JP2003313194A - Method for producing tertiary phosphine bonded with bulky hydrocarbon group - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a tertiary phosphine bonded with bulky hydrocarbon groups, which is useful in organic synthetic reactions as a ligand of a transition metal catalyst, capable of being produced in an industrial scale by a safe and simple operation with a high yield and purity. <P>SOLUTION: The method produces the tertiary phosphine expressed by formula (3) by reacting a dialkyl phoshineous halide with a Grignard reagent in the presence of 0.1 to 5 mole.% of a cupper compound based on the dialkyl phoshineous halide. In formula (3), R<SB>1</SB>and R<SB>2</SB>are each a 4 to 13C tertiary hydrocarbon group, and R<SB>3</SB>is a linear or branched alkyl, alkenyl, or the like. <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 (see, for example, Patent Documents 1 and 2 and 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 alkyllithium reagent or an alkyl or aryl Grignard can be used, for example, as described in the following documents. A method of reacting with a reagent is known.

In particular, when a tertiary alkyl group is introduced into di-tert-butylphosphinas chloride, the reactivity of the alkyl Grignard reagent is low due to the large steric hindrance, and it is described in Non-Patent Document 3. Only alkyllithium reagents are used as in the method. Non-Patent Document 3 describes that di-tert-butylphosphinas chloride and tert-butyllithium are reacted in a benzene-pentane mixed solvent to obtain tri-tert-butylphosphine at a yield of 50%. ing.

However, in this method, tert-butyllithium, which is a tertiary alkyllithium, is used as a raw material, and the production and handling methods thereof have the following problems (i) and (ii). Therefore, it is not a convenient industrial manufacturing method. (I) In order to produce a tertiary alkyl lithium, a highly active lithium fine dispersion is generated at a high temperature (about 200 ° C.),
It must be reacted with a tertiary alkyl halide using a low boiling hydrocarbon as a solvent under an argon stream. Therefore, a reaction in a special container is required, and
Careful attention must be paid to the reaction procedure. (Ii) The produced tertiary alkyllithium is a highly dangerous reagent that spontaneously ignites when contacted with air.

[0006] Patent Document 3 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 target product is low, which is disadvantageous in terms of cost when industrial production is considered. Is. Non-Patent Document 3 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 4, a Grignard reagent prepared from 1- (bromomethyl) -o-carborane and magnesium and di-tert-butylphosphinas chloride are reacted in an 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 4, 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 5 describes that a Grignard reagent prepared from 2-bromo-N, N-dimethylaniline, 2-bromochlorobenzene and magnesium is mixed with 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 target copper complex from the reaction solution, but in addition to the low yield. Therefore, the problem of using aqueous ammonia has not been solved. Patent Document 5 discloses that 1-adamantyl is added to a solution in which di-tert-butylphosphinas chloride, 10 mol% of copper (I) iodide and 20 mol% of lithium bromide are added 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 a 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, by reacting a dialkylphosphinus halide having a tertiary hydrocarbon group with a Grignard reagent such as an alkyl group in the presence of a specific amount of a copper compound, the tertiary phosphine can be produced in high yield and in high yield. They have found that they can be produced with a high degree of purity, and have completed the present invention.

[0016]

[Patent Document 1] Japanese Patent Laid-Open No. 10-81667

[Patent Document 2] Japanese Patent Laid-Open No. 11-158103

[Patent Document 3] International Publication No. 99/9040 pamphlet p. 5-6

[Patent Document 4] US Pat. No. 6,307,087, column 70

[Patent Document 5] 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] "Chemiche Berichte (Che
mische Berichte) "(Germany) 19
67 year 100 volume p. 693

[Non-Patent Document 4] "Bulletin of the Society"
Korean Chemical Societ
y) ”(Korea) 1999 Vol. 20, No. 5, p.
601

[Non-Patent Document 5] "Advanced Synthesis and Catalysis"
s & Catalysis "(Germany) 2001
Year No. 8 p. 793

[0017]

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.

