JP3073346B2 - Method for producing p-alkoxyneophyl m-phenoxybenzyl ethers - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a process for producing p-alkoxyneophyl m-phenoxybenzyl ethers which are useful as insecticides for paddy fields because of their high insecticidal activity and low fish toxicity. More specifically, the present invention provides an improved method for producing from p-alkoxyneophylbromides and m-phenoxybenzyl ether.

[0002]

2. Description of the Related Art In recent years, the development of pesticides has brought a remarkable effect on the control of pests and insects, and has greatly contributed to the stable supply of high-quality agricultural products. Especially in rice cultivation, since various new pesticides have been developed and used, the yield has been stable and the pesticides have contributed greatly to securing food in the world unless extreme weather changes occur. Is without doubt. However, on the other hand, it is also true that the safety of pesticides has been the subject of debate, and therefore the direction of the development of new pesticides is to be effective with as little amount as possible and to be more safe. Have been doing. Also, in the field of insecticides, there is a problem of resistance of insects to pests, and many agents have already been required to reduce their use due to the development of the resistance. That is, conventionally, organic phosphorus-based insecticides and carbamate-based insecticides have been widely used, but their use has been reduced due to problems such as resistance. Under these circumstances, synthetic pyrethroid insecticides have come to the limelight due to their excellent insecticidal effect and low toxicity to humans and animals, and many pyrethroid insecticides have already been put on the market. However, many pyrethroid insecticides developed to date have low toxicity to humans and animals, but are highly toxic to fish, so they cannot be used in paddy fields and the like, and the range of use is naturally limited. Was. Recently, general formula (3)
It has been found that certain substituted neophyll m-phenoxybenzyl ether compounds as shown in Table 1 have an extremely high insecticidal and acaricidal activity, and are also excellent in terms of immediate action and residual effect. Unlike conventional pyrethroid compounds, they have remarkably low toxicity to fish, and thus have been found to be usable for controlling pests in paddy fields, and have been noticed (JP-A-56-154427).
No., 57-64632, 57-72928, 58-
No. 32840).

[0003]

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[Wherein R ₄ and R ₅ each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, or an optionally substituted lower alkyl group, alkenyl group, lower alkoxy group, acyloxy group, lower Represents an alkylthio group, a lower acyl group or an alkoxycarbonyl group;
₆ , R ₇ are a hydrogen 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. Incidentally, among the substituted neophyl m-phenoxybenzyl ethers of the general formula (3), 4
General formula (1) having an alkoxy group at the -position
Is particularly useful because of its high insecticidal effect and low fish toxicity.

[0005]

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[Wherein, R represents a lower alkyl group having 1 to 4 carbon atoms, and R ₁ and R ₂ each independently represent a hydrogen atom, a chlorine atom or a bromine atom. As a method for producing p-alkoxyneophyl m-phenoxybenzyl ethers of the general formula (1), a p-alkoxyneophyl halide is generally used, as shown in the following reaction formula (1). Or m-phenoxybenzyl alcohol, or m-phenoxybenzyl halide and p-alkoxyneophyl alcohol as shown in reaction formula (2) (Chemical formula 6) contrary to reaction formula (1). After condensing the compound with phenols, the compound is further subjected to a dehalogenation reaction, if necessary.

[0007]

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[Wherein R, R ₁ and R ₂ represent the general formula (1)
And X represents a chlorine atom or a bromine atom. ]

[0009]

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Wherein R, R ₁ , R ₂ and X are the same as in the reaction formula (1). In these two production methods, the latter production method is a reaction method as an industrial production method, considering that the production of p-alkoxyneophyl alcohols as one of the raw materials is troublesome at the current technical level. The former method shown in (1) is preferable.

In the former condensation reaction of p-alkoxyneophyl halides and m-phenoxybenzyl alcohol, p-alkoxyneophyl bromides are used as p-alkoxyneophyl halides in view of the reactivity of the halide. By using the compound, the p-alkoxyneophyl m of the general formula (1) can be obtained under a mild condition in a high yield.
Applicants have previously found that phenoxybenzyl ethers can be produced, and filed a patent application (Japanese Patent Application Laid-Open No. Sho 63-2).
64432). That is, in the prior art, for example, in the condensation of 3-chloro-4-ethoxyneophyl bromide with m-phenoxybenzyl alcohol, as seen in Example 1 of the prior art, 2.5 mole ratio of m- to ethoxyneophyl bromide
Phenoxybenzyl alcohol and potassium hydroxide in a molar ratio of 2 were charged into a N, N'-dimethylimidazolidinone solvent, heated to 120 ° C. under a nitrogen stream, and reacted at the same temperature for 5 hours. The corresponding 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether is formed in a yield of approximately 86%.

