CA2356564A1

CA2356564A1 - Nitration of aromatic compounds

Info

Publication number: CA2356564A1
Application number: CA002356564A
Authority: CA
Inventors: Allan James Robertson; Martyn John Earle; Kenneth R. Seddon; Alwar Ramani
Original assignee: Cytec Technology Corp
Current assignee: Cytec Canada Inc
Priority date: 2001-09-05
Filing date: 2001-09-05
Publication date: 2003-03-05
Also published as: CN101426759A; EP1423352A1; WO2003020683A1

Abstract

Aromatic compounds are mononitrated by reaction with a nitrating agent, preferably nitric acid, in a phosphonium salt ionic liquid.

Description

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.

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.

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 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:

R / I + HNO ionic liquid R '~ ~ + H O
3 \ 2 R = H, CH3, C1, Ph, OCH3, C2H5, etc.

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 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 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:

~ /
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, 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 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, 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 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.

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.

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.

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.

75365-20n 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.

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.

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.

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.

Claims

1. 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.

2. A process according to claim 1, wherein the nitrating agent is nitric acid.

3. A process according to claim 1 or 2, wherein the phosphonium salt has a sulfur-containing anion.

4. A process according to claim 3, wherein the phosphonium salt has a bistriflamide anion.

5. A process according to claim 4, wherein the phosphonium salt is trihexyl(tetradecyl)phosphonium bistriflamide.

6. A process according to claim 3, wherein the phosphonium salt has a triflate anion.

7. A process according to claim 6, wherein the phosphonium salt is trihexyl(tetradecyl)phosphonium triflate.

8. A process according to any one of claims 1 to 7, which is carried out at a temperature in the range between room temperature and 100°C.

9. A process according to claim 8, wherein the temperature is in a range between room temperature and 80°C.

10. A process according to any one of claims 1 to 9, wherein the aromatic compound is benzene.

11. A process according to any one of claims 1 to 9, wherein the aromatic compound is toluene.

12. A process according to any one of claims 1 to 9, wherein the aromatic compound is ethylbenzene.

13. A process according to any one of claims 1 to 9, wherein the aromatic compound is anisole.

14. A process according to any one of claims 1 to 9, wherein the aromatic compound is chlorobenzene.

15. A process according to any one of claims 1 to 9, wherein the aromatic compound is naphthalene.