JP2023025324A - Method for recovering palladium catalyst - Google Patents

Abstract

To recover a palladium catalyst used in a coupling reaction between an aromatic halogen compound and an ethynyl compound by a simple method and at high yield.SOLUTION: In a coupling reaction between an aromatic halogen compound represented by the general formula (1) and an ethynyl compound represented by the general formula (2), in the presence of a nitrogen-containing organic solvent, palladium carbon, a phosphorus compound, and a copper compound are added to effect the coupling reaction, and then a nonaqueous organic solvent and water are added to the resultant reaction liquid, followed by recovering palladium carbon by filtration (where R is a polar substituent, X is a halogen element, n is an integer of 1 to 3, A is a hydrocarbon group having a hydroxy group or a trialkylsilyl group).SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a method for recovering a palladium catalyst used in a coupling reaction.

A coupling reaction using an aromatic halogen compound and a palladium catalyst is an important reaction for forming new carbon-carbon bonds. For example, in the Sonogashira coupling reaction, an ethynylbenzene compound in which an ethynyl compound is bound to an aromatic ring can be synthesized by coupling an aromatic halogen compound and an ethynyl compound using a palladium catalyst. As the palladium catalyst used here, organic palladium such as dichlorobis(triphenylphosphine)palladium and tetra(triphenylphosphine)palladium is generally used (see Patent Document 1).

However, palladium is a noble metal and palladium catalysts are very expensive. However, the above-mentioned palladium catalysts are dissolved in organic solvents, and it is very difficult to recover only the palladium catalysts from the organic solvent after the reaction. However, it was difficult to recover it, and it was almost impossible to recover it. As an example of recovery of this palladium catalyst, hydrogen ^is introduced after the reaction to reduce and recover palladium. Equipment is required (see Patent Document 2).

In addition, in a similar Suzuki coupling reaction using a palladium catalyst, examples of recovering the palladium catalyst have been reported, but the compounds are limited to special cases, and the pH of the aqueous layer is used for recovery. must be adjusted, the operation is complicated and industrial adaptation is difficult (Patent Document 3).

Therefore, it has been demanded to recover the palladium catalyst used in the coupling reaction by an industrially simple operation.

China Patent No. 103183722 JP-A-63-319054 Japanese Patent Application Publication No. 2018-516843

An object of the present invention is to recover a palladium catalyst used in the coupling reaction between an aromatic halogen compound and an ethynyl compound by a simple method and in high yield.

（式中、Ｒは極性置換基、Ｘはハロゲン元素、ｎは１から３の整数を示す）
で表される芳香族ハロゲン化合物と下記一般式（２）

（式中Ａは、水酸基を有する炭化水素基または、トリアルキルシリル基を示す）
で表されるエチニル化合物とのカップリング反応において、窒素含有有機溶媒下、パラジウム炭素、リン化合物、銅化合物を加えてカップリング反応を行い、得られた反応液に非水系有機溶媒と水を添加した後、ろ過によりパラジウム炭素を回収することを特徴とする。 The palladium catalyst recovery method of the present invention is represented by the following general formula (1)

(Wherein, R is a polar substituent, X is a halogen element, and n is an integer of 1 to 3)
An aromatic halogen compound represented by the following general formula (2)

(In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group)
In the coupling reaction with the ethynyl compound represented by, palladium carbon, a phosphorus compound, and a copper compound are added in a nitrogen-containing organic solvent to perform the coupling reaction, and a non-aqueous organic solvent and water are added to the resulting reaction solution. After that, palladium carbon is recovered by filtration.

The method of recovering the palladium catalyst used in the coupling reaction of the present invention is carried out using palladium carbon in the Sonogashira coupling reaction, and the palladium precipitated by adding a non-aqueous organic solvent and water after the reaction Carbon can be recovered by filtration. The operation is a very simple method, and by recovering palladium carbon, the catalyst can be recovered industrially.

In addition, since the aromatic compound having an ethynyl group obtained by the coupling reaction has a reactive ethynyl group, it can be used as a raw material for fine chemicals, pharmaceuticals, agricultural chemicals, resins, plastics, electronic materials, and optical materials. It is possible to use Furthermore, by recovering palladium on carbon in a high yield, the production cost of aromatic compounds having an ethynyl group can be reduced.

