Organic Chemistry Lecture 7: Stereochemistry PDF

ORGANIC CHEMISTRY LECTURE 7 STEREOCHEMISTRY  STEREOCHEMISTRY Thalidomide Used as sedative and anti-nausea drug for pregnant women Sold as a mixture of two enantiomers Enantiomer 1- had the desired therapeutic effect Enantiomer 2- responsible for thousan...

ORGANIC CHEMISTRY LECTURE 7 STEREOCHEMISTRY  STEREOCHEMISTRY Thalidomide Used as sedative and anti-nausea drug for pregnant women Sold as a mixture of two enantiomers Enantiomer 1- had the desired therapeutic effect Enantiomer 2- responsible for thousands of catastrophic birth defects in children born to women who took the drug during pregnancy  STEREOCHEMISTRY I. Starch and Cellulose Recall: Stereochemistry is the three-dimensional structure of a molecule Starch Main carbohydrate in the seeds and roots of plants When consumed, it is then hydrolyzed to the simple sugar- glucose Cellulose Nature’s most abundant organic material that gives rigidity to tree trunks and plant stems Complete hydrolysis of cellulose also forms glucose but humans cannot metabolize cellulose to glucose.  STEREOCHEMISTRY I. Starch and Cellulose Starch and cellulose are both composed of the same repeating unit Six-membered ring containing an oxygen atom and three OH groups that are joined by an oxygen atom Differ in the position of O atom joining the ring together In cellulose, the O atom joins two rings using equatorial bonds In starch, the O atom joins two rings using one equatorial and one axial bond.  STEREOCHEMISTRY I. Starch and Cellulose In cellulose, the O atom joins two rings using equatorial bonds In starch, the O atom joins two rings using one equatorial and one axial bond.  STEREOCHEMISTRY I. Starch and Cellulose Isomers because they are different compounds with the same molecular formula (C!H"#O$)% Only the 3D arrangement of atoms are different Cellulose Composed of long chains held together by intermolecular H- bonds thus forming sheets that stack in an extensive three- dimensional network Starch The axial-equatorial ring junction creates chains that fold into a helix  STEREOCHEMISTRY II. The Two Major Classes of Isomers Isomers Are different compounds with the same molecular formula Two major classes of isomers Constitutional (structural) isomers Differ in the way the atoms are connected to each other They have: Different IUPAC names, same or different functional groups, different physical properties, and different chemical properties Stereoisomers Differ only in the way atoms are oriented in space Differ on configuration Identical IUPAC names (except for a prefix like cis or trans) Always has the same functional groups  STEREOCHEMISTRY II. The Two Major Classes of Isomers Configuration A particular three-dimensional arrangement  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules To superimpose an object on its mirror image means to align all parts of the object with its mirror image Chiral A molecule or object that is not superimposable on its mirror image  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules Achiral A molecule or object that is superimposable on its mirror image Identical  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules Test for chirality: Draw the three-dimensional structure of the molecule Draw the mirror image Align all bonds and atoms Example H& O CH&BrCl CHBrClF  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules Achiral: H& O CH&BrCl  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules Chiral: CHBrClF  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules Enantiomers are mirror images that are not superimposable Tetrahedral stereogenic center A carbon atom bonded to four different groups Most chiral molecules contain Any site in a molecule at which the interchange of two groups forms a stereoisomer A molecule with four different groups No stereogenic center- a molecule is not chiral With one stereogenic center- a molecule is always chiral With two or more stereogenic centers- a molecule may or may not be chiral  STEREOCHEMISTRY III. Looking Glass Chemistry- Chiral and Achiral Molecules A plane of symmetry is a mirror plane that cuts a molecule in half, so that one half of the molecule is a reflection of the other half Achiral molecules usually contain a plane of symmetry Chiral molecules do not contain a plane of symmetry  STEREOCHEMISTRY IV. Stereogenic Centers Stereogenic Center on Carbon Atoms That Are Not Part of a Ring To locate a stereogenic center, examine each tetrahedral carbon atom in a molecule, and look a the four groups (not the four atoms) bonded to it NOTE: not stereogenic centers CH2 and CH3 groups sp and sp2 hybridized C  STEREOCHEMISTRY IV. Stereogenic Centers Stereogenic Center on Carbon Atoms That Are Not Part of a Ring To locate a stereogenic center, examine each tetrahedral carbon atom in a molecule, and look a the four groups (not the four atoms) bonded to it  STEREOCHEMISTRY IV. Stereogenic Centers Drawing a Pair of Enantiomers Any molecule with one tetrahedral stereogenic center is a chiral compound and exists as