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Supplementary Material Greener Brominations of Stilbene

Notes to Instructors:
Greener Brominations of Stilbene
It is often useful in organic chemistry courses to discuss bromination within the context of alkene
reactivity, reaction mechanisms, and chemical transformations. Halogenation chemistry can be
used to explain variations within the reactivity of carbon-carbon double bonds as well as present
students with a mechanistically interesting example of an addition reaction. In contrast to a
radical mechanism, the commonly accepted pathway for this addition involves an ionic
mechanism in which the electron-rich alkene acts as a nucleophile, and the bromine is the
electrophile (see Figure 2 in Student Handout). In this way, halogenated compounds can be
reactive intermediates, capable of undergoing a variety of further chemical transformations to
produce the desired product. The experiments in this document provide practical laboratory
experience with the above concepts through the addition of a halogen bromine to an alkene,
(E)-stilbene (trans-stilbene).
Bromination is conventionally carried out with elemental bromine in a solvent that will dissolve
the alkene but not participate in the reaction, such as methylene chloride or carbon tetrachloride.
These solvents introduce risks to human health and the environment. Elemental bromine is
dangerous to handle, particularly by inexperienced students, due to its corrosive nature,
volatility, and ability to cause severe burns upon contact with the skin.
Included in this supplemental information are notes and procedures for two greener brominations
of trans-stilbene, of which versions can be found in the green organic laboratory text by Doxsee
and Hutchison (1), a green procedure for debromination, and a green chemistry metrics exercise.
These experiments offer safe, effective, modern procedures for introducing the bromination of
alkenes into the teaching laboratory and also provide an ideal opportunity for the discussion of
green chemistry, including its incremental rather than absolute nature. As demonstrated in the
laboratory summary, reaction efficiency is lowered in order to introduce safer procedures. Also,
although these procedures are greener, introduction of bromine generally represents an
intermediate step in chemical synthesis which is followed by the removal of bromine. There are
still many opportunities for greener chemistry, including finding ways to accomplish the
chemical transformations without the intermediate introduction of bromine.

Part A: Bromination of trans-stilbene with pyridinium tribromide


Many alternate bromination procedures have been introduced into the undergraduate laboratory
in recent years (2-6). This greener experiment illustrates two key features of green chemistry
the use of safer reagents and the use of alternative solvents. Pyridinium tribromide, a crystalline
solid, is much easier to handle and can be used to effect bromination in relatively safe solvents
such as ethanol. In this reaction, bromine is released into the reaction medium through rapid
equilibrium between pyridinium tribromide and molecular bromine (see Figure 1). Because
bromine is prepared in situ, the student no longer needs to handle the bromine directly.

Notes to Instructors

Page 1

Supplementary Material Greener Brominations of Stilbene


Many texts suggest the use of pyridinium tribromide for bromination reactions, but glacial acetic
acid is the recommended solvent in these sources. We have obtained similar yields when
ethanol, a more benign solvent, is substituted for the corrosive acetic acid.

H Br3

pyridinium tribromide

H Br

+ Br2

pyridinium hydrobromide

Figure 1: Equilibrium between pyridinium tribromide and


pyridinium hydrobromide and bromine.

This experiment provides experience with several basic laboratory techniques including carrying
out a reaction above room temperature, vacuum filtration to isolate a solid product, and melting
point determination. Students learn about the lowering of melting points by impurities by
comparing the melting point of their product before and after rinsing with methanol.
Materials
Item
trans-stilbene
(trans-diphenylethylene)

CAS #

pyridinium tribromide

39416-48-3

ethanol

64-17-5

methanol

67-56-1

stilbene dibromide
(1,2-dibromo-1,2diphenylethane)
melting point capillary
tubes
filter paper

Hazards

103-30-0

5789-30-0

Quantity/Student
2.0 g

Corrosive,
causes burns
Highly flammable
Toxic,
Highly flammable
Irritant

4.0 g
40 mL
5 mL
Small amount for
comparing melting
points

Estimated Lab Time


Approximately 2 hours
Waste Collection and Disposal
The ethanol and methanol can be recovered by distillation. If this is desired, separate waste
containers should be available for the ethanol filtrate and the methanol wash. Student samples,
after evaluation, should be packaged as solid waste for disposal or debrominated and reused (a
green debromination procedure is included in this supplementary material).

