JP2006290818A - Method for producing high-purity aromatic secondary amine - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing high-purity aromatic secondary amine in an industrial scale in no need of a specific pressurized vessel in high yield and selectivity, as the side reaction of partial reduction of the aromatic ring is suppressed. <P>SOLUTION: In the method for producing a specific aromatic secondary amine by hydrogenolysis of a specific tertiary amine by using a transition metal catalyst, a hydrogen donor reagent is used as a reduction agent for the hydrogenolysis reaction. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing an aromatic secondary amine by hydrogenolysis of a tertiary amine.

  Aromatic secondary amines are useful compounds as precursors of tertiary amines widely used as organic electroluminescence and electrophotographic photoreceptors. Aromatic secondary amines are also used as resin aging inhibitors and pharmaceutical intermediates. It is a very useful compound for such applications.

  Conventionally, when synthesizing an aromatic secondary amine compound, a method mainly obtained by a condensation reaction using a corresponding aromatic primary amine as a raw material has been the main method. For example, a method of condensing two aromatic primary amine molecules (for example, see Patent Documents 1 and 2). A method in which an aromatic primary amine and a corresponding phenol are subjected to dehydration condensation (see, for example, Patent Document 3). A method of reacting an aromatic primary amine with a corresponding aromatic nitro compound or a corresponding cyclohexanone derivative (for example, see Patent Document 4). There is a method of condensing an aromatic primary amine and a corresponding aromatic halogen compound (for example, see Patent Documents 5 and 6). However, these production methods are difficult to apply industrially due to high temperature and high pressure conditions, or difficult to obtain and use industrially due to toxicity such as carcinogenicity of the aromatic primary amine as a raw material. There were many.

  As a solution to this problem, a method has been proposed in which a benzylamine and a corresponding aromatic halogen compound are reacted to form a tertiary amine once, and the benzyl group is deprotected by hydrogenolysis to obtain an aromatic secondary amine (for example, And Patent Document 7).

  On the other hand, hydrogenolysis reaction (debenzylation reaction) using formic acid as a reducing agent is disclosed, but the examples described are limited to aliphatic amines such as amino acids and peptide compounds, The effect on group secondary amines was unknown (for example, see Non-Patent Document 1). In addition to formic acid, hydrogen donor reagents can be used as reducing agents, but examples of application to debenzylation reactions are only formic acid or formates, and the applicability of other reagents was unclear (for example, Non-Patent Document 2).

JP 2000-344720 A JP-A-6-100504 JP 2000-95736 A Japanese Patent Laid-Open No. 2002-30047 US Pat. No. 5,576,460 Japanese Patent No. 3161360 WO02 / 076922 B. ElAmin, G.M. M.M. Anantharamiah, G.A. P. Royer, and G.G. E. Means, J.M. Org. Chem. , 44, 3442 (1979). R. A. W. Johnstone, A.M. H. Wilby, I.D. D. Entwistle, Chem. Rev. 85, 129-170 (1985).

The present inventors made a follow-up of the method described in Patent Document 7, but a part of the aromatic ring (a part of Ar ₁ or Ar ₂ in the general formula (1)) was reduced during the hydrogenolysis. It has been found that there is a problem of by-produced impurities. This is a major problem in organic electroluminescence and pharmaceutical intermediates where high purity is required for the product.

  In addition, since chloroform used as a solvent is difficult to industrially use due to toxicity and environmental problems, the present inventors have examined other solvents in the method described in Patent Document 7, It was found that the use of chloroform as a solvent was indispensable as the speed decreased, and impurities in which a part of the aromatic ring was reduced increased. Furthermore, since the method described in Patent Document 7 is performed under a pressurized condition using hydrogen gas, a special pressurizing facility is required.

  An object of the present invention is to provide a method for producing an aromatic secondary amine which overcomes these problems of the prior art. In other words, the generation of impurities in which a part of the aromatic ring in question has been reduced is suppressed, and a special pressurization facility is used with a solvent that can be used industrially with high yield and high selectivity. An object of the present invention is to provide a method for producing a high purity aromatic secondary amine which is not required.

