Glyoxylyl Chloride p-Toluenesulfonylhydrazone1

[14661-69-9]  · C9H10ClN2O3S  · Glyoxylyl Chloride p-Toluenesulfonylhydrazone  · (MW 261.73)

(synthesis of a-diazo esters and amides2)

Physical Data: mp 103-110 °C (dec).

Solubility: sol methylene chloride, chloroform, THF, and warm benzene.

Preparative Methods: not commercially available; however, it can be prepared readily by the reaction of p-Toluenesulfonylhydrazide and Glyoxylic Acid.2

Handling, Storage, and Precautions: anhydrous conditions are required; it is advisable to prepare the reagent freshly prior to use.

Introduction.

Glyoxylyl chloride p-toluenesulfonylhydrazone (1) is a versatile reagent for the synthesis of diazoacetyl esters and amides, which upon heating in the presence of a metal catalysts or irradiation generate reactive carbene intermediates.1 Compound (1) undergoes reaction with alcohols to give the corresponding a-diazoacetyl esters under mild basic conditions. Typically, 2 equiv of Triethylamine are used in this reaction (eq 1). However, sulfinate species have been reported to contaminate the product.1b Corey and Meyers have shown that the formation of this undesired byproduct can be largely circumvented by the use of N,N-dimethylaniline instead of Et3N (eq 2).1b

The existing alternative preparative methods for the a-diazo esters, such as diazotization of glycine esters,3 pyrolysis of N-acyl-N-nitrosoglycine esters,4 base-catalyzed cleavage of a-diazo-b-ketoacetates,5 reactions of alkoxycarbonylmethylenephosphoranes with arenesulfonyl azides,6 or acid-catalyzed decomposition of acetic esters with aryltriazene substituents,7 all suffer from the disadvantage of being multistep synthetic procedures, and that at times harsh conditions (high temperature, strong acid or base) must be employed.

Intramolecular Cyclopropanation.

The resultant a-diazoacetyl ester from the reaction of (1) and an unsaturated alcohol undergoes cyclization in the presence of transition metals to give cyclopropyl derivatives (eqs 3, 4); the reaction proceeds via an intermediary carbene species.1 Owing to the geometric constraints of the intramolecular cyclopropanation, the substituents and the product acquire all-cis configurations.2 This is in contrast to the bimolecular cyclopropanation, which is unable to achieve sterochemical control, resulting in mixtures of products.

C-H and C-C Carbene Insertion Reactions.

Intramolecular carbene insertion at an unactivated bridgehead site is reported from an a-diazoacetyl ester precursor (eq 5).8

Decomposition of 6-(a-diazoacetamide)penicillanate in the presence of copper(II) or rhodium(II) in refluxing benzene resulted in the formation of a cycloheptatriene moiety (eq 6).9

Photoaffinity Labels.

As an application of the carbene insertion reaction in structural studies of macrobiomolecules, radioactively labeled a-diazo esters have been used as photoaffinity labels.10 Such esters are designed to bind specific targetted biological receptors (e.g. enzymes, membrane receptor proteins, nucleic acids, etc.). Photolysis of the complex generates the high-energy carbene species that inserts into C-H or X-H (X = a hetero atom) bonds in the receptor molecule readily at ambient temperature. In the absence of a facile insertion reaction, the resultant unquenched carbene may undergo Wolff rearrangement, thereby wasting a percentage of the reactive species for photoaffinity labeling.11 The structures of a number of such biologically active molecules are shown in (2)-(9); these molecules are prepared typically by the reaction of reagent (1) with the corresponding alcohols in moderate to good yields.10


1. (a) House H. O.; Blankley, C. J. JOC 1968, 33, 53. (b) Corey, E. J.; Myers, A. G. TL 1984, 25, 3559; Corey, E. J.; Myers, A. G. JACS 1985, 107, 5574. (c) Ramaiah, M.; Nagabhushan, T. L. SC 1986, 16, 1049. (d) Clive, D. L. J.; Daigneault, S. CC 1989, 332; Clive, D. L. J.; Daigneault, S. JOC 1991, 56, 3801. (e) Deshmukh, A. R. A. S.; Bhawal, B. M.; Panse, D. G.; Kulkarni, G. H. OPP 1989, 21, 509. (f) Blankley, C. J.; Sauter, F. J.; House, H. O. OSC 1973, 5, 258.
2. (a) Martin, S. F.; Austin, R. E.; Oalmann, C. J. TL 1990, 4731. (b) Martin, S. F.; Austin, R. E.; Oalmann, C. J.; Baker, W. R.; Condon, S. L.; DeLara, E.; Rosenberg, S. H.; Spina, K. P.; Stein, H. H.; Cohn, J.; Kleinert, H. D. JMC 1992, 35, 1710. (c) Martin, S. F.; Oalmann, C. J.; Liras, S. TL 1992, 6727.
3. (a) Womack, E. B.; Nelson, A. B. OSC 1955, 3, 392. (b) Searle, N. E., OSC 1963, 4, 424.
4. White, E. H.; Baumgarten, R. J. JOC 1964, 29, 2070.
5. (a) Regitz, M. CB 1965, 98, 1210; (b) Regitz, M.; Menz, F.; Ruter, J. TL 1967, 739.
6. Harvey, G. JOC 1966, 31, 1587,
7. Baumgarten, R. J. JOC 1967, 32, 484.
8. Cane, D. E.; Thomas, P. J. JACS 1984, 106, 5295. Mori, K.; Tsuji, M. T 1988, 44, 2835.
9. Mak, C. P.; Baumann, K.; Mayerl, F.; Mayerl, C.; Fliri, H. H 1982, 19, 1647.
10. Terasawa, T.; Ikekawa, N.; Marisaki, M. CPB 1986, 34, 931. Middlemas, D. S.; Raftery, M. A. B 1987, 26, 1219. Terasawa, T.; Ikekawa, N.; Morisaki, M. CPB 1986, 34, 935. Kline, T. B.; Nelson, D. L.; Namboodiri, K. JMC 1990, 33, 950. Sen, R.; Singh, A. K.; Balogh-Nair, V.; Nakanishi, K. T 1984, 40, 493. Prestwich, G. D.; Golec, F. A.; Andersen, N. H. J. Label. Comp. Radiopharm. 1984, 21, 593. Prestwich, G. D.; Singh, A. K.; Carvalho, J. F.; Koeppe, J. K.; Kovalick, G. E. T 1984, 40, 529. Ujváry, I.; Eng, W.; Prestwich, G. D. J. Label. Comp. Radiopharm. 1989, 28, 65.
11. Keilbaugh, S. A.; Thornton, E. R. JACS 1983, 105, 3283.

Ioannis Grapsas & Shahriar Mobashery

Wayne State University, Detroit, MI, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.