1 / 30

1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration

Chapter 3. Stereochemistry. 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration - working with R/S [ Home Page -Practice ] 4. Acyclic Molecules with 2 or more stereocenters 5. Cyclic Molecules with 2 or more stereocenters 6. Properties of Stereocenters

Download Presentation

1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Chapter 3 Stereochemistry 1. Stereoisomerism 2. Chirality 3. Naming stereocenters - R/S configuration - working with R/S [Home Page -Practice ] 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 21

  2. Looking for a change in the polarized plane achiral sample no change in the plane

  3. rotates the plane Looking for a change in the polarized plane  CHIRAL

  4. 20 20   D D R-(+)-2-methyl-1-butanol S-(-)-2-methyl-1-butanol 50/50 mixture of S and R 50% S(-5.75o) with 50% R(+5.75o) net rotation = 0 RACEMIC MIXTURE

  5. Specific Rotation  Observed  dependent on (conc.), (cell length), (temp.) Specific Rotation []t = (degrees) l (dm) c (g/mL)  t = temperature  = wavelength l = path length (dm) c = concentration (g/mL)

  6. l c []t =  (+134o) 2.5 (0.2) []t =  +268o []t =  Specific Rotation Example: A sample of 2 g in 10 mL of solution measured in a 25 cm long cell gives an observed  of +134o The specific rotation is? (actuallydeg/cc2g-1)

  7. Optical purityAbsolutely pure (100%) cholesterol has a specific rotation of -39o. synthetic sample may contain: the enantiomer -  (or < -39o) ora diastereomer -  (or < -39o) orother junk -  (or < -39o)

  8. () 1dm (1g pure) [-]t =  () 1dm (?g+crap ) [-]t =  -38.6o (-31.2) 1dm ( ) (-35.1) 1dm ( ) [-]t = [-]t = [-]t = 1dm ( )    observe  = -39o Optical purityAbsolutely pure cholesterol has a specific rotation of -39o.  = less than -39o  = -38.6o 0.99g+0.01g  = -35.1o 0.9g+0.1g  = -31.2o 0.8g+0.2g

  9. +23.1o > +9.2o < 0o Mixisbetween100% S and 50/50(S/R) Pure (S)-(+)-2-bromobutane specific rotation - +23.1o But what if observe optical rotation = +9.2? Not pure, possibly a mix ofRand S!!!! optical purity

  10. observed (100%) +9.2(100%) = +23.1  of pure enantiomer Pure (S)-(+)-2-bromobutane specific rotation - +23.1o But what if observe optical rotation =+9.2? Not pure, possibly a mix ofR and S!!!! optical purity= ---------------------- = 40% 40% optical purity i.e. 40% excessof S isomer 40% excess= 40%S + (60%S/Rmixture) + (30%S+30%R) The sample has 70%S and30%R

  11. (moles 1 isomer) - (moles of other) ee = X 100% (moles of both enantiomers) (.70) - (.30) (1.00) ee = X 100% enantiomeric excess or ee (= optical purity) ee = 40%

  12. Solution of 10 mL of 0.1 M R enantiomer 30 mL of 0.1 M S enantiomer observed rotation = +4.8 What is the specific rotation of each enantiomer?

  13. mole S - mole R (moles of S + R) opt. purity = 2 4 3 - 1 3 + 1 50% opt. purity = = = +4.8 50% = X Solution of 10 mL of 0.1 M R enantiomer 30 mL of 0.1 M S enantiomer observed rotation = +4.8 What is the specific rotation of each enantiomer? X = + 9.6 (S) observed +,  S

  14. What is the optical rotation of a sample of (+)-2-bromobutane ([]25= +23.1) that is 75% optically pure? What percentage of (+) and (-) enantiomers are present in this sample?

  15. 23.1 opt. purity = ee = 75% = 25o D What is the optical rotation of a sample of (+)-2-bromobutane that is 75% optically pure? What percentage of (+) and (-) enantiomers are present in this sample? ([]25 = +23.1)  []  (+)75% + racemic(+/-) or (+)75% + (12.5%(+) +12.5%(-)) or (+)87.5% / (-)12.5% opt pure rotation mix (+)%/(-)% 75% +17.3 87.5/12.5

  16. sodium (S)-(-)-lactate (S)-(+)-lactic acid (S)-(+)-2-bromobutane, = +5.75 (+) or (-) a measured physical property - not predictable These similar “S” compounds rotate light in the opposite direction. NaOH

  17. Resolution (separation): Convert mixture of enantiomers - same properties TO diastereomers- different physical properties, can be separated.

  18. new compounds diastereiomeric mixture 2 equivalents R1 R S + different compound R1 R1 separate remove R1 R R pure R1 S remove R1 pure S R1 Resolution enantiomeric mixture S R non-separable

  19. remove amine ----resolved---- remove amine Resolution by acid-base reactions Pure-Sb racemic mix

  20. CH =CH CH =CH 2 2 Resolution H H • Examples of enantiomerically pure bases H H H R H N HO N H HO H CH3O N N (+)-cinchonine [R=H] (+)-quinidine [R = OCH3] (-)-quinine

  21. []D = -127o HCCl3 from Strycnos seeds (S nux-vomica) brucine Strychnine no methoxy groups

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

  23. []25 = -8.2 []25 = +8.2 D D R S [] = 0 S enantiomeric mixture pure enantiomer Resolution

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

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

  26. CHEMICAL &ENGINEERING NEWS Oct 23, 2000 pg 55 Chiral Drugs Sales top $100 Billion C&ENEWS Oct 1, 2001 pg 79 40% of all dosage-form drug sales in 2000 were single enantiomers. (Now >>50% single enantiomer)

  27. Some drugs are racemic mixtures, e.g. antidepressants: Wellbutrin (bupropion, in Zyban) Effexor (venlafaxine hydrochloride)

  28. Naproxen - S isomer Ibuprofen S isomer particularly active, but R slowly converted to S (R enantiomer liver toxin)

  29. analgesic DarvoN | NovraD antitussive 2S,3R-propoxyphen |2R,3S-propoxyphen R \ S R / S

  30. S R Thalidomide R- sedative, anti-inflammatory, Crohn’s disease S -teratogenic (but thalidomide racemized in the body)

More Related