[0018]

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

[0019]

[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). Halide and the following general formula (2)

[0021]

[Chemical 5]

(In the formula, R ₃ represents a linear or branched alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group or a lower alkoxy lower alkyl group, and X ′ represents chlorine, bromine or And a Grignard reagent represented by the general formula (1)
0.1 to 5 with respect to the dialkylphosphinas halide of
By reacting in the presence of a copper compound in an amount corresponding to mol%, the following general formula (3)

[0023]

[Chemical 6]

A feature is that a tertiary phosphine represented by the formula (wherein R ₁ , R ₂ and R ₃ are as defined above) is produced. The type of copper compound to be added, both inorganic copper compounds and organic copper compounds can be used,
Particularly preferred is copper halide or copper (II) acetylacetonate.

In the above invention, the reaction mixture (a) of the dialkylphosphinus halide represented by the general formula (1) and the Grignard reagent represented by the general formula (2), water or an acidic aqueous solution, From the mixed solution (b) obtained by mixing and stirring a suitable organic solvent as necessary, the aqueous layer is separated and removed, and then the solvent is distilled off from the organic layer under normal pressure or reduced pressure. The desired tertiary phosphine can be produced with high yield and high purity by simple and safe operation.

That is, in the method of the present invention, a dialkylphosphinus halide represented by the general formula (1) and a Grignard reagent represented by the general formula (2) are reacted with a copper compound as a catalyst, thereby causing a side reaction. Reaction proceeds easily without. Moreover, since the amount of the copper compound used is extremely small, the amount of the produced complex of the tertiary phosphine compound and the copper compound produced 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, the target 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 in order to remove by-produced inorganic salts such as magnesium halide. 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). Examples of the Grignard reagent represented by the general formula (2) include methyl magnesium chloride, ethyl magnesium chloride, ethyl magnesium bromide, ethyl magnesium iodide,
n-propyl magnesium chloride, n-propyl magnesium bromide, isopropyl magnesium chloride, isopropyl magnesium bromide, n-butyl magnesium chloride, n-butyl magnesium bromide, sec-butyl magnesium chloride,
Isobutyl magnesium chloride, tert-butyl magnesium chloride, tert-butyl magnesium bromide, n-pentyl magnesium chloride,
Isoamyl magnesium chloride, sec-amyl magnesium chloride, tert-amyl magnesium chloride, n-hexyl magnesium chloride, 2
-Hexyl magnesium chloride, 3-hexyl magnesium chloride, n-heptyl magnesium chloride, n-octyl magnesium chloride, cyclopropyl magnesium chloride, cyclopentyl magnesium chloride, cyclohexyl magnesium chloride, cyclohexyl magnesium bromide, 1-adamantyl magnesium bromide, 2-adamantyl Magnesium bromide, vinylmagnesium chloride, allylmagnesium chloride, 1-propenylmagnesium chloride, 1-methylvinylmagnesium chloride, 2-butenylmagnesium chloride, ethynylmagnesium chloride, 2-methoxyethylmagnesium chloride, 2-phenoxyethylmagnesium chloride, Down Jill magnesium chloride, α
-Methylbenzylmagnesium chloride, p-methylbenzylmagnesium chloride, o-methoxybenzylmagnesium chloride, 2,4-dimethylbenzylmagnesium chloride, phenethylmagnesium chloride, p-methoxyphenethylmagnesium chloride, p- (tert-butyloxy) phenethylmagnesium chloride , 3-phenylpropylmagnesium chloride, diphenylmethylmagnesium chloride, triphenylmethylmagnesium chloride, 2-
Phenyl-2-propyl magnesium chloride, 1-
Phenyl-2-propyl magnesium chloride, 1-
Examples include naphthylmethyl magnesium bromide and methoxymethyl magnesium chloride.

