β-Methoxy-2C-D · 4-Methyl-2,5,β-trimethoxyphenethylamine
#14 BOD SYNTHESIS: A solution of 39.6 g 1-(2,5-dimethoxy-4-methylphenyl)-2-nitrostyrene (see recipe for for its preparation) in 300 mL warm MeOH was prepared. Separately, a solution of 9 g elemental sodium in 150 mL MeOH was also prepared. This sodium methoxide solution was added to the well-stirred nitrostyrene solution, which resulted in a dramatic loss of color. There was then added 75 mL acetic acid, and all was poured into 2 L H2O. This was extracted with 3×100 mL CH2Cl2. The pooled extracts were stripped of solvent, and the 35 g of residue was treated with 5 mL MeOH, allowed to stand for a short while, decanted from some insoluble residue, and the separated clear solution kept at 0 °C overnight. There was the deposition of a yellow crystalline product which, after removal by filtration and air drying, weighed 9.7 g. Recrystallization from 25 mL MeOH gave, after filtering and drying, 8.4 g of canary-yellow crystals of 1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane with a mp of 78–79 °C. Evaporation of the mother liquors from the filtration of the first crop yielded 3.8 g of additional product which, upon recrystallization from 11 mL MeOH, provided another 2.7 g with a mp of 77–78 °C. Further workup of the mother liquors yielded only impure starting nitrostyrene.
A solution of LAH (96 mL of 1 M solution in THF) was cooled, under He, to 0 °C with an external ice bath. With good stirring there was added 2.4 mL 100% H2SO4 dropwise, to minimize charring. This was followed by the addition of 10.8 g 1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane. There was immediate discoloration. After the addition was complete, the reaction mixture was held at reflux on the steam bath for 2 h. After cooling again, the excess hydride was destroyed with 4 mL IPA and the reaction mixture made basic with 15% NaOH. The insoluble inorganic salts were removed by filtration, and the filter cake was washed first with THF, and then with IPA. The bright yellow filtrate and washes were pooled and stripped of solvent under vacuum, yielding 14 g of a yellow oil. This was suspended in 1 L dilute H2SO4 to give an ugly, cloudy, yellow-orange mess. Extraction with 3×75 mL CH2Cl2 removed much of the color, and the remaining aqueous phase was made basic with 25% NaOH, and extracted with 3×75 mL CH2Cl2. Evaporation of the solvent under vacuum gave 9 g of a pale amber oil which was distilled at 115–130 °C at 0.4 mm/Hg. The water-white distillate was dissolved in 15 mL IPA, neutralized with concentrated HCl, and then diluted with 70 mL anhydrous Et2O. After a few min, white crystals formed, and these were removed by filtration and Et2O washed. When air-dried to constant weight, 4.49 g brilliant white crystals of 4-methyl-2,5,β-trimethoxyphenethylamine hydrochloride (BOD) with a mp of 171–172 °C with decomposition, were obtained. The mother liquors on standing deposited 0.66 g additional crystals which were impure and were discarded. Anal. (C12H20ClNO3) C,H.
DOSAGE: 15–25 mg.
DURATION: 8–16 h.
QUALITATIVE COMMENTS: (with 20 mg) “There were some very pleasant visuals starting at 2–2.5 hours and continuing to 4–5 hours after the beginning of the experiment. Open eye visuals seem to come on after staring at particular areas, such as the living room ceiling or at trees. The surroundings tended to move slightly. There was no flowing of the images at all. When looking at the pine trees, the needles appeared crystal clear and sharply defined, with strong contrasts. Though the mental effect is difficult to define, I am not sure it was all that great. I did become tired of the effect (along with the confusion) after 8 hours, and was quite happy to note that it did taper off in the early evening. I am not particularly sure I would want to try this material again.”
(with 20 mg) “For the first three or so hours, the beauty of the experience was marred by a strange discomfort. There was some queasiness, and I felt a sluggishness of mind. Then I began moving in and out of a pleasant place, and finally the discomfort completely dissolved and the experience turned full on. Height of beauty, visual perception. Lights below are amazing. Outside, marvelous sense of Presence. There is not an elation, as often with other materials, but a strong, even powerful sense of goodness, inner strength, solidity.”
(with 25 mg) “This was quite quick. The onset of the experience was apparent within a half hour, and we were both at +++ within the hour. Body load minimal. There was very little visual, compared with some materials. Very interesting eyes-closed, but not continually—just now and then an intense vision might flash. Very benign and friendly and pleasant and good-humored feeling. Superb for conversation and conceptualization.”
