Quininic acid

Other Names Cinchoninic acid, 6-methoxy- 6-Methoxy-4-quinolinecarboxylic acid 6-Methoxy-cinchoninic acid NSC 403610 Quininic acid CA Index Name 4-Quinolinecarboxylic acid, 6-methoxy-CAS Registry Number 86-68-0 Merck Index Number 8062 Chemical Structure 

Chemical/Dye Class Huorescent, Quinoline Molecular Formula C11H9NO3 Molecular Weight 203.19 pH Range 4.0-5.0 

Color Change at pH Yellow fluorescent (4.0) to blue fluorescent (5.0) pKa 5.53 

Solubility Slightly soluble in water, cold ethanol, ether 

Boiling Point (Calcd.) 385.4 22.0°C Pressure 760 Torr Synthesis Synthetic methods -  

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On autoxidation by aeration in tertiary butyl alcohol containing potassium tert-butyl oxide, quininone yields quininic acid (98 per cent.) and meroquinenine terf-butyl ester, CgHi N. CO. O. C4H9, b.b. 127°/20 mm., dj 0-9832, [a]o° -(- 50-0° (EtOH), identified by hydrolysis to meroquinenine (meroquinene) and eonversion of this to the better-known ethyl ester (p. 438). (Doering and Chanley.)... 

Quinine gives in place of (1) quininone, C20H22O2N2 in place of (2) quitenine, C19H22O4N2 and instead of (3) quininic acid, C44H9O3N, the other products being the same. Cinchoninic and quininic acids are quinoline-4-carboxylic and 6-methoxyquinoline-4-carboxylic acids respectively. 

Cinfhoninic and Quininic Acids. The quinoline half is usually presented in the form of one of these acids, early syntheses of which are due to Pictet and Misner and Kaufmann and Payer, ... 

Qne of the methods of making the ethyl ester of quininic acid (37.1.1.27) that should be mentioned is the method described in the following scheme. Reacting p-anisidine and ace-toacetic ester in the presence of sulfuric acid gives 6-methoxylepidine (37.1.1.22). The... 

Synonyms. Neutral Quinine Sulphate Quinine Acid Sulphate. Proprietary Names. Biquin Biquinate Dentojel Myoquin Quinbisan. C2oH24N202,H,S04,7H20 = 548.6 CAS—549-56-4 (anhydrous)... 

Synonyms. Neutral Quinine Hydrobromide Quinine Acid Hydrobromide. 

Synonyms. Neutral Quinine Hydrochloride Quinine Acid Hydrochloride. C2oH24N202,2HC1 = 397.3 CAS—60-93-5 A white powder. 

The relation of quinine and cinchonine to quinoline is shown by their oxidation products. As mentioned in connection with quinoline the alkaloid cinchonine when oxidized yields a mono-carboxy quinoline known as cinchoninic acid. Similarly quinine yields quininic acid which is a meth-oxy derivative of cinchoninic acid. 

The astringency and the mouth feel of coffee is partly attributed to the presence of phenols which are thought to be formed by the degradation of feruloyl quinine acid (61). 

The oxidation of the cinchona alkaloids also led to quinoline and pyridine derivatives. From cinchonine, and cinchonidine, by oxidation with nitric, or chromic acid, cinchoninic acid (V) was obtuned (16,49-51) and related to lepidine (41, 42). Similarly, quinine and quinidine were converted to quininic acid (52, 53), which wras showm to have the structure (VI). Further oxidation of the quinoline acids was shown to lead... 

The starting point for all syntheses of the cinchona bases and related substances is the quinoline portion of the molecule, represented by cinchoninic acid (CXXXVII, R = H) or quininic acid (CXXXVII, R — OCHi). The former product has been obtuned from isatin and acetaldoxime (171), by decarboxylation of quinoline-2,4-dicarboxylic... 

The first successful syntheses of quininic acid (CXXXVII, R = OCHt) were achieved independently in 1912 by Kaufmann and Peyer (183), and Pictet and Misner (184). The former group applied to 6-methoxy-quinoline the method which they had used earlier in the synthesis of cinchoninic acid from quinoline. Pictet and Misner isolated ethyl quininate in small yield directly from the condensation of p-anisidine with formaldehyde and pyruvic acid in the presence of hydrochloric acid. 

Numerous other methods for the syntheds of the methoxy acid were developed subsequently. The pyruvic acid-isatin condensation, and the Thielepape synthesis, were extended by the use of appropriately meth-oxylated starting materials (185, 186). The transformation of m-cresol into quininic acid has been reported by Koelsch (187). In 1931 Rabe and co-workers (188, 189) condensed p-anisidine with acetoacetic ester and obtained a product, which on cyclization with 90% sulfuric acid gave... 

The outstanding contributions of Rabe to the study of the cinchona alkaloids were crowned by the achievement in 1931 of the total synthesis of dihydroquinine (188). The methods used had been developed over the course of a quarter of a century. During this time, as has been indicated in previous sections, processes had been discovered for the synthesis of quininic acid and dl-homocincholoipon. Reactions had been found which served for the condensation of such components, and for the transformation of the resulting toxines into natural alkaloids. 

Among the subsequent modifications, it was found that, if the preparation of lepidine at the stage of dehalogenation is performed in warm alcoholic KOH in the presence of Raney nickel, the lepidine can be easily isolated in addition, such dehalogenation can also be accomplished by zinc and acetic acid. Moreover, the formation of quininic acid via oxidation in acetone was found to be superior to that in 50% pyridine due to the easy isolation of product. ... 

Although the general reaction route of the Ainley and King synthesis is generally followed, each step has been modified in same way to produce large quantities of quinine. Some of the modifications are the removal of chlorine by zinc and acetic acid to form lepidine and the formation of quininic acid in acetone during the oxidation. ... 

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