Stereoselective Reduction of Ketones with Stereoselective Reduction of Ketones with Sodium Borohydride: Making a DiolSodium Borohydride: Making a Diol
Microscale Reduction of BenzilMicroscale Reduction of Benzil
Organic Chemistry Lab II, Spring 2010Dr. Milkevitch
March 22 & 24, 2010
Today’s ExperimentToday’s Experiment
Take a look at some chemistry of the C=O groupTake a look at some chemistry of the C=O group
Reduce the C=0 group to an alcoholReduce the C=0 group to an alcohol
Using the common reagent:Using the common reagent:– Sodium borohydrideSodium borohydride
Purpose:Purpose:– To illustrate the production of an alcohol by the To illustrate the production of an alcohol by the
reduction of a ketonereduction of a ketone– To use TLC and IR spectroscopy to characterize To use TLC and IR spectroscopy to characterize
your resultsyour results
BackgroundBackground
Alcohols : Alcohols : – Useful class of organic compoundsUseful class of organic compounds
Readily availableReadily availableCheap, relatively non-hazardousCheap, relatively non-hazardous
Can be converted to other compoundsCan be converted to other compounds
Reducing agents:Reducing agents: – agents that add H: to compoundsagents that add H: to compounds– Reduce carbonyl group to an alkoxideReduce carbonyl group to an alkoxide
Subsequent protonation yields an alcoholSubsequent protonation yields an alcohol
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Two Useful Hydride AgentsTwo Useful Hydride Agents
Sodium Borohydride:Sodium Borohydride: NaBH NaBH44
Lithium Aluminum HydrideLithium Aluminum Hydride: LiAlH: LiAlH44
Called complex hydridesCalled complex hydrides– Don’t have simple structure like NaH or Don’t have simple structure like NaH or
LiHLiH
Today: Use NaBHToday: Use NaBH44
– Safe to useSafe to use– Highly selective reducing agentHighly selective reducing agent
Uses of Sodium BorohydrideUses of Sodium Borohydride
Reduces aldehydes to Reduces aldehydes to primary alcohols, primary alcohols, ketones to secondary ketones to secondary alcoholsalcohols
Very selective:Very selective:– Only reactive towards Only reactive towards
aldehydes/ketonesaldehydes/ketones– Will not reduce Will not reduce
carboxylic acids or esterscarboxylic acids or esters
Mechanism: Reduction of BenzilMechanism: Reduction of Benzil
Step 2:
Step 3: Repeat of Steps 1, 2•Reaction at the other C=O
Benzoin
Mechanism: Reduction of BenzilMechanism: Reduction of Benzil
Final Product:
hydrobenzoin
But there is more than one product!!!!!
Multiple Products PossibleMultiple Products Possible
Remember, C=O is planarRemember, C=O is planar
Hydride can attack carbon of C=O from Hydride can attack carbon of C=O from above or below the planeabove or below the plane
Therefore, you can have different Therefore, you can have different stereoisomersstereoisomers
What are the Multiple Products?What are the Multiple Products?•Hydrobenzoin has 2 chiral centers!
•Have a meso compound•Pair of enantiomers
Meso Pair of enantiomers
ProcedureProcedureWeigh out 200 mg of benzil into a 25 ml erlenmeyer flaskWeigh out 200 mg of benzil into a 25 ml erlenmeyer flaskAdd 2 ml of 95% ethanol, swirl to mixAdd 2 ml of 95% ethanol, swirl to mixAdd 75 mg of sodium borohydrideAdd 75 mg of sodium borohydrideLet stand 10-15 min with occasional swirlingLet stand 10-15 min with occasional swirlingYellow color should disappear as benzil is reducedYellow color should disappear as benzil is reducedAdd 2 ml of ddHAdd 2 ml of ddH22O slowly O slowly Heat to boiling, solution should be clear and colorlessHeat to boiling, solution should be clear and colorlessFilter off any insoluble impurities if necessary Filter off any insoluble impurities if necessary – Use a pasteur filter pipetUse a pasteur filter pipet– See me or the lab TA to make oneSee me or the lab TA to make one
Transfer the hot, clear solution to a clean 25 ml erlenmeyer flask, using Transfer the hot, clear solution to a clean 25 ml erlenmeyer flask, using a filter pipet a filter pipetAdd an additional 2 ml of hot ddHAdd an additional 2 ml of hot ddH22OOAllow solution to crystallize undisturbed Allow solution to crystallize undisturbed Cool in ice bath, vacuum filterCool in ice bath, vacuum filter
Wash with minimal cold ddHWash with minimal cold ddH22OO
Weigh your productWeigh your product
CharacterizationCharacterization
Do a melting point determinationDo a melting point determination
TLC: dissolve 1-3 mg of your product in ethyl acetateTLC: dissolve 1-3 mg of your product in ethyl acetate– Dissolve 1-3 mg of (+/-)benzoin in ethyl acetate alsoDissolve 1-3 mg of (+/-)benzoin in ethyl acetate also
– Acquire a TLC plate (in oven) Acquire a TLC plate (in oven)
– Spot the TLC plate with small amounts of your product and Spot the TLC plate with small amounts of your product and (+/-)benzoin(+/-)benzoin
– Run TLC plate in 9:1 methylene chloride/ethyl acetateRun TLC plate in 9:1 methylene chloride/ethyl acetateThis mobile phase is located in the hoodThis mobile phase is located in the hood
– Stain with iodine (see Dr. M)Stain with iodine (see Dr. M)
Acquire an IR spectrumAcquire an IR spectrum
– Interpret your resultsInterpret your results