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GB2032922A - Process for the Production of 2- chlorobenzonitrile Derivatives - Google Patents

Process for the Production of 2- chlorobenzonitrile Derivatives Download PDF

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Publication number
GB2032922A
GB2032922A GB7934666A GB7934666A GB2032922A GB 2032922 A GB2032922 A GB 2032922A GB 7934666 A GB7934666 A GB 7934666A GB 7934666 A GB7934666 A GB 7934666A GB 2032922 A GB2032922 A GB 2032922A
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parts
lithium
chloro
chloride
nitrobenzonitrile
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GB7934666A
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GB2032922B (en
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Nippon Kayaku Co Ltd
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Nippon Kayaku Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00Carboxylic acid nitriles

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

A process for the production of 2- chlorobenzonitrile derivatives of the general formula (I): <IMAGE> (wherein n is 1 or 2) comprises reacting a compound of the general formula (II): <IMAGE> with lithium chloride, or a mixture of lithium chloride and anhydrous aluminium chloride, or lithium aluminium chloride in an aprotic solvent.

Description

SPECIFICATION Process for the Production of 2-Chlorobenzonitrile Derivatives This invention relates to a process for producing 2-chlorobenzonitrile derivatives represented by the general formula (I):
(wherein N is a number of 1 or 2) characterized by reacting a compound of the general formula (ill):
(wherein Cl is as defined above) with lithium chloride or a mixture of lithium chloride and anhydrous aluminum chloride or with lithium aluminum chloride in an aprotic solvent.
The compounds represented by the general formula (I) are known as the excellent agricultural chemicals and the intermediates for the preparation of other variety of useful materials.
The following methods are known for the production of 2,6-dichlorobenzonitrile from 2-chloro-6nitrobenzonitrile: 2-chloro-6-nitrobanzonitrile is reduced into 2-chloro-6-aminobenzonitrile and the latter is subjected to a Sandmeyer reaction; and 2-chloro-6-nitrobenzonitrile is treated with chlorine gas (or a mixture thereof with hydrogen chloride gas) or thionyl chloride in a solvent such as dichlorobenzene at high temperature to substitute the nitro group with chlorine. However, the former method is troublesome since it involves many steps such as reduction, diazotization and substitution with chlorine and also releases a large volume of wastes, so that this method is not suited for industrical practice.On the other hand, the latter method uses a material which is poisonous and strongly corrosive and there is also produced nitrogen dioxide gas which is a poisonous and strongly corrosive gas, so that this method has difficulties for practical use.
The process of this invention is capable of producing the object substance with minimized generation of poisonous nitrogen dioxide and very limited release of wastes and with safety by merely reacting a compound of the formula (II) with lithium chloride or a mixture thereof with anhydrous aluminum chloride or with lithium aluminum chloride in an aprotic solvent.
In case of using a mixture of lithium chloride and anhydrous aluminum chloride or lithium aluminum chloride in the process of this invention, the formation of by-products is reduced and the object product can be obtained in a high yield.
It is considered that when a mixture of lithium chloride and anhydrous aluminum chloride is used in this invention, there is formed lithium aluminum chloride with different compositional proportions depending on the mixing ratio of lithium chloride and an hydros aluminum chloride in the reaction system.
A lithium compound, such as lithium carbonate, which can be converted into lithium chloride in the reaction system, may be used in this invention.
Lithium in the lithium compound used in this invention can be easily recovered by mere filtration or in the form of a precipitate by adding an organic solvent such as toluene.
The compounds of the formula (II) used in this invention include 2-chloro-6-nitrobenzonitrile, 4-chloro-2-nitrobenzonitrile, 2,3-dichloro-6-nitrobenzonitrile, 4,5-dichloro-2-nitrobenzonitrile and the like.
The aprotic solvents used in this invention include N,N-dimethylformamide, dimethylsulfoxide, N,N-dimethylacetamide, hexamethylphosphoramide and N-methylpyrrolidone and the like. Dehydrated solvents are preferable. The amount of the solvent used may vary over a wide range and the preferred amount of the solvent is within the range of 0.5 to 10 times the weight of the compound of the formula (II).
The lithium compound (lithium chloride or lithium aluminum chloride) is used such that the lithium content in the lithium compound is preferably 0.1 to 20 gram atoms, more preferably 0.3 to 3 gram atoms, per mole of the compound of the formula (II).
In case of employing a mixture of lithium chloride and anhydrous aluminum chloride or lithium aluminum chloride, it is used in such a ratio that the aluminum content is preferably 0.01 to 10 atoms, more preferably 0.1 to 2 atoms, per atom of lithium.
The reaction of this invention is preferably carried out at a temperature of 1 20 to 2200C, more preferably at 1 50 to 2000C. The reaction time, although not specifically defined, is usually 0.5 to 20 hours.
The compounds of the formula (I), such as 2,6-dichloro-benzonitrile, obtained according to the process of this invention can be easily isolated by an ordinary means such as distillation, recrystallization, etc.
The invention is further described hereinbelow by way of the examples thereof. In the following descriptions of Examples, all the "parts" are by weight unless otherwise specified.
Example Al 4.55 parts of 2-chloro-6-nitrobenzonitrile, 5.3 parts of lithium chloride and 1 5 parts of N,N dimethylformamide were refluxed under heating for 2 hours. The reaction temperature was 178-1 7900. The reaction solution was cooled, added with 1 50 parts of toluene, agitated for 30 minutes and then filtered, and the filtrate was analyzed by gas chromatography. It contained 1.25 parts of 2,6-dichlorobenzonitrile and 2.06 parts of 2-chloro-6-nitrobenzonitrile.