（式中、Ｒは極性置換基、Ｘはハロゲン元素、ｎは１から３の整数を示す）
で表される芳香族ハロゲン化合物である。ここで、Ｒは極性置換基を示し、一般的には、ニトロ基、アミノ基、カルボキシル基、ヒドロキシ基などを示し、アミノ基、ヒドロキシ基は保護基を導入した形でも良い。好ましい極性置換基として、反応性が低いニトロ基を有する化合物、アルカリ性を示すアミノ基が好ましい。特にニトロ基がベンゼン環に一つ結合したニトロベンゼン化合物や、アミノ基がベンゼン環に一つ結合したアニリン類は、工業的に入手が容易であり、特に好ましい。 The details of the production method of the present invention are described below.
The raw material used in the present invention has the following general formula (1)

(Wherein, R is a polar substituent, X is a halogen element, and n is an integer of 1 to 3)
is an aromatic halogen compound represented by Here, R represents a polar substituent and generally represents a nitro group, an amino group, a carboxyl group, a hydroxy group, etc. The amino group and hydroxy group may be in the form of introducing a protective group. As preferred polar substituents, a compound having a nitro group with low reactivity and an amino group exhibiting alkalinity are preferred. In particular, nitrobenzene compounds in which one nitro group is bonded to a benzene ring and anilines in which one amino group is bonded to a benzene ring are readily available industrially and are particularly preferred.

n represents an integer of 1 to 3; Generally, it is difficult to obtain a compound in which three benzene rings are bonded, and n is preferably 1 or 2.

X represents a halogen element such as chlorine, bromine or iodine. Iodine generally has the highest reactivity in the coupling reaction and chlorine has the lowest reactivity. However, iodine compounds are expensive, and chlorine and bromine are particularly preferred.

Particularly preferred aromatic nitrohalogen compounds are 4-chloronitrobenzene, 3-chloronitrobenzene, 2-chloronitrobenzene, 4-bromonitrobenzene, 3-bromonitrobenzene, 2-bromonitrobenzene, 1-chloro-2,4-dinitrobenzene, 3,4-dinitrochlorobenzene, 1-bromo-2,4-dinitrobenzene, 3,4-dinitrobromobenzene and the like.

Preferred aromatic aniline compounds are 4-chloroaniline, 3-chloroaniline, 2-chloroaniline, 4-bromoaniline, 3-bromoaniline, 2-bromoaniline, 1-chloro-2,4-diaminobenzene, 3,4-diaminochlorobenzene, 1-bromo-2,4-diaminobenzene, 3,4-diaminobromobenzene and the like.

（式中Ａは、水酸基を有する炭化水素基または、トリアルキルシリル基を示す）
で表されるエチニル化合物を滴下または投入し、加熱させることで反応が進行する。 In the present invention, the coupling reaction is carried out by adding the aromatic compound having a polar substituent, palladium carbon, phosphorus compound, copper compound, and amine as raw materials to the nitrogen-containing organic solvent, which is the reaction solvent, followed by the following while stirring. general formula (2)

(In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group)
The reaction proceeds by dropping or adding an ethynyl compound represented by and heating.

Here, the nitrogen-containing organic solvent used as the reaction solvent is preferably N,N-dimethylacetamide, dimethylformamide, or N-methyl-2-pyrrolidone, and particularly preferably N,N-dimethylacetamide, which has high reactivity.

Since it is necessary to stir the chloroamine salt generated in the coupling reaction in the form of slurry, the nitrogen-containing organic solvent should be used in an amount of 3 to 10 times the weight of the starting aromatic halogen compound having a polar substituent. It is preferred, and it is particularly preferred to use 3 to 7 times by mass. When the amount of the nitrogen-containing organic solvent used is less than 3 times by mass, a compound such as a dimer formed by coupling the ethynyl compounds used in the reaction together is produced as a by-product, which is not preferable.

The palladium-carbon used in the coupling reaction is obtained by dispersing and supporting palladium (zero valence) on activated carbon as a carrier, and is also called palladium-carbon. Palladium on carbon can be used as either a dry product containing no water or a wet product containing water. Since palladium on carbon readily ignites in the air, it is industrially preferable to use a wet product containing water. The type of palladium on carbon affects the reactivity of the coupling reaction, and the commercially available palladium on carbon manufactured by N E Chemcat is particularly preferred because of its high reactivity. Among the palladium carbons manufactured by N E Chemcat, Type NE, Type K, and Type E, which have particularly high reaction yields, are more preferable. In particular, Type K and Type E are more preferable because the amount of palladium carbon used can be reduced.

