Science of Synthesis

Sato, N., Science of Synthesis, (2004) 16, 758.

The synthesis of pyrazines from alkane-1,2-diamines by formation of two N—C bonds is certainly the oldest and most general synthetic method for pyrazine formation, and it generally involves the condensation of an alkane-1,2-diamine with a 1,2-dicarbonyl compound followed by oxidation of the resulting 1,2-dihydropyrazine ‌28‌ (‌Scheme 9‌). The ethylenediamine or propane-1,2-diamine undergoes condensation with a variety of 1,2-diketones leading to 2,3-disubstituted pyrazines ‌29‌ or their 5-methyl derivatives after oxidative dehydrogenation. Although aromatization is sometimes completed during workup, generally the use of mild oxidizing agents is required (Section ‌16.14.3‌). When glyoxyloyl compounds are condensed with nonsymmetrical 1,2-diamines, two isomeric pyrazines are obtained in comparable ratio; in such a case, the yields are usually lower than in cases giving a single product.[‌97‌–‌99‌] Condensation of 2,3-diaminopropanoic acid with glyoxal gives pyrazinecarboxylic acid ‌29‌ (R1 = CO2H; R2 = R3 = R4 = H).[‌97‌]

‌Meeeee 8‌ Meeeeeeee ee Meeeeeeee ee Meeeeeeeeeee ee 8,8-Meeeeeee eeee 8,8-Meeeeeeee[‌88‌,‌888‌–‌888‌]

‌Meeeeeeeeee 8‌

e ee 88°M/88 Meee.

Meeeeee ee 8,8-eeeeeeeee, α-eeeeeeeeeeeeee eeeeeee ee eeeeeeeee eeeeeeeeeee eee ee eeeeeeee eee eee eeeeeeeeeeee eeee 8,8-eeeeeeee (‌Meeeee 88‌). α-Meeee eeeeeee eee eeeeeeeee eeee e eeeeee ee 8,8-eeeeeeeeeeeee eeeeeeeee; eee eeeeeee, 8-[eeeeee(eeeeeeeeeeeeeeeeeeeeeee)eeeee]eeeee-8-eee ‌88‌, eeeeeeeee eeee ee α-eeeee eeeeee, ee eeeeeee eeeeeeeee eeee eeeeeeeeeeeeeee, eee eee eeeeeee eeeeeeeeeeee eeeeeee ee eeee eeeeeeee ee eee ee eeee 8,8-eeeeeeeeeeeee eeeeeeeee ‌88‌.[‌888‌] Meee(eee)eeeeeeeeeeeee ‌88‌ eeeeeee eeeeeeeeeee eeee eeeeeeeeeeeeeee ee eeeeeeeee eeeeeee ee eeeeeee 8-eeeeeeeeeee-8-eeeeee ‌88‌ (eee eeeeeeeeeeee eeeeeeeeeeeeeee ee eeeeeeeeeeeee eeeeeeee ee eee).[‌888‌] Mee eee ee α-eeeeeeeeeeeeee eeeeeeee ee eeee eeeeeeeee eee eee eeeeeeeeeeee eeee 8,8-eeeeeeee. Mee eeeeeee, eee-8-ee-8-eee ‌88‌, eeeeeeee eee eee eeeeeeeeeeeee 8-eeeeeeeeeeee-8-eeee, eeeeeeee eeee eeeeee-8,8-eeeeeeee ee eee eeeeeeee ee eeeeeee(MM) eeeeeee ee eeeee eeeeeeeeeeeeeeee ‌88‌.[‌888‌] Me eee eeee ee 8,8-eeeee ‌88‌, eee eeeeeeeeeee ee eeeeeeeeeeeeee ‌88‌ eee eeee eeeeeeeeeeee ee eeee eeeeee eeeee eeeee-eeeeeeeee eeeeeeeeee ee 888°M.[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeee ee Meeeeeeeeeee ee 8,8-Meeeeeee eeee α-Meeeeeeeeeeeee Meeeeee ee Meeeeeeee Meeeeeeeeee[‌888‌–‌888‌]

Mee eeeeeeeeeee eeee ee 8-eeeeee-8M-eeeeee-8,8-eeeee (‌88‌) ee eeeeeee ee eeeeeeeee eeeeeee ee eeee eeeeeeeeeeeeeeee eeeee ‌88‌, eeeee eeeeeeeee eeee eeeeeeeeeeeeeee (‌Meeeee 88‌). Mee eeeeeeeee eeeeeeeeeeeeeeeee ee eeeeeeeeee eeee 8-eeeeeeeeeeeeeeeeeee eeee ee eeeeeeeee eeee ee eeeeeee eeeeeeeee ‌88‌.[‌888‌]

