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#159 TMA-3
2,3,4-TRIMETHOXYAMPHETAMINE
SYNTHESIS: To a
solution of 12.4 g
2,3,4-trimethoxybenzaldehyde in 45
mL glacial acetic acid, there was added 7 mL
nitroethane and 4.1 g
anhydrous ammonium acetate, and all was held at reflux tem
perature for
1.5 h. To the cooled and well stirred reaction mixture, H2O was added
slowly, dropping out an oily
crystalline solid mass. This was
separated by filtration, and ground under a quantity of 50% aqueous
acetic acid, and re-filtered. The 6.5 g of crude product was
re
crystallized from boiling MeOH to give, after air drying to constant
weight, 5.0 g of
2-nitro-1-(2,3,4-trimethoxyphenyl)propene, with a mp
of 56-57 °C. Anal. (
C12H15NO5) C,H.
To a gently refluxing suspension of 3.0 g LAH in 300 mL
anhydrous Et2O
under a He
atmosphere, there was added 3.65 g
2-nitro-1-(2,3,4-trimethoxyphenyl)propene by allowing the condensing
Et2O drip into a shunted Soxhlet thimble containing the
nitrostyrene
and effectively adding a warm saturated solu-tion of it dropwise.
Refluxing was maintained for 5 h following the completion of the
addition of the
nitrostyrene. The milky reaction mixture was cooled
and the excess
hydride destroyed by the addition of 200 mL 10% H2SO4.
When the aqueous and
Et2O layers were finally clear, they were
separated, and 75 g of
potassium sodium tartrate was
dissolved in the
aqueous fraction.
NaOH (25%) was then added until the
pH was >9, and
this was then extracted with 3x75 mL
CH2Cl2. Evaporation of the
solvent under vacuum produced 2.5 g of a nearly colorless clear oil
that was
dissolved in 300 mL
anhydrous Et2O which was saturated with
anhydrous HCl gas. The product,
2,3,4-trimethoxyamphetamine
hydrochloride (TMA-3) separated as a fine white solid. This was
removed by filtration,
Et2O washed, and air dried to constant weight.
The yield was 1.65 g of a product which, after re
crystallization from
IPA, had a mp of 148-149 °C. Anal. (
C12H20ClNO3) C,H.
DOSAGE: greater than 100 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 100 mg) There were no effects at all. No
eye dilation, no believable diversion from complete normalcy.
Appetite was normal, as well.
EXTENSIONS AND COMMENTARY: There is a small lesson to be learned from
this completely inactive compound. There is no way of saying that it
is or is not in-active. All that can be said is that trials were made
(in this case using three separate individuals) at an oral level of
100 milligrams. And, at this level, nothing happened. And since a
bottom threshold for mescaline would be perhaps 200 milligrams, it can
be honestly said that the activity of this compound, if expressed
relative to mescaline (using mescaline units) is less than 2 M.U. Had
200 milligrams been inactive, it would have been less than 1.0 M.U.
If 2 grams had been inactive, it would have been less than 0.1 M.U.
But the actual printed form, activity < 2.0 M.U. was accepted by many
readers as indicating that TMA-3 was active, but at dosages greater
than 100 milligrams. All that can be said is, if there is activity,
then it will be at oral levels greater than 100 milligrams At the
moment, as far as I know, this compound is not active in man, but then
I know of no trials in excess of 100 milligrams.
This admonition applies to all the published M.U. values that are
preceded by the "less than" sign, the "<."
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