Aromatic carboxylic acids, decarboxylations,

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). 

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... 

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

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. 

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. 

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. 

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. 

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... 

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). 

The sulfur monomeric radical cations (X-S -Y-COOH) were formed from direct ionization of the sulfur atom in parental aromatic carboxylic acids. These X-S -Y-COOH were found to decay by three competitive pathways (i) fragmentation via the cleavage of the C-S bond producing thiyl-type radicals XS, (ii) deprotonation from the methyl/methylene groups adjacent to the sulfur producing a-(alkylthio)alkyl radicals, and (iii) decarboxylation producing C-centered radicals (for phenylthioacetic acid, vide Scheme 6). The efficiency of each pathway is dependent on the structure of the aromatic carboxylic acid studied. 

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... 

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 ... 

Carboxylic acids that are difficult to decarboxylate comprise in particular the aliphatic acids and simple aromatic carboxylic acids. They can be decarboxylated only by pyrogenic decomposition of their salts in admixture with an alkali hydroxide or lime. In such mixtures an additional charge produced on the carboxyl group makes it possible, by induction, to remove the group R as an anion ... 

The acid derivative of the unknown yields a hydrocarbon (CeHe) in a sodium hydroxide fusion reaction. Since sodium hydroxide fusion is a decarboxylation mechanism for aromatic carboxylic acid, the acid derivative is benzoic acid. This is confirmed by the fact that catalytic hydrogenation of CsHe yields CeHia/ which is the formula for cyclohexane. ... 

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

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

The photoreduction of the above dye, 5,7-diiodo-3-pentoxy-9-fluorenone, in the presence of (phenylthio)-acetic acid and its tetrabutylammonium salt occurs via a photoinduced electron transfer process. On the basis of the known photochemistry of sulfur-containing aromatic carboxylic acids, it is postulated that the existence of the carboxyl group in an ionic form allows a rapid decarboxylation, yielding a neutral very reactive a-alkylthio-type radical (R-S-CH2 ). 

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]. 

An alternative solution to the limitations of the aryl carboxylate salts mentioned previously is a new bimetalhc catalyst system that allows the replacement of aryl hahdes by aryl triflates [14, 67]. The reaction proceeds efficiently with Pdl, Tol-BINAP, Cu O, and 1,10-phenanthroline, affording the corresponding unsymmetrical biaryls (Scheme 22.47). It is noteworthy that the reaction is generally applicable to aromatic carboxylic acid salts, regardless of their substitution pattern. The use of microwave irradiation has proved beneficial for this ARCIS reaction, since under these conditions the Pd(ll) catalyst is almost instantaneously reduced to Pd(0) [68]. Similarly, substituted aryl tosylates have been found to be suitable substrates in decarboxylative couphng reactions with a fuU range of benzoic acids (Scheme 22.47) [69]. 

The ease of therm d decarboxylation has been related to the strength of the acid, that is, the greater the addity, the faster it loses Therefore, the effect of the NHg group at an ortho or para position in aromatic carboxylic acids is expected to inhibit this type of decomposition. The actual results show the opposite to be true and this contradiction is explained on the basis of intramolecular cat2dytic action of the amino groups in the aminobenzoic acids. 

Scheme 3.14 Decarboxylative homocoupling of (hetero)aromatic carboxylic acids, as described by Larrosa...

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