EXPERIMENT 3.

SYNTHESIS USING DIAZONIUM SALTS: SYNTHESIS OF

CHLOROBENZENE BY THE SANDMEYER REACTION

INTRODUCTION AND THEORETICAL BACKGROUND

Primary aromatic amines react with nitrous acid to give an N-nitroso derivative that rapidly
evolves to form a diazonium salt. Diazonium salts are one of the most useful synthetic
intermediates in aromatic chemistry.
Nitrous acid is usually generated "in situ" from sodium nitrite and dilute hydrochloric acid. In
the acid medium, it loses water and generates the nitrosonium ion, which is the electrophile
that triggers the reaction.

This nitrosonium ion is attacked by the amino group of the aromatic amine to give a series of
proton-catalyzed reactions leading to a hydroxyazobenzene, which evolves to give the
diazonium salt. This reaction is commonly known as “diazotisation”.

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Unlike aliphatic diazonium salts, which decompose rapidly, aromatic diazonium salts [RN2+
X] are relatively stable due to the resonance effect of the aromatic ring. In practice,
diazonium salts must be prepared at temperatures between 0 and 5ºC and used quickly.

Some special diazonium salts are slightly more stable and can be stored at room
temperature. This is the case of diazonium tetrafluoroborates [RN2+BF4-] and
hexafluoroantimoniates [RN2+ SbF6-].
The diazonium salts give rise to two types of synthetic transformations: substitution reactions
and diazocoupling reactions (or simply coupling reactions).

a) Substitution reactions
Aromatic diazonium salts decompose at temperatures above 5°C to give a very unstable and
reactive phenyl cation.

If decomposition takes place in the presence of a nucleophilic reagent, a substituted

benzene derivative is obtained.

This type of reaction is sometimes catalyzed by copper, which transforms the amino group
(through the diazonium salt) into a wide variety of functional groups: F, Cl, Br, I, OH, CN, SH,
SCN, NO2, H, etc.

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It is not surprising, then, that this is one of the most used reactions to obtain drugs,
pesticides and a wide variety of commercial products.
This reaction is of interest because it is versatile and is often the only synthetic pathway to
access isomers that cannot be obtained through aromatic electrophilic substitution. Of added
interest is the fact that precursor reagents, aromatic amines, can be easily obtained by
reducing nitro derivatives, which are easily prepared by the nitration of aromatic
hydrocarbons. Therefore, this chain of reactions is a commercial and economic way to
access a large number of derivatives.

b) Coupling reactions
In this type of reaction, the diazonium group acts as an electrophile to give an aromatic
electrophilic substitution reaction. Because the diazonium group is a very weak electrophile,
this reaction only occurs in highly activated substrates such as amines and phenols.

The resulting product is an azocompound. The azo functional group (-N=N-) is an important
chromophore. Azoderivatives are characterized by being strongly coloured compounds with

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considerable dyeing power, which is why this reaction is the synthetic pathway for one of the
most important commercial types of dyes and pigments, known as “azoic”.

In this practical we will prepare chlorobenzene by diazotisation of aniline and subsequent

reaction with a hydrochloric acid solution of copper (I) chloride, a reaction known as
Sandmeyer's reaction.

Sandmeyer reaction

The Sandmeyer reaction is one of the most important substitution reactions. In this reaction
the diazonium group is replaced by a Cl, a Br or a CN group with the help of the
corresponding Cu (I) salts. It has a rather complex mechanism. The diazonium group seems
to be displaced by means of a unimolecular decomposition to form an aryl cation through
nitrogen detachment. Next, this aryl cation reacts with the nucleophile in the medium (Cl-, Br-
or CN-) to give the desired product. Even so, this mechanism has not been fully established
and it seems that in some cases it can be of a radical nature.
The first step is to prepare the diazonium salt by reacting the aromatic amine with the nitrous
acid. As mentioned above, this reaction is commonly referred to as "diazotisation." Nitrous
acid is usually generated "in situ" by adding a sodium nitrite solution to an acidic solution of
the amine hydrochloride (amine previously dissolved in an excess of hydrochloric acid
solution).

