JPH08217780A - Production of trialkylsilyltrialkylsiloxymethylene compound - Google Patents

Abstract

PURPOSE: To industrially and advantageously obtain the subject compound useful as an intermediate, etc., for medicines, agrochemicals and industrial chemicals by reacting a specific aromatic carbonyl compound with chlorosilanes in the presence of a typical metal in an aprotic polar solvent. CONSTITUTION: An aromatic carbonyl compound represented by formula I [Ar is a (substituted)aromatic group; R<1> is H, an alkyl, an aryl or an aralkyl] (e.g. benzaldehyde) is reacted with a chlorosilane represented by formula II (R<2> is an alkyl or an aryl) (e.g. trimethylchlorosilane) in the presence of a typical metal (e.g. powdery magnesium) in an aprotic polar solvent (e.g. N,N- dimethylformamide) at 20-25 deg.C temperature for 5hr to afford the objective trialkylsilyltrialkylsiloxymethylene compound, represented by formula III and useful as an intermediate, etc., for medicines, agrochemicals, industrial chemicals, etc., in high yield at a low cost according to simple operations.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a low molecular weight organosilicon compound useful as an intermediate for medicines, agricultural chemicals, industrial chemicals, and more particularly to a method for producing a trialkylsilyltrialkylsiloxymethylene compound.

[0002]

2. Description of the Related Art Generally, a high molecular silicon compound called silicone is used in many fields including silicone oil, silicone rubber, silicone resin, and electric materials such as transistors due to its excellent heat resistance and processability. in use. These are examples of industrial achievements resulting from the study of the reactivity of low molecular weight organosilicon compounds.

The carbon-silicon bond of the organosilicon compound is cleaved under various conditions, and in recent years, organic synthesis techniques for utilizing this have been developed. That is, the organosilicon compound is
It has attracted attention as an intermediate for synthesizing various organosilicon compounds useful as pharmaceuticals, agricultural chemicals, and industrial chemicals.

Expression

[Chemical 9] [In the formula, Ar is an aromatic group which may have a substituent, R ¹ is a hydrogen atom, an alkyl, aryl or aralkyl group, and R ² is independently an alkyl or aryl group. ] The trialkylsilyltrialkylsiloxymethylene compound represented by the above is also one of such organosilicon compounds.

The silyl ether group --OSi (R ² ) ₃ of the trialkylsilyltrialkylsiloxymethylene compound is easily hydrolyzed by an acid or the like to form --OH. The -OH group derived from a silyl ether group is useful in synthetic chemistry as a functional group of an organosilicon compound.

Regarding the method for producing such an organosilicon compound,

[0007]

[Chemical 10]

[0008] Stannylation and silyl etherification of tributylstannyllithium and trimethylcyanosilane or trimethylchlorosilane from aldehydes, which are shown in, are carried out, and n-butyllithium is added to form C-from the O-Si bond.
Method I for rearrangement to Si bond I (J. Org. Chem. 1988, 53, 2878-28
80, J. Am .. Chem. 1990, 112, 2392-2398), and formula

[0009]

[Chemical 11]

Method for reacting formyltrimethylsilane with Grignard reagent or alkyllithium
II (J. Org. Chem. 1988, 53, 1569-1572), there is a reported example of a method for producing a 1-trialkylsilyl alcohol.

However, in both methods I and II, the reaction temperature must be -78 ° C., so that it is difficult to control the temperature and a special device for cooling is required. Also, the yield
It is as low as 40-60%. Further, in the method II using formyltrimethylsilane as a raw material, the raw material formyltrimethylsilane is expensive and is difficult to synthesize.

[0012] As described above, the conventional method for producing a trialkylsilyltrialkylsiloxymethylene compound is industrially extremely disadvantageous because the operation is complicated and the production cost is high.

[0013]

DISCLOSURE OF THE INVENTION The present invention is to solve the above-mentioned conventional problems, and an object of the present invention is to provide a trialkylsilyltrialkylsiloxymethylene compound which can be carried out at low cost and high yield by a simple operation. It is to provide a manufacturing method of.

