Base Catalysed Ester Hydrolysis

11 Key excerpts on "Base Catalysed Ester Hydrolysis"

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  Catalysis in Micellar and Macromoleular Systems

  • Janos Fendler(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 5 Micellar Catalysis of Hydrolyses, Solvolyses, and Aminolyses A. Carboxylic Esters The hydrolysis and solvolysis of esters can occur through general and specific acid-catalyzed, pH-independent, and general and specific base-catalyzed mechanisms. These reactions can be classified further according to the type of bond fission and the molecularity of the rate determining step. It is important to realize, however, that there are borderline cases in which classification of the molecularity of the reaction is merely a matter of its academic definition. Consequently, it is preferable to consider only the degree and type of solvent participation in the rate determining step. The specific mechanisms involved in carboxylic ester hydrolysis and solvolysis are dis-cussed in numerous texts and reviews (Bell, 1941, 1959; Gould, 1959; Bender, 1960, 1971; Hine, 1962; Bruice and Benkovic, 1966; Ingold, 1969; Jencks, 1969). Of the mechanisms of carboxylic ester hydrolysis, that for the base-catalyzed reaction is the best understood. It generally proceeds by bimolecular attack of hydroxide ion on the carbonyl group forming a tetrahedral inter-mediate followed by elimination with acyl oxygen fission: Ο O N Ο II w 1^ II R — C — O R / + O H , R — C — O R ' • R — C — O H + H O R ' (5.1) I u O H Due to the relative simplicity of carboxylic ester hydrolysis, in general, and that of base-catalyzed ester hydrolysis, in particular, with respect to enzymatic processes, these reactions have served well as model systems in investigations of micellar effects on reaction rates and activation parameters. In addition, the prevalence in biological systems of carboxylic ester hydrolyses catalyzed 104 A. Carboxylic Esters 105 by nucleophiles and by enzymes renders the investigation of micelle catalyzed ester hydrolyses of obvious importance.

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  The Proton: Applications to Organic Chemistry

  • Ross Stewart(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  7 Activation of Organic Molecules by Acids and Bases I. Introduction During the 1920s, studies of homogeneous acid and base catalysis by Br0nsted, Lowry, and others set the stage for the burgeoning interest in mechanistic organic chemistry that was to follow in the next several decades. From the utilitarian point of view acids and bases have long been the dominant catalysts for organic processes, and even with the striking advances in the field of homogeneous transition metal catalysis they continue to be of the greatest importance to practicing organic chemists. Catalysis is generally defined in some such way as the following. A substance brings about catalysis when it increases the rate of a reaction without itself being consumed. It is sometimes used in a looser sense to indicate activation of any sort, even when the agent responsible for the rate increase is consumed in the process. Thus, esters are activated toward hydrolysis by acids, and this is a case of true catalysis, since the activating species, the proton, is regenerated in a later stage of the reaction. Activation can also be brought about by base, but in this case the agent is not regenerated and so catalysis by base is an inappropriate term for the process. The fact that small (i.e., catalytic) amounts of acid are effective here [Eq. (7-1)], whereas small amounts of base are not [Eq. (7-2)], serves as a practical reminder of the definition. Nonetheless, it is R C 0 2 R ' + H 2 0 ^ ± R C 0 2 H + R'OH (7-1) R C 0 2 R -f-NaOH • R C 0 2 N a + R'OH (7-2) convenient to group such reactions as the base-promoted hydrolysis of esters with those other acid and base processes that are truly catalytic, since they fit into a common mechanistic framework, and it is only the adventitious consumption of the activating agent by one of the products that prevents these agents from qualifying as catalysts.

