清華大學(xué)李艷梅有機(jī)化學(xué)第五章立體化學(xué)

1、Stereochemistry第五章第五章 立體化學(xué)立體化學(xué)Organic Chemistry A (1)By Prof. Li Yan-MeiTsinghua UniversityNicolPlane-polarized light平面偏振光（偏振光）NicolLight sourceNon-chiral compounds, like water該化合物“無(wú)旋光性” “無(wú)光學(xué)活性”NicolLight sourceChiral compounds, like lactic acid該化合物具有“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)的旋光性：物質(zhì)使偏振光振動(dòng)平面發(fā)生旋轉(zhuǎn)的性

2、質(zhì)Specific rotation 比旋光度 = 100/(cl)D25 = 100/(cl)D: the D line of a sodium lamp (=589.6nm)：旋光度 c： 樣品的濃度（100mL溶液中樣品的克數(shù)） l： 盛液管的長(zhǎng)度（單位：cm）5.1.2 Asymmetric carbon atomIn the 19th century, several asymmetric crystals were discovered. Also, the solutions obtained from the asymmetric crystals were asymmetri

3、c.Louis PasteurCOOHCOOHHOHOCOOHCOOHHOHO什么樣的化合物具有旋光性？Chirality 手性手性晶體結(jié)構(gòu)中缺少某種對(duì)晶體結(jié)構(gòu)中缺少某種對(duì)稱(chēng)因素，導(dǎo)致實(shí)物與鏡稱(chēng)因素，導(dǎo)致實(shí)物與鏡像互不重合像互不重合從而推測(cè)具有手性的分子，其結(jié)構(gòu)中也因缺少某種對(duì)稱(chēng)因素，導(dǎo)致實(shí)從而推測(cè)具有手性的分子，其結(jié)構(gòu)中也因缺少某種對(duì)稱(chēng)因素，導(dǎo)致實(shí)物與鏡像互不重合物與鏡像互不重合1874 Newzealand Vant Hoff The carbon atom linking four different groups or atoms is called an “asymmetric ca

4、rbon”.不對(duì)稱(chēng)碳原子：與四個(gè)互不相同不對(duì)稱(chēng)碳原子：與四個(gè)互不相同的一價(jià)基團(tuán)相連接的碳原子。的一價(jià)基團(tuán)相連接的碳原子。加加“ * ”表示表示If an symmetric carbon can be substituted and becomes asymmetric, it is called a “prochiral carbon”.Prochiral carbonAny molecule with such a carbon molecule, which is linked to four different groups or atoms, shows some chirality

5、.StereocenterVant Hoff 認(rèn)為含有不對(duì)稱(chēng)碳的分子具有旋光性。認(rèn)為含有不對(duì)稱(chēng)碳的分子具有旋光性。優(yōu)點(diǎn)：使用方便優(yōu)點(diǎn)：使用方便缺點(diǎn)：很多例外缺點(diǎn)：很多例外 有些分子中存在不對(duì)稱(chēng)碳，但卻無(wú)手性：有些分子中存在不對(duì)稱(chēng)碳，但卻無(wú)手性： 有些分子中沒(méi)有不對(duì)稱(chēng)碳，但卻有手性：有些分子中沒(méi)有不對(duì)稱(chēng)碳，但卻有手性：PabcPabcABBAHHH3CCH3ClClHHH3CCH3ClCl5.1.3 Symmetric elementHow to judge chirality of a moleculelA molecule is not tally with its enantiomorph

6、ism.lBut molecules with two asymmetric carbons may be symmetric.l A molecule without asymmetric carbon may be chiral.lIf a molecule lacks some specialized symmetric element, the molecule shows chirality. 結(jié)構(gòu)中缺少某種對(duì)稱(chēng)因素是該分子具結(jié)構(gòu)中缺少某種對(duì)稱(chēng)因素是該分子具有旋光性的原因。有旋光性的原因。C2C3C3分子中的對(duì)稱(chēng)因素：C2C3HHHHHHHHHHHHHHHHC8CHHHHFour p

