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].

In Table 4.3, it should be noted, however, that hard aUcoxide anions (RO ) react with DMC via a Bac2 mechanism to yield exclusively transesterification products (ROC02Me) with no trace of methyl ethers (entry 3). Such a peculiar selectivity is currently under investigation. 

The acid-catalysed hydrolysis of the acylal, 1-phenoxyethyl propionate (13), has been studied using the PM3 method in the gas phase. The kinetics and mechanism of the hydrolysis of tetrahydro-2-furyl and tetrahydropyran-2-yl alkanoates (14) in water and water-20% ethanol have been reported. In acidic and neutral media, kinetics, activation parameters, isotope-exchange studies, substituent effects, solvent effects and the lack of buffer catalysis pointed clearly to an Aai-1 mechanism with formation of the tetrahydro-2-furyl or tetrahydropyran-2-yl carbocation as the rate-limiting step (Scheme 1). There is no evidence of a base-promoted Bac2 mechanism up to pH 12. ... 

A dissociative elimination-addition pathway has also been proposed to account for the kinetics of alkaline hydrolysis of 2,4-dinitrophenyl 4 -hydroxyphenylpropionitrile in 40% (v/v) dioxane-water, although participation of the associative Bac2 mechanism cannot be ruled out since it may be facilitated by the electronic effect of the triple bond. Formation of intermediate (15), having a conjugated and cumulated double-bond system, should favour the ElcB mechanism and thereby account for the contrasting entropies of activation found for hydrolysis of (14) and the corresponding 4 -methoxyphenylpropionate. 

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... 

A Bac2 mechanism is proposed for die saponification of ethyl benzoate in ethanol-water.37 The reactions of aryl benzoates in absolute ethanol with ethoxide, aryloxides and acetophenone oximates occur via a stepwise mechanism in which the formation of the tetrahedral intermediate is rate determining.38 A stepwise mechanism is also supported for the reactions of /7-nitrophenyl-substituted benzoates with hydroxide and / -chlorophcnoxidc. The evidence comes from breaks in Hammett plots as the acyl... 

Rates of reactivity of HO- and H02- towards / -nitrophenyl /V,/V-dimcthylcarba-mate in ROH-H2O mixtures increased with increasing concentrations of IVOil and Bu OII, but the reverse was true for (CH20H)2.43 Kinetic studies of the alkaline hydrolysis of a series of secondary A -thiazolylcarbamates (19 R = H) and tertiary A-methyl-iV-thiazolylcarbamates (19 R = Me) have shown that they proceed by an ElcB and a BAc2 mechanism, respectively 44... 

Kinetic studies at 100 °C revealed that ethyl /V-ethylthionocarbamate, EtOC(S)NHEt, was hydrolysed in acid by an Al mechanism and in base by a BAc2 mechanism.53 The concerted mechanism proposed for the aminolysis at 30 °C in MeCN of aryl /V-ethyl thionocarbamates, (XC6H40)C(S)NHEt, by benzylamine was supported by a negative cross-interaction constant, pxz = —0.87 and failure of the reactivity-selectivity principle.54 Similar conclusions, for the same reasons, were made for the aminolysis of the corresponding thiolocarbamates, (XC6H4S)C(0)NIIFL, by benzylamine in MeCN at 10 °C.55... 

The basic hydrolysis of a series of aryl AM4-X-benzenesull onyl)-/V-methyldithiocarbamates (65 X = MeO, Me, H, Cl, N02, CF3) in 30% aqueous dioxane at 25 °C proceeded via a BAc2 mechanism to give thiophenol, COS, and the corresponding (V-methyIsuI lonamidc, 4-X-CeH4S02NHMe.56... 

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.

Actually, the technical synthesis of adipic acid dinitrile does not begin with, but proceeds via adipic acid diamide (D). In fact, it starts with the bis(ammoniumcarboxylate) A obtained from adipic acid (B) and two equivalents of ammonia. Upon heating in a closed reactor small amounts of the carboxylic acid and ammonia are regenerated from the salt A and react according to the Bac2 mechanism (Figure 6.24) to give diamide D. 

The total hydrolysis of phenylacetonitrile (Formula A in Figure 7.9) to phenylacetic acid (C) can be performed in one or two steps and both under acidic (following the mechanism in Figure 7.8) and basic conditions. In the latter case, the nucleophilic addition of a hydroxide ion to the nitrile carbon atom is the rate-determining step. This is how the imidic acid anion D is formed. Protonation (—> F), deprotonation (—> E) and reprotonation yield the amide B, which one can isolate or further hydrolyse under harsher conditions via the usual BAC2 mechanism (cf. Figure 6.24). 

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