FR2555165A1 - Process for the production of 3-phenoxybenzyl 2-(4'-alkoxyphenyl)-2-methylpropyl ethers - Google Patents

Abstract

Production of 3-phenoxybenzyl 2-(4'-alkoxyphenyl)-2-methylpropyl ethers which consists in reacting a 3-halo-4-alkoxyneophyl halide with a 3-phenoxybenzyl alcohol and in subjecting the product obtained to a hydrodehalogenation reaction.

Description

dans laquelle R est un groupement alkyle inférieur et X et X2 sont chacun un atome d'hydrogène ou de fluor.The present invention relates to a novel process for the production of 3-phenoxybenzyl and 2-alkoxy-4-phenyl-2-methylpropyl ethers represented by formula IV

wherein R is a lower alkyl group and X and X2 are each a hydrogen or fluorine atom.

dans laquelle Y et Yz sont chacun un atome d'hydrogène, de chlore ou de brome, l'un d'entre eux au moins étant du chlore ou du brome, R est un groupement alkyle inférieur et X est un atome d'halogène, avec un alcool phénoxy-3 benzylicrue de formule Il

dans laquelle X1 et X2 ont la même signification que plus haut, en présence d'une base, ce qui donne un oxyde de phénoxy-3 benzyle et d' (alkoxy-4' halogéno-3' phényl)-2

In particular, the invention relates to a process for producing compounds of formula IV above, by reaction of a halogeno-3-alkoxy-4-neophyl halide of formula I

in which Y and Yz are each a hydrogen, chlorine or bromine atom, at least one of which is chlorine or bromine, R is a lower alkyl group and X is a halogen atom, with a phenoxy-3 benzyl alcohol of formula II

in which X1 and X2 have the same meaning as above, in the presence of a base, to give a 3-phenoxy benzyl and 4-alkoxy-4'-halo-3-phenyl) oxide.

<tb> methyl-2 <SEP> propyl, <SEP> of <SEP> formula <SEP> III
<tb><SEP> Y <SEP> CH3 <SEP> o
<tb><SEP> y <SEP> - <SEP> C-CH2-o-CH2- <SEP> 4 <SEP> (III)
<tb><SEP> - <SEP> Y <SEP> CH <SEP> wherein Y1 Y2 R, X1 and X2 have the same meaning as above; this product is then subjected to a hydrogenation reaction to remove the chlorine or bromine atom.

 The present invention also relates to a process for producing compound I, used as a raw material for the preparation of compound III.

 It has recently been discovered that certain 3-phenoxybenzyl ether derivatives, including the compounds of formula IV, possess very good insecticidal and acaricidal activities, in terms of rapid action and residual activity, with only insignificant toxicity, both for men than for animals, including fish, and excellent insect repellents containing these compounds have been proposed.

Japanese Patent Application No. 154,427 / 81 discloses 3-phenoxy-benzyl ethers of formula VI

wherein R is a methyl or ethyl group, R 'is
a hydrogen or halogen atom, or an alkyl group
lower and R "is a halogen atom or a lower alkyl
laughing.

Japanese Patent Application Nos. 72,928 / 82
and 64,632 / 82 describe compounds of formula VI, hereinafter
wherein R 'or R "is a halogen atom, a lower alkyl or a lower alkoxy group, or wherein the benzene ring of the 3-phenoxybenzyl may be substituted with a halogen atom or the like.

 The Applicant has found that among the compounds described in the patent publications cited above, the compounds of formula VI, in which R 'or R "is a lower alkoxy group in the 4-position, and R is a methyl, it is that is, compounds of 3-phenoxybenzyl oxide having a neophyl group substituted only by a lower alkoxy group at the 4-position have a particularly strong insecticidal activity, and it has also been found that when the benzene ring of the neophyl group has a substituent such as a halogen atom or an alkyl group, the excellent activity of the compound is slightly reduced.

ou R, R' et R" ont la même signification que plus haut, ou de son sel, avec un halogénure ou un alcool de phénoxy-3 benzyle, ou bien la réaction d'un composé de formule VIII

dans laquelle X est un atome d'halogène et R, R' et R" ont la même signification que plus haut, avec de l'alcool phénoxy-3 benzylique. Ces demandes décrivent également des procédés de production des composés VII et VIII. Cependant, le processus pour synthétiser le composé VII s'avère très long, ce qui à l'échelle industrielle est très désavantageux.Japanese patent applications, cited above, describe processes for producing compounds, including those of formula IV. In these processes, the preparation uses the reaction of a compound of formula
VII

or R, R 'and R "have the same meaning as above, or its salt, with a halide or a 3-phenoxybenzyl alcohol, or the reaction of a compound of formula VIII

in which X is a halogen atom and R, R 'and R "have the same meaning as above, with 3-phenoxy benzyl alcohol These applications also describe processes for producing compounds VII and VIII. the process for synthesizing compound VII is very long, which on an industrial scale is very disadvantageous.

