JPH0782276A - Silylation of hydroxyl group - Google Patents

Abstract

PURPOSE:To selectively silylate a hydroxyl group without using expensive catalyst or causing unnecessary reductive reaction as side reaction. CONSTITUTION:This process for the silylation of hydroxyl group comprises reacting a compound having hydroxyl group with at least one kind of silylation agent selected from hydrosilanes and disilanes in the presence of a quaternary ammonium halide.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for silylating a hydroxyl group of a compound having a hydroxyl group.

[0002]

2. Description of the Related Art The silylation reaction of a hydroxyl group is used for various organic synthesis, derivatization for reaction analysis and structure determination, production of various compounds for the purpose of surface protection and water retention, and intermediates thereof. Is extremely important in
Therefore, various silylation reactions are known to date. Conventionally, there is known a method of silylating a hydroxyl group using hydrosilanes as a silylating agent in the presence of a Group VIII transition metal catalyst such as metal rhodium, metal palladium or a salt or complex thereof ((1) Comprehensive Organo
metallic Chemistry FRS ed. (1982) Vol.2 pp1-397, (2)
Protective Groups in Organic Synthesis 2nd.ed.pp6
8-85, (3) Bull. Chem. Soc. Jpn. (1989) Vol.62 pp211
1). However, in the above method, the catalyst used is very expensive because it contains a noble metal,
When a silylation reaction is carried out on a hydroxyl group-containing alkene or alkyne compound using the catalyst, there is a problem such that an unnecessary reduction reaction occurs simultaneously.

[0003]

DISCLOSURE OF THE INVENTION The present inventors have proposed a selective hydroxyl group silylation method which does not cause an unnecessary reduction reaction in the alkene and alkyne moieties in the compound without using an expensive catalyst. As a result of extensive studies to find out, a catalytic amount of quaternary ammonium halide was used, and a silylating agent selected from hydrosilanes or disilanes was reacted, so that an unnecessary reduction reaction could be performed without using an expensive catalyst. The present invention has been completed by finding a method capable of selectively silylating a hydroxyl group with almost no concurrent occurrence.

[0004]

Means for Solving the Problems That is, the present invention provides a compound having a hydroxyl group in the presence of a quaternary ammonium halide.
The present invention provides a method for silylating a hydroxyl group, which comprises reacting at least one silylating agent selected from hydrosilanes or disilanes.

The present invention will be described in detail below. The compound having a hydroxyl group which is the target of the silylation reaction of the present invention is not particularly limited as long as it is a compound having a hydroxyl group. For example, it can be used for complex compounds having various functional groups such as amino alcohols, alkenyl alcohols, alkynyl alcohols, epoxy alcohols and hydroxycarboxylic acids.

The quaternary ammonium halides include tetraalkylammonium halides, benzyltrialkylammonium halides, tetraalkylammonium = hydrogen = dihalides, benzyltrialkylammonium = hydrodiene = dihalides, tris (dialkylamino) sulfur (trialkylsilyl) dihalides. And so on. Here, as alkyl,
Examples thereof include alkyl having 1 to 16 carbon atoms such as methyl, ethyl, propyl, butyl, octyl and cetyl.

Specific examples include, for example, tetrapropylammonium fluoride, tetrapropylammonium chloride, tetrapropylammonium bromide, tetrabutylammonium fluoride (hereinafter abbreviated as TBAF), tetrabutylammonium chloride, tetrabutylammonium bromide, Tetraalkylammonium halides such as tetraoctylammonium fluoride and tetracetylammonium fluoride,

Benzyltrimethylammonium fluoride, benzyltriethylammonium fluoride, benzyltriethylammonium chloride, benzyltripropylammonium fluoride, benzyltributylammonium fluoride, benzyltrioctylammonium fluoride, benzyltricetylammonium fluoride and the like. Alkyl ammonium halide,

