JPH0144A - 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl bromide derivatives and methods for producing them - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to formula (I). 2-, which represents a bromine atom and R represents a lower alkyl group;
(3-halogeno-4-alkoxyphenyl)-2-methylpropyl bromide derivative, and represented by formula (II) z [in formula (I[), YI, Yz and R have the same meanings as above] The present invention relates to a method for producing 3-halogeno-4-alkoxybenzenes, which is characterized by reacting methallyl bromide at -30 to 50°C in the presence of an acid catalyst.

[Conventional technology]

Recently, it has been known that certain compounds of 3-phenoxybenzyl ether derivatives have extremely high insecticidal and acaricidal activity, and are also known to have extremely low toxicity to fish.

In particular, it has been proposed that 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ethers having the following structure have extremely high activity. (Other than JP-A-58-32840) (In the formula, R represents a lower alkyl group)
Publication No. 32840 describes a method for producing 2-(4-ethoxyphenyl)-2-methylpropyl chloride as an example of 2-(4-alkoxyphenyl)-2-methylpropyl halide, which is the raw material. Known methods [Chem, Ber, 94.2]
609 (I961)), 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 preferential to the 0-position relative to the ethoxy group, and the yield of the desired p-unit is extremely low, and furthermore, it is difficult to separate the desired product from the mixture. , 2-(ethoxyphenyl)-2-methylpropyl chloride has low thermal stability, and therefore cannot be purified by distillation or the like, which is usually used industrially.

Therefore, the present inventors developed the above 3-phenoxybenzyl 2
-(4-Alkoxyphenyl)-2-methylpropyl ethers As a result of intensive study on an industrially more advantageous manufacturing method, we found that in the following formula (ff)C, y, , y, and R are the formula (I). If 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chloride and 3-phenoxybenzyl alcohol are condensed, the alkoxy in the resulting condensate is The halogen at the 0-position relative to the group can be easily eliminated, and the compound (rV) is not an unstable compound like 2-(4-alkoxyphenyl)-2-methylpropyl chloride, so handling and purification are easy. Because of its ease, it was found that the target product could be obtained in high yield, and was first published in Japanese Patent Application Publication No. 6
0-45542, 59-88440 and 59-73
No. 535 discloses a method for producing the compound 2-(3-halogeno-4-alkoxyphenyl)-2-methylpro and luchloride of the formula (rV), and a condensate of the compound of the formula (IV) and 3-phenoxybenzyl alcohol. The above formula (III
) A method for producing the compound 3-phenoxybenzyl 2-(4-alkoxyphenyl)-2-methylpropyl ether was provided. These series of inventions use the formula (n) compound, which can be obtained at low cost, as a starting material to obtain a compound of formula (! When carried out, 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 the case of 2-(4-alkoxyphenyl)-2-methylpro and chloride. This was an excellent industrial manufacturing method.

However, as shown in JP-A-59-88440, 2-(3-chloro-4-alkoxyphenyl)
- Even if 2-methylpropyl chloride and m-phenoxybenzyl alcohol are reacted in an aprotic polar solvent in the presence of a base, the resulting condensate is 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)- The yield of 2-methylpropyl ether was about 50% at most, which was still unsatisfactory as an industrial method.

The reason for the low yield is 2-(3-halogeno-4-
The carbon atom to which the chlorine atom, which is the leaving group of the alkoxyphenyl)-2-methylpropyl chloride, is bonded is a phenethyl group, and furthermore, the carbon atom at the benzyl position has 2
This was thought to be due to the presence of 3 methyl groups, which are very sterically complex, causing dehydrochlorination and rearrangement reaction before condensation with m-phenoxybenzyl alcohol. 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. As shown in the formula, it was found that high yields could not be expected because the reaction of dehydrochlorination and rearrangement products was in a competitive state. In addition, several types of by-products caused by the rearrangement reaction product 4-alkoxy-isobutenylbenzene derivative were produced, complicating the purification process.

On the other hand, with regard to agricultural chemicals, environmental pollution caused not only by the active ingredients but also by the 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.

