SYNTHESIS: A solution of 5.8 g of homosyringonitrile (see under E for its preparation), 100 mg decyltriethylammonium iodide, and 13.6 g allyl iodide in 50 mL anhydrous acetone was treated with 6.9 g finely powdered anhydrous K2CO3 and held at reflux for 16 h. The color changed from a near-black to a light yellow. The mixture was filtered, the solids washed with acetone, and the solvent from the combined filtrate and washes removed under vacuum. The residue was suspended in acidified H2O, and extracted with 3x100 mL CH2Cl2. The pooled extracts were washed with 2x50 mL 5% NaOH, once with dilute HCl (which lightened the color of the extract) and then stripped of solvent under vacuum giving 12.4 g of an amber-colored oil. This was distilled at 125-137 °C at 0.1 mm/Hg to yield 5.7 g of 3,5-dimethoxy-4-allyloxyphenylacetonitrile as a yellow oil. Anal. (C13H15NO3S) C,H.
A suspension of 4.0 g LAH in 150 mL anhydrous THF under N2 was cooled to 0 °C and vigorously stirred. There was added, dropwise, 2.8 mL 100% H2SO4, followed by 5.5 g 3,5-dimethoxy-4-allyloxyphenylacetonitrile in 10 mL anhydrous THF. The reaction mixture was stirred at 0 °C for a few min, then brought to a reflux on the steam bath for 30 min. After cooling back to room temperature, there was added sufficient IPA to destroy the excess hydride, followed by sufficient 10% NaOH to form granular solids. These were removed by filtration, and washed with 20 mL IPA. The filtrate and washes were stripped of solvent under vacuum andthe residue added to 100 mL dilute H2SO4. This was washed with 2x50 mL CH2Cl2, made basic with aqueous NaOH, and extracted with 2x75 mL CH2Cl2. These extracts were pooled, the solvent removed under vacuum, and the residue distilled at 110-120 °C at 0.4 mm/Hg to give 4.9 g of a colorless oil. This was dissolved in 15 mL IPA, neutralized with concentrated HCl (55 drops required), and diluted with 50 mL Et2O. The product was removed by filtration, washed with Et2O, and air dried to give 4.9 g of 3,5-dimethoxy-4-allyloxyphenethylamine hydrochloride (AL) as white crystals.
DOSAGE: 20 - 35 mg.
DURATION: 8 - 12 h.
QUALITATIVE COMMENTS: (with 24 mg) I first became aware of something in about 10 minutes, a pleasant increase in energy. By 20 minutes it was getting pronounced and was a nice, smooth development. During the next hour positive and negative feelings developed simultaneously. Following a suggestion, I ate a bit of food even though I had not been hungry, and to my surprise all the negative feelings dropped away. I felt free to join the others wherever they were at. I moved into the creative, free-flowing kind of repertoire which I dearly love, and found everything enormously funny. Much of the laughter was so deep that I felt it working through buried depressions inside me and freeing me. From this point on, the experience was most enjoyable. The experience was characterized by clear-headedness and an abundance of energy which kept on throughout the day and evening. At one point I went out back and strolled along to find a place to worship. I had a profound sense of the Presence and great love and gratitude for the place, the people, and the activities taking place. The come-down from the experience was very gradual and smooth. Food tasted wonderful. I went to bed late, and quite ready for bed, although the energy was still running. However, sleep was not long in coming.
(with 24 mg) The onset was extremely gradual and graceful, with the first alert that one could really sense at about 50 minutes. This was succeeded by a slow gentle climb to the peak at one hour and fifteen minutes. The experience itself left all of the sensory modalities functional; speech was cogent and rather fluid. In fact, there was an unusual ease of free association. All throughout the session, the talk was high in spirits and somehow indicative of an inner excitement. Affect was entirely pleasant, but not exalting nor conducive to insight or to problem solving. There were no requirements for withdrawal into the self. The material seemed wholly social in nature. No visual, auditory or olfactory sharpening was in evidence. The plateau for this material seemed unusually long. I was unable to sleep for several hours, and took 25 mg Librium before sleep arrived. The next day was a lethargic and slow one, with the inner feeling that the effects had not worn off until the middle of the day following ingestion.
(with 35 mg) I was a distinct +1 in 35 minutes and a +2 by the end of the hour. My head congestion in no way cleared up, absolving the material from having that particular virtue. The entire experience was somewhat dissociated--I could not connect with my feelings. Although my mind remained clear, there was a hangover feeling at the end of the experiment.
EXTENSIONS AND COMMENTARY: This compound was first explored in Prague by Leminger. He provided only the synthetic details and the statement that it was the most active compound that he had studied, with activity at 20 milligrams, with perceptual changes, color enhancement, and difficult dreams during sleep that night. Some effects persisted for more than 12 hours. Dosages above 35 milligrams remain unexplored.
As AL is one of the most potent 3,4,5-trisubstituted phenethylamines yet described, and since the corresponding amphetamines are of yet greater potency, it would be a good guess that 4-allyloxy-3,5-dimethoxyamphetamine (3C-AL) would be an interesting compound to explore. It could be made from syringaldehyde in reaction with allyl iodide, followed by the formation of a nitrostyrene with nitroethane, followed by reduction with aluminum hydride. It is, as of the present time, both unsynthesized and unexplored.