NeoPilocarpine Pilocarpine

Roylance showed that pilocarpidine on -methylation yielded two products, pilocarpine and neopilocarpine (see below), thus confirming Hamack s suggestion that pilocarpidine is the imino-base corresponding to pilocarpine, Spath and Kunz showed that pilocarpidine, on treatment with alcoholic sodium ethoxide, is converted into isopilocarpidine (nitrate, m.p. 109-111°), which, on quaternary methylation, yields isopilocarpine metho-salts (methopicrate, m.p. 119-120°). The confirmation of these observations by the synthesis of pilocarpidine and isopilocarpidine and their conversion into pilocarpine and isopilocarpine has been described already. 

Neither Harnack (26) nor Merck (165) were able to confirm this by the methylation of pilocarpidine, but subsequently Hurtles, Pyman, and Roylance (48) and also Spath and Kunz (109) obtained pilocarpine by the interaction of pilocarpidine (I) and methyl iodide under mild conditions. The former group also isolated the isomer, neopilocarpine... 

II), as a second product of the methylation, the reaction being analogous to the production of both 1 4- and 1 5-dimethylimidazoles by the methylation of 4(5)-methylimidazole. Neopilocarpine shows none of the typical physiological action of pilocarpine, and possesses merely a weak stimulating action on isolated intestinal muscle (48). It is converted by alkali into the stereoisomeric isoneopilocarpine. (See p. 228 for formulas I, II.)... 

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