modular

13SYNT

719laboratory. program chemistryorganic editor: Joe Jefferspublisher: H.A. Neidig

PURPOSE OF THEEXPERIMENT

EXPERIMENTAL OPTIONS

BACKGROUND REQUIRED

BACKGROUNDINFORMATION

in

Brominating Alkenesprepared by Carl T. Wigal, Lebanon Valley College

Synthesize vicinal dihalides by brominating alkenes. Characterize vici-nal dihalides by using the silver nitrate test and by using melting pointmeasurement to determine the relative stereochemistry.

Using Semi-Microscale Techniques to Brominate AlkenesCinnamic Acidcis-Stilbenetrans-Stilbene

Using Microscale Techniques to Brominate AlkenesCinnamic Acidcis-Stilbenetrans-Stilbene

You should consult your textbook for the Cahn-Ingold-Prelog Systemfor assigning the configuration of a chiral center. You should be famil-iar with techniques for reflux, for vacuum filtration, and for meltingpoint measurement.

The halogenation of alkenes is an important reaction in the chemical in-dustry. For example, over 8 million tons of 1,2-dichloroethane per year areproduced by the addition of chlorine (Cl2)to ethylene. This product isused both as a solvent and in the preparation of polyvinyl chloride, PVC,acommon organic polymer used in household plumbing. The products ob-tained from alkene halogenation are called vicinal dihalides because thetwo halogen substituents are attached to adjacent carbon atoms.

When the halogen used is either bromine (Br2) or chlorine (Cl2),halogenation of alkenes occurs rapidly at room temperature, and the re-sulting vicinal dihalides are stable. Fluorination is a violent reaction thatis difficult to control and is accompanied by several side reactions. Iodin-ation is an endothermic process, resulting in vicinal diiodides that tendto revert to alkenes. Consequently, the most common applications ofalkene halogenation are chlorination and bromination.

Typically,alkenes undergo reactions through electrophilic addition,a process in which the alkene pi (1t)bond is replaced with two sigma (0)bonds. The general mechanism of electrophilic addition involves twosteps, as shown in Figure 1 on the next page.

Copyright @ 1998 by Chemical Education Resources, Inc., P.O. Box 357, 220 South Railroad, Palmyra, Pennsylvania 17078No part of this laboratory program may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photo-copying, recording, or any informationstorage and retrievalsystem, without permission in writingfromthe publisher. Printed in the United IStates of America

168

Figure 1alkene

Electrophilic addition to an

Figure 2 Bromination of cyclohexene

SYNT: 719 BrominatingAlkenes

carbocation

The first step involves reaction of an electron deficientspecies,called anelectrophile (E+),with the electron-rich 1tbond of the alkene. The two elec-trons of the 1tbond shift toward the electrophile, forming a new carbon-electrophile crbond.This step results in formation ofa positively charged in-termediate. In most instances, the positive charge centers on a carbon atom,so the electron-deficient intermediate is called a carbocation.

In the second step, the electrophilic carbocation reacts with anelectron-rich species called a nucleophile (Nu-). The nucleophile do-nates an electron pair to the positively charged intermediate forming acarbon-nucleophile crbond.

Alkene bromination follows the same general mechanism with a fewimportant modifications, as shown in Figure 2. In the first step, the prox-imity of the 1telectrons of the alkene to Br2polarizes the bromine-brominebond. This polarization induces a bond dipole that allows Br2to act as anelectrophile. Electrons flow from the 1tbond to the polarized Br2'forminga carbon-bromine bond and breaking the bromine-bromine bond, pro-ducing a bromide ion (Br-). The positively ch~rged intermediate inbromination is not a carbocation, but a bromonium ion. This cyclic inter-mediate results from a nonbonding electron pair from bromine that stabi-lizes the positive charge on carbon. The bromonium ion is more stablethan a simple carbocation because all atoms of the bromonium ion havean octet of electrons.

8+ 0-

~.B" .....r-Br:

V .bromonium ion

+ ..

~:Br:..

