JPH0653697B2 - Method for producing benzylpropyl ether derivative - Google Patents

Description

TECHNICAL FIELD The present invention relates to a method for producing a benzyl propyl ether derivative, and more particularly to the general formula (I) {In the formula (I), R ₁ and R ₂ are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, or an optionally substituted lower alkyl group, an alkenyl group, a lower alkoxy group, an acyloxy group, a lower group. Represents an alkylthio group, a lower acyl group, or an alkoxycarbonyl group,
R ₃ and R ₄ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group.
m and n are each an integer of 0 to 4, and m + n is 0 to 4. } When producing the benzyl propyl ether derivative represented by the general formula (II) {In the formula (II), R ₁ , R ₂ , m and n have the same meanings as described above, and X represents a halogen atom. } And a neofoil halide derivative represented by the general formula (III) {In the formula (III), R ₃ and R ₄ have the same meanings as described above. } With a 3-phenoxybenzyl alcohol derivative represented by the formula (1), an average molecular weight of polyalkylene glycol, monoalkyl ether of polyalkylene glycol, dialkyl ether of polyalkylene glycol, etc.
The method relates to a method for producing a benzylpropyl ether derivative, which comprises reacting in the presence of a base in a polyalkylene glycol solvent having 00.

2. Description of the Related Art Recently, certain compounds of 3-phenoxybenzyl ether derivatives have extremely high insecticidal and acaricidal activities, and have excellent characteristics in fast-acting and residual effects, and also for humans and animals. Of course, it has been found that the toxicity to fish and the like is low, and an excellent pest control composition containing these compounds as active ingredients is disclosed.

JP-A-56-154427 discloses a 3-phenoxybenzyl ether derivative represented by the formula (IV), {In the formula (IV), R is a methyl group or an ethyl group, R'is a hydrogen atom, a halogen atom or a lower alkyl group, and R "is a halogen atom or a lower alkyl group} Also, JP-A-57-64632 discloses Is the above formula (I
V) A compound in which R ′ or R ″ of the compound may be a group such as a cyano group or a nitro group, and each benzene nucleus of the 3-phenoxybenzyl group may be substituted with a halogen atom or the like is disclosed. Has been done.

Further, JP-A-58-32840 discloses a compound in which R'or R "is a lower alkoxy group and R is a methyl group.

The compounds described in these documents are compounds corresponding to the general formula (I) of the present invention, and a method for producing them is represented by the following reaction formula 1) as described in JP-A-58-32840. With neofoil alcohols like 3-
A method of reacting a phenoxybenzyl halide to obtain a target product and a method of reacting a neophenyl halide with 3-phenoxybenzyl alcohol as shown in the reaction formula 2) to obtain a target product are described. ing.

However, in the method represented by the reaction formula 1), the method for producing neophyl alcohols is complicated and industrially practically impossible. Therefore, the method represented by the reaction formula 2) is advantageous as an industrial production method, and is disclosed in JP-A-58-90.
525 and JP-A-59-88440, dimethyl sulfoxide (DMSO), sulfolane, 1,3-dimethyl-4-imidazolidinone (DMI) and N-methyl are prepared according to the method shown in reaction formula 2). There is a description that a target product can be obtained in a relatively high yield by reacting in an aprotic polar solvent such as pyrrolidone in the presence of a base.

However, it is a relatively expensive solvent such as 1,3-dimethyl-4-imidazolidinone used in these methods, and the reaction yield is not always satisfactory.

Means for Solving the Problems The present inventors have conducted various studies on synthetic methods of the benzylpropyl ether derivative represented by the general formula (I),
It is surprising that the neopheyl halide derivative represented by the general formula (II) is reacted with the 3-phenoxybenzyl alcohol derivative represented by the general formula (III) in an inexpensive polyalkylene glycol solvent in the presence of a base. In particular, it was found that the benzylpropyl ether derivative represented by the general formula (I) can be obtained in a better yield than when the known solvent described in the above publication is used, and the present invention has been completed.