Since palladium on carbon is an expensive catalyst, it is preferably 1.0 mol % or less with respect to the number of moles of the aromatic halogen compound, and more preferably 0.5 mol % or less because it is used in a smaller amount and can be produced at low cost.

The phosphorus compound used in the coupling reaction is preferably an organic phosphorus compound, preferably a hydrocarbon phosphine compound such as triphenylphosphine, trimethylphosphine, triethylphosphine, tri-n-propylphosphine, etc., which are generally available at low cost. Especially preferred is triphenylphosphine, which is available and easy to handle as a granular powder. The amount of the phosphorus compound used is preferably 4.0 equivalents or more with respect to palladium carbon, and more preferably 4.0 to 8.0 equivalents capable of forming a palladium complex.

A copper compound is used as the reaction initiator, and copper iodide, which is commonly available, is preferred. The amount of the copper compound used is preferably 0.1 to 1.0 equivalents, more preferably 0.1 to 0.5 equivalents, relative to palladium carbon.

In the Sonogashira coupling reaction, amines are added in order to trap the halogen produced as a by-product of the reaction. - tertiary amines such as butylamine and secondary amines such as diisobutylamine, diisopropylamine, and diisobutylamine are preferred, are inexpensive and readily available, have a low boiling point and can be removed by concentration, triethylamine, diisopropylamine, Diisobutylamine is more preferred.
The amount of the amine to be added is preferably 1.0 to 3.0 equivalents, more preferably 1.0 to 2.0 equivalents, relative to the starting aromatic halogen compound.

Further, it is preferable to add an alkali metal salt as an additive to the reaction, since the reaction yield may be improved. The alkali metal salt to be added is preferably a lithium salt, a sodium salt or a potassium salt, and includes potassium bromide, sodium bromide, lithium chloride, lithium bromide, lithium iodide and the like. , lithium iodide is more preferred. The amount of the alkali metal salt to be added is preferably 0.1 to 2.0 equivalents relative to the raw material aromatic halogen compound, and is 0.5 to 1.0 equivalents so that the Sonogashira coupling reaction can proceed further. is more preferred.

（式中、Ｂ^１、Ｂ^２は水素原子、または炭化水素基を示す）
で表される。Ｂ^１、Ｂ^２は、互いに同じでも異なっていてもよい。Ｂ^１、Ｂ^２は、好ましくは水素原子または炭素数１から５のアルキル基であり、例えば、水素、メチル基、エチル基、ｎ－プロピル基、イソプロピル基、ｎ－ブチル基、ｎ－ペンチル基などが挙げられる。一般式（３）で表されるエチニル化合物として、例えば２－プロペン－１－オール、２－メチル－３－ブチン－２－オール、３－ブチン－２－オール、３－メチル－４－ペンチン－３－オール、４－ペンチン－３－オール、４－メチル－５－ヘキシン－４－オール、５－ヘキシン－４－オール、等が挙げられる。 As the ethynyl compound, the compound represented by the general formula (2) is used. When A in the general formula (2) is a hydrocarbon group having a hydroxyl group, the ethynyl compound is preferably the following general formula (3)

(Wherein, B ¹ and B ² represent a hydrogen atom or a hydrocarbon group)
is represented by B ¹ and B ² may be the same or different. B ¹ and B ² are preferably a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, such as hydrogen, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, n-pentyl group etc. Examples of ethynyl compounds represented by general formula (3) include 2-propen-1-ol, 2-methyl-3-butyn-2-ol, 3-butyn-2-ol, 3-methyl-4-pentyn- 3-ol, 4-pentyn-3-ol, 4-methyl-5-hexyn-4-ol, 5-hexyn-4-ol, and the like.

