SYNTHESIS: A solution of 11.5 g pellet KOH (85%) in 75 mL EtOH was
treated with 25 g sesamol followed by 27 g methyl iodide. This was
brought to reflux on the steam bath. Salt formation was apparent in
20 min, and refluxing was main-tained for a total of 4 h. The solvent
was removed under vacuum, and residue poured into 400 mL H2O. This
was acidified with HCl and extracted with 3x150 mL CH2Cl2. The pooled
extracts were washed with 3x100 mL 5% NaOH, which removed most of the
color. The solvent was removed under vacuum to provide 24.0 g of
3,4-methylenedioxyanisole as a pale amber oil.
A mixture of 56.4 g POCl3 and 49.1 g N-methylformanilide was allowed
to stand for 40 min and then it was poured into a beaker containing 64
g 3,4-methylenedioxyanisole. There was an immediate exothermic
reaction with darkening and the generation of bubbles. This was
heated on the steam bath for 1 h, then poured into 1 L H2O with
extremely vigorous stirring. The dark brown phase was quite opaque,
and then there was a sudden lightening of color with the generation of
a fine pale yellow solid. Stirring was continued for 2 h, then these
crystals were removed by filtration. This crude product was
recrystallized from 400 mL boiling MeOH yielding, after filtering,
washing, and air drying to constant weight, 44.1 g
2-methoxy-4,5-methylenedioxybenzaldehyde with a mp of 110-111 °C.
Only one positional isomer was visible in the final product by GC, but
extraction of the original mother liquors with CH2Cl2 produced, after
evaporation of the solvent under vacuum, 2 g of a red oil that showed
two earlier peaks on OV-17. These were consistent with about 1% of
each of the two alternate positional isomers that could result from
the Vilsmeier formylation reaction.
A solution of 43 g 2-methoxy-4,5-methylenedioxybenzaldehyde in 185 g
nitroethane was treated with 9.3 g anhydrous ammonium acetate and
heated on the steam bath for 4.5 h. The excess nitroethane was
removed under vacuum to give a residue that spontaneously
crystallized. These solids were washed out mechanically with the aid
of 200 mL cold MeOH, and the brilliant orange crystals recovered by
filtering and air drying to constant weight. There was obtained 35.7
g 1-(2-methoxy-4,5-methylenedioxyphenyl)-2-nitropropene with a mp of
166-167 °C. This was not improved by recrystallization from IPA.
Evaporation of solvent from the methanolic washes gave yellow solids
(4.6 g melting at 184-186 °C) which, on recrystallization from
THF/hexane, melted at 188-190 °C. This showed a molecular weight of
416 by chemical ionization mass spectroscopy (isobutane at 0.5 torr)
and is the C20H20N2O8 adduct of one molecule each of nitrostyrene,
aldehyde, and ammonia that frequently appears as a very insoluble
impurity in aldehyde-nitroethane condensations that are catalyzed by
ammonium acetate.
To a refluxing suspension of 36 g LAH in 1 L anhydrous THF under an
inert atmosphere, there was added 44.3 g
1-(2-methoxy-4,5-methylenedioxyphenyl)-2-nitropropene in hot THF. The
solubility was very low, so that it was necessary to use a heat lamp
on the dropping funnel to maintain a clear solution for addition. The
addition required 2 h and the reflux was maintained for 36 h. The
reaction mixture was then cooled in an ice bath and there was added,
in sequence and commensurate with heat evolution, 36 mL H2O, 36 mL 15%
NaOH, and finally 108 mL H2O. The granular solids were removed by
filtration and washed with THF. The combined filtrate and washes were
stripped of solvent under vacuum yielding 58.8 g of a pale amber oil.
This was dissolved in 100 mL IPA, neutralized with con-centrated HCl
(20 mL was needed) and diluted with 500 mL anhydrous Et2O. More IPA
was required to keep an oil phase from appearing. After the
crystalline product was completely formed, it was removed by
filtration, washed with IPA/Et2O, and finally with Et2O. Air drying
gave 31.1 g of 2-methoxy-4,5-methylenedioxyamphetamine hydrochloride
(MMDA-2) with a mp of 186-187 °C.
DOSAGE: 25 - 50 mg.
DURATION: 8 - 12 h.