Tetraethylammonium = hydrodiene = difluoride, tetrapropylammonium = hydrodiene = difluoride, tetrabutylammonium = hydrodiene = difluoride, tetraoctylammonium = hydrodiene = difluoride, tetracetylammonium =
Tetraalkylammonium such as hydrogenene = difluoride = hydrogenene = dihalide,

Benzyltrimethylammonium = hydrodiene = difluoride, benzyltriethylammonium = hydrodiene = difluoride, benzyltripropylammonium = hydrodiene = difluoride, benzyltributylammonium = hydrodiene = difluoride, benzyltrioctylammonium = hydrodiene = difluoride, benzyltricetylammonium = Hydrogenene = benzyltrialkylammonium such as difluoride =
Hydrogenene dihalide,

Tris (dimethylamino) sulfur (trimethylsilyl) difluoride, tris (diethylamino) sulfur (triethylsilyl) difluoride, tris (dipropylamino) sulfur (tripropylsilyl) difluoride, tris (dibutylamino) sulfur (tributylsilyl) difluoride , Tris (dioctylamino) sulfur (trioctylsilyl) difluoride, tris (dicetylamino) sulfur (tricetylsilyl) difluoride, and other tris (dialkylamino) sulfur (trialkylsilyl) dihalides, among others. Is preferably used.

The amount of the quaternary ammonium halide used is a catalytic amount with respect to the compound having a hydroxyl group, and is usually 0.1.
It is about 002 to 0.05 equivalent. When the amount used is less than 0.002 equivalents relative to the compound having a hydroxyl group, the silylation reaction may not proceed efficiently, and when it is used in excess of 0.05 equivalents, it inherently has it. A desilylation effect may appear.

The silylating agent used is, for example,
Hydrosilane-based silylating agents such as trialkylhydrosilane, dialkylarylhydrosilane, alkyldiarylhydrosilane, and triarylhydrosilane; disilane-based silylating agents such as hexaalkyldisilane, tetraalkyldiaryldisilane, dialkyltetraaryldisilane, hexaaryldisilane, etc. Is mentioned.

Examples of the alkyl include those having 1 to 10 carbon atoms such as methyl, ethyl, propyl, butyl and octyl. Examples of the aryl include phenyl, phenyl substituted with halogen, phenyl substituted with an alkyl group, phenyl substituted with an alkoxy group, and the like. Examples of the halogen include a fluorine atom, a chlorine atom, a bromine atom, and the like as an alkyl group. Is, for example, methyl, ethyl,
Propyl, butyl, octyl and the like having 1 to 10 carbon atoms, and examples of the alkoxy group include methoxy, ethoxy, propoxy, butoxy and the like having 1 to 10 carbon atoms.

Specific examples of hydrosilane-based silylating agents include trialkylsilanes such as triethylsilane, tripropylsilane, trioctylsilane, t-butyldimethylsilane, phenyldimethylsilane, phenyldiethylsilane, and phenyldipropyl. Silane, phenyldioctylsilane, o-chlorophenyldimethylsilane, m-chlorophenyldimethylsilane, p
-Chlorophenyldimethylsilane, p-fluorophenyldimethylsilane, p-bromophenyldimethylsilane, p-methylphenyldimethylsilane, p-butylphenyldimethylsilane, p-octylphenyldimethylsilane, p-methoxyphenyldimethylsilane, p-butoxy Dialkylarylhydrosilanes such as phenyldimethylsilane, methyldiphenylsilane, ethyldiphenylsilane, propyldiphenylsilane, octyldiphenylsilane, methyldi (p-chlorophenyl) silane, methyldi (p-bromophenyl) silane, methyldi (p-fluorophenyl) silane. , Methyldi (p-methylphenyl) silane, methyldi (p-butylphenyl) silane, methyldi (p-octylphenyl) silane, methyldi (p-methoxy) Alkyldiarylhydrosilanes such as phenyl) silane and methyldi (p-butoxyphenyl) silane, triphenylsilane, tri (p-chlorophenyl) silane, tri (p-bromophenyl) silane, tri (p-fluorophenyl) silane, tri ( p
-Methylphenyl) silane, tri (p-butylphenyl) silane, tri (p-octylphenyl) silane, tri (p-methoxyphenyl) silane, tri (p-butoxyphenyl) silane, and other triarylhydrosilanes. .

