Synthesis Of Fluorene Derivatives Containing Steroid Rings And Several Functional Groups

As one of the separation from coal tar, fluorene and fluorene derivatives have been widely used as macromolecular materials, medicines, organic light-emitting diodes(OLED), disinfectants and other fields. Currently, the research on coal tar downstream is relatively backward, and the technology shows many shortcomings, such as high cost, low yield, low purity, difficult separation and pollution. Therefore, the research of fluorene derivatives was given close attention. Steroids such as cholesterol, are a kind of important natural organic compounds. Steroid derivatives, due to their special structure and characteristics of high activities and low toxicity, are used in anticancer drugs, cosmetics, food industry and so on. However, it has not been reported that is the study on the compounds containing steroidrings and fluorine will have significant academic value and application prospect.The main content of the research is:1. Synthesis of intermediates:sixteen compounds,2,4-dinitrobromobenz ene(1a),2,4-dinitro-phenylcholesterylether(1b),2,4-diminophenylcholesteryl-ether(1c),2,7-dibromofluorene(2a),2,7-dibromine-4-nitylfluorene(2b),2,7-dibromine-4-aminofluorene(2c),2,7-dibromine-4-[N-(2-hydroxyl-3-bromo propyl)amino] fluorene(2d),2,7-dibromine-4-[N,N-di(2-hydroxyl-3-bromop ropyl)-amino]fluorene(2f),9-fluorenone(3a),2,7-dibromofluorenone(3b), 2,7-dibromine-4-nitylfluorenone(3c),2,7-dibromine-4-aminofluorenone (3 d),2,7-dibromine-4-[N,N-di(2-hydroxyl-3-bromopropyl)amino]-fluorenone (3e),2-steroid-7-bromine-4-nitylfluorenone(4a),2-steroid-7-bromine-4-aminofluorene(4b),2-steroid-7-bromine-4-[N,N-di(2-hydroxyl-3-bromopro pyl)amino]fluorene(4c), were synthesized. Meantime, the better reaction conditions of 1b,2d,2f,3e and 4c were optimized. The optimal sy nthesis condition of 1b is:TBAB as phase-transfer catalyst, w(NaOH) =50%, n(1a):n(cholesterol)=1.55:1, reacting for 3.5h at 25℃ with tolue ne as solvent, the yield is 72.0%; The optimal synthesis condition of 2d is:TBAB as phase-transfer catalyst, w(NaOH)=40%, n(2c):n(epibro mohydrin)=1:1.2, reacting for 6h at 0℃ with CH2Cl2 as solvent, the y ield is 84.0%;The optimal synthesis condition of 2f is:TBAB as phas e-transfer catalyst, w(NaOH)=40%, n(2c):n(epibromohydrin)=1:2.4, react ing for 8h at 20℃ with CH2Cl2 as solvent, the yield is 96.2%; The optimal synthesis condition of 3e is:TBAB as phase-transfer catalyst, w(NaOH)=40%, n(3d):n(epibromohydrin)=1:2.5, reacting for 9h at 3 0℃ with CH2Cl2 as solvent, the yield is 84.5%; The optimal synthesi s condition of 4c is:TBAB as phase-transfer catalyst, w(NaOH)=50%, n(4b):n(epibromo-hydrin)=1:2.6, reacting for 12h at 50℃ with CH2Cl2 as solvent, the yield is 80.6%.2. Synthesis of target products:four compounds,2,7-dibromine-4-[N-(2-methacrylate-3-bromopropyl)amino]fluorene(2e),2,7-dibromine-4-[N,N-di(2-methacrylate-3-bromopropyl)amino]fluorene(2g),2,7-dibromin e-4-[N,N-di(2-meth-acrylate-3-bromopropyl)amino]fluorenone(3f),2-stero id-7-bromine-4-[N,N-di(2-methacrylate-3-bromopropyl)amino]-fluorene(4 d) was synthesized. Meantime, the better reaction conditions of 2e,2 g,3f and 4d were optimized. The optimal synthesis condition of 2e is:(C2H5)3N as deacid reagent, n(2d):n(methacryloyl chloride)=1:1.4, r eacting for 4h at 0℃ with CH2C12 as solvent, the yield is 96.3%; Th e optimal synthesis condition of 2g is:(C2H5)3N as deacid reagent, n (2f):n(methacryloyl chloride)=1:2.8, reacting for 8h at 0℃ with CH2C 12 as solvent, the yield is 96.1%; The optimal synthesis condition of 3f is:(C2H5)3N as deacid reagent, n(3e):n(methacryloyl chloride)=1:2.1, reacting for 6h at 0℃ with CH2C12 as solvent, the yield is 95.7%; The optimal synthesis condition of 4d:(C2H5)3N as deacid reagent, n (4c):n(methacryloyl chloride)=1:2.3,reacting for 6h at 0℃ with CH2Cl2 as solvent, the yield is 92.0%。3. All synthesized compounds were characterized by IR and NMR spectrum.