Salicylic acids, catalysis with

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

Mechanism I was ruled out by an isotopic labeling experiment. The mixed anhydride of salicylic acid and acetic acid is an intermediate if nucleophilic catalysis occurs by mechanism 1. This molecule is known to hydrolyze in water with about 25% incorporation of solvent water into the salicylic acid. 

With the important exception of acetals (and possibly certain other derivatives) of salicylic acid (compounds H. 1.6-11 see the following section), which are hydrolysed with intramolecular general acid catalysis by the carboxyl group, with EM s of the order of 104 M... 

Suitably substituted acetals have been shown to hydrolyse rapidly by a mechanism that involves intramolecular general acid catalysis similar to that proposed for Glu-35 in (34), The largest effects have been found for acetals with the salicylate ion as the leaving group. For example, the spontaneous hydrolysis (35) of 2-methoxymethoxybenzoic acid [73] occurs 300-fold more rapidly than the same reaction of 4-methoxymethoxybenzoic acid [74] and ca. 600-fold more rapidly than the reaction of 2-methoxymethoxybenzoic acid methyl ester [75] (Capon et al, 1969 Dunn and Bruice, 1970). The... 

Morawetz and Oreskes (1958) postulated that intramolecular general acid catalysis occurs in concert with nucleophilic attack by carboxylate anion in the hydrolysis of the monoanion of succinyl salicylate. At pH 4 the observed hydrolytic rate constant was found to be 10 times greater than that for hydrolysis of acetylsalicylate. A... 

Although metal-promoted hydrolysis of phosphate esters is a topic of very current interest (Section 61.4.4), little work has been published dealing with the effects of metal ions on the hydrolysis of sulfate esters. The acid-catalyzed hydrolysis of aryl sulfates has been shown to occur by an A-l mechanism (Scheme 34).434 Nucleophilic catalysis by amines has been observed in the hydrolysis of p-nitrophenyl sulfate435 and intramolecular carboxyl group catalysis occurs with salicyl sulfate436 as with salicyl phosphate. 

Figure 3.17 Molecular mechanisms giving rise to enhanced hydrolysis rates of glycosides with carboxylic acid groups. In the case of salicyl fi-glucoside, frontside nucleophilic attack is stereoelectronically prohibited and distinction between specific acid catalysis of the hydrolysis of the anion and intramolecular general acid catalysis was made on the basis of solvent isotope effects in related systems. ...

Detailed studies with several systems derived from salicylic acid suggest that the key to the highly eflRcient catalysis is the strong intramolecular hydrogen bond in the salicylate anion produced (Scheme 2.16). This is known to raise the pfCa of the phenolic OH group, to 12.95 at 25 °C in water [42], so is worth some 4-5 kcal mol h even though the pK s of the two groups concerned are not closely matched. 

Figure 7.P29 gives the pH-rate profile for alkaline hydrolysis of two substituted salicylate amides, as compared with benzamide. Consider whether the pH-rate profiles for the salicylamides are more consistent with mechanism (A), intramolecular basic catalysis of water attack, or (B), intramolecular acid catalysis of hydroxide ion attack. 

Several studies on intramolecular catalysis of the solvolysis of phosphate esters have been reported. The larger hydrolysis rate of the zwitterion of 8-hydroxyquinoline phosphate (20) compared with that of pyridyl 3-phosphate (21) was attributed, on the basis of the kinetic isotope effect, to intramolecular general acid catalysis. A similar general acid catalysis by the hydroxy-group seems to operate in the (3-hydroxy-2-pyridyl)methyl phosphate dianion (22), which hydrolyses faster than either the monoanion or the neutral molecule. From a study of 4- and 5-substituted derivatives of salicyl phosphate (23) it is suggested that the negligible solvent isotope effect is inconsistent with preliminary proton transfer, and that here also intramolecular general acid catalysis by the... 

The lability of salicyl -D-glucopyranoside (LI) compared with its para isomer was tentatively attributed to intramolecular general acid catalysis in 1963 [132], in... 

Most of the quantitative work in this area has been done with putative models for lysozyme action. Thus, synchronous acetamido group participation and intramolecular general acid catalysis was held to be responsible for the modest rate enhancement of compound LXI compared with the p-nitrophenyl compound or salicyl glucoside... 

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