SYNTHESIS: A solution was made of 45.2 g
N,N,N',N'-tetramethylethylenediamine and 41.4 g of
1,3-dimethoxybenzene in 300 mL hexane. This was stirred vigorously
under a He atmosphere and cooled to 0 °C with an external ice bath.
There was added 225 mL of 1.6 M butyllithium in hexane which produced
a white granular precipitate. The reaction mixture was stirred for 15
min. There was then added 38 mL of diethyl disulfide which changed
the granular precipitate to a creamy character. Stirring was
continued for an additional 5 min, then the reaction mixture was
poured into 1 L of dilute H2SO4. The two phases were separated, and
the aqueous phase extracted with 2x150 mL Et2O. The organic phases
were combined, and the solvent removed under vacuum to provide 60 g of
2-ethylthio-1,3-dimethoxybenzene as an off-white oil that
spontaneously crystallized. It was distilled nonetheless, boiling at
85-96 °C at 0.4 mm/Hg. This distillate can be recrystallized from
hexane to form long needles with a mp of 45-46 °C. Anal. (C10H14O2S)
C,H.
To a stirred solution of 60 g of 2-ethylthio-1,3-dimethoxybenzene in
300 mL CH2Cl2 there was added 49 g elemental bromine dissolved in 100
mL CH2Cl2. The reaction was not exothermic, and it was allowed to
stir for 2 h. The reaction mixture was washed with H2O, then with
aqueous NaOH, and finally with H2O that contained sodium hydrosulfite.
The solvent was removed under vacuum leaving 84 g of an amber oil as
residue. This was distilled at 105-115 °C at 0.15 mm/Hg yielding 73.3
g of 4-bromo-2-ethylthio-1,3-dimethoxybenzene as a light yellow oil.
Anal. (C11H15BrO2S) C,H.
To a solution of 27 mL diisopropylamine in 150 mL anhydrous THF that
was stirred under a N2 atmosphere and cooled to -10 °C with an
external ice/MeOH bath, there was added in sequence 83 mL of 1.6 M
butyllithium in hexane, 4.4 mL of dry CH3CN over the course of 5 min,
and finally 12.1 g of 4-bromo-2-ethylthio-1,3-dimethoxybenzene which
had been dissolved in 20 mL THF (also added over the course of 5 min).
The color progressed from yellow to orange to deep red-brown.
Stirring was continued for 10 min, and then the reaction mixture was
poured into 300 mL dilute H2SO4. The organic layer was separated, and
was washed with more dilute H2SO4. The aqueous phases were combined,
and extracted with 2x100 mL CH2Cl2. These extracts were pooled with
the original organic phase, and the solvents removed under vacuum.
The residue was distilled into two fractions at 0.3 mm/Hg. The first
fraction boiled at 95-115 °C and weighed 4.9 g. It was made up of
several components, but it contained little nitrile material and was
discarded. The second fraction came over at 145->200 °C and weighed
2.9 g. By thin layer chromatography this fraction was largely
3,5-dimethoxy-4-ethylthiophenylacetonitrile, and was used as such in
the following reduction.
A suspension of 1.25 g LAH in 50 mL anhydrous THF under N2 was cooled
to 0 °C and vigorously stirred. There was added, dropwise, 0.8 mL
100% H2SO4, followed by 2.7 g
3,5-dimethoxy-4-ethylthiophenylacetonitrile, neat, over the course of
5 min. The reaction mixture was stirred at 0 °C for a few min, then
brought to a reflux for 15 min on the steam bath. After cooling back
to room temperature, there was added 15 mL IPA to destroy the excess
hydride and 10% NaOH to bring the reaction to a basic pH and convert
the aluminum oxide to a loose, white, filterable consistency. This
was removed by filtration, and washed with 50 mL portions of IPA. The
filtrate and washes were stripped of solvent under vacuum, and the
residue suspended between 50 mL CH2Cl2 and 50 mL dil. H2SO4. The
organic phase was separated, and extracted with 2x50 mL dilute H2SO4.