:Br:

In the second step, Br-acts as a nucleophile, attacking the electron-defi-cient bromonium ion. The second carbon-bromine crbond of the vicinal

dihalide forms in this step. An important feature of this step is the resultingstereochemistry. Bromide ion adds to the side opposite the carbon-brominebonds of the bromonium ion. This process is called anti-addition.Anti-addition of Br-occursbecauseBr- is blockedfrom one faceof thebromonium ion by the bromine atom. The consequence of anti-addition ofBr2to cyclic alkenes is the formation of trans vicinal dihalides.

Chiral carbon atoms, or chiral centers, are generated in many or-ganic reactions. A chiral carbon is a carbon atom that is bonded to fourdifferent substituents. As a consequence, two different configurationsare possible for a chiral center: rectus(R) or sinister (5).

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SYNT: 719 BrominatingAlkenes 169

In the case of alkene bromination, the formation of the two carbon-bromine crbonds could result in two new chiral centers in the vicinal di-halide. Using the 2n rule, where n is the number of chiral centers in amolecule, a maximum of four stereoisomers could result from alkene

bromination. However, not all stereoisomers are formed during a singlebromination. Bromonium ion formation preserves the stereochemicalintegrity of the starting material. Therefore, trans alkenes form transbro-monium ions and cis alkenes form cis bromonium ions.

Consider the bromination of maleic and fumaric acids, as shown inFigure 3. When maleic acid, the cis isomer, is brominated, the bro-monium ion formed has cis configuration. The product is a mixture oftwo stereoisomers. These stereoisomers are enantiomers having the ab-solute configurations of 2R,3R and 25,35. Enantiomers are moleculesthat contain chiral centers and are non-superimposable mirror images.

maleicacid

fumaric acid

Figure 3 Bromination of maleic acid and fumaric acid

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Anti-addition of Br- to the cis bromonium ion can take place by ei-ther path a or path b in Figure 3. Addition by path a results in 2R,3R,while addition via path b results in 25,35. Addition occurs at the samerate by either path; therefore, the two enantiomers are produced in equalamounts. A mixture containing equal amounts of a pair of enantiomersis called a racemic mixture. A racemic mixture is often designated byplacing (.:t)at the front of the name.

Unlike bromination of maleic acid, bromination of fumaric acid re-sults in a single stereoisomer. The bromination of fumaric acid results ina trans bromonium ion intermediate. Addition of Br- to the trans brom-

onium ion by either path a or path byields the same compound. The ab-solute stereochemistry of the product is 2R,35, which is identical to25,3R. This compound is an example of a meso compound, which is a

170

Figure 4 Configurations of (a) erythroseand (b) threose

SYNT: 719 BrominatingAlkenes

molecule that contains chiral centers, but also contains an internal planeof symmetry. As a result, meso compounds have superimposable mirrorimages. Meso dibromides result from the bromination of sYmmetricallydisubstituted trans alkenes.

If the alkene is not sYmmetrically substituted, a pair of enantiomerswill result. The relative stereochemistry of the enantiomers could haveboth chiral centers having the same configuration (R, R or 5,5) or the op-posite configuration (R,5 or 5,R). The prefixes erythro and threo are usedto differentiate these stereoisomers. Erythro refers to a pair of enanti-omers having a configuration similar to the sugar erythrose. The erythroform is often described as "meso-like" because the molecule would have

a plane of symmetry if the two dissimilargroups wereequivalent.Threorefers to a pair of enantiomers having a configuration similar to thesugar threose. These configurations are shown in Figure 4.

(R,R) (R,S)(S,S) (S,R)

(:t )-erythrose

(a)

(:t)-threose

(b)

In this experiment, you will brominate an alkene using pyridiniumtribromide, a comparatively safe, convenient source of bromine. Youwill characterize your product by measuring its melting point and byconducting a silver nitrate test. Vicinal dihalides react with alcoholic sil-ver nitrate within five minutes to form a precipitate of the correspondingsilver halide. This reaction can serve as a simple test for the presence ofbromine or chlorine atoms. You will determine the relative stereochem-istry of your product by melting point measurement because the stereoi-somers' melting points differ significantly.

