#51 β-D
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3,4,5-Trimethoxy-β,β-dideuterophenethylamine
SYNTHESIS: To a solution of 13.6 g homosyringonitrile (see under
ESCALINE
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for its preparation) in 150 mL acetone containing 200 mg decyltriethylammonium iodide and 30 g of finely powdered anhydrous K2CO3, there was added 20 g methyl iodide. The mixture was held at reflux for 18 h in a heating mantle with effective stirring. This was added to 1 L H2O, acidified with concentrated HCl, and extracted with 3×75 mL CH2Cl2. The extracts were pooled, washed with 2×100 mL 5% NaOH, once with dilute HCl, once with saturated brine, and the solvent was removed under vacuum. The pale yellow residue was distilled at 130–150 °C at 0.3 mm/Hg to yield 12.9 g of 3,4,5-trimethoxyphenylacetonitrile as an off-white solid. Upon crystallization from methylcyclohexane/CHCl3 it was white and had a mp of 77–78 °C. Attempts to prepare this compound by the theoretically appealing route from
3,4,5-trimethoxybenzaldehyde
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to N,N-dimethyl-3,4,5-trimethoxybenzylamine (reductive amination with dimethylamine), to 3,4,5-trimethoxy-N,N,N-trimethylbenzylammonium iodide (methylation with methyl iodide), and then to 3,4,5- trimethoxyphenylacetonitrile (with some source of cyanide ion) gave excellent yields in the first two steps, and no product at all in the last step.
A solution of 20.6 g of 3,4,5-trimethoxphenylacetonitrile in 70 g pyridine was treated with 15 mL 99+% D2O and held at reflux for 24 h. All volatiles were stripped first under vacuum and finally with a hard vacuum at room temperature in a Kugelrohr apparatus. The dark residue was treated again with another 30 mL pyridine and another 15 mL 99+% D2O. The flask was protected with a drying tube and held at reflux for another 24 h. Again, all volatiles were stripped, and the residue distilled at 110–130 °C at 0.25 mm/Hg to yield 16.77 g of an almost white solid. The GCMS verified this chemical to be 3,4,5-trimethoxy-β,β-dideuterophenylacetonitrile, with a parent peak at m/e 209 and no visible peak at m/e 207.
A solution of 250 mL of 1 M LAH in THF was cooled under He to 0 °C and treated with 6.8 mL 100% H2SO4 added very slowly with vigorous stirring. A solution of 18.23 g 3,4,5-trimethoxy-β,β-dideuterophenylacetonitrile in 200 mL anhydrous THF was added slowly, and following the addition stirring was continued for 20 min. The reaction mixture was brought to a reflux for 30 min on a steam bath, cooled again to 0 °C, and the excess hydride destroyed with 15 mL IPA. About 10 mL of 15% NaOH was required to convert the solids to a filterable white consistency. These were removed by filtration, the cake washed with IPA, the filtrates and washes were combined, and the solvent removed under vacuum leaving 17 g of a white oil as residue. This was dissolved in 2 L dilute H2SO4, washed with 3×75 mL CH2Cl2, made basic with aqueous NaOH, and then extracted with 3×75 mL CH2Cl2. Removal of the solvent from these extracts under vacuum yielded 10.3 g of a colorless oil which was distilled at 120–130 °C at 0.3 mm/Hg to provide 9.2 g of a white oil. This was dissolved in 50 mL IPA and neutralized with concentrated HCl, producing spontaneous crystals. These were diluted with 50 mL anhydrous Et2O, removed by filtration, washed first with Et2O/IPA, and then with anhydrous Et2O. After air drying, the final yield of 3,4,5-trimethoxy-β,β-dideuterophenethylamine hydrochloride (β-D) was 10.0 g of white needles.
DOSAGE: 200–400 mg (as the sulfate salt); 178–356 mg (as the hydrochloride salt).
DURATION: 12 h.
QUALITATIVE COMMENTS: (with 200 mg) "The onset was very gradual and very gentle. At about an hour and a half I was rather out of my body (at least I wasn't aware of my body, it felt so light). I was listening to Berlioz Requiem, and it took me to the highest realm. I was totally caught up in the magnificence of the music, of the genius it took to compose it, the love it took to complete it, and the devotion of the composer. I felt as though this music had been written for me. What came next is hard to remember because I was so taken with this experience which came only 1 1/2 hours after ingestion. I wondered what time it was and how come I was having a peak experience so soon, because this material was supposed to reach its peak after two hours. Well, now we can revise the records, heh? Incidentally this material is really good for interior work. It was a magnificent experience—one of the best."
