Transcript Stereochem-2012-ques
Stereochemistry
Arrangements of Atoms in 3-d Space
Stereochemistry
• Stereochemistry: The study of the three-dimensional structures of molecules, particularly
stereoisomers
• Structural isomers: Have the same molecular formula, same types of bonds, but different bonding sequences, “connectivity” • Stereoisomers: Have the same molecular formula, same bonding sequences, but different spatial arrangements & relative orientations
Stereochemistry
CHIRALITY: If an object’s mirror image (i.e. a molecule’s 3-d reflected shape) … “cannot be brought to coincide with itself” (i.e. It is non-superimposable), it is chiral.
Stereochemical
cis-trans
Isomers
• To maintain orbital overlap in the pi bond, C=C double bonds cannot freely rotate.
• Although the two molecules below have the same connectivity, they are NOT identical.
Naming Alkene Stereoisomers : the E-Z Notational System vs. “cis-trans”
Triglycerides & Unsaturated Fatty Acids
Saturated & Unsaturated: cis- vs. trans-
Stereochemical Notation
CH 3 (CH 2 ) 6 CH 2 CH 2 (CH 2 ) 6 CO 2 H C C Oleic acid H H cis and trans are useful when substituents are identical or analogous
Oleic acid, an unsaturated fatty acid, has a cis double bond; (Hs are identical.)
cis and trans references are ambiguous when analogies are not obvious
When there are four different substituents, cis and trans does not work.
Cl Br C C H F
Example
A systematic body of rules for ranking substituents must be used, which is related to, but different from the cis and trans references.
The E-Z Notational System
E
: higher ranked substituents on opposite sides
Z
:higher ranked substituents on same side higher C C
Consider each sp 2 carbon of the double bond separately.
lower
Rank the pair of substituents relative to each other.
The E-Z Notational System
E
: higher ranked substituents on opposite sides
Z
: higher ranked substituents on same side lower C C
Consider each sp2 carbon of the double bond separately.
higher
Rank the pair of substituents relative to each other.
The E-Z Notational System
Compare the pairs
E
: higher ranked substituents on opposite sides
Z
: higher ranked substituents on same side higher lower higher higher C C lower higher
(E) Entgegen
C C lower lower
(Z) Zusammen
The E-Z Notational System
Ranking
The substituents are ranked in order of decreasing atomic number on each carbon.
higher lower higher higher C C lower higher
(E) Entgegen
C C lower lower
(Z) Zusammen
The Cahn-Ingold-Prelog (CIP) System
The system used was devised by
R. S. Cahn Sir Christopher Ingold Vladimir Prelog
Their rules for ranking groups were devised for another kind of stereochemistry, chirality, but have been adapted to alkene stereochemistry.
Example
Higher atomic number outranks lower atomic number Br > F Cl > H higher Br Cl higher C C lower F H lower
Example
Higher atomic number outranks lower atomic number Br > F Cl > H higher Br Cl higher C C lower F H lower (
Z
)-1-Bromo-2-chloro-1-fluoroethene
CIP Rules
When two atoms are identical, compare the atoms attached to them on the basis of their atomic numbers. Precedence is established at the first point of difference. — C H 2 C H 3 outranks — C H 3 — C ( C ,H,H) — C (H,H,H) higher lower
CIP Rules
Work outward from the point of attachment, comparing all the atoms attached to a particular atom before proceeding further along the chain. —C H( C H 3 ) 2 outranks —C H 2 C H 2 CH 3 —C ( C , C ,H) —C ( C ,H,H) higher lower
CIP Rules
higher lower —C H( C H 3 ) 2 outranks —C H 2 C H 2 CH 3 —C ( C , C ,H) —C ( C ,H,H) higher lower
higher
CIP Rules
higher lower lower —C H 2 C H( C H 3 ) 2 outranks —C H 2 C H 2 C H( C H 3 ) 2 higher lower
(Z)
- configuration
CIP Rules
Evaluate substituents one by one. The ranking is not cumulative: Do not add atomic numbers within groups.
