Acetals solvent isotope effect

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

Kivinen proposes that the neutral hydrolysis of acetic anhydride is promoted by water acting as a weak base. The solvent isotope effect, kH20lkDl0 — 3, is suggestive of general base catalysis. 

The oxidation of a-hydroxy acids by benzyltrimethylammonium tribromide (BTMAB) to the corresponding carbonyl compounds shows a substantial solvent isotope effect, A (H20)/A (D20) = 3.57, but no KIE for a-deuteromandelic acid.133 The oxidation of glucose by hypobromous acid is first order in glucose and the acid.134 [l,l-2H2]Ethanol shows a substantial kinetic isotope effect when oxidized by hexamethylenetetramine-bromine (HABR) in acetic acid to aldehyde.135 Kinetics of the oxidation of aliphatic aldehydes by hexamethylenetetramine-bromine have been studied by the same group.136 Dioxoane dibromide oxidizes y-tocopherol to 5-bromomethyl-y-tocopherylquinone, which spontaneously cyclizes to 5-formyl-y-tocopherol.137... 

D KIE of 6.35 has been observed in the oxidation of a-deuteriomandelic acid by pyri-dinium bromochromate to the corresponding oxo acid. The analysis of the D KIE indicated that the reaction involves a symmetric transition state443. The oxidations of phosphinic and phosphorous acids by pyridinium bromochromate exhibits a substantial primary deuterium KIE444. The hydroxyacids, glycolic, lactic, mandelic and malic acids are oxidized by pyridinium hydrobromide perbromide in acetic acid-water mixtures to oxo acids445. The primary KIE in the oxidation of a-deuteriomandelic acid is kn/kn = 5.07, and it does not exhibit a solvent isotope effect. A mechanism involving hydride ion transfer to the oxidant has been proposed445. 

The experimental data for oxidation of benzyl alcohol,1 aliphatic primary and secondary alcohols,2 and cholesterol3 with cetyltrimethylammonium (CTA) dichromate indicated that the reactions occur in a reverse micelle system produced by the oxidant. Michaelis-Menten-type kinetics were observed with respect to the reductants. The product of the oxidation of cholesterol depends on the solvent. In dichloromethane, the product is 7-dehydrocholesterol, whereas with dichloromethane containing acetic acid the product is 5-cholesten-3-one. A low kinetic isotope effect, k /ku = 2.81, was observed in the oxidation of methanol- this, combined with the rate data and the reverse solvent isotope effect [ (H20)/fc(D20) = 0.76], suggests that these reactions... 

It follows from these similarities in solvent properties that equilibrium or rate constants of reactions in which the solvent molecules do not directly participate generally show comparatively small changes when the deuterium content of the medium is altered. This is true even for rates of proton transfer between neutral substrates and acetate ions, which as a rule are reduced by 20-40% on going from H20 to D20 (Bell, 1965). Because of the anionic nature of one of the reactants and of the transition state these reactions are of a type in which solvent-solute interactions through hydrogen bonds are probably particularly large, and yet the solvent isotope effect is fairly small. Reactions in... 

D. G. Oakenfull, T. Riley, V. Gold, J. Chem. Soc., Chem. Comm. 385 (1966). Nucleophilic and General Base Catalysis by Acetate Ion in Hydrolysis of Aryl Acetates Substituent Effects, Solvent Isotope Effects, and Entropies of Activation. 

ALPH does however seem at first sight to apply to acetal formation and hydrolysis if the acetal concerned is part of a 1,8-dioxadecalin system. Thus, Kirby and Martin (1983a) found that the axial epimer [26a] was 60-fold more reactive in acid-catalysed hydrolysis than epimer [26b]. In spontaneous hydrolysis the gross factor favouring the axial epimer fell to 2, but these authors argued with some plausibility, on the basis of different solvent isotope effects (/cH2o/ d2o = 1-74 for [26a] and 1.03 for [26b]), that in the axial case the nitrophenolate and oxocarbonium ion portions of the reactive intermediate recombined far more often than they went on to product. 

Solvent isotope effects in the acid catalyzed hydrolyses of acetals, ketals, and orthoesters... 

The kinetic solvent isotope effect in the hydrolyses of various acetals, with the exclusion of compounds of general formula RCH(OAr)(OR ), is... 

The results obtained for the hydrolyses of ethyl orthoformate and ethyl orthobenzoate in purely aqueous solutions and in 20 % dioxane—water are in agreement with the A1 mechanism [28]. General catalysis cannot be detected, and solvent isotope effects (Table 14) are similar to those found in the hydrolyses of simple acetals. 

Weak general catalysis by acetic acid (just above the limits of experimental error) has been found in the decarboxylation of 4-aminobenzoic acid in the pH region near 5 [78]. Under similar conditions, general catalysis cannot be detected in the decarboxylation of anthranilic acid [77]. The solvent isotope effects are (feH S)H 0/(feD2s)D2o = 4.9 for 4-aminobenzoic acid at 85 °C [78] and rh Q/kno = 4.7 for anthranilic acid in 0.1 M aqueous hydrochloric acid at 5 °C [251]. The latter result (ratio... 

The contributions made by these pathways in proton transfer between amines and their conjugate acids have been determined [193] and the results are shown in Table 13. The rate coefficient kt refers to the direct proton transfer mechanism and k2 is for proton transfer through a solvent bridge. The available evidence for carbon acids suggests that proton transfer occurs directly between acid and base and an intervening solvent molecule is not involved [123,194]. This evidence is mostly based on the magnitude of the solvent isotope effect, and results for reactions involving nitroparaffins, acetals, and diazocompounds have been reviewed [123]. In a different approach to this question, the rate expression for the acid catalysed decomposition of ethyl vinyl ether in water/dimethyl-sulphoxide was measured [195] and shown to consist of two terms (111). 

The large negative entropies of activation and the large solvent isotope effects are no doubt intimately related. It is quite conceivable that these effects arise from a general catalysis by water of the water reaction. General base catalysis is known to occur in the hydrolysis of acetic anhydride by acetate, acetylp3rridinium ion by acetate (Bunton et al., 1961), acetylimidazole by imidazole, N-methyl,N -acetylimidazolium ion by N-methylimidazole, l-(N,N-dimethylcarbamoyl)pyridinium ion by pyridine (Johnson and Rumon, 1965), and ethyl haloacetates by weak bases (Jencks and Carriuolo, 1961). It is most reasonable then that the water reaction be similarily a base-catalyzed process. The isotope effects... 

Hydrolysis of acetals by acid is considered to proceed normally via the A1 mechanism. Electron release in the aldehyde facilitates reaction, the p value being —3.5, indicating stabilization of a cationic intermediate. The solvent isotope-effect k H2O/ D2O is approximately 2.6, which indicates that the acidic property of the solvent is more important than its nucleophilicity. The entropy of activation is positive, 5-20 K l mol-1. Glycopyranosides fit into this generalization, but the acidic hydrolysis of the corresponding furanosides shows negative entropies of activation, indicating a difference in mechanism. 

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