Coupling Reaction of Chloropyrazines and Their N-Oxides with Tetraphenyltin

Abstract

By the coupling reaction of monachloropyrazines, dichloropyrazines, 2-chlaropyrazine 1-oxides, and 2-chloropyrazine 4-oxides with tetraphenyltin, the corresponding phenylpyrazines were prepared in satisfactory yields.While the preparation of phenylpyrazines has been performed mainly by cyclization the only example involving a substitution is the phenylation using phenyllithium5.In the preceding we described that trimethylaluminum exhibits special ability for methylation of pyrazines and pyrazine N-oxides by coupling reaction, and that tetrakis(tripheny1phosphine)palladium is an effective catalyst for this reaction.In a continuation of these works, the present investigation was undertaken to find a convenient method for phenylation of 8 pyrazines, and it will be now described that tetraphenyltin answers our purpose.In the presence of tetrakis(triphenylphasphine)palladium, 2-chlaro-3,6-diisabutyl-pyrazine9 was heated under reflux with tetraphenyltin in dry diaxane, namely, under similar conditions as r e ~o r t e d ~' ~.However, the reaction resulted in recovering the starting material.When dioxane was replaced by dry N,N-dimethylformamide (DMF), and potassium carbonate was added to the reaction mixture, the desired product was obtained in 44% yields under heating at 1 0 0 ' ~ and in 75% yields under reflux.Thus, 2-chloro-3,6-dialkylpyrazines were allowed to react with tetraphenyltin in the presence of the palladium catalyst in DM? under reflux, the corresponding phenylpyrazines were obtained in good yields, as illustrated in Table 1.In the case of the reaction of 2 -c h l o r o -d i p h e n y l p y r a z i n e s , dechlorination HETEROCYCLES, Vol 24, No. 3, 1986 3,6-Diisapropyl-2-phenylpyrazine ( 2 ~) : colorless oil; bp 115-117'~/2 torr; MS: m/z 240 (Mt1, 239 (MI-H); UV: Amax 227 (log E = 4.041, 284 (4.11) nm; 'H-NMR: 6 1.20 (d, J = 6 Hz, 6H, CH(CH3I21, 1.30 (d, J = 6 Hz, 6H, CH(CH3l2), 3.08 (m, J = 6 Hz, lH, CE(CH 1 1, 3.27 (m, J = 6 Hz, lH, CH(CH ) 1, 7.33-7.60(m, 5H, benzene HI, 3 2 3 2 8.45 (s, lH, pyrazine H) ppm; m.Calcd.for C16H20N2: C, 79.96; H, 8.39; N, 11.66.