Organic Ester Formation

Although the mechanism of ester formation has been the subject of some controversy, this process is related to polyborate formation in that both cases likely involve nucleophilic attack of an HO oxygen on B(OH)3 followed by elimination of water from a tetrahedral intermediate, Eq. (4). 

The rate of the esterification reaction is very fast, with the B—O bonds breaking in this process, not the C—0 bond. The equilibrium of Eq. (4) does not lie far to the right, since water competes as a nucleophile in the reverse reaction, and rapid equilibration occurs unless water is removed to drive the reaction to the right. Hence most simple borate esters are readily hydrolyzed, displaying pseudo-first order hydrolysis kinetics. In most cases esterification 

Other borate ester chelates containing tetrahedral boron, shown in Fig. 16a, have been prepared as precursors to solvent-supported borate cations (Fig. 16b) that show catalytic activity toward olefin polymerization [54]. 

An important class of borate esters is the anionic spirocyclic esters, shown in Eq. (7). The reaction of two molar equivalents of 1,2- or 1,3-diol with boric acid to form such spirocyclic esters is accompanied by dramatic decrease in pH, a consequence of the kinetic stability of these esters. This reaction 

Since anionic ester formation proceeds with release of a proton, the reaction is also favored by the presence of proton acceptors or high pH. The observation that ester formation is favored at high pH has led some researchers to conclude that the reaction involves [B(0H)4] as reactant rather than B(0H)3 [55]. However, careful analysis of equilibrium expressions for this process leads to the conclusion that a tetrahedral reactant is not required, and other evidence supporting a tetrahedral reactant is unconvincing [56]. 

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When esterification is the objective water is removed from the reaction mixture to encourage ester formation When ester hydrolysis is the objective the reaction is carried out m the presence of a generous excess of water Both reactions illustrate the applica tion of Le Chatelier s principle (Section 6 10) to organic synthesis... 

Hypochlorous acid undergoes a variety of reactions with organic substances including addition, oxidation, C- and iV-chlorination, and ester formation. On an industrial scale, hypochlorous acid, generated m situ via chlorine hydrolysis, reacts with propylene forming primarily the a-propjlene chlorohydrin isomer. 

Exposure Limits. The Occupational Safety and Health Act (OSHA) of 1990 Hsts a multitude of acetates, phthalates, formates, and acrylates along with the corresponding permissible exposure limits and threshold limit values (76). The PEL data is Hsted in Table 2. If there is potential for exposure to an organic ester for which PEL or TLV data has been identified, then an exposure limit lower than that Hsted is usually selected for working in that environment. 

Angelici and Brink (40) have found that in the reactions of amine with trans-M(CO),(PPhMe2)2+ (M = Mn or Re), the rate of carbamoyl formation follows the order, n-butylamine > cyclohexyl-amine >, isopropylamine > sec-butylamine >> tert-butylamine, implying a strong steric effect in carbamoyl formation. A similar order has been observed in the rate of reaction of organic esters with amines to form amides (41). The data in Table III indicate that a steric effect may be operative in the Ru (CO) /NR3-catalyzed WGSR, since with tertiary amines the rate follows the order, NMeQ > MeNC.H > NEt > NBu0, which does not reflect the basicity of these amines. 

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. 

The organic esters have a greater order of stability, but it is difficult to prepare completely acylated compounds without concurrently anhy-drizing the hexitol unless one uses acid anhydrides or chlorides. Early attempts to prepare higher aliphatic esters of D-mannitol resulted in the formation of mixtures of mannitans and mannides. It is for this reason that caution must be exercised in interpreting some of the work in the literature. The analytical values of the pure compounds and the mixtures are such that one cannot differentiate between them. 

