JP5298678B2 - (Arylloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound production method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an industrially suitable method for producing (aryloyl or heteroaryloyl)methylpentafluorosulfanyl benzene compounds, without requiring to perform complex post treatments, using easily available raw materials, by using a simple method capable of obtaining the (aryloyl or heteroaryloyl)methylpentafluorosulfanyl benzene compounds. <P>SOLUTION: This method for producing the (aryloyl or heteroaryloyl)methylpentafluorosulfanyl benzene compounds is characterized by performing the hydration reaction of (aryloyl or heteroaryloyl)ethynylpentafluorosulfanyl benzene compounds. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

The present invention relates to a method for producing (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compounds. (Aryloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compounds are compounds useful as raw materials for producing pharmaceuticals and liquid crystal materials, for example (see, for example, Patent Document 1).
International Publication No. 2005/047240 Pamphlet

Conventionally, as a method for producing an (allyloyl or heteroaryloyl) methylbenzene compound, for example, an aryl ketone and an aryl halide are reacted in the presence of a phosphorus compound, a palladium compound and t-butoxy sodium while heating under reflux. Is known (see, for example, Non-Patent Document 1). However, this method has a problem that the post-treatment after the reaction becomes complicated because the reaction system is complicated.
Also, a method in which a mercury salt is reacted with a carbon-carbon triple bond (for example, see Non-Patent Document 2), a method in which a transition metal catalyst is reacted (for example, see Non-Patent Document 3), and ultrasonic irradiation. Although a method (for example, refer nonpatent literature 4) is known, in any case, there existed the trouble of reaction operation and the problem of the post-treatment of metals, and it was difficult to adopt as an industrial manufacturing method.
J. et al. Am. Chem. Soc. 122, 1360 (2000) Synlett. , 495 (2002) Synlett. 631 (2004) Tetrahedron Lett. , 47, 5497 (2006)

  An object of the present invention is to solve the above-mentioned problems, without the need for complicated post-treatment, and by a simple method using readily available raw materials, (aryloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound It is in providing the manufacturing method of the industrially suitable (allyloyl or hetero aryloyl) methylpentafluorosulfanyl benzene compound which can obtain (A).

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

(In the formula, Ar represents an aryl group or a heteroaryl group. Any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group, or a halogen atom. .)
(Aryl or heteroaryl) ethynyl pentafluorosulfanylbenzene compound represented by the formula (2)

(In the formula, Ar has the same meaning as described above. 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, or a halogen atom.)
(Allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound represented by the method can be solved.

  According to the present invention, (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound can be obtained industrially by a simple method using raw materials that are not readily required to perform complicated post-treatment. The object is to provide a method for producing a suitable (aryloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound.

  The (aryl or heteroaryl) ethynylpentafluorosulfanylbenzene compound used in the reaction of the present invention is represented by the above general formula (1). In the general formula (1), Ar represents an aryl group or a heteroaryl group. Examples of the aryl group include a phenyl group, a tolyl group, a fluorophenyl group, a xylyl group, a biphenylyl group, a naphthyl group, an anthryl group, On the other hand, examples of the heteroaryl group include a quinolyl group, a pyridyl group, a pyrrolidyl group, a pyrrolyl group, a furyl group, and a thienyl 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, or a halogen atom. For example, a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group Group, alkyl group such as hexyl group; cycloalkyl group such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group; aralkyl group such as benzyl group, phenethyl group; phenyl group, tolyl group, biphenyl group, Aryl groups such as naphthyl group and anthryl group; halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom can be mentioned.

  The hydration reaction of the present invention is not particularly limited as long as it is a reaction capable of adding a water molecule to a triple bond. For example, it is desirable to carry out in the presence of an acid. Carboxylic acids such as acetic acid; sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid; and inorganic acids such as hydrochloric acid and sulfuric acid, preferably carboxylic acids, inorganic acids, Preferably formic acid and sulfuric acid are used. These acids may be used alone or in combination of two or more, and a combination of formic acid and sulfuric acid is desirable. The acid is usually used in the form of an aqueous solution, but its concentration is not particularly limited.

  The amount of the acid used is preferably 0.5 to 10 ml, more preferably 1 to 50 ml, with respect to 1 g of (aryl or heteroaryl) ethynylpentafluorosulfanylbenzene compound.

  Since the reaction of the present invention is a hydration reaction, water must be present. Usually, when an acid is used, it is not necessary to add water separately because it is used as an aqueous solution of an acid. When water is present to control the reactivity, the amount used is preferably 0.01 to 100 ml, more preferably 1 g of (aryl or heteroaryl) ethynylpentafluorosulfanylbenzene compound. 0.1 to 50 ml.

  The reaction of the present invention is performed, for example, by a method of mixing (aryl or heteroaryl) ethynylpentafluorosulfanylbenzene compound, acid and water (or an acid aqueous solution) and reacting them with stirring. The reaction temperature at that time is preferably 0 to 200 ° C., more preferably 20 to 150 ° C., and the reaction pressure is not particularly limited.

