南农生物分离工程超临界演示课件

1、1,超临界流体萃取 ( Supercritical Fluid Extraction ),2,超临界流体的发展,3,Michel Perrut 国际超临界流体发展委员会的奠基人,4,超临界流体的定义,临界状态是物质的气、液两态能平衡共存的一个边缘状态,在这状态下,液体和它的饱和蒸汽密度相同,因而它们的分界面消失,这状态只能在一定温度和压强下实现,此时的温度和压强分别称为“临界温度”和“临界压强”。,5,SOLID,GAS,LIQUID,SUPERCRITICAL,FLUID,Triple,point,Critical,point,Pressure (bar),Temperature (C),7

2、4,31.1C,-56.3C,5.1,Phase diagram for pure CO2, Monterey Bay Aquarium Research Institute,-78 C,1,6,SOLID,GAS,LIQUID,SUPERCRITICAL,FLUID,Pressure (bar),Temperature (K),303,74,7,SOLID,GAS,LIQUID,SUPERCRITICAL,FLUID,Pressure (bar),Temperature (K),303,74,8,SOLID,GAS,LIQUID,SUPERCRITICAL,FLUID,Triple,poin

3、t,Critical,point,Pressure (bar),Temperature (K),303,74,9,SOLID,GAS,LIQUID,SUPERCRITICAL,FLUID,Pressure (bar),Temperature (K),303,74,10,Supercritical Fluid,Both Gas and liquid phases have the same densities in this range. Carbon Dioxide is normally used since its critical point is at 73.8 bar and 31.

4、1 degree Celsius, a very easily reached condition,Two Separate phases of Carbon Dioxide,One Supercritical Phase Of Carbon Dioxide,11,SCFs are intermediate between liquids and gases,12,纯二氧化碳密度随压力与温度的变化,特点: 在临界点附近, 密度有很宽的变化范围; 温度,压力微调 可使密度显著变化 g/L,13,纯二氧化碳在40下的密度,粘度, 自扩散系数密度值随压力的变化关系,Variation of solv

5、ent power of CO2 with pressure,Density (gml-1),Hildebrand parameter (cal cm-3)0.5,310K = 37C 320K = 47 C 330K = 57 C,15,超临界流体的性质,SCF传递特性与气体，液体的特征比较,16,超临界流体的主要特性,密度类似液体，因而溶剂化能力很强，压力和温度微小变化可导致其密度显著变化 压力和温度的变化均可改变相变 粘度, 扩散系数接近于气体，具有很强传递性能和运动速度 SCF的介电常数，极化率和分子行为与气液两相均有着明显的差别,17,Common supercritical flu

6、ids,Supercritical fluids are substances above their critical temperatures and pressures, whose properties are intermediate between those of gases and liquids, and which can be controlled by both temperature and pressure. Carbon dioxideTc = 31.1 C Pc = 73.8 bar FluoroformTc = 25.9 C Pc = 48.2 bar 三氟甲

7、烷 WaterTc = 374.0 C Pc = 220.6 bar AmmoniaTc = 132.4 C Pc = 113.2 bar 氨 EthaneTc = 32.2 C Pc = 48.7 bar 乙烷,18,为什么选用二氧化碳？,温和的临界条件 无毒对设备无腐蚀 阻燃 价廉易得 超临界CO2溶解能力强 适用于化工、医药、食品等工业,19,超临界流体萃取原理： 将超临界流体与待分离的物质接触，使其有选择性地把极性大小、沸点高低和分子量大小的成分依次萃取出来。对应各压力范围所得到的萃取物不可能是单一的，但可以控制条件得到最佳比例的混合成分，然后借助减压、升温的方法使超临界流体变成普通气

8、体，被萃取物质则完全或基本析出。,20,Very soluble Sparingly solubleInsoluble Non-polar andChlorophyll, waxes Sugars, proteins moderately polar molecules and carotenoids Tannins, amino 500 MW叶绿素 蜡 acids and most 类胡萝卜素 pesticides杀虫剂 Examples Triterpenoids三萜类, Alkaloids生物碱 lipids C22,Supercritical CO2 extraction,21,二氧化

