This is a recipe from
PiHKAL. If you're interested in how the hardlinks
were chosen, read
noding PiHKAL for Everything2.
2,5-DIMETHOXY-4-(2-FLUOROETHYL)-AMPHETAMINE
SYNTHESIS: A well-stirred
solution of 0.45 g free base DOB in 2 mL
CH2Cl2 was treated with 0.37 g
triethylamine, cooled to 0 °C, and
there was then added a
solution of 0.39 g
1,1,4,4-tetramethyl-1,4-dichlorodisilylethylene in 2 mL
CH2Cl2. The
reaction mixture was allowed to return to room tem
perature, with
stirring continued for 2 h. The
solvent was removed under vacuum, the
residue suspended in hexane, and the in
soluble by-products removed by
filtration through celite. Removal of the
solvent under vacuum gave
0.60 g
1-(4-bromo-2,5-dimethoxyphenyl)-2-(1-aza-2,5-disila-2,2,5,5-tetramethylcyclopentyl)propane
as a gold-colored impure semi-solid mass which was used without
further purification.
To a
solution of 0.60 g
1-(4-bromo-2,5-dimethoxyphenyl)-2-(1-aza-2,5-disila-2,2,5,5-tetramethylcyclopentyl)propane
in 10 mL
anhydrous Et2O under an inert
atmosphere and cooled to -78 °C
there was added 1.8 mL of a 1.7 M
solution of t-butyl
lithium in
hexane. The resulting yellow
solution was stirred for 20 min, and
then treated with 1.65 mL of a 1.4 M
solution of
ethylene oxide in
Et2O, the stirring was continued for 40 min, then the reaction mixture
allowed to come to room tem
perature over an additional 40 min. There
was added 20 mL hexane, and the tem
perature increased to 50 °C for an
additional 2 h. The reaction mixture was treated with 3 mL H2O and
diluted with 60 mL
Et2O. The organic
phase was washed with saturated
NH4Cl, dried over
anhydrous MgSO4, and after filtering off the
inorganic drying agent, the organic
solvents were removed under
vacuum. The gold-colored
residual oil was
dissolved in 10 mL MeOH and
treated with a 10% KOH. This mixture was heated for 30 min on the
steam bath, returned to room tem
perature, and the
volatiles removed
under vacuum. The residue was
dissolved in 3% H2SO4, washed twice
with
CH2Cl2, brought to
pH 12 with 25%
NaOH, and extracted with 3x50
mL
CH2Cl2. The pooled extracts were combined, dried with
anhydrous
Na2SO4, and the
solvent removed under vacuum to give 0.24 g of
2,5-dimethoxy-4-(2-hydroxyethyl)amphetamine (DOEH) as a white solid
with a mp of 102-104 °C.
To a suspension of 0.94 g DOEH in ice-cold
anhydrous Et2O containing
1.4 g
triethylamine, there was added 2.4 g
trifluoroacetic anhydride
dropwise over the course of 10 min. The reaction mixture was brought
to reflux tem
perature, and held there with stirring for 1 h. After
cooling, 60 mL of
CH2Cl2 was added, and the organic
phase washed with
saturated
NaHCO3. The
solvent was removed under vacuum, providing a
gold-colored solid as a residue. This was
dissolved in 50 mL MeOH,
diluted with 30 mL H2O and, following the addition of 0.76 g solid
NaHCO3 the reaction mixture was stirred at room tem
perature for 3 h.
The excess MeOH was removed under vacuum, and the remaining solids
were suspended in
CH2Cl2 and washed with H2O. After drying the
organic
phase with
anhydrous Na2SO4 and removal of the
solvent under
vacuum, there was obtained 1.34 g
1-(2,5-dimethoxy-4-(2-hydroxyethyl)phenyl)-2-(2,2,2-trifluoroacetamido)propane
as white solid with a mp of 129-131 °C. Anal. (
C15H20F3NO4) C,H.
A well-stirred
solution of 0.09 g
1-(2,5-dimethoxy-4-(2-hydroxyethyl)phenyl)-2-(2,2,2-trifluoroacetamido)propane
in 15 mL
CH2Cl2 was cooled to -78 °C and treated with 0.05 g
diethylaminosulfur trifluoride (DAST) added dropwise. The pale yellow
reaction
solution was stirred an additional 5 min and then brought up
to room tem
perature and stirred for 1 h. There was then added
(cautiously) 3 mL H2O followed by additional
CH2Cl2. The
phases were
separated, the organic
phase washed with H2O, dried with
anhydrous
Na2SO4 and, after filtering off the drying agent, stripped of
solvent
under vacuum. There was thus obtained 0.088 g of
1-
2,5-dimethoxy-4-(2-fluoroethyl)phenyl-2-(2,2,2-
trifluoroacetamido)
propane
as a white solid with a mp of 102-104 °C.