[Problem that the invention seeks to solve]

The present invention solves the above-mentioned problems by providing a 3-phenoxybenzyl ether derivative having a 2-(4-alkoxyphenyl)-2-methylpropyl group as a very useful raw material for an insecticide or various intermediates. An object of the present invention is to provide an improved compound 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 problems] In order to solve the above-mentioned problems, the present inventors conducted intensive studies with the aim of improving the condensation yield. −
When using halogeno-4-alkoxyphenyl)-2-methylpropyl bromides, they are thermally unstable like 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl chlorides; Since the reactivity of the bromine atom, which is a leaving group, is significantly superior to that of the chlorine atom, it is possible to lower the reaction temperature and shorten the reaction time, and the generation of isobutenyl derivatives due to rearrangement reactions during the reaction is suppressed. The present invention was completed based on the discovery that the yield was significantly improved as a result.

That is, in the present invention, in the formula (C formula N), one of Yls Yt 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- shown
(3-halogeno-4-alkoxyphenyl)-2-methylpropylbromide derivative and formula (■) IY.

c In the formula (II), y, y, and R have the same meanings as above.] 3-halogeno-4-alkoxybenzenes represented by 2-(3-halogeno-4) characterized by reacting with lyl bromide
-alkoxyphenyl)-2-/tylpropylbromide derivative.

The compound of the formula (n) according to the present invention is a compound of the formula (n
) is a new compound that can be easily obtained with high purity and high yield by the production method according to the present invention using the compound as a starting material.

When the alkylation reaction with methallyl bromide is carried out using the compound of formula (■) in the same way as the reaction with methallyl chloride in the previously filed JP-A No. 60-45542, the alkylation reaction with methallyl bromide is selectively performed on the alkoxy group. The reaction can be carried out only at the p-position, and there are also fewer 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. The invention is formula (III)
This provides great economic efficiency to industrial methods of producing compounds.

For example, even in the case of monochloroalkoxybenzene in which Yt is chlorine and Y is hydrogen in the compound of formula (U), in the method of the present invention, methallyl bromide is preferentially introduced at the 4-position relative to the alkoxy group. The majority of p-units are produced, and almost no 0-isomer introduced at the 6-position is produced, and this tendency is stronger than when methallyl chloride is used. Also, there are fewer by-products of isobutenyl derivatives. Moreover, when the obtained compound of formula (I) was used in the next condensation step, the condensation yield was also significantly improved.

The compound of formula (II) used as a raw material can be produced industrially at low cost. For example, in the case of O-chlorophenol, it can be produced by ethylation of O-chlorophenol with an alkylating agent, ethoxylation of O-dichlorobenzene, etc. It can be easily obtained according to conventional methods. Furthermore, methallyl bromide can be easily synthesized by bromination of methallyl alcohol and isobutylene.

The compounds of formula (I) according to the present invention include 2-chloro-methoxybenzene, 2,6-cyclomidoxybenzene, 2-
Promomethoxybenzene, 2,6-difuromomethoxybenzene, 2-chloro-ethoxybenzene, 2,6-
By reaction of a compound of formula (II) such as cyclonitoxybenzene, 2-promoethoxybenzene, 2,6-dibromo-ethoxybenzene, 2-chloro-propoxybenzene, 2-promopropoxybenzene and methallyl bromide, the following Manufactured by

Methallyl bromide is used in an amount of 0.5 to 10 moles, preferably 1 to 5 moles, per mole of 2-halogeno-alkoxybenzene represented by formula (II). 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, nitromethane, which is used in the usual Friedel-Crafts reaction,
Solvents such as acetonitrile and carbon disulfide can also be used.

In addition, in the method of the present invention, the reaction is carried out in the presence of an acid catalyst, and acid catalysts include concentrated sulfuric acid, methanesulfonic acid, strongly acidic ion exchange resins (Amberlyst, Nafion, etc.), trifluoromethanesulfonic acid, zeolite, etc. ,
Examples include hydrofluoric acid and boron fluoride.

The proportion of these acid catalysts used is 0.1 to 2.0 mol, preferably 0.5 to 1 mol, per 1 mol of methallyl bromide.
．． Use 2 moles. If the ratio used is out of this range, the reaction will be slow (or more by-products will be produced, resulting in a lower yield).

The reaction temperature is -30 to 50°C, preferably -20 to 30°C.
Perform at °C.

Methallyl bromide tends to deteriorate into polymers such as dimers if it remains in the presence of an acid catalyst for a long time, and if the conditions differ from the above, the reaction rate will be slow (or more by-products will be produced). This is not preferred, and for the same reason, the method of charging each raw material is preferably to dropwise charge methallyl bromide into a mixed solution of the compound of formula (II) 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 explained in detail with reference to Examples, but it goes without saying that the present invention is not limited to these.

