WO2001090058A1

WO2001090058A1 - Nitrile compounds and process for their preparation

Info

Publication number: WO2001090058A1
Application number: PCT/JP2001/004329
Authority: WO
Inventors: Kenzo Fukuda; Yasuo Kondo; Tadashi Ohtsu
Original assignee: Nissan Chemical Industries, Ltd.
Priority date: 2000-05-24
Filing date: 2001-05-23
Publication date: 2001-11-29
Also published as: AU2001260607A1

Abstract

Provided are nitrile compounds useful as intermediates in the production of herbicides and a process for the preparation of the compounds. The process is characterized by reacting a benzene compound of the general formula (1) (wherein R?1 and R2¿ are each independently C¿1-6? alkyl) with hexamethylenetetramine and an acid catalyst and then with hydroxylamine, and subjecting the obtained compound to dehydration to thereby obtain a nitrile compound of the general formula (2) (wherein R?1 and R2¿ are each independently C¿1-6? alkyl).

Description

Description Nitrile compound and method for producing the same

The present invention relates to a 3- (4-cyanophenyl) peracyl derivative useful as a herbicide or an intermediate thereof (described in US Pat. No. 5,127,935 and Japanese Patent Application Laid-Open No. 5-1866436). The present invention relates to a method for producing a nitrile compound which is an important intermediate of the above. Background art

As a method for producing a 3- (4-cyanophenyl) peracyl derivative, Japanese Patent Application Laid-Open No. 9-48771 describes a method of cyanating a 3- (4-halogenophenyl) peracyl derivative with copper cyanide. ing. However, there is no known method of forming a peracyl ring after preparing (4-cyano-5-alkenylsulfonylamino-2-fluorophenyl) carbamate in advance. Also, due to recent environmental considerations, there is a need for a method for producing nitrile compounds that does not use copper or a cyanide compound.

An object of the present invention is to provide an industrially advantageous method for producing a nitrile compound. Disclosure of the invention

The present inventors have conducted intensive studies to solve the above-mentioned problems. As a result, the benzene compound is formylated to form an aldehyde compound, a dihydroquinazoline compound or a mixture thereof, and then the oxime is formed and dehydrated, whereby the important intermediate is obtained. It has been found that a nitrile compound can be produced at a low cost by an easy operation, and the present invention has been achieved.

That is, the present invention (1) Formula U)

(Wherein R ¹ and R ² each independently represent a Ci-Cs alkyl group.) With a hexamethylenetetramine oxalic acid catalyst, followed by hydroxylamine Reaction, and further by a dehydration reaction, the formula (2)

(Wherein R ¹ and R ² each independently represent a Ci-Ce alkyl group.) A production method characterized by obtaining a nitrile compound represented by the formula:

[2] Equation (1)

(1)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.)

(Wherein R ¹ and R ² each independently represent a Ci-C ₆ alkyl group.) The production method according to [1], further comprising the step of producing a nitrile compound represented by the following formula:

[3] Equation (3)

[Wherein R ¹ and R ² each independently represent a Ci-Cs alkyl group. Represented by Aldehyde compound of the formula (4)

(Wherein R ¹ and R ² each independently represent a C i -Cs alkyl group.) Formula (1) produced from a dihydroquinazoline compound represented by

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.).

[4] Equation (5)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.) Formula (3) produced from a benzene compound represented by the following formula:

(Wherein R ¹ and R ² each independently represent a C] -C 6 alkyl group.)

(Wherein Ri and; ² are each independently _n representing a C i -C 6 alkyl group) [3] The production method according to [3], wherein a dihydroquinazoline compound or a mixture thereof is used.

[5] Equation (3)

(Wherein R ¹ and R ² each independently represent a C i -Cs alkyl group.)

(Wherein R ¹ and R ² each independently represent a Ci-Ce alkyl group.) Or reacting a dihydroquinazoline compound or a mixture thereof with a hydroxyamine or a hydroxylamine compound. Equation (1)

(Wherein, R ¹ and: ² each independently represent a C i -Cs alkyl group.)

[6] Equation (5)

(Wherein, R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) A benzene compound represented by the following formula (3): (3)

Wherein R and R ² each independently represent a C i -C 6 alkyl group.

(Wherein R and R ² each independently represent a C i -C 6 alkyl group.) A method for producing a dihydroquinazoline compound represented by the formula:

[7] Equation (3)

(Wherein, R ¹ and R ² each independently represent a C i -Cs alkyl group.)

