 (0.168 g, 23.4%). 98.

Photolvsis in Benzene in the Presence of Sodium

Hydride^ Diazo compound ^ (0.5 g, 0.005 m) was photolyzed

in benzene (220 ml) containing sodium hydride (1 g, 50%

NaH) at 10-15°C for 40 min. After the resulting solution

had been filtered, the filtrate was concentrated and

chromatographed on silica gel to yield 2-phenylimidaz6le

(111, 0.3825 g, 53%) and (0.1382 g, 19.2%).

Thermolvsis in Benzene in the Presence of Copper(I)

Bromide. A benzene solution (50 ml) of ^ (0.5 g, 0.005 m)

was added slowly to a suspension of copper (I) bromide

(1 g) in benzene (100 ml) and the mixture was stirred at

room temperature for 1 hr and then refluxed for 0.5 hr.

Subsequent filtration, concentration of the filtrate and

chromatographic purification on silica gel yielded

2-phenylimidazole (111, 0.337 g, 46%).

Photolvsis in Isopropvlbenzene. A solution of 1

(0.5 g, 0.005 m) in isopropylbenzene was photolyzed for

3 hr. The solvent was removed by vacuum distillation and

the residue was chromatographed on silica gel. Elution with benzene gave 2,3-dimethyl-2,3-diphenylbutane (120,

0.06 g, 6%; mp 115-116°C, lit.^^ mp 119-120°C); exact mass: calcd. 238.17210; obsvd. 238.17230. 99

(53) A. Klages/ Ber., 2638 (1902).

Elution with 1:4 ethyl acetate :benzene gave

2-(2-isopropylphenyl)imidazole (118, 0.2912 g, 31.3%;

mp(benzene) 164°C); IR: 3020(aromatic C-H), 2970(aliphatic

C-H), 1570, 1470, and 1450 (benzene ring), and 775 cm“ ^

(s, ortho-substituted benzene); NMR(CDCl^): 6 1.03(s, 3,

Ç H 3), 1.66(s, 3, ÇH3)/ 3.45(septet, 1, >C-H), 6.90(s, 2,

imidazole H), 7.23(complex, 5, aromatic H), 9.03(br, 1,

NH); exact mass: calcd. 186.11569; obsvd. 186.11600.

Anal. Calcd. for ^^2^ 14^ 3 * 77.38; H, 7.57; N, 15.04.

Found: C, 77.52; H,77.68; N, 14.88.

Further elution with 1:1 ethyl acetate :benzene gave

2-(4-isopropylphenyl)imidazole (119, 0.2463 g, 26.4%; mp(carbon tetrachloride) 200-201°C); IR: 3020 (aromatic

C-H), 2970(aliphatic C-H), 1520 and 1450(benzene ring), and 840 cm”^ (para-substituted benzene); NMR(acetone-dg):

6 1.83(s, 3, ÇH3), 1.30(s, 3, CH^), 2.93(septet, 1,

C-H), 7.10(s, 2, imidazole H), 7.26(d, 2, aromatic H,

J = 8Hz), 7.93(d, 2, aromatic H, J = 8Hz); exact mass: calcd. 186.11569; obsvd. 186.11600. 100

Anal. Calcd. for ^^^2^14^3* 77*38; H, 7.57; 15.04.

Found: C, 77.05; H, 6.96; N, 14.79.

Photolvsis in 2,4,6-Trimethvlbenzene. 2-Diazo

imidazole (1, 0.53 g, 0.0056 m) was dissolved in 2,4,6-

trimethylbenzene (220 ml) and irradiated for 3 hr. After

removal of the solvent by vacuum distillation, the residue

was chromatographed on silica gel. Elution with 1:1

ethyl acetate:benzene gave 2-(2,4,6-trimethylphenyl)

imidazole (121, 0,760 g, 73%; mp(ethyl acetate) 232-233°C);

IR: 3030(aromatic C-H), 1615, 1585, 1465 and 1430(benzene

ring), and 860 cm"”^ (aromatic C-H deformation); NMR

(CDClg/CDgOD): 6 2.03(s, 6, 2 ÇH3), 2.30(s, 3, CH^), 6.88

(s, 2, aromatic H), 6.96(s, 2, imidazole H); exact mass: calcd. 186.11569; obsvd. 186.11617.

Anal. Calcd. for C^2^14^'^2* 77.38; H, 7.57; N, 15.04

Found: C, 77.27; H, 7.43; N, 15.17.

Thermolvsis in 2,4,6-Trimethvlbenzene. A solution of 1 (0.51 g, 0.0054 m) in 2,4,6-trimethylbenzene (150 ml) was thermolyzed at 80°C for 3 hr. Concentration in vacuo, followed by chromatographic purification on silica gel using 1:1 ethyl acetate:benzene gave 2-(2,4,6-trimethyl phenyl) imidazole (121, 0.718, 71%) having identical IR and NMR as an authentic sample. 101

Photolvsis in Anisole. A solution of 1 (0.5 g,

0.005 m) was photolyzed in anisole for 2 hr and the

photolysate was concentrated. The dark red residue was

chromatographed on silica gel using chloroform to give

2-phenoxyimidazole (125, 0.088 g, 10%; mp(chloroform)

184-185°C); IR: 1575 and 1495 (benzene ring), 1220 (C-0),

795 and 690 cm“^ (mono-substituted benzene); NMR(CDCl^):

6 6.65(s, 2, imidazole H), 7.24(canplex, 5, aromatic H);

mass spec: m/e 160.

Anal. Calcd. for CgHgNgO: C, 67.48; H, 5.03; N, 17.48.

Found: C, 67.81; H, 5.02; N, 17.34,

Further elution with 1:2 ethyl acetate:chloroform

gave 2-(2-methoxyphenyl)imidazole (122, 0.22 g, 25.2%; mp(l:l benzene:hexane) 135-136°C, lit.^^ mp 135-136°C);

exact mass: calcd. 174.07930; obsvd. 174.07960.

(54) B. Krieg, R. Schlegel, and G. Manecke, Chem. Ber., 107, 168 (1974).

Elution with ethyl acetate yielded 2-(4-methoxyphenyl)imidazole (123, 0.2109 g, 24.1%; mp(1:1 benzene: petroleum ether) 158-159°C, lit.^^ mp 160-161°C); exact mass: calcd. 174.07930; obsvd. 174.07943. 102

Photolvsis in N,N-Dimethvlaniline. 2-Diazoimidazole

(1/ 0.5 g, 0.005 m) was irradiated in N,N-dimethylaniline

(220 ml) for 2.5 hr. The resulting solution was concen

trated in vacuum and chromatographed on silica gel.

Elution with 1:2 ethyl acetate:chloroform yielded 2-[2-

(N,N-dimethylamino)phenyl]imidazole (126, 0.3981 g,

42.5%; mp(ethyl acetate:hexane) 116-117°C, lit.^^ mp

118-119°C); exact mass: calcd. 187.11094; obsvd. 187.11151,

(55) P. Franchetti and M. Grifantini, J. Het. Chem., 7, 1295 (1970).

Elution with 1:7 isopropanol;ethyl acetate yielded

2-C4-(N,N-dimethylamino)phenyl]imidazole (127, 0.213 g,

22.7%; mp(chloroform) 236-238°C with dec.); IR: 1615 and

1525 (benzene ring), 1360(C-N), and 825 cm” ^(para- substituted benzene); NMR(CDCl^): Ô 2.98(s, 6, 2CH^),

6.7(d, 2, aromatic H, J = 8Hz), 7.06(s, 2, imidazole H),

7.73(d, 2, aromatic H, J = 8 Hz); exact mass: calcd.

187.11094; obsvd. 187.11151.

Anal. Calcd. for C^^H^^N^: C, 70.56; H, 6.99; N, 22.44.

Pound : C, 70.19; H, 6.72; N, 22.95. 103

Photolvsis in lodobenzene. A solution of 1 (0.5 g,

0.005 m) in iodobenzene (125 ml) was photolyzed for 1.5 hr.

Concentration of the solution ^n vacuo gave a dark red

residue which was chromatographed on silica gel. Elution

with petroleum ether gave p-diiodobenzene (0.1448 g,

mp 127-129°C, lit.^^^mp 131-133°C) with spectral properties

identical to that reported.

(56a) Beil..5. 227; (b) The Sadtler Standard Spectra, IR: 4544; NMR: 207.

Elution next with 1:7 ethyl acetate:chloroform

yielded 2-(2-iodophenyl)imidazole (142, 0.1 g, 7%, mp

(benzene:hexane) 157-159°C); IR: 3040(aromatic C-H),

1600 and 1585 (benzene ring), and 770 cm” ^ (ortho-

substituted benzene); NMR(acetone-dg/CD^OD): 6 7.16(s, 2,

imidazole H), 7.23-8.40(complex, 4, aromatic H); exact mass: calcd. 269.96557; obsvd. 269.96640.

Anal. Calcd. for CgH^Ngl: C, 40.02; H, 2.61; N, 10.37;

I, 46.98.

Pound: C, 40.07; H, 2.63; N, 10.25;

I, 46.98. 104 ■.

Further elution yielded 2-(4-iodophenyl)imidazole

(143, 0.122 g, 9%; mp(ethyl acetate) > 275°C); IR; 3020

(aromatic C-H), 1500(benzene ring), and 830 cm~‘^(para-

substituted benzene); NMR(trifluoroacetic anhydride):

6 7.53(s, 2, imidazole H), 7.60(d, 2, aromatic H, J = BHz),

8.00(d, 2, aromatic H, J = 8Hz); exact mass: calcd.

269.96557; obsvd. 269.96614.

Anal. Calcd. for CgH^Ngl: C, 40.02; H, 2.61; N, 10.37;

I, 46.98.

Found : C, 39.77; H, 2.56; N, 10.22;

I, 46.93.

Elution with 1:1 ethyl acetate:isopropanol gave phenyliodoniumimidazolylide (144, 0.1022 g, 7.5%; mp

> 300°C) as a dark solid which decomposed rapidly; IR:

3060(aromatic C-H), 1605 and 1500 cm” ^ (benzene ring);

NMR(CDCl^/CD^OD): 6 7.30(s, 2, imidazole H), 7.40-8.00

(complex, 5, aromatic H); exact mass: calcd. for CgH^Ngl:

269.96557; obsvd. 269.96614; mass spec, m/e: 270 (M^),

204.

Thermolvsis in lodobenzene. 2-Diazoimidazole (1,

0.5 g, 0.005 m) was thermolyzed in iodobenzene (150 ml) 105

for 2 hr at 8G°C. The solution was concentrated vacuo

and chromatographed on silica gel. Elution with 1:7

ethyl acetate :chloroform gave 142 (0.144 g, 10.6%) and

143 (0.3219 g, 24%) both of which were characterized by

IR and NMR. Elution with 1:1 ethyl acetate:isopropanol

gave 144 (0.05 g, 4%) also characterized by IR and NMR.

Photolvsis in Bromobenzene. A bromobenzene (220 ml)

solution of 1 (0.5 g, 0.005 m) was irradiated for 2.5 hr

and then concentrated jji vacuo to a red oil. Chromato graphy on silica gel using chloroform gave 2-bromo-l- phenylimidazole (141, 0.1342 g, 12%; mp(carbon tetra chloride, 197-200°c); IR: 3160(aromatic C-H), 780 and

710 cm”^ (mono-substituted benzene); NMR(CDgCN): 6 7.03-

7.91(complex, aromatic H and imidazole H); exact mass: calcd. 211.97930; obsvd. 221.97981.

Anal. Calcd. for CgH^NgBr: C, 48.46; H, 3.16; N, 12.55;

Br, 35.82.

Found: C, 48.25; H, 2.95; N, 11.91;

Br, 35.28.

Further elution gave 2-(2-bromophenyl)imidazole (138,

0.1921, 17.5%, mp(benzene/hexane) 139-140°C); IR: 3020 106

(aromatic C-H), and 760 cm“ ^ (ortho-substituted benzene);

NMR(CDCl^): 6 7.03(s, 2, imidazole H), 7.10-7.90(conplex,

4, aromatic H), 10.90(s, 1, NH); exact mass; calcd.

221.97930; obsvd. 221.97981.

Anal. Calcd. for CgH^NgBr: C, 48.46; H, 3.16; N, 12.55;

Br, 35.82.

Pound: C, 48.55; H, 3.20; N, 12.47,

Br, 35.37.

Elution with 1:1 chloroform;ethyl acetate gave

2-(4-bramophenyl)imidazole (139, 0.21 g, 19%) which was

recrystallized from ethyl acetate (267-268°C); IR: 3020

(aromatic C-H) and 830 cm“^ (para-substituted benzene);

NMR (CDCl^): 6 7.18(s, 2, imidazole H), 7.53(d, 2, aromatic H, J = 8Hz), 7.75(d, 2, aromatic H, J = 8Hz); exact mass: calcd. 221.97930; obsvd. 221.97981.

Anal. Calcd. for CgH^NgBr: C, 48.46; H, 3.16; N, 12.55;

Br, 35.82.

Pound; C, 49.22; H, 3.31; N, 12.31;

Br, 35.20.

Photolvsis in Pluorobenzene. A fluorobenzene solution (220 ml) of 1 (0.5 g, 0.005 m) was irradiated 107

for 1 hr. The resulting solution was concentrated and

chromatographed on silica gel using 1:1,5 ethyl acetate:

petroleum ether. 2-(2-Pluorophenyl)imidazole was

obtained as a white solid (136, 0.354 g, 43.6%, mp

(benzene) 164-165°C, lit.^^^mp 196-199°C) ; IR: 3060 cm"!

(aromatic C-H); NMR(CDCl^/CD^OD): 6 7.13(s, 2, imidazole

H), 7.25(complex, 3, aromatic H), 8.13(complex, 1,

aromatic H); exact mass: calcd. 162.0593; obsvd.

162.09577.

On further elution using 1:1 ethyl acetate:petroleum

ether 2-(4-fluorophenyl)imidazole was isolated (137;

0.233 g, 29%; mp(chloroform) 194-195°C, lit.^’^m p 196-

198°C); exact mass: calcd. 162.05932; obsvd. 162.05977.

(57a) Belgium Patent,660,836 (Sept. 9, 1965); Chem. Abstr., 63, Pl8097d (1965); (b) Neth. Appl. Patent,6,605, 106 (Oct.l77 1966); Chem. Abstr.,66, P37928x (1967).

Svnthesis of 2-(2-Fluorophenyl)imidazole. 2-Fluoro- benzaldehyde (1.24 g, 0.01 m), glyoxal (0.58 g, 0.01 m), ammonium acetate (5 g), and glacial acetic acid (30 cc) were refluxed for 1 hr. The mixture was then diluted with water (250 cc), filtered through celite, neutralized 108 with ammonia, and subsequently extracted with chloroform.

The chloroform extract after decolorizing with Norit-A was concentrated iji vacuo to give 2-(2-fluorophenyl)- imidazole (136, mp(benzene) 164-165°C) with properties identical to those described for 136 in the previous experiment.

Photolvsis in Benzonitrile. 2-Diazoimidazole (1,

0.5 g, 0.005 m) in benzonitrile (220 ml) was irradiated for 3 hr. Concentration of the resulting solution gave a red oil which was chromatographed on silica gel.

Elution with 1:9 ethyl acetate:chloroform gave 2-(2- cyanophenyl)imidazole (151 0.1243 g, 14.7%; mp(chloroform)

195-197°c); IR: 3030 (aromatic C-H), 2230 (CsN), 1580 and

1500(benzene ring), and 780 cm”^ (ortho-substituted ben zene); NMR (acetone-dg/DMSO-dg); 6 7.20(s, 2, imidazole

H), 7.30-8.20(complex, 4, aromatic H); mass spec, m/e:

169.

