AMINATION

BY
REDUCTION
INTRODUCTION
• Amination by reduction involves the synthesis of amines by reductive
methods.
• Amines may be defined as derivatives of ammonia, where one or
more of the hydrogens are replaced by alkyl, aryl, hydroaryl
(cycloalkyl), aralkyl, or heterocyclic groups.
Amines are divided into three classes-primary, secondary, and tertiary
-depending upon the number of replaced hydrogens in the parent
substance ammonia.
:NH2R or RNH2 1o amine (R may be Ar)
:NHR2 or R2NH 2o amine
:NR3 or R3N 3o amine
NR4+ 4o ammonium salt
Preparation of Primary Amines
• The reduction of nitro, nitroso, hydroxylamino, azoxy, azo, and hydrazo compounds.
• The reduction of nitriles, amides, oximes, and azides.
• The replacement of labile groups, such as nitro, halogen, hydroxyl, and sulfonic
acid by reaction with ammonia or ammonia progenitors, such as urea.
• Intramolecular rearrangement of
(a) hydrazobenzenes and hydroxylamines,
(b) amides
(c) secondary and tertiary amines.
• The hydrolysis of N-substituted amides.
• Direct amination by means of hydroxylamine and sulfuric acid.
Properties
• Amines occur as gases (methylamine: bp,-6.7°C), liquids (aniline: bp,
184°C), and solids (l-naphthylamine: mp, 50°C).
• Boiling point of amines is higher because of hydrogen bonding.
• Most aliphatic amines display some solubility in water. Solubility
decreases with the increase in the number of carbon atoms. Aliphatic
amines display significant solubility in organic solvents, especially
polar organic solvents. 
• Aromatic amines are relatively weak bases as compared to aliphatic
amines.
Uses
• Amines are of very great importance as intermediates in the chemical
process industries.
• They are used in the production of dyes, rubber chemicals, nylon,
pharmaceuticals, gasoline additives, surfactants, textile auxiliaries,
photographic chemicals, chelating agents, sweetening agents,
agricultural chemicals, polyurethanes, inks, plastics, etc.
• In recent years, the production of diamines by reductive methods has
become increasingly important. Hexamethylenediamine is a prime
intermediate, together with adipic acid, in the production of nylon 66.
Methods of Reduction
1. Metal and acid: Iron and acid (Bechamp method) is the major example in
this category, but other metals (tin, zinc) have also been employed. Generally,
hydrochloric acid is preferred, but sulfuric, acetic, and formic acids have also
been used.
2. Catalytic: This method involves the use of hydrogen (or hydrogen containing
gases) and a catalyst such as nickel, copper, platinum, palladium, or
molybdenum sulfide.
3. Sulfide: This is used mainly for the partial reduction of polynitro aromatic
compounds to nitroamines and for the reduction of nitroanthraquinones to
aminoanthraquinones.
4. Electrolytic.
5. Metal and alkali: This method is used mainly for the production of
azoxy, azo, and hydrazo compounds. The latter are important in the
manufacture of the benzidine series.
6. Sodium hydrosulfite (hyposulfite).
7. Sulfite (Piria method). The reaction of sodium'sulfite and bisulfite on
an aromatic nitro compound leads to a mixture of amine and
aminoarylsulfonic
acid.
8. Metal hydrides.
9. Sodium and sodium alcoholate.
10. Strong caustic oxidation reduction.
11. Hydrogenated quinolines and naphthalenes.
Chemical Reactions
Metal and acid reductions are most vigorous and usually yield amines as end products.
When nitrobenzene is treated with zinc and a mineral acid, the resultant product is aniline.
When an alkaline solution is employed, hydrazobenzene is generally obtained, but very
vigorous conditions sometimes result in the formation of aniline.
When zinc dust and water are used, the reaction product is phenylhydroxylamine.
When the compound to be treated contains more than one nitro group,
the products of reduction depend upon the agents used.
Thus, m-phenylenediamine is obtained by the iron and acid reduction
of m-dinitrobenzene, while the alkaline sulfide reduction yields m-
nitroaniline.
With certain compounds containing acid- or alkali-sensitive groups (e.g., esters or
amides), it is necessary to adjust the pH carefully to avoid decomposition and side
reactions. In such reductions on the acid side, it is generally advisable to replace
the normally used mineral acids with organic acids like acetic acid. An example of
the latter is the reduction of nitroanilides, for here the presence of mineral acids
would tend to hydrolyze the anilide to an amine.
Method to be used will depend on
• the degree of reduction desired
• the sensitivity to the process of both starting material and final
product
• the need for avoiding contaminants
• the over-all economics
Reduction products of Nitrobenzene
Bechamp
Reduction
Iron and Acid (Bechamp) Reduction
• Bechamp's discovery in 1854 that nitro compounds could be reduced
in the presence of iron and acetic acid and Perkin's subsequent
application in 1857 of the reaction in the commercial production of
aniline were events of great significance in the development of the dye
industry, and thus in the birth of industrial synthetic organic chemistry.
• Technical progress in the application of this reaction was first made by
substituting hydrochloric acid for the acetic acid originally employed.
Subsequently, it was discovered that the ferrous salt functions in such
a way that reduction can be carried out with far less than the
theoretical quantity of acid.
• Wohl, in 1894 demonstrated that nitrobenzene could be reduced with iron
powder in alcoholic Of aqueous solution, in the presence of magnesium or
calcium chloride, and stated that the absence of free acid is advantageous.
• In 1914, von Girsewald showed that ferrous chloride could be used as the
catalytic agent in reductions.
• Moore, in 1920, found that even sodium chloride could be employed in the
iron reduction of azo compounds to amines. It has been demonstrated that
aniline hydrochloride, aluminum chloride, sodium bisulfate, or other salts
derived from strong acids can be successfully employed.
• All that is required is a salt that acts like an acid in water solution, liberating
hydrogen ions.
Reaction Mechanism

