© 2016 Pearson Education, Inc. Isomers: The Arrangement of Atoms in Space Paula Yurkanis Bruice University of California, Santa Barbara Chapter 4

© 2016 Pearson Education, Inc. Isomers Compounds that have the same molecular formula but different structures.

© 2016 Pearson Education, Inc. Constitutional Isomers Constitutional isomers differ in the way the atoms are connected.

© 2016 Pearson Education, Inc. Stereoisomers: Cis–Trans Isomers Cis–trans isomers result from restricted rotation. Cyclic structures have restricted rotation. Cis: The substituents are on the same side of the ring. Trans: The substituents are on opposite sides of the ring.

© 2016 Pearson Education, Inc. Double bonds restrict rotation. Cis: The hydrogens are on the same side of the double bond. Trans: The hydrogens are on opposite sides of the double bond. Cis–Trans Isomers

© 2016 Pearson Education, Inc. Cis–trans isomers have different physical properties. Cis–Trans Isomers

© 2016 Pearson Education, Inc. cis/trans Isomers All substituents are on one side of  bond All substituents are on different sides of  bond cis trans

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Some Alkenes do not have Cis–Trans Isomers

© 2016 Pearson Education, Inc. Different Conformations Compounds with different conformations (conformers) cannot be separated.

© 2016 Pearson Education, Inc. Different Configurations Compounds with different configurations can be separated. Cis–trans isomers have different configurations.

© 2016 Pearson Education, Inc. Cis-Trans Isomerization in Vision

© 2016 Pearson Education, Inc. cis/trans Isomers cis-2-pentene

© 2016 Pearson Education, Inc. cis/trans Isomers trans-3-heptene

© 2016 Pearson Education, Inc. The E,Z System of Nomenclature For more than two substituents the cis/trans system cannot be used. To use the E/Z system we need to assign priorities to each substituent on each carbon. A new system, the E/Z system is introduced.

© 2016 Pearson Education, Inc. The E,Z System for Designating Geometric Isomers

© 2016 Pearson Education, Inc. E/Z System In case high priorities are on the same side, we assign a Z configuration. In case high priorities are on opposite sides, we assign an E configuration.

© 2016 Pearson Education, Inc. The E,Z System for Designating Geometric Isomers

© 2016 Pearson Education, Inc. E/Z System- Rule 1 The relative priorities of the two groups depend on the atomic numbers of the atoms bonded directly to the sp 2 carbon. The greater the atomic number, the higher is the priority of the group.

© 2016 Pearson Education, Inc. E/Z System Priorities are first assigned based on atomic numbers. I > C 1 2 F > H 1 2 I > C 1 2 F > H 1 2 Z-configuration E-configuration

© 2016 Pearson Education, Inc. The E,Z System for Designating Geometric Isomers If the atoms attached to the sp 2 carbon are the same, the atoms attached to the tied atoms are compared; the one with the greater atomic number belongs to the group with the higher priority.

© 2016 Pearson Education, Inc. E/Z System- Rule 2 If the two substituents attached to the sp 2 carbon start with the same atom, you must move outward and consider the atomic numbers that are attached to the “tied” atoms.

© 2016 Pearson Education, Inc. E/Z System If you can’t decide using the first atoms attached, go out to the next atoms attached. If there are nonequivalent paths, always follow the path with atoms of higher atomic number. path goes to O, not H path goes to C, not H comparison stops here C H O H C H C H Z-configuration

© 2016 Pearson Education, Inc. The E,Z System for Designating Geometric Isomers If an atom is doubly bonded to another atom, treat it as if it were singly bonded to two of those atoms. If an atom is triply bonded to another atom, treat it as if it were singly bonded to three of those atoms. Cancel atoms that are identical in the two groups; use the remaining atoms to determine the group with the higher priority.

© 2016 Pearson Education, Inc. E/Z System- Rule 3 If an atom is doubly (or triply) bonded to another atom, the priority system treats it as if it were singly bonded to two (or three) of those atoms.

© 2016 Pearson Education, Inc. E/Z System Atoms in double bonds are “replicated” at either end of the double bond. path goes to C, not H E-configuration

© 2016 Pearson Education, Inc. Chirality Chiral – Nonsuperimposable on its mirror image. Achiral – Superimposable on its mirror image. If a molecule (or object) has a mirror plane or an inversion center, it cannot be chiral.

© 2016 Pearson Education, Inc. Chiral and Achiral Objects Chiral objects Achiral objects

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Brandy snifter achiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Shears chiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Beer mug achiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Hiking boot chiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Baseball glove chiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? Desk chair achiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? School desk chiral

© 2016 Pearson Education, Inc. Chiral Molecules Chiral molecules have an asymmetric center. An asymmetric center is an atom that is attached to four different groups.

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? cis-1,3-dimethylcyclopentane mirror plane achiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? trans-1,3-dimethylcyclopentane chiral

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Chiral or Achiral? 1,1-dimethylcyclohexane achiral

© 2016 Pearson Education, Inc. Compounds with an Asymmetric Center

© 2016 Pearson Education, Inc. Enantiomers The two isomers are called enantiomers. Enantiomers are different compounds: they can be separated. Enantiomers have the same physical and chemical properties.

