Stereochemistry an introduction Chem 30A Fall 2002 Grazia Piizzi Steve Hardinger Stereochemistry of Tetrahedral Carbons We need one Carbon sp3 hybridized at least to represent molecules as 3D objects For example H H H C Cl Br H C C Br Not appropriate for Stereochem Cl Br H H 2D drawing H Cl H 3D drawing Cl Appropriate for Stereochem Br 2 Let s consider some molecules First pair H H Br Br Cl H Cl A H same molecular formula CH2BrCl same atom connectivity superposable identical same compound B Second pair H F Br C F Cl H Br Cl D same molecular formula CHFBrCl same atom connectivity nonsuperposable stereoisomers two different compounds 3 Thus we can define Stereoisomers Stereoisomers isomers that have same formula and connectivity but differ in the position of the atoms in space Stereochemistry Stereochemistry chemistry that studies the properties of stereoisomers 4 Historical perspective Christiaan Huygens 1629 1695 Dutch astronomer mathematician and physicist He discovers plane polarized light Normal light nonpolarized Horizontally polarized light Light completely blocked Direction of light Horizontal filter Vertical filter 5 Historical perspective Carl Wilhelm Scheele 1742 1786 Oh how happy I am No care for eating or drinking or dwelling no care for my pharmaceutical business for this is mere play to me But to watch new phenomena this is all my care and how glad is the enquirer when discovery rewards his diligence then his heart rejoices In 1769 he discovers Tartaric Acid from tartar the potassium salt of tartaric acid deposited on barrels and corks during fermentation of grape juice HO CO2H HO CO2H Tartaric Acid 6 Historical perspective Jean Baptiste Biot 1774 1862 In 1815 he notes that certain natural organic compounds liquids or solutions rotate plane polarized light Optical Activity IN plane polarized light molecule ule oleculele m c e l mo moleculelecu moleculemo OUT tube containing a liquid organic compound or solution plane polarized light 7 Definitions Optically Active Active the ability of some compounds to rotate plane polarized light Dextrorotatory an optically active compound that rotates plane polarized light in a clockwise direction Levorotatory an optically active compound that rotates plane polarized light in a counterclockwise direction H H Nicotine N N N CH3 H3C CH3 H Methamphetamine 8 Historical perspective In 1819 Racemic Acid was discovered Later shown to have the same formula as Tartaric Acid In 1832 Biot notes that Tartaric Acid from grape juice fermentation rotates plane polarized light in a clockwise direction IN HO HO CO2H HO HO plane polarized light CO2H HO CO2H HO CO2H HO CO2H HO CO2H HO CO2H OUT CO2H HO CO2H CO2H tube containing solution of Tartaric Acid TA plane polarized light rotated clockwise TA is dextrorotatory 9 Historical perspective In 1819 Racemic Acid was discovered Later shown to have the same formula as Tartaric Acid In 1838 Biot notes that Racemic Acid does not rotate plane polarized light IN HO HO CO2H HO HO plane polarized light CO2H HO CO2H HO CO2H HO CO2H HO CO2H HO CO2H OUT CO2H HO CO2H CO2H tube containing solution of Racemic Acid RA plane polarized light unchanged RA is not optically active 10 Historical perspective Louis Pasteur 1822 1895 In 1847 he repeats earlier work on Racemic Acid Crystallization of sodium ammonium salt gives mirror image crystals that he separated by hand Equimolar solutions of separated crystals have equal but opposite optical activity HO CO2 Na D D 12 7 12 7o Tartaric Acid separate dextrorotatory natural crystals HO CO2 NH4 Racemic acid salt D 12 7o Tartaric Acid levorotatory unnatural 11 Historical perspective In 1853 Pasteur studies Mesotartaric Acid same formula as Racemic and HO Tartaric Acid but fails to separate into and crystals HO CO2H CO2H In 1854 he notes that certain plant mold metabolizes tartaric acid but not tartaric acid 12 Historical perspective Joseph A LeBel 1847 1930 In 1874 they propose Jacobus H van t Hoff 1852 1930 Carbon with 4 attachments is Tetrahedral A molecule having a tetrahedral carbon with 4 different attachments may exist as a pair of isomers 13 Therefore Stereoisomers Stereoisomers isomers that differ only in the position of atoms in space and that cannot be interconverted by rotation around a single bond Stereocenter Stereocenter a carbon atom bearing 4 different atoms or group of atoms H F F Br Cl C H Br Cl C D are a pair of stereoisomers Carbon is a stereocenter D 14 another example Stereoisomers of 2 chlorobutane H Cl A Cl H B A B are stereoisomers Carbons are stereocenters A B are nonsuperposable mirror images Enantiomers Enantiomers stereoisomers that are nonsuperposable mirror images Chiral any molecule that is nonsuperposable with its mirror image i e A and B are chiral Achiral any molecule that is not chiral Racemic mixture a 1 1 equimolar mixture of two enantiomers 15 Unsolved Issues HO CO2H HO CO2H Mesotartaric Acid Joseph A LeBel 1847 1930 Jacobus H van t Hoff 1852 1930 could not be separated into crystals and crystals Carbon with 4 attachments is Tetrahedral A molecule having a tetrahedral carbon with 4 different attachments may exist as a pair of isomers 16 In 1877 Hermann Kolbe one of the best organic chemist of the time wrote Not long ago I expressed the view that the lack of general education and of through training in chemistry was one of the reasons of the causes of the deterioration of chemical research in Germany Will anyone to whom my worries seem exaggerated please read if he can a recent memoir by a Herr van t Hoff on The Arrangement of Atoms in Space a document crammed to the hilt with the outpouring of childish fantasy This Dr J H van t Hoff employed by the Veterinary College at Utrecht has so it seems no taste for accurate chemical research He finds it more convenient to mount his Pegasus evidently taken from the stables of the Veterinary College and to announce how on his bold flight to Mount Parnassus he saw the atoms arranged in in space In 1901 van t Hoff received the first Nobel Prize in Chemistry In 1877 Hermann Kolbe 17 Take home problem Stereoisomers of 2 chlorobutane H Cl A Cl H B Enantiomers Remember Enantiomers stereoisomers that are nonsuperposable mirror images Racemic mixture a 1 1 equimolar mixture of two enantiomers Explain why A and B cannot be physically separated a racemic mixture of A and B has no optical activity no rotation of plane polarized light 18 Summary Stereoisomers Stereoisomers isomers that have same formula and