This was stirred for 2 h at about 40 !C during which time there was a definite lightening of color, but no solids formed. The reaction mixture was poured into 600 mL H2O which produced a reddish glob floating in a yellow-orange opaque aqueous phase. The glob was physically removed, dissolved in 30 mL boiling MeOH which, on cooling in an ice bath, deposited off-white crystals. These were removed by filtration, washed with MeOH, and air dried to give 1.5 g of N-[1-(2,5-dimethoxy-4-iodophenyl)-2-propyl]phthalimide as fine white crystals with a slight purple cast. The mp was 103-105.5 !C and the mixed mp with the starting non-iodinated phthalimide (mp 105-106 !C) was depressed (85-98 !C). Extraction of the aqueous phase, after alkalinification, provided an additional 0.15 g product. Anal.
(C19H18NO4) C,H,N.
A solution of 0.75 g
N-(1-(2,5-dimethoxy-4-iodophenyl)-2-propyl)phthalimide in 10 mL EtOH
was treated with 0.3 mL of hydrazine hydrate, and the clear solution was held at reflux on the steam bath overnight. After cooling, there was a crystallization of 1,4-dihydroxyphthalizine that started as small beads but finally became extensive and quite curdy. These solids were removed by filtration and had a mp of about 340 !C
(reference samples melted over a five to ten degree range in the area of 335-350 !C). The filtrate was dissolved in 100 mL CH2Cl2 and extracted with 2x150 mL 0.1 N HCl. The aqueous extracts were washed once with CH2Cl2, made basic with 5% NaOH, and extracted with 3x100 mL
CH2Cl2. Removal of the solvent under vacuum gave 0.5 g of a colorless oil which was dissolved in 300 mL anhydrous Et2O and saturated with anhydrous HCl gas. There was obtained, after filtration, and air drying, 0.35 g of 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) as white crystals that melted at 200.5-201.5 !C. This value did not improved with recrystallization. Anal. (C11H17ClINO2) C,H,N.
DOSAGE: 1.5 - 3.0 mg.
DURATION: 16 - 30 h.
QUALITATIVE COMMENTS: (with 0.6 mg) There was a nice spacey light-headedness for a few hours, and time seemed to move quite slowly. Then a generic sadness came over me, as I reminisced about earlier days (recalling pleasures now gone) and wondered if I would be allowed to be here on the Farm when I am old and not important. There is so much to be done, and I cannot do it all, and no one else cares.
My mood became present-day and healthy by about the seventh hour.
(with 1.6 mg) The general nature of the experience was depressing, with a sad view of life. There was no way I could connect with my emotions. Even my sadness was vague. At about the ninth hour I decided that enough was enough, and this strangely disappointing about-plus-two was aborted with 125 micrograms of LSD. The emotions became present and living within a half hour. I was greatly relieved.
The erotic was not a mechanical attempt but a deeply involved feeling with an archetype of orgasm easily available. It was shaped like a flower, richly colored, with an unusual RSS shape to it. This was a lovely end to a difficult day.
(with 3.0 mg) This is a clear, clean psychedelic. The eyes-closed imagery is excellent, with clearly delineated patterns, pictures, and colors. Perfect for an artist, and next time IUll devote some time to painting. Total ease for the body, but no help for my smoking problem. I still want to smoke. And at sixteen hours into this I am still at 1.5+ but IUll try to go to bed anyway, and sleep.
(with 3.5 mg) I was at a full crashing +++ for about three or four hours. There was none of the LSD sparkle, but there were moments of Tlight-headednessU where one could move sideways with reality. I could leave where I was right over there, and come over here and get a strange but authentic view of where the TthereU was that I had left.
It would be out-of-body, except that the body came over here with me rather than staying there. This doesnUt make sense now, but it sure did then. There was no trace of body impact, and I slept late that evening, but with some guardedness due to the intense imagery. This was no more intense than with 3.0 milligrams, but it was a little bit more to the unreal side.
(with 1.0 mg of the RRS isomer) There was a clear ++ from the second to the eighth hour, but somehow there was not quite the elegance or the push of the racemate. I was sensible, and managed to do several technical chores in a reasonable way. Easy sleep at 15 hours into it.
(with 2.3 mg of the RRS isomer) The water solution of the hydrochloride salt has a slightly sweetish taste! I was at a +++
without question, but there was a slight down mood towards the end.
And it lasted a really long time; I was distinctly aware of residual stuff going on, well into the next day.
