R S Nomenclature.ppt
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Stereochemistry refers to the 3-dimensional arrangement of atoms in molecules. It has its own terminology that must be understood, such as stereoisomers, enantiomers, and diastereomers. Stereochemistry is important in biology as different stereoisomers can have different biological effects. The configuration of atoms around stereocenters determines the properties and activity of molecules. Techniques such as priority rules and Fischer projections are used to define and communicate stereochemistry.
![Enantiomers
nonsuperimposible mirror images
OH
CH3
HO2C
H
OH
CO2H
CH3
H
mirror
plane
(S)(+) lactic acid (R)(-) lactic acid
from muscle tissue from milk
[] = +13.5 [] = -13.5
o
o](https://image.slidesharecdn.com/bkbrs-240214030740-5eea9ae4/85/R-S-Nomenclature-ppt-6-320.jpg)
![Racemic Mixture
o
(g/mL) 1.7598 1.7598 1.7723
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid
Racemic Mixture (Racemate): 50/50 mixture of enantiomers
CO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
R,R S,S](https://image.slidesharecdn.com/bkbrs-240214030740-5eea9ae4/85/R-S-Nomenclature-ppt-32-320.jpg)
![Mycomycin, an antibiotic
C C C
H
CH=CHCH=CHCH2CO2H
C
C
C
C
H
H
Nocardia acidophilus []D = -130
o](https://image.slidesharecdn.com/bkbrs-240214030740-5eea9ae4/85/R-S-Nomenclature-ppt-40-320.jpg)
R S Nomenclature.ppt
- 1. Bedanta Kr Borah Dept. Of Chemistry Debraj Roy College
- 2. Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.
- 3. Definitions • Stereoisomers – Compounds with the same structural formula having different geometrical arrangement of atom/group in space • Enantiomers – Stereoisomers that are mirror images; only properties that differ are direction (+ or -) of optical rotation • Diastereomers – Stereoisomers that are not mirror images; different compounds with different physical properties
- 4. STEREOGENIC CENTER (Chiral Center) Carbon has four different groups attached
- 5. • Arrangement of atoms or groups in space around the stereocenter of the molecule is CONFIGURATION Cl C F Br H Cl C F Br H enantiomers Stereocenter Stereogenic center - Interchange of 2 atom / groups gives a stereoisomer
- 6. Enantiomers nonsuperimposible mirror images OH CH3 HO2C H OH CO2H CH3 H mirror plane (S)(+) lactic acid (R)(-) lactic acid from muscle tissue from milk [] = +13.5 [] = -13.5 o o
- 7. Biological Activity (R)(+) Thalidomide (S)(-) Thalidomide N N O O O O H H a sedative and hypnotic a teratogen N N O O O O H H
- 8. • In the 1960’s thalidomide was given to pregnant women to reduce the effects of morning sickness. • This led to many disabilities in babies and early deaths in many cases.
- 9. S limonene (lemons) R limonene (oranges) CH3 H C CH2 CH3 CH3 H C CH2 H3C
- 10. (R), (S) Nomenclature • Different molecules (enantiomers) must have different names. C C O OH H3C NH2 H natural alanine => •Usually only one enantiomer will be biologically active. •Configuration around the chiral carbon is specified with (R) and (S). Absolute Configuration
- 11. Cahn-Ingold-Prelog Rules Overview Assign priorities 1, 2, 3, & 4(lowest priority) to each group View molecule with the lowest priority away from the viewer Circular Arrow is drawn from the atom / group with 1st priority through the atom with 2nd priority to the atom with 3rd priority. If arrow points clockwise - R(rectus) If arrow points counter- clockwise - S (sinister)