‌Meeeee 88‌ Meeeeeeee ee Meeeeeeeee ee Meeeeeeeeeee ee Meeeee-8,8-eeeeeeee eeee ee Meeee Meeeeeeeeeeeeeee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-Meeeee-8,8-eee(8-eeeee)eeeeeeee (‌88‌, M8 = M; M8 = Me; M8 = M8 = 8-Mee); Meeeeee Meeeeeeee:[‌888‌]

Me e eeee ee 8,8-eee(8-eeeee)eeeeee-8,8-eeeee (8 eeee) ee MeMM (88 eM) eee eeeee eeeeeeee eeeeeee-8,8-eeeeeee (8 eeee) ee ee. Mee eeeeeee eee eeeeee ee eeeeee eee 8 e, eee eee eeeeeee eeeeee eee eeeeeee ee 88 eM. Meeee eee eeeeeee eee eeee eeeeee, eee eeeeeeeeeeee eeee eeeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee) ee ee eeeeeeeeeeeeeeeee ee eeeeee eee eeeeeeeeeeeeeee ‌88‌ (M8 = M; M8 = Me; M8 = M8 = 8-Mee). M eeeeeee ee ‌88‌ (M8 = M; M8 = Me; M8 = M8 = 8-Mee; 8.8 eeee) eee eeeeeeee M (8 eeee) eee eeeeee ee 888°M ee ee eee eeee, eee eee eeeeeee ‌88‌ eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee) eee eeee eeeeeeeeeeeeee.

8-Meeeeeee-8-eeeeeeeeeeeeee (‌88‌, M8 = eMe): Meeeeee Meeeeeeee:[‌888‌]

M-Meeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee (8.88 e, 8.8888 eee) eee eeeeeeeee eeee 8-eeeee-8-eeeeeeeeeee-8-eee (8.88 e, 8.88 eee) ee MMM (88 eM) eeee M8MM8 (8.88 e, 8.88 eee) ee eee eeee, ee 88°M eee 88 e, ee eeee ‌88‌ (M8 = eMe). Meeeeeeeeeeeeee (8.88 e, 8.888 eeee) eee eeeee, eee eee eeeeeee eee eeeeee ee 88°M eee 88 e. Mee eeeeeeeee eeeeeee eee eeeee eeee e eeeeee ee 8–8 e ee e eee. eeee ee MeMM ee MeMM (888 eM) ee 88°M eeeee M8 eee eeeeeee eeeeeeeeee eeee eee eeeeeee. Meeeee eeeeeeee eee eeeeeeeee eee ee eeeeeeeeee 8 e. Mee eeeeeee eee eeeeee eeee M8M eee eeeeeeeee eeee Me8M, eee eee eeeeeee eee eeeeee eeee 8% ee MMe. Mee eeee eeeeeee eee eeeeeeeee eeee Me8M, eee eee eeeeeeee eeeeeee eeeeeeee eeee eeeeee eeee eee. ee MeMe. Meeee eeeeee (Me8MM8), eee eeeeeee eee eeeeeee ee eeeee ee eeee ‌88‌ (M8 = eMe) ee ee eee; eeeee: 8.88 e (88%); ee 88–88°M/88 Meee.

8-Meeeeeeeeeeee-8-eeeee (‌88‌, Me8 = Me); Meeeeee Meeeeeeee:[‌888‌]

Me e eeeeeeeeee eeee ee eeeeeeeeeeeeeee (8.8 e, 88 eeee) ee eeeee eeeeeee (88 eM) (MMMMMMM: eeeeeeeeee) eee eeeee eeeeeeee e eeee ee eee(eeeeee)eeeeeeeeeeee (‌88‌, Me8 = Me; 8.88 e, 88 eeee) ee eeeee eeeeeee (88 eM) eeee e eeeeee ee 8 e. Mee eeeeeeeee eee eeee eee eeeeee eeeee eeeeee eee 8 e. Meeee eee eeeeeee eee eeeeee, e eeeeeeeee eeeeeeeeeee eeeeee, eeeee eee eeeeeeeee eee eeeeeeeeeeeeee (eeeeeee/MeMM 8:8); eeeee: 8.88 e (88%), ee 888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) M 8e8, 888.