PMMA · DOONE · 4-MMA · 4-Methoxy-N-methylamphetamine
#130 METHYL-MA SYNTHESIS: A solution of 20 g methylamine hydrochloride in 150 mL hot MeOH was treated with 10.0 g 4-methoxyphenylacetone and stirred magnetically. After returning to room temperature, there was added 5.0 g sodium cyanoborohydride, followed by cautious addition of HCl as required to maintain the pH at about 6. The reaction was complete after a few days, and the mixture was poured into 800 mL H2O. This was acidified with HCl (HCN evolution!) and washed with 3×75 mL CH2Cl2, which removed most of the yellow color. There was 25% NaOH added to make the reaction mixture strongly basic, and this was extracted with 3×75 mL CH2Cl2. The solvent was removed from the pooled extracts under vacuum, and the 10.3 g of residue distilled at 0.3 mm/Hg. The 9.7 g of colorless oil that distilled at 75–90 °C was dissolved in 50 mL IPA, neutralized with 4.5 mL concentrated HCl, and then diluted with 100 mL anhydrous Et2O. There were generated glistening crystals of 4-methoxy-N-methylamphetamine hydrochloride (METHYL-MA or DOONE) that weighed, after washing with Et2O and air drying to constant weight, 11.0 g and which had a mp of 177–178 °C. The same base can be made by the action of ethyl chloroformate on in the presence of triethylamine to make the carbamate, or the action of formic acid to make the formamide. These can then be reduced with LAH to this same end product.
DOSAGE: greater than 100 mg.
DURATION: short.
QUALITATIVE COMMENTS: (with 110 mg) “One hour into it, my pulse was up over 100, and I was compulsively yawning. There was some eye muscle disturbance, a little like the physical side of , but there was none of its central effects. But all the hints of the cardiovascular are there. By the fourth hour, I am pretty much back to baseline, but the yawning is still very much part of it. I might repeat this, at the same level, but with continuous close monitoring of the body.”
EXTENSIONS AND COMMENTARY: Why would there be interest in this particular compound? The track record from the comparison of active compounds that are primary amines, and their N-methyl homologues, has shown that, in general, the stimulant component might be maintained, but the “psychedelic” contribution is generally much reduced. is, of course, an exception, but then, that particular compound is a one-of-a-kind thing which simply defies all the rules anyway, and I drop it from this kind of reasoning. And as is a pretty pushy stimulant with little if any sensory sparkle, why bother with the N-methyl compound at all?
For a completely silly and romantic reason. When the story became front-page news back in mid-1985, the cartoonist-author of Doonesbury, Gary Trudeau, did a two-week feature on it, playing it humorous, and almost (but not quite) straight, in a hilarious sequence of twelve strips. On August 19, 1985 he had Duke, president of Baby Doc College, introduce the drug design team from USC in the form of two brilliant twins, Drs. Albie and Bunny Gorp. They vividly demonstrated to the enthusiastic conference that their new drug “Intensity” was simply MDMA with one of the two oxygens removed. “Voila,” said one of them, with a molecular model in his hands, “Legal as sea salt.” And what is MDMA with one oxygen atom removed? It is 4-methoxy-N-methylamphetamine or METHYL-MA which, according to the twins, should give the illusion of substance to one’s alter ego. So, I called it Doonesamine, or simply “DOONE” for short. Maybe that was also a homonym for Frank Herbert’s science fiction book, “Dune,” wherein the magical drug “spice” provided a most remarkable alteration of the user’s state of consciousness.
This comic strip presentation was the first nationally distributed allusion to the term “designer drugs,” and perhaps it lent unexpected support for the passage, just a year later, of the Controlled Substances Analogue Enforcement Act of 1986. This intentionally vague piece of legislation makes the giving of, or the taking of, or even the possession with the intent to take, any drug that in any way alters your state of consciousness, a felony. A shameful and desperate effort by the governmental authorities to maintain the image of control in a lost situation.
Enough editorial. Back to historic technicalities. In truth, METHYL-MA is a well studied drug, at least in animals. In both mice and rats, it is an exceptionally potent agent in creating the state of catatonia. Animal studies, prompted by the clandestine synthesis of METHYL-MA, have shown that there is indeed locomotor stimulation and some central effects, but these effects are somehow different than those of a simple amphetamine-like agent. The experimenter’s conclusions, based on its structural resemblance to and its proclivity to produce catatonia in some animal species and the ever-present possibility that there might be unsuspected neurochemical changes to be seen with its use, are that human experimentation should be discouraged. I have come to the same conclusion, but in my case this is based on a much more succinct observation: I tried it and I didn’t like it.
A brief comment on two of the N,N-dimethylhomologues of methoxyamphetamine. One was 4-methoxy-N,N-dimethylamphetamine, . This material, made by the reductive amination of 4-methoxyphenylacetone with dimethylamine, was a colorless oil, which distilled at 70–85 °C at 0.3 mm/Hg. The corresponding 2-methoxy-N,N-dimethylamphetamine was similarly made. was also a colorless oil and had the same bp. Both of them were fluorinated with 18F labelled acetyl hypofluorite (3% and 6% yields respectively) but neither of them was pursued any further in the search for a brain blood flow indicator.
13 May 2016 · Creative Commons BY-NC-SA ·

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.

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.
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,
Box 13675
Berkeley, CA 94701

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