- 12. Assign (R) or (S) • Working in 3D, rotate molecule so that lowest priority group is in back. • Draw an arrow from highest to lowest priority group. • Clockwise = (R), Counterclockwise = (S) =>
- 13. 1 2 3 4 Use Cahn, Ingold, Prelog priorities Place the lowest priority group back (focus down C - 4 bond) (R) clockwise draw arrow from 1-2-3 1 2 3 4 (S) counterclockwise
- 14. Absolute Configuration 1 2 3 4 Use Cahn, Ingold, Prelog priorities Place the lowest priority group back (focus down C - 4 bond) (R) clockwise draw arrow from 1-2-3 1 2 3 4 (S) counterclockwise
- 15. Assigning priorities-CASE 1 • Assign a priority number to each atom attached to the chiral carbon. •Atom with highest atomic number assigned the highest priorities #1. In case of isotopes, high(er)est priority given to the isotope with high(er)est mass number. CASE 1 - four different atoms attached to chiral atom
- 16. Assign Priority to each Atom/Group on Asymmetric Center based on atomic number focus down C-4 bond 4 3 2 1 I Cl H F rotate I F H Cl
- 17. Lactic Acid (S) (R) 4 3 2 1 4 3 2 1 OH CH3 CO2H H OH CH3 HO2C H
- 18. PRIORITY ASSIGNMENT EXAMPLES CASE 2 - In case of ties among 1st atom, go to 2nd atoms, then to 3rd etc until the tie is broken. Consider straight chain groups Me < Et<n-propyl etc Consider effect of branching Et< isopropyl < tert-butyl Consider effect of hetero atom Tert-butyl < CH2OMe
- 19. C.I.P. Priorities CH2CH2CH3 CH(CH3)2 CH2CH2OH CH2CH O CH2CH2CH3 CH=CH2 CO2H CH2Cl Low High CH2CH2Br CH(CH3)2
- 20. Groups possessing multiple bonds Carbon doubly bonded is equivalent to a carbon bonded to two single bond, triple bonded is equivalent to three single bond. C H O CH O O C H C CH C C C CH CH C C C
- 22. Assign Priorities C C O OH H3C NH2 H natural alanine 1 2 3 4 Cl H Cl H * 1 2 3 4 1 2 3 4 => C C O H C H CH2 CH2OH CH(CH3)2 * C C C CH2OH CH(CH3)2 H O O C C H CH2 C * expands to
- 23. A Carbohydrate CHO CH2OH H OH HO H H OH H OH (+) D-Glucose R S R R
- 24. Fischer Projections Vertical bonds move away (dashed bonds) Horizontal bonds approach you (wedge bonds) OH CO2H CH3 H OH CH3 HO2C H OH CO2H CH3 H
- 25. Assigning Absolute Configuration to Fischer Projections OH CO2H CH3 H OH CO2H CH3 H OH CH3 HO2C H (S) (S) (S) rotate
- 26. Rotation of the Projection 90o Reverses Absolute Configuration 90 o 90 o o 90 (S) (R) (S) (R) CH3 H OH HO2C CO2H CH3 H HO H OH CO2H CH3 OH CO2H CH3 H
- 27. Diastereomers Stereoisomers That Are Not Mirror Images 3 3 2 2 opposite stereochemistry at C 3 same stereochemistry at C 2 (S) CO2H OH H Br H CO2H OH H Br H (2S,3S) (2S,3R)
- 28. Fischer Projections with 2 Chiral Centers CO2H CH3 H OH Br H H Br H OH CO2H CH3 (2S,3S) (2S,3R) 2 3 2 3
- 29. 2 Chiral Centers 4 Stereoisomers
- 30. Identical, Enantiomers or Diastereomers? H H CH3 CH3 & CH3 CH3 H H C C a) CH2CH3 CH3 H H Br Br CH2CH3 CH3 & b) OH HO NH2 NH2
- 31. Tartaric Acids CO2H CO2H H OH HO H H OH HO H CO2H CO2H CO2H CO2H H OH H OH HO H HO H CO2H CO2H R,R S,S R,S S,R
