JPH0881456A - Production of 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran derivative - Google Patents

Abstract

PURPOSE: To obtain a 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran derivative useful as an intermediate for producing an agrochemical industrially and advanta geously by treating a phthalide derivative having a specific structure with phos phorus trichloride and chlorine. CONSTITUTION: This compound of formula II is obtained by treating a phthalide derivative of formula I (R is a group or an atom insert to a reaction; (n) is 1-4) with phosphorus trichloride and chlorine preferably at 20-100 deg.C usually for 0.2-24 hours. The amount of phosphorus trichloride is 3-10 mols and that of chlorine is 3-6 mols based on 1 mol of the compound of formula I. For example, when phthalide is used as a compound of formula I, 1,1,3,3-tetrachloro-1,3- dihydroisobenzofuran is obtained as the compound of formula II and when 4,5-dichlorophalide is used as the compound of formula I, 1,1,3,3,5,6- hexachloro-1,3-dihydroisobenzofuran is obtained as the compound of formula II.

Description

Detailed Description of the Invention

[0001]

The present invention relates to 1,1,3,3-tetrachloro-1,3-useful as an intermediate for the production of agricultural chemicals.
The present invention relates to a method for producing a dihydroisobenzofuran derivative.

[0002]

2. Description of the Related Art Conventionally, the formula 3 is disclosed in Japanese Patent Laid-Open No. 5-301860.

[Chemical 3] Of certain benzimidazole compounds having excellent bactericidal activity, and 5-chloro-1,1,3,3-tetrafluoro-6-nitro-1,3-dihydroiso as a production intermediate thereof. It is described that benzofuran is useful, and an advantageous method for producing the intermediate compound for production is desired.

[0003]

Under the circumstances, the present inventors have found that 1,1,3,3-tetrachloro represented by the following general formula (5), which can lead to the production intermediate compound and the like. As a result of various studies on the production method of the -1,3-dihydroisobenzofuran derivative, by reacting phosphorus trichloride and chlorine on the phthalide derivative represented by the following general formula 4, the following formula 1, 1, 3,
The present invention has been completed by finding that a 3-tetrachloro-1,3-dihydroisobenzofuran derivative can be industrially advantageously produced. That is, the present invention is represented by the general formula

[Chemical 4] [In the formula, R represents a group or atom inert to the reaction, and n
Represents an integer of 1 to 4. However, when n is 2 or more, R
May be the same or different. ] The phthalide derivative represented by the formula [5] is characterized by reacting phosphorus trichloride and chlorine.

[Chemical 5] [In the formula, R and n represent the same meaning as described above. ] The manufacturing method of the 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran derivative shown by these is provided.

In the general formula 4, R is, for example, hydrogen atom, halogen atom (fluorine atom, chlorine atom,
Bromine atom, etc.), nitro group, cyano group, C ₁ -C ₄ alkyl group (eg, methyl group, ethyl group, etc.), C ₁ -C ₄ alkoxy group (eg, methoxy group, ethoxy group, etc.) and the like. However, it is not necessarily limited to these. Examples of the phthalide derivative represented by the general formula 4 which is a raw material compound used in the present invention include phthalide and 4-
Chlorophthalide, 5-chlorophthalide, 4,5-dichlorophthalide, 3,4,5,6-tetrachlorophthalide,
4-fluorophthalide, 4,5-dibromophthalide, 4
-Chloro-5-nitrophthalide, 3-nitrophthalide,
4-nitrophthalide, 5-nitrophthalide, 6-nitrophthalide, 4-cyanophthalide, 4-methylphthalide,
Examples include 4,5-dimethoxyphthalide.

In the present invention, chlorine is used as chlorine gas or liquefied chlorine, or both of them are used. The chlorine gas is directly blown into the reaction solution, the method is such that it is communicated with the gas phase portion of the reaction solution, or the gas of the reaction solution is used. It can be made to act by a method of pressurizing the phase portion or a combination thereof, and liquefied chlorine can be made to act by dropping into the reaction liquid. The amount ratio of the reagents used is such that phosphorus trichloride is usually in a proportion of 2 to 100 moles, preferably 3 to 10 moles, and chlorine is usually in a proportion of 2 to 10 moles, relative to 1 mole of the phthalide derivative represented by the general formula 4. Ratio Desirably, the ratio is 3 to 6 mol. The reaction is usually
It is usually carried out at a temperature in the range of 0 to 200 ° C for 0.2 to 24 hours, and preferably at a temperature in the range of 20 to 100 ° C.