The main problem of this synthesis is the poor stability of diazonium salts. In fact, all primary
amines are generally susceptible to reacting with nitrous acid to give diazonium salts.
However, aliphatic diazonium salts decompose very quickly to give complex product
mixtures. Aromatic diazonium salts are only stable enough if they are kept at temperatures
around 0-5°C (at higher temperatures they also decompose rapidly). Thus, it is essential that
diazotisation is made to occur at 0-5ºC by controlling the temperature with the help of an ice
bath and adding ice to the reaction mixture.
The other reagent needed for the Sandmeyer reaction is copper (I) chloride. This reagent,
which is the source of chloride, is also unstable in air and therefore must be prepared by
reduction of a copper (II) salt just before the Sandmeyer reaction. This is because copper (I)
salts are oxidized very easily in air.

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The reaction of the diazonium salt and the acidic solution of copper (I) chloride occurs very
rapidly when the temperature is allowed to rise to room temperature to facilitate the
decomposition of the diazonium salt. In any case, it is advisable to leave the mixture
overnight to ensure the complete reaction of the diazonium derivative. The product of the
Sandmeyer reaction is usually dark brown in colour, due to the fact that many competitive
reactions are produced. These impurities, even in small percentages, make it a laborious
purification process necessary.

There are three main types of competitive reactions:

1. Reaction of the diazonium salt with other nucleophilic species. In the medium there
is a high concentration of chloride ion, so the main reaction is the formation of
chlorobenzene. But there is also a large amount of water, which, despite being a weaker
nucleophile than chloride, effectively competes to give phenol as a by-product.

This by-product is easy to remove from the mixture because of its relative acidity. An
extraction with a solution of NaOH will dissolve the phenol to give the corresponding sodium
phenolate, which is soluble in aqueous medium.

2.- Polymerization reactions. The decomposition product of the diazonium salt may react
with himself it to give polymer by-products that are known as “resins” or “tars”. These resins
are responsible for the mixture’s dark colour and the presence of solid lumps. They can be
easily separated because chlorobenzene (along with some of the by-products) is insoluble in
water but has a relatively high vapour pressure, while resins, due to their polymer structure,
have an extremely low vapour pressure (they are not volatile). So they can be effectively
separated by carrying out a steam distillation. This technique is not a conventional distillation
but a distillation in the presence of a current of water vapour. This is an important purification
technique in chemistry and it is used to obtain a large number of essential oils from their
natural resources.

Steam distillation. This technique can be used to purify high boiling point compounds or
compounds that decompose at high temperatures, because it enables them to co-distill with
water at temperatures below 100°C. This technique is only applicable to water-immiscible
liquids.
In order to understand the basics of this technique, we have to consider the distillation
behaviour of a two-phase system consisting of two immiscible liquids. In a mixture of two
completely immiscible liquids x and y, each liquid exerts its own vapour pressure, regardless
of the other:
PT = Pox + Poy

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Therefore, the vapour pressure of the mixture (PT) will only depend on the temperature,
because it is completely independent of the relative quantities of x and y in the mixture.
Since the boiling point of a mixture is the temperature at which the total vapour pressure is
equal to the atmospheric pressure, unless Pox or Poy are zero, this temperature will always
be lower than the boiling points of x and y. The partial pressures of each component in the
vapour phase match their own steam pressures. This is the reason why the vapour molar
ratio composition (which is the same as the composition of the distillate) is:
Nx Px º wx Mx . Px º
---- = ------ and the weight ratio: ------ = --------------
Ny Py º wy My . Py º

where Mx and My are the molecular weights of each of the components.

That is to say, in the distillation of a mixture of two immiscible liquids, the relative weights of
the components that are collected in the collector are directly proportional to: 1) the vapour
pressure of the liquids at the temperature of distillation, and 2) to their molecular weights. In
addition, the vapour phase will distill at a constant temperature as long as both components
are present in the distillation mixture. Since one of the components is water, the distillation
temperature will always be under 100ºC. Compounds with relatively high molecular weights
distil together with water in a sufficiently large amount to be separated from a complex
mixture in a short time.

In practice, there are two ways to carry out a steam distillation. The first is to pass water
vapour (generated in external equipment) through a heated flask with the product mixture.
The second is more practical from the point of view of the equipment required. It consists of
mixing water and our product in the same flask and heating the mixture so that the water
vapour is generated "in situ". This technique can only be used when the vapour pressure of
the product is high enough for a relatively small amount of steam to be able to drag our
entire product.

