JPH1036337A - Production of aryl vinyl sulfone and its intermediate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an aryl vinyl sulfone which is equivalent to ethylene and useful as an intermediate for organic syntheses and medicines from readily available raw materials by reaction of an arylsulfonylethanol with fuming nitric acid, followed by treatment of the product, a nitric ester with a base. SOLUTION: 2-Arylsulfonylethanol of formula I [R1 and R2 are each H, a halogen, a lower alkyl(amino), nitro and the like] is treated with fuming nitric acid in an amount of 5-15 molar times that of the sulfonylethanol to prepare a nitric ester of formula II, which is treated with a base, for example, sodium hydroxide in an amount of 1-10 molar times, preferably 1.1-5 molar times that of the nitric ester to give the objective compound of formula III with industrial advantage.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing an aryl vinyl sulfone and an intermediate thereof.

[0002]

2. Description of the Related Art Aryl vinyl sulfone is widely used in organic synthesis reactions as an equivalent of ethylene, and is an important compound as a pharmaceutical intermediate. As a method for producing such an aryl vinyl sulfone, for example, a method of dehalogenating β-haloethyl aryl sulfone [Org. Synt
h., 64 , 157 (1985), J. Org. Chem., 58 , 4506 (1993), etc.)
However, there are problems that wastewater containing a halide, having a large environmental load and being highly corrosive is generated, and that the raw material β-haloethylarylsulfone cannot be produced with high yield. Was. In addition, a sulfate ester compound is obtained by a dehydration reaction of 2-arylsulfonylethanol, which is easily available industrially, and then a method of reacting a base with the compound [German Patent No. 842198 (1942)] or a mesylate compound is obtained. Then, a method of allowing a base to act on this (Bull. Korean Chem. Soc., 16 , 6)
70 (1995)]. However, the former method generates severe heat when neutralizing the 100% sulfuric acid used after the reaction, and also requires treatment of a large amount of by-produced sulfate, and the latter method uses expensive mesyl chloride or triethylamine. There is a problem. In addition, none of the methods had satisfactory yields of aryl vinyl sulfone.

[0003]

The inventors of the present invention have conducted intensive studies to develop an industrially advantageous method for producing arylvinylsulfone, and as a result, have found that a novel compound which can be easily obtained in good yield from 2-arylsulfonylethanol. By acting a base on the nitrate compound which is
The inventors have found that aryl vinyl sulfone can be produced in high yield, and have reached the present invention.

[0004]

That is, the present invention provides a compound represented by the following general formula (1): (Wherein, R ₁ and R ₂ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a lower alkylamino group, or a di-lower alkylamino group). Reaction of 2-arylsulfonylethanol and fuming nitric acid with the general formula (2) (Wherein, R ₁ and R ₂ have the same meanings as described above), and then a base is allowed to act on the nitrate compound. (Wherein, R ₁ and R ₂ have the same meanings as described above).

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION 2-ants represented by the general formula (1)
The substituent R ₁, R_TwoTo
Halogen atoms are fluorine, chlorine and bromine atoms
Is a child or iodine atom. As the lower alkyl group,
For example, methyl group, ethyl group, n-propyl group, n-butyl
Group, n-pentyl group, i-propyl group, i-butyl
Group, sec-butyl group, t-butyl group, neopentyl group
Linear or branched alkyl having 1 to 6 carbon atoms
And the like.

Examples of the lower alkoxyl group include methoxy, ethoxy, n-propoxy, n-butoxy, n-pentoxy, i-propoxy, sec-butoxy, t-butoxy and neopentoxy. A straight-chain or branched alkoxyl group having 1 to 6 carbon atoms is exemplified.

[0007] The lower alkylamino group is an amino group substituted with one lower alkyl group, and the lower alkyl group is the same as described above. Examples of such a lower alkylamino group include a methylamino group, an ethylamino group and a t-butylamino group.

[0008] The di-lower alkylamino group is an amino group substituted with two lower alkyl groups, and the lower alkyl groups include the same ones as described above. Examples of the di-lower alkylamino group include a dimethylamino group, a methylethylamino group, a diethylamino group, and a t-butylmethylamino group.

