1. Chapter 6 Stereochemistry

2. Constitutional isomers
Isomer Organization
Isomers
Stereoisomers
Constitutional isomers
Enantiomers
Diastereomers
Conformational
Isomers
Meso
compounds
Epimers
Geometric
Cis/trans
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3. Stereoisomers Same bonding sequence. Different arrangement in space.
Example: HOOC-CH=CH-COOH has two geometric (cis-trans) isomers o o
=>
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4. Chirality “Handedness”: right glove doesn’t fit the left hand.
Mirror-image object is different from the original object
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5. Examples of Handed Objects
Your hands, from the previous slide
Gloves
Scissors
Screws
Golf clubs
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6. How about molecules? Chemical substances can be handed
Handed substances are said to be chiral
Molecules, that are chiral are nonsuperimposable on their mirror image
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7. Chirality in Molecules
cis isomers are achiral (not chiral).
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8. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
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9. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
Enantiomers: nonsuperimposable mirror images, different molecules.
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10. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
Enantiomers: nonsuperimposable mirror images, different molecules.
One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons.
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11. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
Enantiomers: nonsuperimposable mirror images, different molecules.
One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons.
The one enantiomer of carvone is the essence of caraway, and the other, the essence of spearmint.
Most molecules in the plant and animal world are chiral and usually only one form of then enantiomer is found.
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12. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
Enantiomers: nonsuperimposable mirror images, different molecules.
One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons.
The one enantiomer of carvone is the essence of caraway, and the other, the essence of spearmint.
Most molecules in the plant and animal world are chiral and usually only one form of then enantiomer is found.
Nineteen of the twenty known amino acids are chiral, and all of them are classified as left handed.
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13. Chirality in Molecules
The cis isomer is achiral.
The trans isomer is chiral.
Enantiomers: nonsuperimposable mirror images, different molecules.
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14. Stereocenters
Any atom at which the exchange of two groups yields a stereoisomer.
Examples:
Asymmetric carbons
Double-bonded carbons in cis-trans isomers
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15. Mirror Planes of Symmetry
If two groups are the same, carbon is achiral. (animation)
A molecule with an internal mirror plane cannot be chiral.*
Caution! If there is no plane of symmetry, molecule may be chiral or achiral. See if
mirror image can be superimposed.
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16. (R), (S) Nomenclature(Absolute Configuration)
Called the Cahn-Ingold-Prelog convention
Different molecules (enantiomers) must have different
names.
Usually only one enantiomer will be biologically active.
Configuration around the chiral carbon is specified with (R) and (S).
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17. Cahn-Ingold-Prelog Rules
Assign a priority number to each group attached to the chiral carbon.
Atom with highest atomic number assigned the
highest priority #1.
In case of ties, look at the next atoms along the
chain.
Double and triple bonds are treated like bonds to
duplicate atoms.
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18. Assign (R) or (S)
Working in 3D, rotate molecule so that lowest priority group is in back.
Draw an arrow from highest to lowest priority group.
Clockwise = (R), Counterclockwise = (S)
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19. Properties of Enantiomers
Same boiling point, melting point, density
Same refractive index
Different direction of rotation in polarimeter
Different interaction with other chiral molecules
Enzymes
Taste buds, scent
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20. Plane-Polarized Light
Polarizing filter – calcite crystals or plastic sheet.
When two filters are used, the amount of light transmitted depends on the angle of the axes.
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21. Polarimetry Use monochromatic light, usually sodium D
Movable polarizing filter to measure angle
Clockwise = dextrorotatory = d or (+)
Counterclockwise = levorotatory = l or (-)
Not related to (R) and (S)
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22. Biological Discrimination
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23. Racemic Mixtures
Equal quantities of d- and l- enantiomers a 50/50 mixture.
Notation: (d,l) or ()
No optical activity.
The mixture may have different b.p. and m.p. from the enantiomers!
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24. Fischer Projections Flat drawing that represents a 3D 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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25. Fischer Rules Carbon chain is on the vertical line.
