Theory of Aromatic Substitution
According to the theory , a substituent influences the electron
density in following two important ways
1. Inductive effect (-I,+I)
2. Mesomeric effect (-M, +M)
Inductive effect
-I
+I
• Effect produces when substituent
•
attracts the electrons causing all the
position in the ring to be less
reactive than unsbstituted benzene.
• The effect being greater on ortho
•
and para leaving meta more
reactive.
•
• Making them meta directing group.
• Groups which produce –I effect in •
order of decreasing strength are: • -COOH,-HSO3, -NO2, - Halogen, •
CF3 , CCl3
•
Effect produces when substituent
repel the electrons causing all the
position in the ring to be more
reactive than unsbstituted benzene.
The effect make ortho and para
positions more reactive than meta.
Making them ortho / para directing
group.
Groups which produce +I effect in
order of decreasing strength are:
-O, -OH, NH2, alkyl (CH3, C2H5)
Benzyl (C6H5).
Effect of side chain reduces the effect of substituent
Mesomeric effect
• It is defined as the polarity produced in the molecule by the
interaction of two pi bonds or between a pi bond and lone pair of
electrons present on an adjacent atom.
• The mesomeric effect is negative (–M) when the substituent is an
electron-withdrawing group and the effect is positive (+M) when
the substituent is an electron donating group.
• +M EFFECT ORDER :
• –O− > –NH2 > –OR > –NHCOR > –OCOR > –Ph > –CH3 > –F >
–Cl > –Br > –I
• -M EFFECT ORDER :
• –NO2 > –CN > –SO3H > –CHO > –COR > –COOCOR > –COOR
> –COOH > –CONH2 > –COO−
Mesomeric Effect
-M
• Effect produces when substituent •
is an electron withdrawing group.
• Substituent which shows a –M •
effect deactivate all the positions.
• Meta position being less
•
deactivated then ortho and para
making them meta directing
compounds.
•
• E.g. -NO2, Carbonyl group
(C=O), -C≡N, -COOH, -SO3H
etc.
+M
Effect produces when substituent is
from an electron donating group.
Substituent which shows a +M
effect activate all the positions.
Effect being more pronounced on
ortho and para positions making it
ortho / para directing compounds.
E.g. -OH, -OR, -SH, -SR, NH2, -NR2 etc.
Mesomeric effects are stronger than inductive effects
INDUCTIVE EFFECT Vs MESOMERIC EFFECT
• In most of the cases, mesomeric effect is stronger and
outweighs inductive effect.
• For example, the -OH and -NH2 groups withdraw
electrons by inductive effect (-I). However they also
release electrons by delocalization of lone pairs (+M
effect). Since the mesomeric effect is more stronger than
inductive effect the net result is electron releasing to rest
of the molecule. This is clearly observed in phenol and
aniline, which are more reacting than benzene towards
electrophilic substitution reactions.
• Whereas the inductive effect is stronger than the
resonance effect in case of halogen atoms. These are
electronegative and hence exhibit -I effect. However at the
same time they also release electrons by delocalization
(+R effect) of lone pair.
Inductive Effects
Controlled by electronegativity and the polarity of
bonds in functional groups
Halogens, C=O, CN, and NO2 withdraw electrons
through  bond connected to ring
Alkyl groups donate electrons
Sample Problem
Classify each substituent as electron donating or electron
withdrawing?
Solution
Draw out the atoms and bonds of the substituent to clearly see lone pairs and multiple
bonds.
Always look at the atom bonded directly to the benzene ring to determine electrondonating or electron-withdrawing effects.
An O or N atom with a lone pair of electrons makes a substituent electron donating.
A halogen or an atom with a partial positive charge makes a substituent electron
withdrawing.
Nitration
Introduction
• Introduction of one or more nitro groups (-NO2) into a reacting
molecule.
