Post on 07-Sep-2014
transcript
INTRODUCTION TO STEREOCHEMISTRY
Isomers are compounds with the same molecular formula but not identical structures
Constitutional isomers are isomers which have the same molecular formula but differ in the way their atoms are connected
Constitutional Isomers
H3C
CH2
H2C
CH3
butaneChemical Formula: C4H10
CH3
CH
CH3H3C
2-methylpropaneChemical Formula: C4H10
Constitutional isomers are isomers which have the same molecular formula but differ in the way their atoms are connected
Stereoisomers have the same molecular formula, maintain the same connectivity, but differ in the way their atoms are arranged in space
Conformational isomers (or conformers or rotational isomers or rotamers) are stereoisomers produced by rotation about single bonds, and are often rapidly interconverting at room temperature
Conformations of Alkanes and Cycloalkanes
Conformations of Ethane
H3C CH3ethane
Staggered conformation of
ethane
Eclipsed conformation of
ethane
H
H H
H
HH
H
H
H
H
HH
H
H H
H
H H
H
H H
H
HH
Sawhorse Representation
Sawhorse Representation
Newman Projection
Newman Projection
ethane
Staggered conformation of
ethane
Eclipsed conformation of
ethane
H
H H
H
HH
H
H
H
H
HH
H
H H
H
H H
H
H H
H
HH
Sawhorse Representation
Sawhorse Representation
Newman Projection
Newman Projection
Configurational Isomers are stereoisomers that do not readily interconvert at room temperature and can (in principle at least) be separated.
Geometric isomers are configurational isomers that differ in the spatial position around a bond with restricted rotation (e.g. a double bond):
Geometric (Cis and Trans) Isomers
Geometric (Cis and Trans) Isomers result from restriction rotation
Compounds with double bonds cis isomer – have same substituents on the same side of the double bond (= Z with more complex molecules having high priority groups on the same side)
trans isomer – have the same substituents on the opposite side of the double bond (= E with more complex molecules having high priority groups on opposite sides)
Compounds with bonds in a ring: cis isomer – have the same substituents on the same side of the ring trans isomer - have the same substituents on the opposite side of the ring
Cis-trans (Geometric) isomerism in Alkenes
C C
ClCl
H H
cis-1,2-dichloroethene
C C
ClH
Cl H
trans-1,2-dichloroethene
(E)-1,2-dichloroethene(Z)-1,2-dichloroethene
Cis-trans (Geometric) isomerism in Alkenes
C C
ClH
H Cl
1,1-dichloroethene
*If one of the two carbon atoms of the double bond has two identical substituents, there are no cis-trans isomers for that molecule
Identifying cis and trans isomers of Alkenes
Example 11.3Two isomers of 2-butene are shown below. Which is the cis isomer and which is the trans isomer
C C
H
H3C
H
CH3
C C
H
H3C
CH3
H
cis-2-butene trans-2-butene
Naming cis and trans compounds
Example 11.4Name the following geometric isomers.
trans-3,4-dichloro-3-heptene cis-3,4-dimethyl-3-octene
H3C
H2C
CH2
C
C
Cl
Cl
H2C
CH3
H3C
CH2
C
H3C C
H2C
CH2
H2C
CH3
CH3
Identifying Geometric Isomers
Example 11.5Determine whether each of the following molecules can exist as cis-trans isomers:(1) 1-pentene(2) 3-ethyl-3-hexene(3) 3-methyl-2-pentene
1-pentene 3-ethyl-3-hexene
CH2CH3
CC
H3CH2C CH2CH3
H
C C
CH2CH2CH3H
H H
cis-3-methyl-2-pentene
C C
CH3H3C
H3CH2C H
C C
HH3C
H3CH2C CH3
trans-3-methyl-2-pentene
cis-9-octadecenoic acid
Cis and Trans Fatty Acids
O
OH
H H
O
OH
H
H
trans-9-octadecenoic acid
Cis-trans (Geometric) isomerism in Cycloalkanes
Cis-trans isomers are molecules having the same arrangement of atoms but differ in the spatial orientation of their substituents.