7、lanes of symmetric in the molecule ：假如有一個(gè)平面可以將分子分割成兩部分，而其中一部分正：假如有一個(gè)平面可以將分子分割成兩部分，而其中一部分正好是另一部分的鏡象，這個(gè)平面就是分子的對(duì)稱(chēng)面。好是另一部分的鏡象，這個(gè)平面就是分子的對(duì)稱(chēng)面。BrBrHHHClsymmetric plane: the paper plane an infinitude of symmetric planesClHClHClCli：若分子中有一點(diǎn)：若分子中有一點(diǎn)i，通過(guò)，通過(guò)i點(diǎn)畫(huà)直線，如果在離點(diǎn)畫(huà)直線，如果在離i等距離的直線等距離的直線兩端有相同的原子或原子團(tuán)，則點(diǎn)兩端有相同的原子或

8、原子團(tuán)，則點(diǎn)i稱(chēng)為分子的對(duì)稱(chēng)中心。稱(chēng)為分子的對(duì)稱(chēng)中心。has symmetric planehas no symmetric centrehas no symmetric planehas no symmetric centreno chiralityno optical activitychiralitydoes not mach its enantiomorphous formoptical activity如果一個(gè)分子既沒(méi)有對(duì)稱(chēng)面，又沒(méi)有對(duì)稱(chēng)中心，那么該分子如果一個(gè)分子既沒(méi)有對(duì)稱(chēng)面，又沒(méi)有對(duì)稱(chēng)中心，那么該分子具有手性。具有手性。有對(duì)稱(chēng)面無(wú)手性既無(wú)對(duì)稱(chēng)面，又無(wú)對(duì)稱(chēng)中心有手性 5.2.1 R

9、/S system and Fischer projection formulas 5.2.2 Enantiomer 5.2.3 Racemate5.2.1 R/S system and Fischer projection formulas1, D/L systemHH3CHOHOOCHCH3OHCOOHHH3CHOOHCHCH3OHCHODefined as L configurationDefined as D configuration以“乳酸為基準(zhǔn)，衍生化的方法n采用衍生化方法而推出n與旋光性無(wú)關(guān)n衍生過(guò)程中可能會(huì)產(chǎn)生歧義n目前主要應(yīng)用于氨基酸、糖等分子中adcb2, R/S sys

10、temlowest priorityHighest priorityThird prioritySecond priorityR(rectus)adbcS(sinister)基團(tuán)大小？基團(tuán)大小？順序規(guī)則！順序規(guī)則！特點(diǎn)：特點(diǎn)：R/S與構(gòu)型一一對(duì)應(yīng)，不必找基準(zhǔn)與構(gòu)型一一對(duì)應(yīng)，不必找基準(zhǔn)物進(jìn)行衍生物進(jìn)行衍生順時(shí)針逆時(shí)針觀察方向觀察方向觀察方向觀察方向HH3CHOOHCHCH3OHCHOL-D-S-R-Try to decide the R/S configuration in these molecules.?3, Fischer projection formula畫(huà)法：畫(huà)法：COOHHCH3O

11、HHCOOHOHCH3HH3CHOHOOCHCH3OHCOOHHOCH3HCOOHHCH3OHCOOHHOCH3HCOOHHCH3OHCOOH指向紙內(nèi)指向紙內(nèi)指向紙外指向紙外HHOOCClBrHCOOHOHBrClCOOHHBrHCOOHOHBrClCOOHHBrHCOOHOHBr利用利用Fischer投影式判斷投影式判斷R/S構(gòu)型：構(gòu)型：HOOCHBrOH1234最小的基團(tuán)遠(yuǎn)離觀察者，最小的基團(tuán)遠(yuǎn)離觀察者，與與R/S構(gòu)型判斷的要求一致構(gòu)型判斷的要求一致逆時(shí)針逆時(shí)針S構(gòu)型構(gòu)型HOOCBrHOH1234最小的基團(tuán)指向觀察者，最小的基團(tuán)指向觀察者，與與R/S構(gòu)型判斷的要求不一致構(gòu)型判斷的要求不一致

