Pihkal
Page 71
Complex, yes. But both systems are completely straightforward, and flexible for future creations. A few additional examples of similar beta-ethanolamines are scattered throughout Book II and they have, in general, proved to be uninteresting, at least as potential psychedelic compounds.
17 BOM; '-METHOXYMESCALINE; 3,4,5,'-TETRAMETHOXYPHENETHYLAMINE
SYNTHESIS: To a vigorously stirred suspension of 9.0 g '-nitro-3,4,5-trimethoxystyrene (see under the recipe for M for the preparation of this intermediate) in 50 mL anhydrous MeOH there was added a solution obtained from the addition of 2.0 g metallic sodium to 50 mL anhydrous MeOH. The bright orange color faded to a light cream as the nitrostyrene went into solution. After 3 min there was added 30 mL acetic acid, which produced white solids, and this was followed by further dilution with 150 mL H2O. The formed solids were removed by filtration, washed well with H2O, and recrystallized from 150 mL boiling MeOH. After removal of the product by filtration and air drying to constant weight, there was obtained 6.9 g of 1-methoxy-2-nitro-1-(3,4,5-trimethoxyphenyl)ethane as fine, cream-colored crystals. The mp was 143-144 !C, and the Rf by TLC
(silica-gel plates and CH2Cl2 as moving phase) was identical to that of the starting aldehyde. Anal. (C12H17NO6) C,H.
A solution of LAH (50 mL of 1 M solution in THF) was cooled, under He, to 0 !C with an external ice bath. With good stirring there was added 1.25 mL 100% H2SO4 dropwise, to minimize charring. This was followed by the addition of 6 g of solid
1-methoxy-2-nitro-1-(3,4,5-trimethoxyphenyl)ethane over the course of 2 min. There was some gas evolution. After 5 min additional stirring, the temperature was brought up to a reflux with a heating mantle. There was a gentle gas evolution for a few minutes, followed by an exothermic reaction with vigorous gas evolution. Once everything had settled down, the reaction mixture was held at reflux temperature for an additional 2 h. The excess hydride was destroyed by the addition of IPA and 15% NaOH was added to convert the inorganic salts to a loose white filterable mass. The reaction mixture was filtered, and the filter cake washed thoroughly with THF. The combined filtrate and washes were stripped of solvent under vacuum which provided a red-brown liquid. This was dissolved in dilute H2SO4
and washed with 3x75 mL CH2Cl2. After making the aqueous phase basic with NaOH, it was extracted with 2x100 mL CH2Cl2. The pooled extracts were stripped of solvent under vacuum, and the colorless residue distilled at 120-150 !C at 0.3 mm/Hg. There was obtained 2.8 g of a colorless oil which was dissolved in 30 mL IPA and neutralized with concentrated HCl, allowing the spontaneous formation of the hydrochloride salt. This was diluted with 75 mL anhydrous Et2O, yielding 2.8 g 3,4,5,'-tetramethoxyphenethylamine hydrochloride (BOM) as a white crystalline product. This had a mp of 198.5-199.5 !C.
Anal. (C12H20ClNO4) C,H.
DOSAGE: greater than 200 mg.
DURATION: unknown.
EXTENSIONS AND COMMENTARY: There are some indicators of central activity with assays involving both the 120 milligram and the 180
milligram levels, but nothing that can be rated as over a plus one.
It can be seen with the two active members of the BOX series (BOD and BOB) that the potency is about equal to, or a little more (up to a factor of maybe x2), than the analogue without the methoxyl group on the aliphatic chain. If this formula were to hold in the relationship between mescaline and BOM, the active level might well be in the 200-400 milligram range. But at the moment, it remains unknown.
Again, the name of the compound (BOM) is from the RBO-S prefix of this family (from benzyl + oxy), plus the RMS of mescaline (which has provided the ring substitution pattern).
18 4-BR-3,5-DMA; 3,5-DIMETHOXY-4-BROMOAMPHETAMINE
SYNTHESIS: The starting material 3,5-dimethoxy-4-bromobenzoic acid (made from the commercially available resorcinol by the action of methyl sulfate) was a white crystalline solid from aqueous EtOH with a mp of 248-250 !C. Reaction with thionyl chloride produced 3,5-dimethoxy-4-bromobenzoyl chloride which was used as the crude solid product, mp 124-128 !C. This was reduced with tri-O-(t)-butoxy lithium aluminum hydride to produce 3,5-dimethoxy-4-bromobenzaldehyde which was recrystallized from aqueous MeOH and had a mp of 112-114 !C.
