Organic chemistry
This presentation is the property of its rightful owner.
Sponsored Links
1 / 112

By junru wang PowerPoint PPT Presentation


  • 113 Views
  • Uploaded on
  • Presentation posted in: General

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

Download Presentation

By junru wang

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


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

  • 六、光活性混合物的拆分方法


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


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

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


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

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

Cl

Br

H

F


Bromochlorofluoromethane is chiral

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

Cl

Cl

Br

Br

H

H

F

F


Bromochlorofluoromethane is chiral

Cl

Br

Cl

Br

H

H

F

F


Another look


Enantiomers

are enantiomers with respect to each other

nonsuperposable mirror images are called enantiomers

and


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


Chlorodifluoromethaneis achiral


Chlorodifluoromethaneis achiral

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


w

x

y

C

z

The Stereogenic Center

a carbon atom with fourdifferent groups attached to it

also called:

chiral centerasymmetric centerstereocenter


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


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


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


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


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;


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

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


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.


2、对称中心

对称中心


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 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.


对称中心

反映对称性: Sn,n1; S1= ; S2=i


3、对称轴

对称轴


4、更替对称轴


C

Chirality and stereogenic centers

A molecule with a single stereogenic center is chiral.

Bromochlorofluoromethane is an example.

H

F

Cl

Br


C

Chirality and stereogenic centers

A molecule with a single stereogenic center is chiral.

2-Butanol is another example.

H

CH3

CH2CH3

OH


CH3

CH2CH2CH2CH3

CH3CH2CH2

C

CH2CH3

Examples of molecules with 1 stereogenic center

a chiral alkane


OH

Examples of molecules with 1 stereogenic center

Linalool, a naturally occurring chiral alcohol


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


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


H

CH3

D

C

T

Examples of molecules with 1 stereogenic center

Chiral as a result of isotopic substitution


二、构型标记Relative and Absolute Configuration

  • 相对构型

  • 绝对构型


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、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


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:


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


绝对构型(Absolute Conformation)

IUPAC(1970) R、S构型系统命名法:

a>b>c>d


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


1

1

4

3

3

4

2

2

Example

Order of decreasing rank:4>3> 2

anticlockwise

clockwise

R

S


H

H

CH2CH3

CH3CH2

C

HO

C

OH

CH3

H3C

Enantiomers of 2-butanol

(S)-2-Butanol

(R)-2-Butanol


H3C

H

R

H

H

Stereogenic center in a ring

—CH2C=C > —CH2CH2 > —CH3 > —H


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


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.


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


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°


CO2H

OH

H

H

OH

CH3

Fischer projections


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°


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 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

nonsuperposable mirror images; enantiomers

S

S

R

R

cis-1-Bromo-1-chlorocyclopropane


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


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.


chiral

R

R

S

S


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.


CH3CHCHCH3

HO

OH

2,3-Butanediol

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

3

2


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-butanediol

meso form

these two areenantiomers

2R,3R

2S,3S

2R,3S

chiral

chiral

achiral


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


O

HOCH2CH—CH—CH—CHCH

OH

OH

OH

OH

Example

4 stereogenic centers

16 stereoisomers


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?

  • 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 stereoisomers?

3-戊烯-2-醇

R

E

E

S

OH

H

H

HO

R

Z

Z

S

OH

H

H

HO


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


二、单键旋转受阻的化合物

手性轴

三、把手化合物(Ansa – compounds)


四、含其他手性原子的化合物

胺 季胺盐 五价磷化合物 锍盐


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


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

  • 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)


 表 酒石酸的物理性质 


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

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

Nicol prism


Rotation of plane-polarized light

a


Optical Activity

  • Rotation of plane-polarized light

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


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)


产生旋光的原因

两种圆偏振光


 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%)


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


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


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 Significance of Chirality


Biological Significance of Chirality


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.


一、加成反应中的立体化学


立体专一反应(stereospecific reaction)


O

H

CH3COOH

CH3CH

H3C

CH2

C

CH2

O

Example

Chiral, but racemic

Achiral


epoxidation from this direction gives R epoxide

50%

R

S

50%

epoxidation from this direction gives S epoxide


CH3CH

CH3CH

CHCH3

CH2

Example

Chiral, but racemic(外消旋体)

HBr

CH3CHCH2CH3

Br

Br2, H2O

CH3CHCH2Br

OH

Achiral


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


Qs & As


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


H

H

CH3(CH2)5

C

HO

Br

C

CH3

CH3

Stereospecific Reaction

(CH2)5CH3

NaOH

(S)-(+)-2-Bromooctane

(R)-(–)-2-Octanol


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.

+


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%)


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:


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

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


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


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


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


预习下一章

  • 卤代烃


  • Login