Anal. Calcd. for C^^H^N^: C, 70.99; H, 4.17; N, 24.83.

Found: C, 70.59; H, 4.18; N, 24.61.

Elution with 1:1 ethyl acetate;chloroform gave

2- (4-cyanophenyl)imidazole (152, 0.258 g, 31%; 109 mp(isopropanol) 295-260°C) ; IR: 2230 (CsN), 1615 and

1505 (benzene ring), and 840 cm“ ^ (para-substituted benzene); NMR (acetone-dg/DMSO-dg): 6 7.16 (s,2, imidazole

H), 7.76 (d, 2, aromatic H, J = BHz), 8,20(d, 2, aromatic

H, J = 8Hz); mass spec, m/e: 169.

Anal. Calcd. for C^gH^N^: C, 70.99; H, 4.17; N, 24.83.

Found: C, 70.77; H, 4.24; N, 24.72.

Photolvsis in Nitrobenzene. A solution of 1 (0.55 g,

0.0058 m) in nitrobenzene (220 ml) was irradiated for

2 hr. The resulting solution was fractionally distilled to give a blue liquid which on analysis by gas chromato graphy (10% OV-1 on Chrom W, 12' x 1/8", 120°C) and spectral analyses was found to be nitrosobenzene (0.625 g,

82%). After complete removal of the nitrosobenzene and nitrobenzene, the residue was chromatographed on silica gel using ethyl acetate. 2-(4-Nitrophenyl)imidazole was isolated (153; 0.08 g, 7%, mp(ethanol) > 310°C, lit.^^ mp 310-315°C); exact mass: calcd. 189.05382; obsvd.

189.05421. The picrate of 153 was prepared in the standard way (mp 260°C, lit.^® mp 262°C).

(58) F.L. Pyman and E. Stanby, J. Chem. Soc., 125, 2484 (1924) . 110

Thermolysis in Nitrobenzene. A nitrobenzene solution

(220 ml) of 1 (0.55 g, 0.0058 m) was thermolyzed at 60°C

for 2 hr. Fractional distillation of the resulting

solution gave nitrosobenzene (90-100%) which was analyzed by gas-chromatography (10% OV, on Chrom W, 12' x 1/8",

120°C). Chromatographic separation of the residue on

silica gel yielded compound 154 (0.07 g, 4.5%) on elution with 1:4 ethyl acetate:chloroform, which was recrystallized from ethanol (mp 297-300°C); IR: 3015, 2920, 1740(w),

1690(m), 1620(s), 1580, and 1130 cm"^; NMR(DMSO-dg): 6 7.00

7.6 6 (complex, 9), 8.10(s, 3); exact mass: calcd. for

C15H 12N4O: 264.1011; obsvd. 264.09903.

Anal. Calcd. for C, 68.17; H, 4.57.

Found: C, 68.91; H, 4.80.

Further elution with ethyl acetate gave 2-(4-nitrophenyl)imidazole (153, 0.08 g, 7%) which was identified from its spectral data.

Thermolvsis in Hexafluorobenzene. A hexafluorobenzene (50 ml) solution of 2-diazoimidazole (1, 0.5 g,

0.005 m) was heated slowly to reflux and then refluxed for 1 hi'. After removal of the solvent under reduced Ill

pressure the brown residue was chromatographed on silica

gel using benzene. A pale yellow oil was obtained

(0.9019 g, 71.5%) which, on trituration with hexane and

cooling to 0°C, gave a white, highly lacrymatory solid,

identified as llH-hexafluorocyclohepta[b]pyrazine (163).

Purification of 163 was achieved by sublimation (46°C,

0.3 mm, mp 35-36°C); IR (neat): 1705(s, fluorinated C=C),

and 900-1400 cm“ ^(v.s. bands, C-P); NMR(CDClg): 7.41(br, d, imidazole H); ^^P-NMR(in ppm downfield from hexafluoro

benzene) : 67.57 (s, 1, P^),

47.76(d of d, 1, or Fg),

37.46(d of d, 1, F^ or Fg),

35.51(d of d, 1/ Fg or Fg),

31.72(complex, 1, F^), 21.42

(d of d, 1, Fg or Fg); UV:

X „ 218 mu; exact mass: calcd. 252.01221; obsvd. rnsx 252.01303. ,

Anal. Calcd. for CgHgNgFQ: C, 42.87; H, 0.80; N, 11.11.

Found: C, 42.91; H, 0.79; N, 11.31. 112

Photolysis in of, q',q'-Trifluorotoluene. 2-Diazo

imidazole (If 0.53 g, 0.0056 n) was photolyzed in #,#,#-

trifInorotoluene (220 ml) for 2 hr. The resulting solution

was concentrated and chromatographed on silica gel.

Elution with 1:1 ethyl acetate:petroleum ether yielded

2-(3-trifluoromethylphenyl)imidazole (145y 1.037 q, 86.4%/

mp (HgO) 156-157°C, lit.^^ mp 157.5-158.4°C); exact mass:

calcd. 212.05612; obsvd. 212.05646.

(59) R.E. Klem, H.P. Skinner, H. Walba and R.W. Isensee J- Het. Chem.. 7, 403 (1970).

Photolysis in Methyl Benzoate. A solution of 1

(0.5 g, 0.005 m) was photolyzed in methyl, benzoate (220 ml) for 2 hr. Concentration of the resulting solution gave a red oil which was chromatographed on silica gel. Elution with 1:3 acetone:petroleum ether afforded 2-(3-carbometh- oxyphehyl)imidazole (146, 0.6 q, 56%, mp (benzene/ chloroform) 163°C); IR: 3030 (aromatic C-H), 1420(s, ester carbonyl), 1265, 1990 and 1115 cm” ^ (benzoate C-0); NMR

(CDClg/CDgOD): 6 7.03(s, 2, imidazole H), 7.23-8.06(complex,

3, aromatic H), 8.43(t, 1, aromatic meta-H); exact mass: calcd. 202.07422; obsvd. 202.07463. 113

Anal. Calcd. for C^iH^oNgOg: C, 65.34; H, 4.98; N, 13.85.

Pound: C, 65.49; H, 5.11; N, 13.81.

Thermolysis in Methyl. Benzoate. 2-Diazoimidazole

(1/ 0.5 g, 0.005 m) was thermolyzed in methyl benzoate

(150 ml) for 2 hr at 80°C. Concentration of the resulting solution and chromatography of the concentrate on silica gel using 1:3 acetone:petroleum ether yielded 2-(3- carbomethoxyphenyl)imidazole (146; 0.57 g, 54%) which was characterized by IR and NMR as in the preyious experiment.

Photolysis in Acetophenone. An acetophenone solution

(220 ml) of 1 (0.5 g, 0.005 m) was irradiated for 2 hr, and then concentrated yacuo to an oil. Chromatography on silica gel using 1:2 acetone:petroleum ether afforded

2-(3-acetylphenyl)imidazole (147; 0.1 g, 11%; mp(benzene)

157-159°C); IR: 3020(aromatic C-H), and 1690 cm“^(carbonyl);

NMR (CDCI3): Ô 2.36(s, 3, ÇH3), 7.16(s, 2, imidazole H),

7.26-8.13(complex, 3, aromatic H), 8.46(t, aromatic meta-

H), 10.92(br, 1, NH); exact mass: calcd 186.07931, obsyd. 186.07967.

Anal. Calcd. for C^^H^^NgO: C, 70.95; H, 5.41; N, 15.04.

Found: C, 71.30; H, 5.53, N, 14.93. 114

Thermolvsis in Acetophenone. h solution of 1

(0.5 g, 0.005 m) in acetophenone (150 ml) was thermolyzed for 2 hr at 60°C. Concentration of the resulting solution in vacuo and subsequent chromatography on silica gel as in the previous experiment afforded 2-(3-acetylphenyl)- imidazole (147, 0.1 g, 11%) which was identified by IR and NMR. PART II

Rearrangements of 1-(5-Oxazolyl)-1-alkylidenes

115 STATEMENT OF THE PROBLEM

This study is concerned with the chemistry of various

1-(5-oxazolyl)-1-alkylidenes (2_)/ as generated by decom position of 1-diazo-l-(5-oxazolyl)alkanes (^) . The

. i X v * . N2 1 2 principal objectives of this research are to determine

(a) if 2^ isomerizes to 5-aza-2-pyranylidenes (^/ Eq. la),

(b) if 2 undergoes ring opening to N-acyl-3-alkyn-2-one imines (4, Eq. lb), and (c) if 2_ fragments to nitriles (5^) and acetylenic ketones (6, Eq. Ic).

^'3 ( la) A o > . -

R -C3N + R--CSC-C-R- (Ic)

5 6 ^ 116 HISTORICAL

A fascinating carbenic rearrangement is intercon

version of arylmethylenes (7) and cycloheptatrienylidenes

(8) involving cyclopropane intermediates^ (Eq. 2).

R H (2 ) '‘" O ' m # 7 8

(la) G.G. Vander Stouw, Piss. Abstr., 25/ 6974 (1965); (b) R.C. JoineS/ A.B. Turner/ and W.M. JoneS/ J. Am. Chem. Soc./ 91/ 7754 (1969); (c) P. Schissel/ M.E. Kent/ D.J. McAdoO/ and E. Hedeya/ ibid./ 92, 2147 (1970); (d) C. Wentrup and K. Wilczek/ Helv. Chim. Acta, 53/ 1459 (1970); (e) W.G. Baron/ M. Jones/ Jr., and P.P. Gaspar/ J. Am. Chem. Soc./ 92/ 4739 (1970); (f) G.G. Vender StouW/ A.R. Kraska/ and H.’^hechter/ ibid.. 94/ 1655 (1972); (g) T. Mitsuhashi and W.M. JoneS/ ibid., 9ÎT 677 (1972); (h) K.E. Krajca/ T. Mitsuhashi/ and W.M. Jones/ ibid., 3661 (1972); (i) W.M. JoneS/ R.C. Joines, J.A. Meyer^/ T. Mitsuhashi/ K.E. Krajca/ E.E. Waali/ T.L. Davis/ and A.B. Turner/ ibid. 95/ 826 (1973); (j) R.L. Tyner/ W.M. JoneS/ Y. Ohrn/ and J.R. Sabin/ ibid., 96/ 3765 (1974); (k) T.T. Coburn and W.M. JoneS/ ibid., 9?/ 5218 (1974); (1) C. Wentrup/ Tetrahedron/ 30^ 130T (1974); (m) R. Gleiter/ W. Rettig/ and C. Wentrup/ Helv. Chim. Acta. 57/ 2111 (1974).

Similar rearrangements (Eq. 3) have been observed for (2-pyridyl)methylenes (9) and azacyclohepuatrienylidenes

117 118

(10) and it is important to recognize that in isomerizations

of 9 and participation of heterocyclic nitrogen with

the carbenic centers^^'^'^ (Eq. 3) occurs.

(3)

(2a) W.D. Crow and C. Wentrup, Tetrahedron Lett., 6149 (1968); (b) C. Wentrup, Chem. Comm., 1386 (1969); (c) C. Mayor and C. Wentrup, J. Am. Chem. Soc., 97, 7467 (1975); (d) C. Theitaz and C. Wentrup, ibid., 98" 1258 (1976). (3) R.V. Hoffman, G.G. Orphanides, and H. Shechter, J. Am. Chem. Soc., 100, 7927 (1978).

The ease of rearrangement of aryl carbenes prompted

research at The Ohio State University on the generation

and chemistry of 611 electron, 6 membered ring carbenes which are predicted to be highly stabilized and nucleophilic.

Thus 2-furylmethylenes (11a) and 2-thienylmethylenes (lib)

(4) R. Gleiter and R. Hoffman, J. Am. Chem. Soc., 90, 5457 (1968).

(5) R.V. Hoffman and H. Shechter, J. Am. Chem. Soc., 100, 7934 (1978). 119

have been investigated as possible precursors to

of-pyranylidenes (12 a) and Qf-thiopyranylidenes ( 12b )

(Scheme 1).^'^

SCHEME 1

l2a—b lla-b -----

a: X = 0/ b: X = S

2-Furylmethylenes (lia)/ generated by decomposition of the sodium salts of their respective precursor p-tosylhydrazones, undergo ring opening to (Z)-y -6- acetylenic a,p-olefinic carbonyl (13a) products (Eq. 4).

H H 11a > C = C (4) X = a c R %

.3a

2-Thienylmethylenes (lib) generated in a similar manner, on the other hand, give very little ring opening to 120

a,P-unsaturated/ y,6-acetylenic thiocarbonyls (13b); the

major processes are conversions to the corresponding (Z)

and (E) —1, 2-di-(2-thienyl)ethylenes {1^, Eq. 5). That

11b — ^ R-C-CH = CH-C= C^R ' + / / ~ \ / F \ (5)

^ 13b

2-furylmethylenes (11a) and 2-thienylmethylenes (11b) are

indeed generated by decomposition of their respective

tosylhydrazone sodium salts is indicated by trapping with

cyclooctane (15a-b) and styrene (]^). Isomerizations of

' X - ' ' ^ “ 2 15a— b

a: X = 0; b: X = S.

lla-b to a-pyranylidenes (12a) and a-thiopyranylidenes

(12b) were not observed.

Generation of 2-furylmethylene (lia) has also been attempted, involving low-pressure (10"^ Torr) gas-phase - 6 pyrolysis of a-phenylfurfuryl acetate (14) at 600 C. 121

(6) W.S. Trahanovsky and D.L. Alexander, J. Am. Chem. Soc. 101, 142 (1979).

Besides other products, (Z)-y, 6-acetylenic of, p-olefinic

(/ W'^ S 'C — 0 - C - CH,

17 carbonyl compound 13a (R=H, R' = CgHg), the product arising by ring opening of 11a (R=H, R'= CgH^) was obtained.

The behavior of 1-(5-isoxazolyl)-1-alkylidenes (19) generated by pyrolysis of their corresponding tosylhydrazone sodium salts via l-(5-isoxazolyl)-l-diazoelkanes (1Æ) was then examined as potential precursors to 6-aza-2-pyranylidenes (20), another 611 electron, 6 membered ring carbenic system of interest.

R^ ^R'

II N 18 ^ 19 22 122

As shown in Scheme II/ 1-(5-isoxazoyl)-1-alkylidenes 7 (19) behave quite differently than 2-furylmethylenes

(11a) and 2-thienylmethylenes (lib). Fragmentation of 19

(7) D.J. Houser, M.S. Dissertation, The Ohio State University, 1973.

SCHEME II

R 0 II R-CSN + H-CEC-C-R' > N 0 I 21 22 Ni'

t M 21_ + H-C-CSC-R'

24 123

leads to nitriles (21) and alkyl ethynyl ketones ( ^ ) .

l-Nitroso-l-alken-3-ynes (23), ring opened products of

19 were not detected. The acetylenic aldehyde (24)/ derivable from a process involving cycloaddition of the nitroso group to the carbon-carbon double bond of 23, followed by fragmentation was not observed, either.

Further, thermolysis of 1-diazo-l-(3-methyl-5-isoxazolyl)- ethane (^, R and R ' = CH^) yields 3-methyl-5-vinyloxazole

(25, > 83%) by migration of a-hydrogen to the carbenic center; the system showed no collapse of the heterocyclic

2^ ring. There was no evidence for rearrangement of ^ to

6-aza-2-pyranyli denes ( ^ ) .

