JPS63264432A - Production of benzyl propyl ether derivatives - Google Patents

Abstract

PURPOSE:To obtain the title compound which is used as an insecticide, acaricide or a starting substance thereof, in high yield, by reaction of 2-(4-alkoxy- phenyl)-2-methylpropyl bromide with benzyl alcohol in an inert solvent in the presence of a base. CONSTITUTION:The reaction of 2-(4-alkoxyphenyl-2-methylpropyl bromide of formula I (R1, R2 are H, Cl, Br; R is alkyl), especially 2-(3-halogeno-4-alkoxy- phenyl)-2-methylpropyl bromide is novel, with a benzyl alcohol of formula II (R3, R4 are H, F) is carried out in an inert solvent, preferably an aprotic polar solvent in the presence of a base to give 3-phenoxybenzyl-2-(4-alkoxyphenyl)-2- methylpropyl ether derivative such as 3-chloro-4-ethoxy-phenyl)-2-ethyl propyl ether.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing benzylpropyl ethers, and more specifically, the present invention relates to a method for producing benzylpropyl ethers, and more specifically, the general formula (+) ″ [wherein R,
and R2 is a hydrogen atom, a chlorine atom or a bromine atom,
2- (
2-(4-alkoxyphenyl) represented by the general formula (n) [In formula (II), R1, R2 and R each represent the above-mentioned meanings] as 4-alkoxyphenyl)-2-methylpropyl halides. Using -2-methylpropyl bromides, this is subjected to a condensation reaction with benzyl alcohols represented by the general formula (I[l), in which R1 and R# each represent the above-mentioned meanings] 3-phenoxybenzyl 2-(4
-alkoxyphenyl)-2-/tylpropyl ether derivative.

[Conventional technology]

It is known that the benzylpropyl ether derivative represented by the above general formula (1) has high insecticidal and acaricidal activity, and extremely low toxicity to fish.

In particular, among the compounds represented by the general formula (1), R,, R
3-phenoxybenzyl 2-(4-
It has been proposed that alkoxyphenyl)-2-methylpro and ethers have extremely high activity. (Not disclosed in JP-A-58-32840) These neophyll groups p-
A method for producing a compound of formula (1) having an alkoxy group at the position has also been proposed, and in JP-A-58-32840, a neophyll compound of the following formula and a benzyl compound [wherein groups A and B are one of group represents a halogen atom, and the other group represents a 10-M group (wherein M represents a hydrogen atom or an alkali or alkaline earth metal atom, 4
), or both of which represent a hydroxyl group, ] is described, and the following examples are described as specific examples thereof.

1) Condensation is carried out using a compound having an 10H group in A of the neophil compound and a -Br or -CI ring atom in B of the benzyl compound.

2) Condensation is carried out using a compound having a -Ct atom at A of the neophil compound and an -OH group at B of the benzyl compound.

3) A of the neophil compound and B of the benzyl compound are condensed using a compound having an 10H group, respectively.

However, as in 1) and 3) above, methods using 2-(4-alkoxyphenyl)-2-methylpropyl alcohol as the neophyll compound are industrially disadvantageous due to the long reaction route and low yield. So,
Neophil compounds include 2-(4-alkoxyphenyl)
It is easy to see that it is advantageous to choose -2-methylpro and ruhalides.

From this viewpoint, the present inventors investigated the condensation reaction of 2-(4-alkoxyphenyl)-2-methylpropyl halide and m-phenoxybenzyl alcohol, and obtained the following findings. <I proposed the invention first. (
In the synthesis of 4-alkoxy neophyll chloride, the following methods are known, but since nuclear chlorination proceeds preferentially, 4-alkoxy Almost no neofilterolide is obtained.

are known, but the alkylation reaction takes precedence at the ortho position with respect to the alkoxy group, and a large amount of ortho isomers are produced as by-products.

From the above, it is not advisable to maintain the method of direct condensation reaction of 4-alkoxy neofiltraloride and 3-phenoxybenzyl alcohol, so the following formula corresponding to the general formula (■) according to the present invention [In formula (mV), Yz is a hydrogen atom, a chlorine atom, or a bromine atom, and at least one of Yl and Y2 is a chlorine atom or a bromine atom. R is a lower alkyl group.

