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6

(Stereochemistry)
6.1
(Stereochemistry)


Sawhorse projections, Newman projections, Wedge projections



6.2


Isomers
structural isomers

conformational
isomers

Stereoisomers
enantiomers

diastereoisomers
geometrical isomers

CM 328

57

6.2.1 (Structural isomers)


()
Skeletal isomers
CH3 CH CH3
CH3CH2CH2CH3
CH3
n-Butane

Isobutene

Positional isomers
CH3 CH CH3
CH3CH2CH2Cl
Cl
1-Chloropropane
2-chloropropane
Functional isomers
CH3 O CH3
CH2CH2OH
Ethanol

Dimethyl ether

6.2.2 (Conformational isomers)

Acyclic compounds
Ethane
H
H
H
H

HH

H
H

H
H

sawhorse

Newman

Eclipsed

58

H
H

H
H

H
H

Sawhorse

Newman

staggered

CM 328

n-Butane
CH3
H
H3C
H

H
H
H

H
H

H
CH3

(sp)

CH3
H
(ac)

H 3 CH

CH3

CH3

CH3
H

CH3

H3C CH3

CH3

H
H

(sc)

H
CH3

H
CH3

CH3

H
H

CH3
(ap)

Cyclic compounds

Cyclopropane

Envelope

Chair

CM 328

Cyclobutane

Cyclopentane

Boat
Cyclohexane

half-chair

Twist-boat

59

6.3 (Stereoisomers)

(space)

X
C

Y
B


4
(chiral center) asymmetric carbon atom
2
1
1 2
2
(Enantiomers)

HO

CHO
C H

CH3

CHO
C OH

CH3


( 1 )

60

CHO
Cl C Cl

Cl

CH3

CHO
C Cl

CH 3


( )

CM 328

2 ( ) (non-superimposable)

2 ( )
(super-imposable) ( ) (mesomer)
1
1 2
( )
2n n

CHO

CHO

CHO

C H

H C OH

H C OH

HO

H C

HO C H

OH

CH2OH

CHO

HO C H

CH2OH

CH2OH

HO C H
H C OH
CH2OH

: 4 2
(
) < 2n

CM 328

61

COOH
H C OH
H C OH

COOH
H C OH
HO C H

COOH

COOH
HO C H
H

COOH

C OH
COOH

: 3 1 1


(mesomer)

6.4
2

(optically active compounds) (optical
activity)
2
2
1.
dextrorotatory d +
levorotatory l
(Lactic acid)

62

CM 328

COOH
HO

COOH
H

CH3

OH

CH3

l -lactic acid (-)-lactic acid

d -lactic acid (+)-lactic acid

2. 2 (reagent)
(optically active) 2
R

CH

COOH

NH2
L- enantiomer
R

CH

COOH

NH2

D-aminooxidase
O2 , H2O2

D-aminooxidase
O2 , H2O2

O
C

OH + H2O + NH3

D-enantiomer

6.5 (Fisher projection)


Emil Fisher(1891)

()
()
CH3
CH3
CH
3

HO

COOH

Wedge projection
CM 328

HO

HO

COOH

H
COOH

Fisher projection
63

CH3

CH3

CH3
OH
COOH

OH

OH

COOH

Wedge projection

COOH

Fisher projection



1. 180o

CH3
H C OH
COOH

180

COOH
HO C H
CH3

2.

