JPH0570425A - Toluenesulfonyl fluoride derivative - Google Patents

Abstract

PURPOSE:To provide a new toluenesulfonyl fluoride derivative useful as an intermediate for the safe, economical and industrial production of a difluorotoluene derivative useful as an intermediate for agricultural chemicals and pharmaceuticals. CONSTITUTION:The toluenesulfonyl fluoride derivative of formula I, e.g. 2,4- difluoro-3-methylbenzenesulfonyl fluoride. The compound can be produced from a dichlorotoluene compound of formula III by known process e.g. by reacting with chlorosulfuric acid at room temperature or chlorosulfonylating the compound with fuming sulfuric acid and thionyl chloride and fluorinating the resultant dichlorotoluene sulfonyl chloride derivative of formula II with a metal fluoride in a solvent or in the absence of solvent. Desulfonation of the objective compound gives a difluorotoluene compound.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The toluenesulfonyl fluoride derivative obtained in the present invention can be converted into a difluorotoluene derivative useful as an agricultural and pharmaceutical intermediate by a desulfonation reaction.

[0002]

2. Description of the Related Art Conventionally, 2,4-difluorotoluene,
In order to synthesize difluorotoluenes such as 2,6-difluorotoluene, a fluorine atom has been introduced by a method via a diazonium salt by the so-called Balts-Simann reaction. [J. Pharm. Pharmacol. 14 , 5
87-96 (1962)] However, the dinitrotoluenes as a raw material are in danger of exploding, and the intermediate diazonium salt is highly toxic and unstable, resulting in low volumetric efficiency and a large amount of acidic waste liquid. It is difficult to handle, and it is industrially difficult to handle because it has to handle highly corrosive hydrogen fluoride.

[0003]

[Problems to be Solved by the Invention]

[Means for Solving the Problems] In view of the current situation,
The present inventors have conducted extensive studies to solve the problems of the conventional technology,

[0004]

[Formula 2]

The novel toluenesulfonyl fluoride derivative [general formula (I)] represented by the formula (I) is subjected to the desulfonation reaction described in Reference Example 3 to obtain difluorotoluenes.
The present invention has been completed by discovering that it is a useful intermediate.

That is, the present invention has the general formula

[0007]

[Formula 3]

The present invention relates to a toluenesulfonyl fluoride derivative represented by

The toluenesulfonyl fluoride derivative [general formula (I)] of the present invention can be produced by the following scheme.

[0010]

[Formula 4]

The above toluenesulfonyl chloride derivative [general formula (II)] is chlorosulfonylated by a known method from dichlorotoluenes [general formula (III)].
For example, chlorosulphonylation can be easily performed by allowing chlorosulfuric acid to act at room temperature or by using fuming sulfuric acid and thionyl chloride. Examples of the dichlorotoluenesulfonyl chloride derivative [general formula (II)] include 2,4-dichloro-3-methylbenzenesulfonyl chloride and 2,2-dichloro-3-methylbenzenesulfonyl chloride.
4-dichloro-5-methylbenzenesulfonyl chloride and 2,4-dichloro-6-methylbenzenesulfonyl chloride can be mentioned.

The chlorine atom in the toluenesulfonyl chloride derivative [general formula (II)] can be converted into a fluorine atom by applying a known method (for example, JP-A-2-83364), and the toluenesulfonyl chloride derivative [general formula (II) II)] can also be fluorinated with a metal fluoride in a solvent or without a solvent. In that case, the catalyst may or may not be used, but the use of the catalyst shortens the reaction time. When a catalyst is used, a quaternary phosphonium salt such as tetraphenylphosphonium chloride, tetraphenylphosphonium bromide or tetrabutylphosphonium bromide is preferably used.

The amount of the catalyst used is 0.5 mol% based on the benzenesulfonyl chloride derivative [general formula (II)].
Above, preferably 5 to 10 mol% is used.

The alkali metal fluoride to be used is sodium fluoride, potassium fluoride, cesium fluoride or a mixture thereof, and as the alkali metal fluoride, fine particles may be used. For example, spray dry, freeze dry,
Fine particles that can be pulverized or industrially produced may be used. The amount used is 0.5 to 10 equivalents with respect to the halogen atom to be replaced. Preferably, 1 to 3 equivalents are used. When a solvent is used in this reaction, an aprotic polar solvent such as dimethyl sulfoxide, sulfolane and N-methylpyrrolidone, and an aromatic solvent such as dichlorotoluene, trichlorobenzene, chloronaphthalene and methylnaphthalene are used. The reaction proceeds smoothly at room temperature or higher, preferably at 100 to 250 ° C. Further, in the above reaction, it is possible to employ a method in which the resulting aromatic fluorine compound [general formula (I)] is subjected to reactive distillation under atmospheric pressure or reduced pressure and taken out of the reaction system.

[0015]

The toluenesulfonyl fluoride derivative [general formula (I)] of the present invention is a novel compound not described in the literature. Further, by desulfonation, JP-A-57-1390
The difluorotoluenes described in No. 14 can be provided, and have an extremely high industrial value.

[0016]

EXAMPLES Examples will be described below.

