JP2003292498A - Method for producing bulky hydrocarbon group-bound tertiary phosphine - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a bulky hydrocarbon group-bound tertiary phosphine useful as a ligand for transition metal catalysts in organic synthetic reactions, by which the tertiary phosphine can be produced in an industrial scale by simple and safe operations in a high yield and in a high purity. <P>SOLUTION: This method for producing the tertiary phosphine represented by general formula (3) (R<SB>1</SB>and R<SB>2</SB>are each a 4 to 13C tertiary hydrocarbon group; R<SB>3</SB>is an aryl) is characterized by reacting a dialkylphosphinous halide with an aryl Grignard reagent in the presence of a copper compound in an amount of 0.1 to 5 mol. % based on the dialkylphosphinous halide. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a tertiary phosphine having a sterically bulky hydrocarbon group bonded thereto. More specifically, the present invention provides a tertiary phosphine having a sterically bulky hydrocarbon group bonded thereto, which is useful as a ligand of a transition metal catalyst in an organic synthesis reaction, on an industrial scale, in a simple and safe operation. , A high yield and high purity method.

[0002]

BACKGROUND OF THE INVENTION In recent years, a transition metal such as palladium is coordinated with a tertiary phosphine having a sterically bulky hydrocarbon group such as a tert-butyl group or an adamantyl group. Many organic synthesis reactions using catalysts have been reported (for example, see Non-Patent Documents 1 and 2).

Conventionally, tert- has been used as a bulky hydrocarbon group.
As a method for synthesizing a tertiary phosphine compound having a butyl group bonded thereto, di-tert-butylphosphinas chloride and an aryllithium reagent or an alkyl or aryl Grignard reagent can be used, for example, as described in the following documents. A method of reacting with is known.

In Non-Patent Document 3, a yield of 60% is obtained by reacting di-tert-butylphosphinas chloride with a phenyllithium reagent in an ether solvent.
Describes that di-tert-butylphenylphosphine is obtained. However, this method requires the use of metallic lithium, which is dangerous to handle, or expensive alkyllithium, in order to synthesize the aryllithium reagent that is the raw material, which is a safety aspect when considering industrial production. There is a cost problem.

Patent Document 1 discloses that a Grignard reagent prepared from α, α′-dichloro-o-xylene and magnesium in a tetrahydrofuran solvent and 4 equivalents of di-t.
2 with ert-butylphosphinas chloride at 50 ° C
By reacting for 4 hours, α, with a yield of 61.8%,
α'-bis (di-tert-butylphosphino) -o-
It is stated that xylene is obtained.

This method requires 4 equivalents of di-tert-butylphosphinas chloride with respect to the raw material Grignard reagent, but the yield of the desired product is low, which is disadvantageous in terms of cost when industrial production is considered. Is. Non-Patent Document 4 discloses a Grignard reagent prepared from isopropyl bromide and magnesium, and di-ter.
It is described that di-tert-butylisopropylphosphine can be obtained by reacting with t-butylphosphinas chloride.

According to this method, the reaction is not completed, and the desired product can be obtained only as a mixture with the starting material, di-tert-butylphosphinas chloride. In Non-Patent Document 5, the Grignard reagent prepared from 1- (bromomethyl) -o-carborane and magnesium and di-tert-butylphosphinas chloride are reacted in ether under reflux for 2 hours to give a yield. It is stated that 39% gives 1- (di-tert-butylphosphinomethyl) -o-carborane.

According to this method, the desired product is obtained only in a low yield. In Non-Patent Document 1, a Grignard reagent prepared from 2-bromobiphenyl and magnesium in tetrahydrofuran was added with 1.05 mol times of copper (I) chloride and 1.20 mol times of dichloride of 2-bromobiphenyl. -Tert-
After reacting with butylphosphinas chloride under reflux for 8 hours, hexane and ether were added at room temperature, the target copper complex was once taken out as a solid, and then treated with a mixed solution of hexane, ethyl acetate and an aqueous ammonia solution. It is described that 2- (di-tert-butylphosphino) biphenyl can be obtained with a yield of 67%.

In this method, 1.05 mol of copper (I) chloride is used with respect to 2-bromobiphenyl. After the reaction, the target product is once taken out of the system as a solid copper complex,
In order to decompose the copper complex, it is treated with ammonia water, which is highly toxic and causes environmental pollution. Therefore, in this method, the reaction operation is complicated and there is a problem in terms of work safety. In addition, a large amount of waste liquid containing copper and ammonia is generated, which is not preferable as an industrial manufacturing method.