(Wherein R ¹ and R ² each independently represent a Ci-Cs alkyl group.) Or a mixture thereof.

[8] Equation (1)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) Oxime compounds.

[9] Equation (2)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.)

BEST MODE FOR CARRYING OUT THE INVENTION

In formulas (1), (2), (3) and (4), R ¹ and R ² are preferably a normal butyl group, a secondary butyl group, a tertiary butyl group, a propyl group, a isopropyl group And an ethyl group and a methyl group, more preferably a methyl group and an ethyl group.

The benzene compound represented by the formula (5), which is a starting material of the present invention, is produced, for example, by the method described in Japanese Patent Publication No. JP-P5-4959.

The reagents and reaction conditions used for converting the benzene compound into an aldehyde compound, a dihydroquinazoline compound or a mixture thereof are as follows, but are not limited thereto. Hexamethylenetetramine is used in an amount of 0.1 equivalent to 2 equivalents, preferably 0.2 equivalent to 1 equivalent, relative to the starting benzene compound. Acid catalysts include inorganic substances such as trifluoroacetic acid, paratoluenesulfonic acid, methanesulfonic acid, acetic acid, formic acid, sulfuric acid, sulfuric acid, hydrochloric acid, hydrogen chloride gas, hydrobromic acid, hydrogen bromide gas, and hydroiodic acid. Organic acidic compounds can be used alone or as a mixture. The product is present in the form of an aldehyde compound, a dihydroquinazoline compound or a mixture thereof depending on conditions, but the mixture can be subjected to the next reaction as it is.

The reagents and reaction conditions used for converting the aldehyde compound, the dihydroquinazoline compound or a mixture thereof into the oxime compound are as follows, but are not limited thereto. Hydroxylamine or hydroxylamine The compound is hydroxylamine or an aqueous solution thereof, or an inorganic salt or an organic salt such as a hydrochloride, a sulfate, a nitrate, or a phosphate. It is from 0.8 to 2 equivalents, preferably from 1.0 to 1.2 equivalents, based on the mixture. When an inorganic or organic salt of hydroxylamine is used, an inorganic basic compound such as sodium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium acetate, or a neutralizing agent such as amine or pyridine is used as a neutralizing agent. Organic basic compounds can also be added.

The reagents and reaction conditions used when converting the oxime compound to the nitrile compound are as follows, but are not limited thereto. Trifluoroacetic acid, paratoluenesulfonic acid, methanesulfonic acid, acetic acid, sulfuric acid, sulfuric acid, sulfuric acid, hydrochloric acid, hydrogen chloride gas, hydrobromic acid, hydrobromic acid, hydrogen chloride gas, iodine, which can be generally used for a dehydration reaction as a reaction reagent In addition to acidic substances such as hydrofluoric acid, acetic acid, formic acid, etc., thionyloxy chloride salt, pentachloride, Ν, Ν'-carbonyldiimidazole, Ν, Ν'-dicyclohexylcarbodiimid Reagents with high reactivity with water such as pentane, ichlic acid pentate, acetic anhydride, trifluoroacetic anhydride, and tetrachloride titanium can be used, and the amount used is 0.5 equivalent to the starting oxime compound. To 5 equivalents, preferably from 1.0 to 1.5 equivalents. In some cases, dehydration can be performed by azeotropic distillation with a solvent in the presence of the acidic substance.

In any of the above reactions, a solvent can be used. In this case, the solvent may be any solvent that does not react with the reagents used.For example, benzene solvents such as benzene, toluene, chlorobenzene, dichlorobenzene, etc., ester solvents such as ethyl acetate and butyl acetate, and 1, 2 — In addition to halogenated solvents such as dichloroethane, amides such as Ν, Ν-dimethylformamide, Ν, ジメチル -dimethylacetamide, cyclic amides such as 1-methyl-2-pyrrolidinone, tetramethylperylene, Aprotic polar solvents such as tetraureas such as tetraethyl perrea; cyclic ureas such as 1,3-dimethyl-2-imidazolidinone; ethers such as ethylene glycol dimethyl ether and diethylene glycol dimethyl ether; Mixed use of them is also possible. The amount of the solvent used is usually in the range of 1 to 20 times the amount of the starting benzene compound. It is preferably in the range of 3 to 10 times. The double amount is based on the weight. For example, a 20-fold amount means 20 times the weight.

