2,5-Dimethoxyamphetamine (1)
Diethyl malonate was condensed with 2,5-dimethoxybenzaldehyde in the presence of piperidine (2) to give diethyl 2,5-dimethoxybenzalmalonate, which upon catalytic reduction yielded diethyl 2,5-dimethoxybenzylmalonate as a nearly colorless oil. This was methylated in the usual manner with methyl iodide and sodium ethoxide, and the product ester was hydrolyzed to the malonic acid. When heating this acid above 150°C, it was decarboxylated to alpha-methyl-2,5-dimethoxyhydrocinnamic acid, which after recrystallization from ether/hexane gave a cream-colored powder melting at 59.5°C. The acid was heated in a stream of ammonia gas at 220-230°C for two hours, and was then recrystallized from benzene to give alpha-methyl-2,5-dimethoxyhydrocinnamide melting at 99°C. The Hofmann reaction of this amide was carried out as usual except that the amide was added dissolved in dioxane to the hypochlorite solution (3). The yield of distilled 2,5-dimethoxyamphetamine (bp 137-140°C/3 mmHg) was 70%. The HCl salt melts at 117.5°C.
1. JACS 62, 161 (1940)
2. Ber 31, 2585 (1898)
3. JACS 60, 465 (1938)
