SYNTHESIS: To a solution of 10.2 g 3,4-dimethoxybenzaldehyde in 10 mL
EtOH, cooled to 0 °C, there was added a solution of 4.2 g KCN in 40 mL
H2O. With good stirring, there was slowly added 10 mL concentrated
HCl (caution: HCN is evolved) and the two-phase reaction mixture was
allowed to continue stirring until there was the spontaneous formation
of crystals. After a few days standing, these were removed by
filtration and well washed with H2O. All was recrystallized from 75
mL of 50% MeOH and air dried to provide 6.95 g of the cyanohydrin
3,4-dimethoxy-a-hydroxyphenylacetonitrile. The mp was 104-106 °C,
which can be increased to 109 °C by recrystallization from benzene.
A well-stirred suspension of 4.7 g LAH in 500 mL anhydrous Et2O was
brought up to a gentle reflux, and 4.7 g
3,4-dimethoxy-a-hydroxyphenylacetonitrile was leached in from a
Soxhlet thimble, over the course of 3 h. The color of the ether
solution progressed from yellow to green, to an eventual blue. The
reflux was maintained for 16 h. After cooling again, there was added
(carefully) a solution of 27 g H2SO4 in 500 mL H2O. The completely
clear two-phase mixture was separated, and the aqueous phase treated
with 87 g potassium sodium tartrate. The addition of 25% NaOH brought
the pH >9, and this phase was extracted with 4x100 mL CH2Cl2. Removal
of all the organic solvents under vacuum gave a residue that was part
oil and part solid. This was extracted with 4x50 mL boiling Et2O, the
extracts pooled, and saturated with anhydrous HCl gas. The 0.95 g of
pale-yellow crystals that formed were removed by filtration, and
finely ground under 5 mL CH3CN. There remained, after refiltration
and air drying, 0.85 g of 3,4-dimethoxy-beta-hydroxyphenethylamine
hydrochloride, DME, with a mp of 170-172 °C.
DOSAGE: greater than 115 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 115 mg) I was faintly nauseous about an
hour after taking the compound, and perhaps I was more alert than
usual in the evening. Substantially no effects.
EXTENSIONS AND COMMENTARY: The rationale for exploring the
beta-hydroxylated phenethylamines, especially those with oxygens at
the biologically important 3- and 4-positions, has already been
presented. Norepinephrine is a beta-hydroxylated phenethylamine with
oxygens at these two ring positions. With DME, these are masked as
two methyl ethers, and the initials DME stand for
3,4-dimethoxyphenyl-beta-ethanolamine. This is an alternate name for
3,4-dimethoxy-beta-hydroxyphenethylamine.
An exactly analogous compound is 3,4-methylenedioxy-beta-ethanolamine,
where the masking is done with the biologically more fragile
methylenedioxy ether. Originally I had called this compound MDE
(methylenedioxyethanolamine) but that code has been, since 1975, used
exclusively for 3,4-methylenedioxy-N-ethylamphetamine, which is a
recipe all by itself. Under the discussion of members of the BOX
series, there is a methylenedioxyphenethylamine with a methoxyl group
at the beta-position, and it is called BOH (q.v.). There, a reasonable
code name for this specific compound is given, namely BOHH. RBOS
stands for the beta-oxygen function on a phenethylamine; this is the
heart of the BOX family. The RHS which is the third letter of BOHH
stands for the free hydroxyl group. And the final RHS is for
homopiperonylamine (which is the trivial name for the compound without
the hydroxyl group). BOHH, or
3,4-methylenedioxy-beta-hydroxyphenethylamine, or
3,4-methylenedioxy-beta-ethanolamine, has also be assayed in man at up to
100 milligrams without any effects, and must be considered, as of now,
to be inactive centrally. The possible toxic roles of beta-ethanolamines
as potential adrenolytic agents, have been discussed in the BOHD
recipe. And beware of the use of the code name MDE in the very old
literature. It might be this BOHH compound.
Back]
]