FR2800068A1 - Production of hydroxybenzonitrile, by dehydration of hydroxybenzamide with thionyl halide, provides good yield without use of toxic or polluting reagents - Google Patents

Abstract

Preparation of a hydroxybenzonitrile (I) by dehydration of a hydroxybenzamide (II) with thionyl halide.

Description

 The present invention relates to a process for the preparation of a hydroxybenzonitrile by dehydration of a hydroxybenzamide.

The invention relates to a method in the liquid phase.

There are several processes for the preparation, in particular of 2-hydroxybenzonitrile in the liquid phase.

Thus, it is known to dehydrate 2-hydroxysalicylamide in the presence of P2O5. (C.R.H., Science Acad Sciences, 1, $, 1914, 950). The disadvantage of such a technique lies in the fact that the phosphoric acid formed reacts with 2-hydroxybenzonitrile and leads to a hard-to-separate adduct. In addition, the effluents contain phosphate ions, which poses a problem for the environment.

Methods of dehydrating 2-hydroxysalicylamide using phosgene have also been disclosed. This reagent is a problem of manipulation on an industrial scale because of its toxicity.

Depending on the concentration of the reaction medium, intermediate products are formed, namely benzo- (1,3) -oxazine-2,4-dione (Chem Ber, U, 1902, 3649) or disalicyloylamine (Arch Pharm 1927, 235) which have separation difficulties with respect to the desired product.

The object of the present invention is to provide a method for overcoming the aforementioned drawbacks.

It has now been found and this is the object of the present invention a process for preparing a hydroxybenzonitrile by dehydration of a hydroxybenzamide, characterized in that the dehydration reaction is carried out by means of a thionyl halide.

dans ladite formule, R symbolise un ou plusieurs substituants. L'hydroxybenzamide de formule (I) peut être porteur d'un ou plusieurs substituants dans la mesure où il ne gêne par la réaction selon l'invention. According to the process of the invention, the dehydration of a hydroxybenzamide by a thionyl halide is carried out in a liquid phase process. More specifically, the subject of the present invention is a process involving a hydroxybenzamide corresponding to the general formula (I)

in said formula, R represents one or more substituents. The hydroxybenzamide of formula (I) may carry one or more substituents insofar as it does not interfere with the reaction according to the invention.

The number of substituents present on the ring depends on the carbon condensation of the ring and the presence or absence of unsaturations on the ring.

The maximum number of substituents likely to be borne by a ring is easily determined by those skilled in the art.

In the present text, the term "several", generally, less than 4 substituents on an aromatic ring.

Examples of substituents are given below but this list is not limiting in nature. Mention may in particular be made of linear or branched alkyl groups preferably containing from 1 to 6 carbon atoms and even more preferentially from 1 to 4 carbon atoms, linear or branched alkenyl groups preferably having from 2 to 6 carbon atoms. and even more preferably from 2 to 4 carbon atoms, the linear or branched haloalkyl groups preferably having from 1 to 6 carbon atoms and from 1 to 13 halogen atoms and even more preferentially from 1 to 4 carbon atoms and from 1 to 9 halogen atoms, - the hydroxyl group, - the NO 2 group, - the alkoxy groups R 1 -O- or thioether R 1 -S- in which R 1 represents a linear or branched alkyl group having from 1 to 6 atoms carbon and even more preferably from 1 to 4 carbon atoms or the phenyl group; the alkenyloxy groups, preferably an allyloxy group, the acyloxy or aroyloxy groups R 1 -CO-O- in which the R 1 group has the meaning given above, a halogen atom, preferably a fluorine atom, a CF3 group.

As hydroxybenzamides preferably used in the process of the invention, there may be mentioned 2-hydroxybenzamide, 3-hydroxybenzamide or 4-hydroxybenzamide.

As regards the reagent, a thionyl halide which may be thionyl bromide or thionyl chloride is used. The latter is preferred.

It can be used in gaseous form by bubbling in the reaction medium or in liquid form. According to the invention, the hydroxybenzamide and the thionyl halide are reacted.

The ratio of the number of moles of a thionyl halide to the number of moles of hydroxybenzamide may vary because the substrate may serve as a reaction solvent. Advantageously, the ratio is preferably between 1 and 3.

According to the invention, the dehydration reaction is advantageously carried out in the liquid phase comprising a hydroxybenzamide and thionyl halide.

 The starting hydroxybenzamide can serve as a reaction solvent but it is also possible to use an organic solvent.

An inert organic solvent is chosen under the reaction conditions. As examples of suitable solvents for the present invention, there may be mentioned in particular aliphatic or aromatic hydrocarbons, halogenated or not.

As examples of aliphatic hydrocarbons, mention may be made more particularly of paraffins such as in particular hexane, cyclohexane, methylcyclohexane, aromatic hydrocarbons and more particularly aromatic hydrocarbons such as toluene, xylenes, cumene , petroleum fractions consisting of alkylbenzene mixture including Solvesso type cuts.

As regards the aliphatic or aromatic halogenated hydrocarbons, there may be mentioned more particularly perchlorinated hydrocarbons such as in particular tetrachlorethylene; partially chlorinated hydrocarbons such as trichlorethylene, monochlorobenzene and dichlorobenzene.

Monochlorobenzene and toluene are the preferred solvents. It is also possible to use a mixture of organic solvents.

