JPH0231701B2 - ARUKOKISHINEOFUIRUKURORIDORUIOYOBISONOSEIZOHOHO - Google Patents

Description

[Detailed description of the invention]

The present invention relates to alkoxyneofyl chlorides and a method for producing the same, and more specifically, the present invention relates to the formula () {In formula (), R ³ represents a lower acyl group and R ⁴ represents a hydrogen atom or a halogen atom} An alkylating agent and a base are added to the acyloxyneofyl chloride represented by the formula () in the presence or absence of an inert solvent. or expression() {In formula (), R ⁴ represents the same meaning as in formula () above} By reacting an alkylating agent and a base with an alkylating agent and a base in the presence or absence of an inert solvent, the formula ( ) {In formula (), R ¹ represents a lower alkyl group, and R ² represents a hydrogen atom or a halogen atom. However, when R ¹ is a methyl group, R ² is a halogen atom. } The present invention relates to a method for producing a corresponding alkoxyneofyl chloride represented by the following. The alkoxyneophyl chloride represented by the formula () is a new compound and a compound useful as an intermediate for pyrethroid insecticides. In recent years, synthetic pyrethroid insecticides have been in the spotlight as insecticides. This is because, along with its excellent insecticidal power, it is highly effective against pests resistant to organic phosphorus or carbamate agents, and is characterized by relatively low toxicity to humans. However, the disadvantage of this synthetic pyrethroid insecticide is that it is highly toxic to fish, which limits its range of use. Recently, the applicant has applied the general formula () {In formula (), R ⁵ and R ⁶ are the same or different hydrogen atoms, halogen atoms, cyano groups, nitro groups, or optionally substituted lower alkyl groups, lower alkenyl groups, lower alkoxy groups, acyloxy groups, lower alkylthio group, lower acyl group, and methylenedioxy group. ^R7 and ^R8
represent the same or different hydrogen atoms, halogen atoms, lower alkyl groups, or lower alkoxy groups} The 2-phenylpropyl ether derivatives shown in the following have extremely high insecticidal and acaricidal activity, and have excellent immediate and residual effects. The application was made after discovering that it has excellent characteristics and is low toxicity not only to humans but also to fish. (Special application 1982-148279). 2-phenylpropyl ether derivatives in which R ⁵ is substituted at the p-position with an alkoxy group in the above general formula () are insecticides that exhibit particularly excellent effects, and the alkoxyneophyl chlorides shown in the above formula () are Although it is useful as an intermediate raw material for the 2-phenylpropyl ether derivative represented by the formula (), it is a new compound that has never been synthesized before. A possible method for synthesizing alkoxyneophyl chlorides is to react alkoxybenzenes with methallyl chloride in the presence of an acid catalyst, but in this case, the yield to the p-isomer of the product is low and The result is a mixture of o-isomers and p-isomers, and these isomers have similar physical properties, making separation difficult. As a result of various studies on the production method of alkoxyneofyl chlorides, the present inventors found that hydroxyneofyl chlorides obtained by hydrolysis of acyloxyneofyl chlorides are reacted with an alkylating agent in the presence of a base. The inventors discovered that alkoxyneofyl chlorides and alkoxyneofyl chlorides can be easily obtained with high purity, and as a result of intensive study, the present invention was completed. Furthermore, it was found that alkoxyneofyl chlorides can be obtained directly from acyloxyneofyl chlorides in a one-step reaction without isolating hydroxyneofyl chlorides obtained by hydrolysis of acyloxyneofyl chlorides,
The present invention has been completed. In the present invention, the alkoxyneophyl chloride has the general formula () It is indicated by. In formula (), R ¹ represents a lower alkyl group, and R ² represents a hydrogen atom or a halogen atom.
