Process for the preparation of 3,4'-dichlorodiphenyl ether

Background of the Invention

The invention relates to a novel process for preparing 3,4'-dichlorodiphenyl ether which is a potential intermediate in the pharmaceutical and crop protection industry especially for the preparation of Difenoconazole, a systemic fungicide with a novel broad-range activity protecting the yield and crop quality by foliar application or seed treatment.

This being a species of chlorodiphenyl ethers has also been proposed as a growth regulator in US 4124370; and as hydraulic oil in US 3371120 & 3472782.

Various methods are known in the literature for the preparation of diphenyl ethers. Ullmann reaction is the most popular reaction to prepare these diphenyl ethers wherein an alkali metal phenolate is reacted with aryl halides in the presence of copper or copper compounds as catalysts at elevated temperatures.

The Ullmann reaction was modified in several ways to improve the reactivity of otherwise less reactive dichlorobenzenes with phenolate or chlorophenolate.

US 3472782 & 3371120 deseribes reaction between 1,4-dichlorobenzene with 3-chlorophenolate at 165°C in the presence of CuCI / KI catalyst to generate 3,4'-dichlorodiphenyl ether.

EP 51235 applies an improvement in the Ullmann reaction by improving the catalyst to Copper carbonates or copper salts of lower aliphatic carboxylic acids and excess phenol.
Furthermore, it is known that if dimethylformamide is used as a solvent, the Ullmann reaction can be advantageously carried out with activated halobenzenes. The reaction has been described in J. Org. Chem.; 27 [1962] 4098, between nitrophenolates and chloronitrobenzenes to give the corresponding dinitrodiphenyl ethers.

However, in the J. Amer. Chem. Soc. 74 [1952] 5782 it is pointed out that the use of less reactive halobenzenes as adducts and dimethylformamide as solvent does not improve the known low product yields.

US 4766253 describe the process for preparing chlorinated diphenyl ethers. 4-chlorophenolate is reacted with 1,3-dichlorobenzene in the presence of dimethylacetamide & Cuprous oxide as catalyst at 110 -150°C under a low vacuum of 600mbar.

However, this reaction suffers a serious draw back that it requires mild vacuum conditions. Application of vacuum results in lot of frothing along with 1,3-dichlorobenzene distillate and hence the process ends with tedious work up procedure. It is especially not suitable in a large scale manufacture.
Thus there is a need in the art to further stabilize the Ullmann reaction by improving the catalyst combinations to result in a more convenient reaction by way of reaction work up procedure and yield.

The present inventors have now surprisingly found that unlike the prior art descriptions, the combination of CuCl and dimethylacetamide was inactive. Instead use of cuprous chloride as catalyst in the presence of dimethylformamide was appreciably active and also does not require vacuum; and also results in good reaction yields.

Further, none of the above references describes the recovery of unreacted phenol. The present invention is an industrially advantageous process in such a way that the unreacted phenol is recovered and recycled in the reaction sequence.

Detailed description of the invention

It is an object of the present invention to produce 3, 4'-dichlorodiphenyl ether in an industrially advantageous method.

The present invention involves a reaction between 4-chlorophenol and m-dichlorobenzene in the presence of caustic lye and under atmospheric pressure; during this stage water is continuously removed by distillation. After the separation of 4-chlorophenolate, dimethyl formamide and cuprous chloride are added to the reaction mass and continue heating. The organic layer is separated. The aqueous layer is treated with concentrated sulphuric acid and extracted with m-dichlorobenzene. The organic layer contains unreacted p-chlorophenol which is recycled in subsequent batch reaction.
The acids used to acidify the aqueous layer are inorganic acids and the most preferred acid is the sulphuric acid.

Extraction procedures are carried out in halobenzenes and the most preferred being the m-dichlorobenzene.

The following example is descriptive of the various stages involved in the current invention.

Example 1

4-Chlorophenol (128.5 g), m-dichlorobenzene (1325 g) and 44% caustic lye (93.5 g) are taken in a 3-litre 4-neck Round Bottomed Flask. The contents in the flask are heated to reflux and water is collected through dean & stark apparatus. During this sodium salt preparation, the reaction mass turned into dark brown mass. The reflux is continued for 3 hours at 175°C for removal of entire water. Sodium 4-chlorophenolate separates out as white to pale brown solid. The reaction mass is cooled to 140°C. Dimethyl formamide (62 g) and cuprous chloride (1.92 g) are added to the reaction mass. The reaction mass is heated to 165°c and maintained for 5 hours at this temperature.

The reaction mass is cooled to 30°C and 200ml of water is charged; pH adjusted to 12 to 13 with 44% caustic lye. The bye product sodium chloride is removed by filtration on celite bed. The celite bed is washed with 50ml of m-dichlorobenzene. The organic layer is separated and washed with 200ml portions of water; the aqueous layer is acidified with concentrated sulphuric acid to pH 2.0 to 2.5 and extracted with l00ml of m-dichlorobenzene. The unreacted 4-chlorophenol in the organic layer is recycled in the subsequent batch reaction.

The organic layers are extracted with m-dichlorobenzene and the m-dichlorobenzene recovered completely under reduced pressure.

Yield of l-chloro-3-(4-chlorophenoxy) benzene is 80 to 81% (206 to 210 grams) with respect to the reacted phenol.

We Claim:

1. A process for the preparation of 3,4'-dichlorodiphenyl ether by reacting 4-chlorophenol and m-dichlorobenzene in the presence of cuprous chloride catalyst and dimethyl formamide.

2. A process for the preparation of 3,4'-dichlorodiphenyl ether by reacting 4-chlorophenol and m-dichlorobenzene in the presence of Cuprous chloride catalyst and dimethyl formamide at normal pressure .

3. A process of claim 1 wherein the unreacted 4-chlorophenol is recovered in the reaction sequence.

4. A process of claim 2 wherein the unreacted 4-chlorophenol is recovered in the reaction sequence.

5. A process of any of the preceding claims wherein the unreacted 4-chlorophenol is recycled for the preparation of 3,4'-dichlorophenyl ether.