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

_

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: Hydride Reduction of Mechanism: Hydride Reduction of Carbonyl GroupCarbonyl Group

Mechanism: Reduction of BenzilMechanism: Reduction of Benzil

Step 1:

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

Your ReportYour Report

Formal Report not requiredFormal Report not required

Complete experiment worksheetComplete experiment worksheet