© 2016 Pearson Education, Inc. Enantiomers are nonsuperimposable mirror images. Enantiomers

© 2016 Pearson Education, Inc. Chiral and Achiral Molecules Chiral compounds have nonsuperimposable mirror images. Achiral compounds have superimposable mirror images (they are identical molecules).

© 2016 Pearson Education, Inc. Enantiomers A chiral compound and its mirror image are called enantiomers. 2-butanol: enantiomers

© 2016 Pearson Education, Inc. Enantiomers Asparagine: enantiomers mirror plane D -asparagine (from vetch) sweet taste L -asparagine (from asparagus) bitter taste

© 2016 Pearson Education, Inc. How to draw Enantiomers Perspective formulas Interchanging two atoms or groups attached to an asymmetric center produces an enantiomer. Interchanging two atoms or groups a second time brings you back to the original compound:

© 2016 Pearson Education, Inc. Naming Enantiomers Assign relative priorities to the four groups.

© 2016 Pearson Education, Inc. If the lowest priority group is on a hatched wedge, then clockwise = R and counterclockwise = S Naming Enantiomers draw an arrow from 1 to 2 to 3

© 2016 Pearson Education, Inc. If the lowest priority group is not on a hatched wedge, switch a pair so it is on a hatched wedge. Then, name the new compound. Naming Enantiomers

© 2016 Pearson Education, Inc. Naming enantiomers: the R,S system

© 2016 Pearson Education, Inc. Absolute Configuration R and S –Assign priorities to the remaining groups based on atomic numbers. –Clockwise (highest to lowest priority)  R –Counterclockwise  S (R)-2-butanol

© 2016 Pearson Education, Inc. Absolute Configuration Assign priority: –Atomic number of atom directly bonded. –If the same atom is bonded, go to the next atom, etc. –Groups containing multiple bonds are treated as though multiple atoms were attached:

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Absolute Configuration Determine the absolute configuration of the following compounds:

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Absolute Configuration Determine the absolute configuration of the following compounds:

© 2016 Pearson Education, Inc. Plane-Polarized Light

© 2016 Pearson Education, Inc. An Achiral Compound is optically Inactive An achiral compound does not rotate the plane of polarization of plane-polarized light.

© 2016 Pearson Education, Inc. A Chiral Compound is optically Active A chiral compound rotates the plane of polarization of plane-polarized light. If it rotates the plane clockwise = (+) If it rotates the plane counterclockwise = (–)

© 2016 Pearson Education, Inc. R and S Versus (+) and (–) Some R enantiomers are (+) and some are (–). Some S enantiomers are (+) and some are (–).

© 2016 Pearson Education, Inc. Polarimeter

© 2016 Pearson Education, Inc. Copyright © 2010 Pearson Education, Inc. Optical Activity Optical Activity – The ability of a compound to rotate the plane of polarized light. A compound that rotates the plane of polarization is said to be optically active. Chiral compounds are optically active and achiral compounds are optically inactive. A polarimeter is used to make such measurements:

© 2016 Pearson Education, Inc. If one Enantiomer is (+), the other is (–)

© 2016 Pearson Education, Inc. Compounds with two Asymmetric Centers maximum # of stereoisomers = 2 n (n = # of asymmetric centers) 1 and 2 are enantiomers. 3 and 4 are enantiomers.

© 2016 Pearson Education, Inc. Diastereomers 1 and 2 are enantiomers. 3 and 4 are enantiomers. Diastereomers are stereoisomers that are not enantiomers. 1 and 3 are diastereomers. 2 and 3 are diastereomers. 1 and 4 are diastereomers. 2 and 4 are diastereomers. Diastereomers have different physical and chemical properties.

© 2016 Pearson Education, Inc. Two Asymmetric Centers, Four Stereoisomers The cis stereoisomers are a pair of enantiomers. The trans stereoisomers are a pair of enantiomers.

© 2016 Pearson Education, Inc. Identifying an Asymmetric Center An asymmetric center is attached to four different groups. two asymmetric centers, four stereoisomers

© 2016 Pearson Education, Inc. No Asymmetric Centers There are only two stereoisomers: cis and trans.

© 2016 Pearson Education, Inc. There are only two stereoisomers: cis and trans. No Asymmetric Centers

© 2016 Pearson Education, Inc. Two Asymmetric Centers: Three Stereoisomers (a meso compound and a pair of enantiomers) A compound with two asymmetric centers that has the same four groups bonded to each asymmetric center will have three stereoisomers: a meso compound (1) and a pair of enantiomers (2 and 3)

© 2016 Pearson Education, Inc. A Meso Compound has a Superimposable Mirror Image Meso compounds are optically inactive even though they have asymmetric centers.

© 2016 Pearson Education, Inc. Cyclic Meso Compounds For cyclic compounds with the same substituent bonded to two asymmetric centers, cis = a meso compound and trans = a pair of enantiomers.

© 2016 Pearson Education, Inc. Physical Properties of Stereoisomers

© 2016 Pearson Education, Inc. Separating Enantiomers separating by hand separating by chromatography

© 2016 Pearson Education, Inc. Physiological Properties of Enantiomers Enantiomers can have very different physiological properties.

© 2016 Pearson Education, Inc. Oranges and Lemons found in oranges found in spruce trees