Decarboxylation of aromatic carboxylic acids

Decarboxylation of aromatic carboxylic acids has been encountered extensively in facultatively anaerobic Enterobacteriaceae. For example, 4-hydroxycinnamic acid is... 

Sarca and Laali386 have developed a convenient process for transacylation of sterically crowded arenes such as acetylmesitylene [Eq. (5.150)] and tetramethyl- and pentamethylacetophenones to activated aromatics using triflic acid in the presence of imidazolium-type ionic liquids under mild conditions. When the reactions are run without an activated arene acceptor, efficient deacylation takes place. Simple 4-methoxyaryl methyl ketones can be transacetylated with toluene and para-xylene as acceptors with triflic acid.387 Nafion-H has been found to be an efficient catalyst for the decarboxylation of aromatic carboxylic acids as well as deacetylation of aromatic ketones.388... 

Although benzoate is generally metabolized by oxidative decarboxylation to catechol followed by ring cleavage, nonoxidative decarboxylation may also occur (1) strains of Bacillus megaterium transform vanillate to guaiacol by decarboxylation (Crawford and Olson 1978) and (2) a number of decarboxylations of aromatic carboxylic acids by facultatively anaerobic Enterobacteri-aceae have been noted in Chapter 4, Section 4.3.2. 

The strongly acidic sites on the Zr02 surface would result in the polarization of the adsorbed carboxyl group of the carboxylic acid, leading to decarboxylation. Decarboxylation of aromatic carboxylic acids usually occurs on acidic catalysts... 

Scheme 49 Tentative mechanism for the orfho-heteroarylation and subsequent decarboxylation of aromatic carboxylic acids.

Heat-triggered decarboxylation of aromatic carboxylic acids in quinoline solution in the presence of copper metal or copper salts (the copper-quinoline decarboxylation)... 

Scheme 6. Carboxylation and decarboxylation of aromatic carboxylic acids References, pp. 239-276...

The reductive transformation of arene carboxylates to the corresponding aldehydes under aerobic conditions has already been noted. In addition, aromatic aldehydes may undergo both reductive and oxidative reactions, with the possibility of decarboxylation of the carboxylic acid formed ... 

The decarboxylation of carboxylic acid in the presence of a nucleophile is a classical reaction known as the Hunsdiecker reaction. Such reactions can be carried out sometimes in aqueous conditions. Man-ganese(II) acetate catalyzed the reaction of a, 3-unsaturated aromatic carboxylic acids with NBS (1 and 2 equiv) in MeCN/water to afford haloalkenes and a-(dibromomethyl)benzenemethanols, respectively (Eq. 9.15).32 Decarboxylation of free carboxylic acids catalyzed by Pd/C under hydrothermal water (250° C/4 MPa) gave the corresponding hydrocarbons (Eq. 9.16).33 Under the hydrothermal conditions of deuterium oxide, decarbonylative deuteration was observed to give fully deuterated hydrocarbons from carboxylic acids or aldehydes. 

Thus phenol formation from the monocarboxylic acids described above supports the suggestion that the 1,2-oxides of aromatic carboxylic acids may be the intermediates in their biological oxidative decarboxylation reactions. 

The parent trithiatriazepine, (20 R = H), is obtained as a colorless solid of high thermal stability by carefully heating the ester, (20 R = C02Me), with aqueous HCl followed by decarboxylation of the carboxylic acid so formed. The ester has a planar, aromatic structure. 

In the majority of cases thermal cleavage of carbon-carbon bonds consists of decarboxylation of a carboxylic acid RCOOH the tenacity with which the carboxyl group is retained varies within wide limits. Aliphatic acids can normally be decarboxylated only under rather extreme conditions, and the same applies to simple aromatic carboxylic acids unless the attachment of the carboxyl group is weakened by, e.g., ortho- or /rara-hydroxyl groups or by a hetero-ring atom (at a suitable distance from the carboxyl group). On the other hand, many carboxylic acids are known that lose carbon dioxide at or relatively little above room temperature either spontaneously or under the influence of acidic or basic catalysts. In most cases, the decarboxylation occurs by a polar mechanism, in an SE reaction ... 

Scheme 48 Rh-catalyzed decarboxylative o/Tho-heteroarylation of aromatic carboxylic acids.

Su and coworkers established a Pd-catalyzed method for decarboxylative Mizoroki-Heck coupling, in which 1.2 equiv. of p-benzoquinone is used in place of the Ag(l) salt. This method met with some success only with electron-rich (hetero)aromatic carboxylic acids [33]. Subsequently, the same authors reported that the Pd catalyst itself can induce decarboxylative Mizoroki-Heck coupling of aromatic carboxylic acids when dioxygen is used as the terminal oxidant completely replacing the Ag salt [34]. Depending on the structure of the acids, two different Pd catalysts were required for the Mizoroki-Heck coupling to occur Pd(OAc)j worked efficiently for electron-rich aromatic carboxylic acids, while the Pd(OAc)2/SIPr system (SIPr l,3-bis(2,6-diisopropylphenyl), 5-dihydroiniidazol-2-ylidene) enabled the use of electron-deficient substituents (Scheme 22.24) [34]. 

The in situ generation of carbon nucleophiles via extrusion of CO2 from benzoates cannot only be combined with cross-coupling processes but also with 1,2- and 1,4-addition reactions. An example is the rhodium-catalyzed decarboxylative conjugate addition of activated benzoic acids to acrylic esters or amides developed by Zhao et al. (Scheme 19, right side) [65]. A nice application is the decarboxylative addition of aromatic carboxylic acids to nitriles in the presence of... 

