Esterification, mechanism methods

Esters can be hydrolyzed to carboxylic acids under either acidic or basic conditions. Under acidic conditions the mechanism is the exact reverse of the Fischer esterification mechanism shown in Figure 19.3. Again, because the acid and the ester have comparable reactivities, some method must be used to drive the equilibrium toward the desired product—the acid in this case. This can be accomplished by using water as the solvent, providing a large excess of this reagent that, by Le Chatelier s principle, shifts the equilibrium toward the carboxylic acid. 

I. Dhimitruka, J. Santa Lucia Jr, Investigation of the Yamaguchi esterification mechanism. Synthesis of a lux-s enzyme inhibitor using an improved esterification method, Org. Lett. 2006, 8, 47-50. 

Depending on the requirements of the chemical procedure, the processing method may be varied with different mechanical arrangements to remove the by-product, water, in order to drive the esterification reaction toward completion. 

The direct action of nitric acid and its mixtures on the parent alcohol is by far the most important method for the production of nitrate esters on both an industrial and laboratory scale." While such reactions are essentially esterifications they are commonly referred to as 6>-nitrations because the reaction mechanism, involving substitution of hydrogen for a nitro group, is not dissimilar to other nitrations and frequently involves the same nitrating species. 

This method is called the Fischer esterification. It s a condensation reaction where the loss of a water molecule accompanies the joining of the alcohol portion to the acid portion. The acid gives up the OH and the alcohol gives up the H to make the water molecule. All steps in the mechanism are reversible (that is, it establishes an equilibrium), so removing the ester as soon as it forms is helpful. Removal of the ester is normally easy since esters typically have lower boiling points than alcohols and carboxylic acids. Figure 12-20 illustrates the mechanism for the acid-catalyzed formation of an ester by the reaction of an alcohol with a Ccirboxylic acid. 

As appears from the examination of the equations (giving the best fit to the rate data) in Table 21, no relation between the form of the kinetic equation and the type of catalyst can be found. It seems likely that the equations are really semi-empirical expressions and it is risky to draw any conclusion about the actual reaction mechanism from the kinetic model. In spite of the formalism of the reported studies, two observations should be mentioned. Maatman et al. [410] calculated from the rate coefficients for the esterification of acetic acid with 1-propanol on silica gel, the site density of the catalyst using a method reported previously [418]. They found a relatively high site density, which justifies the identification of active sites of silica gel with the surface silanol groups made by Fricke and Alpeter [411]. The same authors [411] also estimated the values of the standard enthalpy and entropy changes on adsorption of propanol from kinetic data from the relatively low values they presume that propanol is weakly adsorbed on the surface, retaining much of the character of the liquid alcohol. 

This is formally the reverse of the BA1,1 cleavage of an ester, and is the only one-stage mechanism for ester formation available for the ionized carboxyl group. Numerous methods are, of course, available which involve initial electrophilic attack on the carboxylate group, followed by a displacement at the carbonyl carbon atom of the intermediate formed, which is often an anhydride. An example134 is the esterification of carboxylic acids in the presence ofp-toluenesulphonyl chloride in pyridine, viz-... 

The combination of carboxyl activation by a carbodiimide and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols.10 The reaction proceeds at room temperature. Carbodiimides are widely applied in the synthesis of polypeptides from amino acids. The proposed mechanism for this esterification reaction involves activation of the acid via isourea 28 followed by reaction with another acid molecule to form anhydride... 

Although the previous two sections of this chapter emphasized hydrolytic processes, two mechanism that led to O or N-acylation were considered. In the discussion of acid-catalyzed ester hydrolysis, it was pointed out that this reaction is reversible (p. 654). Thus it is possible to acylate alcohols by acid-catalyzed reaction with a carboxylic acid. This is called the Fischer esterification method. To drive the reaction forward, the alcohol is usually used in large excess, and it may also be necessary to remove water as it is formed. This can be done by azeotropic distillation in some cases. 

In the case where liquid chromatography is not available, acidic herbicides need to be derivatized because they can dissociate in water and are not usually volatile to be analyzed by gas chromatography. The basic methods used for chlorophenoxy acid herbicides are esterification, silylation, and alkylation, as described in a recent exhaustive review.The derivatization step is performed after preconcentration and cleanup. The step consists of the formation of esters and ethers from the carboxyl and phenol groups of the acidic herbicides. A lot of reagents and chemical mechanisms can be used to perform derivatization reactions. The most employed derivatization reagents are diazomethane, methyliodide, trimethylsulfonium (or anilinium) hydroxide, bis (trimethylsilyl) trifluoroacetamide (BSTFA), pentafluorobenzyl bromide, and anhydride acetate. It should be noted that explosive and hazardous diazomethane was replaced by safer agents. Authors also underline that surface water generally contains humic substances, which can interfere with the derivatization reaction. ... 

Also, one might expect that many met catalysts would have a very high site density, perhaps near 10 cm In 1966 Horiuti and coworkers ( ), using a method we showed ( ) is almost equivalent to the TST method, examined the reported data for 66 metal-catalyzed reactions. They found their assumptions to be valid. (Miyahara, one of Horiuti s coworkers, and Kazusaka later (50) modified the method to take variable orders into account.) Again, a very high site density is required for the postulated mechanism of isopropanol-acetic acid esterification over silica gel, as reported by Fricke and Altpeter ( M). We showed (52), that such a high value for the site density is obtain usjng TST. 

A useful method for preparing enol-acetates from uracil 4-keto-nucleosides uses dimethyl formamide diethyl acetal followed by acetic anhydride 2-keto isomers, or N-3-substituted analogues, did not react. Further studies supported a mechanism involving 0-4 esterification of the nucleoside followed by enoliza-tion, which is intramolecularly catalysed by the dimethylamino group, as illustrated in (63). 

First of all, we collected the main techniques used in the kinetic studies of the reaction (reaction procedures, analytical methods, treatment of experimental data). In fact, unambiguous results can be obtained only if some basic conditions are observed. The survey of the literature shows a great diversity of the catalysts used in epoxy-carboxy esterifications or polyesterifications however, at least in the case of kinetic studies, tertiary amines and ammonium salts are largely predominant. From the fundamental studies carried out with organic models, and mostly in solution, several mechanisms were proposed involving the formation of a complex which can be cyclic or not. 

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