第三章立体化学

Chapter

3

Stereochemistry-EnantiomerismconformationaldiastereomersgeometricopticalStereoisomers立体异构1Constitutional

isomer构造异构构象异构configurational构型异构几何异构光学异构enantiomers对映异构非对映异构2Enantiomerisms (对映异构现象):3Thalidomide4Limonene

(柠檬油精)5Stereochemistry

LanguageSuperimposable

:

Be

indistinguishable

from

their

mirror

imagesNon-superimposable:

Be

distinguishable

from

their

mirrorimages

such

as

your

left

and

right

hands.Chiral:

has

a

non-superimposable

mirror

image

(Greek

="handedness")Achiral:

has

a

superimposable

mirror

imageEnantiomers:

A

pair

of

molecules

that

are

non-superimposablemirror

images

of

each

otherDiastereomers:

are

stereoisomers

that

are

not

enantiomersOptical

activityRacemate:

is

a

50:50

mixture

of

a

pair

of

enantiomers6一.对映异构现象(Enantiomerism):Enantiomerism:

左.右手的关系--手性对映异构体(enantiomers):如两个分子具有对映，而不能重叠的关系,为对映异构体。7What

chirality

means?Chirality(手性):有镜像关系而不能重叠的性质(Greek="handedness")Chiral

objects(手性物质)Achiral

objects(非手性物质)8What

chirality

means?SPIRAL

GALAXIES(漩涡星云)M51The

Whirlpool

Nebula9M83Southern

Pinwheel1.Chirality(手性):C不对称的IClHBrC1893年,England

L.

KelvinIHClBr手性分子(chiral

molecule)不重合CClHCH3CH3HCClCH3CH3非手性分子(achiral

molecule)重合mirror10Chiral and

Achiral

Molecule(手性和非手性分子)Achiral

Molecular

:

superimposable

mirror

image非手性分子与其镜像可以重叠What

chirality

means?11Chiral

Molecular

:

non-superimposable

mirror

image手性分子与其镜像不可以重叠What

chirality

means?Chiral and

Achiral

Molecule(手性和非手性分子)12What

chirality

means?有镜像关系而不能重叠PHYSICSCHEMISTRYBIOLOGY13What

chirality

means?Stereogenic

Centers

otherthan

Carbon:

Si,

N

and

P14Stereogenic

Centers

(手性中心)Stereogenic

carbon(手性碳原子):碳原子连接4个不同取代基2.Chiral

Center(手性中心):C*

XY许多含有手性中心的分子是手性的(例外:meso)许多手性分子含有手性中心(例外:联苯型,丙二烯型)\手性中心的存在与否不是唯一判断手性分子的标准15ZWWhat

chirality

means?Stereogenic

Centers

(手性中心)COOHHCH3OHPHCH3C2H5SOCH2PhPhOOCOOHStereogenic

faces(手性面)(CH2)8163.分子手性和对称因素:17分子本身的对称性对称面(s)对称中心(i)一个分子如具有对称面或对称中心则这个分子无手性---非手性分子(achiral

molecule)Achiral

molecule:有对称面、对称中心或对称轴Symmetry

factors(对称因素):What

chirality

means?18Meso:

possess

two

or

morechirality

cenenters,

achiralmolecularWhat

chirality

means?19COOHNO2COOHNO2COOHNO2COOHNO2Enantiomers:

without

chirality

centers\手性中心的存在与否不是唯一判断手性分子的标准HCH3CH3HCH3HCH3HWhat

chirality

means?204.对映异构体(Enantiomers)镜像关系不重合e.g. (+)乳酸与(-)乳酸HCH3OHCOOHHOCH3HCOOH光学异构体数目2n

n:

手性

C*

的数目e.g. HOOC-CH(OH)-CHCl-CH321光学异构体 对映异构体 手

性

分

子A

mixture

consisting

of

equal

parts

of

any

pair

of

enantiomersracemic

mixture

(外消旋体)22Enantiomer

(对映异构体)相同的沸点、熔点、密度和溶解度不同的光学特性(Optical

Activity)与手性分子发生不同的反应23Enantiomer

Physical

Properties二.光学活性(Optical

Activity):手性分子能改变平面偏振光的振动方向,这种性质叫光学活性(旋光性).比旋光度(Specific

Rotation):测定方法---用旋光仪左旋(dextrorotatory)

(-)右旋(levorotatory)

(+)[a]

=

a

/

L·C24L:

dm C:

g/mlEnantiomer

Physical

Properties25Optical

Activity

(光学活性)对映异构体的旋光方向相反，而数值相同左旋

(levorotatory)

(-)

右旋

(dextrorotatory)(+)一个光学物质的旋光方向

与其构型没有必然的联系，同样构型的两种物质可以

有不同的旋光方向。26四.外消旋体(Racemic

Mixture):等量(+)和(-)的混合物用(–)or(dl)表示通过拆分(Resolution)的方法分离不能用蒸馏,重结晶的方法e.g.

