Methyl salicylate reaction mechanism

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. 

Salicylic acid, however, also contains a carboxyl group which undergoes its own characteristic reactions. By a mechanism similar to that of the formation of aspirin, methanol attacks salicylic acid again in the presence of acid, to form methyl salicylate, our other desired product. Note here,however, that salicylic acid is the acylating agent, forming the intermediate cation and methanol is the nucleophile ... 

Asthmatic attacks due to non-narcotic analgesics, mostly occur in patients with so-called intrinsic or idiosyncratic asthma (often associated with nasal polyposis, sinusitis and eosinophilia of the blood) (McFadden and Austen 1977). About 10% of patients with this kind of asthma show severe reactions to aspirin, methyl-salicylate, pyrazolone derivatives, indomethacin, ibuprofen, diclofenac and sometimes even phenacetin and paracetamol. (Sodium salicylate is often tolerated.) The special reactivity may appear only in later life and concerns a number of chemically unrelated drugs. In some of these patients analgesic therapy with a morphine derivative such as pentazocine (Fortalgesic) or hyoscine butylbromide (Buscopan) may be necessary. However, in other patients, those with aspirin urticaria rather than asthma, the reaction may also rely on a drug-specific allergic mechanism (de Weck 1971). 

To decide the mechanism of hydrolysis of the ionized and unionized forms of aspirin and monosubstituted aspirins is more difficult because these lead to no incorporation of label into the product salicylic acid when reaction is carried out in 0-enriched water, and there is no formation of the methyl salicylate when reaction is carried out in aqueous methanol [77]. Therefore either the reaction does not proceed via a mixed anhydride or this anhydride reacts exclusively by attack at the acetyl group. 

Insufficient data are available to assess accurately the atmospheric fate of methyl salicylate. However, the rate coefficient estimates presented in this section indicate that reaction with NO3 could be an important loss mechanism, limiting the nighttime lifetime of methyl salicylate to as little as a few minutes even under moderately polluted conditions. Canosa-Mas et al. (2002) also report that this species possesses a strong absorption band in the near UV (amax 1-5 x 10" cm molecule" near 315 nm) which, when coupled with the assumption of a unit quantum yield for photodissociation, implies a photolysis lifetime of about 1 min. However, the photolysis quantum yield for methyl salicylate at 308 nm in cyclohexane solution has been reported to be... 

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... 

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