Steam distillation is a technique that is widely used to extract essential oils from plants and
other natural sources without damaging them.

3 .- Reaction of aromatic electrophilic substitution. Some non-diazotized amines may

remain in the reaction medium besides the phenol that is formed during the decomposition.
These strongly activated rings can easily experience aromatic electrophilic substitution by

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reaction with the diazonium cation. The resulting diazocoupling products are the
corresponding azoderivatives, characterized by their yellow-orange colour.

These azo derivatives are also volatile and impurify the chlorobenzene obtained by steam
distillation, giving it its characteristic orange colour. They can be easily separated from
chlorobenzene by washing the crude product with concentrated sulphuric acid (EXTREME
CAUTION). Concentrated sulphuric acid can solubilise all products that contain functional
groups susceptible to protonation, that is, functional groups with a Lewis base character
(C=C, C≡C, C=O, C=N, N=N, -O-, NH2, NH, NR3, -S-, SH, etc.). These functional groups
react with protons to give charged species that are soluble in concentrated acid. Only the
alkyl and aryl halides (the halogen atom is a too weak base) and saturated hydrocarbons are
not protonated. Therefore, this type of washing is a good method for purifying only these two
compounds.

TIMING OF THE EXPERIMENT

3 sessions

REAGENTS TO BE USED

Aniline (7.0 g) HIGHLY TOXIC

Sodium nitrite (6 g) TOXIC
Copper (II) sulfate (25 g) TOXIC
Sodium chloride (12 g) ----
Sodium metabisulfite (6 g) IRRITATING
Sodium hydroxide (4 g) CORROSIVE
Hydrochloric acid (25 mL) CORROSIVE
Sulphuric acid (washings) HIGHLY CORROSIVE

LIST OF TECHNIQUES AND BASIC PROCEDURES

“In situ” preparation of an air-sensitive reagent

Low temperature reaction
Use of iodine-starch indicator paper
Steam distillation
Extraction in basic media

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 Extraction with concentrated sulphuric acid
Extraction with solvents
Drying an organic phase with anhydrous MgSO4
Concentrating on the rotary evaporator
Simple distillation at atmospheric pressure

EXPERIMENTAL PROCEDURE

a) Preparation of copper (I) chloride.

In a 250 mL two-necked round-bottomed flask (note 1), place 25.0 g (0.10 mol) of
CuSO4.5H2O and 100 mL of water and heat the resulting mixture to total dissolution. Next,
add 12 g (0.20 mol) of sodium chloride and stir to get a homogeneous green solution.
Separately, prepare a solution of sodium sulphite by mixing 6 g (0.03 mol) of sodium
metabisulphite and 4 g (0.10 mol) NaOH in 50 mL of water. Add this solution with continuous
stirring to the hot solution of copper (II) chloride, and wash the flask with water. Stir the
mixture well and place the flask in an ice-water bath in an inclined position to favour
subsequent decantation. Leave the mixture to rest so that the copper chloride (I) is cooled
and precipitates in the form of a very fine white powder. Meanwhile, continue with the
diazotisaton reaction.

b) Aniline diazotization

In a 250 mL Erlenmeyer flask (note 1), place 7.0 g (0.075 mol) of aniline and 25 mL of
water. Next, add 25 mL of conc. HCl. If necessary, heat the flask gently and stir to
completely dissolve the amine in the form of its hydrochloride. Finally, cool the flask
externally in an ice-water bath to about 5ºC.
While cooling, prepare a solution of 6 g (0.085 mol) of sodium nitrite in 20 mL of water. Add
ice to the NaNO2 solution to ensure that the temperature stays below 5ºC during
diazotization. It is advisable to check the temperature periodically with a thermometer (note
2)
Then, add the nitrite solution to the amine hydrochloride solution in small proportions, for
about 5-10 minutes, while agitating it in the ice-water bath. After the addition, a clear solution
of the diazonium salt is obtained. After 5 minutes, test a drop of the solution on the starch-
iodide paper (note 3). If it turns blue, there is an excess of nitrous acid. Otherwise, (no
colour), add a little more sodium nitrite solution until the reaction to the starch paper is
positive. Leave the final solution in the ice bath and, if necessary, add a little ice to make
sure the temperature does not exceed 5ºC.

c) Sandmeyer reaction: synthesis of chlorobenzene.

