#16 BOHD SYNTHESIS: A solution of 0.4 g 1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane (see preparation in the recipe for ) in 3.0 mL acetic acid was heated to 100 °C on a steam bath. There was added 1.0 g powdered zinc, followed by additional acetic acid as needed to maintain smooth stirring. After 0.5 h there was added 1.0 mL concentrated HCl and, following an additional few minutes heating, the reaction mixture was poured into 300 mL H2O. After washing the aqueous phase with 3×75 mL CH2Cl2, the mixture was made basic with 25% NaOH, and extracted with 3×50 mL CH2Cl2. Removal of the solvent and distillation of the residue at 130–140 °C 0.25 mm/Hg gave an oil that, on dissolving in IPA, neutralization with concentrated HCl, and the addition of anhydrous Et2O, gave beautiful white crystals of 2,5-dimethoxy-β-hydroxy-4-methylphenethylamine hydrochloride (BOHD). The yield was 0.2 g, and the mp was 180–181 °C. The infrared spectrum was that of an amine salt with a strong OH group present. Anal. (C11H18ClNO3) C,H.
DOSAGE: greater than 50 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 50 mg) “At about the two hour point, there was a precipitous drop of blood pressure (from 120/72 to 84/68) although the pulse stayed steady at 60. This trend had been apparent in earlier trials, and was being watched carefully. No further tests are planned.”
EXTENSIONS AND COMMENTARY: The usual method of making β-ethanolamine such as this is through the reduction of the cyanohydrin of the corresponding benzaldehyde and, in fact, that method is described in the recipe for . This above procedure was actually part of an exploration of different agents that might be used in the reduction of the intermediate nitroalkane. This product was the unexpected result of trying zinc.
Why the potent cardiovascular effect seen by this compound? There are a couple of points that might argue for some adrenolytic toxicity. This material is a β-ethanolamine and, with maybe one or two exceptions, clinically used beta-receptor blockers are β-ethanolamines. In fact, a few of these so-called beta-blockers actually have two methoxy groups on the aromatic rings, also a property of BOHD. The antidiabetic drug (BW 64–9 in the code of Burroughs Wellcome) is identical to BOHD except that the 4-methyl group is on the alpha-carbon instead, and there is a tertiary butyl group on the nitrogen atom. Another point involves the proximity of the β-hydroxy group and the methoxyl oxygen atom in the 2-position of the ring. There is going to be a strong hydrogen-bonding with this orientation, with the formation of a stable six-membered ring. This might help obscure the hydrophilic nature of the free hydroxyl group and allow the compound to pass into the brain easily. If this group is masked by an easily removed group such as an acetate ester, one gets the compound β-acetoxy-2,5-dimethoxy-4-methylphenethylamine () which is similar to BOHD as a hypotensive.
The code-naming procedure used here (and elsewhere here in Book II) is: (1) to use “BO” as the alert to there being an oxygen on the benzyl carbon of a phenethylamine (it is a benzyl alcohol); (2) if there is just one more letter (a third and last letter) it will identify the 2C-X parent from which it has been derived [“B” comes from , “D” comes from , “H” comes from () rather than from , “M” comes from , and in every case the β-substituent is a methoxy group]; and (3) if there are four letters, then the fourth letter is as above, and the third letter (the next to last letter) is the substituent on that benzylic oxygen. With a three letter code, the substituent is a methyl group, an “H” for a third letter of four makes it a hydroxyl group, and an “A” for the third letter is an acetyl group, and an “E” is for an ethyl group. A similar sort of cryptographic music was composed by Du Pont in their three-number codes for the Freons. The first number was one less than the number of carbons in the molecule, the second number was one more than the number of hydrogens in the molecule, the third number was the exact number of fluorines in the molecule, and the rest of the bonds were filled with chlorines, Thus Freon 11 (really Freon 011) was trichlorofluoromethane and Freon 116 was hexafluoroethane.
Complex, yes. But both systems are completely straightforward, and flexible for future creations. A few additional examples of similar β-ethanolamines are scattered throughout Book II and they have, in general, proved to be uninteresting, at least as potential psychedelic compounds.
13 May 2016 · ·

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,
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Berkeley, CA 94701

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