JPH05230010A - Production of p-chlorophenylcarbamic acid ester - Google Patents

Abstract

PURPOSE:To obtain a fluorine-containing p-chlorophenylcarbamic acid ester useful as an intermediate for agricultural chemicals, dyes, pigments, liquid crystals and pharmaceuticals, especially herbicides having high activity from an easily available industrial raw material with simple process. CONSTITUTION:The objective compound of formula II can be produced at a low cost by chlorinating a phenylcarbamic acid ester of formula I (R is H, 1-4C alkyl or alkyl, alkenyl, alkynyl or cycloalkyl which may be substituted with halogen atom, etc.; R' is lower alkyl) with a chlorination agent such as gaseous chlorine, sulfuryl chloride, N-chlorosuccinimide and Cu (II) chloride at -20 to +150 deg.C (preferably room temperature to 120 deg.C) in a solvent or in the absence of solvent preferably in the presence of a catalytic amount of a base. The starting compound of formula I is obtained by converting a compound of formula III to a diazonium salt under acidic condition, hydrolyzing the salt and reacting the resultant compound of formula IV with a compound of the formula R-Y (Y is halogen, etc.) in a proper solvent in the presence of a base.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing parachlorophenylcarbamate having fluorine.

[0002]

2. Description of the Related Art Conventionally, organic chemicals containing fluorine have been used as agricultural chemicals, dyes and pigments,
It is a useful compound as a raw material for liquid crystals and pharmaceuticals. In particular, organic synthetic intermediates having a fluorine atom on the aromatic ring, which are characteristic of new herbicides with high activity in recent years, are mixed with positional isomers and the reaction yield is unfavorable. However, it has been desired to develop a simple and high-yield synthetic method for these.

Compounds industrially important as organic synthetic intermediates having a fluorine atom include parachlorophenylcarbamic acid ester having a fluorine atom. However, this compound has hitherto been disclosed in Japanese Patent Application No. 2-1871.
Although it was synthesized by the method described in No. 63 or the like, this method uses fluorophenol as a starting material, and the hydroxy group must be protected on the synthetic route. As a result, the number of synthetic steps increases and the overall yield also decreases.

An object of the present invention is to provide a method for producing parachlorophenylcarbamic acid ester in high yield by a simple process.

[0005]

The present invention has the general formula (I)

[0006]

[Chemical 3]

(In the above formula, R represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkyl group which may be substituted with a halogen atom or the like; an alkenyl group; an alkynyl group; a cycloalkyl group, and R'is Indicates a lower alkyl group.)
A general formula (II) characterized by chlorinating a phenylcarbamic acid ester represented by

[0008]

[Chemical 4]

(R and R'in the formula are the same as above.)
The method for producing a parachlorophenylcarbamic acid ester represented by That is, the compound represented by the general formula (I) is chlorinated with a chlorinating agent in the absence of solvent or in the presence of a solvent to produce the parachlorophenylcarbamic acid ester represented by the general formula (II). be able to.

This reaction proceeds even without solvent, but a solvent can be used for the purpose of facilitating the operation. Any solvent can be used as long as it does not inhibit the progress of the reaction. For example, aromatic hydrocarbons such as benzene, toluene and xylene, aliphatic hydrocarbons such as hexane and heptane, alcohols such as methanol and ethanol, and acetonitrile. , Acetone, N, N-dimethylformamide,
Examples include aprotic polar solvents such as dioxane, tetrahydrofuran, dimethylsulfoxide, and water. These solvents are used alone or as a mixture.

Examples of the chlorinating agent that can be used in this reaction include gaseous chlorine, sulfuryl chloride, N-chlorosuccinimide, and copper (II) chloride. Reaction temperature is from -20 ℃
The temperature is selected from the range of 150 ° C., but it is preferable to carry out the reaction in the range of room temperature to 120 ° C. because of good yield and easy operation. Further, this reaction proceeds rapidly by using a catalytic amount of base. Examples of usable bases include inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide and alkali metal alcoholates.
Organic bases such as pyridine, triethylamine, dicyclohexylamine and diethylaniline can be mentioned. After the reaction, the desired product can be easily isolated by a usual post-treatment, and can be further purified by recrystallization from a suitable solvent or mixed solvent.

The compound represented by the general formula (I), which is the starting material for this reaction, is synthesized by the following method.