Using Semi-Microscale Techniques to Brominate Alkenes

Equipment

250-mL beaker 2 Pasteur pipets, with latex bulb25-mL filter flask, reflux assembly

with vacuum tubing condenser, with tubingfilter paper 25-mL round-bottom flasklO-mL graduated cylinder thermometer, -10 to 260 0 CHirsch funnel, with adapter sand bath*magnetic stir bar spatulamagnetic wand 2 support standsmelting point capillary tubes 13 x 100-mm test tubemicropipet, 100 to lOOO-IlL 2 utility clamps'stirring hot plate with crystallizing dish filled with sand or magnetic stirrer and electricflask heater filled with sand

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SYNT: 719 BrominatingAlkenes 171

PROCEDURE Chemical Alert

acetic acid-corrosive

cinnamic acid-irritant

ethanol-flammable and irritant

pyridinium tribromide-corrosive and lachrymator

silver nitrate-toxic and oxidizer

Caution: Wear departmentally approved safety goggles at all timeswhile in the chemistry laboratory.

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Reagents and Properties

clampsubstance quantity molar bp mp d- water out mass (0C) (0C) (g/mL)

condenser (g/mol)clamp 1111,., - water in

acetic acid*, glacial 6mL 60.05 118 1.049thermometer--IfI 0 round-

bottom cinnamic acid 450 mg 148.16 133flask

1,2-dibromo-

1,2-diphenylethane t 340.07

2,3-dibromo-3-phenyl-propanoic acidt 307.97

ethanol*,95% 0.5 mL

pyridiniumtribromide* 0.6-1.155 g 319.84

Figure 5 Semi-microscale refluxsilver nitrate*,

apparatus 2% in ethanol 0.5mL

cis-stilbene 300 J1L 180.25 14513mm 1.011

trans-stilbene 300 mg 180.25 124"amount for one bromination

tproduct

Preview

· Assemble the reflux apparatus

· Add the alkene,pyridinium tribromide,and aceticacid·Reflux the reaction mixture

·Allow the reaction mixture to cool to room temperatureto aspirator · Removethe stir bar

- 25-mLfilterflask ·Add water and cool the reaction mixture in an ice-water bath

· Use vacuum filtration to isolate the productFigure 6 Vacuum filtration apparatus · Dry and weigh the product

·Measure the melting point of the product

· Test the product with silver nitrate reagent

1/1.

1. Assembling the Apparatus

2. Brominating the Alkenes[NOTE 1]

NOTE 1: Your laboratory instructorwill designate which alkenes you willbrominate.

NOTE 2: The solid materials are notsoluble at room temperature in aceticacid.

3. Refluxing the Reaction

4. Collecting, Washing, andDrying the Crystals

5. Identifying the Product

SYNT: 719 BrominatingAlkenes

Assemble the reflux apparatus shown in Figure 5 on the previous page.

Caution: Acetic acid is corrosive. Pyridinium tribromide is corro-sive and a lachrymator. Prevent eye, skin, and clothing contact.Avoid inhaling or ingesting these compounds. Use a fume hood todispense these reagents.

Cinnamic Acid

Caution: Cinnamic acid is irritating. Prevent eye, skin, and clothingcontact.

Remove the 25-mL round-bottom flask from the apparatus. Place 450mg of cinnamic acid, 6.0 mL of acetic acid, and 1.155g of pyridiniumtribromide in the round-bottom flask. Add a magnetic stir bar.[NOTE2] Proceed to Part 3.

cis-Stilbene

Remove the 25-mL round-bottom flask from the apparatus. Place 300p.Lof cis-stilbene, 6.0 mL of acetic acid, and 600 mg of pyridiniumtribromide in the round-bottom flask. Add a magnetic stir bar. [NOTE2]Proceed to Part 3.

trans-Stilbene

Remove the 25-mL round-bottom flask from th~ apparatus. Place 300mg of trans-stilbene, 6.0 mL of acetic acid, and 600 mg of pyridiniumtribromide in the round -bottom flask. Add a magnetic stir bar. [NOTE2]Proceed to Part 3.

Reattach the round-bottom flask to the reflux apparatus. Start the flow ofwater through the condenser. Heat the reaction mixture to reflux whilestirring. Reflux for 20 min. After 20 min, remove the flask from the heat.Allow the reaction mixture to cool for 5 min. Turn off the water.

Remove the condenser and use a magnetic wand to remove the stirbar. Add 8.0 mL of distilled or deionized water to the flask. Prepare anice-water bath by half filling a 250-mL beaker with equal volumes of iceand water. Place the flask in the ice-water bath for 15 min.

