ChEss_Piece_Face (Stranger)
07-15-00 00:28
No 28995
      MDMA chirality  Bookmark   

It occurred to me that MDMA is chiral, and most chiral pharmaceuticals have only one active isomer.  For example, only the S isomer of ibuprofen is active, although the R isomer racemizes over time in the body.  Pure S is therefore more potent and faster acting than a racemic mixture, which is what is usually sold OTC.

Does anyone know which isomer of MDMA is the active one, and has anyone toyed around with making enantiomerically pure MDMA?

I happened to notice the other day that Aldrich sells MDMA.HCl!!!  It just so happens that they sell one of the pure isomers in addition to the mixture.

(Hive Bee)
07-15-00 03:57
No 29040
      Re: MDMA chirality  Bookmark   

the S isomer, as with methamphetamine:

07-17-00 07:02
No 29651
      Re: MDMA chirality  Bookmark   

actually it is the R isomer of E THAT IS THE active isomer as it was proven in a J. Pharm. CHem. article in 1984, and to obtain an optically pure isomer of E is about as expensive and time consuming as the synthesis itself with no increase in yield.

07-17-00 13:11
No 29757
      Re: MDMA chirality  Bookmark   

From what I read in PIHKaL, it is actually necessary for the desired effect of MDMA to consume the racemate.

"A penny saved is .72 pennies earned (after capital gains tax)"
-John Galt

07-19-00 05:45
No 30453
      Re: MDMA chirality  Bookmark   

When was the last time someone ran into an illegal drug that was racemically pure, huh?

(Chief Bee)
07-19-00 06:02
No 30464
      Re: MDMA chirality  Bookmark   

Last weekend I saw a couple of guys snorting coke. Coke is pure l-cocaine. smile
07-19-00 16:01
No 30683
      Re: MDMA chirality  Bookmark   

Don't be silly, dude, NONE of the popular synths for MDMA are enantioselective. They produce both enatiomers at equal rates, therefore, all of them produce the racemic modification. Resolution would involve recrystallization of a salt with 2 chiral centers of an enantiomerically pure acid(thus producing diastereomers with differing physical properties) or chromatography.
-John Galt

(Chief Bee)
07-19-00 17:33
No 30705
      Re: MDMA chirality  Bookmark   

None of the MDMA sytntheses, no, but I don't think anybody said that either.
07-20-00 10:03
No 30967
      Re: MDMA chirality  Bookmark   

what I meant to say was no designer drugs and cocaine by definition isn't really illegal doctors still presribe and use it... i do mean use it

07-20-00 13:33
No 31015
      Re: MDMA chirality  Bookmark   

When someone insinuates that one never encounters a completely racemic drug, he is inevitably implying that there is some sort of enantiomeric excess. With the popular MDMA synths, this is impossible. I was just using basic theory to show that, indeed, *ALL* of the XTC that people consume IS racemic, as that is what the dude was asking.
-John Galt

07-20-00 20:44
No 31163
      Re: MDMA chirality  Bookmark   

No, I wasn't asking if street ecstasy was racemic or not, I'm quite aware that it is.  Rhod had it right, I was wondering if any curious bees had tried to isolate the active enantiomer.  This could either be done as in J-G's post, or via ring closing, then opening rxns (you can get pseudoephedrine from ephed/pseudoephed racemate this way).

I guess no bees have gone there.

gaston - thanks for the link with relevant info.  I've only been at this for a little while now, so I didn't even know PiHKAL was online!

07-21-00 03:54
No 31278
      Re: MDMA chirality  Bookmark   

ok...we all seem to agree that the standard synth produces  many enantiomers and as such is a racemic mixture.

and using a chiral "agent" would be usefull in seperating them into thier 2(?) diastereometric salts.

now if we had mdma as a mixture of the s and r forms in (aq.) soln. (R)-(-)-MDMA and (S)-(+)-MDMA....and used (+)-tartaric acid to this soln. this should precipitate out the (S)-(+)-MDMA from solution (by using molar equivelents of the +tartaric acid?equivelent to the amount of the different sterio isomers?).....then follow with (-)tartaric acid for the (R)-(+)MDMA

but,like in methamphetamine, this could compose as much as 50% of the total we perhaps have a slight problem, for wasting half of the product for recemic purity is very unfortunate indeed...

