L. Janda
2001
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Influential Citations
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Journal
Heterocyclic Communications
Abstract
Ethyl (l//-tetrazol-5-yl)acetate is acylated with aroyl chlorides and heteroaroyl chlorides in pyridine. The intermediate acyltetrazoles undergo thermal degradation to ethyl (5-aryl-l,3,4oxadiazol-2-yl)acetates and (5-heteroaryl-l,3,4-oxadiazol-2-yl)acetates, respectively, in good yields. The corresponding acetic acids are obtained by potassium hydroxide mediated hydrolysis of the esters in anhydrous ethanol. Introduction Heteroaryl acetic acids often posses anti-inflammatory and analgesic activities 1,2 and are used in the synthesis of new beta-lactam antibiotics with anti-microbial activity.' Aryloxadiazolyl acetic acids and their derivatives are no exception and their biological activities are well known. ' The previously described multistep syntheses of aryloxadiazolylacetic acids are based on the cyclization of 1,2-diacylhydrazines 6-8 or substituted benzoylhydrazines 9-11 and are inefficient. A simple synthesis of ethyl aryloxadiazolylacetates 3 is described in this paper. The method is based on acylation of ethyl (l//-tetrazol-5-yl)acetate (1) with aroyl chlorides 2 followed by thermal degradation of the acylated tetrazoles to 1,3,4-oxadiazoles 3. Hydrolysis of 3 furnishes acids 4. Acylation of 5-aryl-l//-tetrazoles and a subsequent thermal degradation leading to 2,5-diaryl[l,3,4]oxadiazoles is known. 12-14 This approach has been used in the preparation of several diaryl oxazoles 15 and arylalkyl oxazoles. 16 However, it has never been used for the preparation of oxadiazolylacetic acids starting from esters of (l//-tetrazol-5-yl)-acetic acid. This apparently overlooked application of the general method enhances its synthetic utility and provides a simple two-step synthetic route to aryloxadiazolylacetic acids 4. Vol. 7, No. 5, 2001 Synthesis of 5-aryl-1.3,4-oxadiazolyl-2-acetic acids