Nitro aromatic or Nitro paraffinic compound:
When nitro group attached to carbon. “C-Nitration”
Nitrate ester:
When nitro group attached to oxygen. “O-Nitration”
Nitramine:
When nitro group attached to nitrogen. “N-Nitration”
We shall consider only those nitrations in which nitro group
replaces hydrogen atom & directly attached to carbon, since
these reactions are technically important
Applications of Nitration products
• Aromatic Nitro compounds have paramount importance in organic
chemistry due to their easy availability and conversation into
various functional groups. They are widely used in the synthesis of
• dyes & intermediates,
• pharmaceuticals,
• agrochemicals, and
• pigments
• as well as a variety of fine chemicals such as solvents, perfumes,
explosives and polymers.
i) Naphthol-S yellow, (ii) Flavianic acid (iii) Chloramphenicol, (iv) Azomycin,
(v) musk xylene, (vi) musk ketone, (vii) trinitro toluene, (viii) nitro glycerin,
(ix) nitro benzene, (x) nitro ethane, (xi) nitro cellulose
used as dyes and intermediates (i,ii), drugs(iii,iv),
perfumes (v, vi), explosives (vii, viii, xi), solvents( ix, x) respectively.
•
•
•
•
Nitrating Agents
Fuming NITRIC ACID
Concentrated NITRIC ACID
aqueous NITRIC ACID
Mixtures of NITRIC ACID with
– sulfuric acid,
– acetic acid,
– acetic anhydride,
– phosphoric acid, and
– chloroform.
• Nitrogen pentoxide , N2O5
• Nitrogen tetroxide, N2O4
In order to make an intelligent choice of nitrating system for particular nitration,
it is desirable to know what species are present in the various systems and to
understand the mechanism of the reaction under consideration.
NITRATING AGENTS
Aromatic compounds can be nitrated with hot
concentrated nitric acid
• However, this reaction proceeds slowly, which
is inconvenient (dangerous) since hot, conc.
nitric acid is a powerful oxidizer, and organic
compounds are easily oxidizable.
• To be an effective & efficient nitrating agent,
the nitric acid must be completely ionized,
which does not occur if nitric acid is used alone
in any concentration
Nitronium Ions
• Functions of H2SO4
• It removes the water produced during nitration.
• Being a stronger acid than nitric acid, it protonates nitric acid to form a
nitronium ion which is strong nitrating agent.
• Sulfuric acid reacts with nitric acid to generate a nitronium ion (NO2+), which is a
very powerful electrophile
• The reaction mechanism is similar to an acid catalyzed dehydration.
• Sulfuric acid is a stronger acid than nitric acid, so sulfuric acid protonates nitric acid.
• After protonation, water is eliminated (good leaving group), and the nitronium ion is
generated.
Nitrogen pentaoxide and nitrogen tetraoxide in sulfuric
acid are indicating that they ionize to form nitronium ion
as under
C2H5ONO2 + 3H2SO4
N2O5 + 3H2SO4
N2O4 + 3H2SO4
NO2++ H3O+ +C2H4SO3H + 2HSO42NO2++ H3O+ + 3HSO4NO+ + NO2++ H3O+ + 3HSO4-
each of these solution is powerful nitrating agent
The nitronium ion reacts with benzene to form the sigma complex,
which then loses a proton to generate the aromatic product.
MIXED ACID
Nitro group in aromatic hydrocarbon molecules can be administered more
easily with a mixture of nitric and sulfuric acids (nitrating mixture) in the
liquid phase.
the sulfuric acid act as
 a catalyst,
 A dehydrating agent (usually water is present in the mixture and some is
formed during the reaction.)
 a means of contributing to a fuller use of nitric acid
 and inhibiting oxidation processes.
• Industrially, sulfuric acid is most frequently used as it is highly effective
and less expensive. The other mixtures which can be used are Nitric Acid
plus e.g. Perchloric acid, hydrofluoric acid, boron trifluoride etc.
• The reactions of formation of nitronium ions are very
rapid and equilibrium concentrations of nitronium ions are
present at all times in acid phase during nitration.
• These equilibrium concentrations vary depending on
many variables of which following are most important,
a. the composition of acid mixture
b. the temperature
COMPOSITION OF ACID MIXTURE
Usually water is present in the mixture and some is formed during
the reaction. At high water concentrations nitronium ions are very
few and cannot be detected by spectra. At this level aromatic
compounds which nitrate moderately such as, Toluene can be easily
nitrated.
The nitronium ions concentration generally increases with decrease
in water concentration. The highest concentrations occur at equal
molar amounts of nitric acid and sulfuric acid. At high
concentration of sulfuric acid all of the nitric acid is converted to
nitronium ions.
In solutions weaker than 86 % sulfuric acid, the ionization of nitric acid is
very slight but rapidly rises as the sulfuric acid becomes more concentrated.