A logical extension to lla-b and would appear to be

1-(5-oxazolyl)-1-alkylidenes (27_) as derived from pyrolysis of their corresponding tosylhydrazones, via 1-(5-oxazolyl)-

Q 1-diazoalkanes (26). Preliminary studies involving 124

CH ,CH3

11 N 26s—b 27 S—b

pyrolysis of 2£ (a: R = CH^/ R ' = CH^; b: R=CgHg, R'= CH^)

at 180-200°C have indicated that 27 was rearranging with

(8) Study of system 2£ was initiated by S-I. Hayashi, a post-doctoral fellow at The Ohio State University.

ring opening to N-acyl-3-alkyn-2-one imine (28) and

N-[2-alken-3-ynyl]acylamides (29, Eq. 6).

24 a—b ^ R—C C^ : X h 3 28a-b 29a-b

a: R = CH^, R' = CHg; b: R = CgHg, R' = CHg.

Since characterization of 2^ and 29^ was not complete, and since it appeared worthwhile to probe into the behavior of 27_ at higher temperatures, this more extensive study of 1-(5-oxazolyl)-l-a]kylidenes 27 was undertaken. RESULTS AND DISCUSSION

In this research 1-(5-oxazolyl)-1-alkylidenes (27)

as generated by decomposition of their respective diazo

precursors (^) have been investigated. The diazo systems

(26) were derived from the following g-tosylhydrazones.

(30a-c):

R N-NH-SO

30a-c a: R = CH^, R ' = CH^ ; b: R=CgHg, r '= CH^; c: R = R'=H.

The ketones, 5-acetyl-2,4-dimethyloxazole (31a) and

5-acetyl-4-methyl-2-pheny1oxazo1e (31b), from which p-tosylhydrazones 30a and 30b respectively were prepared, 9 have been reported and were presently synthesized according to Eq. 7.

(9) A. Dorrow and H. Hill, Chem. Ber., 93, 1998 (1960).

125 126

n , m f R-CO„H

0 iï H s 0 0

— (7) a: R = CH^; b: R = CgHg

2,4-Dimethyloxazole-5-carbaldehyde (31c), the precursor to p-tosylhydrazone 30c, has not been previously described. A route to 31c appeared to be reduction of

5-carbethoxy-2, 4-dimethyloxazole (^) prepared according to Scheme III. Reduction of 32 was attempted with

(10) G. Ya Kondrateva and K. Chzhi-khen, Zh. Obshch. Khim., 32, 2348 (1962).

O SCHEME III II Cl O-C-GH3

{j “ (CH3C0)20 t

CH,

0-C H » . J.X. 3 II 0 0 32 31c 127

(a) diisobutyl aluminum hydride,(b) sodium bis(2- methoxyethoxy)aluminum hydride^^^ and (c) lithium aluminum hydride,respectively. However, none of these methods

(11a) L. I. Zakharkin and I.M. Khorlima, Tetrahedron Lett.. 619 (1962); (b) J. Vit, Ora. Chem. Bull.. 1 (1970); (c) L.I. Zakharkin, V.V. Gavrilenko, D.N. Maslin, and I.M. Khorlina. Tetrahedron Lett., 2087 (1963).

were successful for preparing aldehyde 31c or its correspond ing alcohol. Upon attempted use of diisobutyl aluminum hydride or sodium bi s(2-methoxyethoxy)aluminum hydride more than 90% of the starting ester (32) was recovered, and with lithium aluminum hydride no identifiable material was obtained. Further experiments showed that carbaldehyde 31c could be satisfactorily prepared by a modified McFadyen- 12 Stevens route as in Scheme IV. This synthesis and extensions thereof are discussed in Part III.

(12) M. Nair and H. Shechter, J. Chem. Soc., Chem. Commun. 793 (1978). 128

SCHEME IV CH3

32 ^2^4*^2° s.N. // \\ NH-NH„NH-NH^ C^H^SOgClfOC^H^SOgClfOOc^ C

C2H5OB " 3'' u O CH 1) BuLi, 1 equiv. HH-NH-SO.-CnH > ^ 2) 180-200°C, a —C7H7SO2/—N 2

Carbaldehyde 31c is air-sensitive and was handled under

nitrogen for subsequent purposes.

The p-tosylhydrazones 30a-c were prepared efficiently

from 31a-c and p-tosylhydrazide in ethanol. Reactions of

30a-c with sodium hydride (1.1 equiv.) in methylene chloride

(Eq. 8) gave the corresponding sodium salts, 33a-c.

C„H„-S0_-NH-NH2 NaH // \\ (8) 31a-c > 30a-c -- — > A

C2 H5 OH - CHjClj R Na

33a-c

Decompositions of dry sodium salts 33a-c at 180-200°C

(0.1 mm) yield N-acyl-3-alkyn-2-one imines (28a-c; presumably of (Z)-stereochemistry) and N-[2-alken-3-ynyl]acylamides 13 (29a-c; Eq. 9), via diazo compounds 26a-c. 129

(13) Product identification is described in the Experi mental Section.

o 180-200°C R N = II ii 33a-c 26a-c '^C C& + C

28a-c 29a-c

(9)

Photolyses of 33a-b in diethyl ether also result in

28a-b and 29a-b. Table 1 gives the yields and product proportions of 28a-c and 29a-c from these experiments.

As Table 1 shows the ratios of 28; 29 in a particular experiment range from 1.0- 2.5. It can be presumed that the N-acylalkynone imines ^ isomerize to N-alkenynyl- acylamides 22 during the course of the decompositions since isomerization of 28a to 29a was observed when 28a was heated at 100°C in toluene. Thus in actual practice the product ratios are a function of their thermal history and handling. The low yields of products (28c and 29c) obtained for thermolysis of 33c are largely due to the fact that considerable amounts (ca. 52%) of dimers of 28c and

29c were obtained. The dimers are white solids and are TABLE 1

DECOMPOSITIONS OF SODIUM SALTS, 33à-c

33a - c Overall Yield (%) Product Proportions (%) R R' Thermolysi s Photolysis Thermolysi s Photolysis (180-200°C) 28 2£ 28 29 a CH3 CH3 75 65 33.3 66. 6 33.3 66.6 b CH3 50 40 28.5 71.4 33.3 66.6 c CH3 H 17.5 -- 50 50

w o 131

apparently a mixture of isomers; their structural identification has so far proved impossible.

Products 28a-b were separated from 29a-b by vacuum distillation; column chromatography of the residue gave pure 29a-b. Pyrolysate 28c and 29c could not be separated and was difficult to handle because dimers formed readily.

The structures of ^ and 2£ were established, besides their spectral analyses, by their degradation and their conversion to known compounds. Hydrolyses of 28a-b in benzene with hydrochloric acid yields 3-pentyn-2-one (34) and the respective amides (35a-b, Eq. 10). Hydrogenations of 28a-b and 29a-b over palladium/carbon yield N - (1- methylbutyl)acylamides (36, Eq. 11). Further, sodium

H+,H,0 28a-b --- — —> CHg-CO-CzC-CHg + R-CO-NHg (10)

34 35a-b

a : R = CHg; b; R = C^Hg

28a-b — ^ R-CO-NH-C_(CH_)__CH_ (11) 25 u I 2 2 3 29a-b CH.

36a-b

a; R = CHg; b: R = C^Hg 132

14 borohydride in ethanol reduces the carbon-nitrogen double

bonds in 28a-b to N-(l-methyl-2-butynyl)acylamides (37a-b;

Eq. 12).

(14) J. H. Bellman and A. c. Diesing, J. Ore. Chem., 22, 1068 (1957).

NaBH. f 28a-b ^ R-CO-NH-C-C=C-CH- (12)

CH3 37a-b a: R = CHg; b: R =

Thermolysis of 33c in cyclooctane at 150°C gives

(2,4-dimethyl-5-oxazolyl) cyclooctane (^, < 10%, Eq. 13)

along with 28c and 29c. That decomposition of 26 involves

33c ---— // \\ (13) 150°C CHCH 3 38 a discrete carbenic intermediate (27) is hence confirmed by trapping the carbene in cyclooctane.

Decomposition of 33c in styrene at 145°C gives

1-(2, 4-dimethyl-5-oxazolyl)-2-phenylcyclopropane 133

(39, 15%/ Eq. 14). Analysis by gas chromatography-mass

spectrometry showed that 39 apparently is a mixture of

C.H.-CH=CH„ 330 ^ ^ „ (14) 145°C

(Z)- and (E)-isomers. However, for all practical purposes they remained inseparable even by gas chromatography.

Formation of ^ therefore proves that diazo compound 26 and/or its subsequent carbene 22, can be added to olefins.

No attempts were made to maximize the yields of ^ or 39.

On the basis of the observations described and the mechanistic sequence proposed for the decomposition of O 2-furylmethylenes (11a) and 2-thienylmethylenes (Ijb), the following mechanism (Scheme V) may be considered for decompositions of 1-(5-oxazolyl)-1-diazoalkanes (^) . Loss of nitrogen from the diazoalkane 26^ leads to the carbene; 1-(5-oxazolyl)-1-alkylidene (27). The heterocyclic ring in 27 then collapses to imine 28 presumably of 134,

SCHEME V CH -N R ,N=C^ > ' • / '•c. R N \ 26 2 27 28 R'

Hî JJ H HH, IH nuOH 0 0 H,

A A k \ \ " \ iS. \ , R ' 29 R '

(2)-stereochemistry. Probably due to a small-C=N- geometric

barrier, ^ isomerizes to its (E)-isomer (40), followed by

thermally allowed 1,5-hydrogen rearrangement, and then

tautomerization to the N-[2-alken-3-ynyl]acylamide (29). n Since 1-(5-isoxazolyl)-1-alkylidenes (19), unlike

2-furylidenes (11a) and 2-thienyldenes (lib), do not ring- open to ^ but collapse instead to nitriles (21) and

alkyl ethynyl ketones (22), decomposition of 2^ at higher temperatures (300-350°) was studied to see if fragmention occurs. Sodium salts 33a-c were pyrolyzed at 300-350°C and indeed products of fragmentation:nitriles 41 and alkyl 135

alkynyl ketones ^ were obtained along with ring-opened products 28^ and 22 (Eq. 15) . Table 2 gives the yields and product proportions from these experiments. CH3 300-350°C 33a-c ------> X R' — > 28 + 29 + R - C = N + — -

0 C H ^ = C - C - R ' (15) 42a-c

a: R = R' = CH^; b: R = R' = CH^; c: R = R' = H

TABLE 2

PYROLYSIS OF SODIUM SALTS 33a-c at 350°C

33a-c Overall Yields Product Proportions^ (%) (%) R R 28 29 41 42 a CH3 CH3 71.7 12.5 25 37.5 25 b CgHs CH3 65 13.33 20 40 26.66 c CH3 H 75.2 35. 29 23.5 11.76

^Where the total 100%, dimers of 28c and 29c account for the remainder. 136

(:Z)-N-Acyl-3-alkyn-2-one imines (28^) and N-[2-alken-

3-ynyl]acylamides (29_) on pyrolysis at 350°C, however, fail

to give nitriles ^ and the alkyl alkynyl ketones 42.

Therefore, the specific fragmentation of 2J7 observed

suggests (Scheme VI) participation of a lone pair of

electrons from oxazole-oxygen with the empty orbital of the neighboring singlet carbenic center leading to inter mediate 43. Reorganization of the bonds in 4^ could result in a bent allene 44 in which there could be a high

SCHEME VI

44 45

\j/ 28 + 29 41 + 42

degree of delocalization as in 4^. Retro Diels-Alder collapse of this strained, delocalized intermediate 44 —

45 would result in the ring-opened products 28 and 29, 137

and/or the products of fragmentation and 42. Similar participation of oxygen with its neighboring singlet carbenic

center has been suggested for 1-(5-isoxazolyl)-1-alkylidene

(19, Scheme II).

It has been previously described that 1-(5-isoxazolyl)-

1-ethylidene (19_, R and R" = CH^) undergoes a-hydro gen migration to its carbenic center to yield 3-methyl-5- n vinyloxazole (2^) exclusively. Rearrangement of a - hydrogen in 2-furylalkylidenes (11a; R=H, R' = CH^; R=H,

R'sCgHg) to form 2-vinylfurans does take place, though only to a very minor extent. However, 1-(5-oxazolyl)-1- alkylidene 27a-b does not undergo e-hydrogen migration either during pyrolysis or photolysis; vinyloxazoles (46) were not obtained during decomposition of 26a-b (Eq. 16).

26a-b \\ > (16) ''H 46

Thus 1-(5-oxazolyl)-1-alkylidenes {21) undergo bond- reorganization to and/or followed by ring- opening and fragmentation (Scheme VI) faster than e- hydrogen migration (Eq. 16). 138

Finally, just as for 2-furylmethylenes (11a),

2-thienylmethylenes (lib), and 1-(5-isoxazolyl)-1-alhyli- 3 7 denes (19) * isomerization of 1-(5-oxazolyl)-1-alkylidenes

(27) to 5-aza-2-pyranylidenes, (3) did not occur (Eq. 17).

26 > (17)

In summary it has been found that 1-(5-oxazolyl)-1- alkylidenes (27) undergo ring opening (Scheme V) at 180-

200°C whereas at 350°C considerable fragmentation occurs.

There may be further unusual chemistry of ^ at higher temperatures which will lead to better insight into the topology of the system. It is also noted that investigation of 2-furylmethylenes (11a) and 2-thienylmethylenes (11b) at increased temperatures may lead to fragmentation and other new reactions of interest. EXPERIMENTAL

I. General Information

Melting Points. Melting points were determined

using a Thomas Hoover capillary point apparatus and are

uncorrected.

Boiling Points. Boiling points were obtained as the

compounds distilled. Thermometer corrections were not made.

Elemental Analyses. Elemental analyses were performed by Microanalysis, Inc., Wilmington, Delaware, or by the

Scandinavian Microanalytical Laboratory, Herlev, Denmark.

Infrared Spectra. Infrared spectra were determined on a Perkin-Elmer Model 457 Grating Infrared Spectrophoto meter. All spectra were calibrated against polystyrene absorption at 1601 cm“^. The spectra of solid compounds were obtained from KBr wafers, and the spectra of liquids from liquid films unless otherwise stated.

Nuclear Magnetic Resonance Spectra. Nuclear magnetic resonance spectra were recorded on a Varian A-60A or

EM-360L or HA-100 model spectrometers.

Mass Spectrometry. Mass spectra were determined by

Mr. C.R. Weisenberger on a AEI-MS-9 mass spectrometer.

139 140

Gas Chromatography-Mass Spectrometry. Gas

chromatography-mass spectra were obtained on a DuPont

21-490 and a Perkin Elmer 990 models connected by a metal

jet separator.

Column Chromatography. Chromatographic separations

were effected on MN Laboratories' "Silica Gel for Column

Chromatography, " 40-270 mesh.

Gas Chromatography. Gas chromatography was effected

using a Varian Aerograph Model 920 with a thermal

conductivity detector.

II. Preparation of Intermediates.

3-Chloroacetvlacetone. Sulfuryl chloride (94 g,

0.75 m) was added in 4 hr to pentane-2,4-dione (75 g,

0.75 m) in dry benzene (75 ml) at room temperature. The

mixture was stirred for 30 min., concentrated, and then

distilled in vacuo to give 3-chloroacetylacetone (77.8 g,

77%; bp 51-53°C/17 mm, lit.^^ bp 56-59°C/28 mm).

(15) E.R. Buchman and E.M. Richardson, J. Am. Chem. Soc., 67, 395 (1945). 141

5-Acetyl-2/4-dimethyloxazole (31a). A mixture of

3-chloroacetylacetone (26.8 g, 0.2 m) and acetamide

(35,4 g, 0.6 m) in glacial acetic acid (66 g) was reflüxed

for 5 hr, cooled to room temperature, and poured onto ice.

