Greener Bromination of Alkenes
Prepared by Joshua J. Pak, Idaho State University
Modified from “The Evolution of a Green Chemistry Laboratory
Experiment: Greener Brominations of Stilbene” Lallie C. McKenzie,
Lauren M. Huffman, and James E. Hutchison, Journal of Chemical
Education, 2005, 82(2), 306
PURPOSE OF THE Synthesis of vicinal dihalides by brominating alkenes. Introduction to
EXPERIMENT Green Chemistry concepts.
EXPERIMENTAL OPTIONS None
BACKGROUD REQUIRED You should consult your textbook for the Cahn-Ingold-Prelog System
for assigning the configuration of a chiral center. You should be
familiar with techniques for reflux, vacuum filtration, and melting
point measurement.
The Twelve Principles of Modified from Anastas, P. T.; Warner, J. C. Green Chemistry: Theory
Green Chemistry and Practice; Oxford University Press: New York, 1998.
1. Prevent Waste
2. Maximize Atom Economy
3. Design less Hazardous
Chemical Synthesis
4. Design Safer Chemicals and
Products
5. Use Safer Solvents/Reaction
Conditions
The ability of chemists to redesign chemical transformations to
minimize the generation of hazardous waste is an important first step
in pollution prevention. By preventing waste generation, we minimize
hazards associated with waste storage, transportation and treatment.
Atom Economy is a concept, developed by Barry Trost of Stanford
University that evaluates the efficiency of a chemical transformation.
Similar to a yield calculation, atom economy is a ratio of the total
mass of atoms in the desired product to the total mass of atoms in the
reactants. One way to minimize waste is to design chemical
transformations that maximize the incorporation of all materials used
in the process into the final product, resulting in few if any wasted
atoms. Choosing transformations that incorporate most of the starting
materials into the product is more efficient and minimizes waste.
Wherever practicable, synthetic methodologies should be designed to
use and generate substances that possess little or no toxicity to human
health and the environment. The goal is to use less hazardous reagents
whenever possible and design processes that do not produce
hazardous by-products. Often, a range of reagent choices exists for a
particular transformation. This principle focuses on choosing reagents
that pose the least risk and generate only benign by-products.
Chemical products should be designed to affect their desired function
while minimizing their toxicity. Toxicity and ecotoxicity are
properties of the product. New products can be designed that are
inherently safer, while highly effective for the target application. In
academic labs this principle should influence the design of synthetic
targets and new products.
The use of auxiliary substances (e.g., solvents, separation agents, etc.)
should be made unnecessary wherever possible and innocuous when
used. Solvent use leads to considerable waste. Reduction of solvent
volume or complete elimination of the solvent is often possible. In
cases where the solvent is needed, less hazardous replacements
should be employed. Purification steps also generate large sums of
solvent and other waste (chromatography supports, e.g.). Avoid
purifications when possible and minimize the use of auxiliary
substances when they are needed.
6. Increase Energy Efficiency
Energy requirements of chemical processes should be recognized for
their environmental and economic impacts and should be minimized.
If possible, synthetic and purification methods should be designed for
ambient temperature and pressure, so that energy costs associated
with extremes in temperature and pressure are minimized.
7. Use Renewable Feedstocks
Whenever possible, chemical transformations should be designed to
utilize raw materials and feedstocks that are renewable. Examples of
renewable feedstocks include agricultural products or the wastes of
other processes. Examples of depleting feedstocks include raw
materials that are mined or generated from fossil fuels (petroleum,
natural gas or coal).
8. Avoid Chemical Derivatives
Unnecessary derivatization (use of blocking groups, protection/
deprotection, temporary modification of physical/chemical processes)
should be minimized or avoided if possible, because such steps
require additional reagents and can generate waste. Synthetic
transformations that are more selective will eliminate or reduce the
need for protecting groups. In addition, alternative synthetic
sequences may eliminate the need to transform functional groups in
the presence of other sensitive functionality.
9. Use Catalysts
Catalytic reagents (as selective as possible) are superior to
stoichiometric reagents. Catalysts can serve several roles during a
transformation. They can enhance the selectivity of a reaction, reduce
the temperature of a transformation, enhance the extent of conversion
to products and reduce reagent-based waste (since they are not
consumed during the reaction). By reducing the temperature, one can
save energy and potentially avoid unwanted side reactions.
10. Design for Degradation
Chemical products should be designed so that at the end of their
function they break down into innocuous degradation products and do
not persist in the environment. Efforts related to this principle focus
on using molecular-level design to develop products that will degrade
into hazardless substances when they are released into the
environment.