Any of the above reactions can be carried out at a low temperature, a high temperature, or a high pressure, but is preferably from 110 ° C under normal pressure to the boiling point of the solvent used.

In the above three-step reaction, the oxime compound or nitrile compound can be obtained without isolating the intermediate from the benzene compound by continuously or mixedly introducing the reagents using the same solvent. Can also be simplified. Example

Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.

(Example 1)

In a 500 ml reaction flask, (5-ethanesulfonylamino-12-fluorophenyl) ethyl ethyl ester 50.0 g (0.172 mol), 250 g of 1,2-dichloroethane, 250 g of hexamethylenetetramine 33.2 g (0.344 mol) of methanesulfonic acid was added dropwise to a mixed solution of 0.1 g (0.0861 mol), and the mixture was heated and reacted under reflux for 4 hours. Then, the reaction solution was cooled, 30 g of 5% hydrochloric acid was added at 30 ° C or lower, and the organic layer was separated.The aqueous layer was adjusted to pH 7 with a 10% aqueous sodium hydroxide solution, and the precipitated crystals were filtered. After washing with 1,2-dichloroethane and drying, (5-1-ethanesulfonylamino-2-fluoro-41-formylphenyl) ethyl carbenomate (mp 188.8 ° C) and (1-ethanesulfonyl-6-fluoro) 1,2-Dihydroquinazoline-17-yl) 27.2 g of a mixture of carpa and ethyl mitinate was obtained.

(Example 2)

Ethyl ester of (5-ethanesulfonylamino 1-2-fluoro-41-formylphenyl) obtained in Example 1 in a 200-m1 reaction flask and (11-ethanesulfonyl-16-fluoro-1,2-dihydroquinazoline-17) A mixture of 10.0 g of a mixture with ethyl ester of rubamic acid and 50.0 g of benzene is heated to 50 ° C and heated to 50 ° C to obtain 4.00 g of a 50% aqueous hydroxylamine solution (0.04 g). (0594 mol) was allowed to react for 2 hours. After the reaction, cool to 5 ° C, filter, wash with 5 ° C cooled benzene, dry, and dry [5-ethanesulfonylamino-2-fluoro-4- (hydroxyxyliminomethyl) phenyl] capillamine 7.31 g of acid ethyl ester (35% yield from (5-ethanesulfonylamino-2-fluorophenyl) carnoic acid ethyl ester) was obtained. mp 96.1 ° C ₀

(Example 3)

In a 100 ml reaction flask, [5-ethanesulfonylamino-2-fluoro-41- (hydroxyliminomethyl) phenyl] ethyl carbamic acid ester 5.00 g (0.015 mol), 25.0 g of benzene The mixture solution was heated to 60 ° C., and 2.14 g (0.0180 mol) of thionyl chloride was added dropwise and reacted for 2 hours. After the reaction, the mixture was cooled to 10 and 10 g of water was added dropwise. The precipitated crystals are filtered and washed with water.

Cooled to 5 ° C [3 Washed with benzene and dried, and dried (4-cyano-5-ethanesulfonylamino- 1-fluorophenyl) ethyl ester of rubamic acid 3.8

2 g (81%) were obtained. m p 160.2 ° C.

(Example 4)

A 200 ml reaction flask was charged with 5.0 g (0.0344 mol) of (5-ethanesulfonylamino-2-fluorophenyl) ethyl rubmate and 50 g of trifluoroacetic acid, and 4.88 g of hexamethylenetetramine. (0.0344 mol) was added at 30 ° C or less, and the reaction was allowed to proceed for 10 hours. Then, the temperature was raised to 6 Ot, and the reaction was further performed for 3 hours. Then, 6.89 g (0.0688 mol) of 98% sulfuric acid was added.

The mixture was dropped at 60 ° C. and reacted for 2 hours. After the reaction, trifluoroacetic acid was removed by distillation under reduced pressure, and then 50 g of ethyl acetate and 10 g of 20% saline were added to carry out liquid separation. The ethyl acetate layer was washed with 10 g of 20% saline again, and 40 g of ethyl acetate was left at 60 ° C. To this solution was added a 30% aqueous sodium hydroxide solution for neutralization, and then 3.69 g (0.0345 mol) of hydroxylamine sulfate was added. The neutralization was again performed with a 30% aqueous sodium hydroxide solution. And reacted for 5 hours. After reaction, ethyl acetate

After adding 30 g and 10 g of 10% saline solution and stirring, the mixture was separated, and the organic layer was washed twice with 10% saline solution. The obtained ethyl acetate solution was subjected to internal standard quantification using HP LC, and [5— Ethanesulfonylamino-2-fluoro-41- (hydroxyliminomethyl) phenyl] ethyl carbamic acid ester 8.86 g (0.0266 mol, (5-ethanesulfonylamino-1-fluorophenyl) carbamic acid From ethyl ester!] And a rate of 77%).

