Before we start…Slide Number 2Slide Number 3Slide Number 4Why Chirality is Important?Biological significance EpinephrineSlide Number 7Constitutional IsomersStereosiomersSlide Number 10Slide Number 11Slide Number 12Slide Number 13Slide Number 14Slide Number 15Slide Number 16Slide Number 17Slide Number 18R, S ConfigurationSlide Number 20Slide Number 21Slide Number 22Slide Number 23Slide Number 24Historical PerspectiveSlide Number 26Slide Number 27Slide Number 28Slide Number 29Slide Number 30Slide Number 31Slide Number 32Slide Number 33Slide Number 34Slide Number 35Slide Number 36Slide Number 37Slide Number 38Slide Number 39Slide Number 40Slide Number 41Slide Number 42Slide Number 43Slide Number 44Slide Number 45How do we get one enantiomers?Slide Number 47ConclusionsSlide Number 49Before we start… • Mid-term report progress are in – If any questions, concerns : let me know • ACS- Green Chemistry Institute – – 12 principles of green chemistry – 12 principles of Green engineering – Anastas and Warner – (http://www.warnerbabcock.com) • In case of crisis (education version) APP – Download it!! 1Chapter 5 Stereochemistry: Chiral Molecules 2In this chapter: 1. How to identify, codify, and name the three-dimensional arrangement of atoms and molecules 2. How such arrangements can lead to unique properties and behaviors 3Chirality • An object is achiral (not chiral) if the object and its mirror image are identical • A chiral object is one that cannot be superposed on its mirror image 4Why Chirality is Important? Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs Chiral molecules are molecules that cannot be superimposed onto their mirror images. They are different molecules. http://www.youtube.com/watch?feature=player_detailpage&list=PL7B03F168883BC7DF&v=RBtgAz70_JY#t=6 Thalidomide The enantioner on the right fits in specific enzyme producing the desired effect (sedative). The enantiomer on the left due to a different arrangement in space does NOT fit in the same enzyme. It fits in a different enzyme pocket, which causes birth defects. 5Biological significance Epinephrine • Epinephrine or Adrenaline 6Isomerism: Stereoisomers are isomers with the same molecular formula and same connectivity of atoms but different arrangement of atoms in space. Isomers (different compounds with same molecular formula) Constitutional Isomers (isomers whose atoms have a different connectivity) Stereoisomers (isomers that have the same connectivity but differ in spatial arrangement of their atoms) Enantiomers (stereoisomers that are nonsuperimposable mirror images of each other) Diastereomers (stereoisomers that are NOT mirror images of each other) 7Molecular Formula andButanoic acidMethyl propanoateOHOCH3OOC2H6O C4H8O2 OHCH3O CH3andEthanol MethoxymethaneConstitutional Isomers (Dimethyl ether) 8Enantiomers – stereoisomers whose molecules are nonsuperimposable mirror images of each other. (one stereocenter) Diastereomers – stereoisomers whose molecules are not mirror images of each other. (two or more stereocenter) Example: cis and trans double bond isomers are diastereomers Example: cis and trans cycloalkane isomers are diasteromers Stereosiomers 9Enantiomers and Chiral Molecules Chiral molecule: a molecule which is not superposable on its mirror image. A chiral molecule and its mirror image are called a pair of enantiomers. Molecules that are superposable on their mirror image are achiral. Example: 2-butanol is a chiral molecule. I and II are mirror images (figures a and b) and are not superposable (figure c). They are enantiomers. HOH(II)OHH(I)10Molecules Having One Chirality Center Are Chiral 1) A chirality center is a tetrahedral carbon atom that is bonded to four different groups 2) The presence of a single chirality center in a molecule guarantees that the molecule is chiral and that enantiomeric forms are possible 3) A molecule that contains one chirality center is chiral and can exist as a pair of enantiomers 4) Any atom at which an interchange of groups produces a stereoisomer is called a stereogenic center (if the atom is a carbon atom it is usually called a stereogenic carbon) 5) If all of the tetrahedral atoms in a molecule have two or more groups attached that are the same, the molecule does not have a chirality center. The molecule is superimposable on its mirror image and is achiral 11In Class Practice Problem: Which molecule has a chiral center? (2) (1) (4) (3) 12In Class Practice Problem: Is 2-propanol chiral? (1) YES (2) NO 13Example: 2-butanol , in contrast, is chiral. The stereogenic center is indicated by asterisk (*) Me EtOHH*(A)mirrorMeEtHOH*(B)Tetrahedral stereogenic center 14(C)HPhPhHmirror(D)PhHHPhTrigonal stereogenic center ⇒ achiral (C) & (D) are identical Cis and trans alkene isomers contain trigonal stereogenic centers In Class Practice Problem: Does 1,2-diphenyl chiral? (1) YES (2) NO 15Tests for Chirality: Planes of Symmetry Plane of symmetry: an imaginary plane that bisects a molecule in such a way that the two halves of the molecule are mirror images of each other. A molecule with a plane of symmetry cannot be chiral. Example: 2-Chloropropane Me MeClHPlane of symmetry achiral Me EtClHNo plane of symmetry chiral 16Nomenclature of Enantiomers: The R,S System Cahn-Ingold-Prelog System HOH(II)OHH(I)2-Butanol: Using only the IUPAC naming that we have learned so far, these two enantiomers will have the same name: 2-Butanol This is undesirable because each compound must have its own distinct name 17Nomenclature of Enantiomers: The R,S System Cahn-Ingold-Prelog System HOH(II)OHH(I)2-Butanol: The four groups attached to the stereogenic carbon are assigned priorities from highest (a) to lowest (d). Priorities are assigned as follows: (1) Atoms directly attached to the stereogenic center are compared. (2) Atoms with higher atomic number are given higher priority. (3) If priority cannot be assigned based on directly attached atoms, the next layer of atoms is examined. 18R, S Configuration Visualize the molecule so that the lowest priority group is directed away from you, then trace a path from highest to lowest priority. If the path is a clockwise motion, then the configuration at the asymmetric carbon is (R). If the path is a counter-clockwise motion, then the configuration is