Nitration of aryl cyclopropyl ketones using HNO2

Abstract

Arylcyclopropanes containing electron-acceptor substituents in both the benzene and the small ring react with in situ generated nitrous acid with the insertion of an N=O fragment into the three-carbon ring resulting in the formation of substituted isoxazoles and isoxazolines [1][2][3]. We have proposed that aryl cyclopropyl ketones containing an electron-donor type aryl fragment can also be converted to the corresponding heterocycles in the presence of the indicated nitrosylating agent. However, it was found that the cyclopropane fragment of the cyclopropyl 4-methoxyphenyl ketone (1) and cyclopropyl 2-thienyl ketone (2) is not opened by the action of a nitrosyl cation under the conditions of generation of HNO 2 whereas the aromatic ring of the ketones introduced into the reaction undergoes an electrophilic nitration. The major part of the starting material is returned unchanged. It was of interest that cyclopropyl phenyl ketone does not overall react with HNO 2 in the conditions indicated. O MeO O NO 2 MeO S O S O O 2 N CHCl 3 , -10 o C CHCl 3 , -10 o C 4 2 1 3NaNO 2 , CF 3 COOH NaNO 2 , CF 3 COOH In principle, the electrophilic nitration of aromatic substrates in the presence of nitrous acid is an established fact [4] but the formation of nitro-substituted acyl benzenes from aryl ketones using this reagent has not been observed to this time. In this connection we have specifically shown that the conversion of aryl ketone 1 and hetaryl ketone 2 to the nitro-substituted compounds 3 and 4 is significantly increased if the conditions of study [4] are used with a substrate to reagent ratio of 1:3.