a pair of enantiomers Example: 2-Butanol  STEREOCHEMISTRY IV. Stereogenic Centers Drawing a Pair of Enantiomers Place two bonds in the plane, one in front of the plane on a wedge, and one behind the plane on a dash Enantiomer A Arbitrarily place the four groups on any bond to the stereogenic center Enantiomer B Draw a mirror image of the enantiomer A  STEREOCHEMISTRY V. Stereogenic Centers in Cyclic Compounds Always draw the rings as flat polygons and look for tetrahedral carbons that are bonded to four different groups Each ring carbon is bonded to two other atoms in the ring, as well as two substituents attached to the ring When the two substituents on the ring are different, we must compare the ring atoms equidistant from the atom in question Example  STEREOCHEMISTRY V. Stereogenic Centers in Cyclic Compounds Example Because 3-methylcyclohexene has one tetrahedral stereogenic center it is a chiral compound and exists as a pair of enantiomers.  STEREOCHEMISTRY V. Stereogenic Centers in Cyclic Compounds Thalidomide Contains once stereogenic center Used as sedative and anti-nausea drug for pregnant women Sold as a mixture of two enantiomers Enantiomer 1- had the desired therapeutic effect Enantiomer 2- responsible for thousands of catastrophic birth defects in children born to women who took the drug during pregnancy  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer Rules Needed to Assign Priority Rule 1: Assign priorities (1,2,3 or 4) to the atoms directly bonded to the stereogenic center in order of decreasing atomic number. The atom of highest atomic number gets the highest priority (1).  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer Rules Needed to Assign Priority 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 a higher priority.  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer Rules Needed to Assign Priority Rule 3: If two isotopes are bonded to the stereogenic center, assign priorities in order of decreasing mass number.  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer Rules Needed to Assign Priority Rule 4: To assign a priority to an atom that is part of a multiple bond, treat a multiply bonder atom as an equivalent number of singly bonded atoms.  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer Rules Needed to Assign Priority Example  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer How to Assign R or S to a Stereogenic Center Example  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer How to Assign R or S to a Stereogenic Center Step 1: Assign priorities from 1 to 4 to each group bonded to the stereogenic center  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer How to Assign R or S to a Stereogenic Center Step 2: Orient the molecule with the lowest priority group (4) back (dash lines) and visualize the relative position of the remaining three groups (1-3).  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer How to Assign R or S to a Stereogenic Center Step 3: Trace a circle from priority group 1→2→3  STEREOCHEMISTRY VI. Labeling Stereogenic Centers with R or S Adding of R and S to the IUPAC name of the enantiomer How to Assign R or S to a Stereogenic Center Step 3: Trace a circle from priority group 1→2→3  STEREOCHEMISTRY VII. Diastereomers For n stereogenic centers, the maximum number of stereoisomers is 2n. When n = 1, 21 = 2. With one stereogenic center there are always two stereoisomers and they are enantiomers. When n = 2, 22 = 4. With two stereogenic centers, the maximum number of stereoisomers is four, although sometimes there are fewer than four.  STEREOCHEMISTRY VII. Diastereomers How to find and draw all possible stereoisomers for a compound with two stereogenic center Step 1: Draw one stereoisomers by arbitrarily arranging substituents around the stereogenic centers. Then draw its mirror image  STEREOCHEMISTRY VII. Diastereomers How to find and draw all possible stereoisomers for a compound with two stereogenic center Step 1: Draw one stereoisomers by arbitrarily arranging substituents around the stereogenic centers. Then draw its mirror image Rotate one molecule to see if all the atoms align  STEREOCHEMISTRY VII. Diastereomers How to find and draw all possible stereoisomers for a compound with two stereogenic center Step 2: Draw a third possible stereoisomer by switching the positions of any two groups on one stereogenic center only. Then draw its mirror image  STEREOCHEMISTRY VII. Diastereomers Enantiomers: A and B; C and D Diastereomers: A and B to C and D Not mirror images of each other  STEREOCHEMISTRY VII. Diastereomers  STEREOCHEMISTRY VIII. Meso Compounds An achiral compound that contains tetrahedral stereogenic centers 2,3-dibromobutane has two stereogenic centers but fewer than the maximum number of stereoisomers  STEREOCHEMISTRY VIII. Meso Compounds 2,3-dibromobutane has two stereogenic centers but fewer than the maximum number of stereoisomers To find the other two stereoisomers (if they exist), switch the position of two groups on one stereogenic center of one enantiomer only However, the mirror image of C, labeled D, is superimposable on C, so C and D are identical.  