However, when R ¹ is a methyl group, R ² is a halogen atom. Specifically, R ¹ is a methyl group, an ethyl group, n
-propyl group, i-propyl group, n-butyl group,
i-butyl group, sec-butyl group, etc., and ^R2 represents hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, etc. Examples of these alkoxyneophyl chlorides include the following compounds. That is, o-
Examples include ethoxyneofyl chloride, m-ethoxyneofyl chloride, p-ethoxyneofyl chloride, m-chloro-p-ethoxyneofyl chloride, and the like. The acyloxyneofyl chloride used as a raw material in the present invention has the formula () , R ³ is a lower acyl group, R ⁴ is a hydrogen atom,
Represents a halogen atom, specifically R ³ represents an acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, pivalyl group, etc. R ⁴ represents a hydrogen atom, a fluorine atom, a chlorine atom,
Represents a bromine atom, an iodine atom, etc. Examples of these acyloxyneofyl chlorides include the following compounds. That is, p-acetoxyneofyl chloride, m
-acetoxyneofyl chloride, o-acetoxyneofyl chloride, p-propionyloxyneofyl chloride, p-butyryloxyneofyl chloride, p-pivalyloxyneofyl chloride, etc., and these acyloxyneofyl chlorides is the corresponding acyloxy t-
Obtained by chlorinating butylbenzene. In addition, the hydroxyneofyl chloride used as a raw material for another synthesis method in the method of the present invention has the formula () R ⁴ represents the same meaning as in formula () above, and specifically R ⁴ represents a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc. Examples of these hydroxyneofyl chlorides include the following compounds. That is, p-hydroxyneofyl chloride, m
-hydroxyneofyl chloride, o-hydroxyneofyl chloride, etc., and these hydroxyneofyl chlorides can be obtained by hydrolysis of the corresponding acyloxyneofyl chlorides. In the production method of the present invention, the target product alkoxyneofyl chloride obtained from formula () and the alkoxyneofyl chloride obtained from formula () are almost the same in yield and purity. Therefore, it is advantageous for the production method to use the formula () as a raw material and simultaneously carry out hydrolysis and subsequent alkylation reactions in one step in the presence of a base. In addition, in the alkylation reaction, even if the acyl neophyl chloride or hydroxyneophyl chloride has a substituent such as a halogen atom as a nuclear substituent, the alkylating agent is selective only with the acyl group or hydroxyl group. , so there is no increase in by-products. Alkylating agents used in the process of the invention include dialkyl sulfates such as dimethyl sulfate, diethyl sulfate, etc., ethyl bromide, ethyl iodide,
Alkyl halides such as ethyl chloride, n-butyl bromide etc., alkyl sulfates such as sodium ethyl sulfate etc., aromatic sulfonate esters such as ethyl p-toluenesulfonate, methyl benzenesulfonate etc., diazomethane and Dialkyl sulfates are the preferred alkylating agents, although/or olefins such as propylene and the like can be used. The amount used is 0.5 to 50 mol, preferably 0.5 to 50 mol, per 1 mol of the raw material acyloxyneofyl chloride or oxyneofyl chloride.
It is 1.0 to 20 moles. If the amount used is less than this, the yield will be poor and a large amount of by-products will be produced, and if it is more than this, an operation to remove the alkylating agent will be required after the reaction, which is uneconomical. The bases used in the present invention include alkali metal, ammonium, and alkaline earth metal hydroxides, carbonates, phosphates, borates, and organic bases, specifically sodium hydroxide and potassium hydroxide. , lithium hydroxide, ammonium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, ammonium carbonate, calcium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, tribasic sodium phosphate, tribasic potassium phosphate, tribasic ammonium phosphate , dibasic sodium phosphate, dibasic potassium phosphate, sodium pyrophosphate, sodium metaphosphate, sodium tripolyphosphate, sodium metaborate, potassium metaborate, ammonium metaborate, sodium tetraborate, potassium tetraborate, tetraborate Ammonium, sodium pentaborate, potassium pentaborate, ammonium pentaborate, pyridine, triethylamine, 1,8-diazabicyclo[5.4.0] undec-7-ene, 1,4-diazabicyclo[2.2.2]
Examples include octane, and these can be used alone or in a mixture of two or more. The amount of the base used is 0.5 to 50 mol, preferably 1.0 to 20 mol, per mol of acyloxyneofyl chloride or oxyneofyl chloride. If the amount used is less than this, the reaction rate will be very slow and the yield will be poor. If the amount is more than this, more by-products will be produced and stirring will become difficult. Although the use of a solvent is not necessarily essential in the present invention, it is desirable to use a solvent in order to improve the yield. Examples of the solvent include N,