In Patent Document 2, for example, 2-bromo-
A Grignard reagent prepared from 4′-trifluoromethyl-biphenyl and magnesium was prepared by adding 0.91 mole times of copper (I) chloride to di-tert-butylphosphinas chloride and di-tert-butylphosphinas chloride. Was added and reacted for 14 hours under heating,
The suspension obtained by diluting the reaction mixture with ether was filtered, and the obtained solid was treated with ethyl acetate and aqueous ammonia to give 2- (di-tert-butylphosphino) -4′- in a yield of 31%. For example, trifluoromethyl-biphenyl is obtained, and di-te is used by using an approximately equimolar amount of copper (I) chloride with respect to di-tert-butylphosphinas chloride.
The reaction of rt-butylphosphinas chloride with an aryl Grignard reagent is described in the examples.

According to this method, the desired product is obtained only in a low yield. Further, since copper (I) chloride is used in an approximately equimolar amount with respect to di-tert-butylphosphinas chloride, the treatment with ammonia water is essential in order to liberate the target product from the copper complex. There is a similar problem with. Non-Patent Document 6 discloses that a Grignard reagent prepared from 2-bromo-N, N-dimethylaniline, 2-bromochlorobenzene and magnesium was added to copper (I) chloride (di-
15 against tert-butylphosphinas chloride
(Mol%) and then mixed, followed by addition of di-tert-butylphosphinas chloride and reaction at 60 ° C. for 20 hours, and then the reaction solution obtained by mixing with an organic solvent and aqueous ammonia was filtered through Celite. Yield 4
2- (di-tert-butylphosphino) -2 'at 7%
It is stated that dimethylamino-biphenyl is obtained.

In this method, the amount of the copper compound used is smaller than that in the above literature, and the post-treatment is carried out without taking out the copper complex of the target product from the reaction solution, but in addition to the low yield, Therefore, the problem of using aqueous ammonia has not been solved. Patent Document 3 discloses that 1-adamantyl is added to a solution prepared by adding di-tert-butylphosphinas chloride, 10 mol% of copper (I) iodide and 20 mol% of lithium bromide to a solvent. After adding a magnesium bromide solution and reacting at room temperature for 17 hours, the solution in which the solvent was replaced by benzene was filtered through Celite to obtain
It is described that di-tert-butyl (1-adamantyl) phosphine is obtained with a yield of 86%.

In this method, the Grignard reagent is treated with di-t.
In addition to using 2 times the molar amount of ert-butylphosphinas chloride, lithium bromide is used in addition to the copper compound, and after the reaction, solvent replacement with benzene having carcinogenicity,
There are problems in terms of economy, safety, and operability, such as the need for filtration using Celite. Therefore, none of the above methods is industrially satisfactory.

Under such circumstances, a tertiary phosphine having a bulky hydrocarbon group such as a tert-butyl group or an adamantyl group bonded thereto can be produced in a high yield and high purity on an industrial scale by a simple and safe operation. It is expected to develop a manufacturing method in. The present inventors diligently studied to solve the above problems. As a result, a tertiary phosphine is produced in a particularly high yield by reacting a dialkylphosphinus halide having a tertiary hydrocarbon group with an aryl Grignard reagent in the presence of a specific amount of a copper compound. As a result, they have completed the present invention.

[0015]

[Patent Document 1] International Publication No. 99/9040 pamphlet p. 5-6

[Patent Document 2] US Pat. No. 6,307,087, column 70

[Patent Document 3] International Publication No. 02/48160 pamphlet p. 17

[Non-Patent Document 1] "Journal of the Chemical Society (Journalof the
American Chemical Societ
y) ”(America) 1999 Volume 121 p. Four
369-4378

[Non-Patent Document 2] "Journal of Organic
Chemistry (Journal of the Org
anic Chemistry "(USA) 20
Year 2000 Volume 65 p. 1158-1174

[Non-Patent Document 3] "Journal of the Chemical Society (C) (Journal of the Ch
"Economic Society (C))" (UK)
1971 p. 1931

[Non-Patent Document 4] "Chemiche Berichte (Che
mische Berichte) "(Germany) 19
67 year 100 volume p. 693

[Non-Patent Document 5] "Bulletin of the Chemical Society"
Korean Chemical Societ
y) ”(Korea) 1999 Vol. 20, No. 5, p.
601

[Non-Patent Document 6] "Advanced Synthesis and Catalysis"
s & Catalysis "(Germany) 2001
Year No. 8 p. 793

[0016]

OBJECTS OF THE INVENTION The present invention provides, on an industrial scale, a sterically bulky hydrocarbon group-bonded tertiary phosphine useful as a ligand for a transition metal catalyst in an organic synthetic reaction.
The purpose is to produce in high yield and high purity by simple and safe operation.

