SYNTHESIS: A solution of 50 g 2,5-dimethoxybenzaldehyde in 100 g
nitromethane was treated with 5 g of anhydrous ammonium acetate, and
heated on the steam bath for 4 h. The solution was decanted from a
little insoluble material, and the solvent removed under vacuum. The
clear oily residue was dissolved in 100 mL boiling IPA which, after
standing a moment, set up as dense crystals. After returning to room
temperature, these were removed by filtration, the product was washed
with IPA and air dried, yielding 56.9 g 2,5-dimethoxy-beta-nitrostyrene
as spectacular yum-yum orange crystals with a mp of 119-120 °C. An
analytical sample, from ethyl acetate, melted at 120-121 °C.
A suspension of 60 g LAH in 500 mL anhydrous THF was placed under an
inert atmosphere, stirred magnetically, and brought up to reflux
temperature. There was added, dropwise, 56 g of
2,5-dimethoxy-beta-nitrostyrene dissolved in THF, and the reaction
mixture was maintained at reflux for 36 h. After being brought to
room tem-perature, the excess hydride was destroyed with 40 mL IPA,
followed by 50 mL of 15% NaOH. An additional 100 mL THF was required
for easy stirring, and an additional 150 mL H2O was needed for
complete conversion of the aluminum salts to a loose, white,
filterable consistency. This solid was removed by filtration, and the
filter cake washed with additional THF. The combined filtrate and
washes were stripped of solvent under vacuum, and the residue
dissolved in dilute H2SO4. Washing with 3x75 mL CH2Cl2 removed most
of the color, and the aqueous phase was made basic with aqueous NaOH
and reextracted with 3x100 mL CH2Cl2. Removal of the solvent yielded
39.2 g of a pale amber oil that was distilled. The fraction boiling
at 80-100 °C at 0.4 mm/Hg weighed 24.8 g and was water-white product
amine. As the free base, it was suitable for most of the further
synthetic steps that might be wanted, but in this form it picked up
carbon dioxide rapidly when exposed to the air. It was readily
converted to the hydrochloride salt by dissolution in 6 volumes of
IPA, neutralization with concentrated HCl, and addition of sufficient
anhydrous Et2O to produce a permanent turbidity. Crystals of
2,5-dimethoxyphenethylamine hydrochloride (2C-H) spontaneously formed
and were removed by filtration, washed with Et2O, and air dried. The
mp was 138-139 °C.
DOSAGE: unknown.
DURATION: unknown.
EXTENSIONS AND COMMENTARY: I know of no record of 2C-H ever having
been tried by man. It has been assumed by everyone (and probably
correctly so) that this amine, being an excellent substrate for the
amino oxidase systems in man, will be completely destroyed by the body
as soon as it gets into it, and thus be without action. In virtually
all animal assays where it has been compared with known psychoactive
drugs, it remains at the "less-active" end of the ranking.
It is, however, one of the most magnificent launching pads for a
number of rather unusual and, in a couple of cases, extraordinary
drugs. In the lingo of the chemist, it is amenable to "electrophilic
attack at the 4-position." And, in the lingo of the
psychopharmacologist, the "4-position is where the action is." From
this (presumably) inactive thing have evolved end products such as
2C-B, 2C-I, 2C-C, and 2C-N. And in the future, many possible things
as might come from a carbinol group, an amine function, or anything
that can stem from a lithium atom.
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