9、碳超临界萃取的规律： 亲脂性、低沸点成分可在10MPa以下萃取，如挥发油、烃、酯、内酯、醚、 环氧化合物等。天然植物和果实中的香气成分，如桉树脑、麝香草酚、酒花中的低沸点酯类等； 化合物的极性基团( 如-OH、-COOH等)愈多，则愈难萃取。强极性物质如糖、氨基酸的萃取压力则要在40MPa以上； 化合物的分子量愈大， 愈难萃取。分子量在200400范围内的组分容易萃取，有些低分子量、易挥发成分甚至可直接用CO2液体提取；高分子量物质(如蛋白质、树胶等)则很难萃取。,22,超临界流体技术的优缺点,优点 溶解度可调节； 溶剂与产品易分离； 无溶剂残留； 溶剂价格便宜，无毒，来源丰富。,缺点 操作压

10、力较高； 溶剂的压缩成本； 设备投资大； 可供挑选的溶剂种类少。,23,影响超临界萃取的主要因素： 密度：溶剂强度与SCF的密度有关。温度一定时，密度(压力)增加，可使溶剂强度增加。 夹带剂：SCF中加入少量夹带剂（如乙醇等）以改变溶剂的极性。 粒度：溶质从样品颗粒中的扩散，一般来说，粒度小有利于 SCF萃取。 流体体积：提取物的分子结构与所需的SCF的体积有关，增大流体的体积能提高回收率。,24,二 氧 化 碳 气 瓶,贮 罐,夹带剂罐,萃 取 釜,解 析 釜,解 析 釜,分 离 柱,箱冷,计量流,泵压高,泵压高,超临界流体萃取的流程,25, 等温变压工艺,工艺流程： 由萃取和分离两步组成,

11、萃取塔 (T, p1),分离器 (T,p2), 等压变温工艺,萃取塔 (T1, p),换热器,分离器 (T2, p),升温,节流阀,减压,26,超临界流体萃取设备图,27,大型超临界流体萃取装置,28,压缩机,萃取釜,制冷MVC-760L,二氧化碳循环泵,29,超临界流体萃取的应用,医药工业,化学工业,食品工业,化妆品香料,中草药提取 酶，纤维素精制,金属离子萃取 烃类分离 共沸物分离 高分子化合物分离,植物油脂萃取 酒花萃取 植物色素提取,天然香料萃取 化妆品原料提取精制,30,超临界CO2萃取技术在天然药物研制中的应用,国内外采用CO2超临界萃取技术可利用的资源有：紫杉、黄芪、人参叶、大麻

12、、香獐、青蒿草、银杏叶、川贝草、桉叶、玫瑰花、樟树叶、茉莉花、花椒、八角、桂花、生姜、大蒜、辣椒、桔柚皮、啤酒花、芒草、香茅草、鼠尾草、迷迭香、丁子香、豆蔻、沙棘、小麦、玉米、米糠、鱼、烟草、茶叶、等。,31,超临界CO2萃取技术在食品方面的应用,从葵花籽、红花籽、花生、小麦胚芽、可可豆中提取油脂，比传统的压榨法的回收率高，不存在溶剂法的溶剂分离问题,Extraction using scCO2,Extensively used for natural coffee decaffeination; Extraction of Hops for Brewing,33,应用实例：, 从啤酒花中提取

13、有效成分(律草酮-酸、 蛇麻酮-酸)德国、美国80年代工业化， 回收率达97%,从咖啡豆中分离咖啡因 T=70-900C, p=16-20MPa, SCCO2中溶解的咖 啡因用水吸收除去。咖啡因含量可由3%降 至0.02%。, 从甘草中提取甘草素 T = 40oC, p = 35 MPa, 采用SCCO2 C2H5OH H2O体系作萃取剂,34,Hop Extraction - 20th Century,1908EthanolEngland 1942DichloromethaneGermany 1960TrichloroethaneGermany 1961BenzeneEngland 1965

