Bronsted general base catalysis

Gandour et al., 1979. The reference reaction is general base catalysis of the hydrolysis of phenyl dichloroacetate at 25° by external carboxylate of the given pK,. Rate constants calculated from a two point Bronsted plot using the data of Fersht and Kirby (1967)... 

General base catalysis of the cyclization of ethyl 2-hydroxymethyl 4 nitrobenzoate [35], where the acyl group is further activated by electron withdrawal by the nitro-substituent, is characterized by a Bronsted coefficient of 0 97, i.e. unity within the limits of error, suggesting that proton transfer is a diffusion-controlled process (Fife... 

Belke et al. (1971) reported general base and general acid catalysis in cyclization of 2-hydroxymethylbenzamide [equation (18)]. However, with 2-hydroxymethyl-6-aminobenzamide strict general base catalysis by buffer bases is observed with a Bronsted coefficient of O 39 (Fife and Benjamin, unpublished data). In contrast with the unsubstituted amide, the Bronsted plot is nicely linear. An amino-group in the 6-position might assist decomposition of a tetrahedral intermediate as in [37a, b] or a kinetic equivalent. The pH-rate constant profile for spontaneous cyclization at zero buffer concentra-... 

In general acid catalysis, the reaction rate increases because the transition state for the reaction is lowered by proton transfer from a Bronsted acid in general base catalysis, the reaction rate increases by virtue of proton abstraction by a Bronsted base. 

Fig. 18. Bronsted plot for the reactions of nucleophiles with phenyl acetate (PA,D)p-nitrophenyl acetate (PNPA, A) and 2,4-dinitrophenylacetate (DNPA,0) at 25°C. The open symbols (and full lines) represent data for the total reaction, which is in most cases nucleophilic catalysis. The closed symbols (and broken lines) represent general base catalysis of hydrolysis.

The relative sizes of the Hammett p and Bronsted a constants will determine the relative rate of 5-nitrosalicylamide. If intramolecular base catalysis applies, then 5-nitrosalicylamide should hydrolyse more rapidly, since the nitro group will increase the susceptibility of the amide bond to attack by hydroxide ion and increase the efficiency of the phenolic hydroxyl as a general acid catalyst. The value of Jtobs at the plateau region was found to be 18 times smaller for the 5-nitrosalicylamide than for salicylamide a mechanism of intramolecular general base catalysis is, therefore, the preferred mechanism. 

It has been proposed (79) that eaq reacts with Bronsted acids following the Bronsted general acid catalysis law. The work was based on the competition of four acids with acetone and with I- for e aq. The acids... 

When a is intermediate in value, most of the flux is taken by the general acid HA, and general acid catalysis is easily observed. Table 11.1 [4] gives the percentage of the flux taken for given values of a. Similar arguments can be made for base catalysis, i.e. general base catalysis is difficult to characterise when Bronsted (t values are close to 1 and 0. 

General base catalysis of the reaction of a nucleophile (HNu) is kinetically equivalent to general acid catalysis of the reaction of the deprotonated nucleophile (Nu ). A distinction can be made employing cross-correlation effects where the value of the Bronsted a is measured as a function of another parameter such as the nucleophilicity of the attacking nucleophile. 

The absence of scatter in a Bronsted plot for a general base-catalysed reaction can imply that the reaction mechanism involves a rate-limiting proton transfer step. This is because proton transfer to the base in the reaction is closely similar to the equilibrium proton transfer to the base in the reaction which defines the p Ka of the conjugate acid of that base. The observation of scatter, especially for sterically hindered bases (such as 2,6-dimethylpyridine), is evidence that nucleophilic catalysis is operating as opposed to general base catalysis. 

A reaction with mechanism (99) should show general base catalysis but under some conditions this catalysis is difficult to detect and the rate may be dominated by hydroxide ion catalysis. However, recent work has now been carried out on the detritiation of chloroform in which general base catalysis by amines was observed [171(a)]. In the work with chloroform in which general base catalysis was not detected [114], since it was not possible to obtain a Bronsted exponent by measuring catalytic coefficients for a series of bases, an alternative procedure first suggested by Bell and Cox [172] was used. The rate of detritiation of chloroform was measured in a mixed solvent of water with varying amounts of dimethylsulphoxide and a constant concentration of hydroxide ion. As discussed briefly in Sect. 4.4 an acidity function (H ) has been determined for these solvent... 

