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#46 2C-T-13
2,5-DIMETHOXY-4-(2-METHOXYETHYLTHIO)PHENETHYLAMINE
SYNTHESIS: To a
solution of 3.25 g of KOH pellets in 25 mL hot MeOH,
there was added 6.8 g of
2,5-dimethoxythiophenol (see under
2C-T-2 for
its preparation) followed by 4.73 g of
2-methoxyethylchloride. This
mixture was heated on the steam bath for 0.5 h, then added to 500 mL
H2O. This very basic aqueous
phase was extracted with 3x100 mL
CH2Cl2, the extracts pooled, and back-washed with 5%
NaOH. The
solvent was removed under vacuum to give 8.82 g of a white oil.
Distillation gave
2,5-dimethoxyphenyl 2-methoxyethyl sulfide with a bp
115-125 °C at 0.3 mm/
Hg, and a weight of 6.65 g.
A mixture of 10 g POCl3 and 10 g N-
methylformanilide was heated for 10
min on the steam bath. To this claret-colored
solution was added 6.16
g of 2,5-
dimethoxyphenyl 2-methoxyethyl sulfide. There was an
immediate exothermic reaction and gas evolution. The mixture was
heated for 15 min on the steam bath, at which time there was no
starting
sulfide present by TLC. This was then added to 500 mL of
well-stirred warm H2O (pre-heated to 55 °C) and the stirring continued
until only a thin oily
phase remained. This was extracted with
CH2Cl2, the extracts were combined, and the
solvent removed under
vacuum. The residue was extracted with 5 sequential 20 mL portions of
boiling hexane which
deposited
crystals on cooling. Filtering gave a
total of 4.12 g
crystalline solids. Recrystallization from MeOH gave
a poor yield of a cream-colored
crystal with a mp of 68-69 °C. A more
efficient purification was achieved by
distillation (155-168 °C at 0.3
mm/
Hg) yielding 3.50 g of
2,5-dimethoxy-4-(2-methoxyethylthio)benzaldehyde as a pale yellow
solid, with a mp of 67-68 °C. A faster moving (by TLC) trace
component with an intense fluo-rescence persisted throughout the
entire purification scheme, and was still present in the
analytical
sample. Anal. (
C12H16O4S) C,H.
To a
solution of 3.41 g
2,5-dimethoxy-4-(2-methoxyethylthio)benzaldehyde in 50 g of
nitromethane there was added 0.11 g of
anhydrous ammonium acetate, and
the mixture was heated on the steam bath for 2 h, at which time the
starting
aldehyde had largely disappeared by TLC (
silica gel plates
with
CH2Cl2 as the developing
solvent) and a faster moving
nitrostyrene product was clearly visible. The clear orange
solution
was stripped of the excess
nitromethane under vacuum producing a
yellow oil that
crystallized yielding 3.97 g of a yellow solid with a
mp of 99-104 °C. Re
crystallization of a small sample from MeOH
produced (when dry) yellow
electrostatic crystals of
2,5-dimethoxy-4-(2-methoxyethylthio)-beta-nitrostyrene with a mp of 107
°C sharp. From IPA the product is a burnished gold color with the mp
106-107 °C. Anal. (
C13H17NO5S) C,H.
A
solution of LAH (40 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 1.05 mL 100% H2SO4 dropwise, to minimize charring. This was
followed by the addition of 3.07 g
2,5-dimethoxy-4-(2-methoxyethylthio)-beta-nitrostyrene in small portions,
as a solid, over the course of 10 min. There was a considerable
amount of gas evolved, and a little bit of charring. After a few min
further stirring, the tem
perature was brought up to a gentle reflux on
the steam bath, and then all was cooled again to 0 °C. The excess
hydride was destroyed by the cautious addition of 8 mL IPA followed by
3 mL 15%
NaOH which gave the reaction mixture a curdy white granular
character. The reaction mixture was filtered, the filter cake washed
with THF, and filtrate and washes were stripped of
solvent under
vacuum providing about 3 g of a pale amber oil. This was
dissolved in
about 40 mL
CH2Cl2 and extracted with 200 mL dilute H2SO4 in three
portions. All of the color remained in the organic
phase. The pooled
aqueous extracts were washed with
CH2Cl2, then made basic with 25%
NaOH, extracted with 3x75 mL
CH2Cl2, and the combined extracts pooled
and stripped of
solvent under vacuum. The 2 g pale yellow oily
residue was
distilled at 155-165 °C at 0.2 mm/
Hg to give 1.23 g of a
clear white oil. This was
dissolved in IPA, neutralized with
concentrated HCl, and diluted with
anhydrous Et2O to produce
crystals
of
2,5-dimethoxy-4-(2-methoxyethylthio)phenethylamine hydrochloride
(2C-T-13). After filtration, washing with
Et2O, and air drying, this
white
crystalline product weighed 0.89 g.