The reaction may be carried out in an organic solvent, and examples of the organic solvent used include halogenated hydrocarbons such as chloroform, carbon tetrachloride, 1,2-dichloroethane, trichloroethylene, tetrachloroethylene and the like. Examples thereof include solvents, aromatic hydrocarbon solvents such as benzene, toluene and xylene, halogenated aromatic hydrocarbon solvents such as monochlorobenzene and dichlorobenzene, phosphorus oxychloride and the like, and mixtures thereof. The reaction solution after the reaction is
As it is or after distilling away phosphorus trichloride and solvent, etc., gradually add to cold water or ice water, extract with an organic solvent, and wash the organic layer with water or sodium hydrogen carbonate aqueous solution, etc., if necessary, and concentrate. The desired 1,1,3,3-tetrachloro-1, shown by the general formula 5 is obtained by a method of obtaining a product by a usual method or an operation such as filtration of crystals precipitated when added to water. The 3-dihydroisobenzofuran derivative can be isolated. If necessary, it can be further purified by an operation such as distillation, recrystallization or chromatography.

A general formula, which is a raw material compound used in the present invention
The phthalide derivative represented by the chemical formula 4 is, for example, the following reaction formula
Conversion 6

[Chemical 6] [In the formula, R and n represent the same meaning as described above. ] It can be obtained by the method shown in.

[0008]

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. In some cases, the purity of the obtained product was determined by the area percentage method using gas chromatography or the internal standard method (GC-IS method). The yield of the obtained product is determined by the weight of the isolated product or / and the area percentage method using gas chromatography or GC-
It was determined by the IS method. In the GC-IS method, the ratio of the detected intensities of the isolated pure target substance and the internal standard substance is calculated, and after the reaction is completed, a certain amount of the internal standard substance is added to the product obtained by the treatment, Purity was calculated from the detection intensity ratio of gas chromatography. The gas chromatography column used was a megabore capillary column DB-17.
(J & W Scientific Co., Ltd.) 0.53mm × 3
0 m is used and the carrier is helium 5 ml / min.

Example 1 5 g of phthalide was added to 100 g of phosphorus trichloride, and the mixture was stirred at room temperature for 30 hours.
After stirring for a minute, the temperature was raised to 60 ° C. 7.9 g of chlorine gas was blown into this liquid over about 30 minutes. At this time, the temperature of the reaction liquid rose to around 70 ° C. due to the heat of reaction. After the completion of blowing the chlorine gas, stirring was continued for 2 hours while maintaining the temperature of the reaction solution at 80 to 83 ° C. Next, 70 g of phosphorus trichloride in the reaction solution was distilled off, and the residue in the distillation pot was cooled and then gradually added to 100 g of ice water. This is chloroform 50
It was extracted twice with g, and the chloroform layers were combined and washed successively with 100 g of a 1% sodium hydrogen carbonate aqueous solution and 100 g of water. The chloroform layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give a pale yellow oily 1,1,
There were obtained 8.66 g of 3,3-tetrachloro-1,3-dihydroisobenzofuran [yield 70% (value corrected from the purity described below)]. The purity was 78% from the analysis result of the gas chromatography. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 7.3 to 7.9 (4H, m) mass (FD): m / e, parent peak 221 [-Cl ⁺ ]

Example 2 14 g of 4,5-dichlorophthalide was added to 150 g of 1,2-dichloroethane, 28.4 g of phosphorus trichloride was added thereto, and the temperature was raised to 50 ° C. Chlorine gas 15.2 in this liquid
b was blown in for about 1 hour. Due to the heat of reaction, the temperature of the reaction solution rose to around 70 ° C. After the completion of blowing the chlorine gas, the reaction solution was stirred for another hour while maintaining the temperature at 75 to 80 ° C. After cooling the reaction solution, it was gradually poured into 200 g of ice water to separate it. The oil layer and the aqueous layer were extracted with 100 g of 1,2-dichloroethane. Combine oil layers, 1%
It was washed successively with 150 g of an aqueous sodium hydrogen carbonate solution and 150 g of water. After drying the oil layer with anhydrous magnesium sulfate,
1,2-Dichloroethane was distilled off under reduced pressure, and white crystals of 1,1,3,3,5,6-hexachloro-1,3-dihydroisobenzofuran 20.78 g [yield 85% (corrected from the purity described below. Value)] was obtained. The purity was 92% from the analysis result of the gas chromatography. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 7.8 (2H, s) mass (FD): m / e, parent peak 324