Subsequently, the present inventors have further studied the above condensation reaction. As a result, the quantitative relationship between p-alkoxyneophyl bromide and m-phenoxybenzyl alcohol was determined under equimolar or near-molar conditions. However, it was found that the yield described in the prior art was obtained. However, as a result of detailed studies, it has been found that the condensation reaction has an industrial problem depending on the reaction method as described below. That is, one of the starting materials, p-alkoxyneophyl bromides, is naturally a highly reactive compound as compared to the corresponding p-alkoxyneophyl chlorides, and therefore, m-phenoxybenzyl alcohol In the case of condensation with a metal hydroxide, a method is employed in which a batch is charged into an aprotic polar solvent such as N, N'-dimethylimidazolidinone, and then the reaction is carried out by raising the temperature. It was found that the heat generated by the heat was large.

On a 0.6 mole scale of 3-chloro-4-ethoxyneophyl bromide, in the presence of potassium hydroxide,
Equimolar amount of m- in N, N'-dimethylimidazolidinone
In the reaction with phenoxybenzyl alcohol, the reaction flask was immersed in a 100 ° C. oil bath and reacted. When the reaction was initiated, the heat generated was large at the beginning of the reaction, and the temperature of the oil bath was controlled at 100 ° C. The temperature of the reaction solution temporarily rose to 115 ° C., indicating that the degree of heat generation was considerably large. Since the reaction generates such a large amount of heat even when the result is obtained on a small scale, the degree of this heat generation is greatly amplified on an industrial scale, and this may lead to a very dangerous situation. Of course, there are several ways to control this heat generation. For example, one method is to control the apparent heat generation by increasing the amount of solvent used and greatly reducing the substrate concentration in the reaction system.However, this method significantly reduces the volumetric efficiency, thereby lowering productivity and reducing industrial productivity. This is not always the preferred method. In addition, a method of providing a cooling coil or the like in the reactor to control the rapid temperature rise due to heat generation as much as possible is conceivable, but this method not only increases the equipment cost but also requires a technique that is skilled in operation management. This is not always the preferred method because it is required.

[0014]

The object of the present invention is to provide a compound of the general formula (2)

[0015]

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[Wherein, R represents a lower alkyl group having 1 to 4 carbon atoms, and R ₁ and R ₂ each independently represent a hydrogen atom, a chlorine atom or a bromine atom. In the condensation reaction of p-alkoxyneophyl bromides with m-phenoxybenzyl alcohol represented by the formula (1), the exothermicity of the reaction is sufficiently controlled without lowering the yield as compared with the batch charging method. It is another object of the present invention to provide a method for producing a p-alkoxyneophyl m-phenoxybenzyl ether of the general formula (1) in a high yield.

[0017]

Means for Solving the Problems As a method for controlling the heat generated by the reaction, a method in which one of the raw materials is charged continuously or intermittently to cause a reaction is also generally performed. The present inventors have studied diligently about a method in which m-phenoxybenzyl alcohol as a raw material or p-alkoxyneophyl bromide of the general formula (2) is dropped and reacted. Interestingly, the following findings were obtained.

In the general formula (2), R = Et, R ₁ = H, R ₂ =
3-Chloro-4-ethoxyneophylbromide, which is Cl, is dissolved in N, N'-dimethylimidazolidinone, and further charged with potassium hydroxide, and then heated to 100 ° C. under a gentle nitrogen stream. Examination of the stability at the same temperature revealed that, as shown in FIG. 1, 3-chloro-4-ethoxyneophylbromide gradually decomposed and the residual ratio thereof decreased with time. Even if m-phenoxybenzyl alcohol is added dropwise to allow the reaction to proceed, the yield of the desired 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether is clear as compared with the batch charging method. Was found to decrease.

