1. Stereoselective Reduction of Ketones with Sodium Borohydride: Making a Diol Microscale Reduction of Benzil Organic Chemistry Lab II, Spring 2010 Dr. Milkevitch March 22 & 24, 2010

2. Today’s Experiment Take a look at some chemistry of the C=O group Reduce the C=0 group to an alcohol Using the common reagent: –Sodium borohydride Purpose: –To illustrate the production of an alcohol by the reduction of a ketone –To use TLC and IR spectroscopy to characterize your results

3. Background Alcohols : –Useful class of organic compounds Readily available Cheap, relatively non-hazardous Can be converted to other compounds Reducing agents: –agents that add H: to compounds –Reduce carbonyl group to an alkoxide Subsequent protonation yields an alcohol _

4. Two Useful Hydride Agents Sodium Borohydride: NaBH 4 Lithium Aluminum Hydride: LiAlH 4 Called complex hydrides –Don’t have simple structure like NaH or LiH Today: Use NaBH 4 –Safe to use –Highly selective reducing agent

5. Uses of Sodium Borohydride Reduces aldehydes to primary alcohols, ketones to secondary alcohols Very selective: –Only reactive towards aldehydes/ketones –Will not reduce carboxylic acids or esters

6. Mechanism: Hydride Reduction of Carbonyl Group

7. Mechanism: Reduction of Benzil Step 1:

8. Mechanism: Reduction of Benzil Step 2: Step 3: Repeat of Steps 1, 2 Reaction at the other C=O Benzoin

9. Mechanism: Reduction of Benzil Final Product: hydrobenzoin But there is more than one product!!!!!

10. Multiple Products Possible Remember, C=O is planar Hydride can attack carbon of C=O from above or below the plane Therefore, you can have different stereoisomers

11. What are the Multiple Products? Hydrobenzoin has 2 chiral centers! Have a meso compound Pair of enantiomers Meso Pair of enantiomers

12. Procedure Weigh out 200 mg of benzil into a 25 ml erlenmeyer flask Add 2 ml of 95% ethanol, swirl to mix Add 75 mg of sodium borohydride Let stand 10-15 min with occasional swirling Yellow color should disappear as benzil is reduced Add 2 ml of ddH 2 O slowly Heat to boiling, solution should be clear and colorless Filter off any insoluble impurities if necessary –Use a pasteur filter pipet –See me or the lab TA to make one Transfer the hot, clear solution to a clean 25 ml erlenmeyer flask, using a filter pipet Add an additional 2 ml of hot ddH 2 O Allow solution to crystallize undisturbed Cool in ice bath, vacuum filter –Wash with minimal cold ddH 2 O Weigh your product

13. Characterization Do a melting point determination TLC: dissolve 1-3 mg of your product in ethyl acetate –Dissolve 1-3 mg of (+/-)benzoin in ethyl acetate also –Acquire a TLC plate (in oven) –Spot the TLC plate with small amounts of your product and (+/- )benzoin –Run TLC plate in 9:1 methylene chloride/ethyl acetate This mobile phase is located in the hood –Stain with iodine (see Dr. M) Acquire an IR spectrum –Interpret your results

14. Your Report Formal Report not required Complete experiment worksheet