Protocol for synthesis of di- and tri-substituted s-triazine derivatives

The present protocol describes the synthesis of di and tri-substituted s-triazine derivatives• s-Triazine undergoes sequential nucleophilic substitution reaction but order of nucleophile is very crucial.• It is very difficult to substitute any nucleophile except amine once amine is incorporated onto s-triazine.• During the synthesis of O,N-type substituted s-triazine, always O-type should be incorporated first.


Method details
Method details involves synthesis of di-and tri-substituted s-triazine derivatives as drawn in below scheme.
(3) K 2 CO 3 (10 mmol) was added to cyanuric chloride solution while stirring vigorously at 0 °C in a round bottom flask. (4) A cold solution of 4-aminobenzonitrile was added dropwise to the stirring solution of cyanuric chloride and K 2 CO 3 .
(5) The reaction was stirred for 4 h at 0 °C (Note: maintaining temperature at 0 °C is very crucial for the reaction to avoid double incorporation). (6) Monitor the reaction by TLC using 20% MeOH in chloroform as mobile phase in a closed system. (7) Once no starting material appears on TLC, pour the reaction mixture onto crushed ice (1 L) in a beaker. (8) Filter the solid product with distilled H 2 O (3 × 500 mL) and dry under high vacuum to obtain pure product.
(2) MeOH (50 mL) is added to the above solution and stirred vigorously at 0 °C.
(4) The reaction was stirred for 3 h at 0 °C (Note: maintaining temperature at 0 °C is very crucial for the reaction to avoid double incorporation). (5) Monitor the reaction by TLC using EtOAc-hexane (6:4) in a closed system. Step 2: Synthesis of 4-chloro-6-methoxy (

Method validation
All the compounds were obtained in high yields and high purity as confirmed by 1 H-NMR and 13 C-NMR.