The Grignard reagent represented by the general formula (2) can be prepared by the 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. Can be produced by reacting the corresponding halogenated hydrocarbon (R ₃ X ′) with magnesium metal. Examples of the ether solvent used in this reaction include diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, diisoamyl ether, tert-butyl methyl ether, 1,2-dimethoxyethane, 1,
Chain ethers such as 2-diethoxyethane, or tetrahydrofuran, 2-methyltetrahydrofuran,
Examples include cyclic ethers such as tetrahydropyran and 1,4-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 in 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 dialkylphosphinus halide of the general formula (1). Particularly, the Grignard reagent of the general formula (2) is a lower alkyl Grignard reagent (linear or branched carbon number 1 to 1).
4 alkyl group), the unreacted residual Grignard reagent is decomposed by contact with water or an acidic aqueous solution in the post-treatment to become a flammable gas (for example, methane, ethane, propane, etc.). Therefore, from the viewpoint of industrially and safely carrying out the method of the present invention, the general formula (2)
The amount of the Grignard reagent used is preferably 0.9 with respect to the dialkylphosphinus halide of the general formula (1).
~ 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 sulfate (I
I), copper (II) cyanide, copper (II) hydroxide, and diammonium copper (II) chloride.

Examples of the 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 this range, the target tertiary phosphine of the general formula (3) can be efficiently obtained in a particularly high yield.

If 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 will be slow or the catalyst will be deactivated during the reaction, resulting in a 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 It can be appropriately selected from the following methods depending on the type and amount of the compound of the general formula (2) and the type and amount of the copper compound. For example, a method of mixing a Grignard reagent of the general formula (2) and a copper compound in the above-mentioned suitable solvent and adding a dialkylphosphinus halide of the general formula (1) dissolved in the above-mentioned suitable solvent without solvent or Alternatively, a method of mixing the dialkylphosphinas halide of the general formula (1) and the copper compound in an appropriate solvent described above and adding the Grignard reagent of the general formula (2) thereto, or the Grignard of the general formula (2). Examples thereof include a method in which the dialkylphosphinus halide of the general formula (1) and a copper compound are mixed and added to the reagent 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 inorganic salts such as magnesium halide produced as a by-product, a reaction mixture (a) of a dialkylphosphinus halide represented by the general formula (1) and a Grignard reagent represented by the general formula (2), An aqueous layer is separated and removed from a mixed solution (b) obtained by mixing an appropriate amount of water or an acidic aqueous solution such as dilute sulfuric acid with an appropriate organic solvent such as toluene, if necessary, and at normal pressure or reduced pressure. The target tertiary phosphine of the general formula (3) can be obtained by distilling off the solvent used from the obtained organic layer below.

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. 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.