14、MethanolEngland 1970Hexane USA 1980Liquid CO2Australia/UK 1982Supercritical CO2Germany,35,超临界CO2萃取技术在医药保健品方面的应用,在抗生素药品生产中，传统方法常使用丙酮、甲醇等有机溶剂，但要将溶剂完全除去，而不变质非常困难。若采用SCFE法则完全可符合要求。 用SCFE法从银杏叶中提取的银杏黄酮，从鱼的内脏，骨头等提取的多烯不饱和脂肪酸（DHA，EPA），从沙棘籽提取的沙棘油，从蛋黄中提取的卵磷脂等对心脑血管疾病具有独特的疗效。,36,超临界CO2萃取技术在天然香精香料的提取的应用,用SCFE法萃取香

15、料不仅可以有效地提取芳香组分，而且还可以提高产品纯度，能保持其天然香味，如从桂花、茉莉花、菊花、梅花、米兰花、玫瑰花中提取花香精，从胡椒、肉桂、薄荷提取香辛料，从芹菜籽、生姜，芫荽籽、茴香、砂仁、八角、孜然等原料中提取精油，不仅可以用作调味香料，而且一些精油还具有较高的药用价值。,37,超临界CO2萃取技术在化工方面的应用,英国应用超临界技术制备液体燃料。以甲苯为萃取剂，在Pc=100atm, Tc=400-440条件下进行萃取，在SCF溶剂分子的 扩散作用下，促进煤有机质发生深度的热分解，能使三分之一的有机质转化为液体产物。此外，从煤炭中还可以萃取硫等化工产品。,38,Extraction

16、of Ginger Oil with Supercritical Carbon Dioxide,Ginger(姜) is one of the major spices(调味品) used in foods, beverages(饮料) and medicines.,39,History of Technology,Steam distillation,The vessel is filled with ginger material Steam was injected to the bottom of the distillation column Ginger oil accumulat

17、ed in the condenser Oil and water flowed to the flask,Distillation Column,Condenser,Flask,Steam distillation diagram,Steam Generator,Water,Water,4,40,Steam Distillation,Low yield 1 to 2.7% High levels of monoterpene hydrocarbon residue High energy consumption,41,Supercritical Carbon Dioxide Extracti

18、on,Size particle effect The graph shows that smaller particles have a higher yield.,Bhupesh C. Roy, Motonobu Goto, and Tsutomu Hirose, Extraction of Ginger Oil with Supercritical Carbon Dioxide: Experiments and Modeling, Ind. Eng. Chem. Res. 1996, 35, 607-612.,10,42,Supercritical Carbon Dioxide Extr

19、action,Effect of temperature At 24.5MPa, the extraction rate is increasing as the temperature increases At 10.8MPa, the extraction rate is decreasing as the temperature increases,Bhupesh C. Roy, Motonobu Goto, and Tsutomu Hirose, Extraction of Ginger Oil with Supercritical Carbon Dioxide:Experiments

20、 and Modeling, Ind. Eng. Chem. Res. 1996, 35, 607-612.,Effect of temperature on different pressure,P=24.5MPa,P=10.8MPa,11,43,Supercritical Carbon Dioxide Extraction,Effect of temperature At pressure 17.6 MPa, there is no effect on extraction rate by increasing the temperatures,Bhupesh C. Roy, Motono

21、bu Goto, and Tsutomu Hirose, Extraction of Ginger Oil with Supercritical Carbon Dioxide: Experiments and Modeling, Ind. Eng. Chem. Res. 1996, 35, 607-612.,P=17.6MPa,12,44,Supercritical Carbon Dioxide Extraction,Effect of Pressure At temperature 313K, the extraction rate increases at lower pressure A

