SYNTHESIS: A solution of 2.0 g 2,5-dimethoxy-4-(ethylthio)benzaldehyde
(see under 2C-T-2 for its synthesis) in 12 mL nitroethane was treated
with 0.4 g anhydrous ammonium acetate and heated on the steam bath for
3 h. All volatiles were removed under vacuum, leaving a residue that
set up as brilliant red crystals. These were mechanically removed
from the evaporation flask, blown free of nitroethane vapor, and
recrystallized from boiling EtOH, producing 1.8 g pale orange
crystals, with a mp of 110-112 °C. Recrystallization from 20 mL
boiling IPA gave, after filtering and air drying, 1.70 g light orange
crystals of 1-(2,5-dimethoxy-4-ethylthiophenyl)-2-nitropropene with a
mp of 112-113 °C.
A suspension of 1.2 g LAH in 75 mL anhydrous THF was put under an
inert atmosphere and, with good stirring, brought up to a gentle
reflux. A solution of 1.5 g
1-(2,5-dimethoxy-4-ethylthiophenyl)-2-nitropropene in 20 mL anhydrous
THF was added dropwise. Heating and stirring were maintained for an
additional 24 h, and then the reaction mixture was allowed to come
back to room temperature with stirring. There was added 1.4 mL H2O
(dissolved in a little THF), followed by 1.4 mL 15% NaOH and finally
another 4.2 mL H2O. Stirring was continued until all the curdy solids
had turned white. The reaction mixture was filtered, and the filter
cake washed with THF. The filtrate and the washings were combined,
and the solvent removed under vacuum. The residue was 1.1 g of a pale
amber oil. This was dissolved in 6 mL IPA, neutralized with
concentrated HCl (about 8 drops were required) and then diluted with
150 mL anhydrous Et2O. The slightly cloudy solution was stirred for a
couple of min, then there was the formation of a heavy white
crystalline mass. This was removed by filtration, washed with Et2O,
and air dried to provide 1.1 g 2,5-dimethoxy-4-ethylthioamphetamine
hydrochloride (ALEPH-2) with a mp of 128-130 °C with decomposition.
DOSAGE: 4 - 8 mg
DURATION: 8 - 16 h.
QUALITATIVE COMMENTS: (with 4 mg) There was a warm feeling in the
total body and a light pressure in the head that changed with time
into the feeling of a balloon without any anatomical definition. The
usual color perception was not very much increased, and my vision was
not sharpened as it was with DOM. Rather, I noticed waves of
movement, very smooth and not too busy. Both my tactile perception
and auditory acuity were enhanced. The main effect for me was,
paradoxically, an easier handling of the outer world. None of the
jitters of amphetamine. The body feeling is good, healthy, and I am
at peace with the body-mind dualism. These are pretty much personal
comments--I will write up the pharmacological points later.
(with 5 mg) This turned out to be a day of extraordinary visuals and
interpretations. About two hours into it, I felt that the effects
were still climbing, but there was a marvelous onset of visual
distortions and illusions, right at the edge of hallucination. The
logs in the fireplace were in continuous motion. The notepaper I was
writing on seemed to scrunch and deform under the pressure of the pen.
Nothing would stay still; everything was always moving. There was a
phase of unabated inflation. The intensity was noticeably dropping at
the five hour point and I observed considerable residual shakes and a
muscular tremor. Even towards midnight there was some
tooth-rubbiness, but I was able to get a somewhat fretful though
adequate sleep.
(with 5 mg) I was exposed to a number of new environments and it was
difficult to completely separate the experience into what was seen
differently and what was seen for the first time. The Santa Cruz
Mystery Spot should have been bizarre but it was simply hokey. And
yet the boardwalk that should have been depressing was totally
magical. The day was unworldly and I ended up with considerable
muscular weakness. All in all, I handled it well, but I probably
won't do it again.
(with 7 mg) An amazing unification of visual hallucination seen only
in the very fine detail of something, and what must be considered
retinal hallucination. There is no one-to-one correspondence between
the many retinal cells of the high-resolution part of the eye. Thus,
the mind can pick and choose, sometimes from the right eye, and
sometimes from the left. And so a small curve or bump can become
whatever you wish. For a moment. And then it chooses again, but
differently. Is all of our perceived world as subjective as this?
(with 8 mg) Extreme intoxication, but almost no visual phenomena.
Even well into the evening, I know I absolutely could not drive. Why?
I don't know, since this experiment, at least, seemed to be quite free
of strange colors and wiggly lines and streaks of light. It's that I
don't trust that the reality I see is the same reality that the other
driver might see. I am very much the center of the world about me,
and I don't think I could trust anyone else to fully respect my
reality.
EXTENSIONS AND COMMENTARY: As with ALEPH itself, and in most ways with
the entire ALEPH family, there is no predictability of the
dose/response relationship. One person had expressed his psychic
isolation by taking and maintaining a fetal position in relative
hibernation for several hours and with substantial amnesia; this at a
four milligram dose. Yet another person, at fully twice this amount,
was aware of a slight light-headedness that could in no way be
measured as more than a bare threshold. But by the time this erratic
nature had become apparent, the ALEPHS had been assigned and made, up
to and including ALEPH-7.
