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1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereoc

Stereochemistry- Chapter 3. 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters 7. Optical activity

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1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereoc

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  1. Stereochemistry- Chapter 3 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters 7. Optical activity 8. Separation of Enantiomers, Resolution 9. Significance of Chirality in the biological world

  2. Isomers - same molecular formula - different compounds constitutional isomers - different connectivity stereoisomers - same connectivity - different orientation in space (recall cis/trans)

  3. Chirality handednessnot superposable on its mirror image types: planeimaginary plane through an object one half is the mirror image of the other symmetry = superposable center identical parts on an axis equidistant from a point

  4. syn - plane of symmetry anti - point of symmetry . Elements of Symmetry Conformations of2,3-butanediol* . If symmetry is present, the substance is achiral. *meso or R,S (later)

  5. Plane of symmetry Elements of Symmetry achiral

  6. common source of chirality - tetrahedral (sp3) carbon (atom) - bonded to 4 different groups Chiral Center chiral center- carbon (atom) with 4 different groups Enantiomers: stereoisomers nonsuperposable mirror images All chiral centers are stereocenters Not all stereocenters are chiral centers

  7. 2-Butanol - 1chiral center Enantiomers different representations for this enantiomer representation of mirror image or enantiomer

  8. 3-Chlorocyclohexene Enantiomers

  9. A nitrogen chiral center Enantiomers

  10. 2-Chlorobutane Enantiomers How is handedness designated?

  11. increasing priority increasing priority R,S Convention - Priority rules Each atom bonded to the chiral center assigned a priority by atomic number higher atomic number, higher the priority Same atoms bonded to the chiral center look to the next set of atoms priority assigned to 1st point of difference

  12. double (triple) bond atoms viewed as bonded to an equivalent number of atoms by single bonds R,S Convention

  13. Naming Chiral Centers 1. Locate the chiral center, prioritize four substituents 1 (highest) to 4 (lowest) 2. Orient molecule so that lowest priority (4) group is directed away ( behind ) 3. Read three groups toward you (in front) (1) to (3) Clockwise R configuration; counterclockwise S

  14. ( )-3-Chlorocyclohexene R R ( )-mevalonic acid Naming Chiral Centers R

  15. Stereochemistry- Chapter 3 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters 7. Optical activity 8. Separation of Enantiomers, Resolution 9. Significance of Chirality in the biological world

  16. Naproxen Ibuprofen S isomer particularly active, but R slowly converted to S S isomer

  17. R S caraway/dill Assign R/S to stereogenic carbon in coniine R-(-)-coniine poison hemlock Golden pitcher plant Assign R or S to carvone spearmint

  18. molecule with 1 chiral center: 21 = 2 stereoisomers are possible Enantiomers & Diastereomers molecule with 2 chiral centers: a max of 22 = 4 stereoisomers “possible” molecule with n chiral centers: 2n = maximum stereoisomers are possible

  19. 2n 256 (ignore sugar)

  20. 2,3,4-trihydroxybutanal 2 chiral centers Enantiomers & Diastereomers 22 = 4 stereoisomers “possible” & exist 2 pairs of enantiomer (Erythrose) Diastereomers:stereoisomers that are not mirror images

  21. 2,3-Dihydroxybutanedioicacid (tartaric acid) 2n = 4 “possible” but only three stereoisomers exist symmetry plane-superposable (same compound) enantiomers Meso compound: achiral but possessing 2 or more chiral centers Enantiomers & Diastereomers

  22. 2-Methylcyclopentanol diastereomers top bottom enantiomers left right Enantiomers & Diastereomers cis-2-Methylcyclopentanol trans-2-Methylcyclopentanol

  23. 1,2-cyclopentanediol diastereomers cis-1,2-cyclopentanediol (a meso compound) Enantiomers & Diastereomers trans-1,2-cyclopentanediol (enantiomers)

  24. cis-3-methylcyclohexanol Enantiomers & Diastereomers flip: axial-equatorial reverse but still cis

  25. trans-3-methylcyclohexanol Enantiomers & Diastereomers flip: axial-equatorial reverse but still trans

  26. Enantiomers: identical physical and chemical properties inachiralenvironments Properties of Stereoisomers m. pt. 174o 174o pK1 2.98 2.98 Diastereomers: different compounds different physical and chemical properties m. pt. 146o 174o pK1 3.23 2.98