So the problem seems to be converting the (S)MDMA to the prefered (R)MDMA after seperating the racemic mixture??????

now temperature during the synth to mdma is probably a big factor in determining if r or s isomers are produced and i have heard of using chiral catalists to get racemicaly pure products...anyone know if keeping the reactants in the Hg/Al amalgam process at a low temp might favor the (S) or (R) entomers?

07-21-00 03:55
No 31279
      Re: MDMA chirality  Bookmark   

There are stereo-specific syntheses which produce only the desired isomer.

07-21-00 04:17
No 31286
      Re: MDMA chirality  Bookmark   

maybe not pre reaction--->(X)MDMA but maybe some kind of catalitic treatment to the (S) isomer after seperating them?
But this is not pharmacy 300...and it seems that the (S) isomer is active and not unpleasant...but is definatly less prefered than the (R) if it was temperature dependant on what isomer was producduced in greatest quantity then tight controll of the reaction could produce fairly easy controll. I am wondering if having the reaction proceed at a low temperature(in coolant,methylene glycol etc<antifreez>, and a refrigerator coil @ 0 degrees centigrade might be better<but maybe very slow> it would be really nice to have a spectrophotometer at home

(Stranger / Eraser)
09-29-00 18:23
No 55828
      Re: MDMA chirality  Bookmark   

Firstly, there seems to be a descrepency between published articles on whether it's exclusively R or S... sources I read implied the S was active and the R not.

The significance of this, as I see it, is that 50% of the propanone is effectively sacrificed at the step of reductive amination. I'm not quite down with the mechanism yet but that's gotta be when chirality is introduced... if you know the mechanism (which some of you do, I'm sure), then you can predict the product distribution or whether it's entirely racemic (equal distribution).

What I wanna know is whether any one has a stereoselective synth for the active enantiomer?

Please, please, pretty please?

(Hive Bee)
09-29-00 22:32
No 55890
      Re: MDMA chirality  Bookmark   

In my understanding of Shulgin's writings, is that while neither isomer is inactive, one produced more effect. Neither effect was as good as the synergictic effect of both together. So WTF you wanna seperate them or worry about stereo specific synthesese?
(Stranger / Eraser)
10-02-00 20:24
No 56743
      Re: MDMA chirality  Bookmark   

So we can verify the research of others...

If it's true they're synergistic, then I'm not going to do more work for reduced effect. That's silly. But I am curious about which is which and what the difference in effect is.

I gotta feel it.

10-11-00 11:06
No 59321
      Re: MDMA chirality  Bookmark   

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).

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:  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:

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/

10-12-00 14:03
No 59546
      Re: MDMA chirality  Bookmark   

Cheers to Labtop! Thanks for clarifying that for my imaginary friends as they were ready to abandon the sodium borohydride reduction, speculating too much of the racemate being produced was weakening the product. If memory serves me correctly, you were partly responsible for that great post on the borohydride reduction to begin with. Definately one of the easiest reductions my imaginary friends have seen and the yields are great! Any suggestions for getting away from methylamine gas though? Stinks up the neighbourhood. My friends built a nice scrubber but doesn't completely do the job.
10-24-00 03:43
No 62904
      Re: MDMA chirality  Bookmark   

"R"(-)benzylmethylamine [ "R"(-)CHNH2CH3 ], and "S"(+)CHNH2CH3 : can anybody close to chemical suppliers provide us with the prices of these chems, and tell us if you can order them at all ?

Did you really all miss the importance of this easy route to the most potent isomers of MDA and MDMA in pure form?
Expected some more reactions.
If these 2 isomers of benzylmethylamine are obtainable of course, or could be -easily- created in your garage !
The sources I have access to have no info on these compounds.
Psychokitty, do you have access ? Anybody ?
The rest of the steps is childsplay. LT/

10-24-00 05:07
No 62922
      Re: MDMA chirality  Bookmark   

Missed that last question from Buchiguy :

If you follow all the OnePot directions shattered over the board, and use some McGuiver techniques, you will virtually smell nothing.

Use a exhaust fan connected to a box with a in and out opening, with clothhangers in it, 5 to 10, and hang well wetted towels on them, alternating 5 cm above the bottom and the next one touching the bottom, so you create a labyrinth where the air is forced to follow a S-shaped route to the end of the box. The water in the towels will absorb all traces of MeAm gas escaping your setup, especially during the adding of the boro. The clean air will be exhausted out of your working space. Wash the towels periodically in lots of water and use rubber gloves for that.

