Succinic acid, decarboxylation

Delwiche, E. A. Biotin function in succinic acid decarboxylation by... 

When cinnamaldehyde, succinic acid and acetic anhydride are heated in the presence of litharge (PbO), the aldehyde and the succinic acid condense to give the dicarboxylic acid (I), which undergoes decarboxylation to give the pale yellow crystalline 1,8-diphenyloctatetrene (II), Kuhn has shown that as the... 

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Heat. When heated, succinic acid loses water and forms an internal anhydride with a stable ring stmcture. Dehydration starts at 170°C and becomes rapid at 190—210°C (25). Further heating of succinic anhydride causes decarboxylation and the formation of the dilactone of gamma ketopimelic acid (26) (eq. 1). The same reaction takes place at lower temperatures in the presence of alkaU. 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

As the mechanism, a radical and a cationic pathway are conceivable (Eq. 31). The stereochemical results with rac- or mcjo-1,2-diphenyl succinic acid, both yield only trans-stilbene [321], and the formation of a tricyclic lactone 51 in the decarboxylation of norbornene dicarboxylic acid 50 (Eq. 32) [309] support a cation (path b, Eq. 31) rather than a biradical as intermediate (path a). 

This is the decarboxylation of a (3-keto acid which undergoes smoothly even in the absence of an enzyme. Thus, it can be said that the mother nature utilizes an organic reaction with a low activation energy. The second step of the decarboxylation is the conversion of a-ketoglutaric acid to succinic acid (Fig. 3). This is the same type of reaction as the decarboxylation of pyruvic acid. 

Succinic anhydride is dimerised to 1,6-dioxaspiro [4.4] nonane-2,7-dione by heating with sodium hydroxide. Modification of an existing procedure by adding further sodium hydroxide after the initial reaction led to a severe exothermic reaction after heating for some 30 h which fused the glass flask to the heating mantle, probably at a temperature approaching 550°C. The reason for this was not known [1], At elevated temperatures and under influence of alkali, succinic acid condenses decarboxylatively beyond the dimeric spiroacetal, sometimes explosively. Contamination of the anhydride with base is to be avoided [2],... 

Besides Szent-Gyorgi and Krebs, other groups were attacking the problem of carbohydrate oxidation. Weil-Malherbe suggested It is probable that the further oxidation of succinic acids passes through the stages of fumaric, malic, and oxaloacetic acid pyruvic acid is formed by the decarboxylation of the latter and the oxidative cycle starts again. K.A.C. Elliott, from the Cancer Research Laboratories at the University of Pennsylvania, also proposed a cycle via some 6C acid. 

Succinic acids undergo bisdecarboxylation on exposure to lead tetraacetate [264], Contra-polarization at one of the a-carbons through fragmentation of the lead(IV) carboxylate moiety enables a smooth decarboxylation of the remaining functionality. 

Biotin enzymes are believed to function primarily in reversible carboxvlahon-decarboxylation reactions. For example, a biotin enzyme mediates the carboxylation of propionic acid to methylmalonic add, which is subsequently converted to succinic acid, a dtric acid cycle intermediate. A vitamin Bl2 coenzyme and coenzyme A are also essential to this overall reaction, again pointing out the interdependence of the B vitamin coenzymes. Another biotin enzyme-mediated reaction is the formation of malonyl-CoA by carboxylation of acetyl-CoA ( active acetate ). Malonyl-CoA is believed lo be a key intermediate in fatly add synthesis. 

Though the pertinent experiment in the corrin series has not yet been reported, a record of the analogous experiment in the porphyrin series has appeared [84], In contrast to corrins, in haems all four acetate side chains of the parent urogen III have been decarboxylated to methyl groups. In principle, these could be carved out as acetic acid and analysed for chirality if the starting succinate had been stereospecifically labelled with deuterium as well as with tritium. The synthesis of (2/ )-[2-2H,2-3 H]succinic acid was achieved by incubating (37 ,S)-[3-3 H]-... 

Highly conjugated diphenylpolyenes, CjHj (CH= CH) C sHs, are obtained directly from the condensation of olefinic aldehydes such as cin-namaldehyde, C Hj CH=CHCHO, with sodium salts of phenylacetic or succinic acids in the presence of lead oxide and acetic anhydride. ° The unsaturated acids first formed are decarboxylated under the conditions of the condensation. 

COs to form oxalacetate which under anaerobic conditions is reduced to malate. The malate in turn may be converted to fumarate and succinate (Fig, 5). The last step in this series of reactions is blocked by malonate. The second pathway involves the aerobic condensation of pyruvate and oxalacetate followed by oxidation of the condensation product to form -ketoglutarate and succinate. Wood has proposed that the first condensation product of the aerobic tricarboxylic cycle is cfs-aconitic acid which is then converted to succinate by way of isocitric, oxalosuccinic, and a-ketoglutaric acids. The a-ketoglutarate is decarboxylated and oxidized to succinic acid. Isotopic a-ketoglutarate containing isotopic carbon only in the carboxyl group located a to the carbonyl would be expected to yield non-isotopic succinate after decarboxylation. This accounts for the absence of isotopic carbon in succinate isolated from malonate-poisoned liver after incubation with pyruvate and isotopic bicarbonate. 

Side-reactions lead to the formation of lighter acids. For instance, monoperoxyadipic acid can decarboxylate to yield the pentanoic acid radical, precursor of the byproduct valeric acid. The same C5 radical may react with. O2 to yield 5-oxopentanoic acid, which is then oxidized to monoperoxyglutaric acid, a precursor of glutaric acid. An analogous mechanism starting from the butanoic acid radical may yield the byproduct succinic acid. Azelaic acid may form by the coupling of radical species (e.g., between the butanoic acid radical and the pentanoic acid radical), whereas the dimerization of the pentanoic acid radical may yield the by-product sebacic acid. 

Formic, oxalic and malonic acids were never detected during these oxidation experiments. It was verified that formic and oxalic acids were oxidized so rapidly, that they could not accumulate in the reaction mixture and be detected by HPLC. Malonic acid was decarboxylated very rapidly to yield acetic acid. On the other hand, as expected, acetic acid and propionic acid were much less reactive. The initial rates of TOC removal were 13 and 19 mol h mol, respectively, compared to 61 for succinic acid. After 6 h, TOC abatement was 65.9 and 68.5%, respectively. 

Under the usual conditions of the Perkin reaction, cinnamaldehyde gives an excellent yield of 5-phenyl-2,4-pentadienoic acid 890 but decarboxylation occurs when it is heated with phenylacetic acid and acetic anhydride in the presence of lead(n) oxide, 1,4-diphenyl-1,3-butadiene being formed in 30% yield,891 and under these conditions two equivalents of cinnamaldehyde and one of succinic acid give l,8-diphenyl-l,3,5,7-octatetraene.892... 

One reaction it catalyzes in particular is the decarboxylation of a-ketoglutaric acid to succinic acid. 

---