11. Analyze in Real-Time to
It is always important to monitor the progress of a reaction to know
Prevent Pollution
when the reaction is complete or to detect the emergence of any
unwanted by-products. Whenever possible, analytical methodologies
should be developed and used to allow for real-time, in process
monitoring and control to minimize the formation of hazardous
substances.
12. Minimize the Potential for
One way to minimize the potential for chemical accidents is to choose
Accidents
reagents and solvents that minimize the potential for explosions, fires
and accidental release. Risks associated with these types of accidents
can sometimes be reduced by altering the form (solid, liquid or gas)
or composition of the reagents.
o r d e r
t o o b t a i n
BACKGROUND I n
c o m p l e x
m o l e c u l e s ,
i t
INFORMATON
i s
o f t e n
n e c e s s a r y
t o
i n t r o d u c e
m o r e
r e a c t i v e
f u n c t i o n a l groups
more reactive than
s i m p l e
h y d r o c a r b o n s .
A l k e n e s
( o l e f i n s ) Figure 1: The bromination of
h y d r o c a r b o n s
trans-stilbene
c o n t a i n i n g
t h e
c a r b o n c a r b o n
d o u b l e
b o n d
f u n c t i o n a l
g r o u p m a y
b e
h a l o g e n a t e d
t o
f o r m
a l k y l
h a l i d e s ,
w h i c h
a r e
t h e n
c a p a b l e
o f
u n d e r g o i n g
a
v a r i e t y
o f
f u r t h e r
c h e m i c a l
t r a n s f o r m a t i o n s .
I n
t h e
e x p e r i m e n t s
d e s c r i b e d
i n
P a r t s
A
a n d
B ,
y o u
w i l l
b r o m i n a t e
a n
a l k e n e ,
t r a n s - s t i l b e n e ,
a s
s h o w n
i n
F i g u r e
1 .
Br2
Br H
Br H
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.
B r o m i n a t i o n
o f
a n
l k e n e
i s
a n
e x a m p l e
o f
n
a d d i t i o n
r e a c t i o n :
r o m i n e
a d d s
a c r o s s
h e
d o u b l e
b o n d
t o
i e l d
a
v i c i n a l
i b r o m i d e .
A
c o m m o n l y
c c e p t e d
p a t h w a y
f o r
h i s
a d d i t i o n
i n v o l v e s
n
i o n i c
m e c h a n i s m
i n
h i c h
t h e
e l e c t r o n - r i c h
l k e n e
a c t s
a s
a
u c l e o p h i l e
a n d
t h e
r o m i n e
i s
t h e
l e c t r o p h i l e
.
A s
r o m i n e
a n d
t h e
a l k e n e
a p p r o a c h
o n e
a n o t h e r ,
t h e
B r-B r
b o n d
b e c o m e s
p o l a r i z e d
( b e c o m i n g
m o r e
p o s i t i v e
n e a r
t h e
a l k e n e
a n d
m o r e
n e g a t i v e
a t
t h e
o t h e r
e n d ) .
T h e
m o r e
p o s i t i v e l y
c h a r g e d
B r
a t o m
i s
t r a n s f e r r e d
t o
t h e
a l k e n e
t o
y i e l d
a
b r o m o n i u m
i o n
a n d
a
b r o m i d e
a n i o n .
I n
a
a
a
b
t
y
d
a
t
a
w
a
n
b
e
b
s e c o n d
s t e p ,
b r o m i d e
a t t a c k s
o n e
o f
t h e
c a r b o n
a t o m s
o f
t h e
c y c l i c
b r o m o n i u m
i o n
t o
o p e n
t h e
t h r e e m e m b e r e d
r i n g
a n d
y i e l d
t h e
v i c i n a l
d i b r o m i d e .
T h e
s e c o n d
s t e p
i s
a
b i m o l e c u l a r
n u c l e o p h i l i c
s u b s t i t u t i o n
r e a c t i o n
( S N 2 ) .
T h e
n e t
r e s u l t
o f
t h i s
r e a c t i o n
i s
a n t i
a d d i t i o n
o f
b r o m i n e across the double bond.
Br
Br
bromonium ion
Br
Br
Br
Br–
T r a d i t i o n a l l y ,
t h i s
r e a c t i o n
i s
p e r f o r m e d
i n
a
s o l v e n t ,
l i k e
m e t h y l e n e
c h l o r i d e
o r
c a r b o n
t e t r a c h l o r i d e
( b o t h
s u s p e c t e d
c a r c i n o g e n s ) ,
t h a t
w i l l
n o t
p a r t i c i p a t e
i n
t h e
r e a c t i o n
b u t
w i l l
d i s s o l v e
t h e
a l k e n e .
