CS252794B1 - Method of 2,6-dichlorodiphenylamine cleaning - Google Patents

Abstract

Solution se concerns cleaning 2,6-dichloro- diphenylamine from minor product 2-chloro-6-bromo-diphenylamine, characterized by se by that se hydrolysis N-acetyl-2,6- - dichlorodiphenylamine done in present # company catalytic amount zinc dust and arose 2-chlorodiphenylamine se removes it distillation or crystallization.

Description

The present invention relates to a process for purifying 2,6-dichlorodiphenylamine of formula I,

Cl

VNH / 1 /

Cl, which is a key intermediate in the production of the anti-inflammatory drug diclofenac (2- (2,6-dichloroanilino) phenyloetic acid).

and

2,6-Dichlorodiphenylamine is most readily prepared by the Ullmann reaction by heating a suitable 2,6-dichloroaniline-derived anilide, for example 2,6-dichloroacetanilide with excess bromobenzene in the presence of copper powder as a catalyst and an alkali metal carbonate as a hydrogen bromide-binding agent. to a side reaction by partially exchanging chlorine to bromine to give the desired product with variable (3-10%) content of 2-chloro-6-bromo-diphenylamine of formula II

Br

NH / 11 /

Cl

This halogen exchange cannot be prevented by any modification of the reaction conditions. 2,6-Dichlorodiphenylamine and 2-chloro-6-bromo-diphenylamine have such similar physicochemical properties that they cannot be appropriately separated and also the chlorobromo derivatives of other synthesis intermediates, i.e. N-chloroacetyl -2,6-dichlorodiphenylamine and N- (2,6-dichlorophenyl) -2-indolinone, so that it is terminal 254 794. the product 2- (2,6-dichloroanilino) phenylacetic acid (diclofenac) contaminated with a chlorobromo derivative, the presence of which can be detected by NMR, GLG or HPLC.

The literature, in particular the patent, does not disclose a method for separating the chlorobromo derivative.

These disadvantages are overcome by a process for the purification of 2,6-dichlorodiphenylamine prepared by reaction of 2,6-dichloroacetanilide with bromobenzene in the presence of copper powder and subsequent hydrolysis of the intermediate N-acetyl-2,6-dichlorodiphenylamine according to the invention, which consists in N-acetyl-2,6-dichlorodiphenylamine is carried out in the presence of zinc dust. The resulting 2-chlorodiphenylamine is removed by distillation or crystallization.

It has been found that the aromatic-linked bromine atom can be selectively reduced in this case by zinc in a solution of potassium hydroxide in ethanol. The resulting 2-chlorodiphenylamine is already physically chemically different from 2,6-dichlorodiphenylamine so that it can be separated by recrystallization. The reduction does not require a special operation as it can be incorporated into the conventional preparation process.

In the Ullmann reaction, N-acetyl-2,6-dichlorodiphenyl-amine is first formed, which is converted to dichlorodiphenylamine by alkaline hydrolysis in ethanol. Just add a small amount of zinc dust to the hydrolyzed reaction and reduce the bromine practically quantitatively. affects the purity of the product.

The main advantage of the invention is the easy removal of the by-product Ullm _{and the} re-reaction of 2-chloro-6-bromo-diphenylamine simply by adding zinc in the hydrolysis of N-acetyl-2,6-acetyl-2,6-dichlorodiphenylamine, whereby bromine is removed quantitatively and chlorodiphenylamine is removed by crystallization or distillation to give pure product.

Further details are apparent from the exemplary embodiment, which only illustrates the method but does not limit it in any way.

2,6-dichlorodiphenylamine

A mixture of 250 g of 2,6-dichloroacetanilide, 1650 g of bromobenzene, 99 g

252 794 annealed sodium carbonate and 10 g of copper powder are heated to boiling for about 20 hours with stirring. The resulting water is removed azeotropically. After cooling to 80 ° C, the reaction mixture is filtered. The caustic liquor is cooled to 20 and sieved unreacted 2.6. The bromobenzene is then distilled off in vacuo and the residue is hydrolyzed as follows;

Dissolve the residue in 890 cm @ 3 of ethanol, add 100 g of potassium hydroxide and heat to boiling with stirring for 3 hours. Then add 140 cm @ 3 of water and 14 g of zinc powder and heat to boiling for 5 hours. Excess zinc. The reflux condenser is exchanged for a descending condenser and 800 cm @ 3 of ethanol are distilled off. After cooling, 300 cm @ 3 of water, 200 cm @ 3 of hydrochloric acid and 600 cm @ 3 of methylene chloride are added, stirred for 10 minutes and poured into a separatory funnel. The lower layer is drained, dried with 60 g of anhydrous sodium sulfate and the dichloromethane is distilled off. The residue is then distilled under vacuum. purity 99.7% (GLC). The maximum bromo derivative content was 0.1%.

Claims (1)

SUBJECT OF THE INVENTION A process for the purification of 2,6-dichlorodiphenylamine of formula I prepared by reaction of 2,6-dichloroacetanilide with bromobenzene in the presence of copper powder and subsequent hydrolysis of the intermediate N-acetyl-2,6-dichlorodiphenylamine, characterized in that the hydrolysis of N-acetyl-2 is carried out. 6-dichlorodiphenylamine is carried out in the presence of zinc dust, the resulting 2-chlorodiphenylamine being removed by distillation or crystallization