In about 94 % sulfuric acid, the nitric acid is completely ionized to give
nitronium ions
TEMPERATURE
Nitronium ions concentration decreases as we increase the
temperature. At 40 C it is about
10-20 % less then that at 20
C.
This means that while making mixed acid, the temperature of
the vessel must be low enough to get maximum concentration
of nitronium ions.
Aromatic Nitration
• The nitration of aromatic compounds can be represented by the equation
ArH + HNO3
ArNO2 + H2O
• Nitronium ion NO2+ is an electrophilic reactant.
• Carbon atom of aromatic ring contains strong electron density.
• Nitro group can attached to ortho, meta or para positions depending upon the
electron density.
• The amount of these isomeric product will depend upon the substituent.
• Certain substituent cause the electron density to be greater at ortho and para
position than meta position, hence they yield nitration products in which
ortho and para isomers predominate.
• Other substituent cause the electron density to be greater at meta position
rather than ortho and para, hence they are called meta directing.
The isomer distribution arising from the nitration of various monosubstituted benzenes is shown
as
THERMODYNAMICS OF NITRATION
• Nitration reaction is highly exothermic.
• A study of the thermal properties of nitrating acids is essential for an adequate
understanding of this unit process
• The nitration reaction must be controlled by systematic cooling designed to withdraw
the energy evolved
• When all the energy set free by an exothermic reaction is forced to appear as heat,
the quantity of it lost to the cooling mechanism equal the decrease in enthalpy
Q = -∆H
KINETICS OF AROMATIC NITRATION
•
Kinetics of commercial nitration varies greatly. The reaction
times may be from several seconds to many hours.
• Rate =K(HNO3) (ArH)
1
1
• Overall rate = 2
• Generally accepted mechanism which is compatible with the
data is
HNO3 + 2H2SO4
ArH + NO2 +
•
ArHNO2+ + HSO4¯
NO2+ + H3O+ + 2HSO4¯ (Fast) Step - 1
ArHNO2+ ( Slow: Rate determining step) Step – 2
ArNO2 + H2SO4
+ H2O
Step - 3
• The principal phenomenon about rate of reaction is how
easily and how much mass is transferred from one phase
to another.
• The principal factors that affect the rate of reaction are
1. Degree of agitation
2. Temperature,
3. Acid composition and
Engineering factors for nitration
AGITATION:
In aromatic nitration, there are two phases, ORGANIC PHASE and
ACID PHASE. Most nitro hydrocarbon collect in organic phase and
water in the acid phase. The site of nitration usually is at or close to
the interface between the two phases but the most important factor
is the mass transfer (diffusion) of reactants and products.
• Increase in agitation promotes the transfer of reactants from one
phase to another and hence increase rates of reaction.
• Impeller speed also decrease the droplet size in the dispersed
phase, and with small droplets and high speed of agitation mass
transfer of reactants to and from dispersed phase decreases.
1.
2.
3.
4.
5.
TEMPERATURE
The energy of activation for various nitrations is 59-75 kJ/mol. But the
kinetic rate constant for various chemical steps increases with
temperature. This is probably due to the fact that
Solubility of both nitrated and unnitrated aromatic in acid phase increase
with temperature and the main reactions occur in the zone of acid phase
that is adjacent to the interface between phases.
Viscosity decreases with increase in temperature, which helps in mixing of
two phases
The concentration of nitronium ions in the acid also changes with
temperature.
Diffusivity coefficient increases with increase in temperature
Temperature also affects the interfacial surface tension of the two phases
which increases the area of contact between phases. The increase in area
of contact decreases the resistance to mass transfer.
ACID COMPOSITION
• When the nitration medium is nitric acid with strong
sulfuric acid. Rate of nitration of nitrobenzene,
anthraquinone and ethyl benzoate can be measured
easily. The rate of all these nitrations is proportional
to concentration of added nitric acid and aromatic
compound
Rate = k [HNO3 ] [ArH]
• The formation of nitronium ion is directly related to
the ionization of nitric acid.
• The reaction rate sharply rises with increasing sulfuric acid
concentration (decreasing water content) and reaches
maximum at about 90 % sulfuric acid and then falls off at
higher concentrations. The rise in rate with increasing
strength when acid is less than 90 % in due to increase in
nitronium ions concentration.
