SYNTHESIS: A solution of 17.5 g 1,4-naphthaquinone in 200 mL MeOH was
heated to the boiling point, and treated with 28.5 g stannous chloride
at a rate that maintained a continuous rolling boil. At the
completion of the addition, the reaction mixture was saturated with
anhydrous hydrogen chloride, and held at reflux on the steam bath for
2 h. The reaction mixture was poured into 700 mL H2O and treated with
aqueous NaOH. During the addition there was transient development of
a curdy white solid which redissolved when the system became strongly
basic. This was extracted with 3x200 mL CH2Cl2 and the pooled
extracts were washed first with H2O, then with dilute HCl, and finally
again with H2O. Removal of the solvent under vacuum yielded 15.75 g
of a low melting black flaky crystalline material which was distilled
at 160-180 °C at 0.05 mm/Hg to give 14.5 g of an amber, solid mass
with a mp of 78-86 °C. Recrystallization from 75 mL boiling MeOH
provided 1,4-dimethoxynaphthalene as white crystals melting at 87-88
°C.
A mixture of 20.0 g POCl3 and 22.5 g N-methylformanilide was allowed
to stand at room temperature for 0.5 h which produced a deep claret
color. To this there was added 9.4 g 1,4-dimethoxynaphthalene and the
mixture was heated on the steam bath. The reaction mixture quickly
became progressively darker and thicker. After 20 min it was poured
into 250 mL H2O and stirred for several h. The solids were removed by
filtration, and washed well with H2O. The wet crude product (a dull
yellow-orange color) was dissolved in 125 mL boiling EtOH to give a
deep red solution. On cooling, this deposited a heavy crop of
crystals that was removed by filtration, and washed with cold EtOH.
There was obtained, after air-drying to constant weight, 7.9 g
1,4-dimethoxy-2-naphthaldehyde as white crystals with a mp of 119-121
°C. This was not improved by further recrystallization. The
malononitrile derivative, from the aldehyde and malononitrile in EtOH
with a drop of triethylamine, had a mp of 187-188 °C.
A solution of 3.9 g 1,4-dimethoxy-2-naphthaldehyde in 13.5 g
nitromethane was treated with 0.7 g anhydrous ammonium acetate, and
heated on the steam bath for 1 h. The excess reagent/solvent was
removed under vacuum giving a residue that spontaneously crystallized.
This crude product was removed with the aid of a few mL MeOH, and
pressed on a sintered funnel with modest MeOH washing. There was
obtained 3.6 g (when dry) of old-gold colored crystals with a mp of
146-148 °C. Recrystallization from 140 mL boiling EtOH gave 3.0 g
1,4-dimethoxy-2-(2-nitro-vinyl)naphthalene as deep gold-colored
crystals with a mp of 146-147 °C. A small sample, upon
recrystalization from MeOH, melted at 143-144 °C. Anal. (C14H13NO4)
C,H.
A solution of LAH (50 mL of a 1 M solution in THF) was cooled, under
He, to 0 °C with an external ice bath. With good stirring there was
added 1.32 mL 100% H2SO4 dropwise, to minimize charring. This was
followed by the addition of 2.80 g
1,4-dimethoxy-2-(2-nitrovinyl)naphthalene in 40 mL anhydrous THF.
There was an immediate loss of color. After 1 h stirring at 0 °C, the
temperature was brought up to a gentle reflux on the steam bath for 20
min, then all was cooled again to 0 °C. The excess hydride was
destroyed by the cautious addition of 7 mL IPA followed by 5.5 mL 5%
NaOH. The reaction mixture was filtered, and the filter cake washed
with several portions of THF. The combined filtrate and washings were
stripped of solvent under vacuum providing 3.6 g of a pale amber oil
that was distilled at 145-160 °C at 0.2 mm/Hg to give 1.25 g of
product as an absolutely white oil. This was dissolved in 7 mL IPA,
and neutralized with concentrated HCl forming immediate crystals of
the hydrochloride salt in the alcohol solvent. Thirty mL of anhydrous
Et2O was added, and after complete grinding and mixing, the
hydrochloride salt was removed by filtration, Et2O washed, and air
dried to constant weight. The spectacular white crystals of
1,4-dimethoxynaphthyl-2-ethylamine hydrochloride (2C-G-N) weighed 1.23
g and had melting properties of darkening at 190 °C, and decomposing
in the 235-245 °C area. Anal. (C14H18ClNO2) C,H.
DOSAGE: 20 - 40 mg.
DURATION: 20 - 30 h.
QUALITATIVE COMMENTS: (with 24 mg) The effects were interestingly
colored by the reading of Alan Watts' Joyous Cosmology during the
coming-on period. The only body negatives were some urinary retention
and a feeling of a shallow but continuing amphetamine stimulation.
But not enough to be actually jingly, nor to interfere with sleep that
evening. There is not much psychedelic here, but there is something
really going on anyway. This has some similarities to the
antidepressant world.
(with 35 mg) Much writing, much talking, and there was considerable
residual awareness the next day. Somehow this material is not as
friendly as the other 2C-G's.
(with 35 mg) Thinking is clear. No fuzziness, no feeling of being
pushed. None of the walking on the fine middle line between light and
dark that is the excitement and the threat of LSD. This is just a
friend, an ally, which invites you to do anything you wish to.
[comment added two days later] RMy sleep was not deep enough, but it
was pleasant and relatively resting. The whole next day I was feeling
happy, but with an overlay of irritability. Strange mixture. By
bedtime the irritability had become a mild depression. I feel that
there might have been a threshold continuing for a couple of days.
The character of my dreaming had the stamp of drug on it. This
compound, in retrospect, presents some problems that cause a faint
unease.
EXTENSIONS AND COMMENTARY: There is always a wish in the design of new
compounds to find something that is of interesting activity, with an
aromatic ring at some location pretty much away from the site of
activity. This would then allow some subtle fine-tuning of the nature
of the action by putting any of a wide range of electron pushing or
electron pulling groups on that ring. But here, with 2C-G-N, by the
time the ring got put into place, the activity was already on the
wane, and the action was too long, and there are indicators of some
not completely friendly effects. Ah well, some other molecule, some
other time.
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