JP7599202B2 - Method for producing organosilicon compounds having dimethylsilyl groups - Google Patents

Description

The present invention relates to a method for producing an organosilicon compound having a dimethylsilyl group, and more specifically, to a method for producing an organosilicon compound having a dimethylsilyl group by hydrosilylating an alkene with dimethylsilane generated by disproportionating 1,1,3,3,5,5,7,7-octamethyltetrasiloxane in the presence of a catalytic amount of tris(pentafluorophenyl)borane.

Dimethylsilane is a gas at room temperature and pressure, and is highly flammable, so it must be handled with the utmost care. For example, measures to prevent gas leakage, such as installing a gas cylinder filled with dimethylsilane gas inside a cylinder cabinet, are necessary. In addition, when used in a liquid-phase synthesis reaction, it is difficult to accurately introduce a specified amount of dimethylsilane into the reaction solution because it is a gas. This difficulty becomes more pronounced the smaller the reaction scale becomes.
Therefore, a method has been developed in which dimethylsilane is generated from an easily handled precursor and used in the target reaction in the same reaction vessel. For example, Oestreich et al. have reported that dimethylsilane is generated from cyclohexa-2,5-dien-1-yldimethylsilane in the presence of a catalytic amount of tris(pentafluorophenyl)borane, and that this is used for hydrosilylation of alkenes and dehydrogenative condensation with alcohols (see, for example, Patent Document 1 and Non-Patent Document 1). However, there is a problem in that alkyllithium, which is a pyrophoric substance, must be used in the synthesis of cyclohexa-2,5-dien-1-yldimethylsilane. In addition, when styrene, which is a type of terminal alkene, is used as a substrate, only a product in which the generated dimethylsilane and styrene react in a 1:2 ratio is obtained, and a product in which the 1:1 ratio is not obtained.
On the other hand, it is known that 1,1,3,3,5,5,7,7-octamethyltetrasiloxane, which is a stable and easily handled liquid, undergoes a disproportionation reaction in the presence of a catalytic amount of tris(pentafluorophenyl)borane to produce dimethylsilane and hexamethylcyclotrisiloxane (see Patent Document 2 and Non-Patent Document 2). However, this disproportionation reaction is an equilibrium reaction, and there are no known cases in which the generated dimethylsilane has been used in another synthetic reaction in the same reaction vessel.

European Patent Publication No. 2845857 U.S. Patent No. 7,148,370

A. Simonneau, M. Oestreich, Angew. Chem. Int. Ed., 2013, 52, 11905. A. Simonneau, J. Friebel, M. Oestreich, Eur. J. Org. Chem., 2014, 2077. J. Chojnowsk, W. Fortuniak, J. Kurjata, S. Rubinsztajn, J. A. Cella, Macromolecules, 2006, 39, 3802. J.Chojnowsk, S.Rubinsztajn, J.A.Cella, W.Fortuniak, M.Cypryk, J.Kurjata, K.Kazmierski, Organometallics 2005, 24, 6077-6084.

The present invention has been made in consideration of the above circumstances, and aims to provide a simple method for producing an organosilicon compound having a dimethylsilyl group.

（式（Ｂ－１）、（Ｂ－２）中、Ｒ^１～Ｒ^３はそれぞれ独立して、水素原子、又は少なくとも１種のハロゲン原子を含んでいてもよい炭素原子数１～２０の炭化水素基を表す。但し、Ｒ^１～Ｒ^３の２以上が炭化水素基である場合、Ｒ^１～Ｒ^３の２以上の炭化水素基が連結して環状構造を形成していてもよい。）
トリス（ペンタフルオロフェニル）ボラン、および、下記式（Ａ）で表される化合物の存在下、１，１，３，３，５，５，７，７－オクタメチルテトラシロキサンから不均化反応によりジメチルシランを生じさせる工程であって、前記ジメチルシランが前記式（Ａ）で表される化合物をヒドロシリル化し、式（Ｂ）で表されるジメチルシリル基を有する有機ケイ素化合物を生成する工程を含む、製造方法に関する：

（式（Ａ）中、Ｒ^１～Ｒ^３はそれぞれ独立して、水素原子、又は少なくとも１種のハロゲン原子を含んでいてもよい炭素原子数１～２０の炭化水素基を表す。但し、Ｒ^１～Ｒ^３の２以上が炭化水素基である場合、Ｒ^１～Ｒ^３の２以上の炭化水素基が連結して環状構造を形成していてもよい。） As a result of extensive investigations aimed at solving the above-mentioned problems, the present inventors have noted that tris(pentafluorophenyl)borane, which is a catalyst for generating dimethylsilane by the disproportionation of 1,1,3,3,5,5,7,7-octamethyltetrasiloxane, is also known as a catalyst for the hydrosilylation reaction of alkenes. They have discovered that by adding an alkene to a reaction vessel in which the disproportionation reaction is carried out, the disproportionation reaction and the hydrosilylation reaction can proceed simultaneously, thereby efficiently producing the desired organosilicon compound having a dimethylsilyl group, and have completed the present invention.
That is, the present invention includes the following.
<1> A method for producing an organosilicon compound having a dimethylsilyl group represented by the following formula (B-1) or (B-2),