(with 25 mg) “The body load was quite noticeable for everyone. But the general state of mind was excellent; everyone was extremely relaxed and funny. Puns, insults, delightful amusement. Not very much insight work possible. Juices were needed and tolerated well, but no one was particularly hungry. Sleep was difficult for most people, not deep and not too refreshing. Excellent material, but body price a bit too much for the mental effects. Pleasant, and I wouldn’t hesitate to take it again, but nothing very memorable except the tremendous humor and laughter, which was truly delightful.”
EXTENSIONS AND COMMENTARY: This compound, BOD, was the first exploratory member of a new family of phenethylamines. This family is called the BOX series because an oxygen atom has been put on the benzylic carbon (the “benzyl-oxy” or “BO”) of each of several well studied drugs with recognized substituent patterns on the aromatic ring. The “X” would be “D,” as used here with BOD, making reference to , it would be a “B” in making reference to , etc. Actually the original thought was to make the “O” into an “OM” for methoxy, as this would allow more versatility in the naming of things such as ethoxys (“OE”) or hydroxys (“OH”), but the methoxylated 2C-B analogue would have come out as BOMB, so the idea was dropped.
Actually, the concept of naming of drugs with some acronym that is pronounceable has led into some interesting byways. Some examples have been unintended. I have heard pronounced “dome” and pronounced as “do it.” And elsewhere I have mentioned the embarrassing occasions where the TOM and TOET families were pronounced “the toms and twats.” Some examples have had names that have been contractions of popular names, such as for . And there are instances where a name might be proposed simply to irritate the newspaper people. An early street suggestion for PCP was FUK, and a current name for free-base is SNOT. And marijuana is fondly called SHIT by its aficionados. The final “A” on government groups such as the CIA or the DEA or the FDA is strongly reminscent of the final “A” which stands for amphetamine in things such as and . Might there someday be a drug such as 4-cyclopropylmethyl-N-isopropylamphetamine (CIA), or 3,5-dimethoxy-4-ethylamphetamine (DEA)? It has just occurred to me that there is already a 4-fluoro-2,5-dimethoxyamphetamine (FDA), but I have already named it . If all drugs were known only by publicly embarrassing names, there might be less publicity given them by the press.
Back to the commentary on BOD. The rationale for this inclusion of a beta-oxygen atom into the structure of a phenethylamine is based directly on the chemistry that occurs naturally in the brain. The phenethylamine neurotransmitter, , is converted both in the brain and in the body to the equally important transmitter by just this sort of transformation. There is the enzymatic addition of an oxygen atom to the “benzylic” position of . And identical chemistry goes on with in a number of plants and animals, with a similar addition of oxygen to form , so-named for its discovered presence in the salivary glands of Octopus vulgaris. In the first explorations in the “OX” series, this oxygen was intentionally blocked with a methyl group, to ease its entry into the brain, and increase the possibilities of its being active as a psychedelic. As mentioned above, the “D” in “OD” follows from its ring orientation pattern being the same as that of (and this, originally from the mimicking of the pattern of ). All of these D- compounds have the 2,5-dimethoxy-4-methyl ring-substitution pattern.
An interesting complication is also part of this structure package. The added methoxy group (or hydroxy group, see recipe for ) also adds a new asymmetric center, allowing for the eventual separation of the material into two optical isomers. And at such time as the corresponding amphetamine homologues might be made and studied, the presence of yet another chiral center (under the alpha-methyl group) will demand that there be actually two racemic compounds synthesized, and a total of four isomers to contend with, if really careful and thorough work is to be done.
A parallel chemistry to all of this follows the addition of sodium ethoxide (rather than sodium methoxide) to the nitrostyrene. The final product, then, is the ethoxy homologue 2,5-dimethoxy-β-ethoxy-4-methylphenethylamine, or . It is down in human potency by a factor of three, with a normal dosage being 70–75 milligrams. It has a ten hour duration, and is both anorexic and diuretic. There have been no visual effects or insights reported, but rather simply a highly intoxicated state.
Two synonyms, two definitions, and an expression of admiration. The word is synonymous with noradrenalin, and the word is synonymous with adrenalin. The distinctions are that the first in each case is American and the second British. And the term “chiral” indicates a potential asymmetry in a molecule that would allow eventual separation into two optical isomers. The term “racemic” refers to a mixture of these two isomers which has not yet been separated into the individual components. A racemic mixture is called a racemate and, from the point of view of the human animal (which is completely asymmetric), must be considered as a mixture of two structurally identical but optically mirror-image isomers, which can be potentially separated and which will certainly have different pharmacologies. And the admiration? This is directed to the explorer who ventured close enough to an octopus to locate its salivary glands and to discover a phenethylamine there!
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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