  27. Light vibrating in all planes  to direction of propagation Plane-polarized light:light vibrating only in parallel planes Plane-Polarized Light optical activity Plane-polarized lightthe vector sum of left and right circularly polarized light

  28. rotating the plane one way with R center and opposite way with S Optically ActivityEnantiomers (chiral) interact with circularly polarized light result: rotation of plane-polarized light clockwise (+) or counterclockwise (-)

  29. Plane-Polarized Light (polarimeter) Change in the polarized plane? achiral sample no change in the plane

  30. rotates the plane Plane-Polarized Light (polarimeter) Change in the polarized plane?  CHIRAL

  31. Stereochemistry- Chapter 3 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters 7. Optical activity 8. Separation of Enantiomers, Resolution 9. Significance of Chirality in the biological world

  32. observed rotation:, degrees a compound rotates polarized light -dextrorotatory (+) right - levorotatory (-)left T specific rotation []D = S R Optical Activity ( )-(+)-lactic acid ( )-(-)-lactic acid

  33. Example: 0.5g (-)-epinephrine-HCl in 10mL H2O measured in 20 cm cell (25o/D) obs = -5.0o, []D =? 25o R-enantiomer is (-); R or S above? [a] = deg (cm2g-1 )

  34. Racemic mixture: equal amounts of (+) and (-) enantiomers - rotation is 0o Optical Activity For a 50/50 mixture of S and R, = ? 0o

  35. 21o (S)-(+)-2-bromobutane, []D=+23.1o 21o But from the obs, []D=+9.2? Mixisbetween 100% S and 50/50(S/R) optical purity  the sample has70%S and30%R It’s not pure; possibly someR present! If some R, what percent? +23.1o > +9.2o < 0o = 40% 40% excess= 40%S + (60%S/Rmixture) 40% excess= 40%S + (30%S + 30%R)

  36. enantiomeric excess (ee): difference between the percent of 2 enantiomers in a mixture Optical Purity:composition of a mixture of enantiomers ee = optical purity

  37. 6 - 4 6 + 4 ee = x100% rt []D of (+)-2-butanol = +13.5o; obs sample = ? obs +13.5pure obs pure opt pure = = ee 20% = e.g. 6g of (+)-2-butanol plus 4g of (-)-2-butanol, ee = ? = 20% obs = (.20)(+13.5%) = +2.7o

  38. Example:A commercial synthesis of naproxen (Aleve) gives the S enantiomer in 97% ee. What are the percentages of the R & S in this mixture? Enantiomeric Excess 100% sample = 97%S + (3%S and R) 97%S + (1.5%S+1.5%R) 98.5%S + 1.5%R

  39. One strategy: convert enantiomeric pair into 2 diastereomers Resolution - separation of enantiomers diastereomers - different compounds different physical properties Common - reaction forming salt separate diastereomers remove :B leaves pure enantiomers 4

  40. racemic acids - resolved w/ available chiral bases, e.g. (S)- and (R)-1-phenylethanamine Resolution

  41. ----resolved---- Resolution by acid-base reactions Pure-Sb racemic mix

  42. Examples of enantiomerically pure bases CH =CH CH =CH 2 2  [ ]  [ ] Resolution H H H H H H N HO N H HO H CH3O N N (+)-Cinchonine (-)-Quinine 23 = +228 D 25 = -165 D

  43. racemic bases with chiral acids like: []D = -127o HCCl3 from Strycnos seeds (S nux-vomica) brucine Strychnine no methoxy groups

  44. R pure enantiomer R S S [] = 0 R S + S S S S enantiomeric mixture Resolution

  45. []25 = -8.2 []25 = +8.2 D D R S [] = 0 S enantiomeric mixture pure enantiomer Resolution

  46. lipase >69%ee 50/50 mix R-Enzyme

  47. lipase >69%ee A 50/50 enantiomeric mixture of esters forms R-acid and recover S-ester. R-Enzyme

  48. Enzymes as resolving agents racemic mix ethyl ester of (S)- and (R)-naproxin (R)-ester - no effect (S)-now acid different functional gp.

  49. carbohydrates deoxynucleic acid amino acids CHEMICAL &ENGINEERING NEWS Oct 23, 2000, pg 55 Chiral Drugs Sales top $100 Billion

  50. 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 Proteins Chapter 5

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