Tryptamine, N,N-dibutyl-4-hydroxy · 4-Indolol, 3-[2-(dibutylamino)ethyl] · N,N-Dibutyl-4-hydroxytryptamine · 3-[2-(Dibutylamino)ethyl]-4-indolol
#15 4-HO-DBT SYNTHESIS: A solution of 0.50 g 4-acetoxyindole (see under for its preparation) in 5 mL Et2O was stirred and cooled to 0 °C with protection from atmospheric moisture. There was then added 0.5 mL oxalyl chloride. The reaction mixture was stirred for an additional 30 min, and the intermediate indoleglyoxyl chloride separated as a yellow crystalline solid but was not isolated. This was treated with a 40% solution of dibutyl amine in anhydrous Et2O, dropwise, until the pH was 8–9. The reaction was diluted with 100 mL CHCl3 and shaken with 30 mL of a 5% aqueous NaHSO4 followed by 30 mL of a saturated aqueous NaHCO3 solution. After drying over anhydrous MgSO4, the organic solvents were removed under vacuum. The residue was recrystallized from cyclohexane/hexane to give 0.78 g (77%) of 4-acetoxyindol-3-yl-N,N-dibutylglyoxylamide with a mp 123–125 °C. Anal: C,H,N.
To a stirred suspension of 0.50 g LAH in 10 mL anhydrous THF stirred under nitrogen, at room temperature, there was added a solution of 0.78 g 4-acetoxyindol-3-yl-N,N-dibutylglyoxylamide in 10 mL anhydrous THF. This was added dropwise at a rate that maintained the reaction at reflux. When the addition was complete, the reflux was maintained for an additional 15 min and then the reaction was cooled to 40 °C. The excess hydride and the product complex were destroyed by the addition of 1.0 mL EtOAc followed by 3.0 mL H2O. The solids were removed by filtration, the filter cake washed with THF, the filtrate and washings pooled, and the solvents removed under vacuum. The residue was distilled at the KugelRohr and the distillate recrystallized from EtOAc/hexane. Thus there was obtained 0.20 g (35%) of 4-hydroxy-N,N-dibutyltryptamine (4-HO-DBT) with a mp 74–75 °C. C,H,N.
DOSAGE: >20 mg, orally
DURATION: unknown
QUALITATIVE COMMENTS: (with 20 mg, orally) “No effect.”
EXTENSIONS AND COMMENTARY: This was a total disappointment. With the remarkable activity of the diisopropyl compound () this seemed to be a promising candidate for activity. Especially interesting would be the di-sec-butyl isomer with the same branching of the chain right at the position of attachment to the basic nitrogen atom.
Let me ask the chemist who is reading this at the moment, to allow Allow me a moment to present to the non-chemist a lay definition of what is being talked about here. This is one of the most exciting, and most annoying, tidbit tidbits of what could be called isomeric aliphatic chain branching. Please, all non-chemists, forget that I used that phrase. Let me give a simple demonstration of the weird terms (such as methyl, ethyl, propyl, butyl) and prefixes (such as normal, iso, secondary, tertiary) that have been part and parcel of this second half of the book. Let me give you, hypothetically, any number of tennis balls (my metaphor for carbon atoms) from one (initially) to four (at which point I will abandon ship). You are to put them (however many you have) up against the tennis net in every possible way.
You have one tennis ball. There is only one way you can do it. There is the net (the nitrogen atom with an implacable point of attachment, that can touch only one ball at a time, at least in this example), and here is the ball (the carbon atom that has to be attached to it):
N – C one carbon is methyl,
there is only one way it can be attached
Now you have been given two tennis balls:
N – C – C two carbons is ethyl,
there is only one way you can attach them
Now you have been given three tennis balls:
N – C – C – C three carbons is propyl,
this is one way they can be attached
(known as propyl)
But a second possibly possibility emerges:
N – C – C
the third tennis ball can touch the first,
rather than the second ball
(known as isopropyl)
Now you have been given the fourth tennis ball:
N – C – C – C – C four carbon atoms is butyl,
this is one way they can be attached
(known as normal butyl, or n-butyl),
N – C – C – C
the fourth ball can touch the first,
this is another way they can touch
(known as secondary butyl, or sec-butyl)
N – C – C – C
the fourth ball can touch the second,
this is yet another way they can touch
(known as isobutyl, or i-butyl),
(of course, if the fourth ball touches the third, you have the normal butyl as shown above)
N – C – C
the third and fourth ball can touch the first one,
this is the fourth way they can touch
(known as tertiary butyl, or tert-butyl)
You can have one of the four tennis balls touching two of the others at the same time (as well as touching the nitrogen); this formation is known as a cyclopropyl ring. Four of them all touching one another gives a cyclobutyl ring. You can see that when the number of tennis balls gets into the many dozens, the isomer count gets into the many millions, because there can be not just straight out, but ups and downs as well, and little rings and big rings and multiple rings, and cross-linking and everything and anything that can be imagined. That, in a word, is what makes chemistry fun. When two groups that are the same are both attached to the nitrogen atom, you have a di-compound, and with this four-tennis ball analogy, you can have dibutyl, or di-isobutyl, or di-sec-butyl or di-tert-butyl tryptamine and, of course, all possible mixtures.
Back to the rational world. Two n-butyl groups gives the compound 4-HO-DBT, the theme of this recipe. It is not active at 20 milligrams, but I suspect that it will be so at a somewhat higher dose. There is the secondary-isomer, 4-hydroxy-N,N-di-sec-butyltryptamine (, an oil that never crystallized) which should be an isomer of increased activity, but it has not been assayed. The iso-isomer (, mp 152–154 °C) should be yet less active as the steric mess around that important nitrogen atom is much larger, and indeed it is not active at the same 20 milligram level. The tertiary isomer () has yet to be made and, as it is extremely crowded around that innocent nitrogen atom, it may be unmakable. The activity is unknown, as the compound itself is unknown. The four methyl butyl possibilities are all known, and are mentioned in the recipe for .
13 May 2016 · Creative Commons BY-NC-SA ·

About TiHKAL · info

This version of Book II of TiHKAL is based on the Erowid online version created by Bo Lawler with the help of Erowid, from content generously provided in electronic format by the Authors.
The Erowid online version does not always align precisely with the printed version. Text appears to have been inserted, deleted, or changed at various points. Where the two are seen to diverge both the Erowid and print versions are given. Sharp-eyed readers are encouraged to report novel discrepancies.
As with PiHKAL, I’ve again attempted to reproduce the typographic style of the printed edition. I’ve again 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 TiHKAL has been reserved in all forms and it may not be distributed. Book II of TiHKAL may be distributed for non-commercial reproduction provided that the introductory information, copyright notice, cautionary notice and ordering information remain attached.

Ordering information

TiHKAL is the extraordinary record of the authors’ years exploring the chemistry and transformational power of tryptamines. 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 TiHKAL 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.
TiHKAL (ISBN 0-9630096-9-9) is available for US$24.50 (plus $10 domestic first-class shipping) from Transform Press.
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