JP5266708B2 - Process for producing hydroxypentafluorosulfanylbenzene compounds - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an industrially suitable method for producing a hydroxypentafluorosulfanylbenzene compound by which the hydroxypentafluorosulfanylbenzene compound can be obtained by a simple method from an easily available raw material. <P>SOLUTION: The method for producing the hydroxypentafluorosulfanylbenzene compound represented by general formula (2) includes subjecting an oxypentafluorosulfanylbenzene compound represented by general formula (1) (wherein, P is a protective group) to deprotection reaction. <P>COPYRIGHT: (C)2009,JPO&amp;INPIT

Description

The present invention relates to a method for producing a hydroxypentafluorosulfanylbenzene compound. A hydroxypentafluorosulfanylbenzene compound is a compound useful as, for example, a medicine or a liquid crystal material (see, for example, Patent Document 1).
German Patent Application No. 10151491

Conventionally, as a method for producing a hydroxypentafluorosulfanylbenzene compound, for example, 4-nitropentafluorosulfanylbenzene is reduced to 4-aminopentafluorosulfanylbenzene, then reacted with sodium nitrite to diazotize the amino group, Next, a method for obtaining a 4-hydroxypentafluorosulfanylbenzene compound by hydrolysis is known. However, this method is disadvantageous as an industrial production method because it requires a large number of reaction steps, complicated post-treatment, low yields, and a low-safety diazo compound as an intermediate. , See Patent Document 2).
US Patent Application No. 3219690

  An object of the present invention is to solve the above-mentioned problems, and to obtain a hydroxypentafluorosulfanylbenzene compound from an industrially suitable hydroxypentafluorosulfanylbenzene by a simple and safe method and a readily available raw material. It is to provide a method for producing a compound.

  The subject of this invention is general formula (1).

(In the formula, P represents a protecting group. Note that any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.)
A deprotection reaction of the oxypentafluorosulfanylbenzene compound represented by the general formula (2)

（式中、ベンゼン環上の任意の水素原子は、アルキル基、シクロアルキル基、アラルキル基又はアリール基で置換されていても良い。）

(In the formula, any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.)

This is solved by a process for producing a hydroxypentafluorosulfanylbenzene compound represented by

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an industrially suitable method for producing a hydroxypentafluorosulfanylbenzene compound, which can obtain a hydroxypentafluorosulfanylbenzene compound with a simple and safe method and easily available raw materials. .

  The oxypentafluorosulfanylbenzene compound used in the deprotection reaction of the present invention is represented by the general formula (1). In the general formula (1), P is a protecting group, and a functional group that inactivates a hydroxyl group highly reactive with the protecting group here is called a protecting group.

  Examples of the protecting group include ether-based protecting groups such as benzyl group, methoxybenzyl group, dimethoxybenzyl group, t-butyl group and trityl group; acetal-based protection such as methoxymethyl group, tetrahydropyranyl group and ethoxymethyl group Groups; acyl protecting groups such as acetyl group, pivaloyl group, benzoyl group; silyl ether protecting groups such as trimethylsilyl group, triethylsilyl group, t-butyldimethylsilyl group, t-butyldiphenylsilyl group, etc. An ether-type protecting group is preferred, an aralkyl group is more preferred, and a benzyl group is particularly preferred.

  Any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.

  Examples of the alkyl group include alkyl groups having 1 to 20 carbon atoms such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, a heptyl group, an octyl group, a nonyl group, and a decyl group. It is done. These groups include various isomers.

  Examples of the cycloalkyl group include cycloalkyl groups having 3 to 20 carbon atoms such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. These groups include various isomers.

  Examples of the aralkyl group include aralkyl groups having 7 to 20 carbon atoms such as benzyl group, phenethyl group, and phenylpropyl group. These groups include various isomers.

  Examples of the aryl group include aryl groups having 6 to 20 carbon atoms such as a phenyl group, a p-tolyl group, a naphthyl group, and an anthryl group. These groups include various isomers.

  The oxypentafluorosulfanylbenzene compound used in the deprotection reaction of the present invention is, for example, a reaction between a halogeno or organic sulfonyloxypentafluorosulfanylbenzene compound and a hydroxy compound, as shown by the following general formula (3). (Refer to Reference Examples 1 and 2 described later).