• As the concentration of sulfuric acid decreases ( % of water
increases), the percentage of ionization of nitric acid
decrease. At about 86% H2SO4 only 10% of nitric acid ionizes.
• At sulfuric acid concentrations above 90 %, hydrogen bond is
formed between the aromatic compound and sulfuric acid
which decreases the electron density in the ring and hence
the rate of reaction.
Process Equipments For Technical Nitration
 Batch Nitration
 Continuous Nitration
Batch Nitration
• Nitration is usually done in closed cast iron or steel vessels.
Modern practice is to use mild carbon steel.
• Nitrator consists of a cylindrical vessel containing some kind
of cooling surface, a means of agitation, feed inlets and
product outlet lines.
• They are also equipped with a large diameter quick dumping
line for emergency use if the reaction gets out of control.
• The contents of the nitrator are dumped rapidly into a large
volume of water contained in a drowning tub.
Batch Nitration
• Cooling is generally accomplished by coils of tubes through
which either cold water or brine for cooling may be
circulated or hot water and steam for heating.
• For control of temperature in nitrations, a wall jacket is
usually not sufficient enough except in the case of vessels
of very small capacity.
• Advantages of coils:
– High coolant velocity is possible
– More compact so can be installed anywhere in the tank.
• Disadvantages of coils:
– Fouling and scaling problem. Cleaning is no easy.
Batch Nitration
• A common accessory for the nitrator is a suction line in
the vapour space above the liquid charge to remove the
acid fumes and oxides of nitrogen which may be liberated.
• Two factors which are of prime importance in the design
of nitrators are
– Degree of agitations
– Control of temperature
Continuous Nitration
• The actual nitration reactions in a continuous process are carried
out in the same type of vessel as used for batch nitration, with the
exception that an overflow pipe or weir arrangement is provided
for the continuous withdrawal of product and that continuous feed
of reactants is provided.
• Automization is there in continuous processes.
Nitrators
 Schmid Nitrator
 Biazzi Nitrator
Schmid Nitrator
• The material to be nitrated is fed into the top of the nitrator and is
immediately drawn down through the sleeve and thoroughly
mixed with the spent acid and reacting material.
• In the bottom of the nitrator fresh mixed acid is fed in and mixed
with the other reactant by means of agitator and baffles provided.
• The reacting material then pass upwards with high velocity
through the tubes surrounded by refrigerated brine. Product and
spent acid are withdrawn continuously from the nitrator through
the overflow line.
Biazzi Nitrator
• In this apparatus the turbine type agitator provides intensive
agitation. A vortex is formed in the center about the agitator
shaft.
• The reactants fed from the top are immediately drawn into
the vortex thoroughly mixed and circulated down through
the center of the bank of cooling coils.
• The high velocity imparted to the nitrator contents makes for
efficient mixing and heat transfer. Due to throwing of cold
body on hot body flashing and evaporation takes place so
you have to provide suction line for vapours.
Mixed Acid Composition
From technical standpoint of using mixed nitric and sulfuric
acid, there are two primary conditions that must be met.
these are
1. The amount of 100% nitric acid present in nitration must
be enough to satisfy the stoichiometric requirements of
nitration reaction. it is usually present in excess in order to
maintain reasonably fast overall reaction.
2. The amount of 100% sulfuric acid with its associate SO3
must be sufficient to promote reaction
Controlling quantities
• D.V.S (dehydrating value of sulfuric acid)
D.V.S is the ratio of H2SO4 to H2O present at the end of
reaction.
• Nitric ratio
nitric ratio is the ratio of the weights of 100% nitric acid
to weight of material being nitrated.
D V S= 𝐸𝑁
𝑅
𝑆
+𝑊
Where
S= percent of actual sulfuric acid
N= percent of actual nitric acid
W= percent of water
E= water equivalent of material to be nitrated
R = nitric ratio = N/X where X is weight of starting material per 100 kg of mixed acid
RELATIONS BETWEEN D.V.S & STABILITY OF NITRATOR CHARGE
• An important consideration during the nitration of glycerin & related
compounds ( as these type of compounds are used as explosive and may
cause fire during reaction) is the stability of Nitrator charge or stability of
nitrated product with spent acid.
• Any condition which lowers the stability is obviously increasing the hazard.
