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#154 4-TIM
4-THIOISOMESCALINE; 2,3-DIMETHOXY-4-METHYLTHIOPHENETHYLAMINE
SYNTHESIS: The mother liquors from the initial
crystallization of the
2-TIM
nitrostyrene (see under
2-TIM) was the source and raw material
for all 4-TIM chemistry. Once the bulk of the
2-TIM nitrostyrene has
been removed, these mother liquors could be processed to give the
4-TIM
nitrostyrene. The easier procedure was to
evaporate these
mother liquors to a residue under vacuum, and hope for a spontaneous
crystallization. If this failed, flash
chromatography could be used.
For reference purposes, the three
nitrostyrenes involved in the
2-TIM/4-TIM problem movedon
silica gel TLC with CHCl3
solvent in the
following manner:
2,3-dimethoxy-4-methylthio-beta-nitrostyrene (leading
to 4-TIM), Rf = 0.61;
3,4-dimethoxy-2-methylthio-beta-nitrostyrene
(leading to
2-TIM), Rf = 0.54; and
3,4-dimethoxy-beta-nitrostyrene
(leading to DMPEA), Rf = 0.47. For flash
chromatography, a small
portion of the residue from the mother liquor was
dissolved in CHCl3,
and placed on a
silica gel column. CHCl3 was used as the eluding
solvent. The first material breaking through from the column was the
4-TIM
nitrostyrene and on
evaporation of this fraction, seed was
obtained as gold-colored
crystals that had a mp of 71-73 °C. This,
when added to the residues from the described
2-TIM synthesis
nitrostyrenes, started the
crystallization process. The gummy solid
that was produced was triturated under MeOH, and the
crystals so
revealed were removed by filtration. Re
crystallization from 10 mL
MeOH gave 1.9 g of solids. A second re
crystallization from 5 mL MeOH
provided 0.7 g of
pumpkin-colored
crystals of
2,3-dimethoxy-4-methylthio-beta-nitrostyrene with a mp of 70-71 °C.
A
solution of 1.2 g LAH in 20 mL
anhydrous THF was cooled to 0 °C
under He and stirred. There was added, dropwise, 0.8 mL of 100%
H2SO4, followed by 0.9 g of
2,3-dimethoxy-4-methylthio-beta-nitrostyrene
dissolved in 20 mL THF. Stirring was continued for a few min as the
reaction returned to room tem
perature, and then it was heated to a
reflux for 5 min on the steam bath. The reaction was cooled again,
EtOAc was added to destroy the excess
hydride, followed by 25%
NaOH
added dropwise until a white granular
precipitate was obtained. This
was removed by filtration, and the filter cake was washed with 2x35 mL
Et2O. The filtrate was extracted into 50 mL dilute H2SO4 which was
washed with
Et2O and, in turn, made basic again and extracted with
2x50 mL
CH2Cl2. The extracts were pooled, and the
solvent removed
under vacuum to give a residue of crude product. This
distilled
cleanly from 100-115 °C at 0.3 mm/
Hg yielding 0.45 g of a clear white
oil. This was
dissolved in 6 mL IPA, neutralized with 5 drops of
concentrated HCl, and diluted with 25 mL
anhydrous Et2O. There was a
deposition of white solids which were removed by filtration, washed
with
Et2O, and air dried. The
2,3-dimethoxy-4-methylthiophenethylamine hydrochloride so obtained
(4-TIM) weighed 0.3 g and contained a molecule of H2O of
crystallization. The mp was 212-213 °C. Anal. (
C11H18ClNO2SaH2O)
C,H,N.
DOSAGE: greater than 160 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 160 mg) Everything seemed normal. Pulse
was under 80, there was nothing with eyes-closed, my appetite was
normal. The compound was completely inactive.
EXTENSIONS AND COMMENTARY: There has been much noise made about the
effectiveness of an unusual
substitution group at the 4-position of
the
phenethylamine molecule. Here is a
methylthio group at this
position, and it is an inactive compound. I was just a little bit
surprised.
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