H
H
H
H
H
ClCl
H
HH
H H
cis-1,2-dichlorocyclohexane
H
H
H
H
H
ClH
Cl
HH
H H
trans-1,2-dichlorocyclohexane
Naming cis-trans Isomers of Substituted Cycloalkanes
Example 10.6Determine whether the following susbstituted cycloalkanes are cis or trans isomers.
trans-1,2-dimethylcyclopentane cis-1,2-dimethylcyclopentane
H
H
H
H
H CH3
HCH3 H
H
CH3
CH3
H
H
H
H
CH3CH3
HH H
H
CH3 CH3
Conformations of Alkanes and Cycloalkanes
Conformations of Cyclohexane
cyclohexaneChair
conformation of cyclohexane
Boat conformation of
cyclohexane
H
H
H
H
H
HH
H
HH
H H
A E
A
E
A
A
E
E
A
E
A
E
A
E
A
E
A
A
E
A
E
A
E
E
Chair conformation of
cyclohexane
Boat conformation of
cyclohexane
A E
A
E
A
A
E
E
A
E
A
E
A
E
A
E
A
A
E
A
E
A
E
E
Chair-Chair Interconversion
Optical isomers are configurational isomers that differ in the 3D relationship of the substituents about one or more atoms.
Diastereomers are optical isomers (stereoisomers) that are not enantiomers.
Enantiomers are optical isomers that are non-superimposable mirror images.
Chirality
Chiral objects are objects with left-handed and right-handed forms
Achiral objects - objects that have superimposable mirror images
Nonsuperimposable mirror images - a mirror image that is not the same as the image itself - chiral objects have nonsuperimposable mirror images
Assymetric Center
Chirality is not reserved just for objects - molecules can be chiral
Chiral molecules - generally molecules containing an asymmetric center
Asymmetric (chiral) center - tetrahedral atom bonded to four different groups - indicated with an asterisk (*)
Enantiomers nonsuperimposible mirror images
OH
CH3HO2CH
OH
CO2HCH3
H
mirrorplane
(S)(+) lactic acid (R)(-) lactic acid
from muscle tissue from milk[] = +13.5 [] = -13.5
oo
Enantiomeric Excess(Optical Purity)
actually 94.3% (+)
11.4% racemic88.6% (+)
= 88.6% e.e.
x 100 123.0109.0
e.e. =
oobserved rotation = +109
from oranges
o
[] = +123.0
H
from lemons
o[=
(S)-(-) Limonene (R)(+) Limonene
H
x 100 = enantiomeric excess (e.e.)rotation of pure enantiomerobserved rotation
Biological Activity
(R)(+) Thalidomide (S)(-) Thalidomide
N
NO
O
O
O
H
H
a sedative and hypnotic a teratogen
N
NO
O
O
O
H
H
SSRI Efficacy depends on Stereochemistry
ON(CH3)2
F
NC
*
(+/-) Celexa(-) Lexapro
Chiral Molecules with One Asymmetric Center
Molecules with one chiral center would have 2 enantiomers*Chiral molecules would have 2n enantiomers (where n is the number of chiral centers)
Chiral vs Achiral
How to Represent Enantiomers: Perspective Formulas
Perspective Formulas - shows two bonds of the asymmetric center as lines in the plane of the paper, another bond as a solid wedge protruding forward out of the paper, and the fourth bond as a hatched wedge extending behind the paper
Fischer Projections
Fisher Projection - representation of an asymmetric center as the point of intersection of two perpendicular lines
Horizontal lines represent bonds that project out of the plane of the paper
Vertical lines represent bonds that extend back from the plane of the paper away from the viewer
Fischer Projections
Br
H
CH3H3CH2C
Br
H
CH2CH3H3C
Naming Enantiomers -R,S System
STEP 1. Rank the groups/atoms bonded to the asymmetric center in order of priority. - rank in terms of atomic mass. Higher atomic mass, higher priority. - let’s have 1-chloro-1-ethanol as an example.
1. Chlorine = 36 amu 2. Oxygen = 16 amu 3. Carbon = 12 amu4. Hydrogen = 1 amu
STEP 2. Rotate the molecule so that the lowest priority group is pointing away from thereader.
Naming Enantiomers -R,S System
Step 3. Trace your finger around the three highest priority groups in order of the priority.
- If the circle is moving counterclockwise the CIP designation is “S”. If the circle is moving clockwise the CIP designation is “R”.
