Formal Report 3

Experiment No. 5

Synthesis of 1-Bromo-4-chlorobenzene by Sandmeyer Reaction

Francis M. dela Rosaa, Charmaine Sagayapa ,and Aaron John M. Supana*
a
Department of Chemistry, College of Science, De La Salle University, Taft Avenue, Malate, Manila 1004, Philippines

ARTICLE INFO ABSTRACT

Article history: The Sandmeyer reaction was used to prepare 1-bromo-4-chlorobenzene.

Date Performed February 21, 2015 The synthesis was carried out first by reacting 1-bromo-aniline with nitrous
Date Submitted March 11, 2015
acid prepared in situ by adding NaNO2 to the acidified starting material. The
diazonium salt produced was then allowed to react with acidified CuCl
prepared by reacting copper (II) sulfate with NaHSO3 in the presence of NaCl
and a base. The pure 1-bromo-4chlorobenze was isolated from the crude
product by steam distillation. The white crystals obtained were then
Keywords: characterized using Thin-Layer Chromatography and Infrared Spectroscopy.
1-Bromo-4-chlorobenzene TLC analysis shows that the product was TLC-pure. IR absorption peaks at
Steam Distillation 666.58 and 810.75 cm-1 show the characteristic C-Br and C-Cl stretch,
Infrared spectroscopy respectively which confirms the synthesis was successful. The absence of
Thin-Layer Chromatography broad absorption peaks beyond 3200 cm-1 indicates the absence of a 4-
bromophenol impurity.

1. Introduction
The primary aromatic amine reacts with the
The amine group of a primary nitroso ions (from HNO2) yielding
aromatic amine can be replaced by different arenediazonium salts. The diazotization
substituents by means of the Sandmeyer process proceeds even in the presence of a
reaction. The reaction is summarized by a variety of susbtituents on the aromatic ring.
sequence of (1) nitration, (2) reduction, (3) These substituents can be introduced by
diazotization, and (4) nucleophilic substitution replacing the diazonium ion (N2) in a
(McMurry, 2004). This reaction enables the nucleophilic substitution step (McMurry,
conversion of an aryl amine into an aryl 2004). Examples of Sandmeyer reactions are
halide, C6H5X (where X= F, Cl, Br, or I), shown in Figure 1.
phenol, or a benzonitrile.

Figure 1: Examples of
Sandmeyer reactions of
primary aromatic amines
 In the experiment, Sandmeyer reaction temperature and the reaction was completed
was used to synthesize 1-bromo-4- using a steam bath. The mixture was cooled in
chlorobenzene from 4-bromoaniline. The ice afterwards and the crude product was
crude product will be purified by sublimation isolated by vacuum filtration on a Hirsch
and the collected crystals will be characterized funnel. The crude product was pressed in
by thin-layer chromatography and infrared between filter papers and allowed to dry. The
analysis. 1-bromo-4-chlorobenzene product was
purified by sublimation.
The 1-bromo-4-chlorobenzene product
2. Methodology was characterized by Thin-Layer
Chromatography and Infrared Spectroscopy.
2.1. Preparation of CuCl solution Thin-layer chromatography was performed by
dissolving the product in dichloromethane
A mass if 0.2969 g of CuSO4• 5 H2O
(DCM) and comparing it alongside the
was dissolved in 1.00 mL of water. To this
starting material. Two solvent systems were
solution, 148.8 mg of NaCl was added. This
used for the chamber: (1) 8:1 hexane: DCM
solution was mixed with the sodium sulfite
and (2) 1:1 hexane: DCM. Infrared
solution to give a mixture with white
spectroscopy was performed for the product
precipitates. This mixture was placed in an ice
dissolved in chloroform.
bath until the diazotization step was finished.
The supernatant was removed and the CuCl
precipitate was washed with water. After 3. Results, Discussion and Conclusion
washing, the precipitate was dissolved in 0.45
mL of concentrated HCl and this solution was The experiment was performed to
immediately used for the Sandmeyer reaction. synthesize 1-bromo-4-chlorobenzene by
reaction of 4-bromo-benzenediazonium
2.2. Diazotization of 4-Bromoaniline chloride with CuCl. The product was then
characterized using thin-layer chromatography
and infrared spectroscopy.
A mass of 0.1763 g of bromoaniline
was treated with 0.50 mL of 3M HCl. The
dissolution was finished upon heating on a 3.1. Preparation of CuCl solution
sand bath. It was allowed to cool to room
temperature before placing in an ice bath. Blue crystals of copper(II) sulfate
While in the ice bath, beige colored crystals pentahydrate were dissolved in water to form
started to form. To this mixture, a freshly- a blue-colored solution. This solution turns to
prepared 0.20 mL ice-cold solution containing bluish green when NaCl was added. When the
70 mg NaNO2 was added to produce a yellow sodium sulfite solution (which contains
solution. NaHSO3 and NaOH) was added, white
precipitates of CuCl were formed. The
2.3 Sandmeyer Reaction and Characterization reaction for the formation of CuCl is given
of 1-Bromo-4-chlorobenzene below:

To the mixture from Part 3.2, the ice- 2 CuSO4•5 H2O + 4 NaCl + NaHSO3 + NaOH
cold CuCl solution was added dropwise. The ↓
mixture is then allowed to warm to room 2 CuCl + Na2SO4 + 2 HCl + 10 H2O
 The supernatant on top of the The total amount of HCl placed in the
precipitate was not removed until the reaction mixture is more than the required
diazotization process for 4-bromoaniline was amount in order to ensure that the formation
finshed. This was done to protect the CuCl of diazo compounds and the rearrangement of
from being oxidized by air (Williamson & the benzenediazonium ion are both prevented
Masters, 2011). (Williamson & Masters, 2011).
Once the diazonium salt had been
3.2. Sandmeyer Reaction and produced, the CuCl dissolved in HCl was
added to the mixture. The nucleophilic
Characterization of 1-Bromo-4-chlorobenzene substitution which introduces chloride into the
carbon where the diazonio group is attached
The reaction mechanism for the then occurred. Effervescence was observed as
Sandmeyer reaction is shown in Figure 2. The nitrogen gas was produced. The brown CuCl
reaction of an aryl amine begins with the solution imparted a brown color to the thick
diazotization of the primary amine by nitrous foam formed on top of the blue green liquid
acid, HNO2. Due to its instability, the nitrous underneath. The reaction was completed by
acid is formed in situ by reacting sodium heating with a steam bath and the foam
nitrite and hydrochloric acid. Under acidic subsided. The complete scheme of the
conditions, the acid dissociates to form nitroso Sandmeyer reaction is given in Figure 3.If
ions, NO+. Then, the primary aromatic amine excess H3O+ ions are still present in the
attacks the nitroso ion to form an intermediate. mixture and the mixture is not kept cold at 0o
The intermediate undergoes deprotonation and C, 4-bromophenol will be produced as a by-
rearrangement. The hydroxyl group is then product. The mixture was cooled and the
protonated to create a better leaving group for crude product was collected over a Hirsch
the rearrangement that follows. A salt of funnel by suction filtration. The crude product
diazonium chloride is then obtained. was dried between filter papers and the drying
was hastened by using the air dryer. Some of
In the experiment, 4-bromoaniline was the crude product seemed to have melted onto
acidified with excess amount of HCl to yield the filter paper. Thus, the crude product was
the beige crystals of the amine hydrochloride not quantitatively transferred into another
salt. When NaNO2 solution was added into the flask for sublimation. Sublimation was
mixture that contains excess HCl, HONO is performed to isolate the 1-bromo-4-
generated in situ and the diazotization was chlorobenzene product from the other by-
initiated which produced a yellow mixture. products which could be 4-bromophenol or