[0014]

The present invention is based on the formula

[Chemical 12] [In the formula, Ar is an aromatic group which may have a substituent, R ¹ is a hydrogen atom, an alkyl, aryl or aralkyl group, and R ² is independently an alkyl or aryl group. ] In the method for producing a trialkylsilyltrialkylsiloxymethylene compound represented by the formula,

[Chemical 13] [In the formula, Ar and R ¹ have the same meanings as described above. ] An aromatic carbonyl compound represented by

Embedded image (R ² ) ₃ SiCl [III] [wherein, R ² has the same meaning as described above. ] A method for reacting chlorosilane represented by the formula] with an aprotic polar solvent in the presence of a typical metal is provided, thereby achieving the above object.

In the present specification, the "aromatic group" includes a hydrocarbon aromatic group having a ring structure composed of carbon atoms and hydrogen atoms, and hetero atoms such as nitrogen atom, oxygen atom and sulfur atom. Heteroaromatic groups having a ring structure are included. Specific examples of the hydrocarbon aromatic group include a phenyl group and a naphthyl group. Hydrocarbon aromatic group has 4 carbon atoms
Approximately 12 to 6, especially 6 is preferable. Specific examples of the heteroaromatic group include a thienyl group having a sulfur atom, a pyridyl group having a nitrogen atom, an indolyl group and a pyrazolyl group, a furyl group and a pyrrolyl group having an oxygen atom, and a thiazolyl group having a nitrogen atom and a sulfur atom. Etc. The heteroaromatic group has 1 to 3 hetero atoms and about 3 to 9 carbon atoms, particularly 1 to 2 hetero atoms.
And those having about 4 to 5 carbon atoms are preferable.

The hydrocarbon aromatic groups and heteroaromatic groups can have various substituents. The kind of the substituent is not particularly limited and is appropriately selected depending on the use of the obtained trialkylsilyltrialkylsiloxymethylene compound. Specific examples thereof include an alkyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a halogen atom, and a fluorine-substituted alkyl group. It is preferable that about 1 to 3 of these aromatic groups are substituted.

When Ar is a hydrocarbon aromatic group, specific examples of the aromatic carbonyl compound include benzaldehyde, o
-, m-, p-tolualdehyde, o-, m-, p-chlorotolualdehyde, o-, m-, p-anisaldehyde, p-fluorobenzaldehyde, p- (iso-propyl) benzaldehyde, o-, m-, p-
Tolualdehyde, 2,3-dimethoxybenzaldehyde, 2,
4-dimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, p-trifluoromethylbenzaldehyde, acetophenone, butyrophenone, o-chloroacetophenone, diphenylketone and phenylbenzylketone can be mentioned. Preferred aromatic carbonyl compounds are benzaldehyde, o-, m-, p-chlorobenzaldehyde, o
-, m-, p-anisaldehyde, o-, m-, p-ethoxybenzaldehyde and acetophenone.

When Ar is a heteroaromatic group, specific examples of the aromatic carbonyl compound include thiophene aldehyde,
Examples include 4-chlorothiophene aldehyde, furfural, piperonal (heliotropin), valesaldehyde, α-formylpyrrole, and formylpyridine. Preferred are thiophene aldehyde, formyl pyridine and furfural.

R ¹ is a hydrogen atom; an alkyl group such as a methyl, ethyl, propyl and iso-propyl group; an aryl group such as a phenyl group and a naphthyl group; and a benzyl group,
An aralkyl group such as a phenylethyl group is shown. For example, when the above hydrocarbon aromatic group is derived from benzaldehyde, R ¹ is a hydrogen atom. When it is derived from acetophenone or butyrophenone, R ¹ is a methyl group or a butyl group. When derived from diphenylketone or phenylbenzylketone, R ¹ is a phenyl group or a benzyl group. When R ¹ is an alkyl group, an aryl group or an aralkyl group, one having 1 to 12 carbon atoms, particularly one having 1 to 6 carbon atoms is preferable.

R ² is an alkyl group such as methyl, ethyl, propyl, iso-propyl and tert-butyl; or an aryl group such as a phenyl group. R ² has 1 to 1 carbon atoms
0, particularly 1 to 6, is preferable.

Chlorosilanes preferably used in the present invention include trialkylchlorosilanes such as trimethylchlorosilane, triethylchlorosilane, dimethylpropylchlorosilane, tert-butyldimethylchlorosilane and tripropylchlorosilane; and dialkylphenylchlorosilanes such as dimethylphenylchlorosilane. Etc. From the viewpoint of reactivity, production cost, etc., trialkylchlorosilane is preferable.