CH3
OH
COOH
OH
OH

H
COOH

CH3

H
COOH

COOH HO

H
CH3

H
CH3

6.6 (Absolute configuration)


6.6.1 RS
R S (Absolute configuration)
sequence rule
priority
sequence rule
64

CM 328

(atomic number)
R S

R-2-Butanol

Priority : - OH
CHO
H C OH

S-2-Butanol

> -CH2CH3 > -CH3 > H


CHO

HO C H

HO C H
H C OH

CH3
(2R , 3S)-Butanol

CH3
(2S , 3R)-Butanol

sequence rule :
I > Br > Cl > S > P > F > O > N > C > D(deuterium) > H
C(CH3)3 > CCH(CH3)2 > CH2CH3 > CH3
O
O
O
O
O
C OR > C OH > C NH2 > C R > C H
C N > C C H > CH CH2

CM 328

65

6.6.2 DL


R1 CHX R2 X (
, X = OH; , X = NH2)
D X L
CHO

CHO

H C OH

HO C H
CH2OH

CH2OH

D-(+)-glyceraldehyde

COOH
NH2 2 H
H
OH
CH3

COOH
HO
H
CH3
L-(+)-Lactic acid

L-()-glyceraldehyde

L-(+)-Threonine
( NH2 C2
)

CHO
H
OH
HO
H
H
OH
H 5 OH
CH2OH
D-(+)-Glucose
( OH C5
)

6.7 Cis-trans isomers


6.7.1 EZ
(geometrical isomers) - (cis - trans isomers) priority
sequence rule 2 priority
66

CM 328

Br

Cl
C

CH3

Br priority CH3
I priority Cl
Br I

E-1-bromo-2-chloro-2-iodo-propene
H3 C
H

CH3

H3 C

Z - 2 -Butene

Cis -2 Butene
H

CH3

E - 2 Butene

trans 2 - Butene

H3C
CH3
Z- Cis-

CH3

H 3C
H
E- trans-

1,2 Dimethylcyclopropane
6.7.2. re-si
(faces)
()

sequence rule

CM 328

67

Y
C

C
X
re

si

C=C re-si
( 1 2)
re-si
HOOC
H

COOH

si - re
maleic acid

68

si-si
H
HOOC

COOH

re-re
fumaric acid

CM 328

6.8

steroid [
(steroid) axial ()]
[(steroid)
equatorial () ]
H OH

H OH

H O
OH
OH

OH
OH

OH
H

OH

- D-(+)- glucopyranose
CH3

COOH

OH

HO

H
H

- D-(+)- glucopyranose

CH3

HO

OH
OH

steroid ()

6.9 Symmetry elements Chirality


symmetry elements
(chirality)
symmetry elements
1. (A plane of symmetry plane)
2

CM 328

69

COOH
H
H

OH

OH

COOH

2. (A center of symmetry i)
i

CL

HO

i
Cl

OH

3. - (rotation-reflection axis Sn)


0

360
n

Cl
H
H
H

Cl

Cl

S4

Cl
H

70

CM 328

4. (axis of symmetry Cn , n > 1)

360 0
n

(n > 1)


C2
H

C2H5
CH3

CH3
C2H5


(achiral molecule) symmetry elements

1. ()
2. ( i )
3. (Sn)
(chiral molecule)
1. symmetry element (Cn , n > 1 )
2. symmetry elements point group C1

6.10 ( Optical activity)




(optically active compound) (optical
activity)

CM 328

71


1. chiral center
CH3
CH3
H

C OH

HO

C 6 H5

C6 H 5

[] 27D = +42.9 (neat)


[] 27D = - 42.9o (neat)
1-Phenylethanol
2. chiral center

Hexahelicene

Trans-cyclo-octene

Ansa derivative

Paracyclophane

6.11 (Resolution of racemic mixture )





72

CM 328

(+) B (+) A
() B + 2 (+) A
Racemic

chiral

Mixture

reagent

regenerate

(+) B

() B (+) A
Diastereoisomers

regenerate

(-) B


(diastereomeric salts) optically pure)

optically pure

RNH2 + RCOOH

()-
+

()-R H3OOCR

(+)-R H3OOCR
NaOH

RCOO Na+ + (+)-RNH2

CM 328

()-R H3OOCR
NaOH

RCOO Na+ + ()-RNH2

73


phthalic anhydride
racemic hydrogen phthalate ester
(brucine)

