Bromination of alkenes Bromination of alkenes

Author: Dr. Robert D. Craig, Ph.DAuthor: Dr. Robert D. Craig, Ph.DFor Organic Chemistry first For Organic Chemistry first

semestersemester

Preparation of Organic compoundsPreparation of Organic compounds This is This is transtrans-stilbene-stilbene

bromination of bromination of transtrans-stilbene-stilbene

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Meso-Stilbene Di BromideMeso-Stilbene Di Bromide

The bromination of an alkene is illustrated inThe bromination of an alkene is illustrated inthis experiment. In this particular reaction,this experiment. In this particular reaction,bromination of bromination of transtrans-stilbene-stilbenegenerates a compound with two chiralgenerates a compound with two chiralcenters, leading to the possibility that the centers, leading to the possibility that the product could be either the product could be either the meso or the d,l diastereomer. meso or the d,l diastereomer.

a a plane of symmetryplane of symmetry One of the isomers of tartaric acid is a One of the isomers of tartaric acid is a

meso compound:meso compound:

a a plane of symmetryplane of symmetry MesoMeso is a prefix which, by strict definitions, is a prefix which, by strict definitions,

indicates the presence of a 17th chiral center. It indicates the presence of a 17th chiral center. It comes from the Greek for "middle" or "mid", and comes from the Greek for "middle" or "mid", and refers to the fact that the molecule can rotate refers to the fact that the molecule can rotate about its middle. A meso molecule is not a about its middle. A meso molecule is not a diastereomer because rotating either of its chiral diastereomer because rotating either of its chiral centers doesn't change the molecule overall; a centers doesn't change the molecule overall; a meso molecule has an internal plane of meso molecule has an internal plane of reflection, also called a reflection, also called a plane of symmetryplane of symmetry

pyridinium bromide perbromidepyridinium bromide perbromide

CAS [39416-48-3]  CAS [39416-48-3]     C   C55HH66BrBr33N     (MW 319.86)N     (MW 319.86)

The Reaction is stereospecificThe Reaction is stereospecificThe exclusive formation of the meso diastereomerThe exclusive formation of the meso diastereomershows that the reaction is stereospecific andshows that the reaction is stereospecific andoccurs with anti stereochemistry (mechanism occurs with anti stereochemistry (mechanism

below).below).

The bromination reagent in this experiment is The bromination reagent in this experiment is the pyridinium salt of the tribromide ion, the pyridinium salt of the tribromide ion,

BrBr33 which can be used as a source of Br which can be used as a source of Br22 in some in some reactions. reactions.

pyridinium bromide perbromidepyridinium bromide perbromide This solid salt is easier and safer to handle This solid salt is easier and safer to handle

than molecular bromine. It is commonly than molecular bromine. It is commonly known as pyridinium bromide perbromide.known as pyridinium bromide perbromide.

Preparation of Organic compoundsPreparation of Organic compounds

Bromination of an alkene (cyclic or acyclic) Bromination of an alkene (cyclic or acyclic) is an example of an electrophilic addition is an example of an electrophilic addition reaction. The reaction proceeds in two reaction. The reaction proceeds in two stages. stages.

The first stage involves the formation of a The first stage involves the formation of a cyclic bromonium ion intermediate. In cyclic bromonium ion intermediate. In special circumstances,this intermediate special circumstances,this intermediate can isolated or observed using NMR. can isolated or observed using NMR.

nucleophilic attacknucleophilic attack . The second stage is a nucleophilic attack . The second stage is a nucleophilic attack

by a bromide ion on the intermediate, with by a bromide ion on the intermediate, with inversion occurring at the carbon atom inversion occurring at the carbon atom attacked, to yield a vicinal dibromide. attacked, to yield a vicinal dibromide.

MECHANISM FOR REACTION MECHANISM FOR REACTION OF ALKENES WITH OF ALKENES WITH

HALOGENSHALOGENS Step 1:Step 1:

The π electrons act as a nucleophile, The π electrons act as a nucleophile, attacking the bromine, displacing a attacking the bromine, displacing a bromide ion but forming a cationic cyclic bromide ion but forming a cationic cyclic bromonium ion as an intermediate. bromonium ion as an intermediate.

