An efficient and green procedure for the synthesis of tetrazines has been developed based on an old chemistry reported by Carboni in 1958. Both symmetric and asymmetric 3,6-disubstituted 1,2,4,5-tetrazines can be obtained in moderate to high yields from the corresponding gem-difluoroalkenes under aerobic conditions at room temperature. This work represents a rare example that ambient air is utilized as an oxidant for the synthesis of tetrazines.
Synthesis of tetrazines from gem-difluoroalkenes under aerobic conditions at room temperature
3,6−bis([1,1'−biphenyl]−4−ylmethyl)−1,2,4,5−tetra zine (3a). (41 mg, 83%). purple solid;
IR(KBr) nmax/cm−1 2924, 2850, 1488, 1451, 1432, 1388, 851, 750;
1 H NMR (400 MHz, CDCl3) 7.55−7.33 (m, 18H), 4.65 (s, 4H).
13C NMR (100 MHz, CDCl3) δ 169.2, 140.6, 140.4, 134.8, 129.7, 128.8, 127.6, 127.4, 127.1, 40.9;
HRMS (ESI): calcd. for C28H22N4 [M+H]+ 415.19172, found 415.19124.