Carbonic acids, decarboxylation

FIGURE 17.55 Monoesters of carbonic acid decarboxylate easily, but carbonates (acid diesters) do not. 

Practically all pyridazine-carboxylic and -polycarboxylic acids undergo decarboxylation when heated above 200 °C. As the corresponding products are usually isolated in high yields, decarboxylation is frequently used as the best synthetic route for many pyridazine and pyridazinone derivatives. For example, pyridazine-3-carboxylic acid eliminates carbon dioxide when heated at reduced pressure to give pyridazine in almost quantitative yield, but pyridazine is obtained in poor yield from pyridazine-4-carboxylic acid. Decarboxylation is usually carried out in acid solution, or by heating dry silver salts, while organic bases such as aniline, dimethylaniline and quinoline are used as catalysts for monodecarboxylation of pyridazine-4,5-dicarboxylic acids. 

Rearrangements of vinylogous urethanes to vinylogous carbonic acids and decarboxylation are other interesting enamine rearrangements which may be synthetically useful in the formation of cyclic enamines (623,624). 

The Hunsdiecker reaction is the treatment of the dry silver salt of a carboxylic acid with bromine in carbon tetrachloride. Decarboxylation occurs, and the product isolated is the corresponding organic bromide 16). Since dry silver salts are tedious to prepare, a modification of the reaction discovered by Cristol and Firth (77) is now... 

Decarboxylation (Section 22.7) The loss of carbon dioxide from a molecule. /3-Keto acids decarboxylate readily on heating. 

Biotin is a growth factor for many bacteria, protozoa, plants, and probably all higher animals. In the absence of biotin, oxalacetate decarboxylation, oxalosuccinate carboxylation, a-ketoglutarate decarboxylation, malate decarboxylation, acetoacetate synthesis, citrulline synthesis, and purine and pyrimidine syntheses, are greatly depressed or absent in cells (Mil, Tl). All of these reactions require either the removal or fixation of carbon dioxide. Together with coenzyme A, biotin participates in carboxylations such as those in fatty acid and sterol syntheses. Active C02 is thought to be a carbonic acid derivative of biotin involved in these carboxylations (L10, W10). Biotin has also been involved in... 

Photochemical a-cleavage of carboxylic acids results in loss of carbon dioxide (decarboxylation) rather than loss of carbon monoxide. The compound 2,4-dichlorophenoxyacetic acid, commonly known as (2,4-D), has been used extensively as a herbicide. This has posed a problem, because of the slow natural decomposition of 2,4-D in the environment. 2,4-D undergoes a-cleavage, undergoing decarboxylation ... 

Thiamine diphosphate (TDP) is an essential coenzyme in carbohydrate metabolism. TDP-dependent enzymes catalyze carbon-carbon bond-breaking and -forming reactions such as a-keto acid decarboxylations (oxidative and non-oxidative) and condensations, as well as ketol transfers (trans- and phospho-ketolation). Some of these processes are illustrated in Fig. 12. 

The finding that thiamine, and even simple thiazolium ring derivatives, can perform many reactions in the absence of the host apoenzyme has allowed detailed analyses of its chemistry [33, 34]. In 1958 Breslow first proposed a mechanism for thiamine catalysis to this day, this mechanism remains as the generally accepted model [35]. NMR deuterium exchange experiments were enlisted to show that the thiazolium C2-proton of thiamine was exchangeable, suggesting that a carbanion zwitterion could be formed at that center. This nucleophilic carbanion was proposed to interact with sites in the substrates. The thiazolium thus acts as an electron sink to stabilize a carbonyl carbanion generated by deprotonation of an aldehydic carbon or decarboxylation of an a-keto acid. The nucleophilic carbonyl equivalent could then react with other electro-... 

Chemical/Physical. Hydrolysis in distilled water at 25 °C produced 3-chloro-2-propen-l-ol and HCl. The reported half-life for this reaction is only 2 d (Kollig, 1993 Milano et al., 1988). trans-1,3-Dichloropropylene was reported to hydrolyze to 3-chloro-2-propen-l-ol and can be biologically oxidized to 3-chloropropenoic acid which is oxidized to formylacetic acid. Decarboxylation of this compound yields carbon dioxide (Connors et al., 1990). Kim et al. (2003) reported that the disappearance of tra 35-l,3-dichloropropylene in water followed a first-order decay model. At 25 and 35 °C, the first-order rate constants were 0.083 and 0.321/d, respectively. The corresponding hydrolysis half-lives were 8.3 and 2.2 d, respectively. 

Relatively acidic carbon acids such as malonic esters and jS-keto esters were the first class of carbanions for which reliable conditions for alkylation were developed. The reason being that these carbanions are formed using easily accessible alkoxide ions. The preparation of 2-substiuted /i-kcto esters (entries 1, 4, and 8) and 2-substituted derivatives of malonic ester (entries 2 and 7) by the methods illustrated in Scheme 1.5 are useful for the synthesis of ketones and carboxylic acids, since both /1-ketoacids and malonic acids undergo facile decarboxylation ... 