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  Micellar Catalysis

  • Mohammad Niyaz Khan(Author)
  • 2006(Publication Date)
  • CRC Press

    (Publisher)

  2.1.2 H YDROLYSIS OF E STERS The overall reaction for ester hydrolysis may be described as (2.2) The rates of hydrolysis of esters and related compounds are catalyzed by specific acid and specific base catalysts. Fine details of general mechanisms of specific acid and specific base catalyzed hydrolysis of esters are shown in Scheme 2.3 and Scheme 2.4, respectively. It is apparent from Scheme 2.3 that the presence of catalyst (H 3 O + ) should equally increase the rate hydrolysis of ester (i.e., k f value) and the rate of alkanolysis of acid (i.e., k b value) without affecting the ratio k f /k b (i.e., equilibrium concentrations of ester and acid). However, Scheme 2.4 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 (H 2 O) of the specific base catalyst and, consequently, HO – /R 1 O – 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 R 1 OH of Equation 2.2. O + RCH 2 C CH 2 R 1 H O δ+ H 2 + TS 1 RCH C CH 2 R 1 HO H + H 2 O TS 2 RCH O C – CH 2 R 1 H OH – TS 3 CH 2 R 1 O C RCH H – OH – TS 4 RCOOR H O RCOOH R OH k k f b 1 2 1 + ⎯ → ⎯ ← ⎯ ⎯ + 92 Micellar Catalysis 2.1.3 C LEAVAGE OF P HTHALAMIDE UNDER M ILD A LKALINE P H Product characterization studies on the cleavage of phthalamide and related com-pounds under mild alkaline pH ( ≈ 9) reveal the net reaction, which is expressed by Equation 2.3.

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  Surface Modification and Mechanisms

  Friction, Stress, and Reaction Engineering

  • George E. Totten, Hong Liang, George E. Totten, Hong Liang(Authors)
  • 2004(Publication Date)
  • CRC Press

    (Publisher)

  regenerating a proton that can then catalyze further reaction. The mechanism of acid- catalyzed hydrolysis is depicted in Fig. 10. It is of note that reactions involving tetrahedral intermediates are subject to steric and electronic effects. Electron-withdrawing substituents facilitate basic hydrolysis, while electron-donating and bulky substituents Hydrolysis 251 exert the opposite effect [16]. Steric effects in acid-catalyzed hydrolysis are similar to those in base-catalyzed hydrolysis; however, electronic effects are much less important in acid-catalyzed reactions. D. Base-Promoted Hydrolysis Process In base-promoted hydrolysis, also known as saponification, the ester is hydrolyzed with a stoichiometric amount of alkali. The irreversible formation of carboxylate anion leads the reaction to completion. Figure 11 demonstrates that hydroxide ion attacks the carbonyl group to form—similar to the case of acid-catalyzed hydrolysis—a tetrahedral intermediate. Loss of alkoxide generates the acid, which is rapidly deprotonated to the carboxylate anion in basic solution. The hydroxide ion used up in this reaction is not regenerated at the end. Thus, it is not the typical catalytic process. Actually, it is the process converting a strong base (HO − ) into carboxylate anion, being a weak base. Accordingly, it is to emphasize that the net effect is that the base behaves just as a stoichiometric reagent. III. HYDROLYSIS OF DIFFERENT ESTER TYPES A. General Information on Hydrolytic Stability As already shown, hydrolysis applied to organic molecules can be considered a reversal of such reactions as esterification. The same is due to amide formation. Examples of other hydrolytic processes are depicted in Fig. 12. In inorganic chemistry, the hydrolysis process is also called aquation. This type of process might also be referred to “hydrolysis of ceramics.” That specific approach is presented and discussed in Section V.C.

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  Biocatalysis in Organic Synthesis

  The Retrosynthesis Approach

  • Nicholas J Turner, Luke Humphreys(Authors)
  • 2018(Publication Date)
  • Royal Society of Chemistry

    (Publisher)

  Figure 3.2 , if we start with an ester, we can use a hydrolase and water to break the C–O ester bond to give a carboxylic acid and an alcohol.

  Figure 3.2 General transformation catalysed by hydrolases.

  This is exactly the same as if we had hydrolysed the ester chemically under either acidic or basic conditions. For acidic hydrolysis, we use a dilute acid such as hydrochloric acid to catalyse the reaction, whereas for basic hydrolysis we use hydroxide ions such as sodium hydroxide. These methods are easy to carry out, but we must be careful that the conditions of the hydrolysis reaction are compatible with the rest of the functional groups in the molecule, especially if we need to heat the reaction or use a strong acid or base. By comparison, enzyme-catalysed hydrolysis occurs under much milder conditions.

