Carboxylic acids, conversion decarboxylation

The decarboxylation of free carboxylic acids is often difficult except for some activated acids such as aryl carboxylic acid. Conversion of the free carboxylic acids into proper derivatives snch as acid anhydrides or esters makes the transition metal-catalysed decarboxylation reaction easy and these have also been applied to various coupling reactions. Water in a snpercritical stage (374°C, 22 MPa) was used for decarboxylation of free carboxylic acids using 10 wt% Pd on active carbon in a closed pot (Matsnbara et al., 2004) (Scheme 3.14). 

Orotic acid undergoes 5-nitration, 5-bromination in hydrobromic acid with peroxide, 5,5-dibromination following decarboxylation in bromine water, esterification, methylation (rather complicated), conversion into its acid chloride (containing some anhydride) by treatment with thionyl chloride, and conversion into 2,6-dichloropyrimidine-4-carboxylic acid by phosphoryl chloride (62HC(16)422). 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Phenazines — The phenazines are biosynthesized by the shikimic acid pathway, through the intermediate chorismic acid. The process was studied using different strains of Pseudomonas species, the major producers of phenazines. The best-known phenazine, pyocyanine, seems to be produced from the intermediate phenazine-1-carboxylic acid (PCA). Although intensive biochemical studies were done, not all the details and the intermediates of conversion of chorismic acid to PCA are known. In the first step, PCA is N-methylated by a SAM-dependent methyltransferase. The second step is a hydroxylative decarboxylation catalyzed by a flavoprotein monooxygenase dependent on NADH. PCA is also the precursor of phenazine-1-carboxamide and 1-hydroxyphenazine from Pseudomonas species. - - ... 

Both the synthesis of propionate and its metabolism may take place under anaerobic conditions. In Desulfobulbuspropionicum, degradation could plausibly take place by reversal of the steps used for its synthesis from acetate (Stams et al. 1984)—carboxylation of propionate to methylmalonate followed by coenzyme Bi2-mediated rearrangement to succinate, which then enters the tricarboxylic acid cycle. The converse decarboxylation of succinate to propionate has been observed in Propionigenium modestum (Schink and Pfennig 1982),... 

A related method for conversion of carboxylic acids to bromides with decarboxylation is the Hunsdiecker reaction.276 The usual method for carrying out this transformation involves heating the carboxylic acid with mercuric oxide and bromine. 

As pointed out previously, controlled degradation reactions are very difficult with aliphatic or alicyclic hydrocarbons, and most of the relabeling work has been concentrated on aromatic reaction products. Procedures have been extensively described by Pines and co-workers (e.g., 97, 96, also 87, 89-98, 95, 98). For the present purpose, it suffices to note that the 14C contents of the methyl side-chains and the rings in aromatic reaction products are readily estimated by oxidation of the methyl to carboxyl, followed by decarboxylation, while ethyl side-chains may be oxidatively degraded one carbon atom at a time. Radiochemical assays may be made on CO2 either directly in a gas counter, or after conversion to barium carbonate, while other solid degradation intermediates (e.g., benzoic acid or the phthalic acids) may be either assayed directly as solids or burned to CO2. Liquids are best assayed after burning to CO2. 

In Table 9, some conversions of heterocyclic carboxylic acids and esters are shown. The reactions involve amide formation, hydrolysis, and decarboxylation. 

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. 

Notably, nitrile-degrading enzymes (e.g. nitrilase that converts the CN group to carboxylic acid, and nitrile hydratase that produces an amide function) have been described, and they co-exist with aldoxime-degrading enzymes in bacteria (Reference 111 and references cited therein). Smdies in this area led to the proposal that the aldoxime-nitrile pathway, which is implemented in synthesis of drugs and fine chemicals, occurs as a natural enzymic pathway. It is of interest that the enzyme responsible for bacterial conversion of Af-hydroxy-L-phenylalanine to phenacetylaldoxime, an oxidative decarboxylation reaction, lacks heme or flavin groups which are found in plant or human enzymes that catalyze the same reaction. Its dependency on pyridoxal phosphate raised the possibility that similar systems may also be present in plants . 

The oxazole (232) heated with formamide gave the imidazole (233) oxazolium cations undergo similar conversions. Primary amines convert oxazole-4-carboxylic acids (234) at 150°C into imidazoles (235) with accompanying decarboxylation (53CB88) (see CHEC 4.07 and 4.18). 

There is some competing decarboxylation of the ethanoic acid, but the conversions in this kind of reaction are usually good. The key steps in the reaction probably are exchange of carboxylic acid groups on tetravalent lead, cleavage of the Pb-O bond to give the carboxylate radical, decarboxylation, oxidation... 

The carboxylation of pyruvate supplies a significant portion of the thermodynamic push for the next step in the sequence. This is because the free energy change for decarboxylation of /3-keto carboxylic acids such as oxaloacetate is large and negative. The oxaloacetate formed from pyruvate by carboxylation is converted to phosphoenolpyruvate in a reaction catalyzed by phosphoenolpyruvate carboxyki-nase. In many species, including mammals, this reaction involves a GTP-to-GDP conversion. 

In general, in cases where the carbanion can be stabilized by catalytic intervention, as in the initial conversion of a 2-ketoacid to a cyanohydrin, the transition state leading to its formation will be stabilized. In addition, the stability of the carbanion generated by loss of carbon dioxide also depends on its molecular environment. The rate of decarboxylation of pyridine-2-carboxylic acid is enhanced in a nonpolar environment as the zwitterionic ground state is destabilized and the less polar transition state is stabilized.5... 

Decarboxylation of a-keto carboxylic acids.1 The conversion of a-keto carboxylic acids into the morpholine enamine (TsOH) is accompanied by loss of C02 to form the enamine of an aldehyde in almost quantitative yield. The free aldehyde is liberated as usual by acidic hydrolysis. 

In a critical study of the periodate oxidation of raffinose and related oligosaccharides, Courtois and Wickstrom showed78 that 1 mole of raffinose reduces 5 moles of periodate, with the formation of 2 moles of formic acid plus a hexaldehyde. Conversion of the aldehyde to the hexa-carboxylic acid, followed by hydrolysis, gave the expected amounts of glyoxylic acid, glyceric acid, hydroxypyruvic acid, and glycolaldehyde (by decarboxylation of hydroxypyruvic acid). 

This sequence of reactions is incompletely understood but involves numerous oxidations of carbon groups, for example, the conversion of methyl groups to carboxylic acids, followed by decarboxylation. The end product, cholesterol, is the precursor to cholesterol esters in the liver and is transported to the peripheral tissues where it is a precursor to membranes (all cells), bile salts (liver), steroid hormones (adrenals and reproductive tissues), and vitamin D (skin, then liver, and finally kidney). 

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