Benzoic acid, aerobic oxidation

The recent synthesis of (—)-tetracycline by Myers and co-workers incorporates a biocatalytic step in the first stage which oxidizes benzoic acid aerobically to an a,f)-dihydroxy derivative in the presence of a whole-cell mutant strain of Alcaligenes eutrophus. Figure 4.61 shows a reduced tree diagram for the synthesis and Table 4.28 summarizes the metrics parameters. 

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

Formation of benzoic acid has not been observed. These results clearly suggest that in the aerobic oxidation of neat ethylbenzene the cubane complexes cobalt(III) are involved as the catalytic species. 

Recently the Co/Mn/N-hydroxyphthalimide (NHPI) systems of Ishii have been added to the list of aerobic oxidations of hydrocarbons, including both aromatic side chains and alkanes. For example, toluene was oxidized to benzoic acid at 25°C [125] and cyclohexane afforded adipic acid in 73% selectivity at 73% conversion [126], see Fig. 4.46. A related system, employing N-hydroxysac-charine, instead of NHPI was reported for the selective oxidation of large ring cycloalkanes [127]. 

Industrially performed catalytic oxidation reactions often suffer from drawbacks such as poor conversion and selectivity due to overoxidation, corrosive reaction media, lack of solvent and catalyst recycling, and negative environmental impact due to evaporation of the solvents. In order to provide a methodology that addresses these problems, ionic liquids have been investigated as reaction media. For example, the aerobic oxidation of benzyl alcohol and alkylbenzene to benzaldehyde and benzoic acids was performed in l-butyl-2,3-dimethylimidazolium tetrafluoroborate ([C4dmim][BF ]) using palladium and cobalt complexes respectively [34, 35]. 

This substantiates the positive role of O2 in promoting benzaldehye and benzoic acid formation. From the above-mentioned two examples, it is apparent that there are many parallel reactions in the aerobic oxidation of benzyl alcohol, besides the direct dehydrogenation of benzyl alcohol to benzaldehyde, which result in the undesired by-products. On the basis of these studies and other literature evidence, a network of reactions occurring during the aerobic oxidation of benzyl alcohol over Pd/AljOj catalyst is presented in Scheme 12.1. After elucidating the mechanisms of reactions that lead to by-products, the next step in catalyst development is the complete elimination or at least suppression of these byproducts. It is logical to assume that all these reactions may not have the same active sites, and it is important to identify the different active sites for different reactions. 

Aerobic oxidation of alkylbenzenes is a promising subject in industrial chemistry. Many bulk chemicals such as terephthalic acid, phenol, benzoic add, and so on are... 

D-Aspariic Acid Oxidase. Still et al. reported that rabbit kidney and liver contain a soluble enzyme which catalyzes the aerobic oxidation of D-aspartate to oxalacetate plus NH3 with the formation of hydrogen peroxide. In a later study by Still and Sperling the D-aspartic acid oxidase was resolved and reactivated by the addition of FAD. The purified enzyme showed about one-sixth the activity with D-glutamate this, according to these workers, is best explained by the presence of a D-glu-tamic acid oxidase. The activity of n-aspartic acid oxidase is higher than that of D-amino acid oxidase in rabbit kidney and liver, and they are of the same order of activity in pig kidney. In contrast to pig kidney o-amino acid oxidase, which is inhibited by benzoic acid, the D-aspartic acid oxidase was unaffected. 

Methyl benzoate is formed from the 4-ethyl-4-iodo-l-methyl-l//-l,2,4-triazole-catalysed aerobic oxidation of benzaldehyde in THE in the presence of 1,8-diazabycyclo[5.4.0]undec-7-ene (DBU) and methanol. Benzoic acid is the oxidation product if the reaction is performed in the presence of water instead of the alcohol. These reactions are not reconciled with either oxidative or oxygenative mechanism... 

The product particles catalyzed the oxidation of several alcohols in aqueous media under aerobic and mild conditions. For example, benzyl alcohol was transformed quantitatively into benzoic acid in Ih ([benzyl alcohol] = 16.7mM, [Au] = 0.33mM, [KOH] = 50mM, at 27 C, in water). It should also be noted that the star-protected particles exhibited... 

It is only very recently that rhodium-based catalytic systems have been described in efficient oxidative olefination reactions. Inspired by the work of Satoh and Miura on rhodium/copper-catalyzed aerobic oxidative coupling of benzoic acids with internal allqmes or acrylates (Scheme 9.11), Glorius and co-workers described, in 2012, a rhodium-catalyzed directing group assisted olefination of 2-aryloxazolines under air. This method, which necessitated rhodium, silver and copper metal sources, afforded the desired olefin-oxazoline products in moderate-to-good yields (Scheme 9.12). 

Efforts have been made since then to develop new catalytic protocols for the oxidation of alcohols with molecular oxygen as the sole oxidant in water. For instance, the water-soluble Pd(II)-biquinoUne 57 was demonstrated to be efficient for aerobic oxidation of primary and secondary alcohols in water [154]. With a catalyst loading of 1 mol%, secondary alcohols led to ketones in high yields (85-100%), while aliphatic primary alcohols were fully oxidized to the corresponding acids, and benzyl alcohols were transformed to pure benzoic acid or benzaldehydes with a relatively low amount of acids formed. 

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