Microwave Promoted C-H Arylation Of Benzoxazole With Arylation Reagent

The oxazole heterocycles constitute key structural motifs in a wide range of natural products and are thus appealing targets in organic synthesis.As such,2-aryl oxazoles are important structural units found in natural products,functional materials,agrochemicals,and pharmaceutically active compounds.Consequently,various new synthetic methods emerged.Among those protocols,the arylation of the C–H bond represent an elegant and straightforward means for the preparation of the 2-aryl benzoxazole ring system.Over the past years,many successful examples of this class of reactions have been reported.Despite these encouraging advances,the C–H bond arylation of benzoxazole in a general way remains a daunting challenge.Most of these reactions suffer drawbacks such as: lengthy procedures that needs excess reagents,harsh reaction conditions,toxic transition metal and difficulty in the preparation of catalyst.Microwave has been used as an important technique for the synthesis of various products in recent decades due to the notable features such as formation of purer products,higher yields and selectivity,easier manipulation,milder conditions,shorter reaction time,and easier work-up.Also it leads to high efficiency,low waste,low energy,and temperatures requirements,which make it more convenient than traditional methods.Therefore,the microwave-assited direct C-H bond arylation of oxazoles is a significant alternative route to cross-coupling reactions with traditional heating from an environmental and economical viewpoint.In this thesis,the synthetic methods of 2-aryl benzoxazoles were summarized firstly.Then,the applications of microwave in coupling reactions were briefly reviewed.Finally,two different new methods were found to synthesis 2-aryl benzoxazoles under microwave conditions.The main contents of our research are listed below:Ⅰ.A fast and efficient way to synthesis 2-aryl benzoxazoles under microwave conditions was reported（Scheme 1）.A series of 2-aryl benzoxazoles was obtained in moderate to good yields by using benzoxazole and acyl chloride as reactants,K₂CO₃ as base in chlorobenzene/H₂O（V:V = 3/1）at 200 ℃ for 20 min under microwave conditions.This method has the advantages of transition metal-free,short synthetic route,increased safety for small-scale high-speed synthesis,and minimal environment impact.Compared with tradition heating,this system can get an improvement in theyield and high quality of the product.For example,the target product 2-（3-（trifluoromethyl）phenyl）benzoxazole（3h）,2-（m-tolyl）benzoxazole（3k）can achieve to 93%,94%respectively at 200℃ in 20 min.Ⅱ.A simple and highly efficient catalytic protocol for the synthesis of 2-arylbenzoxazole derivatives has been developed（Scheme 2）.Uniquely,625 ppm of palladacycle catalyst of the optimal conditions showed excellent catalytic activitiies for the coupling of benzoxazole and arylbromide under microwave irradiation.A series of desired products were isolated in up to 99% yields within 10 min at 206 o C.Moreover,2-（3-pyridyl）benzoxazole was also obtaned in 98% yields under optimal conditions with employing 625 ppm palladacycle-catalyst.