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Organic chemistry 生物学科 有机化学教学多媒体课件 2006.02. By junru wang. 作业 :. P151: 1 : (2,3,4,6) 3: (3,4) 4: (3,4). 第 4 章 立 体 化 学. Stereochemistry. 胰岛素. 第四章 Stereochemistry 重点讲授内容. 一、分子手性与旋光性 Molecular Chirality:Enantiomers 二、对称性、手性、手性碳与构型标记 三、不含手性碳的旋光活性分子 四、光活性物质的物性与旋光性的测定 五、反应中的立体化学

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By junru wang

Organic chemistry

生物学科

有机化学教学多媒体课件

2006.02

By junru wang


By junru wang

作业:

  • P151:

    • 1: (2,3,4,6)

    • 3: (3,4)

    • 4: (3,4)


By junru wang

第4章 立 体 化 学

Stereochemistry


By junru wang

胰岛素


Stereochemistry

第四章 Stereochemistry重点讲授内容

  • 一、分子手性与旋光性

    Molecular Chirality:Enantiomers

  • 二、对称性、手性、手性碳与构型标记

  • 三、不含手性碳的旋光活性分子

  • 四、光活性物质的物性与旋光性的测定

  • 五、反应中的立体化学

  • 六、光活性混合物的拆分方法


Molecular chirality enantiomers

第一节 分子手性与旋光性Molecular Chirality: Enantiomers


Molecular chirality enantiomers1

第一节 分子手性与旋光性Molecular Chirality: Enantiomers


The ancient egyptians had less care for the chirality of hands

The ancient Egyptians had less care for the chirality of hands

Pharaohs, with two left hands or two right hands—they just didn’t seem to notice.


Chirality

Chirality

A molecule is chiralif its two mirror image forms are notsuperposable upon one another.

A molecule is achiral if its two mirror image forms are superposable.


Bromochlorofluoromethane is chiral

Bromochlorofluoromethane is chiral

It cannot be superposed point for point on its mirror image.

Cl

Br

H

F


Bromochlorofluoromethane is chiral1

Bromochlorofluoromethane is chiral

To show nonsuperposability, rotate this model 180° around a vertical axis.

Cl

Cl

Br

Br

H

H

F

F


Bromochlorofluoromethane is chiral2

Bromochlorofluoromethane is chiral

Cl

Br

Cl

Br

H

H

F

F


Another look

Another look


Enantiomers

Enantiomers

are enantiomers with respect to each other

nonsuperposable mirror images are called enantiomers

and


By junru wang

碳架异构

位置异构

构造异构

官能团异构

(互变异构)

同分异构

构象异构

顺反异构

立体异构

构型异构

对映异构

旋光异构

对映异构:分子式、构造式相同、构型互呈镜像对映关系的立体异构现象


Chlorodifluoromethane is achiral

Chlorodifluoromethaneis achiral


Chlorodifluoromethane is achiral1

Chlorodifluoromethaneis achiral

The two structures are mirror images, but are not enantiomers, because they can be superposed on each other.


The stereogenic center

w

x

y

C

z

The Stereogenic Center

a carbon atom with fourdifferent groups attached to it

also called:

chiral centerasymmetric centerstereocenter


By junru wang

第二节 对称性、手性、手性碳与构型标记

  • 对称性与手性

  • 手性碳与分子手性

  • 手性、对称性与旋光性

  • 构型标记

    • 绝对构型

    • 相对构型


By junru wang

一、旋光性与分子结构的关系

  • 凡是可具有结构不对称性(无反映对称性)的分子都具有旋光性;最常见的旋光活性物质是含有手性碳的化合物。

  • 对称因素:对称面();对称中心(i)

  • 对称性、不对称性与手性:

    凡是具有反映对称性的分子称为非手性分子

    凡是没有反映对称性的分子称为手性分子

  • 不对称性:找不到任何一个对称因素的分子

  • 手性是不对称性之一种

  • 反映对称性———对称分子———无旋光性


By junru wang

一、旋光性与分子结构的关系

  • 对称性与手性:

    有对称性的分子一定是非手性分子

    有手性的分子一定具有非反映应对称性

  • 手性碳与手性分子二者关系

    有手性碳的分子不一定就是手性分子

    手性分子并不一定就含有手性碳

    只有一个手性碳的分子一定就是手性分子


By junru wang

一、旋光性与分子结构的关系

  • 手性碳与手性分子二者关系

    手性分子并不一定就含有手性碳

右手螺旋 左手螺旋


By junru wang

一、旋光性与分子结构的关系

  • 手性、对称性与旋光性

    (1)有反应对称性的分子:物象重合,不具有旋光性,是非手性分子

    (2)无对称性的分子:物象不重合,有旋光性,是手性分子

  • 构型与旋光性

    分子结构的不对称性导致,物象不重合;二者主要差异在于构型不同;


By junru wang

对称因素

手性(chirality):物质的分子与其镜像不能重合的性质,是产生旋光性的充分和必要条件。

1、对称面(Mirror)

反映对称性: Sn,n1; S1= ; S2=i


Plane of symmetry

Plane of symmetry

A plane of symmetry bisects a molecule into two mirror image halves. Chlorodifluoromethane has a plane of symmetry.


Plane of symmetry1

Plane of symmetry

A plane of symmetry bisects a molecule into two mirror image halves.1-Bromo-1-chloro-2-fluoroethene has a planeof symmetry.


By junru wang

2、对称中心

对称中心


Center of symmetry

Center of symmetry

A point in the center of themolecule is a center of symmetry if a line drawn from it to some element, when extended an equal distance in the opposite direction, encounters an identical element.


Center of symmetry1

Center of symmetry

A point in the center of themolecule is a center of symmetry if a line drawn from it to any element, when extended an equal distance in the opposite direction, encounters an identical element.


By junru wang

对称中心

反映对称性: Sn,n1; S1= ; S2=i


By junru wang

3、对称轴

对称轴


By junru wang

4、更替对称轴


Chirality and stereogenic centers

C

Chirality and stereogenic centers

A molecule with a single stereogenic center is chiral.

Bromochlorofluoromethane is an example.

H

F

Cl

Br


By junru wang

C

Chirality and stereogenic centers

A molecule with a single stereogenic center is chiral.

2-Butanol is another example.

H

CH3

CH2CH3

OH


Examples of molecules with 1 stereogenic center

CH3

CH2CH2CH2CH3

CH3CH2CH2

C

CH2CH3

Examples of molecules with 1 stereogenic center

a chiral alkane


Examples of molecules with 1 stereogenic center1

OH

Examples of molecules with 1 stereogenic center

Linalool, a naturally occurring chiral alcohol


Examples of molecules with 1 stereogenic center2

H2C

CHCH3

O

Examples of molecules with 1 stereogenic center

attached to the stereogenic center are:

—H

—CH3

—OCH2

—CH2O

1,2-Epoxypropane: a stereogenic center

can be part of a ring


Examples of molecules with 1 stereogenic center3

CH3

H

C

CH2

CH3

Examples of molecules with 1 stereogenic center

attached to thestereogenic center are:

—H

—CH2CH2

—CH2CH=

—C=

Limonene: a stereogenic center can be part of a ring


Examples of molecules with 1 stereogenic center4

H

CH3

D

C

T

Examples of molecules with 1 stereogenic center

Chiral as a result of isotopic substitution


Relative and absolute configuration

二、构型标记Relative and Absolute Configuration

  • 相对构型

  • 绝对构型


Configuration

Configuration

  • 相对构型

  • Relative configurationcompares the arrangement of atoms in space of one compound with those of another.

  • until the 1950s, all configurations were relative

  • 绝对构型

  • Absolute configuration is the precise arrangement of atoms in space.

  • now we can determine the absolute configuration of almost any compound


1 d l

1、相对构型标记D/L

CHO

CHO

(+)-甘油醛 (-)-甘油醛

D L

D -(+)-甘油醛 L-(-)-甘油醛

常用来确定糖、氨基酸等构型

H

OH

HO

H

CH2OH

CH2OH


By junru wang

D -(+)- 甘油醛 L -(+)- 甘油醛

D-(+)-甘油醛 D-(-)-甘油酸 D-(-)-乳酸

相对构型(Relative Conformation)

化学关联法:


By junru wang

R -(+)- 甘油醛 S -(+)- 甘油醛

2、绝对构型的标记

  • 1970 IUPAC R/S 标记任何一个手性碳(或手性分子)

  • 明确与手性碳相连的4个不同基团的优先次序

  • 用手模型法或透视法判断其构型

Which is which?