The solution was neutralized with concentrated aqueous

sodium hydroxide and the dark brown solid formed was collected by vacuum filtration. Fractional distillation in vacuo yielded 5-acetyl-2,4-dimethyloxazole (31a; 23 g,

82%; bp 104-105°C/24 mm, mp 61-62°C, lit.^ bp 86°C/12 mm, mp 61°C).

5-Acetyl-2,4-dimethyloxazole p-Tosylhydrazone (30a). p-Tosylhydrazide (20.6 g, 0.11 m) in methanol was added to

5-acetyl-2,4-dimethyloxazole (31a, 13.92 g, 0.01 m) in methanol and the mixture was stirred overnight at room temperature. The white solid formed was recrystallized from methanol to give 5-acetyl-2,4-dimethyloxazole p- tosylhydrazone (3pa; 28.78 g, 94%; mp 183-184°C dec., lit.

179-180°C).

(16) D.J. Brown and P.B. Ghosh, J. Chem. Soc. (B), 270 (1969). 142

5-Acetyl-4-methyl-2-phenyloxazole (31b). A stirred mixture of 3-chloroacetylacetone (26.8 g, 0.2 m), benzamide (72.6 g, 0.6 m) and benzoic acid (132 g, 1.1 m) was heated at 180-185°C for 16 hr, cooled to 110°C, and made alkaline with sodium hydroxide solution. The mixture was cooled and extracted with ether. After the ether extract had been dried over magnesium sulfate and concen trated, the black residue was distilled iji vacuo.

5-Acetyl-4-methyl-2-phenyloxazole (31b; 26.08 g, 65%) was obtained as a white solid which was recrystallized from hexane (mp 68°C, lit.^ 68°C).

5-Acetyl-4-methyl-2-phenyloxazole p-Tosylhydrazone

(30b). 5-Acetyl-4-methyl-2-phenyloxazole (jib, 4.02 g,

0.02m) and p-tosylhydrazide (4.11 g, 0.022 m) in methanol were stirred overnight at room temperature. The white solid formed was recrystallized from ethanol to give

5-acetyl-4-methyl-2-phenyloxazole p-tosylhydrazone (30b;

6.3 g, 85%; mp 206-207°C dec.); IR; 3200 (N-H), 1620

()C=N-^-), 1355 and 1175 cm“ ^ (sulfonyl); NMR (CDCl^);

Ô 2.18(s, 3, ÇH3), 2.35(s, 3, ÇH 3), 2.42(s, 3, P-ÇH3-

CgH^SOg-), 7.4 and 7.9 (each m, 10, aromatic H and N-H); mass spec.: m/e 369 (M***), 105. Anal. Calcd. for C^gH^gN303S: C, 61.77; H, 5.18; N, 11.39. Pound: C, 61.58; H, 5.21; N, 11.40. 143

5-Carbethoxy-2/4-dimethyloxazole (32). A mixture of

ethyl 2-chloroacetoacetate (95 g, 0.58 m), potassium

acetate (95 g, 0.92 m), acetic acid (200 ml), and acetic

anhydride (50 ml) was heated at 110°C for 2 hr and then

cooled to 40°C. After ammonium carbonate (95 g) was added,

the mixture was heated for 3 hr at 110°C. After cooling, the mixture was neutralized carefully with sodium carbonate to pH 7. The solution was then extracted with ether, dried over magnesium sulfate, and evaporated. Distillation in vacuo gave 5-carbethoxy-2,4-dimethyloxazole (32; 20 g,

21%; bp 98-103°C/4 mm, mp 55-56°C, lit.^° bp 98-103°C/4 mm, mp 55-56°C);

2,4-Dimethyloxazole-5-carbaldehyde (31c). 1-(2,4-

Dimethyloxazole-5-carboxylic acid)-2-p-tosylhydrazide

(3.09 g, 0.01 m), prepared from ^ according to the procedure described in Part III , p 17 6, was dissolved in dry tetrahydrofuran at 0°C. To this solution under nitrogen was added 1 equivalent of n-butyllithium in hexane. After stirring the mixture at room temperature for 45 min., the solvent was removed and the hydrazide salt was dried under reduced pressure. Upon pyrolyzing the dry lithium salt at

180-200°C (0.1 mm), 2,4-dimethyloxazole-5-carbaldehyde 144

(31c; 0.85 g, 68%) collected in the traps cooled to -78°C.

Aldehyde 31c is air sensitive and had to be handled under

nitrogen. Distillation at 80-90°C (10-13nun) gave 31c of

the following properties; IR: 1695 cm"^ (s, carbonyl);

NMR (CDCI3): Ô 2.36(s, 3, Ç H 3), 2.46(s,,3, ÇH3)/ 9.76(s,

1,-CHO); exact mass: calcd. 125.04767, obsvd. 125.04798.

The semicarbazone of 31c, on crystallization from

ethanol-water, melts at 224-225°C and gave the following

analyses:

Anal. Calcd. for C, 46.15; H, 5.49; N, 30.76.

Pound: C, 46.22; H, 5.50; N, 30.85.

2,4-Dimethyloxazole-5-carbaldehyde p-Tosylhydrazone

(30c). p-Tosylhydrazide (1.86 g, 0.01 m) in ethanol (20 ml)

was added to 2,4-dimethyloxazole-5-carbaldehyde (31c,

1.25 g, 0.01 m) in ethanol (10 ml) and the resulting

mixture was stirred overnight at room temperature under

nitrogen. On cooling the mixture to 0°C, white crystals of

30c (2.2g, 75%) were obtained. The 2,4-diemthyloxazole-5-

carbaldehyde p-tosylhydrazone (30c) was purified by recrystallization from toluene: mp 143-145°C; IR: 3200

(N-H), 1645 C^C=N-N-), 1355 and 1170 cm“ ^ (s, sulfonyl);

NMR(CDCl^): 6 2.28(s, 3, CH^), 2.53(s, 3, CH^), 7.43(d, 2, 145

aromatic H, J = 8Hz), 8.00 (d, 2, aromatic H, J = 8Hz),

9.16(s, 1, HC=N-); exact mass; calcd. 293.08340,

obsvd. 293.08428.

Anal. Calcd for C, 53.23; H, 5.15;

N, 14.32; S, 10.93.

Found: C, 53.33; H, 5.30; N, 14.32; S, 10.83.

Ill. Decomposition of Salts of Tosvlhvdrazones.

General Procedure. The sodium salt of a tosylhydra-

zone was prepared by reaction of sodium hydride (1.1 equiv)

with the tosylhydrazone in dry methylene chloride. After

evolution of hydrogen ceased, the methylene chloride was

removed under reduced pressure. The flask containing the

dry salt was then equipped with a Vigreux column connected

to traps cooled in dry ice/2-propanol, and connected to a vacuum pump. (See figure in Part III , p. 18 5). A vacuum of

0.1-0.05 mm was pulled on the system for 1 hr before

immersing the pyrolysis flask into a preheated oil (180-

200°C) or salt (300-350°C) bath. The products of decom position distilled into the traps.

PhotoIvses. All photolyses were performed at room temperature with a Hanovia 450 watt medium pressure mercury lamp placed in a Pyrex immersion well. The well 146 •

itself was fitted with a photochemical, reactor containing

the solution to be irradiated.

Pyrolysis of the Sodium Salt of 5-Acetvl-2,4-

dimethyloxazole p-Tosylhydrazone (33a) at 180-200°C.

5-Acetyl-2/4-dimethyloxazole p-tosylhydrazone (30a, 1.53g,

0.005 m) was dissolyed in dry methylene chloride and

conyerted to its sodium salt (33a) with sodium hydride

(0.26 g of 50% NaH, 0.0055 m) . Pyrolysis of 33a was

effected as described in the General Section.

The brown-yellow oil collected in the traps (0.46 g,

75% yield) gaye a yellow liquid (bp 64-68°C/0.7 mm) on

distillation. This product was distilled twice in yacuo to

yield pure N-acetyl-3-pentyn-2-one imine (28a); IR: 2100

(m, CSC), 1715(s, carbonyl), and 1630 cm“ ^(s, C=N); NMR

(CCl^): Ô 1.81(s, 3,CH^), 2.03 (s, 3, CH^), 2.08(s, 3, CH^);

exact mass: calcd. 123.06859, obsyd. 123.06879. Imine 28a

is unstable and decomposes rapidly at room temperature.

The pot-residue after removal of 28a was chromato graphed on silica gel using petroleum ether (38-49°C): ether/1:1 as eluent. White crystalline N-[2-pent-en-3- ynyl]acetamide (29a) was obtained which was crystallized from pentane (mp 76.5-77.5°C); IR(nujol mull): 3225(m,

N-H), 2235(CSC), 1660(s, carbonyl), and 1620 cm“ ^(s, C=C); 147

NMR(CCl^); 6 1.91(s, 3, ÇH3), 2.00(s, 3, ÇH3)/ 4.86(br, 1,

CHg")/ 6.00(br, 1, CH„=), 7.00(br, 1, NH); exact mass:

calcd. 123.06859, obsvd. 123.06887.

Anal. Calcd. for C^H^NO: C, 68.19; H, 7.37; N, 11.37.

Found: C, 67.87; H, 7.38; N, 11.39.

The NMR of the crude product revealed that 28a and

29a were present in the ratio of 1:2 or 33.3% of 28a and

66.6% of 29a.

Photolvsis of the Sodium Salt of 5-Acetvl-2,4-

dimethyloxazole p-Tosylhydrazone (33a). Oxazole 30a (1.53g,

0.005 m) was converted into its sodium salt (33a) using

sodium hydride (0.26 g, of 50% NaH, 0.0055 m). The salt

(33a) was ground to a fine powder, suspended in dry ether,

and photolyzed for 2 hr under nitrogen as described in the

General Section. The resultant mixture was filtered and

the filtrate cooled to -78°C. Upon removal of the ether

at low temperatures, an oil (0.39 g, 65%) was obtained whose NMR revealed 28a and 29a to be present in a 1:2 ratio.

Hydrogenation of N-Acetyl-3-pentyn-2-one Imine (28a).

N-Acetyl-3-pentyn-2-one imine (28a, 0.06 g, 0.00048 m) was hydrogenated for 3 hr (15 psi) in ethyl acetate (20 ml) at

25° using 10% by weight of palladium/carbon as catalyst 148

(6 rag). The resulting solution was filtered through Celite

and concentrated in vacuo to give an oil identified from 17 its spectra as N-(1-raethylbutyl)acetamide (36a) ; IR; 3295

(s, N-H), and 1645 cra“^ (s, carbonyl); NMR(CCl^): 6 1.88

(s, 3, CH^CO-), 1.13(coraplex, 11, 1-raethylbutyl H); exact

raass: calcd. 129.11535, obsvd. 129.11573,.

(17) S.I. Gertler and A.p. Yerington, U.S. Dept. Agr., Agr. Research Service, Entoraol. Research Branch ARS-33-14, 12 (1955) .

Hydrogenation of N-(2-Penten-3-ynyl)acetaraide (29a).

N-(2-Penten-3-ynyl)acetamide (29a, 0.06 g, 0.0048 ra) was

hydrogenated for 3 hr. (15 psi) in ethyl acetate (20 ml) at

25°C using palladiura/carbon as catalyst (6 rag). Filtration

and concentration of the resulting solution gave N-(1-methyl- 17 butyl)acetamide (36a) identical in spectral characteristics

to 36a obtained in the previous experiment.

Reduction of the Carbon-Nitrogen Double Bond^^ in

N-Acetyl-3-pentyn-2-one Imine (28a). Sodium borohydride

(0.42 g, 0.00112 m) was added in small amounts to N-acetyl-

3-pentyn-2-one imine (28a, 0.07 g, 0.00056 m) in absolute methanol (20 ml). After the initial reaction, the mixture 149

was warmed for 3 hr and a 20% solution of sodium hydroxide

and then cold water were added. The mixture was extracted

into chloroform, dried over magnesium sulfate, and

concentrated in vacuo to give an oil that was identified

as N-(1-methyl-2-butynyl)acetamide (3la); IR: 3290 (s, N-H),

2250(w, C=C), and 1645 cm"^(s, carbonyl); NMR(CDCl^):

6 1.30 (d, 3, ÇH -CH, 9Hz), 2.08(s, 3, ÇH.), 2.15(s, 3, 3 "3 CH-), 2.30(m, 1, CH), ca. 6.52(br, 1, NH); exact mass:

calcd. 125.08405; obsvd. 125.08365.

Hydrolysis of N-Acetyl-3-pentyn-2-one Imine (28a).

N-Acetyl-3-pentyn-2-one imine (28a, 0.07 g, 0.00056 m) was

stirred overnight under nitrogen in a mixture of ethanol

(10 ml), a drop of concentrated hydrochloric acid, and

2.4-dinitrophenylhydrazine reagent (5 ml of a 0.1 M acidic

solution in ethanol). A yellow precipitate was obtained

which was recrystallized from ethanol to give 3-pentyn-2-one

2.4-dinitrophenylhydrazone (mp 147-148°C, lit.^® mp 149°C).

(18) E.A. Brande, E.R.H. Jones, F. Sondheimer, and J.B. Toogood, J. Chem. Soc., 607 (1949).

Isomerization of N-Acetyl-3-pentyn-2-one Imine (28a),.

N-Acetyl-3-pentyn-2-one imine (28a, 0.07 g, 0.00056 m) was heated under nitrogen for 1 hr in toluene. The resulting 150

mixture was then concentrated m vacuo. The NMR of the

residue revealed that the major product is N-[2-penten-3-

ynyl]acetamide (29a). Purification by chromatography on

silica gel using 1:1/petroleum ether (38-49°C); ether as

developer gave pure 29a (0.03 g, 45% yield), with spectral

properties as described on p. 145.

Pvrolvsis of the Sodium Salt of 5-Acetvl-4-methvl-2-

phenyloxazole p-Tosylhydrazone (33b) at 180-200°C.

5-Acetyl-4-methyl-2-phenyloxazole p-tosylhydrazone (30b,

1.84 g, 0.005 m) was converted to its sodium salt (33b)

using sodium hydride (0.26 g of 50% NaH, 0.0055 m) and

decomposed at 180-200° as described in the General Section.

A red-brown oil and some solid were obtained in the traps.

The oil in the traps was warmed to room temperature,

ether was added and the mixture was filtered. The ether

insoluble product (0.1 g) was identified as benzamide

from IR and NMR by comparison with an authentic sample.

Upon concentrating the filtrate in vacuo, a red oil

(0.46 g, 50%) was obtained. Distillation of the oil in vacuo yielded a yellow liquid (bp 90-100°C/0.5 mm).

Redistillation of the distillate gave pure N-benzoyl-3- pentyn-2-one imine (28b); IR; 2220 (m, Csc), 1680(carbonyl),

1640 (C=N), 1600 and 1490 cm“ ^ (aromatic ring); NMR: 6 1.81 151

(S/ 3/ ÇHg)/ 2.17(s, 3, ÇH^)/ 7.3 (complex, 3, aromatic H),

7.8(complex, 2, aromatic H); exact mass: calcd. 185.08405, obsvd. 185.08432.

The pot-residue, after distilling off 28b, and chromatography on silica gel using 2:1/ether:petroleum ether (28-40°C), yielded N-[2-penten-3-ynyl]benzamide

(29b, mp 77-80°C) as a white solid; IR(nujol mull): 3330

(s, N-H), 2230(CaC), 1665(carbonyl), 1620(C=C), 1600 and

1510 cm“^ (aromatic ring); NMR(CCl^): 6 1.89 (s, 3, CH^),

4.89(br, 1, CH2=), 6.14(br, 1, CH„=), 7.3(complex, 3, aromatic H), 7.8(complex, 2, aromatic H), 8.16(br, 1, NH); exact mass: calcd. 185.08405, obsvd. 185.08432. Both 28b and 29b are highly unstable and hence were not analyzed.

