Organic acids, acid-catalyzed esterification

The most apparent chemical property of carboxylic acids their acidity has already been examined m earlier sections of this chapter Three reactions of carboxylic acids—con version to acyl chlorides reduction and esterification—have been encountered m pre vious chapters and are reviewed m Table 19 5 Acid catalyzed esterification of carboxylic acids IS one of the fundamental reactions of organic chemistry and this portion of the chapter begins with an examination of the mechanism by which it occurs Later m Sec tions 19 16 and 19 17 two new reactions of carboxylic acids that are of synthetic value will be described... 

The kinetics of the acid-catalyzed esterification reaction of 2,4,6-trimethylbenzoic acid in i-PrOH under microwave irradiation have been investigated [84], A simple and practical technique for MW-assisted synthesis of esters has been reported wherein the reactions are conducted either on solid mineral supports or by using a phase transfer catalyst (PTC) in the absence of organic solvents [85], The esterification of enols with acetic anhydride and iodine has also been recorded [86],... 

In general, the acid catalyzed esterification of organic acids can be accomplished easily with primary or secondary alkyl or aryl alcohols, but tertiary alcohols usually give carbonium ions which lead to dehydration. The structure of the acid is also of importance. As a rule, the more hindered the acid is alpha to the carbonyl carbon the more difficult esterification becomes (20A). 

Reaction with Organic Compounds. Many organic reactions are catalyzed by acids such as HCl. Typical examples of the use of HCl in these processes include conversion of HgnoceUulose to hexose and pentose, sucrose to inverted sugar, esterification of aromatic acids, transformation of acetaminochlorobenzene to chloroaruHdes, and inversion of methone [1074-95-9]. 

The vapor-phase esterification of ethanol has also been studied extensively (363,364), but it is not used commercially. The reaction can be catalyzed by siUca gel (365,366), thoria on siUca or alumina (367), zirconium dioxide (368), and by xerogels and aerogels (369). Above 300°C the dehydration of ethanol becomes appreciable. Ethyl acetate can also be produced from acetaldehyde by the Tischenko reaction (370—372) using an aluminum alkoxide catalyst and, with some difficulty, by the boron trifluoride-catalyzed direct esterification of ethylene with organic acids (373). 

The concept of zeolite action was tested in a particular reaction where the enzyme is exposed from the beginning to an acidic environment the esterification of geraniol with acetic acid catalyzed by Candida antarctica lipase B immobilized on zeolite NaA [219]. Lipases have been used for the hydrolysis of triglycerides and due to their ambivalent hydrophobic/hydrophilic properties they are effective biocatalysts for the hydrolysis of hydrophobic substrates [220]. When water-soluble lipases are used in organic media they have to be immobilized on solid supports in order to exhibit significant catalytic activity. 

Many publications advocate the use of solid acid resins in esterification reactions. A comprehensive review of organic reactions catalyzed by resins is that of Harmer and Sun. However, thermal-stability above 140°C and lack of structural integrity at high pressures severely limit the applicability of organic resins as catalysts for esterification and transesterification. 

Ester synthesis of fatty acid ethyl ester. The lipase-catalyzed esterification of fatty acid and alcohol is well-known. It was also favorable for the esterification of poly unsaturated fatty acids under mild conditions with the enzyme. However, the activity of native lipase is lower in polar organic solvents, i.e. ethanol and methanol. The synthesis of Ae fatty acid ethyl ester was carried out in ethanol using the palmitic acid-modified lipase. As shown in Figure 7, the reactivity of the modified lipase in this system was much higher than that of the unmoditied lipase. 

The resolution of (7i,. S )-naproxen 54 using lipase-catalyzed esterification of the free acid with different diols and organic solvents was reported. The (.S)-naproxcn ester 55 was obtained in > 99 % ee when using 1,4-butandiol.79... 

Hydrolytic enzymes such as lipases catalyze hydrolysis of esters in aqueous media, but when used in non-aqueous media such as organic solvents, ionic liquids and supercritical fluids, they catalyze reverse reactions the synthesis of esters. For example, lipases in natural environment catalyze the hydrolysis of fatty acid esters as shown in Figure 6(a). However, when they are used in organic solvents, they catalyze the esterification reaction (Figure 6(b)). 

Topakas, E., H. Stamatis, P. Biely, D. Kekos, B J. Macris, and P. Christakopoulos. 2003. Purification and characterization of a feruloyl esterase from Fusarium oxysporum catalyzing esterification of phenolic acids in ternary water-organic solvent mixtures. J. Biotechnol. 102 33-44. 

Reaction mixtures are complex multicomponent systems, and their phase behavior is dictated by the composition of the mixture and operating conditions. Organic solvents present in the reaction medium as reagents may act as cosolvents and result in solute solubility enhancement (as discussed in Section 4.2). For example, the decrease in reaction rate observed at high ethanol concentrations for the lipase-catalyzed esterification of myristic acid + ethanol in SCCO2 has been, in part, attributed to the solubility enhancement of water, resulting in drying of the enzyme... 

Enzymes can also be used in sc carbon dioxide.185 A Pseudomonas lipase immobilized on silica gel gave better conversions and enantioselectivity in the acetylation of racemic alcohols with acetic anhydride than when used in organic solvents.186 The lipase-catalyzed esterification of glycidol gave 83% enantioselectivity, which is as favorable as when the reaction is run in organic solvents.187 An immobilized lipase has been used in the ethanolysis of cod liver oil.188 Another immobilized lipase has been used to convert oleic acid to various esters.189 The use of a lipase in sc carbon dioxide for analyses of fats in foods cuts solvent use by 98%.190 Polyesters have been made enzymatically in carbon dioxide.191... 

Further development of the SLM-ionic liquid methodology has been coupled with lipase-catalyzed esterification and ester-hydrolysis reactions in the feed gas (interface 1) and receiving phase (interface 2), respectively, to facilitate selective transport of various organic acids with aryl groups (via their esters) from aqueous solutions by utilizing different substrate specificity of lipases in a SLM system (Fig. 5.6-11) [118]. In the enzymatic SLM systems a poly(propene) membrane with water-immiscible [RMIM][X] (R = butyl, hexyl, octyl and X = [PFe]" and [(CF3S02)2N] ) ionic liquid phases were used. 

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