Synthesis of 1-Substituted Hydrocotarnine Derivatives. (2)

Codensation of cotarnine (I) with o-or p-nitrotoluene derivatives and catalytic reduction of the product afforded 1-aminobenzylhydrocotarnine derivatives. Acylation and alkylation of these derivatives gave 1-acylaminobenzyl-and 1-alkylamino-benzylhydrocotarnine derivatives. By the Grignard reaction of cotarnine hydriodide (XXXV) or by the application of malonic acid to I and subsequent reactions shown in Chart 2, 1-aminoalkylhydrocotarnine derivatives (XXXVI and XXXVIII) were obtained. Hofmann degradation of the methiodides of 1-benzylhydrocotarnine (XXXIX) and its derivative, followed by catalytic reduction of the products afforded N, N-dimethyl-2-phenethyl- (or -p-acetamidophenethyl-) 3-methoxy-4, 5-methylenedioxyphenethylamine (XLII and XLIII).