Chemistry 2100

Lecture 8

Constitutional

IsomersStereoisomers ConformationalIsomers

GeometricIsomersEnantiomers Diastereomers

single bond rotation

chiral achiral

sameconnections

differentconnections

notmirrorimages

mirrorimages

Isomers

EnantiomersEnantiomers:Enantiomers: Nonsuperposable mirror images.– As an example of a molecule that exists

as a pair of enantiomers, consider 2-butanol.

OHC

H3C CH2CH3H

HOC

CH3H

CH3CH2Original molecule Mirror image

Enantiomers

Original molecule

OHC

H3C CH2CH3H

OHC

CH3H

CH3CH2

OHC

H3C HCH2CH3

Mirror image The mirror imagerotated by 180°

180° rotate by 180°about the

C-OH bond

OHC

H3C CH2CH3H

OHC

H3C HCH2CH3

The original molecule

The mirror imageturned by 180°

chiral

asymmetric

glycine

NH2H

C

COOH

CH3H2 NH CH3

C

COOH

alanine

plane of symmetry

achiral

NH2

HC

COOH

CH3H2 NH CH3

C

COOH

glycine

H H

glycine

EnantiomersObjects that are nonsuperposable on their mirror images are chiralchiral (from the Greek: cheir, hand).– They show handedness.The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it.– A carbon with four different groups

bonded to it is called a stereocenterstereocenter.

Drawing Enantiomers

thalidomide

N

O

ON

O

O

H

*

(CH3)2CHCH2 CH COOH

CH3

ibuprofen

*

NH2

CH CH3CH2

amphetamine

CH3

Enantiomers matter!

*

Properties of Enantiomers

Optical activity

plane-polarized light

plane-polarized light

plane-polarized light

plane-polarized light

plane-polarized light

Fig. 15-6, p. 435

(±) or (dl) optically inactive raceme

levorotatory (l) (–) rotation "left-hand isomer"dextrorotatory (d) (+) rotation "right-hand isomer"

Assigning Rotation

Multiple Chiral CentersFor a molecule with nn stereocenters, the maximum number of possible stereoisomers is 22nn.– We have already verified that, for a molecule

with one stereocenter, 21 = 2 stereoisomers (one pair of enantiomers) are possible.

– For a molecule with two stereocenters, a maximum of 22 = 4 stereoisomers (two pair of enantiomers) are possible.

– For a molecule with three stereocenters, a maximum of 23 = 8 stereoisomers (four pairs of enantiomers) are possible, and so forth.

2R,3S 2S,3R 2R,3R 2S,3S

C

C

CHO

CH2OH

OHH

HHO

L-threose

C

C

CHO

CH2OH

OH

OHH

H

D-erythrose DC B A

C

C

CHO

CH2OH

OH

H

H

HO

D-threose

C

C

CHO

CH2OH

H

H

HO

HO

L-erythrose

The Four Stereoisomers of a Simple sugar

C

C

Fischer Projections

CHO

CH2OH

OH

H

H

HO

D-threose

CHO

CH2OH

OH

OHH

H

D-erythrose

CHO

CH2OH

H

H

HO

HO

L-erythrose

CHO

CH2OH

OHH

HHO

L-threose

Threose and Erythrose, Fischer-ized

W X Y Z

meso

H

HO HO

H

COOH

COOH

COOH

COOH

OH

OHH

H

COOH

COOH

OHH

HHO

COOH

COOH

OH

H

H

HO

Tartaric Acid

meso

COOH

COOH H H

OH

OH

W X Y Z

COOH

COOH

OH

OHH

H

COOH

COOH

OHH

HHO

COOH

COOH

OH

H

H

HO

COOH

COOH H H

OH

OH

meso

× W X Y Z

COOH

COOH

OH

OHH

H

COOH

COOH

OHH

HHO

COOH

COOH

OH

H

H

HO

Meso form

**

sodium ammonium tartrate

O

OH

CHCNa O CH C

OH

O NH4

O

**

sodium ammonium tartrate

O

OH

CHCNa O CH C

OH

O NH4

O

Stereochemical Reactions

CH3

H

C

O

COOH

H

CH3 C COOH

O[H] *

pyruvic acid lactic acid

*pyruvic acid

lactic acid

CH3

H

C

O

COOH

H

CH3 C COOH

O[H]

(–)

(+)

H COOH

HO

CCH3

H CH3

HO

CCOOH

(–)

(+)

H COOH

HO

CCH3

H CH3

HO

CCOOH

HH

HH

HH

HH

COOH

COCH3

(–)

(+)

H COOH

HO

CCH3

H CH3

HO

CCOOH

HH

HH

HH

HH

COOH

COCH3

CH3CO

COOH

(–)

(+)

H COOH

HO

CCH3

H CH3

HO

CCOOH

HH

HH

HH

HH

COOH

COCH3

CH3CO

COOH

(–)

(+)

H COOH

HO

CCH3

H CH3

HO

CCOOH

HH

HH

HH

HH

COOH

COCH3

CH3CO

COOH

(–)

(+)

H CH3

HO

CCOOH

HH

HH

HH

HH

H COOH

HO

CCH3

COOHCO

CH3

CH3CO

COOH

(–)

(+)

H CH3

HO

CCOOH

HH

HH

HH

HH

H COOH

HO

CCH3

COOHCO

CH3

CH3CO

COOH

(–)

(+)

H CH3

HO

CCOOH

H COOH

HO

CCH3

HH

HH

HH

HH

(+)

HCOOH

HO

CCH3

But, Biologically…

NAD H (+)

HCOOH

HO

CCH3

NAD H (+)

HCOOH

HO

CCH3

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

OCH3C

COOH

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

OCH3C

COOH

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

OCH3C

COOH

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

H+

OCH3C

COOH

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

H+

OCH3C

COOH

NAD H

COOHO

CH3

(+)

HCOOH

HO

CCH3

Chirality of Biomolecules– Because interactions between molecules in living

systems take place in a chiral environment, a molecule and its enantiomer or one of its diastereomers elicit different physiological responses.

– As we have seen, (S)-ibuprofen is active as a pain and fever reliever, while its R enantiomer is inactive.

– The S enantiomer of naproxen is the active pain reliever, but its R enantiomer is a liver toxin!

HOOC

H3C H

HOOC

H3C H

OCH3(S)-Ibuprofen (S)-Naproxen