N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, carboxylic acid amides such as tetramethylurea, phosphoric acid amides such as hexamethylphosphoramide, sulfolane, dimethylsulfoxide, dimethylsulfone sulfur-containing organic solvents such as dioxane, tetrahydrofuran, ethers such as ethylene glycol dimethyl ether, esters such as acetone, methyl ethyl ketones, ethyl acetate, hydrocarbons such as toluene, xylene, benzene, n-hexane, acetonitrile, pyridine, Examples include quinoline, nitrogen-containing organic solvents such as nitrobenzene, and water, and these may be used alone or in combination of two or more. When using a solvent, for 1 part of acyloxyneofyl chloride or hydroxyneofyl chloride
0.1 to 30 parts are used, preferably 1.0 to 10 parts. If the amount used is larger than this, the reaction rate will be reduced and productivity will be reduced. A general embodiment of the manufacturing method of the present invention is as follows. The alkylating agent, base and inert solvent are placed in a reaction vessel and heated to 0-200°C, preferably 10-80°C in a nitrogen stream. At the same temperature, dropwise add an inert solvent solution of acyloxyneofyl chloride or hydroxyneofyl chloride,
Similarly, the mixture is stirred at a predetermined temperature for a predetermined time in a nitrogen atmosphere. The reaction mixture is poured into water, neutralized, and extracted with an organic solvent such as benzene or carbon tetrachloride. After washing the organic layer with water, dehydrating and drying, the solvent is evaporated under reduced pressure to obtain a crude product. This product has high purity and can be used as it is as a raw material for agricultural chemicals such as the above-mentioned insecticides and acaricides, but it can also be further purified by column chromatography or distillation. Although it is not absolutely necessary to use nitrogen during the reaction, less impurity by-products are produced when the reaction is carried out in a nitrogen atmosphere. It is also possible to carry out the reaction even if the order of addition of the acyloxyneofyl chlorides or hydroxyneofyl chlorides, the base, or the alkylating agent is reversed. Next, the details of the present invention will be explained by referring to examples. Example 1 123.4g diethyl sulfate, 96% potassium hydroxide
35.1 g and 100 ml of sulfolane were placed in a flask and heated to 40°C while stirring in a nitrogen stream. p
- A mixture of 47.2 g of acetoxyneofyl chloride and 100 ml of sulfolane was added dropwise for 50 minutes at 40-45°C. The mixture was stirred at 43 to 45°C for 9 hours in the same nitrogen atmosphere. After reaction, discharge into water and carbon tetrachloride
It was extracted and separated into 500 ml. The organic layer was transferred to a flask, approximately the same amount of water was added, and the mixture was stirred at 60°C for 3 hours. After separation, the organic layer was washed twice with water, dehydrated and dried over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 43.2 g of a crude product. As a result of analysis by gas chromatography, this product contained 84.6% p-ethoxyneofyl chloride. Yield 86.0
%. This product was purified by silica gel column chromatography (developing agent: benzene) to obtain a pure p-ethoxyneofyl chloride. bp89゜／0.25mmHg Elemental analysis value (%): C67.64 H8.40 Cl16.52 Calculated value as C ₁₂ H ₁₇ OCl (%):
C67.76 H8.06 Cl16.67 n _D 25.5 1.5202 IR: νmax (cm ^-1 ) 2960, 1610, 1515, 1250,
1185, 1050, 830, 745 cm ^-1 NMR: δ ^CDCl3 (ppm) 1.3-1.6 (9H, CH ₃ ), 36
(s, 2H, CH ₂ Cl), 4.0 (q, 2H, CH ₂ O), 6.7
~7.4 (H of 4H, φ) ppm From the analysis data above, it was confirmed that it was p-ethoxyneofyl chloride. Example 2 0.7 g of p-hydroxyneofyl chloride, 4.0 g of diethyl sulfate, 2.0 g of potassium carbonate and N,
20 ml of N-dimethylformamide was placed in a flask and heated to 50°C while stirring in a nitrogen stream. After stirring at the same temperature for 2 hours, 4.0 g of potassium carbonate was added. After stirring for another 1.5 hours at the same temperature,
2.0 g of diethyl sulfate was added and stirred for 2.5 hours. After cooling to room temperature, it was drained into water. After acidifying with hydrochloric acid, the mixture was extracted with benzene. After washing the extracted layer with water, the organic layer was dehydrated and dried over sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.9 g of crude product.
