Preparation of méta-aryloxy-benzaldéhydes.

The present invention provides an improved process.

for the preparation of meta aryloxy-benzaldehydes, compounds are valuable intermediate products, for example, in the preparation of pesticides containing métaaryloxybenzyle group. These pesticides comprise esters of meta aryloxy-benzyl cyclopropane carboxylic acid and acids chlorophenyl-acetic acids that are remarkable insecticidal properties.

A path possible for the preparation of a meta aryloxy-benzaldehyde is the halogenation of meta ^ - aryl toluene to form the corresponding benzyl halide, followed by conversion of the corresponding benzaldehyde by halide.

However, although this pathway is satisfactory in principle, it has certain drawbacks, namely (1) the-necessity of setting conditions of the halogenating step so as to obtain the maximum efficiency in benzyl halide at the expense of total yield other halogenated products (e.g. halide Hetaryl and halogenated products at core) and (2) that the yield of benzyl halide seldom exceeds 70 %.

It was found that these disadvantages can be minimized by adopting a modified method for grading in the aldehyde mixtures of meta-aryloxytoluenes halogenated in the side chain, especially a mixture halides and Hetaryl. Accordingly, the present invention provides a process for the preparation of meta aryloxy-benzaldehydes according to which in a first step which comprises reacting a mixture of halides of meta aryloxy-benzyl and - Hetaryl corresponding with ammonia and formaldehyde and, in a second step, the resultant product is hydrolyzed under acidic conditions to form the meta aryloxy-benzaldehyde.

Instead of ammonia and formaldehyde, may be used L^V.hexaméthylëne~tetramine in the first step of the inventive method and it will be understood that use of bexamé-to-thylene-tetramine produces a similar result because of the chemical equilibrium existing between this latter compound and ammonia and formaldehyde. Thus, ammonia and formaidéhyde may be considered, as of hexamethylene-tetramine or progenitors thereof may be regarded as " an ammonia generator and formaldehyde.

Although aqueous conditions are not essential for the first step of the inventive method and it is possible to conduct the reaction in a nonaqueous solvent such as chloroform, aqueous conditions can be used conveniently in anticipation of the hydrolysis reaction in the second step of the process. This can allow an aqueous ammonia solution, formalin or hexamethylene tetramine. The first step of the process is an exothermic reaction and, generally, heat is not required.

to initiate the reaction; reaction temperatures between 10 and 150 °c can be used conveniently in practice.

The product of the first step of the method of the invention is a mixture comprising a complex salt of benzyl halide and halide Hetaryl substantially unchanged;

these two products can be isolated and then subjected to a hydrolysis step, but it has been found that this is not necessary and that the hydrolysis of the reaction mixture of the first step is performed easily and efficiently. The hydrolysis is carried out preferably at a pH of between 3 and 6.5 better results being obtained at a pH of between 5 and 6. The acid used to obtain these pH values can be organic or inorganic and suitable examples are acetic acid, phosphoric acid, hydrochloric acid or acid, sulfuric;

it has been found that acetic acid is very useful in this connection, especially acetic acid to 50% by weight. Pages may be hydrolysis with refluxing the reaction mixture acidified or by any other conventional means; at temperatures between 80 and 120 °c are generally usable, temperatures ranging. between 80 and 120 °c being preferable.

It has been found that the first step of the inventive method can be carried out in the presence of the acid used in the hydrolysis step and that the enhanced results are achieved by this means. For example, thickness may be the first step by adding the halides and Hetaryl hexamethylene tetramine solution dissolved in acetic acid and heating the resulting mixture to reflux.

It has been found also that the hydrolysis reaction can be facilitated by the presence of a mineral acid, e.g., hydrochloric acid, and the binder can be added in la first or in the second step of the process according to the invention or, if desired, towards the end of the hydrolysis reaction.

A considerable advantage of the method according to the invention is that it will accept mixtures halides and Hetaryl in any proportion. As the existing business processes for producing the benzyl halide result in the simultaneous production of a little dihalide, it is to say a little halide Hetaryl, the present method allows to transform these mixtures corresponding benzaldehyde by not requiring separation and removal of the dihalide.