On the other hand, m-phenoxybenzyl alcohol and potassium hydroxide were charged into N, N'-dimethylimidazolidinone, and the temperature was raised to a predetermined temperature under a gentle nitrogen flow. When chloro-4-ethoxyneophyl bromide was added dropwise and reacted, the yield of the desired 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was higher than that of the raw material batch charging method. It turned out that a slightly higher yield was obtained without any inconvenience. m
Investigation of the stability of -phenoxybenzyl alcohol in N, N'-dimethylimidazolidinone in the presence of potassium hydroxide showed that the tendency of decomposition like 3-chloro-4-chloroneophylbromide was No stability was observed, indicating that the stability was good. The present invention has been made based on such findings. That is, the present invention provides a compound represented by the general formula (1):

[0020]

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[Wherein R represents a lower alkyl group having 1 to 4 carbon atoms, and R ₁ and R ₂ each independently represent a hydrogen atom, a chlorine atom or a bromine atom. In producing p-alkoxyneophyl m-phenoxybenzyl ethers represented by the formula: m-phenoxybenzyl alcohol and an alkali metal hydroxide were dissolved or suspended in an aprotic polar solvent. The liquid is heated to 70 to 130 ° C., and the solution is treated with the general formula (2)

[0022]

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[Wherein R, R ₁ and R ₂ represent the general formula (1)
The same method as described above) is used for the production of p-alkoxyneophyl m-phenoxybenzyl ethers.

In the present invention, p-alkoxyneophylbromides of the general formula (2) are used as one raw material. The production method can be efficiently produced by a Friedel-Crafts reaction between p-alkoxybenzenes and methallyl bromides under a sulfuric acid catalyst disclosed by the present applicant (reaction formula 3).

[0025]

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The amount of the p-alkoxyneophyl bromide of the general formula (1) and the amount of m-phenoxybenzyl alcohol may be used in a remarkably excessive amount. It is necessary to consider the recovery of the raw material, and the process becomes complicated. Therefore, industrially, it is desirable to carry out the reaction at or near the stoichiometric ratio as much as possible. Therefore, in the present invention, both are 1.0:
It is used in the range of 0.8 to 1.2 molar ratio.

Specific examples of the alkali metal hydroxide used as the base in the present invention include lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide. Among them, potassium hydroxide is particularly preferable. If the amount is too small, not only does the reaction rate decrease, but also the yield of the desired p-alkoxyneophyl m-phenoxybenzyl ether of the general formula (1) is reduced. At the same time, a side reaction is likely to be induced, and at the same time, the unit consumption is not preferable.
Preferably, it is used in the range of 1.2 to 3.0 equivalents.

The reaction of the p-alkoxyneophyl bromide of the present invention with m-phenoxybenzyl alcohol is carried out in an organic solvent. In order for the reaction to proceed smoothly, an aprotic Polar solvents are preferred,
Specifically, N, N-dimethylformamide, N, N-diethylformamide, N, N-dimethylacetamide,
N, N-diethylacetamide, N-methylpyrrolidone,
N, N'-dimethylimidazolidinone, N, N'-dimethylpropyleneurea or dimethylsulfoxide can be mentioned. These solvents are usually used alone, but there is no problem even if two or more kinds are used in combination.

If the amount of the aprotic polar solvent is too small, the reaction is difficult to proceed, and it is not economically preferable to use an extremely large amount of the aprotic polar solvent. Used in an amount of 1 to 10 times by weight based on the alkoxyneophyl bromides;

An object of the present invention is to efficiently control the heat of reaction in the reaction of p-alkoxyneophyl bromides of the general formula (2) with m-phenoxybenzyl alcohol and to obtain a product. An object of the present invention is to produce p-alkoxyneophyl m-phenoxybenzyl ethers of the general formula (1) in high yield. To achieve this object, m-phenoxybenzyl alcohol and alkali metal hydroxide are used. A solution obtained by dissolving or suspending the compound in an organic solvent at 70 to 130 ° C, preferably 80 to 120 ° C.
The p-alkoxyneophyl bromide of the general formula (2) is dropped into this solution to cause a reaction. The p-alkoxyneophyl bromide to be dropped may be used alone or may be diluted with a solvent to be used. The dropping speed is 0.5 Hr or more for dropping the whole amount of p-alkoxyneophylbromide, Preferably 1
Hr or more. If the temperature at the time of dropping the p-alkoxyneophyl bromides of the general formula (2) is too low, the reaction has not progressed at all even after the dropping yield, or the degree of progress has been slight even if it has progressed. However, it is not preferable because a large amount of heat is generated as in the batch charging method, and if the temperature is too high, by-products are likely to occur due to overreaction and the like, and as a result, the yield of the target compound is reduced. Not preferred.

After dropping the p-alkoxyneophyl bromide of the general formula (2) as described above, it is further added at 70 to 130 ° C., preferably 80 to 120 ° C., if necessary.
, The corresponding p-alkoxyneophyl m-phenoxybenzyl ethers of the general formula (1) are produced in high yield. The progress of the reaction can be easily grasped by using analytical means such as high performance liquid chromatography. After the reaction, the p-alkoxyneophyl m-phenoxybenzyl ethers of the general formula (1) produced by the reaction may be isolated as follows.

