Synthesis of esters

Esters are commonly synthesized from carboxylic acids by reaction of the acid with an excess of alcohol containing a catalytic amount of a mineral acid. In cases where practical considerations dictate it, the acid can be converted to an acyl halide (usually the chloride) and then condensed with the appropriate alcohol. A less commonly used procedure involves direct alkylation of the carboxylate ion with an alkyl halide. Even when this latter procedure (Eq. 6.1) involves a silver carboxylate and alkyl chloride, the reaction is of marginal practical value. 

The phase transfer method facilitates the dissolution of carboxylates in nonpolar media. In these solutions, due to relatively poor solvation of anions, carboxylate is an effective nucleophile and reacts readily with alkyl halides. The catalysis of such reactions by amines, ammonium salts and crown ethers and the synthesis of esters by the phase transfer technique is the subject of this chapter. 

Esters can be synthesized by reacting carboxylic acids with alcohols, in the presence of acid catalysts. 

Such dearomatization and aromatization of these electron-rich hgand systems in cooperation with metal centers present new opportunities for homogeneous catalysis. 

Esterification is an important reaction in organic synthesis. It has an assortment of applications in the production of synthetic intermediates, biologically active natural products, fragrances, polymers, polyesters, plasticizers, fatty acids, paints, and pharmaceuticals. Environmentally benign esterification methods catalyzed by pincer complexes that operate via metal-Hgand cooperation are described in this section. 

Esterases of LAB can also catalyze the direct synthesis of esters from glycerides and alcohols via a transferase reaction (alcoholysis) in aqueous systems, that is the transfer of fatty acyl groups from glycerides to alcohols. This topic requires further research (Holland et al. 2005), as well as the pathways of formation of other lipid-derived aroma compounds in LAB. 

A range of acids and alcohols are generated from the different pathways detailed above, thereby providing potential substrates for esterification reactions. Many esters, most generally associated with fruity flavors, are found in fermented foods. LAB esterases can catalyze the formation of esters from acids and alcohols (Liu et al. 2004 Holland et al. 2005). In cheese, acids are present in relatively high concentrations (10 to 10 pg/g), while ethanol, the main alcohol detected (McGugan et al. 1975), is present in low amounts. Ethanol has been shown to be in concentrations limiting the synthesis of ethyl esters in cheeses such as Emmental (Richoux et al. 2008) and Cheddar cheese (Urbach 1995 Liu et al. 2004). 

Interspecies and Intraspedes Variations of Aroma Compound Production 

Flavor-related activities of LAB depend on the species, with some specific activities found only in a small number of species. The branched-chain a-keto acid decarboxylase activity involved in the formation of malty branched-chain aldehydes from branched-chain AA, for example, has been found only in L lactis and not in the Lactobacillus and Leuconostoc strains tested (Fernandez De Palencia et al. 2006). Most LAB, however, display a great strain-to-strain variability, on the genomic level and/or at the phenotypic level. Table 19.3 gives some examples of intra- and interspecies variability of flavor-related LAB properties, such as proteolytic activities, AA-converting enzymatic activities, ester synthesis, and autolysis. 

Gene or activity targeted, conditions Main results 

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Alcohols. The direct synthesis of esters by dehydrogenation or oxidative hydrogenation of alcohols offers a simple method for the preparation of certain types of esters, such as ethyl acetate (96—98) ... 

BAEYER VILLIQER Ketone Oxidation Synthesis of esters or lactones trom ketones with retention of configuration... 

Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

The specificity of enzyme reactions can be altered by varying the solvent system. For example, the addition of water-miscible organic co-solvents may improve the selectivity of hydrolase enzymes. Medium engineering is also important for synthetic reactions performed in pure organic solvents. In such cases, the selectivity of the reaction may depend on the organic solvent used. In non-aqueous solvents, hydrolytic enzymes catalyse the reverse reaction, ie the synthesis of esters and amides. The problem here is the low activity (catalytic power) of many hydrolases in organic solvents, and the unpredictable effects of the amount of water and type of solvent on the rate and selectivity. 

Only a few building blocks are available for the synthesis of ester-containing rigid mesogenic units, namely dihydroxy-, dicarboxy-, or (hydroxy, carboxy)-l,4-phenylenes, 4,4,-biphenylenes, and 2,6-, 1,4-, or 1,5-naphthylenes (Table 2.15). 

Wiskur SL, Fu GC (2005) Catalytic asymmetric synthesis of esters from ketenes. J Am Chem Soc 127 6176-6177... 

The application of / -(diphenylphosphinyl)benzenesulphonic acid (58) to the synthesis of esters of amino-acids has made the work-up much simpler, since the resultant oxide is water-soluble. Diphenylphosphinyl isocyanate (59) can be prepared from diphenylphosphinic amide. 

Activated esters of halogenated alcohols, such as 2-chloroethanol, 2,2,2-trifluoroethanol, and 2,2,2-trichloroethanol, have been often used as substrate for enzymatic synthesis of esters, owing to an increase in the electrophilicity (reactivity) of the acyl carbonyl and avoid significant alcoholysis of the products by decreasing the nucleophilicity of the leaving alcohols. ... 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

The reaction of a carboxylic acid with N,Af -carbonyldiimidazolellH33 (abbreviated as CDI), forming an imidazolide as the first step followed by alcoholysis or phenolysis of the imidazolide (second step), constitutes a synthesis of esters that differs from most other methods by virtue of its particularly mild reaction conditions.t41,[5] It may be conducted in two separate steps with isolation of the carboxylic acid imidazolide, but more frequently the synthesis is carried out as a one-pot reaction without isolation of the intermediate. Equimolar amounts of carboxylic acid, alcohol, and CDI are allowed to react in anhydrous tetrahydrofuran, benzene, trichloromethane, dichloromethane, dimethylformamide, or nitromethane to give the ester in high yield. The solvents should be anhydrous because of the moisture sensitivity of CDI (see Chapter 2). Even such unusual solvent as supercritical carbon dioxide at a pressure of 3000 psi and a temperature of 36-68 °C has been used for esterification with azolides.[6]... 

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],... 

Used industrially as a chemical intermediate for the synthesis of esters, manufacture of varnish, as a tanning agent, and as a food additive (flavor). 

Various nucleophiles other than methanol can be introduced onto the carbonyl carbon. Anodic oxidation of acylsilanes in the presence of allyl alcohol, 2-methyl-2-propanol, water, and methyl /V-methylcarbamate in dichlorometh-ane affords the corresponding esters, carboxylic acid, and amide derivatives (Scheme 24) [16]. Therefore, anodic oxidation provides a useful method for the synthesis of esters and amides under neutral conditions. 

Lipases can catalyze hydrolysis of esters, synthesis of esters, trans-esterification, and synthesis of some polymers. They have been applied in many fields including the food industry, fine chemistry, and the pharmaceutical industry. The low stability of native lipases makes them unsuitable for industrial applications. In order to use them more economically and efficiently, their operational stability can be improved by immobilization. Numerous efforts have been focused on the preparation of lipases in immobilized forms involving a variety of both support materials and immobilization methods [278],... 

Dynamic Kinetic Resolution for the Synthesis of Esters, Amides and Acids Using Lipases... 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

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