The 2-arylsulfonylethanol includes, for example, 2- (phenylsulfonyl) ethanol, 2- (4-chlorophenylsulfonyl) ethanol, 2- (3,4-dichlorophenylsulfonyl) ethanol, 2- (4-bromophenyl) Sulfonyl) ethanol, 2- (4-fluorophenylsulfonyl) ethanol, 2- (4-iodophenylsulfonyl) ethanol, 2- (4-methylphenylsulfonyl) ethanol, 2- (2,4-dimethylphenylsulfonyl) ethanol, 2- (4-ethylphenylsulfonyl) ethanol, 2- (4-i-butylphenylsulfonyl) ethanol, 2- (4-t-butylphenylsulfonyl) ethanol, 2- (4-methoxyphenylsulfonyl) ethanol, 2- (4-methoxyphenylsulfonyl) ethanol (3, -Dimethoxyphenylsulfonyl) ethanol, 2- (4-t-butoxyphenylsulfonyl) ethanol, 2- (3-aminophenylsulfonyl) ethanol, 2- (3-methylaminophenylsulfonyl) ethanol, 2- (3-ethylamino Phenylsulfonyl) ethanol, 2- (3-dimethylaminophenylsulfonyl) ethanol, 2- (3-diethylaminophenylsulfonyl) ethanol, 2- (3-nitrophenylsulfonyl) ethanol and the like.

These 2-arylsulfonylethanols are prepared, for example, by oxidizing a sulfide compound obtained by reacting a thiophenol compound with ethylene oxide or 2-chloroethanol [for example, Japanese Patent Publication No. 4-171.
No. 82, Bull. Korean Chem. Soc., 16 , 670 (1995)] and the like. Further, the substituent on the aromatic ring may be introduced after obtaining the sulfone compound in some cases.

The amount of fuming nitric acid is usually in the range of 5 to 20 moles per mole of 2-arylsulfonylethanol.

The reaction is usually performed in a solvent. Examples of the solvent include halogen-based solvents such as dichloromethane, 1,2-dichloroethane, chloroform, and 1-chlorobutane; and hydrophobic organic solvents such as aliphatic hydrocarbon-based solvents such as hexane and heptane. Each of these solvents is used alone or in combination of two or more, and the amount of the solvent is usually in the range of 1 to 30 times by weight based on 2-arylsulfonylethanol.

In order to react 2-arylsulfonylethanol and fuming nitric acid, for example, 2-arylsulfonylethanol and fuming nitric acid may be mixed in a solvent. The reaction temperature is generally 0-100 ° C, preferably 15-5 ° C.
It is in the range of 0 ° C.

Water is added to the reaction mixture after the reaction to separate into an aqueous layer and an organic layer. The aqueous layer is extracted with a hydrophobic organic solvent, and a solution of a nitrate compound is used as an organic layer. obtain. The nitrate compound may be used as it is in the solution thus obtained, or may be used after being taken out of the solution. To remove the nitrate compound from the solution, for example, the solvent may be distilled off from the solution.

As the nitrate compound, for example, 2-
(Phenylsulfonyl) ethyl nitrate, 2- (4
-Chlorophenylsulfonyl) ethyl nitrate, 2
-(3,4-dichlorophenylsulfonyl) ethyl nitrate, 2- (4-bromophenylsulfonyl) ethyl nitrate, 2- (4-fluorophenylsulfonyl) ethyl nitrate, 2- (4-iodophenylsulfonyl) ethyl nitrite Rate, 2- (4-methylphenylsulfonyl) ethyl nitrate, 2- (2,4-
Dimethylphenylsulfonyl) ethyl nitrate, 2
-(4-ethylphenylsulfonyl) ethyl nitrate, 2- (4-i-butylphenylsulfonyl) ethyl nitrate, 2- (4-t-butylphenylsulfonyl) ethyl nitrate, 2- (4-methoxyphenylsulfonyl) ) Ethyl nitrate, 2- (3,4-dimethoxyphenylsulfonyl) ethyl nitrate, 2-
(4-t-butoxyphenylsulfonyl) ethyl nitrate, 2- (3-aminophenylsulfonyl) ethyl nitrate, 2- (3-methylaminophenylsulfonyl) ethyl nitrate, 2- (3-ethylaminophenylsulfonyl) Examples thereof include ethyl nitrate, 2- (3-dimethylaminophenylsulfonyl) ethyl nitrate, 2- (3-diethylaminophenylsulfonyl) ethyl nitrate, and 2- (3-nitrophenylsulfonyl) ethyl nitrate.

