The condensation of (chlorocarbonyl)phenyl ketene with 1,3-dinucleophiles. I. Synthesis of 4-hydroxy-2-(1 H )-pyridinones and mesoionic 1,3-oxazinium olates

Investigation of the reaction of (chlorocarbonyl)phenyl ketene with 1,3-dinucleophiles such as Schiff bases which were prepared from acetophenone and aryl amides led to the discovery of new synthetic pathways towards 4-hydroxy-3,6-disubstituted-2(1 H )–pyridinones and 2,5-diaryl-6-oxo-5-phenyl-6 H -1,3-oxazin-3-ium-4-olates respectively. These reactions provide a new route to produce 2-pyridinones and cross - conjugated heterocyclic mesomeric betaines in good to excellent yields in a short reaction time.


Introduction
(Chlorocarbonyl)phenyl ketene 2, first described by Nakanishi, represents a highly reactive equivalent of phenylmalonic acid. 1 Chlorocarbonyl ketenes (CCKs) are currently of considerable interest, not only because of mechanistic and theoretical considerations, 2 but also due to their use as synthetic building blocks in the preparation of organic compounds. 3These ketenes have been found to be very effective 1,3-dielectrophilic reagents and react with a wide variety of nucleophiles under mild experimental conditions, and have been used mainly for the synthesis of five-and six-membered heterocycles functionalized with oxo and hydroxyl groups in the 1,3positions. 4,5 ructures containing the 2(1H)-pyridinone (2-pyridone) skeleton are rapidly gaining importance in synthetic and natural product chemistry.Compounds incorporating this nucleus are quite versatile as synthetic intermediates. 6,7For example, treatment of 2-pyridones with phosphorus pentachloride generates 2-chloropyridines.The pyridone nucleus can be partially reduced via catalytic hydrogenation to piperidinones or further reduced to fully saturated piperidines.The diene portion of the molecule can undergo Diels-Alder cycloaddition reactions with dienophiles, or one double bond may act as a dienophile to an added diene. 8Some monocyclic pyridones are important medicinally since they exhibit antiinflammatory activity. 9Among the naturally occurring substances which incorporate the 2(lH)-pyridinone nucleus are ricinine and tenellin.Additional members of this class belong to the Lupinane group of alkaloids, such as cytisine and anagyrine. 10he synthesis of 6-chloro-2,3,5-triphenyl-1,3-oxazine-4-one from the reaction of ketene 2 with N-benzylideneaniline (Schiff base of benzaldehyde) as a [4+2] cycloaddition product has been reported. 11In continuing our previous work on the reaction of chlorocarbonyl ketenes (CCKs) with dinucleophiles, [12][13][14][15][16] we now wish to describe the condensation of (chlorocarbonyl)phenyl ketene with 1,3-dinucleophiles such as Schiff bases prepared from acetophenone and N-substituted benzamides to afford 4-hydroxy-2-(1H)-pyridinone and mesoionic 1,3-oxazinium olate derivatives respectively.

Results and Discussion
Due to our interest in preparing structures containing the 2(lH)-pyridinone skeleton 17 as exhibited in Scheme 1 the 4-hydroxy-3,6-disubstituted-2(1H)-pyridinone derivatives were prepared in a one step procedure from readily available (chlorocarbonyl)phenyl ketene and

Scheme 4
The cycloaddition reactions presented in Schemes 1 and 2 were accomplished by boiling equimolar quantities of (chlorocarbonyl)phenyl ketene and the corresponding 1,3-dinucleophiles (Schiff bases and benzamides) in a dry solvent.These compounds are not reactive enough to react with dielectrophiles such as (chlorocarbonyl)phenyl ketene at ambient temperature.However, when they are converted to other tautomeric forms at high temperature, the nitrogen or hydroxy groups of the tautomeric forms will attack the acyl chloride of the ketene followed by ring closure to produce the products.A plausible mechanism for the reaction of (chlorocarbonyl)phenyl ketene with Schiff bases 1 is proposed in Scheme 5.The structures of compounds 3a-e and 5a, b were deduced from their elemental analyses and their IR, high-field 1 H-and 13 C-NMR spectra.The 1 H-NMR and 13 C-NMR spectra of 4hydroxy-3,6-disubstituted-2(1H)-pyridinone derivatives 3a-e exhibited only one tautomer.

Conclusions
In conclusion we have shown that the condensation reactions of (chlorocarbonyl) phenyl ketene with 1,3-dinucleophiles such as Schiff bases and amides occur efficiently in boiling toluene or xylene, providing a convenient and rapid synthesis of 4-hydroxy-3,6-disubstituted-2(1H)-pyridinone and 1,3-oxazin-3-ium-6-olate derivatives in high yield, by a simple procedure and short experimental time.Furthermore the products are solid and precipitate out from the reaction mixture which makes their purification simple.

Experimental Section
General Procedures.Melting points were measured on a Gallenkamp melting point apparatus and are uncorrected.IR spectra were measured on a Mattson 1000 FT-IR spectrometer.The proton and carbon NMR spectra were recorded with a BRUKER DRX-500 AVANCE spectrometer at 500 and 125.77MHz, respectively.Mass spectra were recorded on a MS-QP2000A Shimadzu mass spectrometer operating at an ionization potential of 70 eV.Elemental analyses were performed using a Heracus CHN-O-Rapid analyzer.