] Using a 4-alkoxy neofilterolide substituted with a halogen nucleus represented by the formula, a condensation reaction is performed between this and m-phenoxybenzyl alcohol, and the resulting condensation reaction product is dehalogenated to form 3-phenoxybenzyl 2-( The present inventors have previously proposed a method for obtaining 4-alkoxyphenyl)-2-methylpropyl ethers.

[Problem that the invention seeks to solve]

The above-mentioned Japanese Patent Application Laid-Open No. 59-88440 proposed by the present inventors
In the method described in the publication, 3-phenoxybenzyl 2- is a condensate obtained by reacting 3-chloro-4-ethoxyneophyl chloride and m-phenoxybenzyl alcohol in an aprotic polar solvent in the presence of a base. The yield of (3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was about 50% at most. In particular, when a halogen-unsubstituted 4-alkoxy neofilterolide having poor thermal stability was used, it was expected that the yield would further decrease.

As a result of investigating the cause in detail, the present inventors found that the reason for the decrease in yield was that the carbon chain to which the chlorine atom, which is the leaving group of 4-alkoxy neofilterlorides, was bonded was a phenethyl group, and that the benzyl It was hypothesized that this was due to the presence of two methyl groups at the carbon position, which is sterically complicated and would be dehydrochlorinated before condensation.

That is, since 4-alkoxy neofilterlorides are also unstable to heat, the reaction that produces benzylpropyl ethers, which are the desired accommodation products, and the quinoid-type intermediate, as shown in the following formula, However, it was found that the rearrangement reaction to form an isobutenyl compound became competitive, and as a result, a high yield could not be expected.

Muko is Double Yu, Ecchi, Sounder, etc. (W,
H, 5under, et, al-) + Journal Opza American Chemical Society (
J.Am.

Chem, Soc, ), 83, 882-885 (19
61) reported that 2,2-dimethylstyrene was produced by solvolysis of 2-phenyl-2-methylpropyl chloride with sodium formate in formic acid;
Journal of the American Chemical Society (J, Am, Ch.
em, Soc, )48°2763-2767 (195
This is expected from reports on the rearrangement reaction of neophyl derivatives such as 6).

An object of the present invention is to provide a method for producing benzylpropyl ethers represented by general formula (1) in high yield, which are used as intermediates for benzylpropyl ethers useful as insecticides.

[Means to solve the problem]

The present inventors have made extensive studies to solve the above problems.

As shown in the reference examples of the present invention, almost no difference was observed in the reactivity of neophyll promide and neophyll chloride, which are not substituted with an alkoxy group at the 4-position, to benzyl alcohol. However, as a raw material, 4 represented by general formula (n), which is a raw material for the method of the present invention,
- When using alkoxy neophyl bromides, they are unstable to heat like 4-alkoxy neofiltrarolides, but the reactivity of the bromine atom, which is a leaving group, is significantly greater than that of the chlorine atom. It has been discovered that the reaction temperature and reaction time can be lowered, and the production of isobutenyl derivatives due to rearrangement reaction during the reaction is suppressed, resulting in a significant improvement in yield. completed.

That is, the method of the present invention provides 3 represented by the general formula (1) above.
-Phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ether derivative manufacturing method, general formula (II) [in formula (II), R+, Rt and R each represent the above-mentioned meanings] The 2-(4-alkoxyphenyl)-2-methylpro and rubromides shown and the general formula (III) [formula ([[
In [), R8 and R4 each represent the above meaning,
] The general formula (r
) is a method for producing the benzylpropyl ether derivative shown in (1), and is characterized by using 4-alkoxyneophyl bromides as one of the 4-alkoxyneophyl halides, which is one of the condensation raw materials.

In the method for producing the compound of formula (1) according to the method of the present invention, for example, unlike the condensation reaction by dehalogenation of a neophyll compound having no alkoxy group, by using bromides in place of chlorides, 20 to 30%
The yield improves dramatically. In addition, halogen S-substituted 4-
Even if the condensation reaction is carried out directly using alkoxyneophyl bromide, the yield of the condensation reaction is completely inferior.

In the benzylpropyl ether derivative represented by the general formula (1) that can be produced by the method of the present invention, R is a lower alkyl group having 1 to 5 carbon atoms, and examples thereof include the following.