The NMR of the crude oil prior to distillation showed that

28b and 29b were present in the ratio of 1:2.5 (28.5% 28b and 71.4% 29b).

Photolvsis of the Sodium Salt of 5-Acetyl-4-methvl-

2-phenyloxazole p-Tosylhydrazone (33b). Tosylhydrazone

30b (1.84 g, 0.005 m) was converted into its sodium salt

(33b) as in the previous experiment and ground to a fine powder. The salt (33b) was suspended in dry ether and photolyzed for 2 hr under nitrogen. The solution was 152

filtered and concentrated vacuor addition of ether

(50 ml) yielded an insoluble residue. The ether-insoluble

product (0.2 g) was filtered and identified by IR and NMR

as benzamide by comparison with an authentic sample. The

NMR of the filtrate upon concentration (0.31 g, 40%)

revealed 28b and 29b to be present in a 1:2 ratio.

Hydrogenation of N-Benzoyl-3-pentyn-2-one Imine (28b).

N-Benzoyl-3-pentyn-2-one imine (28b, 0.1 g, 0.0005 m) was

hydrogenated in ethyl acetate using palladium/carbon as

catalyst (10 mg) for 3 hr at room temperature (15 psi).

The solution, after filtration and concentration in vacuo,

gave an oil which upon passage through a short column of

florisil yielded a white solid, identified as N-(l-methyl- 19 butyl)benzamide (36b) upon recrystallization from

ethanol/water (mp 72-73°C); IR: 3290(s, N-H), and 1630 cm” ^

(s, carbonyl); NMR(CDCl^): 61.30 (complex, 11, 1-methylbutyl

H), 7.53 (complex, 5, aromatic H), 6.00(br, 1, NH); exact mass: calcd. 191.13100, obsvd. 191.3159.

(19) W.C. Krueger, R.A. Johnson, and L.M. Pschigoda, J. Am. Chem. Soc., 93, 4865 (1971). 153

Hydrogenation of N-[2-Penten-3-ynyl1benzamide (29b).

N-C2-Penten-3-ynyllbenzaiTd.de (29b, 0.1 g, 0.0005 m) was

hydrogenated for 3 hr (15 pui) in ethyl acetate using

palladium/carbon (10 mg) as catalyst. Filtration and

concentration of the resulting solution gave N-(1-methyl- 1 Q butyl)benzamide (36b) identical in spectral characteristics

to 36b obtained in the previous experiment.

Reduction of the Carbon-Nitrogen Double Bond^^ in

N-Benzoyl-3-pentyn-2-one Imine (28b). N-Benzoyl-3-pentyn-

2-one imine (28b, 0.1 g, 0.0005 m) was dissolved in

methanol (20 ml) and treated with sodium borohydride

(0.40 g, 0.001 m). The mixture was warmed for 3 hr and

quenched with 20% sodium hydroxide solution and cold water.

The product was extracted into chloroform, dried and

concentrated in vacuo. The resulting yellow oil was

identified as N - (l-methyl-2-butynyl)benzamide (37b); IR:

3290(s, N-H), 2240 (CSC), and 1630 cm"*^ (s, carbonyl); NMR

(CDCI3): 6 1.33(d, 3, ÇH3-CH, 9Hz), 2.00 (s, 3, CH^), 2.47

(m, 1, CH) ; 7.60 (complex, 5,, aromatic H), 7.80 (br, 1, NH) ;

exact mass: calcd. 187.09969; obsvd. 187.09931.

Hydrolysis of N-Benzoyl-3-pentyn-2-one Imine (28b).

N-Benzoyl-3-pentyn-2-one imine (28b, 0.1 g, 0.0005 m) was stirred overnight with a drop of concentrated hydrochloric 154

acid in benzene (10 ml). A precipitate was formed which was filtered and identified as benzamide (mp 127.5-128.5°C).

The filtrate was subjected to gas chromatography-mass spectrometry on a 10' x 1/8", 10% carbowax 20M on Chromosorb

W, column at 115°C. A peak identical in mass to 3-pentyn-

2-one (^) was seen.

The solution was then treated with 2,4-dinitrophenyl hydrazine reagent (5 ml of a 0.1 M acidic solution in ethanol). The yellow precipitate obtained after recrystal lization from ethanol was identified as 3-pentyn-2-one

2.4-dinitrophenylhydrazone (mp 147-148°C, lit.^® mp 149°C).

Decomposition of the Sodium Salt of 2,4-Dimethvloxa- zole-5-carbaldehyde p-Tosylhydrazone (33c) at 180-200°C.

2.4-Dimethyloxazole-5-carbaldehyde p-tosylhydrazone (30c,

2.93 g, 0.01 m) was converted to its sodium salt (33c) in methylene chloride using sodium hydride (0.48 g of 50% NaH,

0.01 m). The dry salt (33c) was pyrolyzed at 180-200° as described in the General Section. A yellow liquid distilled into the traps.

The condensate was warmed to 0°C and ether was added.

A solid separated which was filtered (0.572 g, 52.5%) and the filtrate concentrated in vacuo at 0°C. The NMR of tl resultant oil (0.19 g, 17.5%) showed the product to be a 155

1:1 mixture of N-acetyl-3-butynone imine (28c) and

N-[2-buten-3-ynyl]acetamide (29c). Isomers 28c and 29c

were inseparable and difficult to handle because dimers

formed readily. The ether-insoluble solid could not be

identified. However, mass spectral data showed the solid

to be a dimer of 28c and 29cz exact mass: calcd. for

^12^14^2°2‘ 218.10552, obsvd. 218.10592.

The spectral characteristics of the mixture of 28c

and 29£ are: IR: 3260 (br, NH), 2230 and 2100 (CSC), 1710

and 1670 (carbonyl), 1645(C=N), and 1630 cm"^ (C=C); NMR

(CDCl^) : à 2.20 (s, 3, CH^), 2.30(s, 3, Œ ^ ) , 2.50(s, 3,

CH^), 2.86(br, 2, C C-H), 4.70(br, 1, CHg=), 5.13(br, 1,

CH„=), 8.25(br, NH); exact mass: calcd. 109.05276, obsvd. 109.05303.

Decomposition of the Sodium Salt of 2,4-Dimethvl- oxazole-5-carbaldehyde p-Tosylhydrazone (33c) in

Cvclooctane. 2,4-Dimethyloxazole-5-carbaldehyde p-tosyl hydrazone (30c, 1.46 g, 0.005 m) was converted into its sodium salt (33c), using sodium hydride (0.24 g of 50%

NaH, 0.005 m) and dried as described in the General Section.

The dry salt ( 33c) was powdered and suspended in cyclooctane (50 ml). The mixture was refluxed at 150° until 156

evolution of nitrogen ceased (— 5 min). The reaction

mixture was filtered from the insoluble residue and

concentrated vacuo. The oil that resulted was subjected

to gas chromatography-mass spectrometry on a 6 ' x 1/8",

10% SE-30, column at 220°C and then preparatively gas

chromatographed on a 10' x 1/4"; 15% SE-30 column at 220°C.

(2,4-Dimethyl-5-oxazolyl)cyclooctane (3^) was obtained as

a colorless liquid (0.066 g, 6%); IR; 2920(C-H), and 1600

cm“ ^ (C=N, oxazole ring); NMR(CDClg): 6 1.52 (complex, 15,

cyclooctyl H),2.31(s, 3, CH^), 2.40(complex, 5, CH^ and

CH„); exact mass: calcd. 221.17795, obsvd. 221.17854.

Anal. Calcd for C^^Hg^NO: C, 75.97; H, 10.47; N, 6.32.

Found: C, 76.21; H, 9.97; N, 6.14.

Decomposition of the Sodium Salt of 2,4-Dimethvl-

oxazole-5-carbaldehyde p-Tosylhydrazone (33c) in Styrene.

2,4-Dimethyloxazole-5-carbaldehyde p-tosylhydrazone (30c,

1.46 g, 0.005 m) was converted into its sodium salt (33c)

using sodium hydride (0.24 g of 50% NaH, 0.005 m) as

described in the General Section. The dry salt (33c) was

finely powdered, suspended in styrene (50 ml) and decom posed at 145°C for 5 min until evolution of nitrogen

ceased. The resulting mixture was concentrated under vacuum (0-25°C) and analyzed by gas chromatography-mass 157

spectrometry on a 6 ' x 1/8", 10% SE-30 column at 175°C.

The mixture upon preparative gas chromatography on a

6 ' X 1/4", 10% SE-30 column at 125°C gave (Z) and (E)-l-

(2, 4-dimethyl-5-oxazolyl)-2-phenylcyclopropanes (^; 0.16 g,

15%); IR; 3060 cm”^ (cyclopropyl C-H); NMR; 6 1.38 (complex

2,cyclopropyl H ) ,, 2.20(complex, 8, CH^, CH^, cyclopropyl

H), 7.13(complex, 5, aromatic H ) ; exact mass: calcd.

213.11535, obsvd. 213.11585.

Anal. Calcd for C^^H^^NO: C, 78.82; H, 7.08; N, 6.56.

Found: C, 77.4; H, 6.99; N, 6.31.

Decomposition of the Sodium Salt of 5-Acetvl-2, 4-

dimèthyloxazole p-Tosylhydrazone (33a) at 300-350°C.

5-Acetyl-2,4-dimethyloxazole p-tosylhydrazone (30a, 1.53 g,

0.005 m) upon conversion to its sodium salt (33a) with

sodium hydride (0.26 g, 50% NaH, 0.0055 m) was decomposed

at 300-350°C as described in the General Section. A brown-

yellow oil distilled into the traps (0.44 g, 71.7%). The

NMR of this crude product showed that N-acetyl-3-pentyn-

2-one imine (28a) and N-[2-penten-3-ynyl]acetamide (29a) were present in the ratio of 1:2. The mixture on analysis by gas chromatography-mass spectrometry on a 10' x 1/8",

10% carbowax 20M column at 40-120°C gave peaks corresponding to acetonitrile (41a) and pent-3-yn-2-one (42a). 158

Preparative gas chromatography on a 20' x 1/4", 10%

carbowax 20M coltunn at 110°C yielded acetonitrile (41a;

0.16 g, 37.5%), identical to an authentic sample, and on pent-3-yn-2-one (42a, 0.11 g, 25%) ; IRXCDCl^): 2220

(CaC), and 1670 cm” ^ (carbonyl) ; NMR(CDCl^) : 6 2.00 (t,. 3,

CH ), 2.66(s, 3, CH_); mass spec: m/e 82 (M^). 3

(20) P.A. Chopard, R.J.G. Searle, and P.H. Devitt, J. Ora. Chem., 30, 1015 (1965).

Decomposition of the Sodium Salt of 5-Acetvl-4-

methyl-2-phenyloxazole p-Tosylhydrazone (33b) at 300-350°C.

5-Acetyl-4-methyl-2-phenyloxazole p-tosylhydrazone (30b,

1.84 g, 0.005 m) was converted into its sodium salt (33b)

using sodium hydride (0.26 g of 50% NaH, 0.0055 m) and

decomposed at 300-350°C as described in the General Section.

A red-brown oil collected in the traps (0.69 g, 75%) was warmed to 15°C. Carbon tetrachloride was added and the

solution was filtered under nitrogen from the insoluble

residue. The insoluble product (0.09 g, 10%) was

identified as benzamide by comparison of its IR and NMR with an authentic sample. The NMR of the crude filtrate

showed that N-benzoyl-3-pentyn-2-one imine (28a) and 159

N-C2-penten-3-ynyl]benzamide (29a) were present in the

ratio of 1:1.5. Further analysis of the mixture by gas

chromatography-mass spectrometry on a 10' x 1/8", 10%

carbowax 20M column at 110-150°C revealed the presence

of benzonitrile (41b) and pent-3-yn-2-one (42b).

Preparative gas chromatography on a 20' x 1/4", 10%

carbowax 20M column at 120°C gave benzonitrile (41b;

0.23 g, 40%) identical to an authentic sample, and 20 pent-3-yn-2-one (42b, 0.15 g, 26.6%) with spectral properties identical to 42a described in the previous

experiment.

Decomposition of the Sodium Salt of 2,4-Dimethvl- oxazole-5-carbaldehyde p-Tosylhydrazone (33c) at 300-350°C.

2,4-Dimethyloxazole-5-carbaldehyde p-tosylhydrazone (30c,

2.93 g, 0.01 m) was converted into its sodium salt (33c) using sodium hydride (0.48 of 50% NaH, 0.01 m); the dry salt was pyrolyzed at 300-350°C as described in the General

Section. The yellow liquid (0.819 g, 75.2%) which dis tilled into the traps was treated with carbon tetrachloride at 15°C and filtered under nitrogen to remove insoluble dimeric products (0.32 g, 29.4%). The NMR of the crude filtrate showed the presence of N-acetyl-3-butynone imine

(28c) and N-[2-buten-3-ynyl]acetamide (29c). Further 160

analysis by gas chromatography-mass spectrometry at 80-

120°C on a 15' x 1/8", DC silicone 200 on Chromosorb P

column revealed that acetonitrile (41c) and 2-butynal

(42c) were present. The mixture was then subjected to preparative gas chromatography on a 10' x 1/4" 10% SE-30

column at 80°C and 2-butynal (42c)w a s collected; IR:

2740, 2860(aldehydic C-H), 2300 and 2210 (C=C), and

1665 cm"^ (carbonyl)7 NMR(CDCl^): Ô 2.06 (s, 3, CH^), 9.2

(s, 1, -CHO); exact mass: 68.02621.

(21) L.P. Chelpanova and G. Bondarev, Zh. Ora. Khim., 2, 1561 (1966). p a r t III

A New McPadyen-Stevens Aldehyde Method

161 STATEMENT OF THE PROBLEM

The present study involves development of a general

McPadyen-Stevens method for synthesis of aldehydes. The

objectives of this research are to (1) extend vacuum

pyrolysis of alkali metal salts of various 1-acyl-2-

arylsulfonylhydrazides (O and (2) significantly lower the

temperature of decomposition of 3^ by proper choice of

metal cation M , and the structure of the leaving group

A r S O ® (2). 6

162 HISTORICAL

In 1936 McFadyen and Stevens^^ described reaction

of l-acyl-2-arylsulfonylhydrazides (3) in alkaline medium

to yield aldehydes (4; Eq. 1).^^ The method involved

O O R-^-NH-NH-SOg-Ar + ^OH — > R-Ü-H + ArSO® + + H^O (l) 3 4

(la) J.S. McFadyen and T.S. Stevens, J. Chem. Soc., 584 (1936); (b) E. Mosettig, Ore. Reactions, VIII, 232 (1954).

decomposition of l-acyl-2-arylsulfonylhydrazides (3) by

sodium or potassium carbonates (4-6 equiv.) in ethylene

glycol or ethylene glycol-water at ça. 160°C. Later, 2 Newman and Caflish, discovered that surfaces such as powdered glass, activated charcoal, zinc dust, etc.,

accelerate and improve the conversions of 3_ to £, and that only 1 equiv. of base is needed in the presence of

surfaces.

The McFadyen-Stevens method has been frequently used for preparing stable aromatic and heterocyclic aldehydes

(2) M.S. Newman and E. Caflish, J. Am. Chem. Soc., 80, 862 (1958).