It is noteworthy that the dihalide is not altered to any appreciable extent during the reaction in the first step of the inventive method and is hydrolysis simultaneously with the complex of benzyl halide to form the desired aldehyde in the second stage..

Excellent results with regard to the yield of aldehyde were obtained with mixtures of benzyl bromides and Hetaryl and benzyl chlorides and Hetaryl.

The mixture halides and Hetaryl is obtainable by any convenient means, but it has been found that such a mixture may be readily prepared by a halogenation reaction on toluene appropriate. According to one aspect of the present invention, therefore, the mixture of a meta aryloxy-benzyl halide and meta aryloxy-Hetaryl used as starting material in the process according to the invention may be prepared by a process which comprises 1' halogenation of métaaryloxy-toluene corresponding with a halogen gas at an elevated temperature in the presence of a radical initiator.

The temperature of the halogenation reaction is heavily dependent on the nature of the halogen used and the need to avoid a halogenation using core toluene. A general temperature interval for the halogenation reaction is that of 50 to 250 °c. *

With respect to the bromination, it has been found - that the enhanced results are achieved by contacting the meta -.

aryloxy toluene with bromine gas at a temperature of between - 180 and 25ô °C, preferably in the presence of ultraviolet radiation as radical initiator. For the best are totals in benzyl bromides and Hetaryl, preference is given to a molar excess of the bromine vapor, ' for example at least 10% and typically at least 25 % with respect to the molar amount of the toluene. starting; a molar excess of between 10 and 50 % generally can be used. The use of such an excess bromine inevitably involves the formation of a higher proportion of the bromide Hetaryl that when using a stoichiometric amount or a low bromine molar failure. However, as the method according to the invention can easily be converted as mono - that the dibromides into the corresponding aldehyde, the presence of a higher proportion of dibromide in the resulting brominated mixture does not pose a problem. In total yields benzyl bromides and more than 90 Hetaryl % can be obtained by this route.

In the chlorination of the meta aryloxy-toluene, it has been found that best results are achieved by contacting the meta aryloxy-toluene in a non-polar solvent at a temperature between 40 and 100 °c with chlorine gas, the radical initiator is preferably a peroxide or initiator azoîque, as benzoyl peroxide or the azo isobutyronitrile (of AIBN). The non-polar solvent selected for the chlorination reaction should be such that it does not cause the formation of chlorinated products at core and that it ' is itself substantially unaltered by the conditions existing chlorination. Generally, halogenated hydrocarbons are good solvents for this reaction, for example carbon tetrachloride and benzene '; it was achieved excellent results with. carbon tetrachloride as a solvent. To promote chlorination in the side chain of the chlorination. toluene and suppress the core, it has been found advantageous to prevent the chlorination occurs at high concentrations, for example more than 60 % by weight toluene in the solvent; concentrations of between 5 and 50 % by weight have been found to be generally preferable.

In addition, it does not allow the reaction of toluene is conducted until the end because this tends to give undesirable chlorinated products; thus, the reaction must be stopped to a conversion of between 95 and 99 % with respect to the meta aryloxy-toluene, 98 or 99 conveniently to %• As with the bromination reaction, yield totals in monoet dichloride are typically greater than 90 % and often in excess of 95%.

The nature of the substituent meta-substituted aryloxy in the starting material and in lpfcroduit according to the invention is unimportant, but the product commercially useful because of its importance for the synthesis of synthetic pesticidal pyréthroîdes estest.le meta-phenoxy-benzaldehyde.

It will be appreciated therefore that the present invention provides an interest for the preparation of meta-phenoxy-benzaldehyde from raéta-phenoxy-toluene without the need to isolate a particular intermediate bromide or chloride for conversion to the aldehyde. A large quality of the method is its flexibility, in that it transforms a mixture in any proportions of halide meta-phenoxy-benzyl halide and meta-phenoxy-Hetaryl (it is to say a mixture of mono - and di-halide) in the desired aldehyde.

