JP2000128891A - Production of cycloalkyldiarylphosphines - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cycloalkyldiaryphosphine in which the 2-position of a cycloalkyl is substituted with an alkyl by an industrially readily handleable method in a short process in a high yield by reacting a lithium diaryl phosphide with a cycloalkylsulfonate in an ether-based solvent. SOLUTION: A lithium diaryl phosphide of the formula LiPR1R2 (R1 and R2 are each a substituted or nonsubstituted aryl) is reacted with a cycloalkylsulfonate of the formula: R3OSO2R4 (R3 is a cycloalkyl substituted with an alkyl at the 2-position; R4 is a lower alkyl or phenyl substituted with a lower alkyl) in an ether-based solvent (a cyclic alkyl monoether preferably such as tetrahydrofuran, etc.), to give the objective compound of the formula. Preferably lithium diphenyl phosphide is reacted with menthyl mesylate or menthyl tosylate to give d-neomenthyldiphenylphosphine. The reaction temperature is preferably 25-35 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing cycloalkyldiarylphosphines wherein the 2-position of a cycloalkyl group is substituted with an alkyl group.

[0002]

2. Description of the Related Art Cycloalkyldiarylphosphines in which the 2-position of a cycloalkyl group is substituted with an alkyl group include:
It is a very useful compound as a ligand of a transition metal catalyst used in a hydrogenation reaction, a hydroformylation reaction, a hydrosilylation reaction, etc. of an unsaturated compound. For example, menthyldiphenylphosphine and neomenthyldiphenylphosphine allow asymmetric synthesis by imparting diastereoselectivity to transition metal complexes [eg, Journal of Organic Chemistry (J. Org. Chem.),
39, 270 (1974)].

Conventionally, as a method for producing a cycloalkyldiarylphosphine in which the 2-position of a cycloalkyl group is substituted with an alkyl group, a method comprising reacting a cycloalkyl halide derivative with an alkali metal diarylphosphide [eg, Journal Of Organometallic Chemistry, 210, 9 (19
81)], a method of producing a compound by reacting a Grignard reagent derived from a cycloalkyl halide with a diarylphosphine halide (for example, JP-A-51-88942).
However, any of these methods generally has a drawback that a desired cycloalkyldiarylphosphine can be obtained only in a low yield.

As a method of solving this drawback, an alkali metal diaryl phosphide synthesized from a triaryl phosphine and a cycloalkyl mesylate or tosylate in which the 2-position of a cycloalkyl group is substituted with an alkyl group are treated at 50 ° C. to 100 ° C. A method for producing cycloalkyldiarylphosphine by reacting at a temperature is known (WO 97/41131).

In this method, sodium diaryl phosphide, potassium diaryl phosphide and lithium diaryl phosphide are mentioned as alkali metal diaryl phosphides. However,
When sodium diaryl phosphide and potassium diaryl phosphide are used, the desired cycloalkyl diaryl phosphine can be synthesized in high yield, but it is very difficult to synthesize sodium diaryl phosphide or potassium diaryl phosphide. It requires a long reaction time and has a serious problem in industrial production, such as handling of sodium and potassium involves danger.

On the other hand, if lithium is used as the alkali metal, the above danger of handling and the problem of reaction time in the synthesis can be improved. However, as described in WO 97/41131, the reaction is carried out in an ether solvent. When performed, lithium diaryl phosphide or aryl lithium by-produced during the synthesis of lithium diaryl phosphide is
Since the ether bond of the ether solvent is cleaved and the reaction between the lithium diaryl phosphide and the cycloalkyl mesylate or tosylate is affected, the yield of the desired cycloalkyl diaryl phosphine is greatly reduced. . Therefore, when lithium diaryl phosphide is used, it is strongly proposed to carry out the reaction with a hydrocarbon solvent.

