Pyruvic acid Quinoline

Pyroligneous acid extract Pyruvaldehyde Pyruvic acid Quinoline (-)-Rhodinol Rhodinyl acetate Rhodinyl butyrate Rhodinyl formate Rhodinyl isobutyrate Rhodinyl isovalerate... 

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. 

The Doebner reaction is a three component coupling of an aniline (1), pyruvic acid (2), and an aldehyde (3) to provide a 4-carboxyl quinoline (4). That product can be decarboxylated to furnish quinoline 5. 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

The Doebner reaction can provide the 4-carboxyl quinoline when the Pfitzinger reaction does not." Pfiztinger reaction of pinnacolone with isatin did not provide the desired quinoline. Doebner reaction of aniline with acetaldehyde and pyruvic acid did furnish the quinoline, albeit in only 8% yield. 

Carboxylic acids with labile a-methylene protons react with isatin in the presence of strong aqueous base. In the total synthesis of methoxatin, the coenzyme of methanol dehydrogenase and glucose dehydrogenase, Weinreb employs a Pfitzinger condensation of an isatin 37 and pyruvic acid as a key step to provide the 4-quinolinic acid 38 in 50% yield under the standard basic conditions. ... 

Three-component coupling of an aniline, pyruvic acid, and an aldehyde to provide a quinoline-4-carboxylic acid. 

The homolytic acylation of protonated heteroaromatic bases is, as with alkylation, characterized by high selectivity. Only the positions a and y to the heterocyclic nitrogen are attacked. Attack in the position or in the benzene ring of polynuclear heteroaromatics has never been observed, even after careful GLC analysis of the reaction products. Quinoline is attacked only in positions 2 and 4 the ratio 4-acyl- to 2-acylquinoline was 1.3 with the acetyl radical from acetaldehyde, 1.7 with the acetyl radical from pyruvic acid, and 2.8 with the benzoyl radical from benzaldehyde. 

Pyruvic acid and isatins gave quinoline-2,4-dicarboxylic acids.16 36 Use of malonic acid with isatins gave 2-quinolone-4-carboxylic acids.169 620 Nitromethane and isatin with 50% potassium hydroxide gave 3-nitroquinoline-4-carboxylic acid.623... 

The three-component reaction of pyruvic acid, aldehydes and anilines can also yield pyrrolidine-2,3-dione [198], but in most cases the products of such multicomponent condensations are quinoline carboxylic acids identical to compounds obtained via the reaction of arylidenepyruvic acids [217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228]. 

This reaction makes the wrong ring size But another interesting reaction with pyruvic acid makes the required quinoline 50, esterified without isolation.6... 

Pyruvic acid and isatins gave quinoline-2,4-dicarboxyIic acids. 

C11H9N03 indole-3-pyruvic acid 392-12-1 25.00 1.2743 2 21710 C11H11N 3,4-dimethyl quinoline 2436-92-2 20.86 1.0491 2... 

Similarly, the Doebner reactionl >i b condenses aromatic amines and aldehydes and pyruvic acid derivatives. Reaction of p-toluidine with pyruvic acid (266) gave the aminopyruvic acid (267) in situ and subsequent cyclization and air oxidation under Friedel-Crafts conditions generated the 4-carboalkoxy-quinoline (268).Presumably, the reaction proceeds via initial imine formation (via reaction with benz-aldehyde) followed by condensation with pyruvate (in its enol form).l l Similar cyclization occurs with imines and pyruvate derivatives. ... 

Interestingly, the Fischer indole synthesis does not readily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with pyruvic acid or with a pyruvate ester, followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate, orcopper(II) oxide in, for example, heat-transfer oils, glycerol, quinoline, or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

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. 

This reaction was initially reported by Doebner in 1887. It is the synthesis of cinchoninic acid (or quinolinic acid ) derivatives from the reaction of aromatic amines, aldehydes, and pyruvic acid, involving the removal of hydrogen from the aromatic ring. However, the Doebner reaction failed when 2-chloro-5-aminopyridine, 3-aminopyridine, and 2-aminopyridine" were applied as the aromatic amines. 

Additional feeding using p- C,7a- C-tryptophan, COOH-anthra-nilic acid, U- C-shikimic acid, and 2- C-pyruvic acid failed to implicate any known pathway in the formation of the quinoline portion of streptonigrin 41, 42). Suspicions that a new pathway for quinoline biosynthesis was involved have recently been confirmed and the basic features of the biosynthesis of this portion of streptonigrin have been determined by analysis of the NMR spectrum of the antibiotic derived from feeding UL- Ce-D-glucose (35) to S. flocculus (7, 47). 

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