Tryptamine, N,N-dimethyl-4,5-methylenedioxy · Indole, 3-[2-(dimethylamino)ethyl]-4,5-methylenedioxy · N,N-Dimethyl-4,5-methylenedioxytryptamine · 3-[2-(Dimethylamino)ethyl]-4,5-methylenedioxyindole · 5H-1,3-Dioxolo-[4,5-e]indole-7-ethanamine, N,N-dimethyl
SYNTHESIS: To a well-stirred H2O suspension (160 mL) of 3.7 g methyl-trialkylammonium chloride (Adogen 464) and 138 mL CH2Br2 (under nitrogen), there was added a solution of 100 g 3-methylcatechol in 400 mL H2O containing 80 g NaOH, over the course of 2 h. Stirring was continued for 1 h, then the reaction mixture was subjected to steam distillation. The distillate was cooled, and the phases separated. Extraction of the aqueous phase with CH2Cl2, pooling of the organic phases, and removal of the solvent under vacuum, yielded 85 g (78%) of 2,3-methylenedioxytoluene as a colorless oil.
A mixture of 21 g 2,3-methylenedioxytoluene and 1 g Hg(OAc)2 in 59 60 mL acetic acid was stirred and heated to 80 °C. To this there was added, dropwise, 12.8 g of concentrated nitric acid. Heating and stirring was continued for 2 h. The reaction mixture was quenched by pouring it into ice-H2O, and extracted with Et2O. The extracts were pooled, dried with anhydrous MgSO4, and the volatiles removed under vacuum. The orange solid residue was recrystallized from EtOH to provide 20 g (58%) of a mixture of the ortho- and meta-products, 2,3-methylenedioxy-5-nitrotoluene and 2,3-methylenedioxy-6-nitrotoluene, with a mp 65–67 °C. This unresolved mixture was employed in the next step without further purification.
In a flask equipped with a total reflux packed column and a variable take-off head, 15.0 g of the 2,3-methylenedioxy-5-nitrotoluene/2,3-methylenedioxy-6-nitrotoluene mix was added to a mixture of 100 mL freshly distilled DMF and 12.8 g of N,N-dimethylformamide dimethyl acetal. The reaction mixture was heated to a controlled reflux that kept the head temperature at 50 to 70 °C allowing the removal of methanol MeOH. After 4 h, 90% of the theoretical amount of MeOH (7.4 mL) had been distilled off, and the residual solvent (DMF) was removed under vacuum. The dark residue was dissolved in benzene, washed with H2O, dried with anhydrous MgSO4, and the solvent removed under vacuum. The crude crystalline product was recrystallized from hexane/benzene to provide 4.8 g (50%) of 2,3-methylenedioxy-6-nitro-β-dimethylaminostyrene as red needles with a mp 126–120 °C.
A solution of 3.5 g 2,3-methylenedioxy-6-nitro-β-dimethylaminostryrene in 200 mL benzene was placed in a Parr hydrogenation bomb and treated with 0.35 g of 10% Pd/C. The mixture was shaken for 7 h under 3 atm H2. The catalyst was removed by filtration, and the filtrate was washed first with 2 N H2SO4, followed by aqueous NaHCO3 and H2O. This was dried and the solvent removed under vacuum to give 1.2 g (50%) of 4,5-methylenedioxyindole as a residue. After crystallization from benzene/petroleum ether, it had a mp 111 °C. Anal: C,H,N.
A solution of 4.8 g 4,5-methylenedioxyindole in 60 mL anhydrous Et2O was stirred and cooled with an external ice bath. There was added, dropwise, a solution of 5.0 g oxalyl chloride in Et2O so that the temperature did not exceed 5 °C. The intermediate acid chloride separated as a red solid, and was removed by filtration and washed with Et2O. It was then suspended in 60 mL cold anhydrous Et2O, treated with 7 mL dimethylamine and the mixture stirred for 30 min. The solvent was decanted from the crude solids that formed, and they were suspended in 50 mL H2O. The product was removed by filtration and vacuum dried to provide 5.7 g (77%) 4,5-methylenedioxy-N,N-dimethylindole-3-glyoxylamide N,N-dimethyl-4,5-methylenedioxyindole-3-glyoxylamide as a white solid with a mp 240–243 °C.
To a stirred and cooled solution of 3.8 g LAH in 100 mL anhydrous THF there was added, over the course of 1 h, a solution of 3.7 g 4,5-methylenedioxy-N,N-dimethylindole-3-glyoxylamide N,N-dimethyl-4,5-methylenedioxyindole-3-glyoxylamide in 500 mL anhydrous THF. After 1 h reflux, the cooled reaction mixture was treated with 3.8 mL H2O, followed by 3.8 mL aqueous 5% NaOH and then by an additional 10.4 mL H2O. The solids were removed by filtration and washed with THF. The combined filtrate and washings were dried (MgSO4) and the solvent removed under vacuum. The residual oil was distilled at the KugelRohr (0.5 mm/Hg at 100 °C) to give a distillate that solidified. This was crystallized from benzene/petroleum ether to provide 0.25 g (8%) of 4,5-methylenedioxy-N,N-dimethyltryptamine (4,5-MDO-DMT) with mp 93–95 °C. Anal: C, H. N.
EXTENSIONS AND COMMENTARY: The two aromatic ring positions that are associated with human psychedelic activity are the 4-position (of
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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.
“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 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.
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.Transform Press,
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