3-Thiotrescaline · 3-Thiotrisescaline · 3,4-Diethoxy-5-ethylthiophenethylamine
SYNTHESIS: A solution of 11.5 g 3-bromo-N-cyclohexyl-4,5-diethoxybenzylidenimine (see under 2O was placed in a He atmosphere, well stirred, and cooled in an external dry ice acetone bath to -80 °C. There was light formation of fine crystals. There was then added 25 mL of 1.6 N butyllithium in hexane and the mixture stirred for 15 min. This was followed by the addition of 5.8 g diethyl disulfide over the course of 20 min during which time the solution became increasingly cloudy with the eventual deposition of an insoluble gummy phase. The mixture was allowed to come to room temperature over the course of 1 h, and then added to 400 mL of dilute HCl. The organic phase was separated and stripped of solvent under vacuum. This residue was combined with the original aqueous phase, and the mixture was heated on the steam bath for 2 h. The aqueous mixture was cooled to room temperature, extracted with 3×100 mL CH2Cl2, the extracts pooled, washed with H2O, and the solvent removed under vacuum to yield 11.0 g of an amber oil. This was distilled at 130–150 °C at 0.2 mm/Hg to yield 7.2 g of 3,4-diethoxy-5-(ethylthio)benzaldehyde as a white oil that spontaneously crystallized. The crude product had a mp of 52–57 °C that increased to 57–58 °C upon recrystallization from EtOH. Anal. (C13H18O3S) C,H.
A solution of 14.9 g methyltriphenylphosphonium bromide in 200 mL anhydrous THF was placed under a He atmosphere, well stirred, and cooled to 0 °C with an external ice water bath. There was then added 27.6 mL of 1.6 N butyllithium in hexane which resulted in the generation of a yellow color which was at first transient, and then stable. The reaction mixture was brought up to room temperature, and 6.8 g 3,4-diethoxy-5-(ethylthio)benzaldehyde in 50 mL THF was added dropwise dispelling the color, and the mixture was held at reflux on the steam bath for 1 h. The reaction was quenched in 800 mL H2O, the top layer separated, and the aqueous phase extracted with 2×75 mL of petroleum ether. The organic fractions were combined and the solvents removed under vacuum to give 12.0 g of the crude 3,4-diethoxy-5-ethylthiostyrene as a deep yellow oil.
A solution of 5.6 g of borane-methyl sulfide complex (10 M BH3 in methyl sulfide) in 45 mL THF was placed in a He atmosphere, cooled to 0 °C, treated with 11.6 g of 2-methylbutene, and stirred for 1 h while returning to room temperature. To this there was added the crude 3,4-diethoxy-5-ethylthiostyrene in 25 mL THF and the stirring was continued for 1 h. The excess borane was destroyed with about 2 mL MeOH. There was then added 11.4 g elemental iodine followed by a solution of 2.2 g NaOH in 40 mL hot MeOH. This was followed by sufficient 25% NaOH to minimize the residual iodine color (about 4 mL was required). The reaction mixture was added to 500 mL H2O containing 4 g sodium hydrosulfite. This was extracted with 3×75 mL petroleum ether, and the pooled extracts stripped of solvent under vacuum to yield 24.5 g of crude 1-(3,4-diethoxy-5-ethylthiophenyl)-2-iodoethane as a viscous yellow oil.
This crude 1-(3,4-diethoxy-5-ethylthiophenyl)-2-iodoethane was added to a solution of 11.1 g potassium phthalimide in 80 mL DMF, and all was heated on the steam bath for 1.5 h. It was then flooded with 600 mL H2O, made basic with NaOH, and extracted with 3×100 mL Et2O. Removal of the solvent under vacuum provided 18.5 g of a residue that was dried to a constant weight by heating under vacuum (0.2 mm/Hg). The solid residue was ground under MeOH, and then recrystallized from MeOH providing 1-(3,4-diethoxy-5-ethylthiophenyl)-2-phthalimidoethane as white granular crystals, with a mp of 86.5–87.5 °C. Anal. (C22H25NO4S) C,H.
The recrystallized 1-(3,4-diethoxy-5-ethylthiophenyl)-2-phthalimidoethane was dissolved in n-butanol, treated with 66% hydrazine, and the mixture heated on the steam bath for 1.5 h. This was then added to dilute H2SO4, the butanol separated, the aqueous phase washed with 2×75 mL Et2O. After being made basic with aqueous NaOH, the aqueous phase was extracted with 3×75 mL CH2Cl2 and the solvent removed under vacuum to provide a pale amber oil. This was distilled at 140–155 °C at 0.25 mm/Hg to give about 1 g of a white oil. The distillate was dissolved in 5 mL IPA, neutralized with concentrated HCl, and treated with 10 mL anhydrous Et2O to give a solution from which a white crystalline product slowly separated. These crystals, 3,4-diethoxy-5-ethylthiophenethylamine hydrochloride (3-T-TRIS) weighed 1.1 g and had a mp of 161–162 °C. Anal. (C14H24ClNO2S) C,H.
DOSAGE: greater than 160 mg.
QUALITATIVE COMMENTS: (with 160 mg) There were no effects. At the 9th or 10th hour after having taken the material I was aware of some neurological irritability. I will not try this at any higher dosage, and let me stretch things a bit by a few percent in good conscience and say that this is less active than
EXTENSIONS AND COMMENTARY: The term “M.U.” pops up here and there in a lot of the earlier literature on these phenethylamines. It stands for “
Its intrinsic worth proved, however, to be its very limitation. It was quickly apparent that the principal value, to behavioral researchers, of the reports of new hallucinogenic drugs, was not in the nature of their action but in the amount of stuff needed to produce that action. This was an essential axis against which the animal pharmacologist could plot his findings. A number was wanted, and the
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.
“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.”
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.Transform Press,
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