SYNTHESIS: A solution of 10.0 g 3-methoxy-4-ethoxybenzaldehyde in 150 mL nitromethane was treated with 1.7 g anhydrous ammonium acetate, and heated on the steam bath for 1 h. The excess nitromethane was removed under vacuum, yielding a loose, yellow crystalline mass that was filtered and modestly washed with cold MeOH. The 8.0 g of damp yellow crystals thus obtained were dissolved in 50 mL of vigorously boiling CH3CN, decanted from a small amount of insolubles (probably ammonium acetate residues) and cooled in an ice bath. The crystals so obtained were removed by filtration, washed with 2×5 mL cold CH3CN, and air dried to constant weight. The yield of 4-ethoxy-3-methoxy-β-nitrostyrene was 6.3 g of beautiful yellow crystals.
A solution of 2.3 g LAH in 70 mL anhydrous THF was cooled, under He to 0 °C with an external ice bath. With good stirring there was added 2.3 mL 100% H2SO4 dropwise, to minimize charring. This was followed by the addition of 6.2 g 3-ethoxy-4-methoxy-β-nitrostyrene in anhydrous THF. After a few min further stirring, the temperature was brought up to a gentle reflux on the steam bath, and then all was cooled again to 0 °C. The excess hydride was destroyed by the cautious addition of IPA followed by sufficent 10% NaOH to give a white granular character to the oxides, and to assure that the reaction mixture was basic. The reaction mixture was filtered and the filter cake well washed with THF. The filtrate and washes were combined and stripped of solvent under vacuum. The residue was dissolved in dilute H2SO4. This was washed with 2×75 mL CH2Cl2, which removed the residual yellow color. The remaining aqueous phase was made basic with NaOH, and extracted with 3×75 mL CH2Cl2. These extracts were combined and the solvent removed under vacuum. The residue was distilled at 108–115 °C at 0.4 mm/Hg to give 4.2 g of a mobile, colorless liquid. This was dissolved in 12 mL IPA, neutralized with 60 drops concentrated HCl, and diluted with 100 mL anhydrous Et2O. There was deposited a fine white crystalline product which, after removal by filtration, ether washing, and air drying, yielded 3.8 g of 3-methoxy-4-ethoxyphenethylamine hydrochloride (MEPEA).
DOSAGE: 300 mg or greater.
(with 300 mg) “Whatever changes took place were complete at the end of an hour. The effects were very quiet, very pleasant, and very light. There was nothing psychedelic here, but rather a gentle lifting of spirits. No sensory enhancement or other expected changes.”
EXTENSIONS AND COMMENTARY: This is one of the very few phenethylamines with only two substituents that shows even a hint of central activity. And there is an interesting story attached. I got a call out of absolutely nowhere, from a Stanislov Wistupkin, that he had discovered a number of new psychedelic drugs which he would like to share with me. Two of them were simple phenethylamines, one with an ethoxy group at the 4-position, and one with an allyloxy group there. Both, he said, were mood elevators active between 100 and 300 milligrams. One of them was this material, here called MEPEA, and the other one was 3-methoxy-4-allyloxyphenethylamine, or MAPEA. When I did meet him in person, he gave me a most remarkable publication which had been authored some ten years earlier, by a person named Leminger, now dead. It was all in Czech, but quite unmistakably, right there on the third page, were the structures of MEPEA and MAPEA, and the statement that they were active at between 100 and 300 milligrams. I have not yet made the allyloxy compound, but I feel that it too might be a gentle mood elevator similar to the ethoxy.
A most appealing extension of these materials would be the amphetamine derivatives, things with a 3-methoxy group, and something small and terse on the 4-position. The immediate analogies of MEPEA and MAPEA would be 3-methoxy-4-ethoxy- (and 3-methoxy-4-allyloxy)-amphetamine. And equally interesting would be the 4-hydroxy analogue. This would be an easily made compound from vanillin, one of our most enjoyable spices in the kitchen cabinet, and it would be directly related to the essential oils, eugenol and isoeugenol. This amphetamine compound has already been synthesized, but it is still unexplored in man.
Some years ago a report appeared in the forensic literature of Italy, of the seizure of a small semitransparent capsule containing 141 milligrams of a white powder that was stated to be a new hallucinogenic drug. This was shown to contain an analogue of DOM, 3-methoxy-4-methylamphetamine or MMA. The Italian authorities made no mention of the net weight contained in each dosage unit, but it has been found that the active level of MMA in man is in the area of 40–60 milligrams. The compound can apparently be quite dysphoric, and long lived.
In the Czechoslovakian publication that presented MEPEA and MAPEA. there were descriptions of escaline (E), proscaline (P), and the allyloxy analogue (AL). These are all active in man, and have been entered elsewhere. This is the only published material dealing with psychedelic drugs I have ever been able to find, from the laboratory of Otakar Leminger. What sort of man was this chemist? He worked for years in industry, and only at the time of his retirement did he publish this little gem. He lived at Usti, directly north of Praha, on the Labe river (which is called by the better known name, the Elbe, as soon as it enters Germany). Might there be other treasures that he had discovered, and never published? Was young Wistupkin a student of his? Are there unrecognized notes of Otakar Leminger sitting in some farm house attic in Northern Czechoslovakia? I extend my heartfelt salute to an almost unknown explorer in the psychedelic drug area.
Meyers-Riggs, B. Leminger’s scalines. countyourculture: rational exploration of the underground, 4 May 2012.
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.
“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
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.
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,