3-phenoxybenzyl 2-(4-ethoxyphenyl)-2-methylpropyl ether, 3-phenoxyhensyl 2-(3-chloro-4-ethoxyphenyl)-2
-Methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2-(4-ethoxyphenyl)-2-methylpropyl ether, 3-phenoxy-4-fluorobenzyl 2-(3-chloro-4-ethoxyphenyl)
-2-Methylpropyl ether, 3-phenoxybenzyl 2-(3-bromo-4-ethoxyphenyl)-2-methylpropyl ether, 3-phenoxybenzyl 2-
(3,5-dichloro-4-ethoxyphenyl)-2-methylpropyl ether, 3-phenoxybenzyl 2-
(3,5-dibromo-4-ethoxyphenyl)-2-methylpro-ether, 3-phenoxybenzyl 2-
(4-methoxyphenyl)-2-methylpropyl ether, 3-phenoxybenzyl 2-(3-chloro-4-
methoxyphenyl)-2-methylpropyl ether, 3
-Phenoxybenzyl 2-(3-bromo-4-methoxyphenyl)-2-methylpropyl ether, 3-phenoxybenzyl 2-(3,5-dichloro-4-methoxyphenyl)-2-methylpropyl ether, 3-phenoxy Benzyl 2-(4-isopropoxyphenyl)
-2-methylpropyl ether, 3-phenoxybenzyl 2-(3-70 rho 4-isopropoxyphenyl)
-2-methylpropyl ether, 3-phenoxybenzyl 2-(3-bromo 4-isopropoxyphenyl)
=2-Methylpropyl ether, 3-phenoxybenzyl 3-phenoxybenzylpropyl ether such as 2-(3,5-dichloro-4-isopropoxyphenyl)-2-methylpropyl ether, 3-(fluorophenoxy)benzyl ether , 3-phenoxy-fluorobenzyl ether, and 3-(fluorophenoxy)-fluorobenzylethyl derivatives.

General formula (If
) Among the 2-(4-alkoxyphenyl)-2-methylpropyl bromides represented by halogen-substituted 2-(3-halogeno-4-alkoxyphenyl)-2-
Methylpro and rubromides are new compounds, and these compounds can be obtained as follows.

For example, 2-chloro-methoxybenzene, 2,6-cyclomethoxybenzene, 2-promomethoxybenzene, 2,6-dibromo-methoxybenzene 1,2-chloro-ethoxybenzene, 2,6-cyclonitoxybenzene, 0.5 to 10 moles of methallyl bromide per mole of 2-halogeno-alkoxybenzene such as 2-promoethoxybenzene, 2,6-dibromo-ethoxybenzene, 2-chloro-propoxybenzene, 2-promopropoxybenzene, etc., preferably 0.5 to 10 moles. The reaction is carried out in the presence of an acid catalyst such as concentrated sulfuric acid or trifluoromethanesulfonic acid at -30 to 50°C, preferably -20 to 30°C, and usually 0.5 to 50 mol. It is preferable to carry out the reaction by adding methallyl bromide dropwise over a period of 2 hours.

In the reaction of the present invention, the proportion of 2-(4-alkoxyphenyl)-2-methylpropyl bromide and 3-phenoxybenzyl alcohol is 2-(4-alkoxyphenyl)-2-methylpropyl bromide. A suitable ratio of benzyl alcohol to 1 mole is 1 to 5 molar ratio, preferably 1 to 3 molar ratio. If the ratio used is outside this range, the reaction will be slow and more by-products will be produced, resulting in a lower yield.

