Synthesis Of N-Arylamides By Copper-Catalyzed Para-Selective C-H Amidation Of Simple Arenes With Nitriles

The ubiquitous presence of N-arylamides in natural products, biologically active molecules and organic functional materials make them valuable synthetictargets. The key step to synthesize N-arylamides is how to form the amide skeleton. So, to find a simple, efficient, environment friendly and economic method to form the amide skeleton is an important field in organic synthesis.In the first part of this paper, we introduce the significance on studying the N-arylamides and make a brief overview on the synthesis methods to N-arylamides. The Goldberg reaction is one of the most common methods for the synthesis of N-arylamides, and the C-N coupling between aryl halides and nitrile is also an efficient method, but both require prefunctionalization of arenes to aryl halides. Then, extensive efforts have been devoted to the synthesis of N-arylamides via C–H amidation of arenes, but still face the chanllenges of poor reactivity and selectivity. So, although there are many methods to synthesize N-arylamides, they still have many shortcomings, they need to be improved.In the second part of this pater, a copper-catalyzed and highly para-selective C–H amidation of simple arenes using nitriles as the amino source has been developed. A variety of simple arenes and nitriles can undergo this reaction to afford the desired N-arylamides. When the amount of arene was increased to four equivalents, a further meta-selective C–H arylation of the produced amides occurred, resulting in tandem C-N and C-C bonds formation. Both steric and electronic effects were utilized to control the selectivity, resulting in only para-selective amidation products. Experements were carried to study the mechanism and a possible reaction mechanism has been proposed.In a word, the above-mentioned methods for the synthesis of N-arylamides have the shortcomings on materials and poor selectivity. But, the method introduced in this paper using nitriles as amino sources remedy the previous shortcomings, and make a certain contribution for the synthesis and development of N-arylamides.