You pump (gearpump in case of 100th of liters) your 10% MeAM/MeOH mix into your vessel, or syphon it in, this will also prevent any gas from escaping.

All open pipes must have washing bottles attached.
Adding boro in one with a funnel means you must have another pipe with a big ass washing bottle attached, filled with 10% HCL/water solution, to effectively kill all MeAm smells pushed out by the pressure, building up, when adding boro.
The rest of all your entrances to the vessel must be airtight !!!

While adding boro, you have the exhaust fan intake hose placed near to the funnel, so it takes away directly all fumes escaping there. Stopper the funnel loosely inbetween addings, or the stopper will pop out, caused by the pressure buildup.
Especially airtighten your big lid, which you use to climb in and clean the kettle afterwards, or the other use of this opening for taking out the 100 kg powder produced in the same kettle with a  big ass coal shuffle from SSteel(your 90 liter clean base with the 270 liter acetone, and then bubble HCl gas through, while mixing).
First shuffle the powder away from the valve tap opening in the center of the bottom, or that will be stucked with powder at the end. Then you open that valve for 2 seconds to clear the valve, close it again, remove the first bucket with some powder and acetone in it, and then open the valve a bit again to let the clear acetone slowly out, not disturbing the pile of powder inside the vessel, into several buckets, until no more acetone comes out, close the valve and start gold digging with your shuffle ! Have fun !

The last rests of powder you wash out with the acetone you decant off from the buckets where you shuffled the wet powder in (remember, the result of the crystallization is a big wet mass of toothpaste-like powder mass), and wash the powder, left in the kettle, out into the new bucket you placed under the big ball-valve in the bottom center.

At the end of the 36 hrs reaction,  after adding the 8 x volume of water and tapping your raw freebase, you add a lot of 20% NaOH or KOH solution to your lots of waste water, till pH 13, and then a lot of 33% HCl solution again till pH 7 or slightly lower. This will break up all hydrocarbons. You now have a non-MA smelling solution, it will have a slight perfume smell.
It's neutral, it will not be destructive to plant and animal life. LT/

(Hive Bee)
11-02-00 19:56
No 66110
      Re: MDMA chirality  Bookmark   

Acme's route to "R"(-)benzylmethylamine [ "R"(-)CHNH2CH3 ],

Starting with D-N-Boc-phenylalanine-OH

React this with Ethylchloroformate, TEA (0 C 5 min in THF), and diazomethane (as a 0.3M soln in ether) stir 20 min to get the diazoketone. yield 100% easy chromatography (follow the yellow band)

Homologate this with AgClO4/THF/water(few drops) yield 100% (after adding some brine to ppt silver, filter celite) chromatograph 10% MeOH/DCM or EtOAC/Hex 0.5ČOH

Decarboxylate with NaOH, then TFA/DCM to remove the Boc Viola!  "R"(-)benzylmethylamine [ "R"(-)CHNH2CH3 ], Use the naturally occurring (cheaper) L-N-Boc-phe-OH similarly to get the S
02-28-01 16:27
No 175994
      Re: MDMA chirality  Bookmark   

According to Chemical Abstracts, methylbenzylamine is also known as phenylethylamine, one method of separating the isomers is US 3167566.
03-09-01 03:20
No 177445
      Re: MDMA chirality  Bookmark   

Missing posts : 
    lugh (Stranger) 2-28-01 19:27 No 175994
         Re: MDMA chirality
According to Chemical Abstracts, methylbenzylamine is also known as phenylethylamine, one method of separating the isomers is US 3167566.
    Lilienthal (Moderator) 03-01-01 09:36 No 176075
         Re: MDMA chirality
beta-Phenylethylamine: Ph-CH2-CH2-NH2
alpha-Phenylethylamine (Methyl-benzylamine): Ph-CH(CH3)-CH2-NH2
Completely different structures.

    lugh (Stranger) 03-0x-01 xx:xx No 176xxx
         Re: MDMA chirality
Exactly, thus alpha-phenylethylamine, once the desired isomer is separated, can be used too for chiral reductive amination. Commercially, looking for methyl benzylamine is useless because of it's more common alternative name, xxx-alpha-Phenylethylamine. 
Exactly, thus alpha phenylethylamine, when separated into the required
isomers, provides the reagent needed for chiral reductive amination.