（式中、Ｄ^１，Ｄ^２，Ｄ^３は炭化水素基を示す）
で表される。Ｄ^１，Ｄ^２，Ｄ^３は互いに同じでも異なっていてもよい。Ｒ^１，Ｒ^２，Ｒ^３は、好ましくは炭素数１から５のアルキル基であり、例えば、メチル基、エチル基、ｎ－プロピル基、イソプロピル基、ｎ－ブチル基、ｎ－ペンチル基などが挙げられる。一般式（４）で表されるエチニル化合物として、例えばトリメチルシリルアセチレン、トリエチルシリルアセチレン、トリイソプロピルシリルアセチレン、等が挙げられる。 Further, when A in the general formula (2) is a trialkylsilyl group, the ethynyl compound is preferably the following general formula (4)

(In the formula, D ¹ , D ² and D ³ represent hydrocarbon groups)
is represented by D ¹ , D ² and D ³ may be the same or different. R ¹ , R ² and R ³ are preferably alkyl groups having 1 to 5 carbon atoms, such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group and n-pentyl group. mentioned. Examples of the ethynyl compound represented by general formula (4) include trimethylsilylacetylene, triethylsilylacetylene, triisopropylsilylacetylene, and the like.

In view of industrial availability, the ethynyl compound represented by the general formula (2) includes 2-methyl-3-butyn-2-ol, 3-butyn-2-ol, 2-propene-1 - All is more preferred.

The amount of the ethynyl compound used is preferably 1.0 to 3.0 equivalents relative to the raw material aromatic halogen compound. 0 to 2.0 equivalents are more preferred.

In the Sonogashira coupling reaction, a nitrogen-containing organic solvent as a solvent, an aromatic halogen compound having a polar substituent as a raw material, a palladium carbon as a catalyst, a phosphorus compound as an additive, and a copper as a reaction initiator are placed in a reactor. After adding a compound, an amine as a halogen trap, and an alkali metal salt if necessary, an ethynyl compound is added dropwise and added, followed by heating to proceed with the reaction. The reaction temperature is preferably 80° C. or higher at which the reaction proceeds easily, and more preferably 100° C. or higher at which the reaction proceeds further.

It is possible to track the coupling reaction while analyzing the reaction by gas chromatography or high performance liquid chromatography. The reaction time for the coupling reaction is preferably 1 hour or longer, more preferably 2 hours or longer.

After the coupling reaction is completed, the reaction solution is cooled, and a non-aqueous organic solvent and water are added to precipitate palladium-carbon. The non-aqueous organic solvent used here is preferably a non-polar solvent, and preferably a solvent immiscible with water. Examples include solvents such as n-hexane, n-heptane, benzene, toluene, diethyl ether, methyl-t-butyl ether, chloroform, methylene chloride and ethyl acetate. It is particularly preferable to use toluene and ethyl acetate, which are highly soluble in various compounds.

The amount of the non-aqueous organic solvent used is preferably equal to or greater than the amount of the nitrogen-containing organic solvent used in the reaction, and particularly preferably at least 2 times the amount by mass of the nitrogen-containing organic solvent. When the amount used is small, the amount of palladium-carbon deposited is small, the amount of palladium-carbon recovered is small, and the palladium-carbon is incorporated into the target product, increasing the palladium content.

When the amount of the nitrogen-containing organic solvent used in the reaction is large, the palladium carbon is dissolved or dispersed, so that it is difficult to precipitate even if a non-aqueous organic solvent is added. In this case, it is useful to distill off the nitrogen-containing organic solvent, concentrate the reaction solution, and then add the non-aqueous organic solvent to increase the amount of palladium-carbon deposited. Specifically, in order to concentrate the reaction solution after the coupling reaction, the nitrogen-containing organic solvent is distilled off. Evaporation may be carried out under normal pressure, but in the case of N-dimethylacetamide, dimethylformamide, N-methyl-2-pyrrolidone, etc., which have high boiling points, it is preferable to distill off under reduced pressure. If the distillation temperature is too high, the product may be decomposed. Therefore, the distillation temperature is preferably 150° C. or lower, more preferably 100° C. or lower. The degree of pressure reduction at that time is preferably 26 kPa or less, more preferably 13 kPa or less. The amount to be distilled off is preferably 1/3 or more, more preferably 1/2 or more, of the nitrogen-containing organic solvent used. If the concentration is too high, the slurry concentration of the halogen salt of the amine produced in the reaction will become too high and stirring will not be possible. is preferable, and it is more preferable to leave 1.5 times by mass or more.

