Benzyloxycarbonylhydrazine

(base)

[5331-43-1]  · C8H10N2O2  · Benzyloxycarbonylhydrazine  · (MW 166.18) (.HCl)

[2540-62-7]

(preparation of hydrazides of amino acids for use in peptide synthesis1)

Alternate Names: carbobenzoxyhydrazine; benzyl hydrazinocarboxylate.

Physical Data: mp 67-69 °C; hydrochloride salt, mp 170-170.5 °C

Preparative Method: prepared by reaction between Hydrazine and dibenzyl carbonate.1

Purification: recrystallization from ethyl acetate/hexane, or from ether.

Peptide Synthesis.

Benzyloxycarbonylhydrazine (1) has found use in the preparation of the hydrazides of amino acids and peptides.1 (1) reacts with N-protected (phthaloyl or Boc) amino acid chlorides to give the benzyloxycarbonylhydrazide derivatives (2) (eq 1).1 N-Deprotection (eq 2) leaves the N-terminus available for coupling to a suitable activated carboxylic acid derivative, giving (4) (eq 3); this stepwise elongation procedure may be continued until the desired peptide sequence is obtained. Hydrogenation then affords the peptide hydrazide (5) (eq 4). Preparation by this method, where the protected hydrazide is introduced early, at the amino acid stage, avoids the usual need to expose a complex or sensitive peptide ester to hydrazine. Indeed, the hydrazides of N-phthaloyl amino acids or peptides were previously inaccessible since hydrazine effects removal of the phthaloyl group rather than reacting with the ester. The hydrazide (5) can next be converted to the acyl azide (6) (eq 5) in readiness for coupling with an amino component.


1. (a) Hofmann, K.; Lindenmann, A.; Magee, M. Z.; Khan, N. H. JACS 1952, 74, 470. (b) Hofmann, K.; Haas, W.; Smithers, M. J.; Wells, R. D.; Wolman, Y.; Yanaihara, N.; Zanetti, G. JACS 1965, 87, 620.

Alan Armstrong

University of Bath, UK



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