SYNTHESIS: A solution of 149 g sodium thiosulfate in 300 mL H2O was vigorously stirred. To this there was added, over the course of 10 min, a solution of 43.2 g benzoquinone in 200 mL acetic acid. After an additional 1 h stirring at room temperature, all volatiles were removed under vacuum. The residual syrup slowly set up as crystals which, after grinding under brine, were removed by filtration and washed with additional brine. These were dissolved in MeOH, clarified by filtration through a Celite bed, and the clear filtrate stripped of solvent under vacuum. The yellow, powdery sodium 2,5-hydroxyphenylthiosulfate weighed 67 g when dry. This intermediate was dissolved in aqueous HCl (50 g in 200 mL H2O containing 400 mL concentrated HCl), cooled with an external ice bath, and treated with 250 g zinc dust added at a rate that kept the temperature below 60 °C. About 1.5 h were required, and caution must be taken concerning the poisonous hydrogen sulfide that evolves. An additional 50 mL concentrated HCl was added, and the aqueous phase decanted from the unreacted zinc metal. This was extracted with 6×100 mL Et2O, and these extracts were pooled, washed with brine, and the solvent removed under vacuum to yield 33.1 g of 2,5-dihydroxythiophenol as pale yellow needles with a mp of 118–119 °C.
A solution of 118.6 g KOH pellets in 200 mL H2O was placed under N2, and to it was added 24.0 g 2,5-dihydroxythiophenol. With vigorous stirring, there was then added 160 g methyl sulfate at a rate that maintained the temperature at about 60 °C. This took about 2 h. After the addition was complete, the mixture was held at reflux for 3 h, and allowed to stir at ambient temperature overnight. It was then filtered, and the filtrate extracted with 6×100 mL Et2O, the extracts pooled, washed with 2×50 mL brine, dried over anhydrous Na2SO4, and the solvent removed under vacuum. The residue was distilled at 86–88 °C at 0.04 mm/Hg to provide 25.9 g of 2,5-dimethoxythioanisole as a white oil that crystallized on standing. Its mp was 33–34 °C. An alternate preparation of this compound follows the direct methylation of 2,5-dimethoxythiophenol (see under
To 40 mL dry CH2Cl2 there was added 6.07 g 2,5-dimethoxythioanisole, and this was cooled to 0 °C under N2. To this well stirred solution there was added 13.02 g stannic chloride over the course of 2 min. This was followed by the drop-wise addition of dichloromethyl methyl ether over 5 min, and the reaction mixture allowed to stir for an additional 15 min. After returning to room temperature, it was stirred for an additional 1 h. The reaction mixture was poured over 15 g ice, and the organic phase separated, washed with 3×25 mL 3 N HCl, with 3×50 mL brine and, after drying over anhydrous Na2SO4, the solvent was removed under vacuum. The residue was a solid and, after recrystallization from MeOH/H2O, gave 5.86 g 2,5-dimethoxy-4-(methylthio)benzaldehyde with a mp of 95–97 °C. Purification via the bisulfite complex provided an analytical sample with mp of 99–100 °C. Anal. (C10H12O3S) C,H,S. The malononitrile derivative (from equal weights of the aldehyde and malononitrile in EtOH with a drop of triethylamine as catalyst) was recrystallized from an equal volume of EtOH to give orange crystals with a mp of 185–186 °C. Anal. (C13H12N2O2S) C,H,N,S.
A solution of 2.1 g 2,5-dimethoxy-4-(methylthio)benzaldehyde in 7.5 mL nitromethane was treated with 0.45 g anhydrous ammonium acetate and held at steam bath temperature for 6 h. The deep red solution was stripped of solvent to give a residue that spontaneously crystallized. This was ground up under 12 mL MeOH, filtered, and washed with MeOH to yield, after air-drying, 1.7 g of 2,5-dimethoxy-4-methylthio-β-nitrostyrene as orange solids. Recrystallization from EtOH provided rust-orange colored crystals with a mp of 165.5–166 °C. Anal. (C11H13NO4S) C,H,N,S: calcd, 12.56; found, 11.96.