[0007] WO 97/35866 also discloses that a lithium diaryl phosphide is reacted with a cycloalkyl halide in which the 2-position of a cycloalkyl group is substituted with an alkyl group in a hydrocarbon solvent to form a cycloalkyl group.
A method for producing a cycloalkyldiarylphosphine substituted at an alkyl group is described.

As described above, in the prior art, in order to produce cycloalkyldiarylphosphine with high yield using lithium diarylphosphide, a hydrocarbon solvent is used as a reaction solvent. Before the reaction of lithium diaryl phosphide with cycloalkyl halide or cycloalkyl mesylate or tosylate, lithium diaryl phosphide must be converted from ether solvent to hydrocarbon There is a problem that a complicated operation of solvent replacement with a system solvent is required.

[0009]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems, and it is easy to handle industrially, has a short process, and has a high yield.
It is an object of the present invention to provide a method for producing a cycloalkyldiarylphosphine substituted with an alkyl group.

[0010]

The present invention provides a compound represented by the following general formula (I):

LiPR ¹ R ² (I) wherein, in formula (I), R ¹ and R ² may be the same or different;
Each represents a substituted or unsubstituted aryl group)

A lithium diaryl phosphide represented by the following general formula (II)

R ³ OSO ₂ R ⁴ (II) [In the formula (II), R ³ represents a cycloalkyl group substituted at the 2-position with an alkyl group, and R ⁴ represents a lower alkyl group or a lower alkyl group. Represents a phenyl group. ]

Wherein the cycloalkylsulfonate represented by the general formula (III) is reacted in an ether solvent.

[0015]

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Wherein R ¹ , R ² and R ³ have the same meanings as defined above in the formula (III).

Further, in the method of the present invention, the reaction
It is preferable to carry out at 0 ° C. or lower. Reaction temperature is 50 ° C
Exceeding the formula (I) is presumed to promote the side reaction between lithium diaryl phosphide, which is a reaction raw material, and an ether solvent, and the yield tends to decrease, which is not preferable.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. R ¹ and R ² in the general formula (I) may be the same or different and represent a substituted or unsubstituted aryl group. Examples of the aryl group include monocyclic and multicyclic groups such as phenyl, 1-naphthyl, 2-naphthyl, 2-biphenylyl, 3-biphenylyl, 4-biphenylyl, acenaphthyl, phenanthryl and tetrahydronaphthyl. And a cyclic aryl group. Examples of the substituent of the aryl group include a branched or straight-chain alkyl group having 1 to 12 carbon atoms, and specific examples thereof include those similar to those exemplified for R ³ described below. .

In the lithium diaryl phosphide represented by the general formula (I), it is preferred that both R ¹ and R ² are phenyl.

In the general formula (II), 2 represented by R ³
Examples of the cycloalkyl portion of the cycloalkyl group having an alkyl group at the position include a cycloalkyl group having 5 to 8 carbon atoms, such as a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. Among them, a cyclohexyl group is preferable.

The above cycloalkyl group has an alkyl group at least at the 2-position to the -OSO ₂ R ⁴ group. As the alkyl group substituted at the 2-position, a branched or linear alkyl group having 1 to 12 carbon atoms is preferable, and specifically, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-
Examples thereof include a butyl group, a pentyl group, a hexyl group, an octyl group, a nonyl group, and a decyl group. Among them, an alkyl group having 1 to 5 carbon atoms, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and an n- Butyl group, isobutyl group, sec-
A butyl group, a tert-butyl group, a pentyl group and the like are preferred.

The cycloalkyl group may be substituted at another position in addition to the alkyl group at the 2-position. For example, when the cycloalkyl group is a cyclohexyl group, a carbon atom at the 5-position may be substituted. Those having an alkyl group having 1 to 12 carbon atoms are preferable, and those having an alkyl group having 1 to 5 carbon atoms are more preferable. Examples of the alkyl group include the same as those described above.

