清华大学有机化学第5章(课堂PPT).ppt

,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,*,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,*,Chapter 5,Stereochemistry,第五章 立体化学,Organic Chemistry A(1),By Prof.Li Yan-Mei,Tsinghua University,1,Content,5.1 Introduction,5.2 Molecule with one asymmetric carbon,5.3 Molecule with two asymmetric carbon,5.4 Molecule with more than two asymmetric carbon,5.5 Cyclic compound,5.6 Other chiral molecules,5.7 Measure of polarity and reslution of racemic compounds,5.1.1 Chirality,Nicol,5.1 Introduction,Plane-polarized light,平面偏振光（偏振光）,Nicol,Light source,Non-chiral compounds,like water,该化合物“无旋光性”,“无光学活性”,Nicol,Light source,Chiral compounds,like lactic acid,该化合物具有“旋光性”,为“旋光物质”或“光活性物质”,偏转角,旋光度,物质的旋光性：物质使偏振光振动平面发生旋转的性质,Specific rotation,比旋光度,=100,/(cl),D,25,=100,/(cl),D:the D line of a sodium lamp (,=589.6nm),The Polarimeter,：旋光度,c,：样品的浓度（,100mL,溶液中样品的克数）,l,：盛液管的长度（单位：,cm,）,5.1.2 Asymmetric carbon atom,In the 19,th,century,several asymmetric crystals were discovered.Also,the solutions obtained from the asymmetric crystals were asymmetric.,Louis Pasteur,什么样的化合物具有旋光性？,not,superposable,Chirality,手性,晶体结构中缺少某种对称因素，导致实物与镜像互不重合,从而推测具有手性的分子，其结构中也因缺少某种对称因素，导致实物与镜像互不重合,判据：,实物与镜像不能重合,分子具有手性,充分且必要,1874 Newzealand Vant Hoff,The carbon atom linking four different groups or atoms is called an“,asymmetric carbon,”.,Asymmetric carbon,不对称碳原子：与四个互不相同的一价基团相连接的碳原子。,加“,*,”表示,If an symmetric carbon can be substituted and becomes asymmetric,it is called a“,prochiral carbon,”.,Prochiral carbon,Any molecule with such a carbon molecule,which is linked to four different groups or atoms,shows some chirality.,Stereocenter,Vant Hoff,认为含有不对称碳的分子具有旋光性。,优点：使用方便,缺点：很多例外,有些分子中存在不对称碳，但却无手性：,有些分子中没有不对称碳，但却有手性：,5.1.3 Symmetric element,How to judge chirality of a molecule,A molecule is not tally with its enantiomorphism.,But molecules with two asymmetric carbons may be symmetric.,A molecule without asymmetric carbon may be,chiral,.,If a molecule lacks some specialized symmetric element,the molecule shows,chirality,.,结构中缺少某种对称因素是该分子具有旋光性的原因。,Asymmetric axis,C,2,C,3,C,3,分子中的对称因素：,对称轴,C,n,n,：,轴的阶,C,n,表示该结构具有,n,重轴。当分子绕该轴转动,360,0,/n,的角度后，得到的构象与原分子完全一致。,当分子绕该轴转动一周，可得,n,个与原始构型无法区别的等价构型。,C,2,C,3,1,2,3,4,C,8,Planes of symmetric(mirror plane),C,H,H,H,H,Four planes of symmetric in the molecule,对称面,：假如有一个平面可以将分子分割成两部分，而其中一部分正好是另一部分的镜象，这个平面就是分子的对称面。,symmetric plane:the paper plane,an infinitude of symmetric planes,Symmetric centre,对称中心,i,i,：若分子中有一点,i,，通过,i,点画直线，如果在离,i,等距离的直线两端有相同的原子或原子团，则点,i,称为分子的对称中心。,Symmetric element and chirality,has symmetric plane,has no symmetric centre,has no symmetric plane,has no symmetric centre,no chirality,no optical activity,chirality,does not mach its enantiomorphous form,optical activity,对称因素与对称性,如果一个分子既没有对称面，又没有对称中心，那么该分子具有手性。