Methylamphetamine hydrochloride

This synthetic procedure, using the hydrochloride salt of the amine and sodium cyanoborohydride in methanol, seems to be quite general for ketone compounds related to 3,4-methylenedioxyphenylacetone. Not only were most of the MD-group of compounds discussed here made in this manner, but the use of phenylacetone (phenyl-2-propanone, P-2-P) itself appears to be equally effective. The reaction of butylamine hydrochloride in methanol, with phenyl-2-propanone and sodium cyanoborohydride at pH of 6, after distillation at 70-75 °C at 0.3 mm/ Hg, producedN-butylamphetamine hydrochloride (23.4 g from 16.3 g P-2-P). And, in the same manner with ethylamine hydrochloride there was produced N-ethyl-amphetamine (22.4 g from 22.1 g P-2-P) and with methy lamine hydrochloride there was produced N-methylamphetamine hydrochloride (24.6 g from 26.8 g P-2-P). The reaction with simple ammonia (as ammonium acetate) gives consistently poor yields in these reactions. 

Common Name Desoxyephedrine hydrochloride Metamfetamine hydrochloride Metamphetamine hydrochloride Methaphetamine hydrochloride Methylamphetamine hydrochloride Phenylmethylaminopropane hydrochloride... 

Infra-red Spectrum. Principal peaks at wavenumbers 747, 698, 1060, 1491, 1590, 1085 (methylamphetamine hydrochloride, KBr disk). (See below)... 

Following a single oral dose of 12.5 mg of methylamphetamine hydrochloride to 10 subjects, a mean peak blood concentration of about 0.02 ig/ml was attained in about 2 hours (R. C. Driscoll et al., J. pharm. Sci., 1971, 60, 1492-1495). 

After a minute s standing, the solution became turbid, followed by the slow deposition of very fine white crystals. After standing 1 h at room temperature, these were removed by filtration, Et20 washed, and air dried to constant weight. There was thus obtained 0.3 g 2,6-dimethoxy-4-methylamphetamine hydrochloride (gamma-DOM) with a mp of 203 °C. sharp. 

There were generated glistening crystals of 4-methoxy-N-methylamphetamine hydrochloride (METHYL-MA or DOONE) that weighed, after washing with Et20 and air drying to constant weight, 11.0 g and which had a mp of 177-178 °C. The same base can be made by the action of ethyl chloroformate on 4-MA in the presence of triethylamine to make the carbamate, or the action of formic acid to make the formamide. These can then be reduced with LAH to this same end product. 

After filtering, Et20 washing, and air drying, there was obtained 6.2 g of 2,5-dimethoxy-N-methylamphetamine hydrochloride (METHYL-DMA) as fine white crystals with a mp of 117-118 deg C. The mixed mp with 2,5-DMA (114-116 deg C) was depressed to 96-105 deg C. An alternate synthesis gave the same overall yield of an identical product, but started with 2,5-DMA. It required two synthetic steps. The free base amine was converted to the crystalline formamide with formic acid in benzene using a Dean Stark trap, and this intermediate was reduced to METHYL-MDAwith LAH. 

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