To use copper (I) chloride prepared before, the supernatant layer is decanted. The solid
washed by adding cool water, stirring, letting it separate and decanting it again. Repeat the
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process until the washing waters are almost colourless. Dissolve the solid by adding 30 mL
of concentrated HCl and 20 mL of water to the flask. This solution should be used as soon
as possible as it absorbs oxygen quickly. After it has cooled to about 5ºC in an ice-water
bath, add the solution of the diazonium salt to the copper solution, and wash the flask well.
Once at room temperature, stir the content occasionally for 10 min. Nitrogen is released and
an oil layer appears. Allow the flask to rest overnight for the reaction to be completed.
The next day, attach a distillation device to the flask (note 4) and prepare a steam
generating device by placing a 500 mL flask with water and porous stone in a heating
mantle. Attach a gas output to the neck of the flask. Steam is driven through a bended glass
tube to the bottom of the flask where the product is to be dragged. Heat the steam
generating flask and the steam passes through the reaction flask (which must also be
slightly heated with an air heating gun). During distillation, two immiscible phases, water and
chlorobenzene (in the form of orange oil), collect in the receiver. The steam distillation
finishes when only a single phase distils, that is to say pure water (note 5). VERY
IMPORTANT, in order to correctly carry out the steam distillation, a certain amount of water
must always be left in the flask. So, if the water volume decreases significantly (less than 1/3
of the flask) and distillation has not finished, stop the process, refill the flask with more water
and then resume the distillation.
Once the distillation has finished, separate the distillate from the aqueous phase using the
separatory funnel and collect the chlorobenzene layer. Wash the organic phase twice with a
10% NaOH solution to remove any phenol that may be present. The product thus obtained is
still coloured due to the presence of small amounts of azo-compounds. To eliminate them,
transfer the raw chlorobenzene to an Erlenmeyer flask and wash with concentrated sulphuric
acid (EXTREME CAUTION) by adding an equal volume of concentrated sulphuric acid and
gently stirring. Carefully pour the mixture into the separatory funnel and collect the
chlorobenzene layer. Now, dissolve the product in 25 mL of diethyl ether, and wash the
ethereal solution first with 15 mL of water, then with 10 mL of dilute NaOH solution and
finally with 15 mL of water.
Dry the ethereal solution over anhydrous magnesium sulphate, filter directly into a 100 mL
flask and remove the diethyl ether using the rotary evaporator (note 6). Transfer the product
to a 25 mL pear-shaped flask, add some porous stone fragments and make a simple
distillation to collect the fraction that distils between 128 and 132ºC. Weigh the
chlorobenzene and calculate the yield.

NOTES

Note 1. We must always plan experiments so that we choose the most suitable flasks and
avoid transfers that result in the loss of product. In this case, the copper chloride (I) is
prepared in the same flask in which the Sandmeyer reaction and steam distillation are
carried out. For this last operation a two-necked flask is required.

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Note 2. When the system is well stirred and there is enough ice, the mixture temperature will
be close to 0ºC. We can use a thermometer to check the temperature, and once the
measurement has been made, it must be removed. A thermometer is never used to stir.
Note 3. The so-called starch paper is actually potassium iodide-starch paper. Strips of this
indicator paper are used to detect oxidant reagents such as nitrous acid or chlorine in
solutions. The paper is impregnated with potassium iodide and starch. The potential of the
iodide anion to oxidize to molecular iodine is fairly low so even soft oxidants are capable of
forming iodine on the paper. Although iodine gives a yellow colour, starch amylopectin is
added to increase the sensitivity of the test and form a strongly colourful complex (dark
violet) with iodine.
Note 4. To carry out the steam distillation, the assembly shown below must be set up and
connected to a steam generator with a glass rod (ask the teacher).
The steam generator consists of a 500 mL flask that is attached to a piece with a 90° lateral
gas outlet and a screwdriver adapter on top. A glass tube of 80 cm is set in such a way that
it stops 1 cm short of the bottom of the flask. This tube allows air to enter, in the case of
cooling, and water to come out in the case of overpressure. The side outlet is connected
with a silicone rubber tube to a glass tube that drives the steam to the bottom of the
flask.Once the steam outlet has been connected to our equipment, half fill the flask with
water. Add the porous stone and switch on the heating mantle until it boils vigorously.