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


Experiment Tips
Pyridinium tribromide is very corrosive and a lachrymator. It causes damage to metal surfaces,
especially metal balance pans, and spills should be cleaned up promptly and carefully. Do not
store in an area where it can come in contact with metal shelves or hinges.
This experiment has been extensively student tested and is very reliable. Yields are usually high.
The crude product is a white to pale yellow solid that has a lowered melting point due to
contamination with pyridinium salts. The melting point of pure dibromostilbene is 241 C,
although this is accompanied with decomposition and so there may be variability in reported
values. Mixed melting point determination may help students to establish the identity of their
product (as compared with an authentic sample) and to observe the effects of impurities on
melting point.
Although the reaction typically is run at the scale in which it is written, it has been tested
successfully using one quarter of the reactants and solvent (0.5 g of trans-stilbene, 10 mL of
ethanol, and 1 g of pyridinium tribromide). If desired, the reaction can be run at this smaller
scale, producing enough product for student analysis and reducing waste.
Rinsing with methanol removes the pyridinium salts from the crude product. An opportunity for
further greening of this procedure is probably possible in this step through the substitution of
very cold ethanol for the methanol. The product is more soluble in ethanol than in methanol;
therefore, the yields may be lower if ethanol is used.
The reaction has relatively poor atom economy, and the use of pyridinium tribromide takes the
non-green reagent, bromine, out of student hands, but bromine is still required for its preparation.
While each of these points can be viewed as a limitation of this experiment, they can provide
valuable teaching lessons in the study of green chemistry.
Part B: Bromination of trans-stilbene with hydrogen peroxide and hydrobromic acid
This experiment introduces the same chemical concepts and techniques as those described in the
bromination with pyridinium tribromide with the addition of set up and maintenance of reflux
conditions. The experiment represents adaptations from Olah et al. (7) and Rothenberg and Clark
(8). Olah et al. used hydrogen peroxide and HCl as a chlorination method in water with a phase
transfer catalyst. Barhate et al. also explored halogenation methods involving peroxides and
hydrohalic acids on a variety of substrates and in a number of solvents (9).
Although the mechanistic pathway is not as obvious as for that of the above reaction, many
factors indicate that this bromination occurs through the same bromonium ion pathway. The
formation of the characteristic bromine color suggests that the HBr is oxidized by the hydrogen
peroxide, forming molecular bromine in situ (see Figure 2). Small amounts of 1-bromo-22 HBr + H2O2

EtOH

Br2 + 2 H2O

Figure 2: Molecular bromine is produced in situ by the oxidation of hydrobromic acid by hydrogen peroxide.

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


ethoxy-1,2-diphenylethane produced by the reaction (observable through analysis of 1H NMR of
the crude product) also support literature reports that peroxide and hydrohalic acid halogenations
proceed through the same mechanism as traditional brominations (7,8). The stereochemical
outcome of this reaction is a single meso product, which can be demonstrated by melting point
determination and by the single trans-stilbene product produced by subsequent debromination of
the dibromide. These facts are most consistent with a cyclic bromonium ion mechanism for this
reaction.
Materials
Item
trans-stilbene
(trans-diphenylethylene)

CAS #

ethanol

64-17-5

hydrobromic acid

10035-10-6

hydrogen peroxide

7722-84-1

sodium bicarbonate,
saturated aqueous
solution
stilbene dibromide
(1,2-dibromo-1,2diphenylethane)
syringes
melting point capillary
tubes
filter paper

Hazards

103-30-0

0.5 g
Highly
flammable
Corrosive,
causes burns
Corrosive,
causes burns

144-55-8
5789-30-0

Quantity/Student

10 mL
0.8 mL
0.8 mL
5 mL

Irritant

Small amount for


comparing melting points

Estimated Lab Time


Approximately 2 hours
Waste Collection and Disposal
Collect the aqueous ethanol filtrates in a waste bottle. The ethanol may be recovered by
distillation. Student samples, after evaluation, should be packaged as solid waste for disposal or
debrominated and reused (a green debromination procedure is included in this supplementary
material).

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


Experiment Tips
Hydrobromic acid is corrosive, and hydrogen peroxide (30%) is a strong oxidizer and will
readily damage clothing and body tissues. Students should avoid skin contact and inhalation of
vapors and clean up spills immediately. Students should be reminded that the hydrogen peroxide
used in this experiment is more concentrated (and therefore poses more hazards) than the types
sold for home use.
It would be ideal to reduce the hazards in this reaction by replacing the 30% hydrogen peroxide
with solutions of lower concentration. In the experiment development process, it was found that
decreased solubility of the starting material in 7.5% and 3% hydrogen peroxide reduced the
product yields to some extent. The decreased solubility is due to the fact that when using lower
concentrations of H2O2, there is more water present. This experiment, as it is written, is
extremely reliable with yields typically around 70%. With 7.5% hydrogen peroxide
(commercially available spa chemical Baqua Spa Shock), yields were reduced to 55%, and
they were further lowered to around 49% when using 3% (household) hydrogen peroxide as a
reagent. Although reaction efficiency is affected by the substitution of these hydrogen peroxide
solutions, it may be preferable to do so in order to protect students from the hazards associated
with 30% hydrogen peroxide.
The reaction progress is easy to follow by a color change from a dark yellow or orange solution
to a white solid in a colorless solution. While it is possible for the yellow color to persist due to
other reasons (too little stilbene added, impure HBr), residual yellow color is most often
indicative of an incomplete reaction, requiring additional heating time. The product is generally
obtained as a white crystalline solid with a melting point of 241 C with decomposition.
Chalcone and ethyl cinnamate also have been successfully brominated through this procedure,
offering flexibility in reagent choice. Both of these reagents are non-toxic and inexpensive, and
the bromination of ethyl cinnamate provides the opportunity to work with a liquid reagent as
well as to perform an optional ethanol/water recrystallization of the product. Attempts to
brominate cinnamic acid produced a mix of products due to partial esterification of the starting
materials under the reaction conditions.
Part C: Green debromination of stilbene dibromide
Although many texts suggest debromination of vicinal dibromides with zinc in acetic acid (10),
this simple recycling procedure was developed in a greener solvent, ethanol (see Figure 3).
Literature suggests two possible mechanisms for this reaction, a concerted two electron reduction
by the zinc or two single-electron transfers in rapid succession (11).

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene

Br
n Zn(0)

+
Br

(n-1) Zn(0)

ZnBr2

Figure 3: Debromination of stilbene dibromide by zinc metal either through a concerted two electron
reduction or two rapid single-electron transfers.