The compound represented by the general formula (II) used as a raw material of the compound represented by the general formula (I) produced by the present invention is specifically represented by R ₁ and R ₂ being a hydrogen atom, a fluorine atom, chlorine Atom, bromine atom, methyl group, ethyl group, i-
Propyl group, t-butyl group, trifluoromethyl group, methoxymethyl group, ethoxymethyl group, 1-methoxyethyl group, 1-ethoxyethyl group, isopropenyl group, methoxy group, ethoxy group, n-propoxy group, i- Propoxy group, n-butyloxy group, i-butyloxy group, se
Examples include c-butyloxy group, n-pentyloxy group, methylenedioxy group, difluoromethoxy group, acetoxy group, methylthio group, ethylthio group, i-propylthio group, acetyl group, ethoxycarbonyl group, cyano group, nitro group and the like. R ₃ and R ₄ of the raw material represented by the general formula (III) are hydrogen atom, fluorine atom, chlorine atom, bromine atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl. Group, i-butyl group, sec-butyl group, t-butyl group, methoxy group, ethoxy group, n-propoxy group, i-propoxy group, n-butyloxy group, i
Examples include -butyloxy group and sec-butyloxy group.

Particularly, the method of the present invention comprises a compound in which _one of R ₁ and R _{2 in} the general formula (II) has a lower alkoxy group at the 4-position and a halogen atom at the 3- and / or 5-position, This is an advantageous method for the condensation reaction using a compound in which R ₃ and R _{4 in} formula (III) are each independently hydrogen or a fluorine atom.

In the above-mentioned JP-A-58-32840, the compound described above (compound of formula (V) below) Has a particularly excellent insecticidal effect among the compounds represented by formula (I), and is disclosed in JP-A-59-8844.
No. 0, and Japanese Patent Laid-Open No. 59-73535, a method for producing the same is described.

In the method described in JP-A-59-88440, in order to obtain a compound of the formula (V) or the like, the compound of the following formula (VI) is used as the compound of the general formula (II). {In the formula, Y ₁ and Y ₂ are a hydrogen atom, a chlorine atom, or a bromine atom, and at least one of Y ₁ and Y ₂ is a chlorine atom or a bromine atom. R is a lower alkyl group and X is a halogen atom. } Is used industrially, there is a description that it is extremely advantageous.

The reason is that the compound of formula (VI) is, for example, The compound represented by formula (VI) is a relatively stable compound and can be obtained in a high yield by preferentially reacting only in the para position with respect to the alkoxy group. -Condensation reaction with phenoxybenzyl alcohols,
And the subsequent purification of the condensate is advantageous.

Therefore, in the above-mentioned JP-A-59-88440, the condensation reaction between the compound of formula (VI) and 3-phenoxybenzyl alcohol optionally substituted with fluorine is carried out, and then the method described in JP-A-59-73535 is used. Y ₁ and Y ₂ in the obtained condensation reaction product are dehalogenated by a hydrodehalogenation method to obtain the target compound. At that time, when an organic solvent containing a sulfur atom such as dimethyl sulfoxide is used in the condensation reaction step, it becomes a catalyst poison of the noble metal catalyst used in the hydrodehalogenation step, and the hydrodehalogenation yield decreases. . Therefore, the above-mentioned JP-A-59-88440 is used.
In the condensation step of 1, an aprotic polar solvent containing no sulfur atom such as 1,3-dimethyl-4-imidazolidinone is used.

Since the polyalkylene glycol-based solvent according to the method of the present invention does not contain a sulfur atom, it is a non-advantageous method in the method of obtaining the compound of the formula (V) or the like, which incorporates the hydrodehalogenation step.

From this point of view, typical examples of the compound of the general formula (I) which can be produced by the method of the present invention are shown below.

3-phenoxybenzyl 2- (3-chloro-4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxybenzyl 2- (3,5-dichloro-4-methoxyphenyl) -2- Methylpropyl ether, 3-phenoxybenzyl 2- (3-bromo-4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxy-
4-Fluorobenzyl 2- (3-chloro-4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2- (3,5-dichloro-)
4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2- (3-
Bromo-4-methoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy) benzyl 2
-(3-Chloro-4-methoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenyloxy) benzyl 2- (3,5dichloro-4-methoxyphenyl)
2-Methylpropyl ether, 3- (4-fluorophenoxy) benzyl 2- (3-bromo-4-methoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy) -4 -Fluorobenzyl 2- (3-
Chlor-4-methoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy) -4-fluorobenzyl 2- (3,5-dichloro-4-methoxyphenyl) -2-methylpropyl Ether, 3- (4-fluorophenoxy) -4-fluorobenzyl 2- (3-
Bromo-4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxybenzyl 2- (3-chloro-)
4-methoxyphenyl) -2-methylpropyl ether, 3-phenoxybenzyl 2- (3,5-dichloro-)
4-Ethoxyphenyl) -2-methylpropyl ether, 3-phenoxybenzyl 2- (3-bromo-4-ethoxyphenyl) -2-methylpropyl ether, 3-
Phenoxy-4-fluorobenzyl 2- (3-chloro-
4-ethoxyphenyl) -2-methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2- (3,3
5-dichloro-4-ethoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy) benzyl 2- (3-chloro-4-ethoxyphenyl) -2-
Methyl propyl ether, 3- (4-fluorophenoxy) benzyl 2- (3,5-dichloro-4-ethoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy) benzyl 2- (3-Bromo-4-ethoxyphenyl) -2-methylpropyl ether, 3-
(4-Fluorophenoxy) -4-fluorobenzyl 2
-(3-Chloro-4-ethoxyphenyl) -2-methylpropyl ether, 3- (4-fluorophenoxy)-
4-fluorobenzyl 2- (3,5-dichloro-4-ethoxyphenyl-2-methylpropyl ether, 3-
(4-Fluorophenoxy) -4-fluorobenzyl 2
-(3-Bromo-4-ethoxyphenyl-2-methylpropyl ether, 3-phenoxy-6-fluorobenzyl 2- (3-chloro-4-ethoxyphenyl) -2-methylpropyl ether, 3-phenoxy- 6-Fluorobenzyl 2- (3,5-dichloro-4-ethoxyphenyl) -2-methylpropyl ether, 3-phenoxy-
6-Fluorobenzyl 2- (3-bromo-4-ethoxyphenyl) -2-methylpropyl ether, 3- (2-
Fluorophenoxy) benzyl 2- (3-chloro-4-)
Ethoxyphenyl) -2-methylpropyl ether, 3
-(2-Fluorophenoxy) benzyl 2- (3,5-
Dichloro-4-ethoxyphenyl) -2-methylpropyl ether, 3- (2-fluorophenoxy) benzyl 2- (3-bromo-4-ethoxyphenyl) -2-methylpropyl ether, 3-phenoxy Cibenzyl 2- [3
-Chloro-4- (i-propoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2-
[3,5-Dichloro-4- (i-propoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3-bromo-4- (i-propoxy) phenyl] -2-methylpropyl Ether, 3-phenoxy-4-fluorobenzyl-2- [3-chloro-4- (i
-Propoxy) phenyl] -2-methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2- [3,3
5-dichloro-4- (i-propoxy) phenyl] -2
-Methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2- [3-bromo-4- (i-propoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3-chloro-4 -(1-Methylpropoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3,5-dichloro-
4- (1-methylpropoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3-
Bromo-4- (1-methylpropoxy) phenyl] 2-
Methyl propyl ether, 3-phenoxybenzyl 2-
[3-chloro-4- (n-butoxy) phenyl] -2-
Methyl propyl ether, 3-phenoxybenzyl 2-
[3,5-dichloro-4- (n-butoxy) phenyl]
2-methylpropyl ether, 3-phenoxybenzyl 2- [3-bromo-4- (n-butoxy) phenyl]-
2-methylpropyl ether, 3-phenoxybenzyl 2- [3-chloro-4- (t-butoxy) phenyl]-
2-Methylpropyl ether, 3-phenoxybenzyl 2- [3,5-dichloro-4- (t-butoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl-2- [3-bromo -4- (t-butoxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3-chloro-4- (n-pentyloxy) phenyl] -2-methylpropyl ether, 3-phenyl Enoxybenzyl 2- [3,5-dichloro-4- (n-
Pentyloxy) phenyl] -2-methylpropyl ether, 3-phenoxybenzyl 2- [3-bromo-4-
(N-pentyloxy) phenyl] -2-methylpropyl ether and the like.

The neopheyl halide derivative used as a raw material in the method of the present invention includes, in addition to the method described in JP-A-59-88440, a method of halogenating t-butylbenzenes with sulfuryl halide or a halogen under light irradiation. It can also be synthesized by a known method such as a method of converting to a compound.

Also, is a 3-phenoxybenzyl alcohol derivative known as an alcohol component of synthetic pyrethroid,
Alternatively, it is produced by a known method described in the literature.

In the method of the present invention, neopheyl halide derivatives and 3
-The usage ratio of the phenoxybenzyl alcohol derivative is
When the neofyl halide derivative is used in an amount of 0.2 to 5 mol ratio, preferably 0.5 to 2 mol ratio, relative to 1 mol of the 3-phenoxybenzyl alcohol derivative, when the use ratio is out of this range, The reaction becomes slower, more by-products are produced, and the yield decreases.

As the solvent used in the method of the present invention, polyethylene glycol, polyalkylene glycol such as polypropylene glycol, its dialkyl ether such as polyethylene glycol dimethyl ether, or monoether, or dimethyl ether of ethylene oxide and propylene oxide copolymer, dioctyl ether, etc. Examples thereof include dialkyl ethers and monoethers, and these compounds have an average molecular weight of 300.
˜2500. Among them, polyethylene glycol dimethyl ether having an average molecular weight of about 1000 and dioctyl ether of an ethylene oxide / propylene oxide copolymer having an average molecular weight of about 2200 are particularly preferable. Two or more of these polyalkylene glycol-based solvents may be used in combination, and diglyme, methyl cellosolve, 1,2-diethoxyethane and the like may be used in combination.

The amount of the solvent used is 0.5 to 50 parts, preferably 2 to 2 parts per 1 part of the 3-phenoxybenzyl alcohol derivative.
0 part is appropriate. When the amount used is less than this, the reaction becomes very slow, and when the amount used is more than this, the reaction becomes slow and the productivity is low.

Further, as the base used in the method of the present invention, specifically, sodium hydroxide, potassium hydroxide, alkali metal hydroxides such as lithium hydroxide, calcium hydroxide, alkaline earth metal hydroxides such as magnesium hydroxide, Alkali metal hydride such as sodium hydroxide, sodium methylate, potassium ethylate, alkali metal alcoholate such as potassium t-butoxy, alkali metal oxide such as sodium oxide, alkali metal carbonate such as potassium carbonate and sodium carbonate, sodium Amide, triethylamine, pyridine, etc. are used, and the amount used is 0.5 with respect to 1 mol of the 3-phenoxybenzyl alcohol derivative.
-3 mol, preferably 1-2 mol is suitable. If the amount used is less than this range, the reaction rate is low, and if the amount used is too large, the production of by-products increases and the yield decreases.

When sodium hydroxide or potassium hydroxide is used as the base, an ordinary granular or flake form can be used, but depending on the case, use of a finely powdered form accelerates the reaction and improves the yield.

In this reaction, the water content in the system is 10% or less, preferably 3% or less, relative to the solvent at the start of the reaction.
In some cases, azeotropic dehydration with toluene or xylene during the reaction is effective.

