2-Pyrone reaction with ammonia

When one of the carbonyl carbons is at the oxidation level of acid (as in a 2-pyrone), then the product, reflecting this oxidation level, is a 2-pyridone. Similarly, 4-pyrones react with ammonia or primary amines to give 4-pyridones and the bis-enamines which can be obtained directly from ketones by condensation on both sides of the carbonyl group with DMFDMA, produce 4-pyridones on reaction with primary amines. When one of the carbonyl units is actually a nitrile, then an amino-pyridine results. ... 

The ready availability of pyrones 2 and the enhanced reactivity at their a-position have made them the starting materials of choice for the synthesis of 2-(trifluoromethyl)-4-pyridinols 7 by reaction with ammonia or methylamine [6-8] (Scheme 4). 

Aminomethylfurans are converted into 3-hydroxypyridines by acid and an oxidizing agent, e.g. (219) —+ (220). 2-Hydroxymethylfurans with chlorine in aqueous methanol give 3-hydroxy-4-pyrones. 3-Hydroxypyridines can conveniently be prepared by reaction of 2-acylfurans with ammonia (Scheme 75). Pyrrole and dichlorocarbene give some 3-chloropyridine (Section 3.3.1.7.1). 

Pyrones, which are the ring-oxygen equivalents of pyridones, are simply a- and y-hydroxy-pyrylium salts from which an 0-proton has been removed. There is little to recommend that 2- and 4-pyrones be viewed as aromatic they are perhaps best seen as cyclic unsaturated lactones and cyclic p-oxy-a,P-unsaturated-ketones, respectively, for example 2-pyrones are hydrolysed by alkali, just like simpler esters (lactones). It is instructive that, whereas the pyrones are converted into pyridones by reaction with amines or ammonia, the reverse is not the case - pyridones are not transformed into pyrones by water or hydroxide. Some electrophilic C-substitutions are known for pyrones and benzopyrenes, the oxygen guiding the electrophile ortho or para, however there is a tendency for electrophihe addition to the C-C double bond of the heterocyclic ring, again reflecting their non-aromatic nature. Easy Diels-Alder additions to 2-pyrones are further evidence for diene, rather than aromatic, character. 

Pyrones can in principle add nucleophilic reactants at either C-2 (carbonyl carbon), C-4 or C-6 their reactions with cyanide anion," and ammonia/amines are examples of the latter, whereas the addition of Grignard nucleophiles occurs at carbonyl carbon. 

Ammonia and primary aliphatic and aromatic amines convert 4-pyrones into 4-pyridones ° this must involve attack at an a-position, then ring opening and reclosure in some cases ring-opened products of reaction with two mole equivalents of the amine have been isolated, though such structures are not necessarily intermediates on the route to pyridones. The transformation can also be achieved by, first, hydrolytic ring opening using barium hydroxide (see above), and then reaction of the barium salt with ammonium chloride. ... 

When 1-phenyl-2,4-pentanedione is doubly deprotonated with potassium amide in ammonia, the ensuing aldol reaction with benzophenone gives the expected aldol (19). However, if sodium amide is employed to generate the dianion, the reaction product with benzophenone is the dihydro-7-pyrone (20 equation 36). This result suggests the intermediacy in the latter reaction of a dianion involving the benzyiic position. Further study of this interesting reaction is warranted. 

Tetraethoxypropane (malonaldehyde tetraethylacetal) (XII-41) and diethyl malonate in acetic anhydride give diethyl 3-ethoxyallylidenemalonate (Xn-42), which cyclizes ii polyphosphoric acid or formic acid to the pyrone XII-43. Reaction of W42 with ammonia w henzylamine forms 3-aminoallylidenemalonates (XII-44 R = H, GHjCgHs), which are cyclized to the ethyl a-pyridone-3carhoxylates (XII-4S) in alcoholic sodinm ethoxide or piperidine. ... 

The first synthesis of 4-pyrone derivatives with two CF3 groups was reported in 1988 by Lee and co-workers [22]. Acetone dicarboxylic acid monomethyl ester 47 reacted with isobutylene in sulfuric acid to form 48. Subsequent reaction with MgCL and trifluoroacetic anhydride led to pyrone 49. This compound was converted to the monoester 50, which gave pyrone 51. The latter was reacted with ammonia in methanol to form 4-hydroxypyridine 52 [22] (Scheme 15). 

Ammonia, primaiy amines, and related acyclic nitrogen nucleophiles react with a large variety of pyrones to form pyridones. These reactions often have been used to characterize the pyrones or to remove them from mixtures. Under these circumstances, yields are often not reported and experimental conditions are not optimal, and, therefore, in many instances these reactions are difficult to evaluate, particularly as alternative routes to the somewhat more carefully studied direct ring closures to form pyridones. 

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