As the metal catalyst, typical metals such as Mg, Al and Zn can be used. From the viewpoint of yield, reactivity, etc., milled or powdered magnesium is particularly preferable.

The aprotic polar solvent is not particularly limited as long as it can dissolve the reaction product well, but formamide, N-methylformamide, N, N-dimethylformamide (DMF), N-methylacetamide, N , N-Dimethylacetamide (DMAC), 1,1,3,3, -Tetramethylurea (TM)
U), 2-pyrrolidione, 1-methyl-2-pyrrolidione, N-methylpyrrolidone (NMP), dimethylsulfoxide (DMSO), tetrahydrothiophene-1,1-dioxide and the like can be used.
From the viewpoint of yield, reactivity, etc., N, N-dimethylformamide
(DMF) is preferred.

An embodiment of the method of the present invention will be described below.

First, an aprotic polar solvent (for example, N, N
-Dimethylformamide (DMF)), a typical metal (preferably powdered magnesium) and a chlorosilane of the formula [III]
(E.g., a mixture with trimethylchlorosilane), an aprotic polar solvent (e.g., N, N-dimethylformamide
(DMF)) and a reaction substrate, which is an aromatic carbonyl compound represented by the formula [II] (eg, benzaldehyde, thiophene aldehyde), is added dropwise. The dropping may be performed at a liquid temperature close to room temperature, and the reaction proceeds simultaneously with the start of dropping. The reaction is completed by further stirring at 20 to 25 ° C for 5 to 20 hours. The reaction can be traced by confirming the presence or absence of the raw material (for example, benzaldehyde) by gas chromatography.

After completion of the reaction, the compound of formula I is subjected to isolation and purification by a conventional method such as extraction (for example, ether extraction), washing, silica gel chromatography and vacuum distillation.
A trialkylsilyltrialkylsiloxymethylene compound represented by (for example, 1- (trialkylsilyl) -1-trialkylsiloxytoluene) is obtained.

The silyl ether group --OSi (R) of the trialkylsilyltrialkylsiloxymethylene compound of the present invention is
² ) ₃ is easily hydrolyzed with an acid or the like to form —OH, and has the formula

[Chemical 15] [In the formula, Ar is an aromatic group which may have a substituent, R ¹ is a hydrogen atom, an alkyl, aryl or aralkyl group, and R ² is independently an alkyl or aryl group. ] The trialkyl silyl alcohol shown by these is given.
The silyl ether group and the --OH group derived therefrom serve as the functional group of the organosilicon compound obtained by the method of the present invention.

The hydrolysis can be carried out by adding an acid before the above isolation and purification operation. Specific examples of the acid that can be suitably used include mineral acids such as hydrochloric acid and sulfuric acid.

The scheme of the present invention will be specifically illustrated below.

[0031]

Embedded image

[0032]

[Chemical 17]

[0033]

Embedded image

The trialkylsilyltrialkylsiloxymethylene compounds obtained by the above-mentioned method of the present invention are exemplified below.

[0035]

[Chemical 19]

[0036]

Embedded image

[0037]

[Chemical 21]

[0038]

[Chemical formula 22]

[0039]

[Chemical formula 23]

[0040]

[Chemical formula 24]

[0041]

[Chemical 25]

[0042]

[Chemical formula 26]

[0043]

[Chemical 27]

[0044]

[Chemical 28]

[0045]

[Chemical 29]

[0046]

Embedded image

[0047]

[Chemical 31]

[0048]

Embedded image

[0049]

EXAMPLES The present invention will now be described in detail with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of α-trimethylsilyl-α-trimethylsiloxytoluene DMF 30 ml, trimethylchlorosilane 8.70 g (80 mmol) and
A mixture of DMF (30 ml) and benzaldehyde (1.09 g, 10 mmol) was added dropwise to a mixture of 0.73 g (30 mmol) of powdered magnesium or magnesium powder while maintaining the liquid temperature at 20 to 25 ° C. After stirring for about 5 hours, it was confirmed that benzaldehyde was not present. Then, the reaction solution was added to a mixed solution of 200 ml of water and a saturated aqueous solution of sodium carbonate, and extracted three times with 150 ml of ethyl ether. Then, it was washed 3 times with 150 ml of saturated saline and dried over anhydrous magnesium sulfate. The ethyl ether was evaporated and purified by vacuum distillation to give 1.945 g of α-trimethylsilyl-α-trimethylsiloxytoluene in a yield of 77.
Earned in%. The NMR spectrum is shown in FIG. 1 and the IR spectrum is shown in FIG.

