1. Organic Chemistry, 7th Edition L. G. Wade, Jr.
Chapter 5
Stereochemistry
© 2010, Prentice Hall

2. Book: Wade
Chapter: 5
Chapter 5

3. Stereochemistry -study of the three-dimensional structure of molecules
isomers are grouped into two broad classes: constitutional isomers and stereoisomers.
Constitutional isomers (structural isomers) differ in their bonding sequence
Stereoisomers have the same bonding sequence,but they differ in the orientation of their atoms in space

4. stereoisomers often have remarkably different physical, chemical, and biological properties
Example: cis and trans isomers of butenedioic acid
HOOC-CH=CH-COOH
Different arrangement in space
Cis isomer – maleic acid
Trans isomer – fumaric acid

5. explained why several types of isomers exist
discovery of stereochemistry - most important breakthroughs in the structural theory of organic chemistry
explained why several types of isomers exist
forced scientists to propose the tetrahedral carbon atom
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6. Chirality
What is the difference between your left and your right hand/feet?
they are nonsuperimposable (nonidentical) mirror images of each other
Objects that have left-handed and right-handed forms are called chiral

7. Chirality “Handedness”: Right glove doesn’t fit the left hand.
Mirror-image object is different from the original object -chiral
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8. Achiral
Objects that can be superimposed are achiral.
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9. Other examples in every day life
American vs.English car? –nonsuperimposable mirror images
Screws - right-hand threads and are turned clockwise to tighten
Mirror image - is a left-handed screw, turned counterclockwise to tighten
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10. Chirality and Enantiomerism in Organic Molecules
molecules are either chiral or achiral
superimposable if they can be placed on top of each other
Nonsuperimposable mirror-image molecules are called enantiomers
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11. Stereoisomers
Enantiomers: Nonsuperimposable mirror images, different molecules with different properties.
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12. Asymmetric Carbon Atoms, Chirality Centers, and Stereocenters
What is it about a molecule that makes it chiral?
The most common -a carbon atom that is bonded to four different groups
an asymmetric carbon atom or a chiral carbon atom
most common example of a chirality center (or chiral center)
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13. Chiral Carbons
It’s mirror image will be a different compound (enantiomer).
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14. Achiral Compounds
Take this mirror image and try to superimpose it on the one to the left matching all the atoms. Everything will match.
When the images can be superposed the compound is achiral.
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15. Chirality centers belong to an even broader group called stereocenters
stereocenter (or stereogenic atom) - any atom at which the interchange of two groups gives a stereoisomer
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16. Generalization
1. If a compound has no asymmetric carbon atom, it is usually achiral.
2. If a compound has just one asymmetric carbon atom, it must be chiral.
3. If a compound has more than one asymmetric carbon, it may or may not be chiral.
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17. Assignment
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18. Mirror Planes of Symmetry
Any compound that is chiral must have an enantiomer
Any compound that is achiral cannot have an enantiomer
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19. cis-1,2-dichlorocyclopentane is achiral
mirror image identical with the original molecule
bisecting a carbon atom and its two hydrogen atoms, the part of the molecule that appears to the right of the line is the mirror image of the part on the left
internal mirror plane (σ)

20. Generalization converse is not true, however
cannot find a mirror plane of symmetry, that does not necessarily mean that the molecule must be chiral
no internal mirror plane of symmetry, yet the mirror image is superimposable on the original molecule.

21. (R) and (S) Nomenclature of Asymmetric Carbon Atoms
Example: alanine
Asymmetric C atom and exists in 2 enantiomers
mirror images are different, and this difference is reflected in their biochemistry
enantiomer on the left can be metabolized by the usual enzyme

22. difference between the two enantiomers - lies in the 3D arrangement of the four groups around the asymmetric carbon atom
Any asymmetric carbon - two possible (mirror-image) spatial arrangements
Configurations

23. If we can name the two configurations of any asymmetric carbon atom-way of specifying and naming the enantiomers of any chiral compound
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24. Cahn–Ingold–Prelog convention
most widely accepted system for naming the configurations of chirality centers
asymmetric carbon atom is assigned a letter (R) or (S)
two-step procedure that assigns “priorities”
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25. Assign a relative “priority” to each group bonded to the asymmetric carbon.
Atoms with higher atomic numbers receive higher priorities
Note that we look only at the atomic number of the atom directly attached to the asymmetric carbon, not the entire group
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26. the heavier isotopes have higher priorities
What about isotopes?
the heavier isotopes have higher priorities
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27. In case of ties, use the next atoms along the chain of each group as tiebreakers
higher priority to isopropyl –CH(CH3)2 than ethyl –CH2CH3 or bromethyl –CH2CH2Br
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28. first carbon in the isopropyl group is bonded to two carbons
first carbon in the ethyl group (or the bromoethyl group) is bonded to only one carbon
Ethyl and bromoethyl have identical first atoms and second atoms
bromine atom in the third position gives higher priority than ethyl

