JPH10265449A - Production of substituted benzonitrile - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially advantageously obtain the subject compound which is an intermediate for agrochemicals and medicines by reacting a specific raw material compound with an alkali cyanide and a copper salt in the presence of I, etc. SOLUTION: A compound represented by formula I (X and Y are each F, Cl or Br) is reacted with an alkali cyanide such as NaCN or KCN in an amount of 1.0-3.0 equivalent, preferably 1.0-1.5 equivalent based on 1 equivalent compound of formula I and a copper salt such as CuCl or CuCl2 in an amount of 0.1-1.0 equivalent, preferably 0.4-0.7 equivalent in the presence of an alkali iodide such as NaI or KI in an amount of 0.1-1.0 equivalent, preferably 0.01-0.5 equivalent based on the compound of formula I in a solvent such as N,N- dimethylformamide at an ambient temperature to a boiling point of the solvent, preferably 120-160 deg.C to provide the objective compound of formula II.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a substituted benzonitrile, which is an intermediate for pesticides and pharmaceuticals.

[0002]

2. Description of the Related Art Conventionally, a method of producing benzonitrile by reacting cuprous cyanide with an aromatic halide has been known.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a process for producing a substituted benzonitrile in an industrially advantageous manner.

[0004]

That is, the present invention provides:
(A) General formula (1)

[0005]

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(Wherein, X and Y have the same meanings as described above), characterized by reacting an alkali cyanide and a copper salt in the presence of iodine or an alkali iodide. General formula (2)

[0007]

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(Wherein X and Y have the same meanings as described above), and a method for producing a substituted benzonitrile represented by the formula:

(B) General formula (1)

[0010]

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Wherein X and Y have the same meanings as described above, and an alkali cyanide and a copper salt are reacted in the presence of water with a compound represented by the general formula (2): )

[0012]

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(Wherein, X and Y have the same meanings as described above), and a method for producing a substituted benzonitrile represented by the formula:

(C) General formula (1)

[0015]

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Wherein X and Y have the same meanings as described above, and reacting an alkali cyanide and a copper salt in the presence of iodine or an alkali iodide and water. General formula (2)

[0017]

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(Wherein, X and Y have the same meanings as described above).

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
That is, the present invention is the following production methods (i) to (iii). (A) Production method (i)

[0020]

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(Wherein, X and Y have the same meanings as described above.) That is, an alkali cyanide and a copper salt are added to the compound represented by the general formula (1) in the presence of iodine or an alkali iodide. A method for producing a substituted benzonitrile represented by the general formula (2), characterized by reacting.

Solvents that can be used in this reaction include N, N-dimethylformamide (DMF), N,
N-dimethylacetamide (DMA), dimethylsulfoxide (DMSO), formamide, N-methyl-2-pyrrolidone, hexamethylphosphoramide (HMPA),
And sulfolane.

As the alkali cyanide, sodium cyanide, potassium cyanide or the like is used. The amount of the alkali cyanide used is 1.0 to 1.0 with respect to the compound represented by the general formula (1) (hereinafter also simply referred to as compound (1)). 3.0 equivalents, preferably 1.0 to 1.0.
5 equivalents.

Copper salts include cuprous chloride, cupric chloride,
Examples thereof include cuprous cyanide and copper sulfate, and the amount to be used is 0.1 to 1.0 equivalent, preferably 0.4 to 0.4 equivalent, relative to compound (1).
7 equivalents.

Examples of the alkali iodide include sodium iodide and potassium iodide. The amount of iodine or alkali iodide used is 0.1 with respect to the compound (1).
To 1.0 equivalent, preferably 0.01 to 0.5 equivalent. The reaction temperature is from room temperature to the boiling point of the solvent, preferably from 120 to 160 ° C.

(B) General formula (ii)

[0027]

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(In the formula, X and Y have the same meanings as described above.) That is, the compound represented by the formula (1) is reacted with an alkali cyanide and a copper salt in the presence of water. This is a method for producing a substituted benzonitrile represented by the general formula (2).

The solvent, alkali cyanide and copper salt which can be used for the reaction include the same as described above. The amount of water to be used is 1 to 10 equivalents, preferably 2 to 5 equivalents, relative to compound (1). The reaction temperature is from room temperature to the boiling point of the solvent, preferably from 120 to 160.
° C.

(B) General formula (ii)

[0031]

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(In the formula, X and Y have the same meanings as described above.) Iodine or an alkali iodide can be used in combination with water. For example, even when water is added, a small amount of iodine or an alkali iodide can be used. By adding, halogen exchange can be more effectively prevented. That is, the compound represented by the formula (1) is reacted with an alkali cyanide and a copper salt in the presence of iodine or an alkali iodide and water to obtain a compound represented by the general formula (2). This is a method for producing benzonitrile.