[0013]

[Chemical 5]

(R and R'in the formula have the same meanings as described above, and Y represents a halogen atom, a paratoluenesulfonyloxy group, a methanesulfonyloxy group, a trihalomethanesulfonyloxy group, and a benzenesulfonyloxy group.) The compound of the general formula (I) is synthesized by the general formula (III)
The aniline derivative represented by the formula (1) is converted to a diazonium salt under acidic conditions and then hydrolyzed to give a compound of the general formula (IV), which is converted to R- in the presence of a base in a suitable solvent.
It can be produced by reacting with a compound represented by Y.

The carbamic acid ester of the general formula (III), which is the starting material of this reaction, can be easily prepared by the method described in DE2703838. Although the reaction for obtaining the general formula (IV) is consistently generally carried out in an aqueous solution,
It is also possible to carry out the reaction in the presence of a cosolvent which does not interfere with the progress of this reaction. Examples of the auxiliary solvent include acetone, tetrahydrofuran, dimethyl sulfoxide, methanol, ethanol and the like.

In this reaction, the reaction temperature in the step of forming a diazonium salt is selected from the range of -20 ° C to room temperature, and 0 ° C to 15 ° C is preferable from the viewpoint of easy operation. In addition, the reaction temperature in the step of hydrolyzing the diazonium salt in this reaction is selected from the range of 0 ° C. to the boiling point of the solvent, but a temperature near the boiling point of the solvent is preferable in that the reaction proceeds rapidly.

After completion of the reaction, the product of the general formula (IV) can be obtained by a usual post-treatment, but if necessary, a purification operation such as recrystallization may be carried out. The solvent used in the reaction for producing the compound of the general formula (I) may be any one as long as it does not inhibit the progress of the reaction, for example, benzene, toluene,
Aromatic hydrocarbons such as xylene, aliphatic hydrocarbons such as hexane and heptane, alcohols such as methanol and ethanol, aprotic substances such as acetonitrile, acetone, N, N-dimethylformamide, dioxane, tetrahydrofuran and dimethyl sulfoxide. Examples include polar solvents and water. These solvents are used alone or as a mixture.

Examples of the base used in this reaction include inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide and alkali metal alcoholates, pyridine, triethylamine and dicyclohexylamine. ,
Organic bases such as diethylaniline can be mentioned.
After the reaction, the desired product can be easily isolated by a usual post-treatment, and can be taken out in a more pure form by recrystallization from an appropriate solvent or mixed solvent.

[0019]

INDUSTRIAL APPLICABILITY The method for producing parachlorophenylcarbamic acid ester according to the present invention can directly synthesize fluorobenzene or the like, which is industrially easily available, as a raw material. The parachlorophenylcarbamic acid ester produced by the method of the present invention can be converted into a substance useful in the chemical industry by using a usual organic synthesis method. Furthermore, by various easy operations, it is a herbicide showing a high herbicidal activity with a low dose against weeds and having excellent selectivity for crops. JP-B-63-20428, JP-A-58-38256 It can be converted into a tetrahydrophthalimide derivative described in Japanese Patent Application Laid-Open No. 2-187163 and an oxazolidinedione derivative described in JP-A-62-174065.

[0020]

EXAMPLES Examples of representative compounds are shown below for the production method of the present invention, but the present invention is not limited thereto. Example 1 In a screw cap test tube, methyl 2-fluoro-5-hydroxyphenylcarbamate (193 mg, 1.04 mmol), dicyclohexylamine (10 mg), tetrachloroethylene (2 m
l) and sulfuryl chloride (121 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. After completion of the reaction, chloroform (2 ml) was added and washed with water. The chloroform layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give a white solid (227 mg). This compound, 2-fluoro analysis such ¹ H-NMR -
It was confirmed to be methyl 4-chloro-5-hydroxyphenylcarbamate. Yield 99%.

¹ H-NMR δ (CDCl ₃ + d ₆ -DMSO, PPM)
; 4.12 (3H, s), 3.80 (1H, s), 7.02 (1H, d, J _HF = 10.6H
z), 7.42 (1H, br), 7.76 (1H, d, J _HF = 7.9Hz). IR; ν _{c = o} = 1720cm ^-1 mp; 138.0 to 140.8 ° C.

EXAMPLE 2 2-Fluoro-5-isopropoxyphe was added to a screw cap test tube.
Methyl nylcarbamate (73mg, 0.32mmol), dicyclo
Hexylamine (6mg), tetrachloroethylene (1m
l) and sulfuryl chloride (25 mg), and then at 80 ℃ for 2 hours
It was stirred. After the reaction was completed, add chloroform (1 ml),
Washed with water. Dry the chloroform layer over anhydrous magnesium sulfate.
After drying, it was concentrated under reduced pressure to obtain a white solid (80 mg).
This one is ¹2-fluoro-by analysis such as 1 H-NMR
4-chloro-5-isopropoxyphenylcarbamic acid
It was confirmed to be methyl. Yield 96%.