[0017]

SUMMARY OF THE INVENTION The present invention has the following general formula (1):

[0018]

[Chemical 4]

(Wherein R ₁ and R ₂ each independently represents a tertiary hydrocarbon group having 4 to 13 carbon atoms, and X represents a chlorine or bromine atom). Finus halide and the following general formula (2)

[0020]

[Chemical 5]

(Wherein R ₃ represents an aryl group and X ′ represents a chlorine, bromine or iodine atom) and an aryl Grignard reagent with respect to the dialkylphosphinas halide of the general formula (1). By reacting in the presence of a copper compound in an amount corresponding to 0.1 to 5 mol%, preferably 0.1 to 3 mol%, the following general formula (3)

[0022]

[Chemical 6]

A characteristic feature is that a tertiary phosphine represented by the formula (wherein R ₁ , R ₂ and R ₃ are as defined above) is produced. As the kind of the copper compound to be added, both an inorganic copper compound and an organic copper compound can be used, and copper halide or copper (II) acetylacetonate is particularly preferable.

In the above invention, the reaction mixture (a) of the dialkylphosphinus halide represented by the general formula (1) and the aryl Grignard reagent represented by the general formula (2), and water or an acidic aqueous solution. , Separating and removing the aqueous layer from the mixed solution (b) obtained by mixing and stirring an appropriate organic solvent as necessary, and then distilling the solvent from the organic layer under normal pressure or reduced pressure. Due to
The target tertiary phosphine can be produced in high yield and high purity by a simple and safe operation.

That is, in the method of the present invention, a side reaction is caused by reacting a dialkylphosphinas halide represented by the general formula (1) with an aryl Grignard reagent represented by the general formula (2) using a copper compound as a catalyst. The reaction easily proceeds without accompanying. In particular, the general formula (2)
The reaction easily proceeds even in the sterically complicated aryl Grignard reagent having a substituent at a position adjacent to the carbon atom bonded to the magnesium atom of the Grignard reagent represented by.

Moreover, since the amount of the copper compound used is extremely small, the amount of the formed complex of the tertiary phosphine compound and the copper compound is also extremely small. Therefore, there is no need for an operation such as treatment with aqueous ammonia to release the desired phosphine compound, and the post-treatment may be in accordance with the usual method for synthesizing a tertiary phosphine with a phosphinus halide and a Grignard reagent. That is, in order to remove inorganic salts such as magnesium halide produced as a by-product,
The desired tertiary phosphine compound can be obtained only by treating with an appropriate amount of water or an acidic aqueous solution such as dilute sulfuric acid. At the same time, since the amount of copper compound used per se is much smaller than in the conventional method, the amount of copper contained in the waste liquid is extremely small, and no special treatment is required thereafter. Therefore, the method of the present invention is particularly suitable for production on an industrial scale.

[0027]

DETAILED DESCRIPTION OF THE INVENTION The present invention will be specifically described below. The dialkylphosphinas halide represented by the general formula (1) as a raw material can be synthesized by a known method or according to a known method. For example, as an example of dialkylphosphinas chloride, di-tert-butylphosphinas chloride is described in Chemiesche Berichte 1967, Vol. 100, p. The method described in 692.
t-Amylphosphinas Chloride is a Journal of Chemical Society (C) 1970
p. 2529, each can be synthesized from phosphorus trichloride and the corresponding alkyl magnesium halide.
Further, as an example of the dialkylphosphinas bromide, di-tert-butylphosphinas bromide is described in Chemiesche Berichte 1978, Vol. 111, p.
1420, ter corresponding to phosphorus tribromide
It can be synthesized from t-butyl magnesium halide.

Examples of the dialkylphosphinas halide represented by the general formula (1) include di-tert-butylphosphinas chloride, di-tert-butylphosphinas bromide, di-tert-amylphosphinas chloride, di-tert- Amylphosphinas bromide, tert-amyl-tert-butylphosphinas chloride, bis (1,1-dimethylbutyl) phosphinas chloride, bis (1,1-diethylpropyl)
Examples thereof include phosphinas chloride, di (1-adamantyl) phosphinas chloride, di (1-adamantyl) phosphinas bromide, and (1-adamantyl) -tert-butylphosphinas chloride.

The other raw material, the Grignard reagent, is represented by the general formula (2). In general formula (2), the aryl group of R ₃ is a phenyl group or a naphthyl group, which may be substituted with a lower alkyl group, a lower alkoxy group, a di (lower alkyl) amino group, a phenyl group or a naphthyl group. Good. Among these, the phenyl group and the naphthyl group may be further substituted with a lower alkyl group, a lower alkoxy group, a di (lower alkyl) amino group, a substituted phenyl group or a substituted naphthyl group.