Specific examples of the disilane-based silylating agent include hexamethyldisilane, hexaethyldisilane, hexabutyldisilane, hexaalkyldisilane such as hexa (t-butyl) disilane, tetramethyldiphenyldisilane, tetraethyldiphenyldisilane. , Tetrabutyldiphenyldisilane, tetra (t-butyl)
Diphenyldisilane, tetramethyldi (p-chlorophenyl) disilane, tetramethyldi (p-bromophenyl) disilane, tetramethyldi (p-fluorophenyl) disilane, tetramethyldi (p-methylphenyl)
Tetraalkyldiaryldisilanes such as disilane, tetramethyldi (p-butylphenyl) disilane, tetramethyldi (p-octylphenyl) disilane, tetramethyldi (p-methoxyphenyl) disilane, tetramethyldi (p-butoxyphenyl) disilane, dimethyltetraphenyldisilane, diethyl Tetraphenyldisilane, dibutyltetraphenyldisilane, di (t-butyl) tetraphenyldisilane, dimethyltetra (p-chlorophenyl) disilane, dimethyltetra (p-bromophenyl) disilane, dimethyltetra (p-fluorophenyl) disilane, dimethyltetra (P-Methylphenyl) disilane, dimethyltetra (p-butylphenyl)
Disilanes such as disilane, dimethyltetra (p-octylphenyl) disilane, dimethyltetra (p-methoxyphenyl) disilane, dimethyltetra (p-butoxyphenyl) disilane, hexaphenyldisilane, hexa (p-chlorophenyl) disilane, Hexa (p-bromophenyl) disilane, hexa (p-fluorophenyl) disilane, hexa (p-methylphenyl) disilane, hexa (p-butylphenyl)
Disilane, hexa (p-octylphenyl) disilane,
Hexa (p-methoxyphenyl) disilane, Hexa (p
And hexaaryldisilane such as -butoxyphenyl) disilane.

The amount of the silylating agent used is usually about 1 to 5 equivalent times with respect to the hydroxyl group to be protected. The silylation reaction is usually carried out in a solvent. Examples of the solvent used include aromatic hydrocarbon solvents such as benzene and toluene, ether solvents such as tetrahydrofuran and ethylene glycol dimethyl ether, N-methylpyrrolidone (hereinafter abbreviated as NMP), dimethylformamide, and the like.
Examples of the aprotic polar solvent such as hexamethylphosphoric triamide include aprotic polar solvents such as N-methylpyrrolidone, dimethylformamide, and hexamethylphosphoric triamide. The amount of solvent used is based on the compound having a hydroxyl group.
Usually, it is 5 to 20 times by weight. The reaction temperature for silylation is
Usually, it is −20 to 120 ° C., preferably 0 to 40 ° C., and the reaction time is usually 10 minutes to 5 hours.

[0018]

EFFECTS OF THE INVENTION By reacting at least one silylating agent selected from hydrosilanes or disilanes with a compound having a hydroxyl group in the presence of a quaternary ammonium halide, it is possible to eliminate unnecessary use without using an expensive catalyst. It is possible to selectively silylate a hydroxyl group without causing another reduction reaction.

[0019]

EXAMPLES The present invention will be described below with reference to examples, but it goes without saying that the present invention is not limited to the examples. The analysis of the reaction mixture was carried out using gas chromatography (wide pore column DB-1701).

