Hydrolysis of ester

Esters can undergo hydrolysis using either an acid or a base as a catalyst. Hydrolysis always produces an alcohol from the alkyl portion of the ester. During acid hydrolysis, the acid portion of the ester yields a carboxylic acid. During base hydrolysis of an ester, which is called saponification, the acid portion of the ester yields the carboxylate ion. 

In the reaction, one mole of hydroxide generates one mole of alcohol and one mole of carboxylate ion from one mole of ester. Based on this stoichiometry (the mole relationship as defined by the balanced chemical equation), if the number of moles of base is known, then the amount of ester is known. 

This stoichiometry is the saponification equivalent, used to determine the equivalents of ester. 

In general terms, the reaction of an organic acid and an alcohol may be represented as 

Reactions between acids and alcohols are usually quite slow and require prolonged boiling (refluxing). The reactions between most acyl halides and most alcohols, however, occur very rapidly without requiring the presence of an acid catalyst. 

Amides are usually not prepared by the reaction of an amine with an organic acid. Acyl halides react readily with primary and secondary amines to produce amides. The reaction of an acyl halide with a primary or secondary amine produces an amide and a salt of the amine. 

Because most esters are not very reactive, strong reagents are required for their reactions. Esters can be hydrolyzed by refluxing them with solutions of strong bases. 

The hydrolysis of esters in the presence of strong bases is called saponification (soap-making). 

21 Draw the condensed stmctnral formula for each of the following  

23 What is the ester responsible for the flavor and odor of the following fruit  

24 What flavor would you notice if you smelled or tasted the following  

Draw the condensed structural formulas for the products from acid and base hydrolysis of esters. 

The best results, however, were obtained for the reduction of 62 to (R)-3-hydroxy-acetoacetate using Thermoanaerobium brockii [269]. While acetoacetates differing in their ester moiety were reduced by baker s yeast predominantly to (S)-3-hydroxybu-tanoates, all other 3-keto alkanoates with R (i Hg gave products of (R)- or (S)-configuration [217,253,262,263,265,270-275]. 

A different approach (immobilization of tire substrate instead of the catalyst) has been chosen for e synthesis of etiryl (S)-3-hydroxybutanoate by the bioreduction of an polyethylene glycol (PEG) acetoacetate with dry baker s yeast in toluene with a small amoimt of water. After washings and derivatization, the product was obtained witir an excellent ee of 97% and an overall 5deld of 70% [306], 

The hydrolysis of an ester moiety is regarded by many scientists as a most simple reaction, even sometimes armoying. This was also true for baker s yeast-mediated hydrolyses [307,308]. The first report of an ester hydrolysis has been published in the steroid field, and it was reported as an undesired side reaction [309]. Many different enzymes of baker s yeast may be responsible for the hydrolysis of ester moieties not 

Synthesis of optically active -alkyne-3-ols by yeast-mediated hydrolysis. 

In 70% aqueous acetone, hydrochloric acid is catalytically more active than the resin by a factor of 2 for methyl acetate, 3 for ethyl acetate and 20 for ethyl hexanoate. Hammett and coworkers concluded that the resin catalyst imposes a loss in entropy in the transition state. 

In industrial hydrolysis processes, distillation through reaction can often be employed for the easy separation of products and to eliminate the equilibrium con- 

Namba et al. carried out the hydrolysis of ethyl acetate in aqueous solution in the presence of a variety of zeolites tmd found that ZSM-5 zeolites and dealuminated mor-denites were the most active. The hydrophobic nature of high-silica zeolites seems to be advantageous for reactions in aqueous solutions. 

Research by Overberger [13], Kabanov [14,15], Klotz [16], Kunitake [17] and others [18, 19] has contributed much to development of the catalysis by water-soluble polymers. Among numerous synthetic polymer catalysts, imidazole derivatives are cited in particular because they are constituents of hydrolytic enzymes [1, 20-22]. Polyvinylimidazole (PVI) is several times more catalytically effective than imidazole because of its polyfunctional nature. Let us consider three possible mechanisms of cooperative catalysis (see p. 2). 