Example 2 Preparation of α-trimethylsilyl-α-trimethylsiloxy-4-chlorotoluene DMF 30 ml, trimethylchlorosilane 8.70 g (80 mmol) and
A mixture of DMF (30 ml) and p-chlorobenzaldehyde (1.40 g, 10 mmol) was added dropwise to a mixture of (milled or) powdered magnesium (0.73 g, 30 mmol) while maintaining the liquid temperature at 20 to 25 ° C. After stirring for about 6 hours, it was confirmed that p-chlorobenzaldehyde was not present. Then, the reaction solution was added to a mixed solution of 200 ml of water and a saturated aqueous solution of sodium carbonate, and extracted three times with 150 ml of ethyl ether. Then, it was washed 3 times with 150 ml of saturated saline and dried over anhydrous magnesium sulfate. By evaporating the ethyl ether and purifying by vacuum distillation,
2.248 g of α-trimethylsilyl-α-trimethylsiloxy-
4-Chlorotoluene was obtained with a yield of 79%. The NMR spectrum is shown in FIG. 3 and the IR spectrum is shown in FIG.

Example 3 Preparation of α-trimethylsilyl-α-trimethylsiloxyethylbenzene 30 ml DMF, 8.70 g (80 mmol) trimethylchlorosilane and
A mixture of 30 ml of DMF and 1.21 g (10 mmol) of acetophenone was added dropwise to a mixture of 0.73 g (30 mmol) of powdered magnesium or magnesium powder while maintaining the liquid temperature at 20 to 25 ° C. After stirring for about 6 hours, it was confirmed that acetophenone was not present.
Then, the reaction solution was added to a mixed solution of 200 ml of water and a saturated aqueous solution of sodium carbonate, and extracted three times with 150 ml of ethyl ether. Then, it was washed 3 times with 150 ml of saturated saline and dried over anhydrous magnesium sulfate. Evaporation of ethyl ether and purification by vacuum distillation yielded 1.762 g of α-trimethylsilyl-α-trimethylsiloxyethylbenzene.
Got 66%. The NMR spectrum is shown in FIG. 5 and the IR spectrum is shown in FIG.

Example 4 Preparation of α-trimethylsilyl-α-trimethylsiloxy-2-methylthiophene DMF 30 ml, trimethylchlorosilane 8.70 g (80 mmol) and
A mixture of 30 ml of DMF and 1.12 g (10 mmol) of 2-thiophene aldehyde was added dropwise to a mixture of 0.73 g (30 mmol) of powdered magnesium or powder magnesium while maintaining the solution temperature at 20 to 25 ° C.
After stirring for about 6 hours, it was confirmed that thiophene aldehyde was not present. Then, the reaction solution was added to a mixed solution of 200 ml of water and a saturated aqueous solution of sodium carbonate, and ethyl ether 15
Extracted three times with 0 ml. Then, it was washed 3 times with 150 ml of saturated saline and dried over anhydrous magnesium sulfate. The ethyl ether was evaporated and purified by vacuum distillation to give 1.018 g of α-trimethylsilyl-α-trimethylsiloxy-2-methylthiophene in 52% yield. FIG. 7 shows the NMR spectrum.
The IR spectrum is shown in FIG.

Example 5 Preparation of α-trimethylsilyl-α-hydroxyethylbenzene 150 ml of DMF (N, N-dimethylformamide), 48.76 g (0.45 mol) of trimethylchlorosilane and 7.3 g (0.3 mol) of powdered or powdered magnesium While maintaining the liquid temperature at 20 to 25 ° C into the mixed liquid of, DMF 150 ml and acetophenone 12.1 g (0.1 mol)
The mixed solution of was added dropwise over 4 hours. Continue reaction temperature
After stirring at 22 ° C. for 16 hours, it was confirmed that acetophenone was not present. Then add 120 ml of 6N hydrochloric acid to the reaction solution,
After stirring for 4 hours, the mixture was extracted 3 times with 200 ml of ethyl ether.
Then neutralize with saturated sodium carbonate water, saturated saline solution 200m
It was washed twice with 1 and dried over anhydrous magnesium sulfate. The ethyl ether was evaporated and purified by vacuum distillation to give 10.36 g of α-trimethylsilyl-α-hydroxyethylbenzene in 53.5% yield. The NMR spectrum is shown in FIG. 9 and the IR spectrum is shown in FIG.

