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Stereoisomerism and Chirality

Stereoisomerism and Chirality. Chapter 3. 3.1 Isomers/Stereoisomers. Isomers: different compounds with the same molecular formula Constitutional isomers: isomers with a different connectivity

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Stereoisomerism and Chirality

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  1. Stereoisomerism and Chirality Chapter 3

  2. 3.1 Isomers/Stereoisomers • Isomers: different compounds with the same molecular formula • Constitutional isomers: isomers with a different connectivity • Stereoisomers:isomers with the same connectivity but a different orientation of their atoms in space

  3. 3.2 Chirality • Chiral: from the Greek, cheir, hand • an object that is not superposable on its mirror image • Achiral: an object that lacks chirality; one that lacks handedness • an achiral object has at least one element of symmetry • plane of symmetry:an imaginary plane passing through an object dividing it so that one half is the mirror image of the other half • center of symmetry: a point so situated that identical components are located on opposite sides and equidistant from that point along the axis passing through it

  4. Elements of Symmetry, Fig. 3.1 • Symmetry in objects

  5. Elements of Symmetry • Plane of symmetry (cont’d)

  6. Chiral Center • The most common (but not the only) cause of chirality in organic molecules is a tetrahedral atom, normally carbon, bonded to four different groups • A carbon with four different groups bonded to it is called a chiral center • all chiral centers are stereocenters, but not all stereocenters are chiral centers (see Figure 3.5) • Enantiomers: stereoisomers that are nonsuperposable mirror images • refers to the relationship between pairs of objects

  7. Enantiomers • 2-Butanol • has one chiral center • here are four different representations for one enantiomer • using (4) as a model, here are two different representations for the enantiomer of (4)

  8. Enantiomers • The enantiomers of lactic acid • drawn in two different representations

  9. Enantiomers • 2-Chlorobutane

  10. Enantiomers • 3-Chlorocyclohexene

  11. Enantiomers • A nitrogen chiral center

  12. Fischer Projections • Fischer Projections are planar drawings of a chiral center • horizontal bonds project toward the viewer • vertical bonds project away from the viewer

  13. 3.3 R,S Convention (Cohn-Ingold-Prelog) Naming Chiral Centers: • Priority rules 1. Each atom bonded to the chiral center is assigned a priority based on atomic number; the higher the atomic number, the higher the priority

  14. R,S Convention (Cohn-Ingold-Prelog) • Priority rules 2. If priority cannot be assigned per the atoms bonded to the chiral center, look to the next set of atoms; priority is assigned at the first point of difference

  15. R,S Convention (Cohn-Ingold-Prelog) • Priority rules 3. Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds

  16. Applying the R,S assignment 1. Locate the chiral center, identify its four substituents, and assign priority from 1 (highest) to 4 (lowest) to each substituent 2. Orient the molecule so that the group of lowest priority (4) is directed away from you 3. Read the three groups projecting toward you in order from highest (1) to lowest priority (3) 4. If the groups are read clockwise, the configuration is R; if they are read counterclockwise, the configuration is S (S)-2-Chlorobutane

  17. Naming Chiral Centers • (R)-3-Chlorocyclohexene • (R)-Mevalonic acid

  18. 3.4 A. Enantiomers & Diastereomers • For a molecule with 1 chiral center, 21 = 2 stereoisomers are possible • For a molecule with 2 chiral centers, a maximum of 22 = 4 stereoisomers are possible • For a molecule with n chiral centers, a maximum of 2nstereoisomers are possible

  19. Enantiomers & Diastereomers • 2,3,4-Trihydroxybutanal • two chiral centers and 22 = 4 stereoisomers exist; two pairs of enantiomers • Diastereomers: • stereoisomers that are not mirror images • refers to the relationship among two or more objects

  20. B. Enantiomer, Diastereomer & Meso • 2,3-Dihydroxybutanedioic acid (tartaric acid) • two chiral centers and 2n = 4, but only three stereoisomers exist • Meso compound:an achiral compound possessing two or more chiral centers that also has chiral isomers

  21. 3.5 A. Cyclic Stereoisomers • 2-Methylcyclopentanol

  22. O H H O O H H O cis- 1,2-Cyclopentanediol (a meso compound) H O O H O H H O trans- 1,2-Cyclopentanediol (a pair of enantiomers) Enantiomers & Diastereomers • 1,2-Cyclopentanediol H H H H diastereomers H H H H

