FR2560872A1 - Process using a single solvent for the preparation of esters of 3,5-dibromo-4-hydroxybenzonitrile - Google Patents

Abstract

Process for the production of esters of 3,5-dibromo-4-hydroxybenzonitrile. The process consists in reacting 4-cyanophenol with one or more reactants chosen from Br, Br + Cl and the bromine chloride formed beforehand, in then reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile with an aliphatic, cycloaliphatic or aromatic acid halide and in carrying out these two stages in one and the same reaction medium consisting of a halogenated alkane. The intermediate 3,5-dibromo-4-hydroxybenzonitrile does not have to be isolated and, consequently, the bromination and the esterification can be carried out in one and the same reactor.

Description

 The present invention relates to a novel process for the preparation of 3,5-dibromo-4-hydroxybenzonitrile esters.

 Some 3,5-dichloro-, 3,5-dibromo and 3,5-diis-4-hydroxybenzonitrile esters, also referred to as chioroxynil, bromoxynil and ioxynil, are widely used as herbicides against broadleaf weeds, especially in growing areas.

 Examples of these esters include those formed from 3,5-dichloro-, 3,5-dibromo or 3,5-diiodo-4-hydroxybenzonitriles and aliphatic, cycloaliphatic or aranic or unsubstituted halogenated acids such as such as trichloroacetic acid, propionic acid, 2,2-dichloropropionic acid, n-butanoic acid, n-octanoic acid, 2-ethylhexanoic acid, cyclohexylcarboxylic acid, benzoic acid and benzenesulfonic acid.

 Three syntheses of these herbicides from dihalohydroxybenzonitriles have been described in the prior art.

 U.S. Patent No. 3,592,626 provides a detailed description of two methods. In accordance with one of them, 3,5-dihalo-4-hydroxybenzonitrile is reacted with an organic anhydride in the presence of a condensing agent such as concentrated sulfuric acid or sodium salt or of potassium of the corresponding organic acid. According to the other process, the benzonitrile derivative is reacted with an acid halide, for example chloride, in the presence of a tertiary base such as pyridine, or in the presence of a quaternary ammonium salt. such as tetraalkylammonium chloride.

 Both of these methods have disadvantages and defects.

 In the anhydride process, only one half of the acid equivalent of the anhydride is reacted with hydroxybenzonitrile, the other half is converted to the free acid which has to be removed from the reaction mixture and which is essentially a product. residual. Likewise, the removal of the condensing agent, namely the sulfuric acid or the alkaline salt of the organic acid, requires additional treatment and results in an increase in expenses when the benzonitrile ester has to be obtained under purified form.

 The use of tertiary bases such as pyridine, usually in excess, in the second mentioned method is expensive and complicates the synthesis process for the following reason. Most of the base must be recovered for reuse, which requires an appropriate separation operation such as distillation. The portion of the base which acted as acceptor for the hydrogen chloride formed requires further processing steps, since it must be separated from the ester product.

 The variant of the acid chloride process used in the presence of quaternary salts has the disadvantage of using these rather expensive salts. Their direct recovery for reuse is expensive, to the extent that it is possible, and the separation of these salts from the ester product also involves steps such as solvent addition, neutralization and crystallization.

 U.S. Patent No. 3,671,556 discloses a third process for the preparation of 3,5-dihalo-4-hydroxybenzonitrile esters. It teaches that the esters can be formed by the direct reaction of the hydroxybenzonitrile derivatives with the appropriate acid halides, if the anhydrous solid hydroxybenzonitrile is gradually added to a slight excess of the liquid acid halide, by for example sapryloyl chloride maintained at a temperature above 1200C. The reaction need not be conducted in the presence of a base, acid acceptor, catalyst or any condensing agent; however, it is suggested that in the case where the acid chloride is exceptionally viscous or has a high melting point, a solvent may be used.

 All the above processes naturally provide for the preparation of the esters from a previously isolated reaction dihalohydroxybenzonitrile.

 With regard to the preparation of these dihalohydroxybenzonitrile reactants, E. Muller et al teach in Chem. Ber. 92, 2278 (1959) that p-hydroxybenzonitrile must be dissolved in methanol and in glacial acetic acid, and then treated with bromine. The product is then poured into an aqueous methanolic solution of NaHSO 3.

 U.S. Patent No. 3,349,111 discloses that 3,5-dibromo-4-hydroxybenzonitrile can be prepared by reacting an aqueous suspension of p-hydroxybenzonitrile with an aqueous solution of hydroxide or carbonate alkali metal; reaction of the mixture with bromine; subsequent reaction of this mixture with chlorine; then acidification of the mixture and finally filtration to obtain the product. An alternative method eliminates the base.

