Cinchoninic acid

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Cinchoninic acid—see Quinoline-4-carboxylic acid Cinenic acid... 

Cinchoninone, CigHaaONj, produced by the oxidation of either cinchonine or cinchonidine by chromic acid in presence of sulphuric acid forms pale yellow prisms, m.p. 126-7°, [a]j) -(-71° to -(-76°, is sparingly soluble in light petroleum, easily in ether or chloroform and insoluble in water. The hydrochloride forms minute colourless needles, m.p. 245-7°, [a]r) -(-175-9°. By further oxidation with chromic acid, cinchoninone yields cinchoninic acid and meroquinenine (meroquinene). 

Cinchona PelUtierana, alkaloids, 466 Cinchona spp., alkaloids, 418, 424 Cinchona, total alkaloids. See Totaquina. Cinchonamine, 419, 465 Cinchonhydrines, 440, 452 Cinchonicine (cinchotoxine), 410, 442, 451 Cinchonidine, 419, 427 constitution, 435 apoCinchonidlne, 448, 452 J3-Cinchonidine, 448, 452 Cinchonifine (dihydrocinchonine) 428 Cinchonine, 410, 421, 427, 583 constitution, 435 oxidation, 436 structural formula, 442 /leieroCinchonine (/i-cinchonine), 451 isoCinchonines, 451 Cinchoninic acid, 454 Cinchonino, 421 Cinchoninone, 437, 438, 442 Cinchotenidine, 436 Cinchotenine, 436... 

Buu-Hoi has shown that n-alkyl methyl ketones excluding ethyl methyl ketone, yield primarily 2-monosubstituted cinchoninic acids. It has been demonstrated that the products of the condensation of isatin with aryloxyketones are the corresponding 3-aryloxy-4-quinoline carboxylic acids rather than the isomeric 2-aryloxymethylcinchoninic acids.In the case of simple a-alkoxyketones such as 1-alkoxyethyl methylketones, the preferred products are the 2-alkoxyalkylcinchoninic... 

Octyl Alcohol.—This is the primary normal alcohol of the formula CH3(CH2)gCH20H. It has an odour recalling that of opoponax, and is useful in the blending of perfumes of this type. It boils at 196° to 197°, and has a specific gravity 0"8278. It yields octyl aldehyde on oxidation, whose naphtho-cinchoninic acid compound melts at 234°. 

Thienothiophenes undergo the indophenine reaction with isatin (see Section III,I). Oster reported that thieno[2,3-6]thiophene (1) gave a green product with a ratio of isatin to thienothiophene 1 1, and a blue substance with the ratio of the initial substances 2 1. Steinkopf and HempeP could not obtain this blue substance instead they isolated a brown material with the isatin to thienothiophene 1 ratio 2 3 at +50° they isolated a substance with the ratio 1 1 and at +70°, with ratio 1 2. Steinkopf and PetersdorP found that a reaction of 2-acetylthieno[2,3-6]thiophene with isatin produces 2- or 3-(2-thieno[2,3-6]thienyl) cinchoninic acid. The acid was decarboxylated to 2- or 3 2-thieno[2,3-6]thienyl)quinoline (the site of quinoline group in thienothiophene 1 molecule was not established). 

In the original Doebner-von Miller synthesis of quinolines an arylamine condenses with two molecules of an aldehyde most of the variants have been dealt with in Section 2.08.2.2.3.ii since the intermediate (often used directly) is an a,-unsaturated aldehyde. Two further major variations, the Beyer modification and the Doebner cinchoninic acid synthesis, will be dealt with here, since intermediates are rarely isolated. 

Ketones of the type 200 (where R is not CH3 or CH2) react with isatin to give cinchoninic acids of the type 201.557 572-593 In a number of... 

Cinchoninic Acid.—(2) Carboxylic acids. The only quinoline carboxylic acid of importance is known as cinchoninic acid because it is obtained by oxidizing cinchonine, one of the alkaloids of cinchona bark. It is the quinoline 4-carboxylic acid and by loss of carbon dioxide yields quinoline. By oxidation cinchoninic acid yields pyridine 2-3-4 tricarboxylic acid (p. 858) which by loss of carbon dioxide (3 mol.) yields pyridine. 

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. 

Cinchoninic acid Quinoline mono-carboxylic acid... 

The ordinary small laboratory stirring motor is insufficiently powerful to maintain rapid agitation after most of the cinchoninic acid has precipitated. 

If the mixture is not filtered immediately after acidification, or if the first end point is overrun, isatin is precipitated along with the cinchoninic acid and the product has a deep red color. Such material can be freed of isatin by dissolving it in sodium bicarbonate solution, filtering, and reprecipitating. 

Hydroxycinchoninic acid has been prepared by the rearrangement of N-acetylisatin in alkali, -by the treatment of isatin with malonic acid in glacial acetic acid, and by heating cinchoninic acid with concentrated potassium hydroxide. ... 

Doebner reaction. Formation of substituted cinchoninic acids from aromatic amines on heating with aldehydes and pyruvic acid. 

HYDRO XYCINCHONINIC ACID (Cinchoninic acid, 2-hydroxy-)... 

A simple synthesis of edulein [5 R1 = Me, R2 = Ph, C(7)-OMe] has been reported.17 Syntheses of acronycidine (19 R1 = R2 = R3 = OMe),18 acro-phylline (20),19 and 7-O-demethyle volitrine (19 R1 = R3 = H, R2 = OH)19 by essentially the same method have been described. For example, acid-catalysed cyclization of (21) gave the furoquinolone (22) which was converted into acronycidine (19 R1 = R2 = R3 = OMe) by successive sodium borohydride reduction and methylation with diazomethane.18 Routes for the preparation of cinchoninic acid and its derivatives have been improved.20 The conditions required for the transformation of the 3-hydroxyquinoline derivative (23 R = H) to either the furoquinoline (24) (acetic anhydride, acetic acid) or the open-chain acetate (23 R = Ac), may be of general interest.21... 

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