E. Fisher 1891;

1954 x-ray证实


By junru wang

绝对构型(Absolute Conformation)

IUPAC(1970) R、S构型系统命名法:

a>b>c>d


Example

1

1

4

3

3

4

2

2

Example

2.1 含一个手性碳的化合物

Order of decreasing rank:4 > 3 > 2 > 1


Example1

1

1

4

3

3

4

2

2

Example

Order of decreasing rank:4>3> 2

anticlockwise

clockwise

R

S


Enantiomers of 2 butanol

H

H

CH2CH3

CH3CH2

C

HO

C

OH

CH3

H3C

Enantiomers of 2-butanol

(S)-2-Butanol

(R)-2-Butanol


Stereogenic center in a ring

H3C

H

R

H

H

Stereogenic center in a ring

—CH2C=C > —CH2CH2 > —CH3 > —H


Rules for fischer projections

Rules for Fischer projections

H

Arrange the molecule so that horizontal bonds at stereogenic center point toward you and vertical bonds point away from you.

H

Cl

Br

Cl

Br

F

F


Chiral drugs

H

H3C

CH2CH(CH3)2

C

C

HO

O

Chiral drugs

Ibuprofen is chiral, but normally sold asa racemic mixture. The S enantiomer is the one responsible for its analgesic and antiinflammatory properties.


By junru wang

2.2 含2个手性碳(中心)的化合物

2,3-Dihydroxybutanoic acid

O

3

2

CH3CHCHCOH

HO

OH

What are all the possible R and S combinations of the two stereogenic centers in this molecule?

Carbon-2RRSS

Carbon-3RSRS

4 Combinations = 4 Stereoisomers

enantiomers:2R,3R and 2S,3S

2R,3S and 2S,3R


By junru wang

CO2H

CO2H

R

S

HO

OH

H

H

OH

HO

H

H

R

S

CH3

CH3

CO2H

CO2H

S

R

OH

HO

H

H

OH

H

HO

H

R

S

CH3

CH3

[a] = -9.5°

[a] = +9.5°

enantiomers

diastereomers

enantiomers

[a] = +17.8°

[a] = -17.8°


By junru wang

CO2H

OH

H

H

OH

CH3

Fischer projections


Erythro

CO2H

OH

H

H

OH

CH3

Erythro(赤式)

when carbon chain is vertical, same (or analogous) substituents on same side of Fischer projection

CO2H

H

HO

HO

H

CH3

–9.5°

+9.5°


Threo

CO2H

CO2H

OH

H

H

HO

HO

H

OH

H

CH3

CH3

Threo(苏式)

when carbon chain is vertical, same (or analogous) substituents on opposite sides of Fischer projection

+17.8°

–17.8°


2 3 two stereogenic centers in a ring

2.3 环上含手性碳的化合物Two stereogenic centers in a ring

nonsuperposable mirror images; enantiomers

R

S

R

S

trans-1-Bromo-1-chlorocyclopropane


Two stereogenic centers in a ring

Two stereogenic centers in a ring

nonsuperposable mirror images; enantiomers

S

S

R

R

cis-1-Bromo-1-chlorocyclopropane


Two stereogenic centers in a ring1

Two stereogenic centers in a ring

stereoisomers that are notenantiomers; diastereomers

S

S

R

S

cis-1-Bromo-1-chloro-cyclopropane

trans-1-Bromo-1-chloro-cyclopropane


Cyclic compounds

chiral

R

R

Cyclic compounds

meso

S

R

There are three stereoisomers of 1,2-dichloro-cyclopropane; the achiral (meso) cis isomer and two enantiomers of the trans isomer.


By junru wang

chiral

R

R

S

S


2 4 achiral molecules with two stereogenic centers 2

2.4 Achiral Molecules withTwo Stereogenic Centers(有2个手性中心的非手性分子)

It is possible for a molecule to have stereogenic centers yet be achiral.


2 3 butanediol

CH3CHCHCH3

HO

OH

2,3-Butanediol

Consider a molecule with two equivalently substituted stereogenic centers such as 2,3-butanediol.