Example A2 4.55 parts of 2-chloro-6-nitrobenzonitrile, 2.12 parts of lithium chloride and 15 parts of N,N dimethylformamide were refluxed under heating for 2 hours. The reaction temperature was 1 69- 1 700C. The reaction solution was treated similarly to Example Al and analyzed by gas chromatography, finding 1.27 parts of 2,6-dichlorobenzonitrile and 1.84 parts of 2-chloro-6 nitrobenzonitrile in the reaction solution.
Example A3 4.55 parts of 2-chloro-6-nitrobenzonitrile, 1.06 parts of lithium chloride and 1 5 parts of N,N dimethylformamide were refluxed under heating for 2 hours. The reaction temperature was 1 63- 1 640C. The reaction solution was treated after the manner of Example A7 and analyzed by gas chromatography. It contained 1.14 parts of 2,6-dichlorobenzonitrile and 1.96 parts of 2-chloro-6 nitrobenzonitrile.
Example A4 4.55 parts of 2-chloro-6-nitrobenzonitrile, 1.06 parts of lithium chloride and 1 5 parts of N,N dimethylformamide were refluxed under heating for 3 hours, and the reaction solution was treated similarly to Example Al and analyzed by gas chromatography, finding 1.29 parts of 2,6 dichlorobenzonitrile and 1.45 parts of 2-chloro-6-nitrobenzonitrile.
Example A5 4.55 parts of 2-chloro-6-nitrobenzonitrile, 5.3 parts of lithium chloride and 5 parts of N,N dimethylformamide were mixed and reacted at 1800C for 2 hours, and the reaction solution was treated same as Example Al and then subjected to a gas chromatographic analysis. It contained 1.05 parts of 2,6-dichlorobenzonitrile and 2.46 parts of 2-chloro-6-nitrobenzontrile.
Examples B1--B8 4.55 parts of 2-chloro-6-nitrobenzonitrile and specified quantities (shown in Table 1) of lithium chloride (LiCI), anhydrous aluminum chloride (AICI3) and N,N-dimethylformamide (DMF) were put into a 100-ml four-necked flask and refluxed under heating at about 1650C for a predetermined period of time. The reaction solution was cooled, added with 1 50 parts of toluene, agitated for 30 minutes and then filtered, and the filtrate was analyzed by gas chromatography. The reaction results were as shown in Table 1 below.
Table 1 Conversion Yield of 2-chloro- of 2,6- Selectivity Reaction 6-nitro- dichloro to 2,6-dichloro Example LiCI AIC13 DMF time benzonitrile henzonitrlle benzonftrlle No. (parts) (parts) (parts) (her) {o/o) {o/O) {a/o) B1 1.06 0.56 15 3 41.0 38.9 94.9 B2 1.06 0.56 15 4 59.6 52.9 88.8 B3 1.06 1.11 15 4 53.7 49.0 91.3 B4 1.06 1.11 15 8 66.0 56.7 85.9 B5 1.06 1.11 10 8 79.7 60.4 75.8 B6 0.53 0.56 15 5 51.5 46.5 90.3 B7 0.53 0.56 15 7 64.9 55.9 86.1 B8 0.22 0.56 15 8 46.5 33.9 72.9 Example B9 4.55 parts of 2-chloro-6-nitrobenzonitrile, 1.06 parts of lithium chloride, 0.53 parts of anhydrous aluminum chloride and 1 5 parts of N,N-dimethylformamide were refluxed under heating in a 100ml four-necked flask. The reaction temperature was 1 640 C. After continuing the reaction for 3 hours, the internal temperature was lowered to 1000C and 0.22 parts of anhydrous aluminum chloride was further added in the reaction solution and again refluxed under heating for 3 hours. Anhydrous aluminum chloride was likewise added three times thereafter, 0.11 part each time, refluxing the mixture under heating for 3 hours after each addition, and the resultant reaction solution was treated similarly to Example B1 and analyzed by gas chromatography, finding 3.28 parts of 2,6dichlorobenzonitrile and 0.08 parts of 2-chloro-6-nitrobenzonitrile.Conversion: 97.9%; yield: 77.1%; selectivity: 78.8%.
Example B10 4.55 parts of 2-chloro-6-nitrobenzonitrile, 1 5 parts of N-methyl-2-pyrrolidone and specified quantities (shown in Table 2) of lithium chloride and anhydrous aluminum chloride were mixed and the mixtures were reacted at various reaction temperatures. Each reaction solution was treated after the manner of Example B1 and analyzed by gas chromatography. The reaction results were as shown in Table 2 below.
Table 2 Conversion of 2-chloro-6- Yield of Selectivity to Reaction Reaction nitrobenzo- 2,6-dichloro- 2,6-dichloro LiCI AICI3 temp. time nitrile benzonitrile benzonitrile (parts) (parts) (0C) (hr) {o/0) { /0) {%) 0.42 1.11 170 12 98.7 89.4 90.6 0.42 1.11 180 6 98.2 89.6 91.2 0.42 1.11 190 3 98.0 88.3 90.1 0.35 1.11 170 14 97.6 86.2 88.4 Example B11 4.55 parts of 2-chloro-6-nitrobenzonitrile, 0.92 parts of lithium carbonate, 2.78 parts of anhydrous aluminum chloride and 15 parts of N-methyl-2-pyrrolidone were put into a 1 00-ml fournecked flask and heated, whereby carbonidoxiode gas was evolved.The mixture was reacted at 1 800C for 2.5 hours and the reaction solution was cooled, added with 100 parts of dichloroethane, agitated for 30 minutes and then filtered, and the filtrate was analyzed by gas chromatography, disclosing conversion of 2-chloro-6-nitrobenzonitrile of 98.0%, yield of 2,6-dichlorobenzonitrile of 85.5% and selectivity to 2,6-dichlorobenzonitrile of 87.2%.
Example B12 4.55 parts of 4-chloro-2-nitrobenzonitrile, 0.42 parts of lithium chloride, 1.11 parts of anhydrous aluminum chloride and 1 5 parts of N-methyl-2-pyrrolidone were reacted at 1 800C for 3 hours after the pattern of Example B1. The reaction solution was added with 100 parts of dichloroethane, agitated for 30 minutes and filtered. Dichloroethane was distilled off from the filtrate and the residue was added with water to precipitate the crude crystals. The crude crystals were recrystallized by using a watermethanol mixed solvent to obtain 3.4 parts of 2,4-dichlorobenzonitrile with purity of 99%. Yield: 79.2%.
Example B13 10.9 parts of 2,3-dichloro-6-nitrobenzontrile, 0.84 parts of lithium chloride, 2.22 parts of anhydrous aluminum chloride and 1 5 parts of N-methyl-2-pyrrolidone were reacted at 1 800C for one hour, and the reaction solution was treated similarly to Example B1 2 to obtain 9.4 parts of 2,3,6trichlorobenzonitrile with purity of almost 100%. Yield: 91.9%.
Example B14 A mixture of 0.84 parts of lithium chloride, 2.22 parts of anhydrous aluminum chloride and 50 parts of toluene was refluxed under heating for 30 minutes to produce lithium aluminum chloride, and the resultant mixture was added with 9.13 parts of 2-chloro-6-nitrobenzonitrile and 20 parts of Nmethyl-2-pyrrolidone. After distilling off toluene, the mixture was reacted at 1 800C for 8 hours. The reaction solution was treated in the same way as Example B1 and analyzed by gas chromatography, obtaining the following results: Conversion of 2-chloro-6-nitrobenzonitrile: 98.0%; Yield of 2,6dichlorobenzonitrile: 87.3%; Selectivity to 2,6-dichloro-benzonitrile: 89.1%.

