Enantiomers and Stereoisomers PDF

Enantiomers Enantiomers are non-superimposable mirror image molecules. Any molecule with one stereogenic center exists as a pair of enantiomers. ©2020 McGraw-Hill Education. 1  Drawing Enantiomers To...

Enantiomers Enantiomers are non-superimposable mirror image molecules. Any molecule with one stereogenic center exists as a pair of enantiomers. ©2020 McGraw-Hill Education. 1  Drawing Enantiomers To draw both enantiomers of a chiral compound such as 2-butanol, use the typical convention for depicting a tetrahedron. To form the first enantiomer, arbitrarily place the four groups—H, OH, CH3 and CH2CH3—on any bond to the stereogenic center. Then draw the mirror image. Chapt 5 part 1 ends here ©2020 McGraw-Hill Education. 2  Chapter 5 Part 2 ©2020 McGraw-Hill Education. 3  Stereogenic Centers in Cyclic Compounds Stereogenic centers may also occur at carbon atoms that are part of a ring. To find stereogenic centers on ring carbons: draw the rings as flat polygons; look for tetrahedral carbons that are bonded to four different groups. ©2020 McGraw-Hill Education. 4  Stereogenic Centers 3-methylcyclohexene, enantiomer examples ©2020 McGraw-Hill Education. 5  Some Biologically Active Molecules with Stereogenic Centers on Rings Notice: large molecule but we are only looking for the stereogenic center ©2020 McGraw-Hill Education. 6  Some Biologically Active Molecules with Stereogenic Centers on Rings ©2020 McGraw-Hill Education. 7  Labeling Stereogenic Centers with R or S Enantiomers are two different compounds, distinguished by using the prefix R or S before the name of the molecule RULE 1: Prioritze groups in order of decreasing atomic number. The atom of highest atomic number gets the highest priority (1). ©2020 McGraw-Hill Education. 8  Assigning Priority for R and S RULE 2: If two atoms on a stereogenic center are the same, assign priority based on the atomic number of the atoms bonded to these atoms. One atom of higher atomic number determines the higher priority. Following Rule 1: Following Rule 2: ©2020 McGraw-Hill Education. 9  Assigning Priority for R and S–Multiple Bonds RULE 4: To assign a priority to an atom that is part of a multiple bond, treat a multiply bonded atom as an equivalent number of singly bonded atoms. For example, the C of a C=O is considered to be bonded to two O atoms. ©2020 McGraw-Hill Education. 10  Assigning Priority for R and S–Multiple Bonds Other common multiple bonds are drawn below: ©2020 McGraw-Hill Education. 11  Assigning Priorities to Stereogenic Centers Figure 5.6 ©2020 McGraw-Hill Education. 12  How To Assign R or S once priority is established Example: Label each enantiomer as R or S STEP : Assign priorities from 1 to 4 to each group bonded to the stereogenic center. The priorities for the four groups are given in Rule 2. ©2020 McGraw-Hill Education. 13  How To Assign R or S STEP : Orient the molecule with the lowest-priority group (4) back (on a dashed wedge), and visualize the positions of the remaining three groups. For each enantiomer of butan-2-ol, look toward the lowest priority group, drawn behind the plane, down the C-H bond. ©2020 McGraw-Hill Education. 14  How To Assign R or S-2 STEP : Trace a circle from priority group 1→2 → 3 If tracing the circle goes in the clockwise direction from the noon position, the isomer is named R. If tracing the circle goes in the counterclockwise direction from the noon position, the isomer is named S. ©2020 McGraw-Hill Education. 15  How To Assign R or S The letter R or S proceeds the IUPAC name of the molecule. For the enantiomers of butan-2-ol: ©2020 McGraw-Hill Education. 16  Using models to visualize R, S enantiomers ©2020 McGraw-Hill Education. 17  Prioritize Groups: 1: red 2: blue 3: white 4: Yellow ©2020 McGraw-Hill Education. 18  Put the lowest priority to the back: Look at the rotation based on priority groups These rotate counterclockwise so this is the S isomer 1 2 3 ©2020 McGraw-Hill Education. 19  The other should be R….but be sure Same priority Prioritize Groups: 1: red 2: blue 3: white 4: Yellow ©2020 McGraw-Hill Education. 20  These groups follow a clockwise direction so it is the R isomer 2 1 3 ©2020 McGraw-Hill Education. 21 ©2020 McGraw-Hill Education. 