Affordable Access

Studies in isothiazole chemistry: I. isothiazolo [5,4-b] pyridines. II. approaches to isothiazolynes

Authors
Publication Date
Source
Legacy
Keywords
  • Qd Chemistry
Disciplines
  • Chemistry

Abstract

The first part of this thesis describes investigations on the synthesis and chemistry of isothiazolo[5,4-b] pyridines. The syntheses of a number of alkyl isothiazolo[5,4-b] pyridines from 5-amino-3-methylisothiazole under conditions of the Skraup reaction are described and their nuclear magnetic resonance spectra are discussed. The reactions of 3-methyl- and 3,6-dimethylisothiazolo[5,4-b] pyridine have been studied. In particular they did not undergo nitration under the conditions employed and whereas the 3-methyl compound did not condense with benzaldehyde, 3,6-dimethylisothiazolo[5,4-b] pyridine gave mono-styryl products with benzaldehyde, and p-nitrobenzaldehyde. Potassium permanganate oxidation gave isothiazolo[5,4-b] pyrid-3(2H)-one 1,1-dioxides rather than the expected isothiazolo[5,4-b] pyridine carboxylic acids and chromic acid oxidation resulted in cleavage of the isothiazole ring to give 2,3-disubstituted pyridines. Ethyl 4-hydroxy-3-methylisothiazolo[5,4-b] pyridine-5-earboxylabe was readily obtained by thermal cyclisation of the malonate from 5-amino-3-methylisothiazole and ethoxymethylenemalonic ester. The hydroxyl ester was converted to a number of substituted isothiazolo[5,4-b] pyridines. In addition it has been established that methylation at nitrogen rather than oxygen occurs with both the 4-hydroxy ester and the 4-hydroxy compound which has been shown to exist preferentially in the carbonyl form, namely 3-methylisothiazolo[5,4-b] _7pyrid-4-one. The reaction of 5-amino-3-methylisothiazole with ethylacetoacetate and with acetylacetone under the conditions of the Conrad Limpach reaction and the Combes reaction respectively, did not give isothiazolo[5,4-b] pyridines. The latter gave a product which has been tentatively formulated as 5-acetyl-3,4-dimethylisothiazole. The second part of this work describes the synthesis of 5-amino-3-chloroisothiazole-4-carboxylic acid, 4-amino-3-methylisothiazole- 5-carboxylic acid and 4-aminoisothiazole-3-carboxylic acid and experiments aimed at investigating the possible intermediacy of isothiazolynes. Attempts to generate and trap isothiazolynes by their aprotic diazotisation with isoainyl nitrite in the presence of 2,3,4,5-tetraphenylcyclopentadienone gave only small quantities of isothiazoles in addition to a variety of oxidation products derived from the arynophile. 4-Amino3-methylisothiazole-5-carboxylic acid gave isothiazolyl-substituted products when furan and anthracene were used as trapping agents, and it was found that the reaction of isothiazole-4-diazonium carboxylate hydrochloride and propylene oxide in the presence of furan gave 4,-cyano-1,2,3-thiadiazole. In none of the reactions investigated was there any evidence for the formation of inothiazolyne intermediates.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments