Comparative reactivity of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole against electrophilic compounds

Abstract

A comparative study of reactions of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole with electrophilic compounds in the presence of n‐BuLi, LICA or LICA‐TMEDA is reported. By using LICA‐TMEDA, regioselective reactions of the heterocyclic compounds at the C‐3 methyl group are obtained. With n‐BuLi or LICA and the isoxazole derivative a product mixture at the C‐4 position and the C‐3 methyl group is found. In the case of isothiazole compound, only with methyl iodide and n‐BuLi, the dialkylated product at both positions is formed.

Metalated Heterocycles and Their Applications in Synthetic Organic Chemistry

“…In addition, 1-hydroxypyrazoles have been silylated at C-5 via the usual lithiation−silylation sequence, thus allowing further metalation at C-4, whereas other silylpyrazoles have been recently obtained from silylated β-enaminones or from lithiated (trimethylsilyl)diazomethane . Moreover, 3,5-disubstituted isoxazoles and isothiazoles can be silylated at C-3 after lithiation with different alkyllithiums 75 …”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…Isothiazole derivatives, especially the 1,1-dioxides, undergo 1,3-dipolar cycloadditions with a wide range of dipoles under mild conditions [363]. For instance, isothiazol-3(2H)-one 1,1-dioxides react with nitrile imines and nitrile oxides to give the expected cycloadducts (Scheme 9.116) [364].…”

“…Lithiation of 3-methyl-5-phenylisothiazole with butyllithium occurs selectively at the methyl group (Scheme 9.124). The lithiated species reacts with alkyl halides to give isothiazoles 299 in high yields [363]. It also reacts with a range of aldehydes and ketones to afford the corresponding secondary or tertiary alcohols 300 [381].…”

Isothiazoles (1,2-thiazoles): synthesis, properties and applications

“…108 The alkylation of a lithium derivative of isothiazole 134 with alkyl iodides or bromides gives compounds 136a ± c in up to 83% yields. 109 The condensation of 4-acetyl-5-chloro-3-methylisothiazole (137) with some aromatic and heterocyclic aldehydes involves the methyl group of the acetyl group rather than the methyl group in position 3 of the isothiazole ring to give a,b-unsaturated carbonyl compounds 138. 128 139) reacts with aromatic aldehydes to give the corresponding (3-chloro-4-cyanoisothiazol-5-yl)hydrazones 140.…”