Example 1 1-octanol (130 mg, 1 mmol) and t-butyldimethylsilane (232 mg, 2 mmol) in dimethylformamide (DMF) solution (1.5 ml) in 1M TBAF-tetrahydrofuran (THF) solution 0.02 ml (0.02 mmol) ) Was added and the mixture was allowed to stand at 25 ° C. for 3 hours. Water was added to the reaction mixture, ether extraction was performed, and the obtained organic layer was washed twice with water,
Further, it was washed with saturated saline and dried over anhydrous sodium sulfate. The organic layer was evaporated under reduced pressure and purified by silica gel column chromatography (hexane / ether = 100/1) to obtain 232 mg of 1- (t-butyldimethylsiloxy) octane. Yield is 9 based on 1-octanol
It was 5%. ¹ H NMR δ (CDCl ₃ ); 0.05 (s, 6H), 0.90 (s, 9H), 0.90
(t, 3H, J = 7Hz), 1.10-1.55 (m, 12H), 3.60 (t, 2H, J = 7Hz)

Comparative Example 1 The reaction was carried out in the same manner as in Example 1 except that 1M TBAF-tetrahydrofuran (THF) solution was not added. When the reaction mixture was analyzed,
The conversion rate to 1- (t-butyldimethylsiloxy) octane was 0%. Then, it was further heated at 150 ° C. for 5 hours, and the same analysis revealed that the conversion rate was 0%.

Example 2 In Example 1, 1-octanol (130 mg, 1 mmol)
2-octanol (130 mg, 1 mmol) was used in place of
The reaction and post-treatment were carried out in accordance with Example 1 except that the mixture was left at 25 ° C. for 6 hours and purified by silica gel column chromatography (hexane 100%). 232 mg of 2- (t-butyldimethylsiloxy) octane was obtained, and the yield was 95% based on 2-octanol. ¹ H NMR δ (CDCl ₃ ); 0.05 (s, 6H), 0.90 (s, 9H), 1.12
(d, 3H, J = 7Hz), 0.90-1.50 (m, 13H), 3.58-3.98 (m, 1H)

Comparative Example 2 The reaction was carried out in the same manner as in Example 2 except that 1M TBAF-tetrahydrofuran (THF) solution was not added. When the reaction mixture was analyzed,
The conversion rate to 1- (t-butyldimethylsiloxy) octane was 0%. Then, it was further heated at 150 ° C. for 5 hours, and the same analysis revealed that the conversion rate was 0%.

Example 3 In Example 1, 1-octanol (130 mg, 1 mmol)
Was replaced by benzyl alcohol (108 mg, 1 mmol), left at 40 ° C. for 3 hours, and purified by silica gel column chromatography (hexane 100%), and the reaction and post-treatment were carried out in accordance with Example 1. . 215 mg of benzyl-t-butyldimethylsilyl ether was obtained, and the yield was 97% based on benzyl alcohol. ¹ H NMR δ (CDCl ₃ ); 0.05 (s, 6H), 0.90 (s, 9H), 4.70
(s, 2H), 7.05-7.35 (m, 5H)

Comparative Example 3 The reaction was carried out in the same manner as in Example 3 except that the 1M TBAF-tetrahydrofuran (THF) solution was not added and the mixture was allowed to stand at 25 ° C. for 1 hour. When the reaction mixture was analyzed, the conversion rate to benzyl-t-butyldimethylsilyl ether was 0%. So 15 more
When heated at 0 ° C. for 6 hours and analyzed in the same manner, the conversion was 0%.

Example 4 In Example 1, t-butyldimethylsilane (232 mg,
2mmol) instead of dimethylphenylsilane (273mg, 2
mmol) was used and the reaction and post-treatment were carried out in accordance with Example 1 except that the mixture was allowed to stand at 25 ° C. for 1.2 hours. 257 mg of 1- (dimethylphenylsiloxy) octane was obtained, and the yield was 97% based on 1-octanol. ¹ H NMR δ (CDCl ₃ ); 0.38 (s, 6H), 0.85 (t, 3H, J = 7Hz),
0.90-4.70 (s, 2H) 3.58 (t, 2H), 7.20-7.70 (m, 5H)

Comparative Example 4 The reaction was carried out in the same manner as in Example 4, except that the 1M TBAF-tetrahydrofuran (THF) solution was not added and the mixture was allowed to stand at 25 ° C. for 1 hour. When the reaction mixture was analyzed, the conversion rate to 1- (dimethylphenylsiloxy) octane was 0%.

