Weak base, acetate catalysis

Kivinen proposes that the neutral hydrolysis of acetic anhydride is promoted by water acting as a weak base. The solvent isotope effect, kH20lkDl0 — 3, is suggestive of general base catalysis. 

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

The large negative entropies of activation and the large solvent isotope effects are no doubt intimately related. It is quite conceivable that these effects arise from a general catalysis by water of the water reaction. General base catalysis is known to occur in the hydrolysis of acetic anhydride by acetate, acetylp3rridinium ion by acetate (Bunton et al., 1961), acetylimidazole by imidazole, N-methyl,N -acetylimidazolium ion by N-methylimidazole, l-(N,N-dimethylcarbamoyl)pyridinium ion by pyridine (Johnson and Rumon, 1965), and ethyl haloacetates by weak bases (Jencks and Carriuolo, 1961). It is most reasonable then that the water reaction be similarily a base-catalyzed process. The isotope effects... 

In Chapter 10 we used pyridine as a catalyst in carbonyl substitution reactions, even though it is only a weak base. Catalysis by pyridine involves two mechanisms, and is discussed on p. 200.Acetate ion is another weak base which can catalyse the formation of esters from anhydrides ... 

A possible solution for functionalization of allylic acetates involves the application of hypervalent iodones (21) as aryl source in the presence of a weak base (NaHCOj) and pincer complex (la) catalysis (Figure 4.12) [49]. Under these conditions, a regioselective arylation of the alkene takes place without altering the allylic acetate functionality. 

The catalysis by a protected nucleoside of the aminolysis by butylamine of / -nitrophenyl acetate in benzene (Scheme 3) has been reported. Interestingly, only 2, y, 5 -<9-tris(t-butyldimethylsilyl)cytidine showed any marked catalytic effect, the adenosine, guanosine and uridine analogues behaving merely as weak general base... 

The demonstration that the mechanism of catalysis may change to general base catalysis for weakly basic nucleophiles further complicates the interpretation of such plots. The most useful generalizations that can be extracted from the data for aryl acetates are illustrated in Fig. 18. This is a plot of data for the reactions of oxyanions with three esters, phenyl, 4-nitrophenyl, and 2,4-dinitrophenyl acetates under the same conditions. Only nucleophiles showing normal reactivity are included points for hydro, de ion and a-effect nucleophiles have been excluded. The data are those of Jencks and Gilchrist283, who published a slightly different version of this plot. 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

Push-pull acid-base catalysis has been proposed to account for the proton switch mechanism which occurs in the methoxyaminolysis of phenyl acetate (Scheme 11.14) where a bifunctional catalyst traps the zwitterionic intermediate. A requirement of efficient bi-functional catalysis is that the reaction should proceed through an unstable intermediate which has p values permitting conversion to the stable intermediate or product by two proton transfers after encounter with the bifunctional catalyst the proton transfer with monofunctional catalysts should also be weak. 

Catalytic, enantioselective addition of silyl ketene acetals to aldehydes has been carried out using a variant of bifunctional catalysis Lewis base activation of Lewis acids.145 The weakly acidic SiCU has been activated with a strongly basic phor-phoramide (the latter chiral), to form a chiral Lewis acid in situ. It has also been extended to vinylogous aldol reactions of silyl dienol ethers derived from esters. 

How can this catalysis work At first sight there seems to be no mechanism available. Acetate cannot act as a specific base—it is far too weak (pKaH 4.7) to remove a proton from an alcohol (pKa about 15). If it acted as a nucleophile (Chapters 12 and 13) there would be no catalysis as nucleophilic attack on acetic anhydride would be a nonreaction simply regenerating starting materials. The only thing it can do is to remove the proton from the alcohol as the reaction occurs. 

As described in a previous section, the imidazole group of a histidyl residue is involved in a most direct fashion in the catalytic action of hydrolytic enzymes (see Table 2—1). This fact attracted mudi attention among phyrical organic chemists, and imidazole and imidazole compounds became the first organic bases to have been established as catalysts for ester hydrolysis. Since the weakly basic imidazolyl group is not capable of directly displacing the much mtxe basic alkoxide ions from normal esters, most studies have dealt with the catalysis of the hydrolysis of activated esters, such as phenyl acetates and thiol esters ... 

We have indicated how to determine the various kinetic constants appearing in the expression for specific acid and base catalysis. Let us now consider how to evaluate the various contributions to the rate constant in the case of general acid-base catalysis. For reactions of this type in a solution of a weak acid or base and its corresponding salt, the possible catalysts indicated by equation (7.3.3) are the hydro-nium ion, the hydroxide ion, the undissociated weak acid (or base), and the conjugate base (or acid), In the case of acetic acid the general acid would be the neutral CHjCOOH species and the conjugate base would be the acetate ion (CH3COO"). In this case the apparent rate constant can be written as... 

Brensted p for bases whose conjugate acids have > 7 is 0.95 and represents nucleophilic catalysed hydrolysis (Proctor and Page, 1979). Evidence for an intermediate ester formed during the reaction has been obtained with alkoxide ions and phosphate dianion (Proctor and Page, 1979 Bundgaard and Hansen, 1981). Weakly basic catalysts probably act as general base catalysts. The reaction with acetate exhibits a solvent isotope effect of 2.1, as expected for general base catalysis but not for a... 

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