Phenethylamine hydrochloride

And it has just occurred to me that there is yet another effort that is certainly worth making, inspired by the observation that 2,2-difluoroethyl iodide is commercially available and not prohibitively expensive. It, with 2,5-dimethoxy-thiophenol, and following the obvious steps to the aldehyde, the nitrostyrenc, and the final amine, would produce 2,5-dimethoxy-4-(2,2-difluoroethylthio)-phenethylamine hydrochloride. It lies exactly half way between the highly potent 2C-T-21 (the mono-fluoro), and the yet to be finished 2C-T-22 (the trifluoro). Let s be weird, and call it 2C-T-21.5. I will wager mucho that it will be very potent. 

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 2-carbon analogue, 2C-2-TOET, was made from the same aldehyde intermediate. The appropriate nitrostyrene came smoothly from the aldehyde and nitromethane, and gave glistening pumpkin-orange crystals from methanol, that melted at 93-94 °C. Anal. (C12Hl5N03S) C,H. The final phenethylamine hydrochloride salt was prepared from its reduction with aluminum hydride in THF, and was isolated in the usual manner. It was a white crystalline mass that melted at 226-227 °C. It, as with the other 2-carbon analogues of the TOMs andTOETs, remains untasted as of the moment. 

The cold solution was then allowed to stand overnight and all crystalline material filtered through a sintered glass filter. The filtrate was treated with an additional 300 ml of concentrated hydrochloric acid to yield a heavy white precipitate. The precipitate was filtered, dried and combined with the initial precipitate obtained as described above. The combined precipitated product, 3,4-dihydroxy-N-[3-(4-hydroxyphenyl)-l-methyl-n-propyl-p-phenethylamine hydrochloride, had a melting point of about 184°C to 186°C after recrystallization from boiling 4 N hydrochloric acid. 

DESOXYN DESOXYPHED DESTIM DETREX DEXOPHRINE DEXOVAL N,0-DIMETHYL-PHENETHYLAMINE HYDROCHLORIDE DOPIDRIN... 

This was dissolved in 8 mL IPA, neutralized with 20 drops of concentrated HCI (the salt crystals started to form before this was completed) followed with the addition of 65 mL anhydrous Et20. The white crystalline mass was filtered, washed with Et20, and air dried to provide 1.16 g of 2,5-dimethoxy-3,4-(trimethylene)phenethylamine hydrochloride (2C-G-3) with a mp of 214-216 deg C with decomposition. 

All were suspended in, and ground under, 40 mL anhydrous Et20, refiltered and air dried. The final weight of 2,5-dimethoxy-4-(2-fluoroethylthio)phenethylamine hydrochloride (2C-T-21) was 4.07 g of glistening white crystals. 

Dimethoxy-j -phenethylamine hydrochloride refluxed 1 hr. with ca. 1 mole of acetoacetaldehyde dimethyl acetal in glacial acetic acid, an additional mole of acetal added during 1 hr., and the product isolated as the bromide after 24 hrs. refluxing l-(3,4-dimethoxy-y -phenethyl)-2-methyl-5-acetylpyridinium bromide. Y 93%.—Gontrary to expectations no hydroisoquinoline derivatives (cf. Synth. Meth. 8, 823) were formed. F. e. s. H.-J. Teuber, G. Wenzel, and U.Hochmuth, B. 96, 1119 (1963). 

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