DOSAGE: 25 - 40 mg.
DURATION: 6 - 8 h.
QUALITATIVE COMMENTS: (with 25 mg) I felt it was somewhat noisy as we
went into the experience. This noisiness lasted only about an hour,
then stopped. At the peak, which seemed to be at about 1 to maybe 1.5
hours, some eyes-closed visuals appeared. There was a white field
with colored visuals, at times geometric in shape. These eye-closed
images were pleasant and I enjoyed them when I did not concern myself
with, or listen to, the conversation. There was an eyes-open change
in color, the ivy became a little lighter or maybe a little stronger
in color. I'm not sure which. I felt there was a gradual diminishing
of activity (whatever that undefined activity was) starting at 2 to
2.5 hours, and coming close to baseline at 6 PM. The descent was
pleasant and I would say pleasurable. The experience did not lead to
any confusion which I sometimes notice in other experiences. There
was no problem with
anorexia. We ate constantly during the
experience. The grapes and other fruit were lovely. This is one of
the few times I would say that I would try a higher dose. Maybe 30 or
33 milligrams. I suspect the experience would be similar, with just a
heightened peak at 1 hour and perhaps a little more body effect. It
may well be one to try with one's wife.
(with 28 mg) There was a strange, disturbing twinge exactly eight
minutes after starting this, that asked me, `Should I have done this?'
I answered, `Yes' and the twinge disappeared. And then there was
nothing until the expected time of development, at a half hour when I
felt a light head and slight dizziness. There was a solid plus two
for a couple of hours. I paid careful attention for auditory oddities
that I had noted before, but they were not there. In an earlier trial
(with 20 milligrams) the radio had the sound of being located in the
outdoors with the sounds coming through the wall and into the room
where I was. I was at a neutral baseline at about seven hours.
(with 35 mg) There was a quiet climb, but it was marred with some
tummy unquiet, and an annoying persistence of
diarrhea. I was very
impressed with eyes-closed patterning, which seemed to do its own
thing independently of the music. I was clearly up to a +++, but
there was a feeling that as soon as it got there it started to go away
again. There was no there, there. Yet there were a couple of touches
of introspection, of seriousness which I had to respect.
(with 40 mg) There were four of us, and the entry was individual for
each of us. Two of us were nauseous. One volunteered a statement,
almost a confession, of too much food and drink in the immediate past.
One of us needed his cigarette right now, and then he saw that he was
killing himself, and he swore off. Don't know if it will last,
however. At the two and a half hour point there is a consensus that
this has gone its route and will lose its impact, so three of us
decided to supplement on
2C-T-2. Six milligrams proves to be a little
light so, some four hours later, we each took another six milligrams.
Excellent. In a while we discoved that we were very hungry, and food
tasted marvelous. Headaches acknowledged in the early evening, but
the extension from T-13 to T-2 seemed to be absolutely correct. And
as of the next day, the non-smoker was still a non-smoker.
EXTENSIONS AND COMMENTARY: Most of the
synthetic adventures of putting
a basic something aways out from the
benzene ring, at the
four-position, have involved subtle things such as unsaturated bonds
or three-membered rings. This was the first try with the actual use
of a different atom (an oxygen). What about other
heteroatoms such as
sulfur or
nitrogen or
silicon or
phosphorus, or some-such?
The
sulfur counterpart of 2C-T-13 was named 2C-T-14, and was
immediately launched. The reaction of
2,5-dimethoxythiophenol and KOH
with
2-methyl-thioethyl chloride in hot MeOH gave
2,5-dimethoxyphenyl
2-methylthioethyl sulfide as a white oil (boiling point of 140-160 °C
at 0.3 mm/
Hg). This underwent a normal Vilsmeier reaction
(
phosphorous oxychloride and N-
methylformanilide) to give
2,5-dimethoxy-4-(2-methylthioethylthio)benzaldehyde with a melting
point of 64-64.5 °C from MeOH. This, in
nitromethane containing a
little
ammonium acetate, was heated on the steam bath for 10 hours and
worked up to give an excellent yield of
2,5-dimethoxy-4-(2-methylthioethylthio))-beta-nitrostyrene as garish
orange-red "Las Vegas" colored
crystals from
acetonitrile, with a
melting point of 126-127 °C. And as of the moment, this is sitting on
the shelf waiting to be reduced to the target compound
2,5-dimethoxy-4-(2-methylthioethylthio)phenethylamine hydrochloride,
or 2C-T-14. Will it be active? I rather suspect that it will be, and
I'll bet it will be longer-lived than the oxygen model, 2C-T-13.
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