Mechanisms A and B represent the general basic catalysis. Cooperative interaction between two neutral imidazole molecules enhances the nucleophilic attack on the substrate. Mechanism C is a variety of the general acid catalysis caused by the nucleophilic attack. To prove the polyfunctional character of the catalysis, let us compare activation parameters of polymers with their low-molecular weight analogues. For instance, for a polymeric catalyst the change in enthalpy (AH) is 15.5 kJ/mole, whereas for imidazole this value is 29.4kJ/mole [23]. Additional entropy is obtained from the formation of a transition-state complex in which catalytic and reactive groups are oriented with respect to each other. Besides, with the transition from a low-molecular 

Hydrophobic forces represent one of the most significant kinds of force binding a substrate with a catalyst [27]. Let us consider two cases in which (1) a polymeric catalyst contains hydrophobic binding sites (polysoaps) besides active nucleophyllic centers, and (2) a substrate has long hydrophobic sites. In the former case, an increase in the hydrolysis rate is observed for long-chained esters [28]. Such specificity is at- 

One proposal was using the average length of side chains as a measure of the relative contribution of side alkyl groups to the hydrophobicity of polymers. 

The kinetics of the hydrolysis of nitrophenyl esters of fatty acids, ranging from acetic to caprylic acid, catalyzed by linear alkyl-substituted PEI, were studied earlier 

An ester hydrolyzed in the presence of an acid catalyst produces a carboxylic acid and an alcohol. This hydrolysis, the reverse of esterification, is an equilibrium reaction. 

In order to increase the amount of products from the hydrolysis reaction, large quantities of water are used which shift the equilibrium to the right. 

4 shows that in the presence of specific base catalyst (HO), the net reaction shown by Equation 2.2 loses its reversibility. The hydrolysis product, RCOOH is a stronger acid than the conjugate acid (H2O) of the specific base catalyst and, consequently, HO /RjO reacts irreversibly with product RCOOH to produce a more stable product, RCOO, under such conditions. Thus, it is obvious to say that a specific base cannot catalyze the rate of reverse reaction, i.e., rate of reaction between RCOOH and RjOH of Equation 2.2. 

There are many types of enzyme-catalysed hydrolysis reactions. In this chapter, the hydrolysis of esters and amides will be surveyed quite extensively, while the hydrolysis of nitriles and epoxides will be mentioned briefly at the end. The use of hydrolase enzymes in organic solvents will be discussed also, in connection with the preparation of esters and amides. 

In a number of instances, whole-cell preparations have been preferred as catalysts for selected hydrolysis reactions in most of these cases the micro-organisms are easy to grow and simple to handle and are utilized because of the low cost involved. These cases will be integrated into the discussion as and when appropriate. 

The predictability of the outcomes of such hydrolyses (i.e. the stereochemistry of the more rapidly hydrolysed enantiomer) has been considerably advanced in recent years by the availability of active-site models for some of the more commonly used enzymes (e.g. pig liver esterase, porcine pancreatic lipase and Candida cylindracea lipase). These models have been constructed by analysing the stereoselectivity of the hydrolysis for a wide range of substrates. Recently, X-ray crystallographic data have been reported for two lipases, and such information obviously will lead to more accurate information on the active sites for these enzymes. 

The formation of optically active synthons and the ready availability of such materials for synthesis are important because optically pure end-products often will be a prerequisite for incorporation into ethical drug formulations and important agricultural aids in the future. While one of 

As adumbrated earlier, the hydrolysis of meso-compounds or prochiral compounds can provide optically active intermediates, useful for the synthesis of pharmaceuticals and other high-value materials. A further example is provided by the prochiral diester (17), which is hydrolysed using pie as the catalyst to give the chiral acid (18) (93% e.e., 93% yield). The protected amino acid (18) was converted through a series of conventional chemical steps into the anti-bacterial agent thienamycin. Similarly, the diester (19) provides the hydroxyester (20) on hydrolysis utilizing ppl as the catalyst. Over-reaction can be a problem in this case, and a sample 