163 164

1/2 and is believed to involve the intermediacy of acylimides

(5^, Eq. 2). Efforts to isolate 5 from such processes have

been unsuccessful.

Aliphatic, alicyclic, or other base-sensitive

aldehydes have not been efficiently obtained by this method because of their instabilities in hot alkaline media and their susceptibilities to aldol condensations and

Cannizzaro reactions.^

(3a) M. Sprecher, M. Feldkimel, and M. Wilchek, J. Ore. Chem./ 26, 3664 (1961); (b) H. Babad, W. Herbert, and A.W. Stîîes, Tetrahedron Lett., 2927 (1966).

3a Sprecher and coworkers extended the McFadyen-

Stevens method to preparation of aliphatic aldehydes having no a-H atoms. For example when N '-p-tosylpival- hydrazide (6) is submitted to the usual McFadyen-Stevens conditions for 2 min, a 15% yield of pivalaldehyde (7) is obtained (Eq. 3). However, when the reaction time is 165

e (CH^)gC-CO-NH-NH-SO^-C^H^ + OH — > (CH^)^C-CHO (3)

6 7

reduced to 30 sec, 7 is found in 40% yield, thereby

demonstrating the importance of reducing the contact time

of the aldehyde with the alkaline environment.

H. Babad and coworkerssubsequently employed rapid

distillation techniques in the McFadyen-Stevens method for

synthesis of aliphatic aldehydes containing a-hydrogens.

Their method involves the addition of ^ slowly to a

refluxing aprotic solution of the base and rapid distil

lation of the products from the reaction mixture. However,

the yields of aldehydes are poor (10-35%) and side products

such as the corresponding acids and alcohols are formed.

An attempt has been made^ to reduce the severe

conditions of the McPadyen-Stevens reaction, by changing the leaving group 2 from p-tosyl to o-nitrophenylsulfenyl

(9, Eq. 4). Acyl-o-nitrophenylsulfenylhydrazides 8

(4) S. Cacchi and G. Paolucci, Gazzetta, 104, 221 (1974) .

R-C-NH-NH-S-(f~^ + B® 5 + m —f (4) -^2 M 2. O^N NO, 2 9 R — O—Cl— / p—MsO—C qH^— 166

decompose at room temperature under basic conditions.

Aromatic aldehydes were obtained in moderate yields

(20-60%). However, this method has not been generalized. RESULTS AND DISCUSSION

Oxazole-5-carbaldehydes (10^) have not been previously

described. 2,4-Dimethyloxazole-5-carbaldehyde (_y^) was

.CH3 CH I / ' t R fj R 0 O 10 11 12 12

of interest in determining the specificity of fragmentation

of 1-(5-oxazolyl)-1-alkylidenes (12/ see Results and

Discussion, Part II). A route to lA appeared to be

reduction of 5-carbethoxy-2,4-dimethyloxazole (1^).^

(5) G. Ya. Kondrateva and K. Chzhi-khén, Zh. Obshch. Khim. 32, 2348 (1962).

Diisobutyl aluminum hydride,sodium bis(2-methoxyethoxy)

aluminum hydride^^ and lithium aluminum hydride,

respectively, were employed in attempts to reduce 13.

However, none of these reagents were successful for

preparing aldehyde lA or its corresponding alcohol,

2,4-dimethyloxazole-5-carbinol. More than 90% of ester 167 168

(6a) L.I. Zakharkin and I.M. Khorlina, Tetrahedron Lett., 619 (1962); (b) J. Vit., Ora. Chem. Bull.. 42, 1 (1970); (c) L.I. Zakharkin, V.V. Gavrilenko, D.N. Maslin, and I.M. Khorlina, Tetrahedron Lett., 2087 (1963).

is recovered upon use of diisobutyl aluminum hydride or

sodium bis(2-methoxyethoxy)aluminum hydride, and with

lithium aluminum hydride no identifiable material is

obtained.

Ester ^ was then converted to 1-(2, 4-dimethyloxazole-5-carboxylic acid)-2-p-tosylhydrazide (14, Eq. 5)

for possible conversion to 11 by the McFadyen-Stevens

CH pyridine (5) .CH 3 ^NH-NH-SOg-C^H^ CH method. In following the usual procedure was decomposed with sodium carbonate (4-6 equiv.) in ethylene glycol at 160°C. Neither 2,4-dimethyloxazole-5-carbaldehyde (_H) nor starting material ( j^) was obtained and it was presumed that 11 if formed was destroyed by the 169

hot alkaline environment. Since alkali metal salts of 2 l-acyl-2-arylsulfonylhydrazides (^) are stable and isolable

and if the McFadyen-Stevens reduction involves collapse of

acylimides Eq. 2), then pyrolysis of dry salts of

l-acyl-2-arylsulfonylhydrazides (^) might lead preparatively to the corresponding aldehydes (5). If the pyrolyses are effected under vacuum the aldehydes should distill over as formed, thereby avoiding destruction by any alkaline environment and leaving behind the non-volatile aryl- sulfinate salts.

The lithium salt of was thus prepared using n-butyllithium (1 equiv.) in tetrahydrofuran. After removal of the solvent in vacuo the lithium salt was dried

(0.1 mm) and then pyrolyzed (180-200°C, 10 min) under vacuum (0.1 mm). 2,4-Dimethyloxazole-5-carbaldehyde (11) distilled into traps (-78°C) in 68% yield. The sodium salt of ^ prepared using sodium methoxide (1 equiv.) in methanol and, after removal of the solvent and drying in vacuo, decomposed at 140-155°C to give in 70% yield.

This modified McFadyen-Stevens procedure was then extended to various N-acyl-N'-tosylhydrazides in attempts to generalize the method. Table 3 summarizes the 7 aldehydes synthesized and their yields. TABLE 3

ALDEHYDES BY THE PRESENT McFADYEN-STEVENS METHOD

Yield (%) l-Acyl-2-g-to sylTiydr azi de Aldetiyde Precursor Sodium Lithium salt salt

CHg-(CHg)2-C0_NH-NH-S0^_C^H^ {1^) CH3- (CH2) 2“CH0 (^) 68 70

(CHg) 2 CH- C0-NH-NH-S02-C^H^ (17) (CH3)2CH-CH0 (18) 71 68

(CHg ) 3 C - C0-NH-NH-S02-C^H^ (^) (CH3)3C-CHO (20) 84 60

CH3- (CHg ) 3-CG-NH-NH-SÜ2-C^H^ ( 21) CH3-(CHg)3-CHO (22) 70 72

CgHg-(CH2)2-C0-NH-NH-S02-C^Hy (23) CgHg-(CH2)2-CHO (24) 85 85

CH2=CH- (CH2) g-C0-NH-NH-S02-C^H^ (25^) CH2=CH-(CH2)g-CH0 (26) 60 56

CgH3-C0_NH-NH-S02-C^H^ (27) CgHg-CHO (28) 83

£-CH3-CgH^-C0-NH-NH-S02-C^H^ (2^) £-CH3-CgH^-CHO (^) 80

p-CH30-CgH^-CO_NH-NH-S02-C^H^ (M) £_CH30-CgH^-CH0 (32) 75

^6^5\___ /H (33) A (M) 50 H CO-NH-NH-SO _C_H_ H/^ 'CHO _ CH. ' ' H* N— ^ N — <^^3 Â \ (11) 70 68 o CH o "^0-NH-NH- SO2-C7H 7 (14) c h C ^ o ^ c h o 171

(7) The yields are based on gas-chromatographic analyses on 10% carbowax 20M or 20% SE30/Chr. W columns.

From Table 3 it is seen that volatile aromatic and

aliphatic aldehydes are efficiently prepared by vacuum

pyrolysis of alkali metal salts of l-acyl-2-p-tosyl-

hydrazides. Rapid distillation of the aldehyde, as soon

as formed, makes the method suitable for synthesizing

sensitive aldehydes (such as aliphatic aldehydes possessing

O'-hydrogens) where the conventional McFadyen-Stevens

reduction normally fails.

The yield of aldehyde is lowered if more than

1 equivalent of base (sodium methoxide or n-butyllithium)

is used for preparing salts of the acyltosylhydrazides.

A possible explanation is that excess base abstracts a

second hydrogen from l-acyl-2-arylsulfonylhydrazide (3)

to give a dianion, which cannot decompose to aldehyde

4 for lack of a protic environment (Eq. 6).

35 172

The present vacutun pyrolytic method is convenient

for preparing 0.05 mole quantities of aldehydes. Larger

amounts can be prepared if the vacuum system can handle

the larger volumes of nitrogen produced rapidly. The

yields of aldehydes (especially the less volatile ones)

are lower if the pyrolysis is carried out at higher

pressures, (~10 mm) which can be attributed to inefficient

distillation of the aldehyde from solid residue.

Efforts were then directed to lowering the temper

ature of decomposition of the acylarylsulfonylhydrazide

salts (^). Potassium salts are usually less covalent than

sodium salts and thus might decompose at lower temperatures to give aldehydes. The potassium salt of l-benzoyl-2-p- tosylhydrazide (2_7), prepared from 27_ and potassium hydride (1 equiv.) decomposes at 130-140°C whereas the

sodium salt of 27_ decomposes at 140-155°C and the lithium salt of 27 at 180-200°C.

Attention was next directed to the leaving groups

(£) in ^ in order to lower the temperature of decomposi tion. l-Benzoyl-2-(2,5-dichlorobenzenesulfonyl)hydrazide

(36) was thus studied since the electron withdrawing effects of the chlorine atoms might be expected to facilitate the loss of 2,5-dichlorobenzenesulfinate (37) 173

1) n-BuLi — ^ CgHg-CHO + Ng 6 5 „ 2 ) L 36 Cl 28

Cl (7)

<^)-S02®Li®

Cl 37

from alkali metal salts of 36. The lithium salt of 3 ^ does indeed decompose at 150-160°C as compared to 180-200°C for the corresponding p-tosylhydrazide (27_) salt.

Salts of benzaldehyde p-methoxyhenzenesulfonylhydra- zone (38) have been found to decompose at significantly lower temperatures than their corresponding p-tosylhydra- p zone salts. This effect has been attributed to lowering

H lyP 8 (8) 38 + CH3O —

(8) A. Koch, private communication. 174

of double bond character between nitrogen and sulfur

(38a) by resonance electron donation by the methoxy group

as in 38b. Similarly, the lithium salt of

38a

38b ■

l-valeryl-2-(4-methoxybenzenesulfonyl)hydrazide (40)

decomposes to valeraldehyde at 160°C (Eq. 9).

n /TA 1) n-BuLi CH--(CH )--C-NH-NH-SO (/ \)— OCH_ ------^ ^ \=/ 2) 160°C, -Ng 40 ^ (9)

CH 3 -(CH 2 )3 -CHO + 39

l-p-Toluoyl-2-(2,4,6-triisopropylbenzenesulfonyl)- hydrazide (41), then prepared on the basis that 2,4,6- triisopropylbenzenesulfinate (42) should be a better leaving group than p-toluenesulfinate by virtue of steric strain. 175 CHXCHg) 2 Q ~ ‘ CH-—^ '^C-NH-NH-S—^~^— CH(CH ) . 3^ ^ " 8 M 2) a7 -N^ CH(CH3)2 41 CH(CH3)2 (10)

(:H(CHg)2

Decomposition of lithium salt of occurs at 170-180°C.

Altering the leaving group by changing the substituents

is thus of no particular advantage in lowering the

temperature of decomposition of 1.

As described earlier^ salts of acyl-o-nitrophenyl-

sulfenylhydrazides (8) decompose slowly in solution at

room temperature to yield the corresponding aldehydes

(Eq. 4). The low yields in these reactions were ascribed to competitive nucleophilic attack by the base on the carbonyl group or reductive attack on the sulfur-nitrogen bond of 8. In attempting to improve and extend this method as a low temperature synthesis of aldehydes, the dry lithium salt of 1-benzoyl-2-o-nitrophenylsulfeny1- hydrazide was heated under vacuum at 40-70°C. Benzalde hyde was obtained in < 25% yield. In a further experiment n-butyllithium was added to l-benzoyl-2-o-nitrophenyl- sulfenylhydrazide in tetrahydrofuran at -23°C and the 176 mixture was warmed to 50°C. The yield of benzaldehyde thus obtained was also < 20%. Hence salts of 8 do not

appear to be very promising for efficient synthesis of aldehydes.

The present vacuum pyrolysis is on the whole convenient for preparing aldehydes. However, there is room for further improvement. For instance the problems encountered in scaling up the decomposition might be overcome by devising a better way of adding a salt in small lots to a heated flask under vacuum. Further, the temperature of decomposition may be lowered even more if a good leaving group such as 2,4,6-triisopropylbenzenesulfinate (42) is used in conjunction with a large cation, e.g., cesium or even tetralkylammonium. Room temperature decomposition (or lower) of such salts might then allow isolation of acylimides (^) and study of their chemistry. EXPERIMENTAL

I. General Information

Melting Points. Melting points were determined

using a Thomas Hoover capillary point apparatus and are

uncorrected.

Elemental Analyses. Elemental analyses were

performed by the Scandinavian Microanalytical Laboratory,

Herlev, Denmark.

Infrared Spectra. Infrared spectra were determined

on a Perkin-Elmer Model 457 Grating Infrared Spectro

photometer. All spectra were calibrated against

polystyrene absorption at 1601 cm“^. The spectra of all

compounds were obtained from KBr wafers unless otherwise

stated.

Nuclear Magnetic Resonance Spectra. Nuclear magnetic resonance spectra were recorded on Varian A-60A or EM-360L model spectrometers.

Mass Spectrometry. Mass spectra were determined on a AEI-MS-9 mass spectrometer by Mr. C.R. Weisenberger.

Gas Chromatography. Gas chromatography was effected using a Varian Aerograph Model 920 with a thermal conductivity detector. Relative peak areas were obtained

177 178

by multiplying peak height by peak width at half height.

Where internal standards were used, relative response

factors were calculated from mixtures of known composition.

Column Chromatography. Chromatographic separations were effected on MN Laboratories' "Silica Gel for Column

Chromatography," 70-270 mesh.

II. Preparation of l-Acyl-2-p-tosylhydrazides (2^ Ar=C.yH>y)

General Procedure. The l-acyl-2-p-tosylhydrazides were synthesized from the corresponding (a) carboxylic acid esters or (b) acid chlorides. The two general procedures are as follows:

(a) The carboxylic ester (1 equiv.) was rèfluxed (5 hr) in ethanol with hydrazine hydrate (2 equiv.). On cooling the reaction mixture the acylhydrazide precipitated. The white solid was filtered and dissolved in dry pyridine, whereupon p-tosylchloride (1 equiv.) was added dropwise keeping the temperature of the mixture below 0°C. After addition was complete the mixture was stirred at room temperature overnight and poured onto an ice and hydro chloric acid mixture. The l-acyl-2-p-tosylhydrazide was obtained as a white solid. 179

(b) The acid chloride (1 equiv.) was added dropwise to

p-tosylhydrazide (1 equiv.) in pyridine at 0°C and then

stirred at room temperature overnight. The reaction

mixture was added to ice and hydrochloric acid whereupon

the l-acyl-2-p-tosylhydrazide was obtained as a white

solid.

1-(n-Butyryl)-2-p-tosylhydrazide (15^)- Butyryl- hydrazide was prepared by method a from methyl butyrate

(1.02 g, 0.01 m) and hydrazine hydrate (1.0 g, 0.02 m).