(Example 5)

The 5-ethanesulfonylamino obtained in Example 4 was placed in a 200 ml reaction flask.

After azeotropically dewatering a solution containing 6 g (0.0266 mol) of 2-fluoro-41- (hydroxyliminomethyl) phenyl] rubbamate S at 60 ° C under reduced pressure, the solution was heated to 10 ° The mixture was cooled to C, and 3.80 g (0.0319 mole) of thionyl chloride was added dropwise at 20 ° C or less, and the mixture was reacted for 2 hours. Then, the temperature was raised to 60 ° C. to remove excess thionyl chloride by distillation, and then 60. (The solution was washed twice with 10 g of 10% saline solution at the same time.) The ethyl acetate solution obtained by the liquid separation was analyzed by internal standard quantification by HPLC to obtain (4-cyano-5-ethanesulfonylamino- 2-fluorophenyl) canolenominic acid ethyl ester 7.97 g (95% yield).

(Reference example).

In a 50 ml reaction flask, 3.00 g (0.00951 mol) of (4-cyano-5-ethanesulfonylamino-12-fluorophenyl) carbamic acid ethyl ester,

Mixture of 1.78 g (0.0097 mol) of 3-amino-4,4,4-trifluorocrotonate, 12.0 g of toluene, 12.0 g of N, N-dimethylformamide To the mixture were added 3.94 g (0.0285 mol) of potassium carbonate and 0.05 g (0.0018 mol) of tetrabutylammonium chloride, and the mixture was heated and subjected to reflux dehydration using a Dean-Stark apparatus. (1 ° 7-200 ° C). After reacting for 24 hours, the solvent is distilled off under reduced pressure, dissolved in water, washed twice with ethyl acetate, adjusted to pH 1 with 35% hydrochloric acid, extracted with ethyl acetate, and washed twice with water. The solvent was distilled off to obtain crude crystals of the desired product. This was washed with getyl ether, and 3- (4-cyano-5-ethanesulfonylamino-2-fluorophenyl) -1-6-trifluoromethyl-1,4- (1H, 3H) pyrimidinedione 3.42 g ( Yield 88%). Industrial applicability

According to the production method of the present invention, a nitrile compound as an intermediate of a herbicide can be obtained at a low cost by an easy operation.

Claims

The scope of the claims

1. Equation (1)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.) With hexamethylenetetramine and an acid catalyst, followed by hydroxylamine The reaction and the dehydration reaction further leads to the formula (2)

(2)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) A production process characterized by obtaining a nitrile compound represented by the formula:

2. Equation (1)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.)

(Wherein R and R ² each independently represent a Ci-C 6 alkyl group.) A process according to claim 1, comprising the step of producing a nitrile compound represented by

3. Equation (3)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group).

Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group. Formula (1) produced from a dihydroquinazoline compound represented by the formula:

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) The method according to claim 2, wherein an oxime compound represented by the formula:

4. Equation (5)

(Wherein R ¹ and R ² each independently represent a Ci-Cs alkyl group.)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.) The process according to claim 3, wherein a dihydroquinazoline compound represented by the formula: or a mixture thereof is used.

5. Equation (3)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.)

Wherein R and R ² each independently represent a C i -C 6 alkyl group.) Or a mixture thereof with hydroxylamine or a hydroxylamine compound. Equation (1)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) A method for producing an oxime compound represented by the formula:

6. Equation (5)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.) A benzene compound represented by the following formula (3) (3)

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.)

(Wherein and R ² each independently represent a Ci-C 6 alkyl group.) A process for producing a dihydroquinazoline compound represented by the formula:

7. Equation (3)

(Wherein, R ¹ and R ² each independently represent a C i -C 6 alkyl group.)

(Wherein R ¹ and R ² each independently represent a Ci Cs alkyl group.) Dihydroquinazoline compounds or mixtures thereof.

8. Equation (1)

R ¹ OCO

(Wherein R ¹ and R ² each independently represent a Ci-C 6 alkyl group.)

9. Equation (2)

(Wherein R ¹ and R ² each independently represent a C i -C 6 alkyl group.)