SYNTHESIS: A solution of 5.8 g of homosyringonitrile (see under
ESCALINE for its preparation) and 13.6 g isopropyl iodide in 50 mL dry
acetone was treated with 6.9 g finely powdered anhydrous K2CO3 and
held at reflux on the steam bath. After 6 h another 5 mL of isopropyl
iodide was added, and refluxing continued for an additional 12 h. The
mixture was filtered and the solids washed with acetone. The mother
liquor and washes were stripped of solvent under vacuum, The residue
was taken up in dilute HCl, and extracted with 3x100 mL CH2Cl2. The
pooled extracts (they were quite deeply yellow colored) were washed
with 2x75 mL 5% NaOH, and finally once with dilute HCl. Removal of
the solvent under vacuum yielded 9.8 g of an amber oil, which on
distillation at 125-135 °C at 0.3 mm/Hg provided 6.0 g of
3,5-dimethoxy-4-(i)-propoxyphenylacetonitrile as a pale yellow oil. A
pure reference sample is a white solid with a mp of 33-34 °C. Anal.
(C13H17NO3) C,H,N.
A solution of AH was prepared by the cautious addition of 0.84 mL of
100% H2SO4 to 32 mL of 1.0 M LAH in THF, which was being vigorously
stirred under He at ice-bath temperature. A solution of 5.93 g of
3,5-dimethoxy-4-(i)-propoxyphenylacetonitrile in 10 mL anhydrous THF
was added dropwise. Stirring was continued for 30 min, then the
reaction mixture was brought up to reflux on the steam bath for
another 30 min. After cooling again to room temperature, 5 mL IPA was
added to destroy the excess hydride, followed by about 10 mL of 15%
NaOH, sufficient to make the aluminum salts loose, white, and
filterable. The reaction mixture was filtered, the filter cake washed
with IPA, the mother liquor and washes combined, and the solvent
removed under vacuum. The residue (7.0 g of an amber oil) was
dissolved in dilute H2SO4 and washed with 3x75 mL CH2Cl2. The aqueous
phase was made basic with aqueous NaOH, and the product extracted with
3x75 mL CH2Cl2. The extracts were evaporated to a residue under
vacuum, and this was distilled at 125-140 °C at 0.3 mm/Hg yielding 3.7
g of a colorless oil. This was dissolved in 15 mL IPA, neutralized
with 50 drops of concentrated HCl which allowed the deposition of a
white crystalline product. Dilution with anhydrous Et2O and
filtration gave 3.7 g. of 3,5-dimethoxy-4-(i)-propoxyphenethylamine
hydrochloride (IP) with a mp of 163-164 °C. Anal. (C13H22ClNO3)
C,H,N. The catalytic hydrogenation process for reducing the nitrile
that gives rise to escaline, also works with this material.
DOSAGE: 40 - 80 mg.
DURATION: 10 - 16 h.
QUALITATIVE COMMENTS: (with 75 mg) Starts slowly. I develop some
queasiness, turning into nausea. Feels good to lie down and let go,
but the uneasiness remains. Just beginning to break through in 2
hours. But the occasional sense of relief, the breaking into the
open, were transient as new sources of discomfort were always being
dredged up. Then for some reason I chose to dance. Letting go to
dancing, a marvelous ecstatic experience, flowing with and being the
energy, body feeling completely free. Noticing how this letting go
got one completely out of the feeling of unease, as though attention
simply needs to be put elsewhere. Comedown was very slow, gentle,
euphoric; a very signicant experience. Sleep that night was
impossible, but felt good to simply release to the feelings. Keeping
mind still, no thinking, just allowing feelings to go where they
wished, became more and more ecstatic. Tremendous feeling of
confidence in life and the life process. Complete sense of
resolution.
(with 80 mg) It took about two hours for the body to settle down.
Emotions were true and well felt, a fact that is an all-important
thing to me as it probably is to everyone else I know in this kind of
exploration. Any sense that there is a dulling of the feeling and
emotional area of the self is a negative, to be watched and noted as
are other things such as disturbed sleep, unpleasant dreams, or
irritability or depression the next day. I was interacting with
others with a great deal of intensity. People found themselves
wandering inside and out, listening to music, stirring soup, eating a
bit and enjoying eating, talking, laughing a great deal, and being
silent in great contentment. It's not a very silent material, though.
Talking is too enjoyable. There was a slight descent noted at 6-7
hours, but very gentle and smooth. Slow and pleasant descent until
about 12th hour, when sleep was attempted. Next day, everyone
slightly irritable but good mood anyway. The next night I slept
deeply and well, and awoke whole and in excellent mood.
EXTENSIONS AND COMMENTARY: These two excerpts give the color and
complexity of IP. It has proven to be a completely fascinating
phenethylamine. And, as with all the phenethylamines, there is an
amphetamine that corresponds to it. This would be
3,5-dimethoxy-4-isopropoxyamphetamine, or 3C-IP. The prepa-ration of
it would require access through the O-isopropoxylation product with
syringaldehyde, followed by nitrostyrene formation with nitroethane,
followed by reduction probably with lithium aluminum hydride. It has
not been synthesized, as far as I know, and so it has probably not
been evaluated in man. What would be the active level? It would
probably be more potent than IP, but I would guess not by much. Maybe
in the 30 milligram area.
A moment's aside for a couple of the words that are so much a part of
the chemist's jargon. Room temperature, as used above, means the
natural temperature that something comes to if it is put on the table
and is neither heated nor cooled. The phrase, I discovered during my
year at Gif, is completely un-understandable in French. A room has no
temperature. Only things in rooms have temperatures. Their
expression is more exact. The object achieves, in the French
terminology, a temperature normale d'interieur, or about 15 to 16 °C.
But in common laboratory parlance it has become the temperature
d'ambiance.
And one finds the prefix "iso" used everywhere. Considerable care
should be taken in the two different uses of the prefix "iso" in the
nomenclature with the mescaline analogues. In general, the term "iso"
means the other one of two possibilities. If you are allowed to paint
a house only with green paint or red paint, and green is the color you
actually use, then red could be called iso-green. With isoproscaline
(here) there is a rearranging of the propyl group on the 4-oxygen of
mescaline. It has been replaced with its branched analogue, the other
of two possibilities, the isopropyl group. Everything is still with
the 3,4,5-orientation on the benzene ring. However, with IM
(isomescaline) there is a rearrangement of substitution pattern on the
benzene ring, with the repositioning of the trimethoxyl substitution
pattern from the 3,4,5- arrangement to the 2,3,4- arrangement. It has
been the side-chain that has taken the other of two possible
positions. The term "iso" must always be interpreted in precise
context.
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