Science of Synthesis

Sato, N., Science of Synthesis, (2004) 16, 818.

Displacement of the amino group on pyrazines with nucleophiles proceeds via diazonium intermediates. Fluoropyrazine is obtained in low yield from pyrazinamine by the Balz–Schiemann reaction.[‌353‌] Diazotization of pyrazinamine N-oxides with sodium nitrite in hydrochloric acid or hydrobromic acid leads to the corresponding halopyrazine N-oxides.[‌390‌] Of synthetic value is a significantly improved procedure in which isopentyl nitrite and copper chlorides are used for the formation of chloropyrazine N-oxides, e.g. ‌223‌, from pyrazinamine N-oxides (‌Scheme 99‌).[‌197‌] Bromo-[‌318‌] and iodopyrazines[‌276‌] are also prepared by the diazotization method, but the yields are low to moderate.

‌Meeeee 88‌ Meeeeeeee ee e Meeeeeeeeeeeee M-Meeee eeee e Meeeeeeeeeee M-Meeee[‌888‌]

Meeeeeeeeeeee eeeeeeee ee eeeeeeeeee ee e eeeeeeeee eeeeee eee eee eeeeeeeee ee eeeeeeeeee ‌888‌ eeee eee eeeeeeeeeeeee eeeeeeeeeeeee (‌Meeeee 888‌).[‌888‌,‌888‌,‌888‌,‌888‌,‌888‌,‌888‌] Meeeeee-8-eeeee 8-eeeee eeee eeeeeeeee eeeeeeeeeeeee eeeeeeee ee eeeeeeeeee ee eeee eeeeeee-8-ee 8-eeeee ee 88% eeeee.[‌888‌]

‌Meeeee 888‌ Meeeeeeeee ee Meeeeeeeeeeee eeee Meeeeeeeee[‌888‌,‌888‌,‌888‌,‌888‌,‌888‌]

‌Meeeeeeeeee 888‌

M eeeee eeeee eeeeeeee ee e eeeeeee eeeee ee eeeeeee eeeeeeeee ee eeeeeeee ee eeeeeeeee ee eee eeeeeeee eeee eeeeeeeee eeeeeeeeee eeeeeeee ee eeeeeee eeeeeeee;[‌888‌,‌888‌] ee eeee eeeeeee, 8-eeeeeeeeeeee-8-eee eee eeeeeeeee eeee 8-eeeeeeeeeeeee-8-eee, eee ee eeeeeee eee ‌Meeeee 888‌.[‌888‌] Meeeeeeee, 8-eeeee-8,8-eeeeeeeeeeeeeee-8-ee eeeeeeeee eeeeeeeeeee eee eeeeeeeeee eeeeeee ee eee eeeeeeeee ee eee eeeeeeeeeeeee 8-eeeeeeeeeeeeeee eee eeeeeeee-8,8-eeeee, eeeeeeeeeeee.[‌888‌,‌888‌] Meeeeee, e eeeee eeeee eeee ee e eeeeeee eeeee ee eee eeee eeeeeeeee ee eeeeeeeeeeee, eeee eeee eeeeeeeee eeeeeeeeee eeeeeeee; 8-eeeeeeeeeeee-8-eee eee, eeeeeee, ee eeeeeeeee eeee 8,8-eeeeeeeeeeeeeeeee eeee eee eeeeee eee eeeeee eeee eeeeeeeeee eeeeeeee ee e eeeeee eeeeee ee 888°M.[‌888‌] Me eee eeeee eeee, 8,8-eeeeeeee-8-eeeeeeeeeeee-8-eeeee eeeeeeeee eeeeeeeeeeee ee eee eeeee eeeee ee e eeeee eeeee ee eeeee eee eeeeeeeeeeeee 8-eeeeeeeeeeeee-8-eeeeeeeeeeee.[‌888‌]

‌Meeeee 888‌ Meeeeeeee ee 8-Meeeee-8,8-eeeeeeeeeeeeeee-8-ee[‌888‌]

Meeeeeeeeeee Meeeeeeee

8-Meeeeeeee-8-eeeeee-8-(eeeeeeeeeeeee)-8-eeeeeeeeeeeeeeee 8-Meeee (‌888‌); Meeeeee Meeeeeeee:[‌888‌]

Me e eeeeeee ee 8-eeeeeeeee-8-eeeeeeeeeeeee-8-eeeeeeeeeeeeeee-8-eeeee (8.88 e, 8.88 eeee), MeMe8 (8.88 e, 88.8 eeee), eee MeMe (8.88 e, 88.8 eeee) ee MeMM (88 eM) eee eeeee eeeeeeeee eeeeeee (8.88 eM, 88.8 eeee) ee ee eeeee M8. Meeee eeeeeeee eee 88 eee, eee eeeeeee eee eeeeeee eeee 8% MMe eee eeeeeeeee eeee Me8M, eee eee eeeeeeee eeee eeeee eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8 ee 8:8) ee eeeeee eeeeeeee 8-eeeee ‌888‌ eeeeeeee eeee eeeeeeeeeeee eeeeeee (8.888 e, 88%); eeeee: 8.88 e (88%); ee 88–88°M.

Meeee 8-Meeeeeeeeeeeeee-8-eeeeeeeeeee (‌888‌, M8 = MM8Me; M8 = M); Meeeeee Meeeeeeee:[‌888‌]

MeMM8 (8.88 e, 8.88 eee) eee eeeee ee eeeee eeeeeeee ee eee-eeeeee eeeee M8MM8 (88 eM) eeee eeeeeeee, eee eee eeeeeeeeee eee eeeeee ee 88°M ee eeeee eeeeeeee eeeeeeeeeee. Mee eeeeeeeee eeee eee eeeeeeee ee 8°M, eee e eeee ee eeeee 8-eeeeeeeeeeeee-8-eeeeeeeeeee (8.8 e, 8.888 eee) ee eeeee M8MM8 (88 eM) eee eeeee eeeeeeee eeee eeeeeeee. Mee eeee eee eeeeeee ee eeee ee ee eee eeee ee 88°M. Meeee eeeeeeee eee 8–8 eee, eee eeee eee eeeeee ee ee eee eeeeee eeee eeeeeee eee (888 eM). Mee eeeeeee eeee eee eeeeee eeeeeeeeeee eeee 88% ee MeMM, eee eee eeeeee eeeeee eeee eee eeeeeeeee eeee eeeeeee eeeeeeee ee MeMMe. Mee eeeeeee eee eeeeeeeeeeee ee eeeee, eee eee eeeeeee eee eeeeee eeee e eeeee eeeeee ee Me8M; eeeee: 8 e (88%); ee 888°M.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 8/8, 888.
• 8.Meeeee-Meee, (8888) M 8e8, 888.
• 8.Meeeee-Meee, (8888) M 8e8, 888.