清華大學(xué)有機(jī)化學(xué)立體化學(xué)市公開課金獎(jiǎng)市賽課一等獎(jiǎng)?wù)n件

1、Chapter 5Stereochemistry第五章 立體化學(xué)Organic Chemistry A (1)By Prof. Li Yan-MeiTsinghua University第1頁(yè)Content5.1 Introduction5.2 Molecule with one asymmetric carbon5.3 Molecule with two asymmetric carbon5.4 Molecule with more than two asymmetric carbon5.5 Cyclic compound5.6 Other chiral molecules5.7 Measu

2、re of polarity and reslution of racemic compounds 第2頁(yè) 5.1.1 ChiralityNicol5.1 IntroductionPlane-polarized light平面偏振光（偏振光）第3頁(yè)NicolLight sourceNon-chiral compounds, like water該化合物“無(wú)旋光性” “無(wú)光學(xué)活性”第4頁(yè)NicolLight sourceChiral compounds, like lactic acid該化合物含有“旋光性”為“旋光物質(zhì)”或“光活性物質(zhì)”偏轉(zhuǎn)角旋光度物質(zhì)旋光性：物質(zhì)使偏振光振動(dòng)平面發(fā)生旋轉(zhuǎn)性質(zhì)第

3、5頁(yè)Specific rotation 比旋光度 = 100/(cl)D25 = 100/(cl)D: the D line of a sodium lamp (=589.6nm)The Polarimeter：旋光度 c： 樣品濃度（100mL溶液中樣品克數(shù)） l： 盛液管長(zhǎng)度（單位：cm）第6頁(yè)5.1.2 Asymmetric carbon atomIn the 19th century, several asymmetric crystals were discovered. Also, the solutions obtained from the asymmetric crystal

4、s were asymmetric.Louis Pasteur什么樣化合物含有旋光性？第7頁(yè)第8頁(yè)not superposable第9頁(yè)Chirality 手性晶體結(jié)構(gòu)中缺乏某種對(duì)稱原因，造成實(shí)物與鏡像互不重合第10頁(yè)從而推測(cè)含有手性分子，其結(jié)構(gòu)中也因缺乏某種對(duì)稱原因，造成實(shí)物與鏡像互不重合第11頁(yè)判據(jù)：實(shí)物與鏡像不能重合分子含有手性充分且必要第12頁(yè)1874 Newzealand Vant Hoff The carbon atom linking four different groups or atoms is called an “asymmetric carbon”.Asymmetri

5、c carbon不對(duì)稱碳原子：與四個(gè)互不相同一價(jià)基團(tuán)相連接碳原子。加“ * ”表示第13頁(yè)If an symmetric carbon can be substituted and becomes asymmetric, it is called a “prochiral carbon”.Prochiral carbon第14頁(yè)Any molecule with such a carbon molecule, which is linked to four different groups or atoms, shows some chirality.StereocenterVant Hoff

6、 認(rèn)為含有不對(duì)稱碳分子含有旋光性。第15頁(yè)優(yōu)點(diǎn)：使用方便缺點(diǎn)：很多例外 有些分子中存在不對(duì)稱碳，但卻無(wú)手性： 有些分子中沒(méi)有不對(duì)稱碳，但卻有手性：第16頁(yè)5.1.3 Symmetric elementHow to judge chirality of a moleculeA molecule is not tally with its enantiomorphism.But molecules with two asymmetric carbons may be symmetric.第17頁(yè) A molecule without asymmetric carbon may be chiral.

7、If a molecule lacks some specialized symmetric element, the molecule shows chirality. 結(jié)構(gòu)中缺乏某種對(duì)稱原因是該分子含有旋光性原因。第18頁(yè)Asymmetric axisC2C3C3分子中對(duì)稱原因：對(duì)稱軸 Cn n：軸階Cn表示該結(jié)構(gòu)含有n重軸。當(dāng)分子繞該軸轉(zhuǎn)動(dòng)3600/n角度后，得到構(gòu)象與原分子完全一致。當(dāng)分子繞該軸轉(zhuǎn)動(dòng)一周，可得n個(gè)與原始構(gòu)型無(wú)法區(qū)分等價(jià)構(gòu)型。第19頁(yè)C2C31234第20頁(yè)C8第21頁(yè)P(yáng)lanes of symmetric (mirror plane)CHHHHFour planes o

8、f symmetric in the molecule對(duì)稱面 ：假如有一個(gè)平面能夠?qū)⒎肿臃指畛蓛刹糠郑渲幸徊糠智『檬橇硪徊糠昼R象，這個(gè)平面就是分子對(duì)稱面。第22頁(yè)symmetric plane: the paper plane an infinitude of symmetric planes第23頁(yè)Symmetric centre對(duì)稱中心 ii：若分子中有一點(diǎn)i，經(jīng)過(guò)i點(diǎn)畫直線，假如在離i等距離直線兩端有相同原子或原子團(tuán)，則點(diǎn)i稱為分子對(duì)稱中心。第24頁(yè)Symmetric element and chiralityhas symmetric planehas no symmetric c