A
solution of 0.12 g
1-
2,5-dimethoxy-4-(2-hydroxyethyl)phenyl-2-(2,2,2-
trifluoroacetamido)
propane
in a mixture of 5 mL
CH2Cl2 and 5 mL IPA was treated with 0.2 mL 2 N
KOH, heated on the steam bath for 30 min, and then stripped of
solvents under vacuum. The residue was suspended in
CH2Cl2 and washed
with 20%
NaOH. The organic
phase was dried with
anhydrous Na2SO4
which was removed by filtration, and the combined filtrate and
washings stripped of
solvent under vacuum. The
residual glass (0.08
g) was
dissolved in IPA, neutralized with concentrated HCl and diluted
with
anhydrous Et2O to provide
2,5-dimethoxy-4-(2-fluoroethyl)amphetamine hydrochloride (
DOEF) as a
white
crystalline solid with a mp of 205-208 °C. Anal. (
C13H21ClFNO2)
C,H.
DOSAGE: 2 - 3.5 mg.
DURATION: 12 - 16 h.
QUALITATIVE COMMENTS: (with 2.2 mg) Somewhere between the first and
second hour, I grew into a world that was slightly unworldly. Why?
That is hard to say, as there was no appreciable visual component. I
just knew that the place I was in was not completely familiar, and it
was not necessarily friendly. But it was fascinating, and the music
around me was magical. Time was moving slowly. I had to drive across
the bay at about ten hours into this, and I was comfortable. That
evening I slept well, but my dreams were pointless.
(with 3.0 mg) It took almost three hours to full activity. The first
signs of effects were felt within a half hour, but from then on the
progress was slow and easy, without any discernible jumps. There was
absolutely no body discomfort at all. Completely comfortable. There
was a general humorousness about my state of mind which is always a
good sign. We went to the bedroom at the two and a half hour point,
and proceeded to establish that the material is far from anti-erotic.
Beautiful response, without a mention of any feeling of risk at
orgasm. I myself was not able to reach orgasm until about 5th to 6th
hour, and then it was full and exceptionally delicious. So was the
second one, a couple of hours later, if I remember correctly. All
systems intact, body, mind and emotion. Gentle. Good for writing.
No dark corners apparent at all. For me, not highly visual. Would
take again, higher.
(with 3.0 mg) There was no body threat at any time--very
comfortable. Good eyes closed, with complex imagery to music, but not
too much with eyes-open. My attention span is relatively short, and
easily diverted into new directions--all quite
reminiscent of DOI
both as to dosage and effect. At 13 hours, I am still too alert to
sleep, but a couple of hours later, OK. In the morning there is still
a trace of something going on. This was a valid +++.
EXTENSIONS AND COMMENTARY: I was asked by a student of mine a while
ago, when I told him of this material, just why would anyone just
happen to place a
fluorine atom at the end of the
4-ethyl group of
DOET? It wasn't the sort of thing that someone would just happen to
do. If there were a rationale, then that's fine. But by capricious
impulse, no. But there is a rationale of sorts, which I just hinted
at in the discussion under
2C-T-21.
This argument of reason goes as follows. Assume that I would like to
put a
fluorine atom into a drug that does not normally have one. Why
would I want to? Because I want to have the molecule carry a
radioactive fluorine atom into some inner recess of the brain. Why?
Because by using a
positron-emitting
fluorine I could possibly
visualize the area of the brain that the drug went to. And if it went
there in some abnormal way, the exact measure of that abnormality
might give some clue as to potential brain misfunctioning.
But, if you put a
fluorine atom on a drug, it becomes a totally new
drug and, quite reasonably, a
pharmacologically different drug.
However, a body of evidence is being accumulated that if a
halogen,
such as a
bromine or an
iodine atom, is replaced by a
beta-fluoroethyl
group, the
electronic and polar properties of the drug can be pretty
much the same. So, what
psychedelics have a bromo or an iodo group?
Obviously, DOB and DOI. Thus,
DOEF is a natural candidate for
fluorine-18
positron emission
tomography, and also a natural candidate
for clinical trials. And, voila, it is an active material.
And I'll bet you dollars to doughnuts, that if one were to make the
two-
carbon analog 2,5-dimethoxy-4-(2-fluoroethyl)-phenethylamine, it
would be every bit as much a treasure and ally as is
2C-B or
2C-I. In
fact, I am sure enough about this prediction that I am willing to name
the stuff 2C-EF. It will be easily made from
2C-B by the same
reaction scheme that was used above for
DOEF. And I will even guess
that its activity level will be in the 20-30 milligram area.
Back to PiHKAL?