Book II of PiHKAL: A Chemical Love Story. Alexander & Ann Shulgin #119: ME
SYNTHESIS: To a vigorously stirred suspension of 18.6 g of 5-bromobourbonal in 100 mL CH2Cl2 there was added 14.2 g methyl iodide, 1.0 g decyltriethylammonium iodide, and 120 mL 5% NaOH. The color was a deep amber, and within 1 min the top phase set up to a solid. This was largely dispersed with the addition of another 50 mL of water. The reaction was allowed to stir for 2 days. The lower phase was washed with H2O, and saved. The upper phase was treated with another 100 mL CH2Cl2, 50 mL of 25% NaOH, another g of decyltriethylammonium iodide, and an additional 50 mL of methyl iodide. The formed solids dispersed by themselves in a few h to produce two relatively clear layers. Stirring was continued for an additional 3 days. The lower phase was separated, washed with H2O, and combined with the earlier extract. The solvent was removed under vacuum to give 20.3 g of an amber oil that was distilled at 120–133 °C at 0.4 mm/Hg to yield 15.6 g of 3-bromo-4-methoxy-5-ethoxybenzaldehyde as a white crystalline solid with a mp of 52–53 °C.
A mixture of 15.6 g 3-bromo-4-methoxy-5-ethoxybenzaldehyde and 10 mL cyclohexylamine was heated with an open flame until it appeared free of H2O. The residue was put under a vacuum (0.5 mm/Hg) and distilled at 148–155 °C yielding 19.2 g 3-bromo-N-cyclohexyl-4-methoxy-5-ethoxybenzylidenimine as an off-white crystalline solid with a melting point 66–68.5 °C. Recrystallization from 100 mL boiling MeOH gave a mp of 67–68.5 °C. The C=N stretch in the infra-red was at 1640 cm-1. Anal. (C16H22BrNO2) C,H.
A solution of 17 g 3-bromo-N-cyclohexyl-4-methoxy-5-ethoxybenzylidenimine in 200 mL anhydrous Et2O was placed in an atmosphere of He, stirred magnetically, and cooled with an external dry-ice acetone bath. Then 38 mL of a 1.55 M solution of butyllithium in hexane was added over 2 min, producing a clear yellow solution. There was then added 25 mL of butyl borate at one time, and the stirred solution allowed to return to room temperature. This was followed with 100 mL of saturated aqueous ammonium sulfate. The Et2O layer was separated, washed with additional saturated ammonium sulfate solution, and evaporated under vacuum The residue was dissolved in 200 mL of 50% MeOH and treated with 12 mL of 30% hydrogen peroxide. This reaction was mildly exothermic, and was allowed to stir for 15 min, then added to an aqueous solution of 50 g ammonium sulfate. This was extracted with 2×100 mL CH2Cl2, the pooled extracts washed once with H2O, and the solvent removed under vacuum. The residue was suspended in dilute HCl, and heated on the steam bath for 0.5 h. Stirring was continued until the reaction was again at room temperature and then it was extracted with 2×100 mL CH2Cl2. These extracts were pooled and in turn extracted with 2×100 mL dilute NaOH. The aqueous extracts were reacidified with HCl, and reextracted with 2×100 mL CH2Cl2. After pooling, the solvent was removed under vacuum to yield an oily residue. This was distilled at 118–130 °C at 0.2 mm/Hg to yield 7.5 g of 3-ethoxy-5-hydroxy-4-methoxybenzaldehyde as a distillate that set to white crystals. Recrystallization from cyclohexane gives a product with a mp of 77–78 °C. Anal. (C10H12O4) C,H.
A solution of 7.3 g of 3-ethoxy-5-hydroxy-4-methoxybenzaldehyde in 100 mL acetone was treated with 5 mL methyl iodide and 8.0 g finely powdered anhydrous K2CO3, and held at reflux on a steam bath for 6 h. The solvent was removed under vacuum, and the residue was suspended in H2O. After making this strongly basic, it was extracted with 3×50 mL CH2Cl2, the extracts were pooled, and the solvent removed under vacuum. The residual amber oil was distilled at 110–120 °C at 0.4 mm/Hg to yield 7.3 g of a white oil. This spontaneously set to white crystals of 3,4-dimethoxy-5-ethoxybenzaldehyde which had a mp of 49–49.5 °C. Anal. (C11H14O4) C,H. This same aldehyde can be obtained, but in a less satisfactory yield, by the ethylation of 3,4-dimethoxy-5-hydroxybenzaldehyde described under the preparation of
A solution of 7.2 g 3,4-dimethoxy-5-ethoxybenzaldehyde in 100 mL nitromethane containing 0.1 g anhydrous ammonium acetate was held at reflux for 50 min. The excess nitromethane was removed under vacuum producing 6.8 g of a red oil which was decanted from some insoluble material. Addition of 10 mL hot MeOH to the decantings, gave a homogeneous solution that spontaneously crystallized on cooling. The yellow crystals were removed by filtration, washed sparingly with MeOH and air dried yielding 3.5 g yellow crystals of 3,4-dimethoxy-5-ethoxy-β-nitrostyrene, with a mp of 89.5–90 °C after recrystallization from MeOH. Anal. (C12H15NO5) C,H.