Examples of the tertiary phosphine produced by the method of the present invention include di-tert-butylmethylphosphine, di-tert-butylethylphosphine, di-tert-butyl-n-propylphosphine and di-t.
ert-butyl-isopropylphosphine, di-ter
t-butyl-n-butylphosphine, di-tert-butyl-sec-butylphosphine, di-tert-butyl-isobutylphosphine, tri-tert-butyl-
Phosphine, di-tert-butyl-n-pentylphosphine, di-tert-butyl-isoamylphosphine, di-tert-butyl-tert-amylphosphine, di-tert-butyl-n-hexylphosphine,
Di-tert-butyl-2-hexylphosphine, di-
tert-butyl-3-hexylphosphine, di-te
rt-butyl-n-octylphosphine, di-tert
-Butyl (diphenylmethyl) phosphine, di-ter
t-butyl (triphenylmethyl) phosphine, di-t
ert-butylvinylphosphine, di-tert-butylallylphosphine, di-tert-butylcyclopropylphosphine, di-tert-butylcyclopentylsphine, di-tert-butylcyclohexylphosphine, di-tert-butylbenzylphosphine, di-
tert-butylphenethylphosphine, di-tert
-Butyl (α-methylbenzyl) phosphine, di-te
rt-butyl (p-methylbenzyl) phosphine, di-
tert-butyl (3-phenylpropyl) phosphine, di-tert-butyl (1-adamantyl) phosphine, di-tert-butyl (2-adamantyl) phosphine, di-tert-butyl (2-phenyl-2-propyl) phosphine , Di-tert-butyl (1-phenyl-2-propyl) phosphine, di-tert-butyl (p-methoxyphenethyl) phosphine, di-ter
t-butyl (1-naphthylmethyl) phosphine, di-t
ert-amylmethylphosphine, di-tert-amylethylphosphine, di-tert-amyl-n-propylphosphine, di-tert-amylisopropylphosphine, di-tert-amyl-n-butylphosphine, di-tert-amyl- sec-Butylphosphine, di-tert-amylisobutylphosphine, di-
tert-amyl-tert-butylphosphine, tri-tert-amylphosphine, di-tert-amyl-n-pentylphosphine, di-tert-amylisoamylphosphine, di-tert-amyl-n-hexylphosphine, di-tert- Amyl-2-hexylphosphine, di-tert-amyl-3-hexylphosphine, di-tert-amyl-n-octylphosphine, di-tert-amyl (diphenylmethyl) phosphine, di-tert-amyl (triphenylmethyl) Phosphine, di-tert-amylvinylphosphine, di-tert-amylallylphosphine, di-tert-
Amylcyclopentylphosphine, di-tert-amylcyclohexylphosphine, di-tert-amylbenzylphosphine, di-tert-amylphenethylphosphine, di-tert-amyl (α-methylbenzyl) phosphine, di-tert-amyl (p-methyl) Benzyl) phosphine, di-tert-amyl (3-phenylpropyl) phosphine, di-tert-amyl (1
-Adamantyl) phosphine, di-tert-amyl (2-adamantyl) phosphine, di-tert-amyl (2-phenyl-2-propyl) phosphine, di-t
ert-amyl (1-phenyl-2-propyl) phosphine, di-tert-amyl (p-methoxyphenethyl) phosphine, di-tert-amyl (1-naphthylmethyl) phosphine, bis (1,1-dimethylbutyl)
n-propylphosphine, bis (1,1-dimethylbutyl) sec-butylphosphine, bis (1,1-dimethylbutyl) cyclohexylphosphine, bis (1,1-
Dimethylbutyl) (p-methylbenzyl) phosphine,
tert-amyl-tert-butyl-n-propylphosphine, tert-butyl-tert-amyl-n-
Butylphosphine, tert-amyl-tert-butylisobutylphosphine, tert-amyl-tert
-Butylcyclohexylphosphine, tert-amyl-tert-butylbenzylphosphine, tert-amyl-tert-butylphenethylphosphine, ter
t-amyl-tert-butyl (p-methylbenzyl)
Phosphine, di- (1-adamantyl) ethylphosphine, di- (1-adamantyl) n-butylphosphine,
Di- (1-adamantyl) tert-butylphosphine, di- (1-adamantyl) tert-amylphosphine, di- (1-adamantyl) cyclopentylphosphine, di- (1-adamantyl) cyclohexylphosphine, di- (1-adamantyl) ) Benzylphosphine,
Di- (1-adamantyl) phenethylphosphine, di-
(1-adamantyl) (p-methylbenzyl) phosphine, tri- (1-adamantyl) phosphine, di- (1
-Adamantyl) (2-adamantyl) phosphine, di- (1-adamantyl) (α-methylbenzyl) phosphine, di- (1-adamantyl) (2-phenyl-2-
Propyl) phosphine, di-tert-butyl (2-methoxyethyl) phosphine, di-tert-butyl (2
-Phenoxyethyl) phosphine, di-tert-butyl (p- (tert-butyloxy) phenethyl) phosphine, di-tert-butyl (2,4-dimethylbenzyl) phosphine, di-tert-amyl (2-methoxyethyl) phosphine , Di-tert-amyl (2-phenoxyethyl) phosphine, di-tert-amyl (p- (tert-butyloxy) phenethyl) phosphine, di-tert-amyl (2,4-dimethylbenzyl) phosphine, (1-adamantyl ) -Tert-Butylethylphosphine, (1-adamantyl) -ter
t-butyl-n-butylphosphine, (1-adamantyl) -tert-butylcyclohexylphosphine,
(1-adamantyl) -tert-butylbenzylphosphine, (1-adamantyl) -tert-butyl (p
-Methylbenzyl) phosphine and di-tert-butyl (methoxymethyl) phosphine.