As regards the production of compound VIII, the following operations are described, for example:

<tb><SEP> R "<SEP> CH3 <SEP>R"<SEP> C1H3
<tb> (1) <SEP> R ''<SEP>) -Ç-CH3 <SEP> chloride <SEP> of <SEP> sulfu- <SEP><SEP> -C-CH2Ct
<tb><SEP> R '<SEP> CH3 <SEP> ryl <SEP>R'<SEP> CH3
<Tb>

However, when R 'or R "is a lower alkoxy group in the 4-position, during this process (1), a reaction of chlorination of the ring occurs, preferably, which makes it difficult to obtain the chloride of In the course of process (2) above, the alkylation is preferably in the ortho position relative to the alkoxy group, so that the ortho isomer, a secondary product, is found in large amounts. and it becomes difficult to effectively separate the isomers.As a result, a very pure neophyl alkoxy-4 chloride is obtained only with a low yield.In addition, this compound is unstable and its storage and handling on an industrial scale As a result, it is not industrially advantageous to prepare the compound of formula IV by reacting 4-alkoxy-neophyl chloride with 3-phenylbenzyl alcohol.

The present invention makes it possible to avoid these disadvantages of the prior art, and to obtain at low cost ethers of 3-phenoxybenzyl and 2- (4-alkoxy-phenyl) -2-methylpropyl, not containing halogen atom or alkyl group on the benzene ring of the neophyl group, with only one alkoxy group at the 4-position of this ring
The process according to the invention for the preparation of compound IV consists of reacting a compound of formula I with a compound of formula II in the presence of a base and then removing the halogen atom fixed on the ben zenic ring. of the neophyl group of the compound III, thus obtained, by a hydrogenation reaction, to give the desired product of formula IV.

dans laquelle y1 et Y2 sont chacun un atome d'hydrogène, de chlore ou de brome, au moins un d'entre eux étant chlore ou brome, et R est un alkyle inférieur, avec un halogénure de méthallyle, en présence d'un catalyseur acide.During the production of the compound of formula IV, at low cost on an industrial scale, in accordance with the invention, it is necessary that the starting material of formula I be obtained in high yield. The applicant has found that halogeno-3-alkoxy-4-neophyl halides of formula I can be obtained with a high yield by reacting a 2-haloalkoxybenzene of formula V

wherein y1 and Y2 are each hydrogen, chlorine or bromine, at least one of which is chlorine or bromine, and R is lower alkyl, with a methallyl halide, in the presence of a catalyst acid.

 The Applicant has found that even when y and Y of compound V are respectively chlorine and hydrogen, that is to say when compound V is an alkoxymonochlorobenzene, the resulting product mainly comprises a para isomer obtained by preferential introduction of the methallyl halide at the 4-position relative to the alkoxy group, while the ortho isomer, corresponding to the introduction of the halide at the 6-position relative to the alkoxy group, is difficult to form.

 The starting compound of formula V is available at low cost and in large quantities commercially. For example, when the compound of formula V is lto-chlorophenetole, this compound may be obtained by an ordinary method such as ethylation of chlorophenol with an alkylating agent, or by alcoholysis of o-dichlorobenzene.

 In particular, the compound of formula V used as raw material according to the invention is chloro-2-methoxybenzene, 2,6-dichloro-methoxybenzene, 2-bromo-methoxybenzene, 2,6-dibromethoxybenzene, 2-chloroethoxybenzene, dichloro -2.6 ethoxybenzene, 2-bromoethoxybenzene, 2-chloropropoxybenzene and 2-bromo-propoxybenzene. These compounds are reacted with methallyl chloride or bromide as indicated below, to obtain a compound of formula I, which is isolated and purified, to serve as a raw material for the preparation according to the invention of the compound of formula III, and also as an intermediate product in the production of various organic compounds.

 For the preparation of the halogeno-3-alkoxy-4-neophyl halide of formula I according to the invention, 0.5 to 10 mol, preferably 1 to 5 mol, of methallyl halide are used per mol of halogen-2-alkoxybenzene.

When leaving this range of proportion, the reaction rate is reduced and the formation of secondary product is accelerated, which reduces the yield of desired product.

 The process according to the invention can be carried out in the absence of any solvent, or in a common solvent of the Friedel-Crafts reaction, such as nitromethane, acetonitrile or carbon disulphide.

 In accordance with the invention, the reaction is carried out in the presence of an acidic catalyst: concentrated sulfuric acid or methanesulfonic acid, a strongly acidic ion exchange resin such as Amberlyst or Nation, trifluoromethanesulphonic acid or hydrofluoric acid are particularly suitable. The preferred is trifluoromethanesulfonic acid, however, on an industrial scale concentrated sulfuric acid is often preferred.

The acid catalyst is used in a proportion of 0.1 to 2 moles, preferably 0.5 to 1.2 moles, per mole of methallyl halide. When these proportions are not respected, the reaction rate decreases or the byproducts are formed in large quantities, which reduces the yield.

The reaction temperature is between -200C and + 500C, preferably between OOC and 300C. It is preferable to add the catalyst and the methallyl halide, simultaneously, dropwise, to the compound of formula
V, to operate. When the methallyl halide is in contact with the acid catalyst for a long time, it tends to deteriorate to form a polymer or the like. If the reaction temperature, in the manner of loading the raw materials, differs from that described above, the reaction rate decreases, or the by-products are formed in large quantities.In general, the catalyst and the methallyl halide are added dropwise, simultaneously, in a time interval of 30 minutes to 2 hours, and then the reaction mixture is maintained for an additional 2 to 6 hours after the end of the addition, so that the reaction is complete.