The solvent used in the method of the present invention is
Similar to the method of No.-88440, aprotic polar solvents are preferred, including dimethyl sulfoxide, sulfolane, N-methyl-2-pyrrolidone, N,N-dimethylformamide, 1,3-dimethyl-2-imidazolidinone, and tetramethyl. Examples include urea, N,N-dimethylacetamide, hexamethylphosphoryltriamide, and more preferably dimethyl sulfoxide, N-methyl-2-pyrrolidone, and 1,3-dimethyl-2-imidazolidinone. A suitable amount is 0.5 to 50 parts, preferably 2 to 20 parts, per part of 3-phenoxybenzyl alcohol. If the amount used is less than this, the reaction will be very slow, and if it is more than this, the reaction will be slow and the productivity will be low. Alkali metal hydroxides such as sodium oxide, potassium hydroxide, lithium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, magnesium hydroxide, alkali metal hydrides such as sodium hydride, sodium methylate, potassium ethylate , potassium t-
Examples include alkali metal alcoholades such as butoxide, alkali metal oxides such as sodium oxide, alkali metal carbonates such as potassium carbonate and sodium carbonate, sodium amide, triethylamine, and pyridine, and the amount used is relative to 3-phenoxybenzyl alcohol. 1-10
Moles, preferably 2 to 6 moles are suitable. If the amount used is less than this, the reaction rate will be low, and if it is more than this, byproducts will be produced in large quantities and the yield will be reduced.

When sodium hydroxide or potassium hydroxide is used as a base, a normal granular or flake product can be used, but in some cases, using a finely divided product will speed up the reaction and improve the yield.

In this reaction, the water content in the system is suitably 10% or less, preferably 3% or less based on the solvent at the start of the reaction.

A general embodiment of the invention is as follows.

2-(4-alkoxyphenyl)-2-methylpropyl bromide, 3-phenoxybenzyl alcohol, a base and an aprotic polar solvent were placed in a reactor and heated to 50°C.
to the boiling point, preferably 60°C to the boiling point (60 to 200°C if the boiling point exceeds 200°C), and stirred at the same temperature for 0.5 to 25 hours, preferably 1 to 10 hours. The reaction temperature and reaction time are usually determined depending on the type of 2-(4-alkoxyphenyl)=2-methylpro and lupromide used, since the reaction can be completed at a lower temperature and in a shorter time than in the above-mentioned known method. Although it depends, the reaction temperature is 120°C or less, preferably 90 to 120°C,
The reaction time is within 5 hours, preferably 5 to 10 hours.

After the reaction is completed, the insoluble inorganic salt is filtered off after cooling to room temperature, the solvent is removed from the filtrate by distillation under reduced pressure, and the residue is washed with water and dehydrated to obtain the desired benzylpropyl ether derivative. This product can be used as it is for insecticides and acaricides or as a raw material for their production, but in some cases it can be further purified by vacuum distillation, recrystallization, or column chromatography.

This reaction is usually carried out in an air atmosphere, but in some cases, if the reaction is carried out after replacing the inside of the system with an inert gas such as nitrogen, the production of by-products can be suppressed and the yield can be improved.

The addition order of Mata, 2-(4-alkoxyphenyl)-2-methylpropyl bromide, 3-phenoxybenzyl alcohol and base may be arbitrary, and in some cases they may be charged in parts instead of all at once. is also possible.

〔Example〕

Next, the details of the present invention will be explained by referring to examples.

[Example 1] In a reaction vessel equipped with a stirring bar, a temperature needle, and a condenser, 2-
14.9 g of methyl-2-(3-chloro-4-ethoxyphenyl)propyl bromide, 25 g of 3-phenoxybenzyl alcohol, 5 g of potassium hydroxide flakes
．． 9 g and 1,3-dimethyl-2=imidazolidinone 6 (1 wl) were charged, and while stirring under a nitrogen stream, 12
The mixture was heated to 0°C and stirred at the same temperature for 5 hours.

After cooling the reaction mixture to room temperature, it was drained into 300 ml of water,
It was made weakly acidic using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using 100 ml of benzene, and the benzene layer was thoroughly washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 36.1 g of a composition. As a result of analysis using an internal standard method of gas chromatography, this product contained 49.9% of 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether.

The yield of the target product was 85.9% [vs. 2-methyl-2-(3-chloro-4-ethoxyphenyl)propylbromide].

This product was separated and purified by silica gel column chromatography to obtain 3-phenoxybenzyl 2 with a melting point of 42.5°C.
A pure product of -(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was obtained.