  A methylpentafluorosulfanylbenzene compound can be obtained by the reaction of the present invention (allyloyl or heteroaryloyl). After the reaction is completed, for example, neutralization, extraction, filtration, concentration, distillation, recrystallization, crystallization, column chromatography, etc. It can be isolated and purified by the general method.

  The greatest feature of the present invention is that only one of the two isomers generated by the hydration reaction (only (2) in the present invention) is selectively generated as shown by the following formula. In essence, it is not the separation of the two isomers after formation of the mixture of (2) and (3).

(In the formula, Ar has the same meaning as described above. 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, or a halogen atom.)

Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto. For structure determination, see J.A. Org. Chem. 56, 2912 (1991), the compound of (3) was synthesized separately and determined by comparison with ¹ H-NMR spectra.

Example 1 (Synthesis of 4-benzoylmethylpentafluorosulfanylbenzene)
After adding 0.50 g (1.64 mmol) of 4-phenylethynylpentafluorosulfanylbenzene and 5 ml of formic acid to a 30-ml container equipped with a stirrer, a thermometer and a reflux condenser, the mixture was stirred at 100 ° C. for 6 minutes. Reacted for hours. Further, 1 ml of concentrated sulfuric acid was added and reacted at the same temperature for 3 hours. After completion of the reaction, the reaction solution was cooled, added with 50 ml of chloroform, washed twice with 20 ml of water and with 20 ml of saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was purified by flash column chromatography (developing solvent: hexane, hexane: ethyl acetate = 10: 1 (volume ratio)) to give 4-benzoylmethylpenta as a white solid. 0.49 g of fluorosulfanylbenzene was obtained (isolation yield; 93%).
The physical properties of 4-benzoylmethylpentafluorosulfanylbenzene were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 4.35 (2H, s), 7.35 to 7.37 (2H, m), 7.47 to 7.53 (2H, m), 7 .57 to 7.64 (1H, m), 7.70 to 7.75 (2H, m), 8.00 to 8.04 (2H, m)
CI-MS (m / e); 323 (M + 1)

Example 2 (Synthesis of 2-fluoro-5- [2-oxo-2- (4-pentylphenyl) ethyl] pentafluorosulfanylbenzene)
In a 30-ml container equipped with a stirrer, thermometer and reflux condenser, 0.50 g (1.27 mmol) of 2-fluoro-5- (4-n-pentyl-phenylethynyl) -pentafluorosulfanylbenzene, formic acid After adding 5 ml and 1 ml of concentrated sulfuric acid, the mixture was reacted at 100 ° C. for 8 hours with stirring. Further, 1 ml of concentrated sulfuric acid was added and reacted at the same temperature for 3 hours. After completion of the reaction, the reaction solution was cooled, added with 50 ml of chloroform, washed twice with 20 ml of water and with 20 ml of saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the concentrate was purified by flash column chromatography (developing solvent; hexane, hexane: ethyl acetate = 10: 1 (volume ratio)) to give 2-fluoro-5 as a yellow solid. 0.13 g of [2-oxo-2- (4-pentylphenyl) ethyl] pentafluorosulfanylbenzene was obtained (isolation yield; 25%).
The physical properties of 2-fluoro-5- [2-oxo-2- (4-pentylphenyl) ethyl] pentafluorosulfanylbenzene were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 0.90 (3H, t, J = 7.0 Hz), 1.26 to 1.38 (4H, m), 1.59 to 1.69 ( 2H, m), 2.68 (2H, t, J = 7.7 Hz), 4.31 (2H, m), 7.15 to 7.31 (3H, m), 7.38 to 7.44 ( 1H, m), 7.61-7.64 (1H, m), 7.91-7.97 (2H, m)
CI-MS (m / e); 411 (M + 1)

  According to the present invention, it is not necessary to perform complicated post-treatment, and an (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound can be obtained by a simple method using raw materials that are available, industrially. A method for producing a suitable (aryloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound can be provided.

Claims (4)

General formula (1)

(In the formula, Ar represents an aryl group or a heteroaryl group. Any hydrogen atom on the benzene ring may be substituted with an alkyl group, a cycloalkyl group, an aralkyl group or an aryl group, or a halogen atom. .)
(Aryl or heteroaryl) ethynyl pentafluorosulfanylbenzene compound represented by the formula (2)

(In the formula, Ar has the same meaning as described above. 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, or a halogen atom.)
(Allyloyl or heteroaryloyl) The manufacturing method of the methylpentafluorosulfanylbenzene compound shown by these.   The method for producing a (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound according to claim 1, wherein the hydration reaction is carried out in the presence of an acid.   The method for producing (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound according to claim 2, wherein formic acid is used as the acid.   The method for producing (allyloyl or heteroaryloyl) methylpentafluorosulfanylbenzene compound according to claim 2, wherein a mixture of formic acid and sulfuric acid is used as the acid.