(In the formula, X represents a halogen atom or an organic sulfonyloxy group, and P has the same meaning as described above. The arbitrary hydrogen atom on the benzene ring represents an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group. May be replaced with.)

  In addition, the deprotection reaction of the present invention means a reaction for removing the protecting group. As the method, for example, a method that does not affect the pentafluorosulfanyl group is preferably employed. Is a method of reduction such as a method of reacting with hydrogen in the presence of a metal compound, a method of reacting in liquid ammonia in the presence of a metal (Birch reduction), or a reaction with a strong acid such as trifluoroacetic acid or concentrated hydrochloric acid. Method: Method of reacting with water under acidic conditions; Method of oxidation with 2,3-dicyano-5,6-dichloro-p-benzoquinone, cerium ammonium nitrate, chromium oxide, etc .; Boron compounds such as boron tribromide Examples include a method of contacting with a silicon compound such as iodotrimethylsilyl, preferably a method by reduction, and more preferably a reaction with hydrogen in the presence of a metal compound. It carried out by a method of.

  The metal compound used in the deprotection reaction of the present invention is preferably a compound containing a metal atom of Group 8 of the periodic table, more preferably a compound containing a palladium atom, a platinum atom, a nickel atom, a rhodium atom, or a ruthenium atom. Specifically, palladium / carbon, palladium / barium sulfate, palladium hydroxide / platinum, palladium acetate, palladium chloride, platinum / carbon, platinum sulfide / carbon, palladium-platinum / carbon, platinum oxide, Raney nickel, rhodium / carbon, Examples include ruthenium / carbon, but preferably palladium / carbon, palladium-platinum / carbon, palladium hydroxide, platinum / carbon, and more preferably palladium-platinum / carbon. In addition, you may use these metal compounds individually or in mixture of 2 or more types.

  The amount of the metal compound used is preferably 0.0005 to 0.5 mol, more preferably 0.0003 to 0.3 mol, and particularly preferably 0.0001 to 0.1 mol with respect to 1 mol of the oxypentafluorosulfanylbenzene compound in terms of metal atoms.

  The amount of hydrogen used in the present invention is preferably 0.5 to 50 mol, more preferably 0.7 to 30 mol, particularly preferably 1.0 to 10 mol, per 1 mol of the oxypentafluorosulfanylbenzene compound.

  The reaction of the present invention is preferably carried out in the presence of a solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, water; methanol, ethanol, isopropyl alcohol, t-butyl alcohol Alcohols such as dimethylamine, diethylamine, dipropylamine, pyridine, quinoline, etc .; ketones such as acetone, methylethylketone, methylisobutylketone; N, N-dimethylformamide, N, N-dimethylacetamide, Amides such as N-methylpyrrolidone; Ureas such as 1,3-dimethyl-2-imidazolidinone and 1,3-dimethylimidazolidine-2,4-dione; Sulfoxides such as dimethyl sulfoxide; Sulfones such as sulfolane Nitriles such as acetonitrile and propionitrile; diethyl ether and diisopropyl Examples include ethers such as pill ether, tetrahydrofuran, and dioxane; aromatic hydrocarbons such as benzene, toluene, and xylene. Alcohols are preferable, and methanol and ethanol are more preferable. In addition, you may use these solvents individually or in mixture of 2 or more types.

  The amount of the solvent used is preferably 0.5 to 100 ml, more preferably 0.7 to 50 ml, and particularly preferably 1 to 30 ml with respect to 1 g of the oxypentafluorosulfanylbenzene compound.

  The deprotection reaction of the present invention is carried out by deprotecting the oxypentafluorosulfanylbenzene compound by an appropriate method. Preferred embodiments of this reaction include, for example, an oxypentafluorosulfanylbenzene compound, a metal compound, hydrogen and It is carried out by a method of mixing solvents and reacting with stirring. The reaction temperature at that time is preferably −20 to 200 ° C., more preferably −10 to 150 ° C., and particularly preferably 0 to 100 ° C. The reaction pressure is not particularly limited, but the reaction is carried out at normal pressure or under pressure.