Example-1 Synthesis of 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide A reaction vessel was charged with 208.9 g of 0-chlorophenetol and 15 g of trifluoromethanesulfone M, and mixed for 50 minutes.
The temperature was raised to ℃.

135 g of methallyl bromide was added dropwise to this mixture at 50° C. over a period of 2 hours. After that, 6 was aged at the same temperature for 2 hours.
After the reaction solution was cooled, it was poured into 500+*L of water to separate the oil layer. The oil layer is 30 (Im J of water is 2
After washing with 5% NaOH and 1 water five times, dehydration was performed to obtain a crude product. After removing excess 0-chlorophenetol under reduced pressure, the desired product was distilled.

b, 9.140-142℃ 10.51 cranes 11g Yield 256.6g Yield 88% (based on methallyl bromide) Crude 2-(3-chloro-4-ethoxyphenyl)-2-methyl before distillation purification As a result of HPLC analysis of propyl bromide using an internal standard method, the composition was as follows.

2-(3-chloro-4-ethoxyphenyl)-2-methylpropylbromide 94.2% isomer Undetected dialkyl substituent 1.3% lR11 kinetics v Nini',"(elm-') 2975. 29
30.2880, 1600.1500°1470, 14
00.1300.1270.1060°1040.80
The 0,740,610 1R spectrum is shown in Figure-1.

NMR spectrum δ""3: 1.4 (s, 6H), 1.3~
1.6 (s+3H) 3.5 (s, 2H), 3.9~4
．． 3 (q, 2H) 6.8-7.4 (s, 3H) ppm Elemental analysis results (as CttH+JrCJ!O) CHB
r Cj Actual value (χ) 49.41 5.64 27.30
12.13 Calculated value (χ'I 49.42 5.53
27.40 12.15 Example-2 Synthesis of 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide 159.2 g of 0-chlorophenetol was charged into a reaction vessel. Cool this liquid to -10℃, and at the same temperature, 98%
50 g of sulfuric acid was added over a period of 1-5 minutes. After stirring the mixture thoroughly, 68 g of methallyl bromide was added dropwise at -10°C over a period of 2 hours. Stir at the same temperature for 5 hours.
The ripening reaction occurred.

Post-treatment was carried out in the same manner as described above. Yield 123g Yield 8
4.2% (vs. methallyl bromide).

In addition, as a result of HPLC analysis of crude 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide before distillation purification using an internal standard method, it had the following composition.

2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl bromide 94.8%
Characteristics Undetected dialkyl substituent 1.2% Comparative example-1 Synthesis of 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl chloride 159.2 g of O-chlorophenetol was placed in a 300 m j four-bottle flask. The reactor was charged, kept cool at -10°C, and 50 g of 98% sulfuric acid was added. After stirring this mixture thoroughly, 45.3 g of methallyl chloride was added dropwise at the same temperature over a period of 2 hours. Stir at the same temperature for 5 hours to cause a ripening reaction.
The reaction solution was discharged into water (500 sj) and separated into an oil layer and an aqueous layer. After washing the lower layer of oil with warm water and dehydrating it, remove excess O.
-Chlorophenetol lQa+mHg.

Distilled at 130-170°C, crude 2-(3-
105.8 g of chloro-4-ethoxyphenyl-2-methylpropyl chloride were obtained.

(HPLC internal standard method purity 93.5%, yield 80.0%
/methallyl chloride) Crude 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl chloride was analyzed by IIPLc using the internal standard method, and as a result, it had the following composition.

2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl chloride 93.5% isomer
1.1% dialkyl substituted product 1.3% Example-
Synthesis of 3,4,5 2-(3-chloro-4-methoxyphenyl)-2-methylpropyl bromide 24.0 g of O-chloroanisole was charged into a reaction vessel. Cool this liquid to -10℃, and at the same temperature 98% sulfur #8
．． 25g was added over a period of 1-5 minutes.

While stirring this mixture, 11.36 g of methalinobromide was added dropwise over 1 hour at -10°C. After stirring and aging at the same temperature for 4 hours, the reaction solution was cooled for 100 m
Pour the separated oil layer into 200 m of benzene water.
The extract was washed with water and 1% water (5% NJIO) in that order, and then dehydrated and concentrated with sodium sulfate (anhydrous) to obtain a crude product. Excess O-
After chloroanisole was distilled off under reduced pressure, the residue was purified using silica gel column chromatography to obtain 18 g of the desired product. Yield 77.0% (based on methallyl bromide).