[0043]

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. And it can be manufactured by safe operation. And by using a catalytic amount of a copper compound,
The tertiary phosphine can be produced in high yield and high purity, and the amount of waste liquid generated in the post-treatment after the reaction can be significantly reduced.

In particular, the amount of the copper compound used is determined by the formula (1)
0.1 to 5 with respect to the dialkylphosphinas halide of
By setting the content to be mol%, the objective tertiary phosphine of the general formula (3) can be obtained in an extremely high yield. Furthermore, since the Grignard reagent, which can be easily prepared industrially and has high reactivity, is used as a raw material, various tertiary phosphines having bulky substituents can be produced.

[0045]

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.

[0046]

Example 1 Synthesis of di-tert-butylethylphosphine A 300-mL four-necked flask, which had been purged with nitrogen, was charged with
Di-tert-butylphosphinas chloride 18.1
g (0.1 mol) and copper (I) bromide 0.28 g (0.0
02 mol (corresponding to 2 mol%)) and tetrahydrofuran 6
It was charged with 0 ml. 55 ml (0.11 mol) of a tetrahydrofuran solution of ethyl magnesium chloride having a concentration of 2 mol / liter was added dropwise thereto over 1 hour while maintaining the temperature at 25 ° C to 30 ° C. After completion of dropping, the mixture was stirred at the same temperature for 2 hours. After the reaction solution was returned to room temperature, the disappearance of di-tert-butylphosphinas chloride was confirmed by gas chromatography. Then, 50 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 was distilled off under reduced pressure, and then distillation was carried out.
By collecting the fractions distilled at ℃, the target di-
15.7 g of tert-butylethylphosphine (purity 9
8.0%) was obtained as an oily substance. Yield 88.2%.

[0047]

Example 2 Synthesis of di-tert-butylmethylphosphine (No. 1) A 300-ml four-necked flask having a sufficient nitrogen substitution was used.
Di-tert-butylphosphinas chloride 9.0 g
(0.05 mol) and 0.025 g of copper (I) chloride (0.
25 mmol (corresponding to 0.5 mol%)) and 30 ml of tetrahydrofuran were charged. 55 ml (0.055 mol) of a tetrahydrofuran solution of methylmagnesium bromide having a concentration of 1 mol / liter was added dropwise thereto over 1 hour while maintaining the temperature at 25 ° C to 30 ° C. After the completion of dropping, the mixture was stirred at the same temperature for 5 hours. Disappearance of di-tert-butylphosphinas chloride was confirmed by gas chromatography. Then, add 40 ml of toluene to the reaction mixture.
And 40 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 was distilled off under reduced pressure, followed by distillation, and by collecting fractions distilled at 75 ° C. to 81 ° C. under reduced pressure of 20 torr, 7.4 g of the target di-tert-butylmethylphosphine ( Purity 98.7%) was obtained as an oil. Yield 91.1%.

[0048]

Example 3 Synthesis of di-tert-butylmethylphosphine (Part 2) In Example 2, the addition amount of copper (I) chloride was 0.010 g.
(0.10 mmol (corresponding to 0.2 mol%)), 40
After reacting at 0 ° C. for 10 hours, the same treatment operation was performed to obtain the desired di-tert-butylmethylphosphine 7.1.
g (purity 98.0%) was obtained as an oil. Yield 8
6.6%.

