a,a-DIMETHYL-3,4-METHYLENEDIOXY- PHENETHYLAMINE; 3,4-METHYLENEDIOXYPHENTERMINE
SYNTHESIS: To 150 mL of THF, under an atmosphere of nitrogen, there was added 11.2 g diisopropylamine, and the solution was cooled with external dry ice/IPA. There was then added 48 mL of a 2.3 M solution of butyllithium in hexane, dropwise, with good stirring. This was warmed to room temperature, stirred for a few min, and then all was cooled again in the dry ice bath. Following the dropwise addition of 4.4 g of isobutyric acid there was added 10.5 mL hexamethylphosphoramide. Again, the stirred reaction mixture was brought to room temperature for about 0.5 h. There was then added, drop-wise, 8.5 g 3,4-methylenedioxybenzyl chloride and the mixture allowed to stir overnight at room temperature. The reaction mixture was poured into 100 mL 10% HCl, and the excess THF was removed under vacuum. The acidic aqueous residue was extracted with 2×150 mL Et2O. These extracts were pooled, washed with 10% HCl, and then extracted with 3×75 mL of 4 N Na2CO3. These extracts were pooled, made acidic with HCl, and again extracted with Et2O. After drying the pooled extracts with anhydrous MgSO4, the solvent was removed under vacuum to give a residue that spontaneously crystallized. Recrystallization from hexane yielded 6.5 g of 2,2-dimethyl-3-(3,4-methylenedioxyphenyl)propionic acid as white crystals with a mp of 71-73 °C. The NMR spectrum in CDCl3 showed the alpha-dimethyl groups as a sharp singlet at 1.18 ppm. Anal. (C12H14O4) C,H.
The triethylamine salt of 2,2-dimethyl-3-(3,4-methylenedioxyphenyl)propionic acid (5.4 g amine, 11.4 g acid) was dissolved in 10 mL H2O and diluted with sufficient acetone to maintain a clear solution at ice-bath temperature. A solution of 6.4 g ethyl chloroformate in 40 mL acetone was added to the 0 °C solution over the course of 30 min, followed by the addition of a solution of 4.1 g sodium azide in 30 mL H2O. Stirring was continued for 45 min while the reaction returned to room temperature. The aqueous phase was extracted with 100 mL toluene which was washed once with H2O and then dried with anhydrous MgSO4. This organic solution of the azide was heated on a steam bath until nitrogen evolution had ceased, which required about 30 min. The solvent was removed under vacuum and the residue was dissolved in 30 mL benzyl alcohol. This solution was heated on the steam bath overnight. Removal of the excess benzyl alcohol under vacuum left a residue 13.5 g of 1-(N-(benzyloxycarbonyl)amino)-1,1-dimethyl-2-(3,4-methylenedioxyphenyl)ethane as an amber oil. The dimethyl group showed, in the NMR, a sharp singlet at 1.30 ppm in CDCH3. Anal. (C19H21NO4) C,H. This carbamate was reduced to the primary amine (below) or to the methylamine (see under MDMP).
A solution of 3.27 g of 1-[N-(benzyloxycarbonyl)amino]-1,1-dimethyl-2-(3,4-methylenedioxyphenyl)ethane in 250 mL absolute ethanol was treated with 0.5 g 10% palladium on carbon. This mixture was shaken under hydrogen at 35 pounds pressure for 24 h. The carbon was removed by filtration through Celite, and the filtrate titrated with HCl. The solvent was removed under vacuum, and the residue allowed to crystallize. This produce was recrystallized from an EtOH/EtOAc mixture to provide a,a-dimethyl-3,4-methylenedioxyphenethylamine hydrochloride (MDPH). The white crystals weighed 1.63 g and had a mp of 180-181 °C. Anal. (C11H16ClNO2) C,H,N.
DOSAGE: 160 – 240 mg.
DURATION: 3 – 5 h.
QUALITATIVE COMMENTS: (with 120 mg) The alert was felt in forty minutes and I was pretty much there at an hour and twenty. Quite like MDA, simple, with no lines, no colors, no motion, no fantasy. I am pleasantly stoned. The anorexia is real, as is the impotency. The drop from the 4th to the 6th hour was softened by a modest amount of wine, and this proved to be extremely intoxicating. My speech was slurred, and there was later amnesia for the rather aggressive and uninhibited behavior that occurred. I felt that there was more drug than alcohol contributing to this episode. My dream patterns were disturbingly unreal.
(with 160 mg) A very quiet development. There was no body load whatsoever. And no visual, and I saw it fading away all too soon. This might be a good promoter, like MDPR. I felt refreshed and relaxed on the following morning.
(with 200 mg) This has an inordinately foul taste. I felt slightly queasy. There were short daydreams which were quickly forgotten. I see no values that are worth the hints of physical problems, a little eye mismanagement and some clenching of teeth, and a tendency to sweat. I was able to sleep at only five hours into it, but there were a couple of darts. This is not as rewarding (stoning) as MDA, and has none of the magic of MDMA. It was a short-lived plus two.
EXTENSIONS AND COMMENTARY: What is the train of thought that leads from the structure of a known compound (which is active) to the structure of an unknown one (which may or may not be active)? Certainly the extrapolations involve many what-if’s and maybe’s. The path can be humorous, it certainly can be tortuous, and it often calls for special things such as faith, insight, and intuition. But can one say that it is logical?
Logic is a tricky thing to evaluate. One of the earliest approaches was laid down by Aristotle, in the form of the syllogism. In it there are three lines consisting of two premises and a conclusion, a form that is called a „mood.“ All are statements of relationships and, if the premises are true, there are only certain conclusions that may logically follow. For example:
Every man is a lover. Every chemist is a man. Therefore, every chemist is a lover.
Letting lover be the major term „a“ and letting chemist be the minor term „b“ and letting man be the middle term „m“, this reduces to:
Every m is a,
Every b is m. Therefore, every b is a
and it is a valid mood called Barbara.
Of the 256 possible combinations of all’s and some’s and none’s and are’s and are-not’s, only 24 moods are valid. The reasoning here with MDPH goes:
Some stimulants when given a methylenedioxy ring are MDMA-like.
Some ring-unsubstituted 1,1-dimethylphenylethylamines are stimulants. Therefore, some ring-unsubstituted 1,1-dimethylphenylethyl amines when given a methylenedioxy ring are MDMA-like.
In symbolic form this is:
Some m is a, and Some b is m, then Some b is a
and this is not one of the 24 valid moods. Given the first premise as some m is a, there is only one valid syllogism form that can follow, and this is known as Disamis, or:
Some m is a, and Every m is b, then Some b is a
which translates as:
Some stimulants when given a methylenedioxy group are MDMA-like. Every stimulant is a ring-unsubstituted 1,1-dimethylphenyl ethylamine. Therefore, some ring-unsubstituted 1,1-dimethylphenylethyl amines when given a methylenedioxy group are MDMA-like.
The conclusion is the same. But the second premise is false so the entire reasoning is illogical. What is the false second premise? It is not a fact that every stimulant is a phentermine. There are lots of stimulants that are not phentermines.
So much for applying syllogistics to pharmacology.