Here is some more in-depth info on the subject :
Ref.: 'Quasar' Research Monograph 22.
Absolute Configuration and Psychotomimetic Activity.
G.M.Anderson III, Gisela Braun, Ulrich Braun, David E. Nichols, and Alexander T. Shulgin.
This paper is 8 pages long, so I will highlight the most relevant pieces of it, relevant to the questions and answers (which are all not precise enough or even erronomous to fully understand the matter).
Exerpts:
Most of the known psychotomimetic agents have at least one chiral center within their structures but have been studied only as the racemic mixtures. All of those which have been studied in optically active form are consistent in that the more potent isomer is the isomer with the absolute "R" configuration at the chiral center carrying the nitrogen that correspondents to the amino group of the phenethylamine moiety. (Follows a long list of isomers and their potency in humans).
Finally, the "R" (levo-rotatory) isomer of 3,4-methylenedioxyphenylisopropylamine (MDA) is reported to be three-fold more potent than its optical enantiomer (Marquardt 1978).
With MDMA this potency assignment is reversed !
"S"-MDMA is more effective as a CNS agent than is "R"-MDMA.
Amphetamine (a stimulant, not a psychotomimetic drug), on the other hand, has the "S" or dextro-rotatory form that is the more axtive. (+/- twice as more potent as the "R" isomer, Smith and Davis 1977).
The 3 chemical species : racemic MDMA, "R"-MDMA and "S"-MDMA, were evaluated in normal human subjects as their hydrochloric salts, orally.
Judged as -, +\-, +, ++, and +++. The data represented 35 clinical trials. (follows a plotted graph with 3 lines through data points. The "S"-line is the highest, a +++ at 120 mg dose, followed by the "dl"-line,racemic, a +++ at 160 mg, and the "R"-line with only one + at 200 mg).
It is concluded that the "R"-isomer only slightly interveres the effect in the racemic sample, compared to a pure "S" sample, in contrary to nearly all other psychotomimetic drugs.
Qualitatively, most of the sensory and interpretative properties reported for the racemate are seen in the "S" isomer, including the frequent physical toxocity manifestations of mydriasis and jaw-clenching. The "R"-isomer is free of both side effects, even at the highest doses assayed.
It must be concluded that (in contrast with the previous generality that the activity of racemic psychotomimetic compounds could be largely accounted for by their "R" isomers), with MDMA, the active optical isomer is the absolute "S"-isomer, with the configuration of dextro-amphetamine. **
As an answer to the last question, one direct synthesis for the preparation of the two bases "R"(-)MDMA and "S"(+)MDMA (with "R"-MDA as another possibility as an extra) is as follows :
MDP2P is coupled with "R"(-)benzylmethylamine [ "R"(-)CHNH2CH3 ], and the resulting Schiff base reduced with Raney Nickel.
Catalytic reduction of this "R,R" secondary base provides "R"-MDA (nice aint it, precisely the right, most active MDA isomer, keep that in mind!), (alpha)D= -24.7, agreeing with literature and bought sample from reliable source.
This base is formylated in methyl formate in a sealed tube, and the resulting formamide has a reversed rotation (alpha)D= +12.4 (in ethanol) and a m.p.=99-101.
Reduction of this amide in THF with LAH provides the desired "R"-MDMA, (alpha)D= -18.2, m.p.=181-183 as the HCl salt.
The "S"-isomer can be prepared in an exactly parallel manner (with "S"(+)CHNH2CH3 of course), with the primary amine showing (alpha)D= +25.3, the amide (alpha)D= -12.6, m.p.=101-102, and the final "S"-MDMA with (alpha)D= +17.2 and a m.p.=184-185.
Racemic MDMA m.p.=150-151.
"R" = levo
"S" = dextro
dl = dextro/levo (racemic mix)
May I conclude for you all, the synthesis of specific isomers for MDMA is useless. The difference in effects felt for the "S" isomer and the racemic mix are neglectible !
The synthesis of the d-methamphetamine isomer however, compared to the racemic mix, dl-methamphetamine, is surely worth the trouble, it's effects are noticably different, especially the fucked up state connected with orally administering the dl racemic mix is smoothed down exessively.
The synthesis of "R"-MDA is also worth the trouble, find out yourself if you'r the investigating kind of person.
The synthesis of a racemic mix of dl-methamphetamine into the pure d-form has been posted by Spitball/Drone:
http://hive.lycaeum.org/ubb_board/Forum6/HTML/001137.html
Let's Go for the gold.. 05-27-99 11:00 AM
15 g d-tartaric acid and 12 g dl-methamphetamine.HCl
300 ml Ethanol >98%.
Heat the ethanol to a boil. Slowly, add both d-tartaric acid (a whitish powder) and dl-methamphetamine till both totally dissolve, surplus heat needed when too slow, until boiling again.
Then put the closed flask in the freezer and see the crystal needles formed after a few hours. That's d-methamphetaminebitartrate acid crystals. Filter the crystals off.
An acid/base extraction and then gassing of the freebase with HCl gas gives d-methamphetamine.**
And dwarfer gave us 2 patents explaining the matter a bit more elusive:
British patent nr. 508757
US patent nr. 2276508
Also look at the VillageIdiot pages:
http://www.angelfire.com/de/VillageIdiot/isomers.html
http://www.angelfire.com/de/VillageIdiot/racemateresolution.txt
Now, after reading the US patent, I must say, I've never seen a more unreccognisable form of english explanation before.
If I understand it right, then the above method is not the same as the one outlined in the British and US patent, indicating that with above method you get l-methamphetamine.
The British patent however is as follows, in simple understandable text:
85 Parts of racemic methamphetamine are introduced into a solution of 100 parts of d-tartaric acid in 1000 parts of methyl alcohol. After protracted(?) standing, about 100 parts of the precipitated salt are aspirated off and extracted with hot ethyl alcohol.
Since the d-tartrate of dextro-rotary methamphetamine is readily soluble in both methyl and ethyl alcohol, whereas the d-tartrate of levo-rotary methamphetamine is sparingly soluble both in methyl alcohol and hot ethyl alcohol, an extremely simple separation of the d-tartrates of the optical antipodes of the base is effected.**
In my opinion that means that you must filter off the unwanted l-methamphetamine-d-tartrate crystals precipitated out of the solution, (better recrystalize a few times more by evaporating more solvent and cooling again, to obtain a pure solution of the d-form!) and add a strong base (KOH, NaOH) to the remaining solution until pH 13 to force the freebase d-methamphetamine-d-tartrate out as an oil. Then separate the oil from the solvents, and distillate to be sure, and then gas that clean oil with HCl gas to exactly pH 7 to get your d-methamphetamine.HCl salt. Filter and dry.
I hope this error has not given too much of trouble to experimentors in the past. They made then the wrong l-methamphetamine following those instructions.
Correct me if I'm wrong. LT/
WISDOMwillWIN