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Book II of PiHKAL: A Chemical Love Story, by Alexander & Ann Shulgin #159: TMA-3
#159 TMA-3: 2,3,4-Trimethoxyamphetamine

#159 TMA-3 SYNTHESIS: To a solution of 12.4 g 2,3,4-trimethoxybenzaldehyde in 45 mL glacial acetic acid, there was added 7 mL nitroethane and 4.1 g anhydrous ammonium acetate, and all was held at reflux temperature for 1.5 h. To the cooled and well stirred reaction mixture, H2O was added slowly, dropping out an oily crystalline solid mass. This was separated by filtration, and ground under a quantity of 50% aqueous acetic acid, and refiltered. The 6.5 g of crude product was recrystallized from boiling MeOH to give, after air drying to constant weight, 5.0 g of 2-nitro-1-(2,3,4-trimethoxyphenyl)propene, with a mp of 56–57 °C. Anal. (C12H15NO5) C,H.

To a gently refluxing suspension of 3.0 g LAH in 300 mL anhydrous Et2O under a He atmosphere, there was added 3.65 g 2-nitro-1-(2,3,4-trimethoxyphenyl)propene by allowing the condensing Et2O drip into a shunted Soxhlet thimble containing the nitrostyrene and effectively adding a warm saturated solution of it dropwise. Refluxing was maintained for 5 h following the completion of the addition of the nitrostyrene. The milky reaction mixture was cooled and the excess hydride destroyed by the addition of 200 mL 10% H2SO4. When the aqueous and Et2O layers were finally clear, they were separated, and 75 g of potassium sodium tartrate was dissolved in the aqueous fraction. NaOH (25%) was then added until the pH was >9, and this was then extracted with 3×75 mL CH2Cl2. Evaporation of the solvent under vacuum produced 2.5 g of a nearly colorless clear oil that was dissolved in 300 mL anhydrous Et2O which was saturated with anhydrous HCl gas. The product, 2,3,4-trimethoxyamphetamine hydrochloride (TMA-3) separated as a fine white solid. This was removed by filtration, Et2O washed, and air dried to constant weight. The yield was 1.65 g of a product which, after recrystallization from IPA, had a mp of 148–149 °C. Anal. (C12H20ClNO3) C,H.

DOSAGE: greater than 100 mg.

DURATION: unknown.

QUALITATIVE COMMENTS: (with 100 mg) “There were no effects at all. No eye dilation, no believable diversion from complete normalcy. Appetite was normal, as well.”

EXTENSIONS AND COMMENTARY: There is a small lesson to be learned from this completely inactive compound. There is no way of saying that it is or is not inactive. All that can be said is that trials were made (in this case using three separate individuals) at an oral level of 100 milligrams. And, at this level, nothing happened. And since a bottom threshold for mescaline would be perhaps 200 milligrams, it can be honestly said that the activity of this compound, if expressed relative to mescaline (using mescaline units) is less than 2 M.U. Had 200 milligrams been inactive, it would have been less than 1.0 M.U. If 2 grams had been inactive, it would have been less than 0.1 M.U. But the actual printed form, activity < 2.0 M.U. was accepted by many readers as indicating that TMA-3 was active, but at dosages greater than 100 milligrams. all that can be said is, if there is activity, then it will be at oral levels greater than 100 milligrams at the moment, as far as i know, this compound is not active in man, but then i know of no trials in excess of 100 milligrams.

This admonition applies to all the published M.U. values that are preceded by the “less than” sign, the “<.”

Page updated 30 March 2012 · This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License ·

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. Still others remain to be added.

I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore most of the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice, and in the hope of aligning with more readers’ searches. Typically the change is little more than expanding a prefix and setting it in italics. The errata and changes page has further details.

Cautionary Note

“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.”

Alexander T. Shulgin

Copyright Notice

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.

Ordering Information

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.

Although 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,
Box 13675
Berkeley, CA 94701

510 · 934 · 4930 (voice)
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