Studies On The Carbonylation Of Diarylmethanes And Synthesis Of Bioactive Molecule

Diarylketones is an important class of compounds in organic chemistry, which arewidely used in the field of drugs, functional molecules, advanced materials, plastic,spice and electron industry, as well as useful synthetic architectures in moleculartransformation. An efficient method for preparation of diverse functionalizeddiarylketones from corresponding diarylmethanes with convenient operation procedureand mild conditions has been developed.In this paper, we have mainly explored the carbonylation of diarylmethanes forhighly yielding synthesis of various functionalized diarylketones in the presence ofN-bromosuccinimide (NBS), which is inexpensive and commercially available. Basedon optimizations on various halogenation reagents, solvents and the amount ofhalogenation reagent, we have gotten the optimal reaction conditions. Then thesubstituents effects, steric effects and electronic effects of the substrates have beeninvestigated. Meanwhile we investigated the reaction mechanism and a plausiblemechanism has been proposed.The experimental results indicated that diarylmethanes (diphenylmethane,4-chlorodiphenylmethane,2-iododiphenylmethane,2,4-dichlorodiphenylmethane,diphenylchloromethane and so on) showed good reactivities and refluxed with5.0equivalents of NBS in chloroform for3.0h to afford corresponding products in up to99%yield. Interestingly, when employing3-bromofluorene as the substrate under thestandard reaction conditions, the reaction only afforded the dibrominated product. weare delighted to obtain single crytal structure and confirm it structurally by X-raydiffraction analysis. It demonstrates the reaction proceeds a dihalogenated process. Then,selecting representative monohalogenated diarylmethanes as substrates afforded desiredproducts in high yields. An isotope trace experiment employing5.0equivalents of waterlabeled with18O was performed and the18O-labeled product was confirmed by HRMS.This procedure indicates adamantly that the oxygen atom of product originates from themoist surroundings, which is beneficial to the hydrolysis. Further substrate scopeinvestigation, we took the addition of extra water into consideration to ensure themoisture of reaction system. To our delight, all reactions proceed very well,mono-/dihalo substituents (2-fulorodiphenylmethane,2-chlorodiphenylmethane,4-bromodiphenylmethane,3,4-difulorodiphenylmethane and so on) gave the desired products in82-99%yields. Substrates containing a heterocycle were also tested.3-(4-fluorobenzyl)thiophene led to product in82%yield. Meanwhile, this method hasbeen successfully applied to the synthesis of bioactive2-(3-benzoylphenoxy)propanamide in good yield as well.This method has many advantages, such as mild conditions, convenient operationprocedure, available starting materials, low cost.