Reactions of Alkenes 1: Miniscale Synthesis Reactions of Alkenes 1: Miniscale Synthesis Bromination of Fumaric AcidBromination of Fumaric Acid

Organic Chemistry Lab II, Spring 2010Dr. Milkevitch

March 8 & 10, 2010

HO2C

CO2HBr

Br

Addition ReactionsAddition Reactions

TodayToday: Conduct an addition reaction: Conduct an addition reaction– One of the fundamental reactions of alkenesOne of the fundamental reactions of alkenes

What you will learn/observe:What you will learn/observe:Review/introduce the bromination of alkenesReview/introduce the bromination of alkenes

Bromination fumaric acidBromination fumaric acid– Fumaric acid is alkenyl dicarboxylic acid Fumaric acid is alkenyl dicarboxylic acid

Look at the products formedLook at the products formed– stereoisomers possiblestereoisomers possible

See which product will predominateSee which product will predominateracemic and meso forms possibleracemic and meso forms possible

MP determination may differentiateMP determination may differentiate

Addition ReactionsAddition Reactions

Let’s Look at:Let’s Look at:– Addition reaction:Addition reaction: a fundamental organic reaction a fundamental organic reaction

Two species are added to a substrateTwo species are added to a substrate

Variety of organic families have this reactionVariety of organic families have this reaction

Alkenes have many addition reactionsAlkenes have many addition reactions

Result is an entirely new compoundResult is an entirely new compound

Bromination of alkenesBromination of alkenesAddition of BrAddition of Br22 to an alkene to an alkene

multiple step processmultiple step process

Proceeds through a bromonium ion intermediateProceeds through a bromonium ion intermediate

Both carbons of the original C=C end up with a BrBoth carbons of the original C=C end up with a Br

General Mechanism

C C + Br BrC C

Br HH

HH

cyclic bromonium ion

C C

Br HH

HH

+ Br

+ Br

Br

BrH

HH

H

vicinal dibromideback-side attack

Some Notes on this ReactionSome Notes on this Reaction

Halogen atoms are electrophilic Halogen atoms are electrophilic – and nucleophiles can attack themand nucleophiles can attack them

Examples:Examples:

HO + Br Br HO Br + Br

H3N + Br Br H3N Br + Br

More NotesMore NotesAn alkene can also be viewed as a nucleophileAn alkene can also be viewed as a nucleophile– can attack a halogen atomcan attack a halogen atom

Intermediate is called a bromonium ionIntermediate is called a bromonium ion– note the 3-membered ringnote the 3-membered ring– positive charge on the brominepositive charge on the bromine

3-membered ring has considerable ring strain3-membered ring has considerable ring strain– combined with positive charge on brominecombined with positive charge on bromine– Ring opening reaction likelyRing opening reaction likely– form a stable productform a stable product

Stereochem of this ReactionStereochem of this Reaction

Called anti additionCalled anti addition

Because the 2 bromines “end up” in an anti Because the 2 bromines “end up” in an anti configurationconfiguration

Why? because of the mechanismWhy? because of the mechanism– must be a back-side attack of the nuclophile (Brmust be a back-side attack of the nuclophile (Br - -))

C C

Br HH

HH+ Br

Br

BrH

HH

H

anti-additionanti-configuration of bromines

back-side attack

Mechanism: Bromination of Mechanism: Bromination of Fumaric acidFumaric acid

fumaric acidCO2H = carboxylicacid group

+ Br Br

Br

HO2C

CO2HH

H

cyclic bromonium ion

Br

HO2C

CO2HH

H

back side attack

Br

HO2C

CO2H

H

HBr

Br

2,3-dibromosuccinic acidmeso

HO2C

CO2H

Why Meso ProductWhy Meso ProductBromide can attack Bromide can attack either carboneither carbon of the of the bromonium ionbromonium ion

Br

HO2C

CO2HH

H

back side attack

BrHO2C

CO2H

H

HBr

Br

2S,3R-dibromosuccinic acid

Br

HO2C

CO2HH

H

Br

back side attack atother carbon

Br

Br

HO2C

H

H

CO2H

2R,3S-dibromosuccinic acid

ProcedureProcedureUse a 10 ml RB flaskUse a 10 ml RB flaskAdd 200 mg of fumaric acid to this flaskAdd 200 mg of fumaric acid to this flaskNow, add 2.5 ml of bromine stock solutionNow, add 2.5 ml of bromine stock solutionswirl to mix, add magnetic stirrerswirl to mix, add magnetic stirrerAttach a condenserAttach a condenser

No need to hook up water linesNo need to hook up water lines

Start stirring and heating (low setting…5)Start stirring and heating (low setting…5)should turn orange (~15 min)should turn orange (~15 min)then a precipitate should form, solution turns yellowthen a precipitate should form, solution turns yellowIf it turns clear, add a few more drops (2-3) of If it turns clear, add a few more drops (2-3) of bromine solutionbromine solutionContinue heating for 15 more minutesContinue heating for 15 more minutesRemove solution, put in ice bathRemove solution, put in ice bath

Procedure IIProcedure IICollect product by vacuum filtrationCollect product by vacuum filtration

use a Hirsh funneluse a Hirsh funnelWash crystals with ice-cold waterWash crystals with ice-cold waterRecrystallize from waterRecrystallize from waterAir-dry until next weekAir-dry until next weekNext week:Next week:

weigh crystalsweigh crystalscheck MP of crystalscheck MP of crystalsMP should be 255°-256° CMP should be 255°-256° Cbut a racemic but a racemic compound could form!!!compound could form!!!

has a MP of 166°-167° Chas a MP of 166°-167° CIf it doesn’t melt by 175°C, assume you have the If it doesn’t melt by 175°C, assume you have the meso meso compoundcompound

For Your ReportFor Your Report

Formal lab report required.Formal lab report required.

Conclusion:Conclusion:– State amount of crystals producedState amount of crystals produced– State % yieldState % yield– Report MPReport MP– AnalyzeAnalyze: did you get the racemic mixture : did you get the racemic mixture

or the meso compound?or the meso compound?

Additional Question to AnswerAdditional Question to Answer

It appears that the It appears that the racemic racemic compound compound couldcould be be formed in this reaction. Could you come up with a formed in this reaction. Could you come up with a mechanism by which this could happen? (HINT: it’s mechanism by which this could happen? (HINT: it’s a similar mechanism but something else is different)a similar mechanism but something else is different)

Your ReportYour ReportFormal Report RequiredFormal Report RequiredMake sure to include the mechanism of the reaction Make sure to include the mechanism of the reaction in your report (separate section)in your report (separate section)Results Section:Results Section:– Make sure to Make sure to statestate all results all results

Prove that you made the alkenesProve that you made the alkenes

– Include GC chromatogram (annotated)Include GC chromatogram (annotated)– Determine % of your alkenes Determine % of your alkenes – IR spectrum, annotated (if completed)IR spectrum, annotated (if completed)

Conclusions section:Conclusions section:– Was the experiment successful?Was the experiment successful?

How much of the alkenes are produced?How much of the alkenes are produced?Any leftover 3,3-dimethyl-2-butanol?Any leftover 3,3-dimethyl-2-butanol?

– If unsuccessful, any ideas why?If unsuccessful, any ideas why?

Miniscale Apparatus for DistillationMiniscale Apparatus for Distillation