12、逆時(shí)針逆時(shí)針R構(gòu)型構(gòu)型兩個(gè)規(guī)定：兩個(gè)規(guī)定：規(guī)定之一：規(guī)定之一：Fischer投影式不可在紙面上翻轉(zhuǎn)投影式不可在紙面上翻轉(zhuǎn)1800。COOHHHOCH3COOHOHHCH3翻轉(zhuǎn)翻轉(zhuǎn)1800SR相當(dāng)于發(fā)生一次基團(tuán)交換相當(dāng)于發(fā)生一次基團(tuán)交換結(jié)果：構(gòu)型改變結(jié)果：構(gòu)型改變規(guī)定之二：規(guī)定之二：Fischer投影式可以在紙面上旋轉(zhuǎn)投影式可以在紙面上旋轉(zhuǎn)1800。COOHHHOCH3旋轉(zhuǎn)旋轉(zhuǎn)1800SS相當(dāng)于發(fā)生兩次基團(tuán)交換相當(dāng)于發(fā)生兩次基團(tuán)交換結(jié)果：構(gòu)型不變結(jié)果：構(gòu)型不變CH3OHHCOOH結(jié)論：基團(tuán)交換偶數(shù)次結(jié)論：基團(tuán)交換偶數(shù)次 構(gòu)型不變構(gòu)型不變 基團(tuán)交換奇數(shù)次基團(tuán)交換奇數(shù)次 構(gòu)型改變構(gòu)型改變應(yīng)用：復(fù)雜情

13、況下的應(yīng)用：復(fù)雜情況下的R/S構(gòu)型判斷構(gòu)型判斷HOOCBrHOH最小的基團(tuán)指向觀察者，最小的基團(tuán)指向觀察者，與與R/S構(gòu)型判斷的要求不一致構(gòu)型判斷的要求不一致COOHHHOCH3COOHHHOCH3COOHHHOCH3HOOCHOHCH3COOHHHOCH3COOHHOHCH3COOHHOHCH3COOHHHOCH35.2.2 Enantiomer 含一個(gè)不對(duì)稱(chēng)碳的分子：對(duì)映體及其性質(zhì)COOHHOHCH3COOHOHHCH3n 含一個(gè)不對(duì)稱(chēng)碳原子的分子，其分子內(nèi)既無(wú)對(duì)稱(chēng)面，又無(wú)對(duì)稱(chēng)中心，因此具有手性。n 必定存在一個(gè)與該分子互為實(shí)物與鏡像關(guān)系的分子，二者均有手性，二者互為對(duì)映異構(gòu)體對(duì)映異構(gòu)體。

14、p 互為實(shí)物與鏡像的關(guān)系，因此旋光度大小相等，符號(hào)相反。p 分子中任何兩個(gè)原子之間的距離及相對(duì)位置都相同，因此分子的內(nèi)能相同。p 在非手性環(huán)境下無(wú)區(qū)別（除旋光性）對(duì)映體的性質(zhì)：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)不同！在手性環(huán)境中二者性質(zhì)不同！When in asymmetr

15、ic solution, reacting with asymmetric reagent or reacting with asymmetric catalysts, the reaction rates are different.生命體形成手性環(huán)境生命體形成手性環(huán)境 可識(shí)別不同的手性分子！可識(shí)別不同的手性分子！ 5.2.3 Racemate 外消旋體外消旋體1 mol 左旋體左旋體 1 mol 右旋體右旋體外消旋體外消旋體p 混合物p 旋光度為零p 性質(zhì)與相應(yīng)的左、右旋體不同外消旋化：旋光化合物在物理或化學(xué)因素作用下變成兩個(gè)對(duì)映外消旋化：旋光化合物在物理或化學(xué)因素作用下變成兩個(gè)對(duì)映體的平