Example 3 25 g of 5-chloro-4-nitrophthalide was added to 250 g of phosphorus oxychloride, 80.3 g of phosphorus trichloride was added, and the temperature was raised to 70 ° C. Chlorine gas 41.5g in this liquid
Was blown in for about 1 hour. Due to the heat of reaction, the temperature of the reaction liquid rose to around 90 ° C. After the completion of blowing the chlorine gas, the reaction solution was stirred for another 2 hours while maintaining the temperature at 95 to 100 ° C. Next, about 20 phosphorus oxychloride in the reaction solution
After 0 g was distilled off and the distillation bottom was cooled, it was diluted with 200 g of chloroform, and this was gradually added to 200 g of ice water. The separated chloroform layer and the chloroform layer obtained by extracting the aqueous layer with 100 g of chloroform were combined to give 1%.
It was washed successively with 200 g of an aqueous sodium hydrogen carbonate solution and 200 g of water, and the chloroform layer was dried over anhydrous magnesium sulfate. The chloroform layer was evaporated under reduced pressure to give orange-white crystals of 5-chloro-1,1,3,3-tetrachloro-6-.
32.9 g of nitro-1,3-dihydroisobenzofuran [yield 73% (value corrected from the purity described later)] was obtained. The purity was 88% from the analysis result of gas chromatography. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.1 (1H, s), 7.9 (1
H, s) mass (FD): m / e, parent peak 335

Next, a production example of the phthalide derivative represented by the general formula 4 used as a raw material compound in the present invention will be shown. Reference Example 1 90 g of 4,5-dichlorophthalic acid, 58 g of acetic anhydride and 810 g of toluene were heated under reflux for about 2 hours and then concentrated under reduced pressure to give 4,5-dichlorophthalic anhydride 8
2.8 g (99% yield) was obtained as a white solid. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.11 (2H, s) 4,5-dichlorophthalic anhydride 82.8 g and N, N-
Dimethylformamide (414 g) was charged, and a solution of sodium borohydride (28.8 g) dissolved in N, N-dimethylformamide (331 g) was slowly added dropwise at an internal temperature of 25 to 50 ° C. Then, it stirred at 65 degreeC for about 2 hours. Then, cool to room temperature, and add 331 g of 10% hydrochloric acid water.
After dropping, the mixture was stirred at 100 ° C. for 1 hour. After cooling, the precipitated solid was separated by filtration and dried to give 4,5-dichlorophthalide 6
2.8 g (yield 81%) was obtained. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 5.29 (2H, s), 7.63
(1H, s), 8.00 (1H, s)

Reference Example 2 20 g of 4-chlorophthalic anhydride was dissolved in 80 g of N, N-dimethylformamide, and at room temperature sodium borohydride (8.3 g) of N, N-dimethylformamide 80 was dissolved.
g solution was added dropwise. Then, the reaction solution was stirred at 65 ° C. for 1 hour, then cooled to 20 ° C., and 125 g of 10% hydrochloric acid was added. The mixture was heated to 100 ° C., stirred under heating under reflux for 1 hour, and the crystals precipitated by cooling were filtered, washed with water, and dried under reduced pressure to give white crystals (5).
-Chlorophthalide (8.3 g, yield 45%) was obtained. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.1 to 7.4 (3H, m)
5.3 (2H, s) Next, 7.0 g of 5-chlorophthalide was added to 64 ml of concentrated sulfuric acid, and 7 ml of concentrated nitric acid was added dropwise over 30 minutes with stirring while cooling to 0 ° C. Then, the temperature of the reaction solution is raised to 25 ° C
After stirring for 1 hour, the mixture was poured into 500 ml of ice water. This is extracted twice with 150 ml of ethyl acetate, the oil layers are combined and
The extract was washed with 100 ml of saturated saline and dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure to give 63.4 g (yield 65%) of 5-chloro-4-nitrophthalide as pale yellow crystals.
%) Was obtained. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.4 (1H, s), 7.8 (1
H, dd), 5.4 (2H, s)

Next, the general formula produced by the method of the present invention:
1,1,3,3-tetrachloro-1,3 represented by Chemical formula 5
From the dihydroisobenzofuran derivative 5-chloro-
1,1,3,3-tetrafluoro-6-nitro-1,3
-Examples of conversion to dihydroisobenzofuran are shown. Reference Example 3 5-chloro-1,1,3,3-tetrachloro-6-nitro-1,3-dihydroisobenzofuran 10 g was added to 1,4
- addition of dioxane 100 g, was added to well-dried antimony trifluoride (SbF ₃₎ 18.6 g thereto, warmed, allowed to warm to 0.99 ° C. while distilling off the 1,4-dioxane. Then, the mixture was cooled to 50 ° C., and the reaction liquid diluted with 200 g of chloroform was filtered using Celite as an auxiliary agent. The filter residue was washed with 100 g of chloroform,
The filtrate and washings were washed with 200 g of water. The separated organic layer was further washed with a 0.5% aqueous calcium hydroxide solution, and the organic layer was dried over anhydrous magnesium sulfate. The organic solvent was distilled off under reduced pressure, and brown crystals of 5-chloro-1,1,3,3-
Tetrafluoro-6-nitro-1,3-dihydroisobenzofuran 6.9 g (yield 86%) was obtained. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.4 (1H, s), 8.1 (1
H, s) mass (FD): m / e, parent peak 271