The base is not particularly restricted but includes, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide, potassium carbonate, and the like.
Alkali metal carbonates such as potassium hydrogen carbonate, sodium carbonate and sodium hydrogen carbonate; inorganic bases such as ammonia; triethylamine, diethylamine, diisopropylamine, diisopropylethylamine, 1,5-diazabicyclo [4.3.0] none-5-ene And organic bases such as amine compounds such as 1,8-diazabicyclo [5.4.0] undec-7-ene. The amount of the base to be used is generally 1 to 10 mol times, preferably 1.1 to 5 mol times, relative to the nitrate compound. These bases may be used as an aqueous solution.

The reaction is usually carried out in a solvent, and examples of such a solvent are the same as those described above in the previous reaction. The amount of the solvent used is usually in the range of 1 to 30 times by weight of the nitrate compound.

In order for the base to act on the nitrate compound, for example, the nitrate compound and the base may be mixed in a solvent. When the nitrate compound is used in the above-mentioned solution, the base may be added to the solution. Good. The reaction temperature is usually in the range of 0 to 100 ° C, preferably 15 to 50 ° C.

After the reaction, water is added to the obtained reaction mixture to separate it into an aqueous layer and an organic layer. The obtained aqueous layer is dried by extracting with a hydrophobic organic solvent, and the organic layer is dried. The desired aryl vinyl sulfone can be obtained by a method of distilling off the solvent. The obtained aryl vinyl sulfone may be further purified by washing, recrystallization and the like.

The aryl vinyl sulfone thus obtained is, for example, phenyl vinyl sulfone, (4-chlorophenyl) vinyl sulfone, (3,4-dichlorophenyl) vinyl sulfone, (4-bromophenyl) vinyl sulfone, (4-fluorophenyl) Vinyl sulfone,
(4-iodophenyl) vinylsulfone, (4-methylphenyl) vinylsulfone, (2,4-dimethylphenyl) vinylsulfone, (4-ethylphenyl) vinylsulfone, (4-i-butylphenyl) vinylsulfone,
(4-t-butylphenyl) vinylsulfone, (4-methoxyphenyl) vinylsulfone, (3,4-dimethoxyphenyl) vinylsulfone, (4-t-butoxyphenyl) vinylsulfone, (3-aminophenyl) vinylsulfone (3-methylaminophenyl) vinylsulfone, (3-ethylaminophenyl) vinylsulfone,
(3-dimethylaminophenyl) vinyl sulfone, (3
-Diethylaminophenyl) vinylsulfone, (3-nitrophenyl) vinylsulfone and the like.

[0021]

According to the method of the present invention, arylvinylsulfone can be produced with good yield from 2-arylsulfonylethanol which is industrially easily available by a simple operation.

[0022]

EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 186 mg of 2- (phenylsulfonyl) ethanol (1
(2 mmol) was suspended in 2 ml of chloroform, and 670 mg (10 mmol) of 94% fuming nitric acid was added thereto, followed by stirring at 25 ° C. for 30 minutes. Thereafter, 5 ml of water was added and the mixture was separated, and the obtained aqueous layer was extracted with 3 ml of chloroform to obtain an organic layer. The organic layer was coated with a 20% aqueous sodium hydroxide solution (800 mg, sodium hydroxide 4 mm).
l) was added and the mixture was stirred at 25 ° C for 1 hour. Then 5 ml of water
Was added and the mixture was separated, and the obtained aqueous layer was extracted with 5 ml of chloroform to obtain an organic layer. After the obtained organic layer was dried using magnesium sulfate, the solvent was distilled off, and 168 mg of phenylvinylsulfone (white crystals, purity 96.8%,
Yield 96.8%). The white crystals were washed with a 20% aqueous sodium hydroxide solution and then recrystallized from ethanol. As a result, the purity was 99%. Melting point: 65-66 ° C ¹ H-NMR spectrum (CDCl ₃ , 270 MHz)
δ6.05 (d, 1H, J = 9.90Hz), 6.46 (d, 1H, J = 16.49Hz), 6.68
(dd, 1H, J = 9.90Hz, 16.49Hz), 7.53-7.68 (m, 3H), 7.88-
7.93 (m, 2H) ¹³ C-NMR spectrum (CDCl ₃ , 67.5 MH
z) δ 127.73, 127.80, 129.27, 133.60, 138.35, 139.
44 Mass spectrum (EI-MS) m / z 168 (M +), 125, 7
7, 51, 27