22、t temperature 343K, the extraction rate increases at higher pressure.,Bhupesh C. Roy, Motonobu Goto, and Tsutomu Hirose, Extraction of Ginger Oil with Supercritical Carbon Dioxide: Experiments and Modeling, Ind. Eng. Chem. Res. 1996, 35, 607-612.,Effect of pressure on different temperatures,T=313K,T

23、=343K,13,45,超临界流体萃取金属离子,可能取代传统有机溶剂萃取（煤油和磷酸三丁酯）。 由于SCCO2的非极性使得金属离子在SCCO2的溶解度有限或不溶,但可通过加入一些改性剂（甲醇）或有机配体（含氮、磷、氧的有机物）来增加溶解度。 (1)与金属离子配位降低其极性; (2)增加SCCO2的极性,46,国内超临界萃取公司与产品,47,国外超临界萃取公司与产品,48,超临界流体的应用,超临界萃取,超临界氧化反应 超临界催化反应,超临界聚合反应,SCF,超细颗粒及薄膜材料制备,49,超临界流体在制备超细颗粒及薄膜中的应用,SCF快速膨胀技术,SCF抗溶剂技术,在超临界状态时，当含有溶质的SC

24、F通过特制喷嘴（25-60m）作快速膨胀，在极短时间内10-5 S），组分过饱和度高达106倍，形成大量晶核，因而得到粒径分布很窄,粒度极细的超细颗粒。主要用于药物、陶瓷原料SiO2,CeO2等超细颗粒的制备.,将含有某种溶质的溶液通过喷入SCF，溶剂与SCF互溶后,降低原溶剂对溶质的溶解度，在短时间内形成较大的过饱和度而使溶质结晶析出，得到纯度高，粒径分布均匀的超细颗粒。该技术用于生化药物的微粒制备.,超临界流体,50,Supercritical Fluid Assisted Particle Synthesis,51,Results,A smaller nozzle will yield

25、smaller, less agglomerated particles A pressure closer to supercritical pressure (78 bar for CO2) will yield smaller particles, so 82 bar had smaller particles than 100 bar Concentration of solution,52,超临界流体在超细颗粒制备中的应用,应用于药物、陶瓷、半导体材料等。 材料在超临界流体中与在常用溶剂中制备比较,得到的晶形、颗粒度、抗烧结能力等性质大不相同。在超临界流体中,得到小的、高度微晶化的颗

26、粒;而在常用溶剂中,则得到团聚或非晶态的颗粒,这些颗粒的粒径分布较宽,这对材料的性质是不利的。,53,超临界流体的高分子聚合反应,超临界CO2中的聚合反应,单体 引发剂 聚合方法 温度() 压力(Mp) 分子量(*103),1,1-二氢全氟代 AIBN 溶液聚合 60 20.7 270 辛基丙烯酸酯 丙烯酰胺 AIBN 乳液聚合 60 34.5 4920 7090 丙烯酸 AIBN 沉淀聚合 62 12.5 144 149 苯乙烯 SnCl2 阳离子聚合 100 24 4 正冰片 Ru(H2O)6(TOS) 开环聚合 65 30 20,54,在超临界体系进行高分子合成 与加工特点,1 不使用有

27、害的有机溶剂避免环境污染 2 可改进高分子材料的机械性能及加工性能 3 可按分子量的大小对产品进行分离 4 可通过超临界多元流体对高分子材料进行 染色, 加香及改性，制备缓释材料。,55,超临界流体催化反应,超临界流体,催化加氢,超临界水氧化反应,sc-CO2-氢甲酰化反应,Heck-Stille反应,56,催化加氢,不对称加氢,90.5% 81%ee 9.5%,不饱和烯烃在sc-CO2进行不对称加氢, 具有很高的立体选择性,同时反应没有任何碱参与,而无副产物生成.,Science 1995 Jessop,CO2加氢,CO2 + H2 HCOOH,Ru cat SC CO2 323K,sc-C