A solution of 2.0 g LAH in 100 mL anhydrous THF under He was cooled to 0 °C and vigorously stirred. There was added, dropwise, 1.3 mL of 100% H2SO4, followed by the dropwise addition of a solution of 3.1 g 3,4-dimethoxy-5-ethoxy-β-nitrostyrene in 50 mL anhydrous THF, over the course of 10 min. The mixture was stirred at 0 °C for a while, and then brought to a reflux on the steam bath for 30 min. After cooling again, the excess hydride was destroyed with IPA in THF, followed by the addition of 20 mL 10% NaOH which was sufficient to convert the solids to a white and granular form. These were removed by filtration, the filter cake washed with IPA, the mother liquor and filtrates combined, and the solvents removed under vacuum. The residue was added to 150 mL dilute H2SO4, and the cloudy suspension washed with 2×75 mL CH2Cl2 which removed much of the color. The aqueous phase was made basic with 25% NaOH, and extracted with 3×50 mL CH2Cl2. The solvent was removed from these pooled extracts and the residue distilled at 103–116 °C at 0.25 mm/Hg to provide 2.3 g of a colorless viscous liquid. This was dissolved in 10 mL IPA, neutralized with about 25 drops of concentrated HCl, which produced an insoluble white solid. This was diluted with 40 mL anhydrous Et2O added slowly with continuous stirring. The white crystalline 3,4-dimethoxy-5-ethoxyphenethylamine hydrochloride (ME) was isolated by filtration, washed with Et2O, and air dried, and weighed 2.4 g. It had a mp of 202–203 °C which increased by one degree upon recrystallization from boiling IPA. Anal. (C12H20ClNO3) C,H.
DOSAGE: 200–350 mg.
DURATION: 8–12 h.
QUALITATIVE COMMENTS: (with 200 mg) “It tasted pretty strong. However, the taste was soon gone, and an energetic feeling began to take over me. It continued to grow. The feeling was one of great camaraderie, and it was very easy to talk to people. Everyone was talking to everyone else. I found it most pleasant, energetic and at the same time relaxing, with my defenses down. This material did not seem to lead to introspection; however, it might if one took it without other people around. Heightened visual awareness was mild, but the audio awareness was quite heightened. The feeling of being with everyone was intense.”
(with 250 mg) “Initially I took 200 milligrams of metaescaline, and the experience developed for me very gradually at first, and very pleasantly. After about one half hour I became aware of a wall that seemed to shut me in, not unpleasantly. The wall slowly dissolved, but I was afraid I might get into a negative experience. I felt immediate relief (from this isolation) upon taking the additional 50 mg (at 2:23 into the experiment) as though glad of the decision. I lay down outside on a blanket. There was a marvelous feeling inside, although no imagery. I felt the wall dissolve completely, and I desired to join the group. From this point on the experience was most enjoyable, euphoric. Although not dramatic like some psychedelics, it was most rewarding for me personally. I felt a marvelous bond with everyone present, with clear-headed, excellent thinking, and excellent communication. All in all, a most rewarding and enjoyable experience. Afterwards I felt much strengthened, with good energy and good insight. I have a strong feeling that the group tailored the nature of the experience, and that I and others were most desirous of group interaction. I feel that one could do a lot of other things with it if one turned one’s attention to it.”
(with 275 mg) “Onset of both physical and mental change was slow relative to other psychochemicals. Very gradual internal stirrings were felt at about the hour-and-a-half point. These were mostly feelingful rather than cognitive, and were quite pleasurable. At about the two-and-a-half hour point I grew quite thirsty, and drank a pint of beer. Almost immediately, and quite unexpectedly, I tomsoed to a much higher level and remained there for another three hours until the whole experience waned. [The verb, to tomso, means a sudden rekindling of the drug-induced altered state with a small amount of alcohol. It is explained in the recipe for
(with 400 mg) “Ingested 300 milligrams at about 1:30 in the afternoon. Very quiet climb. Occasional yawns. Matter-of-fact view of the world. No rosy glow. At the end of the second hour, I seem to be stuck at a ++. Take another 100 milligrams at 3:45 p.m. Still tastes awful. Feel a small head-rush fifteen minutes after taking the supplement, and within a half hour I am completely +3. For a while this was a sterner
EXTENSIONS AND COMMENTARY: The reorientation of the single ethyl group of escaline (
There are other distinctions from
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 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.”
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)