,有对称面,无手性,既无对称面，又无对称中心,有手性,5.2.1 R/S system and Fischer projection formulas,5.2.2 Enantiomer,5.2.3 Racemate,5.2 Molecule with one asymmetric carbon,5.2.1 R/S system and Fischer projection formulas,1,D/L system,Defined as L configuration,Defined as D configuration,以“乳酸为基准，衍生化的方法,采用衍生化方法而推出,与旋光性无关,衍生过程中可能会产生歧义,目前主要应用于氨基酸、糖等分子中,2,R/S system,lowest priority,Highest priority,Third priority,Second priority,R,(,rectus,),S,(,sinister,),基团大小？,顺序规则！,特点：,R/S,与构型一一对应，不必找基准物进行衍生,顺时针,逆时针,观察方向,观察方向,L-,D-,S-,R-,Try to decide the R/S configuration in these molecules.,?,3,Fischer projection formula,画法：,指向纸内,指向纸外,利用,Fischer,投影式判断,R/S,构型：,1,2,3,4,最小的基团远离观察者，,与,R/S,构型判断的要求一致,逆时针,S,构型,1,2,3,4,最小的基团指向观察者，,与,R/S,构型判断的要求不一致,逆时针,R,构型,两个规定：,规定之一：,Fischer,投影式不可在纸面上翻转,180,0,。,翻转,180,0,S,R,相当于发生一次基团交换,结果：构型改变,规定之二：,Fischer,投影式可以在纸面上旋转,180,0,。,旋转,180,0,S,S,相当于发生两次基团交换,结果：构型不变,结论：基团交换偶数次 构型不变,基团交换奇数次 构型改变,应用：复杂情况下的,R/S,构型判断,最小的基团指向观察者，,与,R/S,构型判断的要求不一致,5.2.2 Enantiomer,含一个不对称碳的分子：对映体及其性质,S-,L-(+),R-,D-(-),含一个不对称碳原子的分子，其分子内既无对称面，又无对称中心，因此具有手性。,必定存在一个与该分子互为实物与镜像关系的分子，二者均有手性，二者互为,对映异构体,。,互为实物与镜像的关系，因此旋光度大小相等，符号相反。,分子中任何两个原子之间的距离及相对位置都相同，因此分子的内能相同。,在非手性环境下无区别（除旋光性）,对映体的性质：,In symmetric environment,In asymmetric environment,The enantiomer shows no difference.Melting point,boiling point,even reaction rate in asymmetric solution are the same.,在手性环境中二者性质不同！,When in asymmetric solution,reacting with asymmetric reagent or reacting with asymmetric catalysts,the reaction rates are different.,生命体形成手性环境,可识别不同的手性分子！,5.2.3 Racemate,外消旋体,1 mol,左旋体 ,1 mol,右旋体,外消旋体,混合物,旋光度为零,性质与相应的左、右旋体不同,外消旋化：旋光化合物在物理或化学因素作用下变成两个对映体的平衡混合物，因而失去旋光性的过程。,A equimolar mixture of two enantiomers,Using reactants and solvents with no,chirality,racement,is always obtained.,利用非手性原料，在非手性条件下只能得到外消旋体,Racement,show different properties,e.g.melting point,to pure,enantiomers,.,Racemization,is such a process in which an,chiral,compound is converted into two,enantiomers,and thus loses its optical reactivity.,5.3.1 Molecule with two same asymmetric carbons,5.3.2 Optical activity and conformation,5.3.3 Molecule with two different asymmetric carbons,5.3 Molecule with two asymmetric carbon,当一个分子含有,n,个不对称碳原子，其异构体数最多为,2,n,个。,含有多个不对称碳原子的,Fischer,投影式的画法：,5.3.1 Molecule with two same asymmetric carbons,Enantiomer,对映异构体,Diastereomers,非对映异构体,共有,3,个异构体,meso compound,内消旋体,非对映异构体的性质不同！,meso compound,内消旋体,单一化合物,旋光度为零,性质与那一对对映异构体均不同,symmetric,but unstable.,stable,still symmetric?,问题？,全重叠式，不优势！,5.3.2 Optical activity and conformation,旋光性与构象,1,meso compound,利用,Fischer,投影式模型分析，分子具有对称面，无手性。,平面分析,利用立体分析，分子应有手性。