・Elemental analysis results CzslhtCl (hCHC1 Calculated value 73.07 6.62 8.63 Actual measurement
72.93 6.65 8.701.2
8(s, 6H), 1.4(t, 3H), 3.35(
s, 21 (), 4.0 (q, 2H), 4.39 (s, 2
1(), 6.68-7.32(n+, 12H) [Example 2] In Example 1, 2-methyl-2-(3-chloro-4-
Exactly the same procedure was performed except that 13.9 g of 2-methyl-2-(3-chloro-4-methoxyphenyl)propyl bromide was used instead of 2-methyl-2-(3-chloro-4-methoxyphenyl)propyl bromide to obtain the crude 3- phenoxybenzyl
34.2 g of 2-(3-chloro-4-methoxyphenyl)-2-methylpropyl ether was obtained. As a result of analysis using the internal standard method of gas chromatography,
The desired 3-phenoxybenzyl 2-(3-chloro-4
It contained 45.7% of -methoxyphenyl)-2-methylpropyl ether. Therefore, the yield of the target product is 78.8
% [vs. 2-methyl-(3-chloro-4=methoxyphenyl)propyl bromide].

This product was separated and purified by silica gel column chromatography to obtain pure oily 3-phenoxybenzyl 2-(3-chloro-4-methoxyphenyl)-2-methyl pro-ether.

・Elemental analysis results CzJh5C103 CHC1 Calculated value 72.63 6.35 8.93 Actual value
72.58 6.42 8.881.24 (s, 6H)
, 3.36 (s, 2H), 3.87 (s, 38), 4.
18 (s, 2H), 6.58-7.4 (m, 12H) [
Example 3 In Example 1, 2-methyl-2-(3-chloro-4-
Exactly the same procedure was carried out to obtain the crude 3-methyl-2-(3-bromo-4-ethoxyphenyl)propyl bromide, except that 16.8 g of 2-methyl-2-(3-bromo-4-ethoxyphenyl)propyl bromide was used instead of ethoxyphenyl)propyl bromide. phenoxybenzyl
37.4 g of 2-(3-bromo-4-ethoxyphenyl)-2-methoxypropyl ether was obtained. As a result of analysis using the internal standard method of gas chromatography, the target 3-phenoxybenzyl 2-(3-bromo-
It contained 50.1% of 4-ethoxyphenyl)-2-methylpropyl ether. Therefore, the yield of the target product is 82.
3% [vs. 2-methyl-(3-bromo-4-ethoxyphenyl)propyl bromide].

This product was separated and purified by silica gel column chromatography to obtain pure oily 3-phenoxybenzyl 2-(3-bromo 4-ethoxyphenyl)-2=methylpropyl ether.

・Elemental analysis result CzsHzvBrOzCHBr Calculated value 65.94 5.98 17.55 Actual value
65.73 5.89 17.68DCh ・NMR spectrum δ (PPIll) MS 1.2 (t, 3H), 1.23 (s, 6H), 3.3
3 (s, 2H), 3.98 (q, 2H), 4.20 (s
, 2H), 6.6-7.54 (m, 12H) [Example 4
] In Example 1, 2-methyl-2-(3-chloro-4-
The same procedure was repeated except that 15.3 g of 2-methyl-2-[3-chloro-4-(n-propyl)phenyl]propyl bromide was used instead of ethoxyphenyl)propyl bromide. 35.5 g of 3-phenoxybenzyl 2-(3-chloro-4-(n-propyl)phenyl]-2-methyl bromine ether was obtained.As a result of analysis by gas chromatography internal standard method, Target 3-phenoxybenzyl 2-[
It contained 46.2% of 3-chloro-4-(n-propyl)phenyl]-2-methylpropyl ether.

Therefore, the yield of the target product was 77.2% [vs. 2-methyl-[
3-chloro-4-(n-propyl]phenyl]propyl bromide].

This product was separated and purified by silica gel column chromatography to obtain pure oily 3-phenoxybenzyl 2-[3-chloro-4-(n-propyl)phenyl] 2-methylpropyl ether.

・Elemental analysis result CzaHzwCIOzCHC1 Calculated value 73.48 6.88 8.34 Actual value
73.54 6.93 8.51DC13 ・NMR spectrum δ (pp resistance MS 1.12 (t, 3H), 1.23 (s, 6H), 1.4
2 (m, 2H), 3.31 (s, 2H), 4.18 (s
, 2H), 6.6-7.6 (m, 12H) [Example 5] In Example 1, instead of using 1,3-dimethyl-2-imidazolidinone, N-methyl-2-pyrrolidone was used. 35.5 g of crude 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was obtained in exactly the same manner except that .