The general embodiments of the present invention are as follows. A neoylyl halide derivative, a 3-phenoxybenzyl alcohol derivative, a base and a polyalkylene glycol solvent are placed in a reaction vessel and the temperature is 50 ° C to the boiling point, preferably 80 ° C.
To boiling point (however, if the boiling point exceeds 200 ° C, 8
The mixture is heated to 0 to 200 ° C. and stirred at the same temperature for 0.5 to 50 hours, preferably 3 to 30 hours. After cooling to room temperature, the reaction solution is discharged into water, extracted with an organic solvent such as benzene, washed with water, dehydrated and desolvated to obtain the desired benzylpropyl ether derivative.

This product can be used as it is for insecticides and acaricides, but in some cases, it can be further purified by distillation under reduced pressure or column chromatography.

Next, the present invention will be described with reference to examples.

Example 1 In a 200 ml four-necked flask, 50 g of dimethyl ether of polyethylene glycol having an average molecular weight of 1000, 2- (3
-Chloro-4-ethoxyphenyl) -2-methylpropyl chloride 12.4 g (0.05 mol), m-phenoxybenzyl alcohol 25.0 g (0.125 mol)
Then, 5.6 g (0.1 mol) of flaky caustic potash was charged, and the mixture was heated and stirred at 120 ° C. for 10 hours under a nitrogen stream.
Subsequently, 2- (3-chloro-4-hydroxyphenyl) -2-methylpropyl chloride produced as a by-product during the reaction
-Ethylation was carried out, and 0.8 g of diethylsulfate was added at the same temperature to obtain the desired product, and then the reaction was terminated by keeping the temperature for 1 hour and stirring.

After the reaction solution was cooled to room temperature, it was discharged into 200 ml of water and the oil portion separated was extracted with 200 ml of benzene. The benzene solution was washed with 100 ml of water, and this operation was repeated twice, followed by drying over anhydrous sodium sulfate, and then, after removing the solvent, the solvent was removed under reduced pressure to obtain 54.9 g of an oily substance. As a result of analysis by gas chromatography of the internal standard method, 3-phenoxybenzyl 2- (3-chloro-4-ethoxyphenyl) -2-methylpropyl ether was found to be 2
It was included at 3.7%. (Yield 60.2%) The oily substance 10.0 g was separated and purified by column chromatography on silica gel to obtain 1.6 g of a purified product (crystal). The freezing point, elemental analysis value and NMR spectrum of this crystal are shown below.

Freezing point 42.2 ° C Elemental analysis value C ₂₅ H ₂₇ ClO ₃ NMR spectrum αCDCl ₃ 1.25 (6H, s), 1.2 (3H, t), 3.35 (2H, s), 3.94 (2H, q), 4.2 (2H, s), 6 0.5-7.5 (12H, m) p
pm Example 2 Instead of dimethyl ether of polyethylene glycol having an average molecular weight of 1000 in Example 1, an average molecular weight of 22 was used.
The reaction and post-treatment operations were carried out in the same manner except that 50 g of dioctyl ether, which was a copolymer of ethylene oxide and propylene oxide of 00, was used, and 52.4 g of an oily substance was obtained. As a result of analysis by gas chromatography of the internal standard method, 3-phenoxybenzyl 2-
22.9 g of (3-chloro-4-ethoxyphenyl) -2-methylpropyl ether was contained. (Yield 5
Example 3 In a 200 ml four-necked flask, 50 g of dimethyl ether of polyethylene glycol having an average molecular weight of 1000, 2- (4
-Chlorophenyl) -2-methylpropyl chloride 1
0.2 g (0.05 mol), 25.0 g (0.125 mol) of m-phenoxybenzyl alcohol and 5.6 g (0.1 mol) of flaky caustic potash were charged, and 120 ° C. under a nitrogen stream. The mixture was kept warm for 10 hours.

