Note: Descriptions are shown in the official language in which they were submitted.
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TITLE: NITRATION OF AROMATIC COMPOUNDS
FIELD OF THE INVENTION:
The present inver_tion relates to nitration of
aromatic compounds.
BACKGROUND OF THE INVENTION:
Nitration of aromatic compounds is of considerable
commercial importance, as nitrated aromatic products find
utility as dyes, explosives, pharmaceuticals, perfumes,
plastics and solvents. Nitration processes are known that
use a mixture of nitric acid and sulfuric acid (hence, these
methods are referred to as "mixed acid methods"), wherein
sulfuric acid acts as a catalyst. Unfortunately, these
processes produce large quantities of waste dilute sulfuric
acid, and the disposal or recovery of this acid waste
presents a serious environmental problem. Recovery involves
an energy-intensive and expensive process of reconcentrating
sulfuric acid that has been diluted by the water produced in
the nitration reaction. The mixed acid method also produces
nitrocresol and cyanide by-products, which require expensive
waste-water treatment to remove. Further, the mixed acid
method is not selective and produces a mixture of isomers
and polynitrated compounds that are difficult to separate
from each other.
Efforts have been made to develop alternative
methods that avoid the use of sulfuric acid. These
alternative methods include nitration with nitronium salts
(such as [N02] [BF4] ) , oxides of nitrogen (such as N02, N204,
N205, HN03) in conjunction with boron trifluoride (a Lewis
acid) and HN03 in conjunction with lanthanide (III)
triflates.
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Efforts to increase the selectivity of nitration
process have involved using solid catalysts such as clays or
zeolites in combination with alkyl nitrates or acyl nitrates
as nitrating agents. However, the nitrating reagents, such
as acyl and alkyl nitrates, used in these methods are
explosive (as is nitric acid itself in the presence of solid
acidic catalysts) and are therefore hazardous to use.
Nitration of aromatics with alkyl nitrates requires protic
or Lewis acid activation.
Copper (II) nitrate supported on montmorillonite
clay quantitatively nitrates toluene in the presence of
acetic anhydride, but this reaction achieves para-
regioselectivity only under conditions of high dilution and
long reaction times (i.e. over 120 hours). Para-selectivity
may be achieved using HR zeolite or HY zeolite as a solid
inorganic catalyst and a combination of liquid nitrogen
dioxide and gaseous oxygen as the nitrating agent. Zeolites
have al:~o been used in the vapour phase nitration of
aromatic compounds using nitrogen dioxide and other methods.
However, the existing alternatives to mixed acid
nitration have several disadvantages. For example, methods
that use solid acid catalysts (such as clays, zeolites,
metal triflates, etc.) typically have low selectivity and
produce mixed isomers, require large quantities of the solid
catalyst, and are corrosive to the industrial plant. Many
of these processes require a large excess of nitric acid or
another nitrating agent (i.e. on the order of 8:1 nitrating
agent to aromatic) and therefore produce a lot of waste.
Also, these processes are carried out in chlorinated organic
solvents, such as methylene chloride, which are difficult to
contain and environmentally hazardous if released.
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Moreover, the nitrating agents used in many of these
processes, such as acyl anc~ alkyl nitrates, are explosive.
S'~TMMARY OF THE INVENTION:
The present invention provides a process for the
nitration of an aromatic compound, the process comprising
contacting an aromatic compound with a nitrating agent in
the presence of a phosphonium salt ionic liquid.
DESCRIPTION OF PREFERRED EMBODIMENTS:
The current invention provides a novel process for
the nitration of aromatic compound that may be used to
obtain nitrated aromatic compounds in high yield and with
high selectivity. This process provides several advantages
over existing methods. For example, the current process can
avoid the use of sulphuric acid and thereby avoid many of
the hazardous waste products that are associated with
conventional mixed acid nitration methods. The current
process also avoids the use of chlorinated organic solvents
(e. g. methylene chloride), which are environmentally
hazardous, in favour of phosphonium salts, which have zero
vapour pressure and are therefore more easily contained.
