Rate of alkaline hydrolysis

Fig. 4.2. Conelation of acid dissociation constants of benzoic acids with rates of alkaline hydrolysis of ethyl benzoates. [From L. P. Hammett, J. Am. Chem. Soc. 59 96 (1937).]...

As expected, the rate of alkaline hydrolysis of p-hydroxybenzotrifluoride is considerably higher than that of the unsubstituted benzotrifluoride [3 ] (equation 39). 

The relative rates of alkaline hydrolysis of acetate, chloro-, dichloro-, and trichloroacetates have been compared and are 1 760 1.6X 10" 10. ... 

The aforementioned exception and the rather limited experimental material available do not allow any conclusions about the general applicability of the Hammett equation, using the same a- and p-values as for benzenes, to be drawn with certainty. The present author has pointed out that large deviations should be expected with strong - -M-substituents, as is also indicated from the rates of alkaline hydrolysis of methyl 5-amino- and 5-acylamino-2-thenoates. From the chemical shifts in the NMR spectra of thiophenes and benzenes it appears that another set of cr-values should be used in the thiophenes series which seems plausible since the transmission of the sub-... 

The rates of alkaline hydrolysis of ethyl benzoate, ethyl 2-thenoate, and 3-thenoate are very similar. Also, the acid constants of benzoic acid (pAfl = 4.20) and 3-thenoic acid (pKa " 4.08) are of the same magnitude, whereas 2-thenoic acid (piCa = 3.49) is stronger. 

The carbonyl group reactivities in thiophenes and benzenes are very similar, as shown by the similar rates of alkaline hydrolysis of esters and by the great similarity of the thiophenealdehydes to benzaldehyde in numerous carbonyl group reactions. This has been ascribed to the counteracting —I- -M effects of the thienyl group in this kind of reactions. ... 

Bowden has studied the application of the Hammett equation to the kinetics of the reaction of c/s-3-substituted acrylic acids with diphenyldiazom ethane (59) and with methanol (69) and the rates of alkaline hydrolysis of c -3-substituted methyl acrylates (69). The sets studied are reported in Table XII. Results of the... 

Rates of hydrolysis may be influenced by the presence of dissolved organic carbon, or organic components of soil and sediment. The magnitude of the effect is determined by the structure of the compound and by the kinetics of its association with these components. For example, whereas the neutral hydrolysis of chlorpyrifos was unaffected by sorption to sediments, the rate of alkaline hydrolysis was considerably slower (Macalady and Wolf 1985) humic acid also reduced the rate of alkaline hydrolysis of 1-octyl 2,4-dichlo-rophenoxyacetate (Perdue and Wolfe 1982). Conversely, sediment sorption had no effect on the neutral hydrolysis of 4-chlorostilbene oxide, although the rate below pH 5 where acid hydrolysis dominates was reduced (Metwally and Wolfe 1990). 

Newman and his co-workers (Newman and Hishida, 1962 Newman and Leegwater, 1968) have studied the effects of 6-methyl and 6-chloro substituents on the rates of alkaline hydrolysis of methyl 2-benzoyl- and 2-acetylbenzoates [17]. The 6-substituted esters hydrolysed faster than the... 

Studies using the 1,8-naphthalene and 4,5-phenanthrene templates have been made (Bowden and Last, 1970, 1973a). The rates of alkaline hydrolysis of the methyl 8-formyl-1-naphthoate [23] and 4-formylphenanthrene-4-carboxylate [24] are very fast and have dramatic enhancements over... 

The nitrogen atoms of the twisted amides discussed on pages 107-108 are to a greater or lesser extent pyramidal, and incipient lone pairs electron density is thus available for reactions with electrophiles. The classic example is the cage lactam [57] first prepared by Pracejus (1959), which has an amide nitrogen with near normal amine basicity. Brown and coworkers have measured rates of alkaline hydrolysis of a series of anilides [58] and [59] with related structures and find that the rate increases with increasing divergence... 

C=0 group, or sp3 carbon. This last point can perhaps be best appreciated by comparing the rate of-alkaline hydrolysis of methyl p-toluenesulfinate (140) (Bunton and Hendy, 1962) with the rate of alkaline hydrolysis of methyl p-toluate (141) (Jafife, 1953) under the same conditions. One sees that the... 

The differences in the rates of alkaline hydrolysis of /3-lactams have been shown to depend primarily on the basicity of the amino leaving group [76]. The rate of alkaline hydrolysis increases as the pKa of the leaving group increases. Several structural features affecting the pKa of the leaving amino group are summarized in Table 5.4, the details of which follow. 

The change from a A3-cephem to a A2-cephem system increases the rate of alkaline hydrolysis two- to three-fold (Table 5.4.K) [72],... 

Transition metal ions cause a dramatic increase in the rate of hydrolysis of /Madam antibiotics [75][133][134], For example, copper(II) and zinc(II) ions increase the rate of alkaline hydrolysis ca. 108-fold and 104-fold, respectively [76], It has been suggested that the metal ion coordinates with both the carboxylate group and the /3-lactam N-atom of penicillins (A, Fig. 5.20). This complex stabilizes the tetrahedral intermediate and, thus, facilitates cleavage of the C-N bond catalyzed by the HO ion [74] [75], Such a model appears applicable also to clavulanic acid, imipenem, and monobactams, but it re-... 