The amounts of the solvent, alkali cyanide, copper salt, alkali iodide and water that can be used in the reaction are as follows:
Same as above. The reaction temperature is from room temperature to the boiling point of the solvent, preferably from 120 to 160 ° C.

[0034]

The compounds of the present invention will be described more specifically with reference to examples and reference examples.

Example 1 Preparation of 2,3-dichloro-6-trifluoromethylbenzonitrile

[0036]

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2-bromo-3,4 in 15 ml of DMF
-Dichlorobenzotrifluoride 3.0 g (purity 84.2)
%), And 0.8 g of potassium cyanide, 0.6 g of cuprous chloride.
g, and 0.68 g of potassium iodide were added, and the mixture was heated and stirred at 150 ° C. for 10 hours. The organic layer was washed with diluted hydrochloric acid, water, and then with saturated saline, dried over anhydrous magnesium sulfate, filtered, and the mother liquor was concentrated under reduced pressure. As a result of analyzing the obtained residue by gas chromatography, the yield of 2,3-dichloro-6-trifluoromethylbenzonitrile was 1.8.
It was 8 g (yield: 91.2%).

Example 2 Preparation of 2,3-dichloro-6-trifluoromethylbenzonitrile

[0039]

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In the same manner as in Example 1, sodium cyanide was used instead of potassium cyanide and potassium iodide.
The reaction was carried out using 6 g and 0.61 g of sodium iodide, and the same treatment was carried out to obtain the desired product. Analytical value 1.79 g (yield 8
7.0g)

Example 3 Preparation of 2,3-dichloro-6-trifluoromethylbenzonitrile

[0042]

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In 54 ml of DMF, 2-bromo-3,4-
18 g of dichlorobenzotrifluoride (purity 84.2
%), And 4.8 g of potassium cyanide, 3.6 cuprous chloride
g, potassium iodide 1.0 g and water 3.6 g, and
Heated to reflux for an hour. Thereafter, water was extracted until the internal temperature reached 150 ° C, and the reaction was continued at 150 ° C for 6 hours. After cooling, ethyl acetate and water were added, and after stirring, insoluble materials were removed by filtration through celite, followed by liquid separation. The organic layer
After washing with water and saturated saline and drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (ethyl acetate: hexane = 1: 9) to obtain the desired 2,3.
-Dichloro-6-trifluoromethylbenzonitrile 1
1.24 g (purity 93.9%) were obtained. 85.3% yield

Example 4 Preparation of 2,3-dichloro-6-trifluoromethylbenzonitrile

[0045]

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In 54 ml of DMF, 4.8 potassium potassium cyanide was added.
g, cuprous chloride 3.6 g, potassium iodide 1.0 g and water
After adding 3.6 g, water was extracted until the internal temperature reached 150 ° C. After cooling, 18 g (purity 84.2%) of 2-bromo-3,4-dichlorobenzotrifluoride was added,
The mixture was heated under reflux at 150 ° C. for 10 hours. After cooling, Example 3
In the same manner as in the above, 11.2 g (purity: 93.7%) of the desired product was obtained. 84.8% yield

Reference Example Production of 2,3-dichloro-6-trifluoromethylbenzonitrile

[0048]

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2-bromo-3,4-dichlorobenzotrifluoride (3.56 g), cuprous cyanide (1.4 g), DMF
After heating and refluxing for 7 hours while stirring 40 ml, the mixture was poured into a dilute aqueous hydrochloric acid solution, and extracted twice with ethyl acetate.
After washing with dilute hydrochloric acid, water and then a saturated saline solution, the extract was dried over anhydrous magnesium sulfate and filtered. The mother liquor was concentrated under reduced pressure and separated by silica gel column chromatography (hexane).
1.9 g of 2,3-dichloro-6-trifluoromethylbenzonitrile were obtained. Yield 65.3%

[0050]

The process for producing a substituted benzonitrile of the present invention is an industrially superior process with a high yield. The compounds according to the present invention are useful as intermediates for agricultural chemicals and medicines, particularly as intermediates for agricultural and horticultural fungicides.

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Claims (3)

[Claims] 1. A compound of the general formula (1) (Wherein, X and Y are the same or different and each represent a fluorine atom, a chlorine atom or a bromine atom) with an alkali cyanide and a copper salt in the presence of iodine or an alkali iodide. General formula (2) characterized by reacting (Wherein, X and Y have the same meanings as described above). 2. A compound of the general formula (1) Wherein X and Y have the same meanings as described above, and an alkali cyanide and a copper salt are reacted in the presence of water with the compound represented by the general formula (2). 4] (Wherein, X and Y have the same meanings as described above). 3. A compound of the general formula (1) Wherein X and Y have the same meanings as described above, and reacting an alkali cyanide and a copper salt in the presence of iodine or an alkali iodide and water. Formula (2) (Wherein, X and Y have the same meanings as described above).