—C H 2 O H outranks —C (CH 3 ) 3 —C ( O ,H,H) —C (C,C,C) higher lower
CIP Rules
An atom that has double or triple bonds to another atom is considered to be replicated as a substituent on that atom. See oxygen: —C H= O outranks —C H 2 O H —C ( O , O ,H) —C ( O ,H,H) higher lower
Question
The molecules above are (E) configurations.
True (A) False (B)
Question
The molecules above are (Z) configurations.
True (A) False (B)
Disubstituted Cyclohexanes cis-trans Isomerism
Cyclic Stereoisomers
In cyclic structures (rings)
cis
and
trans
notation is used to distinguish between stereoisomers just as in C=C double bonds, Cis — identical groups are positioned on the SAME side of a ring -drawn as being planar. Trans — identical groups are positioned on OPPOSITE sides of a ring -drawn as being planar.
Cycloalkane Stereochemistry cis -trans Isomers
Cyclohexane Stereochemistry
Drawings: cis isomers & the need for perspective Are the methyl groups axial or equatorial?
What is the actual conformational shape of the cyclohexane ring?
H CH 3
Chair Conformers
cis-1,4-dimethylcyclohexane
H
ring-flip
CH 3 H
cis-1,4-dimethylcyclohexane
3 C H CH 3 H
Cyclohexane Stereochemistry
Trans
isomers
H 3 C H
Chair Conformers
trans-1,4-dimethylcyclohexane
H CH 3 CH 3
ring-flip
H
trans-1,4-dimethylcyclohexane
CH 3 H
Stereochemistry
cis-
1,2-disubstituted-cyclohexane
axial equatorial
Stereochemistry
trans
-1-
tert
-Butyl-3-Methylcyclohexane
Cyclohexane Stereochemistry Cis -Trans Isomers Position 1,2 1,3 1,4 cis trans e,a or a,e e,e or a,a e,e or a,a a,e or e,a e,a or a,e e,e or a,a a = axial; e = equatorial
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. mirror images C. different molecules D. constitutional isomers E. cis and trans isomers
Question
Consider the molecule below. What is the maximum number of methyl groups that can be in the equatorial position at the same time?
A. 0 B. 1 C. 2 D. 3 E. 4
Conformations of Fused Rings
Stability of Fused Rings
Trans-fused cyclohexane rings are more stable than cis-fused
Conformations of Fused Rings
Worksheet 7 (Part 2): Ambrox
Many Bicyclic Systems
.
• There are many important structures that result when one ring is fused to another.
• Camphor, which you smelled the first day of class, and camphene are fragrant natural products isolated from evergreens.
Bicyclic Compounds Nomenclature
Representing compounds with two fused rings .
To name a bicyclic compound, include the prefix “bicyclo” in front of the
total carbon
alkane name. For example, the compounds below could both be named, bicycloheptane.
Bicyclic Compounds Nomenclature
The two molecules are not identical, therefore they cannot have the same name.
Count the number of carbons connecting the bridgeheads.
Bicyclic Compounds Nomenclature
1. Start numbering at a bridgehead carbon and number the longest carbon chain connecters first.
1. Then give the substituents the lowest numbers possible.
• Practice with SKILLBUILDER 4.5.
Bicyclic Compounds Nomenclature
Decalin = Bicyclo[4.4.0]decane
Decalin-like
Structure of Steroids
A B C D • Fundamental framework of steroids is a tetracyclic carbon framework.
Steroids
Structure of Cholesterol
CH 3 CH 3 CH 3 CH 3 H CH 3 H H HO Cholesterol is an important steroid endogenously produced in all plants and animals.
Cholesterol
CH 3 H CH 3 CH 3 CH 3 CH 3 H H HO • Cholesterol is essential to life. It is the biosynthetic precursor of a large number of important molecules: Sex hormones, Vitamin D, Bile acids, Corticosteroids
Hormonal Steroids
• There are many biologically important steroids, two related to primary sex traits are:
Vitamin D
3 CH 3 CH 3 CH 3 CH 3 H HO • Insufficient sunlight can lead to a deficiency of vitamin D 3 , interfering with Ca 2+ transport and bone development. Rickets may result; as well as very bad moods.