In the general formula (II), R ⁴ represents a lower alkyl group or a phenyl group substituted with a lower alkyl group. As the lower alkyl group, an alkyl group having 1 to 4 carbon atoms (for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, te
rt-butyl group and the like). Examples of the phenyl group substituted with a lower alkyl group include a 2-methylphenyl group and 3-
Examples include a methylphenyl group and a 4-methylphenyl group. Among them, the case where R ⁴ is a methyl group or a 4-methylphenyl group is preferable.

As the lithium diaryl phosphide represented by the general formula (I), lithium diphenyl phosphide is preferably used.

In the cycloalkyl sulfonate represented by the general formula (II), R ³ is a 2-isopropyl-5-methylcyclohexyl group, and R ⁴ is a methyl group or 4
-A compound that is a methylphenyl group is preferred, specifically, menthyl mesylate, neomenthyl mesylate, isomenthyl mesylate, neoisomenthyl mesylate,
Menthiltosylate, neomenthyltosylate, isomenthyltosylate or neoisomenthyltosylate can be mentioned, among which menthyl mesylate or mentiltosylate is more preferably used. These are d-body,
It may be an l-form or a dl-form.

As the cycloalkyldiarylphosphine represented by the general formula (III), a compound wherein R ¹ and R ² are phenyl groups and R ³ is a 2-isopropyl-5-methylcyclohexyl group is preferred. Include menthyldiphenylphosphine, neomenthyldiphenylphosphine, isomenthyldiphenylphosphine or neoisomenthyldiphenylphosphine, among which neomenthyldiphenylphosphine is preferred. These may be d-, l-, or dl-form.

In the most preferred embodiment of the present invention, 1-menthyl mesylate or tosylate is reacted with lithium diphenylphosphine to obtain d-neomenthyldiphenylphosphine.

As the ether solvent used in the method of the present invention, for example, two solvents per molecule such as 1,2-dimethoxyethane, 2-methoxyethyl ether, 1,4-dioxane and tetrahydrofurfurylethyl ether are used. Polyether having the above ether bond, dialkyl ether, dicycloalkyl ether, diaryl ether,
Monoalkyl monoaryl ether, monocycloalkyl monoaryl ether, monoalkyl monocycloalkyl ether and cyclic alkyl monoether (cyclic alkyl ether containing one ether bond in the cyclic structure)
And the like.

Among them, dialkyl ethers such as dimethyl ether, diethyl ether, di-n-propyl ether, diisopropyl ether and di-n-butyl ether;
Diaryl ethers such as diphenyl ether, monoalkyl monoaryl ethers such as anisole are preferred, and cyclic alkyl monoethers such as tetrahydrofuran (THF) and tetrahydropyran are more preferably used. Further, a cyclic alkyl monoether substituted with a lower alkyl group can also be used, and examples thereof include tetrahydrofuran substituted with an alkyl group such as a methyl group, an ethyl group, an n-propyl group, and an isopropyl group. These may be used alone or as a mixture of two or more.

The amount of the cycloalkyl sulfonate represented by the general formula (II) is 0.5 equivalent to a large excess (molar ratio) with respect to the lithium diaryl phosphide represented by the general formula (I), Preferably 0.5 to 1.2 equivalents (molar ratio) are used, more preferably 0.9 to 1.1 equivalents (molar ratio). The ether solvent is generally used in an amount of 1 volume to a large excess with respect to the reaction raw materials.

The reaction temperature is preferably 50 ° C. or lower, more preferably 10 ° C. to 50 ° C., further preferably 20 ° C. to 40 ° C., particularly preferably 25 ° C. to 35 ° C.

The lithium diaryl phosphide represented by the general formula (I) and the cycloalkyl sulfonate represented by the general formula (II), which are raw materials for the method of the present invention, are prepared according to the method described in US Pat. No. 5,710,340. Can be manufactured. Further, since the cycloalkyldiarylphosphine represented by the general formula (III) has an asymmetric carbon,
Although there are various isomers, the production method of the present invention is applicable in all cases.

[0033]

Next, the present invention will be described in more detail by way of examples.