  As a result of intensive studies to solve the above problems, the present inventors have solved the above problem by using a hydrogen donating reagent as a reducing agent when performing a hydrogenolysis reaction, and achieved a high yield and a high yield. The inventors have found that a high-purity aromatic secondary amine can be obtained with a selectivity, and have completed the present invention.

  That is, the present invention provides the following general formula (1)

（式中、Ｒは炭素数１〜３０の置換もしくは無置換のアルキル基またはアリールアルキル基を表す。Ａｒ_１およびＡｒ_２は各々独立して置換もしくは無置換のアリール基を表す。）
で表される三級アミンを遷移金属触媒を用いて加水素分解することにより、一般式（２）

(In the formula, R represents a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms or an arylalkyl group. Ar ₁ and Ar ₂ each independently represent a substituted or unsubstituted aryl group.)
Hydrogenolysis of the tertiary amine represented by the general formula (2) using a transition metal catalyst

（式中、Ａｒ_１およびＡｒ_２は各々独立して置換もしくは無置換のアリール基を表す。）
で表される芳香族二級アミンを製造する方法において、加水素分解に用いる還元剤として水素供与試剤を用いることを特徴とする芳香族二級アミンの製造方法に関する。

(In the formula, Ar ₁ and Ar ₂ each independently represent a substituted or unsubstituted aryl group.)
In the method for producing an aromatic secondary amine represented by the formula (2), the present invention relates to a method for producing an aromatic secondary amine, wherein a hydrogen donor reagent is used as a reducing agent used for hydrogenolysis.

  Next, the present invention will be described in more detail.

  The tertiary amine used in the present invention is a compound represented by the above general formula (1). In the general formula (1), R represents a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms or an arylalkyl group. Examples of such a substituent include a benzyl group, a methyl group, 4-biphenyl. Rylmethyl group, diphenylmethyl group, fluorenyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, or substituted benzyl group, such as 4-methoxybenzyl group, 2-methoxybenzyl group, 4-hydroxybenzyl group 4-acetylaminobenzyl group, 4-acetoxybenzyl group, 4-chlorobenzyl group, 4-bromobenzyl group, 4-methylbenzyl group, 4-aminobenzyl group, 3-aminobenzyl group, 2-aminobenzyl group, 4-nitrobenzyl group, 4-acetylbenzyl group and the like can be mentioned. Of these, a benzyl group is preferred.

In the general formula (1), Ar ₁ and Ar ₂ each independently represent a substituted or unsubstituted aryl group. Examples of such an aryl group include a phenyl group, a 4-biphenylyl group, 3 -Biphenylyl group, 2-biphenylyl group, 1-naphthyl group, 2-naphthyl group, o-tolyl group, m-tolyl group, p-tolyl group, anthryl group, phenanthryl group, terphenylyl group and the like can be mentioned.

  Further, specific examples of the compound represented by the general formula (1) include N, N-diphenylbenzylamine, N-1-naphthyl-N-phenylbenzylamine, N-phenyl-Nm-tolylbenzyl. Examples include amine, di (p-tolyl) benzylamine, N, N-di (4-biphenylyl) benzylamine, N, N-di (4-p-terphenylyl) benzylamine and the like.

  These tertiary amines can generally be obtained by reacting benzylamine with the corresponding aromatic halide using a transition metal catalyst. However, the tertiary amine obtained by this method often contains a small amount of a halogen element derived from an aromatic halide as a raw material. These halogen elements are generally considered to be contained as inorganic compounds or organic compounds, but in many cases, they are considered to be contained in the form of inorganic salts. However, it has been found that when a tertiary amine containing a large amount of halogen element is used in this reaction, the reaction rate is remarkably reduced. For this reason, it is appropriate to use a tertiary amine used as a raw material having a content of a halogen element as an impurity of 1% by weight or less, preferably 0.1% by weight or less. The tertiary amine having a low halogen element content is washed by dispersing the obtained tertiary amine in a polar solvent such as water-containing methanol, or the obtained tertiary amine is temporarily washed with an organic solvent. And a method of obtaining the target product from the organic layer by crystallization operation after washing with water and phase separation.