[0049]

Example 4 Synthesis of di-tert-butylisopropylphosphine A 300-mL four-necked flask, which was fully purged with nitrogen, was charged with
Di-tert-butylphosphinas chloride 9.0 g
(0.05 mol) and 0.05 g of copper (I) chloride (0.0
01 mol (corresponding to 1 mol%)) and tetrahydrofuran 3
It was charged with 0 ml. A Grignard reagent solution prepared in 50 ml of tetrahydrofuran from 4.7 g (0.060 mol) of isopropyl chloride and 1.7 g (0.072 mol) of metallic magnesium was added thereto at 25 ° C to 30 ° C. The solution was added dropwise over 1 hour while maintaining the temperature. After completion of dropping, the mixture was stirred at the same temperature 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, add 20 ml of toluene and 5 to the reaction mixture.
% Aqueous solution of 30% sulfuric acid 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 the desired di-t
8.2 g (purity 95.0%) of ert-butylisopropylphosphine was obtained as an oily substance. Yield 92.7%.

[0050]

Example 5 Synthesis of di-tert-butyl (n-butyl) phosphine A 300 ml four-necked flask with a sufficient nitrogen substitution was used.
5.6 g of n-butyl chloride (0.060
Mol) and metallic magnesium 1.7 g (0.072 mol)
Then, a Grignard reagent solution prepared in 100 ml of tetrahydrofuran and 0.13 g of copper (II) acetylacetonate (0.0005 mol (corresponding to 1 mol%)) were charged. A solution prepared by dissolving 9.0 g (0.05 mol) of di-tert-butylphosphinas chloride in 30 ml of tetrahydrofuran was added dropwise thereto over 1 hour while maintaining the temperature of 20 ° C to 25 ° C. After completion of dropping, the mixture was stirred at the same temperature for 2 hours. After that, 30 ml of toluene and 20 ml of 5% sulfuric acid aqueous solution were 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 was distilled off under reduced pressure, followed by distillation, and by collecting the fractions distilled at 111 ° C. under reduced pressure of 19 torr, the desired di-tert-
Butyl (n-butyl) phosphine 9.4 g (purity 98.
0%) was obtained as an oil. Yield 91.1%.

[0051]

Example 6 Synthesis of tri-tert-butylphosphine In a 200 ml four-necked flask, which was fully purged with nitrogen,
Di-tert-butylphosphinas chloride 9.0 g
(0.05 mol) and 0.05 g of copper (I) chloride (0.0
005 mol (corresponding to 1 mol%)) and 20 ml of tetrahydrofuran were charged. There terr-
A Grignard reagent solution prepared in 50 ml of tetrahydrofuran was prepared from 6.0 g (0.065 mol) of butyl chloride and 1.9 g (0.078 mol) of metallic magnesium while maintaining the temperature of 20 ° C to 25 ° C. It dripped over 1 hour. After the completion of dropping, the mixture was stirred at a temperature of 35 ° C to 40 ° C for 3 hours. By gas chromatography
The disappearance of tert-butylphosphinas chloride was confirmed. Then, 20 ml of toluene and 20 ml of 5% sulfuric acid aqueous solution were added to the reaction liquid 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, followed by distillation, and by collecting the fractions distilled at 111 to 113 ° C. under reduced pressure of 15 torr, 9.2 g of the target tri-tert-butylphosphine (purity 99.0%) was obtained as an oily substance. Yield 90.2%.

[0052]

Example 7 Synthesis of di-tert-butylbenzylphosphine In a 200 ml four-necked flask with a sufficient nitrogen substitution,
A Grignard reagent solution prepared in advance in 50 ml of tetrahydrofuran from 8.2 g (0.065 mol) of benzyl chloride and 2.1 g (0.085 mol) of metallic magnesium, and 0.055 g of copper (II) bromide.
(0.0003 mol (corresponding to 0.6 mol%)) was charged. Thereto, 9.0 g (0.05 mol) of di-tert-butylphosphinas chloride was added dropwise as it was without being dissolved in a solvent at a temperature near 40 ° C. over 1 hour. After the completion of dropping, the mixture was stirred at a temperature of 40 ° C to 45 ° C for 3 hours. After returning the reaction solution to room temperature, 20 ml of toluene and 20 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 to obtain 0.5 to
By collecting the fractions distilled at 145 ° C. to 150 ° C. under reduced pressure of rr, 10.6 g of target di-tert-butylbenzylphosphine (purity 98.5%)
Was obtained as an oily substance. Yield 88.3%.