A number of other proton transfer reactions from carbon which have been studied using this approach are shown in Table 8. The results should be treated with reserve as it has not yet been established fully that the derived Bronsted exponents correspond exactly with those determined in the conventional way. One problem concerns the assumption that the activity coefficient ratios cancel, but doubts have also been raised by one of the originators of the method that, unless solvent effects on the transition state are intermediate between those on the reactants and products, anomalous Bronsted exponents will be obtained [172(c)]. The Bronsted exponents determined for menthone and the other ketones in Table 8 are roughly those expected by comparison with the values obtained for ketones using the conventional procedure (Table 2). For nitroethane the two values j3 = 0.72 and 0.65 which are shown in Table 8 result from the use of different H functions determined with amine and carbon acid indicators, respectively. Both values are roughly similar to the values (0.50 [103], 0.65 [104]), obtained by varying the base catalyst in aqueous solution. The result for 2-methyl-3-phenylpropionitrile fits in well with the exponents determined for malononitriles by general base catalysis but differs from the value j3 0.71 shown for l,4-dicyano-2-butene in Table 8. This latter result is also different from the values j3 = 0.94 and 0.98 determined for l,4-dicyano-2-butene in aqueous solution with phenolate ions and amines, respectively. However, the different results for l,4-dicyano-2-butene are to be expected, since hydroxide ion is the base catalyst used in the acidity function procedure and this does not fit the Bronsted plot observed for phenolate ions and amines. The primary kinetic isotope effects [114] also show that there are differences between the hydroxide ion catalysed reaction (feH/feD = 3.5) and the reaction catalysed by phenolate ions (kH /kP = 1.4). The result for chloroform, (3 = 0.98 shown in Table 8, fits in satisfactorily with the most recent results for amine catalysed detritiation [171(a)] from which a value 3 = 1.15 0.07 was obtained. 

It is easy to understand why general base catalysis was difficult to detect in the detritiation of chloroform [114]. If hydroxide ion and buffer components fall on the same Bronsted plot with slope j3 = ca. 1.0 it can be shown that in solutions containing 0.1 M buffer species, the contribution by buffers to the rate of detritiation is only about one tenth of that due to hydroxide ion [114]. This amount of general base catalysis is virtually undetectable. The more recent studies in which general catalysis has been detected [171(a)] were carried out using base catalysts which were specially chosen. General base catalysis was easily observed for... 

General base catalysis by formate, acetate, imidazole, phosphate, and methoxyamine is also observed in the hydrolysis of ethyl trifluorothiol-acetate the Bronsted exponent j8 is 0 33. In acetate buffers a careful kinetic study demonstrated inhibition by acetic acid. Therefore, the acetate reaction also involves a tetrahedral intermediate according to scheme C. No complex formation of the substrate with acetic acid, which could alternatively cause inhibition, could be found. Scheme C accounts for the acetate catalysis and inhibition by acetic acid. In scheme C, a general base mechanism is written, the same mechanism which unequivocally applies to the water reaction. 

General base catalysis of Sn 2-type reactions of ordinary aliphatic alcohols by oxy-anions is observed in the cydization of 4-chlorobutanol [26], and of the sulfonium cation 2.6 [27] (Scheme 2.12) at 50 °C and 40 °C, respectively. (Amine buffers prefer to demethylate 2.6.) In all cases (including the reaction of 2.5 discussed above) catalysis by oxyanions shows a low solvent deuterium isotope effect and a Bronsted coefficient p of 0.26 + 0.1. This reaction may be something of a curiosity, but there is little doubt that it has been properly identified. 

The common nucleophile in ribonuclease enzymes, and thus in relevant models, is the 2 -OH group of the central nucleotide. The work of the Williams group [31] confirmed the mechanism of hydrolysis of uridyl esters (Scheme 2.14, base = U) with good, substituted-phenol leaving groups as a relatively simple process, described by the simple general base catalysis mechanism (Bronsted p = 0.67), with 2.10 2.11 as the rate determining step (Scheme 2.14), followed by rapid breakdown of the presumed phosphorane (pentacovalent addition) intermediate dianion... 

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