Pyridones, acidity mechanism

Faulkner (1923 1927) reported that mutarotation occurred much more readily in a mixture of pyridine and cresol than in either by itself. Swain and Brown (1952) extended this work and found that a-pyridone, where an acidic and a basic group are incorporated in the same molecule, is an excellent catalyst, 0 05 M concentration giving rise to a reaction 50 times faster in benzene solution than a solution of 0 05 M phenol and 0-05 M pyridine. A 0-001 M solution of a-pyridone was 7000 times more effective than equivalent concentrations of phenol and pyridine. A concerted mechanism was proposed [4]. 

Pyridines with an a- or y-carboxymethyl group (e.g. 685) undergo facile decarboxylation by a zwitterion mechanism (685 — 688) somewhat similar to that for the decarboxylation of 3-keto acids (cf. Section 3.2.3.1.1). Carboxymethylpyridines often decarboxylate spontaneously on formation thus, hydrolysis of (689) gives (690). The corresponding 2- and 4-pyridone and 2- and 4-pyrone acids are somewhat more stable, e.g. (691) decarboxylates at 170°C. 3-Pyridineacetic acid shows no pronounced tendency to decarboxylate. 

The mechanism of the reactions of aromatic unsaturated ketones with malonamide was described in [154]. The expected product of (3-addition— <5-ketamide—was isolated and fully characterized. The proposed mechanism of the formation of the terahydropyridone cycle in [154] was similar to one suggested in [134, 153] for cyanamide. The first stage of the reaction is an addition of the CH-acid to the ethylene bond of the unsaturated ketone and generation of the (3-adduct, which can easily undergo a cyclization leading to dihydro derivatives of 2-pyridone 146 (Scheme 3.45). 

Photodimerization of 2-pyridone (46) in the presence of the 2,2/-biphenyldi-carboxylic acid host (45) also proceeded via a catalytic process. First, irradiation of the 1 2 inclusion complex of 46 and 45 in the solid state gave the trans-anti dimer (47) in 92 % yield [27], The mechanism of this stereoselective photoreaction was investigated through X-ray analysis of this complex. In the complex, two 46 molecules are arranged in ideal positions for yielding 47 by dimerization [27], Secondly, a catalytic dimerization reaction of 46 was carried out. Photoirradiation for 20 h of a 1 4 mixture of powdered 45 and 46 under occasional mixing in the solid state gave 47 in 81 % yield. These data clearly show that molecules of... 

Tetrakis(pyridin-2-yloxy)silane, Si(OPy)4 (6), is a very mild dehydrating agent that can be employed to form amides from acids and amines at 20 °C in THF (Scheme 2), without the need to use any basic promoter such as tertiary amines or 4-(dimethylamino)pyridine. The proposed mechanism (Scheme 3) implicates an intermediate (A) formed from Si(OPy)4 and the acid (7) which reacts with the amine (8) to give the amide (9), with 2-pyridone and silica, (Si02)n, as by products.5... 

Dimethyl-4-pyridone exchanges as the free base at lower acidities but as the conjugate acid at acidities above H, -3.5. A similar changeover in mechanism occurs at -2.7 for l,2,6-trimethyl-4-pyridone. A comparison of rate data from l,2,6-trimethyl-4-pyridone, 4-methoxy-2,6-dimethylpyridine and... 

Danishefsky etal. [61] reported an improved route to (20/ .J)-camptothe-cin in connection with their original total synthesis [60, 62-64], Reaction of tricyclic compound (14) with sodium hexamethyldisilazide and benzalde-hyde afforded a 90% yield of the benzylidene acid (15). A mechanism similar to a Stobbe condensation with participation of the methoxycarbonyl function on the pyridone ring is suggested for this reaction step. Ozonolysis of this compound (15) Scheme 2.2) afforded a 96% yield of the acid (16) which, upon esterification, provided (17) in 81% yield. Compound (17) is readily converted to (20/ S)-camptothecin. 

Under normal conditions there is little or no urinary excretion of either nicotinamide or nicotinic acid. This is because both vitamers are actively resorbed from the glomerular filtrate. It is only when the concentration is so high that the resorption mechanism is saturated that there is any significant excretion. The main urinary metabolites of niacin are Nhmethyl nicotinamide and onward metabolic products, methyl pyridone-2-carboxamide and methyl pyridone-4-carboxamide. 

A key feature of enzyme catalysis is observed regeneration of the catalyst (via the reversible pathway). 2-Aminophenol, which is both a stronger acid and base than a-pyridone, is not as potent a catalyst. In the presence of 2-aminophenol a concerted mechanism of catalysis is not possible. 

Nitramino- or acetic acid-acetic anhydride i 222 nd by heating 2-nitramino-5- nitropyridine with sulphuric acid some workers22i obtained 2-hydroxy-5-nitropyridine rather than 2-amino-3,5-dinitropyridine (p. 172). The mechanism of the conversion of nitramines into pyridones by acid is unknown. 2-Nitramino-5-nitropyridine also gives 2-hydroxy-5-nitropyridine and nitrous oxide quantitatively with warm dilute alkali22i. 

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