¹ H-NMR δ (CDCl ₃ , PPM); 1.36 (6
H, d, J _HF = 6.0Hz), 3.80 (3H, s), 4.52 (1H, sep, J ＝
6.0Hz), 6.82 (1H, br), 7.10 (1H, d, J _HF = 10.4Hz), 7.8
5 (1H, d, J _HF = 7.7 Hz). IR; ν _{c = o} = 1700 cm ⁻¹ mp; 78.5 to 83.2 ° C.

Example 3 A screw cap test tube was charged with methyl 2-fluoro-5-cyclopentyloxyphenylcarbamate (116 mg, 0.46 mmol).
Add dicyclohexylamine (7 mg), tetrachloroethylene (1 ml) and sulfuryl chloride (60 mg) to
The mixture was stirred at 0 ° C for 2 hours. After the reaction was completed, chloroform (1m
l) was added and washed with water. The chloroform layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give a white solid (120
mg) was obtained. This product was analyzed by ¹ H-NMR to give 2
It was confirmed to be methyl-fluoro-4-chloro-5-cyclopentyloxyphenylcarbamate. yield
91%.

¹ H-NMR δ (CDCl ₃ , PPM); 1.50-
2.08 (8H, br), 3.80 (3H, s), 4.79 (1H, m), 6.81 (1
H, br), 7.09 (1H, d, J _HF = 10.6Hz), 7.85 (1H, d, J
_HF = 7.5 Hz). IR; ν _{c = o} = 1710 cm ⁻¹ mp; 106.5 to 112.2 ° C.

EXAMPLE 4 Methyl 2-fluoro-5-propargyloxyphenylcarbamate (130 mg, 0.58 mmol), dicyclohexylamine (7 mg), tetrachloroethylene (2 ml) and sulfuryl chloride (10 mg) were placed in a screw cap test tube, 2 at ℃
Stir for hours. After completion of the reaction, chloroform (1 ml) was added and washed with water. The chloroform layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give a white solid (137 mg). This product was confirmed to be methyl 2-fluoro-4-chloro-5-propargyloxyphenylcarbamate by ¹ H-NMR analysis and the like. Yield 92%.

¹ H-NMR δ (CDCl ₃ , PPM); 2.56 (1
H, t, J = 2.3Hz), 3.81 (3H, s), 4.77 (2H, d, J = 2.3H
z), 6.82 (1H, br), 7.13 (1H, d, J _HF = 10.3Hz), 8.02
(1H, d, J _HF = 7.3Hz). IR; ν _{c = o} = 1715cm ^-1 mp; 125.1-127.8 ° C.

EXAMPLE 5 Isobutyl 2-fluoro-5-methoxyphenylcarbamate (100 mg, 0.41 mmol), dicyclohexylamine (6 mg) and tetrachloroethylene (1.5 ml) were placed in a screw cap test tube.
And sulfuryl chloride (70 mg) were added, and the mixture was stirred at 80 ° C. for 2 hours. After completion of the reaction, chloroform (2 ml) was added and washed with water. The chloroform layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give a pale yellow oil (113 mg).
This product was analyzed by ¹ H-NMR to give 2-fluoro-
It was confirmed to be isobutyl 4-chloro-5-methoxyphenylcarbamate. The yield was quantitative.

¹ H-NMR δ (CDCl ₃ , PPM); 0.98 (6
H, d, J = 6.8Hz), 2.00 (1H, t sep, J = 6.5, 6.8Hz),
3.89 (3H, s), 3.97 (2H, d, J = 6.5Hz), 6.85 (1H, b
r), 7.12 (1H, d, J _HF = 10.4Hz), 7.88 (1H, d, J _HF =
6.5 Hz). IR; ν _{c = o} = 1715 cm ^-1 .

Example 6 Methyl 2-fluoro-5-methoxyphenylcarbamate (75 mg, 0.63 mmol) and hexane (1 ml) were placed in a 25 ml eggplant-shaped flask and cooled to -20 ° C. Chlorine gas (2m
After l) was passed through a flask and stirred at -20 ° C for 5 minutes, nitrogen gas was introduced to remove excess chlorine gas. The obtained solution was washed with water, the organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain a white solid (117 mg). This product was analyzed by ¹ H-NMR to give 2-fluoro-4-
It was confirmed to be methyl chloro-5-methoxyphenylcarbamate. Yield 80%.

