JPH045659B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention is based on the formula () [In formula (), one of Y ₁ and Y ₂ represents a chlorine atom or a bromine atom, the other represents a hydrogen atom, a chlorine atom, or a bromine atom, and R represents a lower alkyl group. ] 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropylbromide derivative,
and expression () [In formula (), Y ₁ , Y ₂ and R have the same meanings as above. ] The present invention relates to a method for producing 3-halogeno-4-alkoxybenzenes represented by the following, which is characterized by reacting methallyl bromide at -30 to 50°C in the presence of an acid catalyst. [Prior Art] Recently, it has been known that certain compounds of 3-phenoxybenzyl ether derivatives have extremely high insecticidal and acaricidal activity, and that they have extremely low toxicity to fish. It is being In particular, 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2 having the following structure:
-Methylpropyl ethers are known to have extremely high activity. (Outside of JP-A No. 58-32840) (In the formula, R represents a lower alkyl group.) JP-A-58-32840 describes 2-(4-alkoxyphenyl)-2-methylpropyl halide as an example of its raw material. There is a description of a method for producing 4-ethoxyphenyl)-2-methylpropyl chloride, which is prepared by a known method [Chem.Ber. 94 , 2609 (1961)].
That is, 2-(4-ethoxyphenyl)-2-methylpropyl chloride is obtained by reacting phenetol and methallyl chloride at 0 to 10°C in the presence of concentrated sulfuric acid. However, in this case, the bonding position of the chloroalkyl group in the side chain is preferentially at the o-position relative to the ethoxy group, and the yield of the desired p-isomer is very low. However, since 2-(ethoxyphenyl)-2-methylpropyl chloride has low thermal stability,
Normally, industrial purification such as distillation cannot be used. Therefore, the present inventors have intensively investigated an industrially more advantageous manufacturing method for the above-mentioned 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ethers, and found that the following formula () [In the formula, Y ₁ , Y ₂ and R have the same meanings as in the above formula (). ] 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chloride and 3-
When condensed with phenoxybenzyl alcohol,
The halogen at the o-position relative to the alkoxy group in the obtained condensate can be easily eliminated, and the compound () is 2-(4-alkoxyphenyl)-2-
Since it is not an unstable compound like methylpropyl chloride, it is easy to handle and purify, and it was found that the desired product could be obtained in high yield.
-45542, 59-88440 and 59-73535,
A method for producing the compound of formula () 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chloride, a method for producing a condensate of the compound of formula () and 3-phenoxybenzyl alcohol, and The above formula () compound 3-phenoxybenzyl 2-(4
-alkoxyphenyl)-2-methylpropyl ether is provided. In these series of inventions, the formula () compound, which is available at low cost, is used as a starting material to obtain the formula () compound, and when the formula () compound is subjected to an alkylation reaction with methacryl chloride, It is possible to selectively react only at the p-position with respect to alkoxy groups, and the yield of the condensation reaction is also improved compared to that of 2-(4-alkoxyphenyl)-2-methylpropyl chloride, allowing industrial production. It was an excellent legal method. However, as shown in JP-A-59-88440, 2-(3-chloro-4-alkoxyphenyl)-2-methylpropyl chloride and m-phenoxybenzyl alcohol are mixed in an aprotic polar solvent. Even if the reaction is carried out in the presence of a base, the resulting condensate 3-phenoxybenzyl 2-(3-chloro-
The yield of 4-ethoxyphenyl)-2-methylpropyl ether was at most about 50%, which was still unsatisfactory as an industrial method. The reason for the low yield is that the carbon atom to which the chlorine atom, which is the leaving group of 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chloride, is bonded is a phenethyl group. , Furthermore, because there are two methyl groups at the benzyl carbon atom, it is sterically very complicated, and m-
Before condensation with phenoxybenzyl alcohol,
This was thought to be due to dehydrochlorination causing a rearrangement reaction. In fact, 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chloride is difficult to react with to form the desired condensation product, benzylpropyl ether, and is unstable to heat. After dehydrochlorination as shown in the formula below, It was found that high yields could not be expected as a result of the competitive reaction resulting in rearrangement products. In addition, several types of by-products are generated due to the rearrangement reaction product 4-alkoxy-isobutenylbenzene derivative,
Complicated the purification process. On the other hand, with regard to agricultural chemicals, environmental pollution caused not only by active ingredients but also by impurities contained therein is a problem, and it is desirable to have fewer impurities, whether they are caused by raw materials or reactions. Therefore, raw materials and intermediates that contain fewer impurities and fewer side reactions are desired. [Problems to be Solved by the Invention] The present invention solves the problem of 2-(4-alkoxyphenyl)-2 among 3-phenoxybenzyl ether derivatives.
