SYNTHESIS: To a well stirred solution of 25 g ethanolamine hydrochloride in 75 mL MeOH there was added 4.45 g of 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by 1.1 g sodium cyanoborohydride. Concentrated HCl in MeOH was added as required, over the next few days, to maintain the pH at about 6 as determined with external, dampened universal pH paper. The reaction mixture was added to 300 mL H2O and made strongly acidic with an excess of HCl. After washing with 3x100 mL CH2Cl2 the aqueous phase was made basic with 25% NaOH, and extracted with 4x100 mL CH2Cl2. Removal of the solvent under vacuum yielded 3.5 g of a viscous off-white oil that was distilled at 160 deg C at 1.3 mm/Hg to give 2.0 g of a white viscous oil. The pot residue remained fluid, but was discarded. This distillate was dissolved in 8.0 mL IPA to give, eventually, a clear solution. This was neutralized with concentrated HCl and diluted with 100 mL anhydrous Et2O. The loose white crystals of 3,4-methylenedioxy-N-(2-hydroxy-ethyl)amphetamine hydrochloride (MDHOET) that formed were removed by filtration, washed with Et2O, and air dried. These weighed 2.3 g, and had a mp of 147-148 deg C. Anal. (C12H18ClNO3) N.
DOSAGE: greater than 50 mg.
DURATION: unknown.
EXTENSIONS AND COMMENTARY: Most compounds with bare, exposed polar groups like hydroxyls are not centrally active, as they simply do not have any way of getting into the brain. MDHOET is certainly not very active, if it is active at all.
There was one report that at very high doses some central effects were indeed observed. With quantities in the several hundreds of milligrams a picture emerged of changes in perceived color and depth perception, but without euphoria. It was said to resemble a mild dose of ketamine. This is an interesting comment, in that ketamine has found its major medical use as an anesthetic, and MDHOET is among the most effective of all the N-substituted MDA derivatives assayed in several animal analgesia models.
#108 MDIP; N-ISOPROPYL-MDA;
(3,4-METHYLENEDIOXY-N-ISOPROPYLAMPHETAMINE)
SYNTHESIS: To a well stirred and cooled solution of 14.75 g isopropylamine in 100 mL MeOH there was added 4.45 g of 3,4-methylenedioxyphenylacetone (see under MDMA for its preparation) followed by a 1:1 mixture of concentrated HCL and MeOH, sufficient to bring the pH to about 4. This was followed with 1.1 g sodium cyanoborohydride, and stirring was continued overnight. When the pH increased to over 6 there was added an additional 0.5 g of the borohydride, and additional methanolic HCl was added as needed to maintain the pH there. When the pH became stable, the reaction mixture was brought soundly acid with the addition of yet additional HCl, and all solvents were removed under vacuum. The residues were added to 500 mL H2O and washed with 3x100 mL CH2Cl2. The aqueous phase was made basic with 25% NaOH, and extracted with 4x100 mL CH2Cl2. Removal of the solvent under vacuum yielded 2.8 g of an amber liquid that was distilled at 95-110 deg C at 0.3 mm/Hg. There was obtained about 2 mL of a white oil that was dissolved in 10 mL of IPA, neutralized with about 20 drops of concentrated HCl producing spontaneous crystals. These were diluted with some 40 mL of anhydrous Et2O, removed by filtration, washed with Et2O, and then air dried. There was obtained 1.6 g of 3,4-methylenedioxy-N-isopropylamphetamine hydrochloride (MDIP) with a mp of 186-186.5 deg C with prior sintering at 185 deg C. Anal. (C13H20ClNO2) N.
DOSAGE: greater than 250 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 250 mg) At 35 minutes there was an
extremely slight head disturbance which increased over the next few
minutes. I would have missed it if there had been any sensory input
at all. At the one hour point there was a slight physical malaise,
but no 'open window' of any kind, either like MDMA or like LSD. At
the most, this was a threshold, and in another half hour, I was
completely baseline.
EXTENSIONS AND COMMENTARY: The structure of MDIP can be looked at as
exactly that of MDE but with an additional methyl group (one carbon)
hanging off the ethyl that is on the nitrogen. And with that slight
additional weight, the activity has disappeared. On those occasions
where research has shown a compound to be inactive, there has been
some study made that could be called a "primer" experiment. Why not
take advantage of the fact that an "inactive" compound might well be
sitting in some receptor site in the brain without doing anything?
Might its presence, wherever it might be, have some effect if only a
person were to explore it in the correct way? Might it augment or
interfere with the action of another compound? Many experiments of
this kind have been performed, geared to milk additional information
out of a new trial of a new material.
Here is an example of a primer experiment that involved MDIP. Some
five hours following an inactive trial with 120 milligrams of MDIP
(maybe a slight disturbance at one hour, nothing at two hours) a
calibration dose of 80 milligrams of MDMA was taken. The effects of
the MDMA were noted at the 33 minute point, and an honest plus one was
achieved at one hour. At this point a second 80 milligrams was added
to the inventory that was already on board, and the general
intoxication and the eye effects that followed were completely
explained by the MDMA alone. It was obvious that the two drugs did
not see one-another.
Sometimes an experiment can involve the assay of an unknown material at the supplement time of an active drug. This has been called "piggybacking." Here is an example. At the five hour point of an experiment with 140 milligrams of MDE (this had been a light experience, a plus one which had not laster more than two hours) a dosage of 200 milligrams of MDIP rekindled a +1 experience, a pleasant intoxication of the MDE sort, but one that was quite invested with tremor and some feelings of eye-popping. It was almost as if the physical toxic effects outweighed the mental virtues. Imagine an iceberg, with the bulk of its mass underwater. The MDE had had its own modest effects, and had submerged into invisibility, and the response to a little bit of an otherwise inactive MDIP was to refloat a bit of the otherwise unseeable MDE.