JPS62120325A - Desilylation of silyl ether compound - Google Patents

Abstract

PURPOSE:To desilylate a silyl ether compound and obtain a hydroxyl group compound, by reacting a silyl ether compound with a catalytic amount of an easily and inexpensively available and easily handleable bisulfate using water or an alcohol as reaction solvent. CONSTITUTION:A silyl ether compound of formula I (R is aliphatic, alicyclic or aromatic hydrocarbon group; R<1>-R<3> are alkyl or aryl) is desilylated to obtain a hydroxyl group compound of formula II. The desilylation reaction is carried out in the presence of >=1/1,000 equivalent (preferably 1/100-1.5 equivalent) of a bisulfate of formula III (M is alkali metal such as Li, Na, K, etc.) in water or an alcohol solvent at room temperature. EFFECT:The reaction can be carried out on a water-soluble substrate as well as fat-soluble substrate without causing the change of ester bond or double bond if any. When the substrate contains ketal or tetrahydropyranyl ether, these can be simultaneously cleaved according to the reaction conditions.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for desilylating silyl ether compounds by removing the silyl groups of various silyl ether compounds to produce the corresponding hydroxyl group compounds.

Silylation is one of the methods used to protect a hydroxyl group when reacting a functional group other than the hydroxyl group of a compound having a hydroxyl group in various synthetic reactions.

For example, the following reaction is an example of a reaction in which silylation is utilized.

■) Synthesis of synthetic intermediates for β-lactam antibiotics (“Tetrahedron φ Letters J 1983.

02H PNB = p-nitrobesidyl 2) Synthesis of glosstaglandin derivatives ([Journal Op Organic Chemistry J
1984, 49, 4096) 3) Compactin, which has a cholesterol-lowering effect.

Meyinolin partial intermediate synthesis (“Tetrahedron Letters J1984゜O8iφ2
Bu R= H (Compactin) R= CH3 (Mevinolin) Thereafter, the silyl group in the compound is removed and returned to a hydroxyl group.

Conventional technology Conventionally, the desilylation method for silyl ether compounds is as follows:
The following examples are known.

(tetra-n-butylammonium fluoride (n-Bu4NF) in anhydrous tetrahydrofuran (THF))
or a method of reacting in acetic acid-water (
[Journal of the American Chemical Society (J, Am.

Chem, Soc, ) J 1972, 94.6190
) (11 Hydrofluoric acid (H
F) How to make Tetrahedron Letters (
Tetrahedron Letters, )J 1
979.3981 ) (11lyi N-bromosuccinimide (NBS) in dimethyl sulfoxide (DMSO)
How to make it work (“Synthesis”)
) J 1980.234) OV) Method of acting with lithium boron tetrafluoride (LiBF4) ("Tetrahedron Letters" 198\, 21, 35) /LiBF4 R-0-8i +R-OH (v) Hydrochloric acid aqueous solution ( HCe)
1)/H(Jaq R-0-3i 10R-OH Problems to be Solved by the Invention Since these are required to be used in an amount of 1 equivalent or more relative to the substrate (silyl ether compound), it is not economical. In addition, reactions using HF are dangerous and require special consideration.Furthermore, 1 these reactions must be carried out in anhydrous solvents. In addition, methods using aqueous solutions such as hydrochloric acid and acetic acid are also frequently used, but the disadvantage of this method is that the use of water makes post-treatment of the reaction complicated.

Means for Solving the Problems The present inventors have investigated inexpensive and safe alternatives to these special reagents, reagents that achieve the objectives with ease of reaction and catalyst amount, and have found that when bisulfate is used, It was discovered that desilylation can be carried out in a catalytic amount and independent of reaction conditions, leading to the present invention.

The object of the present invention is to obtain the general formula (1) % formula % (wherein R is an aliphatic hydrocarbon group, an alicyclic hydrocarbon group or an aromatic hydrocarbon group, and R1, R2 and R3 are the same or different In the method of desilylating a silyl ether compound represented by an alkyl group or an aryl group to a hydroxyl group compound represented by the general formula (2) (wherein R has the same meaning as above), the silyl ether An object of the present invention is to provide a method for desilylating a silyl ether compound, which is characterized by reacting the compound with a bisulfate represented by the general formula (3) (wherein M is an alkali metal).

