An efficient metal catalyst free approach to synthesize 5-(4-(1,2,4,5 tetrazin-3-yl)benzylamino)-5-oxopentanoic acid

Despite the wide use of 1,2,4,5- tetrazines in biomaterials and materials science, currently there does not exist synthetic method(s) that can yield significant amount of 1,2,4,5- tetrazines without the use of potentially toxic metal catalysts. Here, we report a less energy intensive and more efficient metal catalyst free approach for the synthesis of an asymmetric tetrazine. A range of operating parameters such as extraction pH and temperature were regulated to achieve a practical yield nearly 1.5 times greater than the yields reported in the literature for similar synthetic procedures.