4-Thiobuscaline · 3,5-Dimethoxy-4-n-butylthiophenethylamine
#149 TB SYNTHESIS: A solution was made of 12.1 g N,N,N′,N′-tetramethylethylenediamine and 13.8 g of 1,3-dimethoxybenzene in 200 mL 30–60 °C petroleum ether. This was stirred vigorously under a He atmosphere and cooled to 0 °C with an external ice bath. There was added 66 mL of 1.6 M butyl lithium in hexane which produced a white granular precipitate. The reaction mixture was brought up to room temperature for a few minutes, and then cooled again to 0 °C. There was then added 18.7 g of di-n-butyl disulfide (this reagent was quite yellow, but was used without any purification) which changed the granular precipitate to a strange salmon color. Stirring was continued while the reaction mixture was brought up to room temperature and finally up to reflux. The reaction mixture was then added to 600 mL of dilute H2SO4. The two phases were separated, and the aqueous phase extracted with 2×75 mL Et2O. The organic phases were combined and the solvent removed under vacuum. The residue weighed 33.0 g and was a dark yellow oil. Efforts to remove this color by reductive extraction of a CH2Cl2 solution with aqueous sodium hydrosulfite were futile. The residue was distilled at 0.3 mm/Hg to give two fractions. The first boiled at 95–115 °C, weighed 4.1 g and was largely recovered dibutyl disulfide. The product 2-n-butylthio-1,3-dimethoxybenzene boiled at 115–135 °C and weighed 19.5 g. It was a pale amber oil that could not be induced to crystallize. Anal. (C12H18O2S) C,H.
To a stirred solution of 19.5 g of 2-n-butylthio-1,3-dimethoxybenzene in 75 mL CH2Cl2 there was added 14.5 g elemental bromine dissolved in 75 mL CH2Cl2. The evolution of HBr was evident, but the reaction was not exothermic. The reaction was allowed to stir for 1 h and then heated briefly to a reflux on the steam bath. It was then washed with H2O containing sodium hydrosulfite which discharged the residual color. After washing with saturated brine, the solvent was removed under vacuum leaving 26.0 g of a pale amber oil. This was distilled at 120–140 °C at 0.4 mm/Hg yielding 4-bromo-2-n-butylthio-1,3-dimethoxybenzene as a yellow-orange oil. It could not be crystallized. Anal. (C12H17BrO2S) C,H.
To a solution of 11.5 mL diisopropylamine in 50 mL hexane that was stirred under N2 there was added 50 mL of 1.6 M butyllithium. After 15 min stirring, the reaction mixture became very viscous, and it was diluted with 150 mL anhydrous THF. After cooling in an ice bath there was added 2.0 mL CH3CN followed in 1 min with 6.0 g of 4-bromo-2-n-butylthio-1,3-dimethoxyanisole a bit at a time over the course of 1 min. There was the immediate formation of a deep red color. After stirring for 0.5 h, the mixture was poured into dilute H2SO4. The organic layer was separated, and the aqueous layer extracted with 3×75 mL CH2Cl2. These extracts were pooled, dried with anhydrous K2CO3, and the solvent was removed under vacuum. The residue was distilled at 0.25 mm/Hg and yielded two fractions. The first fraction boiled at 125–145 °C, weighed 0.8 g and was discarded. The second fraction came over at 145–175 °C as a light yellow oil and weighed 2.2 g. This product, 4-n-butylthio-3,5-dimethoxyphenylacetonitrile, was reduced as such without further purification or analysis.