Materials
Item
stilbene dibromide
(1,2-dibromo-1,2diphenylethane)
ethanol
zinc powder or dust
trans-stilbene
(trans-diphenylethylene)
melting point capillary
tubes
filter paper

CAS #
Hazards
Provided by students
from bromination
Irritant
experiment
Highly
64-17-5
flammable
7440-66-6
103-30-0

Quantity/Student
0.5 g
16 mL
0.125 g
Small amount for
comparing melting points

Estimated Lab Time


1-2 hours
Waste Collection and Disposal
The unreacted zinc dust can be allowed to dry and then discarded as nonhazardous solid waste.
Collect the ethanol filtrates in a waste bottle. The ethanol may be recovered by distillation.
Student samples, after evaluation, should be packaged as a reagent for future bromination
laboratories.
Experiment Tips
After a short reflux of stilbene dibromide and zinc powder in ethanol and a hot filtration, pure
trans-stilbene crystallizes. All reagents and the zinc bromide byproduct are non-toxic, and yields

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


are around 70%. After debromination, the product often has a higher and sharper melting point
than that of commercial trans-stilbene (96%), indicating that the bromination and subsequent
debromination have served to purify the alkene.
The zinc powder is very inexpensive, but the necessary ethanol can cost more than transstilbene. If the ethanol is recovered by distillation, this procedure is not only greener but also
cost-effective. If recovering the ethanol, one should note though that zinc dibromide is corrosive
and can cause burns. If this procedure is to be done on a large scale instead of as a laboratory
experience, continuous extraction should be used instead of the hot filtration.
An added benefit of this procedure is that it can be used to illustrate the stereochemistry of the
original stilbene dibromide. Since the product of the debromination is pure trans-stilbene, the
starting material must be the meso form of stilbene dibromide as demonstrated in Figure 3 above.
Part D: Assessing the efficacy of bromination reactions: An introduction to green
chemistry metrics
This section introduces the evaluation processes used for green chemistry and describes some of
the metrics employed in the process. It contains a series of guiding questions and is intended to
expose students to the process, metrics, and challenges of green chemical assessment. As an
additional exercise, students also can compare their results to the traditional bromination
procedure involving liquid bromine in a halocarbon solvent, such as that featured in reference 12.
1. In order to assess the greenness of a chemical reaction, each alternative procedure must be
evaluated to identify hazardous materials or inefficient procedures. Read over both bromination
procedures in this handout. Which reaction do you think is the greenest? Why?
Answers will vary. This question is meant to elicit general impressions and to begin the
evaluation process.
2. Write a balanced equation for each reaction.
Reaction from Part A, pyridinium tribromide:

H
+
H

Notes to Instructors

Br

H Br3

EtOH

H
H

H Br

Br

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Supplementary Material Greener Brominations of Stilbene


Reaction from Part B, hydrogen peroxide and hydrobromic acid:

Br

+ 2 HBr + H2O2
H

H
H

EtOH

2 H2O

Br

NOTE: It is important that students include all reagents and by-products in the equations.
3. Metrics allow for measured, objective analysis for comparison of competing procedures,
emphasizing measures of efficiency and cost, in addition to the comparison of chemical hazards.
Atom economy (13) was developed to quantify the theoretical reaction efficiency and calculates
the fraction of reactants converted to the product. Clear explanations of atom economy and its
applications are provided by Trost in articles in Science and Accounts of Chemical Research
(13,14).
Calculate the atom economy for both the reaction that you performed and the alternative
bromination procedure. How do they compare?
Reaction from Part A, pyridinium tribromide:
MW product

MW
reagent

100%

340.07

180.24 + 319.8

MW stilbene

dibromide

100%
pyridinium )
MWtrans stilbene + MWtribromide

100%

68.0%

Reaction from Part B, hydrogen peroxide and hydrobromic acid:


MW product

MW
reagent

100%

340.07

180.24 + 2(80.92) + 34.01

MW stilbene

dibromide
100%

c ) + MW hydrogen )
MWtrans stilbene + 2( MW hydrobromi
acid
peroxide

100%

90.4%

NOTE: If students calculate an atom economy of greater than 100% for Part B, they probably
have not included the two equivalents of HBr required in the reaction.
The atom economy for the reaction in Part B (90.4%) is better than for the reaction in Part A
(68.0%), which produces pyridinium bromide in stoichiometric quantity as waste. It is worth
noting that the waste produced in Part B is water, a greener by-product than pyridinium
bromide.

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


4. Effective mass yield uses the actual masses of reagents used and products generated in the
reaction to gauge reaction efficiency and takes into account relative toxicity of the method by
focusing only on the hazardous components of the waste stream. Hudlicky et al. present a
thorough description of effective mass yield in their article in Green Chemistry (15). Calculate
the effective mass yield for both the reaction that you performed and the alternative bromination
procedure. For this purpose, consider ethanol as a benign material. How do they compare?
Reaction from Part A, pyridinium tribromide:
NOTE: Unless students have completed both procedures, they should calculate effective mass
yield assuming 100% yield (3.74 g).
mass

massstilbene

product
=
dibromide

100
%

100%

mass
mass
mass
+
nonbenign
trans stilbene
pyridinium

material
tribromide

3.74

100% = 62.3%
2.00
+
4.00

Reaction from Part B, hydrogen peroxide and hydrobromic acid:


NOTE: Unless students have completed both procedures, they should calculate effective mass
yield assuming 100% yield (0.94 g).
mass

product
=

100%
mass
nonbenign

material

0.94

100%
0.50
+
0.24
+
0.57

massstilbene

dibromide
100%

mass
mass
mass
+
+
trans stilbene
hydrogen
hydrobromic

peroxide
acid

= 71.8%

5. Use the following procedure to perform an economic analysis of the preparation of


dibromostilbene via each route:
a. Identify the costs of all required materials. Use the largest quantity listed in
the catalog of either Aldrich Chemical Company or Acros Organics. Be sure to
include all substances used, whether as reagents, catalysts, or solvents.
b. Record the total amounts of each material used and the waste generated.
c. Calculate the cost for each starting material, reagent, and solvent and
determine the total cost of the experiment.
d. Add in costs for waste generated. Assume it will cost $25/L to dispose of
liquid waste and $25/kg to dispose of solid waste and that products and solvents
are not recycled.
Note: All calculations here are based on prices from the 2004-2005 Acros Organics catalog.

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


Reaction from Part A, pyridinium tribromide:
(E)-stilbene (trans-stilbene) [103-30-0]
$143.10/500 g = $0.286/g
2.0 g = $0.57
Pyridinium tribromide [39416-48-3]
$203.10/500 g = $0.406/g
4 g = $1.62
Ethanol [64-17-5]
$38.00/4 L = $0.0095/mL
40 mL = $0.38
NOTE: Due to the variable quantities that students will use, the amount of wash methanol has
not been included in the cost calculation and waste analysis provided here. Students should
include this material in their analyses.
Unless students have completed both procedures, they should calculate cost assuming 100%
yield (3.74 g). In this case, the total cost, is $2.57/3.74 g = $0.69/gram of product. If actual
yields are available for both reactions, the cost should be adjusted to the actual cost/gram, using
the students reported chemical yield. For example, if the yield was 60%, then the cost per gram
is $0.69/0.6 = $1.15.
As calculated above and excluding wash methanol (see note above), the experiment will generate
40 mL of liquid waste (ethanol containing excess pyridinium tribromide and pyridine
hydrobromide) and no solid waste. The cost of this waste should be calculated as $1.00 for 40
mL. Since the theoretical yield of product is 3.74 g, the cost of waste disposal per gram of
product is $1.00/3.74 = $0.27.
Total product cost (at 100% yield) including waste disposal cost: $0.96/g
Reaction from Part B, hydrogen peroxide and hydrobromic acid:
(E)-stilbene (trans-stilbene) [103-30-0]
$143.10/500 g = $0.286/g
2.0 grams = $0.14
HBr (ca. 48 wt % sol. in water) [10035-10-6]
$75.80/2.5 L = $0.03/mL
0.8 milliliters = $0.02
H2O2 (30%) [7722-84-1]
$65/2.5 L = $0.026/mL
0.8 milliliter = $0.02

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene

Ethanol [64-17-5]
$38.00/4 L = $0.0095/mL
10 milliliters = $0.09
NOTE: Due to the variable quantities that students use, the amounts of aqueous sodium
bicarbonate and additional wash ethanol have not been included in the cost calculation and
waste analysis provided here. Students should include these materials in their analyses.
Unless students have completed both procedures, they should calculate cost assuming 100%
yield. In this case, the total cost is $0.28/0.94 g = $0.30/gram of product.
As calculated above, the experiment will generate 11.6 mL of liquid waste (excluding wash
solvents, see note above) and no solid waste. The cost of this waste should be calculated as
$0.29 for 11.6 mL. Since the theoretical yield of product is 0.94 g, the cost of waste disposal per
gram of product is $0.29/0.94 = $0.32.
Total product cost (at 100% yield) including waste disposal cost: $0.61/g
6. After consideration of the above calculations, which reaction do you think is the greenest?
Why? Is this different from your original assessment (Question 1)?
Answers will vary.
7. Which metric affected your decision the most? What are some of the challenges that you
noticed in applying metrics to evaluate the greenness of reactions?
Answers will vary. This question is meant to point out the difficulties of comparing reactions
and evaluating them reliably.
Literature Cited
1. Doxsee, K. M.; Hutchison, J. E. Green Organic Chemistry: Strategies, Tools, and Laboratory
Experiments Brooks/Cole: Pacific Grove, CA, 2004.
2. Smith, R. E., IV; McKee, J. R.; Zanger, M. The Electrophilic Bromination of Toluene:
Determination of the Ortho, Meta, and Para Ratios by Quantitative FTIR Spectrometry. J. Chem.
Educ. 2002, 79, 227.
3. McGowens, S. I.; Silversmith, E. F. Organic Reactions Involving Bromine: Puzzles for the
Organic Laboratory. J. Chem. Educ. 1998, 75, 1293.
4. Schatz, P. F. Bromination of Acetanilide. J. Chem. Educ. 1996, 73, 267.
5. Cooley, J. H.; Abobaker, N. M. Steric Hindrance by Bromination of Alkylbenzenes:
Experimental Demonstration. J. Chem. Educ. 1995, 72, 463.

