Efficient synthesis of unsymmetrical trisubstituted 1,3,5-triazines catalyzed by hemoglobin

Background: 1,3,5-triazines are important bioactive compounds that have been extensively studied in organic chemistry. In this work, a green and efficient process for the synthesis of unsymmetrical trisubstituted 1,3,5-triazines from isothiocyanate (1) with amidines (2) and 1,1,3,3-tetramethylguanidine (TMG, 3) was developed. Results: Under optimal conditions (isothiocyanate (0.1 mmol), amidines (0.1 mmol), 1,1,3,3-tetramethylguanidine (0.1 mmol), HMSO (1 mL), hemepmtein (heme concentration: 0.05 mol%), TBHP (3 equiv), room temperature, 10 min), high yields of 1,3,5-triazines (81%-96%) could be obtained when HbRb (Hemoglobin from rabbit blood) was used as the catalyst. Conclusion: This enzymatic method demonstrates the great potential for the synthesis of unsymmetrical trisubstituted 1,3,5-triazines and extends the application of enzyme catalytic promiscuity in organic synthesis.

Automated summary

The research introduces a green and efficient method for the synthesis of unsymmetrical trisubstituted 1,3,5-triazines from isothiocyanate, amidines, and 1,1,3,3-tetramethylguanidine, achieving high yields under optimal conditions with Hemoglobin from rabbit blood as the catalyst. This enzymatic approach demonstrates the potential for extending the application of enzyme catalytic promiscuity in organic synthesis.