π electrons act as a nucleophileπ electrons act as a nucleophile

bromonium ionbromonium ion

The second stage The second stage This second stage is like an Sn2 process. This second stage is like an Sn2 process.

Cyclic alkenes such as cyclohexene Cyclic alkenes such as cyclohexene provide evidence that the reaction is an provide evidence that the reaction is an anti addition, anti addition,

The bromine atoms being introduced trans The bromine atoms being introduced trans to one another.to one another.

transtrans addition. addition.

Step 2:Step 2: Attack of the nucleophilic bromide from the Attack of the nucleophilic bromide from the side away from the bromonium center in side away from the bromonium center in an SN2 like fashion opens the cyclic an SN2 like fashion opens the cyclic bromonium ion to give overall bromonium ion to give overall transtrans addition. addition.

The second stageThe second stage It is important to realize that if two different It is important to realize that if two different

groups are present on one or both of the groups are present on one or both of the sp2 carbon atoms of the alkenesp2 carbon atoms of the alkene

linkage, chiral carbon centers are linkage, chiral carbon centers are generated on bromination of these carbon generated on bromination of these carbon atoms. In the case with atoms. In the case with transtrans-stilbene, two -stilbene, two chiral centers are generated, yielding the chiral centers are generated, yielding the meso dibromide. meso dibromide.

mechanism of the brominationmechanism of the bromination Because of The absence of the d,l Because of The absence of the d,l

diastereomer confirms that thediastereomer confirms that the

reaction is stereospecifically anti. (Syn reaction is stereospecifically anti. (Syn addition would have given d,l.)addition would have given d,l.)

Stereochemistry of the Addition of Stereochemistry of the Addition of Bromine to Bromine to transtrans-stilbene -stilbene

Br2

+

Br

Br

Br

Br

relative, not absolute, configurations shown

mechanism of the brominationmechanism of the bromination

Bromination of alkenes using a BrBromination of alkenes using a Br 22/CCl/CCl44 solution (a red-brown color) is frequently solution (a red-brown color) is frequently used as a qualitative test for the presence used as a qualitative test for the presence of unsaturation in a compound. of unsaturation in a compound.

Rapid loss of color from the reagent is a Rapid loss of color from the reagent is a positive test.positive test.

Microscale procedureMicroscale procedure

From pdf! (and book p 735)From pdf! (and book p 735) Microscale procedureMicroscale procedure

In a reaction tube, dissolve 50 mg of E-In a reaction tube, dissolve 50 mg of E-stilbene in 1 mL of acetic acid by heating stilbene in 1 mL of acetic acid by heating on a steam bath on a steam bath

Microscale procedureMicroscale procedure Then add 100 mg of pyridinium Then add 100 mg of pyridinium

hydrobromide perbromide.hydrobromide perbromide.

Mix by swirling!Mix by swirling!

If necessary rinse crystals of the reagent If necessary rinse crystals of the reagent down the walls of the flask with a little down the walls of the flask with a little acetic acid and continue heating for an acetic acid and continue heating for an additional 1 to 2 min.additional 1 to 2 min.

Microscale procedureMicroscale procedure The dibromide separates in small platesThe dibromide separates in small plates

Cool this mixture under the tap, collect the Cool this mixture under the tap, collect the product on a Wilfilter (Fig 4.14 of page 74)product on a Wilfilter (Fig 4.14 of page 74)

Or on a Hirsh funnelOr on a Hirsh funnel

Cleaning UpCleaning Up And wash it with methanol to remove any And wash it with methanol to remove any

color, the yield of colorless crystals (mp color, the yield of colorless crystals (mp 236 236 ooC – 237 C – 237 ooC) is 80 mg.C) is 80 mg.

