Acid-catalyzed hydrolyses

Most acid-catalyzed hydrolyses of carboxylic acid derivatives proceed by the A2 mechanism, as shown for ester hydrolysis ... 

The functionalized [4]radialene 86 offers opportunities for further transformations by hydrolytic cleavage of the O-silylenol moieties and by oxidative desilylation (Scheme 16). Base- and acid-catalyzed hydrolyses lead to different products (130 and 131, respectively)60. By analogy with the formation of 1,4-diketones by oxidative coupling of two siloxyalkene molecules, treatment of 86 with the iodonium salt Phl+—O—+I—Ph BF4 in dichloromethane leads to 132 which is immediately... 

It should be mentioned that neutral and acid-catalyzed hydrolyses of the o-quinone methide of benzene have also been studied.155 So far, no value of pAR has been reported. 

Bennet, A. J. Sinnott, M. L. Complete kinetic isotope effect description of transition states for acid-catalyzed hydrolyses of methyl a- and /j-glucopy rariosides. J. Am. Chem. Soc. 1986, 108, 7287-7294. 

Fig. 9 Why acid-catalyzed hydrolyses of nitriles are inherently slower than for analogous amides despite a smaller thermodynamic barrier. The distortions in starting material and product are compared for acetonitrile and iVW-dimethylacetamide. The total angular distortion is greater for the nitrile. Reproduced with permission from Ref.9...

The Aac2 mechanism (Figure 6.22) of ester hydrolysis represents an SN reaction at the carboxyl carbon, which follows the general mechanism of Figure 6.5. Acid-catalyzed hydrolyses of carboxyhc esters that are derived from primary or from secondary alcohols take place according to the Aac2 mechanism. The reverse reactions of these hydrolyses follow the same mechanism, namely, the acid-catalyzed esterifications of carboxylic acids with alcohols. In the esterifications, the same intermediates are formed as during hydrolysis, but in the opposite order. 

Palustrine (73) is the main alkaloid of several Eqnisetnm species, whereas its A-formyl derivative, palustridine (74), and its 18-deoxy derivative 75 are minor alkaloids of E. palustre (75 - 77). These alkaloids are elaborated from spermidine and a substituted C10 carboxylic acid. Palustridine afforded palustrine by acid-catalyzed hydrolyses. 

Anionic micellar systems were found to increase the rate of the acid catalyzed hydrolysis of acetylsalicylic acid (Nogami et al., 1962), methantheline bromide (Nogami and Awazu, 1962), n-butyl acetate, t-butyl acetate, ethyl p-aminobenzoate, and ethyl o-aminobenzoate (Sakurada et al., 1967), but decreased that of methyl benzoate slightly (Sakurada et al., 1967). The acid catalyzed hydrolysis of anionic amphi-philes also generally tend to be accelerated by micellization (Table 5). The rates of the acid catalyzed hydrolyses of sodium sulfoethyl do-decanoate, sodium undecanoate, and sodium sulfobutyl caprylate are significantly greater in micellar than in non-micellar solutions while that of sodium dodecyl sulfoacetate is unaffected by micelle formation (Meguro and Hikota, 1968). 

A third possibility of a mechanism leading to general acid catalysis is the equilibrium formation of a hydrogen-bonded addition compound of substrate and general acid, followed by slow decomposition of the addition complex to the products [27], Such a mechanism is not very likely for reactions in aqueous solutions. However, it has been suggested for the general acid catalyzed hydrolyses of ethyl orthoformate and ethyl orthoacetate in 60 % aqueous dioxane [28]. 

On the other hand, the AV values for the acid catalyzed hydrolyses of methyl and ethyl acetates are near —10 cm3, as expected (Table 1). These findings indicate that there cannot be much charge separation in the transition states. Consequently, the following transition state models may now be excluded [37], viz. 

It can be seen from Table 3 that AS values referring to ester hydrolysis are in the range —2 to +15 eu (entropy units = cal. degree-1 ) if the mechanism is Al, or in the range —15 to —30 eu if the mechanism is A2. However, if other reactions are included the Al and A2 ranges overlap. For the acid catalyzed hydrolyses of ethylene and isobutylene oxides, the AS values are —6 and —4 eu [49], respectively. The mechanism is some form of A2 in both cases (see Sect. 6.3). On the other hand, AS = —3.8 eu has been found for the acid catalyzed hydrolysis of 2,4,4,5,5,-pentamethyl-l,3-dioxolane [51], which may be an example of an Al reaction or possibly an A2+ reaction with strong steric hindrance (see Sect. 7.4). 

Acid catalyzed hydrolyses of acetals, ketals, and orthoesters... 

Rate coefficients and Arrhenius parameters of the acid catalyzed hydrolyses of acetals, ketals, and orthoesters in water at 20 °C... 

The factor q depends on the alkyl group R and the constants p, and p2 depend on the alkyl groups R and R" in RCH(OR )(OR ). The standard reaction with the rate coefficient k0 is the hydrolysis of dimethyl formal. According to the more recent study by Kreevoy and Taft [162], the structure—reactivity relationship for the acid catalyzed hydrolyses of 21 diethyl acetals and ketals of non-conjugated aldehydes and ketones in... 

However, the rate coefficient k0 refers to the acid catalyzed hydrolyses of the anions of the substrates rather than to uncatalyzed reactions. Intra-... 