- It is an object of the present invention to provide a compound that is an extremely advantageous raw material for insecticides having a methylpropyl group or various intermediates, and that has improved the above-mentioned problems, and a method for producing the same. More specifically, it is an object of the present invention to provide a raw material compound that produces fewer by-products and provides a higher condensation yield in the next condensation step. [Means and effects for solving the problem] In order to solve the above problem, the present inventors conducted extensive studies with the aim of improving the condensation yield, and as a result, the 2-(3 -When using halogeno-4-alkoxyphenyl-2-methylpropyl bromides, the reactivity of the bromine atom, which is a leaving group, is significantly superior to that of chlorine atom, so the reaction temperature can be lowered and the reaction time can be reduced. The present invention was completed by discovering that the production of isobutenyl derivatives due to the rearrangement reaction during the reaction is suppressed and the yield is significantly improved. [In formula (), one of Y ₁ and Y ₂ represents a chlorine atom or a bromine atom, the other represents a hydrogen atom, a chlorine atom, or a bromine atom, and R represents a lower alkyl group. ] 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropylbromide derivative,
and expression () [In formula (), Y ₁ , Y ₂ and R have the same meanings as above. ] The 2-(3-alkoxybenzene shown by
This is a method for producing -halogeno-4-alkoxyphenyl)-2-methylpropyl bromide derivative. The compound of formula () according to the present invention is a novel compound that can be easily obtained with high purity and high yield by the production method according to the present invention using the compound of formula () that is available at low cost as a starting material. When the alkylation reaction with methallyl bromide is carried out using the compound of formula (), similar to the reaction with methallyl chloride in the previously filed Japanese Patent Application Laid-Open No. 60-45542, p selectively reacts with respect to the alkoxy group. It is possible to react only at the - position, and in addition, there are few by-products due to the rearrangement reaction. Furthermore, when the compound of the present invention is used, by-products in the next condensation step are reduced, and the condensation yield is significantly improved, so that the present invention provides great economic efficiency to the industrial production method of compounds of formula (). For example, even in the case of monochloroalkoxybenzene in which Y ₁ is chlorine and Y ₂ is hydrogen in the compound of formula (), in the method of the present invention, methallyl bromide is selectively introduced at the 4-position relative to the alkoxy group, and p The - isomer is the majority, and the o-isomer introduced at the 6-position is hardly produced, and this tendency is stronger than when methallyl chloride is used. Furthermore, there is little by-product of isobutenyl derivatives. Furthermore, when the obtained compound of formula () was used in the next condensation step, the condensation yield was also significantly improved. The raw material compound of formula () can be produced industrially at low cost. For example, in the case of o-chlorophenetol, conventional methods such as ethylation of o-chlorophenol with an alkylating agent or ethoxylation of o-dichlorobenzene are used. can be easily obtained according to the law. Furthermore, methallyl bromide can be synthesized by bromination of methallyl alcohol and isobutylene. The compound of formula () according to the present invention is 2-chloro-
Methoxybenzene, 2,6-dichloro-methoxybenzene, 2-bromo-methoxybenzene, 2,
6-dibromo-methoxybenzene, 2-chloro-
Ethoxybenzene, 2,6-dichloro-ethoxybenzene, 2-bromo-ethoxybenzene, 2,
6-dibromo-ethoxybenzene, 2-chloro-
It is produced as follows by reacting a compound of formula () such as bropoxybenzene or 2-bromo-bropoxybenzene with methallyl bromide. 0.5 methallyl bromide per mol of 2-halogeno-alkoxybenzene represented by formula ()
~10 moles are used, preferably 1 to 5 moles. If the usage ratio is out of this range, the reaction will be slow or more by-products will be produced, resulting in a significant drop in productivity. Although the method of the present invention can be carried out without a solvent, it is also possible to use solvents such as nitromethane, acetonitrile, carbon disulfide, etc., which are commonly used in Friedel-Crafts reactions. In addition, in the method of the present invention, the reaction is carried out in the presence of an acid catalyst, and the acid catalyst may include concentrated sulfuric acid,
Examples include methanesulfonic acid, strongly acidic ion exchange resins (Amberlyst, Nafion, etc.), trifluoromethanesulfonic acid, zeolite, hydrofluoric acid, boron fluoride, and the like. The proportion of these acid catalysts used is 0.1 to 2.0 mol, preferably 0.5 mol, per 1 mol of methallyl bromide.