Similarly, the yield and physical property values obtained when 0-promophenetol or 2-chloropropoxybenzene was used in place of 0-chloroanisole are shown in the table below.

(Left below) Next, using the compound of the present invention 2-(3-halogeno-4-alkoxyphenyl)-2-methylpro and rubromides, 3
-2-(3-halogeno-4-alkoxyphenyl)-2 when condensed with phenoxybenzyl alcohols
- Comparison with the case of using methylpropyl chlorides is shown in Reference Examples and Reference Comparative Examples.

Reference Example In a reaction vessel equipped with a stirrer, thermometer and cooler, 2-(3
-chloro-4-ethoxyphenyl)-2-methylpropylbromide 14.9 g, 3-phenoxybenzyl alcohol-), 25 g, flaked potassium hydroxide 5.9 g
and 1,3-dimethyl-2-imidazolidinone 60-1
was inserted, heated to 120°C while stirring under a nitrogen stream, and stirred at the same temperature for 5 hours.

After cooling the reaction mixture to room temperature, it was poured into 300 mj of water and made weakly acidic using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using 100 ml of benzene, 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 36.1 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
It contained 49.9% of -ethoxyphenyl)-2-methylpropyl ether.

The yield of the target product was 85.9% [2-(3-chloro-4-ethoxyphenyl)-2-methylpro and lupromide].

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 result C□H*qCIOs CHC1 Calculated value (%) 73.0? 6.62 8.6
3 Actual measurement value (%)? 2.93 6.65 8.7
ONMR spectrum δ well: 1.2B(s, 6H), 1.4(t,
3H) , 3.35(s, 2H), 4, (I(q, 2H
), 4.39 (s, 2H), 6.68 ~ 7.32 (s
, 12H) pP - Reference side comparative example 2-(3
-chloro-4-ethoxyphenyl)-2-methylpropyl chloride 6.2 g, 3-phenoxybenzyl alcohol 6.0 g, flaky sodium hydroxide 6.0 g and 1,3-dimethyl-2-imidazolidinone 30- The mixture was heated to 140° C. while stirring under a nitrogen stream, and stirred at the same temperature for 15 hours.

After the reaction mixture was cooled to room temperature, it was discharged into 200 sl of water and made weakly acidic using concentrated hydrochloric acid. The precipitated oil layer was extracted three times using Benzene 50-1, 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, 42% of 3-phenoxybenzyl 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl ether was found.
．． It contained 3%.

The yield of the target product was 50.2% [to 2-(3-chloro-4-ethoxyphenyl)-2-methylpropyl chloride].

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.

〔Effect of the invention〕

As is clear from the above explanation, the compound of the present invention has 3-phenoxybenzyl 2- which is useful as an insecticide with low fish toxicity.
It is important as a raw material intermediate for (4-alkoxyphenyl)-2-methylpropyl ether derivatives, and the well-known 2-(3
-Chloro-4-ethoxyphenyl)-2-methylpropyl chloride causes fewer side reactions, provides a condensate with 3-phenoxybenzyl alcohol in extremely high yield, and is industrially more useful.

[Brief explanation of the drawing]

Figure 1 is 2-(3-chloro-4-ethoxyphenyl)-
The IR spectrum of 2-methylpropyl bromide is shown. Patent applicant Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Claims] 1. Formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) [In formula (I), one of Y_1 and Y_2 represents a chlorine atom or a bromine atom, and the other represents a hydrogen atom. , represents a chlorine atom or a bromine atom, and R represents a lower alkyl group. ] 2-(3-halogeno-4-alkoxyphenyl)-2
-Methylpropyl bromide derivative. 2. Formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) [In formula (II), one of Y_1 and Y_2 represents a chlorine atom or a bromine atom, and the other represents a hydrogen atom, a chlorine atom, or a bromine atom. and R represents a lower alkyl group. Formula (I), which is characterized by reacting 3-halogeno-4-alkoxybenzenes represented by 3-halogeno-4-alkoxybenzenes at -30 to 50°C in the presence of an acid catalyst, includes mathematical formulas, chemical formulas, tables, etc. ▼(I) [In formula (I), Y_1, Y_2 and R have the same meanings as above. ] A method for producing a 2-(3-halogeno-4-alkoxyphenyl)-2-methylpropyl bromide 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 formula (n) is mixed with an acid catalyst, and then the reaction is carried out while adding methallyl bromide. Method.