有机氟化合物

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,2021/3/13,*,单击此处编辑母版标题样式,*,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,有机氟化合物,有机氟化学开展史上的里程碑,1771年：HF (Scheele),1886年：F2 ( Moissan),1896年: 氟代乙酸乙酯的合成,20世纪30年代: 含氟制冷剂的合成,1938年：美国杜邦公司偶然发现的聚四氟乙烯,二次世界大战期间：曼哈顿工程的实施(全氟化合物),1954年：高生理活性的氟代氢化可的松的合成,有机氟化学从诞生起一直和社会需求严密地联系在一起。社会对有机氟化合物的需求推动了有机氟化学学科的开展,2,Journal of Fluorine Chemistry ( Journal),Chemistry of Organic Fluorine Compounds II,-A Critical Review,Milos Hudlicky and A. E. Pavlath Ed. ( Book),International Symposium on Fluorine Chemistry,( meeting),3,研究根底和创新是开展氟产品的源泉,4,含氟材料,耐高温、耐酸碱、耐氧化、室外耐久性,低外表张力-疏水、疏油等,5,1943：PTFE (工业化) 不易加工；不透明,1989：Teflon AF (combine the chemical inertness of,PTFE with optical transparency and process ability),用不同折射率的Taflon AF作芯材和皮层材料可研制用于280“超级光纤,6,有机氟化合物：自然界几乎不存在,13 种,人造物质,氟原子的特点:高电负性和小的原子体积与氢原子相近,7,Fluorine:,1),Stabilize cations,by the interaction of the vacant,p orbital,of the carbocation with the filled orbitals of fluorine,2),Fluorine bonded directly to a,carbanionic center,:,destabilizing,by,I,replusive interaction,But, CF,3,stabilizing,3) as a,hydrogen bond acceptor,because of its available electron density.,8,Steric effect of Fluorine,Replacement of carbon-hydrogen bond with a carbon-fluorine bond does not typically present a major steric perturbation in a molecule.,9,Analysis of Organic Fluorine Compounds,19,F NMR,10,Fluorine-containing molecules,:,Electron distribution;,the acidity or basicity of neighboring group,dipole moments,reactivity and stability,11,Saturated fluorocarbons(hydrocarbon analogous):,Lowest: dielectric constants,surface tensions,refractive indexes,Greater: densities,viscosities,compressibilities,12,C,6,F,14,C,6,H,14,bp (o,0,C) 57 69,d( g/cm,3,n,D,13,Fluorous Chemistry: Separation Technologies,Harvath, I.; Rabai, I.,Science,1994, 266, 72,Immiscible with hydrocarbon solvents at low temperature,These immiscible become homogenous at higher temperature,14,Work-up,15,Acid Strength,Acid,p,Ka,CH,3,SO,3,CF,3,SO,3,C,6,H,5,C,6,F,5,CH,3,CO,2,CF,3,CO,2,16,17,Fluorinated olefin,18,19,Fluorinated alkanes,20,21,22,23,24,含氟生物活性物质,25,J. Fried,J. Am. Chem. Soc,.,1954, 76, 1455,The beginning of a new era of fluorine in biological Chemistry,9,-fluoro-hydrocortisone acetate (activity 11 times greater than that of the corresponding hydrocarbon),26,The lower pK,a,of the 11-hydroxyl group and its increased,ability to donate a hydrogen bond, as well as its increased,resistance to metabolic inactivation by oxidation.,27,Fluorinated compounds have been approved by the FDA as drugs:,anticancer, antiviral, antibacterial, antidiabetic, antimalarial, antimalarial, antifungal, antidepressant, antipyschotic, antiinflammatory, and anesthetic agents.,Marked fluorine-containing drugs: 107 compounds,28,29,除草剂,杀虫剂,杀菌剂,三氟甲基的芳香化合物和杂环化合物。,30,代血液,31,含氟麻醉剂,32,Effects of Fluorine on Biological Reactivity,1),the,high carbon- fluorine bond strength,(108 Kcal/mole) renders the fluorine substituent,resistant to many such metabolic transformations,Vitamin D3,33,2) Fluorine may also be employed as a,leaving group in addition-elimination processes,where its superior leaving group ability relative to hydrogen is important.,Such applications have led to,the development of very effective mechanism-based enzyme inhibitors.,34,3),Fluorine on a carbon adjacent to the carbonyl group increases the electrophilicity of the carbonyl carbon and therefore the,tendency of nucleophiles to add,.,Inhibition is probably due to the formation of a stable hemiketal with the active site,35,36,4),Fluorine has been employed as a replacement for both hydroxyl and hydrogen,Difluoromethylene units have been employed as isosteric replacements for oxygen,In fact, no other functional group that can replace oxygen matches so well the steric and electronic demand of oxygen.,37,The C,sp3,-F bond of 1.40Ais slightly shorter than,the C,sp3,-OH bond,Competitive inhibitor of acylCoA:cholesterol acyltransferase,Angew. Chem. Int. Ed.,2001, 40, 4461,38,5),Fluorine has been identified as improving the lipophilicity of a molecule and hence its distribution within an organism.,CF,3,group,the lipophilicity of substituents,X ,H 0,39,6),Fluorine has a useful short-lived isotope:,18,F,half-life of 110 minutes,decays by positron emission,Positron emission tomography,(,PET,),Introduction of 18F-substituted materials into living tissue is an essential part of PET,40,18,F-labeled fluorodopa, the chemistry and metabolism of brain,41,向有机分子引入氟的方法,42,亲核氟化试剂,i-Pr,2,NH(HF),3,43,亲电氟化试剂,44,5-fluorouracil,45,氟取代其他基团,46,1) 光催化脱重氮-氟化反响,2一步法,47,M. A. Subramanian ( DuPont),Science,2002,(297), 1665,Oxidation-reduction potential,E,0, 1 Co,3+,+ e,-,Co,2+,(F,2,),1 ,E,0,0 Cu,2+,+ 2e,-,Cu,0,( HF,+O,2,),E,0, 0 Zn,2+,+ 2e,-,Zn,0,( HF,+O,2,) ( inert toward C-H bond),48,Fluorination using KF in ionic liquid,J. Am.Chem. Soc.,2002,124, 10278,H,2,O,49,50,Trifluoromethylation,Chen et al. .,1989, 705,51,Mechanism of Trifluoromethylation:,52,Preparation of FSO,2,CF,2,CO,2,CH,3,53,含氟合成子,54,Z : E,92:8,Z : E,89:11 68% yield,55,56,57,Thank you,58,汇报结束,谢谢大家,!,请各位批评指正,