I got it. As a result of analysis by gas chromatography, this product contained 74.2% p-ethoxyneofyl chloride. Yield 82.7%. This product was purified by silica gel column chromatography (developing agent: benzene) to obtain a pure p-ethoxyneofyl chloride. The elemental analysis values, IR and NMR analysis values of this product were completely the same as those of Example 1. Example 3 In the same manner as in Example 1, m-chloro-p-ethoxyneofyl chloride was synthesized from m-chloro-p-acetoxyneofyl chloride and diethyl sulfate. A pure product was isolated in the same manner as in Example 1, and the following identification was made. bp109゜～112゜/0.5mmHg Elemental analysis value (%): C58.59, H6.84, Cl28.27 Calculated value as C ₁₂ H ₁₆ OCl ₂ (%):
C58.31, H6.53, Cl28.69 IR: νmax (cm ^-1 ) 2980, 1610, 1500, 1480,
1400, 1300, 1260, 1070, 820, 740 NMR: _δCDCl3 (ppm) 1.2-1.6 (OH, _CH3 ), 3.6
(s, 2H, −CH ₂ Cl) 4.1 (q, 2H, CH ₂ O), 6.8
~7.4 (3H, H of φ) MS spectrum: Parent ion 246 The presence of Cl2 was observed in about 66% of the M+2 parent ion and about 11% of the M+4 parent ion. From the above analysis data, it was confirmed that it was m-chloro-p-ethoxyneofyl chloride. In order to show the synthesis method and usefulness of the starting materials for the compounds of the present invention, below, reference is made to examples of synthesis of 2-(alkoxyphenylpropyl ether derivatives produced using the compounds of the present invention as raw materials and test examples of insecticidal effects). These are shown as examples and reference test examples. Reference Example 1 254 g of p-acetoxyt-butylbenzene, 500 g of carbon tetrachloride, and 2.5 g of benzoyl peroxide were placed in a flask and heated to 60°C while purging the system with nitrogen. While stirring under high-pressure mercury lamp irradiation, 170 g of chlorine was blown in at 60 to 83°C for 7 hours. After cooling to room temperature, it was drained into water and separated. The organic layer was treated with a 1% aqueous sodium sulfite solution until it became neutral. After drying over sodium sulfate, the solvent was evaporated under reduced pressure to give an oily crude product.
Obtained 289g. As a result of gas chromatography analysis, it was found that unreacted p-acetoxyt
It contained 44.7% of -butylbenzene, 49.3% of the target p-acetoxyneofyl chloride, 3.5% of a dichloride whose side chain was further chlorinated, and 0.7% of a nuclear chloride. The selectivity of the target p-acetoxyneofyl chloride with respect to the reacted raw materials was 89.1%. The crude product obtained here is purified by distillation under reduced pressure.
- 105.0 g of acetoxyneofyl chloride was obtained (bp 127°-131°C/1.7-1.8 mmHg). The above purified p-acetoxyneofyl chloride
Put 4.0g and 40ml of methanol into a flask,
Heated to 45°C. Concentrated hydrochloric acid while stirring at the same temperature.