 In any of the processes of the prior art for the preparation of dihalohydroxybenzonitriles, the product can not be esterified in situ, that is to say that in each of the processes of the prior art, the product dihalohydroxybenzonitrile must be isolated. of the reaction mixture containing the product before the esterification can be carried out, because the reaction media / brominating solvents of the prior art are incompatible with the reaction media / esterification solvents of the prior art.

 In accordance with the present invention, it has been discovered that 3,5-dibromo-4-hydroxybenzonitrile esters can be prepared in high yields from 4-cyanophenol in a single solvent.

 Bromination can be carried out by reaction of 4-cyanophenol with 1) bromine; or 2) bromine and chlorine successively or at the same time; or 3) preferably bromine chloride previously formed in the presence of a halogenated aliphatic alkane, preferably a halogenated C2-C4 alkane, the reaction being followed by an esterification of 3,5-dibromo-4-hydroxybenzonitrile with a aliphatic, cycloaliphatic or aromatic acid halide without isolation of the intermediate of the reaction medium.

The whole reaction can be illustrated by the following diagram

<tb><SEP> OH <SEP> aliphatic, <SEP> OH
<tb><SEP> 1 <SEP> halogenated <SEP> 21r <SEP> i <SEP> 3t <SEP> i <SEP> ç
<tb><SEP>?<SEP> halogenated <SEP> + <SEP>"
<tb><SEP> o
<tb><SEP> GOLD <SEP> s1 <SEP> iphatigue, <SEP> oc1
<tb> Xr <SEP> fl + r <SEP> r <SEP> halogEd <SEP> Xrt <SEP> + <SEP> HClt
<tb><SEP> N <SEP> aN
<Tb>
Organic groups designated by the symbol
R include all of the usual organic, ie, aliphatic, cycloaliphatic, or aromatic acid moieties that are available as the corresponding acid chloride.

 The invention relates to the discovery that 4-cyanophenol can be brominated, by means of bromine chloride previously formed, into 3,5-dibromo-4-hydroxybenzonitrile which, in turn, can be esterified with a aliphatic, cycloaliphatic or aromatic acid halide; the two reactions taking place successively in one and the same solvent, namely a halogenated aliphatic solvent.

Detailed comments on the properties of the preformed bromine chloride are given in "Bromine Chloride: An Alternative to Brominen, Ind. Eng.
Chem. Prod. Res. Develop. Volume 12 N 3, 1973, Miles and Scheider.

 Preferred acid halides are chlorides, in particular straight and branched chain aliphatic acid chlorides having 3 to 18 carbon atoms and especially 4 to 12 carbon atoms. substituted aliphatic acids of which one or more of the hydrogen atoms have been replaced by a functional group such as a halogeno group. Advantageous aromatic acids to be used are aralkanoic acids such as benzoic acid and similar acids whose aromatic portion is substituted with functional groups such as C1-C5 alkyl, halo, sulfonyl, trifluoromethyl, nitro etc.

 Acid chlorides which are preferred for use in the process of the present invention are those whose boiling point is greater than about 1000 ° C, although acid chlorides of lower boiling point may be present in the process of the present invention. Cutter used, in which case the reaction is conveniently conducted at a high pressure sufficient to achieve a reaction temperature of about 1000C or more while maintaining the acid chloride in the liquid phase.

 The halogenated aliphatic solvents which can be used in the single solvent process of the present invention should naturally be inert to the previously formed bromine chloride and the selected acid halide. In addition, the solvent must dissolve both 4-cyanophenol and the halogenated phenol, in this case bromoxynil, at reflux. The halogenated aliphatic solvents are preferably C2 to C halogenated alkanes whose boiling points are greater than about 100 C. The most preferred halogenated aliphatic solvents are 1,1,1- and 1,1 2-trichloroethanes; and 111,1,2- and 1,1,2,2-tetrachloroethanes.

 The bromination and esterification reaction mixtures are heated under reflux until the respective reactions are complete, at temperatures above 1000.degree. C. and especially above 110.degree.

 Atmospheric pressure is usually used to conduct the reactions according to the process of the present invention. However, both above and below atmospheric pressures can also be used whenever it is desirable to proceed in this manner.

 The following examples are given by way of illustration so that one skilled in the art can better understand the invention, and it should be noted that they should not be construed as limiting in any way whatsoever. the scope of the invention.