• It has been demonstrated experimentally that increasing D.V.S favors high
stability of the nitrator charge while decreasing the D.V.S results in lowering
stability. This might be due to the fact that increasing D.V.S. tends to drive the
reaction further towards completion whereas too low a D.V.S. would permit
accumulation of incompletely nitrated material which would favor oxidation
reaction.
• D.V.S. ratio is always on the high, safer side, kind of automatic safety
factor.
Preparation Nitrobenzene
Batch process
1. The reactor is charged with benzene, and then the nitrating acid
(56-60 wt % H2SO4, 27-32 wt% HNO3, and 8-17 wt % H2O) is
added slowly below the surface of benzene.
2. The temperature can be raised to about 90oC toward the end of
reaction to promote completion of reaction.
3.Usually a slight excess of benzene is used to ensure that little or
no nitric acid remains in the spent acid.
4. The batch reaction time generally is 2-4 hours, and typical yields
are 95-98 wt % based on benzene charged.
• Based on yield of 1000 kg of nitrobenzene, material
requirements for the process are as follows:
Material
Quantity, kg
Benzene
650
Sulfuric acid
720
Nitric acid
520
Water
110
Sodium carbonate
10
Separation
• The reaction mixture is fed into a conical shaped tank
where it is allowed to settle for 4-24 hrs. The spent acid
settles to the bottom and is drawn off to be refortified.
• Depending upon the desired purity of the nitrobenzene,
the product can be distilled.
• The nitrobenzene is sent to neutralization tank
Neutralization
• The neutralization vessel is also a conical shaped tank with
air pipes within it to agitate the content
• First warm water is fed to the neutralizing tank and then
nitrobenzene is blown in to it.
• The charge is thoroughly agitated and warms with live steam
until neutral ( 30 mins. or more) and then allowed to settle.
• The supernatant acid water is drawn off from the outlet
provided at top end.
• The nitrobenzene is now given a neutralizing wash with warm
sodium carbonate solution at 40-50 oC till neutral to
phenolphthalein.
• A final wash with warm water is given and the product is sent
to storage tank.
Continuous process
• A typical continuous process for the production of the
nitrobenzene is given in Figures. Benzene and the nitrating acid
(56-65 wt % H2SO4, 20-26 wt.% HNO3, and 15-18 wt. % water)
are fed into the nitrator, which can be a stirred cylindrical reactor
with internal cooling coils and external heat exchangers or a
cascade of such reactors.
• The basic sequence of operations for a continuous
process is the same as that for a batch process; however,
for a given rate of production, the size of the nitrator is
much smaller in the continuous process. A 0.114-m3 (30gal) continuous nitrator has roughly the same production
capacity as a 5.68-m3 (1500-gal) batch reactor.
• The nitration in continuous process can take place with
elimination of heat of reaction,
• adiabatically, or isothermally.
Adiabatic Continuous Process
• The processes where the heat of nitration is used to directly
boil off water, benzene and nitrobenzene from the nitrator.
• This method eliminate the need to remove the heat of reaction
by excessive cooling.
• The excess heat can be used in the sulfuric acid
reconcentration step.
• An additional advantage of this method is the reduction in
reaction times to 0.5-7.5 minutes.
• The nitration step is carried out at higher than usual
temperatures 120-160 o C. because excess benzene is
used, the higher temperature allows water to be removed
as a water-benzene azeotrope. The water is separated
and the benzene phase, containing approximately 8 %
nitrobenzene, is recycled back into the reactor.
• The adiabatic process integrates nitration with sulfuric
acid concentration, thus using the heat of nitration to reconcentrate the spent sulfuric acid. This is achieved by
circulating a large volume of sulfuric acid through the
nitrator, absorbing the heat of nitration without undue
temperature rise. the spent acid is then flash concentrated
under vacuum.
Isothermal Continuous Process
• The isothermal process is different from the adiabatic process
only in the nitration section.
• In the isothermal process, typically a minimum of 2 nitrators in
series is used with up to 4 nitrators in large plants. Spent acid
and crude nitrobenzene are usually separated through gravity
settlers, but in some designs centrifugal separation is used.
• The spent acid is stripped free of dissolved nitrobenzene and
nitric acid either by steam stripping or through benzene
extraction-prenitration. It is then reconcentrated and recycled.