SYNTHESIS: A mixture of 102 g POCl3 and 115 g N-methylformanilide was allowed to stand for 0.5 h at room temperature during which time it turned a deep claret color. To this there was added 45 g 3,4-methylenedioxytoluene and the mixture was held on the steam bath for 3 h. It was then added to 3 L H2O. Stirring was continued until the oil which had separated had become quite firm. This was removed by filtration to give a greenish, somewhat gummy, crystalline solid, which was finely ground under 40 mL MeOH and again filtered giving, when air dried, 25 g of an almost white solid. Recrystallization of a small sample from methylcyclopentane gave ivory-colored glistening crystals of 2-methyl-4,5-methylenedioxybenzaldehyde with a mp of 88.5–89.5 °C. In the infra-red, the carbonyl was identical to that of the starting -1) but the fingerprint was different and unique, with bands at 868, 929, 1040 and 1052 cm-1.
A solution of 23 g 2-methyl-4,5-methylenedioxybenzaldehyde in 150 mL nitroethane was treated with 2.0 g anhydrous ammonium acetate and heated on the steam bath for 9 h. The excess solvent was removed under vacuum to give a dark yellow oil which was dissolved in 40 mL hot MeOH and allowed to crystallize. The solids were removed by filtration, washed modestly with MeOH and air dried, to give 21.2 g of 1-(2-methyl-4,5-methylenedioxyphenyl)-2-nitropropene as beautiful yellow crystals with a mp of 116–118 °C. Recrystallization of an analytical sample from MeOH gave lustrous bright yellow crystals with a mp of 120–121 °C. Anal. (C11H11NO4) C,H,N.
A suspension of 54 g electrolytic elemental iron in 240 g glacial acetic acid was warmed on the steam bath, with frequent stirring. When the reaction between them started, there was added, a portion at a time, a solution of 18.2 g 1-(2-methyl-4,5-methylenedioxyphenyl)-2-nitropropene in 125 mL warm acetic acid. The orange color of the nitrostyrene solution became quite reddish, white solids of iron acetate appeared, and a dark tomato-colored crust formed which was continuously broken back into the reaction mixture. Heating was continued for 1.5 h, and then all was poured into 2 L H2O. All the insolubles were removed by filtration, and these were washed well with CH2Cl2. The filtrate and washes were combined, the phases separated, and the aqueous phase extracted with 2×100 mL additional CH2Cl2. The combined organics were washed with 5% NaOH, and the solvent removed under vacuum. The residue weighed 15.9 g, and was distilled at 90–110 °C at 0.4 mm/Hg to give 13.9 g of 2-methyl-4,5-methylenedioxyphenylacetone that spontaneously crystallized. A small sample from methylcyclopentane had a mp of 52–53 °C, another from hexane a mp of 53–54 °C, and another from MeOH a mp of 54–55 °C. Anal. (C11H12O3) H; C calcd, 68.73; found 67.87, 67.84.
To a stirred solution of 30 g methylamine hydrochloride in 200 mL warm MeOH there was added 13.5 g 2-methyl-4,5-methylenedioxyphenylacetone followed, after returning to room temperature, by 7 g sodium cyanoborohydride. There was added HCl as needed to maintain the pH at approximately orange on external damp universal pH paper. After a few days, the reaction ceased generating base, and all was poured into 2 L dilute H2SO4 (caution, HCN evolved). This was washed with 3×75 mL CH2Cl2, made basic with 25% NaOH, and the resulting mixture extracted with 3×100 CH2Cl2. The pooled extracts were stripped of solvent under vacuum and the residue, 15 g of a pale amber oil, was distilled at 95–110 °C at 0.4 mm/Hg. There was obtained 12.3 g of a white oil that was dissolved in 60 mL IPA, neutralized with approximately 5.5 mL concentrated HCl, and crystals of the salt formed spontaneously. These were loosened with the addition of another 10 mL IPA, and then all was diluted by the addition of an equal volume of anhydrous Et2O. The white crystals were separated by filtration, Et2O washed, and air dried to give 14.1 g of 2,N-dimethyl-4,5-methylenedioxyamphetamine hydrochloride (MADAM-6) as a brilliant white powder with a mp of 206–207 °C. Anal. (C12H18ClNO2) C,H.
DOSAGE: greater than 280 mg.
QUALITATIVE COMMENTS: (with 180 mg) “There is a hint of good things there, but nothing more than a hint. At four hours, there is no longer even a hint.”
(with 280 mg) “I took 150 milligrams, waited an hour for results, which was niente, nada, nothing. Took supplements of 65 milligrams twice, an hour apart. No effect. Yes, we giveth up.”
EXTENSIONS AND COMMENTARY: The structure of MADAM-6 was designed to be that of
How fascinating it is, that a small methyl group, something that is little more than one more minor bump on the surface of a molecule that is lumpy and bumpy anyway, can so effectively change the action of a compound. A big activity change from a small structure change usually implies that the bump is at a vital point, such as a target of metabolism or a point of critical fit in some receptor site. And since 6-MADAM can be looked upon as 6-bump-MDMA, and since it is at least 3× less potent than
Anyway, MADAM-6 is not active. And the equally intriguing positional isomer, the easily made
13 Jun 2018 · · Isomer Design
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,
Berkeley, CA 94701
510 · 934 · 4930 (voice)
510 · 934 · 5999 (fax)