[0055]

INDUSTRIAL APPLICABILITY The present invention provides an aromatic carbonyl compound and chlorosilane in an aprotic polar solvent with a typical metal,
Particularly preferably, it can be reacted directly in the presence of Mg,
Furthermore, since the reaction selectivity is good, separation and purification are easy. Further, the reactor is extremely simple and the raw materials are easily available, so that it can be produced at low cost. Furthermore, the target compound can be obtained in high yield, and an inexpensive intermediate which is important as a medicine, agricultural chemical or industrial chemical can be provided.

[Brief description of drawings]

1 shows the NMR spectrum of the compound obtained in Example 1. FIG.

FIG. 2 shows an IR spectrum of the compound obtained in Example 1.

FIG. 3 shows an NMR spectrum of the compound obtained in Example 2.

FIG. 4 shows an IR spectrum of the compound obtained in Example 2.

5 shows an NMR spectrum of the compound obtained in Example 3. FIG.

FIG. 6 shows an IR spectrum of the compound obtained in Example 3.

FIG. 7 shows an NMR spectrum of the compound obtained in Example 4.

FIG. 8 shows an IR spectrum of the compound obtained in Example 4.

FIG. 9 shows an NMR spectrum of the compound obtained in Example 5.

FIG. 10 shows an IR spectrum of the compound obtained in Example 5.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI technical display location // C07B 61/00 300 C07B 61/00 300 (72) Inventor Toru Tsuruhara Sanra, Neyagawa, Osaka 8-1, Higashimachi Orient Chemical Industry Co., Ltd. (72) Inventor Yoshio Ishino 1-6-50 Morinomiya Morinomiya, Joto-ku, Osaka City, Osaka Prefecture (72) Inventor, Osaka Municipal Industrial Research Institute Ikuzo Nishiguchi Saito, Osaka City, Osaka Prefecture 1-6-50 Morinomiya Morinomiya, Osaka City Institute of Industrial Research (72) Inventor Hiroshi Maekawa 1-6-50 Morinomiya Morinomiya, Joto-ku, Osaka Prefecture Osaka City Institute of Industrial Research

Claims (6)

[Claims] (1) Formula (1) [In the formula, Ar is an aromatic group which may have a substituent, R ¹ is a hydrogen atom, an alkyl, aryl or aralkyl group, and R ² is independently an alkyl or aryl group. ] In the method for producing a trialkylsilyltrialkylsiloxymethylene compound represented by the formula: [In the formula, Ar and R ¹ have the same meanings as described above. ] And an aromatic carbonyl compound represented by the formula: embedded image wherein (R ² ) ₃ SiCl [III] [wherein, R ² has the same meaning as described above. ] The method including the step of reacting with a chlorosilane represented by the formula (1) in the presence of a typical metal in an aprotic polar solvent. 2. The method of claim 1, wherein the aromatic carbonyl compound is a heteroaromatic aldehyde. 3. The method of claim 1, wherein the chlorosilane is a trialkylchlorosilane. 4. The formula: [In the formula, Ar is an aromatic group selected from the group consisting of a thienyl group, a furyl group and a pyridyl group, and R ² is independently an alkyl group. ] The trialkyl silyl trialkyl siloxy methylene compound shown by these. 5. The formula: [In the formula, Ar is an aromatic group which may have a substituent, R ¹ is a hydrogen atom, an alkyl, aryl or aralkyl group, and R ² is independently an alkyl or aryl group. ] In the method for producing a trialkylsilyl alcohol represented by the formula: [In the formula, Ar and R ¹ have the same meanings as described above. ] And an aromatic carbonyl compound represented by the formula: embedded image wherein (R ² ) ₃ SiCl [III] [wherein R ² has the same meaning as described above]. ] The process including the step of reacting chlorosilane represented by the formula (1) in an aprotic polar solvent in the presence of a typical metal; and hydrolyzing the resulting trialkylsilyltrialkylsiloxymethylene compound. 6. The formula: [In the formula, Ar is an aromatic group selected from the group consisting of a thienyl group, a furyl group and a pyridyl group, and R ² is independently an alkyl group. ] The trialkyl silyl alcohol shown by these.