9、entrehas no symmetric planehas no symmetric centreno chiralityno optical activitychiralitydoes not mach its enantiomorphous formoptical activity對(duì)稱原因與對(duì)稱性假如一個(gè)分子既沒(méi)有對(duì)稱面，又沒(méi)有對(duì)稱中心，那么該分子含有手性。第25頁(yè)有對(duì)稱面無(wú)手性既無(wú)對(duì)稱面，又無(wú)對(duì)稱中心有手性第26頁(yè) 5.2.1 R/S system and Fischer projection formulas 5.2.2 Enantiomer 5.2.3 Racemate5.2 Mo

10、lecule with one asymmetric carbon第27頁(yè)5.2.1 R/S system and Fischer projection formulas1, D/L systemDefined as L configurationDefined as D configuration以“乳酸為基準(zhǔn)，衍生化方法采取衍生化方法而推出與旋光性無(wú)關(guān)衍生過(guò)程中可能會(huì)產(chǎn)生歧義當(dāng)前主要應(yīng)用于氨基酸、糖等分子中第28頁(yè)2, R/S systemlowest priorityHighest priorityThird prioritySecond priorityR(rectus)S(sinis

11、ter)基團(tuán)大小？次序規(guī)則！特點(diǎn)：R/S與構(gòu)型一一對(duì)應(yīng)，無(wú)須找基準(zhǔn)物進(jìn)行衍生順時(shí)針逆時(shí)針觀察方向觀察方向第29頁(yè)L-D-S-R-第30頁(yè)Try to decide the R/S configuration in these molecules.?第31頁(yè)3, Fischer projection formula畫法：第32頁(yè)指向紙內(nèi)指向紙外第33頁(yè)第34頁(yè)利用Fischer投影式判斷R/S構(gòu)型：1234最小基團(tuán)遠(yuǎn)離觀察者，與R/S構(gòu)型判斷要求一致逆時(shí)針S構(gòu)型第35頁(yè)1234最小基團(tuán)指向觀察者，與R/S構(gòu)型判斷要求不一致逆時(shí)針R構(gòu)型第36頁(yè)兩個(gè)要求：要求之一：Fischer投影式不可在紙面上翻

12、轉(zhuǎn)1800。翻轉(zhuǎn)1800SR相當(dāng)于發(fā)生一次基團(tuán)交換結(jié)果：構(gòu)型改變第37頁(yè)要求之二：Fischer投影式能夠在紙面上旋轉(zhuǎn)1800。旋轉(zhuǎn)1800SS相當(dāng)于發(fā)生兩次基團(tuán)交換結(jié)果：構(gòu)型不變第38頁(yè)結(jié)論：基團(tuán)交換偶數(shù)次 構(gòu)型不變 基團(tuán)交換奇數(shù)次 構(gòu)型改變應(yīng)用：復(fù)雜情況下R/S構(gòu)型判斷最小基團(tuán)指向觀察者，與R/S構(gòu)型判斷要求不一致第39頁(yè)第40頁(yè)5.2.2 Enantiomer 含一個(gè)不對(duì)稱碳分子：對(duì)映體及其性質(zhì)S-L-(+)R-D-(-)含一個(gè)不對(duì)稱碳原子分子，其分子內(nèi)既無(wú)對(duì)稱面，又無(wú)對(duì)稱中心，所以含有手性。必定存在一個(gè)與該分子互為實(shí)物與鏡像關(guān)系分子，二者都有手性，二者互為對(duì)映異構(gòu)體。第41頁(yè)互為實(shí)物與

13、鏡像關(guān)系，所以旋光度大小相等，符號(hào)相反。分子中任何兩個(gè)原子之間距離及相對(duì)位置都相同，所以分子內(nèi)能相同。在非手性環(huán)境下無(wú)區(qū)分（除旋光性）對(duì)映體性質(zhì)：第42頁(yè)In symmetric environmentIn asymmetric environmentThe enantiomer shows no difference. Melting point, boiling point, even reaction rate in asymmetric solution are the same.在手性環(huán)境中二者性質(zhì)不一樣！When in asymmetric solution, reacting w

14、ith asymmetric reagent or reacting with asymmetric catalysts, the reaction rates are different.第43頁(yè)生命體形成手性環(huán)境 可識(shí)別不一樣手性分子！第44頁(yè) 5.2.3 Racemate 外消旋體1 mol 左旋體 1 mol 右旋體外消旋體混合物旋光度為零性質(zhì)與對(duì)應(yīng)左、右旋體不一樣外消旋化：旋光化合物在物理或化學(xué)原因作用下變成兩個(gè)對(duì)映體平衡混合物，因而失去旋光性過(guò)程。第45頁(yè)A equimolar mixture of two enantiomersUsing reactants and solven

15、ts with no chirality, racement is always obtained. 利用非手性原料，在非手性條件下只能得到外消旋體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.第46頁(yè) 5.3.1 Molecu

