Ester formation product removal

Lipases are enzymes that catalyze the in vivo hydrolysis of lipids such as triacylglycerols. Lipases are not used in biological systems for ester synthesis, presumably because the large amounts of water present preclude ester formation due to the law of mass action which favors hydrolysis. A different pathway (using the coenzyme A thioester of a carboxylic acid and the enzyme synthase [Blei and Odian, 2000]) is present in biological systems for ester formation. However, lipases do catalyze the in vitro esterification reaction and have been used to synthesize polyesters. The reaction between alcohols and carboxylic acids occurs in organic solvents where the absence of water favors esterification. However, water is a by-product and must be removed efficiently to maximize conversions and molecular weights. 

All the steps in ester formation are reversible, but the equilibrium in the C-O bond-making and -breaking processes are not very favorable, and an excess of one reactant (usually the alcohol) or removal of one product (most often water) is required to give a good yield of ester. 

While still useful for large-scale esterification of fairly robust carboxylic acids, Fischer esterification is generally not useful in small-scale reactions because the esterification depends on an acid-catalyzed equilibrium to produce the ester. The equilibrium is usually shifted to the side of the products by adding an excess of one of the reactants—usually the alcohol—and refluxing until equilibrium is established, typically several hours. The reaction is then quenched with base to freeze the equilibrium and the ester product is separated from the excess alcohol and any unreacted acid. This separation is easily accomplished on a large scale where distillation is often used to separate the product from the by-products. For small-scale reactions where distillation is not a viable option, the separation is often difficult or tedious. Consequently Fischer esterification is not widely used for ester formation in small-scale laboratory situations. In contrast, intramolecular Fischer esterification is very effective on a small scale for the closure of hydroxy acids to lactones. Here the equilibrium is driven by tire removal of water and no other reagents are needed. Moreover the closure is favored entropically and proceeds easily. 

In addition to feeding of components into the reactor, if the sign on v(f) is negative, products are continuously removed, for example, reactive distillation. This is done for reactions (1) that reveal product inhibition, that is, the product slows the reaction rate, (2) that have a low equilibrium constant (removal of product does not allow equilibrium to be reached), or (3) where the product alters the reaction network that is proceeding in the reactor. A common class of reactions where product removal is necessary is ester formation where water is removed. 

Active ester formation by the mixed anhydride method is accompanied by the side reaction of esterification at the carbonate moiety of mixed anhydride 51 which generates mixed carbonate 52 (Scheme 12).This decreases the yields, but is more of a nuisance than an obstacle as the side products do not interfere with crystallization of the esters as the former are soluble in the crystallizing solvent. More mixed carbonate is formed from derivatives of the hindered amino acids and proline none is formed from a-unsubstituted acids. A-Hy-droxysuccinimide gives rise to much less byproduct than 4-nitrophenol other phenols generate intermediate amounts. Less byproduct is generated when the reagent is isopropyl chloroformate. The impurity can be readily removed from a solution of the ester by adsorption of the compounds on reverse-phase chromatography beads followed by separation by selective displacement. ... 

Effect of Acyl Donors. TTie synthesis of glucose fatty acid esters was investigated with continuous by-product removal in a stirred-tank membrane reactor by azeotropic distillation using EMK containing 20% hexane as reaction solvent and different fatty acids as acyl donors. From previous studies on the lipase-catalyzed synthesis of glucose esters in a solid-phase system (17,19,22,23), it was already known that the fatty acid chainlength had a considerable influence on product formation. This was due... 

Acylation of cellulose by transesterification involves reaction of the cellulose alcohol with an ester, leading to an equilibrium that can be displaced toward ester formation by the removal of one of the products obtained. Heinze et have prepared such cellulose esters by very effective transesterification reactions (Fig. 37). 

The mechanism is very similar to the mechanism of ester formation. Notice the second molecule of ammonia, which removes a proton, and the loss of chloride ion—the leaving group—to form the amide. Ammonium chloride is formed as a by-product in the reaction. 

Another interesting use of reaction solvents is frequently made in reactions that involve an equilibrium in which one of the products is water (e.g., ester formation, enamine synthesis, dehydration of hydrates). Under these circumstances, selection of a solvent such as benzene or carbon tetrachloride permits the rapid removal of the water on a continuous basis by azeotropic distillation (see Sec. 1.8.3). 

As an alternative to landfilling or high-temperature incineration, the acid-catalyzed decomposition in alcohol efficiently and safely converts the composite materials to alkyl levulinate at moderate temperatures. The product composition obtained by heating particle board chips in ethanol with sulforic acid catalyst for 30 min at 200°C was similar to that obtained from ordinary wood treatment. The charcoal product was removed by filtration the ethanol, water, and ethyl formate product flash-distilled and the ester levulinate separated from the resinous product by extraction into diethyl ether. In this case, the resinous products also contained the UF binding resins that were initially present in the waste board. The UF resin-derived components were intimately mixed with or chemically attached to the lignin resin there was no way to extract and separate the lignin from the UF component. 

In acid-catalyzed esterification reactions (an esterification is a reaction that produces an ester), the alcohol part of the ester is commonly used as the solvent for alcohols with low boiling points. In the conversion of 21 70, butanol is used as the solvent to generate the butyl ester. Formation of an ethyl ester would use ethanol as a solvent and formation of a methyl ester would use methanol. If an ester is formed from an alcohol with a high boiling point, a solvent such as benzene or toluene is often used and an excess of the alcohol is then added to that solvent. Azeotropic distillation (Chapter 18, Section 18.6.3) using these solvents allows removal of the water product and facilitates formation of the ester. 

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