- 32. Racemic Mixture o (g/mL) 1.7598 1.7598 1.7723 m.p. C 168-170 168-170 210-212 [] (degrees) - 12 + 12 0 (R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid Racemic Mixture (Racemate): 50/50 mixture of enantiomers CO2H CO2H H OH HO H H OH HO H CO2H CO2H R,R S,S
- 33. Meso Compound Internal Plane of Symmetry Optically Inactive o rotate 180 superimposible CO2H CO2H H OH H OH HO H HO H CO2H CO2H R,S S,R mirror plane
- 34. 2,3,4-trichlorohexane How many stereoisomers? Cl Cl Cl 3 asymmetric centers 8 stereoisomers * * * 2n, n= # asymmetric centers (3)
- 35. n = 3; 2n = 8 CH3 CH2CH3 H Cl Cl H H Cl Cl H H Cl Cl H CH3 CH2CH3 CH3 CH2CH3 Cl H H Cl H Cl Cl H Cl H H Cl CH3 CH2CH3 H Cl H Cl H Cl CH3 CH2CH3 Cl H Cl H Cl H CH3 CH2CH3 Cl H H Cl H Cl CH3 CH2CH3 H Cl Cl H Cl H CH3 CH2CH3 S S R R R S
- 36. A Carbohydrate CHO CH2OH H OH HO H H OH H OH (+) D-Glucose R S R R
- 37. Internal Planes of Symmetry CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 Both are Meso
- 38. Asymmetric Centers on Rings Br Br Br Br 1(R),2(S) cis 1,2-dibromocyclohexane nonsuperimposible but A flips into B A B Br Br Meso
- 39. Allenes can be Chiral C C C H CH3 C C Cl H C CH3 H Cl H
- 40. Mycomycin, an antibiotic C C C H CH=CHCH=CHCH2CO2H C C C C H H Nocardia acidophilus []D = -130 o
- 41. Reactions that Generate Chirality Centers Hydrogenation, syn CH3 CH3 CH2CH3 CH2CH3 H2, Pt/C CH2CH3 CH2CH3 CH3 CH3 H H CH2CH3 CH2CH3 H CH3 H CH3 product is meso
- 42. Bromination Trans is formed exclusively No Meso is formed (cis) racemic mixture S S R R Br Br Br Br Br2
- 43. Bromonium Ion is Opened Equally from Both Sides Br2 Br Br Br Br R R S S racemic mixture Br Br Br Br Br Br + -
- 44. trans alkene + anti addition = MESO CH2CH3 CH2CH3 H H Br2 CH2CH3 CH2CH3 H H Br Br Br Br CH2CH3 CH2CH3 H H meso
- 45. cis Alkene + anti addition = racemic mixture H CH2CH3 CH2CH3 H Br2 Br Br CH2CH3 CH2CH3 H H R R CH2CH3 CH2CH3 H H Br Br CH2CH3 CH2CH3 H H Br Br S S Br H H CH2CH3 CH2CH3 Br Br Br H H CH2CH3 CH2CH3 a b a b
- 46. Brominations Often Generate Asymmetric Centers Br2 R R S S racemic mixture CH3 CH3 H H CH3 CH3 Br Br H H CH3 CH3 Br Br H H CH3 CH3 H H CH3 CH3 H H Br Br CH3 CH3 Br Br H H S R meso Br2
- 47. Asymmetric Center is Generated Racemic Mixture Formed H-Br H H Br Br a) b) Br H a) Br H b) (R) (S)
- 48. Asymmetric Induction PPh2 PPh2 RuCl2 CH3 OH H2 Ru(BINAP)Cl 2 CH3 H OH 96% e.e. Noyori and Knowles shared Nobel Prize in Chemistry, 2001
- 49. Preparation of (L)-Dopa for Treatment of Parkinson’s HO HO CH2C CO2H NH2 H l-(-) Dopa HO HO CH2CH2NH2 Dopamine cannot cross blood-brain barrier C=C NH2 CO2H H HO HO H2 Rh(DIOP)Cl2 enz.
- 50. Relevance of Stereochemistry (S,S) (R,S) useful decongenstants d-pseudoephedrine and l-ephedrine 4 stereoisomers * * 2 asymmetric centers EPHEDRA from Ma Huong NHCH3 CH3 OH
- 51. One-step synthesis Pseudophed * d-(S)- "Meth" l-(R) - Vicks (methamphetamine) "desoxyephedrine" NHCH3 CH3
- 52. -(p-isobutylphenyl)propionic acid CH3 CO2H H (S)(+) ibuprofen (R)(-) ibuprofen CH3 HO2C H anti-inflammatory 80-90% metabolized to (S)(+)
- 54. How Sweet it is! Sucrose O HO OH O CH2OH O CH2OH CH2OH HO HO OH Sucralose or Splenda O Cl HO OH O CH2OH O CH2Cl CH2Cl HO HO Sucralose is 600 times sweeter and does not get metabolized.
- 56. Radiosensitizer of Choice Until 2004 Okadaic acid 17 asymmetric centers O OH HOOC OH O H O O H H O OH H OH O O