SYNTHESIS: A solution of 0.4 g
1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane (see
preparation in the recipe for BOD) in 3.0 mL acetic acid was heated to
100 °C on a steam bath. There was added 1.0 g powdered zinc, followed
by additional acetic acid as needed to maintain smooth stirring.
After 0.5 h there was added 1.0 mL concentrated HCl and, following an
additional few minutes heating, the reaction mixture was poured into
300 mL H2O. After washing the aqueous phase with 3x75 mL CH2Cl2, the
mixture was made basic with 25% NaOH, and extracted with 3x50 mL
CH2Cl2. Removal of the solvent and distillation of the residue at
130-140 °C 0.25 mm/Hg gave an oil that, on dissolving in IPA,
neutralization with concentrated HCl, and the addition of anhydrous
Et2O, gave beautiful white crystals of
2,5-dimethoxy-beta-hydroxy-4-methylphenethylamine hydrochloride (BOHD).
The yield was 0.2 g, and the mp was 180-181 °C. The infrared spectrum
was that of an amine salt with a strong OH group present. Anal.
(C11H18ClNO3) C,H.
DOSAGE: greater than 50 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 50 mg) At about the two hour point, there
was a precipitous drop of blood pressure (from 120/72 to 84/68)
although the pulse stayed steady at 60. This trend had been apparent
in earlier trials, and was being watched carefully. No further tests
are planned.
EXTENSIONS AND COMMENTARY: The usual method of making
beta-ethanolamine such as this is through the reduction of the
cyanohydrin of the corresponding benzaldehyde and, in fact, that
method is described in the recipe for DME. This above procedure was
actually part of an exploration of different agents that might be used
in the reduction of the intermediate nitroalkane. This product was
the unexpected result of trying zinc.
Why the potent cardiovascular effect seen by this compound? There are
a couple of points that might argue for some adrenolytic toxicity.
This material is a beta-ethanolamine and, with maybe one or two
exceptions, clinically used beta-receptor blockers are
beta-ethanolamines. In fact, a few of these so-called beta-blockers
actually have two methoxy groups on the aromatic rings, also a
property of BOHD. The antidiabetic drug Butaxamine (BW 64-9 in the
code of Burroughs Wellcome) is identical to BOHD except that the
4-methyl group is on the alpha-carbon instead, and there is a tertiary
butyl group on the nitrogen atom. Another point involves the
proximity of the beta-hydroxy group and the methoxyl oxygen atom in
the 2-position of the ring. There is going to be a strong
hydrogen-bonding with this orientation, with the formation of a stable
six-membered ring. This might help obscure the hydrophilic nature of
the free hydroxyl group and allow the compound to pass into the brain
easily. If this group is masked by an easily removed group such as an
acetate ester, one gets the compound
beta-acetoxy-3,4-dimethoxy-4-methylphenethylamine (BOAD) which is
similar to BOHD as a hypotensive.
The code-naming procedure used here (and elsewhere here in Book II)
is: (1) to use RBOS as the alert to there being an oxygen on the
benzyl carbon of a phenethylamine (it is a benzyl alcohol); (2) if
there is just one more letter (a third and last letter) it will
identify the 2C-X parent from which it has been derived [RBS comes
from 2C-B, RDS comes from 2C-D, RHS comes from homopiperonylamine
(MDPEA) rather than from 2C-H, RMS comes from mescaline, and in every
case the beta-substituent is a methoxy group]; and (3) if there are
four letters, then the fourth letter is as above, and the third letter
(the next to last letter) is the substituent on that benzylic oxygen.
With a three letter code, the substituent is a methyl group, an RHS
for a third letter of four makes it a hydroxyl group, and an RAS for
the third letter is an acetyl group, and an RES is for an ethyl group.
A similar sort of cryptographic music was composed by Du Pont in their
three-number codes for the Freons. The first number was one less than
the number of carbons in the molecule, the second number was one more
than the number of hydrogens in the molecule, the third number was the
exact number of fluorines in the molecule, and the rest of the bonds
were filled with chlorines, Thus Freon 11 (really Freon 011) was
trichlorofluoromethane and Freon 116 was hexafluoroethane.
Complex, yes. But both systems are completely straightforward, and
flexible for future creations. A few additional examples of similar
beta-ethanolamines are scattered throughout Book II and they have, in
general, proved to be uninteresting, at least as potential psychedelic
compounds.
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