Horizontal bonds pointing up with respect to the plane of the paper.
Vertical bonds pointing down with respect to the plane of the paper.
Highest oxidized carbon at top.
Rotation of 180 in plane doesn’t change molecule.
Do not rotate 90!
Do not turn over out of plane!
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26. Fischer Structures
Easy to draw, easy to find enantiomers, easy to find internal mirror planes.
Examples:
=>
A meso compound
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27. Fischer (R) and (S)
Lowest priority (usually H) comes forward, so assignment rules are backwards!
Clockwise is (S) and counterclockwise is (R).
Example:
(S)
Mirror image, both would be R
(S)
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28. Diastereomers Stereoisomers that are not mirror images.
Molecules with 2 or more chiral carbons.
Geometric isomers (cis-trans), since they are not mirror images.
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29. Ring Compounds Cis-trans isomers possible. May also have enantiomers.
Example: trans-1,2-dimethylcyclopentane
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30. Two or More Chiral Carbons
Enantiomer? Diastereomer? Meso? Assign (R) or (S) to each chiral carbon.
Enantiomers have opposite configurations at each corresponding chiral carbon.
Diastereomers have some matching, some opposite configurations.
Meso compounds have internal mirror plane.
Maximum number is 2n, where n = the number of chiral carbons.
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31. Examples * * * * enantiomers *
A meso compound, contains 2 or more stereocenters and a plane of symmetry *
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32. Fischer-Rosanoff Convention
Before 1951, only relative configurations could be known.
Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were assigned D and same as (-)-glyceraldehyde were assigned L.
With X-ray crystallography, we now know absolute configurations: D is (R) and L is (S).
No relationship to dextro- or levorotatory, meaning that some D enantiomers are (R) and some are (S).
Anyone who can look at a structure and determine which way it will rotate polarized light receives an automatic Noble Prize! There is a lot we do not know!
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33. D and L Assignments *
Penultimate carbon is the stereocenter farthest away from the carbonyl group. If the higher priority group is on the left, then (L), if on the right then (D) sugar. * * * * *
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34. Properties of Diastereomers
Diastereomers have different physical properties: m.p., b.p.
They can be separated easily.
Enantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated.
Enantiomers are difficult to separate
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35. Resolution of Enantiomers
Pasteur was the first to resolve an enatiomeric mixture, using a magnifying glass and tweezers.
Animals can consume a racemate and metabolize on of the two enantiomers, while the other is recovered in their waste products.
Chemical means, described on the next slide
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36. Chemical Resolution of Racemate
React a racemic mixture with a chiral compound to form diastereomers, which can
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37. Stereochemistry Review
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38. Compare the physical properties of enantiomers.
a. Different physical properties.
b. Same physical properties.
c. Cannot determine.
d. Same chemical properties.
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39. Answer a. Different physical properties. b. Same physical properties.
c. Cannot determine.
d. Same chemical properties.
Enantiomers have the same physical properties, such as melting point or boiling point.
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40. Identify as R, S, or achiral.
a. R
b. S
c. Achiral
d. Cannot be determined.
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41. Answer a. R b. S c. Achiral d. Cannot be determined.
Br > Cl > CH3 > H
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42. Identify as R, S, or achiral.
a. R
b. S
c. Achiral
d. Cannot be determined.
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43. Answer a. R b. S c. Achiral d. Cannot be determined.
I > CH3CH2 > CH3 > H
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44. Identify as R, S, or achiral.
a. R
b. S
c. Achiral
d. Cannot be determined.
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45. Answer a. R b. S c. Achiral d. Cannot be determined.
CH(CH3)2 > CH2CH2CH3 > CH2CH3 > CH3
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46. Identify as R, S, or achiral.
a. R
b. S
c. Achiral
d. Cannot be determined.
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47. Answer a. R b. S c. Achiral d. Cannot be determined.