Heating mantles are electrical resistances protected by a mesh of ceramic fabric that adopt
a hemispherical shape the size of the flask. They can only be used for flasks of appropriate
sizes. Heat mantles are very powerful and are used to heat large amounts of liquid quickly or
to generate a large amount of steam.
Some heating mantles have a progressive control (the more you turn the dial, the hotter it
gets), but most consist of two resistors and have just two or three settings: setting I, the

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bottom resistor is heated; setting II, the upper resistor is heated; and setting III, both
resistors are heated at the same time.
Note 5. To analyze the composition of the distillate, collect a drop in a small watch glass and
observe how many phases there are.
Note 6. One of the most common operations in an organic chemistry laboratory is the
elimination of a volatile solvent from a reaction or extraction mixture. This can be done by
simple distillation but there is a more efficient and faster system: distillation in the so-called
rotary evaporator. It basically consists of an electric motor that rotates a tube ending in an
NS joint to which the flask with the solution is coupled. The flask is rotated at a
predetermined speed while the whole system is lowered so that it is submerged in a hot
water bath (at a temperature that can also be selected). Coupled to the system there is a
condenser that condenses the vapours which are collected in a collecting flask. The whole
set forms a closed system that is connected to a vacuum system (a vacuum pipe or a
vacuum pump). To start or break the vacuum there is also a glass stopcock.
The rotary evaporator system is effective for two main reasons. On the one hand, the
distillation takes place under vacuum, which lowers the boiling point of the solvent. On the
other hand, the rotation of the flask forms a fine liquid film through the internal walls, so the
surface of evaporation increases considerably. These two effects together make the
solvents evaporate very quickly.

One important advantage of a rotary evaporator is that it makes it possible to evaporate

relatively high boiling point solvents at a constant and low temperature so that unstable
products do not decompose.
The temperature of the bath should always be chosen depending on the solvent to be
evaporated. Normally 30-40ºC is sufficient for solvents such as diethylther, hexane, acetone,
dichloromethane or chloroform. For solvents such as toluene, ethanol or others, 50-60°C is
more appropriate. Note that under vacuum solvents usually foam when they boil so you
should always put the liquid to be evaporated in a large flask that under no circumstances is
more than half full.
You should never place a hot solvent directly on the steam rotary, since under vacuum there
can be a sudden evaporation that makes you lose product.
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Never use an Erlenmeyer flask or one that is not spherical since the vacuum can break it by
implosion.
The procedure for placing a flask on the rotary evaporator is as follows:
1. Connect the vacuum system and set the heating bath at the appropriate temperature.
2. Put the flask in the end joint and hold it. Next, gently close the stopcock to seal the system
under vacuum.
3. The rotation starts, first very tightly and then at the required speed.
4. At first, the solvent foams a lot due to the dissolved air, which is why it has to be
monitored. If necessary, open the stopcock for a moment. Rotation is maintained until no
further evaporation of the solvent is observed.
5. Stop rotation and open the stopcock slowly so that air can flow in.
6. Let air fill the system while holding the flask.
7. Remove the flask, turn the vacuum off and switch the bath off.
8. If the solvent collecting flask is full, empty it and recover the solvent.

QUESTIONS AND TASKS

1. Why should the diazotisation reaction be carried out at low temperature?

2. How do you explain that nitrogen is released?
3. What is the limiting reagent of the reaction?
4. If we were preparing p-chlorotoluene from p-toluidine (p-methylaniline) using the same
reaction, what would be the main organic by-products. Draw them.
5. What is the chlorobenzene treatment with sulphuric acid for?
6. Why is the first distillation a steam distillation?
7. How do you explain that the water (b.p. 100ºC) and chlorobenzene (p.eb. 132ºC) mixture
co-distils below 100°C.
8. Indicate which layer (upper or lower) is chlorobenzene in each of the different washes.
9. Which of the following products could be purified by steam distillation: 1-
methylnaphthalene, benzoyl chloride, 1,4-butanediol, tetralin (tetrahydronaftalene).

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