Synthesis Of Quinoxaline Polycyclic Heterocyclic Compound

Quinoxalines and their derivatives is one of the most important classes of azaheterocycles. It has been demonstrated that the quinoxalines can be recognized as anticancer reagents and inhibitors of reversetranscripatase as well as unpathogenic microorganisms. Additionally, quinoxaline derivatives have also been widely used in medicine, sterilization, weeding, and plant growth regulating and optical materials.Heterocyclic ketene aminals (HKAs) have some biological activities such as anticancer, bactericidal, and pesticides. HKAs are also a class of versatile synthons in organic synthesis to build some kinds of organic heterocyclic compounds, which possess many biological activities.We developed a synthetic protocol for the synthesis of polycyclic quinoxaline heterocyclic derivatives (9) based on the one step reaction of dichloroquinoxaline (4) and HKAs (7). Firstly, the synthesis of two kinds of intermediates2,3-dichloroquinoxaline (4) and HKAs (7):(i) the o-phenylenediamine (1) reacted with diethyl oxalate (2) afforded1,4-dihydroquinoxaline-2,3-dione (3), then through the halogenated synthesis of reaction with POCl3given the intermediate (4);(ii)3,3-bis(methylthio)-1-phenylprop-2-en-1-ones (6) were synthesized from substituted acetophenones (5), and then compounds (6) were reacted with different kinds of diamines to give the HKAs materials (7a-7m);(iii) finally, fourteen polycyclic quinoxaline heterocyclic derivatives (9a-9n) were synthesized by the "one-pot" reaction of intermediate (4) and HKAs (7a-7j) with yields (45%-60%) under the conditions of refluxing in DMSO and catalyzed by K2CO3. While we obtained three regional selective substitution products with good yields (70%-78%) based on the reaction of intermediate (4) with five-member ring HKAs (7k-7m) in the same reaction conditions.All target compounds and intermediates were unambiguously characterized by IR,1H NMR,13C NMR, and HRMS spectroscopy. The X-ray diffraction analysis of selected single crystal of9a was carried out. This synthesis method has some characteristics such as the raw materials are cheap; the synthetic route is simple and the reaction conditions are mild. So far, our synthesis route and target compounds have not seen in literatures. The simple synthesis of polycyclic quinoxaline heterocyclic derivatives will laid the molecular basis of the structural diversity of nitrogen heterocyclic compounds for the further pharmacological activity research.