As a result of gas chromatography analysis, this
3-phenoxybenzyl 2-(3-chloro9-4-ethoxyphenyl)-2-methylpropyl ether 51.2
It contained %.

The yield of the target product was 86.7% [vs. 2-methyl-2-(3-chloro-4-ethoxyphenyl)propylbromide].

[Example 6] In Example I, the reaction temperature was 90°C and the reaction time was 10
The reaction was carried out in exactly the same manner except that the reaction was carried out at a different time, and crude 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was obtained.
1g was obtained. As a result of analysis by gas chromatography, this product contained 46.7% of 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether.

The yield of the target product was 80.5% [vs. 2-methyl-2-(3-chloro-4-ethoxyphenyl)propylbromide].

[Comparative Example 1] 2-methyl-2-(
6.2 g of 3-chloro-4-ethoxyphenyl)propyl chloride, 6.0 g of 3-phenoxybenzyl alcohol
, 6.0 g of flaked sodium hydroxide and 1.3
-Dimethyl-2-imidazolidinone (30 IIl) was charged, heated to 140° C. with stirring under a nitrogen stream, and stirred at the same temperature for 15 hours.

After cooling the reaction mixture to room temperature, it was extracted into 200 ml of water and made weakly acidic using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using benzene 50+a I, and the combined benzene layers were thoroughly washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 12.2 g of a composition. As a result of analysis using the internal standard method of gas chromatography, this product was found to be 3-phenoxybenzyl 2-(3-chloro-4-
ethoxyphenyl)-2-methylpropyl ether 4
It contained 2.3%.

The yield of the target product was 50.2% [vs. 2-methyl-2-(3-chloro-4-ethoxyphenyl)propylbromide].

This product was separated and purified by silica gel column chromatography, and 3-
A pure product of phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was obtained.

[Example 7] 10.3 g of 4-ethoxyneophylpromide, 8.5 g of 3-phenoxyhensyl alcohol, 3.9 g of 45% caustic soda and 50 ml of dimethyl sulfoxide were heated and stirred at 120°C for 5 hours. Made it react.

The reaction solution was cooled to room temperature, poured into water, extracted with benzene, and the benzene extract was washed with water and then dried. The crude ether obtained by distilling off benzene under reduced pressure was separated and purified by column chromatography (silicage JLt 300 g, solvent H: benzene: n-hexane 2:3) to obtain 13.0 g of the desired ether. Ta. Yield: 86.
3% (vs. 4-ethoxyneophilpromide).

[Comparative Example 2] 10.6 g of 4-ethoxy neofiltraloride, 12.0 g of 3-phenoxybenzyl alcohol, 2.5 g of flaky caustic soda, and 50 ml of dimethyl sulfoxide
The temperature was raised to 120°C and reacted for 5 hours, but since a considerable amount of unreacted 4-ethoxy neofilterloride remained, the temperature was further raised to 1,40°C and heated for a total of 8 hours. The reaction was terminated by stirring.

The reaction solution was treated in the same manner as in Example 4, separated and purified to obtain 9.0 g of the desired ether. Yield 48.0% (vs. 4-
ethoxyneophyl chloride).

Reference Example 1 21.3 g of neofilpromide, 24.0 g of m-phenoxybenzyl alcohol, 6.0 g of granular potassium hydroxide.
7g and dimethyl sulfoxide 100ml were placed in a container, heated to 120°C, stirred at the same temperature for 8 hours, cooled to room temperature, drained into 30kl of water, and diluted with benzene 1001.
Extracted twice. The benzene layer was washed with water and then dried over anhydrous sodium sulfate. Distill the solvent to give 3-phenoxybenzyl
Crude 2-phenyl-2-methylpropyl ether 3
3.8 g was obtained. As a result of analysis by gas chromatography, the purity of this product was 87.5%. (Yield 89.2% based on neofilpromide) This product was purified by column chromatography to obtain a pure product.

nA” ' 1.5789 ・Elemental analysis result CzxHzaO□ Calculated value (%) C84,10H7,28 Actual value (%)
C83,24H7,22 Reference Example 2 16.8 g of neofilterolide, 24 g of m-phenoxybenzyl alcohol, 6.7 g of granular potassium hydroxide and 100 ml of dimethyl sulfoxide were placed in a reaction vessel,
After heating to 120°C and stirring at the same temperature for 10 hours, the resulting reaction-completed liquid was cooled to room temperature, and the crude product of 3-phenoxybenzyl 2-phenyl-2-methylpropyl ether was prepared in exactly the same manner as in Reference Example 1. 32.6g was obtained.