(In formulae (B-1) and (B-2), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)
The present invention relates to a production method including a step of producing dimethylsilane by a disproportionation reaction from 1,1,3,3,5,5,7,7-octamethyltetrasiloxane in the presence of tris(pentafluorophenyl)borane and a compound represented by the following formula (A), the dimethylsilane hydrosilylating the compound represented by formula (A) to produce an organosilicon compound having a dimethylsilyl group represented by formula (B):

(In formula (A), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)

Here, one embodiment of the manufacturing method of the present invention is
<2> The production method according to the above item <1>, wherein the disproportionation reaction and the hydrosilylation reaction are carried out in the same reaction vessel.
Moreover, one embodiment of the manufacturing method of the present invention is
<3> The manufacturing method according to <1> or <2> above,
The method further comprises a step of purifying the organosilicon compound having a dimethylsilyl group obtained in the above step.

In another aspect, the present invention provides a method for producing a pharmaceutical composition comprising the steps of:
<4> A method using tris(pentafluorophenyl)borane as a catalyst,
The present invention relates to a method for producing an organosilicon compound having a dimethylsilyl group by using an alkene and 1,1,3,3,5,5,7,7-octamethyltetrasiloxane, and using tris(pentafluorophenyl)borane as a catalyst.

According to the present invention, instead of directly using dimethylsilane, which is difficult to handle because it is a flammable gas, dimethylsilane is generated by the disproportionation reaction of 1,1,3,3,5,5,7,7-octamethyltetrasiloxane, which is a stable and easy-to-handle liquid, and this is then used in the hydrosilylation reaction of an alkene, thereby providing a simple method for producing an organosilicon compound having a dimethylsilyl group, which is a useful building block in synthetic chemistry. In addition, since the catalyst for generating dimethylsilane from 1,1,3,3,5,5,7,7-octamethyltetrasiloxane is the same as the catalyst for the hydrosilylation reaction of an alkene, there is no need to use multiple catalysts.

Specific examples will be given to explain the details of the present invention, but the invention is not limited to the following content and can be modified as appropriate without departing from the spirit of the invention.

（式（Ａ）及び式（Ｂ－１）～（Ｂ－２）中、Ｒ^１～Ｒ^３はそれぞれ独立して、水素原子、又は少なくとも１種のハロゲン原子を含んでいてもよい炭素原子数１～２０の炭化水素基を表す。但し、Ｒ^１～Ｒ^３の２以上が炭化水素基である場合、Ｒ^１～Ｒ^３の２以上の炭化水素基が連結して環状構造を形成していてもよい。） <Method for producing organosilicon compound having dimethylsilyl group>
The method for producing an organosilicon compound having a dimethylsilyl group according to one embodiment of the present invention is characterized by comprising a reaction step in which dimethylsilane generated by a disproportionation reaction of 1,1,3,3,5,5,7,7-octamethyltetrasiloxane in the presence of tris(pentafluorophenyl)borane hydrosilylates an alkene represented by the following formula (A) to produce an organosilicon compound having a dimethylsilyl group represented by the following formulas (B-1) to (B-2).

(In formula (A) and formulas (B-1) and (B-2), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)

As a result of extensive investigations into methods for producing organosilicon compounds having dimethylsilyl groups, the inventors have discovered that, without using dimethylsilane gas, which is difficult to handle, dimethylsilane can be generated by the disproportionation reaction of 1,1,3,3,5,5,7,7-octamethyltetrasiloxane in the presence of tris(pentafluorophenyl)borane and used in the hydrosilylation reaction of various alkenes, which can provide a simple method for producing organosilicon compounds having dimethylsilyl groups, which are useful building blocks in synthetic chemistry.
In a preferred embodiment of the method for producing an organosilicon compound having a dimethylsilyl group of the present invention, dimethylsilane generated by a disproportionation reaction of 1,1,3,3,5,5,7,7-octamethyltetrasiloxane is used to hydrosilylate an alkene represented by formula (A) in the same reaction vessel as the disproportionation reaction. Since the same catalyst can be used, the disproportionation reaction and hydrosilylation can be carried out in the same reaction vessel, making it possible to more simply produce an organosilicon compound having a dimethylsilyl group without directly using dimethylsilane, which is difficult to handle.