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


6. Berthelot, J.; Fournier, M. A simple, safe, and easy bromination of alkene using TBABr3: An
organic laboratory experiment. J. Chem. Educ. 1986, 63, 1011.
7. Ho, T.-L.; Gupta, B. G. B.; Olah, G. A. Synthesis 1977, 676-677.
8. Rothenberg, G.; Clark, J. H. Org. Proc. Res. Dev. 2000, 4, 270-274.
9. Barhate, N. B.; Gajare, A. S.; Wakharkar, R. D.; Bedekar, A. V. Tetrahedron 1999, 55,
11127-11142.
10. Fieser, L. F.; Williamson, K. L. Organic Experiments; Houghton Mifflin: New York, 1998;
pp 243-244.
11. Totten, L. A.; Jans, U.; Roberts, A. L. Environ. Sci. Technol. 2001, 35, 2268-2274.
12. Durst, H. D.; Gokel, G. W. Experimental Organic Chemistry; McGraw-Hill: San Francisco,
1987; pp 240-241.
13. Trost, B. M. Science 1991, 254, 1471-1477.
14. Trost, B. M. Acc. Chem. Res. 2002; 35(9), 695-705.
15. Hudlicky, T.; Frey, D. A.; Koroniak, L.; Claeboe, C. D.; Brammer, L. E. Green Chemistry
1999, 1, 57-59.

Notes to Instructors

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Supplementary Material Greener Brominations of Stilbene


Student Handout:
Greener Brominations of Stilbene
In order to obtain complex molecules, it is often necessary to introduce more reactive
functionality than is possible from simple hydrocarbons. Alkenes (olefins) hydrocarbons
containing the carbon-carbon double bond functional group may be halogenated to form
alkyl halides, which are then capable of undergoing a variety of further chemical
transformations. In the experiments described in Parts A and B, you will brominate an alkene,
trans-stilbene, as shown in Figure 1. This reaction is representative of any other alkene
bromination.

Br

Br2

Br

Figure 1: The bromination of trans-stilbene

Bromination of an alkene is an example of an addition reaction in which bromine adds


across the double bond to yield a vicinal dibromide. A commonly accepted pathway for this
addition involves an ionic mechanism in which the electron-rich alkene acts as a nucleophile (a
species that attacks centers bearing more positive charge) and the bromine is the electrophile (a
species that that is attracted to and tends to accept electrons). As bromine and the alkene
approach one another, the BrBr bond becomes polarized (becoming more positive near the
alkene and more negative at the other end). The more positively charged Br atom is transferred
to the alkene to yield a bromonium ion and a bromide anion. In a second step, bromide attacks
one of the carbon atoms of the cyclic bromonium ion to open the three-membered ring and yield
the vicinal dibromide. The second step is a bimolecular nucleophilic substitution reaction (SN2).
The net result of this reaction is anti addition of bromine, as opposed to syn addition.
Br

Br

Br +

Br
Br

bromonium ion

Br

Figure 2: General mechanism of bromination across a double bond. The Br-Br bond becomes polarized,
so the bromine attacks first as an electrophile and then as a nucleophile.

Traditionally, this reaction is performed in a solvent, like methylene chloride or carbon


tetrachloride (both suspected carcinogens), that will not participate in the reaction but will
dissolve the alkene. Some brominations may also be carried out in glacial acetic acid, a volatile
and corrosive liquid. The traditional reagent, elemental bromine, is also dangerous to handle,
because it is highly corrosive and causes severe burns upon contact with the skin. While this
reaction works very well on most substrates, it can be dangerous to do in an instructional
laboratory setting. For these reasons, two greener alternatives to this reaction are presented.
Student Handout

Page 1

Supplementary Material Greener Brominations of Stilbene


Part A: Bromination of trans-stilbene with pyridinium tribromide
An alternative to traditional bromination is presented below. The largest modification is that
instead of using liquid bromine, an alternative reagent, pyridinium tribromide, popularized by
Djerassi and Scholz (1), is used. This reagent provides for gradual release of bromine into the
reaction medium because it is in rapid equilibrium with pyridinium hydrobromide and molecular
bromine (see Figure 3). An additional advantage of pyridinium tribromide is that it is an easily
weighed solid, in contrast to liquid bromine. As the bromine is consumed in the reaction, more
is produced by the pyridinium tribromide. Because the dangerous reagent is produced in situ, it
no longer needs to be handled directly (2). Another benefit of this reaction is that a more benign
solvent, ethanol, can be used instead of a chlorinated solvent.
N

H Br3

pyridinium tribromide

H Br

+ Br2

pyridinium hydrobromide

Figure 3: Equilibrium between pyridinium tribromide and


pyridinium hydrobromide and bromine.

The biggest drawback to this reaction is the lower atom economy as compared to the
traditional bromination procedure. Aside from the desired product, pyridinium hydrobromide is
also produced as waste. Pyridinium tribromide also is corrosive and can cause significant
damage to metal equipment, especially balances.
Experimental Procedure
SAFETY PRECAUTIONS: Pyridinium tribromide is corrosive and is also a
lachrymator. Avoid contact with this material and wipe up any spills immediately,
particularly on the balance. Ethanol is flammable; do not use open flames near
flammable solvents.
Reaction
1

Into a 125-ml Erlenmeyer flask, place 40 ml of ethanol and 2.0 g of (E)-stilbene along with a
magnetic stir bar. (Be sure to record the exact mass of the stilbene you use.) Clamp the
Erlenmeyer flask in place on a hot plate (3). Using the hot plate for both heating and stirring,
dissolve the stilbene (4).

