JP2003081920A - Method for producing aromatic nitro compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an aromatic nitro compound useful as a raw material for medicines, or agrochemicals without using a strong acid, thereby reducing loads such as the treatment of waste liquid. SOLUTION: This method for producing the aromatic nitro compound having at least one substitutable hydrogen atom on the aromatic ring is carried out a nitration reaction in the presence of a group III element nitrate, a carboxylic anhydride and a rare earth catalyst represented by general formula: RE(OSO2 Rf)3 (RE is a rare earth atom; Rf is a perfluoroalkyl which may have one or more substituents) as a catalyst.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for nitrating an aromatic compound, and the compound produced by the present invention can be used as a raw material for medicines, agricultural chemicals and the like.

[0002]

2. Description of the Related Art As a method for nitrating an aromatic compound,
A method in which concentrated nitric acid is used as a nitrating agent in the presence or absence of concentrated sulfuric acid or acetic anhydride is widely used (see, for example, New Experimental Chemistry Course 14-3). However, in this method, a large amount of water is required for the subsequent treatment in order to carry out the reaction using an excess amount of nitric acid, and the treatment cost is also required when a large amount of acid waste liquid is discarded. However, there is a problem as an industrial mass production method. As a method without using an excessive amount of nitric acid, nitrate was used as a nitrating agent, and aluminum chloride (George AO
lah, “Nitration: Methods and Mechanisms”, VCH Pub
lishers Inc., New York (1988)), a method of performing a nitration reaction by adding trifluoroacetic anhydride (USP 3,634,520 and USP 3,715,323), and stoichiometry using a rare earth catalyst. Method with a certain amount of nitric acid (USP5,7
No. 28,901) is also known, but it is not satisfactory in terms of yield.

[0003]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a nitration reaction method for aromatic compounds which does not use nitric acid which is a strong acid. And for other purposes,
It is intended to provide a method for producing a nitrated aromatic compound having an excellent reaction yield.

[0004]

The inventors of the present invention have conducted extensive studies to solve such problems, and as a result, in the nitration of aromatic compounds, a rare earth catalyst was used as a catalyst. The present invention has been newly found that the reaction proceeds well when the group III element is used as a nitrating agent and the reaction is carried out in the presence of a carboxylic acid anhydride. The present invention relates to a method of nitrating an aromatic compound having at least one substitutable hydrogen in an aromatic ring, wherein a catalyst of the following general formula (1) RE (OSO ₂ Rf) _{3 is} used as a catalyst.
(1) (wherein RE represents a rare earth element and Rf represents a perfluoroalkyl group which may have a substituent), a rare earth catalyst, a group III element nitrate, and a carboxylic acid anhydride The method for producing an aromatic nitro compound is characterized in that it is carried out in the presence of

Examples of the aromatic compound as a raw material include known compounds to which this type of reaction is applied, and those in which at least one carbon atom constituting an aromatic ring has a substitutable hydrogen. If Specific examples include benzene, thiophene, pyrrole, furan, monocyclic aromatic compounds such as pyridine, naphthalene, anthracene, naphthacene, pentacene, indene, azulene, heptalene, indacene, acenaphthylene, fluorene, phenalene, phenanthrene, triphenylene, pyrene. , Condensed polycyclic aromatic hydrocarbons such as chrysene and perylene, ring assembly aromatic hydrocarbons such as biphenyl and terphenyl, indole, isoindole, quinoline, isoquinoline, quinazoline, purine, xanthene, carbazole, acridine, phenazine, phenanthroline , Benzofuran, dibenzofuran, benzothiophene, dibenzothiophene, and other condensed heterocyclic aromatic compounds can be shown.
A compound in which one or more substituents are substituted can be shown.

In the case of an aromatic compound having a substituent,
The substituent is not particularly limited as long as it does not inhibit the reaction, and examples thereof include a halogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, a thio group, an amino group, an acylamino group, a nitro group, a hydroxyl group, an alkylamino group. A group or the like can be shown, and another kind of substituent may be present on these substituents. Suitable aromatic compounds include benzene, toluene, xylene, lower alkyl-substituted benzenes such as trimethylbenzene, and the like.

The group III element nitrate used in this reaction may be any group IIIA or group IIIB nitrate, and one or more nitrates selected from these elements may be used. . Specifically, scandium,
Yttrium, lanthanum, cerium, praseodymium,
Neodymium, samarium, europium, gadolinium. It can be terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, boron, aluminum, gallium, indium, thallium. Further, these nitrates may contain water of crystallization. Examples of preferable nitrates include scandium, yttrium, ytterbium, aluminum and indium, and more preferable examples include scandium, aluminum and indium.

