Catalysed esterification

In the presence of an added catalyst such as p-toluenesulphonic acid, simple esterification reactions and polyesterification reactions are second order [48]. Thus the kinetics of the catalysed reaction of lauric acid and lauryl alcohol in a medium of lauryl laurate closely parallels those of the polymer-forming reaction between adipic acid and 1,10-dodecanediol in a medium of polyester product. Second-order rate coefficients for the two reactions were [35], respectively, 45x10 equiv kg sec and 16 X 10 equiv kg sec . 

The catalysed reaction can be analysed in a general fashion, allowing for simultaneous occurrence of catalysed and uncatalysed reactions. Thus, if 

In cases where this equation was applied [35], an approximate value was first found for fe2 by treating the reaction as if it were pure second order. This value was then combined with values for found independently, at the same temperature and in the absence of catalyst. The result was that the first term in the integrated equation was insignificant in comparison with the last two, so that the reaction could justifiably be treated as a simple second-order process. 

The polycondensation of adipic acid and diethylene glycol catalysed by p-toluenesulphonic acid was thus shown to be second order over a wide range of molecular weights [48, 54]. During the initial portions of the reaction the kinetics were more complex, perhaps because of changes in the character of the reaction medium. 

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Continuous lipase catalysed esterification of oleic acid... 

Figure 4.4 Continuous two-phase hpase catalysed esterification of oleic acid in the CCS (a) Both phases once through, (b) Aqueous phase full recycle organic phase 90% recycle.

The reaction mechanism for the heterogeneous and homogeneous acid-catalysed esterification were reported to be similar (17). However, there is a major difference concerning the snrface hydrophobicity. Reaction pockets are created inside a hydrophobic environment, where the fatty acid molecules can be absorbed and react further. Water molecules are unlikely to be absorbed on sites enclosed in hydrophobic areas. 

Helminen J, Leppamaki M, Paatero E and Minkkinen (1998) Monitoring the Kinetics of the Ion-exchange Resin Catalysed Esterification of Acetic Acid with Ethanol Using Near Infrared Spectroscopy with Partial Least Squares (PLS) Model, Chemometr Intell Lab Syst, 44 341. 

Solid Acid Catalysed Esterification of Amino Acids and Other Bio-Based Acids... 

The acid supplies proton which catalyses esterification. 

The combined catalysis by 18-crown-6 and tetra-n-butylammonium bromide produces higher yields in shorter reaction times than either of the catalysts separately (Table 3.7) [21] and almost quantitative yields have been reported for solid solid liquid triphase catalysed esterification using silica impregnated with tetramethylammonium chloride [22]. 

Resin-catalysed esterification of carboxylic acids (Table 3.10)... 

Phase-transfer catalysed esterification of alcohols and phenols with acid chlorides... 

Before we turn to "mechanisms" let us repeat how a catalyst works. We can reflux carboxylic acids and alcohols and nothing happens until we add traces of mineral acid that catalyse esterification. We can store ethene in cylinders for ages (until the cylinders have rusted away) without the formation of polyethylene, although the formation of the latter is exothermic by more than 80 kjoule/mol. We can heat methanol and carbon monoxide at 250 °C and 600 bar without acetic acid being formed. After we have added the catalyst the desired products are obtained at a high rate. 

M. Blanco and D. Serrano, On-hne monitoring and quantihcation of a process reaction by near-infrared spectroscopy. Catalysed esterification of butan-l-ol by acetic acid. Analyst, 125, 2059-2064 (2000). 

Note that in nature, these are all enzyme-catalysed reactions. This makes the reactions totally specific. It means possible competing Sn2 reactions involving attack at either of the two methylene carbons in SAM are not encountered. It also means that where the substrate contains two or more potential nucleophiles, reaction occurs at only one site, dictated by the enzyme. The enzymes are usually termed methyltransferases. Thus, in animals an A-methyltransferase is responsible for SAM-dependent A-methylation of noradrenaline (norepinephrine) to adrenaline (epinephrine), whereas an O-methyltransferase in plants catalyses esterification of salicylic acid to methyl salicylate. 