  There is also another advantage to carrying out a hydrolysis reaction using an enzyme: stereoselectivity. If we use a chiral ester as a substrate for the hydrolysis reaction, then the hydrolase enzyme will catalyse the reaction of one enantiomer of the ester faster than the other. This is because the enzyme itself is chiral and so will interact with enantiomers at different rates. As shown in Figure 3.3 , if we take a chiral ester that is a racemic mixture, then the hydrolase enzyme will hydrolyse one ester at a much faster rate, resulting in kinetic resolution.

  Figure 3.3 Kinetic resolution of an epoxide substrate catalysed by a hydrolase.

  In this particular example, we are interested in the chiral epoxide that is in the alcohol part of the ester that was hydrolysed. Instead of a racemic mixture of epoxides (which would be difficult to separate), at the end of the reaction we now have an ester and an alcohol, which we can separate easily.

  As we have already mentioned, both lipases and esterases will catalyse the hydrolysis of esters. However, when the ester is chiral, the two classes of enzymes prefer different substrates. As shown in Figure 3.4

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  Ester Formation and Hydrolysis and Related Reactions

  • R.G. Compton, C.H. Bamford, C.F.H. Tipper†(Authors)
  • 1972(Publication Date)
  • Elsevier Science

    (Publisher)

  (ii) General base catalysis The simplest generalization to emerge from the work described above on References pp. 202-207 194 HYDROLYSIS A N D FORMATION O F ESTERS OF ORGANIC ACIDS nucleophilic catalysis, is that the mechanism is only important when the leav- ing group is not too much more strongly basic than the nucleophile. Accord- ingly, general base catalysis is likely to be involved in reactions where the hydrolysis of esters with poor leaving groups, for example, those of simple aliphatic alcohols, is catalyzed by nucleophiles of low basicity. Such catalysis is observed only for very reactive esters, that is, those with strongly electron- withdrawing substituents in the acyl group. reported that imidazole catalyzes the hydrolysis of dimethyl oxalate. In the light of our present knowledge it would appear that this is a system where general base catalysis would be expected, although recently Vuori and KoskikalWW were unable to detect catalysis of dimethyl oxalate hydrolysis by acetate or phosphate. The first clear demonstration of general base catalysis came with the work of Jencks and C a r r i u o l ~ ~ ~ ~ on the hydrolysis of several ethyl haloacetates. They found that a range of general bases catalyzes the hydrolysis of ethyl dichloroacetate and difluoroacetate (Table 39), and catalysis is also observed with ethyl chloro and trichloroacetate, ethyl oxamide, and protonated glycine ethyl ester. The experimental evidence that these reactions do, in fact, represent general base catalysis, rather than nucleophilic catalysis of hydrolysis, is very strong.

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  Enzyme-Based Organic Synthesis

  • Cheanyeh Cheng(Author)
  • 2022(Publication Date)
  • Wiley

    (Publisher)