Step 4. Name the enantiomer in terms of its R or S configuration.- the name for this isomer is (S)-1-chloro-1-ethanol
Naming Enantiomers -R,S System
Assigning Priorities to Groups
1. Oxygen (from CH2OH) = 162. Carbon (from CH2CH3) = attached to carbon3. Carbon (from CH3) = attached to hydrogen4. Hydrogen = 1
Naming Enantiomers -R,S System
Lactic Acid
(S) (R)
4
3 2
1
4
32
1OH
CH3 CO2HH
OH
CH3HO2CH
Plane-Polarized Light
Plane-Polarized Light through an Achiral Compound
Plane-Polarized Light through a Chiral Compound
Polarimeter Measures Optical Rotation
Specific Rotation, [α]
[α] = α / cl a = observed rotation
c = concentration in g/mLl = length of tube in dm
Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counter-clockwise rotation
Specific Rotations of some Common Organic Compounds
Compound [a] # * centersPenicillin V +233.0 3Sucrose +66.5 10 Camphor +44.3 2MSG +25.5 1Cholesterol -31.3 8Morphine -132.0 5
DiastereomersStereoisomers That Are Not Mirror Images
3 322
opposite stereochemistry at C3
same stereochemistry at C2 (S)
CO2H
OHH
Br H
CO2H
OHH
BrH(2S,3S) (2S,3R)
Fischer Projections with 2 Chiral Centers
CO2H
CH3
H OH
Br H H Br
H OH
CO2H
CH3
(2S,3S) (2S,3R)
2
3
2
3
Identical, Enantiomers or Diastereomers?
H
H
CH3
CH3
&
CH3
CH3
H
H CC
a)
CH2CH3
CH3
H
H
Br
Br
CH2CH3
CH3&
b)
OH
HO
NH2
NH2
Tartaric AcidsCO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
CO2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,R S,S
R,S S,R
Racemic Mixture
o
(g/mL) 1.7598 1.7598 1.7723
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid
Racemic Mixture (Racemate): 50/50 mixture of enantiomers
CO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
R,R S,S
Meso CompoundInternal Plane of Symmetry
Optically Inactive
orotate 180
superimposible
CO2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,S S,R
mirror plane
2,3,4-trichlorohexaneHow many stereoisomers?
Cl
Cl
Cl3 asymmetric centers
8 stereoisomers
* **
2n, n= # asymmetric centers (3)
n = 3; 2n = 8
CH3
CH2CH3
H Cl
Cl H
H Cl Cl H
H Cl
Cl H
CH3
CH2CH3
CH3
CH2CH3
Cl H
H Cl
H Cl Cl H
Cl H
H Cl
CH3
CH2CH3
H Cl
H Cl
H Cl
CH3
CH2CH3
Cl H
Cl H
Cl H
CH3
CH2CH3
Cl H
H Cl
H Cl
CH3
CH2CH3
H Cl
Cl H
Cl H
CH3
CH2CH3
S
S
R
R
R
S
A Carbohydrate
CHO
CH2OH
H OH
HO H
H OH
H OH
(+) D-Glucose
R
S
R
R
Internal Planes of Symmetry
CH3CH3
CH3CH3
CH3CH3
CH3 CH3
Both are Meso
Asymmetric Centers on Rings
Br
Br
Br
Br
1(R),2(S) cis 1,2-dibromocyclohexane
nonsuperimposible but A flips into B
A B
BrBr
Meso
BrominationTrans is formed exclusively
No Meso is formed (cis)
racemic mixture
S SR RBr BrBr Br
Br2
Preparation of (L)-Dopafor Treatment of Parkinson’s
HO
HO
CH2C
CO2H
NH2
H
l-(-) Dopa
HO
HO
CH2CH2NH2
Dopaminecannot cross blood-brain
barrier
C=CNH2
CO2HH
HO
HO
H2Rh(DIOP)Cl2
enz.
Relevance of Stereochemistry
(S,S)(R,S)useful decongenstants
d-pseudoephedrine and l-ephedrine
4 stereoisomers
**
2 asymmetric centers
EPHEDRA from Ma Huong
NHCH3
CH3
OH
One-step synthesis
Pseudophed
*
d-(S)- "Meth"l-(R) - Vicks
(methamphetamine)"desoxyephedrine"NHCH3
CH3
a-(p-isobutylphenyl)propionic acid
CH3 CO2HH
(S)(+) ibuprofen (R)(-) ibuprofen
CH3HO2C
H
anti-inflammatory 80-90% metabolized to (S)(+)
Model of Thalidomide
How Sweet it is!
Sucrose
O
HOOH
O
CH2OH
OCH2OH
CH2OH
HO
HO
OH
Sucralose or Splenda
O
Cl
HOOH
O
CH2OH
OCH2Cl
CH2Cl
HO
HO
Sucralose is 600 times sweeter and does not get metabolized.
Sildenafil (Viagra) and Caffeine
NN
N
N
CH3
H
O
CH3CH2O
S
N
N
CH3
O
O
N
N
N
N
CH3
O
O
CH3
CH3
Radiosensitizer of Choice Until 2004
Okadaic acid17 asymmetric centers
O
OH
HOOC
OH
OH
O
OH
HO
OH
HOH
O
O