JPH021149B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel silylation method. In general, silylating agents are used for purposes such as protecting the functional groups of organic compounds, increasing thermal stability, increasing solubility in nonpolar solvents, and increasing reactivity. , silylamine, silylamide, silyl acetate, silyl ether, etc. are known. However, these conventional silylation agents have drawbacks such as usually requiring the presence of strong bases, acids, or catalysts during the silylation reaction, and producing large amounts of by-products such as inorganic salts and amine hydrochlorides. have. In view of the above drawbacks, the present inventors have conducted extensive research and found that when O-silylketene acetal [ ] is used as a silylating agent, the above drawbacks are completely eliminated;
We have discovered that active organic compounds (organic compounds active for silylation, such as organic compounds having hydrogen or reactive sites active for silylation, etc.) can be obtained quantitatively under mild conditions,
The present invention has now been completed. That is, the present invention provides an alcohol, a carboxylic acid, a mercaptan, an amide, a ketone, or an α,β-unsaturated ketone and a compound of the general formula (In the formula, R represents a hydrogen atom or a lower alkyl group, and R ¹ , R ² , R ³ , and R ⁴ represent a lower alkyl group.) O-silylketene acetal []
This is a method for silylation of alcohols, carboxylic acids, mercaptans, amides, ketones, or α,β-unsaturated ketones, characterized by reacting them in the presence of an organic solvent without a catalyst. Examples of the silylating agent according to the present invention include ketene, methyl, trimethylsilyl, acetal, methylketene, methyl, trimethylsilyl, acetal, methylketene, methyl, triethylsilyl acetal, and the like. O-silylketene acetal according to the present invention []
When an active organic compound is silylated using as a silylating agent, there is no need to use acids, bases, catalysts, etc., and the reaction proceeds quantitatively even under very mild conditions that are neutral or close to neutral. The reaction rate is extremely fast, and silylation can be carried out in a short time under mild conditions, usually at temperatures of 0 to 60°C, and by-products of the silylation reaction can be easily removed even at low temperatures. Since it is only a fatty acid ester, it is usually possible to quantitatively obtain a highly pure silylated product by simply removing it together with a solvent (usually a low-boiling organic solvent is used during the silylation reaction). . The silylating agent according to the present invention is also highly active so that even tertiary alcohols can be easily silylated, and can be silylated under extremely mild conditions. Therefore, its excellent characteristics are particularly effectively exhibited when the compound is unstable or when the compound is a natural compound and has an unstable functional group. In addition, when silylating a carbonyl compound, the reactivity of O-silyl ketene acetal [ ] differs depending on the structure and properties of the carbonyl compound, and the contribution of the keto type, such as chain ketones and cyclohexanone, is When silylating large carbonyl compounds or α,β-unsaturated ketones, 1,2-addition or α,β-addition to the carbonyl group, respectively
The corresponding O-silyl ketene acetal [ ] adduct, in which each oxygen atom is trialkylsilylated by 1,4-addition to an unsaturated ketone, is obtained at once in good yield, and the enol type is obtained. When a carbonyl compound with a large contribution is silylated, an adduct is not obtained, but a corresponding O-trialkylsilyl compound whose hydroxyl group is silylated is obtained. O-silylketene acetal according to the present invention []
When using as a silylating agent, the active organic compound can be easily silylated, for example, as follows. That is, the active organic compound and the O-silylketene acetal are combined, preferably under an inert gas atmosphere, usually in the presence of an organic solvent such as dichloromethane or acetonitrile (preferably one with a low boiling point). A highly pure silylated product can be obtained quantitatively by simply reacting at 0 to 60°C and removing the by-product fatty acid ester by distilling off together with the solvent. In addition, a preferred method for producing O-silylketene acetal [] is the method of Ainsworth et al. (C.
Ainsworth et al.J.Organomet.Chem., 46 , 59