While the reaction mixture is cooling in the ice bath, assemble a vacuumfiltration apparatus, as shown in Figure 6 on the previous page. Turn onthe water to the aspirator and moisten the filter paper with a few dropsof water. Filter the crystalline solid using the vacuum filtration appara-tus. Wash the crystals with 3.0 mL of water. Allow the crystals to dry inthe Hirsch funnel by pulling air through the funnel for 15 min. Weighyour dried product and record its mass.

Caution: Ethanol is flammable and irritating. Keep away fromflames or other heat sources. Silver nitrate is toxic and oxidizing.Prevent eye, skin, and clothing contact. Avoid inhaling fumes andingesting these compounds.

@ 1998 Chemical Education Resources

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--

SYNT: 719 Brominating Alkenes 173

Measure and record the melting point of the product. Using a small testtube, dissolve approximately 10 mg of the product in 0.5 mL of 95%ethanol. To this test tube, add 0.5 mL of 2% ethanolic silver nitrate.Allow the test tube to stand for 5 min. Record the presence or absenceof a precipitate.

6. Cleaning Up Place your recovered materials in the appropriate labeled collection con-tainers as directed by your laboratory instructor. Clean your glasswarewith soap or detergent.

Caution: Wash your hands thoroughly with soap or detergent be-fore leaving the laboratory.

Using Microscale Techniques to Brominate Alkenes

Equipment

250-mL beaker

conical vial reflux assembly*condenser, with tubing5.0-mL conical vial

elastomeric connector

reflux assembly*condenser, with tubingelastomeric connector5.0-mL round-bottom flask

25-mL filter flask,

with vacuum tubingfilter paperforceps t'use reflux assembly indicated by your laboratory instructor

tor a magnetic wand

~stirring hot plate with crystallizing dish filled with sand or magnetic stirrer and electricflask heater filled with sand

Reagents and Properties

substance quantity

10-mL graduated cylinderHirsch funnel, with adaptermagnetic stir bar or spin vanemelting point capillary tubes100-I1Lmicropipet2 Pasteur pipets, with latex bulbsanctbatht

spatula2 support stands13 x100-mm test tubethermometer, -10 to 260°C2 utility clamps

acetic acid*, glacialcinnamic acid

1,2-dibromo-1,2-diphenylethane t

2,3-dibromo-3-phenyl-propanoic acidt

ethanol*, 95% 0.5 mL

pyridiniumtribromide* 200-385 mg 319.84

2mL

150mg

@ 1998 Chemical Education Resources

J

molar bp mp d I.

mass (0C) (0C) (g/mL) t(g/mol)

'II60.05 118 1.049 i

148.16 133 ,_i

-I

340.07

307.97

174SYNT: 719 Brominating Alkenes

silver nitrate*,2% in ethanol

cis-stilbene

trans-stilbene"amounts for one bromination

tproduct

0.5 mL

100 ilL

100 mg

180.25 14513mm

180.25

1.011

124

Preview

· Assemble the reflux apparatus

· Add the alkene, pyridinium tribromide, and acetic acid· Reflux the reaction mixture

· Allow the reaction mixture to cool to room temperature· Remove the stir bar

· Add water and cool the reaction mixture in an ice-water bath

· Use vacuum filtration to isolate the product

· Dry and weigh the product

· Measure the melting point of the product

· Test the product with silver nitrate reagent

PROCEDURE Chemical Alert

1. Assembling the Apparatus

2. Brominating the Alkenes[NOTE1]

NOTE 1: Your laboratory instructorwill designate which alkenes you willbrominate.

NOTE 2: The solid materials are notsoluble at room temperature in aceticacid.

acetic acid-corrosive

cinnamic acid-irritant

ethanol-flammable and irritant

pyridinium tribromide-corrosive and lachrymatorsilver nitrate-toxic and oxidizer

Caution: Wear departmentally approved safety goggles at all timeswhile in the chemistry laboratory.

Depending upon your glassware, assemble the reflux apparatus shownin Figure 7(a) or 7(b).

Caution: Acetic acid is corrosive. Pyridinium tribromide is corro-sive and a lachrymator. Prevent eye, skin, and clothing contact.Avoid inhaling or ingesting these compounds. Use a fume hood todispense these reagents.

