Malonic acids oxidative decarboxylation

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. 

A typical chemical system is the oxidative decarboxylation of malonic acid catalyzed by cerium ions and bromine, the so-called Zhabotinsky reaction this reaction in a given domain leads to the evolution of sustained oscillations and chemical waves. Furthermore, these states have been observed in a number of enzyme systems. The simplest case is the reaction catalyzed by the enzyme peroxidase. The reaction kinetics display either steady states, bistability, or oscillations. A more complex system is the ubiquitous process of glycolysis catalyzed by a sequence of coordinated enzyme reactions. In a given domain the process readily exhibits continuous oscillations of chemical concentrations and fluxes, which can be recorded by spectroscopic and electrometric techniques. The source of the periodicity is the enzyme phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate by ATP, resulting in the formation of fructose-1,6 biphosphate and ADP. The overall activity of the octameric enzyme is described by an allosteric model with fructose-6-phosphate, ATP, and AMP as controlling ligands. 

Saponification of the diester followed by acidification gives the corresponding malonic acid which is then decarboxylated. The decarboxylation step may require high temperatures (150-250 °C). Treatment of malonic acids with a catalytic amount of Cu(I) oxide in acetonitrile is reported to accelerate the decarboxylation step and affords the monoacid products in good yield under milder conditions. ... 

Oxidative decarboxylation [1, 554-557 after citation of ref. 70a]. A simplified procedure for oxidative decarboxylation of disubstituted malonic acids has been described by Tufariello and Kissel.70b The malonic acid is oxidized by lead tetraacetate in refluxing benzene containing 2 equivalents of pyridine. Carbon dioxide is evolved and a g< m-diacetate is formed. This is readily hydrolyzed by either acid or base to the ketone. Yields are satisfactory (45-70%). 

Oxalic and malonic acids, as well as a-hydroxy acids, easily react with cerium(IV) salts (Sheldon and Kochi, 1968). Simple alkanoic acids are much more resistant to attack by cerium(IV) salts. However, silver(I) salts catalyze the thermal decarboxylation of alkanoic acids by ammonium hexanitratocerate(IV) (Nagori et al., 1981). Cerium(IV) carboxylates can be decomposed by either a thermal or a photochemical reaction (Sheldon and Kochi, 1968). Alkyl radicals are released by the decarboxylation reaction, which yields alkanes, alkenes, esters and carbon dioxide. The oxidation of substituted benzilic acids by cerium(IV) salts affords the corresponding benzilic acids in quantitative yield (scheme 19) (Hanna and Sarac, 1977). Trahanovsky and coworkers reported that phenylacetic acid is decarboxylated by reaction with ammonium hexanitratocerate(IV) in aqueous acetonitrile containing nitric acid (Trahanovsky et al., 1974). The reaction products are benzyl alcohol, benzaldehyde, benzyl nitrate and carbon dioxide. The reaction is also applicable to substituted phenylacetic acids. The decarboxylation is a one-electron process and radicals are formed as intermediates. The rate-determining step is the decomposition of the phenylacetic acid/cerium(IV) complex into a benzyl radical and carbon dioxide. 

However, this two-step method is of relative low overall efhciency. Therefore, the efhcient and one-step direct decarboxylative azidation of carboxylic acids is developed. In 2014, S.F. Kirsch and co-workers disclosed a direct decarboxylative azidation of malonic acid monoesters to construct the ot-azidoesters with NaNa in the presence of IBX-SO3K and substoichiometric amounts of Nal in aqueous DMSO (Scheme 6.31a) [89]. The experimental procedure is very simple and yields are high. In addition, the method shows high functional group compatibihty. Mechanistic studies revealed that oxidative iodination initially occurs at the eno-lizable position of the malonic acid monoesters to form the intermediate A, which then undergoes decarboxylation to generate the intermediate B. Tautomerization of... 

Scheme 6.31 Decarboxylative oxidative azidation of malonic acid monoestos...

The dicarboxylic acids found in basin brines (i.e., oxalic, malonic, and succinic) are expected to be less stable under hydrothermal conditions than monocarboxylic acids of comparable chain lengths. The stability of these acids has been discussed previously to the extent that structural factors make a-, and y-carboxyl acids susceptible to homogeneous decarboxylation. The mechanisms for decarboxylation of jff-carboxyl acids and their derivatives in solvents of varying polarity have been especially well studied and the results are believed to be generally applicable to a- and y-carboxyl acids as well (Clark 1969). For this reason, the following detailed discussion of the mechanism for homogeneous decarboxylation of dicarboxylic acids is based primarily on malonic acid. Finally, oxidation of dicarboxylic acids may be predicted, although the process has not been well studied. 

Inherently, the decarboxylation of p-keto acids and malonic acids (1) proceeds very smoothly, as the resulting product bearing anion adjacent to carbonyl group stabilizes as its enolate form (2) [Eq. (1)]. Enzyme-mediated reaction sometimes utilizes this facilitated decarboxylation. Indeed, isocitric acid (3) was oxidized to the corresponding keto acid, which subsequently decarboxylated to a-ketoglutaiic acid (4) by means of isocitrate dehydrogenase (EC 1.1.1.41) [Eq. (2)]. Another example is observed in the formation of acetoacetyl-CoA (5), which occupies the first step of fatty acid biosynthesis. A p-keto carboxylate 6, derived from the acetylation of malonyl-CoA with acetyl-CoA, decarbox-ylates to 5 by the action of 3-ketoacyl synthase [Eq. (3)]. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

An analogous sequence on acid, 29 (obtained by decarboxylative hydrolysis of the malonic ester), leads to carbromal (30). Dehy-drohalogenation of 30 by means of silver oxide affords the corresponding olefin, ectylurea (31), itself a sedative-hypnotic. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

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