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#45 2C-T-9
2,5-DIMETHOXY-4-(t)-BUTYLTHIOPHENETHYLAMINE
SYNTHESIS: To a well-stirred ice-cold suspension of 2.8 g
p-dimethoxybenzene and 3.2 mL N,N,N',N'-
tetramethylethylenediamine in
100 mL petroleum
ether under an inert
atmosphere of He, there was
added 13 mL of a 1.6 N
solution of
butyllithium in hexane. The
suspended
dimethoxybenzene became opaque and there was a pale yellow
color generated. The reaction mixture was warmed to room tem
perature
which converted it to light white solids. After an additional 0.5 h
stirring, there was added, slowly, 3.6 g of
di-(t)-butyldisulfide.
The yellow color deepened, the solids
dissolved and, after 1 h, the
color was a clear deep brown. This
solution was poured into 100 mL
dilute HCl and the organic
phase was separated. The aqueous fraction
was extracted with 3x75 mL
CH2Cl2. The combined organic
phases were
washed with dilute aqueous
NaOH, with H2O, and then stripped of
solvents under vacuum. The residue was
distilled at 95-105 °C at 0.5
mm/
Hg to provide 3.7 g of
2,5-dimethoxyphenyl (t)-butyl
sulfide as a
white, mobile liquid. Anal. (C12H18O2S) C,H. A solid derivative was
found in the nitration product,
2,5-dimethoxy-4-(t)-butylthio-1-nitrobenzene, which came from the
addition of 0.11 mL of concentrated HNO3 to a
solution of 0.23 g of
the above
sulfide in 5 mL ice cold acetic acid. Dilution with H2O
provided yellow solids which, on re
crystallization from MeOH, had a mp
of 92-93 °C. Anal. (C12H17NO4S) C,H. Attempts to make either the
picrate salt or the
sulfonamide derivative were not satisfactory.
A mixture of 72 g POCl3 and 67 g N-
methylformanilide was heated for 10
min on the steam bath. To this claret-colored
solution was added 28 g
of
2,5-dimethoxyphenyl (t)-butyl
sulfide, and the mixture heated for
10 min on the steam bath. This was then added to 1 L of H2O and
stirred overnight. The
residual brown oil was separated from the
water mechanically, and treated with 150 mL boiling hexane. The
hexane
solution was decanted from some in
soluble tars, and on cooling
deposited a dark oil which did not
crystallize. The remaining hexane
was removed under vacuum and the residue combined with the above
hexane-in
soluble dark oil, and all
distilled at 0.2 mm/
Hg. An early
fraction (70-110 °C) was largely N-
methyl-
formanilide and was
discarded. Crude
2,5-dimethoxy-4-(t-butylthio)benzaldehyde came over
at 120-130 °C and weighed 12.0 g. This was never satisfactorily
crystallized despite the successful formation of seed. It was a
complex mixture by TLC, containing several components. It was used
for the next step as the crude
distilled fraction.
To a
solution of 10 g impure
2,5-dimethoxy-(t-butylthio)benzaldehyde
in 75 mL of
nitromethane there was added 1.0 g of
anhydrous ammonium
acetate, and the mixture was heated on the steam bath 1.5 h. Removal
of the excess
solvent/reagent under vacuum produced an orange oil that
was (not surprisingly) complex by TLC and which would not
crystallize.
A hot hexane
solution of this oil was allowed to slowly cool and stand
at room tem
perature for several days, yielding a mixture of yellow
crystals and a brown viscous syrup. The solids were separated and
re
crystallized from 40 mL MeOH to give 3.7 g
2,5-dimethoxy-4-(t)-butylthio-beta-nitrostyrene as fine lemon-yellow
crystals, with a mp of 93-94 °C. A second crop of 1.4 g had a mp of
91-92 °C. Anal. (C14H19NO4S) C,H.
A
solution of LAH (70 mL of a 1 M solution in THF) was cooled, under
He, to 0 °C with an external ice bath. With good stirring there was
added 2.1 mL 100% H2SO4 dropwise, over the course of 20 min. This was
followed by the addition of 4.7 g
2,5-dimethoxy-4-(t)-butylthio-beta-nitrostyrene in 20 mL
anhydrous THF.