Examples of the aryl group of R ₃ include phenyl group, 2-methylphenyl group, 3-methylphenyl group,
4-methylphenyl group, 2-ethylphenyl group, 4-ethylphenyl group, 4-propylphenyl group, 2-isopropylphenyl group, 3-cyclopropylphenyl group, 3
-Butylphenyl group, 4-sec-butylphenyl group,
4-tert-butylphenyl group, 2-cyclohexylphenyl group, 3-vinylphenyl group, 4-vinylphenyl group, 4- (2-propenyl) phenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4- Ethoxyphenyl group, 4-isopropyloxyphenyl group, 4-
Butyloxyphenyl group, 4-tert-butyloxyphenyl group, 4-tert-amyloxyphenyl group,
2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 2,5-dimethylphenyl group, 2,6-dimethylphenyl group, 3,4-dimethylphenyl group, 3,5-dimethylphenyl group, 2, 4,6-trimethylphenyl group, 2-methyl-4-methoxyphenyl group, 4-dimethylaminophenyl group, 2-phenylphenyl group, 3-phenylphenyl group, 4-phenylphenyl group, 2- (2
-Methylphenyl) phenyl group, 2- (2-isopropylphenyl) phenyl group, 2- (4-tert-butylphenyl) phenyl group, 2- (2-methoxyphenyl)
Phenyl group, 2- (2-dimethylaminophenyl) phenyl group, 2- (2-phenylphenyl) phenyl group, 2
-(1-naphthyl) phenyl group, 2- (1- (2-methyl) naphthyl) phenyl group, 1-naphthyl group, 2-naphthyl group, 2- (1-phenyl) naphthyl group, 1- (2-
(2-methylphenyl)) naphthyl group, 2- (1- (2
-Methylphenyl)) naphthyl group, 2- (1- (2-methoxyphenyl)) naphthyl group, 2- (1- (1-naphthyl)) naphthyl group, 1- (2- (1- (2-methyl))
And naphthyl)) naphthyl group and 2- (1- (1- (2-methyl) naphthyl)) naphthyl group.

In the general formula (2), X'represents a chlorine, bromine or iodine atom. The Grignard reagent represented by the general formula (2) corresponds to the general formula (2) in a usual method for preparing a Grignard reagent, that is, in an ether solvent or a mixed solution of an ether solvent and a hydrocarbon solvent. It can be produced by reacting an aryl halide (R ₃ X ′) with magnesium metal.

As the ether solvent used in this reaction, for example, diethyl ether, dipropyl ether,
Diisopropyl ether, dibutyl ether, diisoamyl ether, tert-butyl methyl ether, 1,
Chain ethers such as 2-dimethoxyethane and 1,2-diethoxyethane, or tetrahydrofuran and 2-
Methyltetrahydrofuran, tetrahydropyran, 1,
Examples include cyclic ethers such as 4-dioxane. These ether solvents may be used alone or in combination of two or more.

Examples of the hydrocarbon solvent include aliphatic hydrocarbons such as pentane, hexane, cyclohexane, heptane and octane, or benzene, toluene, o-xylene, m-xylene, p-xylene and ethylbenzene. Aromatic hydrocarbons may be mentioned. These hydrocarbon-based solvents may be used alone or in combination of two or more.

In the present invention, the Grignard reagent obtained by the above-mentioned preparation method can be used as it is for the reaction with the dialkylphosphinus halide of the general formula (1) as an inert solvent solution without isolation. The reaction of the dialkylphosphinas halide of the general formula (1) with the Grignard reagent of the general formula (2) in the present invention is carried out in an inert solvent. The inert solvent used for dissolving the dialkylphosphinus halide of the general formula (1) is not particularly limited as long as it is inert with respect to the reaction raw material and the reaction product. Examples of such an inert solvent include toluene,
Hydrocarbon-based solvent such as xylene, hexane, heptane,
Examples include ether solvents such as diethyl ether and tetrahydrofuran, and mixed solvents thereof.

The amount of the Grignard reagent of the general formula (2) used in the present invention is 0.5 to 5 equivalents relative to the dialkylphosphinas halide of the general formula (1), preferably 0.9. ~ 1.5 equivalents. As the copper compound used in the present invention, inorganic copper or organic copper can be used. Examples of the inorganic copper include copper (I) chloride, copper (II) chloride, copper (I) bromide, copper (II) bromide, copper (I) iodide, copper (I) oxide, and copper (II) oxide. , Copper (I) carbonate, copper (II) carbonate, copper (II) sulfate, copper (II) cyanide, copper (II) hydroxide, and copper (II) diammonium chloride.

