Studies On Synthesis Of N-heterocyclic Carbene Precursors By Using Chan-Lam Coupling Reaction

Many nitrogen heterocyclic compounds have good biological activity, so they are worthy of more and more attention. So far, people have created a lot of nitrogen heterocyclic compound drugs. The main methods of synthesis of these nitrogen heterocyclic compound is to build the C-N bond, the reaction condition of traditional methods like Ullmann and Goldberg is so rigorous. Buchwald and Hartwig found the method that building C-N bond by palladium catalyst under organic phosphine ligands made a major breakthrough in the field, and made it possible for us to obtain the C-N bond compounds that using mild and adjustable methods before can't get easily. But, these reactions are sensitive to air and humidity, functional group tolerance is limited, and the price of palladium catalyst is high, these defects restrict the development of the construction of C-N bond compounds. In 1998, Chan, Lam and Evans reported the use of copper as a catalyst to build C-N bond method, it could react at room temperature, and it was not affected by air, humidity, tolerance level for functional groups were also greatly improved, it has made significant progress compared with the traditional coupling reaction.Because NHCs(N-heterocyclic carbenes) showed excellent catalytic performance, the investigation of the NHCs was very important in recent years. The C-N coupling is the key step in the synthesis of NHC precursor, so the study of the coupling reaction is becoming more and more urgent. In this paper, the main research was focused on using Chan-Lam cross-coupling reaction to build C-N bond compounds, further synthesis of NHC precursors synthesized by cyclization. Mainly using Chan-Lam cross-coupling reaction synthesis of a series of C-N bond compounds as Buchwald-Hartwig coupling method was difficult to synthesis, finally obtained the corresponding new NHC precursors. We used o-phenylenediamine,3-methoxybenzene-1,2-diamine,3-fluorobenzene-1,2-diamine,3-nitrob enzene-1,2-diamine as substrate, then we got 13 C-N coupling products through the Chan-Lam coupling and 11 five-member ring NHC precursors. Then we also used two1,3-diamine as substrate, and got two C-N coupling product through the Chan-Lam coupling and Buchwald-Hartwig coupling. Finally we got two six-member ring NHC precursors. All compounds have been characterized by nuclear magnetic resonance(1H NMR and13 C NMR) and high resolution mass spectrometry.The main innovation points of this paper was to use Chan-Lam coupling methods on the synthesis of a series of aryl groups containing strong electron withdrawing and donating groups benzinidazoles NHC precursors, which products were difficult to synthesis by Buchwald Hartwig coupling reaction.Finally, we obtained some new NHC precursors with higher yield, and the reaction conditions are mild and controllable.