~1.2 mol is used. If the ratio used is outside this range, the reaction will be slow or more by-products will be produced, resulting in a lower yield. The reaction temperature is -30~50℃, preferably -20~30℃
Perform at °C. Methallyl bromide tends to deteriorate into polymers such as dimers if it stays in the presence of an acid catalyst for a long time, and if the conditions differ from the above, the reaction rate will slow down and more by-products will be produced, so this is not preferred. do not have. For the same reason, it is preferable to charge each raw material by dropping methallyl bromide into a mixed solution of the compound of formula () and the catalyst to carry out the reaction. Usually, methallyl bromide is added dropwise in 0.5 to 2 hours, and after the dropwise addition is completed, the aging reaction is continued for another 2 to 6 hours to complete the reaction. [Example] Next, the method of the present invention will be specifically explained with reference to Examples, but it goes without saying that the present invention is not limited to these. Example 1 2-(3-chloro-4-ethoxyphenyl)-2
-Synthesis of methylpropyl bromide In a reaction vessel, 208.9 g of o-chlorophenetol,
15 g of trifluoromethanesulfonic acid was charged, mixed, and heated to 50°C. 135 g of methallyl bromide was added dropwise to this mixture at 50° C. over a period of 2 hours. Thereafter, an aging reaction was carried out at the same temperature for 2 hours. After cooling the reaction solution, pour it into 500ml of water.
The separated oil layer was separated. The oil layer is 2 with 300ml of water.
After washing with 5% NaOH and water 5 times, dehydration was performed to obtain a crude product. After removing excess o-chlorophenethole under reduced pressure, the desired product was distilled. bp140-142℃/0.5mmHg Yield 256.6g Yield
88% (based on methallyl bromide) As a result of HPLC analysis of crude 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide before distillation using the internal standard method, the following composition was found: It was hot. 2-(3-chloro-4-ethoxyphenyl)-2
-Methylpropyl bromide 94.2% Isomer Undetected dialkyl substituent 1.3% IR frequency ν ^fiLm _nax (cm ^-1 ) 2975, 2930, 2880, 1600, 1500,
1470, 1400, 1300, 1270, 1060, 1040, 800,
The 740 and 610 IR spectra are shown in Figure 1. NMR spectrum δ ^CDCL3 _TMS : 1.4 (s, 6H), 1.3-1.6 (s, 3H), 3
.Five
(s, 2H), 3.9-4.3 (q, 2H), 6.8-7.4 (m,
3H) ppm Elemental analysis results (as C ₁₂ H ₁₆ BrClO) C H Br Cl Actual value (%) 49.41 5.64 27.30 12.13 Calculated value (%) 49.42 5.53 27.40 12.15 Example 2 2-(3-chloro-4-ethoxyph enyl)-2
-Synthesis of methylpropyl bromide A reaction vessel was charged with 159.2 g of o-chlorophenetol. Cool this liquid to -10℃, and at the same temperature
50 g of 98% sulfuric acid was added over 1-5 minutes. After stirring the mixture well, 68 g of methallyl bromide was added dropwise at -10°C over a period of 2 hours. The mixture was stirred at the same temperature for 5 hours to undergo a ripening reaction. Post-treatment was carried out in the same manner as described above. Yield 123g
Yield 84.2% (based on methallyl bromide). In addition, crude 2-(3-chloro-4-
As a result of HPLC analysis of ethoxyphenyl-2-methylpropyl bromide using an internal standard method, it had the following composition. 2-(3-chloro-4-ethoxyphenyl)-2
-Methylpropyl bromide 94.8% Isomer Undetected dialkyl substituent 1.2% Comparative example 1 2-(3-chloro-4-ethoxyphenyl)-2
-Synthesis of methylpropyl chloride 159.2 g of o-chlorophenetol was placed in a 300 ml four-necked flask, kept cool at -10°C, and 98% sulfuric acid 50
