Synthesis And Application Of Functional Aryl Phosphonates By Pd-Catalyzed Cross-coupling Of Aryl Halides With Diethyl H-phosphonate

Phosphonates containing carbon-phosphorus bond are important organophosphorus compounds, with important applications in flame retardants, pesticide, medicine, materials and phosphine ligands. It exhibits remarkable biological properties, such as antitumour, anti-inflammatory, hypolipidemic, antimicrobial, anti-HIV agents, insecticidal effect, playing an important role in the discovery of drug and functional material molecules. Therefore, phosphonates containing carbon-phosphorus bond have attracted considerable attention and much effort has been focused on the development of efficient synthetic methods.The synthetic methods of carbon-phosphorus bond formation now are based on three types of reactions:organic phosphorus and halohydrocarbons as the substrates to build C-P bond; the addition of phosphinic acid to olefins and alkynes to build C-P bond; transition metal-catalyzed C-H activation/functionality to build C-P bond. Phosphonates with functional groups play an important role in the discovery of functional organic materials such as flame retardant materials, therefore, the development of mild, high efficiency and high selectivity synthetic method has important significance for functional phosphonates.4-Bromobenzyl alcohol and diethyl phosphite were selected as model substrates for a palladium-catalyzed C-P cross-coupling reaction. With Pd(OAc)2(2mol%) as the catalyst, PPh3(6mol%) as the ligand and Et3N as the base, diethyl phosphite could undergo C-P cross-coupling reaction in ethanol at80℃for24hours to produce the corresponding diethyl aryl phosphonates in moderate yield.The scope and generality of the present process was also explored. Our research shows that a variety of substituents on the aryl ring, such as-CH2OH,-OH or-NH2were applicable, affording the diethyl aryl phosphonates products in moderate yields. Our research shows that the nature of the substituted halogen on the aryl ring is very important to the reaction outcome. The reactivity of different ortho substituted halogen on the aryl ring follows the sequence of I> Br> Cl. Para-iodoaryl benzyl alcohol or (para-bromoaryl) benzyl alcohol can smoothly be converted to the desired products in moderate yields, however, the use of aryl chloride to effect such transformations afforded inferior results under similar reaction conditions. The possible reaction mechanism is also provided in the paper.Diethyl aryl phosphonates with different functional groups were then applied to the grafting reaction to phosphonitrile. The optimum condition is proved to K2CO3(7equiv) as the base, THF as solvent, refluxing at70℃, moderate yield can be acquired.This thesis has developed a practical, simple and efficient method to synthesize diethyl aryl phosphonates. This protocol is not only a valuable addition to the tool box of the synthesis of diethyl aryl phosphonates, but also enriches the contents of palladium-catalyzed C-P forming reactions, which should be of considerable interest of the valuable synthetic building blocks for medicinal and material science.