Not specific enough, here's some more on the subject :
.	    CH3
.      ! (R)-(+)-1-Phenylethylamine for resolution of
.     / \ racemates, for synthesis.
. [Ph]   NH2 a.k.a. D-alpha-Methylbenzylamine.  C8H11N.
.     CH3
.      _ (S)-(-)-1-Phenylethylamine for resolution of
.      - racemates, for synthesis.
.      . a.k.a. L-alpha-Methylbenzylamine.  C8H11N.
.     / \
. [Ph]   NH2
.     CH3
.      | DL-1-Phenylethylamine, for synthesis. 
.     / \ a.k.a. DL-alpha-Methylbenzylamine.  C8H11N
. [Ph]   NH2

All three have physical and chemical data in common, but some not :
(R)-(+)-1-                       (S)-(-)-1-               DL-1
> M=121.18 g/mol                    idem                  idem
> 1L=0.95 kg                        idem                  idem
> Boil.range=80-81*C                idem                184-186*C
> Flash point=75*C                  idem                  idem
> Mix not well with H2O             idem                20*C 42g/L
> Refractive index
  1.5265                           1.5259                1.5253
> Specific rotation
  ([alpha]20*/D - undiluted):
  +35* to +37*                  -37* to -39*              N.A.

Both enantiomers can be used as chiral auxilliary's, as they readily  form imines with carbonyl compounds, which may be used as catalysts for enantioselective reactions :
H.T.Dieck, J.Dietrich: Chem.Berichte 117, 694 (1984).
H.Brunner, B.Reiter, G.Riepl: Chem.Berichte 117, 1330 (1984).
J.M.Hawkins, K.B.Sharpless: J.Org.Chem. 49, 3863 (1984).

As inducing auxilliaries, e.g. for asymmetric Strecker synthesis:
D.M.Stout, et al.: J.Org.Chem. 48, 5369 (1983).
P.K.Subramian, R.W.Woodard: Synth.Commun. 16, 337 (1986).

Beilstein database Registry Number: 2410916.
Merck FT-IR Atlas: 1903.
Beilstein Manual of Organic Chemistry: 12, 1092, I 469, II 586, III 2386, IV 2425.

Beilstein database Registry Number: 2204907.
Merck FT-IR Atlas: 1904.
Beilstein Manual of Organic Chemistry: 12, 1093, I 470, II 587, III 2388.

.        NH2 2-Phenylethylamine, for synthesis. 
.     /\/ Phenethylamine.  C8H11N
. [Ph]

This totally different compound is not contributing to this discussion.

For those who wonder why all this typing :
The "R" (levo-rotatory) isomer of 3,4-methylenedioxyphenylisopropylamine a.k.a. 3,4-methylenedioxyamphetamine ("R"-MDA) is reported to be three-fold more potent than its optical enantiomer (Marquardt 1978).
And he didn't lie.

So, if you are the perfectionist I expect you to be/becoming, why not go for the best there is for yourself. HeHe, LT/ wink

03-13-01 00:11
No 178179
      Re: MDMA chirality  Bookmark   


Place 125 g. of ammonium formate, 75 g. of acetophenone and a few chips of porous porcelain in a 250 ml Claisen flask with fractionating side arm, insert a cork carrying a thermometer extending nearly to the bottom of the flask, and attach a short condenser set for downward distillation to the side arm. Heat the flask with a small flame or in an air bath; the mixture first melts to two layers and distillation occurs. The mixture becomes homogeneous at 150-155' and reaction takes place with slight frothing. Continue the heating, more slowly if necessary, until the temperature rises to 185' (about 2 hours); acetophenone, water and ammonium carbonate distil. Stop the heating at 185', separate the upper layer of acetophenone from the distillate, and return it without drying to the flask. Heat the mixture for 3 hours at 180-185' and then allow to cool; the acetophenone may be recovered from the distillate by extraction with 20 ml of benzene (1). Transfer the reaction mixture to a 250 ml. separatory funnel and shake it with 100 ml of water to remove formamide and ammonium formate. Run off the crude a-phenylethylformamide into the original Claisen flask; extract the aqueous layer with two 15 ml portions of benzene, transfer the benzene extracts to the flask, add 75 ml of concentrated hydrochloric acid and a few chips of porous porcelain. Heat the mixture cautiously until about 30 ml of benzene are collected, and boil gently for a further 40 minutes; hydrolysis proceeds rapidly to alpha-phenylethylamine hydrochloride except for a small layer of unchanged acetophenone. Allow the reaction mixture to cool, remove the acetophenone by extraction with 25 ml of benzene and then with three 15 ml portions of the solvent (1). Transfer the aqueous acid solution to a 500-ml roundbottomed flask equipped for steam distillation, cautiously add a solution of 62.6 g. of sodium hydroxide in 125 ml of water, and steam distil: heat the distillation flask so that the volume remains nearly constant. Most of the amine is contained in the first 500 ml of distillate; stop the operation when the distillate is only faintly alkaline. Discard the residue in the flask which contains inter alia a little dl-a-phenylethylamine. Extract the distillate with five 25 ml. portions of benzene, dry the extract with sodium hydroxide pellets, and distil off the benzene but use a flask having an inset side arm and a soda lime guard tube; the amine attacks cork and rubber and absorbs carbon dioxide from the air. Collect the a-phenylethylamine at 184-186` (2). The yield is 45 g.