Examples of organic copper include anhydrous copper (II) acetate, copper (II) acetate, copper (II) acetylacetonate, copper (II) benzoate, copper (II) benzoylacetonate, and copper citrate. (II), copper (II) dipivaloyl methanate, copper (II) ethylacetoacetate, copper (II) 2-ethylhexanoate, copper (II) oleate, copper (II) stearate, copper thiocyanate ( I), copper (I
I) Trifluoroacetylacetonate may be mentioned.

Among these copper compounds, copper (I) bromide, copper (II) bromide, copper (I) chloride, copper (II) chloride and other halogenated copper compounds or copper (II) acetylacetonate are used. It is preferable. The amount of the copper compound used is 0.1 to 5 mol% with respect to the dialkylphosphinas halide of the general formula (1). By using the copper compound in an amount within this range, the target tertiary phosphine of the general formula (3) can be efficiently obtained in a particularly high yield.

When the amount of the copper compound used is less than 0.1 mol% with respect to the dialkylphosphinus halide of the general formula (1), the reaction rate is slow or the catalyst is deactivated in the middle of the reaction. The yield does not proceed sufficiently. Also,
When the amount of the copper compound used exceeds 5 mol%, the reaction proceeds sufficiently, but the yield decreases due to the following reasons. It is known that a tertiary phosphine coordinates with a copper compound to form a complex (in organic synthesis 1
979 p. 87, it is described that copper (I) chloride forms a complex with triphenylphosphine in a molar amount of 3). When the amount of the copper compound used increases, the amount of the complex with the desired phosphine compound formed also increases, which causes a decrease in yield. Further, in order to decompose the formed complex and release the desired phosphine compound, treatment with ammonia or the like is required, and when industrially carried out, problems such as a large environmental load of the generated waste liquid occur. However, according to the present invention, the target tertiary phosphine can be produced in a sufficiently high yield without treatment with ammonia.

Considering the reaction rate, yield, operability of the post-treatment, etc., the particularly preferable amount of the copper compound used is 0.1 to 3 mol% based on the dialkylphosphinus halide of the general formula (1). is there. The reaction of the present invention varies depending on the kind of the compound of the general formula (1) or the general formula (2) used, but generally proceeds at a temperature between −70 ° C. and the boiling point of the solvent used. However, preferably 20
It is a temperature between 0 ° C and the boiling point of the solvent used. The reaction time varies depending on the type and amount of the compound of the general formula (1) and the general formula (2) used, the type and amount of the copper compound, the reaction temperature, and the solvent used, but it is 1 hour to 1 day, and many In the case of, the reaction is completed in 2 to 12 hours.

In the present invention, the order of addition of the dialkylphosphinus halide of the general formula (1), the Grignard reagent of the general formula (2) and the copper compound in the reaction operation and the method of addition are, for example, the above-mentioned suitable solvent. In which the Grignard reagent of the general formula (2) and the copper compound are mixed, and the dialkylphosphinus halide of the general formula (1) dissolved in a suitable solvent or without any solvent is added, or General formula (1) in a solvent
The method of mixing the dialkylphosphinas halide of (1) and the copper compound and adding the Grignard reagent of the general formula (2) thereto, or the Grignard reagent of the general formula (2),
Examples thereof include a method of mixing and adding the dialkylphosphinus halide of the general formula (1) and the copper compound in the above-mentioned suitable solvent. However, the present invention is not limited to these methods.

The treatment method after completion of the reaction may be based on the usual method for synthesizing tertiary phosphine compounds using phosphinas halide and Grignard reagent. That is, in order to remove by-produced inorganic salts such as magnesium halide, a reaction mixture (a) of a dialkylphosphinus halide represented by the general formula (1) and an aryl Grignard reagent represented by the general formula (2) , An appropriate amount of water or an acidic aqueous solution such as dilute sulfuric acid and, if necessary, an appropriate organic solvent such as toluene are mixed to obtain a mixed solution (b), and the aqueous layer is separated and removed at normal pressure or By distilling off the solvent used from the obtained organic layer under reduced pressure,
The desired tertiary phosphine of the general formula (3) can be obtained.

In the present invention, an organic solvent may be added to and mixed with the obtained reaction mixture (a), and then water or an acidic aqueous solution may be added and mixed with the obtained solution, or an organic solvent may be added. The reaction mixture (a) may be added to and the mixed solution may be added to or mixed with water or an acidic aqueous solution.
The mixing method is not particularly limited. The tertiary phosphine obtained by the above method can be purified by distillation, recrystallization, or the like, if necessary, to obtain a product of higher purity.

