5.3 Designating Configurations Enantiomers are NOT identical, so they must not have identical names How would you name these molecules? Their names must be different, so we use the Cahn- Ingold-Prelog system to designate each molecule as either R or S. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-1

5.3 Designating Configurations The Cahn, Ingold and Prelog system 1.Using atomic numbers, prioritize the 4 groups attached to the chirality center 2.Arrange the molecule in space so the lowest priority group faces away from you 3.Count the group priorities 1…2…3 to determine whether the order progresses in a clockwise or counterclockwise direction 4.Clockwise = R and Counterclockwise = S A handheld model can be very helpful visual aid for this process Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-2

The Cahn, Ingold and Prelog system 1.Using atomic numbers, prioritize the 4 groups attached to the chirality center. The higher the atomic number, the higher the priority – Prioritize the groups on this molecule 5.3 Designating Configurations Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-3

5.3 Designating Configurations The Cahn, Ingold and Prelog system 2.Arrange the molecule in space so the lowest priority group faces away from you – This is the step where it is most helpful to have a handheld model Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-4

5.3 Designating Configurations 1.Using atomic numbers, prioritize the 4 groups attached to the chirality center 2.Arrange the molecule in space so the lowest priority group faces away from you Complete steps 1 and 2 for the following molecule Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-5

5.3 Designating Configurations The Cahn, Ingold and Prelog system 3.Counting the other group priorities, 1…2…3, determine whether the order progresses in a clockwise or counterclockwise direction 4.Clockwise = R and Counterclockwise = S Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-6

5.3 Designating Configurations Designate each chirality center below as either R or S. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-7

5.3 Designating Configurations When the groups attached to a chirality center are similar, it can be tricky to prioritize them Analyze the atomic numbers one layer of atoms at a time First layer Second layer 1 4 Tie 2 3 Is this molecule R or S? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-8

Analyze the atomic numbers one layer of atoms at a time First layer Second layer 5.3 Designating Configurations 1 4 Tie 2 3 The priority is based on the first point of difference, NOT the sum of the atomic numbers Is this molecule R or S? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-9

5.3 Designating Configurations When prioritizing for the Cahn, Ingold and Prelog system, double bonds count as two single bonds Determine R or S for the following molecule Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-10

5.3 Designating Configurations Handheld molecular models can be very helpful when arranging the molecule in space so the lowest priority group faces away from you Here are some other tricks that can use – Switching two groups on a chirality center will produce its opposite configuration Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-11

5.3 Designating Configurations Switching two groups on a chirality center will produce its opposite configuration You can use this trick to adjust a molecule so that the lowest priority group faces away from you With the 4 th priority group facing away, you can designate the configuration as R Work backwards to show how the original structure’s configuration is also R Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-12

5.3 Designating Configurations Practice with SkillBuilder 5.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-13

5.3 Designating Configurations The R or S configuration is used in the IUPAC name for a molecule to distinguish it from its enantiomer Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-14

5.4 Optical Activity Because the structures of enantiomers are so similar, many of their properties are identical. If you have a sample of a chiral compound, imagine how can its enantiomeric purity be assessed? In other words, how can one enantiomer be distinguished from another? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-15

5.4 Optical Activity Enantiomers have opposite configurations (R vs. S), so they will rotate plane-polarized light in opposite directions What is plane-polarized light? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-16

5.4 Optical Activity To get light waves that travel in only one plane, light travels through a filter When plane polarized light is directed through a sample of a pure chiral compound, the plane that the light travels on will rotate. Compounds that can rotate the plane or plane- polarized light are called optically active Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-17

5.4 Optical Activity Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-18

5.4 Optical Activity Enantiomers will rotate the plane of the light to equal degrees but in opposite directions The degree to which light is rotated depends on the sample concentration and the pathlength of the light Standard optical rotation measurements are taken with 1 gram of compound dissolved in 1 mL of solution, and with a pathlength of 1 dm for the light Temperature and the wavelength of light can also affect rotation and must be reported with measurements that are taken Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-19

5.4 Optical Activity Consider the enantiomers of 2-bromobutane R and S refer to the configuration of the chirality center (+) and (-) signs refer to the direction that the plane of light is rotated The optical activity was measured at 589 nm, which is the Sodium D line wavelength Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-20

5.4 Optical Activity There is no relationship between the R/S configuration and the direction of light rotation (+/-) Should the chirality center below be designated R or S? As long as its bonds are not rearranged, its configuration CANNOT change It is levorotatory (-) at 20°C, while at 100°C, it is dextrorotatory (+) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-21

5.4 Optical Activity The magnitude and direction of optical rotation can not be predicted from a chiral molecule’s structure or configuration. It can ONLY be determined experimentally Predict the optical rotation for a racemic mixture (a sample with equal amounts of two enantiomers) Can you predict the optical rotation for a sample of 2- methylbutane Practice with SkillBuilder 5.5 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-22

5.4 Optical Activity For unequal amounts of enantiomers, the enantiomeric excess (% ee) can be determined from the optical rotation For a mixture of 70% (R) and 30% (S), what is the % ee? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-23

5.4 Optical Activity If the mixture has an optical rotation of +4.6, use the formula to calculate the % ee and the ratio of R/S Practice with SkillBuilder 5.5 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 5-24