Esters general base-catalysed

Intramolecular general base catalysed reactions (Section II, Tables E-G) present less difficulty. A classification similar to that of Table I is used, but since the electrophilic centre of interest is always a proton substantial differences between different general bases are not expected. This section (unlike Section I, which contains exclusively unimolecular reactions) contains mostly bimolecular reactions (e.g. the hydrolysis of aspirin [4]). Where these are hydrolysis reactions, calculation of the EM still involves comparison of a first order with a second order rate constant, because the order with respect to solvent is not measurable. The intermolecular processes involved are in fact termolecular reactions (e.g. [5]), and in those cases where solvent is not involved directly in the reaction, as in the general base catalysed aminolysis of esters, the calculation of the EM requires the comparison of second and third order rate constants. 

Neighbouring-group participation in the hydrolysis of esters and amides has been reviewed. The effects of urea, Na+ and Li+ on the intramolecular general-base-catalysed glycolysis of phenyl salicylate (217) in glycol-acetonitrile solvent at constant water concentration have been reported. ... 

A typical role for the histidine imidazole ring is shown below, in the enzyme mechanism for a general base-catalysed hydrolysis of an ester. The imidazole nitrogen acts as a base to remove a proton from water, generating hydroxide that attacks the carbonyl. Subsequently, the alkoxide leaving group is reprotonated by the imidazolium... 

Now let us see how the imidazole grouping of histidine can be involved in the general acid-catalysed and general base-catalysed hydrolysis of esters by enzymes. In essence, the chemical and enzymic reactions are very similar. This is to be... 

General base catalysed halogenation of carbon acids often involves a rate-determining proton transfer from carbon, and halogenation is a technique which is frequently used for obtaining rates of proton transfer. The technique has been developed particularly by Bell [34] to measure rates of proton transfer from ketones. Other carbon acids have been studied, however, for example, esters [35], sulphonates [36], nitro-paraffins [37], and cyanocarbons [38]. Under chosen conditions which may vary depending upon the substrate, the mechanism, illustrated for acetone in eqns. (19) and (20),... 

In a general base-catalysed reaction, proton transfer is not complete before the ratedetermining step (as it was in SBC) but occurs during the rate-determining step. A simple example is the catalysis by acetate ion of the formation of esters from alcohols and acetic anhydride. 

If we now extend our consideration of base-catalysed (BAC2), and acid-catalysed (Aac2), hydrolysis to esters in general, including aliphatic ones (RC02Et), we see that there is a close similarity between the transition states (42b or 42a) for the rate-limiting step in each of the two pathways they are both tetrahedral and differ... 

Following the disclosure of the outstanding catalytic ability of imidazole compared to other bases, the catalysis of the POCL reaction by imidazole was studied in more detail [163], and it was concluded that the POCL reaction mechanism included the concurrent catalysis by two imidazole molecules, by what was described as general-base and nucleophilic pathways, respectively. The mechanism for this was suggested to be a base catalysis of imidazole catalysis by imidazole itself as previously reported for imidazole-catalyzed reaction of esters [164, 165], Despite this, it was not until the introduction [151] of 1,1 -oxalyldiimidazole (ODI) as a chemiluminescence reagent, and the postulation of its intermediate appearance in the imidazole-catalysed POCL reaction, that the... 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

With the exception of the parent compounds, where the Michael adducts are isolated, acrylic esters [see, e.g. 6,7,31,105,111 ] and nitriles [6,7], and vinyl ketones [26, 113, 115] generally yield the cyclopropanes (Table 7.6) under the standard Makosza conditions with chloroform. Mesityl oxide produces a trichlorocyclopropy-lpropyne in low yield (10%) [7]. When there is no substituent, other than the electron-withdrawing group at the a-position of the alkene, further reaction occurs with the trichloromethyl anion to produce spiro systems (35-48%) (Scheme 7.12) [7, 31]. Under analogous conditions, similar spiro systems are formed with a,p-unsaturated steroidal ketones [39]. Generally, bromoform produces cyclo adducts with all alkenes. Vinyl sulphones are converted into the dichlorocyclopropane derivatives either directly or via the base-catalysed cyclization of intermediate trichloromethyl deriva-... 

Stable cobalt (III) ion complexes with which ligand exchange does not occur were prepared by the scheme of equation (32) (Alexander and Busch, 1966 Buckingham et al., 1967a, b, c), and were isolated and characterized. Large rate enhancements in hydrolysis are observed in comparison with the uncomplexed esters for attack of Hj O at pH 1-4, but it is of greatest interest that the reactions are markedly catalysed by general bases. It has been observed that... 

---