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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.
Notes to Instructors
Page 1
H Br3
pyridinium tribromide
H Br
+ Br2
pyridinium hydrobromide
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
Notes to Instructors
Page 2
EtOH
Br2 + 2 H2O
Figure 2: Molecular bromine is produced in situ by the oxidation of hydrobromic acid by hydrogen peroxide.
Notes to Instructors
Page 3
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
Notes to Instructors
Page 4
Notes to Instructors
Page 5
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
Notes to Instructors
Page 6
H
+
H
Notes to Instructors
Br
H Br3
EtOH
H
H
H Br
Br
Page 7
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%
MW
reagent
100%
340.07
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
Page 8
massstilbene
product
=
dibromide
100
%
100%
mass
mass
mass
+
nonbenign
trans stilbene
pyridinium
material
tribromide
3.74
100% = 62.3%
2.00
+
4.00
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%
Notes to Instructors
Page 9
Notes to Instructors
Page 10
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
Page 11
Notes to Instructors
Page 12
Br
Br2
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.
Page 1
H Br3
pyridinium tribromide
H Br
+ Br2
pyridinium hydrobromide
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
Page 2
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).
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
Page 3
Student Handout
Page 4
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
Page 5
MW
reagent
100%
MW
reagent
100%
Student Handout
Page 6
product
mass
nonbenign
material
100%
product
mass
nonbenign
material
100%
Student Handout
Page 7
Student Handout
Page 8
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
0.0056
0.44
Theoretical
mass of
product (g)
0.13
Page 1
Sample Calculations:
Atom Economy (Reaction III)
MW product
MW
reagent
MW stilbene
340.07
dibromide
100% =
100% =
100% = 90.4%
in
product
mass reagent
100%
utilized
acid
atoms
utilized
0.50 + 0.44
=
=
atoms
100% = 71.8%
100%
0.50
+
0.24
+
0.57
mass
waste
and
byproducts
peroxide
wasted
atoms
mass product
acid
wasted
atoms
mass product
= 9.83
product
mass
nonbenign
material
100%
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
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.
Page 3