JPH03120235A - Production of p-alkoxyneophyl alcohols - Google Patents

Abstract

PURPOSE:To obtain the subject substance from a readily available raw material in good yield by reacting a p-alkoxyphenyl halide with metallic Mg, providing a p-alkoxyphenylmagnesium halide and then reacting the resultant compound with isobutylene oxide. CONSTITUTION:A p-alkoxyphenyl halide is dripped into activated metallic Mg while stirring the metallic Mg in anhydrous THF at ambient temperature to the refluxing temperature of the solvent and further reacted for several hr to provide a p-alkoxyphenylmagnesium halide. Isobutylene oxide is directly reacted or dissolved in the same solvent as described above and reacted therewith at 20-50 deg.C for 1-10hr to afford the subject substance. The resultant subject substance is an important intermediate for producing p-alkoxyneophyl m- phenoxybenzyl ether-based inseciticides having low toxicity to fishes.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention can be used as an important intermediate in the production of neophilic enoxybenzyl ether insecticides, which have recently attracted attention due to their low toxicity to fish. The present invention relates to a method for producing p-alkoxyneophyl alcohols.

More specifically, the present invention provides a new and efficient production method using p-alkoxyphenyl halide as a raw material.

[Problems to be solved by conventional techniques and inventions] In recent years,
It was found that p-alkoxyneophyltophenoxybenzyl ether represented by the following formula (1) has high insecticidal activity, and it is less toxic to fish than conventional pyrethroid insecticides, so it is used in rice fields. It is attracting attention because it can be used as an insecticide.

Various methods have already been disclosed as methods for producing this formula (Rino p-AJ recoxy neophyll-phenoxy benzyl ether).

Typical methods include: (a) A method of condensing p-alkoxyneophyl halide and miphenoxybenzyl alcohol.

(b) A method of producing by condensing 3-halogeno-4-alkoxyneophyl halide and -phenoxybenzyl alcohol, followed by dechlorination reaction.

(c) A method of condensing tophenoxybenzyl halide and p-alkoxyneophyl alcohol.

and so on.

Among these production methods, when considering the reactivity of intermediates during etherification, the method of production from (1%) -phenoxybenzyl halide and p-alkoxyneophyl alcohol is attractive as an industrial production method. It's a method. However, a drawback of this method lies in the method for producing one of the raw materials, p-alkoxyneophyl alcohol.

Conventionally, the following methods are known for producing p-alkoxyneophyl alcohol.

(1) Anisole is reacted with methallyl chloride under a sulfuric acid catalyst to form p-methoxyneophyl chloride, and then metal magnesium is reacted to form p-methoxyneophyl alcohol via p-methoxyneophylmagnesium chloride. how to.

(2) p-methoxy (or p-ethoxy)phenylacetonitrile is reacted with methyl iodide to produce p-methoxy (
or p-ethoxy) neophyll cyanide, then hydrolyzed to convert it into the corresponding carboxylic acid, and then reduced with lithium aluminum hydride to produce p-methoxy (or p-ethoxy) neophyll alcohol; [ Chemical Abstracts.

511, 2830 (1957); Japanese Patent Publication No. 58-13
No. 1931 (1983)] However, method (1) involves the Friedel-Crach reaction of anisole and methallyl chloride, which involves the by-product of the isomer O-methoxy neofiltraloride. In addition, method (2) requires a long process and requires expensive auxiliary raw materials such as methyl iodide and lithium aluminum hydride. Furthermore, like method (1), the total yield is low.

As described above, the current state of the art for producing p-alkoxyneophyl alcohol, which is conventionally known, is that there is no method that is satisfactory from an industrial standpoint.

Based on the current state of p-alkoxyneophyl alcohol production technology as described above, the present inventors have conducted extensive studies on a method for producing p-alkoxyneophyl alcohol in good yield from industrially easily available raw materials.

As a result, by using p-alkoxyhalogenophenol, which can be easily produced from p-halogenophenol, as a raw material, the desired p-alkoxyneophyl It was discovered that alcohol can be obtained in good yield, and by further developing this knowledge, the present invention was completed.

That is, the present invention is a method for producing p-alkoxyneophyl alcohol, which is characterized in that p-alkoxyphenyl halide is reacted with metallic magnesium to form p-alkoxyphenylmagnesium halide, and then reacted with isobutylene oxide.

The method of the present invention is a novel manufacturing method that has not been previously known.

In the present invention, p-alkoxyphenyl halide is used as a raw material. This p-alkoxyphenyl halide can be easily produced by O-alkylation of p-halogenophenol.

The p-alkoxyphenyl halide is specifically p-alkoxyphenyl chloride, p-alkoxyphenyl bromide or p-alkoxyphenyl iodide, and more specifically p-methoxyphenyl chloride, p-ethoxyphenyl chloride, p-n
-propoxyphenyl chloride, p-1so-propoxyphenyl chloride, p-n-butoxyphenyl chloride, p-5ec-butoxyphenyl chloride,
ρ-1so-butoxyphenyl chloride, p-ta
rt-butoxyphenyl chloride, p-methoxyphenyl bromide, p-ethoxyphenyl bromide, p
-tobropoxyphenyl bromide, p-1so-propoxyphenyl bromide, p-tobutoxyphenyl bromide, p-5ee-butoxyphenyl bromide,
G1-1so-butoxyphenyl bromide, 1)-t
ert-butoxyphenyl bromide, p-methoxyphenyl iodide, p-ethoxyphenyl iodide, 9-n-propoxyphenyl iodide, p-1
Examples include so-butoxyphenyl iodide, p-fl-butoxyphenyl iodide, p-3eC-butoxyphenyl iodide, I)-iso-butoxyphenyl iodide, and 9-tert-butoxyphenyl iodide.

