5.1 overview of isomerism isomers - vanderbilt …chapter 5: stereoisomerism- three-dimensional...
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Chapter 5: Stereoisomerism- three-dimensional arrangement of atoms (groups) in space
5.1 Overview of Isomerism
Isomers: different chemical compounds with the same formula
Constitutional isomers: same formula, but different connectivity of atoms (or groups)
Stereoisomers: molecules with the same connectivity but different spatial arrangement of atoms (groups)
H
H3C
H
CH3
H
H3C
CH3
H
cis-1,2-dimethylcyclopropane trans-1,2-dimethylcyclopropane
H3C
H H
CH3 H3C
H CH3
H
cis-2-butene trans-2-butene93
different carbon skeleton different functional group different position of FG
C5H12 C4H10O
OHbutanol
O
diethyl etherNH2
NH2
C4H11N
5.2 Introduction to Stereoisomerism
Enantiomers: non-superimposable mirror image isomers.
Enantiomers are related to each other much like a right hand is related to a left hand
Enantiomers have identical physical properties, e.g., bp, mp, etc.
Chirality (derived from the Greek word for hand). Enantiomers are said to be chiral.
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Chirality Center: Chiral molecules most commonly contain a carbon with four different groups; the carbon is referred to as a chiral center, or asymmetric center, or stereogenic center, or stereocenter.
CO2H
H
HO
H3CHO2C
H
OH
CH3
CO2H
H
HO
H3CH3C
HO
H
CO2H
CO2H
H
HO
H3CH
CO2H
HO
H3C
CO2H
H
HO
H3CHO
HO2C
H
CH3
CO2H
H
HO
H3CCO2H
OH
H
H3C
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5.3 Designating Configuration Using the Cahn-Ingold-Prelog System – Assigning the Absolute Configuration
1a. Look at the four atoms directly attached to the chiral carbon atom and rank them according to decreasing atomic number.
priority of common atoms: I > Br > Cl > S > P > F > O > N > C > H
1b. If the two atoms attached to the chiral carbon are identical (designated A and B below), look at all the atoms directly attached to the identical atoms in questions (designated A-1, A-2, A-3 and B-1, B-2, B-3). Assign priorities to all these atoms based on atomic number (1 is the highest priority, 3 the lowest).
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A-1
B-1
A-2
A
B
B-2
A-3
B-3
X
Group A
Group B
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1c. Compare the highest priority atoms, i.e. compare A-1 with B-1. If A-1 is a higher priority atoms than B-1, then A is higher priority than B. If A-1 and B-1 are the same atom, then compare the second highest priority atoms directly bonded to A and B (A-2 with B-2); if A-2 is a higher priority atom than B-2, then A is higher priority than B. If A-2 and B-2 are identical atoms, compare A-3 with B-3.
1d. If a difference still can not be found, move out to the next highest priority group (A-1 and B-1 in the diagram) and repeat the process.
1e. Multiple bonds are considered equivalent to the same number of single bonded
atoms.
H = C C H
CC
C C
H
O =
HO
O C
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2a. Orient the molecule so that the lowest priority atom is in the back (away from you). Look at the remaining three groups of priority 1–3. If the remaining three groups are arranged so that the priorities 1→2→3 are in a clockwise fashion, then assign the chiral center as R (“rectus” or right). If the remaining three groups are arranged 1→2→3 in a counterclockwise manner, then assign the chiral center as S (“sinister” or left).
CO2H
H
HO
H3C
4
12
3
OH
CO2HH3C H
1
234
orient lowest priority group away
counterclockwise = S
H3C
HO
H
CO2H
4
2
1
3CH3
CO2HHO H
3
214
orient lowest priority group away
clockwise = R
2b. Or use the “Hand Rule.” Orient the lowest priority group up. Point your thumb in the direction of the lowest priority group. If you need to use your right hand so that your fingers point in the direction of the group priorities in the order 1→2→3, then the stereogenic center is assigned R (“rectus” or right). If your left hand is required so that your fingers point in the direction of the group priorities 1→2→3, the the stereogenic center is assigned S (“sinister” or left).