Figure 2. Reaction Mechanism for the Sandmeyer Reaction (Reprinted from Williamson and
Masters, 2011)
the diazo compound. The separation is based bromoaniline, being capable of interacting
on differences on the temperature at which the more with the polar stationary phase migrates
solid phase is directly converted to gaseous at a slower rate compared to 1-bromo-4-
phase. Since the sublimation points of the chlorobenzene. It was also observed that a
product and the byproducts are unknown, the single spot is observed for Lane 3 which
intermolecular forces of attraction for 1- means that no impurity is present. A summary
bromo-4-chlorobenzene and 4-bromophenol of the retention factors for the starting material
were used instead as a basis. Since 4- and the product is given in Table 2.
bromophenol is capable of hydrogen bonding,
it may be inferred that it has a higher
sublimation point over the product. The target
product, 1-bromo-4-chlorobenzene sublimes
first and as its gaseous form reaches the
centrifuge filled with ice, it was deposited in
the form of white crystals. These crystals were
weighed to obtain the % yield. Table 1
summarizes the numerical data obtained for
the collected product and the % yield.

Table 1. Summary of Numerical Data

Mass of 4-bromoaniline (g) 0.1763 Figure 3. Representation of TLC plate using (a)
8:1 of hexane: DCM and (b) 1:1 of hexane:
Actual Mass of Product (g) 0.0372 DCM
Theoretical Mass of Product (g) 0.1962
% Yield 18.96 Table 2. TLC Measurements and Rf values
Mobile Phase: 50% hexane:50% DCM
The product was tested whether it still Solvent Front: 36 mm
contained other impurities by thin-layer
Distance Retention
chromatography. The samples used were 4- Travelled factor
bromoaniline and 1-bromo-4-chlorobenzene.
Lane 1:
These were dissolved in dichloromethane 8 0.235
(DCM) and loaded onto silica plates as 4-bromoaniline
follows: (1) 4-bromoaniline (2) bromoaniline: Lane 2 8 0.235
1-bromo-4chlorobenzene, and (3) 1-bromo-4- Co-spot 27 0.794
chlorobenzene. The first mobile phase used
Lane 3
was an 8:1 mixture of hexane: DCM. This
mobile phase generated the plate shown in 4-bromoaniline/ 1- 27 0.794
Figure 3a. As seen on the figure, no spots bromo-4-
chlorobenzene
were seen for Lane 2 and Lane 3. The sample
could have been very dilute or it has been
carried over at a higher distance since the Infrared spectroscopy was done by
mobile phase is highly nonpolar. The polarity applying a thin film of the product on NaCl
of the mobile phase was adjusted and changed plate after it was dissolved chloroform. The IR
to a 1:1 mixture of hexane: DCM. The plate spectrum is shown in Figure 4. The
using this solvent system generated the plate characteristic peaks for the carbon-carbon
representation on Figure 3b. The stretching in the aromatic ring are shown at
 Figure 4. Infrared spectrum of 1-bromo-4-chlorobenzene

1472.22 and 1886.69 cm-1. The peak at 665.58 product underwent sublimation. Thin-layer
cm-1 associated with C-Br stretching confirms chromatography result shows that the crystals
that the bromide substituent in the ring is that were obtained are free of impurities.
unaffected by the reaction. The success of the Infrared analysis confirms that the 1-bromo-4-
synthesis of 1-bromo-4-chlorobenzene was chlorobenzene was successfully prepared
confirmed by the presence of a sharp strong based on the characteristic C-Cl stretch peak
peak at 810.75 cm-1 which arises from the observed at 810.75 cm-1.
C-Cl stretching (Solomons & Frhyle, 2011).
Another thing to consider is the absence of a
broad absorption band at 3400-3650 cm-1 References
which should appear if the collected product
after sublimation is contaminated with 4- McMurry, J. (2004). Organic Chemistry. 6th
edition, USA: Thomson Learning Inc.
bromophenol.
Solomons, G., & Fryhle, C. B. (2011). Organic
4. Conclusion chemistry (10th ed.) Asia: John Wiley & Sons,
Inc.
White crystals of 1-bromo-4-chlorobenzene
were successfully prepared by the Sandmeyer Williamson, K. and Masters, K.M. (2011).
reaction using bromoaniline as the starting Macroscale and microscale organic experiments,
material, HNO2 as source of nitroso ions, and 6th edition, USA: Houghton Mifflin Company
CuCl as the source of the nucleophile. A %
yield of 18.96 was obtained after the crude