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.