Also, the current process does not require explosive
nitrating agents (for example the aryl or alkyl nitrating
agents). The current nitration process does not require
solid acid catalysts, nor Lewis acids. The current process
results in a mononitrated product, without concommitant
dinitrated compounds.
The preferred nitrating agent is nitric acid,
especially fuming nitric acid. Nitric acid is a preferred
ntirating agent because it is relatively inexpensive and
readily available. However, other nitrating agents may be
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used for the nitration of an aromatic compound in a
phosphonium salt. Suitable nitrating agents include nitrate
salts, and mention is made of NaN03, and KN03, in combination
with H2S04. According to this embodiment, H2S04 can react
with NaN03 or KN03 to produce HN03 and Na2S04 or K2S0q,
respectively, and the production of waste HZS04 can be
avoided.
The nitrating agent, say nitric acid, and the
aromatic compound to be nitrated may be used in
approximately stoichiometric amounts to produce mononitrated
products in high yield, with little or no production of
polynitrated aromatic compounds. The molar ratio of
nitrating agent to aromatic compound can be in the range
1:1.3 to 1.3:1. Preferably a modest excess of nitrating
agent, say 1.2:1, is used. The efficient use of nitric
acid, which is a relatively inexpensive nitrating agent,
contributes to the overall economy of the current nitration
process. Also, the phosphonium salt solvent may be
recovered for reuse. Phosphonium salts may be stable under
treatment with fuming nitric acid and moderate heating, for
example 80°C, for extended periods of time (at least 3
days ) .
To illustrate, nitration of an aromatic compound
with nitric. acid proceeds according to the following scheme,
using optionally substituted benzene as example, to produce
a nitrated aromatic compound and water:
N02
R / I + HNO ionic liquid R '~ ~ + H O
3 \ 2
R = H, CH3, C1, Ph, OCH3, C2H5, etc.
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In general, the process of nitration may be
carried out over a wide range of temperatures, for example
from -75°C up to the upper limit at which ionic liquids
decompose, at about 300°C. Preferably, the reaction is
carried out at a temperature where the reaction mixture
(which comprises an aromatic compound, a nitrating agent and
a phosphonium salt) is a liquid. Preferably, the reaction
may be carried out at temperatures between 0°C and 120°C,
more preferably between room temperature and 100°C. The
pressure can range between 1 mbar and 100 bar, but the
reaction is conveniently carried out at atmospheric
pressure. The time of reaction may vary with temperature,
but is usually about 12 to 24 hours.
The nitrated aromatic products may be purified
from the reaction mixture by any of several methods. For
example, the reaction product may be purified by the method
of steam distillation, the method comprising:
a) adding water;
b) distilling at for example 120-140°C and
atmospheric pressure; and
c) allowing the distillate to separate into
phases: a nitrated product phase, and an aqueous phase that
contains any residual or unreacted nitric acid.
In some cases, it may be convenient to isolate the
nitrated aromatic by vacuum distillation, provided that the
product has a boiling point that is below the temperature at
which either the nitrated aromatic or the phosphonium salt
decomposes. In some cases, it may be convenient to isolate
the nitrated aromatic compound by extracting the reaction
mixture with an organic solvent, for example petroleum ether
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or cyclohexane, and subsequently evaporating the organic
solvent. However, further extractions may be required if
the particular phosphonium salt used can also dissolve in
the organic solvent.
The phosphonium salt may be recovered for reuse
(recycled) by removal of water that has been produced by the
reaction. This can be done, for example, by vacuum
distillation or by any other convenient method. The
phosphonium salt can be re-used many times without loss of
activity or selectivity.
The aromatic compounds for use in the inventive
process may be any known hydrocarbon compound containing one
or more aromatic ring systems. Examples of aromatic ring
systems include: phenyl, naphthalenyl, anthracenyl,
phenanthrenyl, pyrenyl and coronenyl.