Reference Example 1 Synthesis of 2,4-dichloro-3-methylbenzenesulfonyl chloride A 2 l 4-necked flask equipped with a condenser, a mechanical stirrer, a thermometer and a dropping funnel was charged with chlorosulfuric acid 93.
2 g was charged, and 322 g of 2,6-dichlorotoluene was added dropwise little by little with good stirring. The temperature rose to 40 ° C due to the heat of reaction. After confirming the disappearance of the raw materials by gas chromatography, the reaction solution was put into ice, extracted with ether, concentrated, and then distilled to give 409 g (yield 79%) of 2.
4-Dichloro-3-methylbenzenesulfonyl chloride was obtained. The boiling point was 140 to 141 ° C / 1 to 2 mmHg.

Reference Example 2 Synthesis of 2,4-dichloro-5-methylbenzenesulfonyl chloride 2,4 instead of 2,6-dichlorotoluene in Reference Example 1
-A similar reaction was carried out using dichlorotoluene. 42
8 g (yield 82%) of 2,4-dichloro-5-methylbenzenesulfonyl chloride was obtained. Boiling point is 140-1
It was 41 ° C / 3-4 mmHg.

Example 1 Synthesis of 2,4-difluoro-3-methylbenzenesulfonyl fluoride In a 200 ml four-necked flask equipped with a condenser, mechanical stirrer and thermometer, spray-dried potassium fluoride 23 0.2 g (0.4 mol), tetraphenylphosphonium bromide (TPPB) 4.2 g (0.01 mol) and 50 ml of anhydrous sulfolane were added, and azeotropic dehydration was performed with toluene, and then 2,4-dichloro-3-. 26.0 g (0.1 mol) of methylbenzenesulfonyl chloride was added,
The reaction was carried out at 200 ° C. for 1.5 hours. Reaction complete solution
After extraction with tell, the extract was washed with water, dried and concentrated. The residue was distilled to obtain 16.8 g (yield 80%) of 2,4-difluoro-3-methylbenzenesulfonyl fluoride. The boiling point was 110 ° C./10 mmHg.

Confirmation data is shown below. NMR (CCl ₄ ): δ 2.33 (t, J = 2Hz, 3H)
7.07 (t, J = 8.5 Hz, 1H) 7.6 to 8.0
(M, 1H) IR (neat) (cm ^-1 ): 1600, 1450, 14
25, 1230, 1195, 1150, 1090, 96
5,800 MS: m / z = 210 (M ⁺ )

Example 2 Synthesis of 2,4-difluoro-5-methylbenzenesulfonyl fluoride 2,4-dichloro-5-methylbenzene instead of 2,4-dichloro-3-methylbenzenesulfonyl chloride of Example 1 The reaction was performed at 180 ° C. for 4 hours using sulfonyl chloride to obtain 16.3 g (yield 77%) of 2,4-difluoro-5-methylbenzenesulfonyl fluoride. The boiling point was 103 to 105 ° C./15 mmHg.

NMR (CCl ₄ ): δ 2.37 (s, 3H)
7.03 (t, J = 9.2 Hz, 1H) 7.82 (t, J
= 7.5 Hz, 1H) IR (neat) (cm ^-1 ): 1620, 1590, 14
95, 1420, 1290, 1220, 1180, 11
45,1050,810,780 MS: m / z = 210 (M ⁺ ).

Example 3 1,3-Dimethylimidazolidinone was used in place of the anhydrous sulfolane solvent of Example 1, and the reaction was carried out at 200 ° C. for 2 hours to give 2,4-difluoro-3-methylbenzenesulfonyl fluoride. 12.4 g (yield 61%) was obtained.

Example 4 Synthesis of 2,4-difluoro-3-methylbenzenesulfonyl fluoride In a 200 ml four-necked flask equipped with a condenser, mechanical stirrer and thermometer, spray-dried potassium fluoride 23 0.2g (0.4mol), DMI 50ml,
After azeotropic dehydration with toluene, 2,4-dichloro-3
-26.0 g of methylbenzenesulfonyl chloride (0.
1 mol) was added and the reaction was carried out at 200 ° C. for 6 hours. After the reaction completed liquid was extracted with ether, the extract was washed with water, dried and concentrated. The residue was distilled to obtain 13.4 g (yield 66%) of 2,4-difluoro-3-methylbenzenesulfonyl fluoride. The boiling point was 110 ° C./10 mmHg.

Reference Example 3 Synthesis of 2,6-difluorotoluene 100 ml of water and 4 ml of sodium hydroxide were added to a 500 ml beaker.
0 g was added and dissolved. 2,4-difluoro-3-
42 g of methylbenzenesulfonyl fluoride was added dropwise to 1
Stir for hours. To this, 500 ml of methylene chloride was added to extract organic matter, and the aqueous layer was concentrated with a rotary evaporator, and 1 l of methanol was added to the obtained solid matter. The insoluble inorganic matter was filtered off and then concentrated to about 100 ml. Further, 1 l of ether was added, and the mixture was well stirred, the insoluble matter was filtered off, and the solvent was distilled off to obtain crude sodium 2,4-difluoro-3-methylbenzenesulfonate.

Next, a 1 l 4-neck reaction flask was equipped with a stirrer, a thermometer, a T-shaped tube, a Liebig type cooling tube, and a dropping funnel. To this, sodium 2,4-difluoro-3-methylbenzenesulfonate was charged, and 600 g of 80% sulfuric acid was added dropwise. After completion of dropping, the mixture was heated to distill off an azeotrope of 2,6-difluorotoluene and water. Separate the distillate 2
0.3 g (yield 79%) of 2,6-difluorotoluene was obtained.

Claims (1)

[Claims] Claim 1: A toluenesulfonyl fluoride derivative represented by.