Reference Example 4 56.3 g of 1,1,3,3,5,6-hexachloro-1,3-dihydroisobenzofuran and 563 g of 1,4-dioxane were charged, and antimony trifluoride (SbF) was added thereto.
₃ ) 110 g was added and the temperature was raised to 150 ° C.
Dioxane was removed. After stirring at 150 ° C for about 30 minutes, the mixture was diluted with 200 g of cooled chloroform and filtered through Celite. After concentrating the obtained filtrate under reduced pressure, the product obtained under reduced pressure was sublimated to obtain 31 g of 1,1,3,3-tetrafluoro-5,6-dichloro-1,3-dihydroisobenzofuran. (Yield 71%) was obtained as a white solid. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 7.79 (2H, s) In a 50 ml _three -necked flask, 1,1,3,3-tetrafluoro-5,6-dichloro-1,3-dihydroiso Benzofuran 2.0 g, potassium nitrite 2.62 g, cuprous chloride (C
uCl) 0.16 g and N, N-dimethylformamide 2
0 g was charged, and the mixture was vigorously stirred at 125 ° C. for about 6 hours under a nitrogen stream. After that, the reaction solution was mixed with 20 g of toluene and 10%.
The solution was poured into 30 g of an aqueous solution of NaOH and separated. The aqueous layer was washed twice with 20 g of toluene, then the aqueous layer was adjusted to pH 2 to 4 with hydrochloric acid, and extracted with 40 g of toluene. The extract is concentrated to give the desired 1,1,3,3-tetrafluoro-5-hydroxy-6-nitro-1,3-dihydroisobenzofuran.
1.5 g (yield 77%) was obtained. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 1.61 (1H, brs), 7.4
9 (1H, s), 8.49 (1H, s) mass (FD): m / e, parent peak 253 1,1,3,3-tetrafluoro-5-hydroxy-6
-Nitro-1,3-dihydroisobenzofuran 3.72
g was added to thionyl chloride (22.5 g), and N, N-dimethylformamide (2.89 g) was added thereto with stirring under cooling to 30 ° C or lower. Then, the mixture was stirred at 85 to 87 ° C. for 3 hours, and then excess thionyl chloride was distilled off and then cooled. To this, 100 g of toluene and 100 g of water were added, extraction and liquid separation were performed, and the toluene layer was sequentially washed with 100 g of a 7% sodium hydrogen carbonate aqueous solution and 100 g of water. The toluene layer was dried over anhydrous magnesium sulfate, and toluene was distilled off under reduced pressure to give brown crystals of 5-chloro-1,1,3,3.
There were obtained 4.03 g of 3-tetrafluoro-6-nitro-1,3-dihydroisobenzofuran [yield 91% (value corrected from the purity described below)]. The purity was 90% from the analysis result of the gas chromatography. ¹ H-NMR (CDCl ₃ / TMS) δ value (ppm): 8.1 (1H, s), 7.9 (1
H, s) mass (FD): m / e, parent peak 271

[0016]

According to the present invention, the 1,1,3,3-tetrachloro-1,3-dihydroisobenzofuran derivative represented by the general formula 5 can be industrially advantageously produced.

Claims (2)

[Claims] 1. A general formula: ## STR1 ## [In the formula, R represents a group or atom inert to the reaction, and n
Represents an integer of 1 to 4. However, when n is 2 or more, R
May be the same or different. ] The compound represented by the general formula: ## STR00002 ## characterized in that phosphorus trichloride and chlorine are allowed to act on the phthalide derivative represented by [In the formula, R and n represent the same meaning as described above. ] The manufacturing method of the 1,1,3,3- tetrachloro- 1,3- dihydro isobenzofuran derivative shown by these. 2. R _{n of the} formula 1 is a 4,5-dichloro group or a 5-chloro-4-nitro group (R _{n of the} formula 2 is a 5,6-dichloro group or 5-chloro-6- The method according to claim 1, which is a nitro group.