g was added. After stirring the mixture thoroughly, 45.3 g of methallyl chloride was added dropwise at the same temperature over a period of 2 hours. The mixture was stirred at the same temperature for 5 hours to undergo a ripening reaction. The reaction solution is discharged into water (500 ml) and the oil layer and water layer are separated. After washing the lower layer of oil with warm water and dehydrating it, remove excess o-chlorophenetol (10 mmHg),
Distilled at 130-170℃, crude 2-(3-
105.8 g of chloro-4-ethoxyphenyl)-2-methylpropyl chloride was obtained. (HPCL internal standard method purity 93.5%, yield 80.0%/
(methallyl chloride) crude 2-(3-chloro-4-ethoxyphenyl)-
As a result of analyzing 2-methylpropyl chloride by HPLC using the internal standard method, it had the following composition. 2-(3-chloro-4-ethoxyphenyl)-2
-Methylpropyl chloride 93.5% Isomers 1.1% Dialkyl substituted products 1.3% Examples 3, 4, 5 2-(3-chloro-4-methoxyphenyl)-2
-Synthesis of methylpropyl bromide A reaction vessel was charged with 24.0 g of o-chloroanisole. Cool this liquid to -10℃, and at the same temperature 98%
8.25 g of sulfuric acid was added over 1-5 minutes. While stirring the mixture, 11.36 g of methallyl bromide was added dropwise at -10°C over 1 hour. The mixture was stirred and aged at the same temperature for 4 hours. After cooling, the reaction solution was poured into 100ml of water and the separated oil layer was mixed with benzene.
Extracted with 200ml (100ml x 2). The extract is water, 5
After washing in this order with % NaOH and water, the mixture was dehydrated with sodium sulfate (anhydrous) and concentrated to obtain a crude product. excessive o
- After chloroanisole was distilled off under reduced pressure, the product was purified using silica gel column chromatography to obtain 18 g of the desired product. Yield 77.0% (based on methallyl bromide). Similarly, change to o-chloroanisole and o
The yield and physical property values when carried out using -bromophenethole or 2-chloropropoxybenzene are shown in the table below.

〔Effect of the invention〕

As is clear from the above description, the compound of the present invention is frequently used as a raw material intermediate for 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ether derivatives useful as low fish toxicity insecticides. 3-(3-chloro-4-ethoxyphenyl)-2-methylpropyl chloride is produced with fewer side reactions and in extremely high yield.
It gives a condensate with phenoxybenzyl alcohol and is industrially more useful.

[Brief explanation of drawings]

Figure 1 shows the IR spectrum of 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide.

Claims (1)

[Claims] 1 Formula () [In formula (), one of Y ₁ and Y ₂ represents a chlorine atom or a bromine atom, the other represents a hydrogen atom, a chlorine atom, or a bromine atom, and R represents a lower alkyl group. ] 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropylbromide derivative. 2 formula () [In formula (), one of Y ₁ and Y ₂ represents a chlorine atom or a bromine atom, the other represents a hydrogen atom, a chlorine atom, or a bromine atom, and R represents a lower alkyl group. ] Formula () characterized by reacting 3-halogeno-4-alkoxybenzenes represented by methallyl bromide at -30 to 50°C in the presence of an acid catalyst. [In formula (), Y ₁ , Y ₂ and R have the same meanings as above. ] A method for producing a 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropylbromide derivative. 3. The method according to claim 2, wherein the acid catalyst is trifluoromethanesulfonic acid or concentrated sulfuric acid. 4. The method according to claim 2, wherein the 3-halogeno-4-alkoxybenzene represented by the formula () is mixed with an acid catalyst, and then the reaction is carried out while adding methallyl bromide.