 The compound of formula I thus obtained is substantially free of ortho isomer, therefore it is not usually necessary to purify it. Its purification is an easy operation because, unlike the 4-alkoxy neophyl halide, it is a stable compound. During the subsequent etherification reaction, the ether can be obtained in high yield.

 This compound of formula III according to the invention can be obtained, for example, by a process described in the patents cited above, in which a compound of formula VIII is reacted with a 3-phenylbenzyl alcohol, in the presence of a base such as aqueous sodium hydroxide solution, in a solvent such as dimethylsulfoxide, to give a compound of formula VI.

However, when the halogeno-3-alkoxy-4-neophyl halide of formula I, wherein the benzene ring of the neophyl group is substituted with an alkoxy group and a chlorine or bromine atom, is reacted with a phenoxy alcohol In the case of dimethyl sulfoxide used as a solvent, the yield of product is relatively low.

It should also be noted that when a sulfur-containing polar solvent, such as dimethylsulfoxide, is used in the etherification reaction, sulfur-containing by-products are formed which remain in very small amounts in the reaction medium. compound of formula
III, even after purification by recrystallization. These sulfur-containing by-products act as a poison for the catalyst during the subsequent hydrodehalogenation stage carried out in the presence of a hydrogenation catalyst, which results in a serious drop in the yield of the desired product of formula IV.

Therefore, during the production of the compound of formula III by etherification reaction of the product of formula I by the compound of formula II, according to the process of the invention, it is preferred to carry out the reaction in the presence of a neutral polar solvent, not containing sulfur. Particularly suitable neutral polar solvents are 1,3-dimethylimidazolidinone, N-methylpyrrolidone-2, tetramethylurea, diglyme and hexamethylphosphoric triamide.

The preferred is 1,3-dimethyl imidazolidinone, because its use allows to achieve high yields.

The amount of solvent used is between 0.5 and 50, and preferably 2 and 20 parts, for 1 part of 3-phenyl benzyl alcohol. When the amount of solvent is lower, the rate of reaction decreases seriously.

When the amount of solvent is greater, the reaction rate decreases and productivity is reduced.

 As a base, an alkali metal hydroxide may be used as sodium, potassium or lithium hydroxide; an alkaline earth metal hydroxide, such as calcium or magnesium hydroxide; an alkali metal hydride such as sodium hydride; an alkali metal alkoxide, such as sodium methoxide, potassium ethoxide or potassium tert-butoxide; an alkali metal oxide, such as sodium oxide; an alkali metal carbonate, such as potassium or sodium carbonate; sodium amide; triethylamine; or pyridine. The base is used in an amount of 0.5 to 3 moles, preferably 1 to 2 moles, per mole of 3-phenylbenzyl alcohol. When this quantity is lower, the conversion rate is low. When the amount of base is greater than this range, large amounts of side products are formed which reduce the yield.

 The preferred base is sodium or potassium hydroxide. It is desirable to use the alkali in solid form because the reaction is accelerated and the yield is improved when using common alkali, granular or chip, or in some cases, finely pulverized. The water content of the reaction system does not exceed 10%, preferably 3%, based on the solvent at the initial stage of the reaction. In some cases it is effective to carry out azeotropic dehydration with toluene or xylene during the reaction.

 A general embodiment of the etherification step according to the invention is carried out as follows.

As regards the proportions, 0.2 to 5 moles, and preferably 0.4 to 2 moles, of a halogeno-3-alkoxy-4-neophyl halide of formula I are used per mole of phenoxy alcohol. Benzyl compound of formula II. When the proportion is not in this range, the rate of reaction decreases and the formation of by-products is accelerated, which reduces the yield.

The compounds of formulas I and II, a base and a solvent are charged in a reaction vessel and the whole is heated to 500C at the boiling point, preferably 800C at the boiling point (when the latter is greater than 2000C 80 ° to 2000 ° C. The mixture is stirred at this temperature for 30 minutes to 50 hours, preferably 3 to 30 hours After cooling to room temperature, the insoluble mineral salt is removed by filtration. The residue is rinsed with water and then dried to give a 3-phenoxy-benzyl ether of 2- (2-alkoxy-3-halogeno-phenyl) -2-methylpropyl or 4-alkoxy-dihalogeno. -3 ', 5' phenyl) -2-methylpropyl of the formula
III.This product is purified by distillation under vacuum or by column chromatography, and is optionally recrystallized.

 Suitable compounds of formula III are those having a monohalogenated benzene ring in the neophyl group as 3-phenoxy benzyl ether and 3- (3-chloro-4-alkoxyphenyl) -2-methylpropyl, phenoxy-3-oxide. benzyl and (3-bromo-4 'alkoxy-phenyl) -2-methyl-2-propyl, or 3-phenoxy-4-fluoro-benzyl ether and (3-chloro-4'-alkoxy-phenyl) -2-methylpropyl ; or those which have a dihalogenated benzene ring in the neophyl group as 3-phenoxybenzyl ether and (3'-dichloro-5'-alkoxy-4'-phenyl) -2-methylpropyl.A compound of the formula III desired may be obtain by a suitable choice of the compounds of formulas I and II. In the process according to the invention, the monochlorosubstituted compound is preferred from the point of view of the subsequent hydrodehalogenation which, from product III, will give the desired product IV. For this reason, 3-chloro-4-alkoxy neophyl chloride is particularly preferred among the products of formula I.

