Synthetic Strategy To Unsymmetrical Trisubstituted S-triazines

1,3,5-triazine is an important class of chemicals,which plays an extremely important role in many fields.In biomedicine,1,3,5-triazine is an important building block of many bioactive drugs,and exhibits outstanding performance in the treatment of brain diseases.In agricultural production,1,3,5-triazine is a highly effective herbicide.In material chemistry,1,3,5-triazine is present in many optoelectronic materials,semiconductors,and polymer films.In organic synthesis,1,3,5-triazine is an important class of nitrogen-containing ligands.In addition,a variety of oxidation reagents and esterification reagents have been designed based on 1,3,5-triazine.So far,many methods to synthesize 1,3,5-triazine have been reported.These synthetic methods can be roughly divided into three categories:1)Cyclotrimerization of nitriles.This method often requires acid as a catalyst,and the reaction needs to be carried out under high temperatures.Aromatic nitriles have higher reactivity,while aliphatic nitriles are difficult to react.This method is only suitable for the synthesis of symmetric 1,3,5-triazine.2)Synthesis of 1,3,5-triazine with amidines or guanidines as substrates.This strategy requires the introduction of a carbon synthon,such as styrene,benzaldehyde,benzaldehyde,toluene,DMF,DMSO,etc.1,3,5-Triazine is prepared via the reaction of two amidine molecules or two guanidine molecules with a carbon synthon.This method requires the participation of metal catalyst,oxidant,and base.For the synthesis of asymmetric tri-substituted 1,3,5-triazines,it seems powerless.3)Synthesis of 1,3,5-triazine via the coupling of trichlorotriazine with various coupling partners.This method could achieve unsymmetrical trisubstituted 1,3,5-triazines with the ability to adjust the substituents on demand.However,the disadvantages are obvious,includinglong reaction steps,tedious work-up procedures,low comprehensive yield,and poor economy.This paper designed a new strategy for the synthesis of l,3,5-triazine through a three-step reaction.1)Amide,oxalyl chloride and amidine compounds are used as substrates to synthesize triazone;2)Transform triazone intro chlorine-substituted 1,3,5triazine with POCl3 as chlorination reagent;3)Coupling of 2-chloro-1,3,5-triazine with nucleophile on demend.Our strategy to prepare 1,3,5-triazine has the following advantages:1)The triazone skeleton can be constructed by one-pot cooking method,and two different substituents can be introduced,which is in line with atom economy,simple postreaction processing,and pure product can be obtained without column chromatography;2)No metal catalysts and ligands are needed,and the use of additives such as alkalis and oxidants is avoided;3)The substituents on the triazine ring can be flexibly adjusted according to needs,which shortens the synthesis path,reduces post-processing steps,and improves the yield of the final product.In this paper,melting point,LR-MS or HR-MS,1H NMR and 13C NMR of triazones,2-chloro-1,3,5-triazines and tri-substituted asymmetric 1,3,5-triazines have been measured and characterized.