After adding the non-aqueous organic solvent, or after distilling off the nitrogen-containing organic solvent and adding the non-aqueous organic solvent, water is continuously added for liquid-liquid separation. Water is necessary for dissolving the amine halogen salt precipitated in the reaction, and the amount used is preferably equal to or greater than the amount of the nitrogen-containing organic solvent used in the reaction, and is used at least 2 times the mass of the nitrogen-containing organic solvent. is particularly preferred.

After adding water, the halogen salt of amine produced by the reaction dissolves and palladium carbon precipitates. This palladium on carbon is recovered by filtration. Since the shape of palladium carbon is generally very fine, it is preferable to use a filter with a size of 1 micrometer or less, and it is particularly preferable to use a filter with a size of 0.5 micrometer or less. Also, when there is a large amount of palladium carbon to be filtered, it is very useful to connect a 3 micrometer filter and a 0.5 micrometer filter in series for filtration. The material of the filter is not particularly specified, but a filter unnecessary for organic solvents and water is required, and a cotton filter, a PTFE (polytetrafluoroethylene) filter, or the like is more preferable.

（式中、Ｒは極性置換基、Ａは水酸基を有する炭化水素基または、トリアルキルシリル基、ｎは１から３の整数を示す）
で表されるエチニル基を有する芳香族化合物を取得することができる。 After adding water, agitate for 10 minutes or more to filter palladium carbon, and then allow to stand for 10 minutes or more to separate the oil layer and the water layer. After that, the organic layer is collected, washed with water, concentrated, and then recrystallized to obtain the desired compound of the following general formula (5).

(Wherein, R is a polar substituent, A is a hydrocarbon group having a hydroxyl group or a trialkylsilyl group, n is an integer of 1 to 3)
An aromatic compound having an ethynyl group represented by can be obtained.

R in the general formula (5) is the same as R in the general formula (1), and A is the same as A in the general formula (2), and the description of each is omitted. Examples of aromatic compounds having an ethynyl group represented by general formula (5) include 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol, 2-methyl-4-(3 -nitrophenyl)-3-butyn-2-ol, 2-methyl-4-(2-nitrophenyl)-3-butyn-2-ol, 2-methyl-4-(2,4-dinitrophenyl)-3 -butyn-2-ol, 2-methyl-4-(3,4-dinitrophenyl)-3-butyn-2-ol, 2-methyl-4-(2,4,6-trinitrophenyl)-3- butyn-2-ol, 4-(4-nitrophenyl)-3-butyn-2-ol, 4-(3-nitrophenyl)-3-butyn-2-ol, 4-(2-nitrophenyl)-3 -butyn-2-ol, 3-(4-nitrophenyl)-2-propen-1-ol, 3-(3-nitrophenyl)-2-propen-1-ol, 3-(2-nitrophenyl)- 2-propen-1-ol, 1-nitro-4-[2-(trimethylsilyl)ethynyl]benzene, 1-nitro-3-[2-(trimethylsilyl)ethynyl]benzene, 1,3-dinitro-4-[2 -(trimethylsilyl)ethynyl]benzene, 1,3-dinitro-5-[2-(trimethylsilyl)ethynyl]benzene, 2-methyl-4-(4-aminophenyl)-3-butyn-2-ol, 2-methyl -4-(3-aminophenyl)-3-butyn-2-ol, 2-methyl-4-(2-aminophenyl)-3-butyn-2-ol, 2-methyl-4-(2,4- diaminophenyl)-3-butyn-2-ol, 2-methyl-4-(3,4-diaminophenyl)-3-butyn-2-ol, 2-methyl-4-(2,4,6-triamino Phenyl)-3-butyn-2-ol, 4-(4-aminophenyl)-3-butyn-2-ol, 4-(3-aminophenyl)-3-butyn-2-ol, 4-(2- aminophenyl)-3-butyn-2-ol, 3-(4-aminophenyl)-2-propen-1-ol, 3-(3-aminophenyl)-2-propen-1-ol, 3-(2 -aminophenyl)-2-propen-1-ol, 1-amino-4-[2-(trimethylsilyl)ethynyl]benzene, 1-amino-3-[2-(trimethylsilyl)ethynyl]benzene, 1,3-diamino -4-[2-(trimethylsilyl)ethynyl]benzene, 1,3-diamino-5-[ 2-(trimethylsilyl)ethynyl]benzene, and the like.

EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples.
In the examples, the reaction yield (%) of the aromatic compound having an ethynyl group represented by the general formula (5) was analyzed using GC (gas chromatography) under the following conditions. From the area, the ratio of the peak area of each compound to the area excluding the peak area of the nitrogen-containing organic solvent was determined.

Here, the reaction yield of the aromatic compound having an ethynyl group represented by the general formula (5) (referred to as the "coupling compound" in the following formula) is the raw material aromatic having a polar substituent. It is a numerical value indicating how far the target coupling product has progressed from the group halogen compound (referred to as "starting material" in the following calculation formula), and was calculated as follows.
Area % of coupling body/(Area % of coupling body + Area % of raw material) × 100 (%)

<Purity analysis>
Column: DB-5 (0.25 mm × 30 m × 0.25 μm) (Agilent J & W)
Carrier gas: Helium Inlet temperature: 300°C
Detector temperature: 300°C
Column temperature: 50°C (Hold for 2 minutes) → 10°C/min → 300°C (Hold for 3 minutes)
Column flow rate: 3.65 mL/min Purge flow rate: 5.0 min/min Split ratio: 20
Sample volume: 1 μL
Sample Preparation: Weigh 0.5 g of sample into a 10 mL volumetric flask and make up to volume with acetonitrile.

The retention times of the compounds under the above conditions are as follows.
4-chloronitrobenzene (4-CNB): 12.6 minutes 3-chloronitrobenzene (3-CNB): 12,9 minutes 3-bromoaniline (3-BAN): 14.1 minutes 2-methyl-4-(4 -Nitrophenyl)-3-butyn-2-ol (4-CNB coupling): 19.8 min (m/z = 205 from GC-MS analysis, identified as coupling from similarity search)
2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol (3-CNB coupling): 19.5 minutes (m/z = 205 from GC-MS analysis, cup from similarity search (identified as a ring body)
2-methyl-4-(3-aminophenyl)-3-butyn-2-ol (3-BAN coupling): 18.8 minutes (m / z = 175 from GC-MS analysis, cup from similarity search (identified as a ring body)
Moreover, commercially available reagents were used for the reagents used in the experiment. Palladium carbon manufactured by NE Chemcat was purchased from commercially available reagents of Fuji Film Wako Pure Chemical.

Moreover, the palladium catalyst recovery rate was calculated as follows. The amount of palladium carbon recovered was measured by putting the cake obtained by filtration into a vacuum dryer, drying under reduced pressure of 0.13 kPa or less at a can internal temperature of 40 ° C. to 45 ° C. for 2 hours. The amount of palladium-carbon used was the net amount (g) of palladium-carbon obtained by excluding the water component from the added palladium-carbon.
(amount of palladium carbon recovered)/(amount of palladium carbon used (dry equivalent))×100 (%).

[Example 1]
In a 200 mL flask equipped with stirring and a condenser, 25 g of N,N-dimethylacetamide (DMAc), 5.0 g (31.7 mmol) of 4-chloronitrobenzene (4-CNB), 5% palladium carbon (Pd/c; Type K , Pd content 4.7%, 55 mass% water content) 0.639 g (0.127 mmol, 0.4 mol % / 4-CNB), triphenylphosphine 0.166 g (0.634 mmol), copper iodide (I ) 0.0484 g (0.254 mmol), diisopropylamine 4.82 g (47.6 mmol, 1.5 equivalents/4-CNB), lithium bromide 1.65 g (19.0 mmol) were added, and 2-methyl-3-butyne -2-ol 5.34g (63.5mmol, 2.0eq/4-CNB) was added dropwise at 20-30°C. After completion of dropping, the mixture was placed in an oil bath and reacted at a reaction temperature of 110 to 115° C. for 6 hours. After 6 hours, the reaction solution was analyzed by gas chromatography to find that the target reaction yield of 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol was 95.9%. After cooling, 50 g of ethyl acetate and then 50 g of water were added in the range of 20 to 30° C. and stirred for 30 minutes or longer. Thereafter, filtration was performed using a 0.5 μm filter (manufactured by PTFE), and 0.201 g of a cake containing black palladium carbon was recovered. The content of palladium on carbon in this cake was 89%, the amount recovered was 0.179 g, and the recovery rate was 62%. Thereafter, the organic layer and the aqueous layer are separated, washed twice with water, the solvent is concentrated, and recrystallization is performed using toluene to give 2-methyl-4-(4-nitrophenyl)-3-butyne-2- got oars.