(S)-(+)-Lactic acid(Left Hand)
(R)-(-)-Lactic acid(Right Hand)
H
HO2C CH3OH
4
2
3
1H
CO2HH3CHO
4
2
3
1
H3C
HO
H
CO2H
4
2
1
3CO2H
H
HO
H3C
4
12
3
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You must be able to draw tetrahedral carbons properly!!
LINEAR ALKANES: You should draw the carbon backbone in the plane of the paper, and draw substituents either coming towards you (with wedges) or going away from you (with dashes). Note that each carbon should look like a tetrahedron.
Correct Incorrect • •• •
HC
HO2C CH3OH
In the plane of the paperand in the same plane as the tetrahedral carbon (adjacent position off the tetrahedral carbon)
Wedge: projecting outof the plane of the papertoward you
Dash: projecting behind the plane of the paperaway from you
Dash and Wedge are onadjacent position off the tetrahedral carbon
HC
HO2C CH3OH
HC
CO2HH3CHO
HC
HO2C CH3OH
Cl
Cl
Cl
ClOH OH
Br
Br
OH OH
BrBr
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Interchanging any two groups inverts the stereochemistry. Switch the lowest priority group to the desired position. Then switch the other two groups. The “double-switch” does not change the stereochemistry.
CH3C
HO2C HOH
CO2HC
HH3CHO switch the H and OH
CO2HC
OHH3CH
inverts the stereochemistry
switch the CH3 and CO2H
CH3C
OHHO2CH
inverts the stereochemistry
12
3clockwise = R
switch the H and CH3HC
HO2C CH3OH
switch the OH and CO2H H
CHO CH3
CO2H1
2
3
left hand = S
inverts the stereochemistry inverts the
stereochemistry
5.4 Optical Activity – samples enriched in one enantiomer will rotate plane polarized light and are said to be optically active. The optical rotation is dependent upon the substance, the sample concentration, the path length through the sample, temperature, and the wavelength of light.
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101
589 nm - D-line of a sodium lamp
Plane polarized light: light that oscillates in only one plane
Polarimeter
0 ° + α 0 °- α
dextrorotatory (d): rotates lightto the right (clockwise)
levororotatory (l): rotates lightto the left (counterclockwise)
CH3CH
HOHO2C CH3
CH
HO2CHO
C
CHO
CH2OHHOH C
CHO
HOH2C OHH
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α : angle (# of degrees) plane polarized light is rotated by an optically active sample. Expressed in degrees.
Enantiomers will rotate plane polarized light the same magnitude (α) but in opposite directions (+ or -)
90% (+) + 10% (-) will rotate light 80% of pure (+) 75% (+) + 25% (-) will rotate light 50% of pure (+) 50% (+) + 50% (-) will be optically inactive
50:50 mixture of enantiomers (+/-): racemate or racemic mixture
Each individual molecule may be chiral; however, the bulk property of the substance is achiral (if it is in an achiral environment). Specific Rotation [α]D: a standardized value for the optical rotation
[α]λ = T α l • c
α = optical rotation in degrees l = path length in dm c = concentration of sample in g/mL T = temperature in °C λ = wavelength of light, usually D for the
D-line of a sodium lamp (589 nm)
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103
[α]D = +14.5° (c 10, 6N HCl)
for alanine:
The specific rotation is a physical constant of a chiral molecule
The [α]D may also depend upon solvent, therefore the solvent is usually specified.
HO2C
NH2H
An optically pure substance consists exclusively of a single enantiomer.