CH=CH2 > CH(CH3)2 > CH2CH3 > CH3
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48. Identify as R, S, or achiral.
a. R
b. S
c. Achiral
d. Cannot be determined.
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49. Answer a. R b. S c. Achiral d. Cannot be determined.
C6H5 > HC≡C > C(CH3)3 > CH(CH3)2
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50. Identify the type isomer for (R) 2-pentanol.
a. Dextrorotatory isomer.
b. Levorotatory isomer.
c. Has to be experimentally determined.
d. Neither.
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51. Answer a. Dextrorotatory isomer. b. Levorotatory isomer.
c. Has to be experimentally determined.
d. Neither.
Dextrorotatory and levorotatory isomers must be experimentally determined.
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52. Classify 2R,3S-2,3-dichloropentane and 2S,3S-2,3-dichloropentane.
a. Enantiomers
b. Diastereomers
c. Conformational isomers
d. Constitutional isomers
e. Identical
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53. Answer a. Enantiomers b. Diastereomers c. Conformational isomers
d. Constitutional isomers
e. Identical
Diastereomers are stereoisomers that are not mirror images.
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54. Classify 2S,3S-2,3-dichloropentane and 2R,3R-2,3-dichloropentane.
a. Enantiomers
b. Diastereomers
c. Conformational isomers
d. Constitutional isomers
e. Identical
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55. Answer a. Enantiomers b. Diastereomers c. Conformational isomers
d. Constitutional isomers
e. Identical
Enantiomers are mirror image isomers.
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56. Classify 2R,3S-2,3-dichlorobutane and 2S,3R-2,3-dichlorobutane.
a. Enantiomers
b. Diastereomers
c. Conformational isomers
d. Constitutional isomers
e. Identical
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57. Answer a. Enantiomers b. Diastereomers c. Conformational isomers
d. Constitutional isomers
e. Identical
The compounds are identical.
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58. Classify 2R,3R-2,3-dichlorobutane and 2S,3S-2,3-dichlorobutane.
a. Enantiomers
b. Diastereomers
c. Conformational isomers
d. Constitutional isomers
e. Identical
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59. Answer a. Enantiomers b. Diastereomers c. Conformational isomers
d. Constitutional isomers
e. Identical
The compounds are enantiomers.
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60. Identify the number of stereoisomers for 3-bromo-2,4,5-trichlorohexane.
a. 6 stereoisomers
b. 8 stereoisomers
c. 12 stereoisomers
d. 16 stereoisomers
e. 24 stereoisomers
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61. Answer a. 6 stereoisomers b. 8 stereoisomers c. 12 stereoisomers
d. 16 stereoisomers
e. 24 stereoisomers
The number of stereoisomers is 24 or 16.
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62. Define meso compound. a. A meso compound is an achiral molecule.
b. A meso compound has a plane of symmetry.
c. A meso compound has chiral carbons.
d. All of the above.
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63. Answer a. A meso compound is an achiral molecule.
b. A meso compound has a plane of symmetry.
c. A meso compound has chiral carbons.
d. All of the above.
A meso compound has chiral carbons, is achiral, and has a plane of symmetry.
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64. Identify a pair of diastereomers.
a. A and B
b. A and D
c. B and C
d. None
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65. Answer
a. A and B
b. A and D
c. B and C
d. None
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66. Identify a pair of enantiomers.
a. A and B
b. A and D
c. B and C
d. A and C
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67. Answer
a. A and B
b. A and D
c. B and C
d. A and C
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68. Identify a meso compound.
a. A
b. B
c. C
d. A and D
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69. Answer
a. A
b. B
c. C
d. A and D
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70. Compare the physical properties of diastereomers.
a. Different physical properties.
b. Same physical properties.
c. Cannot determine.
d. Same chemical properties.
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71. Answer a. Different physical properties. b. Same physical properties.
c. Cannot determine.
d. Same chemical properties.
Diastereomers have different physical properties, such as melting point or boiling point.
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72. End of Chapter 6
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