SYNTHESIS: A solution of 39.6 g
1-(2,5-dimethoxy-4-methylphenyl)-2-nitrostyrene (see recipe for 2C-D
for its preparation) in 300 mL warm MeOH was prepared. Separately, a
solution of 9 g elemental sodium in 150 mL MeOH was also prepared.
This sodium methoxide solution was added to the well-stirred
nitrostyrene solution, which resulted in a dramatic loss of color.
There was then added 75 mL acetic acid, and all was poured into 2 L
H2O. This was extracted with 3x100 mL CH2Cl2. The pooled extracts
were stripped of solvent, and the 35 g of residue was treated with 5
mL MeOH, allowed to stand for a short while, decanted from some
insoluble residue, and the separated clear solution kept at 0 °C
overnight. There was the deposition of a yellow crystalline product
which, after removal by filtration and air drying, weighed 9.7 g.
Recrystallization from 25 mL MeOH gave, after filtering and drying,
8.4 g of canary-yellow crystals of
1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane with a mp of
78-79 °C. Evaporation of the mother liquors from the filtration of
the first crop yielded 3.8 g of additional product which, upon
recrystallization from 11 mL MeOH, provided another 2.7 g with a mp of
77-78 °C. Further workup of the mother liquors yielded only impure
starting nitrostyrene.
A solution of LAH (96 mL of 1 M solution in THF) was cooled, under He,
to 0 °C with an external ice bath. With good stirring there was added
2.4 mL 100% H2SO4 dropwise, to minimize charring. This was followed
by the addition of 10.8 g
1-(2,5-dimethoxy-4-methylphenyl)-1-methoxy-2-nitroethane. There was
immediate discoloration. After the addition was complete, the
reaction mixture was held at reflux on the steam bath for 2 h. After
cooling again, the excess hydride was destroyed with 4 mL IPA and the
reaction mixture made basic with 15% NaOH. The insoluble inorganic
salts were removed by filtration, and the filter cake was washed first
with THF, and then with IPA. The bright yellow filtrate and washes
were pooled and stripped of solvent under vacuum, yielding 14 g of a
yellow oil. This was suspended in 1 L dilute H2SO4 to give an ugly,
cloudy, yellow-orange mess. Extraction with 3x75 mL CH2Cl2 removed
much of the color, and the remaining aqueous phase was made basic with
25% NaOH, and extracted with 3x75 mL CH2Cl2. Evaporation of the
solvent under vacuum gave 9 g of a pale amber oil which was distilled
at 115-130 °C at 0.4 mm/Hg. The water-white distillate was dissolved
in 15 mL IPA, neutralized with concentrated HCl, and then diluted with
70 mL anhydrous Et2O. After a few min, white crystals formed, and
these were removed by filtration and Et2O washed. When air-dried to
constant weight, 4.49 g brilliant white crystals of
4-methyl-2,5,beta-trimethoxyphenethylamine hydrochloride (BOD) with a mp
of 171-172 °C with decomposition, were obtained. The mother liquors
on standing deposited 0.66 g additional crystals which were impure and
were discarded. Anal. (C12H20ClNO3) C,H.
DOSAGE: 15 - 25 mg.
DURATION: 8 - 16 h.
QUALITATIVE COMMENTS: (with 20 mg) There were some very pleasant
visuals starting at 2-2.5 hours and continuing to 4-5 hours after the
beginning of the experiment. Open eye visuals seem to come on after
staring at particular areas, such as the living room ceiling or at
trees. The surroundings tended to move slightly. There was no
flowing of the images at all. When looking at the pine trees, the
needles appeared crystal clear and sharply defined, with strong
contrasts. Though the mental effect is difficult to define, I am not
sure it was all that great. I did become tired of the effect (along
with the confusion) after 8 hours, and was quite happy to note that it
did taper off in the early evening. I am not particularly sure I
would want to try this material again.
(with 20 mg) For the first three or so hours, the beauty of the
experience was marred by a strange discomfort. There was some
queasiness, and I felt a sluggishness of mind. Then I began moving in
and out of a pleasant place, and finally the discomfort completely
dissolved and the experience turned full on. Height of beauty, visual
perception. Lights below are amazing. Outside, marvelous sense of
Presence. There is not an elation, as often with other materials, but
a strong, even powerful sense of goodness, inner strength, solidity.
(with 25 mg) This was quite quick. The onset of the experience was
apparent within a half hour, and we were both at +++ within the hour.
Body load minimal. There was very little visual, compared with some
materials. Very interesting eyes-closed, but not continually--just
now and then an intense vision might flash. Very benign and friendly
and pleasant and good-humored feeling. Superb for conversation and
conceptualization.
(with 25 mg) The body load was quite noticeable for everyone. But
the general state of mind was excellent; everyone was extremely
relaxed and funny. Puns, insults, delightful amusement. Not very
much insight work possible. Juices were needed and tolerated well,
but no one was particularly hungry. Sleep was difficult for most
people, not deep and not too refreshing. Excellent material, but body
price a bit too much for the mental effects. Pleasant, and I wouldn't
hesitate to take it again, but nothing very memorable except the
tremendous humor and laughter, which was truly delightful.
EXTENSIONS AND COMMENTARY: This compound, BOD, was the first
exploratory member of a new family of phenethylamines. This family is
called the BOX series because an oxygen atom has been put on the
benzylic carbon (the "benzyl-oxy" or "BO") of each of several well
studied drugs with recognized substituent patterns on the aromatic
ring. The "X" would be "D," as used here with BOD, making reference
to 2C-D, it would be a "B" in BOB making reference to 2C-B, etc.
Actually the original thought was to make the "O" into an "OM" for
methoxy, as this would allow more versatility in the naming of things
such as ethoxys ("OE") or hydroxys ("OH"), but the methoxylated 2C-B
analogue would have come out as BOMB, so the idea was dropped.
Actually, the concept of naming of drugs with some acronym that is
pronounceable has led into some interesting byways. Some examples
have been unintended. I have heard DOM pronounced "dome" and DOET
pronounced as "do it." And elsewhere I have mentioned the embarrassing
occasions where the TOM and TOET families were pronounced "the toms
and twats." Some examples have had names that have been contractions
of popular names, such as XTC for ecstasy. And there are instances
where a name might be proposed simply to irritate the newspaper
people. An early street suggestion for PCP was FUK, and a current
name for free-base methamphetamine is SNOT. And marijuana is fondly
called SHIT by its aficionados. The final "A" on government groups
such as the CIA or the DEA or the FDA is strongly reminscent of the
final "A" which stands for amphetamine in things such as TMA and MDMA.
Might there someday be a drug such as
4-cyclopropylmethyl-N-isopropylamphetamine (CIA), or
3,5-dimethoxy-4-ethylamphetamine (DEA)? It has just occurred to me
that there is already a 4-fluoro-2,5-dimethoxyamphetamine (FDA), but I
have already named it DOF. If all drugs were known only by publicly
embarrassing names, there might be less publicity given them by the
press.
Back to the commentary on BOD. The rationale for this inclusion of a
beta-oxygen atom into the structure of a phenethylamine is based
directly on the chemistry that occurs naturally in the brain. The
phenethylamine neurotransmitter, dopamine, is converted both in the
brain and in the body to the equally important transmitter
norepinephrine by just this sort of transformation. There is the
enzymatic addition of an oxygen atom to the "benzylic" position of
dopamine. And identical chemistry goes on with tyramine in a number
of plants and animals, with a similar addition of oxygen to form
octopamine, so-named for its discovered presence in the salivary
glands of Octopus vulgaris. In the first explorations in the "OX"
series, this oxygen was intentionally blocked with a methyl group, to
ease its entry into the brain, and increase the possibilities of its
being active as a psychedelic. As mentioned above, the "D" in "OD"
follows from its ring orientation pattern being the same as that of
2C-D (and this, originally from the mimicking of the pattern of DOM).
All of these D- compounds have the 2,5-dimethoxy-4-methyl
ring-substitution pattern.
An interesting complication is also part of this structure package.
The added methoxy group (or hydroxy group, see recipe for BOHD) also
adds a new asymmetric center, allowing for the eventual separation of
the material into two optical isomers. And at such time as the
corresponding amphetamine homologues might be made and studied, the
presence of yet another chiral center (under the alpha-methyl group)
will demand that there be actually two racemic compounds synthesized,
and a total of four isomers to contend with, if really careful and
thorough work is to be done.
A parallel chemistry to all of this follows the addition of sodium
ethoxide (rather than sodium methoxide) to the nitrostyrene. The
final product, then, is the ethoxy homologue
2,5-dimethoxy-beta-ethoxy-4-methylphenethylamine, or BOED. It is down in
human potency by a factor of three, with a normal dosage being 70-75
milligrams. It has a ten hour duration, and is both anorexic and
diuretic. There have been no visual effects or insights reported, but
rather simply a highly intoxicated state.
Two synonyms, two definitions, and an expression of admiration. The
word norepinephrine is synonymous with noradrenalin, and the word
epinephrine is synonymous with adrenalin. The distinctions are that
the first in each case is American and the second British. And the
term "chiral" indicates a potential asymmetry in a molecule that would
allow eventual separation into two optical isomers. The term
"racemic" refers to a mixture of these two isomers which has not yet
been separated into the individual components. A racemic mixture is
called a racemate and, from the point of view of the human animal
(which is completely asymmetric), must be considered as a mixture of
two structurally identical but optically mirror-image isomers, which
can be potentially separated and which will certainly have different
pharmacologies. And the admiration? This is directed to the explorer
who ventured close enough to an octopus to locate its salivary glands
and to discover a phenethylamine there!
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