Nucleophilic catalysis phosphate buffer

Catalysis by phosphate buffers of various active acyl compounds (344 X = O, S), (345 X = O, S) and (346) has been examined to assess its role as a nucleophile and general base.313 In water at pH 8.5 phosphate dianion functions as both nucleophile and base towards (344 X = S) the Nu role accounts for about 80-93% of the reaction, hi D2O the process is totally nucleophilic. For (345 X = S), the Nu- role is 40-50% of the reaction and for (346) the phosphate dianion adopts an entirely nucleophilic role, while the monoanion acts as a general base. 

Nucleophilic Catalysis. The presence of other ions in solution can influence the rates of substitution and elimination reactions in two principal ways. First, various anions may increase the rates of substitution reactions in proportion to their respective nucleophilicities (22.32). an effect referred to here as "nucleophilic catalysis." This phenomenon has been documented in a number of laboratory studies of nucleophilic substitution and dehydrohalogenation reactions which employed a phosphate buffer to maintain constant pH in solution (5.331. Using the hydrolysis of a halo-organic compound by HPO42- as an example, this mechanism may be portrayed as follows (3.341 ... 

As an example we can refer to nucleophilic catalysis of hydrolysis of benzoate esters by a phosphate buffer (Figure 5.4)... 

Fig. 5.5 Nucleophilic catalysis by phosphate buffer. (Reproduced from O.A. El Seoud, M.-F. Ruasse, W.A. Rodrigues, J. Chem. Soc., Perkin Trans. 2 (2002) 1053—1058. Copyright 2002 Royal Society of Chemistry).

A more recent paper by Cunningham and Schmir242 on the hydrolysis of 4-hydroxybutyranilide XL in neutral and alkaline solution suggests that intramolecular nucleophilic attack by the neighbouring hydroxyl group is followed by bifunctional catalysis by phosphate or bicarbonate buffers of the conversion of the tetrahedral intermediate to products. A quantitative comparison was made between the effects of buffer on the hydrolysis of 4-hydroxybutyranilide and on the hydrolysis of 2-phenyliminotetrahydrofuran, since both reactions proceed via identical intermediates. The mechanism suggested243 states that the cyclisation of the hydroxyanilide ion yields an addition intermediate whose anionic form may either cleave to products or revert to reactant and whose neutral form invariably gives aniline and butyrolactone, viz. 

The reaction of benzylpenicillin with imidazole is dominated by imidazole buffer catalysis and hence the rate term which is first order in imidazole is difficult to determine (Bundgaard, 1976a, 1972). The rate constant reported for imidazole is similar to that for phosphate dianion which is surprising if they both represent nucleophilic catalysed hydrolysis. 

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