This is a recipe from
PiHKAL. If you're interested in how the hardlinks
were chosen, read
noding PiHKAL for Everything2.
#26 2C-F
2,5-DIMETHOXY-4-FLUOROPHENETHYLAMINE
SYNTHESIS: A
solution of 76.6 g
2,5-dimethoxyaniline in 210 mL H2O
containing 205 mL
fluoroboric acid was cooled to 0 °C. with an
external ice bath. There was then added, slowly, a
solution of 35 g
sodium nitrite in 70 mL H2O. After an additional 0.5 h stirring, the
precipitated solids were removed by filtration, washed first with cold
H2O, then with MeOH and finally
Et2O. Air drying yielded about 100 g
of the
fluoroborate salt of the aniline as dark purple-brown solids.
This salt was pyrolyzed with the cautious application of a flame, with
the needed attention paid to both an explosion risk, and the evolution
of the very
corrosive boron trifluoride. The liquid that accumulated
in the receiver was
distilled at about 120 °C at 20 mm/
Hg, and was
subsequently washed with dilute
NaOH to remove
dissolved
boron
trifluoride. The product,
2,5-dimethoxyfluorobenzene, was a fluid,
straw-colored oil that weighed 7.0 g.
To a vigorously stirred
solution of 40.7 g
2,5-dimethoxyfluorobenzene
in 215 mL
CH2Cl2 cooled with an external ice bath, there was added 135
g of
anhydrous stannic
chloride. There was then added, dropwise, 26 g
of
dichloromethyl methyl
ether at a rate that precluded excessive
heating. The reaction mixture was allowed to come to room tem
perature
over the course of 0.5 h, and then quenched by dumping into 500 g
shaved ice containing 75 mL concentrated HCl. This mixture was
stirred for an additional 1.5 h. The separated organic layer was
washed with 2x100 mL dilute HCl, then with dilute
NaOH, then with H2O
and finally with saturated brine. Removal of the
solvent under vacuum
yielded a solid residue that was re
crystallized from aqueous
EtOH
yielding 41.8 g
2,5-dimethoxy-4-fluorobenzaldehyde with a mp of 99-100
°C.
A
solution of 2.5 g
2,5-dimethoxy-4-fluorobenzaldehyde in 15 mL acetic
acid containing 1 g
nitromethane was treated with 0.2 g
anhydrous
ammonium acetate, and heated on the steam bath for 4 h. After
cooling, and following the judicious addition of H2O,
crystals
separated, and additional H2O was added with good stirring until the
first signs of oiling out appeared. The solids were removed by
filtration, and re
crystallized from
acetone to give 2.0 g of
2,5-dimethoxy-4-fluoro-beta-nitrostyrene with a mp of 159-162 °C.
To a suspension of 2.0 g LAH in 200 mL cool
anhydrous Et2O under an
inert
atmosphere, there was added a THF
solution of 2.0 g
2,5-dimethoxy-4-fluoro-beta-nitrostyrene. The reaction mixture was
stirred at room tem
perature for 2 h and then heated briefly at reflux.
After cooling, the excess
hydride was destroyed by the cautious
addition of H2O, and when the reaction was finally quiet, there was
added 2 mL of 15%
NaOH, followed by another 6 mL of H2O. The basic
in
solubles were removed by filtration, and washed with THF. The
combined filtrate and washes were stripped of
solvent, yielding a
residual oil that was taken up in 10 mL of IPA, neutralized with
concentrated HCl, and the generated solids diluted with
anhydrous
Et2O. The white
crystalline 2,5-dimethoxy-4-fluorophenethylamine
hydrochloride (2C-F) was re
crystallized from IPA to give an air-dried
product of 0.5 g with a mp of 182-185 °C.
DOSAGE: greater than 250 mg.
DURATION: unknown
QUALITATIVE COMMENTS: (with 250 mg) Even at 250 milligrams, the
effects were slight and uncertain. There may have been some
eyes-closed imagery above normal, but certainly not profound. At
several hours there was a pleasant lethargy; sleep was completely
normal that night.
EXTENSIONS AND COMMENTARY: A number of graded acute dosages were
tried, and it was only with amounts in excess of 100 milligrams that
there were any baseline disturbances at all. And at no dose that was
tried was there any convincing indication of believable central
effects.
The three-
carbon amphetamine analogue of 2C-F would quite logically be
called DOF (
2,5-dimethoxy-4-fluoroamphetamine). It has been prepared
by reaction of the above
benzaldehyde with
nitroethane (giving
1-(2,5-dimethoxy-4-fluorophenyl)-2-nitropropene, with a melting point
of 128-129 °C from
ethanol) followed by LAH reduction to DOF (the
hydrochloride salt has a melting point of 166-167 °C, after
re
crystallization from
ether/
ethyl acetate/
ethanol). Animal studies
that have compared DOF to the highly potent DOI and DOB imply that the
human activity will be some four to six times less than these two
heavier
halide analogues. As of the present time, no human trials of
DOF have been made.
Back to PiHKAL?