Pyruvic acid aldehydes

The direction of MCR involving pyruvic acid, aldehyde, and l-aryl substituted l,2,4-triazole-3,5-diamine was different from the directions of all other processes that were discussed earher. It was established [53] that this treatment yielded 3-(5-ammo-lH-l,2,4-triazol-3-ylamino)furan-2(5H)-one 39 instead of triazolopyri-midine carboxylic acids 38 (Scheme 16). 

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]. 

The reaction of trioses takes place in a similar manner (Figure 4.50). D-Glyceraldehyde or 1,3-dihydroxyacetone dehydration yields 1,2-diulose methylglyoxal (also known as pyruvic acid aldehyde or pyruvaldehyde) and the intramolecular Cannizzaro reaction of methylglyoxal yields lactic acid (racemate). 

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. 

Alternatively, the pyruvic acid can first condense with the aldehyde. Addition of the aniline to the P-position of 18 provides the same intermediate (13), as above. The mechanism could be substrate dependent. 

Catalytic reduction of the nitrile 79 in the presence of semicarbazide affords initially the semicarbazone of 80. Hydrolysis-interchange, for example in the presence of pyruvic acid, gives the aldehyde 80. Condensation with the half ester of malonic acid leads to the acrylic ester 81 the double bond is then removed by means of catalytic reduction (82). Base catalyzed reaction of the... 

Pyruvic Acid Compounds.—Lubrzynska and Smedley have recently shown that a number of aldehydes such as heliotropin, anisic aldehyde, benzaldehyde, and cinnamic aldehyde, condense with pyruvic acid in slightly alkaline solution, with the formation of )8-unsaturated-a-ketonic acids. For example, if heliotropin and pyruvic acid in alkaline solution be left standing for about eight days at ordinary temperature, dihydroxy-methylene-benzal-pyruvic acid is formed. This body forms yellow needles, melting at 163° Similarly, anisic aldehyde yields methoxy-benzal-pyruvic acid, melting at 130° and cinnamic aldehyde yields cinnamal-pyruvic acid, melting at 73°. 

Doebner showed that certain aldehydes, citral, for example, form condensation products with pyruvic acid and )8-naphthylamine, known as naphthocinchoninic acids. The reaction takes place as follows —... 

Pyruvic acid is not stable at ambient temperature when it is stored for a long period of time. It can only be stored in a refrigerated room. A bottle of this acid was stored in a laboratory at 25°C and detonated, probably because of the overpressure created by the formation of carbon dioxide. Indeed, with diacids and complex acids the decomposition is made by decarboxylation. In this particular case, this decomposition should give rise to acetaldehyde. It could be asked whether, in the exothermic conditions of this decomposition, a polymerisation of this aldehyde (see Aldehydes-ketones on p.310) did not make the situation worse. 

Indole 2-carboxylic acids can be readily decarboxylated to afford an indole. Hence, using pyruvic acid as an aldehyde equivalent in the coupling with 24 gave... 

Biochemical reactions include several types of decarboxylation reactions as shown in Eqs. (1)-(5), because the final product of aerobic metabolism is carbon dioxide. Amino acids result in amines, pyruvic acid and other a-keto acids form the corresponding aldehydes and carboxylic acids, depending on the cooperating coenzymes. Malonyl-CoA and its derivatives are decarboxylated to acyl-CoA. -Keto carboxylic acids, and their precursors (for example, the corresponding hydroxy acids) also liberate carbon dioxide under mild reaction conditions. 

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

In some cases a choice of multicomponent or linear protocol for the treatment of pyruvic acids, aminoazole, and aldehydes allows obtaining different heterocycles. For instance, MCR involving 5-aminopyrazoles or sequence pathway via preliminary synthesis of arylidenpyruvic acids led to positional isomers 36 and 37, respectively (Scheme 15) [4, 61, 68]. It is interesting to note that the same strategy applied to 3-amino-l,2,4-triazole or to amino-W-aryl-lH-pyrazole-4-carboxamide reactions gave no effect and the final compound for both the protocols were the same [52, 61, 62]. 

The results describing formation of regioisomers in the case of MCR involving 3-amino-l,2,4-triazole, aldehydes, and pyruvic acid were also published [62]. The treatment was carried out in boiling DMF and a mixture of two regioisomeric compounds 30 and 49 (Scheme 22) were isolated and characterized (49 without separation). 

Formation of pyranoanthocyanins through reaction of flavylium cations with compounds possessing a polarizable double bond, namely vinylphenol derivatives (including vinylflavanols and hydroxycinnamic acids) and enolizable aldehydes and ketones (e.g., acetaldehyde and pyruvic acid). 

Multifunctional acids containing a carbonyl group such as pyruvic acid [CH3C(0)C00H] are typically measured using the derivatization techniques used for aldehydes and ketones, such as the DNPH method (e.g., see Lee et al., 1995). 

---