Reference Example 1: Synthesis of lithium diphenyl phosphide A solution of triphenyl phosphine (10.0 g, 38.1 mmol) in anhydrous tetrahydrofuran (THF) (70 ml) was mixed with lithium (1.06 g, 153 mmol) at room temperature under an argon atmosphere. ) For 2 hours. Then, tert-butyl chloride (3.52 g, 3
8.1 mmol) and refluxed for 30 minutes under an argon atmosphere. Lithium diphenyl phosphide was obtained as a dark red solution and the conversion to lithium diphenyl phosphide was 95% or more.

Reference Example 2 Synthesis of Menthyl Mesylate (-)-Menthol (5.95 g, 38.1 mmol) in pyridine (24 ml)
To the solution was added methanesulfonyl chloride (5.24 g, 4
5.7 mmol), and the mixed solution was reacted for 4 hours under ice cooling. Thereafter, the excess pyridine is neutralized with concentrated hydrochloric acid,
Extraction with toluene, separation of the organic layer, and evaporation of the solvent gave l-menthyl mesylate as a colorless oil in a quantitative yield.

Example 1 l-menthyl mesylate prepared according to Reference Example 2 above
(8.93 g, 38.1 mmol) in anhydrous THF (70 ml) was added to anhydrous THF solution containing 7.33 g (38.1 mmol) of lithium diphenyl phosphide prepared according to Reference Example 1 above, and the mixture was allowed to stand at 30 ° C. for 3 hours. After the reaction, add water
(80 ml) was added. After the organic layer was separated and the solvent was distilled off, methanol (80 ml) and water (8 ml) were added, and the mixture was crystallized to obtain 8.66 g of colorless crystals of d-neomenthyldiphenylphosphine in a 70% yield. did. ¹ H-
The analysis values of NMR, ¹³ C-NMR, and optical rotation coincided with the analysis values of the sample.

The optical isomer of neomenthyldiphenylphosphine was analyzed by gas chromatography in the following manner. [Gas chromatography analysis conditions] Column: Silicone SE-30GC grade Uniport HP (manufactured by GL Sciences Inc.) Column temperature: Increased from 100 ° C to 220 ° C Detector temperature: 220 ° C (Detector: FID) Carrier gas: Nitrogen gas (50 ml / min) In the following examples, analysis was performed under the same conditions.

Example 2 To an anhydrous THF solution containing 7.33 g (38.1 mmol) of lithium diphenyl phosphide prepared according to Reference Example 1 above was added l-menthyl mesylate (8.9%) prepared according to Reference Example 2 above.
3 g, 38.1 mmol) in anhydrous THF (70 ml) was added, and the mixed solution was allowed to react at 30 ° C. for 3 hours.
0 ml) was added. After separating the organic layer and evaporating the solvent,
Methanol (80 ml) and water (8 ml) were added for crystallization,
8.66 g of colorless crystals of d-neomenthyldiphenylphosphine were obtained with a yield of 70%.

Example 3 l-menthyl mesylate prepared according to the above reference example 2
(8.93 g, 38.1 mmol) in anhydrous THF (70 ml) was added to anhydrous THF solution containing 7.33 g (38.1 mmol) of lithium diphenyl phosphide prepared according to Reference Example 1 above, and the mixed solution was allowed to stand at 20 ° C. for 4 hours. After the reaction, add water (8
0 ml) was added. After separating the organic layer and evaporating the solvent,
Methanol (80 ml) and water (8 ml) were added for crystallization,
8.41 g of colorless crystals of d-neomenthyldiphenylphosphine were obtained with a yield of 68%.

Example 4 l-menthyl mesylate prepared according to the above reference example 2
(8.93 g, 38.1 mmol) in anhydrous THF (70 ml) was added with anhydrous THF solution containing 7.33 g (38.1 mmol) of lithium diphenyl phosphide prepared according to the above Reference Example 1, and the mixed solution was heated at 40 ° C. for 2 hours. After the reaction, add water (8
0 ml) was added. After separating the organic layer and evaporating the solvent,
Methanol (80 ml) and water (8 ml) were added for crystallization,
8.29 g of colorless crystals of d-neomenthyldiphenylphosphine were obtained with a yield of 67%.