Example 5 1 M of 1-octanol (130 mg, 1 mmol) and t-butyldimethylsilane (174 mg, 1.5 mmol) in dry N-methylpyrrolidone (NMP) solution (2.0 ml) under a stream of argon.
TBAF-tetrahydrofuran (THF) solution 0.02 m
l (0.02 mmol) was added, and the mixture was stirred at 25 ° C for 30 minutes. When the reaction mixture was analyzed, the conversion rate to 1- (t-butyldimethylsiloxy) octane was 1 based on 1-octanol.
It was 00%.

Example 6-18 Under an argon stream, the alcohol and hydrosilane solutions shown in Table 1 were used. To this was added 0.02 ml (0.02 mmol) of 1M TBAF-tetrahydrofuran (THF) solution, and Table 1 was added.
The reaction was carried out under the reaction conditions (temperature, time) described in 1. The results of analyzing the reaction mixture are shown in Table 1. The conversion rate and isolated yield were calculated based on the raw material alcohol.

[0030]

[Table 1]

Comparative Example 5 The reaction was carried out according to Example 6 except that (PPh ₃ ) ₃ RhCl (Wilkinson catalyst) (19 mg, 0.02 mmol) was used in place of TBAF (0.02 mmol) in Example 6. Carried out. When the reaction mixture was analyzed, the conversion rate to 1- (triethylsiloxy) octane was 5% or less.

Comparative Example 6 The reaction was carried out in the same manner as in Example 15 except that (PPh ₃ ) ₃ RhCl (Wilkinson catalyst) (19 mg, 0.02 mmol) was used in place of TBAF (0.02 mmol). Carried out.
When the reaction mixture was analyzed, the conversion rate to cinnamyl = triethylsilyl ether was 29%, and phenylpropyl = triethylsilyl ether (double bond reductant)
The conversion rate was 71%.

Comparative Example 7 The reaction was carried out according to Example 16 except that (PPh ₃ ) ₃ RhCl (Wilkinson catalyst) (19 mg, 0.02 mmol) was used in place of TBAF (0.02 mmol) in Comparative Example 7. Carried out.
When the reaction mixture was analyzed, 4-triethylsilyl-
The conversion rate to 1-trimethylsiloxy-3-butene (hydrosilylated product) was 60%.

Example 19 In Example 6, instead of TBAF (0.02 mmol), benzyltrimethylammonium = hydrogen =
Example 6 except difluoride (4 mg, 0.02 mmol) was used.
The reaction was carried out according to. When the reaction mixture was analyzed, the conversion rate of 1-octanol to 1- (trimethylsiloxy) octane was 84%.

Example 20 In Example 6, instead of TBAF (0.02 mol),
The reaction was carried out according to Example 6 except that tris (dimethylamino) sulfur (trimethylsilyl) difluoride (6 mg, 0.02 mmol) was used. When the reaction mixture was analyzed, the conversion rate of 1-octanol to 1- (trimethylsiloxy) octane was 92%.

Example 21 1-octanol (130 mg, 1 mmol) under an argon stream,
Acetophenone (120 mg, 1 mmol) and triethylsilane (174 mg, 1.5 mmol) in dry N-methylpyrrolidone (N
MP) solution (2.0 ml) to which 1M TBAF-tetrahydrofuran (THF) solution 0.02 ml (0.02 mmol) was added,
The mixture was stirred at 0 ° C for 120 minutes. When the reaction mixture was analyzed,
The conversion rate of 1-octanol to 1- (t-butyldimethylsiloxy) octane was 99%, and the conversion rate of acetophenone to α- (triethylsiloxy) phenethyl alcohol was 10%.