2 Wearing disposable gloves, add 4.0 g of pyridinium tribromide and mix thoroughly. You
may need to wash down the inside of the flask with a little ethanol to make sure that all the
solid material dissolves in the reaction medium.
3

After another 5 min of heating, remove from heat, being careful not to burn yourself on the
glassware. The product dibromide will immediately begin to precipitate or crystallize.

Student Handout

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Supplementary Material Greener Brominations of Stilbene


Workup and Isolation
4

Let the reaction mixture cool to room temperature and then chill the mixture in an ice bath.
Collect the product by vacuum filtration. Set aside a small amount of this crude product so
that you can measure its melting point later.

Wash the crystals with a small amount of ice-cold methanol to remove any adsorbed
pyridinium salts. Dry your compound (by drawing air through it while it sits in the filter
funnel).

Characterization
6

Measure the melting point. Also measure the melting point of your crude material. If time
allows, you should also record the melting point of (E)-stilbene in order to check the
calibration of your MelTemp. Determine the percentage yield of this purified product (you
will need its mass).

If time permits, confirm the identity of your compound by performing mixture melting points
with an authentic sample of stilbene dibromide obtained from your TA. You might also try a
mixture melting point of a sample containing your product and the starting material.

Retain a sample of your purified stilbene dibromide in a vial for later analysis using Infrared
Spectroscopy (IR).

Part B: Bromination of trans-stilbene with hydrogen peroxide and hydrobromic acid


The bromination with pyridinium tribromide is an example of a reaction which has been
made safer, yet has considerable opportunities for improvement. Although the solvent and
bromination reagent are less hazardous, pyridinium tribromide is corrosive and can cause
significant damage to metal equipment. While molecular bromine has been removed from the
teaching lab, the hazard is not eliminated entirely because the reagent is synthesized from
pyridine and bromine. Another drawback to this reaction is the relatively poor atom economy;
while the desired product is obtained, a quantitative amount of pyridinium bromide is produced
as waste.
Recent literature suggests greener methods of bromination which have high atom
economy, use less corrosive materials, and eliminate liquid bromine and chlorinated solvents
(5,6). In this reaction (see Figure 4), hydrobromic acid and hydrogen peroxide are used to
generate molecular bromine, and the solvent is ethanol. The by-product in this reaction is just
water.

2 HBr + H2O2

EtOH

Br2 + 2 H2O

Figure 4: Molecular bromine is produced in situ by the oxidation of hydrobromic acid by hydrogen peroxide.

Student Handout

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Supplementary Material Greener Brominations of Stilbene


Experimental Procedure
SAFETY PRECAUTIONS: Care must be taken when using concentrated acid
and/or 30% hydrogen peroxide. Both are corrosive, can cause eye and skin burns,
and are harmful if inhaled. Be careful to avoid contact with skin and refrain from
breathing these compounds. Neutralize all excess acid in the provided containers,
and clean up all spills immediately. Acid will make holes in your clothes (and
your skin), so try not to spill any. Ethanol is flammable so use caution.
1 Prepare a 100 ml round-bottom flask with a stir bar, and prepare a 90-100 C water bath.
2 Measure out 0.5 g stilbene, and add it to the flask with 15 mL of ethanol. Fit with a reflux
condenser and heat the reaction with stirring. Allow the solids to dissolve. Add a little more
ethanol if everything doesnt go in.
3 Once dissolved, slowly add 0.8 mL of HBr (about 2.5 equivalents), and let the solution heat
and stir. The precipitate caused by the addition of acid should go back into solution, but it
may not. Continue even if it does not all go back in.
4 Measure out 0.8 mL of 30% hydrogen peroxide (also about 2.5 equivalents) and add it drop
wise to the reaction. The color should change from clear and colorless (or cloudy white if the
precipitate did not go back in) to dark golden yellow.
5 Let the reaction reflux and stir for about 20 minutes or until the color disappears and the
mixture becomes a cloudy white.
6 Remove the reaction from the heat and let it cool. Once at room temperature, neutralize (pH
5 to 7) the solution with a concentrated NaHCO3 solution. It may only take a little,
depending on how much excess acid you have. Check pH with pH paper.
7 Once neutralized, put the flask on ice to further cool it and cause more crystals to precipitate.
Collect the crystals by vacuum filtration, rinsing with very cold water and a little bit of very
cold ethanol. Let air flow over the product to help dry it. Record your yield and product
melting point (literature m.p. 241C dec.).
8 If time permits and you find it necessary, recrystallize the stilbene dibromide from ethyl
acetate.
9 Retain a sample for IR spectroscopy.
Part C: Debromination of stilbene dibromide
Vicinal dibromides, such as stilbene dibromide, can be readily debrominated by zinc in either
acetic acid or ethanol to produce the corresponding alkene. Literature suggests two possible
mechanisms for this reaction, a concerted two electron reduction by the zinc or two singleelectron transfers in rapid succession (7). Each of these mechanistic paths would lead to the
single stereoisomer which is formed by this reaction (see Figure 5).

Student Handout

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Supplementary Material Greener Brominations of Stilbene

Br
n Zn(0)

+
Br

(n-1) Zn(0)

ZnBr2

Figure 5: Debromination of stilbene dibromide by zinc metal either through a concerted two electron
reduction or two rapid single-electron transfers.