Optical purity of a optically active substance is expressed as the enantiomeric excess = % one enantiomer – % other enantiomer
ee = ______________________________ • 100
(observed α)
(α of the pure enan;omer)
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5.5 Stereoisomeric Relationships: Enantiomers and Diastereomers
Isomers: different chemical compounds with the same formula
Constitutional isomers: same formula, but different connectivity of atoms (or groups)
Stereoisomers: same connectivity but different spatial arrangement of atoms (groups)
enantiomers: non-superimposable, mirror image isomers
diastereomers: non-superimposable, non-mirror image isomers
H
H3C
H
CH3
H
H3C
CH3
H
cis-1,2-dimethylcyclopropane trans-1,2-dimethylcyclopropane
H3C
H H
CH3 H3C
H CH3
H
cis-2-butene trans-2-butene
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105
Diastereomeric relationships occur when more than one chiral center is present in a molecule.
OH
CH3
OH
CH3
OH
CH3
OH
CH3(1R, 2S) (1S, 2R) (1R, 2R) (1S, 2S)
enantiomers enantiomers
diastereomers (non-superimposable, non-mirror image)
Enantiomers must have the opposite stereochemistry (configuration) at all chiral centers.
In general, enantiomers have identical physical properties except optical rotation (which is equal in magnitude but opposite in sign). Diastereomers may have completely different physical properties.
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Maximum number of stereoisomers = 2n. where n = number of structural units capable of stereochemical variation. Structural units include chiral centers and cis and/or trans double bonds.
HO
CH3 H
CH3
H H
H
H****
****
Cholesterol: eight chiral centers 28 = 256 possible stereoisomers (only one of which is naturally occurring)
OH
C
H
CH3CH
CH
H3C
H3C
H
H
OHH
H
H3C
H
OHH
H3C
H
H
HHO
H
H3C
H
HHO
(S) (S)
(R) (R)
trans
trans
cis
cis
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5.6 Symmetry and Chirality
Monarch butterfly: bilateral symmetry=
mirror symmetry
Whenever winds blow butterflies find a new place on the willow tree
-Basho (~1644 - 1694)
Point (center) of symmetry
Mirror symmetry
Mirror symmetry & axis (6 fold) of symmetry
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Molecules are not chiral if they contain a plane of symmetry: a plane that cuts the molecule in half so that one half is the mirror image of the other half. Molecules (or objects) that possess a mirror plane of symmetry are superimposable on their mirror image and are termed achiral.
CO2H
CH3
H
H HO2C
CH3
H
H
CO2H
CH3
H
HH
H
CH3
CO2H
achiral chiral
Chiral center (stereogenic, asymmetric)
C CC
HOH
HH
H H
O
O
symmetryplane
C CC
HOH
HH
H OH
O
OCH3
H
Not asymmetry
plane
108
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Meso Compounds: molecules that contain chiral atoms but are achiral because they also possess a plane of symmetry.
Br
H
Br
H
Br
H
Br
H
Br
H
H
Br
H
Br
Br
H
meso (achiral) chiral
HO2CCO2H
OH
OH
HO2CCO2H
OH
OHHO2C
CO2HHO
OH
H
HCO2H
OHH
HO2C
HOH
HO2C
CO2HH
OH
OH
H
CO2H
OHH
HO2C
HHO
mirror plane
no mirror plane
5.7 Fischer Projections - representation of a three-dimensional molecule as a flat structure. A tetrahedral carbon is represented by two crossed lines:
vertical line is going back behind the plane of the paper (away from you)
horizontal line is coming out of the plane of the page (toward you)
carbon substituent
(R)-(+)-glyceraldehyde (S)-(-)-glyceraldehyde
OHHCHO
CH2OHCH2OHCCHO
HOH
CHO
CH2OHH OH
HHOCHO
CH2OHCH2OHCCHO
HHO
CHO
CH2OHHO H
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Manipulation of Fischer Projections 1. Fischer projections can be rotated by 180° (in the plane of the
page) only!
180° 180°
CHO
CH2OHH OH
CHO
CH2OHHHO
(R) (R)CHO
CH2OHOHH
CHO
CH2OHHO H
(S) (S)
180 ° 180 °
Valid Fischer
projection
Valid Fischer
projection
111
a 90° rotation inverts the stereochemistry and is illegal!