Most hterature references to pharmaceutical primary process monitoring are for batch processes, where a model of the process is built from calibration experiments [110, 111]. Many of these examples have led to greater understanding of the process monitored and can therefore be a precursor to design of a continuous process. For example, the acid-catalysed esterification of butan-l-ol by acetic acid was monitored through a factorial designed series of experiments in order to establish reaction kinetics, rate constants, end points, yields, equilibrium constants and the influence of initial water. Statistical analysis demonstrated that high temperatures and an excess of acetic acid were the optimal conditions [112]. 

Lipase-catalysed esterification instead of ester hydrolysis is also being used, a.o. by Glaxo Wellcome for a kinetic resolution that yields (IS, 2. -tranx-2-methoxycyelo-... 

Lipase-catalysed esterification and transesterification reactions have a wide range of applications in the synthesis of aroma compounds. 

In the literature concerning solid-catalysed esterifications, kinetic studies of other ester-forming reactions are scarcely reported. Reactions of... 

Fig. 15. Taft correlation with steric substituent constants (Es) in the vapour phase esterification of carboxylic acids with ethanol over Na-poisoned silica—alumina at 250°C ( ) [126] and in homogeneous acid-catalysed esterification at 40°C (°) [419], Acids 1, acetic, 2, propionic, 3, butyric, 4, isobutyric, 5, isovaleric, 6, pivalic, 7, 2-ethylbutyric.

The homogeneous acid-catalysed esterification has been thoroughly studied and a lot of information on its mechanism has been accumulated. The assumed close relation to the heterogeneous mechanism can, therefore, be made use of in mechanistic considerations about the esterification catalysed by ion exchangers. 

In most homogeneously catalysed esterifications, the protonated species is considered to be formed from the acid (or from the ester in transesterification) [397,398,467]. Starting with this view, Bochner et al. [449] assumed a mechanism for heterogeneous esterification [see eqn. 

GeloPujic, M., Guibejampel, E., Loupy, A., Galema, S.A. and Mathe, D., Lipase-catalysed esterification of some alpha-D-glucopyranosides in dry media under focused microwave irradiation, /. Chem. Soc., Perkin Trans. 1, 1996, 2777. 

The acid-catalysed esterification reaction usually proceeds via an acyl-oxygen fission process. This involves the cleavage of the bond between the original carbonyl-carbon atom and an oxygen of an hydroxyl group in the intermediate (6) arising from nucleophilic attack by an alcohol molecule on the pro-tonated carboxylic acid group (5). 

The process of acid-catalysed esterification in the presence of benzene, or, better, of toluene, is greatly facilitated if the water produced in the reaction is removed by distillation in a Dean and Stark water separation unit. This allows the separation and removal of water from the azeotrope, the organic phase being returned continuously to the reaction flask. Examples are provided in Expt 5.145. These include examples of the synthesis of esters where either the alcohol... 

Marty, A. Chulalaksananukul, Condoret, J. S. Willemot, R. M. Durand, G. Comparison of Lipase-Catalysed Esterification in Supercritical Carbon Dioxide and in w-Hexane. Biotechnol. Lett. 1990, 12, 11-16. 

N. R. Pedersen, R. Wimmer, J. Emmersen, P. Degn, and L. H. Pedersen, Effect of fatty acid chain length on initial reaction rates and regioselectivity of lipase-catalysed esterification of disaccharides, Carbohydr. Res., 337 (2002) 1179-1184. 

Table 2.1 Lipase-catalysed esterification of 4,6-O-benzylidene glycopyranosides...

Figure 3.11 Solvent-free, acid catalysed esterification [PTSA = p-toluenesulfonic acid ...

Microwave heating and catalysis have been successfully used in the solvent-free synthesis of cosmetic fatty esters (Villa et al., 2003). Two kinds of reaction were performed acid-catalysed esterification (Figure 3.11) and phase-transfer catalysed alkylations, both reactions affording near quantitative yields when microwave heating was used. It should be noted that diethyl ether and water were used in the purification of the product, and alternative purification/separation procedures would be required if this process was performed on an industrial scale, due to the flammability risk of diethyl ether. 

Fig. H. Mechanism for the acid-catalysed esterification of a carboxylic acid.

Imagine the reaction between a chiral, but racemic alcohol and a chiral, but racemic carboxylic acid, to give an ester in an ordinary acid-catalysed esterification (Chapter 12). 

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