The tertiary phosphines produced by the present invention are exemplified in Tables 1 to 4.

[0044]

[Table 1]

[0045]

[Table 2]

[0046]

[Table 3]

[0047]

[Table 4]

[0048]

INDUSTRIAL APPLICABILITY According to the present invention, a tertiary phosphine having a sterically bulky hydrocarbon group bonded thereto, which is useful as a ligand of a transition metal catalyst in an organic synthesis reaction, can be conveniently prepared on an industrial scale. In addition, it can be produced in high yield and high purity by safe operation.

[0049]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. In the following examples, the purity (%) is an area percentage value in gas chromatography analysis.
Further, the addition amount of the copper compound is also shown in terms of mol% with respect to the dialkylphosphinas chloride.

[0050]

Example 1 A four-necked flask having a capacity of 300 ml, which had been sufficiently replaced with nitrogen, was charged with 40 ml of tetrahydrofuran and di-te.
18.1 g of rt-butylphosphinas chloride (0.
1 mol) and 0.14 g (0.001 mol (corresponding to 1 mol%)) of copper (I) bromide were charged. A Grignard reagent solution prepared in 100 ml of tetrahydrofuran from 13.5 g (0.12 mol) of chlorobenzene and 3.5 g (0.14 mol) of metallic magnesium was added thereto at a temperature of 25 ° C to 30 ° C. While maintaining the temperature, the solution was added dropwise over 1 hour. After the completion of dropping, the mixture was stirred at a temperature of 35 ° C to 40 ° C for 3 hours. After the reaction solution was returned to room temperature, the disappearance of di-tert-butylphosphinas chloride was confirmed by gas chromatography. Then, 40 ml of toluene and 30 ml of 5% sulfuric acid aqueous solution were added to the reaction solution to separate the layers, and then the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent is distilled off under reduced pressure, and then distillation is carried out at 110 to 112 ° C. under reduced pressure of 5 torr.
By collecting the fractions distilled in
19.9 g of ert-butylphenylphosphine (purity 9
9.0%) was obtained as a viscous oil. Yield 89.0
%.

[0051]

Example 2 Synthesis of Di-tert-butylphenylphosphine (Part 2) In the same manner as in Example 1, except that 18.8 g (0.12 mol) of bromobenzene was used instead of chlorobenzene, di-tert-butylphosphine was used. -Butylphenylphosphine 1
9.6 g (purity 99.1%) was obtained. Yield 88.5%.

[0052]

Example 3 Synthesis of di-tert-butyl (2-methylphenyl) phosphine In a 500 ml four-necked flask, which had been sufficiently replaced with nitrogen,
100 ml of tetrahydrofuran and 40 ml of toluene from 20.5 g (0.12 mol) of 2-bromotoluene and 3.1 g (0.13 mol) of metallic magnesium in advance.
And a Grignard reagent solution prepared in a mixed solvent with 0.05 g (0.0005 mol (0.
5 mol% equivalent)). Then, 18.1 g (0.10 mol) of di-tert-butylphosphinas chloride dissolved in 30 ml of tetrahydrofuran was added thereto at 25 ° C.
While maintaining the temperature of 30 to 30 ° C., the solution was added dropwise over 1 hour.
After the dropping was completed, the mixture was stirred at 50 ° C. for 4 hours. After returning the reaction solution to room temperature, it was subjected to di-tert by gas chromatography.
-The disappearance of butylphosphinas chloride was confirmed. Then, 30 ml of a 5% aqueous solution of sulfuric acid was added to the reaction solution for liquid separation, and then the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent is distilled off under reduced pressure, and then distillation is carried out at 112 to 114 ° C. under reduced pressure of 3 torr.
By collecting the fractions distilled in
ert-butyl (2-methylphenyl) phosphine 2
1.5 g (purity 99.0%) was obtained. Yield 91.0%.

[0053]

Example 4 Synthesis of di-tert-butyl (2-methylphenyl) phosphine (Part 2) In Example 3, the addition amount of copper (I) chloride was 0.02 g.
(0.0002 mol (corresponding to 0.2 mol%)), 50
After reacting at 12 ° C for 12 hours, the same treatment is carried out.
rt-butyl (2-methylphenyl) phosphine 20.
0 g (purity 98.8%) was obtained. Yield 84.0%.