EXAMPLE 1
Synthesis of octanoic acid ester of 3,5-dibromo-4-hydroxybenzonitrile
65 g (0.54-6 moles) of 4-cyanophenol were suspended in 200 ml of 1,1-, 2-trichloroethane with mechanical stirring and 60 ml (10% excess) of bromine chloride were added. added dropwise at a rate of one moleiminute. When the addition of bromine chloride was complete, the reaction mixture was refluxed for 2 hours to complete the reaction. 100 ml (7% excess) of octanoyl chloride was slowly added to the refluxing solution. The solution was refluxed for 6 hours after the end of the addition of acid chloride. The solution was then cooled and 10 ml of methanol were added to react with the excess acid chloride, and the solvent was evaporated. was distilled off under vacuum. The residue which solidifies upon cooling is obtained in 90% yield (198 g), mp 38-420 ° C. The purity of the product was found to be 96.5% according to the gas chromatography profile.

EXAMPLE 2
Synthesis of butyric acid ester of 3,5-dibromo-4-hydroxybenzonitrile
The procedure is the same as that used in Example 1. Instead of octanoyl chloride, 61 moles are used instead of 7% of butyryl chloride.

A total of 190 g of product, m.p. 70-750 ° C., is obtained in a yield of 98%. The purity of the product was found to be 97.7% according to the gas chromatography profile.

Claims (10)

 A process for the preparation of 3,5-dibromo-4-hydroxybenzonitrile esters from 4-cyanophenol, characterized in that it consists of  a) reacting 4-cyanophenol with one or more reactants selected from the group consisting of bromine; bromine and chlorine; and the previously formed bromine chloride  b) subsequently reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile thus formed with an acid halide selected from the group consisting of aliphatic, cycloaliphatic and aromatic acid halide; and  c) conducting the two steps of the above process in a single reaction medium consisting of a halogenated alkane.  2. Process for preparing 3,5-dibromo4-hydroxybenzonitrile esters from 4-cyanophenol, characterized in that it consists  a) reacting the 4-cyanophenol with bromine chloride previously formed;  b) subsequently reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile thus formed with an acid halide selected from the group consisting of aliphatic, cycloaliphatic and aromatic acid halide; and  c) conducting the two above steps in a single reaction medium consisting of a halogenated alkane.  3. Process for preparing 3,5-dibromo4-hydroxybenzonitrile esters from 4-cyanophenol, characterized in that it consists of  a) reacting 4-cyanophenol with previously formed bromine chloride w  b) subsequently reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile thus formed with an acid halide selected from the group consisting of aliphatic, cycloaliphatic and aromatic acid halide; and  c) conducting the above two steps in a C2-C4 halogenated alkane.  4. Process according to claim 3, characterized in that the single halogenated C2-C4 alkane has a boiling point greater than 1000C.  5. Process according to Claim 4, characterized in that the halogenated C2-C4 alkane is chosen from the group comprising 1,1,1-trichloroethane, 1,1,2-trichloroethane, 1,1,1-trichloroethane and 1,1,1-trichloroethane. , 1,2-tetrachloroethane and 1,1,2,2-tetrachloroethane.  6. Process according to claim 4, characterized in that the halogenated C2-C4 alkane is 1,1,2-trichloroethane.  7. Process for the preparation of 3,5-dibromo4-hydroxybenzonitrile esters from 4-cyanophenol, characterized in that it consists of  a) reacting 4-cyanophenol with previously formed bromine chloride  b) subsequently reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile thus formed with an aliphatic acid halide; and  c) conducting the two above steps in a single reaction medium consisting of a halogenated alkane.  The process according to claim 7, wherein the aliphatic acid halide is a halide of a straight or branched chain alkenoic acid having 3 to 18 carbon atoms, unsubstituted or substituted by one or more halo groups.  9. Process according to claim 8, characterized in that the aliphatic acid halide is butyryl chloride or octanoyl chloride.  Process for the preparation of 3,5-dibromo-4-hydroxybenzonitrile esters from 4-cyanophenl, characterized in that it consists of  a) reacting the 4-cyanophenol with previously formed bromine chloride;  b) subsequently reacting the intermediate 3,5-dibromo-4-hydroxybenzonitrile thus formed with an aromatic acid halide 2 and  c) carrying out the above operations in a single reaction medium consisting of a halogenated alkane, the aromatic acid halide being preferably an unsubstituted benzoic acid halide or benzoic acid substituted by one or more functional groups selected between C1-C6 alkyl halo, sulfonyl, trifluoromethyl and nitro.