  23. B. Cyclic Stereoisomers • cis-3-Methylcyclohexanol

  24. Enantiomers & Diastereomers • trans-3-Methylcyclohexanol

  25. Isomers, Fig. 3.5

  26. 3.6 Properties of Stereoisomers • Enantiomers have identical physical and chemical properties in achiral environments • i.e.: mp., bp, density, pKa, solubility • Diastereomers are different compounds and have different physical and chemical properties • meso tartaric acid, for example, has different physical and chemical properties from its enantiomers (see Table 3.1)

  27. 3.7 A.Plane-Polarized Light • Ordinary light:light vibrating in all planes perpendicular to its direction of propagation • Plane-polarized light:light vibrating only in parallel planes • Optically active: refers to a compound that rotates the plane of plane-polarized light. This optical property distinguishes one enantiomer from its optical antipode.

  28. Plane-Polarized Light • plane-polarized light is the vector sum of its left and right circularly polarized components • circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer • the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization

  29. B. Measuring Optical Rotation • Polarimeter:a device for measuring the extent of rotation of plane-polarized light

  30. Optical Activity • observed rotation:the number of degrees, , through which a compound rotates the plane of polarized light • dextrorotatory (+):refers to a compound that rotates the plane of polarized light to the right • levorotatory (-):refers to a compound that rotates of the plane of polarized light to the left

  31. C O O H C O O H H C C H O H 3 H O 3 ( ( S R ) ) - - ( ( - + ) ) - - L L a a c c t t i i c c a a c c i i d d 2 1 2 1 = + 2 . 6 ° = - 2 . 6 ° [ a ] [ a ] Optical Activity • specific rotation:observed rotation when a pure sample is placed in a tube 1.0 dm in length and concentration in g/mL (density); for a solution, concentration is expressed in g/ 100 mL C C H H D D

  32. C.Racemic Mixture • Racemic mixture:an equimolar mixture of two enantiomers • because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific rotation is zero • Resolution:the separation of a racemic mixture into its enantiomers

  33. D. Optical Purity • Optical purity: a way of describing the composition of a mixture of enantiomers • Enantiomeric excess: the difference between the percentage of two enantiomers in a mixture • optical purity is numerically equal to enantiomeric excess, but is experimentally determined

  34. Enantiomeric Excess Example: a commercial synthesis of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), gives the S enantiomer in 97% ee Calculate the percentages of the R and S enantiomers in this mixture: The mixture is 97% S and 3% racemic. Racemic = 1.5% R + 1.5% S. So, the mixture is 98.5% S and 1.5% R.

  35. 3.8 A.Resolution • One means of resolution is to convert the pair of enantiomers into two diastereomers • diastereomers are different compounds and have different physical properties • A common reaction for chemical resolution is salt formation • after separation of the diastereomers, the enantiomerically pure acids are recovered

  36. Resolution • racemic acids can be resolved using commercially available chiral bases, e.g. 1-phenylethanamine • racemic bases can be resolved using chiral acids such as

  37. B. Resolution • Enzymes as resolving agents

  38. Amino Acids are chiral except Glycine • the 20 most common amino acids have a central carbon, called an a-carbon, bonded to an NH2 group and a COOH group • in 19 of the 20, the a-carbon is a chiral center • 18 of the 19 a-carbons have the R configuration, one has the S configuration • in the D,L system, all have the L configuration • at neutral pH, an amino acid exists as an internal salt • in this structural formula, the symbol R = a side chain

  39. Proteins • proteins are long chains of amino acids covalently bonded by amide bonds formed between the carboxyl group of one amino acid and the amino group of another amino acid

  40. 3.8 Chirality in the Biological World • Except for inorganic salts and a few low-molecular-weight organic substances, the molecules of living systems are chiral • Although these molecules can exist as a number of stereoisomers, generally only one is produced and used in a given biological system • It’s a chiral world!

  41. A. Chirality in the Biological World • Consider chymotrypsin, a protein-digesting enzyme in the digestive system of animals • chymotrypsin contains 251 chiral centers • the maximum number of stereoisomers possible is 2251 • there are only 238 stars in our galaxy!

  42. B. Chirality in the Biological World • Enzymes are like hands in a handshake • the substrate fits into a binding site on the enzyme surface • a left-handed molecule will only fit into a left-handed binding site and • a right-handed molecule will only fit into a right-handed binding site • enantiomers have different physiological properties because of the handedness of their interactions with other chiral molecules in living systems

  43. Chirality in the Biological World • a schematic diagram of an enzyme surface capable of binding with (R)-glyceraldehyde but not with (S)-glyceraldehyde

  44. Stereoisomerism and Chirality End Chapter 3

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