D- -Tartaric acid

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

The purified commercial di-n-butyl d-tartrate, m.p. 22°, may be used. It may be prepared by using the procedure described under i o-propyl lactate (Section 111,102). Place a mixture of 75 g. of d-tartaric acid, 10 g. of Zeo-Karb 225/H, 110 g. (136 ml.) of redistilled n-butyl alcohol and 150 ml. of sodium-dried benzene in a 1-litre three-necked flask equipped with a mercury-sealed stirrer, a double surface condenser and an automatic water separator (see Fig. Ill, 126,1). Reflux the mixture with stirring for 10 hours about 21 ml. of water collect in the water separator. FUter off the ion-exchange resin at the pump and wash it with two 30-40 ml. portions of hot benzene. Wash the combined filtrate and washings with two 75 ml. portions of saturated sodium bicarbonate solution, followed by lOu ml. of water, and dry over anhydrous magnesium sulphate. Remove the benzene by distillation under reduced pressure (water pump) and finally distil the residue. Collect the di-n-butyl d-tartrate at 150°/1 5 mm. The yield is 90 g. 

In a copper or iron kettle of 4-I. capacity is placed a solution of 200 g. of d-tartaric acid and 700 g. of sodium hydroxide in 1400 cc. of water. A 12-I. flask through which cold water is run is placed in the mouth of the kettle in order to prevent loss of water vapor, and the mixture is boiled gently over an open flame for four hours. The solution is now transferred to a 12-I. flask or crock and partially neutralized with 1400 cc. of commercial hydrochloric acid (density 1.19). To the still alkaline solution is now added just enough sodium sulfide to precipitate all the iron or copper which has been dissolved from the kettle (Note i). The filtered solution is then just acidified with hydrochloric acid, boiled to expel all hydrogen sulfide, and made very faintly alkaline to phenolphthalein with sodium hydroxide solution. To the hot solution is then added a concentrated solution of 300 g. of anhydrous calcium chloride which causes an immediate precipitation of calcium tff-tartrate and mesotartrate. 

The calcium salt of the principal product, d/-tartaric acid, crystallizes with four molecules of water, while the secondary product, meso-tartaric acid, forms a calcium salt which crystallizes with three molecules of water. The amount of sulfuric acid actually required may readily be calculated from the percentage of calcium found on analysis in the regular way or it may be estimated by igniting a sample, and titrating the residue with standard acid. 

The f-base-d-acW salt no longer can be obtained pure when the solution contains about equal proportions of the salts of d- and f-amines. For this reason, also, an initial resolution of the df-amine with d-tartaric acid is not feasible. 

The present method is adapted from that of Loven. The resolution has been carried out with d-a-bromocamphor-TT-sulfonic acid (f-form) 2.3 with /-and d/-malic acids (d- and /-forms) with /-quinic acid and d-tartaric acid (d- and /-forms) and with d- and /-6,6 -dinitrodiphenic acids (d- and /-forms). Methods employing d-benzyimethylacetyl chloride, d-oxymeth-ylenecamphor, /-quinic acid, and d-camphoric anhydride are of theoretical interest only. The d/-amine is not resolved by the active camphor-lo-sulfonic acids or mandelic acids. ... 

Two mols, for example, 270 grams, of racemic a-methylphenethylamine base are reacted with one mol (150 grams) of d-tartaric acid, thereby forming dl-a-methylphenethylamine d-tartrate, a neutral salt. The neutral salt thus obtained is fully dissolved by the addition of sufficient, say about 1 liter, of absolute ethanol, and heating to about the boiling point. The solution is then allowed to cool to room temperature with occasional stirring to effect crystallization. The crystals are filtered off and will be found to contain a preponderance of the levo enantiomorph. 

D,L-3-Hydroxy-N-methyl-morphinan Phenyl trimethyl ammonium chloride D-Tartaric acid... 

Similar results are found with the threose derivatives 11 and 13. Both aldehydes can be readily synthesized in either enantiomeric form from l- and D-tartaric acid. The open-chain aldehyde 11 with Grignard reagents affords predominantly the all-.v> n(xj/o)-diastereomer 12. The steric demand of the nucleophile apparently does not affect the diastereoselectivity, and the extremely high selectivity observed with [(l,3-dioxolan-2-yl)methyl]magnesium bromide is attributed to the presence of the dioxolane moiety, which is thought to stabilize the a-chelated transition state. 

L)-(+)- and (D)-(-)-Tartaric acids (99+ and 99%, respectively) were obtained from the Aldrich Chemical Company, Inc., and used as received. 

The (S.S)-diamine can be obtained as the mono-(-)-tartrate salt by using the same procedure with D-(-)-tartaric acid. 

Fig. 22. Molecular geometry and thermal ellipsoids (75% probability) of D(+)-tartaric acid at 295, 160, 105, and 35 K.

Some other methods of resolution include the use of /-malic acid [(+)-form], /- and d/-malic acids [(+)- and (—)-forms], /-malic acid and d-tartaric acids [(+)- and (—)-forms], d-a-bro-mocamphor-TT-sulfonic acid [(—)-form], /-quinic and d-tartaric acids [(+)- and (—)-forms], 2,3,4,6-tetraacetyl-D-glucose [(+)-form], " and barium (—)-bornyl sulfate [(+)- and (—)-forms]."... 

The product of either of the outlined methods, 2-amino-1-phenylpropane (amphetamine) is separated into isomers using D-tartaric acid, and separating the necessary dextroamphetamine, D-2-amino-1-phenylpropane (8.1.2.2) [6,7]. 

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