[0054]

Example 5 Synthesis of di-tert-butyl (2-methoxyphenyl) phosphine A 300 ml four-necked flask with a sufficient nitrogen substitution was used.
In advance, 12.2 g of 2-bromoanisole (0.06
5 mol) and 2.1 g (0.085 mol) of metallic magnesium, a Grignard reagent solution prepared in 65 ml of tetrahydrofuran, and copper (II) chloride 0.1
3 g (0.0010 mol (corresponding to 2 mol%)) was charged. 9.0 g (0.05 mol) of di-tert-butylphosphinas chloride was not added to the solvent as it was, and was added dropwise over 1 hour while maintaining the temperature at 25 ° C to 30 ° C. After the completion of dropping, the mixture was stirred at 50 ° C. for 3 hours. When the reaction liquid was returned to room temperature and then analyzed by gas chromatography, di-tert-butylphosphinas chloride was found to be a trace amount. After that, toluene 6 was added to the reaction solution.
5 ml and 50 ml of water were added for liquid separation, and the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent and low boiling point components are distilled off under reduced pressure to obtain the desired di-t.
ert-butyl (2-methoxyphenyl) phosphine 1
1.9 g (purity 95.0%) was obtained. Yield 89.7%. Mass (CI method) M / z 253 (M ⁺ +1: base)

[0055]

Example 6 Synthesis of di-tert-butyl (2-phenylphenyl) phosphine In a 500 ml four-necked flask, which was fully nitrogen-substituted,
Di-tert-butylphosphinas chloride 9.0 g
(0.05 mol) and 0.07 g (0.0
005 mol (corresponding to 1 mol%)) and 50 ml of tetrahydrofuran were charged. A Grignard reagent solution prepared in 100 ml of tetrahydrofuran from 14.0 g (0.060 mol) of 2-bromobiphenyl and 1.7 g (0.072 mol) of metallic magnesium in advance was added thereto. While maintaining the temperature of ° C, the mixture was added dropwise over 1 hour. After completion of dropping, the mixture was stirred at reflux temperature for 4 hours. After the reaction solution was returned to room temperature, the disappearance of di-tert-butylphosphinas chloride was confirmed by gas chromatography. Then, 30 ml of toluene in the reaction solution
And 30 ml of a 5% aqueous solution of sulfuric acid were added for liquid separation, and then the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent and the low boiling point component were distilled off under reduced pressure to obtain a crude crystal, which was recrystallized from MeOH to obtain the desired di-tert-butyl (2-phenylphenyl) phosphine (13.2 g).
(Purity 99.0%) was obtained. Yield 87.5%. Melting point 84
-85 ° C.

[0056]

Example 7 Synthesis of di-tert-butyl (2,4,6-trimethylphenyl) phosphine A 300 ml four-necked flask with a sufficient nitrogen substitution was used.
20 ml of tetrahydrofuran, 9.0 g (0.05 mol) of di-tert-butylphosphinas chloride,
0.05 g of copper (I) chloride (0.0005 mol (1 mol%
Equivalent)) and prepared. A Grignard reagent solution prepared in 100 ml of tetrahydrofuran from 14.9 g (0.075 mol) of mesityl bromide and 2.2 g (0.090 mol) of metallic magnesium was added thereto at 50 ° C. for 1 hour. It dripped over. After the dropping is completed,
The mixture was stirred under reflux at 73 ° C for 4 hours. After returning the reaction solution to room temperature, 40 ml of toluene and 30 ml of a 5% sulfuric acid aqueous solution were added to the reaction solution to separate the layers, and then the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent was distilled off under reduced pressure, a small amount of MeOH was added, the whole was cooled to −30 ° C., and the precipitated solid was collected by filtration. The target j-te
11.9 g (purity 97.5%) of rt-butyl (2,4,6-trimethylphenyl) phosphine was obtained as a white solid. Yield 88.0%. Melting point 36-37 [deg.] C.

[0057]

Example 8 Di-tert-butyl (1-naphthyl)
Synthesis of phosphine A four-necked flask with a capacity of 500 ml, which was sufficiently replaced with nitrogen,
Di-tert-butylphosphinas chloride 18.1
g (0.1 mol) and copper (I) chloride 0.20 g (0.0
02 mol (corresponding to 2 mol%)) and tetrahydrofuran 2
0 ml and 20 ml of toluene were charged. There,
In advance, 24.8 g of 1-bromonaphthalene (0.12
Mol) and 3.5 g (0.14 mol) of metallic magnesium, a Grignard reagent solution prepared in 180 ml of tetrahydrofuran was added dropwise over 1 hour while maintaining the temperature at 25 ° C to 30 ° C. 65 after dropping
The mixture was stirred at 0 ° C for 3 hours. After the reaction solution was returned to room temperature, the disappearance of di-tert-butylphosphinas chloride was confirmed by gas chromatography. Then, 30 ml of toluene and 30 ml of 5% sulfuric acid aqueous solution were added to the reaction solution to separate the layers, and then the organic layer was washed with water and dried over anhydrous sodium sulfate. The oily substance obtained by distilling off the solvent under reduced pressure was recrystallized from 150 ml of methanol to obtain the target di-
tert-Butyl (1-naphthyl) phosphine 23.6
g (purity 98.5%) was obtained as white crystals. Yield 8
5.4%. Melting point 95-97 [deg.] C.

