台灣大學開放式課程 有機化學乙 蔡蘊明教授 本著作除另有註明, 作者皆為蔡蘊明教授, 所有內容皆採用創用 CC 姓名標示 - 非商業使用 - 相同方式分享 3.0 台灣授權條款釋出

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1 台灣大學開放式課程 有機化學乙 蔡蘊明教授 本著作除另有註明, 作者皆為蔡蘊明教授, 所有內容皆採用創用 姓名標示 - 非商業使用 - 相同方式分享 3.0 台灣授權條款釋出

2 hapter S Stereochemistry ( 立體化學 ): chiral molecules ( 掌性分子 ) Isomerism constitutional isomers butane isobutane 分子式相同但鍵結方式不同 stereoisomers ( 立體異構物 ) l l l l cis-1,2-dichloroethene trans-1,2-dichloroethene 分子式相同, 鍵結方式相同, 但是在空間中的安排方式不同

3 鏡像與掌性 (chirality)

4 Enantiomers ( 鏡像異構物 ; 對掌體 ) O 2-butanol 此分子具有掌性 (this molecule is chiral) 3 O 3 O Two mirror images not superposable The two mirror images are enantiomers ( 鏡像異構物 ; 對掌異構物 )

5 hiral molecule A molecule that is not superposable ( 重疊 ) on its mirror image is called a chiral molecule 反之則稱為 achiral Enantiomers are differed by the arrangement of the groups in space Enantiomers are stereoisomers

6 Stereoisomers that are not enantiomers Diastereomers ( 非鏡像異構 ) l l l l cis-1,2-dichloroethene trans-1,2-dichloroethene diastereomers stereoisomers enantiomers diastereomers

7 Q: 3 3 O 2-propanol hiral? 3 O 3 O 3 3 superposable same molecule achiral

8 In fact, 2-propanol has a plane of symmetry must be achiral the plane containing --O

9 Why is 2-butanol chiral? The presence of a tetrahedral carbon with four different groups attached 3 O * 2 the presence of a stereocenter or a chiral center (chirality center) or a stereogenic center or an asymmetric center chiral center, 常用星號標記 3 with one stereocenter must be chiral with more than one stereocenter may not be chiral with no chiral center may be chiral

10 Problem for practice: 3 3 Is there any chiral center? Is it chiral?

11 Nomenclature of enantiomers ahn-ingold-prelog system (R,S-system): <1> Priority of the four groups on chiral center 先比第一個接在 chiral center 上的原子序數原子序高者 priority 高 ( 同位素質量高者優先 ) 3 O 2 3 four atoms: O,,, lowest highest

12 第一個原子相同時, 比其上 priority 高者依此原則一直比到分出高下 3 O (,,) (,,) 2 3 winner priority: 1 O

13 <2> O priority 最低者反對觀察者 <3> 3 Me O 1 Et 2 priority clockwise: (R) counterclockwise: (S) O (R)-2-butanol

14 <4> Multiple bonds Y Y 視為 視為 Y Y Y Y Y 例 2 ( 3 ) 2 (,,) (,,) 3 3 (,,) (,,) higher priority

15 Practice: 3 3 l l (R) (R) must be the same molecule

16 Properties of enantiomers Most properties are the same: bp, mp, density. (unless in a chiral environment) The most distinct property: they rotate plane-polarized light ( 平面偏極光 ) in opposite direction they are optically active they are optical isomers ( 光學異構物 )

17 Plane-polarized light? Ordinary light 由無數個平面光所組成 end on view: 光是一種電磁波, 每一平面光亦可拆解為相互垂直的電波和磁波 E B light propagation 當光通過某些被稱為 polarizer 的物質時, 光會與之作用而只有一平面光通過, 此一平面光就被稱為平面偏極光 (plane-polarized light)

18 平面偏極光在通過由單一對掌體所構成的溶液時, 會與之作用而產生電波和磁波的相位差 (phase difference) E B light propagation end on view: Rotation occurs 順時針旋轉 dextrorotatory or d or (+) 逆時針旋轉 levorotatory or l or ( )

19 Polarimeter ( 偏光儀 ) sodium D line (5890 Ǻ) 最亮 最暗 方向相同 方向相垂直光無法通過

20 Specific rotation ( 比旋光度 ) [α] t D = α c x l observed rotation specific rotation cell length in dm ( 公寸 ) concentration in g/ml Problem: 若測得 +90 o 怎知不是 270 o? Solution: 將濃度減半 +90 o +45 o 270 o 135 o 可區別了 Usually requires to measure at two different conc.

