Carboxylic acids as catalysts

Figure 4.10 is plot of the Bronsted relationship for hydrolysis of an enol ether. The plot shows that the effectiveness of the various carboxylic acids as catalysts is related to their dissociation constants. In this particular case, the constant a is 0.79 ... 

Phenolic esters (1) of aliphatic and aromatic carboxylic acids, when treated with a Lewis acid as catalyst, do undergo a rearrangement reaction to yield ortho- and para-acylphenols 2 and 4 respectively. This Fries rearrangement reaction is an important method for the synthesis of hydroxyaryl ketones. 

Addition of nucleophilic solvents such as alcohols and carboxylic acids can be effected by using strong acids as catalysts.10... 

When variable-valence metals are used as catalysts in the oxidation of hydrocarbons, the chain termination via such reactions manifests itself later in the process. This case has specially been studied in relation to the oxidation of paraffins to fatty acids in the presence of the K Mn catalyst [57], which ensures a high oxidation rate and a high selectivity of formation of the target product (carboxylic acids). As the reaction occurs, alcohols are accumulated in the reaction mixture, and their oxidation is accompanied by the formation of hydroxyperoxyl radicals. The more extensively the oxidation occurs, the higher the concentration of alcohols in the oxidized paraffin, and, hence, the higher is the kinetic... 

In a slightly less convenient procedure, but one which has general versatility, carbonylation of aryl (or vinyl) palladium compounds produces aryl, heteroaryl, and vinyl carboxylic acids. As with the other procedures, immediate upon its formation, the carboxylate anion migrates to the aqueous phase. Consequently, haloaromatic acids can be obtained from dihaloarenes, without further reaction of the second halogen atom, e.g. 1,4-dibromobenzene has been carbonylated (90% conversion) to yield 4-bromobenzoic acid with a selectivity for the monocarbonylation product of 95%. Additionally, the process is economically attractive, as the organic phase containing the catalyst can be cycled with virtually no loss of activity and ca. 4000 moles of acid can be produced for each mole of the palladium complex used [4],... 

In 1989, Rebek and co-workers reported a simple system based on Kemp s triacid that served as a mimic of an enolizing enzyme [86]. This early mimic, however, had the enolizing substrate covalently attached to the triacid skeleton. In addition, the mimic did not possess any oxyanion hole functionalities. However, 2 years later the Rebek group reported a true enolizing catalyst that hosted a carboxylic acid as the oxyanion hole component (Scheme 4.8) [87]. The rate of enolization of the quinuclidone substrate was enhanced by a factor of 10 in the presence of 2.5 mM of the receptor (R = n-Pr). 

Acylation of arenes. These mixed anhydrides have been used Tor acylation of arenes. However these reagents are sensitive to moisture and tend to disproportionate. One solution is to generate the reagents in situ. Thus acyl trifluoro-acetates can be generated in the presence of the arene from a carboxylic acid, TFAA, and 85% phosphoric acid (as catalyst) in CHjCN. Ketones of the type O II... 

One of the most characteristic types of ground-state reaction for alkenes is electrophilic addition, often involving a proton acid as addend or catalyst. In the excited state similar reactions can occur, with water, alcohols or carboxylic acids as commonly encountered addends. However, there is a variety of photochemical mechanisms according to the conditions or substrate used. In a few instances it is proposed that the electronically excited state is attacked directly by a proton from aqueous acid, for example when styrenes are converted to l-arylethanols (2.47 the rate constant for such attack is estimated to be eleven to fourteen orders of magnitude greater than that for attack on the ground state, and the orientation of addition is that expected on the basis of relativecarbonium ion stabilities (Markowni-kov addition). 

Apart from these synthetically impractical examples of hydrolysis of chloro-fluorocarbons, there are useful applications converting some chlorofluorocarbons to fluonnated carboxylic acids. As an alternative to the use of the highly corrosive fuming sulfuric acid, normally used in batch processes, a continuous hydrolytic process for converting 1,1,1-trichlorotrifluoroethane (CFC-113a), available by isomerization of CFC-113 [44], to trifluoroacetic acid has been developed [45] (equation 45). It uses metal chloride catalysts deposited on high-surface-area supports Unreacted CFC-113a can be recycled. 

During the preparation of these polyesters, considerable concentrations of carboxyl groups are probably present. This emphasizes the fact that this type of catalyst is compatible with an acid environment. As discussed above, carboxylic acids as well as the weakly basic aromatic amines were suitable initiators. However, more basic aliphatic amines acted as inhibitors of these catalysts. 

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

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... 

Finally a fourth way to achieve asymmetric induction in the Passerini reaction is by way of a chiral catalyst, such as a Lewis acid. This approach is not trivial since in most cases the Lewis acid replaces the carboxylic acid as third component, leading to a-hydroxyamides or to other kinds of products instead of the classical adducts 7 (vide infra). After a thorough screening of combinations of Lewis acids/ chiral ligands, it was possible to select the couple 13 (Scheme 1.6), which affords clean reaction and a moderate ee with a model set of substrates [17]. Although improvements are needed in order to gain higher ees and to use efficiently sub-stoichiometric quantities of the chiral inducer, this represents the first example of an asymmetric classical Passerini reaction between three achiral components. 

Chemical esterification methods use an alcohol and a carboxylic acid in the presence of a mineral acid as catalyst. Sulfuric acid, which is commonly used, leads to the formation of undesirable byproducts, requiring a difficult separation step (3). Moreover, in this case, the starting material is a high-value component (fatty acid). Consequently, researchers are interested in the alcoholysis reaction using a vegetable oil with low cost and largely produced in Brazil as a raw material for ester synthesis. 

Organoaluminum compounds are widely used in the production of polyolefines and stereoregular elastomers (as components of catalyst complex), as raw stock in the production of higher alcohols and carboxylic acids, as additives for reactive fuels, etc. 

Allylic oxidation (acyloxylation) can also be achieved with copper catalysts and stoichiometric amounts of peresters or an alkylhydroperoxide in a carboxylic acid as solvent [108], via a free radical mechanism (Fig. 4.40). The use of water-soluble ligands [109] or fluorous solvents [110] allows recycling of the copper catalyst. In view of the oxidants required, this reaction is economically viable only when valuable (chiral) products are obtained using asymmetric copper catalysts [111-113]. The scope of the reaction is rather limited however. 

In the compntation of Reaction 6.22, the lowest energy TS involves the imidazole as the proton donor and it leads to the major prodncL The lowest energy TS that leads to the minor prodnct involves the carboxylic acid as the donor. The predicted ee is 75 percent, in fine agreement with the experiment. This study should spur further exploration of tuning the stereoselectivity through catalysts with multiple binding opportunities. 

Monomers have been prepared in benzene solvent by Knoevanagel reaction between 4-vinyl benzaldehyde and malonic derivatives at room temperature, by use of two catalysts chosen according to the nature of compounds (Table I). For carboxylic acids as malonic or cyanacetic acids piperidine can be used for esters as ethylmalo-nate or ethyl cyanacetate piperidinium benzoate is prefered. 

Under neutral or basic conditions with palladium catalysts, another mechanism involving a carbalkoxy complex may operate (Scheme 3) [3]. It is proposed that reaction of an alcohol with a Pd" species forms a labile alkoxy complex. Coordination and insertion of CO into the Pd-0 bond yields the carbalkoxy complex. Insertion of an olefin into the Pd-C02R bond gives an alkyl complex which reacts with HX to yield predominantly the branched carboxylic acid as product, and to regenerate the Pd". 

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