Example 2 2- (phenylsulfonyl) ethanol was replaced by 2-
(3-nitrophenylsulfonyl) ethanol 231m
Except for using g (1 mmol), the same operation as in Example 1 was carried out to obtain (3-nitrophenyl) vinylsulfone 217 m
g (purity 96%, yield 97.7%). Melting point: 100-104 ° C ¹ H-NMR spectrum (CDCl ₃ , 270 MHz)
δ 6.26 (d, 1H, J = 9.57 Hz), 6.61 (d, 1H, J = 16.49 Hz), 6.77
(dd, 1H, J = 9.57Hz, 16.49Hz), 7.86 (m, 1H), 8.25 (m, 1H),
8.51 (m, 1H), 8.71 (m, 1H) 13 C-NMR spectrum (CDCl _3, 67.5MH
z) δ 122.91, 128.03, 130.23, 130.85, 133.30, 137.
04, 141.62, 148.18 Mass spectrum (EI-MS) m / z 213 (M +), 170

Example 3 186 mg of 2- (phenylsulfonyl) ethanol (1
(2 mmol) was suspended in 2 ml of chloroform, and 670 mg (10 mmol) of 94% fuming nitric acid was added thereto, followed by stirring at 25 ° C. for 30 minutes. Thereafter, 5 ml of water was added and the mixture was separated, and the obtained aqueous layer was extracted with 3 ml of chloroform to obtain an organic layer. After the obtained organic layer was dried using magnesium sulfate, the solvent was distilled off to obtain 226 mg of 2- (phenylsulfonyl) ethyl nitrate (white crystals, yield 97.8%). Melting point: 73-74 ° C. ¹ H-NMR spectrum (CDCl ₃ , 270 MHz)
δ3.54 (t, 2H, J = 6.27Hz), 4.80 (t, 2H, J = 6.27Hz), 7.57
-7.75 (m, 3H), 7.91-7.95 (m, 2H) 13 C-NMR spectrum (CDCl _3, 67.5MH
z) δ 53.26, 65.34, 127.87, 129.52, 134.36, 138.
62

Example 4 2- (phenylsulfonyl) ethanol was replaced by 2-
(3-nitrophenylsulfonyl) ethanol 231m
By operating in the same manner as in Example 3 except that g (1 mmol) was used, 275 mg (yield 99.5%) of 2- (3-nitrophenylsulfonyl) ethyl nitrate was obtained. Melting point: 83-85 ° C. ¹ H-NMR spectrum (CDCl ₃ , 270 MHz)
δ3.63 (t, 2H, J = 5.94Hz) 、 4.88 (t, 2H, J = 5.94Hz) 、 7.87
(m, 1H), 8.29 ( m, 1H), 8.67 (m, 1H), 8.79 (m, 1H) 13 C-NMR spectrum (CDCl _3, 67.5MH
z) δ 53.57, 65.10, 123.52, 128.86, 131.09, 133.
62, 141.10, 148.45

Claims (4)

[Claims] 1. The general formula (1) (Wherein, R ₁ and R ₂ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a lower alkylamino group, or a di-lower alkylamino group). Reaction of 2-arylsulfonylethanol and fuming nitric acid with the general formula (2) (Wherein, R ₁ and R ₂ have the same meanings as described above), and then a base is allowed to act on the nitrate compound. (Wherein, R ₁ and R ₂ each have the same meaning as described above). 2. A nitrate compound represented by the general formula (2). 3. The method for producing a nitrate compound according to claim 2, wherein the 2-arylsulfonylethanol represented by the general formula (1) and fuming nitric acid are reacted. 4. The process according to claim 1, wherein the amount of fuming nitric acid is 5 to 15 times the molar amount of the 2-arylsulfonylethanol.