Butyrylhydrazide (1.00 g, 0.01 m) obtained (1.01 g, 99%) was treated with p-tosyl chloride (1.9 g, 0.01 m) as in method a to give 1-n-butyryl-2-p-tosylhydrazide (13; 2.15 g

85%; mp (ethanol) 127°C, lit.^^ mp 125~127°C); exact mass; calcd. 256.08815; obsvd. 256.08879.

l-Isobutyryl-2-p-tosylhydrazide ( ^ ) . Isobutyryl- hydrazide (1.00 g, 0.009 m), prepared (method a) from methyl isobutyrate (1.02 g, 0.01 m) and hydrazine hydrate

(1.0 g, 0.02 m), was reacted with p-tosylchloride (method a, 1.9 g, 0.01 m) to yield l-isobutyryl-2-p-tosylhydrazide

(17; 2.09 g, 83%; mp (ethanol) 131-132°C, lit.^^ mp 130-

132°C); exact mass: calcd 256.08815; obsvd, 256.08879.

l-Pivaloyl-2-p-tosylhydrazide (1^). Pivaloyl chloride (6.02 g, 0.05 m) reacted with p-tosylhydrazide 180

(9.3 g, 0.05 m) according to method b to form 1-pivaloyl-

2-2-tosylhydrazide ( l.Og, 81%; mp (ethanol) 157-158°C,

lit.^^ mp 158-160°C); exact mass; calcd. 270^-10380; obsvd. 270.10447.

1-Valeryl-2-p-tosylhydrazide (21.). Valeryl chloride

(6.02 g, 0.05 m) when treated with p-tosylhydrazide (9.3 g,

0.05 m) according to method b yielded 1-valeryl-2-p- tosylhydrazide (2^; 10.8 g, 85%; mp (ethanol/water) 98-

100°C); IR: 3210 (N-H), 1679(carbonyl), 1340 and 1170 cm“ ^

(sulfonyl); NMR(CDCl^): 6 1.03(complex, 7, C^H^), 2.03

(complex, 3, -CH„-CO-), 2.40(s, 3, CH^), 7.26 and 8.0

(complex, 4, aromatic H), 8.3(br, N-H); exact mass: calcd. 270.10380; obsvd. 270.10447.

1-Hydro cinnamoyl- 2-p-to sylhydrazide ( ^ ) . Hydro- cinnamoyl chloride (8.43 g, 0.05 m) and p-tosylhydrazide

(9.3 g, 0.05 m) were reacted according to method b to yield l-hydrocinnamoyl-2-p-tosylhydrazide (23; 13 g, 82%; mp (ethanol): 145-147°C, lit.^ 177-178°C); exact mass: calcd. 318.10380; obsvd. 318.10445.

(9) A. Bhati, R.A.W. Johnstone and B.J. Millard, J. Chem. Soc. (C), 358 (1966). 181

1- ( 10-Undecenoyl) -2-jg-tosylhydrazide (2^).

jg-Tosylhydrazide (9.3 g, 0.05 m) and 10-undecenoyl

chloride (10.12 g, 0.05 m) (method b) gave l-(10-undecenoyl)

2-£-tosylhydrazide (2^, 12.3 g, 70%; mp (ethanol) 98-99°C),

IR: 3330 (N-H), 1670(carbonyl), 1345 and 1160 cm“ ^

(sulfonyl); NMR(CDCl-): Ô 1.30 and 2.30(complex, 16,

-(CH„)p-), 2.40(s, 3, CH-), 4.83(complex, 1, ), ^ a j H H 5.06 (complex, 1, / -- \ ), 5.86 (complex, 1, ), H H g 7.30 and 7.83(complex, 4, aromatic H), 8.50(br, 1, NH);

exact mass: calcd. 352.18205; obsvd. 352.18281.

Anal. Calcd. for C^gH^gNgOgS: C, 61.33; H, 8.00; N, 7.94;

S, 9.09.

Found: C, 61.46; H, 8.00; N, 7.88;

S, 9.10.

If the temperature is not controlled during the

reaction, bis-(10-undecenoyl)-tosylhydrazide is obtained

as an impurity. Chromatographic separation on silica using

1:9, ethylacetate :benzene as eluent becomes necessary to get pure 25.

1-Cinnamoyl-2-p-tosylhydrazide ( ^ ) . Cinnamoyl chloride (5.52 g, 0.033 m) and p-tosylhydrazide (6.16 g,

0.033 m) according to method b yields l-cinnamoyl-2-p- tosylhydrazide (^; 8 g, 80%; mp (ethanol) 185-186°C); 1 8 2

IR; 3340(N-H), 1660(carbonyl), 1639(C=C), 1350 and 1170

cm"^ (sulfonyl); NMR(CDCl-): ô 2.30(s, 3, Œ _ ) , 6.36 (d, 1, CLH_ H N— / , J = 16 Hz), 7.56(complex, 10, aromatic H and

C.H^ H \ — / ); exact mass: calcd. 316.08815; obsvd. H 316.08891.

Anal. Calcd for C^gH^^NgOgS: C, 60.74; H, 5.09; N, 8.85;

S, 10.13.

Found: C,60.73; H, 5.18; N, 8.81;

S, 10.08.

If during reaction the temperature rises above 0°C, bis-cinnamoyl-p-tosylhydrazide is also obtained.

Purification of ^ is achieved by chromatographic separation on silica gel using 1:1 benzene:ethylacetate as eluent.

1-(2,4-Dimethyloxazole-5-carboxylic acid)-2-p-tosyl hydrazide (1£). 2,4-Dimethyloxazole-5-carboxylic acid hydrazide (7 g, 0.045 m) prepared according to method a 5 from 5-carbethoxy-2,4-dimethyloxazole (13; 8.4 g, 0.05 m) and hydrazine hydrate (5 g, 0.01 m) reacts with p-tosyl chloride (8.6 g, 0.045 m) as described in method a to give

1-(2,4-dimethyloxazole-5-carboxylic acid)-2-p-tosylhydrazide

(14; 10 g, 72%; mp (ethanol) 169-170°C): IR: 3330(N-H),

1670(carbonyl), 1345 and 1160 cm“ ^ (sulfonyl); NMR(CDCl^): 183

6 2.26(s, 3, Œ g ) , 2.40(s, 3, ÇH3) / 2.46(s, 3, ÇH^),

7,30 and 7.86(conplex 4, aromatic H), 8.50{br, N-H);

exact mass: calcd. 309.02831; obsvd. 309.02900.

Anal. Calcd for C^^H^gN^O^S: C, 50.47; H, 4.88; N, 13.58;

S, 10.36.

Pound: C, 50.47; H, 4.91; N, 13.40;

S, 10.34.

l-Benzoyl-2-2 T-to sylhydrazide (2%) . p-Tosylhydrazide

(9.3 g, 0.05 m) and benzoyl chloride (7.02 g, 0.05 m)

as in method b yields l-benzoyl-2-p-tosylhydrazide (27 ;

13.05 g, 90%; mp (ethanol) 172-173°C, lit.^° mp 175-176°C);

exact mass: calcd. 290.07250; obsvd. 290.07374.

(10) G.P. Schiemenz and H. Engelhard, Chem. Ber.,'92, 1336 (1959).

1-(p-Toluoyl)-2-p-tosylhydrazide (^) . According to

method b p-toluoyl chloride (15.4 g, 0.1 m) reacts with p-tosylhydrazide (18.6 g, 0.1 m) to give 1- (p-toluoyl)-2- p-tosylhydrazide^^ (29, 25.8 g, 85%, mp(ethanol) 195-196°C);

exact mass: calcd. 304.08815; obsvd. 304.08885.

(11) L. Secchi, A. Frigerio, 0. Attanasi, L. Caglioti, and P. Gasparrini, Ann. Chim. (Rome), 65, 37 (1975). 184

room temperature for 45 min; (3) removal of solvent; and

(4) drying the salt vacuo (0.1 mm, 1 h). Decomposition

of the dry lithiüm salt at 180-200°C (0.1 mm) for 10 min

gave the corresponding aldehyde which distilled through a

Vigreux column into traps cooled to -78°C (see Figure 1).

Table !4 gives the aldehydes and their yields by

procedures a and/or b.

The pyrolytic method is convenient for decomposing

up to 0.05 m quantities of salts of acyltosylhydrazides.

For larger amounts a vacuum system that can handle the

large volumes of nitrogen produced rapidly is needed. A

large Pyrex flask connected to the vacuum system will usually handle the pressure surges that may occur (see

Figure 1 ). A major drawback in decomposing large amounts

(10-15 g) of acyltosylhydrazide salts is the inefficient transmission of heat through the entire solid being heated

and therefore incomplete decomposition and low yields.

A practical pressure for decomposition is 0.1 mm. When higher pressure (> 10 mm) is used slow distillation of less volatile aldehydes causes a drop in the yields unless prolonged heating is effected (20-30 min). Heating Tape ■> Vacuum

3£ Flask Vigreux Column

Dry Ice Traps Pyrolysis Flask

Oil or Salt Bath

Figure 1. Vacuum Pyrolysis Apparatus TABLE 4

DECOMPOSITION OF SODIUM AND LITHIUM SALTS OF 1-ACYL-2-&-T0SYLHYDRAZIDES

Based equiv.)ml Yield (%) G.C. Column l-Acyl-2-E-tosyl- Aldebyde Method temperature, hydrazide (a) (b) NaOCH- n-BuLi (a) (b) internal I.IM soln 2.4M soln standard

15 (2.56g, 0.01m) 9.09 4.16 CH^- (CH^) 2-CHO ( W 68 70 10% Carbowax 20M (I4.5'x%") ( 5 4°C , i sobutyr- aldehyde) 17 (2.56g, 0.01m) 9.09 4.16 (CH3) 2-CH-CHO (^) 71 68 (54 C, n-butyr- aldehyde) 19 (2.70g, 0.01m) 9.09 4.16 (CH3)3-C-CHO (20) 84 60 " (80°C,valeraldehyde)

21 (2.70g, 0.01m) 9.09 4.16 CH^CCH^) 3-CHO (2^) 70 72 (94 C, n-butyr- aldehyde)

23 (1.59g, 0.005m) 4.54 2.08 CgHg-(CH2)2-CH0 (24) 85 85 (230 cinnam aldéhyde)

25 (1.76g, 0.005m) 4.54 2.08 CH2=CH(CH2)q-CHO (26) 60 56 20% SE 30/Chr.W (15'X ^")(220°C benzaldehyde)^ 00 o\ Table (continued)

1-Acyl-2-g-tosyl- G.C. column bydrazide NaOCHg n-BuLi Aldebyde Method temp./ (a) (b) internal I.IM soln 2.4M soln standard

27 (1.45g, 0.005m) 4.54 2.08 CgH^-CHO (28^) 83 20% SE 30/Cbr W (15'X h " ) (220°C benzaldehyde)

22 (1.52g, 0.005m) 4.54 2.08 p-CH^-C^H^-CHO (30) 80 (180 C, benz- aldebyde)

31 (1.60g, 0.005m) 4.54 2.08 p-CH^O-CgH^CHO (^) 75 (220°C, benz- aldebyde)

33 (2.61g, 0.008m) 7.27 3.33 / (34) 50 (220"c, benz- CHO aldebyde)

14 (2.5g, 0.008m) 7.27 3.33 (11) 70 68 10% carbowax 20M (17.5' xh") (200°C, benz- aldebyde).

09 188

IV. Miscellaneous l-Acvl-2-arvlsul£onvlhvdrazides

l-Benzovl-2-(2,5-dichlorobenzenesulfonvl)hydrazide

(36). Benzoylhydrazide (1.36 g, 0.01 m) prepared from

benzoyl chloride (1.4 g, 0.01 m) and hydrazine hydrate

(1.0 g/ 0.02 m) was dissolved in pyridine (10 ml) at 0°C.

2/5-Dichlorobenzenesulfonyl chloride (2.45 g, 0.01 m) was

added slowly at 0°C. The mixture then was stirred at room

temperature for 1 hr and poured into ice/hydrochloric acid to give 1-benzoyl-2-(2,5-dichlorobenzenesulfonyl)hydrazide

(36; 2.5 g, 72%; mp (ethanol) 187-188°C); exact mass; calcd. 343.97891; obsvd. 343.97967.

Pvrolvsis of the Lithium Salt of l-Benzovl-2(2,5- dichlorobenzenesulfonyl)hydrazide (36). The lithium salt was prepared by adding n-butyllithium (2.08 ml, 2-4 M soln in hexane, 0.005 m) to ^ (1.7 g, 0.005 m) in tetrahydro furan according to method III (b). The dry lithium salt on pyrolysis at 150-160°C yielded benzaldehyde (55%, analyzed on 20% SE 30/Chr. W at 220° with benzonitrile at internal standard).

l-Valeryl-2-(4-methoxybenzenesulfonyl)hydrazide (40)« 12 4-Methoxybenzenesulfonylhydrazide was prepared by adding

4-methoxybenzenesulfonyl chloride (10.33 g, 0.05 m) in 189

carbon tetrachloride dropwise to hydrazine hydrate (5 g,

0.1 m)/ keeping the temperature below 20°C. After stirring

the mixture for 2 hr the precipitate of (4-methoxybenzene- 12 sulfonyl)hydrazide was filtered (8.7 g, 86%). The hydrazide

formed (4.04 g, 0.02 m), on dissolution in dry pyridine

(15 ml) and treatment with valeryl chloride (2.41 g, 0.02 m)

according to method II (b), gave l-valeryl-2-(4-methoxy

benzenesulfonyl )hydrazide (;^; 4.5 g, 80%; mp (ethanol)

95°; exact mass: calcd. 286.09871; obsvd. 286.09945.

(12) A.B. Dzhidzhelava, M. Ya. Konovalova, V.I. Kostenko, and N.N. Dykhanov, Zh. Obshch. Khim., 35, 831 (1965).

Pvrolvsis of the Lithium Salt of l-Valeryl-2-(4- methoxybenzene sulfonyl) hydrazi de (^) . The lithium salt of

40 was prepared according to method III (b) from 40 (2.86 g,

0.01 m) and n-butyllithium (4.16 ml, 2.4 M soln in hexane,

0.01 m). The dry salt pyrolyzed at 160°C to yield benzaldehyde (65%, analyzed on 20% SE 30/Chr. W at 220° with benzonitrile as internal standard).

l-p-Toluoyl-2-[2,4,6-triisopropylbenzenesulfonyl) hydrazide (^) . p-Toluoyl chloride (4.08 g, 0.025 m) and

2,4,6-triisopropylbenzenesulfonylhydrazide (7.45 g, 0.025 m) 190

according to method II (b) yielded l-p-toluoyl-2-(2,4,6-

triisopropylbenzenesulfonyl)hydrazide (8.92 g, 85%; mp

(ethanol) 201-202°C}; exact mass; calcd. 416.21334;

obsvd. 416.21317.

Pvrolvsis of the Lithium Salt of l-p-Toluovl-2-

(2,4,6-triisopropylbenzenesulfonyl)hydrazide. The lithium

salt of (1.04 g, 0.0025 m) was made using n-butyl

lithium (1.04 ml, 2.4 M soln in hexane, 0.0025 m)

according to method III (b). The dry salt, on pyrolyses

at 170-180°C, gave p-tolualdehyde (72%, analyzed on 20%

SE 30/Chr. W at 180° using benzaldehyde as internal standard). REFERENCES

PART I

1. W. von E. Doering and C.H. DePuy, J. Am. Chem. Soc., 75, 5955 (1953).

2. R. Gleiter and R. Hoffmann, J. Am. Chem. Soc., 90, 5457 (1968).

3. E. Wasserman, L. Barash, A.M. Trozzolo, R.W. Muwayand and W.A. Yager, J. Am. Chem. .Soc., 86, 2304 (1964).

4. a. R.A. Moss, J. Pro. Chem., 3296 (1966). b. R.A. Moss and J.R. Przybyla, ibid.,33, 3816 (1968).