QUALITATIVE COMMENTS: (with 25 mg) Had some not-too-pleasant jangly
effects--this is not the smoothest of drugs. Duration: onset at 1
1/2 hours (dose after lunch), acute 3 to 4 hours, seconal at 11 hours
to stop residual effects so I could sleep. Occasionally from 5 to 10
hours acute abdominal distress, resembling gas pains but unable to
defecate. Abdominal muscles tight and hard. This occurred for about
15 minutes every hour or so. Rather unpleasant.
(with 30 mg) There was the first subtle note at 45 minutes, and the
slow development makes the changes easy to assimilate, but difficult
to quantitate. My awareness is truly enhanced. Nothing is distorted,
so there can be no misrepresentation as a result. This would be a
good material to introduce someone to the slow-on slow-off type of
experience. It would be impossible for any person, at this level, on
this drug, to have a bad experience. This is very much like a slow
MDA, perhaps 80 milligrams of it, and fully as controllable. The
N-methyl of this is a must.
(with 40 mg) The chemical is primarily a visual enhancer with only an
extremely modest amount of visual distortion. The retinal activity
was of a minor and non-threatening nature. The chemical seemed to
facilitate empathic communication and the emotions felt strong and
clean. Conversation flowed easily, without inhibitions or
defensiveness. Anorexia accompanied experience. There was no
impotence. There was some restless movement which dissipated with
exercise (walking and playing frisbee). Next day woke feeling
energetic, no muscular stiffness, alert. I would repeat this
experience.
(with 50 mg) I was coming on within 40-60 minutes, easy and slow, but
the body was +3 before the mind. The mental was strange for the first
2-3 hours--I called it 'High Sierras'--realistic, dispassionate, not
kind. Some dark areas are persistent. Watched last half of Circus of
Dr. Lao and the whole feeling changed from pornographic to erotic.
Delightful. Some fantasy. On coming down, sleep was difficult. The
body feels unexpectedly depleted. Rubber legs and handwriting jerky.
EXTENSIONS AND COMMENTARY: A comparison of this material to MDA was
often made by subjects who were familiar with both. But it is hard to
separate that which is intellectualized from that which is felt. An
awareness of the chemical structure immediately shows, of course, the
close resemblance. There is the complete MDA molecule, with the
addition of a methoxy group. And for the non-chemist, the name itself
(MMDA-2) represents the second possible methoxy-MDA. Certainly one
property that is shared with MDA is the broad variety of opinions as
to the quality of its action. Some like it much, and some like it not
at all. The N-methyl homologue was indeed made, for direct evaluation
in comparison to N-methyl MDA (which is MDMA).
The phenethylamine analog of MMDA-2 has been prepared by the
condensation of the above benzaldehyde with nitromethane (in acetic
acid with ammonium acetate catalyst, giving an equal weight of the
nitrostyrene as deep orange crystals with a mp of 166-167 °C from
ethyl acetate) followed by lithium aluminum hydride reduction (in
ether). The product, 2-methoxy-4,5-methylenedioxyphenethylamine
hydrochloride (2C-2) melted at 218-219 °C. There were no effects
observed at up to 2.6 milligrams, but no higher trials were made. The
4-carbon homologue was made similarly (from the aldehyde and
nitropropane but using tert-butylammonium acetate as a reagent in 100%
excess and isopropanol as solvent, giving orange crystals melting at
98-99 °C from methanol) followed by reduction (with lithium aluminum
hydride in ether) to give
1-(2-methoxy-4,5-methylenedioxyphenyl)-2-aminobutane hydrochloride
(4C-2) with a mp of 172-174 °C. This material has never even been
tasted.
The Tweetio homologue of MMDA-2 has been tasted, however. This is
2-ethoxy-4,5-methylenedioxyamphetamine, or EMDA-2. The allyl ether of
sesamol (3,4-methylenedioxy-allyloxybenzene) was rearranged to the
2-allyl phenol which was, in turn, converted to the ethyl ether.
Reaction with tetranitromethane gave the nitrostyrene intermediate
which had a mp of 120-121 °C. The final hydrochloride salt of EMDA-2
had a mp of 188-188.5 °C. At 135 milligrams, there have been reported
eyes-closed visual phenomena, with intense colors. The overall
duration is similar to MMDA-2 (some 10 hours) and there are reported
sleep disturbances. At 185 milligrams, the feelings were intensified,
there were "marvelous eyes-closed visuals (the colors were
incredible), good concentration, but distinct body-tingles and
rushes." The time span was about 12 hours from start to finish, but it
proved to be impossible to sleep afterwards. This homologue is thus
about a third the potency of MMDA-2.
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