Issue in Honor of Prof. Domenico Spinelli ARKIVOC 2002 (xi) 227-235
Synthesis of pyrazole-4-carbohydrazide derivatives of pharmaceutical interest
Giuseppe Daidone*, Demetrio Raffa, Fabiana Plescia, Benedetta Maggio, and Angela Roccaro
Dipartimento di Chimica e Tecnologie Farmaceutiche Via Archirafi, 3- I-90123 Palermo, Italy E-mail:
[email protected]
This paper is dedicated to Professor Domenico Spinelli on the occasion of his 70th birthday (received 23 Oct 02; accepted 26 Dec 02; published on the web 03 Jan 03)
Abstract
New 1-phenyl- or 1-methyl-5-benzamidopyrazole-4-carbohydrazide derivatives were prepared in 70–90% yields from 1-methyl- or 1-phenyl-6-phenylpyrazolo[3,4-d]1,3-oxazin-4(1H)-one derivatives and hydrazine hydrate. Small quantities of the isomeric 5-aminopyrazole-4-(Nbenzoyl) hydrazides were detected in some reaction mixtures, proving that intramolecular benzoyl migration can take place in the 5-benzamidopyrazole-4-carbohydrazide molecule. The direct formation of pyrazole-4-carbohydrazides from 5-benzamidopyrazole-4-carboxylic acid ethyl esters and hydrazine hydrate was unsuccessful.
Keywords: Pyrazole-4-carbohydrazides, pyrazole-4-(N-benzoyl)carbohydrazides, intramolecular benzoyl migration
Introduction
In the course of our medicinal chemistry researches, we needed to prepare pyrazole-4carbohydrazide derivatives 2a–h (Schemes 1 and 2) in view of their potential pharmacological activities. In the literature it is reported that some benzohydrazides are used to inhibit fibrosis and to treat fibrosing disorder.1 Several aryl- and heteroaryl- hydrazides produce inhibitory effects on glutamic acid decarboxylase (GAD), GABA-a-oxoglutarate amino transferase (GABA-T) and monoamine oxidase.2,3 Moreover, Isoniazid®, namely pyridine-4-carbohydrazide, is the drug of choice in the treatment of tubercolosis.4
A review of the literature5 revealed that 1-phenyl-5-benzamidopyrazole-4-carboxylic acid ethyl ester 1 (Scheme 1) when refluxed for 5 h in hydrazine hydrate afforded the 5-amino derivative 3, by losing the benzoyl moiety, instead of the hydrazide derivative 2a.
ISSN 1424-6376 Page 227 ©ARKAT USA, Inc
