N-Hydroxy-MDA · 3,4-Methylenedioxy-N-hydroxyamphetamine
#114 MDOH SYNTHESIS: To a well stirred solution of 14.8 g hydroxylamine hydrochloride in 120 mL MeOH there was added 3.6 g of 3,4-methylenedioxyphenylacetone (see under for its preparation) followed by 1.0 g sodium cyanoborohydride. The oxime, prepared from the ketone and hydroxylamine in MeOH with pyridine, may be substituted for these two components. Concentrated HCl was added over the course of a couple of days, to keep the pH near neutrality. When the reaction was complete, it was added to H2O, made strongly acidic with HCl, and washed with 3×100 mL CH2Cl2. The aqueous phase was made basic with 25% NaOH, and reextracted with 3×100 mL of CH2Cl2. The extracts were pooled, and the solvent removed under vacuum to give 1.7 g of an oily residue which, with pumping under a hard vacuum for a few minutes, changed to a white solid. This can be Kugelrohred if the vacuum is sufficiently good to keep the temperature during the distillation below 100 °C. The extremely viscous distillate formed crystals immediately upon wetting with IPA. It was dissolved in 20 mL of warm IPA and neutralized with concentrated HCl, with the titration end-point being red rather than orange on universal pH paper. Modest addition of Et2O allowed the formation of 3,4-methylenedioxy-N-hydroxyamphetamine hydrochloride (MDOH) as white crystals, which weighed 1.4 g when air dried. If the temperature of distillation exceeded 100 °C, there was extensive decomposition during distillation, with the formation of 3,4-methylenedioxyamphetamine () and the oxime of the ketone. Under these circumstances, the only base isolated was MDA. The surest isolation procedure was to obtain MDOH as the free base, as a crystalline solid which could be recrystallized from 5 volumes of boiling IPA. The free base had a mp of 94–95 °C (and should not be confused with the oxime of 3,4-methylenedioxyphenylacetone which has a mp of 86–88 °C since the mixed mp is depressed, mp 56–62 °C, or with the free base of MDA which is an oil). Anal. (C10H13NO3) N. The hydrochloride salt had a mp of 149–150 °C (and should not be confused with the hydrochloride of MDA which has a mp of 185–186 °C since the mixed mp is depressed, mp 128–138 °C). Anal. (C10H14ClNO3) N. Acetic anhydride can serve as a useful tool for distinguishing these materials. MDA gives an N-acetyl derivative with an mp of 92–93 °C. MDOH gives an N,O-diacetyl derivative with a mp of 72–74 °C. Methylenedioxyphenylacetone oxime gives an O-acetyl derivative that is an oil.
DOSAGE: 100–160 mg.
DURATION: 3–6 h.
QUALITATIVE COMMENTS: (with 100 mg) “I felt hampered the first hour by some internal barrier, which prevented total enjoyment. However, this began to break through in a wonderful way just before the supplement was offered. Since I felt I was beginning to move through the barrier, I declined the supplement, particularly since I was anxious to compare the after-effects with my first experience. I had found the first time very remarkable, but felt unusually tired for several days following. I feel it is important to know whether this is a specific drug-induced effect, or the result of psychological phenomena. The experience continued in a rich, meaningful way. There was a marvelous inner glow, the warmth from all the other participants was wonderful to feel, nature was most beautiful. There were no dramatic breakthroughs, or rushes of insight or energy, but just a wonderful contemplative space where things gently unfolded as you put your attention on them.”
(with 100 mg) “The material came on fairly rapidly. In about 30 minutes, I was intensely intoxicated, and more deeply than with . It was a glorious feeling, and beauty was everywhere enhanced. With eyes closed it felt marvelous, and it was appealing to pursue the inner experience. I did notice an internal dryness which was characteristic of MDMA, and I had similar difficulty in urinating, but not as intense as with MDMA.”
(with 120 mg) “The colors of the market-place, of all the fresh foods, constituted a beautiful mosaic. Nothing practical, simply a real treasure to be used with individual intention and enjoyment. Everything was seen with new eyes, new meanings, faces, figures, the colors of the rainbow subconsciously individually applied. A ‘soul-scape’. The following day very exhausted, tired, back-pain.”
EXTENSIONS AND COMMENTARY: The first time that MDOH was synthesized, it had inadvertently and unknowingly been converted to . And the search for proper dosage and characterization of effects of this product was, of course, the rediscovery of the dosage and the effects of MDA. It is one of the world’s most remarkable coincidences that after the second synthesis of MDOH, when MDOH had really and truly been actually prepared, the brand new search for proper dosage and characterization of effects revealed that they were almost identical to the earlier observations for (the inadvertently produced) MDA.
This reminds me of my speculations in the discussion of both and the HOT compounds (, , ) where they also showed paired molecular structures with their prototypes that differ only by a single oxygen atom. Again, might there be some metabolic interconversion within the body? The immediate thought would be that the oxygen atom (the hydroxy group) might be metabolically removed, and the effects of either drug are due to the action of . But the opposite direction is in many ways more appealing, the in vivo conversion of MDA to MDOH. Why more appealing? For one thing, oxidative changes are much more common in the body than reductive changes. For another, the conversion of amphetamine to N-hydroxyamphetamine is an intermediate in the conversion of amphetamine to phenylacetone, a known metabolic process in several animal species. And that intermediate, N-hydroxyamphetamine, is a material that gives the famous cytochrome P-450 complex that has fascinated biochemists studying the so-called NADPH-dependent metabolism.
I would put my money on the likelihood of going to MDOH if it should turn out that the two drugs interconvert in the body. And in that case, it would be MDOH, or another metabolite on down the line that is common to both MDA and MDOH, that is the factor intrinsic to the intoxication that is produced. Human metabolic studies are needed, and they have not yet been done.
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.
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