In this procedure, you will be debrominating the product from the above bromination
reactions in order to recycle it for future laboratory experiments. The solvent, reagent, and byproduct are all non-toxic, and the procedure is neither time- nor energy-intensive. Although a
bromination followed immediately by removal of the added bromine atoms would not usually be
viewed as using green chemistry, the recycling and reuse of trans-stilbene improves the
efficiency of the reaction and reduces the waste, thereby improving the greenness of the
reactions.
Experimental Procedure
SAFETY PRECAUTIONS: Zinc and ethanol are flammable; do not use open
flames near these compounds. Although no specific health risks are associated
with zinc dust, always avoid inhalation of particulate matter. The by-product,
zinc dibromide, is corrosive and can cause burns.
1
2
3
4
5

6
7

Prepare a 100 ml flask with a stir bar, and prepare a hot (90-100 C) water bath.
Measure out 0.5 g stilbene dibromide, and add it to the flask with 10 mL of ethanol.
Add 1.25 equivalents of zinc powder.
Fit with a reflux condenser and heat the reaction to reflux with stirring. Allow the reaction to
reflux and stir for 30 minutes.
Prepare a hot filtration set-up with a stemless funnel, 50 mL Erlenmeyer flask, fluted filter
paper, and a watch glass. Just before the reaction is complete, add 3 mL of ethanol to the
Erlenmeyer flask and heat the set-up. Hint: Many technique-based texts do not emphasize
the importance of preheating a hot filtration system to reflux, however it is important that the
filter paper is kept hot throughout the filtration.
Remove the reflux condenser from the reaction. Using the clamp as a handle, pour a small
amount of the hot solution slowly from the round-bottom flask into the filter paper. Replace
the watch glass and allow the hot solution to filter. Repeat until all solution is filtered.
Remove the flask from the heat and allow it to cool to room temperature. A few crystals
should begin to form.

Student Handout

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Supplementary Material Greener Brominations of Stilbene


8
9

Place the flask in ice and allow crystallization to proceed.


Collect the crystals by vacuum filtration, rinsing with a little bit of very cold ethanol. Let air
flow over the product to help dry it. Record your yield and product melting point (literature
m.p. 122-124 C).
10 If time permits, confirm the identity of your compound by performing mixture melting points
with an authentic sample of trans-stilbene obtained from your TA. You might also try a
mixture melting point of a sample containing your product and the starting material.
Part D: Assessing the efficacy of bromination reactions: An introduction to green chemistry
metrics
This section introduces the evaluation processes used for green chemistry and describes some of
the metrics employed in the process. As an additional exercise, you also can compare your
results to the traditional bromination procedure involving liquid bromine in a halocarbon solvent,
such as that featured in reference 8.
1. In order to assess the greenness of a chemical reaction, each alternative procedure must be
evaluated to identify hazardous materials or inefficient procedures. Read over both bromination
procedures in this handout. Which reaction do you think is the greenest? Why?
2. Write a balanced equation for each reaction.
3. Metrics allow for measured, objective analysis for comparison of competing procedures,
emphasizing measures of efficiency and cost, in addition to the comparison of chemical hazards.
Atom economy (9) was developed to quantify the theoretical reaction efficiency and calculates
the fraction of reactants converted to the product. Clear explanations of atom economy and its
applications are provided by Trost in articles in Science and Accounts of Chemical Research
(9,10).
Calculate the atom economy for both the reaction that you performed and the alternative
bromination procedure. How do they compare?
Reaction from Part A, pyridinium tribromide:
MW product

MW
reagent

100%

Reaction from Part B, hydrogen peroxide and hydrobromic acid:


MW product

MW
reagent

100%

Student Handout

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Supplementary Material Greener Brominations of Stilbene


4. Effective mass yield uses the actual masses of reagents used and products generated in the
reaction to gauge reaction efficiency and takes into account relative toxicity of the method by
focusing only on the hazardous components of the waste stream. Hudlicky et al. present a
thorough description of effective mass yield in their article in Green Chemistry (11). Calculate
the effective mass yield for both the reaction that you performed and the alternative bromination
procedure. For this purpose, consider ethanol as a benign material. How do they compare?
Reaction from Part A, pyridinium tribromide:
mass

product

mass
nonbenign

material

100%

Reaction from Part B, hydrogen peroxide and hydrobromic acid:


mass

product

mass
nonbenign

material

100%

5. Use the following procedure to perform an economic analysis of the preparation of


dibromostilbene via each route:
a. Identify the costs of all required materials. Use the largest quantity listed in
the catalog of either Aldrich Chemical Company or Acros Organics. Be sure to
include all substances used, whether as reagents, catalysts, or solvents.
b. Record the total amounts of each material used and the waste generated.
c. Calculate the cost for each starting material, reagent, and solvent and
determine the total cost of the experiment.
d. Add in costs for waste generated. Assume it will cost $25/L to dispose of
liquid waste and $25/kg to dispose of solid waste and that products and solvents
are not recycled.
6. After consideration of the above calculations, which reaction do you think is the greenest?
Why? Is this different from your original assessment (Question 1)?
7. Which metric affected your decision the most? What are some of the challenges that you
noticed in applying metrics to evaluate the greenness of reactions?
Notes
1. Djerassi, C.; Scholz, C. R. J. Am. Chem. Soc. 1948, 70, 417-418.
2. When a reagent is generated in (rather than added to) the reaction medium it is said that the
reagent is prepared in situ.
3. The purpose of the clamp is to allow you to remove the flask from the hot plate without
burning yourself in the event that the solution starts to boil vigorously.