  In the deprotection reaction of the present invention, it is desirable that an acid be present in order to increase the reactivity. Examples of the acid used include organic acids such as formic acid, acetic acid, propionic acid, chloroacetic acid, and trifluoroacetic acid. An inorganic acid such as hydrochloric acid or sulfuric acid. In addition, you may use these acids individually or in mixture of 2 or more types.

  The amount of the acid used is preferably 0.01 to 20 mol, more preferably 0.05 to 10 mol, particularly preferably 0.1 to 6 mol, per 1 mol of the oxypentafluorosulfanylbenzene compound.

  A hydroxypentafluorosulfanylbenzene compound is obtained by the deprotection reaction of the present invention. After completion of the reaction, for example, neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, sublimation, column chromatography, etc. It is isolated and purified by a simple manufacturing method.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Reference Example 1 ([P = benzyl group]; synthesis of 4-benzyloxypentafluorosulfanylbenzene)
In a 100 ml glass container equipped with a stirrer and a thermometer, 5.0 g (22.5 mmol) of 4-fluoropentafluorosulfanylbenzene, 1.35 g (33.8 mmol) of 60% sodium hydride, and 1,1 previously dried After adding 25 ml of 3-dimethyl-2-imidazolidinone, 3.65 g (33.8 mmol) of benzyl alcohol was added at room temperature while stirring, and the mixture was reacted at the same temperature for 12 hours. After completion of the reaction, 50 ml of toluene and 50 ml of ethyl acetate were added to the reaction solution, and the organic layer was washed 5 times with 100 ml of saturated brine and dried over anhydrous magnesium sulfate. After filtration, the obtained filtrate was concentrated, and again added to 200 ml of water, and filtered to remove 1,3-dimethyl-2-imidazolidinone mixed therein. The obtained residue was dried under reduced pressure to obtain 5.62 g of 4-benzyloxypentafluorosulfanylbenzene as a white solid (isolation yield: 81%).
4-Benzyloxypentafluorosulfanylbenzene is a novel compound represented by the following physical property values.

¹ H-NMR (CDCl ₃ , δ (ppm)); 5.10 (2H, s), 6.96 to 6.99 (2H, m), 7.29 to 7.43 (5H, m), 7.65 to 7.70 (2H, m)
CI-MS; 310 (M)

Example 1 (Synthesis of 4-hydroxypentafluorosulfanylbenzene)
In a glass container with a capacity of 100 ml equipped with a stirrer and thermometer, 4.0 g (12.9 mmol) of 4-benzyloxypentafluorosulfanylbenzene, platinum-palladium / carbon (50% water-containing product, trade name; ASCA2 (N. 1.0 g, acetic acid 420 mg (6.99 mmol) and ethanol 50 ml were added, and the mixture was reacted at 70 ° C. for 2 hours with stirring under a hydrogen atmosphere (normal pressure). After completion of the reaction, the reaction solution was cooled to room temperature and then filtered. The obtained filtrate was concentrated to obtain 2.67 g of 4-hydroxypentafluorosulfanylbenzene as a pale yellow solid (isolated yield; 94%).
The physical properties of 4-hydroxypentafluorosulfanylbenzene were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 5.33 (1H, s), 6.85 (2H, d, J = 9.0 Hz), 7.62 to 7.67 (2H, m)
CI-MS; 220 (M)

Reference Example 2 ([P = benzyl group]; synthesis of 2-benzyloxypentafluorosulfanylbenzene)
In a 200 ml glass container equipped with a stirrer and a thermometer, 20 g (90 mmol) of 2-fluoropentafluorosulfanylbenzene, 5.4 g (135 mmol) of 60% sodium hydride and 1,3-dimethyl- After adding 100 ml of 2-imidazolidinone, 14.6 g (135 mmol) of benzyl alcohol was added at room temperature while stirring, and the mixture was reacted at the same temperature for 18 hours. After completion of the reaction, 500 ml of toluene and 300 ml of saturated sodium chloride aqueous solution were added to the reaction liquid and the phases were separated. The organic layer (toluene layer) was washed 3 times with 300 ml of saturated aqueous sodium chloride solution and twice with 300 ml of water, and then with anhydrous magnesium sulfate. Dried. After filtration, the concentrate obtained by concentrating the filtrate was purified by silica gel column chromatography (developing solvent: hexane) to obtain 23.47 g of 2-benzyloxypentafluorosulfanylbenzene as a white solid (isolated yield) 84%).
2-Benzyloxypentafluorosulfanylbenzene is a novel compound represented by the following physical property values.

