Pyrazine reaction with dimethyl acetylenedicarboxylate

In another paper, the same authors investigated the 1,3-dipolar cycloaddition on 2-(lH)-pyrazine scaffolds 72 and electron-rich azides, using Cu(0) and CUSO4 as pre-catalysts. To demonstrate the versatility of this approach, they reported the generation of different templates (73 in Scheme 25) as an application of cUck chemistry . They also investigated the Diels-Alder reaction of the so obtained triazoles with dimethyl acetylenedicarboxylate (DMAD), under microwave irradiation. The latter reaction allowed obtaining various pyridinones in good yields (74 and 75 in Scheme 25) [57]. 

Dimethyi-l-phenacylpyrazinium bromide (from 2,5-dimethylpyrazine and phenacyl bromide) and dimethyl acetylenedicarboxylate has been shown to give 6-benzoyl-7,8-bis(methoxycarbonyl)-1,4-dimethylpyrroIo[ 1,2-a] pyrazine (25) and 7,8-bis(methoxycarbonyl)-l,4-dimethylpyrrolo[l,2-fl]pyrazine (26) (723), and 1,2,5-trimethylpyrazinium iodide and dimethyl acetylenedicarboxylate also gave a 1% yield of (26). Addition reactions of 2-methyl- (724), 2,6-dimethyl- (724), 2,5-dimethyl- (725), and 2,3,5,6-tetramethylpyrazine (725), with dimethyl acetylenedicarboxylate have also been investigated. 

Various complex derivatives of the ring system have been prepared starting from pyrazine intermediates. Frequently the yields from these reactions tend to be low and of little synthetic value. Thus reaction of dimethyl acetylenedicarboxylate with the ylid 29 gave a mixture of compounds 30a and 30b in 5 and 16% yields, respectively. The corresponding reaction with ylid 31 gave a 8.5% yield of a mixture containing two parts of 32 and one part of 33. 

Butler has described that the treatment of l-ethoxycarbonylmethyl-2,3,4,5-tetraarylpyrazolium salts with base in the presence of DM AD (dimethyl acetylenedicarboxylate) affords l-(2 -amino-vinylpyrroles) and pyrrolo[l,2-a] pyrazines <93JCS(Pl)883> a mechanism has been proposed for this unexpected behavior. Reaction of l,3,4,5-tetraaryl-2-methylpyrazolium salts (141) with ethoxide base produces the fragmentation of the pyrazole ring with formation of 1,2-bisimines (142) the mechanism is represented in Scheme 2 <94JCR(S)12>. In both cases the structures of the resulting products were supported by x-ray determinations. 

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