Study On Synthesis Of Quinoxaline And Its Derivatives

As a kind of important chemical intermediate, quinoxaline and its derivatives have been widely applied to medicine,pesticide,dye, feedstuff and so on. In recent years, many researchs have proved that quinoxaline compounds possesed extensive pharmacological activity in treatment of obesity, antitumor etc. Therefore, their research value and application prospect have attracted considerable interest.We focused the study on the synthesis methods of quinoxaline, nitration of its aromatic ring and chlorination of its heterocycle. In this paper, we thought about environmental protection, the cost of material, the feasibility of industrialization, workup easily, and obtained 2,3(1H,4H)-quinoxalinedion(DHQX), 6-nitro-2,3(1H,4H)-quinoxalinedion (NTQX,), 6,7-dinitro-2,3(1H,4H)–quinoxalinedion(DNQX), 2,3-dichlo- roquinoxaline(DCQX), 6–nitro-2,3-dichloroquinoxaline(TCQX),and 6,7- initro-2,3-dichloro-quinoxaline(NCQX). A more reasonable, easily, efficient and simple reactive route to synthesize above-mentioned compounds was developed by systematically investigating the yield, the purity and physical character of intermediates.In this paper, the innovative improvement of the cyclization and chlorination of quinoxaline was:1. DHQX was prepared via reactingο-phenylenediamine with ethyl- oxalate in hydrochloric acid, the mixture was stired at 75-80℃for 2h. Compared to the method of no-medium in literature, the reaction temperature reduced nearly 100℃and the time decreased 4h. The yield simultaneously raised 20%, the purity and physical character of the product was very good and need not recrystallize2. Using POCl3/DMF as chlorination agent for the chlorination of heterocycle, DCQX was prepared via reacting DHQX with POCl3/DMF at 110℃for 1h. Compared to the chlorination method of SOCl2/DMF in literature, the reaction temperature reduced nearly 50℃and the time decreased 2h. The yield simultaneously raised 10%. It is more important that the method delected a great quantity of dioxane which was required in the chlorination method of SOCl2 /DMF, and could sharply reduce reaction cost. At the same time, its postprocessing was rather simple, the quality of the compound was better. and suitable to the industrialization. Furthermore, the method may be used to synthesize DCQX,TCQX and NCQX.During the course of experiment, The optimum reaction conditions of these compounds were investigated by orthogonal experiments with high yield and good phsical character. The yields of all six intermediates exceeded 80%, among of which the yield of NTQX was 99%, DCQX was 92%.In addition, the purity of some compounds was detected by HPLC with normalization method was determined in the paper: DCQX is 97.7%, TCQX is 98.1%, NCQX is 98.6%.Above all, these routes used to synthesize quinoxaline and its derivatives in this paper are more simple than those of literature, innovate the stern reaction conditions, reduce reaction cost, improve the quality of target products and suitable to the industrialization.