Anal. (C9H9BrO3) C,H. This aldehyde, with nitroethane and anhydrous ammonium acetate in acetic acid, was converted to the nitrostyrene 1-(3,5-dimethoxy-4-bromophenyl)-2-nitropropene, with a mp of 121-121.5
!C. Anal. (C11H12BrNO4) C,H,N. This was reduced at low temperature with just one equivalent of LAH, to minimize reductive removal of the bromine atom. The product 3,5-dimethoxy-4-bromoamphetamine hydrochloride (4-BR-3,5-DMA) was isolated in a 37% yield and had a mp of 221-222 !C. Anal. (C11H17BrClNO2) C,H,N.
DOSAGE: 4 - 10 mg.
DURATION: 8 - 12 h.
QUALITATIVE COMMENTS: (with 3 mg) This is certainly no placebo. At about 2 hours I felt some analgesia and numbing in my extremities, but if there were any sensory distortions, they were barely perceptible.
(with 6 mg) There is a very shallow threshold, no more.
(with 10 mg) I can certainly confirm the indications of anesthesia that were hinted at. It was for me central in nature, however. I could (this at three hours) pierce a skin pinch on my left arm with no bother except for the emerging of the needle due to skin resistance.
There was little bleeding. And multiple needle prickings into the thumb abductor were not felt. A quick plunge of the tip of my little finger into boiling water elicited reflex response, but no residual pain. Judgment was OK, so I stayed out of physical trouble, luckily!
The perhaps ++ was dropping in the fourth or fifth hour, and by the tenth hour there were few effects still noted, except for some teeth-rubbiness and a burning irritation at the pin-prick area, so feeling is back. No sleep problems at just past midnight.
EXTENSIONS AND COMMENTARY: Here is a complex and, at the moment, totally undefined drug. There were two independent reports of analgesia, yet a thorough screen in experimental animals, conducted by a major pharmaceutical house, failed to confirm any of it. A ++
report does not necessarily reflect a psychedelic effect, since this quantitative measure of the level of activity represents the extent of impairment of function, regardless of the nature of the drug producing it. In other words, if you were experiencing the effects of a drug that would in your judgment interfere with safe and good driving, this would be a ++ whether your performance was being limited by a psychedelic, a stimulant, a hypnotic or a narcotic. None of the quantitative reports ever mentioned any sensory distortion (analgesia is a loss, not a distortion) or visual effect. Perhaps 4-BR-3,5-DMA showed its ++ as a narcotic. But then, the rats had said no.
19 2-BR-4,5-MDA; 6-BR-MDA; 2-BROMO-4,5-METHYLENEDIOXYAMPHETAMINE
SYNTHESIS: A solution of 3,4-methylenedioxyamphetamine (MDA) in acetic acid was treated with elemental bromine, generating the hydrobromide salt of 2-bromo-4,5-methylenedioxyamphetamine in a yield of 61% of theory. The mp was 221-222 !C. Anal. (C10H13Br2NO2) C,H,Br.
DOSAGE: 350 mg.
DURATION: unknown.
EXTENSIONS AND COMMENTARY: Both the synthetic and the pharmacological details for this compound are sparse. There has been only a single report of the human activity of this drug in the literature, and the statement has been offered that the effects are amphetamine-like. No other qualitative comments have been made available, and neither I nor anyone in my circle has tried it, personally. Someday, perhaps. But at that high level, perhaps not.
20 2C-B; 4-BROMO-2,5-DIMETHOXYPHENETHYLAMINE
SYNTHESIS: A solution of 100 g of 2,5-dimethoxybenzaldehyde in 220 g nitromethane was treated with 10 g anhydrous ammonium acetate, and heated on a steam bath for 2.5 h with occasional swirling. The deep-red reaction mixture was stripped of the excess nitromethane under vacuum, and the residue crystallized spontaneously. This crude nitrostyrene was purified by grinding under IPA, filtering, and air-drying, to yield 85 g of 2,5-dimethoxy-'-nitrostyrene as a yellow-orange product of adequate purity for the next step. Further purificatio
n can be achieved by recrystallization from boiling IPA.
In a round-bottomed 2 L flask equipped with a magnetic stirrer and placed under an inert atmosphere, there was added 750 mL anhydrous THF, containing 30 g LAH. There was then added, in THF solution, 60 g 2,5-dimethoxy-'-nitrostyrene. The final solution was a dirty yellow-brown color, and it was kept at reflux temperature for 24 h.