ALEPH-3 was intended to be the methallylthio compound,
2,5-dimethoxy-4-(beta-methallylthio)amphetamine. The thioether
(2,5-dimethoxyphenyl beta-methallyl sulfide) was easily made from
2,5-dimethoxythiophenol (see 2C-T-2 for its preparation) with 3.4 g
dissolved in a solution of 1.7 g KOH in 25 mL boiling EtOH, and 2.72 g
methallyl chloride, heated 1 h on the steam bath, poured into 250 mL
H2O, extracted with 3x100 mL CH2Cl2, and solvent removal yielding 4.4
g of the sulfide as an amber oil. An effort to convert this to
2,5-dimethoxy-4-(beta-methallylthio)benzaldehyde (7.2 g POCl3, 6.7 g
N-methylformanilide, 4.2 g of the crude sulfide from above, 15 min
heating on the steam bath, H2O hydrolysis, hexane extraction of the
residues from a CH2Cl2 extraction) produced 3.1 g of a
peppermint-smelling oil that distilled at 140-160 °C at 0.3 mm/Hg and
which did indeed have an aldehyde group present (by proton NMR) but
the rest of the spectrum was a mess, and the project was abandoned.
Several years later, this entire project was reinitiated, and the
aldehyde was obtained as a yellow crystal, but again it was not
pursued. At that time, the earlier try had been totally forgotten,
and a brand new ALEPH- (or 2C-T-) number had been assigned; i.e., 20.
Thus, the corresponding phenethylamine
(2,5-dimethoxy-4-(beta-methallylthio)phenethylamine), had it ever been
made, which it was not, would have been called either 2C-T-3 or
2C-T-20, and the amphetamine homologue would probably have been
ALEPH-20.
A closely related 2C-T-X compound was also started quite a while later
--this was the allylthio homologue of the methallyl material 2C-T-3 or
2C-T-20. Its place in the flow of things is evident from its
numbering, 2C-T-16. A mixture of 2,5-dimethoxythiophenol and KOH and
allyl chloride in MeOH gave 2,5-dimethoxyphenyl allyl sulfide as a
white oil which boiled at 110-125 °C at 0.25 mm/Hg. This, with POCl3
and N-methylformanilide provided
2,5-dimethoxy-4-(allylthio)benzaldehyde which distilled at 140-160 °C
at 0.4 mm/Hg and could be recrystallized from MeOH as a pale yellow
solid. Reaction of this aldehyde in nitroethane in the presence of
ammonium acetate (steam bath for 2.5 h) provided
2,5-dimethoxy-4-allylthio-beta-nitrostyrene as red crystals from
acetonitrile. Its mp was 114-115 °C. Anal. (C13H15NO4S) C,H. This
has not yet been reduced to the final amine,
2,5-dimethoxy-4-allylthiophenethylamine, 2C-T-16. The corresponding
amphetamine would be, of course, ALEPH-16.
ALEPH-5 was to be the cyclohexylthio analogue
(2,5-dimethoxy-4-cyclohexylthioamphetamine). The thioether
(2,5-dimethoxyphenyl cyclohexyl sulfide) was successfully made from
1.7 g 85% KOH pellets in 25 mL hot EtOH, 3.4 g 2,5-dimethoxythiophenol
(again, see under 2C-T-2 for its preparation), and 4.9 g cyclohexyl
bromide, 3 h on the steam bath, into 500 mL H2O, extraction with 3x100
mL CH2Cl2, washing the extracts with 5% NaOH, and evaporation to yield
5.2 g of an amber oil. The aldehyde, (made from 6.1 g POCl3 and 5.4 g
N-methylformanilide, heated until claret colored, then treated with
5.0 g of the above crude thioether, heating for 20 min on the steam
bath, into 300 mL H2O, and over-night stirring) was obtained as 3.1 g
of a flesh-colored solid that was clearly neither pure nor completely
correct. Repeated partitioning with organic solvents and cooling and
scratching the residues finally provided a pale orange crystal (1.3 g,
mp 88-93 °C) which, after twice recrystallizing from MeOH, gave 0.4 g
of pale yellow crystals with a mp 95-96 °C and a textbook perfect NMR
in CDCl3 (CHO, 1H (s) 10.41; ArH 2H (s) 6.93, 7.31; OCH3, 6H, (2s) at
3.88 and 3.92; CH, 1H br. at 3.34; and (CH2)5 10H br. at 1.20-2.34).
The nitrostyrene was prepared from 200 mg of the above aldehyde in 1.2
mL nitroethane and 0.1 g ammonium acetate overnight on the steam bath,
the solvent removed to give an orange oil that spontaneously
crystallized after a few months' standing. This was never
characterized, but sits there on the shelf to be reduced to ALEPH-5
some inspired day. The two-carbon homo-logue of this
(2,5-dimethoxy-4-cyclohexylthiophenethylamine) will someday be called
2C-T-5 (if it is ever made).
The remaining members of this family, ALEPH-4, ALEPH-6, and ALEPH-7
have actually been prepared and they have all been entered here in
Book II, under their own names.
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