In formula (A), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom, and the "hydrocarbon group" may have a branched structure and/or a cyclic structure and may be any of a saturated hydrocarbon group, an unsaturated hydrocarbon group, an aromatic hydrocarbon group, etc. Also, while "when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of the hydrocarbon groups R ¹ to R ³ may be linked to form a cyclic structure," examples of alkenes represented by formula (A) which form a cyclic structure include those represented by the following formula:

Specific examples of R ¹ to R ³ include a hydrogen atom, an alkyl group such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, an n-hexyl group, an n-heptyl group, an n-octyl group, an n-nonyl group, an n-decyl group, an n-undecyl group, an n-dodecyl group, an n-tridecyl group, an n-tetradecyl group, an n-pentadecyl group, an n-hexadecyl group, an n-heptadecyl group, an n-octadecyl group, an n-nonadecyl group, or an n-icosyl group; a cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group; a phenyl group, a 4-methylphenyl group, a 2,4-dimethylphenyl group, a 1-naphthalene group, or a phenyl group; aromatic hydrocarbon groups such as a 2-naphthyl group, a 1-phenanthryl group, a 2-phenanthryl group, a 3-phenanthryl group, a 4-phenanthryl group, a 9-phenanthryl group, a 1-anthryl group, a 2-anthryl group, a 9-anthryl group, a 1-pyrenyl group, a 2-pyrenyl group, a 4-pyrenyl group, a 1-triphenylenyl group, and a 2-triphenylenyl group; aralkyl groups such as a benzyl group, a phenethyl group, a 1-naphthylmethyl group, and a 2-naphthylmethyl group; alkenyl groups such as a vinyl group and an allyl group; and substituted phenyl groups which may have a substituent containing a halogen atom, such as a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-iodophenyl group, and a 4-trifluoromethylphenyl group.

From the viewpoint of availability, R ¹ to R ³ are preferably a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom, more preferably an alkyl group or alkenyl group having 1 to 20 carbon atoms, or an aromatic hydrocarbon group having 6 to 20 carbon atoms, which may contain at least one halogen atom; even more preferably an alkyl group or alkenyl group having 1 to 10 carbon atoms, or an aromatic hydrocarbon group having 6 to 10 carbon atoms which may contain at least one halogen atom; particularly preferably a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, a vinyl group, an allyl group, a phenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 4-acetoxyphenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 4-nitrophenyl group, or a 2,4-dimethylphenyl group; and most preferably a methyl group, an ethyl group, an n-propyl group, a phenyl group, a 4-methylphenyl group, a 4-chlorophenyl group, or a 4-trifluoromethylphenyl group.

The amount of tris(pentafluorophenyl)borane used (charged amount) in the reaction step is, in terms of the amount of substance relative to the alkene having the structure represented by formula (A), usually 0.01 mol% or more, preferably 0.1 mol% or more, more preferably 1 mol% or more, and usually 40 mol% or less, preferably 20 mol% or less, more preferably 10 mol% or less. Within the above range, an organosilicon compound having a dimethylsilyl group can be produced more efficiently.

(solvent)
The reaction step is usually carried out in a solvent. The type of solvent used in the reaction step is preferably a solvent that does not contain oxygen or nitrogen atoms. Examples of the solvent include hydrocarbon solvents such as pentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylene, and trifluoromethylbenzene; and halogenated hydrocarbon solvents such as dichloromethane, chloroform, 1,2-dichloroethane, and o-dichlorobenzene.

(Reaction conditions)
The reaction temperature in the reaction step is usually −20° C. or higher, preferably 0° C. or higher, more preferably 20° C. or higher, and usually 70° C. or lower, preferably 50° C. or lower, more preferably 30° C. or lower. Within the above range, an organosilicon compound having a dimethylsilyl group can be produced more efficiently.
The reaction time of the reaction step is usually 1 hour or more, preferably 2 hours or more, more preferably 6 hours or more, and usually 72 hours or less, preferably 48 hours or less, more preferably 24 hours or less.
The reaction step is usually carried out under an inert atmosphere such as nitrogen or argon.

(Other processes)
In the method for producing an organosilicon compound having a dimethylsilyl group according to the present embodiment, in addition to the above-mentioned reaction step, any other step may be included. The optional step may include a purification step for increasing the purity of the organosilicon compound having a dimethylsilyl group. In the purification step, a purification method that is usually performed in the field of organic synthesis, such as filtration, adsorption, column chromatography, distillation, etc., may be adopted. Specifically, after the reaction step, for example, the reaction mixture may be purified by silica gel column chromatography.

