Ephedrine salts

For the assay of ephedrine in the total alkaloids a colorimetric method based on the biuret reaction was used by Feng and Read and is described in detail by Feng. Krishna and Chose separated ephedrine and iji-ephedrine by treating the dry mixed hydrochlorides with dry chloroform in which the ephedrine salt is virtually insoluble and the -ephedrine salt soluble. ... 

Ephedrine, CjqHjsON, crystallises from ether in rhombs, m.p. 118-9°, [a]n"° + 51 2° (EtOH), and, unlike ephedrine, is sparingly soluble in water. The hydrochloride, B. HCl, crystallises in colourless, slender needles, m.p. 181-2°, + 62-05° (HjO), and, unlike the ephedrine salt,... 

C. (+)- and (-)-a-(Isopropylideneaminooxy) propionic acid-(-)-ephedrine salts. A solution of 36.6 g. (0.200 mole) of (— )-ephedrine monohydrate (Note 7) in 800 ml. of ethyl acetate containing 6% of ethanol (Note 8) is placed in a 2-1. beaker, d,l-a-(Isopropylideneaminooxy)propionic acid (29.0 g., 0.200 mole) is dissolved in this solution by stirring (Note 9). The beaker is covered securely with a rubber dam, cooled for a short period in an ice bath, placed in a refrigerator at 0-5°, and allowed to remain undisturbed for 8-16 hours after crystallization has begun (Note 10). The solid mass of crystals is filtered by suction, and the funnel is covered with a rubber dam to remove most of the solvent. The solid product is placed in a 500-ml. beaker, 250 ml. of ethyl acetate is added (Note 11), and the mixture is heated until all the solid has dissolved. The solution is cooled, placed in a refrigerator for several hours, and filtered the crystalline precipitate is dried in air. The yield of the (—)-ephedrine-(+)-a-(isopropylideneaminooxy)propionic acid salt is 22-25 g. (71-81%) m.p. 115-119° (Notes 12 and 13) [ ]2°d -4.2° (c 1.5, chloroform). 

TAPA has been prepared only as described in this procedure.5 a-(Isopropylideneaminooxy)propionic acid has been prepared and resolved by the present procedure 6 and has been prepared directly from a-bromopropionic acid and resolved as the (—)-ephedrine salt by crystallization from hydrocarbon mixtures.5... 

A number of methods for the synthesis of piperazic acid (7) and related derivatives are currently available as a result of growing interest in natural product chemistry and in their potential in medicinal chemistry. Their chemistry and conformational properties have been comprehensively reviewed. 2451 Racemic piperazic acid is obtained by condensation of penta-2,4-dienoic acid with phthalazinedione and subsequent reductive deprotection of the resulting A,A -bis(phthaloyl)-l,2,3,6-tetrahydropyridazine-3-carboxylic acid.12431 Resolution of racemic piperazic acid is achieved by fractional crystallization of the ephedrine salt of Nl-(benzyloxycarbonyl)piperazic acid from ethyl acetate. 246,2471 A typical route to enantiomerically pure (3S)-piperazic acid 56 starts from chiral 2-amino-5-hydroxyvaleric acid 55 as shown in Scheme 12.1248 Convenient stereoselective syntheses have been reported for 5-hydroxy- and 5-chloropiperazic acids as important constituents of natural cyclic peptides and depsipep-tides.1249,2521... 

Unsymmetrically substituted diene iron tricarbonyl complexes are formed as racemic mixtures of compounds having planar chirality. Optically pure diene iron tricarbonyl complexes can been prepared by classical chromatographic separation of diastereomeric mixtures of a-methylbenzylamine and ephedrine salts, and of semioxa-mazones and oxazohdines derivatives. Direct asyimnetric complexation to cychc dienes can be achieved 73% ee using iron pentacarbonyl in the presence of a chiral l-aza-1,3-butadiene. 