  The aromatic secondary amine obtained by the present invention is a compound represented by the above general formula (2), for example, diphenylamine, m-tolylphenylamine, di (p-tolyl) amine, 1-naphthylphenylamine. , Di (4-biphenylyl) amine, di (4-p-terphenylyl) amine, and the like.

  In the present invention, a hydrogen donating reagent is used as a reducing agent used for hydrogenolysis. Examples of the hydrogen donating agent include formic acid, formates, cyclohexene, 1,4-cyclohexadiene, hydrazine, phosphinic acid, phosphinates, phosphorous acid, phosphites, sodium borohydride and the like. Examples of the formate salts include ammonium formate, sodium formate, and potassium formate. Of these, formic acid or ammonium formate is preferred. Furthermore, it is preferable to use formic acid because it is easily available and the product is easily isolated.

  The amount of the reducing agent used is not particularly limited, but is in the range of 1 to 50 times mol, preferably 2 to 10 times mol, of the raw material tertiary amine. When the amount used is less than 1 molar amount, the reaction is not completed. On the other hand, if the amount is more than 50 times the molar amount, impurities may increase.

  As the transition metal catalyst used in the present invention, a catalyst generally used in a hydrogenation reaction can be used. For example, examples of the metal species include Pd, Pt, Ru, Rh, and the like, and both water-containing products and dry products can be used. Specific examples include 5% Pd carbon powder, 10% Pd carbon powder, 20% Pd carbon powder, and 20% palladium hydroxide-carbon powder.

  In the present invention, it is preferable to add water as an additive. This is because impurities generated by a dehydration condensation reaction between the produced aromatic secondary amine and formic acid or phosphoric acid are suppressed by the addition of water and the selectivity is improved. The amount of water to be added is not particularly limited, but is in the range of 1 to 200 times mole amount, preferably 10 to 30 times mole amount with respect to the tertiary amine of the raw material. If the amount used is less than 1 mol, impurities due to dehydration condensation increase, and if it is more than 200 mol, production efficiency decreases.

  In the present invention, the reaction solvent may or may not be used, but in many cases, the tertiary amine as a raw material is a solid, so it is preferable to use a solvent. As the solvent to be used, an aromatic hydrocarbon is preferable because the solubility of the tertiary amine as a raw material is relatively high. For example, benzene, toluene, xylene and the like can be mentioned.

  In this invention, reaction temperature is the range of 0-150 degreeC, Preferably it is the range of 50-100 degreeC. When the reaction temperature is low, the reaction rate decreases and the production efficiency decreases. On the other hand, when the reaction temperature is too high, a part of the aromatic ring is reduced or impurities that cause dehydration condensation increase, which is not preferable.

  In the present invention, the pressure during the reaction is not particularly limited. The reaction may be performed under pressure or atmospheric pressure, and in some cases under reduced pressure. For example, an absolute pressure range of 0 to 1.1 MPa, preferably a special manufacturing apparatus is not required, and therefore atmospheric pressure is used.

  In the reaction of the present invention, it is preferable to feed a hydrogen-donating reagent after charging other raw materials. This makes it possible to control the amount of reaction heat and by-product carbon dioxide gas.

  According to the present invention, a side reaction in which a part of an aromatic ring is reduced is suppressed, and a high-purity aromatic secondary amine is produced in a high yield and high selectivity without using a special pressure vessel. Can be produced on a scale.

  The present invention will be described in more detail with reference to the following examples. However, these examples show the outline of the present invention, and the present invention is not limited to these examples.

[Measurement of reaction yield and conversion]
The apparatus used for the measurement is shown below.

Device: GC-17A (manufactured by Shimadzu Corporation)
Column: Capillary column NEUTRA BOND-5 (manufactured by GL Sciences)
(0.32mm ID x 30m)
Detector: FID (hydrogen flame ionization detector)
[Measurement of bromine element content]
The apparatus and conditions used for the measurement are shown below.

    Pretreatment: About 5 mg of a sample was accurately weighed, sealed and burned, and then absorbed into an absorbing solution to obtain an IC test solution.

