Chemistry 2100 Chapter 15 Isomers same connections mirror images Enantiomers different connections Constitutional Isomers Stereoisomers chiral single bond rotation
achiral not mirror images Diastereomers Geometric Isomers Conformational Isomers Enantiomers Enantiomers: Nonsuperposable mirror images. As an example of a molecule that exists as a pair of enantiomers, consider 2butanol. OH C H H3 C CH2 CH3
Original molecule HO H C CH 3 CH3 CH2 Mirror image Enantiomers OH C H H3 C CH2 CH3 Original molecule 180 OH H C CH 3 CH3 CH2 Mirror image
The mirror image turned by 180 rotate by 180 about the C-OH bond OH C CH CH 2 3 H3 C H OH The original molecule C H H3 C CH2 CH3 OH C CH CH 2
3 H3 C H The mirror image rotated by 180 glycine alanine H COOH COOH C C H2 N CH3 CH3
chiral asymmetric NH2 H glycine glycine H COOH COOH C C H2 N H
CH3 H3 CH plane of symmetry achiral NH2 H 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 Enantiomers matter! NH2CH3 CH2 CH * CH3 amphetamine CH3 (CH 3 )2 CHCH2 CH COOH * ibuprofen O N *
O N O O thalidomide H The R,S System Because enantiomers are different compounds, each must have a different name. Here are the enantiomers of the over-thecounter drug ibuprofen. The R,S system is a way to distinguish 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, Properties of Enantiomers
Optical activity plane-polarized light plane-polarized light plane-polarized light plane-polarized light plane-polarized light Fig. 15-6, p. 43 Assigning Rotation dextrorotatory (d) levorotatory (l) () or (dl) (+) rotation "right-hand isomer"
() rotation "left-hand isomer" optically inactive raceme 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
The Four Stereoisomers of a Simple sugar CHO H C OH HO C H 2R,3S CHO HO C H
H C OH HO C H H C OH H C OH
HO C H CH2 OH L-threose A CHO CHO CH2 OH D-threose B 2S,3R CH2 OH D-erythrose C
2R,3R CH2 OH L-erythrose D 2S,3S Fischer Projections C C Threose and Erythrose, Fischer-ized Tartaric Acid COOH HO H H
OH COOH COOH H HO COOH OH H OH HO H H H
OH HO H COOH COOH COOH W X Y COOH Z meso
COOH HO H H OH COOH COOH H HO COOH OH H OH H
OH H H OH H OH COOH COOH COOH W X Y
COOH Z meso COOH HO H H OH COOH COOH H HO COOH
OH H OH H OH H H OH H OH COOH COOH
COOH W X Y meso Meso form COOH Z O O * Na O C CH * CH
OH OH C O NH 4 sodium ammonium tartrate O O * Na O C CH * CH OH OH
C O NH 4 sodium ammonium tartrate Stereochemical Reactions O CH3 C COOH pyruvic acid [ H] CH3 O H *C COOH H lactic acid
O CH3 C COOH pyruvic acid [ H] CH3 O H * C COOH H lactic acid HO C H CH3 COOH
(+) HO C H COOH CH3 () HO C H H H H H H
H H H CH3 COOH (+) HO C H COOH CH3 () HO O
C COOH C CH3 H H H H H H H H H
CH3 COOH (+) HO C H COOH CH3 () O C COOH O C
H H H H H C COOH CH3 H CH3 HO H H
H CH3 COOH (+) HO C H COOH CH3 () O C COOH O
C H H H H H C COOH CH3 H CH3 HO
H H H CH3 COOH (+) HO C H COOH CH3 () O C COOH
O C H H H H H C COOH CH3 H CH3
HO H H H CH3 COOH (+) HO C H COOH CH3 () O C
COOH O C H H H H H C COOH CH3 H
CH3 HO H H H CH3 COOH (+) HO C H COOH CH3 () O
C COOH O C H H H H H C COOH CH3
H CH3 HO H H H CH3 COOH (+) HO C H COOH CH3 ()
But, Biologically HO C H CH3 COOH (+) HO C NAD H H CH3 COOH (+)
HO C NAD H H CH3 COOH (+) HO O NAD
C CH3 H COOH H CH3 COOH (+) O C CH3 COOH
C CH3 O NAD HO H COOH H CH3 COOH
(+) O C CH3 COOH C CH3 O NAD HO
H COOH H CH3 COOH (+) O C CH3 COOH
C CH3 O NAD HO H COOH H CH3 COOH
(+) H+ O C CH3 COOH C CH3 O NAD HO
H COOH H CH3 COOH (+) H+ O C
CH3 COOH C CH3 O NAD HO H COOH H CH3
COOH (+) 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, H C is H a liver toxin! H C but its R enantiomer 3 H HOOC (S)-Ibuprofen
3 HOOC (S)-Naproxen OCH3