[0058]

Example 9 Synthesis of (di-tert-amyl) phenylphosphine A 300 ml four-necked flask with a sufficient nitrogen substitution was used.
Tetrahydrofuran 20 ml and di-tert-amylphosphinas chloride 10.4 g (0.050 mol)
And 0.13 g of copper (II) acetylacetonate (0.
0005 mol (corresponding to 1 mol%)). A Grignard reagent solution prepared in 45 ml of tetrahydrofuran from 6.8 g (0.060 mol) of chlorobenzene and 1.9 g (0.080 mol) of magnesium metal was added thereto at a temperature of 40 ° C to 45 ° C. While maintaining the temperature, the solution was added dropwise over 1 hour. After completion of dropping, the mixture was stirred at the same temperature for 3 hours. When the reaction liquid was returned to room temperature and then analyzed by gas chromatography, di-tert-amylphosphinas chloride was found in a trace amount. Then, 20 ml of toluene and 5% aqueous sulfuric acid solution 2 were added to the reaction solution
0 ml was added for liquid separation, and the organic layer was washed with water and dried over anhydrous sodium sulfate. Further, the solvent and low-boiling point components are distilled off under reduced pressure to obtain 12.0 g of the objective (di-tert-amyl) phenylphosphine (purity 94.4%).
Was obtained as a viscous oil. Yield 90.5%. Mass (CI method) M / z 251 (M ⁺ +1: base)

[0059]

COMPARATIVE EXAMPLE 1 The same operation as in Example 1 was conducted except that the amount of copper (I) bromide added was 2.8 mg (0.02 mmol (equivalent to 0.02 mol%)). According to gas chromatography analysis, the conversion rate to di-tert-butylphenylphosphine was 11%.

[0060]

COMPARATIVE EXAMPLE 2 The same reaction and treatment as in Example 1 except that the added amount of copper (I) bromide was 2.2 g (0.015 mol (corresponding to 15 mol%)) was carried out under reduced pressure. The boiling point component was distilled off to obtain 12.1 g (purity 95.0%) of the target di-tert-butylphenylphosphine as a viscous oily substance. Yield 52.0%.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4H039 CA41 CA90 CD20 CD90                 4H050 AA02 AD11 BA05 BA37 BA45                       BB31 BB44 BC34 WA15 WA26

Claims (6)

[Claims] 1. The following general formula (1): (In the formula, R ₁ and R ₂ each independently have 4 to 4 carbon atoms.
13 represents a tertiary hydrocarbon group, and X represents a chlorine or bromine atom. ) And a dialkylphosphinus halide represented by the following general formula (2): (In the formula, R ₃ represents an aryl group and X ′ represents a chlorine, bromine or iodine atom.), And an aryl Grignard reagent represented by the formula (1) with respect to the dialkylphosphinus halide of 0.1. The reaction is carried out in the presence of a copper compound in an amount corresponding to ˜5 mol%, the following general formula (3): (In the formula, R ₁ , R ₂ and R ₃ are as defined above.)
The manufacturing method of the tertiary phosphine shown by these. 2. The reaction is performed in the presence of a copper compound in an amount corresponding to 0.1 to 3 mol% with respect to the dialkylphosphinus halide represented by the general formula (1). 1. The method for producing the tertiary phosphine according to 1. 3. A reaction mixture (a) of a dialkylphosphinas halide represented by the general formula (1) and an aryl Grignard reagent represented by the general formula (2), water or an acidic aqueous solution, and, if necessary, an organic solution. 3. The solvent is distilled off under normal pressure or reduced pressure after the aqueous layer is separated and removed from the obtained mixed liquid (b) by mixing and stirring with a solvent. Method for producing tertiary phosphine. 4. The copper compound is copper halide or copper (I
I) Acetylacetonate, The manufacturing method of the tertiary phosphine in any one of Claims 1-3 characterized by the above-mentioned. 5. The method for producing a tertiary phosphine according to claim 1, wherein X in the dialkylphosphinus halide represented by the general formula (1) is a chlorine atom. 6. The dialkylphosphinas halide represented by the general formula (1) is di-tert-butylphosphinas chloride or di-tert-amylphosphinas chloride. Method for producing tertiary phosphine.