After cooling, the excess hydride was destroyed by the dropwise addition of IPA. Then 30 mL 15% NaOH was added to convert the inorganic solids to a filterable mass. The reaction mixture was filtered and the filter cake washed first with THF and then with MeOH.
The combined mother liquors and washings were freed of solvent under vacuum and the residue suspended in 1.5 L H2O. This was acidified with HCl, washed with with 3x100 mL CH2Cl2, made strongly basic with 25% NaOH, and reextracted with 4x100 mL CH2Cl2. The pooled extracts were stripped of solvent under vacuum, yielding 26 g of oily residue, which was distilled at 120-130 !C at 0.5 mm/Hg to give 21 g of a white oil, 2,5-dimethoxy-phenethylamine (2C-H) which picks up carbon dioxide from the air very quickly.
To a well-stirred solution of 24.8 g 2,5-dimethoxyphenethylamine in 40
mL glacial acetic acid, there was added 22 g elemental bromine dissolved in 40 mL acetic acid. After a couple of min, there was the formation of solids and the simultaneous evolution of considerable heat. The reaction mixture was allowed to return to room temperature, filtered, and the solids washed sparingly with cold acetic acid. This was the hydrobromide salt. There are many complicated salt forms, both polymorphs and hydrates, that can make the isolation and characterization of 2C-B treacherous. The happiest route is to form the insoluble hydrochloride salt by way of the free base. The entire mass of acetic acid-wet salt was dissolved in warm H2O, made basic to at least pH 11 with 25% NaOH, and extracted with 3x100 mL CH2Cl2.
Removal of the solvent gave 33.7 g of residue which was distilled at 115-130 !C at 0.4 mm/Hg. The white oil, 27.6 g, was dissolved in 50
mL H2O containing 7.0 g acetic acid. This clear solution was vigorous stirred, and treated with 20 mL concentrated HCl. There was an immediate formation of the anhydrous salt of 2,5-dimethoxy-4-bromophenethylamine hydrochloride (2C-B). This mass of crystals was removed by filtration (it can be loosened considerably by the addition of another 60 mL H2O), washed with a little H2O, and then with several 50 mL portions of Et2O. When completely air-dry, there was obtained 31.05 g of fine white needles, with a mp of 237-239
!C with decomposition. When there is too much H2O present at the time of adding the final concentrated HCl, a hydrated form of 2C-B is obtained. The hydrobromide salt melts at 214.5-215 !C. The acetate salt was reported to have a mp of 208-209 !C.
DOSAGE: 12 - 24 mg.
DURATION: 4 - 8 h.
QUALITATIVE COMMENTS: (with 16 mg) A day at the Stanford museum.
Things were visually rich, yet I felt that I was reasonably inconspicuous. The Rodin sculptures were very personal and not terribly subtle. I saw Escher things in the ceiling design, when I decided to sit in a foyer somewhere and simply pretend to rest.
Walking back, the displays seen in the bark of the eucalyptus trees, and the torment and fear (of others? of themselves?) in the faces of those who were walking towards us, were as dramatic as anything I had seen in the art galleries. Our appetites were enormous, and we went to a smorgasbord that evening. A rich experience in every possible way.
(with 20 mg) The drug effect first became known to me as a shift of colors toward golden and rose tones. Pigments in the room became intensified. Shapes became rounder, more organic. A sensation of lightness and rivulets of warmth began seeping through my body.
Bright lights began pulsing and flashing behind my closed lids. I began to perceive waves of energy flowing through all of us in unison.
I saw all of us as a gridwork of electrical energy beings, nodes on a bright, pulsating network of light. Then the interior landscape shifted into broader scenes. Daliesque vistas were patterned with eyes of Horus, brocades of geometric design began shifting and changing through radiant patterns of light. It was an artistUs paradise Q representing virtually the full pantheon of the history of art.
(with 20 mg) The room was cool, and for the first hour I felt cold and chilled. That was the only mildly unpleasant part. We had been hanging crystals earlier that day, and the visions I had were dominated by prismatic light patterns. It was almost as if I became the light. I saw kaleidoscopic forms Q similar to, but less intense than, when on acid Q and organic forms like Georgia OUKeefe flowers, blossoming and undulating. My body was flooded with orgasms Q
practically from just breathing. The lovemaking was phenomenal, passionate, ecstatic, lyric, animal, loving, tender, sublime. The music was voluptuous, almost three-dimensional. Sometimes the sound seemed distorted to me, underwater like. This was especially so for the less good recordings Q but I could choose to concentrate on the beauty of the music or the inadequacy of the sound's quality, and mostly chose to concentrate on the beauty.