Accordingly, a particular aspect of the present invention relates to a process for the preparation of meta-phenoxy-benzaldehyde according to which

(has) a mixture is prepared halide meta-phenoxy-benzyl halide and meta-phenoxy-Hetaryl by halogenation of meta-phenoxy-toluene with a halogen gas at an elevated temperature in the presence of a radical initiator;

(d) reacting the mixture of halides prepared in (has) with ammonia and formaldehyde or hexamethylene tetramine and

(d) hydrolyzing the reaction product of (d) under acidic conditions to form the meta-phenoxy-benzaldehyde.

The method according to the invention is further illustrated in the following examples strips.

(has) preparation of bromide meta-phenoxy-benzyl and - Hetaryl

Is treated 3 a-phenoxytoluene (430 grams; 2,337 mole) with a stream of bromine (473 grams; 2,956 mole) under a nitrogen atmosphere in a 5 liter container an ultraviolet radiation source and so arranged that bromine is introduced ' near the ultraviolet source and that the bodies in response circulate thoroughly. The bromine is thus present in molar excess of 26.5 % relative to phenoxytoluene. When the addition is complete (about 3 hours), allowed, cooling the reaction mixture overnight while passing therethrough a nitrogen stream. This gives 627 g of bromination product having the following composition:

3-phenoxy toluene (untransformed) 2.1 % 3-phenoxy benzyl bromide 61.5% bromide 3-phenoxy Hetaryl 36.4 %

(b.) Preparation of meta-phenoxy-benzaldehyde

The bromination mixture resulting from (has) above is added to 1 liter of glacial acetic acid and 350 g of hexamethylene tetramine (2.5 mole) followed by the addition 1 liter of water.

After heating at reflux (105 °c) during 4 hours, added 500 cm. ^ of concentrated hydrochloric acid and 5 minutes later 700^centimeters of water and the mixture is heated at reflux for 15 minutes and still.

After cooling to room temperature by immersion in ice water, the reaction mixture is treated by extracting at methylene dichloride (3 x 500 ^ centimeters). The combined extracts are washed to neutrality (pH of 7 - 8) with a saturated solution of sodium bicarbonate and then washed once with 1 liter of aqueous solution to 10 % ice hydrochloric acid and once with 1 liter of water. After drying over anhydrous sodium sulfate, methylene dichloride is evacuated by distillation and the rest product is degassed to constant weight under high vacuum (0.1 mm Hg) to give 430.5 g (2,172 mole) of 3-phenoxy-benzaldehyde. NMR analysis of the product indicates that its purity is 95 % and analysis by chromatography gazliquide indicates that any bromide and benzyl bromide Hetaryl have reacted. The yield of 3-phenoxybenzaldehyde (2,172 mole) is 93 % with respect to the 3 a-phénoxyt'phénoxyt' oluene starting (2,737 mole).

Such as II

Preparation of meta-phenoxy-benzaldehyde from bromides benzyl Hetaryl corresponding

M-phenoxytoluene bromine (33.65 grams) as obtained in the example 1 (has) is added to a solution of hexamethylene tetramine (16.8 grams) dissolved in chloroform (140 cms ^). The mixture is stirred overnight and then filter to obtain the salt (41.5 grams) is dissolved in acetic acid (35 cm ' *) and water (35 cm) and heated at reflux for 4 hours.

After addition of concentrated hydrochloric acid (27 cm ' *), the heating is continued at reflux for 0.5 hour yet. The reaction mixture cooled is processed by extraction with methylene chloride (3 x 20 cm), the organic extract is washed to neutrality with an aqueous solution of sodium bicarbonate and then the solvent is evaporated and the residue is distilled to give m-phenoxybenzaldehyde (14.6 grams, 61 %) in the form of a colorless liquid, boiling point 140 and 141° / 1 mm-Hg.

Such as III

Preparation of meta-phenoxy-benzaldehyde from chloridesbenzyl Hetaryl corresponding

A blend of 3 a-phénoxybenzyle chloride and 3 a-phénoxybenzal (50 grams), containing 60 % of monochloride and 40 % dichloride, is added to a solution of hexamethylene tetramine (35 gm) dissolved in acetic acid (100 cm). Water is added (100 cm) and the mixture is heated at reflux for 4 hours, followed by the addition of concentrated hydrochloric acid and the mixture is heated at reflux for 15 minutes and still.

