Chemistry 2100

Chapter 15

Constitutional

IsomersStereoisomers

ConformationalIsomers

GeometricIsomers

Enantiomers Diastereomers

single bond rotation

chiral achiral

sameconnections

differentconnections

notmirrorimages

mirrorimages

Isomers

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

as a pair of enantiomers, consider 2-butanol.

OH

CH3C

CH2CH3

H

HO

CCH3

HCH3CH2

Original molecule Mirror image

Enantiomers

Original molecule

OH

CH3C

CH2CH3

H

OH

CCH3

HCH3CH2

OH

CH3C

HCH2CH3

Mirror image The mirror imagerotated by 180°

180° rotate by 180°about the

C-OH bond

OH

CH3C

CH2CH3

H

OH

CH3C

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

Enantiomers

Objects that are nonsuperposable on their mirror images are chiral (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 stereocenter.

Drawing Enantiomers

thalidomide

N

O

ON

O

O

H

*

(CH3)2CHCH2 CH COOH

CH3

ibuprofen

*

NH2

CH CH3CH2

amphetamine

CH3

Enantiomers matter!

*

The R,S SystemBecause enantiomers are different compounds, each must have a different name.– Here are the enantiomers of the over-the-

counter drug ibuprofen.

– The R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other.

The R,S System

The first step in assigning an R or S configuration to a stereocenter is to arrange the groups on the stereocenter in order of priority.– Priority is based on atomic number.– The higher the atomic number, the

higher the priority.

R,S Priority of Some Groups

The R,S System

• To assign an R or S configuration:1. Assign a priority from 1 (highest) to 4

(lowest) to each group bonded to the stereocenter.

2. Orient the molecule in space so that the group of lowest priority (4) is directed away from you. The three groups of higher priority (1-3) then project toward you.

3. Read the three groups projecting toward you in order from highest (1) to lowest (3) priority.

4. If reading the groups 1-2-3 is clockwise, the configuration is R. If reading them is counterclockwise, the configuration is S.

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 Centers

For a molecule with n stereocenters, the maximum number of possible stereoisomers is 2n.– 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

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 acidlactic acid

CH3

H

C

O

COOH

H

CH3 C COOH

O[H]

(–)

(+)

H

COOH

HO

CCH3

HCH3

HO

CCOOH

(–)

(+)

H

COOH

HO

CCH3

HCH3

HO

CCOOH

HH

HH HH

HH

COOH

CO

CH3

(–)

(+)

H

COOH

HO

CCH3

HCH3

HO

CCOOH

HH

HH HH

HH

COOH

CO

CH3

CH3CO

COOH

(–)

(+)

H

COOH

HO

CCH3

HCH3

HO

CCOOH

HH

HH HH

HH

COOH

CO

CH3

CH3CO

COOH

(–)

(+)

H

COOH

HO

CCH3

HCH3

HO

CCOOH

HH

HH HH

HH

COOH

CO

CH3

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

(+)

H

COOH

HO

CCH3

But, Biologically…

NAD H (+)

H

COOH

HO

CCH3

NAD H (+)

H

COOH

HO

CCH3

NAD H

COOH

OCH3

(+)

H

COOH

HO

CCH3

O

CH3CCOOH

NAD H

COOH

OCH3

(+)

H

COOH

HO

CCH3

O

CH3CCOOH

NAD H

COOH

OCH3

(+)

H

COOH

HO

CCH3

O

CH3CCOOH

NAD H

COOH

OCH3

(+)

H

COOH

HO

CCH3

H+

O

CH3CCOOH

NAD H

COOH

OCH3

(+)

H

COOH

HO

CCH3

H+

O

CH3CCOOH

NAD H

COOH

OCH3

(+)

H

COOH

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