HO
Cholesterol: Biochemical Reactions
CH 3 CH 3 CH 3 CH 3 H CH 3 H H + H 2
H 2
Cholic Acid
H H 2 H
Cholic Acid
•What functions are H O CH 3 CH 3 O OH present?
CH 3 H • Is the A/B ring system H H cis or trans?
H O
|
O H H
H
•Oxidation in the liver degrades cholesterol to produce Cholic acid which is the most abundant of the bile acids.
Cortisone
O CH 3 O H O O CH 3 H H H O H •What principal functions are present?
•Corticosteroids are involved in maintaining electrolyte levels, in the metabolism of carbohydrates, and in mediating allergic reactions by suppressing the immune system.
•What principal functions are present?
Progesterone
H 3 C H O H 3 C H H O • Supresses ovulation during pregnancy.
Conformations of Multi-fused Rings
• Trans-fused cyclohexane ring is more stable than cis-fused cyclohexane ring.
DIAMOND:
Molecular Chirality: Enantiomers
Chirality
Chirality
“I call any geometrical figure, or group of points, hands are homochirally similar.”
chiral,
and say that it has chirality, if its image in a plane mirror … cannot be brought to coincide with itself. Two equal and similar right
Sir William Thomson (Lord Kelvin) The Baltimore Lectures, 1904
Chirality
A molecule is
chiral
if its two mirror image forms are not superimposable upon one another. A molecule is
achiral
if its two mirror image forms are superimposable.
Tetrahedral Atoms
Achiral:
Chirality in Three Dimensions
Br
Bromochlorofluoromethane is chiral
Cl H It cannot be superimposed point for point on its mirror image.
F
Bromochlorofluoromethane is chiral
Br Cl F H Cl Br H F To show nonimsuperposability, rotate this model 180 ° around a vertical axis.
Enantiomers
Chirality & nonsuperimposable mirror images
constitutional isomers
Isomers
stereoisomers
constitutional isomers
Isomers
stereoisomers enantiomers diastereomers
Stereochemistry
• Two types of stereoisomers:
enantiomers
• pairs of compounds that are nonsuperimposable mirror images of each other
diastereomers
• stereoisomers that are not mirror images of each other – Eg. geometric isomers (cis-trans, E-Z isomers)
Stereochemistry
• Many molecules and objects are achiral : – identical to its mirror image – not chiral
Stereochemistry
• Cis-1,2-dichlorocyclopentane is achiral even though it contains 2 chiral carbon atoms: – It contains an internal mirror plane of symmetry • Any molecule that has an internal mirror plane of symmetry is achiral even if it contains chiral carbon atoms.
Question
Both cis- and trans-1,2-dimethylcyclohexane are chiral.
True (A) False (B)
Question
How many of the following compounds contain an internal mirror plane of symmetry?
A) 1 B) 2 C) 3 D) 4
Question
Which of the following molecules is chiral?
B A C D
The chiral carbon atom
w x C z y a carbon atom with four different groups attached to it also called: chiral center; chiral carbon asymmetric center asymmetric carbon stereocenter stereogenic center
Stereoisomers
• There are 8 chiral carbon atoms in chlolesterol, which can have a total of 2 8 stereoisomers.
• SEE: SKILLBUILDER 5.7.
Symmetry and Chirality
• Molecules with an even number of chiral centers that have a plane of symmetry are achiral and called MESO compounds.
• Another way to test if a compound is a MESO compound is to see if it is identical to its mirror image. If identical, it is NOT chiral. It is achiral. • Meso compounds have less than the predicted number of stereoisomers based on the 2 n formula.
• SEE: SKILLBUILDER 5.8.
Enantiomers
Stereochemistry
• Enantiomers are different stereochemical compounds: They have the same boiling point, melting point, density. Their physical/chemical properties are identical.