The concentration of the starting hydroxybenzamide in the reaction solvent can vary widely from 10 to 100% by weight and is preferably selected from 30 to 90% by weight.

The process of the invention is advantageously carried out at a temperature of between 60 ° C. and 200 ° C., preferably between 80 ° C. and 180 ° C.

The process of the invention is generally carried out under atmospheric pressure.

According to a preferred variant of the process of the invention, the reaction is carried out under a controlled atmosphere of inert gas. It is possible to establish an atmosphere of rare gases, preferably argon, but it is more economical to use nitrogen.

According to a practical embodiment of the invention, the reactants are introduced in any order but it is preferable to introduce the hydroxybenzamide and the reaction solvent, to bring the reaction medium to the desired temperature and then to add progressively thionyl halide.

The duration of addition of the thionyl halide depends on the reaction temperature and is shorter as the temperature is higher. Thus, it can vary between 30 minutes and 10 hours.

At the end of the addition of the thionyl halide, the reaction medium can be maintained while stirring, for example between 30 minutes and 1 hour, in order to complete the reaction.

The hydracid formed is removed in a conventional manner, for example by nitrogen bubbling or distillation.

Hydroxybenzonitrile is recovered according to the usual methods used by those skilled in the art.

Thus, the reaction solvent can be removed by distillation and the product at the bottom of the distillation can be recovered.

If necessary, purification may be carried out, for example by recrystallization from a suitable solvent, for example an aromatic hydrocarbon, especially toluene or monochlorobenzene; or by draining or distilling.

The process of the invention provides access to 2-hydroxybenzonitrile with a very good reaction yield.

An exemplary embodiment of the invention given for illustrative and non-limiting purposes is given below.

In the examples, the abbreviations thus used are defined. The conversion ratio (TT) corresponds to the ratio between the number of transformed substrates and the number of moles of substrate involved.

The yield (RR) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate engaged.

The yield (RT) corresponds to the ratio between the number of moles of product formed and the number of moles of substrate transformed.

<U> Example 1 </ U> In a 5 liter reactor maintained under a nitrogen atmosphere, 137.14 g (1 mol) of salicylamide and 1.5 kg (1.356 I) of monochlorobenzene are charged. The reaction mixture is heated with stirring at a temperature of 110 ° C. If there are traces of water in the reaction mixture, the water must be distilled off by monochlorobenzene-water azeotrope (B = 90 ° C., P = 90 ° C.). = 760 mmHg).

208.5 g (175 ml) of thionyl chloride are added via a dip tube over a period of three hours.

Throughout the addition of the thionyl chloride, SO 2 and HCl are released which are neutralized on a soda ash column.

At the end of the addition, the mixture is stirred for 30 minutes. at 110 C.

Excess thionyl chloride and monochlorobenzene are removed by distillation at 70 ° C. under 100 mm Hg.

2-hydroxybenzonitrile is recovered at the bottom of the boiler.

 The results obtained are as follows - TT = 94, 9% - RR = 91% - RT = 95.8%

Claims (1)

 RFVFNDICATIONS 1 - Process for preparing a hydroxybenzonitrile by dehydration of a hydroxybenzamide, characterized in that the dehydration reaction is carried out using a thionyl halide. 2 - Process according to claim 1 characterized in that the hydroxybenzamide corresponds to the general formula (I)

    in said formula, R represents one or more substituents. 3 - Process according to claim 2 characterized in that the hydroxybenzamide corresponds to the formula (I) wherein R represents a linear or branched alkyl group preferably having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms, - a linear or branched alkenyl group preferably having from 2 to 6 carbon atoms and even more preferably from 2 to 4 carbon atoms, - a linear or branched haloalkyl group preferably having from 1 to 6 carbon atoms. carbon and 1 to 13 halogen atoms and even more preferably 1 to 4 carbon atoms and 1 to 9 halogen atoms, - a hydroxyl group, - a group NO 2, - an alkoxy group R 1 -O- or thioether R 1 -S- in which R 1 represents a linear or branched alkyl group having from 1 to 6 carbon atoms and even more preferably from 1 to 4 carbon atoms or a phenyl group; an alkenyloxy group, preferably an allyloxy group, an acyloxy or aroyloxy group R1-CO-O- in which an R group has the meaning given above, a halogen atom, preferably a fluorine atom, - a group CF3. 4 - Process according to claim 1 characterized in that the hydroxybenzamide is 2-hydroxybenzamide, 3-hydroxybenzamide or 4-hydroxybenzamide. 5 - Process according to claim 1 characterized in that the thionyl halide is thionyl chloride. 6 - Process according to one of claims 1 to 5 characterized in that the ratio between the number of moles of a thionyl halide and the number of moles of hydroxybenzamide varies between 1 and 3. 7 - Method according to one of claims 1 to 6 characterized in that the reaction is conducted in a reaction solvent. 8 - Process according to one of claims 1 to 7 characterized in that the organic solvent is an aliphatic or aromatic hydrocarbon, halogenated or not, preferably monochlorobenzene or toluene. 9 - Process according to one of claims 1 to 8 characterized in that the temperature of the reaction is between 60 C and 200 C, preferably between 80 C and 180 C. 10 - Method according to one of claims 1 characterized in that the process is conducted at atmospheric pressure and under a controlled atmosphere of inert gas.