The aromatic compounds to be nitrated may contain
substituents, provided that the substituents do not
interfere with the nitration process. When there is more
than one substituent present, the substituents may be the
same or different. Examples of substituents include:
alkyl, alkenyl and alkynyl, especially C1-C6 alkyl, C2-C6
alkenyl or C2-C6 alkynyl, any of which may optionally be
substituted with one or more substituents selected from, for
example, halogen or hydroxy; halo e.g. fluoro, chloro, bromo
or iodo; alkoxy, especially C1-C6 alkoxy optionally
substituted by halogen e.g. methoxy, ethoxy, n-propoxy, iso-
propoxy, difluoromethoxy, trifluoromethoxy or
tetrafluoroethoxy; aryl e.g. optionally substituted phenyl;
aryloxy, e.g. optionally substituted phenyloxy; cyano;
nitro; amino; mono- or di-C1-C6 alkylamino; hydroxylamino;
acyl , a . g . acetyl or trif luoroacetyl ; S (O) nCl-C6 alkyl or
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S(O)nCl-C5 haloalkyl, wherein n is 0, 1 or 2, e.g.
methylthio, methylsulphinyl, methylsulphonyl,
trifluoromethylthio, trifluoromethylsulphonyl or
trif luoromethylsulphinyl ; SCN; SF5 ; COOR4 ; CORE ; CONR4R5 or
CONHS02R4, wherein R' and RS are each independently hydrogen
or C1-C6 alkyl optionally substituted with one or more
halogen atoms and R6 is a halogen atom or a group R4.
Mention is made of aromatic compounds that
comprise a phenyl ring, substituted or unsubstituted.
Mention is also made of aromatic compounds comprising a
diphenyl ether, the phenyl rings of which are independently
optionally substituted by one or more groups selected from:
halo; hydroxy; COOR4, CORE, CONR4R5 or CONHSOZR4, wherein R4
and R5 are each independently hydrogen or C1-C6 alkyl
optionally substituted with one or more halogen atoms and R6
is a halogen atom or a group R4.
The ionic liquid used in the current invention may
be a phosphonium salt according to the general formula:
R1 R2
~ /
P X- Formula (I)
~R3
wherein:
each of R1, R2, R3, and R' is independently a
hydrocarbyl group or a hydrogen, provided that not more than
one of the R1 to R4 groups is a hydrogen; and
X- is an anion, provided X- is not a hydroxyl
group; for example, suitable anions include halides,
phosphinates, alkylphosphinates, alkylthiophosphinates,
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sulphonates, tosylates, aluminates, borates, arsenates,
metallates; cuprates, sulfates, triflate, bistriflamide, and
carboxylates, for example trifluoroacetate.
In many cases, the phosphonium salt will be a
tetrahydrocarbylphosphonium salt, wherein each of R1, R2, R3,
and R4 is independently an alkyl group of 1 to 30 carbon
atoms, a cycloalkyl group of 3 to 7 carbon atoms, an alkenyl
group of 2 to 30 carbon atoms, an alkynyl group of 2 to 30
carbon atoms, an aryl group of 6 to 18 carbon atoms, or an
aralkyl group. It is possible for two of R1, R2, R3, and R4
together to form an alkylene chain.
The phosphonium salt should be liquid at the
desired temperature for carrying out the nitration reaction,
but it is not necessary for the phosphonium salt to be
liquid at room temperature in all cases. Phosphonium salts
that melt at low temperatures, for example at temperatures
less than 100°C and preferably less than 50°C, may be
suitable for nitration reactions carried out at slightly
elevated temperatures (i.e. in the range of 50°C to 100°C).