[0053]

Example 8 Synthesis of di-tert-amylcyclohexylphosphine A 300-mL four-necked flask, which was fully nitrogen-substituted, was charged with
Di-tert-amylphosphinas chloride 10.4
g (0.05 mol) and 0.10 g of copper (I) chloride (0.
001 mol (corresponding to 2 mol%)) and 30 ml of tetrahydrofuran were charged. A Grignard reagent solution prepared in 50 ml of tetrahydrofuran from 8.3 g (0.060 mol) of cyclohexyl chloride and 2.0 g (0.08 mol) of magnesium metal was added thereto at 25 ° C to 30 ° C. The solution was added dropwise over 1 hour while maintaining the temperature. After the completion of dropping, the mixture was stirred at a temperature of 35 ° C to 40 ° C for 6 hours. After returning the reaction solution to room temperature, 20 ml of toluene and 20 ml of a 5% sulfuric acid aqueous solution were 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 and low-boiling point components were distilled off under reduced pressure to obtain 12.4 g (purity 94.9%) of the target di-tert-amylcyclohexylphosphine as an oily substance. Yield 90.2%. Mass (CI method) M / z 257 (M ⁺ +1: base)

[0054]

Comparative Example 1 The amount of copper (I) chloride added in Example 6 was 3 mg (corresponding to 0.05 mol% with respect to di-tert-butylphosphinas chloride), and the reaction was carried out at the reflux temperature for 10 hours. According to gas chromatography analysis, the conversion rate to tri-tert-butylphosphine was 15%.

[0055]

Comparative Example 2 The amount of copper (I) chloride added in Example 6 was 0.75 g (corresponding to 15 mol% with respect to di-tert-butylphosphinas chloride), and after the same reaction and treatment, The solvent and low-boiling components were distilled off under reduced pressure to obtain 5.9 g of tri-tert-butylphosphine (purity 93.8%) as an oily substance. Yield 54.4
%.

   ─────────────────────────────────────────────────── ─── Continued front page    F-term (reference) 4H039 CA90 CE90                 4H050 AA02 AB40 BA05 BA37 BA40                       WA15 WA26

Claims (10)

[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 a linear or branched alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aralkyl group or a lower alkoxy lower alkyl group,
X'represents a chlorine, bromine or iodine atom. ) Is reacted with a Grignard reagent represented by the formula (1) in the presence of a copper compound in an amount corresponding to 0.1 to 5 mol% with respect to the dialkylphosphinus halide of the general formula (1), General formula (3) (In the formula, R ₁ , R ₂ and R ₃ have the same meanings as described above.) A method for producing a tertiary phosphine. 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 a Grignard reagent represented by the general formula (2), water or an acidic aqueous solution, and if necessary, an organic solvent. The mixture according to claim 1 or 2, wherein the mixture is stirred, and the aqueous layer is separated and removed from the obtained mixed liquid (b), and then the solvent is distilled off under normal pressure or reduced pressure. 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 carbon atom bonded to the magnesium atom of the Grignard reagent represented by the general formula (2) is a primary carbon, and the carbon atom according to any one of claims 1 to 4. Method for producing tertiary phosphine. 6. The carbon atom bonded to the magnesium atom of the Grignard reagent represented by the general formula (2) is a secondary carbon, and the carbon atom according to any one of claims 1 to 4. Method for producing tertiary phosphine. 7. The carbon atom bonded to the magnesium atom of the Grignard reagent represented by the general formula (2) is a tertiary carbon, and the carbon atom according to any one of claims 1 to 4. Method for producing tertiary phosphine. 8. 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. 9. The dialkylphosphinas halide represented by the general formula (1) is di-tert-butylphosphinas chloride or di-tert-amylphosphinas chloride. Method for producing tertiary phosphine. 10. The dialkylphosphinas halide represented by the general formula (1) is di-tert-butylphosphinas chloride, and the Grignard reagent represented by the general formula (2) is tert-butylmagnesium halide. The method for producing a tertiary phosphine according to claim 9, which is characterized in that: