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#37 CPM
CYCLOPROPYLMESCALINE; 4-CYCLOPROPYLMETHOXY-3,5-DIMETHOXYPHENETHYLAMINE
SYNTHESIS: To a
solution of 2.8 g
homosyringonitrile (see under E for
synthesis) in 20 ml
acetone containing about 50 mg
decyltriethylammonium iodide, there was added 3.0 g
cyclopropylmethyl
chloride and 5.0 g NaI. Stirring was continued during a color change
from pale yellow to blue. There was then added 2.9 g of finely
powdered
anhydrous K2CO3, resulting in a beautiful turquoise color.
The mixture was held at reflux on the steam bath for 3 h, which
discharged all color. The
solvent was removed under vacuum, and the
residues were added to 100 mL H2O. This
solution was extracted with
3x75 mL
CH2Cl2, the extracts were pooled, washed with 2x50 mL 5%
NaOH,
and the organic
solvent removed under vacuum. The
residual oil
weighed 4.2 g, and was
distilled at 140-155 °C at 0.4 mm/
Hg to yield
4-cyclopropylmethoxy-3,5-dimethoxyphenylacetonitrile as a colorless
oil weighing 2.8 g which spontaneously
crystallized. Its mp was
44-44.5 °C after re
crystallization from MeOH/H2O. Anal. (
C14H17NO3)
C,H.
A suspension of 1.3 g LAH in 65 mL
anhydrous THF under He was cooled
to 0 °C with stirring, and 0.85 mL of 100% H2SO4 was slowly added.
Then, with continued stirring, a THF
solution of 2.7 g of
4-cyclopropylmethoxy-3,5-dimethoxyphenylacetonitrile in 50 mL THF was
added dropwise. After the addition was complete, the mixture was
brought to a boil briefly on the steam bath, cooled, and treated with
sufficient IPA to destroy the excess
hydride. Then there was added an
amount of 15%
NaOH sufficient to produce a loose filterable solid form
of
aluminum oxide. This was removed by filtration, and the filter
cake washed with THF. The pooled filtrate and washes were stripped of
solvent, and the residue was
dissolved in dilute H2SO4, washed with
2x50 mL
CH2Cl2, made basic with aqueous
NaOH, and then extracted with
2x50 mL of
CH2Cl2. After removal of the
solvent, the residue was
distilled at 128-140 °C at 0.4 mm/
Hg to yield 2.5 g of a white oil.
This was
dissolved in 10 mL IPA, and treated with 30 drops of
concentrated HCl which was just sufficient to demonstrate acidity as
judged by external dampened
pH paper. The addition of 25 mL
anhydrous
Et2O to the stirred
solution allowed, in a few minutes, the product
4-cyclopropylmethoxy-3,5-dimethoxyphenethylamine hydrochloride (CPM)
to spontaneously
crystallize as a fine white solid. The yield was 1.8
g, and a second crop of 0.8 g was obtained from the IPA/
Et2O mother
liquors. The mp was 172-173 °C. Anal. (
C14H22ClNO3) C,H.
DOSAGE: 60 - 80 mg.
DURATION: 12 - 18 h.
QUALITATIVE COMMENTS: (with 70 mg) I was surprised at the fast
development of this drug, with the knowledge that it was a
long-laster. Twenty minutes into it I was aware of some changes, and
by the end of one and a half hours there was a complete plus three.
The most remarkable property is the eyes-closed imagery. No, not just
imagery but fantasy. It is not completely benign, but it locks into
music with an extraordinary fit. I was at one moment keenly aware of
my body touching the rug, the
tactile aspects of my surroundings, and
then I would find that my world was simply my personal sphere of
reality that kept engulfing everything about me, all completely
augmented by the music. Constructed by the music. I hoped that I
wouldn't offend anyone else around me with this growing world of mine.
Eyes open, there was not that much of note. Not much insight. Not
much in the way of visuals. By the eighth hour an effort to sleep
showed me how exposed and vunerable I was, and when I closed my eyes I
needed my guards against this fantasy world. Even at the twelth hour
there was no easy way to relax and sleep. Use higher dosages with
caution.
(with 70 mg) There is a goodly amount of eyes-closed patterning but I
found external sounds to be irritating. Voices, and even music,
seemed to be intrusive. I didn't want to share my space with anyone.
I was reminded of mescaline, in that I kept losing the awareness of
the drug's role in my experience. Visual exaggerations are probably
right around the corner. The
residual effects were too much to
ignore, but 100 milligrams of
phenobarb at about the twelth hour
allowed me to lie down quietly.
(with 80 mg) A wild day of profound
philosophy, with discussions of
the art of molecules, the origins of the universe, and similar weighty
trivia. Much day-dreaming in erotic areas, but by and large, it went
on a bit too long. I was tired.
EXTENSIONS AND COMMENTARY: In the literary world, the guy who is on
your side, your leader, your champion, is the
protagonist and the guy
he battles, your enemy, is the ant
agonist. These same roles are
played in the world of
pharmacology, but the names are slightly
changed. A drug which does the needed or expected thing is called the
agonist rather than
protagonist, but the drug that gets in its way is
still called the ant
agonist.
The
cyclopropylmethyl group plays an interesting role in the world of
narcotics. There are numerous examples of
opiates with a
methyl group
attached to a
nitrogen atom which are famous for being valuable in
producing
analgesia and
sedation. These run the gamut from natural
alkaloids such as
morphine and
codeine, to
synthetic variants such as
Dilaudid and Percodan. And yet, with most of these narcotics, when
the
methyl on the
nitrogen is removed, and a
cyclopropylmethyl group
put into its place, the
agonist becomes an antagonist.
Oxycodone (the
active narcotic thing in Percodan) becomes
Naltrexone, a drug that
will immediately snap a
heroin victim out of his overdose.
Cyclopropylmescaline (CPM) is a molecule that is very simply mescaline
itself, with a
methyl group removed from an oxygen atom and a
cyclopropylmethyl group put on instead. Might CPM be not only
inactive, but actually block the action of mescaline? Interesting
concept. But it turned out to be entirely wrong.
The
amphetamine analog of CPM should be easily made from the
alkyl-ation of
syringaldehyde with
cyclopropyl chloride, followed by
conventional reaction of the resulting
aldehyde with
nitroethane, and
finally a reduction step. There is no reason to believe that the
resulting compound
3,5-dimethoxy-4-cyclo-propyloxyamphetamine (3C-CPM)
would be any shorter acting than CPM.
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