Isomers: The Arrangement of Atoms in Space University of California, Chapter 4 Isomers: The Arrangement of Atoms in Space Paula Yurkanis Bruice University of California, Santa Barbara

Isomers Compounds that have the same molecular formula but different structures.

Constitutional Isomers Constitutional isomers differ in the way the atoms are connected.

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.

Cis–Trans Isomers 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 have different physical properties.

cis/trans Isomers cis trans All substituents are All substituents are on one side of  bond All substituents are on different sides of  bond

Figure: 04-01-01UN Title: Diagrams of cis- and trans-2-Butene Caption: The electrostatic potential maps, ball-and-stick models, and structures of the two isomers of 2-butene. These isomers are called geometric isomers. They have the same molecular geometry; they differ in their relative arrangement in space. Notes: The cis isomer is the one where the same substituents are on the same side of the plane or the carbon-carbon double bond. The trans isomer is where they are on opposite sides.

Some Alkenes do not have Cis–Trans Isomers

Different Conformations Compounds with different conformations (conformers) cannot be separated.

Different Configurations Compounds with different configurations can be separated. Cis–trans isomers have different configurations.

Cis-Trans Isomerization in Vision

cis/trans Isomers 3 2 5 4 1 cis-2-pentene 3 2 3 5 5 2 4 4 1 1

cis/trans Isomers 1 2 3 4 5 6 7 trans-3-heptene 2 6 4 1 2 3 6 4 7 5 3 1 7 5

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

The E,Z System for Designating Geometric Isomers

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.

The E,Z System for Designating Geometric Isomers

E/Z System- Rule 1 The relative priorities of the two groups depend on the atomic numbers of the atoms bonded directly to the sp2 carbon. The greater the atomic number, the higher is the priority of the group.

E/Z System Priorities are first assigned based on atomic numbers. 1 2 F > H E-configuration I > C 1 2 F > H Z-configuration

The E,Z System for Designating Geometric Isomers If the atoms attached to the sp2 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.

E/Z System- Rule 2 If the two substituents attached to the sp2 carbon start with the same atom, you must move outward and consider the atomic numbers that are attached to the “tied” atoms.

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 1 2 C H O comparison stops here path goes to C, not H Z-configuration

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.

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.

E/Z System path goes to C, not H Atoms in double bonds are “replicated” at either end of the double bond. 1 2 E-configuration

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.

Chiral and Achiral Objects

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

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

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

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

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

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

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

Chiral Molecules Chiral molecules have an asymmetric center. An asymmetric center is an atom that is attached to four different groups.

Compounds with an Asymmetric Center

Enantiomers The two isomers are called enantiomers. Enantiomers are different compounds: they can be separated.

Enantiomers are nonsuperimposable mirror images.

Chiral and Achiral Molecules Chiral compounds have nonsuperimposable mirror images. Achiral compounds have superimposable mirror images (they are identical molecules).

Enantiomers A chiral compound and its mirror image are called enantiomers. 2-butanol: enantiomers

Enantiomers mirror plane Asparagine: enantiomers Vetch photo: http://www.kaweahoaks.com/html/common_vetch.html L-asparagine (from asparagus) bitter taste D-asparagine (from vetch) sweet taste enantiomers

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:

Assign relative priorities to the four groups. Naming Enantiomers Assign relative priorities to the four groups.

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

Then, name the new compound. Naming Enantiomers 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: the R,S system Figure: 08-01-14UN Title: Determining Configuration of Chiral Center Step 1 Caption: The first step in determining the configuration of a stereocenter is to number attached groups in descending order of priority using the Cahn-Ingold-Prelog rules. Notes: The higher the atomic number, the higher the priority. This is similar to the E,Z system learned earlier.

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

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:

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

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

Plane-Polarized Light

An Achiral Compound is optically Inactive An achiral compound does not rotate the plane of polarization of plane-polarized light.

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 = (–)

R and S Versus (+) and (–) Some R enantiomers are (+) and some are (–). Some S enantiomers are (+) and some are (–).

Polarimeter

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: Copyright © 2010 Pearson Education, Inc.

If one Enantiomer is (+), the other is (–) A mixture of equal amounts of two enantiomers- such as (R)-(+)-2-methyl-1-butanol and (S)-(-)-2-methyl-1-butanol is called a racemic mixture or a racemate.

Compounds with two Asymmetric Centers maximum # of stereoisomers = 2n (n = # of asymmetric centers) 1 and 2 are enantiomers. 3 and 4 are enantiomers.

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.

Two Asymmetric Centers, Four Stereoisomers The cis stereoisomers are a pair of enantiomers. The trans stereoisomers are a pair of enantiomers.

Identifying an Asymmetric Center An asymmetric center is attached to four different groups. two asymmetric centers, four stereoisomers

There are only two stereoisomers: cis and trans. No Asymmetric Centers There are only two stereoisomers: cis and trans.

There are only two stereoisomers: cis and trans. No Asymmetric Centers There are only two stereoisomers: cis and trans.

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)

Superimposable Mirror Image A Meso Compound has a Superimposable Mirror Image Meso compounds are optically inactive even though they have asymmetric centers.

trans = a pair of enantiomers. 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.

Physical Properties of Stereoisomers

Separating Enantiomers separating by hand separating by chromatography

Physiological Properties of Enantiomers Enantiomers can have very different physiological properties.

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