(with 6.3 mg of the RSS isomer) I was at a benign one-and-a-half plus at about two hours, and finally flattened out at a ++. Would I double this dose? Probably not, but half again (to 9 or 10 milligrams) would feel safe for a plus 3. By evening I was near enough baseline to drive into town for a social obligation, but even when trying to sleep later that night there was some residue of imagery; remarkably, it was all in slow motion. The fantasies were slow-paced and sluggish. It would have been interesting to have explored eyes-closed during the day.
EXTENSIONS AND COMMENTARY: Again, as with every other psychedelic amphetamine analogue which has a chiral center and has been explored as the individual optical isomers, it is the RRS isomer that is the more potent. And again, the other isomer, the RSS isomer, still shows some activity. The same was true with DOB, and DOM, and MDA. The only exception was MDMA, but then that is more of a stimulant, and there is virtually no psychedelic component to its action. Rat studies, where there is a measure of the discrimination of a test compound from saline, have shown the RRS isomer to have about twice the potency of the RSS isomer. That the RRS is more potent is certain, but the above reports would suggest that the factor would be closer to times-four rather than times-two.
A number of studies with DOI in animal models have shown it to have an extremely high binding capacity to what are called the 5-HT2
receptors. Serotonin is a vital neurotransmitter in the brain, and is strongly implicated in the action of all of the phenethylamine psychedelics. The place where it acts, at the molecular level, is called its receptor site. As an outgrowth of the cooperative studies of the medicinal chemists working closely with the neuropharmacologists, a number of compounds have emerged that interact with these sites. But this one interacts with these sites and not those, and that one interacts with those sites and not these. So, there has developed a collection of sub-divisions and sub-subdivisions of receptor sites, all related to serotonin, but each defined by the particular compound that interacts most tightly with it.
Thus, there were serotonin R1S receptors, and then there were R1S and R2S receptors, and then R1a and R1bS and R2aS and R2bS receptors, and on and on. These are called 5-HT receptors, since the chemical name for serotonin is 5-hydroxytryptamine, and the scientist would never want to let the layman know just what he is talking about. DOI has been synthesized with a variety of radioactive iodine isotopes in it, and these tools have been of considerable value in mapping out its brain distribution. And by extrapolation, the possible localization of other psychedelic compounds that cannot be so easily labelled. A small neurochemical research company on the East Coast picked up on these properties of DOI, and offered it as a commercial item for research experiments. But I doubt that they are completely innocent of the fact that DOI is an extremely potent psychedelic and that it is still unrecognized by the Federal drug laws since, in their most recent catalog, the price had almost doubled and a note had been added to the effect that telephone orders cannot be accepted for this compound.
The four-carbon butylamine homologue (the ARIADNE analogue) of DOI has been synthesized. A mixture of the free base of 1-(2,5-dimethoxyphenyl)-2-aminobutane (see preparation under DOB) and phthalic anhydride was fused, cooled, and recrystallized from either methanol or cyclohexane to give crystals of N-[1-(2,5-dimethoxyphenyl)-2-butyl]phthalimide with a melting point of 76-77 !C and an analysis (C20H21NO4) C,H,N. This was iodinated with iodine monochloride in acetic acid to give N-[
1-(2,5-dimethoxy-4-iodophenyl)-2-butyl]phthalimide which was chromatographically distinct from the uniodinated starting material (silica gel, CH2Cl2 ), but which did not crystallize. This was treated with hydrazine hydrate in ethanol to provide 1-(2,5-dimethoxy-4-iodophenyl)-2-aminobutane hydrochloride which was crystallized from CH3CN/EtOH to give white crystals with a mp of 217-218.5 !C and an analysis (C12H19CINO2) C,H,N. This butyl homolog of DOI has been assayed at up to four milligrams, and is without any central effects whatsoever. An experiment with 12.4 microcuries of 131I labelled material with the whole body scanner showed most of it accumulating in the gut and liver, with almost none to the brain.
For those who find such statistics interesting, the parent compound DOI vies with DOB as probably the most potent of the phenethylamine psychedelics as of the moment, and certainly one of the most long lived.
A very important, centrally pivotal, and completely paradoxical compound in this area, is the N,N-dimethyl homologue of DOI, or 2,5-dimethoxy-N,N-dimethyl-4-iodoamphetamine (IDNNA). This compound was the starting point of the study of a large number of homologues and it deserves, and has received, a separate recipe.
