Pyrazinones irradiation products

The dechlorination of the C-3 and C-5 position of the pyrazinone system was described to be fast under microwave irradiation [29]. Contrary to the reported de-chlorination [26] via palladium-catalyzed reaction with sodium formate 100 °C for 2-4 h and at the C-5 position in 2-3 days, a dramatic rate enhancement was observed under microwave irradiation (Scheme 12). The mono-reduction at C-3 was performed at 190 °C in DMF in merely 5 min, and the reduction of C-5, starting from the mono-reduction product, was performed in n-butanol in 55 min to afford the fois-reduction product in good overall yield. 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

When a blank reaction was run by purging the solution of pyrazinone (Scheme 22, pyrazinone b) in o-DCB with ethylene gas and irradiating it at 190 °C for 100 min, only a mere 53% conversion of the starting material was observed. Microwave-enhanced hydrolysis of the sensitive imidoyl chloride moiety of the cycloadduct using aqueous NaOH resulted in a yield of only 12%. However, the situation changed dramatically when the vial was pre-pressurized with ethylene gas at 5 bar. The reaction was completed after 30 min of microwave irradiation at 190 °C, and the hydrolyzed product was isolated in 87% yield. The reaction could be completed in a mere 10 min when carried out at 220 °C at an increased ethylene pressure of 10 bar, or in 20 min at 190 °C at 10 bar ethylene pressure. 

In a typical reaction, a series of C - O linked pyrazinone-triazoles were irradiated with an excess (3.5 equiv) of DMAD in o-DCB. The reactions were completed in 6-20 min at 180 °C, using a maximum irradiation power of 200 W. After spontaneous elimination of the corresponding isocyanate or cyanogen chloride, the pyridines and pyridinones were formed in combined yields of 71-99%. It is noteworthy that the pyrazinones with an aryl moiety at the N-1 position yielded pyridines as major products, while those with ben-zyUc or alkyl ester moieties at the N-1 position furnished the corresponding pyridinones as major products. 

In a similar fashion, the C - C hnked pyrazinone-triazoles were reacted with an excess of DMAD (3.5 equiv) under microwave irradiation conditions at a pre-selected temperature of 190 °C (Scheme 29). The reactions proceeded smoothly in o-DCB in 10-20 min, using a maximum irradiation power of 200 W. Differing from the C - O analogues, the C - C linked pyrazinone-triazoles generated the corresponding pyridinones as the exclusive products. 

The heating behavior of ionic liquids combined with organic solvents under microwave irradiation has also been the subject of a recent paper by Ondruschka and coworkers [84]. Kappe et al. have used microwaves for inter and intramolecular hetero Diels-Alder reactions of 2(ll-f)-pyrazinones using dichloroethane as a solvent with small amounts of ionic liquid as heating aids (Scheme 7.26) [85], The conventional reaction can take up to 2 days to reach completion. With the micro-wave heating the reaction time could be reduced to 50 min in the absence of the ionic liquid and only 18 min in its presence. Product yields were reported to be similar to those obtained by use of conventional heating. Interestingly, when the... 

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