3- Methoxy phenethylamine

HC1 to an end-point determined by damp external pH paper. There was the immediate formation of solids which were removed by filtration and washed first with IPA and then with Et20. This provided 1.0 g of 3,5-diethoxy-4-methoxy-phenethylamine hydrochloride (SB) as white crystals, with a mp of 186-187 °C. Anal. (C CINC ) C,H. 

The following were isolated largely by chromatography and identified by spectral properties and by comparison with known bases N-formylnormacromerine, metanephrine, V-methylmetanephrine, syne-phrine, N- methyltyramine, V-methyl-4-methoxy- -phenethylamine, iV-methyl-3,4-dimethoxy-/3-phenethylamine, tyramine, hordenine, macromerine, and normacromerine (37). 

Cathine (d-norpseudoephedrine), cathinine, and ephedrine have been isolated from the leaves of Catha edulis.14 Examination of Erica lusitanica yielded p-methoxy-/ -phenethylamine, which had previously been shown to be absent in 16 other Erica species and 28 other Ericaceous plants.15 Phenylacetamide has been isolated from Vepris ampody.lSa... 

Leander and his group have demonstrated that labeled tyrosine and dopa as well as tyramine and dopamine, are specifically incorporated in low yields into cryptostyline in C. eryihroglossa. In addition, 3-hydroxy-4-methoxy-phenethylamine was incorporated more efficiently than the 3-methoxy-4-hydroxy... 

The thermal condensetion of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxy-phenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy4-hydroxy-phenethyl-p-benzyloxyphenylacetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the 1-(p-benzyloxybenzyl)-6-meth-oxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline, which is methylated with formaldehyde and formic acid giving 1 (p-benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydro-isoquinoline with a yieid of 90%. 

The preferred conformations of methoxy groups attached to aromatic rings in the phenethylamines have recently been investigated using theoretical approaches, gas phase experimental methods, and nuclear magnetic resonance (NMR) techniques for the molecules in aqueous solution. Ab initio theoretical calculations and experimental gas phase results have indicated that when two... 

Adding the second alpha-methyl to MDA gives a compound that apparently is only weakly active in man (199). Again, the 3,4-methylenedioxy substitution seems anomalous. This may also be due to an indirect effect, such as release of endogenous neurotransmitter from nerve terminals. However, neither this a,a-dimethylated MDA analog nor a,a-dimethyl-4-methoxy-/3-phenethylamine had any ability to induce the release of 3H-serotonin from rat whole brain synaptosomes (160). 

M m-methoxy-toluene (or analog), 30 ml HCI, 30 ml benzene cool to 0° and with cooling and stirring saturate with HCI. Add 0.15 M formaldehyde and then more HCI for fifteen minutes. Stir at room temperature for two hours and dry, evaporate in vacuum the benzene layer to get about 30% 2-methyl-4-methoxy-benzyl-CI (or analog). 0.5 M (l), 0.8 M NaCn, 5 g Nal or K1 in 250 ml dry acetone stir and boil twenty hours. Filter, wash precipitate with 100 ml acetone and dissolve precipitate with 75 ml benzene. Wash with 100 ml water and dry, evaporate in vacuum to get about 80% yield 2-methyl-4-methoxy-benzyl-CN (II). 0.1 M (ID in 60 ml 10N NH3 in methanol 4 g Ni-Cr20 and shake in autoclave at 70-100 atmospheres H2 and 120° to get about 80% yield of the phenethylamine. 

The formula on the next page is designed to methylate amphetamines, which are usually more stimulating and pleasant than the non-methylated versions. This formula is also described for the p-methoxy derivative and it too may be used to methylate most phenethylamines without substantive modification. They were taken from JMC, 15, 214. The alcohol p-anisyl is replaced with trimethoxybenzyl, you get mescaline. 

EXTENSIONS AND COMMENTARY The two aromatic ring positions that are associated with human psychedelic activity are the 4-position (of psilocybin fame) and the 5-position (of 5-methoxy-this-and-that fame). Here is a compound with both positions oxygen-substituted (with the methylenedioxy ring that is so effective in the phenethylamine world) and it has not been looked at in man, to my knowledge. I snooped around in the literature associated with this kind of DMT substitution, and the world of di-oxygen substitution to be found at these two potent focal points is almost unknown. Aside from the 4,5-methylenedioxy-diisopropyltryptamine,... 

The 5-position on the indole ring of the tryptamine family is analogous to the 4-position in the phenethylamine family. And yet, here, with the 5-methoxy group of 5-MeO-DMT being replaced with the 5-methylthio group of 5-MeS-DMT, the activity actually seemed to decrease by a factor of two. Is this a generality of the tryptamines, or is this an anomaly of this one pair of compounds ... 

EXTENSIONS AND COMMENTARY Some fifty years ago this material was given the name reciprocal mescaline in that it was believed to exacerbate the clinical symptoms in schizophrenic patients. In the original report, one finds Thus we have di scovered an extremely remarkable dependency of the intoxicating action upon the position of the three methoxy groups. Mescaline, the 3,4,5-trimethoxy-B-phenethylamine, produces in the normal subject a much stronger over-all intoxication than in the schizophrenic patient, whereas 2,3,4-trimethoxy-B-phenethylamine has quite the opposite effect. It has little action in healthy individuals, being almost without intoxicating properties, but it is very potent in the schizophrenic. The metabolic conversion products of the reciprocal mescaline will be further studied as soon as the study of the metabolism of the proper mescaline is complete. ... 

The following bases were isolated as their hydrochlorides JV-methyl-4-methoxy-jS-phenethylamine, hordenine, iV-methyltyramine, syne-phrine, and O-methylsynephrine (38). 

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