90°
90 °
CHO
CH2OHH OH
(R)
90 °
H
OHCH2OHOHC
(S)
≠
This is not the correct conven;on for Fischer projec;ons
Should be projec;ng toward you Should be projec;ng away you
This is the correct conven;on for Fischer projec;ons and is the enan;omer
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2. If one group of a Fischer projection is held steady, the other three groups can be rotated clockwise or counterclockwise.
holdsteady
120° 120°
holdsteady hold
steady
holdsteady
120°
holdsteady
120°
holdsteady
CHO
CH2OHH OH
holdsteady
CHO
HHO CH2OH
CHO
CH2OH
HO H
holdsteady
H
CH2OH
OHC OH
(R) (R)
(S) (S)
113
Assigning R and S Configuration to Fischer Projections 1. Assign priorities to the four substituents according to the Cahn-Ingold-Prelog rules 2. Perform the two allowed manipulations of the Fischer projection to place the lowest priority group at the top or bottom. 3. If the priority of the other groups 1→2→3 is clockwise then assign the carbon as R, if the priority of the other groups 1→2→3 is counterclockwise then assign the center as S.
CH3
HCO2HH2N
3
2
4
1
1-2-3 clockwise = R
CO2H
CH3
H NH2
2
1
3
4CO2H
HH2N CH3
2
3
4
1
CO2H
CH3
H2N H1
2
3
4
place at the top
hold steadyrotate otherthree groupscounterclockwise
H
CH3
HO2C NH2 12
3
4
1-2-3 counterclockwise = S
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Fischer projections with more than one chiral center: CO2H
NH2H
CH3
H OH
CO2H
HH2N
CH3
HO H
CO2H
HH2N
CH3
H OH
CO2H
NH2H
CH3
HO H
mirror images(enantiomers)
non-mirror image(diastereomers)
mirror images(enantiomers)
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5.8 Conformationally Mobile Systems
not really a plane of symmetry
(S)(S)
(R)(R)
H
H
CH3
CH3 H3C
CH3
H
H
(S)(S)
(R)(R)
enantiomers
(S)(S)
(R)(R)CH3
H
H
CH3(S)(S)
(R)(R)
CH3
H3C
H
HH
H3C
H
CH3
plane of symmetry
CC
HH3C
HH
H CH3
CC
HH3C
HH
H3C H
H
H3C HH3C
HHH
CH3HH3C
H H
The gauche conformation of butane is chiral
1,2-dimethylcycloheane and the gauche conformation of butane are chiral; however, . . . .
The chair-chair interconversion coverts one enantiomer to the other.
Rotation about the C2-C3 bond coverts one chiral conformation into its enantiomer.
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5.9 Resolution of Enantiomers - a process of separating a racemate into pure enantiomers.
Crystallization
Chiral resolving agents. The enantiomers of the racemate must be temporarily converted into diastereomers.
N(S)(S)
(R)(R)
(R)(R)
(S)(S)N
H
H
H3C CO2HC(R)(R)
NH2H
H3C CO2HC(S)(S)
HH2N
+
H3C CO2C(R)(R)
NH2H
N(S)(S)
(R)(R)
(R)(R)
(S)(S)N
H
H
N(S)(S)
(R)(R)
(R)(R)
(S)(S)N
H
H
H
H
•
•
(-)-sparteine
H3O+
H3O+
H3C CO2C(S)(S)
HH2N
H3C CO2HCNH2H
H3C CO2HCHH2N
(S)-(+)
(R)-(–)
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Chapter 6 Chemical Reactivity and Mechanisms 6.1 Enthalpy (ΔH) - the heat (energy) exchange between the reaction and its environment at constant pressure
Bond breaking processes require heat from the environment. Homolytic: symmetrical bond breaking process
Heterolytic: unsymmetrical bond breaking processes Bond dissociation energy (ΔH°) – energy required for homolytic cleavage of a covalent bond. Table 6.1 (p. 238)
Heat of reaction (ΔH°) - total enthalpy change bond during a reaction. ΔH°products – ΔH°reactant = ΔH°reaction
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