Various lipases and esterases have been used for the enantioselective hydrolysis of esters. For example, Burkholderia cepacia lipases (PS, Amano Enzyme Inc.) and Candida antarctica lipases (CAL, Novozymes) have been widely used for their wide substrate specificities, high 

The enantioselectivity of a reaction is usually expressed in terms of ee of the product. However, when a racemic substrate reacts in a selective enzymatic reaction, the ee of the product as well as that of the substrate will depend on total conversion. A better measure of enantioselectivity in this type of reaction is the -value, which is the ratio of the specificity constants of the two enantiomers. When is more than 50, the reaction is often selective enough for practical use. 

When S-substrate reacts faster than -substrate, 

When R is aryl, mono-, di- and triesters usually hydrolyse by breaking their P-O linkages, whether the conditions be acidic, neutral or alkaline. This can be demonstrated by using heavy water containing the 0 isotope, when none of it appears in the resulting alcohol. 

Dialkyl esters usually hydrolyse at all pH values by breaking their 0-C bonds. Tri- and monoalkyl esters, on the other hand, undergo scission at their P-0 bonds under alkaline conditions, but at lower pH at least some rupture of 0-C linkages occurs. All acyl esters rupture at their 0-C links at alkaline pH, but under other conditions rupture may be at either P-0 or 0-C. 

Monoesters hydrolyse most rapidly at pH 4 and in basic or more acid media they are relatively stable. This suggests that the monoacid anion (R0)P(0)(0H)0 is less stable than the other species (R0)P(0)02. The hydrolysis rates of monoester anions vary considerably and are related to the electron donor capacities of the group R involved (Table 5.29). 

In neutral or acid conditions, mono-, di- and trialkyl phosphates with common radicals R tend to hydrolyse at the same rate, whereas under alkaline conditions, trialkyl esters are considerably less stable than the mono- and dialkyl esters. 

While aminoethyl phosphoric acid (5.348b) is very stable in both acidic and alkaline solutions, the remaining acids (5.348) undergo rapid hydrolysis at room temperature. Aminoethyl phosphoric acid undergoes only 5% hydrolysis after 5 h at 100°C in M HCl, whereas carbamyl phosphate is completely hydrolysed in boiling water after 2 min. 

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The most common situation studied is that of a film reacting with some species in solution in the substrate, such as in the case of the hydrolysis of ester monolayers and of the oxidation of an unsaturated long-chain acid by aqueous permanganate. As a result of the reaction, the film species may be altered to the extent that its area per molecule is different or may be fragmented so that the products are soluble. One may thus follow the change in area at constant film pressure or the change in film pressure at constant area (much as with homogeneous gas reactions) in either case concomitant measurements may be made of the surface potential. 

Reflux Distillation Unit. The apparatus shown in Fig. 38 is a specially designed distillation-unit that can be used for boiling liquids under reflux, followed by distillation. The unit consists of a vertical water-condenser A, the top of which is fused to the side-arm condenser B. The flask C is attached by a cork to A. This apparatus is particularly suitable for the hydrolysis of esters (p. 99) and anilides (p. 109), on a small scale. For example an ester is heated under reflux with sodium hydroxide solution while water is passed through the vertical condenser water is then run out of the vertical condenser and passed through the inclined condenser. The rate of heating is increased and any volatile product will then distil over. 

Ester hydrolysis is the most studied and best understood of all nucleophilic acyl sub stitutions Esters are fairly stable in neutral aqueous media but are cleaved when heated with water m the presence of strong acids or bases The hydrolysis of esters m dilute aqueous acid is the reverse of the Eischer esterification (Sections 15 8 and 19 14)... 

Saponification (Section 20 11) Hydrolysis of esters in basic solution The products are an alcohol and a carboxylate salt The term means soap making and denves from the process whereby animal fats were converted to soap by heating with wood ashes... 

Acetal resins are generally stable in mildly alkaline environments. However, bases can catalyse hydrolysis of ester end groups, resulting in less thermally stable polymer. 

