Quinine salt

HaO). Quinine salicylate, 2[B. CgH4(OH)(COOH)]. HaO, forms colourless needles, m.p. 187° (dec.), which slowly become pink in air. It is soluble in water (1 in 77 at 25°), alcohol (1 in 11 at 25°), or chloroform (1 in 37 at 25°). The foregoing are the most important quinine salts used in medicine, but many other salts have been used, e.g., the tannate, formate, valerate, ethylcarbonate, lactate, cacodylate, etc., as well as double salts such as quinine bismuth iodide. Descriptions of many of these salts will be found in the British Pharmaceutical Codex for 1934. 

Numerous new salts and additive compounds of cinchona alkaloids, and especially of quinine, have been described, of which only a few can be mentioned as examples quinine additive compounds with sulph-anilamide, t quinine salts of (+) and (—)-pantothenic acid, °( > quinine sulphamate and disulphamate, °( organo-mercury compounds of quinine and cinchonine such as quinine-monomercuric chloride. Various salts and combinations of quinine have also been protected by patent, e.g., ascorbates and nicotinates. 

Interestingly, Jacobsen et al. have also reported that addition of a /3-hydroxy ammonium salt to the reaction medium accelerates the isomerization in the presence of an /V-benzylated quinine salt epoxidation of cw-stilbene with (27) gives Zrarax-stilbene oxide with 90% ee as the major product (trans cis= >96 4).109 In 2000, Adam et al. reported that the isomerization ratio was related to the triplet-quintet energy gap of the radical intermediate which was affected by the... 

A derivative from trans-crotonic acid via quinine salt resolution... 

R)-Hydroxy-4-pentenoic44,322 (R-94) and 3(R)-hydroxy-3(R)-methyl-4-hexenoic (R-99, R = H)4S acids were obtained from the racemic acids by recrystallization of their quinine salts. Compound R-94 served322 as the substrate for the synthesis of 2-deoxy-L-eri/t/iro-pen-tose as in 94 —> 98. The enantiomeric acid R-99 was employed46 for the preparation of D-everniicose (see 99 — 105). 

Potassium dioxalato-nitroso-pyridino-ruthenate yields with quinine hydrochloride twro isomeric quinine salts, a dextro- and a lsevo-modi-fication, which differ in solubility. The isomers are separated by fractional crystallisation. The dextro-salt is the less soluble, and crystallises in long needles with rotation of [a]n+252 in a solution of equal volumes of alcohol and chloroform. The ltevo-salt is more soluble, 1 Charoimat, Oonipt. rend., 1924, 178, 1423. 

The corresponding ammonium salts are obtained from the quinine salts by treating them with ammonia in an alcoholic chloroform solution. They are viscous substances with rotation of an 425. On mixing equivalent quantities of the two active salts in solution a crystalline racemate is produced. Alkali or alkali carbonates decompose the salts, so that the sodium or potassium salt cannot be produced by decomposing the quinine salts with these reagents. 

The determination of quinicine, the oxidative decomposition product of quinine, has been reported by polarography [74]. Quinicine was determined in the presence of a 1000-fold excess of quinine in quinine salts and injectibles. The assay was rendered specific for quinicine in the presence of quinine by the... 

The values for the dissociation constants are k1=2-95 xl0 3, k2 =3-28 x 10 6. The diquinine salt contains five molecules of water and melts with decomposition at 112° C. By fractional crystallisation of the appropriate quinine salt, l-a-seleninobutyric acid, [tz]d -25°, [M]d =82°, is isolated its barium salt is also known. 

The acid itself was chosen for the conjugate addition as the intermediate can then be resolved by crystallisation of the quinine salt. Conjugate addition of HC1 was successful and the acid was reduced to the alcohol with UAIH4 before esterification in the usual way.1... 

The -)-erythro-isomer of 2,3-dihydroxy-3-methylpentanoic acid (73) has been synthesized by Crout and Whitehouse, and shown to be identical with the naturally occurring (-)-acid obtained from strigosine.45 trans-Hydroxylation of E-3-methylpent-2-enoic acid with tungstic oxide-hydrogen peroxide gave the ( )-erythro-acid, which was resolved as the quinine salts. The absolute configuration of the (-)-erythro-ac d (73) was determined by degradation (Scheme 4). Methylation,... 

The key intermediate, 3-methyl-5-oxo-3-cyclohexene-1-carboxylic acid(V), was resolved as the (-)-quinine salt. A new approach to determining the optical purity of carboxylic acids is discussed. 

Racemic V could not be resolved with primary optically active bases presumably because they reacted in a Michael fashion. Formation of the quinine salt and five recrystallizations from a benzene/hexane mixture yielded an acid (after hydrolysis) whose specific rotation was [a]jP -47°. However, since the maximum specific rotation is unknown, an absolute method of determining optical purity is needed. The usual method is treatment with an optically pure derivatizing reagent to form covalent diastereo-mers, whose ratio can be determined by NMR or chromatography. 

Figure 1A. 13C NMR spectrum (25.2 MHz) of the quinine salt of 3-methyl-5-oxo-3-cyclohexene-...

Strychnine salt Quinine salt Brucine salt... 

Hydriodate of quinine consists of sulfate of quinine, 95 parts iodide of potassium, 40 parts. The product corresponds to 100 parts of hydriodate of quinine. Iodized hydriodate of quinine consists of 70 parts iodide of potassium, 50 parts iodine, 20 parts. To be triturated together with a little alcohol. Corresponds to 100 parts of the above quinine salt. See USD, Fifteenth Edition, 1884, p. 1216. 

The quinine salt of p-arsanilic acid forms white needles, M.pt. 202° C., and the cinchonidine salt small prisms, decomposing at 180° C., both compounds being soluble in alcohol. ... 

This acid may be isolated as follows Anhydrous arsenic acid, 28 4 jiarts, is dissolved in 0 parts of water by the aid of heat, and 13-1 parts of methylketole added. The mixture is warmed on the water-bath until a crystalline product separates. This is triturated with water, filtered, and well washed with w ater to remove excess of arsenic acid. The product is dissolved in dilute sodium hydroxide solution, filtered, and the filtrate acidified with hydrochloric acid. The arsinic acid separates in fine needles, M.pt. 180° to 182° C., 93 per cent, yield. It dissolves readily in absolute alcohol or acetic add, but is insoluble in other organic solvents. The sodium salt is readily soluble in water its crystals contain 2-5 molecules of water of crystallisation, and it melts with decomposition at 225° to 235° C. A quinine salt is known, C2oH24N202.CgHiflNAs03.2jH20, which is readily soluble in methyl and ethyl alcohols, ad tion of water causing it to separate in fine needles. It sinters at 155° C. and melts at 170° to 172° C. 

A nice complement to the Haller-Bauer reaction (Section II.B) is the decarbonylation of aldehydes with (Ph3P)3RhCl (Wilkinson s catalyst) A recent example comes from the work of Baldwin and Barden and is shown in Figure 5. Interestingly, partial optical resolution was achieved in this synthesis by use of an optically active copper catalyst for the preparation of the labeled phenylcyclopropane carboxylic acid. The resolution to optical purity was then accomplished by recrystallization of the quinine salt of the acid. 

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