5. H. Durr and F. Werndorf, Anqew. Chem. Int. Edn., 13, 483 (1974).

6. a. H. Durr and H. Kober, Anqew. Chem. Int. Edn., 10, 342 (1971). b. H. Durr and H. Kober, Tetrahedron Lett., 1259 (1972). c. H. Durr, H. Kober, V. Fuchs, and P. Orter, Chem. Comm., 973 (1972). d. M. Jones, Jr., A.M. Harrison, and K.R. Pettig, J. Am. Chem. Soc., 9^, 7462 (1969). e. D. Schonleber, Chem. Ber., 102, 1789 (1969).

7. H. Durr, H. Kober, I. Holberstadt, U. Neu, T.T. Coburn, T. Mitsuhashi, and W.M. Jones, J. Am. Chem. Soc., 95, 3818 (1973).

8. a. H. Durr and G.S. Scheppers, Chem. Ber., 103, 380 (1970). b. H. Durr and L. Schrader, ibid., 102, 2026 (1969).

9. a. F. Angelico, Atti. Acad. Naz. Lincei., 14, II, 167 (1905). b. R.F. Bartholomew and J.H. Tedder, J. Chem. Soc., (C), 1601 (1968).

10. a. M. Nagarajan, Ph.D. Thesis, The Ohio State University (1978). b. M. Nagarajan and H. Shechter, J. Am. Chem. Soc., 101, 2198 (1979). 191 192

11. J.M. Tedder and B. Webster, J. Chem. Soc., 1638 (1962).

12. E. Meyer, J. Prakt. Chem., 90, 1 (1914).

13. a. D.G. Farnum and P. Yates, Chem. and Ind., 659 (1960). b. D.G. Farnum and P. Yates, J. Am. Chem. Soc., 84, 1399 (1962). c. H. Relmlinger, A. von Overstraeter, and H.G. Viehe, Chem. Ber., 94, 1036 (1961). d. H. Relmlinger and A. von Overstraeter, ibid., 3350 (1966).

14. a. W.L. Magee, Ph.D. Thesis, The Ohio State University, 1974. b. W.L, Magee and H. Shechter, J. Am. Chem. Soc., 99, 633 (1977).

15. Y.F. Shealy, R.F. Struck, L.B. Holum, and J.A. Montgomery, J . Orq. Chem., 26, 2396 (1961).

16. U.G. Kang and H. Shechter, J. Am. Chem. Soc.,, 100, 651 (1978).

17. W.A. Sheppard and O.W. Webster, J. Am. Chem. Soc., 9^, 2697 (1973).

18. a. E. Melendez and J. Vilarrasa, An. Quim., 70, 966 (1974). b. J. Vilarrasa and R. Grandes, J . Het. Chem., 11 867 (1974).

19. K.L. Kirk and L.A. Cohen, J. Am. Chem. Soc., 95, 4619 (1973).

20. J.M. Tedder In; Advances in Heterocvclic Chemistry, Vol. 8, Academic Press, New York, 1967, p. 18.

21. J. Thiele, Ann. Chem., 270, 46 (1892).

22. a. P.B. Shevlin, J. Am. Chem. Soc., 94, 1379 (1972). b. P.B. Shevlin and S. Kammula, ibid., 99, 2617 (1977). c. S.F. Dyer and P.B. Shevlin, ibid., 101, 1303 (1979). 193 23. B.T. Storey, W.W. Sullivan, and C.L. Mayer, J. Orq. Chem., 29, 3118 (1964).

24. P.P. Caspar and G.S. Hammond in Carbenes, Vol. II, J. Wiley and Sons, 1975, p. 207.

25. a. V. Franzen and L. Fikentschen, Ann. Chem., 617, 1 (1958). b. W. Kirmse, Carbene Chemistry, Academic Press, New York and London, 1971, p. 430.

26. Diazodiphenylmethane apparently reacts carbenically with alcohols to give ethers via a betaine mechanism; D. Bethell, A.R. Newall, G. Stevens, and D. Whittaker, J. Chem. Soc., B, 749 (1969).

27. High Resolution NMR Spectra Catalog, Varian Associates, 1962, Spectrum No. 100.

28. a. W.L. Jorgensen and L. Salem, The Organic Chemists Book of Orbitals, Academic Press, New York, 1973, p. 234. b. S.F. Dyer and P.B. Shevlin, J. Am. Chem. Soc., 101, 1303 (1979).

29. W. Ando, Acc. Chem. Res., 10, 181 (1977) .

30. a. W. Ando, T. Yagihara, S. Tozune, I. Imai, J. Suzuki, T. Toyama, S. Nakaido, and T. Migita, J. Org. Chem., 1721 (1972). b. W. Ando, J. Suzuki, Y. Saiki, and T. Migita, Chem. Comm., 365 (1973). c. W. Ando, Y. Saiki, and T. Migita, Tetrahedron, 29 3511 (1973).

31. R.J. Gillespie, J. Murray-Rust, P. Murray-Rust, and A.E.A. Porter, Chem. Comm., 83 (1978).

32. I.B.M. Band, D. Lloyd, M.I.C. Singer, and F.I. Wasson Chem. Comm., 544 (1966).

33. The assignments made are based on gated and off- resonance C-NMR studies.

34. a. F.J. Weigert and J„D. Roberts', Inorg. Chem., 12, 313 (1973). b. W. McFarlane, J. Chem. Soc., A, 1660 (1967). c. E. Bullock, D.G. Tuck, and E.J. Woodhouse, J. Chem. Phvs., 38, 2318 (1963). 194

35. J.A. Pople, W.G. Schneider, and H.J. Bernstein, High Resolution Nuclear Magnetic Resonance, McGraw- Hill, New York, 1959, p. 102.

36. A.W. Johnson, Ylid Chemistry, Academic Press, New York and London, 1966, p. 260.

37. Photolysis of bis(trifluoromethyl)diazomethane and benzene gives the valence isomer (analogous to 117) of 7,7-bis(trifluoromethyl)cycloheptatriene; D.M. Gale, W.J. Middleton, and C.G. Krespan, J. Am. Chem. Soc., 8%, 657 (1965); ibid., 88, 3617 (1966).

38. Photolysis of diazocyclopentadiene (3_) in benzene at lower temperatures results in increased ring expansion as compared to substitution.

39. H. Walba and R.W. Isensee, J. Org. Chem., 26, 2789 (1961).

40. D.S. Wulfman, G. Linstrumelle, and C.F. Cooper, The Chemistry of Diazo and Diazonium Groups, Part 2, J. Wiley & Sons, 1978, p. 935.

41. a. The assignments of the benzene substitution products as ortho, meta, or _para-substituted phenylimidazoles were made by (1) comparison with literature physical constants and/or (2) by analyses of their 650-1000 cm-1 infrared absorptions. Strong bands for benzene derivatives in the 650- 1000 cm-1 region are due to out-of-plane deformation vibrations of hydrogen atoms. The specific absorptions for substituted phenylimidazoles (see Experimental) allow reliable recognition of the type of substitution, except when the benzene ring is heavily substituted with highly polar groups such as nitro or fluoro. b. L.J. Bellamy, The Infrared Spectra of Complex Molecules, Chapnan and’ Hall, London, 1975. c. All p-substituted phenylimidazole derivatives of the present study other than 2-(4-nitrophenyl)- imidazole exhibit characteristic aromatic AgBgNMR patterns. 195

42. A similar dimethylation reaction occurs during decomposition of 3-diazopyrrole M in N,N-dimethyl- anilinelO and is believed to involve a nitrogen ylide,

43. M.J.S. Dewar and K. Narayanaswami, J. Am. Chem. Soc. 86, 2422 (1964).

44. L.E. Hihkel, G.O. Richards, and O. Thomas, J. Chem. Soc., 1437 (1937).

45. a. J.A. Berson, Acc. Chem. Res., 1, 152 (1968); b. F.G. Klaner, Anqew. Chem. Int. Edn., 13, 268 (1974). c. J.A. Berson, P.W. Grubb, R.A. Clark, D.R. Harter, and M.R. Willcott, III, J. Am. Chem. Soc., 89, 4076 (1967).

46. The structure of 154 is as yet unclear. The IR spectrum of 154 has no well defined bands and the NMR spectrum shows only the presence of aromatic protons and/or imidazole protons.

47. J. Glinka, The Ohio State University, unpublished results.

48. O.W. Webster, private communication.

49. a. M. Jones, J. Orq. Chem., 33, 2538 (1968). b. W.L. Magee, The Ohio State University, private communication.

50. Orq. Svn., Coll. Vol. II, 411.

51. W.J. Eilbeck and F. Holmes, J. Chem. Soc. A, 3.1, 1777 (1967).

52. K. Fromherz and H. Spiegelberg, Helv. Phvsiol. et Pharmacol. Acta, 6, 42 (1948).

53. A. Klages, Ber., 2638 (1902).

54. B. Krieg, R. Schlegel, and G. Manecke, Chem. Ber., 107, 168 (1974).

55. P. Franchetti and M. Grifantini, J. Het. Chem., 7 1295 (1970).

56. a. Beil 5, 227. b. The Sadtler Standard Spectra, IR: 4544; NMR; 207. 196

57. a. Belgium Patent/ 660,836 (Sept. 9, 1965); Chem. Abstr., 63, P18097d (1965). b. Neth. Appl. Patent 6,605,106 (Cot.17, 1966); Chem. Abstr. 66, P37928x (1967).

58. P.L. Pyman and E. Stanby, J. Chem. Soc., 125, 2484 (1924) .

PART II

1. a. G.G. Vander Stouw, Piss. Abstr., 25, 6974 (1965). b. R.C. Joines, A.B. Turner, and W.M. Jones, J. Am. Chem. Soc., 91, 7754 (1969). c. P. Schissel, M.E. Kent, D.J. McAdoo, and E. Hedeya, ibid., 92, 2147 (1970). d. C. Wentrup and K. Wilczek, Helv. Chim. Acta, 53, 1459 (1970) . e. W.G. Barbon, M. Jones, Jr., and P.P. Gaspar, J. Am. Chem. Soc., 9^, 4739 (1970). f. G.G. Vander Stouw, A.R. Kraska, and H. Shechter, ibid., 94, 1655 (1972) . g. T. Mitsuhashi and W.M. Jones, ibid., 94, 677 (1972) . h. K.E. Krajca, T. Mitsuhashi, and W.M. Jones, ibid. 3661 (1972). i. W.M. Jones, R.C. Joines, J.A. Meyers, T. Mitsuhashi, K.E. Krajca, E.E. Waali, T.L. Davis, and A.B. Turner, ibid., 95, 826 (1973). j. R.L. Tyner, W.M. Jones, Y. Ohrn, and J.R. Sabin, ibid., 9^, 3765 (1974). k. T.T. Coburn and W.M. Jones, ibid., 96, 5218 (1974). 1. C. Wentrup, Tetrahedron, 30/ 1301 (1974). m. R. Gleiter, W. Rettig, and G. Wentrup, Helv. Chim. Acta, 5%, 2111 (1974) .

2. a. W.D. Crow and C. Wentrup, Tetrahedron Lett., 6149 (1968). b. C. Wentrup, Chem. Comm., 1386 (1969). c. C. Mayor and C. Wentrup, J. Am. Chem. Soc., 97. 7467 (1975). d. C. Theitaz and C. Wentrup, ibid., 98, 1258 (1976). 197 3. R.y. Hoffman, G.G. Orphanides, and H. Shechter, J. Am. Chem. Soc., 100, 7927 (1978).

4. R. Gleiter and R, Hoffman, J. Am. Chem. Soc., 90, 5457 (1968).

5. R.V. Hoffman and H. Shechter, J. Am. Chem. Soc., 100, 7934 (1978).

6. W.S. Trahanovsky and D.L. Alexander, J. Am. Chem. Soc. 101, 142 (1979).

7. D.J. Houser, M.S. Dissertation, The Ohio State University, 1973.

8. Study of system 2^ was initiated by S-I. Hayashi, a post-doctoral fellow at The Ohio State University.

9. A. Dorrow and H. Hill, Chem. Ber., 93, 1998 (1960).

10. G. Ya Kondrateva and K. Chzhi-khen, Zh. Obshch. Khim. 2348 (1962).

11. a. L.I. Zakharkin and I.M. Khorlima, Tetrahedron Lett., 619 (1962). b. J. Vit., Org. Chem. Bull., 42, 1 (1970). c. L.I. Zakharkin, V.V. Gavrilenko, D.N. Maslin, and I.M. Khorlina, Tetrahedron Lett., 2087 (1963).

12. M. Nair and H. Shechter, J. Chem. Soc., Chem. Comm., 793 (1978).

13. Product identification is described in the Experi mental Section.

14. J.H. Bellman and A.C. Diesing, J. Org. Chem., 22, 1068 (1957).

15. E.R. Buchman and E.M. Richardson, J. Am. Chem. Soc., 395 (1945) .

16. D.J. Brown and P.B. Ghosh, J. Chem. Soc. (B), 270 (1969).

17. S.I. Gertler and A.P. Yerington, U.S. Dept. Agr., Agr. Research Service, Entomol. Reserach Branch ARS-33-14, 12 (1955). 1.98

18. E.A. Brande, E.R.H. Jones, P. Sondheimer, and J.B. Toogood, J. Chem. Soc., 607 (1949).

19. W.C. Krueger, R.A. Johnson, and L.M. Pschigoda, J. Am. Chem. Soc., 93, 4865 (1971).

20. P.A. Chopard, R.J.G. Searle, and F.H. Devitt, J. Org. Chem., 1015 (1965).

21. L.F. Chelpanova and G. Bondarev, Zh. Orq. Khim., 2, 1561 (1966).

PART III

1. a. J.S. McFadyen and T.S. Stevens, J. Chem. Soc., 584 (1936). b. E. Mosettig, Orq. Reactions, VIII, 232 (1954) .

2. M.S. Newman and E. Caflish, J. Am. Chem. Soc., 8J), 862 (1958).

3. a. M. Sprecher, M. Feldkimel, and M. Wilchek, J. Orq. Cnem., 26, 3664 (1961;. b. H. Babad, W. Herbert, and A.W. Stiles, Tetrahedron Lett., 2927 (1966).

4. S. Cacchi and G. Paolucci, Gazzetta, 104, 221 (1974).

5. G. Ya. Kondrateva and K. Chzhi-khen, Zh. Obshch. Khim. 32, 2348 (1962).

6. a. L.I. Zakharkin and I.M. Khorlina, Tetrahedron Lett., 619 (1962) . b. J. Vit., Orq. Chem. Bull., U, 1 (1970). c. L.I. Zakharkin, V.V. Gavrilenko, D.N. Maslin, and I.M. Khorlina, Tetrahedron Lett., 2087 (1963).

7. The yields are based on gas-chromatographic analyses on 10% carbowax 20M or 20% SE30/Chr. W. columns.

8. A Koch, private communication.

9. A. Bhati, R.A.W. Johnstone and B.J. Millard, J. Chem. Soc. (C), 358 (1966). 199

10. G.P. Schiemenz and H. Engelhard, Chem. Ber., 92, 1336 (1959).

11. L. Secchi, A. Prigerio, 0. Attanasi, L. Caglioti, and P. Gasparrini, Ann. Chim. (Rome), 65, 37 (1975).

12. A.B. Dzhidzhelava, M. Ya. Konovalova, V.I. Kostenko, and N.N. Dykhanov, Zh. Obshch. Khim., 35, 831 (1965).