0.4 g was added dropwise. After stirring for another 2 hours,
The organic layer was washed with water, dehydrated and dried over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 3.2 g of an oil. This material crystallized when allowed to cool. Recrystallization from n-hexane gave colorless needle crystals. mp65.5~67.5℃. Elemental analysis value (%): C64.84 H7.24 Cl19.43 Calculated value as C ₁₀ H ₁₃ OCl (%):
C65.04 H7.10 Cl19.20 IR: νmax 3200, 2960, 1605, 1450, 1370,
1240, 1185, 830, 750, 730 cm ^-1 NMR: δCDCl ₃ 1.4 (s, 6H, CH ₃ ), 3.56 (s,
2h, CH ₂ ), 6.7-7.2 (4H, H of φ) ppm From this, it was confirmed that the needle-like crystals were p-hydroxyneofyl chloride. Reference Example 2 p-ethoxyneofyl chloride 8.93g
(0.042 mol), 8.0 g (0.04 mol) of 3-phenoxybenzyl alcohol, 3.9 g of 45% NaOH and 50 ml of dimethyl sulfoxide were heated and stirred at 140°C for 3 hours. 1.8 g of 45% NaOH was added, and the reaction was continued at the same temperature for an additional 4 hours. The reaction solution was discharged into 500 ml of water, extracted with benzene, the benzene extract was washed with water, and then dried over sodium sulfate. Benzene is distilled off under reduced pressure.
The obtained crude ether was subjected to column chromatography on 250 g of silica gel (developing solvent: toluene/n-
Hexane) to obtain 7.5 g (yield: 50%) of 3-phenoxybencyl 2-(4-ethoxyphenyl)-2-methylpropyl ether. mp 35.4-36.2℃ NMRδCDCl ₃ 1.25 (6H, s) 1.30 (3H, t) 3.35
(2H, s) 3.92 (2H, q) 4.20 (2H, s) 6.6~
7.4 (13H, m) ppm Reference test example Compound of Reference Example 2 {3-phenoxybenzyl 2-(4-ethoxyphenyl)-2-methylpropyl ether} 20 parts, Solpol SM-100 (Toho Chemical registration) Mix 20 parts of product name) and 60 parts of xylene to make an emulsion. Dilute the prepared emulsion with water and
Prepare to 100 and 20 ppm concentrations. Sweet potato leaves were immersed in each chemical solution for 10 seconds, air-dried, placed in a plastic cup with a diameter of 10 cm, and 2nd instar larvae of Spodoptera were released and left in a constant temperature room at 25°C. After 48 hours of treatment, the number of live and dead insects was investigated and the mortality rate was calculated. The results are shown as the average value of three consecutive results. (A) was similarly tested as a control compound.

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Claims (1)

[Claims] 1 Formula () {In formula (), R ¹ represents a lower alkyl group, and R ² represents a hydrogen atom or a halogen atom. However, when R ¹ is a methyl group, R ² is a halogen atom. } Alkoxyneophyl chloride. 2. The compound according to claim 1, wherein the compound of formula () is p-ethoxyneofyl chloride. 3 formula () {In formula (), R ³ represents a lower acyl group, and R ⁴ represents a hydrogen atom or a halogen atom. } Formula () characterized in that an alkylating agent and a base are allowed to act on the acyloxyneophyl chloride represented by the formula () in the presence or absence of an inert solvent. {In formula (), R ¹ represents a lower alkyl group, and R ² represents a hydrogen atom or a halogen atom. However, when R ¹ is a methyl group, R ² is a halogen atom. } A method for producing an alkoxyneofyl chloride. 4 The compound of formula () is p-acetyloxyneofyl chloride, and the compound of formula () is
4. The method according to claim 3, wherein p-ethoxyneofyl chloride is used. 5 formula () {In formula (), R ⁴ represents a hydrogen atom or a halogen atom. } Formula () characterized in that an alkylating agent and a base are allowed to act on the hydroxyneofyl chloride represented by the formula () in the presence or absence of an inert solvent. {In formula (), R ¹ represents a lower alkyl group, and R ² represents a hydrogen atom or a halogen atom. However, when R ¹ is a methyl group, R ² is a halogen atom. } A method for producing an alkoxyneophyl chloride. 6. The method according to claim 3 or claim 5, wherein the alkylating agent is diethyl sulfate.