 The compound of formula III thus obtained is then hydrodehalogenated during a catalytic hydrogenation stage, to give the product of formula IV corresponding.

According to the process according to the invention, the compound of formula IV can be obtained from the compound of formula
III, for example by a catalytic hydrogenation process, a hydrogenation process with a reducing agent such as lithium aluminum hydride, or a dehalogenation process with a metal and a neutral polar solvent. The most advantageous on an industrial scale is the hydro-genation process, more particularly catalytic hydrogenation. With regard to the catalytic hydrogenation process, the compound of formula IV can be obtained, for example as follows: compound of formula
With hydrogen, in the presence or absence of a base and a solvent, in the presence of a catalyst, at a given temperature, under atmospheric pressure or under high pressure. A compound of the formula IV is then separated by a suitable method from the reaction mixture. The alkali metal hydroxide, carbonate, acetate or alkoxide, for example potassium hydroxide or sodium hydroxide, potassium or sodium carbonate, acetate or sodium methoxide; an alkaline earth metal hydroxide as calcium hydroxide; or an aliphatic, aromatic or heterocyclic base such as triethylamine, ethylenediamine, diethylaniline, pyridine or 1,5-diaza-bicyclo-n-4, 4-unsecene-5 (DBU). Preferred are the alkali metal hydroxides, and sodium hydroxide is particularly advantageous from an economic point of view. The amount of base varies over a wide range: in general, 0 to 10 moles, preferably 1 to 6 moles of base per mole of the compound of formula III are used.

 When operating in a solvent, it is possible to use, in addition to water, an alcohol such as methanol, a polyol such as ethylene glycol, acetic acid, an acetate or other organic solvent. The latter can be used in the form of a mixture with water: a mixture of water and methanol is more particularly preferred. The amount of solvent may range from 0 to 100 parts by volume per volume part of the raw material of formula III. From the point of view of the reaction rate, the volumetric efficiency of the reaction, etc., an amount of 2 to 10 parts by volume is desirable.

 Suitable catalysts are nickel, especially Raney nickel, palladium such as palladium on carbon or platinum. Palladium coal is particularly advantageous. The amount of catalyst used is 0.1 to 20% by weight, preferably 2 to 7%, based on the compound of formula III.

 The hydrodehalogenation reaction according to the invention can be carried out under atmospheric pressure.

However, it is preferred to operate under high pressure, in particular between 5 and 60 kg / cm 2.

 The reaction temperature can vary over a wide range: it oscillates in general between 500 and 2200C, preferably between 800 and 1500C.

 Thus, during the hydrodehalogenation reaction according to the invention, only the chlorine or bromine atom, attached to the benzene ring of the neophyl group, is removed. Even when this nucleus is substituted by two halogen atoms, chlorine bromine can easily be removed, virtually without removal of the fluorine atom attached to the benzene ring of the 3-phenoxybenzyl group. Thus, can the desired product of formula IV be obtained.

 Can thus be obtained by removal of chlorine or bromine of the compound of formula III, including the following compounds of formula IV: 3-phenoxy benzyl ether and (methoxy-4 'phenyl) -2-methyl-propyl oxide, 3-phenoxy-4-fluoro-benzyl and 2- (4-methoxy-phenyl) -2-methylpropyl, [4-fluoro-phenoxy] -3-benzyl benzyl ether and 2- (4-methoxy-phenyl) -2-methylpropyl 4-Fluoro-4-phenoxy-4-fluoro-benzyl ether and 2- (4-methoxy-phenyl) -2-methylpropyl, 3-phenoxybenzyl ether and (4-ethoxyphenyl) 2-methyl-2-propyl, 3-phenoxy-4-fluoro-benzyl ether and 2- (4-ethoxy-phenyl) -2-methylpropyl, 4-fluoro-4-phenoxy benzyl ether and (ethoxy) 4'-phenyl) -2-methyl-propyl, (4-fluoro-phenoxy) -3-fluoro-4-benzyl-benzyl ether and 2- (4-ethoxy-phenyl) -2-methyl-propyl ether, 3-phenoxy-fluoro oxide 6-Benzyl and 2- (2-ethoxy-phenyl) -2-methylpropyl, phenyl-3-fluorophenyl and (4-ethoxy-4-phenylphenyl) -2mulphoxide; 2-ethylpropyl, 3-phenoxybenzyl ether and 2- (2-isopropoxy-phenyl) -2-methylpropyl, 3-phenoxy-4-fluoro-benzyl ether and 2- (2-isopropoxy-phenyl) -2-methyl-2-phenylpropyl propyl, 3-phenoxybenzyl ether and 2- (2-methylpropoxy-phenyl) -2-methylpropyl, 3-phenoxybenzyl and 2- (n-butoxy-phenyl) -2-methylpropyl oxide, phenoxypoxide 3-Benzyl and 2- (2-tert-butoxy-phenyl) -2-methylpropyl, or 3-phenoxybenzyl ether and (n-pentyloxy-4'-phenyl) -2-methyl-2-propyl.

