Esters BAC2 mechanism

In basic solution, a mechanism similar to the Bac2 mechanism for ester hydrolysis is believed to operate ... 

The above results pertain to reactions in solution. In the gas phase reactions can take a different course, as illustrated by the reaction of carboxylic esters with MeO, which in the gas phase was shown to take place only by the Bal2 mech-anism, ° even with aryl esters, ° where this means that an Sn2 mechanism takes place at an aryl substrate. However, when the gas-phase reaction of aryl esters was carried out with MeO ions, each of which was solvated with a single molecule of MeOH or H2O, the Bac2 mechanism was observed. 

Fig. 43 Carbamate prodrugs [129a,b] are targets for abzyme cleavage to release a mustard [130] of enhanced cytotoxicity. ElcB hydrolysis of aryl carbonates involves the anion [131]. TSAs [132] and [133] were used to generate antibodies to catalyse a BAc2 mechanism for hydrolysis whose kinetic behaviour was evaluated with ester [134].

Further evidence for this mechanism is that a small but detectable amount of 180 exchange (see p. 332) has been found in the acid-catalyzed hydrolysis of benzamide.551 (180 exchange has also been detected for the base-catalyzed process,562 in accord with the Bac2 mechanism). Kinetic data have shown that three molecules of water are involved in the ratedetermining step,563 suggesting that, as in the Aac2 mechanism for ester hydrolysis (0-10), additional water molecules take part in a process such as... 

Carboxylic esters of any alcohol are saponified quantitatively (see above) in basic solution according to the BAC2 mechanism (Figure 6.24). The BAac2 mechanism is an SN reaction at... 

Transesterifications in basic solutions can also follow the BAC2 mechanism. The reactions also can release the corresponding alcohols with retention of configuration from sterically uniform esters with the substructure —C(=0)—O—CR R2R3. This kind of reaction is used, for example, in the second step of a Mitsunobu inversion, such as the following, which you have already seen in Figure 2.34 ... 

Table 6.6 shows that saponifications according to the BAC2 mechanism are also slowed down when the esters are derived from sterically demanding alcohols. However, this structural variation takes place at a greater distance from the reaction center than the structural variation of Table 6.5. The substituent effects in Table 6.6 are therefore smaller.

Fig. 6.21. Bac2 mechanism of the basic hydrolysis of carboxylic esters.

That a single solvent molecule clustered to a nucleophile can drastically change the reaction pathway has been demonstrated by studying the reaction of phenyl acetate with methoxide ion in the gas phase [671, 672]. Alkaline hydrolysis of esters in solution is known to proceed by attack of the nucleophile at the carbonyl carbon atom to form a tetrahedral intermediate, followed by cleavage of the acyl-oxygen bond (Bac2 mechanism) cf. Eq. (5-138a). 

Studies of reaction kinetics, and use of isotopic labelling (180) [3], have established the general mechanism for base-catalysed hydrolysis of esters (i) of most primary and secondary alcohols (Bac2 mechanism [3]) shown in Fig. 7. 

It is possible to shift ester hydrolyses away from the normal Aac2 or Bac2 mechanisms by structural changes in the substrate. When the ester is derived from a tertiary alcohol, acid-catalyzed hydrolysis often shifts to a mechanism involving alkyl-oxygen fission. This shift is due to the stability of the carbonium ion that can be formed by C-O heterolysis, and probably also to a decrease in the rate of nucleophilic attack at the carbonyl group because of steric factors. Alkenes, as well as alcohols, may be produced from the carbonium ion, since water can function either as a nucleophile or as a Br0nsted base. 

Tertiary benzoyloxymethylsulfonamides (17) undergo hydrolysis via pH-independent and acid- and base-catalysed processes. Reactions are also buffer catalysed for buffer species with pXa values > 10.5. For the pH-independent pathway, hydrolysis takes place via formation of an Al-sulfonyliminium ion (Scheme 2). The mechanism of the acid-catalysed process involves pre-equilibrium protonation of the substrate followed by iminium ion formation. The base-catalysed pathway involves the normal Bac2 mechanism of ester hydrolysis. The buffer-catalysed reaction gives rise to a curved Brpnsted plot, with values of 1.6 and 0.25 for nucleophiles with pXa values <12.5 and >13, respectively. This is indicative of nucleophilic catalysis associated with a change in rate-limiting step from formation of the tetrahedral intermediate for buffer species with pXa > 13 to decomposition of the tetrahedral intermediate for buffer species with pXa < 12.5. ... 

The dissociative mechanism of acyl transfer ElcB), which prevails for the alkaline hydrolysis of 2,4-dinitrophenyl 4-hydroxybenzoate, could not be detected in a series of extended analogues. Thus, kinetic studies of the alkaline hydrolysis of the 2,4-dinitrophenyl esters of 4-(4 -hydroxyphenyl)benzoic acid (24), 4-(4 -hydroxyphenyl) azobenzoate (26 Z = Y = N), Al-(4 -hydroxybenzylidene)-4-aminobenzoate (26 Z = CH, Y = N) and 4 -hydroxy-fran5-stilbene-4-carboxylate (26 Z = Y = CH) showed that these compounds did not form the corresponding ElcB intermediates (25) and (27), but instead reacted through the usual Bac2 mechanism. ... 

The cyclization kinetics of 11 model l-[2-(methoxycarbonyl)phenyl]-3-(2-substitut-ed phenyl)triazenes (177) have been examined in aqueous methanolic buffer solutions at various pH values. 3-(2-Substituted phenyl)benzo[fi ][l,2,3]triazin-4(3 f)-ones (178) were identified as the cyclization products. The log fcobs vs pH plot was linear with a slope of unity. The assumed and confirmed Bac2 mechanism involving specific base catalysis begins by deprotonation of the triazene giving rise to the conjugate base, continues with formation of a tetrahedral intermediate, and ends with elimination of the methanolate ion (Scheme 32). Desilylation with methanolic HCl of the substituted anilide (179), a compound formed by a Ugi reaction, led to a facile intramolecular conversion to an ester (180). This reaction was the key step in a... 

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