Lipase has been used in organic solvents to produce useful compounds. For example, Zark and Klibanov (8) reported wide applications of enzymes to esterification in preparing optically active alcohols and acids. Inada et al (9) synthesized polyethylene glycol-modified lipase, which was soluble in organic solvent and active for ester formation. These data reveal that lipases are very useful enzymes for the catalysis different types of reactions with rather wide substrate specificities. In this study, it was found that moditied lipase could also synthesize esters and various lipids in organic solvents. Chemically moditied lipases can help to solve today s problems in esteritication and hopefully make broader use of enzymatic reactions that are attractive to the industry. 

Esters are widespread in fruits and especially those with a relatively low molecular weight usually impart a characteristic fruity note to many foods, e.g. fermented beverages [49]. From the industrial viewpoint, esterases and lipases play an important role in synthetic chemistry, especially for stereoselective ester formations and kinetic resolutions of racemic alcohols [78]. These enzymes are very often easily available as cheap bulk reagents and usually remain active in organic reaction media. Therefore they are the preferred biocatalysts for the production of natural flavour esters, e.g. from short-chain aliphatic and terpenyl alcohols [7, 8], but also to provide enantiopure novel flavour and fragrance compounds for analytical and sensory evaluation purposes [12]. Enantioselectivity is an impor-... 

Immobilisation of an Acetobacter aceti strain in calcium alginate resulted in improvement of the operational stability, substrate tolerance and specific activity of the cells and 23 g phenylacetic acid was produced within 9 days of fed-batch cultivation in an airlift bioreactor [133]. Lyophilised mycelia of Aspergillus oryzae and Rhizopus oryzae have been shown to efficiently catalyse ester formation with phenylacetic acid and phenylpropanoic acid and different short-chain alkanols in organic solvent media owing to their carboxylesterase activities [134, 135] (Scheme 23.8). For instance, in n-heptane with 35 mM acid and 70 mM alcohol, the formation of ethyl acetate and propylphenyl acetate was less effective (60 and 65% conversion yield) than if alcohols with increased chain lengths were used (1-butanol 85%, 3-methyl-l-butanol 86%, 1-pentanol 91%, 1-hexanol 100%). This effect was explained by a higher chemical affinity of the longer-chain alcohols, which are more hydrophobic, to the solvent. 

In a broader sense, the term esterification may include all reactions in which esters, both of organic and inorganic acids, are formed. We shall limit the discussion in this section, however, to ester formation from organic carboxylic acids and alcohols... 

J. Baratti, and C. Triantaphylides, lipase-catalyzed ester formation in organic solvents. An easy preparative resolution of a-substituted cyclohexanols, Tetrahedron Lett. 1985, 26, 1857-1860. 

Lower members of the series of salts formed between organic sulfoxides and perchloric acid are unstable and explosive when dry. That from dibenzyl sulfoxide explodes at 125°C [1], Dimethyl sulfoxide explodes on contact with 70% perchloric acid solution [2] one drop of acid added to 10 ml of sulfoxide at 20° C caused a violent explosion [3], and dibutyl sulfoxide behaves similarly [4]. A fatal explosion resulted from mistakenly connecting a DMSO reservoir to an autopipette previously used with perchloric acid [5], (The editor has met a procedure for methylthiolation of aromatics where DMSO was added to excess 70% perchloric acid he did not feel justified in trying to scale it up.) Explosions reported seem usually to result from addition to excess sulfoxide. Aryl sulfoxides condense uneventfully with phenols in 70% perchloric acid, but application of these conditions to the alkyl sulfoxide (without addition of the essential phosphoryl chloride) led to a violent explosion [4]. Subsequent investigation showed that mixtures of phenol and perchloric acid are thermally unstable (ester formation ) and may decompose violently, the temperature range depending on composition. DSC measurements showed that sulfoxides alone... 

Retinoic acid is insoluble in water but soluble in many organic solvents. It is susceptible to oxidation and ester formation, particularly when exposed to light. Topically applied retinoic acid remains chiefly in the epidermis, with less than 10% absorption into the circulation. The small quantities of retinoic acid absorbed following topical application are metabolized by the liver and excreted in bile and urine. 

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