They differ in rotation of plane polarized light, doing so in equal but opposite directions. (polarimetry) They behave differently with other chiral molecules • Enzymes • Receptors: eg. taste and scent
Importance of Stereochemistry
• Enzymes are capable of distinguishing between : stereoisomers
Red Wine / Stereochemistry
Absolute Configuration
In 1847, Louis Pasteur performed the first resolution of enantiomers from a racemic mixture of tartaric acid salts.
The different enantiomers formed different shaped crystals, which he microscopically separated with tweezers.
O CH 3
Smells
O CH 3 H 3 C CH 2 ( –)-Carvone spearmint oil H 3 C CH 2 (+)-Carvone caraway seed oil
Chiral drugs Ibuprofen
is chiral, but normally sold as a racemic mixture, which is 50% of each enantiomer H 3 C H C CH 2 CH(CH 3 ) 2 HO C O The enantiomer above is responsible for its analgesic and anti-inflammatory properties.
Stereochemistry
• The pharmacological activity of many drugs depends on their stereochemistry:
(S)-(+)-ketamine anesthetic (R)-(-)-ketamine hallucinogen
Stereochemistry
A Sedative or a Potent Teratogen?
Chirality and Chiral Carbon Atoms
A molecule with a single stereogenic center is chiral. A carbon atom with four different substituents is a stereogenic center and chiral.
2-Butanol is an example.
H CH 3 C OH CH 2 CH 3
Examples of molecules with 1 chiral carbon
CH 3 CH 3 CH 2 CH 2 C CH 2 CH 2 CH 2 CH 3 CH 2 CH 3 a chiral alkane
Examples of molecules with 1 chiral carbon
OH Linalool, a naturally occurring chiral alcohol
Examples of molecules with 1 chiral carbon
H 2 C CHCH 3 O 1,2-Epoxypropane: a chiral carbon can be part of a ring attached to the chiral carbon are: —H —CH 3 —OCH 2 —CH 2 O
Examples of molecules with 1 chiral carbon
H CH 3 C CH 3 CH 2 Limonene: a chiral carbon can be part of a ring attached to the chiral carbon are: —H —CH 2 CH 2 —CH 2 CH= —C=
Examples of molecules with 1 chiral carbon
H D C T CH 3 Chiral as a result of isotopic substitution
Optical Rotation
Relative Configuration and Absolute Configuration
Optical Activity
• Chiral compounds are optically active: – capable of rotating the plane of polarized light • Enantiomers rotate the plane of polarized light by exactly the same amount but in opposite directions.
(S)-(+)-d-2-butanol +13.5
o rotation (R)-(-)-l-2butanol -13.5
o rotation
Optical Activity
• Compounds that rotate the plane of polarized light to the right (clockwise) dextrorotary.
are called •
d
• (+) IUPAC convention • Compounds that rotate the plane of polarized light to the left (counterclockwise) are called levorotary.
•
l
• (-) IUPAC convention
Optical Activity
Configuration
Relative configuration
compares the arrangement of atoms in space of one compound with those of another.
Absolute configuration
is the precise arrangement of atoms in space.
Configuration
Relative configuration
compares the arrangement of atoms in space of one compound with those of another.
Until the 1950s, all configurations were relative
Absolute configuration
is the precise arrangement of atoms in space.
Now, the absolute configuration of almost any compound can be determined
Relative configuration: Optical Rotation
Pd CH 3 CHCH CH 2 CH 3 CHCH 2 CH 3 [ OH a ] + 33.2
° OH [ a ] + 13.5
° No bonds are made or broken at the chiral carbon in this experiment. Therefore, when (+)
d
-3-buten-2-ol and (+)
d
-2-butanol have the same sign of rotation, the arrangement of atoms in space at the chiral carbon atom is analogous. The two have the same relative configuration.