68 DOM; STP; 2,5-DIMETHOXY-4-METHYLAMPHETAMINE
SYNTHESIS: To a solution of 54.9 g 2,5-dimethoxy-4-methylbenzaldehyde (see the recipe for 2C-D for its preparation) in 215 g glacial acetic acid there was added 19.5 g anhydrous ammonium acetate and 30.6 g nitroethane. This mixture was heated for 3 h on the steam bath, the reaction mixture was cooled in a wet ice bath, allowing the spontaneous formation of yellow crystals. As much H2O as possible was added (just short of a persistant cloudy oily character) and after a few additional h standing, the crystalline 1-(2,5-dimethoxy-4-methylphenyl)-2-nitropropene was removed by filtration and recrystallized from boiling acetic acid. The yield, after drying to constant weight, was 28.3 g and the mp was 87-88 !C.
Anal. (C12H15NO4) C,H,N.
A suspension of 9.5 g LAH in 750 mL well stirred anhydrous Et2O was held at reflux under an inert atmosphere, with the return of the condensed solvent passing through a Soxhlet thimble containing 9.5 g 1-(2,5-dimethoxy-4-methylphenyl)-2-nitropropene. After the addition of the nitrostyrene was complete, the stirred suspension was maintained at reflux for an additional 4 h, then cooled to room temperature and allowed to continue stirring overnight. The excess hydride was destroyed by the addition of 750 mL 8% H2SO4, cautiously, until the hydrogen evolution ceased, then at a speed that allowed the formed solids to disperse. The phases were separated, the aqueous phase washed once with Et2O, treated with 225 g potassium sodium tartrate, and finally made basic (pH >9) with 5% NaOH. This was extracted with 3x150 mL CH2Cl2, the extracts pooled, and the solvent removed under vacuum. The residue was 9.6 g of a clear oil which spontaneously formed crystals with a mp of 60.5-61 !C from hexane.
These solids were dissolved in 150 mL anhydrous Et2O, and saturated with anhydrous HCl gas. After standing at room temperature for 2 h, the crystalline 2,5-dimethoxy-4-methylamphetamine hydrochloride (DOM) was removed by filtration, washed with Et2O, and air dried to constant weight. There was obtained 8.25 g of glistening white crystals that had a mp of 190.5-191.5 !C. The sulfate had a mp of 131 !C. Anal.
(C12H20ClNO2) C,H,N.
The above nitrostyrene may also be converted to the final amine product through the intermediary of the corresponding phenylacetone.
To a well stirred suspension of 10.4 g powdered iron in 20 mL glacial acetic acid held at reflux temperature, there was added 4.9 g 1-(2,5-dimethoxy-4-methylphenyl)-2-nitropropene as a solid. Refluxing was continued for 2 h and then all was filtered through wet Celite.
After washing with 300 mL H2O followed by 300 mL Et2O, the combined filtrate and washes were separated, and the aqueous phase extracted with 2x100 mL Et2O. The organic phase and extracts were combined and washed with 2x100 mL saturated K2CO3 and the solvent was removed under vacuum yielding a reddish oil weighing 3.3 g. This was distilled at 111-115 !C at 0.5 mm/Hg to give a pale green solid. After recrystallization from benzene, there was obtained 2.8 g 1-(2,5-dimethoxy-4-methylphenyl)-2-propanone as white crystals with a mp of 57-59 !C. This ketone has also been described as a pale-yellow oil with a bp of 115-118 !C at 0.4 mm/Hg. A solution of 0.7 g 1-(2,5-dimethoxyphenyl-4-methyl)-2-propanone in 20 mL MeOH was treated with 6.0 g ammonium acetate, 0.3 g sodium cyanoborohydride, and 3 g Linde 3 A molecular sieves. The mixture was stirred overnight, the solids removed by filtration, and the filtrate dissolved in 100 mL
H2O. The solution was acidified with dilute H2SO4, and washed with 2x25 mL CH2Cl2. The aqueous phase was made basic with aqueous NaOH, and the product extracted with 2x25 mL CH2Cl2. The solvent was removed under vacuum, and the residue distilled (at 160 !C at 0.2
mm/Hg) to give colorless product which was dissolved in 3 mL IPA, neutralized with concentrated HCl, and diluted with 50 mL anhydrous Et2O. There was obtained 0.18 g of 2,5-dimethoxy-4-methylamphetamine hydrochloride (DOM) as a white solid with a mp of 187-188 !C.