16、衡混合物，因而失去旋光性的過(guò)程。體的平衡混合物，因而失去旋光性的過(guò)程。A equimolar mixture of two enantiomersl Using reactants and solvents 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利用非手性原料，在非手性條件下只能得到外消旋體l Racement show different properties, e.g. melting point, to pure enantiomers. l Racemization is such

17、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 carbonsp 當(dāng)一個(gè)分子含有當(dāng)一個(gè)分子含有n個(gè)不對(duì)稱(chēng)碳原子，其異構(gòu)體數(shù)最多為個(gè)不對(duì)稱(chēng)碳原子，其異構(gòu)體數(shù)最多

18、為2n個(gè)。個(gè)。p 含有多個(gè)不對(duì)稱(chēng)碳原子的含有多個(gè)不對(duì)稱(chēng)碳原子的Fischer投影式的畫(huà)法：投影式的畫(huà)法：CCCOOHHOOCOHHHOHCOOHCOOHHOHHOHCOOHHHOOHHCOOHCOOHHOHHOHCOOH5.3.1 Molecule with two same asymmetric carbonsCOOHHHOHOHCOOHCOOHHOHOHHCOOHEnantiomer 對(duì)映異構(gòu)體對(duì)映異構(gòu)體Diastereomers 非對(duì)映異構(gòu)體非對(duì)映異構(gòu)體共有共有3 3個(gè)異構(gòu)體個(gè)異構(gòu)體COOHCHOHCHOHCOOH*meso compound內(nèi)消旋體內(nèi)消旋體非對(duì)映異構(gòu)體的性質(zhì)不同！非對(duì)映

19、異構(gòu)體的性質(zhì)不同！COOHCOOHHOHHOHmeso compound 內(nèi)消旋體內(nèi)消旋體p 單一化合物p 旋光度為零p 性質(zhì)與那一對(duì)對(duì)映異構(gòu)體均不同symmetric, but unstable. stable, still symmetric? 問(wèn)題問(wèn)題 ？COOHCOOHHOHHOHCOOHHOOCHHOHHO全重疊式，不優(yōu)勢(shì)！全重疊式，不優(yōu)勢(shì)！5.3.2 Optical activity and conformation 旋光性與構(gòu)象旋光性與構(gòu)象1, meso compoundCOOHCOOHHOHHOH利用利用Fischer投影式投影式模型分析，分子具有模型分析，分子具有對(duì)稱(chēng)面，無(wú)手

20、性。對(duì)稱(chēng)面，無(wú)手性。平面分析平面分析COOHHOOCHHOHHO利用立體分析，分子利用立體分析，分子應(yīng)有手性。應(yīng)有手性。立體分析立體分析COOHHOOCOHOHHHOHCOOHHOOCOHHHCOOHHCOOHOHHOHCOOHCOOHHOHHHOCOOHHOHOHHCOOHHCOOHHOOHHHOOCConformation analysis2, enantiomersHCOOHOHHOHCOOHHCOOHHOOHHCOOHCOOHHOHOHHCOOHCOOHHOHHHOCOOHCOOHHCOOHHHOOHCOOHHOOCOHHHOHCOOHHOOCHOHHOHCOOHHOCOOHOHHH5

21、.3.3 Molecule with two different asymmetric carbonsHCH3ClClHC2H5HCH3ClClHC2H5HCH3ClHClC2H5HCH3ClHClC2H5(i)(ii)(iii)(iv)StereoisomerDiastereomer 5.4.1 Epimer 5.4.2 Pseudoasymmetric carbon 5.4.1 Epimer 差向異構(gòu)體差向異構(gòu)體EpimerHCOOHOHHClHCOOHHOClHClHC2H5ClHC2H5如果兩個(gè)光學(xué)異構(gòu)體僅有一個(gè)不對(duì)稱(chēng)碳原子的構(gòu)型相反，其它不對(duì)稱(chēng)碳原子的構(gòu)型都相同，這兩個(gè)光活異構(gòu)體則互