[Example 2]
Starting materials were charged under the conditions described in Example 1, and a coupling reaction was carried out to obtain the target 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol (reaction yield: 95.9%). got After that, the nitrogen-containing organic solvent was distilled off under reduced pressure, and finally the pressure was reduced to 2.67 kPa, and the temperature of the reactor was raised to 85°C. let me out After cooling, 25 g of ethyl acetate and then 25 g of water were added and stirred for 30 minutes or more. After that, the operation of Example 1 was performed, and 0.294 g of cake containing black palladium carbon was recovered. The content of palladium on carbon in this cake was 90%, the amount recovered was 0.265 g, and the recovery rate was 92%.

[Example 3]
4-chloronitrobenzene (4-CNB) 5.0 g (31.7 mmol) used in Example 1 was changed to 3-chloronitrobenzene (3-CNB) 5.0 g (31.7 mmol). A reaction was carried out using the raw materials. After 6 hours, gas chromatography analysis of the reaction solution showed that the desired reaction yield of 2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol was 85.1%. Thereafter, the nitrogen-containing organic solvent was distilled off under the conditions described in Example 2, followed by solid-liquid separation using ethyl acetate and water. Recovered. The content of palladium carbon in this cake was 90%, and the recovery amount was 0.259 g, and the recovery rate was 90%.

[Example 4]
4-chloronitrobenzene (4-CNB) 5.0 g (31.7 mmol) used in Example 1 was changed to 3-bromoaniline (3-BAN) 5.0 g (24.8 mmol), N,N-dimethyl Acetamide 25 g, 5% palladium carbon (Pd/c; Type K, Pd content 4.7%, 55 mass% water content) 0.498 g (0.0990 mmol, 0.4 mol% / 3-BAN), triphenylphosphine 0 .130 g (0.495 mmol), 0.0377 g (0.198 mmol) of copper(I) iodide, 3.76 g (37.1 mmol, 1.5 equivalents/3-BAN) of diisopropylamine are added, and 2-methyl-3- 3.12 g (37.1 mmol, 2.0 equivalents/3-BAN) of butyn-2-ol was added dropwise at 20 to 30° C., and the reaction was carried out according to the procedure described in Example 1. After 6 hours, the reaction solution was analyzed by gas chromatography to find that the target reaction yield of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol was 96.7%. Thereafter, ethyl acetate and water were added under the conditions described in Example 1, and 0.155 g of cake containing black palladium carbon was recovered. The content of palladium on carbon in this cake was 88%, and the recovery amount was 0.137 g, with a recovery rate of 61%.

[Example 5]
The procedure of Example 1 was repeated except that the solvent N,N-dimethylacetamide (DMAc) in Example 1 was changed to N-methyl-2-pyrrolidone (NMP). Gas chromatography analysis of the reaction mixture after 6 hours showed that the desired reaction yield of 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol was 35.0%. Thereafter, ethyl acetate and water were added in the same manner as in Example 1, and 0.171 g of cake containing black palladium carbon was recovered. The content of palladium on carbon in this cake was 89%, the amount recovered was 0.152 g, and the recovery rate was 53%.

[Comparative Example 1]
In a stirred, condenser-equipped 200 mL flask, 25 g of tetrahydrofuran (THF), 5.0 g (31.7 mmol) of 4-chloronitrobenzene (4-CNB), 0.285 g (0.285 g) of palladium acetate (Pd(OAc) ₂ ) were added. 127 mmol) was charged, then the same raw materials as in Example 1 were charged, and 5.34 g of 2-methyl-3-butyn-2-ol (63.5 mmol, 2.0 equivalents/4-CNB) was added at 20 to 30°C. dripped with After completion of dropping, the mixture was placed in an oil bath and reacted at a reaction temperature of 80 to 85° C. for 18 hours. As a result of analyzing the reaction solution by gas chromatography, the production of 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol could not be confirmed by GC. Thereafter, as described in Example 1, ethyl acetate and water were added to try to recover the palladium catalyst, but it could not be recovered at all.

