SYNTHESIS: A solution of 11.5 g 3-bromo-N-cyclohexyl-4,5-diethoxybenzylidinimine (see under ASB for its preparation) in 150 mL anhydrous Et2O 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 4.3 mL dimethyldisulfide over the course of 20 min, during which time the solution became increasingly cloudy and then thinned out again. The mixture was allowed to come to room temperature over the course of an additional h, and then added to 400 mL of dilute HCl. There was the generation of a lot of yellow solids, and the Et2O phase was almost colorless. This was separated, the solvent removed under vacuum, and the residue combined with the original aqueous phase. This phase was then heated on the steam bath for 2 h. The aqueous solution 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 9.4 g of an amber oil which spontaneously crystallized. This was distilled at 125–132 °C at 0.2 mm/Hg to yield 7.1 g of 3,4-diethoxy-5-(methylthio)benzaldehyde as a white oil that spontaneously crystallized. The crude product had a mp of 73–74 °C that actually decreased to 72–73 °C after recrystallization from MeOH. Anal. (C12H16O3S) C,H.
A solution of 16.2 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 30 mL of 1.6 N butyllithium in hexane which resulted in the generation of a clear yellow solution. The reaction mixture was brought up to room temperature, and 7.0 g 3,4-diethoxy-5-(methylthio)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 hexane 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-methylthiostyrene as a pale amber-colored oil.
A solution of 6.0 mL 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 12.6 g of 2-methylbutene, and stirred for 1 h while returning to room temperature. To this there was added a solution of the impure 3,4-diethoxy-5-methylthiostyrene in 25 mL THF. This was stirred for 1 h during which time the color deepened to a dark yellow. The excess borane was destroyed with about 2 mL MeOH (all this still in the absence of air). There was then added 11.4 g elemental iodine followed by a solution of 2.4 g NaOH in 30 mL of boiling MeOH, added over the course of 10 min. This was followed by sufficient 25% NaOH to discharge the residual iodine color (about 4 mL was required). The reaction mixture was added to 500 mL water, and sodium hydrosulfite was added to discharge the remaining iodine color (about 4 g). This was extracted with 3×100 mL petroleum ether, the extracts pooled, and the solvent removed under vacuum to provide 25.9 g of crude 1-(3,4-diethoxy-5-methylthiophenyl)-2-iodoethane as a pale yellow fluid oil. Thin layer chromatographic analysis of this material on silica gel plates (using a 90:10 mixture of CH2Cl2/methylcyclopentane as solvent) showed largely the iodo-product (Rf 0.9) with no visible starting aldehyde (Rf 0.7).
To this crude 1-(3,4-diethoxy-5-methylthiophenyl)-2-iodoethane there was added a solution of 12 g potassium phthalimide in 90 mL anhydrous DMF, and all was held at reflux in a heating mantle. The reaction progress was followed by TLC, and at 1.5 h it was substantially complete. After adding to 500 mL 5% NaOH, the organic phase was separated, and the aqueous phase was extracted with 2×75 mL Et2O. The organic fractions were combined, and the solvent removed under vacuum providing 19.3 g of an amber oil. The residual volatiles were removed by distillation up to 170 °C at 0.2 mm/Hg. The distillate weighed 7.0 g and contained little if any phthalimide by TLC. The pot residue was a viscous amber oil, and also weighed 7.0 g. About half of this was employed in the following hydrolysis step, and the rest was rubbed under an equal volume of MeOH providing 1-(3,4-diethoxy-5-methylthiophenyl)-2-phthalimidoethane as a white solid. A small sample was recrystallized from an equal volume of MeOH to give white crystals with a mp of 79.5–81 °C. Re-recrystallization from MeOH produced an analytical sample with a mp of 83–84 °C. Anal. (C21H23NO4S) C,H.
A solution of 3.2 g of the impure 1-(3,4-diethoxy-5-methylthiophenyl)-2-phthalimidoethane in 150 mL of n-butanol there was added 20 mL of 66% hydrazine, and the mixture was heated on the steam bath for 2 h. This was added to 600 mL of dilute H2SO4, and the two layers were separated. The butanol layer was extracted with 2×100 mL dilute H2SO4. These extracts were added to the original aqueous phase, and this was washed with 3×75 mL CH2Cl2. This was then made basic with 5% NaOH, extracted with 3×75 mL CH2Cl2, and the solvent from these pooled extracts removed under vacuum. The residue (which weighed 9.7 g and contained much butanol) was distilled at 140–145 °C at 0.3 mm/Hg to give 0.7 g of a colorless oil. This was dissolved in 3.0 mL IPA, neutralized with concentrated HCl, and diluted with 12 mL anhydrous Et2O to give a solution that immediately crystallized to provide white crystals of 3,4-diethoxy-5-methylthiophenethylamine hydrochloride (5-TASB). These weighed 0.7 g after washing with Et2O and drying to constant weight. The mp was 182–183 °C, and an analytical sample was dried at 100 °C for 24 h. Anal. (C13H22ClNO2S) C,H.
DOSAGE: about 160 mg.
DURATION: about 8 h.
QUALITATIVE COMMENTS: (with 120 mg) “Maybe there is something at about hour 5. My talking with innocent people had hints of strangeness. And there was the slightest suggestion of some physical effect. Call it an overall (+).”
(with 160 mg) “I am immediately warm at the extremities. An awareness grows upon me for a couple of hours. I am a little light-headed, and I feel that there is more physical than there is mental, and it is not all entirely nice. I am slightly hyperreflexive, and there is a touch of diarrhea. I am happy that I held this at 160 milligrams. I am mentally flat at the eighth hour, although there are some physical residues. The effects are real, but I don’t want to go higher. Some trace physical memory seems to stay with me as a constant companion.”
EXTENSIONS AND COMMENTARY: There is a ponderousness about adding a couple of ethyl groups and a sulfur that seems to say, “no fun.” 5-TASB has something going for it (but not much) and 3-TASB is quite a bit more peppy and, actually, 4-TASB has quite a bit of life. But there is a sense of “why bother?” There were a couple of bouts of light-headedness, but there was no unexpected excitement discovered in this methodical study. No surprises. Keep the chain lengths down.
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. Still others remain to be added.
I have tried here to expunge any artifacts introduced by the earlier transcriptions and restore most of the typographic niceties found in the printed edition. I’ve also made minor changes to some chemical names in line with current nomenclature practice, and in the hope of aligning with more readers’ searches. Typically the change is little more than expanding a prefix and setting it in italics. The errata and changes 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.”
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.
Although 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,