22  Diastereomers A molecule with n stereogenic centers has a maximum number of stereoisomers as 2n. When n=2, 22 = 4 there are 4 stereoisomers some of them may be the same molecule. Some of the stereoisomers will not be mirror images of each other. Diastereomers are non-mirror image stereoisomers or they are configurational isomers that are not enantiomers The complexity of this must be kept in mind when isolating these isomers Basically, find the stereoisomers, then label them as enantiomers or diastereomers ©2020 McGraw-Hill Education. 23  Stereocenters of 2,3-dibromopentane. Example from Textbook: Find all the possible stereoisomers of 2,3- dibromopentane. ©2020 McGraw-Hill Education. 24  Finding All Possible Stereocenters After drawing the compound and the mirror image, place B directly on top of A; and rotate B 180 degrees and place it on top of A to see if the atoms align. In this case, the atoms of A and B do not align, making A and B nonsuperimposable mirror images—i.e., enantiomers. A and B are two of the four possible stereoisomers of 2,3- dibromopentane. ©2020 McGraw-Hill Education. 25  Finding All Possible Stereocenters Switching the positions of H and Br (or any two groups) on one stereogenic center of either A or B forms a new stereoisomer (labeled C in this example), which is different from A and B. The mirror image of C is labeled D. ©2020 McGraw-Hill Education. 26  Summary of Stereoisomers of 2,3- dibromopentane A and B are enantiomers. C and D are enantiomers. A and C are diastereomers. A and D are diastereomers. B and C are diastereomers. B and D are diastereomers. A and C are nonsuperimposable, etc Figure 5.8 ©2020 McGraw-Hill Education. 27  Stereoisomers of 2,3-dibromobutane Find all the stereoisomers of 2,3-dibromobutane. two stereogenic centers, the maximum number of stereoisomers is 4. ©2020 McGraw-Hill Education. 28  Stereoisomers of 2,3-dibromobutane 2,3-dibromobutane, arbitrarily form one stereoisomer A, and then draw its mirror image, B. ©2020 McGraw-Hill Education. 29  Stereoisomers of 2,3-dibromobutane To find the other two stereoisomers if they exist, switch the position of two groups on one stereogenic center of one enantiomer only. Switching the positions of H and Br on one stereogenic center of A forms C, which is different from both A and B. Mirror image of C is D but these are identical…only 3 isomers exist ©2020 McGraw-Hill Education. 30  Meso Compounds Compound C contains a plane of symmetry, and is achiral and is a meso compound. Meso compounds generally contain a plane of symmetry so that they possess two identical halves. ©2020 McGraw-Hill Education. 31  Stereoisomers of 2,3-dibromobutane Figure 5.9 Pair of enantiomers: A and B Pairs of diastereomers: A and C; B and C ©2020 McGraw-Hill Education. 32  R and S Assignments in Compounds with Two or More Stereogenic Centers When a compound has more than one stereogenic center, R and S configurations must be assigned to each of them. One stereoisomer of 2,3-dibromopentane (2S,3R)-2,3-dibromopentane Use the rules for the R,S configurations at each stereogenic center …assign each group on each center with the proper priority ©2020 McGraw-Hill Education. 33  R and S Assignments in Compounds with Two or More Stereogenic Centers If you use priorities as stated on the previous One stereoisomer of 2,3-dibromopentane slide, then this will work (2S,3R)-2,3-dibromopentane out Identical compounds have the same R,S designations at every tetrahedral stereogenic center. Enantiomers have exactly opposite R,S designations. Diastereomers have the same R,S designation for at least one stereogenic center and the opposite for at least one of the other stereogenic centers. ©2020 McGraw-Hill Education. 34  1,3-Dibromocyclopentane Stereoisomers two stereogenic centers, it has a maximum of four stereoisomers..but Cis-isomer is a meso compound Only 3 isomers because of Trans-isomer has an enantiomer pair meso compound C ©2020 McGraw-Hill Education. 35  Summary–Types of Isomers Figure 5.10 ©2020 McGraw-Hill Education. 36  Determining the Relationship Between Molecules Figure 5.11 ©2020 McGraw-Hill Education. 37  How do properties of enantiomers differ from each other The chemical and physical properties of two enantiomers are identical except in their interaction with chiral substances. They have identical physical properties, except for how they interact with plane-polarized light. Basically optical activity…ability to rotate plane polarized light right or left Plane Optically Plane polarized Ordinary Polarizing active polarized light light in light filter molecules is rotated one direction ©2020 McGraw-Hill Education. 