28、O2 可以溶解三甲基膦配体的Ru催化剂,使其成为高分散均相体系, 而且还可溶解大量H2, 使体系达到高的H2/CO2混合比, Ru的加氢活性很高,比液相反应提高1-2个数量级。,Chem. Rev 1999 Jessop,57,The rates of formic acid production by CO2 hydrogenation,1.Ru,N(C2H5)3,benzene,50atm,RT 2.Rh,none,THF,95atm,40 3.Ru,N(C2H5)3,DMSO,40atm,RT 4.Ru(1),N(C2H5)3,THF,205atm,50 5.Rh,NH(CH3)2,wa

29、ter,40atm,RT 6.Ru(1),N(C2H5)3,scCO2,205atm,50 7.Ru(2),N(C2H5)3,scCO2,205atm,50.,1.溶解钌膦配合物催化剂,使 之成为高分散的均相系统, 和氢气能互溶,多相反应变成均相反应.,2.消除了使用有机溶剂 可能带来的环境污染,优点:,Nature,1994,by Philip G. Jessop,58,sc-CO2氢甲酰化反应,在超临界条件下, 此反应可以提高直链醛与支链醛的比例,且反应速度比非极性溶剂中快. 原因是气体在sc-CO2中溶解度大而增加反应物浓度的缘故.,Science 2003 J cole,Heck-St

30、ille 反应,在sc-CO2中利用钯-膦配合物催化碳-碳偶合反应, 可得到比常规溶剂更高的转化率和选择性. 由于钯-膦配合物在sc-CO2中溶解度大大提高, 从而使反应以均相催化进行.,Chimia 1999 Reetz,(转化率99%,选择性99%),59,Science, 2003, by D. J. Cole-Hamilton,scCO2/IL中连续流动氢甲酰化反应,60,Biocatalysis in Ionic Liquids using scCO2 as mobile phase,Enzyme suspended in IL phase Substrates injected u

31、sing flow of scCO2 Substrate more soluble in IL than in scCO2 Product has good solubility in scCO2 and readily extracted IL and enzyme reused IL does not dissolve in scCO2,Chem. Commun., 2002, 992.,94% yield, 0.1kg/litre reactor volume/hour,Continuous process reported by Reetz and Leitner, combines

32、green solvents:,61,J.Am.Chem.Soc.1996,by Philip G. Jessop,Photographs showing the interior of the window-equipped reactor vessel under various conditions,CO2 at 30 ; CO2 at 32 .,N(C2H5)3 under: 1 atm of CO2 gas; Increasing pressure of CO2.,reaction mixture at 50 : Start; Complete.,62,Catalyst activi

33、ty histories during hexene isomerization on a shell-type -Al2O3 catalyst,Angew. Chem. Int. Ed. Engl. 1981, by H. Tiltscher,Enhancing the stability of porous catalysts with supercritical reaction media,63,超临界流体在催化反应中的应用,反应速率、产率、选择性等可用压力调节，可将非均相反应变成均相反应，改善非均相反应的传质速度，用环境友好溶剂取代有害溶剂，可将化学反应与分离过程结合起来等。 1.反

34、应装置：通常超临界反应装置的压力设定值高达40MPa, 因此要做好安全防范措施。 2.加氢反应在超临界加氢反应中,由于H2能混溶在超临界相中从而消除了从气相到超临界相的传质阻力,因此在超临界流体中进行加氢反应具有很大的优越性。,64,超临界流体在催化反应工程中的应用,3. 超临界异构化反应，一般说来,在常用溶剂中异构化产物主要是反式产物且在低压气相反应中初始顺反产率比不受温度的影响。但在超临界相中由于空间位阻和中间产物易从催化剂表面脱附,顺式成为主要产物,并且顺反比随压力的增加而增加。 4.氢甲酰化反应烯烃的氢甲酰化反应对于有机合成具有重要意义,它可以将烯烃转化为醛或酮等重要有机化合物。研究发

35、现烯烃氢甲酰化反应控制步骤是加氢步骤,因此若将氢甲酰化反应置于超临界相中进行则可提高反应速率。丙烯的氢甲酰反应在SCCO2中比在烃类溶剂中目的产物的选择性高。,65,超临界流体在催化反应中的优势,超临界流体,66,超临界流体在催化反应中的应用展望,超临界流体在催化反应中的应用还刚刚开始,但其独特的性 能和已有成功应用都证明了其在催化反应中运用的巨大潜力。,基础研究和应用研究仍处于对具体过程的探索,没有一般 适用的超临界流体动力学方程和模型。,67,Oxidation in Supercritical Carbon Dioxide Peracid oxidations in scCO2,R.S.