 The following examples illustrate, without limitation, the present invention.

EXAMPLE 1
Synthesis of (3-chloro-2-ethoxy-4-phenylphenyl) -2-methylpropyl (or 3-chloroethoxy-4-ethoxyphenyl) chloride
208.6 g (1.33 moles) of o-chlorophenetole are loaded into a 500 ml four-necked flask. 39.2 g (0.4 mole) of 98% sulfuric acid and 90.6 g (1 mole) of methallyl chloride are added dropwise simultaneously by means of two funnels at 100 ° C. over 2 hours. This mixture is then stirred at the same temperature for an additional 2 hours.

The reaction solution is poured into about 0.5 liter of water. The mixture is stirred well in a settling funnel so that it separates into an oily bottom layer and an aqueous layer. The oily layer is rinsed with 200 g of a 3% aqueous solution of sodium hydroxide, and then three times with 200 g of water, and finally it is dehydrated under reduced pressure to obtain 287.8 g of chloride. (3-chloro-ethoxy-phenyl) -2-methyl-2-propyl crude.

This crude product is analyzed by gas chromatography, which reveals that it comprises 96.5% of 2- (3-chloro-2-ethoxy-4-phenylphenyl) -2-methylpropyl chloride and 3.5% of (chloro) chloride. 3'-ethoxy-2'-phenyl-2-methyl-2-propyl.

et -CH2CH3), 3,6 (2H,

4,0ru 4,2 (2H, q, -CH2CH3),
6,8 s 7,4 (3H, m, protons aromatiques) ppm.The crude product is purified by distillation under vacuum to give 167.4 g of the pure product sought (fraction of 1270 to 1340C / 1.5 mmHg)
Purity (gas chromatography, surface%): 96.3%
Yield: 67.7% based on methallyl chloride
Elemental analysis for C12H16Cl2O
Calculated: C: 58.31 H: 6.53 Cl: 28.69
Found: C: 58.11 H: 6.41 Cl: 28.72
NMR Spectrum g CDC83 1.3 S 1.6 (9H,

and -CH2CH3), 3.6 (2H,

4.0ru 4.2 (2H, q, -CH 2 CH 3),
6.8 s 7.4 (3H, m, aromatic protons) ppm.

EXAMPLE 2
The reaction and the after-treatment are identical to those of Example 1, except that the 39.2 g of 98% sulfuric acid are replaced by 11.6 g of trifluoromethanesulphonic acid. 293.8 g of crude chloride (3-chloro-ethoxy-4-phenyl) -2-methylpropyl are obtained.

This crude product is analyzed by gas chromatography, which reveals that it comprises 96% of the desired chloride of (chloro-3'-ethoxy-4'-phenyl) -2-methylpropyl, and 4% of chloro-3'-ethoxychloride. 2 'phenyl) -2-methyl-2-propyl (isomer).

This crude product, by distillation under reduced pressure, gave 67.7 g of unreacted o-phenol, and 175.1 g of desired pure product (1310 to 1350 ° C / 5 mm Hg).

Purity (gas chromatography: surface%): 93.6%
Yield: 70.9% (relative to methallyl chloride)
Reference example
2- (4-ethoxy-phenyl) methyl-2-propyl chloride (p-ethoxyneophyl chloride) is synthesized by the following method, as described in Japanese Patent Application No. 72928/82. 98% sulfuric acid in a 500 ml four-necked flask, 200 g of phthalole are added dropwise, while maintaining the temperature at 450 ° C. 10 hours, a mixed solution of 90 g of methallyl chloride and 165 g of phenetole, maintaining the temperature between 0 and 100 C. This mixture is maintained at 250C for 15 hours, then poured into ice water. separates an organic layer, which is rinsed thoroughly with an aqueous solution of sodium hydroxide, then with water, and dried over anhydrous sodium sulfate to obtain 451.2 g of crude chloride ( 2-ethoxy-2-phenyl-2-methyl-propyl This product is analyzed by gas chromatography, which reveals that it comprises 22% of 2- (2-ethoxy-phenyl) -2-methylpropyl chloride, and 78% of 2-(2-ethoxy-phenyl) -2-methylpropyl chloride (isomer).

EXAMPLE 3
Synthesis of 3-phenoxy benzyl ether and (3-chloro-2-ethoxy-4-phenyl) -2-methylpropyl.

3 liters (3.156 g) of 1,2-dimethyl-2-imidazolidinone (hereinafter referred to as DMI), 618 g (2.5 moles) of purified chloride, were charged to a 4-liter, 4-liter flask. (3-chloro-4'-ethoxy-phenyl) -2-methylpropyl, obtained as in Example 1, 1251 g.
(6825 moles) m-phenoxybenzyl alcohol (manufactured by
Ethyl Corp.), and 280 g (5 moles) of potassium hydroxide in the form of chips, and stirred at 1200C under a stream of nitrogen for 15 hours to complete the reaction.