Since alkyl groups with 4 carbon atoms or less can increase
the melting point for the ionic liquid, more preferred are
phosphonium salts according to formula (I) wherein each of
R1, R2, R3, and R4 is independently an alkyl. group of 4 to 20
carbon atoms. For example, Rl, R2, R3, and R4 may be n-butyl,
isobutyl, n-pentyl, cyclopentyl, isopentyl, n-hexyl,
cyclohexyl, (2,4,4'-trimethyl)pentyl, cyclooctyl, tetradecyl,
etc. The degree of asymmetry and the degree of branching of
the hydrocarbyl groups are important determinants of the
melting point of the phosphonium salt: the melting point
tends to decrease as the degree of asymmetry and branching
is increased. Therefore, preferred compounds are those in
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which R1, R2, R3, and R4 are not identical and/or are
branched.
Phosphonium salts include compounds according to
formula (I) wherein each of R1, R2, R3, and R4 is
independently an aryl or aralkyl group. Aryl-containing
salts may be less preferred in view of the possibility that
the aryl and/or aralkyl groups may become nitrated under the
reaction conditions used. However, an aryl-containing
phosphonium~salt that has become nitrated may also be a
suitable solvent for nitration of aromatic compounds.
Examples of aryl and aralkyl groups include phenyl,
phenethyl, toluyl, xylyl, and naphthyl.
It is possible for the groups of R1, R2, R3, and R4
to bear substituents, or to include heteroatoms, provided
that the substituents or heteroatoms are inert (e.g. do not
undergo nitration or oxidation) under the reaction
conditions used, do not adversely affect the desired
reaction, and do not adversely affect the desired properties
of the ionic liquid. Acceptable substituents include alkoxy
and acetyl, and acceptable heteroatoms include oxygen.
Preferred anions form liquid salts at temperatures
below about 100°C and preferably below about 50°C when
combined with a cation described above. Suitable types of
anions include: anions based on nitrogen, phosphorus, boron,
silicon, selenium, tellurium, aluminum, copper, arsenic,
antimony, bismuth, or halogens; oxoanions of metals;
halides; phosphinates, mono- and dialkylphasphinates,
alkylthiophosphinates, sulphonates, tosylates, aluminates,
borates, arsenates, cuprates, sulfates, nitrates, and
organic anions, for example trifluoroacetate, bistriflamide
and triflate. Of those anions that contain alkyl groups,
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the alkyl groups each independently has any of the values
given to R1, R2, R3, and R4 of the phosphonium cation (as
defined above). In many cases, sulfur-containing anions,
such as triflates, bistriflamides or sulfates, may be
preferred. Specific examples of preferred anions include:
chloride; bromide; perchlorate; fluoride; sulfate;
sulfonate; fluorosulfonate; trifluoromethylsulfonate;
triflate; bistriflamide; dicyclohexylphosphinate;
diisobutylphosphinate;
bis(2,4,4'-trimethylpentyl)phosphinate;
diisobutyldithiophosphinate; tetrafluoroborate;
tetrachloroborate; hexafluorophosphate; hexafluoroantimonate
and hexafluoroarsenate.
For some applications, phosphonium salts according
to formula (I) that are hydrophobic or water immiscible may
be preferred. For example, some applications may involve
washing the~reaction mixture with water, in which case it
may be advantageous to use a phosphonium salt that is
immiscible with water and forms a two-phase system when
mixed with water. The term "water immiscible" is intended
to describe compounds that form a two phase system when
mixed with water but does not exclude ionic liquids that
will dissolve water, provided that the two-phase system
forms. Therefore, phosphonium salts that have a larger
total number of carbons, equal to or greater than 20 and in
particular greater than 25 or 26, are preferred because they
are more hydrophobic.
Thus the given phosphonium salt ionic liquid
consists of two components, which are a positively charged
phosphonium cation and a negatively charged anion. In
general, any salt which can be a fluid at or near the
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reaction temperature or exist in a liquid state during any
stage of the reaction can be used as the ionic liquid.
Moisture sensitive anions may react with the water
that is produced by the nitration reaction, and it is
therefore preferred that X- is an anion that is not moisture
sensitive. Moisture sensitive anions include: transition
metal halide complexes such as tetrachloroaluminate,
tetrachloroferrate, or trichlorocuprate.