S o m e
b r o m i n a t i o n s
m a y
a l s o
b e
c a r r i e d
o u t
i n
g l a c i a l
a c e t i c
a c i d ,
a
v o l a t i l e
a n d
c o r r o s i v e
l i q u i d . T h e
t r a d i t i o n a l
r e a g e n t ,
e l e m e n t a l
b r o m i n e ,
i s
a l s o
d a n g e r o u s
t o
h a n d l e ,
b e c a u s e
i t
i s
h i g h l y
c o r r o s i v e
a n d
c a u s e s
s e v e r e
b u r n s
u p o n
c o n t a c t
w i t h
t h e
s k i n .
W h i l e
t h i s
r e a c t i o n
w o r k s
v e r y
w e l l
o n
m o s t
s u b s t r a t e s ,
i t
c a n
b e
d a n g e r o u s
t o perform
i n
a n
i n s t r u c t i o n a l
l a b o r a t o r y
s e t t i n g .
F o r
t h e s e
r e a s o n s ,
t w o
g r e e n e r
a l t e r n a t i v e s
t o
t h i s
r e a c t i o n
a r e
p r e s e n t e d .
An alternative to traditional bromination is presented below. The
Bromination of trans-stilbene
largest
modification is that instead of using liquid bromine, an
with pyridinium tribromide
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).
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). An additional
advantage of pyridinium tribromide is that it is an easily weighed
solid, in contrast to liquid bromine. Another benefit of this reaction is
that a more benign solvent, ethanol, can be used in the place of a
chlorinated solvent.
Figure 3: Equilibrium between
+
Br2
N H Br3–
N H Br2–
pyridinium tribromide and
The biggest drawback to this reaction is the lower atom economy
pyridinium hydrobromide and
bromine (many atoms from reagents are wasted) 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.
Bromination of trans-stilbene
The bromination with pyridinium tribromide is an example of a
with hydrogen peroxide and reaction that has been made safer, yet has considerable opportunities
hydrobromic acid for continued 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
reports have described a greener method of bromination that has a
high atom economy, uses 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 in an ethanol solvent. The only byproduct of this reaction is water.
Figure 4: Molecular bromine is
2 HBr + H2O2
Br2 + 2 H2O
produced in situ by the oxidation
of hydrobromic acid by
EtOH
hydrogen peroxide.
Equipment Magnetic stir bar
100 mL round-bottom flask
Water-jacketed condenser with tubing
Sand bath in crystallizing dish or hot water bath
Thermometer (-10 to 260 C)
25 mL graduated cylinder
Disposable syringe (1 - 3 mL)
250 mL or 400 mL beaker for ice bath
Hirsch funnel with adapter
50 mL filter flask
Filter circles (Whatman Grade 4 - 1.5cm dia.)
50 mL beaker or watch glass for end product crystals
Reagents and Properties
Item
trans-stilbene (transdiphenylethylene)
hydrobromic acid
hydrogen peroxide
sodium bicarbonate, saturated
aqueous solution
stilbene dibromide (1,2dibromo-1,2diphenylethane)
CAS #
103-30-0
Hazards
Quantity/Student
2.0 g
10035-10-6
7722-84-1
144-55-8
Corrosive, causes burns
Corrosive, causes burns
1.3 ml
0.8 ml
Up to 5 ml
5789-30-0
Irritant Small amount for
comparing melting points
PROCEDUE 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 inhaling these compounds.
Neutralize all excess acid in the provided containers, and clean up all
spills immediately. Acid will damage in your clothes and your skin,
so try not to spill any. Ethanol is flammable so use caution.
Assembling the Apparatus Connect the 100mL round-bottom flask to a water-jacketed condenser
(don’t forget to grease the joints). Connect the tubing such that water
comes in the bottom opening on the side of the condenser and leaves
through the opening above. Clamp the apparatus to a support stand,
and lower it into the sand or water bath.
a
1 0 0
m l
r o u n d Bromination of Alkene 1. P r e p a r e
b o t t o m
f l a s k
w i t h
a
s t i r
b a r ,
a n d
p r e p a r e
a
9 0 - 1 0 0 ° C
w a t e r
b a t h
in a 125-250 ml beaker.
2.
M e a s u r e
o u t
0 . 5
g
s t i l b e n e ,
a n d
a d d
i t
t o
t h e
f l a s k
w i t h
1 5
m L
o f
e t h a n o l .
Affix
a
r e f l u x
c o n d e n s e r
a n d
h e a t
t h e
r e a c t i o n
w i t h
s t i r r i n g .
