Acetals specific/general acid catalysis

Aryl but not alkyl tetrahydropyranyl acetals show general acid catalysis, for the same reason [13] but aryl methyl acetals do not, because the methoxymethyl car-benium ion is not sufficiently stable. (This situation can lead to enforced general acid catalysis, when the specific acid catalyzed reaction requires nucleophilic assistance if the nucleophile is the conjugate base of the general acid this will be observed as general acid catalysis.) At the other extreme, sufficient stabilization of the carbenium ion can have the same effect, as shown by the observation of general acid catalysis of tropolone diethyl acetal 2.1 (Scheme 2.10) [14]. And even... 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

The difference between the hydrolysis of an orthoester and the hydrolysis of an acetal is that profanation and C-O bond cleavage occur together in the former. In the hydrolysis of an acetal, the protonated form of the acetal is produced as an intermediate in the reaction. While we will not go into details here, the hydrolysis of the orthoester constitutes a case of what is known as general acid catalysis, while that of an acetal is specific acid catalysis. 

In the case of apparent general acid catalysis of acetylimidazole hydrolysis, the mechanism can be defined as a specific acid-general base process by comparison with the general base catalysis of N-methyl,N -acetylimidazolium ion. The rate of disappearance of N-methyl,N -acetylimidazolium ion in water at 25° is proportional to the concentration of the basic form of buffer components such as acetate, phosphate, N-methylimidazole, etc., (equation 30) (Wolfenden and Jencks, 1961). The buffer terms show a 1 1 correlation with the general acid-catalyzed rate of acetylimidazole disappearance (Jencks and Carriuolo, 1959) in water at 25°, when the rate expression for the latter reaction is written in terms of equation (32) rather than equation (31), that is, in terms of a general base-catalyzed hydration of protonated acetylimidazole (pX= 3-6). 

The interpretation of the observed rate increase of the reaction of epichlorohydrin with iodide ion in the presence of acetic acid was questioned by Long and Paul, who suggested that specific effects of the medium brought about by 4.0 M acetic acid may be responsible for the rate increase rather than general acid catalysis.72 However, the alternative mechanism for acid-catalyzed epoxide hydrolysis proposed by these workers, an A-l mechanism involving a carbocation intermediate, has been ruled... 

Besides specific proton catalysis, general acid catalysis by oximes may contribute to the advanced degradation of concentrated pyridinium aldoxime solutions. In fact, addition of 2-PAM to HI 6 accelerated not only the cleavage of the aminal-acetal bridge of the latter (Eyer et al, 1988), but also isonicotinamide deamination (Korte and Shih, 1993). Due to this molecular canibalism , concentrated solutions of HI 6 and HLd 7 seem to be condemned to increased degradation and cannot be stockpiled in dissolved form. 

An obvious starting point was to look for general acid catalysis of the attack of nucleophiles on a methyoxymethyl acetal known to be subject to efficient carboxyl-catalyzed hydrolysis. Participation by nucleophiles other than water in the hydrolysis of the salicylic acid derivative 3.17 could not be convincingly distinguished from specific salt effects (the range of nucleophiles is limited by the requirement that the COOH group (pKa 3.77) be protonated) [49]. On the other hand there is clear involvement of nucleophiles, including carboxylate anions, in the reaction of the dimethylammonium system 3.18 [44] (Scheme 2.24). The difference is presumably simply quantitative. 

Intermolecular general acid catalysis of the hydrolysis of acetals and ketals Fig. 8 shows, in general terms, the reaction profile for the specific acid-catalysed hydrolysis of an acetal or a ketal. 

The stereochemical requirements for observation of intramolecular general acid catalysis seem quite severe - less effective participation is observed in the hydrolysis of 8-methoxymethoxy 1-naphthoic acid and none at all in the hydrolysis of (2-methoxymethoxyphenyl) acetic acid. Hydrolysis of 2-methoxymethoxy-3-methyl benzoic acid is quite strongly sterically accelerated [136] but this is also true of its specific acid-catalysed reactions. 

Bronsted and Grove (J. Amer. Chem. Soc. 1930, 52, 1394) showed that the hydrolysis of dimethyl acetal in water is specifically catalysed by hydrogen ions there is no "spontaneous reaction, nor does the reaction show general acid catalysis. Their measured values of the first-order rate constant k, determined by a dilatometric method in solutions of perchloric acid over a range of concentrations in water at 20 °C are given in table 1. 

It was pointed out in the mechanistic discussion concerning acetal and ketal hydrolysis that general acid catalysis occurs only for acetals and ketal having special structural features. Usually, specific acid catalysis operates. The question of whether general acid catalysis could be observed in intramolecular reactions has been of interest because intramolecular general acid catalysis is postulated to play a part in the mechanism of action of the enzyme lysozyme, which hydrolyzes the acetal linkage present in certain polysacharides. One group of molecules that has been examined as a model system are acetals derived from o-hydroxybenzoic acid (sali-... 

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