There was an immediate loss of color. After a few min further
stirring, the mixture was allowed to come to room tem
perature, and the
stirring was continued for 5 h. The excess
hydride was destroyed by
the cautious addition of 10 mL IPA followed by 6 mL 15%
NaOH and
finally 6 mL H2O. The loose white solids were removed by filtration,
and the filter cake washed with THF. The filtrate and washes were
combined and, after stripping off the
solvent under vacuum, there was
obtained 4.66 g of a pale yellow oil. Without any further
purification, this was
distilled at 0.2 mm/
Hg. A first fraction came
over at up to 120 °C and was a light colorless oil that was not
identified. The correct product
distilled at 130-160 °C as a pale
yellow viscous oil that weighed 1.66 g. This was
dissolved in 10 mL
IPA, neutralized with 20 drops of concentrated HCl and diluted with 80
mL
anhydrous Et2O. After standing a few min there was the spontaneous
generation of white
crystals of
2,5-dimethoxy-4-(t)-butylthiophenethylamine hydrochloride (2C-T-9)
which were removed by filtration, and air dried. The weight was 1.10
g.
DOSAGE: 60 - 100 mg.
DURATION: 12 - 18 h.
QUALITATIVE COMMENTS: (with 90 mg) 2C-T-9 tastes the way that old
crank-case motor oil smells. I was up to something above a plus two
at the third hour. Although there were no visuals noted, I certainly
would not choose to drive. Somehow this does more to the body than to
the head. I feel that the effects are waning at maybe the sixth hour,
but there is a very strong body memory that makes sleeping difficult.
Finally, at sometime after midnight and with the help of a glass of
wine, some sleep.
(with 125 mg) There was a steady climb to a +++ over the first couple
of hours. So far, the body has been quite peaceful without any strong
energy push or stomach problems, although my tummy insists on being
treated with quiet respect, perhaps out of habit, perhaps not. At the
fifth hour, the body energy is quite strong, and I have the choice of
focusing it into some activity, such as love-making or writing, or
having to deal with tapping toes and floor-pacing. For a novice this
would be a murderously difficult experience. Too much energy, too
long a time. I suppose I could get used to it, but let me judge by
when I get to sleep, and just what kind of sleep it is. It turned out
that sleep was OK, but for the next couple of days there was a
continuing awareness of some residue in the body--some kind of
low-level poisoning. I feel in general that there is not the
excitement or creativity to connect with, certainly not enough to
justify the cost to the body.
EXTENSIONS AND COMMENTARY: The three-
carbon analog of 2C-T-9 (this
would be one of the ALEPH series) has never been made and, for that
matter, none of the higher numbered 2C-T's have had the
amphetamine
counterparts
synthesized. They are, as of the present time, unknown
compounds. This nifty reaction with
di-(t)-butyl disulfide worked so
well, that three additional
disulfides that were at hand were
immediately thrown into the chemical program, with the quick
assignment of the names 2C-T-10, 2C-T-11, and 2C-T-12.
The lithiated
dimethoxybenzene reaction with
2,2-dipyridyl disulfide
produced
2,5-dimethoxyphenyl 2-
pyridyl sulfide which
distilled at
135-150 °C at 0.4 mm/
Hg and could be re
crystallized from
cyclohexane
containing 2%
EtOH to give a product that melted at 66-67.5 °C. Anal.
(C13H13NO2S) C,H. This would have produced
2,5-dimethoxy-4-(2-pyridylthio)phenethylamine (2C-T-10) but it was
never pursued.
The same reaction with di-(
4-bromophenyl)
disulfide produced
2,5-dimethoxyphenyl 4-bromophenyl sulfide which
distilled at 150-170
°C at 0.5 mm/
Hg and could be re
crystallized from MeOH to give a
product that melted at 72-73 °C. Anal. (C14H13BrO2S) C,H. This was
being directed towards
2,5-dimethoxy-4-(4-bromophenylthio)phenethylamine (2C-T-11) but it
also was abandoned.
The same reaction with N,N-
dimorpholinyl disulfide produced virtually
no product at all, completely defusing any plans for the synthesis of
a novel
sulfur-
nitrogen bonded base
2,5-dimethoxy-4-(1-morpholinothio)phenethylamine (2C-T-12). One
additional effort was made to prepare a 2C-T-X thing with a
sulfur-
nitrogen bond. The acid
chloride intermediate in the
preparation of
2,5-dimethoxythiophenol (as described in the recipe for
2C-T-2) is
2,5-dimethoxybenzenesulfonyl chloride. It reacted smoothly
with an excess of
diethylamine to produce
2,5-dimethoxy-N,N-
diethylbenzenesulfonamide which
distilled at 155 °C
at 0.13 mm/
Hg and which could be re
crystallized from a 4:1 mixture of
cyclohexane/
benzene to give a product with a melting point of 41-42 °C
and an excellent proton
NMR. This amide proved totally refractory to
all efforts at reduction, so the target compound,
2,5-dimethoxy-4-diethylaminothiophenethylamine, has not been made. It
has not even been given a 2C-T-X number.
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