3

2


Three stereoisomers of 2 3 butanediol

CH3

CH3

CH3

H

HO

OH

OH

H

H

HO

OH

H

OH

H

H

CH3

CH3

CH3

Three stereoisomers of 2,3-butanediol

2R,3R

2S,3S

2R,3S

chiral

chiral

achiral


Three stereoisomers of 2 3 butanediol1

Three stereoisomers of 2,3-butanediol

meso form

these two areenantiomers

2R,3R

2S,3S

2R,3S

chiral

chiral

achiral


Three stereoisomers of 2 3 butanediol2

CH3

CH3

CH3

H

HO

OH

OH

H

H

HO

OH

H

OH

H

H

CH3

CH3

CH3

Three stereoisomers of 2,3-butanediol

these two areenantiomers

2R,3R

2S,3S

2R,3S

chiral

chiral

achiral


Example2

O

HOCH2CH—CH—CH—CHCH

OH

OH

OH

OH

Example

4 stereogenic centers

16 stereoisomers


Cholic acid

CH3

HO

H

CH3

CH2CH2CO2H

H

H3C

H

H

OH

HO

H

Cholic acid

11 stereogenic centers

211 = 2048 stereoisomers

one is "natural" cholic acid

a second is the enantiomer of natural cholic acid

2046 are diastereomers of cholic acid


How many stereoisomers

How many stereoisomers?

  • maximum number of stereoisomers = 2n

  • where n = number of structural units capable of stereochemical variation

  • structural units include stereogenic centers and cis and/or trans double bonds

  • number is reduced to less than 2n if meso forms are possible


How many stereoisomers1

How many stereoisomers?

3-戊烯-2-醇

R

E

E

S

OH

H

H

HO

R

Z

Z

S

OH

H

H

HO


By junru wang

2、3 - 戊二烯的对映异构体

手性轴

第三节 不含手性碳原子化合物的对映异构体

一、丙二烯型化合物


By junru wang

二、单键旋转受阻的化合物

手性轴

三、把手化合物(Ansa – compounds)


By junru wang

四、含其他手性原子的化合物

胺 季胺盐 五价磷化合物 锍盐


By junru wang

第四节 光活性物质的性质与旋光性的测定

旋光异构体的物性比较

旋光性的测定


By junru wang

表 2-甲基-1-丁醇对映体物理性质比较 

一般条件下,对映体性质完全相同

差别:1、对平面偏振光的旋转方向不同2、在手性环境中的反应速度不同


Properties of enantiomers

Properties of Enantiomers

  • Same Bp, Mp, density

  • Same refractive index

  • Different direction of rotation in polarimeter

  • Different interaction with other chiral molecules

    • Enzymes

    • Taste buds(味蕾), scent(香气)


By junru wang

 表 酒石酸的物理性质 


History

History

  • 1848 巴黎师范大学 Lewis Pasteur

  • 化学成绩中等

  • Besanson皇家学院

  • 重复结晶学实验

  • 280C以下结晶, 酒石酸钠按


Polarized light

Polarized light

ordinary (nonpolarized) light consists of many beams vibrating in different planes

plane-polarized light consists of only those beams that vibrate in the same plane


Polarization of light

Polarization of light

Nicol prism


Rotation of plane polarized light

Rotation of plane-polarized light

a


Optical activity

Optical Activity

  • Rotation of plane-polarized light

  • Enantiomers rotate light in opposite directions, but same number of degrees.


Polarimetry

Polarimetry

  • Use monochromatic light, usually sodium D

  • Movable polarizing filter to measure angle

  • Clockwise = dextrorotatory = d or (+)

  • Counterclockwise = levorotatory = l or (-)

  • Not related to (R) and (S)


By junru wang

产生旋光的原因

两种圆偏振光


By junru wang

 t :温度  :光源波长 L:样品管长度 C:样品浓度  :旋光度

[ ]t =

L(dm) ×C(g/ml)

比旋光度(Specific Rotation)

右旋酒石酸的比旋光度为:[  ]D = +3.79 °(乙醇,5%)


By junru wang

旋光性的测定

  • 左旋和右旋 ( - ) and ( + ) ( laevorotatory and dextrorotatory )

  • 比旋光度 ( specific rotation)

  • [α]tD= α/ ( c ╳ l)

  • 钠光D:5893A

  • 影响α的因素:溶剂;温度;C;l;;[α];

  • 外消旋体 ---- 一对对映异构体的等量混合物 Racemic mixture, racemate


By junru wang

有旋光性的化合物一定能测出旋光度吗?

