2,3,4-Trimethoxybenzyl chloride

Monoformylpiperazine is reacted molecule for molecule with 2,3,4-trimethoxybenzyl chloride in the presence of 114 molecules of sodium carbonate and in suspension in ethyl alcohol, during 2 to 3 hours. 

Michael addition of a dithiane anion 20, generated from the dithiane 19 with butyllithium, to the butenolide 21 creates the enolate 22 which has been efficiently alkylated in situ by 3,4,5-trimethoxybenzyl chloride to give 24 (mp 146-146.5 °C) in 65% overall yield. Protona-tion of 22 furnished the Michael adduct 23, which again can be deprotonated16 with LDA at — 78 °C to give 22 and alkylated (trimethoxybenzyl chloride, THF, HMPA, 3 h at — 78 °C, 18 h at 20 °C) to yield 24. Both variants are equally completely diastereoselective giving rise to the trans- product. 

Mescaline has been synthesized in 42% overall yield in five steps from 2,6-dimethoxyphenol.1 Analogues of mescaline with the NH2 group replaced by a pyrrolidine, a piperidine, a morpholine, and a jV-methylpiperazine group have been prepared from 3,4,5-trimethoxybenzyl chloride.2 A process for the determination of mescaline in plasma by g.l.c.-mass spectrometry has been described,3 and behavioural effects of the alkaloid have been studied.4-11... 

C 0IIMClO4 4521-61-3) see Dilazcp Hcxobendinc Trimetliobenzamide Trimetozine Troxipide 23,4-trimethoxybenzyl chloride (C 0H, CIO2 1133-49-9) see Trimetazidine... 

The synthesis is outlined as follows gallic acid3,4,5-tri-methoxybenzoic acid — methyl ester of the 3,4,6-trimethoxybenzoic acid — 3,4,5-trimethoxybenzyl alcohol 3,4,5-trimethoxybenzyl chloride - 3,4,5-trimethoxyphenylacetonitrile — mescaline. The reduction of the methyl ester and of the nitrile has been achieved using lithium aluminum hydride. 

NaH-dispersion followed by purified p-toluenesulfonyl chloride added with ice-cooling to a soln. of 2-nitro-3,4,5-trimethoxybenzyl alcohol in anhydrous benzene, and stirred 13 hrs. at room temp. -> 2-nitro-3,4,5-trimethoxybenzyl tosylate. Y 90-94%.— Tosylation in pyridine was not successful. K. I. H. Williams, D. S. Tarbell et al.. Am. Soc. 82, 3982 (1960). 

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