22、為差向異構(gòu)體。 5.4.2 Pseudoasymmetric carbon 假不對(duì)稱(chēng)碳原子假不對(duì)稱(chēng)碳原子COOHCHOHCHOHCHOHCOOH有幾個(gè)不對(duì)稱(chēng)碳原子？*？是否不對(duì)稱(chēng)碳是否不對(duì)稱(chēng)碳取決于取決于2C和和4C的構(gòu)型的構(gòu)型COOHOHHOHHOHHCOOHCOOHHOHHOHHOHCOOHCOOHHOHOHHHOHCOOHCOOHOHHHOHOHHCOOHCOOHHOHOHHOHHCOOHCOOHOHHHOHHOHCOOHCOOHHOHHOHOHHCOOHCOOHOHHOHHHOHCOOHmesomesoThe third carbons of these four isomers ar

23、e asymmetric.COOHOHHOHHHOHCOOH共四個(gè)異構(gòu)體：共四個(gè)異構(gòu)體：COOHHOHHOHOHHCOOHRRSSCOOHOHHOHHOHHCOOHCOOHOHHHOHOHHCOOHRSRS33333C 為非不對(duì)稱(chēng)碳為非不對(duì)稱(chēng)碳均有旋光性均有旋光性互為對(duì)映異構(gòu)體互為對(duì)映異構(gòu)體3C 為不對(duì)稱(chēng)碳為不對(duì)稱(chēng)碳均無(wú)旋光性均無(wú)旋光性為內(nèi)消旋體為內(nèi)消旋體互為非對(duì)映異構(gòu)體互為非對(duì)映異構(gòu)體假不對(duì)稱(chēng)碳假不對(duì)稱(chēng)碳COOHOHHOHHHOHCOOH(R)(R)COOHHOHHOHOHHCOOH(S)(S)(i)(ii)Optical StereomerC3 is symmetricCOOHOHHOHH

24、OHHCOOH(R)(S)COOHOHHHOHOHHCOOH(R)(S)(iii)(iv)(r)(s)Not optical MesoC3 is asymmetric 5.5.1 Cyclopropane, cyclobutane, and cyclopentane 5.5.2 derivatives of Cyclohexane關(guān)鍵：平面分析 構(gòu)象分析 5.5.1 Cyclopropane, cyclobutane, and cyclopentane1, CyclopropaneAAAAAAATrans-Cis-ABBAABBACis-Trans-AAAAAA2, Cyclobutane3,

25、 CyclopentaneLearn on your own5.5.2 Derivatives of Cyclohexane順順-1,2-二取代二取代平面分析：平面分析：構(gòu)象分析：構(gòu)象分析：Rotation Conformation transition (i)(i)(i)(i)Rotation Conformation transition (ii)aa(ii)ee(iii)eeConformation transition (iii)aa(iv)(iv)(v)(v)(vi)(vi)結(jié)論：就環(huán)己烷而言，平面分析與構(gòu)象分析的結(jié)論相同。 5.6.1 Allene type compounds 5

26、.6.2 Diphenyl compounds 5.6.3 Spiro compounds 5.6.2 Compounds with stereocenters other than carbon 5.6.1 Allene type compoundsC C CabdcCCCabdcCCCCH3CH3HH如果任何一端或兩端的碳原子上連有相同取代基，則分子中存在如果任何一端或兩端的碳原子上連有相同取代基，則分子中存在對(duì)稱(chēng)面，該分子無(wú)手性。對(duì)稱(chēng)面，該分子無(wú)手性。CCCDCAACCCAAAACCCBBAA反之，則該分子有手性。反之，則該分子有手性。CCCDCABCCCDCAB5.6.2 Diphen

27、yl 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.ABBA 5.6.3 Spiro compounds5.6.2 Compounds with stereocenters other than carbonPabcPabcAlso, 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-activities5.7.1 Measure of polarity (Learn on your own)D25 = 100/(cl) 5.7.2 Reslution of racemic compounds 1, Chemical methods50% D-Acid50