Novel ring transformation of mesoionic oxazoles into 2(1H)-pyrazinones by the reaction with TosMIC

A Novel Methodology for Synthesis of 1,5,6-Trisubstituted 2(1<i>H</i>)-Pyrazinones of Biological Interest

“…On the other hand, 4-acetyl (7b) and 4-formyl (7c) derivatives afforded poor con- version (entries 2 and 3). The molecular structures of 3a 14) and 4a 17) were previously confirmed by X-ray diffraction study of single crystals. A tentative mechanism which accounts for the formation of 3 is described in the communication.…”

“…In our previous communication, 14) we examined the reaction of 1a with TosMIC under varying reaction conditions to determine the optimum conditions and reported the isolated yields of 3a-i which were shown in Table 1. The best conditions to obtain the 2-pyrazinones 3a-i were achieved using 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) as the base in N,Ndimethylformamide (DMF) at 0°C under O 2 atmosphere with bubbling by O 2 throughout the reaction.…”

“…The pathway of the reaction was elucidated to conduct the reaction under an atmosphere of 18 O 2 and the carbonyl group of amide in 3a contained more than 67% of the 18 O label. 14) In this study, two new substrates 1j and k were subjected to the reaction (Table 1, entries 10 and 11). In addition, imidazo[1,5-a] pyrazin-8(7H)-one derivatives (4a-h, j, k) were also isolated as a side product as shown in Table 1.…”

“…A tentative mechanism which accounts for the formation of 3 is described in the communication. 14) Thus, initial nucleophilic attack by the TosMIC anion on C-2 of 1 gave rise to an adduct which is converted to the 2-pyrazineones (3) via a ring closure followed by auto-oxidation.…”

The Fascinating Chemistry of Mesoionic 4-Trifluoroacetyl-1,3-oxazolium-5-olates and Related Compounds

“…60 The reaction of 5 with p-toluenesulfonylmethyl isocyanate (TosMIC) in the presence of a base such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) affords 2(1H)-pyrazinones 52 in moderate yields. 26,62 The origin of the C-2 carbonyl oxygen atom in the product 52a* (R 1 = Me, R 2 = Ph) was shown to be molecular oxygen by 18 Compounds 5 undergo tandem ring opening and ring closure on addition of hydroxylamine to afford 6-trifluoromethyl-1,2,4-oxadiazin-6-ols 62 in high yields (Scheme 37). 66 In this reaction, initial attack at the C-2 position, ring opening, and extrusion of carbon dioxide are followed by intramolecular cyclization (Scheme 38).…”