This reaction mass is cooled to room temperature. An insoluble substance is removed by filtration under reduced pressure. The filtrate was rinsed with 300 ml (320 g) of DMI to give 2155 g of washing stock solution. By vacuum distillation of this solution, 3274 g of DNI are collected and 1845 g of a residue containing a mineral substance are obtained.

It is confirmed that the residue contains 3-phenoxy benzyl ether and (3-chloro-4-hydroxy-phenyl) -2-methylpropyl (deethylated product) side product of the reaction. This product has the following physical properties:

Melting point: 680-690C
NMR spectrum zCDCE3

6.7 H 7.4 (12H, m, aromatic protons)
In order to recover the desethylated compound as an ethyl compound, the residue is charged to a 5-liter, four-necked flask together with 3 liters of water. 38.5 g (0.25 mole) of diethyl sulfate are added dropwise at 500.degree. The mixture is stirred at this temperature for 1 hour. The temperature is raised to 900 ° C. and stirring is continued at this temperature for 2 hours in order to decompose the excess of diethyl sulfate. The reaction mass is cooled to 500C, and its pH is adjusted to 3 to 4 with 30 g of concentrated hydrochloric acid. The mixture is allowed to stand. It separates a lower oily layer, which is washed with 3 liters of water at 500C. This washing is repeated twice. The resulting oily product, which contains water, is dehydrated with an evaporator under reduced pressure, leaving a residue of 1774 g.

This residue was distilled under reduced pressure in a Smith thin film evaporator to remove low unreacted raw materials (2100C / 0.1 mm Hg). The residue is thus partitioned into a 990 g low boiling fraction and a 770 g high boiling fraction.

A mixed solution of the 770 g high boiling fraction and 1540 ml ethanol was cooled to -100 ° C and stirred at that temperature for 2 hours to form crystals. These are filtered and dried.

According to the analysis by gas chromatography, according to the conventional internal method, this product comprises 96.3% of 3-phenoxy benzyl ether and of 2-chloro-3'-ethoxy-4-phenylphenyl) methyl -2-propyl, and 0.6% isomer oxide of 3-phenoxy benzyl and (3-chloro-ethoxy-4 'phenyl) -2-dimethyl-1 ethyl.

Yield in crystals: 869.5 g (81.5%)
These crystals have the following characteristics
Solidification point: 42.20C
Elemental analysis for C25H27ClO3
CH Cl
Calculated: 73.07 6.62 8.63
found: 73.25 6.55 8.33
NMR spectrum dCDCt3
1.25 (6H, s), 1.2 (3H, t), 3.36 (2H, s), 3.92
(2H, q), 4.2 (2H, s), 6.6 ~ 7.4 (12H, m) ppm
EXAMPLE 4
Synthesis of 3-phenoxy-4-fluoro-benzyl ether and (3-chloro-2-ethoxy-4-phenyl) -2-methylpropyl.

30 ml of DMI, 6.2 g, are loaded into a 100 ml flask.
(0.025 mol) of purified chloride of (3-chloro-ethoxy-4-phenyl-2-phenylpropyl), obtained in Example 1, 8.5 g (0.039 mol) of 3-phenoxy-4-fluoro-4-methyl alcohol and 2.2 g (0.039 mol) of potassium hydroxide in the form of chips, and stirred at 1200C under a stream of nitrogen for 15 hours to complete the reaction.

The reaction mass is cooled to room temperature and then poured into 200 ml of a 5% aqueous solution of hydrochloric acid. The resulting oily product is extracted with 100 ml of benzene. This benzene extract is rinsed with 100 ml of water three times and then dried over anhydrous Glauber salt. Benzene is distilled off under reduced pressure to obtain 13.8 g of oily product. According to gas chromatographic analysis, as above, this product contains 62.4% of 3-phenoxy-4-fluoro-benzyl ether and (2-chloro-2-ethoxy-4-phenyl) -2-methylpropyl. Yield = 80.5%.

This oily product is isolated and purified by column chromatography using silica gel, giving 7.3 g of pure product, oily in appearance, which has the following characteristics:
n20 = 1.156
D
Elemental analysis for C25H26ClFO3
CH Cl F
Calculated: 70.01 6.11 8.26 4.43
Found: 70,12 6,00 8,58 4,21
NMR spectrum aCDCE3
1.27 (6H, s), 1.42 (3H, t), 3.30 (2H, s),
4.05 (2H, q), 4.34 (2H, s), 6.6s 7.4
(1 1H, m) ppm
EXAMPLE 5
Synthesis of 3-phenoxy benzyl ether and (3-bromo-2-ethoxy-4-phenyl) -2-methylpropyl.

In a 100-ml flask are charged, 30 ml of DMI, 7.3 g (0.025 mol) of 2- (bromo-3'-ethoxy-4-phenyl) -2-methylpropyl chloride, obtained as in the method of Example 1, except that o-chlorophenetole is replaced by o-bromophenetol, 8.5 g (0.039 mol) of m-phenoxybenzyl alcohol and 2.2 g (0.039 mol) of hydroxide. of potassium in chips, and stirred at 1200C under a stream of nitrogen for 15 hours to complete the reaction.