A solution of LAH under N2 (20 mL of a 1 M solution in anhydrous THF) was cooled to 0 °C and vigorously stirred. There was added, dropwise, 0.53 mL 100% H2SO4, followed by 2.0 g 4-n-butylthio-3,5-dimethoxyphenylacetonitrile in 10 mL anhydrous THF. The reaction mixture was stirred at 0 °C for a few min, then brought to room temperature for 1 h, and finally to a reflux for 1 h on the steam bath. After cooling back to room temperature, there was added IPA (to destroy the excess hydride) followed by 10% NaOH which brought the reaction to a basic pH and converted the aluminum oxides to a loose, white, filterable consistency. These were removed by filtration, and washed with THF and IPA. The filtrate and washes were stripped of solvent under vacuum, the residue was suspended in 150 mL of dilute NaOH and extracted with 3×100 mL CH2Cl2. These extracts were pooled and extracted with 2×75 mL dilute H2SO4. Emulsions required that a considerable additional quantity of H2O be added. The aqueous phase was made basic, and extracted with 2×100 mL CH2Cl2. After combining these extracts, the solvent was removed under vacuum providing a residue that was distilled. The product distilled at 138–168 °C at 0.4 mm/Hg as a white oil weighing 0.7 g. This was dissolved in a small amount of IPA, neutralized with concentrated HCl and, with continuous stirring, diluted with several volumes of anhydrous Et2O. After filtering, Et2O washing, and air drying, 4-n-butylthio-3,5-dimethoxyphenethylamine hydrochloride (TB) was obtained, weighed 0.6 g, and had a mp of 154–155 °C. Anal. (C14H24ClNO2S) C,H.
DOSAGE: 60–120 mg.
DURATION: about 8 h.
QUALITATIVE COMMENTS: (with 35 mg) “I was aware of something at about an hour, and it developed into a benign and beautiful experience which never quite popped into anything psychedelic. At the fifth hour there was a distinct drop, and I made what might be thought of as a foolish effort to rekindle the state with an additional 20 milligrams but it was too little and too late. There was no regeneration of anything additional.”
(with 60 mg) “A very subtle threshold, probably, and six hours into it there seems to have been little if any effect. My memory of it is not that certain and now I am not sure that there had been anything at all.”
(with 80 mg) “I am vaguely aware of something. The body discomfort may reflect the use of sardines in tomato sauce for lunch, but still things are not quite right. Five hours into it I am still in a wonderful place spiritually, but there seem to be some dark edges. I might be neurologically sensitive to this.”
(with 120 mg) “The course of the action of this is extremely clear. The development was from 5 p.m. to 7 p.m. [the experiment started at 4 p.m.] and by 10 p.m. I was dropping and by midnight I went to bed and slept well. Food was not too interesting, and a glass of wine before sleeping produced no noticeable effect. This was an uneventful experience that never really made it off the ground. It was pleasant, but certainly not psychedelic.”
EXTENSIONS AND COMMENTARY: There is a term “dose-dependent” in pharmacology. When there is a complex action produced by a drug, then each of the components of this mixture of effects should be expected to become more intense following a bigger dose of the drug. This is certainly true with most of the actions of psychoactive drugs.
As to the psychedelic aspects of some drugs, there can be visual effects, eyes-open (edge-ripples or colors or retinal games) or eyes-closed (images of the elaborately decorated doors of the mosque, or of an orchestra floating suspended by its music) or fantasy (you are moving beyond the confines of your body and invading someone else’s space). The same applies to tactile enhancement, to the anaesthetic component, to the depth of insight realized from a drug. The more the drug, as a rule, the more the effect, up to the point that new and disruptive effects are realized. This latter is called toxicity.
As to the stimulant component, the same is true. The person gets wired up, and there is no sleep because there is no hiding from a cascade of images and meanings, and the body lies there unwilling to yield guard since both the pounding heart and the interpretive psyche are demanding attention. These aspects also intensify with increasingly higher doses.
But an exception to this is the euphoria-producing aspect of a drug. One sees with increasing doses a continuing “threshold” that makes you aware, that fluffs the senses, but which seems not, at any level, to take over or to command the ship. It is truly a catalytic on or off. You are or you are not. In the “Tomso” effect, this action is produced by alcohol. There is disinhibition with alcohol which allows a central intoxication from the drug regardless of the amount of drug used (see under TOMSO). One sees again, here with TB, the case of a perpetual series of “thresholds.” Never the psychedelic or the stimulant action that increases with increased dose. Always the simple and ephemeral catalyst of euphoria without substance and without body. It is a compound that can never be pinned and labeled in the butterfly collection since it defies an accepted classification.
This action was seen first with the compound called and when it was called an anti-depressant, it proved to be commercially interesting. It is fully possible that TB would be of value to certain depressed people in exactly the same way.
13 May 2016 · Creative Commons BY-NC-SA ·

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

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.
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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