29. when you break a bond, you always add two imaginary atoms
Treat double and triple bonds as if each were a bond to a separate atom
imagine that each pi bond is broken and the atoms at both ends duplicated
when you break a bond, you always add two imaginary atoms
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30. When you assign the priorities:
put the fourth-priority group away from you and view the molecule with the first, second, and third priority groups radiating toward you
Draw an arrow from the first-priority group, through the second, to the third
arrow points clockwise - asymmetric carbon atom is called (R)
arrow points counterclockwise - chiral carbon atom is called (S)

31. Assign Priorities Atomic number: F > N > C > H
Once priorities have been assigned, the lowest priority group (#4) should be moved to the back if necessary.
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32. Assign Priorities Counterclockwise (S)
Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group 1. Ignore Group 4.
Clockwise = (R) and Counterclockwise = (S)
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33. Example
Clockwise (R)
When rotating to put the lowest priority group in the back, keep one group in place and rotate the other three.
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34. Example (Continued) 3 1 4 2
Counterclockwise (S)
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35. Solved Problem 1 Solution
Draw the enantiomers of 1,3-dibromobutane and label them as (R) and (S). (Making a model is particularly helpful for this type of problem.)
Solution
The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first priority, the (–CH2CH2Br) group second priority, the methyl group third, and the hydrogen fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign (R) or (S) as shown.
Copyright © 2006 Pearson Prentice Hall, Inc.
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36. Properties of Enantiomers
Same boiling point, melting point, and density.
Same refractive index.
Rotate the plane of polarized light in the same magnitude, but in opposite directions.
Different interaction with other chiral molecules:
Active site of enzymes is selective for a specific enantiomer.
Taste buds and scent receptors are also chiral. Enantiomers may have different smells.
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37. Optical Activity
Enantiomers rotate the plane of polarized light in opposite directions, but same number of degrees.
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38. Polarimetry common method used to distinguish between enantiomers
based on their ability to rotate the plane of polarized light in opposite directions
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39. Polarimeter Clockwise Counterclockwise Dextrorotatory (+)
Levorotatory (-)
Not related to (R) and (S)
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40. Specific rotation angular rotation - characteristic physical property
The rotation (α) observed in a polarimeter depends on the concentration of the sample solution and the length of the cell, as well as the optical activity of the compound
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41. To use the rotation of polarized light - standardize the conditions for measurement
Specific rotation [α] - rotation found using a 10-cm (1-dm) sample cell and a concentration of 1 g/mL.
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42. Specific Rotation
Observed rotation depends on the length of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light.
[] =
 (observed)
c  l
Where  (observed) is the rotation observed in the polarimeter, c is concentration in g/mL and l is length of sample cell in decimeters.
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43. Biological Discrimination of Enantiomers
Biological systems commonly distinguish between enantiomers
two enantiomers may have totally different biological properties
any chiral probe can distinguish between enantiomers, and a polarimeter is only one example of a chiral probe
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44. capable of distinguishing between enantiomers
Enzymes are chiral
capable of distinguishing between enantiomers
only one enantiomer of a pair fits properly into the chiral active site of an enzyme
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45. Example: epinephrine
hormone secreted by the adrenal medulla
synthetic epinephrine is given to a patient – (-) form has the same stimulating effect as the natural hormone
(+) form lacks this effect and is mildly toxic

46. Biological Discrimination
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47. Biological systems - capable of distinguishing between the enantiomers of many different chiral compounds
Example 2: nose is capable of distinguishing between some enantiomers
receptor sites for the sense of smell must be chiral, therefore, just as the active sites in most enzymes are chiral

