Study On Cu?OAc?₂-Catalyzed Synthesis Of 1,3,5-Triazine Derivatives

1,3,5-Triazines are very important skeletons of many biologically active compounds,such as herbicides,insecticides,fungicides,anticarcinogens and antivirals.In addition,they are also widely used as organic dyestuff,liquid crystals,fluorescent brighteners,electroluminescent materials,gas generating agents,solid propellants and pyrotechnics.Therefore,a more simple,efficient and broad method for synthesis of 1,3,5-triazines is extremely in demand.Herein,we develop the synthesis of 1,3,5-triazine derivatives directly by oxidative coupling of amidine hydrochlorides and alcohols in air with Cu?OAc?₂ as a catalyst.Based on our previous work about the synthesis of quinazolines from substituted amidines and aromatic alcohols,benzamidine hydrochloride and benzyl alcohol were chosed as our primary subsrtates.With a series of option experiments,the optimal condition should be Cu?OAc?₂ as catalyst,Na2CO3 as base,toluene as solvent and under reflux for 24 h in air.Notablely,no ligand need to be involved in this reaction,excellent reaction results can be achieved with 0.1 mmol Cu?OAc?₂.With the optimized reaction conditions,several substituted aromatic alcohols and different substituted amidine hydrochlorides were conducted to research the influence of electronic and steric effect.Target products can be obtained efficiently either electron donating groups or electron withdrawing groups on para-position of aromatic alcohols except for Br and NO2.Steric effect of aromatic alcohols affected this reaction seriously.Tiny Electronic effect exposed on amidine hydrochlorides.After research on aromatic alcohols,we found that high efficient reaction can be occurred with fatty alcohols involved in,such as methanol,ethanol and n-butanol.Besides,1,3,5-triazines can also be obtained via solvents DMF or DMSO and amidine hydrochlorides.Through the whole research,27 products obtained by aromatic alcohols and 7 products obtained by fatty alcohols,DMF and DMSO were characterized by 1HNMR,13 CNMR and necessary HRMS.We developed a strategy for synthesis of 1,3,5-triazine derivatives via Cu?OAc?₂ catalyst in this work.The method is simple,efficient,easy separation of products,broad substituents,warm reaction conditions and using air as the oxidant.All these advantages brought it industrial applications potential.