Use this material to prepare the Use this material to prepare the diphenylacetylene after determining the diphenylacetylene after determining the percent yield and the melting pointpercent yield and the melting point

From pdf is the same!From pdf is the same! In a 4" test tube, 100 mg of In a 4" test tube, 100 mg of transtrans-stilbene is -stilbene is

dissolved in 2 mL of glacial acetic acid by dissolved in 2 mL of glacial acetic acid by heating in a bath of boilingheating in a bath of boiling

water, and then 200 mg of pyridinium bromide water, and then 200 mg of pyridinium bromide perbromide is added. The mixture is stirred perbromide is added. The mixture is stirred constantly with continuedconstantly with continued

heating at 100 ßC for 7 minutes. The reaction heating at 100 ßC for 7 minutes. The reaction mixture is cooled to room temperature, and the mixture is cooled to room temperature, and the product collected byproduct collected by

suction filtration and washed with methanol.suction filtration and washed with methanol.

http://www.aug.edu/~tcrute/lab_experimenhttp://www.aug.edu/~tcrute/lab_experiments/3411%20lab%20Br2%20stilbene-briefts/3411%20lab%20Br2%20stilbene-brief%20report.doc%20report.doc

CHEM3411CHEM3411 Stereochemistry of the Addition of Bromine to Stereochemistry of the Addition of Bromine to transtrans-stilbene-stilbene You will prepare dl- and meso-1,2-dibromo-1,2-diphenylethane (two diastereomers of stilbene dibromide) by an addition reaction to trans-stilbene. These products will not You will prepare dl- and meso-1,2-dibromo-1,2-diphenylethane (two diastereomers of stilbene dibromide) by an addition reaction to trans-stilbene. These products will not

be formed in equal amounts. Isolation by recrystallization and melting point determination of one diastereomer will allow characterization of the diastereomer ratio.be formed in equal amounts. Isolation by recrystallization and melting point determination of one diastereomer will allow characterization of the diastereomer ratio. Before you come to labBefore you come to lab Review textbook concerning the bromination of alkenes. It is essential that you perform a Review textbook concerning the bromination of alkenes. It is essential that you perform a high yieldinghigh yielding recrystallization to yield recrystallization to yield purepure product, thus you should review product, thus you should review

recrystallization in Zubrick. Complete usual pre-lab. Read the sections of your textbook about meso and dl (or chiral) diastereomers.recrystallization in Zubrick. Complete usual pre-lab. Read the sections of your textbook about meso and dl (or chiral) diastereomers. ProcedureProcedure Bromination of trans-stilbeneBromination of trans-stilbene Carry out the reaction in the fume hood. To a 50 mL Erlenmeyer flask is added 0.3 g (record exact mass) of Carry out the reaction in the fume hood. To a 50 mL Erlenmeyer flask is added 0.3 g (record exact mass) of transtrans-stilbene and 3.0 mL of dichloromethane. To this stirred -stilbene and 3.0 mL of dichloromethane. To this stirred

mixture is added sufficient 10% bromine/dichloromethane solution to ensure, mixture is added sufficient 10% bromine/dichloromethane solution to ensure, based on colorbased on color, a slight excess of bromine (usually 3 mL or less). Stopper and clamp the , a slight excess of bromine (usually 3 mL or less). Stopper and clamp the flask and place in an ice-water bath for crystallization. The bromine color may disappear to leave an overall yellow color. Take the cooled sample to the bench and flask and place in an ice-water bath for crystallization. The bromine color may disappear to leave an overall yellow color. Take the cooled sample to the bench and suction-filter the crude product. Rinse the crystals with about 1 mL of cold dichloromethane. Blot dry to yield the crude product.suction-filter the crude product. Rinse the crystals with about 1 mL of cold dichloromethane. Blot dry to yield the crude product.

Preparation of a pure samplePreparation of a pure sample Precisely weigh a small portion (certainly less than 0.1 g- actually about 0.05 g works quite well) of the crude product and recrystallize from methanol. Use your 125 mL Precisely weigh a small portion (certainly less than 0.1 g- actually about 0.05 g works quite well) of the crude product and recrystallize from methanol. Use your 125 mL

Erlenmeyer to ensure enough capacity for the proper amount of solvent. Hot, gravity filtration is probably unnecessary for lack of insoluble impurities. Isolate the product Erlenmeyer to ensure enough capacity for the proper amount of solvent. Hot, gravity filtration is probably unnecessary for lack of insoluble impurities. Isolate the product by suction filtration through the cone shaped porcelain funnel (Hirsh funnel). Dry the crystals as much as possible by allowing air to suck through them for several by suction filtration through the cone shaped porcelain funnel (Hirsh funnel). Dry the crystals as much as possible by allowing air to suck through them for several minutes.minutes.