According to the findings of Kreevoy and Taft [162], the rate coefficients for the acid catalyzed hydrolyses of acetals and ketals can be fitted into the same structure—reactivity relationship. Therefore it is to be expected that the same A1 mechanism is operative for acetals and for ketals, at least as far as they are non-conjugated. 

These findings are not surprising since the alpha carbon atoms of these diazo compounds carry an aromatic ring. However, it has been observed recently by Dahn et al. [210] that solvent isotope effects are larger than 1 in the acid catalyzed hydrolyses of various secondary diazoketones (such as 3-diazo-2-butanone), ethyl a-diazopropionate, and l,l,l-trifluoro-2-diazopropane. Similar results have been obtained by Jugelt and Berseck... 

As in the case of other acid-catalyzed hydrolyses, the first step involves protonation of the most basic atom in the molecule. (In the case of ethyl orthoformate, all three oxygen atoms are equally basic.)... 

Emmons reported two kinds of acid-catalyzed hydrolyses of oxaziridines, which depended upon the nature of the substituent groups. Both paths were proposed to proceed via the 0-conjugate acid with subsequent fission of either the C-0 (path 1) or the N-0 bond (path 2). Simple isomerization to the nitrone was also observed. 

For the removal of toe isopropylidene ketal a variety of acid-catalyzed hydrolyses have been described. Typical conditions are Dowex 50-W (H l/HaO, 70 °C and 60-80% HOAc, 25 °C or reflux. 

Acid-catalyzed hydrolyses of alkyl- and vinyl-substituted epoxides 254... 

A summary of bimolecular rate constants for the acid-catalyzed hydrolysis of a series of alkyl-, vinyl- and phenyl-substituted epoxides is given in Table 1. Propylene oxide (7) is 6.6 times more reactive than ethylene oxide, and from a study of its reaction in H2018, it was shown that 70% of the glycol product results from addition of solvent to the secondary carbon and 30% from addition of solvent to the primary carbon. The reactivity per primary carbon of ethylene oxide is one-half of the observed reactivity of ethylene oxide, and thus the introduction of a methyl group on ethylene oxide results in an increase in reactivity at the primary carbon by a factor of 4 and an increase in reactivity at the secondary carbon by a factor of 9. These results are consistent with A-2 mechanisms for the acid-catalyzed hydrolyses of ethylene oxide and propylene oxide, in which some amount of positive charge generated on carbon at the transition state is stabilized by a methyl group. 

In closely related studies, the acid-catalyzed hydrolyses of cis- and trans-jl-mc-thylstyrene oxides (42a and 44a)51 52 and of cis- and trans-anethole oxides (42b and 44b)53 have been reported (Scheme 12). Reactions of the cis and trans epoxides in... 

The cis/trans hydrolysis ratio from the acid-catalyzed hydrolysis of indene oxide (53a, Scheme 17) is 75 25,62,63 and that from acid-catalyzed hydrolysis of 5-met-hoxyindene oxide (53b) is 80 20.61 Thus, the introduction of a methoxy group into position 5 does not result in any significant change in the cis/trans hydrolysis ratio. There is evidence that 54b, which is stabilized by the 5-methoxy group, is sufficiently stable to be trapped by external nucleophiles. The very similar cis/tram diol product ratio from acid-catalyzed hydrolyses of both 53a and b suggest that 54a is also a discrete intermediate. 

The stereochemical outcomes of the acid-catalyzed hydrolyses of 1,2,3,4-tetrahy-dronaphthalene 1,2-oxide 59a and its 6-methoxy derivative 59b (Scheme 18) are quite different from those of the corresponding indene oxide systems. For example, acid-catalyzed hydrolysis of 59a yields only 5% of cis diol 61a and 95% of tram diol 62a.66 However, acid-catalyzed hydrolysis of its 6-methoxy derivative 59b yields 80% of cis diol 61b and 20% of tram diol 62b.67 One might argue that carbocation 60a does not have a sufficiently long lifetime compared to solvent relaxation, whereas 60b does, and that this difference in lifetime leads to different mechanisms... 

Whereas acid-catalyzed hydrolyses of 65a and b yield almost exclusively trans diol products, the acid-catalyzed hydrolysis of 67a yields 85% of cis diol and 15% of trans diol.69 The reaction of 67 with H+ also yields a single carbocation conformation 68, in which the hydroxyl group is forced to occupy an equatorial position (Scheme 21). The major cis diol product can be rationalized by energetically favored axial attack of water on carbocation 68. In unpublished work, we have also determined that the acid-catalyzed hydrolysis of 67b, which is much more reactive than 67a and yields a stabilized carbocation 68b, also yields cis and trans diols in a ratio of 85 15. Axial attack of water on 68 to yield cis diol is therefore favored over equatorial attack to yield trans diol, but not to the same extent that axial attack of water on carbocation 66 is favored. 

The acid-catalyzed hydrolyses of both cz.s-a net hole oxide (121) and trans-anethole oxide (124) yield identical product mixtures of 20% erythro and 80% threo 1 -(p-methoxyphenyl)-1,2-propanediols, suggesting that there is a common benzylic car-bocation intermediate (127) and common product-forming steps.108 These results indicate that rotation about the (%-C bond of the carbocation intermediate 127 is faster than attack of water on the carbocation. However, the ratio of diol and ketone products from the pH-independent reaction of cw-anethole oxide is very different than that from trans-anethole oxide, so rotation about the Ca-Cp bond in the transformation of 121 to 124 is not rapid compared to the rates of ketone and diol product formation. 

---