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Book II of PiHKAL: A Chemical Love Story, by Alexander & Ann Shulgin #153: 3-TIM
#153 3-TIM: 3-Thioisomescaline; 2,4-Dimethoxy-3-methylthiophenethylamine

#153 3-TIM SYNTHESIS: A mixture of 3.1 g POCl3 2.8 g N-methylformanilide was heated on a steam bath until it was a deep claret color (about 5 min). To this there was then added 3.0 g of 2,6-dimethoxythioanisole (see under 4-TM for its preparation), and heating was continued for 30 min. The reaction mixture was then added to 75 mL H2O and stirred overnight. The dark oily mixture was extracted with 3×75 mL CH2Cl2, the extracts pooled, and the solvent removed under vacuum. The residue was extracted with 3×20 mL boiling hexane, each extract being poured off from the insoluble residue. Pooling and cooling these extracts yielded 1.5 g of 2,4-dimethoxy-3-(methylthio)benzaldehyde as an off-white crystalline solid with a mp of 67–69 °C. Recrystallization from either MeOH or cyclohexane tightened the mp, but lowered it to 67–68 °C and 66–67 °C, resp. Anal. (C10H12O3S) C,H.

To a solution of 1.3 g 2,4-dimethoxy-3-(methylthio)benzaldehyde in 60 mL nitromethane there was added 0.3 g anhydrous ammonium acetate and the mixture was heated at reflux for 3 h. The hot solution was decanted from a little insoluble material, and the excess nitromethane was removed under vacuum. The residue dissolved in 10 mL hot MeOH. On cooling, yellow crystals of 2,4-dimethoxy-3-methylthio-β-nitrostyrene were obtained which were removed by filtration and air-dried, and weighed 0.9 g. The mp was 130–133 °C and could be improved to 136–137 °C following recrystallization from MeOH (10 g/g). Anal. (C11H13NO4S) C,H.

A well-stirred solution of 0.6 g LAH in 10 mL anhydrous THF was cooled to 0 °C under He. There was added, dropwise, 0.4 mL of 100% H2SO4, followed by 0.6 g of 2,4-dimethoxy-3-methylthio-β-nitrostyrene dissolved in a little THF. Stirring was continued for a few min as the reaction returned to room temperature, and then it was heated to a reflux for 5 min on the steam bath. The reaction was cooled again, and 25% NaOH was added dropwise until a white granular precipitate was obtained. This was removed by filtration, and the filter cake was washed with 2×25 mL Et2O. The filtrate was extracted into 25 mL dilute H2SO4 which was, in turn, made basic again and extracted with 2×25 mL CH2Cl2. The extracts were pooled, and the solvent removed under vacuum to give a residue of crude product. This was distilled from 120–140 °C at 0.3 mm/Hg yielding 0.25 g of a clear white oil. This was dissolved in 5 mL IPA, neutralized with about 3 drops of concentrated HCl, and diluted with 15 mL anhydrous Et2O. Scratching with a glass rod instigated crystallization of bright white solids which were filtered, washed with Et2O, and air dried. The weight of 2,4-dimethoxy-3-methylthiophenethylamine hydrochloride (3-TIM) was 0.2 g and the mp was 204–206 °C with decomposition. This hydrochloride appeared to be a hemihydrate. Anal. (C11H18ClNO2Sa1/2 H2O) C,H,N.

DOSAGE: greater than 240 mg.

DURATION: unknown.

QUALITATIVE COMMENTS: (with 240 mg) “Briefly I thought that there might have been an alert at the 2 to 3 hour point, but I now think it was nothing. During the following day I had a mild stomach upset off and on, but I can’t believe that it was connected with 3-TIM.”

EXTENSIONS AND COMMENTARY: Isomescaline itself is not active, but there is no way of knowing just how “non-active” it really is. If it were to be active just beyond the levels assayed, then the introduction of a sulfur into the molecule in place of an oxygen could have increased the potency to where it might have some effect. The absence of any activity from this TIM, and the other two TIMs, might well suggest that isomescaline is really very “non-active,” if that makes sense!

Page updated 30 March 2012 · This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License ·

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. 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.

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.

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,
Box 13675
Berkeley, CA 94701

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