21 3 O 3 O [α] 25 D = 13.52o [α] 25 D = o (R)-( )-2-butanol (S)-(+)-2-butanol 互為鏡像, 旋光方向相反, 幅度相同 (R), (S) 為命名, 人為決定 (+), ( ) 為性質, 無法預測 二者無關

22 The origin of optical activity For achiral compound: 3 O 3 3 O 3 no net rotation Mirror images: must present Rotate light in opposite direction

23 For a mixture of 50% d form, 50% l form (+)-2-butanol Me O Et (S) a racemic mixture ( 外消旋 ) or a racemate or a racemic modification Me Et O (R) mirror images must present in this orientation in equal amount by probability no net rotation If only (S)-form present: Me O Et Mirror image does not exist, rotation can not be cancelled net rotation observed

24 Optical purity or enantiomeric purity Only one enantiomer present: optically pure or enantiomerically pure or enantiopure Estimation of optical purity: enantiomeric excess (ee) 鏡像超越值 % ee = moles of one enant. - moles of the other moles of both 100 = observed rotation specific rotation 100

25 例 A sample of 2-butanol: [α] = o optical purity = = 50% This mixture consists of 75% (+)-form, 25% ( )-form % ee = 50

26 Fischer projection formulas 直的代表凹入紙面 Me O Me O Et Et 橫的代表凸出紙面 (R) Fischer projection formula 使用規則 : <1> 不可翻面 Me O O Me Et Et (R) (S)

27 <2> 不可轉 90 o Me Me O Et Et O (R) (S) <3> 可以轉 180 o Et Me O O Me Et (R) (R) 例 Me O O Me Et Et (R) (S)

28 With more than one chiral center * * ,3-dibromopentane Two chiral centers: in principle 2 2 = 4 isomers enantiomers diastereomers 3 3 (stereoisomers but not enantiomers) *Diastereomers exhibit completely different properties

29 * * 3 3 2,3-dibromobutane enantiomers In fact: 3 same molecule A plane of symmetry exists Must be achiral 3 A compound with more than one chiral center but is achiral A meso compound ( 內消旋化合物 )

30 2,3-Dibromobutane with 2 chiral centers has only 3 stereoisomers ompound with n chiral centers should have 2 n possible stereoisomers

31 命名 3 (2R,3R)-2,3-dibromobutane 3 3 (2S,3S)-2,3-dibromobutane 3 3 meso-2,3-dibromobutane 3

32 yclic compounds trans-1,2-dimethylcyclopentane Me Me Me Me enantiomers (2R,3R) (2S,3S) cis-1,2-dimethylcyclopentane has a plane of symmetry 3 3 meso

33 1,4-Dimethylcyclohexane as a plane of symmetry achiral trans cis (there is no chiral center: not meso) Note: 沒有 chiral center 並不一定為 achiral 例 enantiomeric but with no chiral center

34 1,3-Dimethylcyclohexane cis achiral and meso trans a pair of enantiomers

35 1,2-Dimethylcyclohexane cis flipping A simple view: quickly interconverting (each conformer is chiral if fixed) achiral and meso

36 1,2-Dimethylcyclohexane trans (S,S) (R,R)

37 Separation of enantiomers: resolution ( 拆分 ) <1> By hands 1848 Pasteur O 2 Na O O O 2 Na separate O 2 Na O O O two kinds of crystals O O 2 N 4 O 2 N 4 O 2 N 4 a racemate of sodium ammonium salt of (±)-tartaric acid ( 酒石酸 ) Rotation exists even when crystals dissolved O (+) O 2 Na O O 2 N 4 ( )

38 <2> By conversion to diasteromers (R,S)-A + (R)-B (R)-A (R)-B + (S)-A (R)-B diastereomers separable by usual means resolved (R)-A + (R)-B (S)-A + (R)-B

39 Absolute configuration 絕對構造 Q: ow do we know the absolute configuration? Before 1951: only relative configurations are known 相對構造 onfigurations are correlated with each other through chemical methods (chemical correlation) 例 Me 2 O Me 2 l + l + 2 O Et Et No bond at the chiral center is broken They have the same configuration (retention of configuration) The two structures are correlated Know one absolute structure, the other one will be known

40 Glyceraldehyde was chosen as a standard for correlation O O 2 O O O (+) ( ) arbitrarily assigned: (R) (S) 2 O Other compounds are correlated with glyceraldehyde 例 O O 2 O O O O 2 O O O O 2 N 2 (+)-glyceraldehyde ( )-glyceric acid (+)-isoserine O 3 O O ( )-lactic acid These compounds are correlated with (+)-glyceraldehyde

41 1951 Bijvoet X-ray diffraction: (+)-tartaric acid = O O 2 O O 2 O 2 O O O 2 (+)-tartaric acid correlation O O O 2 O ( )-lactic acid O O 2 O (+)-glyceraldehyde The arbitrary assignment was correct!!

42 Stereoceneters other than carbon R 2 R 1 R 4 R 1 R 2 Si R 4 R 3 R 3 R1 R 2 + N R 4 R 3 X a quaternary ammonium salt ( 四級銨鹽 ) R 2 R 1 S O a sulfoxide R 1 R 2 Invert quickly R 1 R 2 N N R 3 R 3 R 2 R1 Ge R 4 R 3

43 Biological importance Natural products usually contain multiple chiral centers and exist as one enantiomer O O progesterone ( 黃體激素 ) substrate Enzymes ( 酶 ) catalyze many biological reactions and only recognize one enantiomeric form of their substrates through a three-point binding enzyme does not fit