48. Racemic Mixtures Equal quantities of d- and l- enantiomers.
Notation: (d,l) or ()
No optical activity.
The mixture may have different boiling point (b. p.) and melting point (m. p.) from the enantiomers!
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49. Many reactions lead to racemic products, especially when an achiral molecule is converted to a chiral molecule
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50. Racemic Products
If optically inactive reagents combine to form a chiral molecule, a racemic mixture is formed.
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51. specify the optical purity (o.p.) of the mixture
mixtures that are neither optically pure (all one enantiomer) nor racemic (equal amounts of two enantiomers)
specify the optical purity (o.p.) of the mixture
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52. Optical Purity
Optical purity (o.p.) is sometimes called enantiomeric excess (e.e.).
One enantiomer is present in greater amounts.
observed rotation
rotation of pure enantiomer
X 100
o.p. =
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53. Calculate % Composition
The specific rotation of (S)-2-iodobutane is . Determine the % composition of a mixture of (R)- and (S)-2-iodobutane if the specific rotation of the mixture is -3.18.
3.18
15.90
o.p. =
X 100
= 20%
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54. The enantiomeric excess (e. e
The enantiomeric excess (e.e.) is a similar method for expressing the relative amounts of enantiomers in a mixture
calculate the excess of the predominant enantiomer as a percentage of the entire mixture

55. Chiral Compounds without Asymmetric Atoms
Some compounds are chiral because they have another asymmetric atom which is not carbon
P, S, N – serving as chirality center
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56. Conformational Enantiomerism
Some molecules are so bulky or so highly strained
they cannot easily convert from one chiral conformation to the mirror-image conformation
cannot achieve the most symmetric conformation because it has too much steric strain or ring strain
molecule is conformationally locked
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57. Nonmobile Conformers
The planar conformation of the biphenyl derivative is too sterically crowded. The compound has no rotation around the central C—C bond and thus it is conformationally locked.
The staggered conformations are chiral: They are nonsuperimposable mirror images.
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58. Allenes
contain the C=C=C with two C=C double bonds meeting at a single carbon atom
central carbon atom is sp hybridized and linear
two outer carbon atoms are sp2 hybridized and trigonal
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59. Allenes
Some allenes are chiral even though they do not have a chiral carbon.
To be chiral, the groups at the end carbons must have different groups
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60. 2,3-Pentadiene Is Chiral
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61. Fischer Projections Flat representation of a 3-D molecule.
A chiral carbon is at the intersection of horizontal and vertical lines.
Horizontal lines are forward, out-of-plane.
Vertical lines are behind the plane.
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62. Fischer Projections (Continued)
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63. Fischer Rules Carbon chain is on the vertical line.
Highest oxidized carbon is at top.
Rotation of 180 in plane doesn’t change molecule.
Do not rotate 90!
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64. 180° Rotation
A rotation of 180° is allowed because it will not change the configuration.
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65. 90° Rotation
A 90° rotation will change the orientation of the horizontal and vertical groups.
Do not rotate a Fischer projection 90°.
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66. Fischer Mirror Images
Fisher projections are easy to draw and make it easier to find enantiomers and internal mirror planes when the molecule has 2 or more chiral centers. C H 3 l
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67. Fischer (R) and (S)
Lowest priority (usually H) comes forward, so assignment rules are backwards!
Clockwise is (S) and counterclockwise is (R).
Example:
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68. Diastereoisomers defined as stereoisomers that are not mirror images
either geometric isomers or compounds containing two or more chirality centers
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69. Diastereomers
Molecules with two or more chiral carbons.
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70. Alkenes-Double Bonds
Cis-trans isomers (geometric isomers) are not mirror images, so these are diastereomers.
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71. Rings
Cis-trans isomerism is also possible when there is a ring present
Achiral
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72. Two or More Chiral Carbons
When compounds have two or more chiral centers they have enantiomers, diastereomers, or meso isomers.
Enantiomers have opposite configurations at each corresponding chiral carbon.
Diastereomers have some matching, some opposite configurations.
Meso compounds have internal mirror planes.
Maximum number of isomers is 2n, where n = the number of chiral carbons.
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73. Comparing Structures
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74. Meso Compounds Meso compounds have a plane of symmetry.
If one image was rotated 180°, then it could be superimposed on the other image.
Meso compounds are achiral even though they have chiral centers.
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75. Number of Stereoisomers
The 2n rule will not apply to compounds that may have a plane of symmetry. 2,3-dibromobutane has only 3 stereoisomers: (±) diastereomer and the meso diastereomer.
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76. Properties of Diastereomers
Diastereomers have different physical properties, so they can be easily separated.
Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.
Enantiomers are difficult to separate.
Convert enantiomers into diastereomers to be able to separate them.
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77. Summary 1

78. Study the problems from the book according to the theory Pages 215-217
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79. Summary Chirality Cahn-Ingold-Prelog rule (CIP) Assigning priorities
Racemates
Optical purity
Nonmobile conformers
Allenes
Diastereoisomers
Meso compounds

80. 26.03.2019 (Tuesday) second quiz Chapters 3 and 4 Be on time!