Apparatus: Ion chromatograph IC-2001 (manufactured by Tosoh Corporation)
Column: TSK guard column Super IC-AP (4.6 mm ID x 1 cm) + TSK gel Super IC-AP (4.6 mm ID x 15 cm) (manufactured by Tosoh Corporation)
Eluent: 2.7 mmol / l-NaHCO ₃ + 1.8 mmol / l-Na ₂ CO ₃
Flow rate: 0.8 ml / min Detector: Electrical conductivity detector (IC-2001 built-in) + UV-visible detector UV-8020 [measurement wavelength is 210 nm] (manufactured by Tosoh Corporation)
Example 1
In a 200 ml flask equipped with a thermometer and a condenser, 71.1 g of toluene, 12.4 g of N-1-naphthyl-N-phenylbenzylamine, 14.4 g of water, 10% Pd carbon powder and water-containing product (manufactured by NE Chemcat) , PE type) 2.5 g (dry base weight). After raising the internal temperature to 75 ° C., 9.2 g of formic acid was slowly dropped from the dropping funnel. Simultaneously with the start of dropping, the generation of exhaust gas was confirmed, and the entire amount was dropped over about 2 hours. After completion of the dropwise addition, the internal temperature was gradually raised, and aging was performed for 10 hours in a reflux state (about 90 ° C.). The reaction solution was analyzed by gas chromatography, and the reaction yield and the conversion rate were determined. %, And the impurities in which the raw material and part of the aromatic ring were reduced were not detected.

  Thereafter, the reaction mixture was filtered to remove the Pd catalyst. The obtained organic layer was concentrated, recrystallized from toluene and hexane, and the obtained crystal was dried. As a result, 6.7 g of N-phenyl-1-naphthylamine (yield 76.0%, purity 99.7) was obtained. %)was gotten. At this time, impurities in which a part of the aromatic ring was reduced and a dehydration condensation product with formic acid were not detected.

  In addition, it was 120 ppm when the quantity of the bromine element contained in the raw material N-1-naphthyl-N-phenylbenzylamine was measured by the closed combustion-ion chromatography method.

Example 2
In a 200 ml flask equipped with a thermometer and a condenser, 78.3 g of toluene, 18.1 g of N, N-di (4-biphenylyl) benzylamine, 15.8 g of water, 10% Pd carbon powder and water-containing product (N Chemchem Cat) Manufactured, PE type) 3.6 g (dry base weight) was charged. After raising the internal temperature to 75 ° C., 10.1 g of formic acid was slowly dropped from the dropping funnel. Simultaneously with the start of dropping, the generation of exhaust gas was confirmed, and the entire amount was dropped over about 1 hour. After completion of the dropwise addition, the internal temperature was gradually increased, and aging was performed for 8 hours in a reflux state (about 90 ° C.). When the reaction solution was analyzed by gas chromatography, it was found that 98.0% di (4-biphenylyl) amine as the target product and 0.6% dehydration condensation product with formic acid were produced. Impurities that were partially reduced were not detected.

  Thereafter, tetrahydrofuran was added to the reaction mixture to dissolve the product, and the Pd catalyst was removed by filtration. The obtained organic layer was concentrated, toluene was added for recrystallization, and the obtained crystal was dried. As a result, 12.7 g (yield 80.0%, purity 99.9) of di (4-biphenylyl) amine was obtained. %)was gotten. At this time, impurities in which a part of the aromatic ring was reduced and a dehydration condensation product with formic acid were not detected.

  In addition, it was 150 ppm when the quantity of the bromine element contained in the raw material N, N-di (4-biphenylyl) benzylamine was measured by a closed combustion-ion chromatography method.

Examples 3-6
An aromatic secondary amine was produced in the same manner as in Example 1 except that the tertiary amine as a raw material was changed as shown in Table 1 in Example 1. The reaction solution was analyzed by gas chromatography in the same manner as in Example 1 to determine the reaction yield and the conversion rate. The results are shown in Table 1.