Claims (6)

Claims
1. A process for producing 2-chlorobenzonitrile derivatives of the general formula (I):
(wherein N is 1 or 2), which process comprises reacting a compound of the general formula (ill):
(wherein n is as defined above) with lithium chloride, a mixture of lithium chloride and anhydrous aluminum chloride, or lithium aluminum chloride in an aprotic solvent.
2. A process according to claim 1, wherein the compound of formula (II) is 2-chloro-6nitrobenzonitrile.
3. A process according to claim 1, wherein the compound of formula (II) is 4-chloro-2nitrobenzonitrile.
4. A process according to claim 1, wherein the compound of formula (II) is 2,3-dichloro-6nitrobenzonitrile.
5. A process according to claim 1, wherein the compound of formula (II) is 4,5-dichloro-2dinitrobenzonitrile.
6. A process according to claim 1 substantially as described in any one of the Examples.
GB7934666A 1978-10-11 1979-10-05 Process for the production of 2-chloro-benzonitrile derivatives Expired GB2032922B (en)

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JP12487578A JPS5551047A (en) 1978-10-11 1978-10-11 Preparation of 2,6-dichlorobenzonitrile

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GB2032922A true GB2032922A (en) 1980-05-14
GB2032922B GB2032922B (en) 1982-12-22

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JP7482125B2 (en) * 2018-11-16 2024-05-13 アリスタ ライフサイエンス インコーポレイテッド Process for the preparation of 2,6-dichlorobenzonitrile

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JPS5551047A (en) 1980-04-14
JPS614390B2 (en) 1986-02-08

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