16、le with two same asymmetric carbons 5.3.2 Optical activity and conformation 5.3.3 Molecule with two different asymmetric carbons5.3 Molecule with two asymmetric carbon第47頁(yè)當(dāng)一個(gè)分子含有n個(gè)不對(duì)稱碳原子，其異構(gòu)體數(shù)最多為2n個(gè)。含有多個(gè)不對(duì)稱碳原子Fischer投影式畫法：第48頁(yè)5.3.1 Molecule with two same asymmetric carbonsEnantiomer 對(duì)映異構(gòu)體Diastereome

17、rs 非對(duì)映異構(gòu)體共有3個(gè)異構(gòu)體meso compound內(nèi)消旋體非對(duì)映異構(gòu)體性質(zhì)不一樣！第49頁(yè)meso compound 內(nèi)消旋體單一化合物旋光度為零性質(zhì)與那一對(duì)對(duì)映異構(gòu)體均不一樣第50頁(yè)symmetric, but unstable. stable, still symmetric? 問(wèn)題 ？全重合式，不優(yōu)勢(shì)！第51頁(yè)5.3.2 Optical activity and conformation 旋光性與構(gòu)象1, meso compound利用Fischer投影式模型分析，分子含有對(duì)稱面，無(wú)手性。平面分析利用立體分析，分子應(yīng)有手性。立體分析第52頁(yè)COOHHOOCOHOHHHOHCOOH

18、HOOCOHHHCOOHHCOOHOHHOHCOOHCOOHHOHHHOCOOHHOHOHHCOOHHCOOHHOOHHHOOCConformation analysis第53頁(yè)2, enantiomersCOOHHOHOHHCOOHCOOHHOHHHOCOOHCOOHHCOOHHHOOHCOOHHOOCOHHHOHCOOHHOOCHOHHOHCOOHHOCOOHOHHH第54頁(yè)5.3.3 Molecule with two different asymmetric carbonsStereoisomerDiastereomer第55頁(yè) 5.4.1 Epimer 5.4.2 Pseudoasy

19、mmetric carbon 5.4 Molecule with more than two asymmetric carbon第56頁(yè)5.4.1 Epimer 差向異構(gòu)體EpimerHCOOHOHHClHCOOHHOClHClHC2H5ClHC2H5假如兩個(gè)光學(xué)異構(gòu)體僅有一個(gè)不對(duì)稱碳原子構(gòu)型相反，其它不對(duì)稱碳原子構(gòu)型都相同，這兩個(gè)光活異構(gòu)體則互為差向異構(gòu)體。第57頁(yè) 5.4.2 Pseudoasymmetric carbon 假不對(duì)稱碳原子有幾個(gè)不對(duì)稱碳原子？是否不對(duì)稱碳取決于2C和4C構(gòu)型第58頁(yè)mesomesoThe third carbons of these four isomers

20、 are asymmetric.第59頁(yè)共四個(gè)異構(gòu)體：RRSSRSRS33333C 為非不對(duì)稱碳都有旋光性互為對(duì)映異構(gòu)體3C 為不對(duì)稱碳均無(wú)旋光性為內(nèi)消旋體互為非對(duì)映異構(gòu)體假不對(duì)稱碳第60頁(yè)Optical StereomerC3 is symmetricNot optical MesoC3 is asymmetric第61頁(yè) 5.5.1 Cyclopropane, cyclobutane, and cyclopentane 5.5.2 derivatives of Cyclohexane5.5 Cyclic compound關(guān)鍵：平面分析 構(gòu)象分析第62頁(yè) 5.5.1 Cyclopropane

21、, cyclobutane, and cyclopentane1, CyclopropaneAAAAAAATrans-Cis-第63頁(yè)ABBAABBACis-Trans-AAAAAA第64頁(yè)2, Cyclobutane3, CyclopentaneLearn on your own第65頁(yè)5.5.2 Derivatives of Cyclohexane順-1,2-二取代平面分析：構(gòu)象分析：第66頁(yè)Rotation Conformation transition (i)(i)(i)(i)第67頁(yè)Rotation Conformation transition (ii)aa(ii)ee(iii)e

22、eConformation transition (iii)aa第68頁(yè)(iv)(iv)第69頁(yè)結(jié)論：就環(huán)己烷而言，平面分析與構(gòu)象分析結(jié)論相同。第70頁(yè) 5.6.1 Allene type compounds 5.6.2 Diphenyl compounds 5.6.3 Spiro compounds 5.6.2 Compounds with stereocenters other than carbon5.6 Other chiral molecules第71頁(yè) 5.6.1 Allene type compounds第72頁(yè)假如任何一端或兩端碳原子上連有相同取代基，則分子中存在對(duì)稱面，該分子

23、無(wú)手性。反之，則該分子有手性。第73頁(yè)5.6.2 Diphenyl compoundsIf 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.第74頁(yè) 5.6.3 Spiro compounds第75頁(yè)5.6.2 Compounds with stereocenters other than carbonAlso, molecules with N, S, Si, As show this property. 第76頁(yè)第77頁(yè) 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-activities5.7 Measure of polarity and reslution of racemic compounds第78頁(yè)5.7.1 Measure of polarity (Lear