The following list provides examples of preferred
phosphonium salts according to the current invention:
trihexyl(tetradecyl)phosphonium chloride;
tripentyl(tetradecyl)phosphonium chloride;
trioctyl(tetradecyl)phosphonium chloride;
trihexyl(tetradecyl)phosphonium bromide;
trihexyl(tetradecyl)phosphonium triflate;
trihexyl(tetradecyl)phosphonium bistriflamide;
trihexyl(tetradecyl)phosphonium
diisobutyldithiophosphinate;
trihexyl(tetradecyl)phosphonium sulfate;
trihexyl(tetradecyl)phosphonium
dicyclohexylphosphinate;
trihexyl(tetradecyl)phosphonium tetrafluoroborate;
and
triisobutyl(tetradecyl)(methyl)phosphonium
tosylate.
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Some of the phosphonium salts of formula (I) are
novel. For example, phosphonium hydrocarbylphosphinates and
phosphonium hydrocarbylthiophosphinates are the subject of
Canadian Patent Application Serial 2,343,456, filed on March
30, 2001. The novel salts can be made from compounds of
formula (I) in which the anion is a good leaving group, for
example a halogen or acetate or tosylate, in an ion exchange
reaction with a salt of the desired anion. The salt can be,
for example, an ammonium or an alkali metal salt.
The invention is further illustrated in the
following examples.
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EXAMPLE 1: Nitration of benzene in
trihexyl(tetradecyl)phosphonium bistriflamide
2.0 g of trihexyl(tetradecyl)phosphonium
bistriflamide and 1.56 g of benzene were placed in a 50 ml
round bottomed flask. 1.50 g of 100% nitric acid was added
slowly to the flask over 5 minutes. The contents of the
flask were heated at 80°C for 2 hours.
After 2 hours of reaction at 80°C, the contents of
the flask were worked up as usual. Analysis of the product
by weight, GC and NMR revealed that nitrobenzene was
produced in essentially quantitative yield.
EXAMPLE 2: Nitration of various aromatic compounds in
trihexyl(tetradecyl)phosphonium bistriflate at 80°C
The following aromatic compounds were nitrated
essentially as described in Example 2: benzene, toluene,
o-xylene, m-xylene, p-xylene and naphthalene. The aromatic
compound to be nitrated was dissolved in 2.0 g of
trihexyl(tetradecyl)phosphonium triflate, and fuming nitric
acid way, added. The equivalent ratio of aromatic compound
to nitric acid was 1:1.2. Then, the contents of the flask
were heated to 80°C and the reaction was allowed to proceed
for 6 hours.
Upon completion of the 6 hour reaction period, the
contents of each flask were worked up and the products were
analyzed to determine conversion and product distribution.
Product distribution was determined by GC and NMR analysis.
Results are presented in Table 1. No polynitrated aromatics
were detected in the reaction products.
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TABLE 1:
Product
Distribution
(%)
Conversion
No. Arene (%) Ortho Meta Para
1 PhH >90 n/a
2 PhCH3 >95 54.0% 5.0% 40.5%
3 o-xylene 87.63 3-nitro 4-nitro
(50%) (50%)
4 m-xylene 87.4 4-nitro 2-nitro
(87.5%) (12%)
p-xylene >95 n/a
6 naphthalene 80 1-nitro 2-nitro
(94%) (6%)
EXAMPLE 3: (Comparative)
In a comparative experiment without phosphonium
5 ionic liquid solvent, nitric acid and toluene were
maintained at 80°C for one day. It was found that there had
occurred. 48% conversion to mononitrotoluenes.
EXAMPLE 4: Nitration of aromatic compounds in
trihexyl(tetradecyl)phosphonium bistriflamide at 80°C
The following reactions were carried out using the
method described in Example 2. Various aromatic compounds
to be nitrated were dissolved in
trihexyl(tetradecyl)phosphonium bistriflimide. Fuming
nitric acid was added in a ratio of 1.2 equivalents of
nitric acid to 1 equivalent of aromatic compound. The
reaction was carried out at 80°C for 6 hours.