Example 5 1-menthyl mesylate (1
0.7 g (45.7 mmol) in anhydrous THF (70 ml) was mixed with lithium diphenyl phosphide prepared according to Reference Example 1 above.
An anhydrous THF solution containing 7.33 g (38.1 mmol) was added, and the mixed solution was reacted at 30 ° C. for 3 hours.
l) was added. After the organic layer was separated and the solvent was distilled off, methanol (80 ml) and water (8 ml) were added to carry out crystallization.
8.66 g of colorless crystals of d-neomenthyldiphenylphosphine were obtained at a% yield.

Comparative Example 1 Triphenylphosphine (10.0 g, 38.1 mmol) in anhydrous TH
The F (70 ml) solution was reacted with shredded sodium (3.50 g, 153 mmol) under an argon atmosphere under reflux conditions. As a result, it took 16 hours to obtain a conversion to sodium diphenyl phosphide of 95% or more. The sodium diphenyl phosphide was obtained as a dark red solution. To a THF solution of sodium diphenyl phosphide was added a solution of menthyl mesylate (8.93 g, 38.1 mmol) prepared in Reference Example 2 in THF (70 ml), and the solution was added at 65 ° C. under an argon atmosphere at 65 ° C.
After reacting for an hour, water (80 ml) was added to the reaction solution. After separating the organic layer and evaporating the solvent, methanol was added,
Crystallization was performed to obtain colorless crystals of neomenthyldiphenylphosphine at a yield of 68%.

[0043]

According to the present invention, it is easy to handle industrially,
In addition, cycloalkyldiarylphosphines having an alkyl group at least at the 2-position of the cycloalkyl group can be produced in a short step and in a high yield. That is, according to the present invention, the use of lithium diaryl phosphide, which has a low risk of handling and is easy to synthesize, and the ether-based solvent used in the synthesis of lithium diaryl phosphide does not need to be solvent-substituted, and is used as it is. By using the compound, a cycloalkyldiarylphosphine having an alkyl group at the 2-position of the cycloalkyl group can be produced in high yield.

The cycloalkyldiarylphosphines having an alkyl group at the 2-position of the cycloalkyl group obtained by the present invention can be used as a catalyst for transition metal catalysts used in hydrogenation reactions, hydroformylation reactions and hydrosilylation reactions of unsaturated compounds. It is a compound useful as a ligand.

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Claims (6)

[Claims] 1. The following general formula (I) LiPR ¹ R ² (I) wherein, in the formula (I), R ¹ and R ² may be the same or different;
Each represents a substituted or unsubstituted aryl group] and a lithium diaryl phosphide represented by the following general formula (I
I) R ³ OSO ₂ R ⁴ (II) [In the formula (II), R ³ represents a cycloalkyl group substituted at the 2-position with an alkyl group, and R ⁴ is substituted with a lower alkyl group or a lower alkyl group. Represents a phenyl group. Wherein the cycloalkyl sulfonate represented by the general formula (III) is reacted in an ether solvent. [In the formula (III), R ¹ , R ² and R ³ are as defined above.]
A method for producing a cycloalkyldiarylphosphine represented by the formula: 2. The method according to claim 1, wherein the reaction temperature is 50 ° C. or lower. 3. The method according to claim 1, wherein the ether solvent is at least one selected from dialkyl ethers, diaryl ethers, monoalkyl monoaryl ethers and cyclic alkyl monoethers. 4. The method according to claim 3, wherein the ether solvent is a cyclic alkyl monoether. 5. The method according to claim 1, wherein the cycloalkyl sulfonate represented by the formula (II) is menthyl mesylate or tosylate. 6. The method according to claim 1, wherein the lithium diaryl phosphide of the formula (I) is lithium diphenyl phosphide.