After the reaction solution was cooled to room temperature, it was discharged into 200 ml of water and the oil portion separated was extracted with 200 ml of benzene. The benzene solution was washed with 100 ml of water, and this operation was repeated twice, followed by drying with anhydrous sodium sulfate, and after excess, desolvation under reduced pressure gave 56.3 g of an oily substance. As a result of analysis by gas chromatography using an internal standard method, 24.8% of 3-phenoxybenzyl 2- (4-chlorophenyl) -2-methylpropyl ether was contained. (Yield 76.2%) 10.0 g of the above oily matter was separated and purified by column chromatography on silica gel to obtain 1.7 g of a purified product (oily matter). Refractive index of this oil, elemental analysis value, NMR
The spectrum was as follows.

n ¹⁷ _D 1.5832 Elemental analysis C ₂₃ H ₂₃ ClO ₂ NMR spectrum αCDCl ₃ 1.26 (6H, s), 3.25 (2H, s), 4.27 (2H, s), 6.6 to 7.3 (13H, m)
ppm Comparative Example 1 Reaction and post-treatment operations were carried out in exactly the same manner as in Example 1, except that 1,3-dimethyl-2-imidazolidinone (DMI) was used instead of dimethyl ether of polyethylene glycol having an average molecular weight of 1000. Then, 53.8 g of an oily substance was obtained.

As a result of analysis by gas chromatography using an internal standard method, 20.2% of 3-phenoxybenzyl 2- (3-chloro-4-ethoxyphenyl) -2 methylpropyl ether was contained. (Yield 52.7%) Comparative Example 2 Reaction was performed in exactly the same manner as in Example 3 except that dimethyl sulfoxide (DMSO) was used instead of dimethyl ether of polyethylene glycol having an average molecular weight of 1000,
Post-treatment operation was carried out to obtain 58.8 g of an oily substance. As a result of analysis by gas chromatography using an internal standard method, 3-phenoxybenzyl 2- (4-chlorophenyl) -2-methylpropyl ether was contained at 21.3%. (Yield 68.4%)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location C07C 49/84 C 7457-4H 67/31 69/76 Z 9279-4H 201/12 205/34 7188 -4H 253/30 255/54 9357-4H 319/20 7419-4H 323/19 7419-4H

Claims (4)

[Claims] 1. A general formula (I) {In the formula (I), R ₁ and R ₂ are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally substituted lower alkyl group, an alkenyl group, a lower alkoxy group, an acyloxy group, a lower alkylthio. Group, a lower acyl group or an alkoxycarbonyl group, and R ₃ and R ₄ each independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group. m and n are each an integer of 0 to 4, and m + n is 0 to 4. }
In producing the benzylpropyl ether derivative represented by the general formula (II) {In the formula (II), R ₁ , R ₂ , m and n have the same meanings as in the general formula (I), and X represents a halogen atom. } And a general formula (III) {In formula (III), R ₃ and R ₄ have the same meaning as in formula (I). } And a 3-phenoxybenzyl alcohol derivative represented by the following formula in a polyalkylene glycol-based solvent having an average molecular weight of 300 to 2500 of polyalkylene glycol, monoalkyl ether of polyalkylene glycol, or dialkyl ether of polyalkylene glycol: A method for producing a benzylpropyl ether derivative, which comprises reacting in the presence of 2. A benzylpropyl ether derivative represented by the general formula (I) is 3-phenoxybenzyl 2- (3-
A process according to claim 1 which is chloro-4-ethoxyphenyl) -2-methylpropyl ether. 3. The method according to claim 1, wherein the polyalkylene glycol-based solvent is dimethyl ether of polyethylene glycol having an average molecular weight of 1,000. 4. The method according to claim 1, wherein the polyalkylene glycol-based solvent is a dioctyl ether of a copolymer of ethylene oxide and propylene oxide having an average molecular weight of 2200.