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At the end of the 6 hour reaction time, the
contents of the flask were worked up, conversion was
determined, and product distribution was determined by GC
and NMR analysis. Results are presented in Table 2. No
polynitrated aromatics were detected in the reaction
products.
TABLE 2:
Product
Distribution
(%)
Conversion
No. Arene (%) Ortho Meta Para
1 PhH >90 n/a
2 PhCH3 >95 60.4 2.4 36.0
3 o-xylene 87.63 3-nitro:l 4-nitro:l
4 m-xylene 87.4 4-nitro
only
5 p-xylene >95 n/a
6 naphthalene 80 1-nitro 2-nitro
(94) (6)
EXAMPLE 5: Nitration of various aromatic compounds in
trihexyl(tetradecyl)phosphonium bistriflamide at room
temperature
The series of reactions described in Example 4 was
repeated at room temperature, i.e. without applying heat for
12 hours. The overall yields and product distribution from
these reactions were determined by GC and NMR analysis and
are presented in Table 3. No polynitrated aromatics were
detected in the reaction products.
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TABLE 3:
Product
Distribution
(%)
Conversion
No. Arene (%) Ortho Meta Para
1 PhH >90 n/a
2 PhCH3 75 60.4 2.4 36.5
3 o-xylene 15 3-nitro:l 4-nitro:l
4 m-xylene 25 4-nitro
only
p-xylene 25 n/a
6 naphthalene ~ 69 1-nitro 2-nitro
(94) (6)
EXAMPLE 6:
A second series of reactions, under conditions
5 identical with those of Example 5, was carried out using
benzene, toluene, ethylbenzene, anisole, chlorobenzene,
naphthalene, nitrobenzene, benzyl alcohol and acetophenone.
The overall yields and product distribution from these
reactions are presented in Table 4. Benzyl alcohol and
acetophenone did not undergo nitration under these
conditions. Benzyl alcohol oxidized to the corresponding
aldehyde and acid with 25% conversion (10% benzaldehyde and
89.2% benzoic acid). Acetophenone did not undergo reaction.
No polynitrated aromatics were detected in the reaction
products.
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TABLE 4:
Product
Distribution
(%)
Conversion
No. Arene (o) Ortho Meta Para
1 PhH >90 n/a
2 PhCH3 75 60.4 2.4 36.5
3 PhEt 51.5 43.29 3.0 53.6
4 anisole 52 36.0 - 63.98
PhCl 38.7 71 - 28.2
6 naphthalene 69 1-nitro - 2-nitro
(94.8) (5.2)
7 PhN02 0 n/a
EXAMPLE 7:
Trihexyl(tetradecyl)phosphonium triflate was
5 synthesised by the reaction of
trihexy7.(tetradecyl)phosphonium chloride (l.Oeq) and sodium
trifluoromethanesulfonate (1.05eq) in acetone over a period
of 2 to 9 hours. The total reaction mixture was
concentrated and the residue was dissolved in chloroform or
ether. The organic layer was washed with deionised water
till the organic layer did not show the presence of chloride
ions by silver nitrate test, then dried over anhydrous MgS04,
filtered and concentrated on a rotary evaporator. The ionic
liquid thus obtained was subjected to high vacuum.
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EXAMPLE 8:
Trihexyl(tetradecyl)phosphonium bistriflamide was
synthesised by the reaction of
trihexyl(tetradecyl)phosphonium chloride (l.Oeq) and
lithiumbistriflamide (1.05eq) in acetone over a period of 2
to 9 hours. The total reaction mixture was concentrated and
the residue was dissolved in chloroform or ether. The
organic layer was washed with deionised water till the
organic layer did not show the presence of chloride ions by
silver nitrate test, then dried over anhydrous MgS04,
filtered and concentrated on a rotary evaporator. The ionic
liquid thus obtained was subjected to high vacuum.
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