HO H
Two possibilities
H 2 , Pd HO H H OH H 2 , Pd H OH But in the absence of additional information, we can't tell which structure corresponds to (+)
d
-3-buten-2-ol, and which one to ( –)
l
-3-buten-2-ol.
HO H
Two possibilities
H 2 , Pd HO H H OH H 2 , Pd H OH Nor can we tell which structure corresponds to (+)-2-butanol, and which one to ( –)-2-butanol.
HO H
Absolute configurations
H 2 , Pd HO H [ a H ] +13.5
OH ° H 2 , Pd [ a ] +33.2
° H OH [ a ] –13.5° [ a ] –33.2°
Relative configuration
HBr CH 3 CH 2 CHCH 2 OH CH 3 [ a ] -5.8
° CH 3 CH 2 CHCH CH 3 [ a ] + 4.0
° 2 Br Not all compounds that have the same relative configuration have the same sign of rotation. No bonds are made or broken at the chiral carbon in the reaction shown, so the relative positions of the atoms are the same. Yet the sign of rotation can change.
Absolute Configuration
The
R,S
system of nomenclature Rank the 4 groups (atoms) bonded to the chirality center There is NO DIRECT CORRELATION between (R) and (S) configurations, and the relative configuration / the optical rotation: (+)/(-)
The Cahn-Ingold-Prelog (CIP) Rules Treat the single carbon atom as a double bond, but taking into account the tetrahedral geometry
1. Rank the substituents at the stereogenic carbon center according to their atomic number.
2. Orient the molecule so that lowest-ranked substituent points away from you.
3. If the order of decreasing precedence traces a clockwise path, the absolute configuration is
R
. If the path is anticlockwise, the configuration is
S
.
Orient the lowest priority
(4)
away from you: [
Highest is (1)]
Switch any 2 substituents and the new configuration is opposite R S; S R
Clockwise = R configuration Counterclockwise = S configuration
Designating Configurations
• The groups attached to the chiral center are the same (-CH 2 -) below.
• Analyze the atomic numbers of the next atoms in the bonding sequence.
4 1 Adjacent atoms: Tie Next atoms:: 2 3
Designating Configurations
• Double bonds count as two single bonds.
Question
• Is the following molecule is
R
or
S
?
A = R B = S-
Naming from the Perspective Formula
1. Rank the groups bonded to the asymmetric carbon 1 4 2 3 2. If the group (or atom) with the lowest priority is bonded by hatched wedge,
3. If necessary, rotate the molecule so that the lowest priority group (or atom) is bonded by a hatched wedge 4.
Enantiomers of 2-butanol
CH 3 CH 2 H C OH H 3 C (
S
)-2-Butanol H CH 2 CH 3 HO C CH 3 (
R
)-2-Butanol
Question
What is the stereochemical designation of the following molecule?
A. (R) B. (S) C. non-chiral (achiral)
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
Question
Indicate the relationship of the pair of molecules shown .
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
chiral carbon in a ring
H 3 C H
R
H H —CH 2 C=C > —CH 2 CH 2 > —CH 3 > —H
Question
H
A B
The S-isomer is an effective sedative. The R- is a teratogen in humans, but not rats. In the structures above, which is the R-isomer, A or B?
Question
What is the stereochemical designation of the following molecule?
A. (R) B. (S) C. non-chiral (achiral)
Fischer Structures
“The Horizontal Bonds Point Towards You!” Emil Fischer,
1815-1919 (the second) Nobel Prize in Chemistry, 1902
Rules for Fischer projections
H Br Cl F
Arrange the molecule so that horizontal bonds at chiral carbon point toward you and vertical bonds point away from you.
Rules for Fischer projections
H Br Cl F
Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
Rules for Fischer projections
H Br Cl F Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back.
Question
What is the stereochemical designation of the indicated chirality center?
A. (R) B. (S) C. non-chiral (achiral)
Disubstituted Cyclohexanes Stereoisomerism
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers
Question
Indicate the relationship of the pair of molecules shown.
A. same molecules B. enantiomers C. diastereomers D. different molecules E. constitutional isomers