A method of extraction has been described by Chou (165) Powdered Ma Huang was extracted with cold benzene in the presence of diluted sodium carbonate. The benzene extract was extracted with dilute hydrochloric acid and the acid solution of the alkaloids clarified. After adding enough solid potassium carbonate to the acid solution, the alkaloids were extracted with chloroform. This solution was concentrated, dried over sodium sulfate, and evaporated to dryness. Ephedrine has been separated from -ephedrine by means of the oxalate, the ephedrine salt being much less soluble in cold water. 

Feng and Read (104) found that the low yield of alkaloids obtained by previous workers was due to incomplete alkalinization of the herb before extraction with chloroform or ether. Hot extraction and the use of sodium hydrate to liberate the alkaloids has been found satisfactory. The ammonia-chloroform process has been critically studied and it was found that a large excess of ammonia was necessary to hberate the alkaloids. Feng (103) extracted Ephedra equisetina, first with 80% alcohol and finally with 0.2 % acetic acid. After working up the extracts, ephedrine was separated from f -ephedrine by crystallization of the hydrochlorides from 95% alcohol. -Ephedrine may be recovered from the mother liquors. Ghose and Krishna (114, 117, 118) described other methods of extraction and the preparation of alkaloid concentrates. They separated ephedrine from -ephedrine by extracting the dry hydrochlorides with chloroform, in which only the f -ephedrine salt is soluble. 

N-Bz-Leu anilide N-Bz-N-methyl-Leu N-(2-Bz-1 -methylvinyl) -Leu Z-Erythro-/3-methyl-Leu 2i-Erythro-/3-methyl-D-Leu Z-Erythro-/3-methyl-D-Leu (- -)-ephedrine salt Z-Leu Z-D-Leu Z-Leu amide Z-DL-Leu amide Z-Leu-NHBzl Z-Leu-NHCHjCHjOH Z-Leu(-f-) ephedrine salt... 

Pht-Leu-OCHaCN N-[5-(6-Purinylthio)valeryl]-Leu-OEt rAreo-N,/3-dimethyl-Leu(—) ephedrine salt rAreo-d-hydroxy-Leu... 

Z-Phe Boc-hydrazide Z-Di Phe-NHCHjCN Z-Phe-NHC,Hii Z-DL-Phe-OCHjCN Z-Phe-0-2,2-diphenylethyl Z-Phe-N,N -diphenyl hydrazide Z-D-Phe (+) ephedrine salt N"-2i-Phe- -nitroanilide... 

Z-DL-Val-OBhae Z-D-Val (+) ephedrine salt N-Z-Val 4-(methyl-sulfonyl)phenyl ester... 

Chiral 2- and 3-methyldihydrocinnamic acids are obtainable in optical yields of 4—68% by hydrogenation of the appropriate unsaturated acid esterified with various ephedrine salts/ while the 3-methyl derivative is formed in up to 48.5% optical purity by Friedel-Crafts reactions of chiral 3-chlorobutanoic acids. ... 

Resolution of 42 was accomplished by traditional methods. Conversion of 42 to hydroxy acid 53 was followed by resolution as its ephedrine salt. Variants of the Diels-Alder reaction were developed. For example, use of thallium cyclopentadienide (rather than sodium cyclopentadienide) provided a more stable, less basic nucleophile for use in generation of 37. 

Examples of the first group of syntheses are given in Scheme 115 [1054-1059]. The condensation of 2-methyl-1,3-cyclopentanedione (385), the synthesis of which has been described in Chapter II, Scheme 33, with methyl 5-oxo-6-heptenoate (384) [1031] and direct cyclization of the triketone formed led to the diketo acid (386), which was resolved into its enantiomers by the crystallization of the ephedrine salts. The less soluble salt of the dextrorotatory isomer formed corresponds to the natural (i-series. The successive reduction of the keto group and the A -bond in this led to the trans-C/D compound (390), consisting of a mixture of the and... 

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