CH2CH3

  • 1965 制出两个纯品

  • 无旋光度

  • 0.0000010

CH3(CH2)5

(CH2)3CH3

CH2CH2CH3


By junru wang

第五节 反应中的立体化学与手性化合物制备

反应中的立体化学

加成反应

亲核取代

消除反应

手性化合物制备


Biological discrimination

Biological Discrimination


Biological significance of chirality

Biological Significance of Chirality


Biological significance of chirality1

Biological Significance of Chirality


Many reactions convert achiral reactants to chiral products

Many reactions convert achiral reactants to chiral products.

  • It is important to recognize, however, that if all of the components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture.

  • more simply stated as "Optically inactive starting materials can't give optically active products."

  • Remember: In order for a substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the other.


By junru wang

一、加成反应中的立体化学


By junru wang

立体专一反应(stereospecific reaction)


Example3

O

H

CH3COOH

CH3CH

H3C

CH2

C

CH2

O

Example

Chiral, but racemic

Achiral


By junru wang

epoxidation from this direction gives R epoxide

50%

R

S

50%

epoxidation from this direction gives S epoxide


Example4

CH3CH

CH3CH

CHCH3

CH2

Example

Chiral, but racemic(外消旋体)

HBr

CH3CHCH2CH3

Br

Br2, H2O

CH3CHCH2Br

OH

Achiral


By junru wang

加成反应中立体化学规律

  • (1)顺式加成:B2H6;H2/Pd;冷稀的KMnO4;

    • 顺式烯烃—内消旋化合物

    • 反式烯烃---外消旋混合物

  • (2)反式加成: Br2;HOX;HX;H2SO4

    • 顺式烯烃—外消旋混合物

    • 反式烯烃---内消旋化合物


By junru wang

Qs & As


By junru wang

二、亲核取代中的立体化学

  • SN2: 构形反转

  • SN1: 外消旋化(构型反转/构型保持)

SN2

three-dimensionalarrangement of bonds inproduct is opposite to that of reactant

nucleophile attacks carbonfrom side opposite bondto the leaving group


Stereospecific reaction

H

H

CH3(CH2)5

C

HO

Br

C

CH3

CH3

Stereospecific Reaction

(CH2)5CH3

NaOH

(S)-(+)-2-Bromooctane

(R)-(–)-2-Octanol


By junru wang

rearrangementsare possible.

More than 50%

Less than 50%

Ionization step gives carbocation; three bonds to stereogenic center become coplanar

Leaving group shields one face of carbocation; nucleophile attacks faster at opposite face.

+


Stereochemistry of an s n 1 reaction

H

CH3

Br

C

CH3(CH2)5

H

CH3

OH

C

CH3(CH2)5

Stereochemistry of an SN1 Reaction

R-(–)-2-Bromooctane

H

CH3

H2O

C

HO

(CH2)5CH3

(R)-(–)-2-Octanol (17%)

(S)-(+)-2-Octanol (83%)


By junru wang

三、消除反应之立体化学

  • E2:反式共平面消除

  • (1)反式共平面消除活化能最小

  • (2)C -C 逐渐形成P轨道最大重叠有利

X

C C

Y

B:


By junru wang

第六节 外消旋体的拆分

外消旋体

非外消旋体

(+)A (- )A

  • 拆分(Resolution): 外消旋体分离成旋光体的过程

  • 提供手性环境和条件,使对映异构体表现出不同性质而得以拆分

一、化学分离法

与光活胺成盐、或与光活醇成酯使之转化为物理性质不同的非对映异构体


Resolution of enantiomers

Resolution of Enantiomers

React a racemic mixture with a chiral compound to form diastereomers, which can be separated.


By junru wang

二、生物分离法

三、晶种结晶法

四、其他方法

手性色谱法,动力学拆分法,生成分子化合物法等。


Chromatographic resolution of enantiomers

Chromatographic Resolution of Enantiomers


By junru wang

手征性分子

旋光活性

含C*的分子

手征性分子

本章小结

分子中没有对称因素→手征性分子→产生立体异构现象→异构体能使偏振光的振动平面发生旋转→旋光异构现象

旋光异构现象

手征性和

旋光异构

表示方法

透视式和投影式

命名(标记)

相对构型——D/L命名法

绝对构型——R/S命名法

旋光异构体

表示方法和命名


By junru wang

含一个C*的化合物

含两个不相同C*的化合物

含两个相同C*的化合物

环状化合物

各 论

对映异构体 手性条件下性质不同,非手性条件下性质相同。

非对映异构体 物理性质不同,化学性质基本相同,但在同一反应中,反应速率不同。

旋光异构体性质


By junru wang

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