(with 275 mg) "I begin to feel it in 15 minutes, stomach getting squeamish. Looking up into the clouds, becoming absorbed in them, watching light grow in intensity, stomach feelings disappeared. Became totally absorbed by the music. Listening to Boito's Prologue to Mephistopheles—exquisitely beautiful, dramatic. Lying on the couch, the music continuing, I was suddenly filled with enormous power. I realized that raw, male power was pouring through me as I had never before experienced it. I was wild, totally self satisfied, and completely oblivious of others and their needs. I wanted to strike out, to win, to conquer. I felt what conquerers have felt in the past, the unbridled passion to vanquish everything. I could see how such misguided power could lead nations to war. Wanting still more power, I was about to find out if God would grant me the power to destroy the world if I wished it, when I felt a gentle kiss on my brow. My wife had leaned over just in time to save the world."
(with 275 mg) "Never had I had such a magnificent appreciation of God. It was clear that if I minded my business and turned to Him to learn as I had been doing today, then I could continue to grow and learn in a most wonderful way. It became crystal clear to me that I didn't have to help anybody or heal anybody, as everyone can turn directly to the source for their needs. An earth-shaking experience."
(with 300 mg) "I had extreme nausea, and vomited. This had a very hard impact on me, and I had to retreat with a paranoia that swept over me without warning. I lay down and let it sweep on, and through this came several very important insights. At least they were important to me. It was about the fourth hour before I could emerge from my retreat, and at that time I knew that I had answered some troublesome personal problems. It was a satisfactory day, but I probably shall not repeat it."
(with 350 mg) "Strong body awareness started within 15 minutes. Visual activity started within half an hour. Visuals were typical kinds, but seemed to arrive earlier. A strong experience of pleasantness started and continued throughout the experience. I tended to internalize to some extent. Ended on a water bed at maybe an hour and a half, pulled covers over me, and went inward with considerable visuals but not much insight. I felt good about where I was. I would not mind being there again, so something was going well. I am not sure how long this continued. The visuals decreased somewhere around the 5th or 6th hour. After 8 or 9 hours, activity considerably decreased. I felt quite clear and reasonably centered. Would I do this again? The answer is yes."
(with 500 mg) "I consumed the material over a period of twenty minutes, and at the 1 hour 45 minute point, haven't had any nausea, but I am still careful not to bounce around. Am absolutely grounded even though I am completely into the experience. No more that state in which it is possible to seriously consider trying to rise two inches above the floor and skim, as I do so expertly in dreams. As a matter of fact I haven't had those dreams for some time now. This material doesn't allow the straddling of realities as does ordinary
mescaline
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. I know where my realities are, and reality is, basically, where my center is. Thus I am grounded in the physical reality even when the doors are open to non-physical levels."
EXTENSIONS AND COMMENTARY: The
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and the β-D are two of five obvious deuterium isomer derivatives of
. The three remaining are: (1)
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(4-methoxy-3,5-bis-trideuteromethoxyphenethylamine); (2)
(2,6-dideutero-3,4,5-trimethoxyphenethylamine); and (3)
α-D
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(α,α-dideutero-3,4,5-trimethoxyphenethylamine). I fully expect both 3,5-D and 2,6-D to be indistinguishable from
in effect, since it is known that not much metabolism takes place in man at these locations of the molecule.
The last compound,
, could be quite a different matter. The principal metabolite of
3,4,5-trimethoxyphenylacetic acid
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, and this product requires enzymatic attack at the exact position where the deuteriums will be located. To the extent that they are harder to remove (come off more slowly or to a lesser degree), to that extent the molecule will be more potent in man, and the dosage required for effects will be less. The compound will be easily made by the reduction of 3,4,5-trimethoxyphenylacetonitrile with lithium aluminum deuteride. And if there is a believable difference between α-D and
, it will be necessary to synthesize each of the two optically active α-mono-deutero analogs. That will be quite a challenge.
Some years ago I performed a fascinating series of experiments with another isotopically labeled
derivative. This was β-14C labeled material, which I self-administered on three occasions, at three different levels. One dosage was with 350 milligrams, a second a few weeks later was with 4 milligrams, and a third was a few weeks later yet, with about 60 micrograms. In each case, exactly the same absolute quantity of radioactivity was administered, so the metabolic distribution was equally visible. Only the weight dosage was different. Urinary analysis was run for each experiment for the presence of unchanged
, and for the primary metabolite, 3,4,5-trimethoxyphenylacetic acid. The smaller the dosage, the proportionately larger amount of
was oxidized to the inactive acetic acid, and the smaller amount was excreted in an unchanged state. It seemed to me that there might be a finite capacity of the body to oxidatively deaminate
, and at larger and larger dosages, this capacity became increasingly depleted. Perhaps this is why
requires such a large dosage to be effective in man.
11 Aug 2018 · · Isomer Design
#50 4-D	#52 DESOXY
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
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.
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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