Pilone, G. J., Kunkee, R. E., Carbonic Acid From Decarboxylation by... 

Examples of the cleavage of support-bound carbonates are given in Table 3.36. Depending on the structure of the carbonate, acidolytic, base-induced, nucleophilic, or photolytic cleavage can be used to release the alcohol. Acidolysis of the benzylic C-O bond of resin-bound benzyl carbonates leads to the release of an unstable carbonic acid ester, which undergoes decarboxylation to yield the alcohol. 

Decarboxylation of carbonate complexes is usually effected by acid hydrolysis with the formation of a C02 free oxide or hydroxide complex.128 All such reactions involve a protonated (bicarbonate) intermediate but there are some useful deferences which, in many instances, may be reconciled with the three main structural types of carbonate complexes. Both unidentate and chelate carbonates readily yield C02 on acidification, while there is a greater resistance to C02 loss when the carbonate is a bridging ligand. Unidentate carbonate complexes decarboxylate with the initial formation of a bicarbonate intermediate and subsequent loss of C02 without rupture of the M—O bond, viz. structure (3). By contrast, in chelate carbonate complexes, cleavage of the M—O bond occurs (with ring opening) with the formation of a bicarbonate aqua ion before the loss of C02, viz. equation (5).29... 

Cyclizations conducted by the thiohydroxamate method are even less common than those conducted by the fragmentation method, but there is every reason to believe that thiohydroxamate cyclizations should be generally applicable.119 Precursors are formed from carboxylic acids, and require the inclusion of an extra carbon since decarboxylation occurs. This feature may be very useful when normal precursors containing carbon-heteroatom bonds are unstable or difficult to prepare. The thiohydroxamate... 

We have presented evidence that pyrrole-2-carboxylic acid decarboxylates in acid via the addition of water to the carboxyl group, rather than by direct formation of C02.73 This leads to the formation of the conjugate acid of carbonic acid, C(OH)3+, which rapidly dissociates into protonated water and carbon dioxide (Scheme 9). The pKA for protonation of the a-carbon acid of pyrrole is —3.8.74 Although this mechanism of decarboxylation is more complex than the typical dissociative mechanism generating carbon dioxide, the weak carbanion formed will be a poor nucleophile and will not be subject to internal return. However, this leads to a point of interest, in that an enzyme catalyzes the decarboxylation and carboxylation of pyrrole-2-carboxylic acid and pyrrole respectively.75 In the decarboxylation reaction, unlike the case of 2-ketoacids, the enzyme cannot access the potential catalysis available from preventing the internal return from a highly basic carbanion, which could be the reason that the rates of decarboxylation are more comparable to those in solution. Therefore, the enzyme cannot achieve further acceleration of decarboxylation. In the carboxylation of pyrrole, the absence of a reactive carbanion will also make the reaction more difficult however, in this case it occurs more readily than with other aromatic acid decarboxylases. 

Pocker, Y., and Guilbert, L. J. Carbonic anhydrase catalysed hydrolysis and decarboxylation. Kinetic studies of enzyme-catalysed decomposition of mono- and disubstituted derivatives of carbonic acid. Biochemistry 13, 70-78 (1974). 

Except for some activated acids, for example aryl carboxylic acids, decarboxylation of free carboxylic acids is often difficult [17]. Under the reaction conditions used for of the deuteration in Scheme 6 (i.e. Pd/C catalyst, in deuterium oxide at 250 C/4-5 MPa), decarboxylation was observed - a carboxyl group is exchanged with a D atom, accompanied by H-D exchange reaction on all carbons [18]. 

The /3-keto acid decarboxylates by the same mechanism as the alkylmalonic acid in the malonic ester synthesis. A six-membered cyclic transition state splits out carbon dioxide to give the enol form of the substituted acetone. This decarboxylation usually takes place spontaneously at the temperature of the hydrolysis. 

Previous work on this reaction has included the use of triethanolamine as catalyst, as well as triethylamine as catalyst and solvent. [21-24] The use of elevated temperatures (>75°C) can lead to uncontrolled decarboxylation of malonic acid before condensation, giving acetic acid, which is then too weak a carbon acid to condense. This difficulty means that often up to 3 equivalents of the malonic acid need to be used to achieve good conversion. Our aim in this work was therefore to find a catalyst which would cause the condensation to occur efficiently, but at low enough temperatures to avoid decomposition of the malonic acid. Using THF as solvent and a 1 1 ratio of malonic acid to aldehyde, with 15g of catalyst per mole of reagent, we obtained high levels of conversion of aldehyde in a reasonable time (Table 3). 

Scheme 4.351665 illustrates the most common method for synthesising carbonates — reaction of the hydroxyl group with a chloroformate in the presence of base - and a particularly mild method of deprotection, hydrogenolysis, giving toluene and a carbonic acid monoester that decarboxylates to liberate the free hydroxyl.666 Alkoxycarbonyl groups can be easily installed on carbohydrates by reaction with the appropriate chloroformate in the presence of TMEDA at low... 

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