Visible-Light-Promoted Synthesis Of 3-phosphonylated Benzothiophene In Water

Green chemistry,is also called sustainable chemistry,modern synthetic chemistry vigorously advocates the use of cleaner and renewable energy,the development of efficient synthesis route with atomic economy and step economy,and the use of green recyclable solvents to replace traditional harmful organic solvents to minimize environmental damage caused by organic conversion.Water is a green solvent,which is non-toxic to health and the environment.It is also the safest and cheapest solvent which is a good medium for various organic transformations.Visible light is an abundant,reliable and renewable energy,which can replace traditional heating methods and be used in organic synthesis conversion.Therefore,the development of new strategies for green and efficient organic synthesis promoted by visible light using water as solvent is an important research direction for organic synthetic chemists.The benzothiophene derivatives skeleton is one of the dominant structures in drug discovery.The benzothiophene core is widely present in natural products and drugs with biological activity.These molecules have a variety of biological activities,including anti-cancer,anti-inflammatory,anti-microbial,anti-diabetic,antiosteoporosis,anti-convulsant,etc.Organophosphorus compounds occupy an important position in material chemistry,biochemistry and organic synthesis.Synthetic chemists often modify the structure of pharmaceutical molecules through phosphonylated.The signi ficance of this modification is that the introduction of phosphono functional groups can usually adjust and improve the biological responsiveness of the parent molecule,and significantly improve the bioavailability and efficacy of pharmaceutical molecules.It is worth emphasizing that,there is no report on the new synthetic method of green and efficient synthesis of phosphonylated benzothiophenes promoted by visible light with water as solvent.In this paper,a novel green synthesis strategy for the efficient synthesis of phosphonylated benzothiophenes by radical tandem cyclization reactions promoted by visible light in the aqueous phase is developed.Using a series of 2-arynylbenzyl sulfide(seleno)ethers and diphenyl phosphorus oxides as the reaction substrates,2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile(4CzIPN)as a photocatalyst,in the presence of dilauroyl peroxide(LPO),under visible-light irradiation in water medium at room temperature for 12 hours to produce a series of 3phosphonylated benzothio(seleno)phenes.Through the 2,6-di-tert-butyl-p-methylphenol(BHT)radical capture experiment and fluorescence quenching experiment,a plausible mechanism was proposed.4CzIPN was excited to the excited state(4CzIPN*)under the irradiation of blue light.4CzIPN*reacts with 1 through a single electron transfer(SET)process give the intermediate 1' and 4CzIPN·-.Simultaneously,diaryl phosphorus oxides react with LPO under visible-light irradiation to generate the phosphoryl radical,and then react with 1' to produce the intermediate 5,followed by an intermolecular nucleophilic substitution to generate the final product 3.