SYNTHESIS: To a solution of 39.2 g 2,4,5-trimethoxybenzaldehyde in 160 mL nitromethane there was added 7.0 g anhydrous ammonium acetate, and the mixture was heated on the steam bath for 2 h. The excesssolvent/reagent was removed under vacuum, leaving a deeply colored residue that spontaneously crystallized. This was mechanically removed and triturated under 60 mL cold MeOH. Filtration, washing with cold MeOH and air drying, gave 49.3 g of bright orange crystals. Trial recrystallizations from EtOAc gave a mp of 132–133 °C; from CH3CN, 130.5–131.5 °C. The entire product was recrystallized from 1.1 L boiling IPA to provide, after filtration, IPA washing, and air drying, 34.5 g of β-nitro-2,4,5-trimethoxystyrene as yum-yum orange crystals with a mp of 132–133 °C. Literature values are usual one-degree ranges, anywhere in the area of 127–130 °C.
To a suspension of 30 g powdered LAH in 800 mL of well stirred and refluxing anhydrous THF there was added a solution of 34.9 g β-nitro-2,4,5-trimethoxystyrene in 200 mL anhydrous THF. The mixture was maintained at reflux for an additional 36 h, cooled, and the excess hydride activity destroyed by the addition of 30 mL H2O followed by 30 mL 15% NaOH, and finally with another 90 mL H2O. The solids were removed by filtration, washed with THF, and the pooled mother liquor and washings stripped of solvent under vacuum. The residue was dissolved in CH2Cl2, washed with both 5% NaOH and then H2O, removing much of the color. It was then extracted with 3×75 mL N HCl. The pooled red-colored acid extracts were washed with CH2Cl2, made basic with 25% NaOH, and extracted with 3×75 mL CH2Cl2. Removal of the solvent gave some 25 g of residue which was dissolved in 100 mL IPA and neutralized with concentrated HCl. The crystalline mass that formed was diluted with an equal volume of Et2O, and the solids removed by filtration. Washing with cold IPA, followed by Et2O and air drying, gave 17.7 g of 2,4,5-trimethoxyphenethylamine hydrochloride (TMPEA) as a white product. The reported melting point was 187–188 °C.
DOSAGE: greater than 300 mg.
QUALITATIVE COMMENTS: (with less than 300 mg) “Since it was not easy, however, to judge the extent of a ‘Rausch’-action from experiments on animals, some injections of beta-2,4,5-trimethoxyphenethylamine were administered to the author, and finally a control test was carried out with an equal quantity of
(with 300 mg) “Under double blind conditions, I was unable to distinguish this from a placebo. Both were without any of the changes described after the ingestion of psychotomimetic drugs.”
(with 200 mg, followed after 45 minutes, with 100 mg
EXTENSIONS AND COMMENTARY: The code letters used for this drug are not as ambiguous as they might seem at first glance. A large number of the 2-carbon homologues are given names based on the code for the 3-carbon compound. On that basis, this should be 2C-TMA-2, since it is the 2-carbon counterpart of
There have been just two reports published of self-experimentation with TMPEA, and these comments are taken from them.
The first is presented here, word for word, as it was originally published (this was in 1931). It leaves much to be desired. The administration was by injection (intramuscular injection?). The dose was not given, but it was less than those reported by Beringer in his studies with
The second, reported some 40 years later, is not really contradictory. Here the TMPEA was administered orally, and the subject surrounded himself with a battery of psychological tests. This might allow statistics to provide an aura of validity to the observations. But the comments are pretty self-explanatory. The drug was not active in its own right, but when employed preliminary to
This is an area of research that deserves more attention. The simple compound that results from the stripping of all three of the O-methyl groups from TMPEA is the extremely potent neurotoxin,
About PiHKAL · info
This version of Book II of PiHKAL is based on the Erowid online version, originally transcribed by Simson Garfinkle and converted into HTML by Lamont Granquist. I drew also on “Tyrone Slothrop’s” (Unfinished) Review of PIHKAL to enumerate the many analogues mentioned in PiHKAL but not described at length. Many, many others have since been added.
I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice. Typically the change is little more than expanding a prefix or setting it in italics. The history page has further details.
“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
The copyright for Book I of PiHKAL has been reserved in all forms and it may not be distributed. Book II of PiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.
PiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of phenethylamines. This book belongs in the library of anyone seeking a rational, enlightened and candid perspective on psychedelic drugs.
Though Sasha and Ann have put Book II of PiHKAL in the public domain, available to anyone, I strongly encourage you to buy a copy. We owe them — and there’s still nothing quite like holding a real book in your hands.
PiHKAL (ISBN 0-9630096-0-5) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.Transform Press,
Berkeley, CA 94701
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