That is, the reaction mass is discharged into water, extracted and separated with a water-immiscible organic solvent such as benzene or dichloroethane, and then the obtained organic layer is dried and filtered with a dehydrating agent such as anhydrous sodium sulfate. The residue obtained by evaporating the organic solvent under reduced pressure can be isolated by crystallization with a solvent such as alcohol or by using a means such as column chromatography. Alternatively, the reaction mass is cooled after the reaction, the precipitated inorganic salt is filtered, the filtrate is subjected to distillation under reduced pressure to distill off the reaction solvent, and the residue is washed with water and separated to further obtain an oil layer such as alcohol. It can also be isolated by crystallization using a solvent. Alternatively, the reaction mass is cooled after the reaction, the precipitated inorganic salt is filtered, the filtrate is subjected to distillation under reduced pressure to distill off the reaction solvent, and the residue is washed with water and separated to obtain an oil layer. Alternatively, it can be isolated by crystallization.

[0033]

The present invention will be described in more detail with reference to the following examples. Example 1 66.0 g of m-phenoxybenzyl alcohol in 0.3 ml of N, N'-dimethylimidazolidinone (0.3
3 mol) and 23.6 g of 95% potassium hydroxide (0.
40 mol) and slowly under a gentle stream of nitrogen.
The temperature was raised to 0 ° C. After being kept under stirring at the same temperature for 1 hour, 3-chloro-4-ethoxyneophylbromide 8 was added.
7.5 g (0.3 mol) was added dropwise over about 2 hours. During this time, the temperature of the reaction solution was 100 ° C. to 101 ° C., and almost no heat generation was observed. After the addition, the reaction was carried out at the same temperature for 4 hours and further at 120 ° C. for 4 hours. After cooling the reaction mass, the reaction mass was discharged into water, extracted with benzene, and the benzene layer obtained after further washing with water was analyzed by high performance liquid chromatography.
The yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether, which is the desired product, is 94.8%.
(Vs. 3-chloro-4-ethoxyneophylbromide).

Comparative Example 1 m-phenoxybenzyl alcohol (66.0 g, 0.3 ml) in 350 ml of N, N'-dimethylimidazolidinone
3 mol), 87.5 g (0.3 mol) of 3-chloro-4-ethoxyneophylbromide and 23.6 g (0.40 mol) of 95% potassium hydroxide, and then, while stirring, adding a gentle nitrogen gas. The temperature was raised in a 100 ° C. oil bath under an air stream. Exothermicity of the reaction liquid started around 85 ° C., and the liquid temperature rose to 110 ° C. in about 10 minutes. After further reacting at 100 ° C. for 4 hours and further at 120 ° C. for 4 hours, the reaction mass was treated in the same manner as in Example 1, and as a result of analysis, it was confirmed that 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was recovered. The rate was 92.6% (vs. 3-chloro-4-ethoxyneophylbromide).

COMPARATIVE EXAMPLE 2 3-chloro-4-ethoxyneophylbromide 87.5 in 350 ml of N, N'-dimethylimidazolidinone
g (0.3 mol) and 95% potassium hydroxide 23.6
g (0.40 mol), the temperature was raised to 100 ° C. under a gentle stream of nitrogen under stirring, and 66.0 g (0.33 mol) of m-phenoxybenzyl alcohol was required for about 2 hours. And dropped. During this time, heat generation of the reaction solution was hardly observed. Thereafter, the reaction was carried out at 100 ° C. for 4 hours and further at 120 ° C. for 4 hours. After the reaction, the reaction mass was treated in the same manner as in Example 1. As a result of analysis, the yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was 84.3%.
(Vs. 3-chloro-4-ethoxyneophylbromide).

Example 2 A reaction was carried out in the same manner as in Example 1 except that the dropping temperature and time of 3-chloro-4-ethoxyneophylbromide were changed to 90 ° C. and 3 hours, respectively.
The yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was 94.1%, and almost no exotherm was observed during the dropwise addition of 3-chloro-4-ethoxyneophyl bromide and during the subsequent reaction. Was.

Example 3 In Example 1, the dropping temperature and time of 3-chloro-4-ethoxyneophylbromide were changed to 120 ° C. and 1.5
The procedure was performed in the same manner as in Example 1 except that the time was changed. After the reaction, the reaction mass was treated in the same manner as in Example 1. As a result of analysis, the yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was 93.4% (vs. 3-chloro-4-ethoxyneo). Filbromide).