As the carboxylic acid anhydride used in the reaction, monobasic acid anhydrides and dibasic acid anhydrides are generally used, and one or more selected from them can be used. Specifically, aliphatic monobasic anhydrides such as acetic anhydride, propionic anhydride, valeric anhydride, isovaleric anhydride, butyric anhydride, isobutyric anhydride, pivalic anhydride, hexanoic anhydride, decanoic anhydride, etc. Compounds, aliphatic dibasic acid anhydrides such as succinic anhydride, maleic anhydride, glutaric anhydride, benzoic anhydride, 3-chlorobenzoic anhydride, 3-nitrobenzoic anhydride, 3-acetyl Aromatic monobasic acid anhydrides such as benzoic anhydride, aromatic dibasic acid anhydrides such as phthalic anhydride, and the like can be widely exemplified. Suitable carboxylic acid anhydrides are aliphatic monobasic acid anhydrides and aromatic monobasic acid anhydrides. More preferably, it is an aliphatic monobasic acid anhydride, and most preferably,
These are acetic anhydride, propionic anhydride, valeric anhydride, isovaleric anhydride, butyric anhydride, isobutyric anhydride or pivalic anhydride which are industrially available at low cost.

The catalyst used in the present invention is a rare earth catalyst represented by the general formula (1), and has the general formula (1):
In RE, scandium, yttrium,
Lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium,
Dysprosium, holmium, erbium, thulium,
The rare earth atoms of ytterbium and lutetium are preferred. RE may be one kind or two or more kinds of rare earth atoms. Further, Rf may be a perfluoroalkyl group such as a trifluoromethyl group, a pentafluoroethyl group, a nonafluorobutyl group, or a group having a perfluoroalkoxy group in the side chain of the polymer such as Nafion resin. .

The amount of the rare earth catalyst used is usually 0.01 to 200 mol%, preferably 0.1 to 100 mol%, and more preferably 1 to 30 mol with respect to the aromatic compound as a raw material. %. If the amount is less than the above range, the reaction becomes slow, so that it is not economical. On the other hand, if the amount exceeds the above range, it may be used in a large amount, but the reaction rate is not substantially improved, so that there is no economical advantage. The amount of the group III element nitrate used is not less than the theoretical amount as a nitrating agent, and the amount of NO ₃ contained in the nitrate is equal to or more than the molar amount of the nitro group to be introduced into the aromatic compound. It should be. The amount of the carboxylic acid anhydride to be used may be an equimolar amount or more with respect to the nitro group to be introduced, preferably an equimolar amount to 10 times molar amount, more preferably 3 times to 7 times molar amount. .

The reaction of the present invention can be carried out without solvent, but a solvent may be used. As the solvent, a halogenated hydrocarbon represented by dichloromethane, chloroform, dichloroethane, chlorobenzene, etc., acetonitrile,
Nitrile compounds represented by propylonitrile, butyronitrile, malononitrile, adiponitrile, etc.,
Although nitro compounds such as nitromethane can be widely used as a solvent, halogenated hydrocarbons, nitrile compounds and nitro compounds are preferable from the viewpoint of high solubility of raw materials and catalysts. Moreover, it does not interfere even if these mixed solvents are used. The amount of the solvent used is usually 1 to 100 times by weight, preferably 2 to 5 times that of the aromatic compound.
It is 0 times by weight, more preferably 3 to 20 times by weight. It may be used in a large amount exceeding the above range, but it is not practical because the reaction rate is significantly reduced.

The reaction temperature varies depending on the reaction solvent used and the amount of catalyst, but it is usually in the range of -100 ° C to 100 ° C, and preferably in the range of room temperature to 50 ° C. The reaction time also varies depending on the reaction conditions, but is usually 10 minutes to 1
The reaction ends at 00 hours.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION After the completion of the nitration reaction of the present invention, post-treatment is carried out according to a conventional method to obtain a nitro compound which is a target compound. For example, an organic solvent having a relatively low boiling point which is usually used as an extraction solvent in the reaction mixture, for example, benzene, toluene, diethyl ether, dichloromethane, chloroform, etc. are added and washed with water,
The target compound, a nitro compound, can be obtained from the organic layer. Further, if necessary, isolation and purification can be further carried out by column chromatography, distillation, recrystallization and the like.

The reason why the nitration reaction proceeds well in the presence of the rare earth catalyst, the group III element nitrate, and the carboxylic acid anhydride is shown below. The rare earth-based catalyst is considered to have a catalytic action for the nitration reaction as a so-called Lewis acid. As the first step of the reaction, a rare earth catalyst acts on the reaction of the group III element nitrate with the carboxylic acid anhydride to produce a mixed acid anhydride of carboxylic acid and nitric acid such as acetyl nitrate. In the second step of the reaction, the rare-earth catalyst accelerates the reaction in which the mixed acid anhydride of carboxylic acid such as acetyl nitrate and nitric acid produced in the first step serves as a nitrating agent to nitrate aromatic compounds. It is considered that

[0015]

EXAMPLES The present invention will be described in more detail below with reference to examples. Example 1 Scandium tris (trifluoromethanesulfonate) 146.7 mg, m-xylene 318.5 mg, acetic anhydride 1.42 ml, scandium nitrate tetrahydrate 303 mg, and acetonitrile 5 ml were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. Then, the ether layer was concentrated under reduced pressure, and the remaining product was analyzed by HPLC. The yield of 2-nitro-m-xylene was 16%, and the yield of 4-nitro-m-xylene was 79%.