(with 24 mg) I am totally into my body. I am aware of every muscle and nerve in my body. The night is extraordinary Q moon full.
Unbelievably erotic, quiet and exquisite, almost unbearable. I cannot begin to unravel the imagery that imposes itself during the finding of an orgasm. Trying to understand physical/spiritual merging in nature Q .
EXTENSIONS AND COMMENTARY: Four quotations were chosen arbitrarily from literally hundreds that have worked their ways into the files.
The vast majority are positive, ranging from the colorful to the ecstatic. But not all are. There are people who choose not to go into the corporeal but, rather, prefer the out-of-body experience.
They express discomfort with 2C-B, and seem to lean more to the Ketamine form of altered state, one which dissociates body from mind.
There have been reports of several overdoses that prove the intrinsic safety of this compound. Prove is used here in the classic British sense; i.e., to challenge. RThe proof of the pudding is in the eating,S is not a verification of quality, but an inquiry into the quality itself. (The French simplify all this by using two separate verbs for prove.) One overdose was intentional, the other accidental.
(with 64 mg) I found only mild visual and emotional effects at the 20
milligram dose, so I took the remaining 44 milligrams. I was propelled into something not of my choosing. Everything that was alive was completely fearsome. I could look at a picture of a bush, and it was just that, a picture, and it posed no threat to me. Then my gaze moved to the right, and caught a bush growing outside the window, and I was petrified. A life-form I could not understand, and thus could not control. And I felt that my own life-form was not a bit more controllable.S This was from the comments of a physician who assured me that he saw no neurological concerns during this dramatic and frightening experience.
(with 100 mg) I had weighed correctly. I had simply picked up the wrong vial. And my death was to be a consequence of a totally stupid mistake. I wanted to walk outside, but there was a swimming pool there and I didnUt dare fall into it. A person may believe that he has prepared himself for his own death, but when the moment comes, he is completely alone, and totally unprepared. Why now? Why me? Two hours later, I knew that I would live after all, and the experience became really marvelous. But the moment of facing death is a unique experience. In my case, I will some day meet it again, and I fear that I will be no more comfortable with it then than I was just now.
This was from the comments of a psychologist who will, without doubt, use psychedelics again in the future, as a probe into the unknown.
Many of the reports that have come in over the years have mentioned the combination of MDMA and 2C-B. The most successful reports have followed a program in which the two drugs are not used at the same time, nor even too closely spaced. It appears that the optimum time for the 2C-B is at, or just before, the final baseline recovery of the MDMA. It is as if the mental and emotional discoveries can be mobilized, and something d
one about them. This combination has several enthusiastic advocates in the psychotherapy world, and should be the basis of careful research when these materials become legal, and accepted by the medical community.
A generalized spectrum of 2C-B action can be gleaned from the many reports that have been written describing its effects. (1) There is a steep dose response curve. Over the 12 to 24 milligram range, every 2
milligrams can make a profound increase or change of response.
Initially, one should go lightly, and increase the dosage in subsequent trials by small increments. A commonly used term for a level that produces a just perceptible effect is Rmuseum level.S This is a slightly-over-threshold level which allows public activities (such as viewing paintings in a museum or scenery watching as a passenger in a car) to be entered into without attracting attention.
There can be considerable discomfort associated with being in the public eye, with higher doses. (2) The 2C-B experience is one of the shortest of any major psychedelic drug. Wherever you might be, hang on. In an hour or so you will be approaching familiar territory again. (3) If there is anything ever found to be an effective aphrodisiac, it will probably be patterned after 2C-B in structure.
There are two RTweetiosS known that are related to 2C-B. (See recipe #23 for the origin of this phrase.) The 2-EtO- homologue of 2C-B is 4-bromo-2-ethoxy-5-methoxyphenethylamine, or 2CB-2ETO. The unbrominated benzaldehyde (2-ethoxy-5-methoxybenzaldehyde) had a melting point of 47.5-48.5 !C, the unbrominated nitrostyrene intermediate a melting point of 76-77 !C, and the final hydrochloride a melting point of 185-186 !C. The hydrobromide salt had a melting point of 168.5-169.5 !C. It seems that one gets about as much effect as can be had, with a dosage of about 15 milligrams, and increases above this, to 30 and to 50 milligrams merely prolong the activity (from about 3 hours to perhaps 6 hours). At no dose was there an intensity that in any way resembled that of 2C-B.