The silyl ether compounds to be subjected to the desilylation method of the present invention are various compounds represented by the above general formula (1),
It may also contain an ester bond and a double bond. Furthermore, in the present invention, the silyl ether compound is water-soluble,
Any fat-soluble one may be used.

As the bisulfate, alkali metal salts such as lithium hydrogen sulfate, potassium hydrogen sulfate, and sodium hydrogen sulfate can be used, with potassium salts and sodium salts being particularly preferred.

The amount of bisulfate is catalytic (generally from 1/100 to 1.5 equivalents relative to the silyl ether compound).

Desilylation according to the present invention can be performed using methanol, ethanol,
It is carried out in common solvents such as ethylene glycol sodium, alcohol, or water; other organic solvents can also be used as co-solvents.

Moreover, the desilylation according to the present invention proceeds effectively at room temperature, and the desired hydroxyl group compound is obtained.

In order to prove this point, some examples will be illustrated. However, the present invention is not limited to these examples.

Example 1 In this example, dimethyl(1,1-dimethylethyl)(phenylmethoxy)silane is prepared by silylating benzyl alcohol by a conventional method, which is then desilylated according to the present invention, and the starting material and desilylated The chemical reaction products were identified.

1.08 g (10 mmol) of benzyl alcohol with N,
885 μm (13 mmol) of imidazole and 3-butyldimethylchlorosilane (t-BuM
1.8089 (12 mmol) of e2Si(J) was added and stirred at room temperature for 15 hours. Benzene 1 in the reaction solution
After adding 00 mA', the organic solvent layer was washed with water and Na2S
It was dried with O4 and the solvent was distilled off. The obtained oil was subjected to silica gel column chromatography, and dimethyl(1,1-dimethylethyl)(phenylmethoxy)silane (silyl ether form-1) was quantitatively detected from the benzene-hexane (1:1) eluate. (Journal of the American Chemical Society, 197
4.96.3214).

(2) Desilylation of silyl ether silyl ether prepared as above -1222xrm
g (o, 2 mmol) and stirred for 5 hours, Et
2050 rats were added and passed through. The solvent was distilled off from the r liquid, and the obtained oil was subjected to silica gel column chromatography, and benzyl alcohol 68rn9 was obtained from the benzene eluate (yield 62.7%).

In the same manner, the amount of KH3O was increased (1.1 equivalents relative to silyl ether-1), and a desilylation reaction was carried out at room temperature for a reaction time of 5 hours. The yield in this case is 60.4
%Met.

Comparative Example The same silyl ether 1 was reacted according to the conventional desilylation method using Bu4NF.

That is, 1200 ml (0.9 mmol) of /lyl ether compound was dissolved in s ml of anhydrous THF, and Bu4NF
258 to (0.99 mmol) was added, and the reaction was carried out at room temperature for 5 hours with stirring. Benzene 100 mA' was added to the reaction solution, the organic solvent layer was washed with water, and Na2
After drying with SO4, the solvent was distilled off. The resulting residue was subjected to silica gel column chromatography, and benzyl alcohol (40°2) was obtained from the benzene eluate.

The yield in this case was 41.3%.

Examples 2 to 9 The following silylated ethers 2 to 9 were prepared in the same manner as the silylation in Example 1 (except for silylated ethers 8 and 9).

Incidentally, silyl ethers 8 and 9 were prepared as follows.

Dissolve 1.08 I (10 mmol) of Sunawachi, Hensyl alcohol and 1.5159 (15 mmol) of Et3N in 50 mA' of THF, and add 3,023 g of diphenylmethylchlorosilane (Φ2MeSiCg) under water cooling.
(13 mmol) was added. 1 while stirring at room temperature.
After carrying out the reaction for 5 hours, the reaction solution was mixed with water, 100 ml of benzene was added to the r solution, the organic solvent layer was washed with water, and Na2S
It was dried with O4 and the solvent was distilled off. The obtained oil was subjected to silica gel column chromatography, and silyl ether compound-8 was quantitatively obtained from the benzene-hexane eluate.