Examples 2 to 5 The same experiment as in Example 1 was conducted except that the nitrate shown in Table 1 was used as the nitrate. The yield of the obtained nitro compound is shown in Table 1.

[0017]

[Table 1]

Example 6 Tris (trifluoromethanesulfonic acid) scandium 146.7 mg, benzene 243.4 mg, acetic anhydride 1.4
2 ml, scandium nitrate tetrahydrate 303 mg, and acetonitrile 5 ml were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. After that, the ether layer was concentrated under reduced pressure, and the remaining product was subjected to HPLC.
Was analyzed by. The yield of nitrobenzene was 81%.

Examples 7 to 8 Experiments were conducted in the same manner as in Example 6 except that the nitrate shown in Table 2 was used as the nitrate. The yield of nitrobenzene is shown in Table 2.

[0020]

[Table 2]

Example 9 Tris (trifluoromethanesulfonic acid) scandium 146.7 mg, toluene 276 mg, acetic anhydride 1.42 m
1, scandium nitrate tetrahydrate (303 mg) and acetonitrile (5 ml) were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. After that, the ether layer was concentrated under reduced pressure, and the remaining product was subjected to HPLC.
Was analyzed by. The yield of 2-nitrotoluene is 52%, 4
The yield of -nitrotoluene was 35%.

Example 10 Scandium tris (trifluoromethanesulfonate) 146.7 mg, anisole 324 mg, acetic anhydride 1.42
ml, scandium nitrate tetrahydrate 303 mg, and acetonitrile 5 ml were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. After that, the ether layer was concentrated under reduced pressure, and the remaining product was subjected to HPLC.
Was analyzed by. The yield of 2-nitroanisole is 59
%, The yield of 4-nitroanisole was 27%.

Example 11 Tris (trifluoromethanesulfonic acid) scandium 146.7 mg, toluene 276 mg, acetic anhydride 1.42 m
1, aluminum nitrate nonahydrate tetrahydrate (375 mg) and acetonitrile (5 ml) were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. Then, the ether layer was concentrated under reduced pressure, and the remaining product was analyzed by HPLC. The yield of 2-nitrotoluene was 50% and the yield of 4-nitrotoluene was 34%.

Example 12 Tris (trifluoromethanesulfonic acid) scandium 146.7 mg, anisole 324 mg, acetic anhydride 1.42
ml, aluminum nitrate nonahydrate tetrahydrate (375 mg) and acetonitrile (5 ml) were sequentially added, and the mixture was stirred at room temperature for 2 hours. 20 ml of water was added to the reaction solution, and the product was extracted with ether. Then, the ether layer was concentrated under reduced pressure, and the remaining product was analyzed by HPLC. The yield of 2-nitroanisole was 56% and the yield of 4-nitroanisole was 25%.

[0025]

INDUSTRIAL APPLICABILITY According to the present invention, it becomes possible to carry out a nitration reaction for an aromatic compound, which has heretofore required an excessive amount of nitric acid, with a stoichiometric amount of nitrate. This leads to a mild reaction condition and a reduction in the processing load of the reaction waste liquid, which is of great industrial and practical value.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4H006 AA02 AB84 AC51 BA08 BA09                       BA36 BA37 BA50                 4H039 CA72 CD10

Claims (3)

[Claims] 1. A method of nitrating an aromatic compound having at least one substitutable hydrogen in an aromatic ring, wherein a catalyst represented by the following general formula (1) RE (OSO ₂ Rf) ₃ (1) In the formula, RE represents a rare earth element, and Rf represents a perfluoroalkyl group which may have a substituent), a rare earth catalyst represented by the formula III, a nitrate of a Group III element of the periodic table, and nitro in the presence of a carboxylic acid anhydride. A method for producing an aromatic nitro compound, characterized by comprising: 2. A catalyst represented by the following general formula (1) RE (OSO ₂ Rf) ₃ (1) (wherein RE represents a rare earth element and Rf represents a perfluoroalkyl group which may have a substituent). In the presence of a rare earth catalyst and a carboxylic acid anhydride represented by), nitration of an aromatic compound is carried out with a nitrating agent consisting of a nitrate of a group III element of the periodic table. Method. 3. A nitrate of a group III element of the periodic table is scandium, yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium. Terbium, dysprosium, holmium,
Erbium, thulium, ytterbium, lutecium,
The nitration method according to claim 2, which is a nitrate of at least one element selected from the group consisting of boron, aluminum, gallium, indium and thallium.