Comparative Example 3 A reaction was carried out in the same manner as in Example 1 except that the dropping temperature and time of 3-chloro-4-ethoxyneophylbromide were changed to 65 ° C. and 3 hours, respectively. In the course of raising the reaction temperature to 100 ° C. after dropping, remarkable heat generation of the reaction solution was observed, and the temperature rose 7 ° C. higher than the oil bath temperature.

Comparative Example 4 In Example 1, the dropping temperature and time of 3-chloro-4-ethoxyneophylbromide were respectively changed to 135 ° C. and 2 hours, and the subsequent reaction temperature and reaction time were changed to 135 ° C. and 6 hours. The reaction was carried out in the same manner as in Example 1 except that the reaction was changed to No heat was generated during the dropping, but the yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was 7
8% (vs. 3-chloro-4-ethoxyneophylbromide).

EXAMPLE 4 60.1 g (0.3 mol) of m-phenoxybenzyl alcohol and 9 in 400 ml of dimethyl sulfoxide
26.6 g (0.36 mol) of 5% potassium hydroxide was charged, and the temperature was gradually increased to 100 ° C. under a gentle nitrogen stream.
At the same temperature, 87.5 g (0.3 mol) of 3-chloro-4-ethoxyneophyl bromide was added dropwise over about 2 hours.
Thereafter, the reaction was carried out at the same temperature for 4 hours and further at 120 ° C. for 4 hours. Almost no heat generation was observed during the dropping and the reaction. After the dropwise addition, the same temperature is further added for 4 hours for 120 hours.
The reaction was performed at 4 ° C. for 4 hours. After the reaction, the reaction mass was treated in the same manner as in Example 1. As a result of analysis, the yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether was 90.1%.

Example 5 In Example 4, N, instead of dimethyl sulfoxide was used.
The reaction was carried out in the same manner as in Example 4 except that N'-dimethylpropylene urea was used. The yield of 3-chloro-4-ethoxyneophyl m-phenoxybenzyl ether is 9
1.8%.

[0042]

The method of the present invention is an industrially valuable production method in which rapid heat generation due to the reaction can be suppressed and the desired product can be obtained in high yield.

[Brief description of the drawings]

FIG. 1. In N, N′-dimethylimidazolidinone.
It is a test result of the temporal stability of m-phenoxybenzyl alcohol and 3-chloro-4-ethoxyneophylbromide at 100 ° C. in the presence of 5 molar ratio of potassium hydroxide.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-63-264432 (JP, A) JP-A-59-88440 (JP, A) JP-A-61-200937 (JP, A) JP-A-61-2009 17524 (JP, A) JP-A-58-90525 (JP, A) JP-A-4-253393 (JP, A) JP-A-2-149535 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07C 41/16 C07C 43/257-43/29

Claims (5)

(57) [Claims] 1. A compound represented by the general formula (1): [Wherein, R represents a lower alkyl group having 1 to 4 carbon atoms;
₁ and R ₂ each independently represent a hydrogen atom, a chlorine atom or a bromine atom. In producing the p-alkoxyneophyl m-phenoxybenzyl ethers represented by the formula (1), a solution prepared by dissolving or suspending m-phenoxybenzyl alcohol and an alkali metal hydroxide in an aprotic polar solvent is 70- The solution was heated to 130 ° C., and the solution was treated with the general formula (2) in the solution. Wherein R, R ₁ and R ₂ are the same as those of the general formula (1), wherein p-alkoxyneophyl bromides represented by the general formula (1) are dropped and reacted.
-Alkoxyneophyl m-phenoxybenzyl-
Method for producing tellurium. 2. The method according to claim 1, wherein the reaction temperature is 70 to 130 ° C. 3. The use amount of the p-alkoxyneophyl bromide of the general formula (2) and m-phenoxybenzyl alcohol in a molar ratio of 1.0: 0.8 to 1.2. The described method. 4. The method according to claim 1, wherein the amount of the alkali metal hydroxide used is 1.0 to 2.0 mol ratio to the p-alkoxyneophyl bromide of the general formula (2). 5. An aprotic polar solvent comprising N, N-dimethylformamide, N, N-dimethylacetamide, N, N
One or more selected from -diethylformamide, N, N-diethylacetamide, N-methyl-2-pyrrolidone, N, N'-dimethylimidazolidinone, N, N'-dimethylpropyleneurea or dimethylsulfoxide The method according to claim 1, wherein the solvent is