L TOPIC 4 STEREOCHEMISTRY Chapter 5 OBJECTIVES 1 2 3 4 5 D M Collard 2007 Discuss the three dimensional structure of organic molecules Recognize enantiomers diastereomers meso compounds Provide R S designations of stereocenters Calculate optical rotations enantiomeric excesses Use molecular models to determine the 3D arrangement of atoms in chiral molecules S 5 1 2 RECOGNIZING ISOMERS Isomers Compounds with same molecular formula but different structures Constitutional Isomers Stereoisomers Different connectivity Same connectivity different three dimensional arrangement Diastereomers Enantiomers Stereoisomers which are not enantiomers includes geometic isomers Non superposable mirror images CHIRALITY ENANTIOMERS An object molecule which has a non superposable mirror image is chiral the opposite of chiral is achiral S 5 3 5 5 5 7 Prob 5 30 31 33 35a b f Important small print In spite of Solomon and Fryhle s foonote regarding the dictionary definition of superposable and superimposable and their preference for the former most chemists refer to non superimposability of mirror images as a requirement for chirality This instructor will undoubtedly use superimposability in lecture and on exams D M Collard 2007 Symmetry Mirror Planes and Centers of Inversion Another test for chirality is to assess whether the object itself has a mirror plane of symmetry or point of symmetry point of inversion Objects molecules with mirror planes or centers of inversion are achiral NOT chiral CH3 COOH C H3C H3C Cl Cl H3C Objects molecules without a mirror plane or point of inversion are chiral They are non superposable on their mirror images Enantiomers Molecules can be chiral Pairs of molecules which are non superposable mirror images of one another are called enantiomers Enantiomers are examples of stereoisomers molecules which differ only in the spatial arrangement of atoms Molecules with a single carbon atom bearing four different substituents can exist as a pair of enantiomers which differ in the arrangement configuration of these substituents A A The carbon is stereogenic The carbon is a stereocenter B A 1 1 mixture of enantiomers is called a racemic mixture You must be able to recognize when pairs of molecules are identical superposable or entaniomers non superposable mirror images D M Collard 2007 D C D C B Problem Which of the following are identical to the first structure Problem Which of the following are identical to the first structure H H3 C CH3 OH COOH COOH COOH HO H H3C H OH Problem Which of the following are identical to the first structure COOH H3 C D M Collard 2007 OH H H HOOC COOH OH CH3 H CH3 OH Designating Configuration Stereocenters are designated as having either R or S configurations Assign priorities to the substituents using the Cahn Ingold Prelog system briefly atoms are ranked in order of atomic number if isotopes are present the heavier isotope has higher priority if two atoms are identical the next set of attached atoms is considered View the molecule with the lowest priority 4 substituent pointing away from you Trace from highest priority 1 to second priority 2 to third 3 Clockwise R Counterclockwise S F e g Br D H Cl HO D deuterium 2H D H CH3 H Ranking Substituents If the atoms joined to the chiral center are identical you must consider the set of three atoms connected to them C CH3 3 CH CH3 2 CH2CH3 C C C C C C C H CH2OH C O H H C C H H CH3 C H H H C CH3 3 C C C C A double bond is considered to be two bonds to the next atom H H CH2OH C O C C O O H D M Collard 2007 C O H H C C C H CH2 Examples of Chiral Molecules CH3 O CH3 H H2N CH2CO2H CO2H H HO CO2H H CH2 H3C S alanine an amino acid S malic acid R carvone from apples spearmint Problem What is the configuration of each stereocenter chiral carbon atom in each of the following compounds CH3 N O H NH2 CH2 H H 3C D M Collard 2007 H3C H H O O O H O O L S 5 13 FISCHER PROJECTIONS Prob 5 35k l molecules with one stereocenter Orient the molecule so that substituents oriented up and down are pointing away from you and then apply a steamroller C D http www r r a org uk aandp html B A Converting a Fischer projection back into a 3D tetrahedral representation CH3 HO H CH2CH3 Problem Which of the following represent the S enantiomer of 2 phenyl 1ethanol which ones are R Me Ph Ph OH H H Me OH Ph H Ph OH Ph D M Collard 2007 OH H Me Me H HO Me Problem Which of the following are identical to the first structure You should be able to work out how Fischer projections can be redrawn without inverting the configuration COOH H H OH H3C CH3 COOH HO OH HOOC H CH3 H COOH r otate by 90o rotate by 180o COOH HO OH CH3 r otate by 270o COOH H H COOH OH H3C H CH3 CH3 OH swap hor izontal substit uent s swap vertical substituents rotate set of subst ituents S 5 1 5 4 5 11 WHY IS STEREOCHEMISTRY IMPORTANT Chirality in Nature Most biomolecules are chiral and only exist as one enantiomer in nature NH2 H OH O N H O H2N OH H H CH CH3 2 O OH Carbohydrates sugars e g glucose HO H H OH H H H Nucleotides in DNA e g cytosine Problem What is the configuration of each stereocenter chiral carbon atom in each of the above compounds D M Collard 2007 N O H H Amino acids in proteins e g valine HO HO HO Interaction between the Body Receptors and Chiral Drugs R R Chiral Pharmaceuticals Thalidomide The racemate of thalidomide was marketed in Europe in early 1960s for treatment of morning sickness One enantiomer is a sedative However the other causes birth defects Today both enantiomers of any pharmaceutical must be tested for efficacy and side effects Recent studies have shown that thalidomide may be effective against HIV cancer leprosy and other inflammatory disorders O H O NH O O Problem Which enantiomer of thalidomide is shown above D M Collard 2007 S 5 8 5 9 ROTATION OF PLANE POLARIZED LIGHT Enantiomers have identical physical and chemical properties in the absence of other chiral molecules except for their influence on planepolarized light Polarimetry Optical Rotation The observed rotation is The observed specific rotatation is c l where c concentration of solution in g mL and l pathlength in dm 1 dm 10 cm 10 1 m and depend on solvent temperature and wavelength of the polarized light Generally the sodium D line is used for the light source and the experiment is done at room temperature 25 C The specific rotation is then noted as 25 D conc solvent The specific rotation of an optical pure chiral compound is a property like melting point or boiling point The specific