biostudies-literatureUnknown25(17)Alghamdi ZSMinistry of Education ? Kingdom of Saudi ArabiImam Abdulrahman Bin Faisal UniversityAn efficient synthesis of s-tetrazines by solid-phase methods is described. This synthesis route was compatible with different solid-phase resins and linkers and did not require metal catalysts or high temperatures. Monosubstituted tetrazines were routinely synthesized using thiol-promoted chemistry, using dichloromethane as a carbon source, while disubstituted unsymmetrical aryl or alkyl tetrazines were synthesized using readily available nitriles. This efficient approach enabled the synthesis of s-tetrazines in high yields (70-94%), eliminating the classical solution-phase problems of mixtures of symmetrical and unsymmetrical tetrazines, with only a single final purification step required, and paves the way to the rapid synthesis of s-tetrazines with various applicatOrganic letters3104-3108https://www.ebi.ac.uk/biostudies/studies/S-EPMC10167685biostudies-literatureSolid-Phase Synthesis of s-Tetrazines.PMC10167685Alghamdi ZSGambardella AKlausen MBradley MLilienkampf AfalseSolid-Phase Synthesis of s-Tetrazines.An efficient synthesis of s-tetrazines by solid-phase methods is described. This synthesis route was compatible with different solid-phase resins and linkers and did not require metal catalysts or high temperatures. Monosubstituted tetrazines were routinely synthesized using thiol-promoted chemistry, using dichloromethane as a carbon source, while disubstituted unsymmetrical aryl or alkyl tetrazines were synthesized using readily available nitriles. This efficient approach enabled the synthesis of s-tetrazines in high yields (70-94%), eliminating the classical solution-phase problems of mixtures of symmetrical and unsymmetrical tetrazines, with only a single final purification step required, and paves the way to the rapid synthesis of s-tetrazines with various applicat2023-01-01T00:00:00Z2023 May2025-04-22T00:31:53.158Z2025-04-05T19:36:41.174ZS-EPMC101676853708329910.1021/acs.orglett.3c00955