The reaction mass is cooled to room temperature and then poured into 200 ml of aqueous 5% hydrochloric acid solution. The resulting oily product is extracted with 100 ml of benzene. The benzene extract is rinsed three times with 100 ml of water and then dried over anhydrous Glauber salt. The benzene is distilled off under reduced pressure to give 14.2 g of an oily product.

According to gas chromatographic analysis, this product contains 58.3% of 3-phenoxy benzyl ether and (3-bromo-3'-ethoxy-4-phenyl) methyl-2-propyl. Yield: 72.7%. This oily product is isolated and purified by column chromatography using silica gel, which gives 8.8 g of pure, oily product.

This product has the following characteristics
Elemental analysis for C25H27BrO3
CH Br
calculated: 65.93 5.99 17.55
found: 65.65 5.82 17.65 NMR spectrum 6 CDCt3
1.26 (6H, s), 1.2 (3H, t), 3.35 (2H, s), 3.92
(2H, q), 4.4 (2H, s), 6.6 s 7.4 (12H, m) ppm
EXAMPLE 6
Synthesis of 3-phenoxy benzyl ether and 2- (4-ethoxy-phenyl) -2-methylpropyl.

500 g (0.146 mol) of 3-phenoxybenzyl ether and 2- (3-chloro-4-ethoxyphenyl) -2-methylpropyl, 7.5 g (0.188 mol) were charged into a 500 ml autoclave. ) of sodium hydroxide in chips, 7.2 g of 5% carbon palladium (50% wet), 108 ml of methanol and 36 ml of water. The autoclave is hermetically sealed and purged with nitrogen. Then hydrogen is introduced until a pressure of 8 kg / cmG. The mixture is stirred at an internal temperature of 1100C for 12 hours, with addition of 8 to 10 kg / cm2G of hydrogen, to complete the reaction.

The reaction mixture is cooled to room temperature, and the gas is released. 120 ml of benzene are introduced into the autoclave to dissolve the oily layer. An insoluble substance is removed by filtration. After rinsing with 30 ml of benzene, the resulting mother rinse solution is shaken well, then left for the benzene layer to separate. The latter is rinsed with 120 ml of water three times and then the water is separated off. The benzene is distilled off under reduced pressure and an oily product is obtained. According to the analysis by gas chromatography, this product comprises 98.5% of 3-phenoxybenzyl and 4-ethoxyphenyl ether. 2-methyl-2-propyl, and 0.58 of 3-phenoxybenzyl and unreacted 2-chloro-ethoxy-4-phenyl-2-methylpropyl ether.

The amounts of 3-phenoxy-toluene and 4-ethoxy-neophylic alcohol, formed by cleavage of the ether bond, are each less than 0.2%. The yield of oily product is 53.6 g <96%).

This oily product has the following characteristics:
solidification point: 31.20C
elemental analysis for C25H2803
CH
Calculated: 79.75 7.5
found: 79.86 7.69
3CDCf3 NMR Spectrum
1.25 (6H, s), 1.3 (3H, t), 3.35 (2H, s), 3.92
12H, q), 4.2 (211, s), 6.6 7.4 (13H, m) ppm
EXAMPLE 7
500 g of 50 g (0.11 mol) of 3-phenoxybenzyl ether and purified 2-bromo-3-ethoxy-4-phenyl-2-methylpropyl are obtained in a 500 ml autoclave obtained as in Example 5. 4.8 g (0.121 mol) of sodium hydroxide in chips, 2 g of 5% carbon palladium (50% wet), 90 ml of methanol and 30 ml of water. The autoclave is sealed and purged with nitrogen. Then, hydrogen is introduced until a pressure of 10 kg / cm 2 G is obtained. The mixture is stirred at an internal temperature of 800 ° C. for 12 hours. hours with supply of 8 to 10 kg / cmG of hydrogen, to complete the reaction. The reaction mixture is cooled to room temperature and the gas is released. 100 ml of benzene are charged to the autoclave to dissolve the oil.

An insoluble substance is removed by filtration. After rinsing with 20 ml of benzene, the rinsing mother solution is thoroughly shaken and allowed to stand to obtain a benzene layer. This layer is rinsed three times with 100 ml of water. The benzene is distilled off under reduced pressure to obtain an oily product. According to the gaseous chromatographic analysis, the oily product contains 98.5% of the desired oxide of 3-phenoxybenzyl and 2- (2-ethoxy-phenyl) -2-methylpropyl, and 0.3% of material. first 3-phenoxy benzyl ether and 2- (3-bromo-2-ethoxy-4-phenyl) -2-methylpropyl. The amounts of 3-phenoxytoluene and 4-ethoxy-neophylic alcohol, formed by cleavage of the ether bond, are each less than 0.2%. The yield of oily product is 41v2 g (98%).

This oily product has the following characteristics
Solidification point: 33.10C
Elemental analysis for C25H2803
CH
Calculated: 79.75 7.5
found: 79.50 7.22
NMR spectrum sCDCe3
1.25 (6H, s), 1.3 (3H, t), 3.35 (2H, s), 3.92
(2H, q), 4.2 (2H, s), 6.6 s 7.4 (13H, m) ppm
EXAMPLE 8
Synthesis of 3-phenoxy-4-fluoro-benzyl ether and 2- (4-ethoxy-phenyl) -2-methylpropyl.