(6.1)
CH3
O
O
OH
C O CH C6H13
C
O + (+) C6H13 CH CH3
COOH
C
(+) 2-Octanol
O
(-)-Brucine
CH3
O
C O CH C6H13-(+)
COO- Brucine-(-)

CH3
O
C O CH C6H13-(+)

CH3
O
C O CH C6H13 (-)

COO-Brucine-(-)

COO-Brucine-(-)

HCl
CH3

O
C O CH C6H13-(+)
COO-Brucine-(-)

OH-

OH
(+) C6H13 CH CH3 +
(+) 2-Octanol

COOCOO-

6.1

74

CM 328

6.12 (Polarimeter)
:
, Nicol prism (polarizer), Nicol prism
(analyzer)

6.2
Nicol prism
plane-polarised light
analyzer analyzer
90O (zero point)

optically inactive
analyzer () analyzer

dextrorotatory isomer d-isomer analyzer
levorotatory isomer l-isomer

( 6.1)

CM 328

75

analyzer
0.01O
( 5O)

()

()

()

6.3 analyzer () () ()

6.13 Optical rotation


()

(optical rotation)
1. ()
2.
3. ()
4.
5. sodium D line (5893) mercury
green line (5461 )
Specific rotation optical rotation 1 1
1
specific rotation
obs.
[] tD =
C I
76

CM 328

[] tD specific rotation
obs. ()

t
C
l
D sodium D line (5893)
specific rotation
obs.
[] tD =
dI
d
(+) ()
optical rotation

optical rotation optically inactive

6.14 , Optical purity Enantiomeric excess


d l 50 : 50 optical rotation
d l
optically inactive
(racemic modification)

d-
(+)- l ()- optical rotation (+)

d l specific rotation []net
[]net = fd [d] + fl [l]
CM 328

77

fd fl d l [d] [l]
specific rotation d l fl = 1 fd [l] = [d]

[]net = fd [d] + (1 fd ) [d]


= fd [d] [d ] + fd [d]
= [d] (2 fd 1)
d > l
l > d
[]net = [l] (2 fl 1)
(2 fd 1) (2 fl 1) enantiomeric excess (ee) optical purity

Optical purity
[ ]obs.
Optical purity (%) =
100
[ ]max.
[]obs. = specific rotation
[]max = specific rotation

78

CM 328

6.1
( Molecular model )




109.5O
sp3-
sp2-
120O
sp-
180O

(covalent bonding radii)


H , C , N O
0.3 , 0.77 , 0.70 0.67
C , N , O 0.70 , 0.62 0.55
6.1



CM 328

79

6.1

CH
1.09
NH
1.00
OH
0.96
CC
1.54
CN
1.47
CO
1.43
C Cl
1.76
C Br
1.94
CI
2.14

()

C=C
1.35
C=N
1.30
C=O
1.22

CC
CN

1.2
1.16

C C ,
C N C O 1.5 C H , N H O H
1
5 .
CC , CN
C O
3.5 .
C = C , C = N C = O
3 .
CH , NH
O H

1. (Acyclic compounds)
1. H2O CH4
H2O CH4 Wedge projection

2. Ethane (CH3 CH3) 1-Bromo-2-chloroethane (Cl CH2 CH2 Br) C C


80

CM 328

. Sawhorse projections
. Newman projections
3. (Fischer projections)

Cl

CH3

CH3

CH2Cl
H

CH3

Br

Br

Br

Br

CH3
()

CH2Br
()

()

3.1 Wedge projection


3.2 (Chiral center)

3.3 (Absolute configurations)


RS
3.4 (Optically active)
3.5 (Mesomer)

4. Lactic acid 2
COOH
COOH
HO

C
CH3

(+)- Lactic acid

CM 328

OH

CH3
(-)-Lactic acid

81

4.1 (+) Lactic acid d Lactic acid () Lactic acid

4.2 (+) ()
4.3 Lactic acid 2 RS
4.4 (+) Lactic acid Wedge projections
C

5. D-(+)-Glucose (puranose ring)

5.1 D-(+)- Glucose (


) OH C-5
C-1 CHO [D-(+ )-Glucopyranose ]