Surface-active agents used as adjuvants in pharmaceutical preparations to improve drug dissolution may affect the stability of /3-lactams. Thus, the presence of micelles of cetyl(trimethyl)ammonium bromide (CTAB) enhanced up to 50-fold the rate of alkaline hydrolysis of penicillins [140]. In the case of cephalosporins, micelle-promoted catalysis of the intramolecular degradation process (see Sect 5.2.2) was also observed [85][141], It has been proposed that the negatively charged penicillins and cephalosporins are attracted by the cationic micelles. This attraction increases substrate concentration in the micellar phase, in turn accelerating the rate of HO- ion attack. Ion exchange at the micellar surface and electrostatic stabilization of the transition state may also contribute to the increased rate [142][143],... 

H. Chaimovich, V. R. Correia, P. S. Araujo, M. V. Aleixo, I. M. Cuccovia, A Quantitative Analysis of the Effect of Hexadecyl-Trimethylammonium Bromide Micelles on the Rate of Alkaline Hydrolysis of Benzylpenicillin , J. Chem. Soc., Perkin Trans. 2 1985, 925-928. 

The rates of alkaline hydrolysis of a series of amino derivatives of 4-fluoro-(183 X = NH2) and 2-fluoro-pyrimidines (184 X = NH2) have been compared, revealing that the former hydrolyse more rapidly. Some difluoro analogues (184 X = F) with amino and alkyl substituents were also studied, the 4-fluoro substituent departing the more readily. 

Complexation with caffeine and theophylline-7-acetate depresses the rate of alkaline hydrolysis of substituted phenyl benzoates and is consistent with the formation of molecular complexes with 1 1 stoichiometry between the hosts and esters stacking of the xanthines is excluded as an explanation in the range of concentrations studied. Inhibition of hydrolysis is attributed to repulsion of the hydroxide ion from the host-ester complex by the extra hydrophobicity engendered by the xanthine host, as well as by the weaker binding of the transition state to the host compared with that in the host-ester complex. ... 

The effects of micelles of cetyltrimethylammonium bromide (CTABr), tetradecyl-trimethylammonium bromide (TTABr) and sodium dodecyl sulfate (SDS) on the rates of alkaline hydrolysis of securinine (223) were studied at a constant [HO ] (0.05 m). An increase in the total concentrations of CTABr, TTABr and SDS from 0.0 to 0.2 M causes a decrease in the observed pseudo-first-order rate constants (kobs) by factors of ca 2.5, 3, and 7, respectively. The observed data are explained in terms of pseudophase and pseudophase ion-exchange (PIE) models of micelles. Cationic micelles of CTABr speed attack of hydroxide ion upon coumarin (224) twofold owing to a concentration effect. ... 

For a surface active betaine ester the rate of alkaline hydrolysis shows significant concentration dependence. Due to a locally elevated concentration of hydroxyl ions at the cationic micellar surface, i.e., a locally increased pH in the micellar pseudophase, the reaction rate can be substantially higher when the substance is present at a concentration above the critical micelle concentration compared to the rate observed for a unimeric surfactant or a non-surface active betaine ester under the same conditions. This behavior, which is illustrated in Fig. 10, is an example of micellar catalysis. The decrease in reaction rate observed at higher concentrations for the C12-C18 1 compounds is a consequence of competition between the reactive hydroxyl ions and the inert surfactant counterions at the micellar surface. This effect is in line with the essential features of the pseudophase ion-exchange model of micellar catalysis [29,31]. 

The effects of dilution of the micellar surface charge on the rate of alkaline hydrolysis of a betaine ester surfactant have been investigated for a mixture of decyl betainate and a nonionic surfactant with a similar CMC. It was shown that the relation between micellar composition and the hydrolysis rate essentially parallels the relation between micellar composition and counterion binding to mixed micelles made up of ionic and nonionic surfactants [20]. 

Problem 16.41 Assign numbers from 1 for least to 4 for most to show relative rates of alkaline hydrolysis of compounds I through IV and point out the factors determining the rates. 

Taft reaction constants, p, for the hydrolysis of aliphatic esters, are available for only a few systems. Using independently determined values of Es and o, Bowden ex a/.220, found that the rates of alkaline hydrolysis of simple methyl arylaliphatic carboxylates in 80% methanol are correlated very well by the modified Taft equation152... 

In this work the rates of alkaline hydrolysis in 70% dioxan-water and those of acid-catalyzed ester formation in methanol were compared for the cis (31a) and trans (31b) substituted compounds. This was expected to isolate the steric effects of the cis substituents, since inductive and resonance effects should be similar in the cis and the trans compounds. The results are summarized in Table 34, and show the trend already observed for orf/m-substituted... 

The hydroxide-catalysed hydrolysis of aliphatic amides is generally first-order in hydroxide ion. Bruylants and Kezdy30 showed that, for a series of alkyl amides RCONH2 ranging from R = CH3 to R = C13C, the rates of alkaline hydrolysis obey the Taft relationship... 

The rate of alkaline hydrolysis of 3,4,6,7,8,9-hexahydro-2H-pyrido-[2,l-h]oxazinium perchlorates to the thermodynamic l-(3-hydroxypropyl)-... 

Figure 26-3 Plot of log 105 Ka for the dissociation of substituted benzoic acids in water at 25° against log 105 k for the rates of alkaline hydrolysis of substituted ethyl benzoates in 85% ethanol-water at 30°...

---