  Enzyme-Based Organic Synthesis , First Edition. Cheanyeh Cheng. © 2022 John Wiley & Sons, Inc. Published 2022 by John Wiley & Sons, Inc. 83 4.1 Hydrolysis of Ester Bond 4.1.1 Ester Hydrolysis with Esterases Esterases (E.C. 3.1.1.1, carboxyl ester hydrolases) are one of the large versatile enzyme groups of hydrolases. They are interested in synthetic chemistry for their ability to catalyze the cleavage and formation of ester bonds. They have been described widely existing in animals, plants, and microorganisms as intra- or extracellular proteins. They have shown many advantages in organic synthesis such as a wide substrate tolerance, high regio- and stereospecificity, not requiring cofactors, and exceptionally robust catalysts of being able to act in the presence of organic solvents. Due to these reasons they have been included in the catalysts with the highest number of indus-trial applications and used for the production of optically pure fine chemicals in the areas of food and drinks, textile and leather, paper, and pharmaceuticals [1–3]. The three-dimensional structure of esterases belongs to the α / β -hydrolase superfamily, that is, a definite order of α -helices and β -sheets, and has a conserved catalytic triad composed of Ser-Asp-His and located in a highly conserved GXSXG sequence. The mechanism for ester hydrolysis or formation is composed of four steps: (i) the sub-strate is bound to Ser residue yielding a tetrahedral intermediate and stabilized by His and Asp residues, (ii) the alcohol is released and an acyl-complex is formed, (iii) the nucleophilic attack of the acyl-complex by either water in hydrolysis or alcohol or ester in ( trans -)esterification forms again a tetrahedral intermediate, and (iv) the res-olution of the intermediate yields the product (an acid or an ester) and free enzyme [2, 3]. The esterases catalyzed hydrolysis is classified in nonselective and selective transformations and is described separately as the following examples.

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  Physical Organic Chemistry — 3

  Plenary Lectures Presented at the Third IUPAC Conference on Physical Organic Chemistry, Montpellier, France, 6 - 10 September, 1976

  • A. Fruchier(Author)
  • 2017(Publication Date)
  • Pergamon

    (Publisher)

  Pure & Appi. Chem., Vol. 49, pp 0 1009-1020. Pergamon Press, 1977. Printed in Great Britain. MECHANISMS AND CATALYSIS IN VINYL ESTER HYDROLYSIS Erkki K. Euranto Department of Chemistry, University of Turku, SF-20500 Turku 50, Finland Abstract - A critical survey of literature concerning the catalysis, mechanisms, and kinetics in vinyl ester hydrolysis is presented together with new results. The relatively fast alkaline and acid-catalysed hydrolyses usually take place with acyl-oxygen fission. General base and nucleophilic catalyses are known. Appreci-able neutral ester hydrolysis by general base catalysis of water occurs generally· The unsymmetrically acid-catalysed partition of the tetrahedral intermediate formed in the neutral hydrolysis has been found to lead to acid catalysis if the ester has electronegative substituents. Vinyl esters differ from other esters by the possi-ble electrophilic addition to the double bond. Thus mercury(ll) and thallium(lll) ions catalyse the reaction, and acid catalysis takes place by AS E 2 mechanism at high acidities or when the formed carbenium ion is structurally stabilized.

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  Biotransfrmtns Prepartv Organic Chemistry

  The Use of Isolated Enzymes and Whole Cell Systems in Synthesis

  • H. G. Davies, Ralph Green, D. R. Kelly, Stanley M. Roberts(Authors)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  —2— Hydrolysis and Condensation Reactions In this Section the enzyme catalysed hydrolysis reactions of esters, amides, epoxides and nitriles are reviewed. The formation of esters and amides using enzymes is also discussed. 2.1. CLEAVAGE AND FORMATION OF CARBOXYLIC ACID ESTER BONDS 2.1.1. Esterases and Lipases Of the wide range of esterases available commercially, very few have been widely utilized in organic transformations. The most commonly used ester-ases have been pig liver esterase (E.C. 3.1.1.1), porcine pancreatic lipase (E.C. 3.1.1.3) and -chymotrypsin (E.C. 3.4.21.1); others, such as the lipase from the yeast Candida cylindracea, are gaining popularity. Various micro-organisms have been employed for certain hydrolyses and these are included in the following discussion where they perform similar reactions but in better yield, or where they afford better enantiomeric excesses than the reactions catalysed by isolated, partially purified, esterases or lipases. Generally, esterases and lipases have been used for two basic transform-ations. (i) Cleavage of a racemic ester to afford an optically active ester and an optically active acid. Thus by chemical hydrolysis of the resulting optically active ester both the (R) and the (S) acids may be obtained. This method has been utilized to provide starting materials for elegant syntheses of many natural products. (ii) Removal of the acyl group from a racemic acylate to produce an optically active alcohol. Similarly, the recovered acylate may then be chemically hydrolysed to the chiral alcohol, thereby enabling both optically active alcohols to be available for further synthesis. In addition, pro-chiral diesters have been hydrolysed to give high yields of optically active mono-esters. Increasingly, enzymes are becoming used as 25 26 2. HYDROLYSIS AND CONDENSATION REACTIONS catalysts in esterification and transesterification.