(1) The acetophenone may be recovered by washing the benzene solution with dilute alkali, drying with anhydrous magnesium sulphate and distilling ; the fraction b.p. 198-205' is collected.

(2) The b.p. under diminished pressure has been given as 80-81' 118 mm. To obtain a very pure sample of the amine, dissolve 1 part (by weight) of the above product with a solution of 1.04 parts of crystallised oxalic acid in 8 parts of hot water, add a little decolourising carbon, and filter. The filtered solution deposits crystals of the acid oxalate; about 5 g. of this salt remains in each 100 ml of mother liquor, but most can be recovered by evaporation and further crystallization, the amine may be liberated from the acid oxalate with sodium or potassium hydroxide, steam distillation, and purification as above. The salt provides a convenient method of obtaining a known weight of the amine in water, since it can be weighed out and decomposed with alkali hydroxide.


(-)-a-Phenylethylamine: Add 31.25 g of D-tartaric acid (0.208 mole) to 450 ml of methanol in a one-liter Erlenmeyer flask, and heat the mixture almost to boiling. To the hot solution, add cautiously 25 g of D,L-a phenlylethylamine (26.6 ml; 0.206 mole);  too rapid addition will cause the mixture to boil over. Since crystallization occurs slowly, the solution must be allowed to stand at room temperature for about 24 hours. The (-)-amine-(+)-hydrogen tartrate separates as prismatic crystals. Collect the product by suction filtration, and wash it with a little methanol. Yield: 18.l grams(65%).

A second crop (3.8 grams) may be obtained by concentrating the combined mother liquor and washings to 225 ml, and allowing crystallization to proceed at room temperature for 24 hours.

Partially dissolve the product (21.9 grams) in about 90 mI of water and add 12.5 ml of 50% sodium hydroxide solution in order to convert the amine salt to the free base. Reextract the amine with ether, and dry the extract, over anhydrous magnesium sulfate for about ten minutes. Remove most of the ether by heating the extract on the steam bath, and distill the residue (considerable foaming) to obtain (-)-a-phenylethylamine. Yield: 6.9 grams, 55%; bp: 184-186'; L(+)-a-Phenylethylamine: Allow the methanolilc solution remaining from the isolation of the (-)-amine(+)-hydrogen tartrate to evaporate to dryness (done most easily by leaving the solution in an evaporating-dish in the hood overnight), and recover the remainder of the amine by treating the residual salt with sodium hydroxide, extracting with ether, and distilling as described above.

The (+)-amine is isolated by treating a hot ethanolic solution of the recovered amine with an amount of sulfuric acid in ethanol slightly greater than that necessary to convert the excess (+)-amine to the neutral sulfate salt. The resulting cyrstals of (+)-a-phenylethylamine sulfate yield the (+)-amine.

Dissolve 12.5 g (0.103 mole) recovered amine, in 88 ml of 95% ethanol. (This solution contains 0.062 mole excess (+)-amine, and 0.041 mole racemic amine. Heat the solution to boiling and add to it a solution of concentrated sulfuric acid (3.2 g of 98% H2SO4; 0.032 mole H2SO4) in 180 ml of 95% ethanol. After allowing the mixture to cool slowly to room temperature, collect the crystalline (+)-amine sulfate by suction filtration and wash it thoroughly with ethanol. Yield: 7.8 g (74%).

Isolate the free (+)-amine as described above (treatment with sodium hydroxide, extraction, and distillation) using 40 ml of water and 5 ml of 50% sodium hydroxide for each 10 g of the sulfate salt. Yield: 4.4 g (59%); bp: 184-186'