When a nitro compound is introduced into such a system

The amine hydrochloride produced may be presumed to react further

with iron and nitrobenzene
Aniline behave similarly to ammonia. They unite with water to form
weakly dissociated bases, e.g., arylammonium hydroxides.
These, like ammonium hydroxide, precipitate the hydroxides of the
heavy metals from solutions of their salts. The last step [Eq. (6») shows
the completion of the "catalytic" cycle and emphasizes the role of iron
in the regeneration of the "catalyst," ferrous chloride, .and the amine.
The arylaInines dissociate on solvation only to a slight extent, forming
weak bases as

It is this hydrolysis of the amine salt that gives the acidic medium in
which the Bechamp reduction takes place.
Chemical and Physical Factors
• Amount of Iron Used :
The range of iron generally used is about 2.5-5.0 moles per mole of
nitro compound. This has been found satisfactory for a wide variety of
aromatic amines.
• Physical Condition of Iron :
A clean, finely divided, soft, gray cast iron yields the best results. Since
the reaction velocity for nitro compound reduction is a function of the
rate of iron oxidation, it is clear that the use of finely divided iron
shortens the time of reaction.
• Amount of Water Used:
Theoretical considerations involving the progressive oxidation of the iron
indicate the desirability of using 4-5 moles of water per mole of nitro
compound treated.
• Amount of Acid Used :
This reaction requires the presence of small amounts of ferrous ion to act as
a catalyst. Generally about 0.05-0.2 of an equivalent of acid is used. The acids
usually employed in the reduction process are hydrochloric and sulfuric.
• Effect of Agitation :
The best results are obtainable only when the nitro compound, iron, and
water-soluble catalyst are in intimate contact. Mow has developed the use of
rotary mills using freely moving ponderous agitators, such as iron balls, for
the reduction of nitro, nitroso, and azo compounds to amines with iron in
aqueous emulsion in order to effect grinding action during the reduction.
• Reaction Temperature :
It is necessary, to remove the surplus heat generated while maintaining the reduction at the
optimum reaction temperature.
• Additions of Solvents :
This makes for a smoother and more rapid reduction.
• Testing for Completion :
The reaction is considered complete when an aliquot no longer increases its take-up of
sodium nitrite on further reduction with a stronger reducing agent, such as zinc and
hydrochloric acid.
• Yields of Amine :
In plant practice, yields in the range of 85-98 per cent of theory are obtained with the
Bechamp reduction. Method and rate of addition of the nitro compound, temperature,
agitation, addition of a solvent or an emulsifying agent may all influence the yield.
• Work-Up of Reaction Mixture
• Recovery of By-Products
• Continuous Processing
 Catalytic
Hydrogenation
Historical Introduction
• The first recorded catalytic hydrogenation of an organic compound was a reduction of a nitrile to
an amine.
• In 1863, Debus passed hydrogen cyanide with hydrogen over platinum black and obtained
methylamine.
• Saytzeff, in 1871, hydrogenated nitrobenzene in the vapor phase over palladium black and
obtained aniline.
• The classical researches of Sabatier in collaboration with Senderens and others in this field, based
on the discovery of the catalytic activity of nickel in all types of hydrogenations, started in 1897.
• Senderens obtained a German patent in 1901 on the production of aniline by passing
nitrobenzene vapor over heated nickel, copper, cobalt, iron, or palladium in the presence of
hydrogen or water gas.
• In the same year, Sabatier and Senderens described a vapor-phase reduction of nitrobenzene to
aniline over a copper catalyst, using hydrogen or water gas, in a yield of 98 per cent of theory.
One year later, the same workers found that nitroethane could be reduced to ethylamine at 200°C
over a nickel catalyst.
Feasible Reactions with Catalyst
In addition to nitro compounds, nitroso, hydroxylamino, azoxy, azo, and
hydrazo compounds can also be reduced to amines. Nitriles, amides,
thioamides, and oximes of both aldehydes and ketones can be
hydrogenated to amines.