実施例７
温度計およびコンデンサーの付いた１００ｍｌフラスコに、トルエン１０ｍｌ、水１．０ｇ、Ｎ−１−ナフチル−Ｎ−フェニルベンジルアミン ０．３１ｇ、２０％水酸化パラジウム炭素粉末・含水品（デグッサ製、Ｅ１０１ ＮＥ／Ｗタイプ）１２４ｍｇ（ドライベース重量）およびギ酸アンモニウム０．６３ｇを仕込んだ。その後、徐々に昇温し、還流状態で１８時間反応させた。ガスクロマトグラフィーにて反応液を分析したところ、目的物であるＮ−フェニル−１−ナフチルアミンが９８．４％、原料の三級アミンが１．６％、ギ酸との脱水縮合生成物および芳香環の一部が還元された不純物は未検出であった。

Example 7
In a 100 ml flask equipped with a thermometer and a condenser, 10 ml of toluene, 1.0 g of water, 0.31 g of N-1-naphthyl-N-phenylbenzylamine, 20% palladium hydroxide carbon powder / water-containing product (Degussa, E101 NE / W type) 124 mg (dry base weight) and 0.63 g ammonium formate were charged. Then, it heated up gradually and was made to react for 18 hours by a recirculation | reflux state. The reaction solution was analyzed by gas chromatography. As a result, N-phenyl-1-naphthylamine as the target product was 98.4%, the tertiary amine as a raw material was 1.6%, dehydration condensation product with formic acid, and aromatic ring. Impurities that were partially reduced were not detected.

Example 8
In a 100 ml flask equipped with a thermometer and a condenser, 40 ml of toluene, 1.55 g of N-1-naphthyl-N-phenylbenzylamine, 309 mg of 20% palladium hydroxide carbon powder and water-containing product (Degussa, E101 NE / W type) (Dry base weight) and 1.2 g of formic acid were charged. Then, it heated up gradually and was made to react in a recirculation | reflux state for 20 hours. When the reaction solution was analyzed by gas chromatography, the target product, N-phenyl-1-naphthylamine, was 75.7%, the amount of raw material tertiary amine was 3.8%, and a dehydration condensation product with formic acid was obtained. 17.9% was produced. An impurity in which a part of the aromatic ring was reduced was not detected.

Example 9
A 100 ml flask equipped with a thermometer and a condenser was charged with 35.6 g of toluene, 3.1 g of N-1-naphthyl-N-phenylbenzylamine, 0.62 g of 10% palladium carbon powder and dried product (manufactured by Nacalai Tesque). . After the internal temperature was raised to 75 ° C., 2.3 g of formic acid was slowly dropped from the dropping funnel. Simultaneously with the start of dropping, the generation of exhaust gas was confirmed, and the entire amount was dropped over about 30 minutes. After completion of the dropwise addition, the internal temperature was gradually raised, and the reaction was carried out for 4 hours in a reflux state (about 90 ° C.). Analysis of the reaction solution by gas chromatography revealed that 98.7% of the target product, N-phenyl-1-naphthylamine, a dehydration condensation product with the raw material tertiary amine and formic acid was not detected, and the aromatic ring The impurity in which a part of the impurity was reduced was 0.6%.

  In addition, it was 2.2 weight% when the quantity of the bromine element contained in N-1-naphthyl-N-phenyl benzylamine which is a raw material was measured with the closed combustion-ion chromatography method.

Example 10
Into a 100 ml flask equipped with a thermometer and a condenser, 17.8 g of toluene, 4.1 g of N, N-di (4-biphenylyl) benzylamine, 4.1 g of cyclohexene, 10% Pd carbon powder / water-containing product (N Chemchem Cat) Manufactured, PE type) 0.82 g (dry base weight) was charged. The temperature was gradually raised, and the reaction was carried out in a reflux state (about 90 ° C.) for 8 hours. Analysis of the reaction solution by gas chromatography revealed that 99.5% of the target product di (4-biphenylyl) amine was produced, and impurities in which the raw material and part of the aromatic ring were reduced were not detected. It was.

  In addition, it was 500 ppm when the quantity of the bromine element contained in the raw material N, N-di (4-biphenylyl) benzylamine was measured by a closed combustion-ion chromatography method.