^ Flash Subsequently, desilylation was carried out under various reaction conditions according to the present invention in the same manner as the desilylation procedure of Example 1. The reaction conditions and the results obtained are shown in the table. In addition to the results of Example 1 and Comparative Examples, the table also shows the results of comparative reactions conducted for each silyl ether.

In these Examples, spectral data and related literature for some of the hydroxyl compounds obtained by the desilylation method according to the present invention are as follows.

0H 6'"Synthetic Communications J 1974゜Sat, 155 Ibid." Indian Journal of Chemistry J Section B, 1980, 19B.

Same as above Same as above 3 3' KH8O4MeOH room temperature (a
,,l-) Same as above Same as above Same as above 44'aKI(s04'MeoH room temperature (0,1) Same as above times Above NaH8O4 Same as above Same as above (0,
1) Bu4NF anhydrous chamber @ s 7.3 (1,1)
THF 5 54.6 Bu4NF Anhydrous Room temperature 5゜(1,1) THF LiBF Anhydrous Room @24゜(3) CH,CN 24 86.8 Same as above 85.6 Same as above 4'c KHSO3(o,l) Same as above 4'd NaH3O45
4'a KHSO3 (0, l ) 6 IG (SO4 same as above)
Times above NaH3O4(Ool) Same as above 6' KHSO3(0,l) 7 0HKH8O4 H C2H4(OH)270~ io 93,78
0°C THF-H20 room temperature 43. 88.2 (5:1) MeOH room temperature 5 92.5 MeOH room temperature 47 83.7 Same as above Same as above Same as above 96.2 MeOH room temperature 1 78.7 MeOH room temperature 48 88.4 aO0 As is clear from the table, 5 Bisulfuric acid according to the present invention When desilylation is carried out using salts, higher yields are obtained compared to conventional desilylation methods.

Effects of the Invention In the method of the present invention, desilylation is carried out by reacting a catalytic amount of an inexpensive bisulfate salt, which is solid and easy to handle, with a silyl ether compound to obtain the corresponding hydroxyl compound. Furthermore, even if ester bonds and double bonds exist in the substrate, desilylation can be carried out without changing them.

Furthermore, if a ketal or tetrahydropyranyl ether is present in the substrate, by selecting conditions such as solvent and reaction time, it is possible to cleave only the silyl ether, or to cleave the ketal and tetrahydropyranyl ether simultaneously. It is also possible. The method of the present invention can be applied to silyl ether compounds having various functional groups, and is the most suitable as an industrial method.

Claims (1)

[Claims] 1 General formula (1) R-O-SiR^1R^2R^3 (wherein R is an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, or an aromatic hydrocarbon group, R^1, R^2 and R^3 are the same or different alkyl groups or aryl groups) A silyl ether compound represented by the general formula (2) R-OH (wherein R has the same meaning as above) A method of desilylation to a hydroxyl group compound represented by the following formula (3) is characterized in that the silyl ether compound is reacted with a bisulfate represented by the general formula (3) MHSO_4 (wherein M is an alkali metal). A method for desilylation of silyl ether compounds. 2. The method according to claim 1, wherein the alkali metal (M) in the general formula (3) is lithium, sodium or potassium. 3. A method for desilylating a silyl ether compound according to claim 1, wherein the desilylation reaction is carried out using a catalytic amount of the bisulfate. 4. The method according to claim 3, wherein the amount of bisulfate is 1/1000 equivalent or more, preferably 1/1
A method for desilylating a silyl ether compound selected from a range of 00 to 1.5 equivalents. 5. A method for desilylating a silyl ether compound according to claim 1, wherein the desilylation reaction is carried out in a solvent selected from water and alcohol.