,立体分析,COOH,HOOC,OH,OH,H,H,OH,COOH,HOOC,OH,H,H,COOH,H,COOH,OH,H,OH,COOH,COOH,H,OH,H,HO,COOH,HO,H,OH,H,COOH,H,COOH,HO,OH,H,HOOC,Conformation analysis,2,enantiomers,COOH,H,OH,OH,H,COOH,COOH,HO,H,H,HO,COOH,COOH,H,COOH,H,HO,OH,COOH,HOOC,OH,H,HO,H,COOH,HOOC,H,OH,H,OH,COOH,HO,COOH,OH,H,H,5.3.3 Molecule with two different asymmetric carbons,Stereoisomer,Diastereomer,5.4.1 Epimer,5.4.2 Pseudoasymmetric carbon,5.4 Molecule with more than two asymmetric carbon,5.4.1 Epimer,差向异构体,Epimer,H,C,O,O,H,O,H,H,C,l,H,C,O,O,H,H,O,C,l,H,C,l,H,C,2,H,5,C,l,H,C,2,H,5,如果两个光学异构体仅有一个不对称碳原子的构型相反，其它不对称碳原子的构型都相同，这两个光活异构体则互为,差向异构体,。,5.4.2 Pseudoasymmetric carbon,假不对称碳原子,有几个不对称碳原子？,？,是否不对称碳,取决于,2,C,和,4,C,的构型,meso,meso,The third carbons of these four isomers are asymmetric.,共四个异构体：,R,R,S,S,R,S,R,S,3,3,3,3,3,C,为非不对称碳,均有旋光性,互为对映异构体,3,C,为不对称碳,均无旋光性,为内消旋体,互为非对映异构体,假不对称碳,Optical,Stereomer,C3 is symmetric,Not optical,Meso,C3 is asymmetric,5.5.1 Cyclopropane,cyclobutane,and cyclopentane,5.5.2 derivatives of Cyclohexane,5.5 Cyclic compound,关键：平面分析 构象分析,5.5.1 Cyclopropane,cyclobutane,and cyclopentane,1,Cyclopropane,A,A,A,A,A,A,A,Trans-,Cis-,A,B,B,A,A,B,B,A,Cis-,Trans-,A,A,A,A,A,A,2,Cyclobutane,3,Cyclopentane,Learn on your own,5.5.2 Derivatives of Cyclohexane,顺,-1,2-,二取代,平面分析：,构象分析：,Rotation,Conformation transition,(i),(i),(i),(i),Rotation,Conformation transition,(ii)aa,(ii)ee,(iii)ee,Conformation transition,(iii)aa,(iv),(iv),结论：就环己烷而言，平面分析与构象分析的结论相同。,5.6.1 Allene type compounds,5.6.2 Diphenyl compounds,5.6.3 Spiro compounds,5.6.2 Compounds with stereocenters other than carbon,5.6 Other chiral molecules,5.6.1 Allene type compounds,如果任何一端或两端的碳原子上连有相同取代基，则分子中存在对称面，该分子无手性。,反之，则该分子有手性。,5.6.2 Diphenyl compounds,If on 2,2,6,6 sites there are large groups which block the rotation of the benzene rings,the two phenol rings are not on the same plane.,5.6.3 Spiro compounds,5.6.2 Compounds with stereocenters other than carbon,Also,molecules with N,S,Si,As show this property.,5.7.1 Measure of polarity,(Learn on your own),5.7.2 Reslution of racemic compounds,5.7.3 Enantiomer excess percentage,5.7.4 Configuration and bio-activities,5.7 Measure of polarity and reslution of racemic compounds,5.7.1 Measure of polarity,(Learn on your own),D,25,=100,/(cl),5.7.2 Reslution of racemic compounds,1,Chemical methods,50%D-Acid,50%L-Acid,50%D-Acid,50%D-Acid-D-Base,50%L-Acid-D-Base,2,Enzymatic methods,50%D-Compound,50%L-compound,Enzyme,Enzyme,Used up,NR,3,Crystal seeds,4,Column chromatography,5.7.3 Enantiomer excess percentage,%ee,=,R+S,R-S,%R-%S,=,If R=S=50%ee=0%,If R=100,S=0%ee=100%,Meso,Pure chiral compound,5.7.4 Configuration and bio-activities,构型与生理活性,抗疟药有氯喹啉有,(+),、,(-),之分，但二者的抗活性、强度的均相同。,氯霉素：,(-),氯霉素：有生理活性,(+),氯霉素：无生理活性,多巴：,(-),多巴：抗镇颤麻痹作用，用于治疗帕金森病,(+),多巴：无生理活性,S-(-),多巴,1,、有与无,2,、强与弱,茛菪碱（茄科植物茛菪、曼陀罗、天仙子等）是,R-(+),茛菪碱和,S-(-),茛菪碱组成的外消旋体。,二者都可以作为抗胆碱药。但前者的中枢兴奋作用比后者强,8,50,倍。正因为前者毒性大，故而毒性也大。因此临床上使用的是（,）茛菪碱，取名“阿托品”、“颠茄碱”。,3,、相对抗,(-)-,依托唑啉具有利尿作用，而,(+)-,依托唑啉具有抗利尿作用,3,、作用类型、强度均不同,反应停（,halidomide,，,-,苯肽茂二酰亚胺，塞利多米）,镇静作用,强烈致畸作用,Thank you!,88,