STEREOCHEMISTRY VIII. Meso Compounds Compound C is therefor achiral It contains a plane of symmetry It possesses two identical halves  STEREOCHEMISTRY IX. R and S Assignments in Compounds with Two or More Stereogenic Centers When a compound has more than one stereogenic center, R or S configuration must be assigned to each of them Identical compounds have the same R, S designations at every tetrahedral stereogenic center Enantiomer have exactly opposite R, S designations Diastereomers have the same R, S designations for at least one stereogenic center and the opposite for at least one of the other stereogenic centers  STEREOCHEMISTRY X. Disubstituted Cycloalkanes 1,3-dibromocyclopentane Stereoisomers but not mirror images of each other thus they are diasteromers  STEREOCHEMISTRY X. Disubstituted Cycloalkanes 1,3-dibromocyclopentane Finding if other two stereoisomers exist, draw the mirror image of each compound and determine whether the compound and its mirror image are superimposable The cis isomer is superimposable on its mirror image, making them identical A is achiral meso compound  STEREOCHEMISTRY X. Disubstituted Cycloalkanes 1,3-dibromocyclopentane Finding if other two stereoisomers exist, draw the mirror image of each compound and determine whether the compound and its mirror image are superimposable The trans isomer B is not superimposable on its mirror image, labeled as C, making B and C different compounds. B and C are enantiomers  STEREOCHEMISTRY XI. Isomers- A Summary There are two major classes of isomers: constitutional isomers and stereoisomers. There are only two kinds of stereoisomers: enantiomers and diastereomers.  STEREOCHEMISTRY XII. Isomers- A Summary The chemical and physical properties of two enantiomers are identical except in their interaction with chiral substances Optical Activity Plane-polarized light Passing light through a polarizer allows light in only one plane to come through Has an electric vector that oscillates in single plane  STEREOCHEMISTRY XII. Isomers- A Summary Optical Activity Polarimeter an instrument that allows plane-polarized light to travel through a sample tube containing an organic compound. Then an analyzer slit is rotated to determine the direction of the plane of the polarized light exiting the sample tube Two results are possible: The plane of polarization is not changed The plane of polarization is changed  STEREOCHEMISTRY XII. Isomers- A Summary Optical Activity Achiral The light exits the sample tube unchanged and the plane of the polarized light is in the same position it was before entering the tube Optically inactive A compound that does not change the plane of polarized light  STEREOCHEMISTRY XII. Isomers- A Summary Optical Activity Chiral The plane of the polarized light is rotated through an angle 𝛼 The angle 𝛼 (measured in degrees), is called the observed rotation Optically active A compound that rotates the plane of polarized light  STEREOCHEMISTRY XII. Isomers- A Summary Optical Activity A clockwise rotation: dextrorotatory d or (+). A counterclockwise rotation: levorotatory l or (-). Two enantiomers rotate plane-polarized light to an equal extent but in opposite direction.  STEREOCHEMISTRY XII. Isomers- A Summary Racemic Mixtures Two enantiomer rotate plane-polarized light to an equal extent but in opposite directions, the rotations cancel, and no rotation is observed An equal amount of two enantiomers. Optically inactive. The physical properties of two enantiomers and their racemic mixture are summarized in the table below  STEREOCHEMISTRY XII. Isomers- A Summary Specific Rotation The observed rotation depends on the number of chiral molecules that interact with polarized light Thus it depends on the concentration of the sample and the length of the sample tube  STEREOCHEMISTRY XII. Isomers- A Summary Enantiomeric Excess Sometimes in the laboratory we have neither a pure enantiomer nor a racemic mixture, but rather a mixture of two enantiomers in which one enantiomer is present in excess of the other. Also called as optical purity Tells us how much more there one enantiomer is present in excess of the racemic mixture the specific rotation 𝛼 of a mixture and the specific rotation 𝛼 of a pure enantiomer  STEREOCHEMISTRY XII. Isomers- A Summary The Physical Properties of Diastereomers Not mirror images of each other, and as such, their physical properties are different, including optical rotation. On the right is the physical properties of the three stereoisomers of tartaric acid  STEREOCHEMISTRY XII. Isomers- A Summary The Physical Properties of Diastereomers Because two 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 they can be separated by common physical techniques.  STEREOCHEMISTRY XIII. Chemical Properties of Enantiomers Two enantiomers have exactly the same chemical properties except for their reaction with chiral, non-racemic reagents  REFERENCE Smith, J.G. (2011). Organic Chemistry (3rd ed.). New York: McGraw-Hill. QUIZ QUIZ QUIZ