The application discloses a kind of single-substituted 1,2,4,5-
tetrazine compounds based on five-membered heterocyclic ring and preparation method thereof.The single-substituted 1,2,4,5-
tetrazine compounds based on five-membered heterocyclic ring keep high
reaction rate (10 4 ~10 5 M ‑1 s ‑1 ), improve the LUMO+1 orbital energy of single-substituted
tetrazine compound to improve its stability, or improve the reaction ability of tetrazine compound under the same or similar LUMO+1 orbital energy, so that the single-substituted 1,2,4,5-tetrazine compounds based on five-membered heterocyclic ring have higher stability when the
reaction rate is certain, have higher
reaction rate when the stability is certain, provide a new idea for breaking the limitation of orbital energy and reaction ability with trans-
cyclooctene, can promote the retro Diels-
Alder reaction of 1,2,4,5-tetrazine compound and trans-
cyclooctene in vivo, and is of great significance to the field of
medicine.