酸奶中的乳酸HCH3OHCOOHHOCH3HCOOH27CH3HHClClCH3mesoHCH3CH3HClClCH3CH3HHClClracemate五.内消旋体(Meso

Compound):分子中有对称面---非手性分子(achiral

molecule)内消旋和外消旋有什么差别？内消旋是非手性分子外消旋是具有手性的两个对映异构体的等量混合物二者都无旋光性，但本质不同。28六.构型标记法:1.D,L标记法CHOHOCHOHH

OHCH2OHD-(+)-甘油醛CH2OHL-(-)-甘油醛不够完善,只用于糖类和氨基酸的构型标记.292.R,S构型标记法Cahn-Ingold-Prelog

提出30Rule

1:

原子序数。Cahn

–

Ingold

-Prelog31Rule

2:与手性碳相连的两个原子相同时-CH2(CH2)2CH3

>-CH2CH3

>-CH3

>-HCahn

–

Ingold

-PrelogRule

3:

Isotopes（同位素）

T>D>H.Rule

4:

双键和三键C=OC=COCCOHCHHCCC

CHC

CC

CC

CC

CH32C

CRule

5:

R

构型优先于S

构型，顺式

（Z)

优先于反式

(E)Expression

of

Enantiomers对映异构体的表示法Fischer

Projection：The

rules:中心33横向---向前纵向---向后Rules:1.

Not

remove

out

of

the

paper---180*n,

the

same

compounds----90*n,

the

enantiomersrotation

180°keeptheoriginalfigure

原化合物CH3HCOOHOHHCH3OHOHCOOHCH3COOHHThe

enantionmer

oftheoriginal对映体3435CH3HCOOHCH3HCOOHOHSOHS2.

将其中一个取代基位置不变，顺或逆转其它三个基团，得到的化合物，原有空间关系不变。Rules:36FischerSawhorseNewmannCHOOHHHHOCH2OHOHHCHOH

CH2OHHOHHOHOHOHCCH2OH37（1）手当模型：CH3HCOOHOHS

构型CH3（2）

HCOOHOH

固定，其它基团顺时针方向转OHS

构型（3）CH3HCOOHOHS

构型HCH3

COOHOH实际是S

构型COOHH

CH3OH平面是R

构型Determination

of

R,S

Methods3839Difference

of diastereomers

and

meso？内消旋是非手性分子;外消旋是具有手性的两个对映异构体的等量混合物。HCH3CH3HClClCH3CH3HClHClCH3HHClClCH3Meso内消旋Racemate外消旋Diastereomers and

Meso40非对映异构体和内消旋HHCH3

CH3HHCl

ClBr

BrCH3CH3ClHHBrCH3CH3ClHHBrCH3

CH3赤式（erythro):

同侧2-氯-3-溴丁烷苏式

(threo):

异侧2-氯-3-溴丁烷假手性碳：CH3CH3HHHClClClSRS(2S,3s,4R)-2,3,4-三氯戊烷With

two

chiral

carbons？41C2H5CH3HHOHClCH3C2H5HHOHClCH3C2H5HHOHClCH3C2H5HHOHCl构象异构体对映异构体非对映异构体？？Conformation and

Configuration:(构象异构和构型异构)42434445对映异构体的合成和化学：Formation

of

stereogenic

centers(手性中心的产生)：46非手性化合物外消旋体474849Resolution

of enantiomers(外消旋体的拆分):Rules：

Enantiomers

to

DiastereomersDiastereomers

之间physical

property

的差别Enantiomers

与手性化合物反应速度的不同501.

化学分离法:H+(+)-acidH+(-)-acid(±)-acid

+

(-)-baseRacemic无旋光有旋光(+)-acid-(-)-base’salt(diastereomers)(-)-acid-(-)-base’salt(m.p.,or

s.有差别)常用的生物碱:(-)-番木鳖碱,(-)-奎宁,(-)-马钱子碱,(+)-辛可宁Resolution

methods51522.

色谱分离法：手性柱拆分外消旋体：利用旋光性化合物对对映体的吸附速度不同进行分离。3.生物分离法:Enzyme及细菌等具有旋光性,作用时具有较强的选择性.4.播种结晶法:53对映异构体与手性试剂及非手性试剂的反应：1.

不断裂与手性碳相连的键的反应：CH2.C2H5HClCH3HClC2H5HC2H5ClCH2ClCl.Cl2(S)-2-氯丁烷(R)-1,2-二氯丁烷手性碳的构型不变，但符号可能改变。54例：不断裂与手性碳相连的键的反应CH3CH3CH3HHHHHClHClHClClCl.+

ClCH3(S)-2-氯丁烷CH3内消旋CH32S,3S-二-氯丁烷Diastereomers55HCH3CH3HHCH3CH3HHHCl2Cl2CH3HHCH3HClCH3HCH3HHClRacemate非手性化合物与非手性试剂反应56CH3HHHCl

ClCH3HCH3CH3HCH3HCH3ClClHCH3CH3HClClCl2Cl2Diastereomers手性化合物与非手性试剂反应57%

ee (

对映体过量百分率）

= R

%

- S

%% O.P

(光学纯度百分率）= [a

]观察

/

[

a

]纯

·

100%2

断裂与手性碳相连的键的反应58Why

chiralityis

important?59Why

chiralityis