After cooling to room temperature, the

the reaction mixture is treated with chloride extraction

3

methylene (3 x 50 cm). The combined extracts are washed to neutrality with an aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate and then evaporated to give 3rphénoxybenzaldéhyde (41.9 gm, 97% yield)• Example VI

Preparation of meta-phenoxy-benzaldehyde from bromides benzyl and corresponding Hetaryl

A formalin solution (40 %, 50 cms ^) is cooled to 10 °c and then treated with an aqueous solution of ammonia (35 %, 25 centimeters ^) during 15 min. The mixture of bromides (25 grams) crude, as obtained in the example 1 (has), is added and the mixture is stirred under an atmosphere of nitrogen for 4 hours.. The mixture is then acidified with acetic acid

3

(50 cm) and heated at reflux for 3 hours. - After cooling, the reaction mixture is treated with toluene (25 cm) and the extract is washed to neutrality with a sodium bicarbonate solution, the solution to the toluene.

3 a-phénoxybphénoxyb.enzaldéhyde crude is diluted with an equal amount of ethanol and then stirred with a saturated aqueous solution of sodium bisulfite. The bisulfite resulting is separated by filtration and washed with toluene until it either free of colored impurities. After drying under vacuum is obtained 20.5 g of * bisulfite 3-phenoxybenzaldehyde purified, that by treating âvec acid mineral. 3-phenoxybenzaldehyde diluted gives the pure.

Efficiency with respect to the mixture^; chlorides is 77 %.

Examples V to VII

Preparing a mixture of meta-phenoxybenzylë■and chloride meta-phénoxybenzal.

Is obtained by bubbling chlorine in urte heated solution at reflux (80 °c) meta-phenoxy-toluene (10 gm) and initiator (0.25 grams) in carbon tetrachloride (100 cms ^) as solvent. Conducting a series of tests with different reaction times and different initiators and the results are presented in table I according.

Based on these results, it is shown that the selectivity (it is to say the sum of the in % weight of mono - and dichloride) is dependent on the presence of an initiator ràdicalaire and that prevents the complete conversion of toluene (see the example VI wherein the selectivity is relatively poor when ' is allowed to.

reaction continues until complete conversion).

In another series of experiments, it is found that the selectivity also depends on the concentration of toluene in the solvent, namely that the selectivity decreases when the concentration of toluene increases "

*) with nitrogen purge

Of AIBN azoisobutyronitrile -

LP - behzoyle peroxide

*. *) chlorinated products at core

Example VIII.

Preparation of meta-phenoxy-benzaldehyde from chlorides benzyl Hetaryl corresponding

A formalin solution (40 %_T- 150 cm " *) is refroi -,

10 °c to die process and then treated with an aqueous solution of ammo-to-3

iBTS (35, 96, 75 cm) during 15 min. A blend of 3 a-phénoxybenzyle chloride and 3 a-phénoxybenzal containing 70 % of monochloride and 30 % mixing dichlorides (.50 grams) is added and the mixture is stirred under an atmosphere of nitrogen for 3 hours. The mixture is then acidified with acetic acid (150 centimeters ^), stirred for 3 hours still cold and then heated at reflux for 4 hours. After cooling, the reaction mixture is treated with toluene (100 cm. ^) and the extract is washed to neutrality with a sodium bicarbonate solution. The solution to the toluene 3-phenoxybenzaldehyde crude is diluted with an equal amount of ethanol and then stirred with a saturated aqueous solution of sodium bisulfite.. The bisulfite adduct of resulting is separated by filtration and washed with toluene. After vacuum drying, is obtained 63.0 g of product 3-phenoxybenzaldehyde/bisulphite purified by treatment with dilute mineral acid gives the 3-phenoxybenzaldehyde pure.

Efficiency with respect to the crude mixture of chlorides is 95 %