Hydrolysis nucleophilic catalysis

Ester hydrolysis can also be promoted by nucleophilic catalysis. If a component of the reaction system is a more effective nucleophile toward the carbonyl group than hydroxide ion or water under a given set of conditions, an acyl-transfer reaction can take place to form an intermediate ... 

The extent to which intramolecular nucleophilic catalysis of the type depicted in mechanism I is important is a function of the leaving ability of the alkoxy group. This has been demonstrated by the study of the hydrolysis of a series of monoesters of phthalic acid ... 

Nucleophilic participation is important only for esters of alcohols that have pK <13. Specifically, phenyl and trifluoroethyl esters show nucleophilic catalysis, but methyl and 2-chloroethyl esters do not. This result reflects the fete of the tetrahedral intermediate that results fi om nucleophilic participation. For relatively acidic alcohols, the alkoxide group can be eliminated, leading to hydrolysis via nucleophilic catalysis ... 

Nucleophilic catalysis is catalysis by a general base (electron-pair donor) acting by donating its electron pair to an atom (usually carbon) other than hydrogen. Nucleophilic catalysis is exemplified by the imidazole-catalyzed hydrolysis of a phenyl acetate. (The tetrahedral intermediates are not shown.)... 

We should distinguish between the phrases nucleophilic attack and nucleophilic catalysis. Nucleophilic attack means the bond-forming approach by an electron pair of the nucleophile to an electron-deficient site on the substrate. In nucleophilic catalysis this results in an increase in the rate of reaction relative to the rate in the absence of the catalyst. However, nucleophilic attack may not result in catalysis. Thus, if methylamine is reacted with a phenyl acetate, the reaction observed is amide formation, not hydrolysis, because the product of the nucleophilic attack is more stable than is the ester to hydrolysis. 

Yet another distinction is between intermolecular catalysis, in which the catalytic function and the reaction site are on different molecules, and intramolecular catalysis, in which the catalytic function and the reaction site are within the same molecule. All of the above examples constitute intermolecular catalyses. The following reaction, the hydrolysis of a monomaleate ester, is an intramolecular nucleophilic catalysis. 

These data are for the nucleophilic catalysis of the hydrolysis of p-nitrophenyl acetate by imidazoles and benzimidazoles at pH 8.0. Tbe apparent second-order catalytic rate constants are defined by... 

Kinetic Studies. The pioneering work of Hierl et al. (8) and Delaney et al. (9) had established that hydrolysis of jr-nitro-phenylcarboxylates was an excellent means of observing the nucleophilic catalysis by 4-(dialkylamino) pyridine functionalized polymers. Hydrolysis of p-nitrophenylacetate in a buffer at pH 8.5 showed that the polymer was a slightly better catalyst than the monomeric analog PPY (Table II). However, preliminary results indicate that the polymer bound 4-(dialkylamino) pyridine is more effective as a catalyst than the monomeric analog in the hydrolysis of longer carbon chain p-nitrophenylcarboxylates, such as p-nitrophenylcaproate. 

Ester hydrolysis, general base and nucleophilic catalysis, 5,237... 

General base and nucleophilic catalysis of ester hydrolysis and related reactions, 5, 237... 

Nuclear motion, the principle of least, and the theory of stereoelectronic control, 24, 113 Nucleophiles, partitioning of carbocations between addition and deprotonation. 35, 67 Nucleophilic aromatic photosubstitution, 11,225 Nucleophilic catalysis of ester hydrolysis and related reactions, 5,237 Nucleophilic displacement reactions, gas-phase, 21, 197... 

Even more efficient bimetallic cooperativity was achieved by the dinuclear complex 36 [53]. It was demonstrated to cleave 2, 3 -cAMP (298 K) and ApA (323 K) with high efficiency at pH 6, which results in 300-500-fold rate increase compared to the mononuclear complex Cu(II)-[9]aneN at pH 7.3. The pH-metric study showed two overlapped deprotonations of the metal-bound water molecules near pH 6. The observed bell-shaped pH-rate profiles indicate that the monohydroxy form is the active species. The proposed mechanism for both 2, 3 -cAMP and ApA hydrolysis consists of a double Lewis-acid activation of the substrates, while the metal-bound hydroxide acts as general base for activating the nucleophilic 2 -OH group in the case of ApA (36a). Based on the 1000-fold higher activity of the dinuclear complex toward 2, 3 -cAMP, the authors suggest nucleophilic catalysis of the Cu(II)-OH unit in 36b. The latter mechanism is comparable to those of protein phosphatase 1 and fructose 1,6-diphosphatase. 

A.1 Equilibrium data for anhydride formation 225, A.2 Intramolecular nucleophilic catalysis of ester hydrolysis 226, A.3 Intramolecular nucleophilic catalysis of amide... 

A. 6 Intramolecular nucleophilic catalysis of the hydrolysis of sulphonamides 238 B Reactions of the hydroxyl group 239... 

The second relevant set of data is for the formation of the anhydride from substituted succinic acid derivatives. Equilibrium constants for the formation of the anhydride from the acid are available for the various methyl-substituted compounds (Table A.l) and the derived EM s are compared in Table 5 with those for intramolecular nucleophilic catalysis in the hydrolysis of half-esters... 

A.3 Intramolecular nucleophilic catalysis of amide hydrolysis by the carboxyl group... 

A.5 Intramolecular nucleophilic catalysis by the carboxyl group of the hydrolysis ofphosphate andphosphonate esters... 

Fig. 7.2. a) The most common mechanism of base-catalyzed ester hydrolysis, namely specific base catalysis (HCT catalysis) with tetrahedral intermediate and acyl cleavage. Not shown here are an W mechanism with alkyl cleavage observed with some tertiary alkyl esters, and an 5n2 mechanism with alkyl cleavage sometimes observed with primary alkyl esters, particularly methyl esters, b) Schematic mechanism of general base catalysis in ester hydrolysis. Intermolecular catalysis (bl) and intramolecular catalysis (b2). c) The base-catalyzed hydrolysis of esters is but a particular case of nucleophilic attack. Intermolecular (cl) and intramolecular (c2). d) Spontaneous (uncatalyzed) hydrolysis. This becomes possible when the R moiety is... 

---