5.2 D-(+)-Glucopyranose (Chair form)


OH C-1 - - D-(+)-Glucopyranose

82

CM 328

6. (Biphenyls)

Optically active Optically inactive


7. (Allenes)
CH3

H
C C C
H
CH3

()

H
H

C C C

CH3
CH3 CH3
C C C
H
H
H

()

()

Optically active Optically inactive


8. (Geometrical isomers)
. 2 ,4- Hexadiene

EZ
Scis (cisoid) S-trans
(transoid)
H2 C

CH2

S-cis

CH2
CH2
S-trans


. 2 , 4 Heptadiene

S trans EZ
CM 328

83

2. (Cyclic compounds)
1. (Cyclohexane)
(Cyclohexane) 3 conformers Chair
conformer , Boat comformer Twist-boat conformer

Chair

Boat

Twist-boat

Chair conformer
Boat comformer Chair conformer Chair
2 ring flip boat

Chair

Boat

Chair

1.1 Conformer conformer

1.2 a axial e equatorial


axial equatorial ring flip
1.3 Chair conformer boat conformer
1.4 boat conformer twist boat conformer
Conformers
2.
2.1 Chair conformers methylcyclohexane
conformers
84

CM 328

2.2 Chair conformers Cis- Trans-isomers 1,2-;


1,3- 1,4Dimethylcyclohexane Cis trans-isomers
Conformers
2.3 Chair conformer tert- butylcyclohexane
conformer
3. Cis- trans Decalin
H

H
H
cis decalin
trans decalin
3.1 Cis trans decalin conformers conformers
3.2 Cis decalin trans- decalin

4. 3,5-Dichlorocyclohexanol
3-Bromo-5-chlorocyclohexanol
Cl

Br
OH

Cl
3,5- Dichlorocyclohexanol

OH
Cl
3-Bromo-5-chlorocyclohexanol

4.1 3,5-Dichlorocyclohexanol
3-Bromo-5-chlorocyclohexanol
4.2

CM 328

85

5. (Cholic acid) (bile acid)



CH3 CH

12

CH3
HO

17

COOH

H
Cholic acid

OH

5.1 ()
5.2 OH A (- -) OH

5.3
6. 2 norborneol ([2.2.1] heptan2ol)

OH
a. 2norborneol

b. 2norborneol

86

CM 328

7. symmetry elements symmetry elements


chiral achiral
H

COOH

Cl

Cl

COOH

COOH

COOH

Cl

Cl

Cl

OH

HO

HO

H
OH

OH Cl
H

CH2

CH2

CH2
COOH
COOH
O 2N
HOOC
NO2

CM 328

Cl

OH

HO

OH
H

OH
H H
OH

OH
H
OH
H
CH2

O
HOOC

(CH2)n
O

NO2
HOOC
HOOC
NO2

87


1. Absolute configurations RS
.
.
CH2OH
Cl
NH2

CH2

HC

C6 H5
H

CH3

CH3CH2
H

.
C

CH2CH3

CH3CH2

Cl

HO

.
H

Cl

HO
Br

CHO

CH2Br

CH3
Br

CHO

H
COOH

2. Structural isomers Stereoisomers


.

