Carboxylic acids ester formation, acid-catalysed

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

Melt-spun PET always contains small concentrations of copolymerized diethylene glycol (3-oxa-l,5-pentanediol). The major mode of formation of these ether linkages does not apparently take place through a simple dehydration reaction between two glycol molecules, catalysed by traces of acidic impurities or by the free carboxylic acid of terephthalic acid (TA) or its proton. The reaction appears to involve the ester linkage [41]. In addition to diethylene glycol moieties, some dioxan (about one-tenth the proportion of diethylene glycol) was also produced. The rate of formation of these ether compounds was proportional to the concentration of hydroxyl and ester, with a rate coefficient k of about 33... 

Such esterifications and acetal formations are achieved through enzyme catalyses. However, such reactions are relatively rare in aqueous conditions chemically. This is because the reversed reactions, hydrolysis, are much more favorable entropically. Kobayashi and co-workers found that the same surfactant (DBSA) that can catalyze the ether formation in water (5.2 above) can also catalyze the esterification and acetal formations reactions in water.52 Thus, various alkanecarboxylic acids can be converted to the esters with alcohols under the DBSA-catalyzed conditions in water (Eq. 5.6). Carboxylic acid with a longer alkyl chain afforded the corresponding ester better than one with a shorter chain at equilibrium. Selective esterification between two carboxylic acids with different alkyl chain lengths is therefore possible. 

It is in many ways unfortunate that the study of cationic polymerization has, from its very start, been so intimately linked with the very complicated and ill-understood chemistry of the metal halides. This connection is largely fortuitous and there is the promise of much progress in this field when these two problems can be attacked independently. On the one hand, we need to know much more about the complex acids and esters which are formed when water, alcohols, carboxylic acids, and alkyl halides react with metal halides on the other hand, a study of olefin polymerizations catalysed by simple acids such as HBr [14], HC104 [25], and H2S04 [26] should be rewarding, because they would presumably be unobscured by the complications and uncertainties accompanying the formation of the initiating species when this involves a metal halide. 

An interesting preparation of alkyl carboxylates in high yield (Table 3.14) from the sodium salt of the carboxylic acids under mild phase-transfer catalytic conditions involves their reaction with alkyl chlorosulphate [50] and has been used with success in the preparation of alkyl esters derived from p-lactam antibiotics. The procedure is also excellent for the production of chloromethyl esters, particularly where the carboxylic acids will not withstand the classical Lewis acid-catalysed procedure using an acid chloride and formaldehyde, or where the use of iodochloromethane [51] results in the formation of the bis(acyloxy)methane. The procedure has been applied with some success to the synthesis of chloromethyl A-protected a-amino carboxylates [52],... 

In fact, acetal formation is even more difficult than ester formation while the equilibrium constant for acid-catalysed formation of ester from carboxylic acid plus alcohol is usually about 1, for... 

We have already mentioned that one of the factors that makes acyclic ftemiacetals unstable is the unfavourable decrease in entropy when two molecules of starting material (aldehyde or ketone plus alcohol) become one of product. The same is true for acetal formation, when three molecules of starting material (aldehyde or ketone plus 2 x alcohol) become two of product (acetal plus H2O). We can improve matters if we tie the two alcohol molecules together in a diol and make a cyclic acetal we discuss cyclic acetals in the next section. Alternatively, we can use an orthoester as a source of alcohol. Orthoesters can be viewed as the acetals of esters or as the triesters of the unknown orthoacids —the hydrates of carboxylic acids. They are hydrolysed by water, catalysed by acid, to ester + 2 x alcohol. 

Hundreds of impressive examples of enantioselective lipase-catalysed reactions are known, including industrial processes as in the case of the BASF method of chiral amine production (Collins et al. 1997 Breuer et al. 2004 Schmid and Verger 1998). However, the classical problem of substrate acceptance or lack of enantioselectivity (or both) persists. We were able to meet this challenge in model studies regarding the hydrolytic kinetic resolution of the ester rac-1 with formation of carboxylic acid 2, catalysed by the lipase from Pseudomonas aeruginosa. The wild-type (WT) lipase is only slightly (S )-selective, the selectivity factor amounting to a mere E = 1.1 (Scheme 1). 

The classical method for making tert-butyl esters involves mineral acid-catalysed addition of the carboxylic acid to isobutene but it is a rather harsh procedure for use in any but the most insensitive of substrates [Scheme 6.33].80-82 Moreover, the method is hazardous because a sealed apparatus is needed to prevent evaporation of the volatile isobutene. A simpler procedure [Scheme 6.34] involves use of tert-butyl alcohol in the presence of a heterogeneous acid catalyst — concentrated sulfuric acid dispersed on powdered anhydrous magnesium sulfate. 3 No interna] pressure is developed during the reaction and the method is successful for various aromatic, aliphatic, olefinic, heteroaromatic, and protected amino acids. Also primary and secondary alcohols can be converted into the corresponding /erf-butyl ethers using essentially the same procedure (with the exception of alcohols particularly prone to carbonium ion formation (e.g. p-... 

Ester formation is a standard organic reaction between an alcohol and a carboxylic acid, which is an equilibrium reaction that has been shown to occur under catalysis by either acid or base. In polyesterification involving an organic acid, the substrate is itself the catalyst. It has been noted (Pilati, 1989) that, among the many reaction mechanisms, Scheme 1.1 is the most likely for acid-catalysed esterification, with the second reaction being the rate-determining step. 

Phenolic ester formation between a phenol and a higher carboxylic acid catalysed by a 4A molecular sieve has been described with a modification that after 1 hour at 120 C under nitrogen, boric oxide B2O3, was added, presumably to absorb water and the refluxing continued for 5 hours at 185°C (ref.1). 

In fact, acetal formation is even more difficult than ester formation while the equilibrium constant for acid-catalysed formation of ester from carboxylic acid plus alcohol is usually about 1, for acetal formation from an aldehyde and ethanol (shown above), the equilibrium constant is fC = 0.0125. For ketones, the value is even lower in fact, it is often very difficult to make the acetals of ketones (sometimes called ketals) unless they are cyclic (we consider cyclic acetals later in the chapter). However, there are several techniques that can be used to prevent the water produced in the reaction from hydrolysing the product. 

Other recent relevant developments have been the replacement of conventional acid catalysts with greener analogues. Direct esterification of carbo Q lic acids and alcohols continues to be a focus of attention. As examples, diphenylammonium triflate 8 and bulky diatylammonium sulfonates were shown to catalyse ester condensation of carboxylic acids and alcohols efficiently, and without the need for azeotropic water removal in the former case. Pentafluorophenylammonium triflate 9 was shown to be an efficient and cost-effective catalyst not only for esterification, but also for thioesterification, transesterification and macrolactone formation without requiring a dehydrating system. The superior catal)4ic efficiency of 9 relative to 8 was ascribed to the lower basicity of the pentafluoroaniline counter amine compared to diphenylamine. In related work, polyaniline... 

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