Example 11
To a 100 ml flask equipped with a thermometer and a condenser, 17.8 g of toluene, 3.1 g of N-1-naphthyl-N-phenylbenzylamine, 6.6 g of 50% aqueous phosphinic acid solution, 10% Pd carbon powder and water-containing product (N -0.62 g (dry base weight) made by Echemcat, PE type) was charged. The temperature was gradually raised, and the reaction was carried out in a reflux state (about 90 ° C.) for 14 hours. Analysis of the reaction solution by gas chromatography revealed that 99.4% of the target N-phenyl-1-naphthylamine was produced, and the tertiary amine and a part of the aromatic ring as raw materials were reduced. Was not detected.

Example 12
In Example 2, the reaction was carried out in the same manner as in Example 2 except that 0.78 g of sodium bromide was added as a bromine source (1.0% by weight with respect to the raw material). After reacting at reflux for 18 hours, the reaction mixture was analyzed by gas chromatography. As a result, production of di (4-biphenylyl) amine, which was the target product, was 12.8%, and most of the rest was the raw material. The conversion rate remained at 13%. Thus, the progress of the reaction was significantly slowed by the addition of sodium bromide.

Examples 13-16
The same as Example 12 except that the amount of sodium bromide added in Example 12 was changed to 0.002%, 0.05%, 0.1%, and 0.5% by weight with respect to the raw material. The reaction was carried out. The conversion of the reaction was confirmed by gas chromatography as in Example 12. The conversion after the reaction for 18 hours is shown in FIG. Example 12 is also shown in FIG. As apparent from FIG. 1, it can be seen that the addition of sodium bromide significantly reduces the reaction rate.

Comparative Example 1
In a 100 ml flask equipped with a thermometer and a condenser, 91.0 g of chloroform, 9.6 g of ethanol, 0.62 g of N-1-naphthyl-N-phenylbenzylamine, 20% palladium hydroxide carbon powder / water-containing product (manufactured by Degussa, E101 NE / W type) 62 mg (dry base weight) was charged. After replacing the system with hydrogen gas, the reaction was carried out by stirring for 24 hours at room temperature with a balloon filled with hydrogen. Analysis of the reaction solution by gas chromatography revealed that 98.1% of the target N-phenyl-1-naphthylamine was produced and the raw material had disappeared, but impurities in which a part of the aromatic ring was reduced were also present. A total of 1.2% was produced.

Comparative Example 2
In a 100 ml flask equipped with a thermometer and condenser, 80.8 g of methylene chloride, 9.6 g of ethanol, 0.62 g of N-1-naphthyl-N-phenylbenzylamine, 20% palladium hydroxide carbon powder and water-containing product (manufactured by Degussa) , E101 NE / W type) 62 mg (dry base weight) was charged. After replacing the system with hydrogen gas, the reaction was carried out by stirring at room temperature for 4 hours with a balloon filled with hydrogen. When the reaction solution was analyzed by gas chromatography, the amount of N-phenyl-1-naphthylamine, which was the target product, was 65.2%, the remaining amount of the raw material was 31.5%, Impurities whose parts were reduced were also generated in a total of 2.3%.

It is the figure which showed the relationship between NaBr addition amount and reaction conversion rate.

Claims (6)

General formula (1)

(In the formula, R represents a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms or an arylalkyl group. Ar ₁ and Ar ₂ each independently represents a substituted or unsubstituted aryl group.)
Hydrogenolysis of the tertiary amine represented by the general formula (2) using a transition metal catalyst

(In the formula, Ar ₁ and Ar ₂ each independently represent a substituted or unsubstituted aryl group.)
A method for producing an aromatic secondary amine represented by the formula: wherein a hydrogen donor reagent is used as a reducing agent used for hydrogenolysis. The method for producing an aromatic secondary amine according to claim 1, wherein in the general formula (1), R is a benzyl group. The method for producing an aromatic secondary amine according to claim 1 or 2, wherein the hydrogen donor reagent used is formic acid or formate. Furthermore, water is added as an additive, The manufacturing method of the aromatic secondary amine of Claims 1-3 characterized by the above-mentioned. The method for producing an aromatic secondary amine according to claim 1, wherein an aromatic hydrocarbon is used as a reaction solvent. The method for producing an aromatic secondary amine according to claim 1, wherein the hydrogenolysis reaction is performed under atmospheric pressure.

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