88

CH3

O
C6H5CH2COCH3

CH2

O
C6H5OCCH2CH3

CM 328

. CH3NH

H2N

CH2 CH3

CH3

OH

HO

.
Cl

Cl

Cl
Cl

3. T F
.........
.........(Cn ,n > 1)
........
.........
......... dl
......... cis / trans
.........cis trans isomers
.........Tertiary amine
......... erythro threo structural isomers
......... meso
......... meso
.........Boat conformer
......... Bicyclic Bridgering norborneol
2n n
........Norborneol 8
........Norborneol

CM 328

89

6.2
()--
(Resolution of racemic mixture ()--Phenylethylamine)

1-
Leukart reaction
O
Ph-C-CH3

O
H-C-ONH4

Acetophenone ammonium formate

NH2
Ph-CH-CH3

CO2

(+- )-Phenylethylamine

H2 O

1-
(+) ()-1
(optically inactive)
(+)--phenylethylamine ()--phenylethylamine

1. ()-phenylethylamine (+)-tartaric acid
2.
3. ()-phenylethylamine-(+)-hydrogentartrate (+)--phenylethylamine-(+)-hydrogentartrate

4. ()--phenylethylamine
5. ()--phenylethylamine
6. (+)--phenylethylamine

90

CM 328

CH3
()- Ph CH NH2

COOH
H C OH
HO C H
COOH
(+)-Tartaric acid
CH3
OH OH
+ (+) Ph CH NH3 OOC CH CH COOH
(+)--phenylethylamine-(+)-hydrogentartrate ()
CH3
OH OH
+ + (-) Ph CH NH3 OOC CH CH COOH
()--phenylethylamine-(+)-hydrogentartrate ()

NaOH
CH3
(+)- Ph CH NH2 + (+)sodium tartrate
(+)--Phenylethylamine
CM 328

NaOH
CH3
(-)- Ph CH NH2 + (+)sodium tartrate
(-)--Phenylethylamine
91


1. () --phenylethylamine
O
2HCOONH4
Ph-C-CH3

CH3 O
Ph-CH-NH-C-H

HCl
H2 O
Phenylethyl
formamide

CH3
Ph-CH-NH2 HCl
NaOH

CH3
Ph-CH-NH2

()--phenylethylamine
72 (0.6 ) 12 (2 )
250 boiling chip 4-5
Claisen Still head heating mantle oil bath

150-155 OC 185 OC 2

( )
180-185 OC 3
250 2
75 -phenylethyl
formamide 2 20

75 boiling chip 4-5
-phenylethyl formamide 40
40 phenylethyl formamide -phenylethylamine hydrochloride
4 20
-phenylethylamine hydrochloride
500 (62.5 125 )
92

CM 328

2. () --phenylethylamine ( Resolution of ()--phenylethylamine)


. () --phenylethylamine
(+)-tartaric acid 12.5 (0.083 ) (!)
75 Erenmeyer flask 250 [(+)-tartaric
acid ]
()--phenylethylamine 10 (0.082 ) 75
(+)-tartaric acid
()-phenylethylamine (+)hydrogentartrate
( 1) flask


10 .
8.5 (77%) 190-200 OC
10% NaOH

25 .

flask ( 2) 5
( 20D 1.5222) anhydrous potassium carbonate 2-4
flask-
()
CM 328

93

flask () (
3) flask -

optical rotation
specific rotation optical purity
1 ( 168170 OC
[ ]20D = 19O 21O
2 flask

3
Optical rotation (8O 9O) 2.1
6.8 . 10 . blank (
) optical rotation

( ) --phenylethylamine ( ) --phenylethylamine
() --phenylethylamine
(+) Tartaric acid
( ) --phenylethylamine

94

(oC)
184 -186
-

[ ]D

0O
+12.0O(20 OC)

H2O (), CH3OH ()


H2O (), CH3OH ()

184 -186

- 40.3O(22 OC)

H2O (), CH3OH ()

CM 328


1. R- S- -phenylethylamine
2. ()--phenylethylamine meso-tartaric acid
3. R optical rotation 2.70O
25O sodium D line 0.120
10 .
() specific rotation
() specific rotation R
() Specific rotation S
() optical rotation R ()
0.041 20 .
4. d [] tD = +55O
[] tD 11O
()
() enantiomeric excess optical purity ()
()
5. () ()-hydratropic acid (C6H5-CHCH3COOH)

CM 328

95