¹ H-NMR δ (CDCl ₃ , PPM); 3.81 (3
H, s), 3.90 (3H, s), 6.82 (1H, br), 7.12 (1H, d, J _HF
= 10.4Hz), 7.87 (1H, s, J _HF = 7.3Hz). IR; ν _{c = o} = 1730 cm ^-1 mp; 78.6-82.2 ° C.

Example 7 A screw cap test tube was charged with methyl 2-fluoro-5-methoxyphenylcarbamate (105 mg, 0.53 mmol), triethylamine (3 mg), tetrachloroethylene (1 ml) and sulfuryl chloride (50 mg), and the mixture was heated to 80 ° C. It was stirred for 2 hours. After completion of the reaction, chloroform (1 ml) was added and washed with water. The chloroform layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a white solid (106 mg) of methyl 2-fluoro-4-chloro-5-methoxyphenylcarbamate. The result of analysis of ¹ H-NMR spectrum and the like of this product was the same as above. Yield 86%.

Reference Example 1 2-fluoro-4-chloro-5 was placed in a 25 ml eggplant-shaped flask.
-Methyl hydroxyphenylcarbamate (219 mg, 1.
0 mmol), potassium carbonate (200 mg), acetonitrile (10 ml)
And methyl iodide (1 ml) were added, and the mixture was reacted under heating under reflux for 2 hours. After the reaction was completed, water (5 m
l) was added, and the mixture was extracted with ethyl acetate (5 ml × 3). The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain a yellow solid (212 mg) of methyl 2-fluoro-4-chloro-5-methoxyphenylcarbamate. The result of analysis of ¹ H-NMR spectrum and the like of this product was the same as above. Yield 91%.

Reference Example 2 In the same manner as in Reference Example 1, methyl 2-fluoro-4-chloro-5-hydroxycarbamate (230 mg, 1.05 mmol) and isopropyl bromide (250 mg) were used to prepare 2-fluoro-4-chloro-5-. Methyl isopropoxycarbamate (225mg)
Got Yield 82%.

Reference Example 3 In the same manner as in Reference Example 1, methyl 2-fluoro-4-chloro-5-hydroxycarbamate (220 mg, 1.0 mmol) and propargyl paratoluene sulfonate (210 mg) were added to 2-fluoro-4-chloro-. Methyl 5-propargyloxycarbamate (237 mg) was obtained. Yield 92%.

Reference Example 4 As in Reference Example 1, methyl 2-fluoro-4-chloro-5-hydroxycarbamate (225 mg, 1.0 mmol) and cyclopentyl bromide (308 mg) were added to 2-fluoro-4-chloro-5-. Methyl cyclopentyloxycarbamate (26
6 mg) was obtained. Yield 93%.

Reference Example 5 In a 50 ml eggplant-shaped flask, 2-fluoro-4-chloro-
Methyl 5-cyclopentyloxyphenylcarbamate (288 mg, 1 mmol), ethanol (10 ml) and 2N aqueous sodium hydroxide solution (10 ml) were added, and the mixture was stirred with heating under reflux for 5 hr. After the reaction was completed, water (10 ml) was added to the obtained mixture, and the mixture was extracted with ethyl acetate (5 ml × 3). The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a yellow oil (224 mg). This one is ¹ H-NM
It was confirmed by analysis such as R that it was 2-fluoro-4-chloro-5-cyclopentyloxyaniline. yield
98%.

¹ H-NMR δ (CDCl _3, PPM); 1.50-
2.10 (8H, m), 4.15 (1H, br), 4.60 (1H, m), 6.41 (1H,
d, J _HF = 7.5 Hz), 7.03 (1H, J _HF = 10.2 Hz). IR; 3470, 2970, 1635, 1515 cm ^-1 .

Claims (1)

[Claims] 1. A compound represented by the general formula (I): (However, in the above formula, R represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkyl group which may be substituted with a halogen atom or the like; an alkenyl group; an alkynyl group; a cycloalkyl group, and R'is a lower alkyl group. The general formula (II) is characterized by chlorinating a phenylcarbamate represented by the formula (II) (However, in the above formula, R represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkyl group which may be substituted with a halogen atom or the like; an alkenyl group; an alkynyl group; a cycloalkyl group, and R'is a lower alkyl group. The method for producing the parachlorophenylcarbamic acid ester represented by