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  Organic Synthesis Using Biocatalysis

  • Animesh Goswami, Jon D. Stewart(Authors)
  • 2015(Publication Date)
  • Elsevier

    (Publisher)

  Chapter 5

  Hydrolysis and Formation of Carboxylic Acid and Alcohol Derivatives

  Romas Kazlauskas    Department of Biochemistry, Molecular Biology & Biophysics and The Biotechnology Institute, University of Minnesota, Saint Paul, MN, USA

  Abstract

  Hydrolases are the enzymes most widely used for organic synthesis. The five most useful and commercially available hydrolases for organic synthesis are the lipases from Candida antarctica , from Candida rugosa and from Burkholderia cepacia , the esterase from pig liver and the protease subtilisin. Hydrolases accept a broad range of substrates, including many typical intermediates in organic synthesis. Beside hydrolysis of carboxylic acid derivatives in water or water–organic solvent mixtures, hydrolases also catalyze the formation of these derivatives in organic solvents. This chapter explains how to plan hydrolase-catalyzed reactions by choosing hydrolases and substrates that are likely to be resolved efficiently and where products are easily separated. Examples include kinetic resolutions (using hydrolysis or acylation), desymmetrizations of prochiral substrates, and dynamic kinetic resolutions.

  Keywords

  lipase esterase protease hydrolysis transesterification vinyl esters kinetic resolution desymmetrization of prochiral substrates dynamic kinetic resolution

  1. Introduction – hydrolases commonly used in organic synthesis

  Hydrolases catalyze cleavage of substrates by the addition of water. This chapter focuses on hydrolases that cleave carboxylic acid derivatives such as esters and amides: lipases, esterases, and proteases. By carrying out reactions in organic solvents without water, hydrolases can also catalyze acyl transfer reactions to make esters and amides.

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  Proton Transfer

  • C.H. Bamford, R.G. Compton, C.F.H. Tipper†(Authors)
  • 1977(Publication Date)
  • Elsevier Science

    (Publisher)

  A typical example is the acid catalyzed enolization of ketones [ 17, 26). A third possibility of a mechanism leading to general acid catalysis is the equilibrium formation of a hydrogen-bonded addition compound of substrate and general acid, followed by slow decomposition of the addition complex to the products [27]. Such a mechanism is not very likely for reactions in aqueous solutions. However, it has been suggested for the general acid catalyzed hydrolyses of ethyl orthoformate and ethyl orthoacetate in 60 5% aqueous dioxane [ 281 . As discussed in Vol. 2, pp. 354 and 372, logarithms of second-order rate coefficients for acid or base catalysis are linearly related to the pK values of the acids or bases, respectively (Bronsted relation). General base catalysis is indicated when the experimental rate data fit eqn. (20). The most likely mechanism for such a case is rate-determining proton transfer from the substrate, HS, to the base, viz. (a) HS + OH- __f H,O + Products (Slow, with or without formation of an unstable H S + B BH++Products i in termed iate ) However, there is another possibility which involves fast equilibrium deprotonation of the substrate, HS, and subsequent slow proton transfer from a general acid to another position of S-, viz. (b) HS+ OH- S- + H 2 0 (fast) S- + H,O - OH- + Products (Slow, with or without formation of a second S- +BH+ - B+Products unstable intermediate) Other examples are known in which the rate-determining reaction step is a nucleophilic attack of the base on a carbon atom rather than a proton abstraction. They belong to quite a different category, called nucleophilic catalysis. If the logarithms of the second-order rate coefficients for nucleophilic catalysis are plotted against the pK values of the bases Bronsted slopes much larger than 1 (ca. 1.5-2) may be obtained [29]. In some cases, the data do not follow the Bronsted relationship. As it may be References p p . 89-95

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