AnalysisAnalysis Measure the mass of your crude product (mixture of diastereomers). Account for the mass removed for recrystallization, and calculate the percent yield of the reaction Measure the mass of your crude product (mixture of diastereomers). Account for the mass removed for recrystallization, and calculate the percent yield of the reaction

based on the limiting reactant. For your recrystallized product, measure the melting point to identify the diastereomer (literature values: dl-stilbene dibromide- 113-114°C based on the limiting reactant. For your recrystallized product, measure the melting point to identify the diastereomer (literature values: dl-stilbene dibromide- 113-114°C and meso-stilbene dibromide 237°C). Measure the mass of the pure diastereomer and, based on the amount of crude product you purified, calculate the ratio of products and meso-stilbene dibromide 237°C). Measure the mass of the pure diastereomer and, based on the amount of crude product you purified, calculate the ratio of products assuming the remaining mass is the other diastereomer.assuming the remaining mass is the other diastereomer.

Turn in the carbon copies of your prelab and raw data from your observation at this time. You will complete your report in your notebook and turn in the original portions Turn in the carbon copies of your prelab and raw data from your observation at this time. You will complete your report in your notebook and turn in the original portions for the prelab and results in addition to your additional analysis (see next page) for grading.for the prelab and results in addition to your additional analysis (see next page) for grading.

Brief Report Guidel ineBrief Report Guidel ine In your notebook, following the section on in-lab data and observations complete the following:In your notebook, following the section on in-lab data and observations complete the following: Summarize the results (calculated in the analysis above) ofSummarize the results (calculated in the analysis above) of yield of reaction (based on limiting reactant and the mass of the crude product mixture of diastereomers- show calculations!)yield of reaction (based on limiting reactant and the mass of the crude product mixture of diastereomers- show calculations!) ratio of meso to dl diastereomers (based on the pure sample- mass of pure compared to the recrystalized crude- show calculations)ratio of meso to dl diastereomers (based on the pure sample- mass of pure compared to the recrystalized crude- show calculations) observed melting point with a comparison to the expected melting point possibilitiesobserved melting point with a comparison to the expected melting point possibilities your conclusion about the identity of pure product that was isolated from the mixtureyour conclusion about the identity of pure product that was isolated from the mixture Discuss the following concisely:Discuss the following concisely: Show mechanism(s) that account for the formation of each diastereomer. Explain why each might occur. (Hint: a particular mechanism might give both diastereomers. Show mechanism(s) that account for the formation of each diastereomer. Explain why each might occur. (Hint: a particular mechanism might give both diastereomers.

There also might be more than one mechanism that will make a particular diastereomer) Suggest (with good reasons to back up your suggestions) particular parts of the There also might be more than one mechanism that will make a particular diastereomer) Suggest (with good reasons to back up your suggestions) particular parts of the procedure that were the weak points (inherent problems with the general method involved and, if appropriate, any mistakes you made that affected your measurements) in procedure that were the weak points (inherent problems with the general method involved and, if appropriate, any mistakes you made that affected your measurements) in your ability to measure the ratio of diastereomer.your ability to measure the ratio of diastereomer.

REU: Research Experiences REU: Research Experiences for Undergraduatesfor Undergraduates

University of Nevada NSF-REU summer University of Nevada NSF-REU summer program in chemistry. program in chemistry.

Program in the summer of 2011 or 2012. Program in the summer of 2011 or 2012. Students interested in the REU program in Students interested in the REU program in

general should consult the NSF web site for a general should consult the NSF web site for a listing of programs available nation-wide: listing of programs available nation-wide:

REU: Research Experiences REU: Research Experiences for UndergraduatesResearch for UndergraduatesResearch

Experience for Undergraduates (REU) Experience for Undergraduates (REU) ProgramProgram

A program funded by the National Science A program funded by the National Science Foundation (NSF)Foundation (NSF)

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..

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How to synthesize a compound?How to synthesize a compound?

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Determination of configurationDetermination of configuration ..

The Preparation of compoundsThe Preparation of compounds ..

StilbeneStilbene Stilbene used as a LASER dyeStilbene used as a LASER dye