The production of diamines, both aliphatic and aromatic, has become

of increasing importance during recent years. Hexamethylenediamine,
produced by catalytic hydrogenation of adiponitrile, is an essential
component in the manufacture of nylon 66.
Sokol'skii and Shmonina studied the rate of hydrogenation of nitro benzene in 0.1 N sodium hydroxide
and in neutral alcohol in the presence of a nickel catalyst and in the presence of a nickel catalyst plus
rhodium.

They conclude that in alkali the reaction is

in neutral alcohol the reaction is

Reaction Conditions
• Catalytic reductions can be carried out in batches or in continuous
processes, in the liquid phase or in the vapor phase.
• This method has many advantages over other methods of reduction,
particularly for large-volume production.
• With low-cost hydrogen, as is the case when by-product hydrogen is
available from other installations or when large hydrocarbon steam
units are installed, this process cannot be matched by other methods
of reduction in so far as economics and quality of product are
concerned.
• Catalytic reductions have been carried out under an extremely wide range of
reaction conditions.
• Temperatures of 20°C to over 300°C have been described.
• Pressures from atmospheric to several thousand pounds have been used.
• Catalysts have included nickel, copper, cobalt, chromium, iron, tin, silver, platinum,
palladium, rhodium, molybdenum, tungsten, titimium and many others. They have
been used as free metals, in finely divided form for enhanced activity, or as
compounds (such as oxides or sulfides). Catalysts have been used singly and in
combination, also on carriers, such as alumina, magnesia, carbon, silica, pumice,
clays, earths, barium sulfate, etc., or in unsupported form.
• Reactions have been carried out with organic solvents, without solvents, and in
water dispersion.
• Finally, various additives, such as sodium acetate, sodium hydroxide, sulphuric acid,
ammonia, carbon monoxide, and others, have been used for special purposes.
Catalytic Vapor-phase Reduction Low-boiling Mononitro
Compounds
Attractive features :
1) continuous conversion of reactants to finished amine
2) minimum operating labor requirements
3) low steam and power costs as a result of utilizing the heat in vapors leaving the catalytic
chamber
4) absence of industrial-waste problems, e:g., disposal of iron oxide sludge