Optically Active Acids and Esters. Enantioselective hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or the corresponding acids. Several representative examples are summarized ia Table 4. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often ia a highly enantioselective manner. For example, the hydrolysis of (R)-methyl hydratropate [34083-55-1] (40) catalyzed by Hpase P from Amano results ia the corresponding acid ia 50% yield and 95% ee (56). Various substituents on the a-carbon (41—44) are readily tolerated by both Upases and proteases without reduction ia selectivity (57—60). The enantioselectivity of many Upases is not significantly affected by changes ia the alcohol component. As a result, activated esters may be used as a means of enhancing the reaction rate. 

Optically Active Alcohols and Esters. In addition to the hydrolysis of esters formed by simple alcohols described above, Hpases and esterases also catalyze the hydrolysis of a wide range of esters based on more complex and synthetically useful cycHc and acycHc alcohols (Table 5). Although the hydrolysis of acetates often gives the desirable resolution, to achieve maximum selectivity and reaction efficiency, comparison of various esters is recommended. 

Two more examples ia Table 5 iaclude the hydrolysis of esters of trans-alcohols that proceed with high efficiency practically regardless of the nature of the substituents (72) and resolution of P-hydroxynitriles with Upase from Pseudomonas sp. In the latter case the enantioselectivity of the hydrolysis was improved by iatroduciag sulfur iato the acyl moiety (73). 

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

Acidic Hydrolysis. Hydrolysis of esters by use of water and a mineral acid leads to an equiUbrium mixture of ester, alcohol, and free carboxyHc acid. Complete reaction can only be achieved by removal of alcohol or acid from the equiUbrium. Because esters have poor solubiUty in water, the reaction rate in dilute acids is fairly low. Therefore, emulsifiers such as sulfonated oleic acid or sulfonated aromatic compounds (TwitcheU reagent) are added to facihtate the reaction. 

Hydrolysis of Ethyl Esters. The hydrolysis of esters (other than ethyl sulfates) is not a commercial route for producing ethanol. An indirect hydration of ethylene actually takes place during the proposed (153) hydrolysis of ethyl sulfite cataly2ed by silver sulfate. 

Pyridazinecarboxylic acids can also be prepared by hydrolysis of esters, nitriles and amides in the presence of acids or alkali. Another interesting method is partial decarboxylation of... 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Hydrolysis of esters is speeded up by both acids and bases. Soluble aflcylaiyl sulfonic acids or sulfonated ion exchange resins are suitable. 

A catalyst is defined as a substance that influences the rate or the direction of a chemical reaction without being consumed. Homogeneous catalytic processes are where the catalyst is dissolved in a liquid reaction medium. The varieties of chemical species that may act as homogeneous catalysts include anions, cations, neutral species, enzymes, and association complexes. In acid-base catalysis, one step in the reaction mechanism consists of a proton transfer between the catalyst and the substrate. The protonated reactant species or intermediate further reacts with either another species in the solution or by a decomposition process. Table 1-1 shows typical reactions of an acid-base catalysis. An example of an acid-base catalysis in solution is hydrolysis of esters by acids. 

Specific acid and base Hydrolysis of esters Ri COOR. + H.O = Ri COOH + R.OH... 

One approach, called enzymatic resolution, involves treating a racemic mixture with an enzyme that catalyzes the reaction of only one of the enantiomers. Some of the most commonly used ones are lipases and esterases, enzymes that catalyze the hydrolysis of esters. In a typical procedure, one enantiomer of the acetate ester of a racemic alcohol undergoes hydrolysis and the other is left unchanged when hydrolyzed in the presence of an esterase from hog liver. 

The carbonyl group reactivities in thiophenes and benzenes are very similar, as shown by the similar rates of alkaline hydrolysis of esters and by the great similarity of the thiophenealdehydes to benzaldehyde in numerous carbonyl group reactions. This has been ascribed to the counteracting —I- -M effects of the thienyl group in this kind of reactions. ... 

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