SYNTHESIS: A solution of 10.4 g of
3-bromo-N-cyclohexyl-4-methoxy-5-ethoxybenzylidenimine (see under ME
for its preparation) in 150 mL anhydrous Et2O in a He atmosphere was
cooled with an external dry ice acetone bath to -80 °C with good
stirring. The addition of 52 mL 1.6 M butyllithium in hexane produced
a thick precipitate which was stirred for 5 min. There was then added
8.5 mL of dimethyl disulfide and the reaction mixture gradually became
thinner and lighter. The dry ice bath was removed and the reaction
allowed to come to room temperature over the course of 15 min. This
was then added to 400 mL of dilute HCl. The two phases were
separated, and the aqueous phase was heated on the steam bath for 1 h
which generated a separate yellow oily phase. On cooling, this set to
a yellow solid, which was removed by filtration, washed with H2O, and
sucked relatively free of H2O. These yellow solids weighed 14.4 g and
were ground under 20 mL of cold cyclohexane which removed almost all
the color and, after filtering and air drying, there remained 12.9 g
of an off-white crystalline solid that melted at 83-84 °C.
Recrystallization from cyclohexane produced
3-ethoxy-4-methoxy-5-(methylthio)benzaldehyde as a white fluffy
crystalline material with a melting point of 84-85 °C. Anal.
(C11H14O3S) C,H.
To a solution of 8.0 g 3-ethoxy-4-methoxy-5-(methylthio)benzaldehyde
in 100 mL nitromethane, there was added 0.5 g anhydrous ammonium
acetate and the mixture was heated on the steam bath for 1.5 h, at
which time most of the aldehyde had disappeared and there was a
sizeable quantity of nitrostyrene as well as a cascade of wrong things
down to the origin, as seen by TLC on silica gel, with CH2Cl2. The
excess nitromethane was removed under vacuum, and the residual red oil
was dissolved in 25 mL of hot MeOH and decanted from a small amount of
insoluble material. With cooling in an ice bath for 20 min, bright
yellow crystals were formed which were removed by filtration, washed
with MeOH and air dried, producing 4.1 g
3-ethoxy-4-methoxy-5-methylthio-beta-nitrostyrene which melted at 80-82
°C. This sample, on resolidification and remelting, melted at 109-110
°C. This higher-melting polymorphic form was also produced by
recrystallization of the product from cyclohexane. The two polymorphs
were chromatographically and analytically identical. Anal.
(C12H15NO4S) C,H.
AH was prepared in the usual manner from a suspension of 3.0 g LAH in
100 mL anhydrous THF, cooled to 0 °C, well stirred in an inert
atmosphere of He, and treated with 2.0 mL of 100% H2SO4 added
dropwise. There was then added a solution of 2.4 g
3-ethoxy-4-methoxy-5-methylthio-beta-nitrostyrene in 20 mL anhydrous THF.
The reaction was exothermic, and had come nearly to a boil at the
half-addition point. The reaction was cooled again to 0 °C and the
remaining nitro-styrene then added. This was brought to a reflux
briefly on the steam bath, then cooled again and stirred for an
additional 1 h. IPA was carefully added to decompose the excess
hydride followed by sufficient 10% NaOH to convert the aluminum oxide
to a white, easily filterable mass. This was filtered, the filter
cake washed with additional IPA, and the filtrate and washes combined
and the solvent removed under vacuum. This was dissolved in 100 mL of
dilute H2SO4, which was washed with 2x50 mL CH2Cl2. The aqueous phase
was made basic with sodium hydroxide, extracted with 2x50 mL CH2Cl2,
and the extracts pooled, dried over anhydrous K2CO3, and stripped of
solvent under vacuum to yield a nearly colorless residue. This was
distilled at 125-135 °C at 0.3 mm/Hg producing 2.0 g of a water-white
oil. This was dissolved in 8 mL IPA, neutralized with 23 drops of
con-centrated HCl and, with good stirring, diluted with 20 mL
anhydrous Et2O. The product
3-ethoxy-4-methoxy-5-methylthiophenethylamine hydrochloride (5-TME)
was removed by filtration, washed with Et2O, and air dried to provide
a white solid that weighed 2.0 g and melted at 168-169 °C. Anal.
(C12H20ClNO2S) C,H.
DOSAGE: greater than 200 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 200 mg) There was a noticeable tinnitus,
but then that comes and goes at odd times without any reason needed.
There was perhaps a brush of light-headedness at the third hour point,
but other than that, nothing. No effect that can be ascribed to
today's drug trial.
EXTENSIONS AND COMMENTARY: Nothing comes to mind. This, along with
most of the di- and triethylated thiomescaline analogues, represents a
lot of synthetic effort without useful qualitative data. If there is
any activity, it would only be seen with monster dosages, and why put
the body through such potential impact?
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