Student Handout

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Supplementary Material Greener Brominations of Stilbene


4. Be careful not to turn the hot plate up too far the hot plate will be slow to heat at first, and
then heat extremely fast. Once hot, it will take a very long time to cool down again!
5. Ho, T. L.; Gupta, B. G. B.; Olah, G. A. Synthesis 1977, 676-677.
6. Barhate, N. B.; Gajare, A. S.; Wakharkar, R. D.; Bedekar, A. V. Tetrahedron 1999, 55,
11127-11142.
7. Totten, L. A.; Jans, U.; Roberts, A. L. Environ. Sci. Technol. 2001, 35, 2268-2274.
8. Durst, H. D.; Gokel, G. W. Experimental Organic Chemistry; McGraw-Hill: San Francisco,
1987; pp 240-241.
9. Trost, B. M. Science 1991, 254, 1471-1477.
10. Trost, B. M. Acc. Chem. Res. 2002; 35(9), 695-705.
11. Hudlicky, T.; Frey, D. A.; Koroniak, L.; Claeboe, C. D.; Brammer, L. E. Green Chemistry
1999, 1, 57-59.

Student Handout

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Supplementary Material Greener Brominations of Stilbene

Data and Sample Calculations Used to Generate Table 1


Data for all three bromination reactions have been compiled and placed in the table below. These values were used to calculate atom
economy, percent experimental atom economy, E factor, and effective mass yield for each reaction. Sample calculations are included.
The results of all calculations are posted in Table 1 of the main document and in this section.
Reaction, reagent, solvent and product data:

Reaction Reagent

II

III

transstilbene
bromine
transstilbene
pyridinium
tribromide
transstilbene
hydrogen
peroxide
hydrobromic
acid

MW of
Moles
Reagent
Used
(g/mol)

Mass of
MW of Moles
Reagent
Utilized Used in
Used
Atoms Product
(g)

Mass of
Utilized
Atoms
(g)

Mass of
Wasted
Atoms
(g)

Mass
of
MW of
Solvent Solvent product
Used
(g/mol)
(g)
CH2Cl2

70.91

340.07

9.52

EtOH

31.57

340.07

3.74

340.07

0.94

180.24

0.028

5.04 180.24

0.028

5.04

159.81

0.029

4.63 159.81

0.028

4.47

0.16

180.24

0.011

2.00 180.24

0.011

2.00

319.86

0.013

4.00 159.81

0.011

1.77

2.23

180.24 0.0028

0.50 180.24

0.0028

0.50

EtOH

7.89

0.24

H2O

0.98

34.01

0.007

0.24

80.92

0.007

0.57 79.90

Data and Sample Calculations

0.0056

0.44

Theoretical
mass of
product (g)

0.13

Page 1

Supplementary Material Greener Brominations of Stilbene

Sample Calculations:
Atom Economy (Reaction III)
MW product

MW
reagent

MW stilbene

340.07
dibromide
100% =
100% =

180.24 + 2(80.92) + 34.01


c ) + MW hydrogen )

MWtrans stilbene + 2( MW hydrobromi


acid
peroxide

100% = 90.4%

Percent Experimental Atom Economy (Reaction III)


mass reagent

in
product

mass reagent

100%

masstrans stilbene + masshydrobromic

utilized
acid
atoms
utilized
0.50 + 0.44

=
=
atoms
100% = 71.8%

100%
0.50
+
0.24
+
0.57

masstrans stilbene + masshydrogen + masshydrobromic


peroxide
acid

E Factor (Reaction III) -

mass

mass ethanol + mass water + mass hydrogen + mass hydrobromic

waste
and
byproducts

peroxide
wasted
atoms

mass product

acid
wasted
atoms

mass product

7.89 + 0.98 + 0.24 + 0.13


0.94

= 9.83

Effective Mass Yield (Reaction III)


mass

product

mass
nonbenign

material

100%

Data and Sample Calculations

100%
mass
mass
mass
+
+
trans stilbene
hydrogen
hydrobromic

peroxide
acid

massstilbene

dibromide

0.94

100%
0.50 + 0.24 + 0.57

= 71.8%

Page 2

Supplementary Material Greener Brominations of Stilbene


Table 1:

Reaction

Atom Economy a

Method of
Calculation or
Determination

MW product

MW
reagent

I Bromine
in methylene
chloride f
II Pyridinium
tribromide in
ethanol
III HBr and
H2O2 in
ethanol

100%

Percent
Experimental
Atom Economy b
mass reagent

in
product

mass reagent

100%

E Factor c

mass

waste
and
byproducts

mass product

Effective Mass
Yield d,e
mass

product

mass
nonbenign

material

100%

100%

98.3%

7.46

11.8%

68.0%

62.3%

8.96

62.3%

90.4%

71.8%

9.83

71.8%

ideal is 100% b ideal is 100% c ideal is 0 d ideal is 100% e EtOH and H2O were considered benign f The
analytical comparison was based on the bromination of stilbene procedure found in Durst, H. D.; Gokel, G. W.
Experimental Organic Chemistry; McGraw-Hill: San Francisco, 1987; pp 240-241.
Note: For brevity and simplicity and given that the yields of these reactions are typically comparable, theoretical yield of product was
used in calculations. Although this provides for a relative comparison of the reaction through the use of these metrics, actual
comparisons of greenness depend on percentage yield as well. An opportunity to extend the metrics exercise includes comparison
with actual percentage yields from each type of reaction.

Data and Sample Calculations

Page 3

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