A l l o w
t h e
s o l i d s
t o
d i s s o l v e .
A d d
a
l i t t l e
m o r e
e t h a n o l
i f
solid remains undissolved.
3. O n c e all solids are d i s s o l v e d ,
s l o w l y
a d d
0 . 8
m L
o f
H B r
( a b o u t
2 . 5
e q u i v a l e n t s ) ,
a n d
l e t
t h e
s o l u t i o n
h e a t
a n d
4.
5.
Collecting, Washing, and 6.
Drying the Crystal
7.
s t i r .
T h e
p r e c i p i t a t e
c a u s e d
b y
t h e
a d d i t i o n
o f
a c i d
s h o u l d
g o
b a c k
i n t o
s o l u t i o n ,
b u t
i t
m a y
n o t .
C o n t i n u e
e v e n
i f
i t
d o e s
n o t
a l l
g o
b a c k
i n .
M e a s u r e
o u t
0 . 8
m L
o f
3 0 %
h y d r o g e n
p e r o x i d e
(
a b o u t
2 . 5
e q u i v a l e n t s )
a n d
a d d
i t
d r o pw i s e
t o
t h e
r e a c t i o n .
T h e
c o l o r
s h o u l d
c h a n g e
f r o m
c l e a r
a n d
c o l o r l e s s t o
d a r k
g o l d e n
y e l l o w .
R e f l u x
t h e
r e a c t i o n
a n d
s t i r
f o r
a b o u t
2 0
m i n u t e s , o r
u n t i l
t h e
yellow c o l o r
d i s a p p e a r s
a n d
t h e
m i x t u r e
b e c o m e s
a
c l o u d y
w h i t e .
R e m o v e
t h e
r e a c t i o n
f r o m
t h e
h e a t
a n d
l e t
i t
c o o l .
O n c e
a t
r o o m
t e m p e r a t u r e ,
n e u t r a l i z e
t h e
s o l u t i o n
( p H
5
t o
7 )
w i t h
a
c o n c e n t r a t e d
N a H C O 3
s o l u t i o n .
I t
m a y
o n l y
t a k e
a
l i t t l e ,
d e p e n d i n g
o n
h o w
m u c h
e x c e s s
a c i d
y o u
h a v e .
C h e c k
p H
w i t h
p H
p a p e r .
O n c e
n e u t r a l i z e d ,
p u t
t h e
f l a s k
o n
i c e
t o
f u r t h e r
c o o l
i t
a n d
c a u s e
m o r e
c r y s t a l s
t o
p r e c i p i t a t e .
C o l l e c t
t h e
c r y s t a l s
b y
v a c u u m
f i l t r a t i o n ,
r i n s i n g
w i t h
v e r y
c o l d
w a t e r
a n d
a
l i t t l e
b i t
o f
v e r y
c o l d
e t h a n o l .
L e t
a i r
f l o w
o v e r
t h e
p r o d u c t
t o
h e l p
d r y
i t .
R e c o r d
y o u r
y i e l d
a n d
p r o d u c t
m e l t i n g
p o i n t
( l i t e r a t u r e
m . p .
8.
2
R
s
f
4
e
t
r
1 °C
d e c . ) .
c r y s t a l l i z e
t h e
i l b e n e
d i b r o m i d e
o m
xylene (or ethyl acetate).
I R
s p e c t r o s c o p y and melting
Identifying the Product 9. Obtain
point .
Cleaning Up
10. Place recovered materials in the appropriate labeled collection
containers as directed by your laboratory instructor. Clean your
glassware with soap.
Post-Laboratory Questions 1. Calculate the percent yield of your bromination reaction.
2. Compare the melting point of your product(s) to the data provided.
(+)-1,2-dibromo-1,2-diphenylethane
meso-1,2-dibromo-1,2-diphenylethane
110 °C
238 °C
3. Draw your product in its correct stereochemical configuration and
compare your result with your prediction from Pre-Laboratory
Assignment.
4. Draw the mechanism for the bromination of trans-2-butene. Be
sure to draw all intermediates clearly.
References:
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.
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, 1112711142.
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.
________________________________________
Name
___________
Section
___________
Date
Bromination of Alkenes
Pre-Laboratory Assignment
1. What safety issues should be considered when using HBr and H2O2?
2. Calculate theoretical yield for the bromination reaction.
3. Provide all applicable principles of Green Chemistry in this experiment.
5. (a) Look up and draw the structure of trans-cinnamic acid, cis-stilbene, and trans-stilbene. (b)
Predict the relative stereochemistry of each products and draw the predicted structures.