The optical isomers of DOM have been prepared in two ways. The racemic base has been resolved as the ortho-nitrotartranilic acid salt by recrystallization from EtOH. The (+) acid provides the (+) or RSS
isomer of DOM preferentially. Also, the above-mentioned 1-(2,5-dimethoxy-4-methylphenyl)-2-propanone can be reductively aminated with optically active alpha-methyl benzylamine with Raney Nickel. This amine is isolated and purified by recrystallization of the hydrochloride salt. When optically pure, the benzyl group was removed by hydrogenolysis with palladium on carbon. The mp of either of the optical isomers, as the hydrochloride salts, was 204-205 !C.
DOSAGE: 3 - 10 mg.
DURATION: 14 - 20 h.
QUALITATIVE COMMENTS: (with 1.0 mg) There is almost certainly an effect. Physically there is a slight dryness in the mouth, and my eyes are noticeably dilated. There is an eerie feeling overall.
(with 2.3 mg) Mood elevation at 2-3 hrs. After 3 hours, emotional effects become more pronounced, enhancement of color also. Very little distortion of perception, no disorientation, no creeping or flowing, but color enhancement considerable. The emotional content and empathy for others was closer to mescaline than to amphetamine, a welcome change. No suggestion of nausea at any time. Unable to sleep at ten hours, so I took 3/4 grain Seconal. Headache and listlessness next morning, probably due to the Seconal.
(with 3 mg) In the middle of the experience I found that I was able to separate components of complex things so as to evaluate them separately. There is no need to respect their normal purpose. The sharpness of observation is enhanced, but one can focus at every different depth of a thing or a concept. Colors are not just brighter; there are more of them. There is a profoundness of meaning inherent in anything that moves. A line of thought or a bit of personal history ties the thinker to the objects that had been thought of, or once experienced. It is this relationship that will prove productive. Not like in a movie which is circular in its totalness, but as in true life where the future is the result of your own involvement with everything about you.
(with 4 mg) The first four hours were largely directed to the body.
There was a shuddering, and a tight jaw, and I am not particularly motivated to talk to anyone. It is more arousing (like amphetamine) than depressing (like phenobarb). I am feeling just a little sick at the three hour point, but a bit of regurgitation clears this up. Then at the fourth hour, it went totally outside of me. I saw the clouds towards the west. THE CLOUDS!!! No visual experience has ever been like this. The meaning of color has just changed completely, there are pulsations, and pastels are extremely pastel. And now the oranges are coming into play. It is a beautiful experience. Of all past joys, LSD, mescaline, cannabis, peyote, this ranks number one. Normally I have no color effects with mescaline. A dynamic experience. Feels good, too.
(with 5 mg) There was the magnification of light, color and odors.
It was all very pleasant and beautiful, except that I had an overwhelmingly negative feeling. This at times grew to considerable intensity, and I f
eel it was clearly due to anger. At times the negativity disappeared completely, and I broke into the most enjoyable, even hilarious experiences. I alternated about 50-50
between joy and discomfort. As the evening drew on, I became withdrawn and pensive. It seemed clear that I had made all the wrong decisions Q choice of partner, place to live, isolation, no meaningful activity. The greatest shocker was that my practice of meditation, which is one of my central focuses, and which I thought had brought me much peace and understanding, seemed to be a delusional solution to my unhappiness and isolation. The experience continued unabated throughout the night with much tension and discomfort. I was unable to get any sleep. I hallucinated quite freely during the night, but could stop them at will. While I never felt threatened, I felt I knew what it was like to look across the brink to insanity.
(with 8 mg) The very quiet development picks up speed betweeen the first and second hour. There is a rich curly-imaged eyes-closed show that interlocks closely with music. It is occasionally an off-beat fantasy and not directly knit together, and even occasionally unenjoyable. But always intense and completely appropriate to the music. There is a continuous thirst, and little urine. Napping seems OK at 16 hours, but real sleep must wait until the 20 hour point.
Overall a rolling +++, and I am looking forward to a repeat some day.
(with 10 mg) If on this page I shall have expressed it to you then it is true that DOM has the glory and the doom sealed up in it. All that's needed to unseal it is to surround it with a warm living human for a few hours. For that human for those hours all the dark things are made clear.
(with 12 mg) The first awareness was at 30 minutes and it was in the tummy. The development was extremely rapid, something more like LSD
than previously remembered. The body tremor feels like poisoning, there is no escaping the feeling of being disabilitated, but at least there is no nausea. This transition ended and the trauma cleared completely at about the second hour. The music was exceptional, the erotic was exceptional, the fantasy was exceptional. Listz's RA Christmas Cantata #1,S part 1, with eyes closed was an experience without precedent. There were some residual effects still noted the next day. This may be a bit much for me.
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