500 g (0.117 mol) of purified 3-phenoxy-4-fluoro-benzyl ether and 2- (3-chloro-4-ethoxy-phenyl) -2-methylpropyl ether are obtained from a 500 ml autoclave. Example 4, 5.6 g (0.14 mol) of sodium hydroxide in chips, 5 g of 5% palladium carbon (50% moisture), 90 ml of methanol and 30 ml of water. The autoclave is hermetically sealed. After purging with nitrogen, hydrogen is introduced to a pressure of 10 kg / cm 2 G. This mixture is stirred at an internal temperature of 100 ° C. for 15 hours, with a hydrogen supply of 8 to 10 kg / cm 2 to complete the reaction.

The reaction mixture is cooled to room temperature and the gas is released. To dissolve the oil, 100 ml of benzene are charged into the autoclave. An insoluble substance is removed by filtration. After rinsing with 20 ml of benzene, the resulting rinse solution is shaken well and then allowed to stand to separate the benzene layer. This layer is rinsed 3 times with 100 ml of water. The benzene is distilled off under reduced pressure, leaving the oily product. According to the gas chromatographic analysis, the oily product contains 97.2% of 3-phenoxy-4-fluorobenzyl ether and
(2-ethoxyphenyl) -2-methylpropyl and 1% of raw material, 3-phenoxy-4-fluoro-benzyl ether and 2- (3-chloro-2-ethoxy-4-phenyl) -2-methylpropyl. The amounts of 3-phenoxytoluene and 4-ethoxy-neophylic alcohol, formed by cleavage of the ether bond, are each less than 0.1%. The amount formed of 3-phenoxybenzyl ether and 2- (2-ethoxy-4-phenyl) -methylpropyl, probably due to the replacement of the fluorine atom by the hydrogen atom, is less than 0, 5%.

Yield of oily product: 45.1 g (95%).

This product has the following characteristics
n20: 1,5635
Elemental analysis for C25 H27F03
CHF
Calculated: 76.12 6.9 4.82
CHF
found: 75.95 6.98 4.69
NMR spectrum SCDCt3 1.28 (6H, s), 1.39 (3H, t), 3.29 (2H, s), 3.92 (2H, q), 4.32 (2H, s), 6. , 6 ~ 7.4 (12H, m) ppm

Claims (9)

claims  1. Process for producing 3-phenoxybenzyl ethers and 2- (4-alkoxy-phenyl) -2-methylpropyl, represented

 in which X1 and X2 have the same meaning as above, in the presence of a base, in order to obtain a 3-phenoxy benzyl oxide and (4-alkoxy-3'-halo-3-phenyl)

Dhénoxv-3 benzvlictue of formula II  in which Y1 and YZ are each a hydrogen, bromine or chlorine atom, at least one of which is a chlorine or bromine atom, R has the same meaning as above and X is an atom halogen, with an alcohol

in which R is a lower alkyl group and X 'and are each a hydrogen or fluorine atom, characterized in that a halogeno-3-alkoxy neophyl halide of formula I is reacted <tb> <SEP> CH3 <SEP> xl <tb> <SEP> RO- (O> -C-CHLOCHZ- <SEP> X <SEP> X <tb> <SEP> C1H3 <SEP> O2 <tb> by <SEP> the <SEP> formula <SEP> IV <SEP> hereinafter <tb> wherein yl, Y2, R, X1 and X2 have the same meaning as above and then subjecting this product to a hydrodehalogenation reaction. <tb> <SEP> Y <SEP> CH3 <SEP> X <tb> <SEP> RO-2C1-CH2-O-CR2Q1 <SEP> X <SEP> (III) <tb> <SEP> Y1 <SEP> CH3 <SEP> O2 <tb> methyl-2 <SEP> propyl <SEP> of <SEP> formula <SEP> III 2. Process according to claim 1, characterized in that the product of formula I is a chloro-3-alkoxy-4 neophyl chloride. 3. Method according to claim 1 or 2, characterized in that it operates in a neutral polar solvent, not containing a sulfur atom. 4. Process according to claim 3, characterized in that the neutral, polar, non-sulfur-containing solvent is 1,3-dimethylimidazolidinone-2. 5. Method according to one of claims 1 to 4, characterized in that the hydrodehalogenation of the compound of formula III is carried out by catalytic hydrogenation in the presence of a base and a catalyst. 6. A process for the production of a halogeno-3-alkoxy-4-neophyl halide of formula I, used as raw material for the production of compound IV, characterized in that a halogeno-2-alkoxybenzene of formula V is reacted

 wherein y1 and Y2 are each hydrogen, bromine or chlorine, at least one of which is a bromine or chlorine atom, and R is a lower alkyl group, with a methallyl halide in the presence of an acid catalyst, between -20 and + 500C. 7. Process according to claim 6, characterized in that the acidic catalyst is trifluoromethanesulphonic acid. 8. Process according to claim 6, characterized in that the acidic catalyst is concentrated sulfuric acid. 9. Method according to one of claims 6 to 8, characterized in that the acid catalyst and the methallyl halide are added simultaneously to the halogeno-2-alkoxybenzene of formula V.