Study On Synthesis Of Nitrogen-Containing Heterocyclic Compounds In Ionic Liquid Systems

Nitrogen-containing heterocyclic compounds are an important class of heterocycles and applied in many areas, such as functional materials, medicine, pesticide and biological fields, so study on the synthesis of them is of great significance. The traditional methods of synthesis caused serious environmental pollution because of using a great deal of toxic and harmful, volatile organic solvents in the processes of reaction and separation. Ionic liquids, considered as novel solvents, have become a hot area of green chemistry. Functionalized ionic liquids have marched far beyond solvents, showing their significant role in organic synthesis as catalysts. In this paper, the synthesis of nitrogen-containing heterocyclic compounds in ionic liquid systems was investigated based on requirements of the development of green chemistry.Firstly, applications of several ionic liquids that bear group in imidazolium cation, caprolactam cation, or acyclic tri-alkanyl-ammonium cation in the synthesis of 3,7-dinitro-1,3,5,7-tetraazabicyclo[3.3.1]nonane (DPT) were invested and the results showed that the quaternary ammonium salt-type ionic liquid [TMPSA][HSO4] was the best one. In the presence of 10 mol%of [TMPSA][HSO4] (based on urea), the yield of DPT was obtained with 70% under the optimum conditions. Next, a facile and efficient method for the synthesis of 2,5,7,9-tetranitro- 2,5,7,9-tetraazabicyclo[4.3.0]nonane-8-one has been developed in this paper. In the procedure, the precursor compound 2,5,7,9-tetrahydro-2,5,7,9-tetraazabicyclo [4.3.0]nonane-8-one dihydrochloride was prepared in high yield catalyzed by task-specific Br(?)nsted- acidic ionic liquids that bear group in acyclic tri-alkanyl-ammonium cation and the subsequent nitration of the precursor compound gave the desired product (yield 57% based on urea).Secondly, a functionalized ionic liquid,3-(N,N-dimethyldodecylammonium) propanesulfonic acid hydrogen sulfate ([DDPA][HSO4]) has been found to be an effective catalyst for assembling 3,4-dihydropyrimidine-2-(1H)-ones via three-component Biginelli reaction in water. The yield of corresponding product was 91% when the Biginelli reaction of benzaldehyde, methyl acetoacetate, urea was selected as model in 20 min at 90℃. The products could be separated by simple filtration and the catalyst could be recycled up to next time without any treatment. Subsequently, N,N,N',N'-Tetramethyl-N,N'-bis(3-sulfopropyl)-ethylenediammonium bis(hydrogensulfate) ([TMEDAPS][HSO4]) catalyzed condensation reaction of 1,2-ketone and 1,2-diaminobenzene derivative proceeded rapidly to afford corresponding quinoxaline derivatives with 84～95% yields in water. [TMEDAPS][HSO4] bears two Br(?)nsted-acidic functional groups and has the structure of quaternary ammonium salt as phase transfer catalyst. The catalyst was active in the reaction and could be reused without obviously decreasing the catalytic activity.Furthermore, applications of PEG1000-DAIL/toluene thermoergulated system in the synthesis of tetrahydro-β-carboline derivatives were invested and good results were obtained with 88～93% yields. The catalyst could be easily separated from products by decantation and recycled without obviously decreasing the catalytic activity.Lastly, corresponding pyrrole derivatives with 78～95% yields were synthesized via ultrasonic-assisted Paal-Knorr condensation of amine and 2,5-hexanedione using [DDPA][HSO4] as catalyst. The reaction time of aniline and 2,5-hexanedione was shortened from 40min to 5min. The method showed certain practical value for high yield, shorter reaction time, and simple procedure. The ionic liquid could be recycled without obviously decreasing the catalytic activity. Then 1-butyl-3-methylimidazolium dihydrogen phosphate ([BMIm][H2PO4]) catalyzed three-component reaction of aldehyde,1,2-diketones and ammonium acetate under microwave irradiation to afford corresponding 2,4,5-trisubstituted imidazole derivatives with 86～96% yields. The attractive features of this protocol are short reaction time (only a few minutes), high yields, and the easy workup procedure. [BMIm][H2PO4] could be recycled without obviously decreasing the catalytic activity.