Cinnamic Acid

Caution: Cinnamic acid is irritating. Prevent eye, skin, and clothingcontact.

Remove the 5.0-mL conical vial (or round-bottom flask) from theapparatus. Place 150mg of cinnamic acid, 2.0 mL of acetic acid, and 385mg of pyridinium tribromide in the conical vial (flask). Add a magneticstir bar. [NOTE21 Proceed to Part 3.

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Figure 7 Microscale reflux apparatuswith (a) conical vial or (b) round-bottomflask and elastomeric connectors

_ to aspirator

- 25-mLfilterflask

Figure 8 Vacuum filtration apparatus

3. Refluxing the Reaction

4. Collecting, Washing,andDrying the Crystals

@ 1998 Chemical Education Resources

SYNT: 719 Brominating Alkenes175

water out

condenser

water in

round-bottomflask

conical vial

stir bar

(a) (b)

cis-Stilbene

Remove the 5.0-mL conical vial (or round-bottom flask) from theapparatus. Place 100}.lLof cis-stilbene, 2.0 mL of acetic acid, and 200mgof pyridinium tribromide in the conical v~al(flask). Add a magnetic stirbar. [NOTE2) Proceed to Part 3.

trans-Stilbene

Remove the 5.0-mL conical vial (or round-bottom flask) from theapparatus. Place 100 mg of trans-stilbene, 2.0 mL of acetic acid, and 200mg of pyridinium tribromide in the conical vial (flask). Add a magneticstir bar. [NOTE2) Proceed to Part 3.

Reattach the conical vial (flask) to the reflux apparatus. Start the flow ofwater through the condenser. Heat the reaction mixture to reflux whilestirring. Reflux for 15 min. After 15 min, remove the vial (flask) from theheat. Allow the reaction mixture to cool for 5 min.

Remove the condenser and use forceps or a magnetic wand to re-move the stir bar. Add 2.5 mL of distilled or deionized water to the coni-

cal vial (flask). Prepare an ice-water bath by half-filling a 250-mLbeakerwith equal volumes of ice and water. Place the vial (flask) in the ice-water bath for 15 min.

While the reaction mixture is cooling in the ice bath, assemble a vacuumfiltration apparatus, as shown in Figure 8.

Turn on the water to the aspirator and moisten the filter paper with afew drops of water. Filter the crystalline solid using the vacuum filtra-tion apparatus. Wash the crystals with 3 mL of water.

Allow the crystals to dry in the Hirsch funnel by pulling air throughthe funnel for 15 min. Weigh your dried product and record its mass.

176 SYNT:719 BrominaringAlkenes

5. Identifying the Product Caution: Ethanol is flammable and irritating. Keep away fromflames or other heat sources. Silver nitrate is toxic and oxidizing.Prevent eye, skin, and clothing contact. Avoid inhaling fumes andingesting these compounds.

Measure and record the melting point of the product. Using a small testtube, dissolve approximately 10 mg of the product in 0.5 mL of 95%ethanol. To this test tube, add 0.5 mL of 2% ethanolic silver nitrate.Allow the test tube to stand for 5 min. Record the presence or absence ofa precipitate.

6. Cleaning Up Place your recovered materials in the appropriate labeled collection con-tainers as directed by your laboratory instructor. Clean your glasswarewith soap or detergent.

Caution: Wash your hands thoroughly with soap or detergent be-fore leaving the laboratory.

Post-Laboratory Questions 1. (a) Compare the melting point of your product(s) to the data pro-vided. In each case, identify the product you produced.

compound mp (0C)

2,3-dibromo-3-phenylpropanoic acid

(~)-threo

(~)-erythro

(~)-1,2-dibromo-1,2-diphenylethane

meso-1,2-dibromo-1,2-diphenylethane

94

203

110

238

(b) Draw your product in its correct stereochemical configuration.(c) Compare your results with your predictions for Pre-LaboratoryAssignment question 4.

2. Calculate the percent yield that you obtained from your alkenebrominations.

3. (a) When silver nitrate solution was added to your product, whatdid you observe?(b) Explain your observations.

4. Write reactions for the brominations you performed, in each caseshowing the intermediate bromonium ion that formed.

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