Technical Problems :
5) limited per-pass conversion, thus necessitating separation of aniline from nitrobenzene (unless
the heat of reaction is gainfully employed, this will constitute a significant item of expense)
6) sensitivity of catalytic operations which may result in overreduction and relatively low yields of
amine compared with competitive processes, particularly Beschamp reductions.
Metals for Catalyst
• Although nickel and copper are considered the most active catalysts for a large number of
hydrogenation processes, it is not always advisable in the reduction of nitro compounds to
employ the most active catalysts.
• Other factors such as stability, wide plateaus of temperature effectiveness, and high throughput
per catalyst volume and life are important. It has been found that the metals both preceding and
following hydrogen in the electrochemical series can be used as catalysts.
• Thus, nickel, iron, tin, copper, silver, platinum, nickel-copper and cobalt, molybdenum; and
tungsten as sulfides are all mentioned.
• Working under favorable conditions with a nickel catalyst, Brown and Henkel obtained a 95 per
cent yield of aniline from nitrobenzene.
• When tin is employed as a catalyst, good results are obtained in the reduction of nitrobenzene to
aniline. The catalyst made from the hydroxide prepared by precipitation with sodium carbonate
from a stannous chloride solution is the best.
Vapor-phase reduction of nitrobenzene
 The effects of "rate of feed" for nitrobenzene

It can be seen that at only one point is the curve for tin below that of copper; in
most places, the values for tin are above those for copper. Tin is likewise superior to
nickel at all but the highest rates of feed.
 The effect of "How of hydrogen" in the presence of the same catalysts.

It will be noted that the curve for tin has a shape different from that of the other two
curves. Thus, the decrease in yield with too much or too little hydrogen is more rapid for tin
than for nickel or copper. However, the region within which high yields are secured is as
wide or wider with tin than with other catalysts.
Manufacture
of
Aniline
Continuous fluid-bed vapor-phase reduction of nitrobenzene
Catalytic vapour-phase reduction of nitrobenzene
• The reaction is carried out at very slight pressure (about 5 psig) over a
reduced copper carbonate catalyst at temperatures ranging from about
200°C at the entrance to the catalytic reactor to 350°C at the exit.
• The process starts by vaporizing a descending film of nitrobenzene in the
tubes of an evaporator by an ascending stream of preheated hydrogen gas
stream of 6,000 cu m per hr, which has been preheated in a heat exchanger.
• Hydrogen (free of CO) and nitrobenzene vapor are passed over a catalyst
contained in two chambers in series, each of 50 cu m volume.
• The catalyst is first reduced in a circulating hydrogen gas stream at 200 °C.
• This temperature is obtained by passing the hydrogen over a heater
containing superheated water under high pressure.
• With fresh catalyst, the reaction temperature is 170 °C on entering the first
chamber. Gases leaving the second chamber will have a temperature of 350-
370°C under the above condition.
• The reaction is strongly exothermic, and temperature control is accomplished by
a stream of relatively cool hydrogen which is diverted from the circulating stream
ahead of the heat exchanger and regulated by a valve.
• The entering temperature to the first catalyst chamber must be increased as the catalyst deteriorates.
It is necessary to reactivate the catalyst after 1,200 tons of nitrobenzene has been passed through the
system, at which time the entrance temperature to the first catalyst chamber will be 280°C.
• Reactivating is accomplished by roasting (carefully controlled oxidation with air) followed by reduction
with hydrogen. This process can be repeated four to five times. After a total of 2,600 tons of
nitrobenzene has passed through the system, it is possible to increase the service life further by
having an ammoniacal copper carbonate solution percolate through the catalyst, which will serve to
reduce another 1,400 tons of nitrobenzene.
• One filling of the contact chambers will, therefore, serve in the reduction of
about 4,000 tons of nitrobenzene, which is equivalent to a usage of 0.07 kg
copper per 100 kg aniline. The normal production capacity of the plant is 300
tons of aniline per month.
• After passing through a heat exchanger, the reaction products are separated from
the circulating gas stream by two water-cooled tubular condensers followed by a
separate cooler with impingement plates.
• Aniline and water are separated in a separator. The former Bows to storage tanks
and from there to distillation in a 24-plate bubble-cap column. The latter is
passed to a continuous extraction column in which dissolved aniline is extracted
by a descending stream of nitrobenzene that is to be used as feedstock.
• The yield is 98 per cent of theory based on distilled aniline.