The intramolecular version of palladium-catalyzed decarboxylative cross-coupling reaction of aromatic carboxylic acids with organic halides also worked well. For example, 2-bromophenyl-tethered benzoic acids 116 underwent cyclization in the presence of Pd(OAc)2/PPh3 and K2CO3 in NMP to give 117 in high yields (Scheme 22.27) [51]. A mechanism that involved a sequence of oxidative addition, cyclization of carboxylate 118, decarboxylation of 119, and reductive elimination was proposed. Indole-2-carboxylic acid 121 was also applicable to this type of cyclization. 

Decarboxylation reactions performed on activated or aromatic carboxylic acids, e.g., /1-keto acids, is a well-known synthetic transformation. However, the reaction has also been applied on other systems, e.g., N-carboxythiopyri-dones, N-acyloxyphthalimides and by thermolysis of peresters [104-106]. 

Reaction No. 5 (Table 11) is part of a synthetically useful method for the alkylation of aromatic compounds. At first the aromatic carboxylic acid is reductively alkylated by way of a Birch reduction in the presence of alkyl halides, this is then followed by an eliminative decarboxylation. In reaction No. 9 decarboxylation occurs probably by oxidation at the nitrogen to the radical cation that undergoes decarboxylation (see... 

The decarboxylation of aromatic acids is most often carried out by heating with copper and quinoline. However, two other methods can be used with certain substrates. In one method, the salt of the acid (ArCOO ) is heated, and in the other the carboxylic acid is heated with a strong acid, often sulfuric. The latter method is accelerated by the presence of electron-donating groups in ortho and para positions and by the steric effect of groups in the ortho positions in benzene systems it is... 

A. Joll, T. Huynh and A. Heitz, Off line tetramethylammonium hydroxide thermochemolysis of model compound aliphatic and aromatic carboxylic acids decarboxylation of some ortho and/ or para substituted aromatic carboxylic acids, J. Anal. Appl. Pyrol., 70, 151 167 (2003). 

Benzoic acid [65-85-0], C6H5COOH, the simplest member of the aromatic carboxylic acid family, was first described in 1618 by a French physician, but it was not until 1832 that its structure was determined by Wnfiler and Liebig. In the nineteenth century benzoic acid was used extensively as a medicinal substance and was prepared from gum benzoin. Benzoic acid was first produced synthetically by the hydrolysis of benzotrichloride. Various other processes such as the nitric acid oxidation of toluene were used until the 1930s when the decarboxylation of phthalic acid became the dominant commercial process. During World War II in Germany the batchwise liquid-phase air oxidation of toluene became an important process. 

Like the related fatty acid synthases (FASs), polyketide synthases (PKSs) are multifunctional enzymes that catalyze the decarboxylative (Claisen) condensation of simple carboxylic acids, activated as their coenzyme A (CoA) thioesters. While FASs typically use acetyl-CoA as the starter unit and malonyl-CoA as the extender unit, PKSs often employ acetyl- or propionyl-CoA to initiate biosynthesis, and malonyl-, methylmalonyl-, and occasionally ethylmalonyl-CoA or pro-pylmalonyl-CoA as a source of chain-extension units. After each condensation, FASs catalyze the full reduction of the P-ketothioester to a methylene by way of ketoreduction, dehydration, and enoyl reduction (Fig. 3). In contrast, PKSs shortcut the FAS pathway in one of two ways (Fig. 4). The aromatic PKSs (Fig. 4a) leave the P-keto groups substantially intact to produce aromatic products, while the modular PKSs (Fig. 4b) catalyze a variable extent of reduction to yield the so-called complex polyketides. In the latter case, reduction may not occur, or there may be formation of a P-hydroxy, double-bond, or fully saturated methylene additionally, the outcome may vary between different cycles of chain extension (Fig. 4b). This inherent variability in keto reduction, the greater variety of... 

In a process developed by Myers et al., aromatic carboxylic acids were directly employed as substrates for Heck olefinations, albeit in the presence of a large excess of silver carbonate [38]. This base both facilitates the decarboxylation step and acts as an oxidant, generating arylpalladium(II) intermediates. In related processes, arylphosphonic [39] and arylboronic acids [40] were used as aryl sources in the presence of an oxidant. 

The pyrazinecarboxylic acids have properties similar to the pyridinecarboxylic acids and aromatic carboxylic acids in general. The pKa of pyrazine-2-carboxylic acid is 2.92 it is thus considerably stronger than pyridine-2-carboxylic acid (pff0 5.52), and comparable in acidic strength to pyridazine-3-carboxylic acid (pKa 3.0). The pKa values of pyrazine-2,3-dicarboxylic acid are 0.9 and 3.57.231 Pyrazinecarboxylic acids form colored salts with Fe11 ions and they are readily esterified and decarboxylated. 

Radiolytic e.s.r. studies of the reactions of SO4, Cl2, and Brf radicals with organic compounds are currently being carried out in this laboratory by Fessenden et al. One of the interesting findings is the selective decarboxylation by SO4 radicals of certain aliphatic and aromatic carboxylic acids, whereas earlier studies with OH had shown that decarboxylation is not important in such cases. For example, it has been reported that the reaction of OH with malonic acid results mainly in hydrogen abstraction, with only 10% decarboxylation in acid solution and <0-5% in alkaline solution (Behar et al., 1973). 

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