¹ H-NMR (CDCl ₃ , δ (ppm)); 5.19 (2H, s), 6.98 to 7.10 (2H, m), 7.31 to 7.46 (6H, m), 7.75 to 7.88 (1H, m)
CI-MS; 310 (M)

Example 2 (Synthesis of 2-hydroxypentafluorosulfanylbenzene)
In a glass container with a capacity of 200 ml equipped with a stirrer and a thermometer, 22 g (70.9 mmol) of 2-benzyloxypentafluorosulfanylbenzene, platinum-palladium / carbon (50% water-containing product, trade name; ASCA2) (Chemcat)) 4.4 g, 33.8 g (297 mmol) of trifluoroacetic acid and 100 ml of methanol were added, and the mixture was allowed to react at room temperature for 2 hours under stirring in a hydrogen atmosphere (normal pressure). After completion of the reaction, the reaction solution was cooled to room temperature and then filtered. The obtained filtrate was concentrated, 300 ml of a 10% aqueous sodium chloride solution was added and the layers were separated, and the organic layer was dried over anhydrous magnesium sulfate. After washing the residue with 200 ml of chloroform, the filtrate was concentrated under reduced pressure to obtain 10.3 g of 2-hydroxypentafluorosulfanylbenzene as a pale purple solid (isolated yield; 66%).
2-Hydroxypentafluorosulfanylbenzene is a novel compound represented by the following physical property values.

¹ H-NMR (CDCl ₃ , δ (ppm)); 5.98 (1H, brs), 6.96 to 7.09 (2H, m), 7.37 to 7.43 (1H, m), 7.63 to 7.67 (1H, m)
CI-MS; 220 (M)

  The present invention relates to a method for producing a hydroxypentafluorosulfanylbenzene compound. A hydroxypentafluorosulfanylbenzene compound is a compound useful as, for example, a medicine or a liquid crystal material.

Claims (5)

In the presence of at least one compound selected from the group consisting of palladium / carbon, palladium-platinum / carbon, palladium hydroxide and platinum / carbon , general formula (1)

(In formula, P shows an aralkyl group . In addition, the arbitrary hydrogen atoms on a benzene ring may be substituted by the alkyl group, the cycloalkyl group, the aralkyl group, or the aryl group.)
A oxypentafluorosulfanylbenzene compound represented by the formula (2) is reacted with hydrogen:

A process for producing a hydroxypentafluorosulfanylbenzene compound represented by the formula: In the presence of a base, general formula (4)

(In the formula, X represents a halogen atom or an organic sulfonyloxy group. Note that any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.)
And an organic sulfonyloxypentafluorosulfanylbenzene compound represented by the general formula (5)

(In the formula, P represents an aralkyl group .)
The presence of at least one compound selected from the group consisting of palladium / carbon, palladium-platinum / carbon, palladium hydroxide and platinum / carbon. The reaction is carried out by reacting an oxypentafluorosulfanylbenzene compound with hydrogen, represented by the general formula (2)

The process for producing a hydroxypentafluorosulfanylbenzene compound according to claim 1, which is represented by the formula: General formula (1)

(In formula, P shows an aralkyl group. In addition, the arbitrary hydrogen atoms on a benzene ring may be substituted by the alkyl group, the cycloalkyl group, the aralkyl group, or the aryl group.)
In the presence of a base, the oxypentafluorosulfanylbenzene compound represented by general formula (4)

(In the formula, X represents a halogen atom or an organic sulfonyloxy group. Note that any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group.)
And an organic sulfonyloxypentafluorosulfanylbenzene compound represented by the general formula (5)

(In the formula, P represents an aralkyl group .)
The process for producing a hydroxypentafluorosulfanylbenzene compound according to claim 1, which is obtained by reacting with a hydroxy compound represented by formula (1) .   The method for producing a hydroxypentafluorosulfanylbenzene compound according to any one of claims 1 to 3, wherein P is a benzyl group. Benzyloxypentafluorosulfanylbenzene represented by the formulas (6) and (7).