To a gently refluxing mixture of 1.4 g LAH in 40 mL anhydrous THF under an inert atmosphere there was added, dropwise, 1.7 g 2,5-dimethoxy-4-methylthio-β-nitrostyrene in 25 mL THF. The refluxing was continued for 18 h, and the stirring continued for another day at room temperature. There was then added 1.5 mL H2O (diluted with a little THF), 1.5 mL 15% NaOH, and finally 4.5 mL H2O. The white aluminum oxide salts were removed by filtration, and the filter cake washed with THF. The filtrate and washings were combined and stripped of solvent under vacuum yielding a straw-colored residue that crystallized (mp 81–92 °C without purification). This residue was dissolved in 25 mL IPA and neutralized with concentrated HCl. The slightly pink solution spontaneously crystallized. There was added 100 mL anhydrous Et2O, and the white crystalline mass of 2,5-dimethoxy-4-methylthiophenethylamine hydrochloride (2C-T) was removed by filtration, washed with Et2O, and air dried. The final weight was 1.0 g, and had a mp of 232–237 °C. Recrystallization from EtOH provided an analytical sample with mp 240–241 °C. IPA was not a good recrystallization solvent. Anal. (C11H18ClNO2S) C,H,N,S.
DOSAGE: 60–100 mg.
DURATION: 3–5 h.
QUALITATIVE COMMENTS: (with 60 mg) “Poetry was an easy and natural thing. Both the reading of it and the writing of it. This is a potential
(with 75 mg) “I am already aware at a quarter of an hour into it! It develops very quickly but very quietly. There are no visuals at all but, rather, a tactile sensitivity, with warm close feelings. This could be very erotic. There is some fantasy to music, but nothing very demanding. The viewing of pictures doesn’t do much either. The drop-off was extremely relaxed, with a good body feeling. At the fifth hour I was able to drift into an excellent, deep sleep with busy dreams. In the morning I felt refreshed and active, without apparent deficit.”
(with 75 mg) “I got up to a thin and fragile plus two, but there was a continuing feeling of a hooded cloak brought down over my head. Nothing obvious—it is transparent—but it somehow separated me from everything around me. I do not think the overall experiment was worth it.”
(with 100 mg) “Material all right, but a little bit along the lines of a ‘generic’ psychedelic effect. Sharper edges than
(with 125 mg) “There was some physical tummy uncertainty, but once that was past, talking was extremely easy. This is probably really psychedelic, but I am not really sure why, as there is not much in the way of visuals. Dropping was noted just after hour number three, and I was at baseline three hours later.”
EXTENSIONS AND COMMENTARY: The earliest work with the sulfur atom was with the three-carbon chain materials, the ALEPHs. It was only after a considerable time of working with them, and trying to come to peace with their property of being so different from person to person as to potency, that the two-carbon homologues were looked at. Although the first of these (this compound, called 2C-T) was prepared at the same time as ALEPH-1, there was a lapse of about four years between their trials. The relatively low potency of 2C-T was a bit discouraging. But the methodical pursuit of the higher 2C-T’s (to parallel the higher ALEPHs) proved to be a treasure house, and they have been explored much further than any of the ALEPHs.
A note on the “T” in 2C-T. Many, in fact most, of the 2C’s have their name based on the last letter of the amphetamine prototype.
Both of the homologous mono-ethoxy Tweetios of 2C-T have been synthesized and evaluated. The 2-EtO-homologue of 2C-T is 2-ethoxy-5-methoxy-4-methylthiophenethylamine, or plus one state, and what did occur, lasted for only 4 hours.
The 5-EtO-homologue of 2C-T is 5-ethoxy-2-methoxy-4-methylthiophenethylamine, or Halcion was needed to allow sleep. There were a lot of dreams, and the next day was restful.
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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