ALKYLATION OF METHYL NICOTINATE OR ISONICOTINATE WITH ALKYL BROMIDE

During the N-alkylation of methyl nicotinate or methyl isonicotinate w ith alkyl bromide in aprotic solvents, a series of reactions are shown to occur successively in the same pot. After the formation of the pyr idinium unit, a nucleophilic attack of the methyl ester by the bromide ion released in the first quaternarization step takes place. This is followed by the formation of new ester groups because of nucleophilic attack of the alkyl bromide by the carboxylate group formed in the sec ond step. [GRAPHICS] Furthermore, as a side reaction, the methyl bromi de produced in the ester cleavage reaction is shown to react with star ting methyl nicotinate (or isonicotinate). Such a reaction lowers the yield of the alkyLation according to the rate constants of the differe nt steps. This ester cleavage reaction by BR- is not observed with eth yl esters, so that N-alkylation products can be obtained alone in good yields by the use of ethyl nicotinate. A detailed mechanism is propos ed for these reactions and all rate constants are obtained from the ex perimental measurements of the reaction kinetics by H-1 NMR.