（式（Ｂ－１）～（Ｂ－２）中、Ｒ^１～Ｒ^３はそれぞれ独立して、水素原子、又は少なくとも１種のハロゲン原子を含んでいてもよい炭素原子数１～２０の炭化水素基を表す。但し、Ｒ^１～Ｒ^３の２以上が炭化水素基である場合、Ｒ^１～Ｒ^３の２以上の炭化水素基が連結して環状構造を形成していてもよい。）
なお、Ｒ^１～Ｒ^３は、「式（Ａ）で表されるアルケン」のものと同義である。 The specific type of dimethylsilyl-containing organosilicon compound having a structure represented by formula (B-1) or (B-2) produced by the reaction step is not particularly limited and can be appropriately selected depending on the production purpose.

(In formulae (B-1) and (B-2), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)
In addition, R ¹ to R ³ have the same meaning as in the "alkene represented by formula (A)".

The present invention will be explained in more detail below with reference to examples, but these can be modified as appropriate without departing from the spirit of the present invention. Therefore, the scope of the present invention should not be interpreted as being limited to the specific examples shown below.

Example 1
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). 4-Chlorostyrene (127 μL, 1.0 mmol) was added to this solution. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane ( ^H MD ₂ M ^H , 328 μL, 1.0 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a monohydrosilylated product (61%) and a dihydrosilylated product (10%) were obtained.

Example 2
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). 1-Octene (157 μL, 1.0 mmol) was added to this solution. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane ( ^H MD ₂ M ^H , 328 μL, 1.0 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a monohydrosilylated product (12%) and a dihydrosilylated product (44%) were obtained.

Example 3
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). To this solution, cyclohexene (101 μL, 1.0 mmol) was added. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane ( ^H MD ₂ M ^H , 328 μL, 1.0 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a monohydrosilylated product (46%) and a dihydrosilylated product (12%) were obtained.

Example 4
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). 4-Chlorostyrene (127 μL, 1.0 mmol) was added to this solution. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane ( ^H MD ₂ M ^H , 164 μL, 0.5 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a monohydrosilylated product (25%) and a dihydrosilylated product (4%) were obtained.

Example 5
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). 1-Octene (127 μL, 1.0 mmol) was added to this solution. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane ( ^H MD ₂ M ^H , 164 μL, 0.5 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a dihydrosilylated product (>95%) was obtained.

Example 6
In a glove box with a nitrogen atmosphere, B(C ₆ F ₅ ) ₃ (25.6 mg, 0.05 mmol) was dissolved in dichloromethane (1.0 mL). 1-Octene (127 μL, 1.0 mmol) was added to this solution. Furthermore, 1,1,3,3,5,5,7,7-octamethyltetrasiloxane (164 μL, 0.5 mmol) was added and stirred at room temperature. After 15 hours, ¹ H NMR (internal standard: mesitylene) of the reaction mixture was measured, and it was confirmed that a monohydrosilylated product (10%) and a dihydrosilylated product (31%) were obtained.

The manufacturing method of the present invention makes it possible to easily manufacture organosilicon compounds having dimethylsilyl groups. The organosilicon compounds having dimethylsilyl groups manufactured are useful building blocks in synthetic chemistry, and are useful as various functional materials or raw materials for them.

Claims (4)

A method for producing an organosilicon compound having a dimethylsilyl group represented by the following formula (B-1) :

( In formula (B-1) , R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)
A production method comprising the steps of: generating dimethylsilane by a disproportionation reaction from 1,1,3,3,5,5,7,7-octamethyltetrasiloxane in the presence of tris(pentafluorophenyl)borane and a compound represented by the following formula (A), wherein the dimethylsilane hydrosilylates the compound represented by formula (A) to produce an organosilicon compound having a dimethylsilyl group represented by formula (B -1 ):

(In formula (A), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.) The method according to claim 1, wherein the disproportionation reaction and the hydrosilylation reaction are carried out in the same reaction vessel. The method according to claim 1 or 2,
The method further comprises a step of purifying the organosilicon compound having a dimethylsilyl group obtained in the above step. A process using tris(pentafluorophenyl)borane as a catalyst, comprising the steps of:
A method for producing an organosilicon compound having a dimethylsilyl group represented by the following formula (B-1) using a compound represented by the following formula (A) and 1,1,3,3,5,5,7,7-octamethyltetrasiloxane, comprising using tris(pentafluorophenyl)borane as a catalyst.

(In formula (A) and formula (B-1), R ¹ to R ³ each independently represent a hydrogen atom or a hydrocarbon group having 1 to 20 carbon atoms which may contain at least one halogen atom. However, when two or more of R ¹ to R ³ are hydrocarbon groups, two or more of R ¹ to R ³ may be linked to form a cyclic structure.)