N-Methylation of 2-Furylhenzothiazoles. The Influence of Substituents on the Rate of Quaternizationa,b

Recently we reported the preparation and properties of some 2-(2or · 3-furyl)benzothiazoles1• Like many other thiazoles2 , due to their weak basic character they can give quaternary salts. Comparing 2-(2-methyl-3-furyl)benzothiazoles with the 2-(5-methyl-2-furyl) analogue it was observed that the nucleophilicity (and basicity) of benzothiazole nitrogen is influenced by the position of the methyl group in the furane nucleus. The effect was illustrated by hydrochloride formation and with quaternization by methylation1. In the present paper we wish to discuss further the quaternization of several furyl-substituted benzothiazoles since noticeable substituent dependance of the rate during methylation with dimethylsulphate has been observed. N-alkylation of organic bases is a very well known reaction, sometimes refered to as a Menshutkin's reaction3• Many nitrogen heterocycles, including thiazoles, have been investigated 'in this sense4 • Simple bimolecular kinetics invariable were observed, and the reaction is usually r egarded as a pure SN2 process. Surprisingly, only a limited interest has been paid so far to benzothiazole N-alkylation. The observed difference in the Tate of N-methylation could be related to the nucleophilicity of benzothiazole nitrogen and its substituent dependance. It was shown5 that the benzothiazole system is very efficient in transmitting substituent effects from the benzo-ring to the group bonded at the thiazole nucleus. The effects are transmitted through the thiazole nucleus mainly by nitrogen6. Consequently the electron density of thiazole nitrogen should be greatly influenced by the substituent effects from the benzo-group. Regarding the position of substituents 5 and 6 they can be considered as »meta« and »para« respectively6 • The substituents (CH3, Br, Cl) of the compounds elaborated in present studies were located at position 5 of the furane nucleus and/or position 6 of the benzo-ring. Substituents at the benzo-ring can be regarded as »para« when explaining their effects on electron density of thiazole nitrogen.