38  Optical Activity Plane-polarized (polarized) light is light that has an electric vector that oscillates in a single plane. Plane-polarized light arises from passing ordinary light through a polarizer. A polarimeter is an instrument that allows polarized light to travel through a sample tube containing an organic compound and permits the measurement of the degree to which an organic compound rotates plane-polarized light. Optically active compound rotates plane polarized light Optically inactive does not ©2020 McGraw-Hill Education. 39  Plane-Polarized Light With achiral compounds, the light that exits the sample tube remains unchanged. A compound that does not change the plane of polarized light is said to be optically inactive. ©2020 McGraw-Hill Education. 40  Rotation of Plane-Polarized Light With chiral compounds, the plane of the polarized light is changed ©2020 McGraw-Hill Education. 41  Optical Activity Summary The rotation of polarized light can be clockwise or counterclockwise. If the rotation is clockwise, the compound is called dextrorotatory. The rotation is labeled d or (+). If the rotation is counterclockwise, the compound is called levorotatory. The rotation is labeled l or (-). Two enantiomers rotate plane-polarized light to an equal extent but in opposite directions. (e.g., if enantiomer A rotates polarized light +5 degrees, the same concentration of enantiomer B rotates it −5 degrees) No relationship exists between R and S prefixes and the (+) and (-) designations that indicate optical rotation. ©2020 McGraw-Hill Education. 42  Racemic Mixtures An equal amount of two enantiomers is called a racemic mixture or a racemate. A racemic mixture is optically inactive. Because two enantiomers rotate plane-polarized light to an equal extent but in opposite directions, the rotations cancel, and no rotation is observed. ©2020 McGraw-Hill Education. 43  Racemic Mixtures Table 5.2 The physical Properties of Enantiomers A and B Compared Property A alone B alone Racemic A + B Melting point identical to B identical to A may be different from A and B Boiling point identical to B identical to A may be different from A and B Optical rotation equal in magnitude but equal in magnitude but 0 opposite in sign to B opposite in sign to A ©2020 McGraw-Hill Education. 44  Optical Purity Enantiomeric excess (optical purity) is a measurement of how much one enantiomer is present in excess of the racemic mixture. It is denoted by the symbol ee. Enantiomeric excess = ee = % of one enantiomer – % of the other enantiomer. Consider the following example—If a mixture contains 75% of one enantiomer and 25% of the other, the enantiomeric excess is 75%−25%=50%. Thus, there is a 50% excess of one enantiomer over the racemic mixture or 50% ee. ©2020 McGraw-Hill Education. 45  Enantiomeric Excess The enantiomeric excess can also be calculated if the ©2020 McGraw-Hill Education. 46  Physical Properties of Stereoisomers: overview Since enantiomers have identical physical properties, they cannot be separated by common physical techniques like distillation. Diastereomers and constitutional isomers have different physical properties, and therefore can be separated by common techniques. Figure 5.12 ©2020 McGraw-Hill Education. 47  So why are enantiomers, etc important Two enantiomers have exactly the same chemical properties except for their reaction with chiral, non-racemic reagents…allow very specific reactions The name of a compound indicates specifically what that compound is…. not only the substituents, but location, configuration, etc Chemical activity in biological systems in many cases involve chiral chemicals reacting with chiral centers …. See next slide and other examples in textbook ©2020 McGraw-Hill Education. 48  Chemical Properties of Enantiomers Many drugs are chiral and often must react with a chiral receptor or chiral enzyme to be effective. (S)-ibuprofen is the active component agents in Motrin and Advil. (R)-fluoxetine is the active component in Prozac. ©2020 McGraw-Hill Education. 49  Chemical Properties of Enantiomers One enantiomer of a drug may effectively treat a disease whereas its mirror image may be ineffective or toxic. Changing the orientation of the substituents on naproxen converts it from a common anti-inflammatory agent into a harmful liver toxin. ©2020 McGraw-Hill Education. 50  End chapter 5 Chapter 5 HW: 45 a,e; 47a, 48b,d; 50a,b,c; 51a; 53a,b; 56a,c; 58b; 61 compare only a; 65a,d ©2020 McGraw-Hill Education. 51