36、 Oakes, A.A. Clifford and C.M. Rayner, unpublished results,68,Sulfoxide formation in scCO2,Clean sulfoxide formation No sulfone formation, even using excess oxidant,69,Sulfone formation in scCO2,Diastereoselective Sulfur Oxidation,Oxidation of cysteine derivatives often gives low selectivity in conv

37、entional solvents:,Significant substrate modification and low temperatures are required to achieve even moderate selectivity.,No d.e. observed,50% d.e.,S. Nakamura et al., Bioorg. M. Ali, R.S. Oakes, A.A. Clifford and C.M Rayner, unpublished results.,73,Stereochemistry confirmed by X-ray Crystallogr

38、aphy,Other substrates,Replacing the Cbz group with Boc has a significant effect on selectivty,No diastereoselectivity observed in conventional solvent Major isomer is now syn!,R.S. Oakes, A.A. Clifford, K.D. Bartle, M. Thornton Pett, and C.M. Rayner, Chem. Commun., 1999, 247; M. Ali, R.S. Oakes, A.A

39、. Clifford and C.M Rayner, unpublished results.,Solvent Stabilisation in a Supercritical Fluid,In a SCF we can change the solvent density and hence the number of stabilising solvent molecules. Therefore, as density changes so does stabilisation: Low density - low stabilisation. Medium density - high

40、 stabilisation. High density - repulsion comes in to effect hence reduced stabilisation. EVIDENCE: Variation of solubility with density (e.g. naphthalene),Low density Small number of interactions,Medium density Many interactions,High density Significant repulsive forces,76,超临界水中的氧化反应,超临界水氧化是一种对有机废料处

41、理的新技术。优点是被处理的有机物和氧在超临界水(P218atm, T374)中完全互溶, 可使有机物迅速地分解成二氧化碳、水、氮气以及盐类等无害成份。可处理酚类化合物, 卤代烃化合物等. 与传统湿式空气氧化法,焚烧法和生化处理法相比, 具有明显的优势。,77,Supercritical fluid chromatography (SFC),a. mobile phase is a supercritical fluid.,b. first proposed in 1958 by J. Lovelock. first report use was in 1962 by Klesper et al

42、, who used it to separate thermally-labile porphyrins(卟啉).,c. permits the separation and determination of a group of compounds that are not conveniently handled by either GC or LC. non-volatile or thermally labile so that the GC are in-applicable, contain no functional groups for detection by spectr

43、oscopic or electrochemical techniques employed in LC.,78,Theory of SFC,a. One of advantages is that supercritical fluid have lower densities and viscosities than liquids. This results in larger diffusion coefficients for solutes in SFC than LC. This results in Better efficiencies and higher optimum

44、linear Velocities in SFC than LC. b. SFC have higher densities than gas, so that mobile phase has a greater chance of interacting with the solute than that in GC (i.e., carrier gas). This makes the mobile phase important in determining the retention of solutes on the system and give more flexibility

45、 in optimizing the separation. For example, retention of solutes in SFC can be changed by using a different column (i.e. different stationary phases) as in GC, or by changing the mobile phase strength as in LC.,79,c. One major advantage of SFC is its ability to use detector available for either GC o

46、r LC, such as FID, UV-Vis, and Fluorescence detectors. This gives it a wide range of both universal and selective detections for use in either analytical or preparative-scale work. d. Depending on which supercritical fluid is used, it is also possible to use SFC at lower T than GC. This makes it more useful in the separation of therma