The present invention is accomplished by first reacting p-alkoxyphenyl halide with metallic magnesium to form p-alkoxyphenylmagnesium halide, and then reacting with isobutylene oxide.

p-alkoxyphenylmagnesium halide, which is a Grignard reagent, can be prepared in an ether solvent such as diethyl ether or tetrahydrofuran, or in an ether solvent and a solvent such as benzene, toluene, or xylene, according to the method for preparing the Grignard reagent. It is prepared in a mixed solvent system with

For example, p-alkoxyphenyl halide is added dropwise to activated metallic magnesium in anhydrous tetrahydrofuran with stirring at room temperature to the reflux temperature of the solvent, and the reaction is further carried out at the same temperature for several hours to quantitatively obtain p-alkoxyphenyl halide.
- Can be converted to alkoxyphenylmagnesium halide.

The amount of metallic magnesium to be used may be the theoretical amount, i.e. 1.0 equivalent to p-alkoxyphenyl halide, but it is usually slightly in excess of the theoretical amount, i.e. from 1.1 to 1.0.
It is preferable to use about 1.5 equivalents.

Moreover, various shapes of metal magnesium can be used, such as a tape shape, a powder cane shape, or a shaved shape.

In addition, when preparing this Grignard reagent, it is preferable to use a method of activating metallic magnesium.
Specifically, the reaction proceeds rapidly by adding a catalytic amount of methyl bromide, methyl iodide, iodine or dibromoethane, or by placing the reaction system in a nitrogen atmosphere or under reduced pressure.

In the present invention, p-alkoxyneophyl alcohol is obtained by reacting ρ-alkoxyphenylmagnesium halide prepared as described above with isobutylene oxide.

Isobutylene oxide can be used either as it is or in the form of a solution by dissolving it in the above-mentioned solvent, and it is sufficient to drop it into the Grignard reagent solution prepared by the above-mentioned method for reaction.The amount of isobutylene oxide to be used is The amount is 1.0 equivalent or more, preferably 1.1 to 2.0 equivalents, based on p-alkoxyphenyl halide as a raw material.

The reaction temperature ranges from 0°C to the boiling point of the solvent, preferably from 20 to 50°C, and the reaction may be carried out under these conditions for 1 to 10 hours.

After the reaction, the reaction mixture is poured into an aqueous solution of ammonium chloride, dilute hydrochloric acid, dilute sulfuric acid, etc., extracted with an organic solvent such as benzene, washed with water, further dehydrated with a dehydrating agent such as magnesium sulfate or sodium sulfate, and the solvent is distilled off. After removal, ρ-alkoxyneophyl alcohol, which is the target compound of the present invention, can be obtained by column chromatography separation or vacuum distillation.

Hereinafter, the present invention will be explained in detail with reference to Examples.

Of course, the examples specifically illustrate the invention;
It is clear that the invention is not limited to the scope of this example.

〔Example〕

Example 1 A 200 d four-tube flask with sufficient nitrogen exchange was charged with 2 g of magnesium metal (0.12 g atoms), 20 m of anhydrous tetrahydrofuran and a catalytic amount of ethyl bromide. While thoroughly stirring, a solution of 20.1 g (0.1 mol) of p-ethoxyphenyl bromide dissolved in anhydrous tetrahydrofuran 5 (ld) was added dropwise at reflux temperature over approximately 2 hours. The reaction was further continued at the same temperature for 2 hours. p-ethoxyphenylmagnesium bromide was prepared by

Next, 8.4 g (0.degree. 12 moles) of isobutylene oxide was added dropwise to this solution over a period of approximately 1 hour while maintaining the temperature at 20 to 30.degree. C., and the reaction was further allowed to proceed at the same temperature for 1 hour.

The reaction mixture was poured into 100 d of saturated ammonium chloride aqueous solution, stirred thoroughly, and then diluted with 200 d of benzene.
After extraction, the benzene layer was washed with water and dehydrated by adding Glauber's salt. After filtering the Glauber's salt and distilling off the solvent benzene, 9.3 g of p-ethoxyneophyl alcohol was purified by silica gel column chromatography.
I got it. Yield: [,9%1tp-ethoxyphenyl bromide) Elemental analysis value (%) Actual value: C = 74.03 Calculated value as C1xH + mOt: C = 74.19I
R spectrum (cm-') 3400.162G.

(KBr tablet method) 1195.1050°NMR
Spectrum (solvent: CDCj!s) 1.21 (3,6N
), 1.37(t, 31(), 2.26(S, IH
).

3.31 (S, 2H), 3.89 (q, 2R).

6.63-7.25 (s, 4H) H-9,51 H=9.34 1520.1255°30 Example 2 18.7 g of p-methoxyphenyl bromide in place of p-ethoxyphenyl bromide in Example 1 (
0.1 mol) was used in the same manner as in Example 1 to obtain 8.3 g of p-methoxyneophyl alcohol having a melting point of 45.5 to 46.5°C. Yield: 46.1% (
For p-alkoxyphenyl bromide), elemental analysis,
Its structure was confirmed from IR spectrum and NMR spectrum.

〔Effect of the invention〕

According to the present invention, p-alkoxyneophyl alcohol can be produced in substantially one step with a good yield using p-alkoxyphenyl halide, which is industrially available or easily produced. This is an industrially valuable method for producing fill alcohol.

Claims (1)

[Claims] 1. A method for producing p-alkoxyneophyl alcohol, which comprises reacting p-alkoxyphenyl halide with metallic magnesium to form p-alkoxyphenylmagnesium halide, and then reacting isobutylene oxide.