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
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
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
Two Useful Hydride Agents
Sodium Borohydride: NaBH4
Lithium Aluminum Hydride: LiAlH4
Called complex hydrides
– Don’t have simple structure like NaH or
LiH
Today: Use NaBH4
– Safe to use
– Highly selective reducing agent
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
Mechanism: Hydride Reduction of
Carbonyl Group
Mechanism: Reduction of Benzil
Step 1:
Mechanism: Reduction of Benzil
Step 2:
Benzoin
Step 3: Repeat of Steps 1, 2
•Reaction at the other C=O
Mechanism: Reduction of Benzil
Final Product:
hydrobenzoin
But there is more than one product!!!!!
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
What are the Multiple Products?
•Hydrobenzoin has 2 chiral centers!
•Have a meso compound
•Pair of enantiomers
Meso
Pair of enantiomers
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 ddH2O 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 ddH2O
Allow solution to crystallize undisturbed
Cool in ice bath, vacuum filter
– Wash with minimal cold ddH2O
Weigh your product
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
Your Report
Formal Report not required
Complete experiment worksheet