The original aqueous phase and these two extracts were combined, made
basic with aqueous NaOH, and extracted with 3x50 mL CH2Cl2. These
extracts were stripped of solvent under vacuum. The residue was
distilled at 112-135 °C at 0.2 mm/Hg to give 1.1 g of a slightly
yellow viscous liquid. This was dissolved in 4 mL IPA, neutralized
with 14 drops of concentrated HCl and, with continuous stirring,
diluted with 10 mL anhydrous Et2O. The product was removed by
filtration, washed with Et2O, and air dried to give 1.0 g of
3,5-dimethoxy-4-ethylthiophenethylamine hydrochloride (TE) as white
crystals with some solvent of crystallization. The crude mp of
101-106 °C was only slightly improved by recrystallization from CH3CN
(mp 106-109 °C). But upon fusion and resolidification, the melting
point was 167-168 °C and this sample was further dried by heating at
100 °C for 24 h before analysis. Anal. (C12H20ClNO2S) C,H.
DOSAGE: 20 - 30 mg.
DURATION: 9 - 12 h.
QUALITATIVE COMMENTS: (with 20 mg) I feel it in my ovaries. It is
very sensuous. This is total energy, and I am aware of my every
membrane. This has been a marvelous experience, very beautiful,
joyous, and sensuous. But maybe the dose is a little too high as
there is too much body tingling. I am jangly.
(with 20 mg) The predominant characteristic was the feeling of clean
burning, pure energy, a long-lasting clear-headedness and clarity of
thought, and an ease of talking and sharing. I did not have a strong
feeling of Presence, but more a wonderful feeling of converting energy
into action. I found that my initial look inwards was always a look
of fear, and I wondered if this might not be the same feeling that
others express as excitement. They were certainly of the same nature,
they arose at the same point on the fringe of the unknown, and they
point to a basic difference in attitude. The excitement is for the
new, and is based on trust. The fear is a return to the past, and is
defensive, with reluctance to reexperience past pain. The aftermath
of this experience was the most profound of any that I have had in a
long time. For the following week, I found myself on a new level of
functioning, very energetic and very much in the flow of life and free
of mental distractions. I have become a great deal more aware of the
traps of meditation, and how you can build walls around yourself and
around certain concepts, if you are not careful.
(with 22 mg) Totally developed at 2 hours, to a +++. No clearing of
the sinuses, so it is not a decongestant. There is a lot of visual
activity. In the group there is good communication, and a lot of
laughter.
(with 25 mg) There is a disconnection, there is complex depth without
definition. Without music, this is almost negative, as I can find no
definition. But talking gives me some structure. And I got into some
pretty extraordinary conversations. About President Hoover, Omni
magazine, the colors of spices, and a couple of personal relatives.
This is extra-good for ideas and talking. It is indeed a clean
experience, and superb for communication.
(with 30 mg) I was at a plus three for certainly three hours. There
were some visuals, some eyes-closed fantasy, but little imagery.
Somehow I could at no time interlock with music. It seemed always to
get in the way. Sexual activity is an excellent way to relieve the
muscular tension and the body's heaviness. There was little hunger
and I ate lightly, and I felt somehow depleted. Sleep OK at the
twelth hour. The AM was fine, but on retrospect the experience was
overall strangely cloudy, not negative, but there was not enough
mental to balance the physical.
(with 30 mg) My alert was in 40 minutes, and I was completely
developed by 2 hours. There was a large measure of erotic fantasy,
but the body load was also quite heavy. I had a slight cloak effect,
where I was over-energized but somehow under a blanket of quietness.
I would certainly repeat this, but at maybe 25 milligrams.
EXTENSIONS AND COMMENTARY: Although the ethyl group (of the ethylthio
on the 4-position) is just one carbon atom longer than the methyl
group (of TM) that small change already produces hints and indicators
of some physical toxicity. The propyl compound (see TP) is still of
similar potency, but appears to be yet more difficult, physically.
The butyl homolog never made it off the ground at all as a
psychedelic, but the physical difficulties seem less as well. All
that was left to come through was the euphoria. If this 4-position
sulfur analogue series of mescaline is ever to be more carefully
explored, it must almost certainly be with the shortest possible chain
(TM, as a psychedelic) or with long, long chains (the four-carbon
chain of the butyl group in TB), as a feel-good compound.
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