[Comparative Example 2]
In a stirred, 200 mL flask equipped with a condenser, 25 g of tetrahydrofuran (THF), 5.0 g (24.8 mmol) of 3-bromoaniline (3-BAN), 0.222 g (0.222 g) of palladium acetate (Pd(OAc) ₂ ) were added. 0994 mmol) was charged, then the same raw materials as in Example 1 were charged, and 5.34 g (63.5 mmol, 2.0 equivalents/3-BAN) of 2-methyl-3-butyn-2-ol was added at 20 to 30°C. dripped with After completion of dropping, the mixture was placed in an oil bath and reacted at a reaction temperature of 80 to 85° C. for 18 hours. As a result of analyzing the reaction solution by gas chromatography, the production of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol was 100%, and the reaction proceeded entirely. After that, an attempt was made to recover the palladium catalyst by adding ethyl acetate and water as described in Example 1, but it could not be recovered at all.

[Comparative Example 3]
The reaction was carried out as described in Example 1 except that the solvent N,N-dimethylacetamide (DMAc) used in Example 1 was replaced with 2-propanol (IPF). After completion of dropping, the mixture was placed in an oil bath and reacted at a reaction temperature of 80 to 85° C. for 18 hours. As a result of analyzing the reaction solution by gas chromatography, the reaction yield of 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol was 5.2% and the reaction hardly proceeded. Thereafter, ethyl acetate and water were added in the same manner as in Example 1, and 0.186 g of cake containing black palladium carbon was recovered. The content of palladium on carbon in this cake was 88%, and the recovery amount was 0.164 g, with a recovery rate of 57%.

The results of Examples and Comparative Examples are summarized in the table below. In addition, in order to make a judgment in the case of industrial implementation, it was distinguished by × ~ ◎. In the reaction using palladium on carbon, it was necessary to use a nitrogen-containing organic solvent as the reaction solvent, and palladium on carbon was recovered at a recovery rate of 50 to 60%. In addition, concentration after the reaction was performed to distill off the nitrogen-containing organic solvent, thereby improving the recovery rate of palladium carbon. On the other hand, when general-purpose palladium acetate was used, the palladium acetate used in the reaction could not be recovered at all.

◎ indicates that the yield of the target product is high and a large amount of palladium-carbon is recovered, ◯ indicates that the yield is high and palladium-carbon is recovered, and △ yields palladium-carbon even though the yield is low. Those with low yields and those from which the palladium catalyst could not be recovered were evaluated as x.

As shown in Table 1, the conditions of Example 2 are industrially preferable conditions because the reaction yield is high and the recovery rate of palladium carbon is also high.
This recovered palladium-carbon can be replaced with new palladium-carbon by appropriate treatment at a palladium manufacturer, etc., making effective use of scarce palladium.

The method for recovering palladium on carbon according to the present invention is very simple and can recover palladium on carbon only by filtration, and is therefore very useful in industrial production. In addition, scarce palladium carbon can be recovered, reused, or re-reacted, so the amount of scarce palladium used can be reduced.

Claims (4)

General formula (1) below

(Wherein, R is a polar substituent, X is a halogen element, and n is an integer of 1 to 3)
An aromatic halogen compound represented by the following general formula (2)

(In the formula, A represents a hydrocarbon group having a hydroxyl group or a trialkylsilyl group)
In the coupling reaction with the ethynyl compound represented by, palladium carbon, a phosphorus compound, and a copper compound are added in a nitrogen-containing organic solvent to perform the coupling reaction, and a non-aqueous organic solvent and water are added to the resulting reaction solution. After that, a method for recovering a palladium catalyst by recovering palladium carbon by filtration. 2. The method for recovering a palladium catalyst according to claim 1, wherein a non-aqueous organic solvent and water are added to the reaction solution obtained by the coupling reaction after distilling off the nitrogen-containing organic solvent. 3. The method for recovering a palladium catalyst according to claim 1, wherein said nitrogen-containing organic solvent is N-methyl-2-pyrrolidone or N,N-dimethylacetamide. 4. The method for recovering a palladium catalyst according to any one of claims 1 to 3, wherein the polar substituent of the aromatic halogen compound is a nitro group or an amino group.