Example 22 1-octanol (130 mg, 1 mmol) under an argon stream,
2-Octanone (128 mg, 1 mmol) and triethylsilane (174 mg, 1.5 mmol) in dry N-methylpyrrolidone (N
MP) solution (2.0 ml) to which 1M TBAF-tetrahydrofuran (THF) solution 0.02 ml (0.02 mmol) was added,
The mixture was stirred at 0 ° C for 30 minutes. When the reaction mixture was analyzed, 1
The conversion rate of -octanol to 1- (triethylsiloxy) octane was 89%, and the conversion rate of 2-octanone to 2- (triethylsiloxy) octane was 5%.

Example 23 1-Octanol (130 mg, 1 mmol) and hexamethyldisilane (220 mg, 1.5 mmol) in dry N under an argon stream.
-Methylpyrrolidone (NMP) solution (2.0 ml) with 1 M T
BAF-tetrahydrofuran (THF) solution 0.02 ml
(0.02 mmol) was added, and the mixture was stirred at 25 ° C for 45 minutes. When the reaction mixture was analyzed, the conversion rate of 1-octanol to 1- (trimethylsiloxy) octane was 99%.

Examples 24-29 Under an argon stream, the alcohol and disilane solutions shown in Table 2 were used, and 0.02 ml (0.02 mmol) of 1M TBAF-tetrahydrofuran (THF) solution was added thereto, and the reaction conditions shown in Table 1 were added. The reaction was carried out at (temperature, time). The results of analyzing the reaction mixture are shown in Table 1. The conversion rate and isolated yield were calculated based on the raw material alcohol.

[0040]

[Table 2]

Example 30 1M-TBAF-tetrahydrofuran (THF) solution (0.02 ml, 0.02 mmol) in 2 ml of ethylene glycol dimethyl ether (DME) solution of 1-octanol (130 mg, 1 mmol) and allyldimethylsilane (300.6 mg, 3 mmol) Was added and reacted at 25 ° C. for 1 hour. Water was added to the reaction mixture, extraction was carried out with ether, and the obtained organic layer was washed with water and saturated saline and then dried over anhydrous sodium sulfate. The organic layer was evaporated under reduced pressure and purified by silica gel chromatography (100% hexane) to give 159 mg of 1- (dimethylallylsiloxy) octane. The yield was 70%.

Continuation of front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical display location C07F 7/18 DJS // C07B 61/00 300 (72) Inventor Yoshihiro Yoshida Minami Oimazato, Higashisei-ku, Osaka Prefecture 4-17-26-417 (72) Inventor Akihiro Maeda 4-4-24 Tenjin-cho, Suma-ku, Kobe City, Hyogo Prefecture

Claims (6)

[Claims] 1. A method for silylating a hydroxyl group, which comprises reacting a compound having a hydroxyl group with at least one silylating agent selected from hydrosilanes or disilanes in the presence of a quaternary ammonium halide. 2. The method for silylating a hydroxyl group according to claim 1, wherein the amount of the quaternary ammonium halide used is 0.002 to 0.05 equivalent relative to the compound having a hydroxyl group. 3. A quaternary ammonium halide is a tetraalkylammonium halide, a benzyltrialkylammonium halide, a tetraalkylammonium = hydrogen = dihalide, a benzyltrialkylammonium = hydrodiene = dihalide and a tris (dialkylamino) sulfur (trialkylsilyl). The method for silylating a hydroxyl group according to claim 1 or 2, which is selected from dihalides. 4. The method for silylating a hydroxyl group according to claim 1, wherein the tetraalkylammonium halide is tetrabutylammonium fluoride. 5. The silylating agent is selected from trialkylhydrosilane, dialkylarylhydrosilane, alkyldiarylhydrosilane, triarylhydrosilane, hexaalkyldisilane, tetraalkyldiaryldisilane, dialkyltetraaryldisilane and hexaaryldisilane. 4. The method for silylating a hydroxyl group as described in 4. 6. The silylating agent is triethylsilane, ter
t-butyldimethylsilane, phenyldimethylsilane,
A material selected from methyldiphenylsilane, hexamethyldisilane and dimethyltetraphenyldisilane.
~ 4 silylation method of the hydroxyl group.