(1972)), but according to this method, O
- Silylketene acetal [ ] cannot be isolated. The present inventors have discovered that the reason why O-silylketene acetal [ ] cannot be isolated is due to the organic amine present in the reaction mixture. O-silylketene acetal according to the present invention []
The reaction formula for producing O-silylketene acetal [] by the method of Ainsworth et al. is as follows. In order to obtain lithium amide (Li.Z), a method known per se is usually followed in which alkyl lithium (Li.R ⁵ ) and an organic amine (HZ) are reacted. Li・R ⁵ +H・Z→Li・Z+H・R ⁵ Thus, after O-silyl ketene acetal [ ] is produced by the method of Ainsworth et al., which is known per se, the organic amine (H Z) is removed as its quaternary ammonium salt from the reaction mixture, and then the O-silylketene acetal [ ] is isolated. According to this method, O-silylketene acetal [] can be easily isolated. If the organic amine (H・Z) is not removed from the reaction mixture, the O-silylketene acetal [ ] cannot be isolated, and depending on the usual separation methods such as distillation and extraction, the organic amine (H -Z) cannot be removed from the reaction mixture. Examples of fatty acid esters include acetate esters such as methyl acetate, propionate esters such as methyl propionate, and the like. Examples of lithium amide (LiZ) include lithium diisopropylamide, lithium-2,2,
Examples include those known per se such as 6,6-tetramethylpiperidide. Examples of silyl halides include trimethylsilyl chloride and triethylsilyl chloride. O-silylketene acetal according to the present invention []
can be easily manufactured, for example, as follows. That is, an organic amine and an alkyl lithium are mixed together, preferably under an inert gas atmosphere, usually in the presence of an organic solvent such as tetrahydrofuran.
℃ to room temperature, preferably around 0℃ to obtain the corresponding lithium amide by a method known per se, and then react this with fatty acid ester [ ] at -80℃ to room temperature, preferably below -20℃. to produce a lithiofatty acid ester, which was then combined with a silyl halide [ ] in the same manner, -
By the method of Ainsworth et al., O-
After producing the silyl ketene acetal [ ], the organic amine present in the reaction mixture is converted into its quaternary ammonium salt by a method known per se, such as a method using an alkyl halide or dialkyl sulfuric acid, for example, to form an insoluble or removed from the reaction mixture by removing it as a poorly soluble precipitate,
Thereafter, the O-silylketene acetal is isolated by a separation method known per se, such as distillation. In addition, in this invention, a lower alkyl group means a C1-C5 alkyl group. Examples are shown below. Examples 1 to 13 Alcohol, carboxylic acid,
Organic compounds with hydrogen active for silylation such as mercaptans or amides (RXH(2))
(5 mmole) and an organic solvent (3 ml) such as dichloromethane or acetonitrile, and while stirring,
O-silyl ketene acetal (1) (5-20 mmole)
After dropping, react at 15 to 55°C with stirring. The reaction mixture is concentrated under reduced pressure to quantitatively obtain highly pure silylated product (3). The results are shown in Table 1. Note that in Examples 1 to 12, O-silylketene acetal (1) represented by formula (1a) was used;
In No. 13, O-silylketene acetal (1) represented by formula (1b) was used.

【formula】

【formula】

【table】

【table】

[Table] Example 14 Using the O-silyl ketene acetal (1) used in Example 1, an organic compound having a carbonyl group that is easily enolized, such as β-diketone, such as 5,5-dimethyl-1 , 3-cyclohexanedione is treated in the same manner as in Example 1 to obtain its silylated product quantitatively with high purity. Examples 15-16 Using the O-silylketene acetal (1) used in Example 1, cyclohexanone (Example 15) or α,β-unsaturated ketone, i.e., 2-cyclohexen-1-one (Example 16) was treated in acetonitrile in the same manner as in Example 1 to obtain a silylated product of high purity and quantitatively. The results are shown in Table 2.

【table】

Claims (1)

[Scope of Claims] 1 Alcohol, carboxylic acid, mercaptan, amide, ketone or α,β-unsaturated ketone, and the general formula (In the formula, R represents a hydrogen atom or a lower alkyl group, and R ¹ , R ² , R ³ , and R ⁴ represent a lower alkyl group.) O-silylketene acetal []
A method for silylating alcohols, carboxylic acids, mercaptans, amides, ketones, or α,β-unsaturated ketones, the method comprising reacting them in the presence of an organic solvent without a catalyst.