Purity of this product by gas chromatography: 85.6
% (yield 84.0% based on neofilpromide)
), and a pure product obtained by column chromatography purification had exactly the same physical properties as Reference Example 1.

Next, an example of synthesis of raw materials will be shown.

Reference Example 3 Synthesis of 2-methyl-2-(3-chloro-4-ethoxyphenyl)propyl bromide 208.9 g of 0-chloroanisole and 15 g of trifluoromethanesulfonic acid were charged into a reactor, mixed, and heated at 50°C.
The temperature rose to .

135 g of methallyl bromide was added dropwise to this mixture at 50° C. over a period of 2 hours. After that, 0 was aged at the same temperature for 2 hours.
After the reaction solution was cooled, it was poured into 500 ml of water to separate the oil layer. The oil layer was diluted twice with 300 ml of water and 5% NaO.
After washing with H and water 5 times in that order, the product was dehydrated to obtain a crude product. After removing excess 0-chloroanisole under reduced pressure, the desired product was distilled.

b, p, 140-142°C 10.5 mmHg Yield 1256.6g Yield 88% (for methallyl bromide) TR vibration frequency ν22,"(C11-') 2975,2930,2
980, 1600, 1500° 1470, 1400.1
300.1270.1060°1040.800,74
0,610 1.4 (s, 6) 1), 1.3-1.6 (s, 3H),
3.5 (s, 2M).

3.9-4.3 (q, 2H) + 6.8-7.4 (m,
3) 1) ppIl/elemental analysis results (C+tH+*BrC
CHOr C1 Actual value (χ) 49.41 5.64 27.30
12.13 Calculated value (χ) 49.42 5.53 2
7.40 12.15 Reference Example 4.5.6 Synthesis of 2-(3-chloro-4-methoxyphenyl)-2-methylpro and lupromide 24.0 g of 0-chloroanisole was charged into a reaction vessel. This liquid was cooled to -10°C, and at the same temperature, 98% sulfuric acid
．． 25g was added over 1-5 minutes.

While stirring this mixture, 11.36 g of methallyl bromide was added dropwise over 1 hour at -10°C. 4 at the same temperature
After cooling, the 0 reaction solution obtained by stirring and aging for a period of time was 100 Il.
Pour the separated oil layer into 200 mj of benzene
! (100mj!X2). The extract is water,
After sequentially washing with 5% NaOH and water, the mixture was dehydrated with sodium sulfate (anhydrous) and concentrated to obtain a crude product. After removing excess 0-chloroanisole under reduced pressure, the residue was purified using silica gel column chromatography to obtain 18 g of the desired product. Yield 7
7.0% (vs. methallyl bromide).

The following table shows the yield and physical property values obtained in the same manner using O-purmophenetol and 2-chloropropoxybenzene instead of O-chloroanisole.

〔Effect of the invention〕

According to the method of the present invention, the desired 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-merolbrobyl ether neck represented by general formula (1) can be produced at a lower temperature and in a shorter time. It is obtained in high yield and is industrially advantageous.

Claims (2)

[Claims] (1) General formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R_1 and R_2 are hydrogen atoms, chlorine atoms, or bromine atoms, R is a lower alkyl group, R_3 and R_4 is a hydrogen atom or a fluorine atom. ] In the method for producing the 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ether derivative, there are general formula (II) ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (II) [Formula (II) ), R_1, R_2 and R each have the above meaning. ] 2-(4-alkoxyphenyl)-2-methylpropylbromides and general formula (III) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (III) [In formula (III), R_3 and R_4 are Each has the above meaning. ] The general formula (
A method for producing a benzylpropyl ether derivative represented by I). (2) The manufacturing method according to claim 1, wherein the inert solvent is an aprotic polar solvent.