4-Pyrones reaction with amines

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. 

Scheme 10 Reactions of pyrones 21 with amines in the presence of an acid...

Enamine (235) obtained from cyclic ketones and the acetal of /V-methyl-2-pyrrolidone gave a fused 2-pyrone [83IJC(B)1083]. 2//-Chromenes were obtained from of 3,5-dichlorosalicylaldehyde and enamines (94RRC183) (Scheme 42). The pyran ring is formed by a reaction of aminals of conjugated w-dimethylaminoaldehydes with cyclic /1-dicarbonyl compounds (94IZV285) (Scheme 43). 

On the other hand, lower reaction temperature (0-30 °C) was indispensable to decrease the background reaction. Under these conditions, a wide range of other 0C, 3-unsaturated ketones and substituted 2-pyrones had been converted into bicyclic chiral compounds 17 in high yield, diastereomeric ratio, and enantiomeric excess (Table 10.8). Interestingly, theauthors noted that, incontrastto 2-pyrone, electron-rich dienes bearing neither a hydrogen-bond acceptor nor donor such as cyclopentadiene and cyclohexadiene were inactive for the Diels-Alder reaction with benzylideneace-tone catalyzed by lp and TFA. They propose that the activation of 2-pyrone by the multifunctional amine IP is also required for the D-A reaction to occur [30],... 

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. ... 

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. ... 

The remaining qmtheses of pyridine side-chain acids from nonpyridine precursors involves typical condensation reactions. The preparations of acids containing a partially reduced pyridine nucleus were performed either through condensation reactions or by the treatment of pyrones with amines. 

Ethylenediamine is probably unique in that it reacts with t-butyl chromone-2 Carboxylate to give a 4-imino derivative [181] this reaction is reversible and is probably explained by the stabilisation of the pyrone ring through hydrogen bonding as shown in (77). It is noteworthy that although t-butyl esters are more resistant than the methyl or ethyl homologues to attack by amines [153], t-butyl chromone-2-carboxylate was recently reported [182] to be converted into an enamine (78) by reaction with benzylamine. 

Thus, the reaction of 2-R -chromones with amines usually starts with the attack by the amino group on the C-2 atom. In the case of secondary amines or in the presence of a substituent at the 5-position, the reaction can stop after 1,4-nucleophilic addition however, in most cases, it is accompanied by pyrone ring opening giving the corresponding aminovinyl ketones, whose structural features and subsequent transformations provide a variety of products. An exception is the reaction of 2-R -chromones with 2-aminoethanol pointing to the possibility of an attack by the amine on the carbonyl group. 

Analogously, the reactions of ketene aminals with ketene or dimethyl ketene gave y-amino-a-pyrones and the linear acylation products, respectively 422). 

It is interesting to note that such pyrone complexes have also been isolated from the carbonylation of products obtained from the reaction of 184.a with a secondary amine.126 Park invokes two vinylketene complexes (201 and 202) as key intermediates in the transformation, although none... 

Chromanones,4 In the presence of this amine 4-mcthyl-6-hydroxy-2-pyrone (1) undergoes decarboxylative dimerization to form a coumarochromanone (2) in 42 yield. The pyrone group in 2 undergoes decarboxylative Diels Alder reactions (8, 32G 9, 175 176) with acetylenes to form 4-chromanoncs (3). 

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