2/16/18 CHEM 109A Organic Chemistry https://labs.chem.ucsb.edu/zakarian/armen/courses.html Chapter 4 Isomers The arrangement of atoms in space Problem 81. One of the chair conformers of cis-1,3- dimethylcyclohexane is 5.4 kcal/mol less stable than the other. How much strain energy does the1,3-diaxial interaction introduce? 1 2/16/18 Isomers Isomers are compounds with different structures but the same molecular formula. isomers constitutional isomers stereoisomers (different bond connectivity) (same bond connectivity, different configuration (different 3D arrangement)) OH O C3H8O enantiomers diastereomers (isomers that are (isomers that are not mirror images) enantiomers) E or Z, cis or trans, one asym. center: R vs. S RSR vs RRR, two or more: RR vs. SS etc. RSR vs. SRS etc. meso compounds cis–trans: Diastereomers will always have hydrogens H H H H H H’s are still H there cis trans 2 2/16/18 Which is Cis and Which is Trans? E–Z: Diastereomers which group is the higher priority at this carbon? and this carbon? lower priority higher priority H’s are still there Z E • priority is determined by atomic weight; if same, move to the next heaviest atom 3 2/16/18 E and Z Isomers E and Z Isomers 4 2/16/18 Chiral and Achiral Objects A chiral object has a nonsuperimposable mirror image. An achiral object has a superimposable mirror image. Chiral and Achiral Objects no plane or center of symmetry: chiral if there is a center of symmetry, or a plane of symmetry: achiral 5 2/16/18 Enantiomers Enantiomers are nonsuperimposable mirror images. Chiral and Achiral Molecules A chiral compound has a nonsuperimposable mirror image. An achiral compound has a superimposable mirror image. (it and its mirror image are identical molecules). 6 2/16/18 Enantiomers The two stereoisomers are called enantiomers. Enantiomers are different compounds: they can be separated. Enantiomers have the same physical and chemical properties. (except: 1. rotation of polarized light; 2. When react with other enantiomeric compounds) Enantiomers HO OH H O H O N N HO OH (-)-morphine (+)-morphine binds to opioid receptors in the brain does not binds to opioid receptors in the brain 7 2/16/18 Compounds with an Asymmetric Center Compounds with an Asymmetric Center Problem 69. How many asymmetric centers does Mecavor have? HO O O O O Mecavor 8 2/16/18 Asymmetric Center versus Stereocenter Asymmetric center: an atom attached to four different groups. Stereocenter: an atom at which the interchange of two groups produces a stereoisomer. How to Draw Enantiomers Perspective formulas Br Br Skeletal structures Fischer projections 9 2/16/18 R and S configuration. Naming Enantiomers Assign relative priorities to the four groups. R and S configuration. 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 10 2/16/18 Naming Enantiomers If the lowest priority group is on a vertical bond, then clockwise = R and counterclockwise = S Naming Enantiomers If the lowest priority group is on a horizontal bond, then counterclockwise = R and clockwise = S 11 2/16/18 Plane-Polarized Light An Achiral Compound is Optically Inactive An achiral compound does not rotate the plane of polarization of plane-polarized light. 12 2/16/18 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 place counterclockwise = (–) R and S versus (+) and (–) Some R enantiomers are (+) and some are (–). Some S enantiomers are (+) and some are (–). 13 2/16/18 A Polarimeter If One Enantiomer is (+), the Other is (–) 14 2/16/18 Enantiomeric Excess Enantiomeric excess tells us how much of an excess of one enantiomer is in a mixture. For example, if the sample of 2-bromobutane has an observed specific rotation of +9.2, then the enantiomeric excess is 40%. In other words, the excess of one of the enantiomers comprises 40% of the mixture. Compounds with Two Asymmetric Centers maximum # of stereoisomers = 2n (n = # of asymmetric centers) 1 and 2 are enantiomers. 3 and 4 are enantiomers. 15 2/16/18 Diastereomers: stereoisomers that are not enantiomers 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. Perspective Formulas of the Four Stereoisomers 16 2/16/18 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 17 2/16/18 No Asymmetric Centers There are only two stereoisomers: cis and trans. No Asymmetric Centers There are only two stereoisomers: cis and trans. 18 2/16/18 Two Asymmetric Centers: Three Stereoisomers (a Meso Compound and a Pair of Enantiomers) A Meso Compound Has a Superimposable Mirror Image Meso compounds are optically inactive even though they have asymmetric centers. 19 2/16/18 A Meso Compound Has a Plane of Symmetry A Meso Compound A compound with two asymmetric centers that has the same four groups bonded to each asymmetric center will have three stereoisomers: a meso compound and a pair of enantiomers. 20 2/16/18 A Meso Compound For cyclic compounds with the same substituents bonded to two asymmetric centers, cis = a meso compound and trans = a pair of enantiomers. Naming Stereoisomers 21 2/16/18 Naming Stereoisomers Naming Stereoisomers 22 2/16/18 Physical Properties of Stereoisomers Nitrogen and Phosphorus Can Be Asymmetric Centers 23 2/16/18 Amine Inversion If one of the four groups attached to N is a lone pair, the enantiomers cannot be separated, because they interconvert as a result of amine inversion. A Receptor is a Protein Proteins are Chiral Molecules Because a receptor is chiral, it binds one enantiomer. A right-handed glove fits only a right hand. 24 2/16/18 A Receptor Binds One Enantiomer Each enantiomer binds to a different receptor in the nose. Physiological Properties of Enantiomers Enantiomers can have very different physiological properties. 25 2/16/18 Separating Enantiomers separating by hand separating by chromatography 26 .