JPS62258373A - Production of 2,3-dihydro-7-hydroxy-benzofuran derivative - Google Patents

Abstract

PURPOSE:To efficiently obtain the titled compound through one step, by the presence of a 8-hydroxyquinoline derivative in a reaction system in hydrolyzing a 2,3-dihydro-7-halobenzofuran derivative in an aqueous alkali solution in the presence of a copper compound catalyst. CONSTITUTION:A compound expressed by formula I (X represents halogen atom, preferably Cl; R and R' represent H or lower alkyl) is hydrolyzed in an aqueous alkali solution in the presence of 0.001-1mol, preferably 0.01-0.1mol, based on 1mol said compound, copper compound (especially cupric compound) catalyst and 0.01-100mol, preferably 1-50mol, based on 1mol said copper compound, 8-hydroxyquinoline derivative expressed by formula II (R<1>-R<6> represent H, alkyl, aryl, etc.), especially 8-hydroxyquinoline to obtain the aimed compound expressed by formula III useful for an intermediate for an insecticide at an extremely improved conversion through one step in high yield.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 2,3-dihydro-7-hydroxybenzofuran derivatives.

2,3-dihydro-7-hydroxybenzofuran derivatives such as 2,3-dihydro-2,-1dimethyl-7-hydroxybenzofuran are 2,3-dihydro-2,λ-dimethylbenzo-7-furanylmethelcarbamate, i.e. It is an important compound as an intermediate for the active ingredient of insecticide known as carbofuran.

[Conventional technology]

Various methods have been proposed for producing carbofuran. For example, Japanese Patent Publication ShogJ-77rj discloses a method for finally producing carbofuran through several steps of reaction using ρ-bromophenol and methallyl halide as starting materials. has been done.

The publication describes 2,3-dihydro-11, cordimethyl-?
- Hydrolyzing bromobenzofuran using sodium hydroxide and cupric oxide as a catalyst.2. J-dihydro-2,-
A method for making monodimethyl-7-hydroxybenzofuran is presented.

In this reaction, the reaction rate is not necessarily sufficient, and in the case of alkaline hydrolysis of chlorobenzofuran, which is inexpensive and has industrial significance, the reaction hardly progresses. have

On the other hand, Tokukai Akira! Two seven! /l” Publication No. 2 contains 2,2-
By reacting dimethyl-,2,3-dihydro-7-balobenzofuran with metals such as lithium, sodium, and magnesium, the resulting metal compound is oxidized, and then hydrolyzed to produce p,2,2-dimethyl. -2,! -dihydro-7
Although a method for producing -hydroxybenzofuran is described, since this reaction is a multi-stage reaction, there is a desire to develop a method for efficiently carrying out hydrolysis in one stage.

[Problems to be Solved by the Invention] The E4A M ha 2,J-dihydro-7-valopenzo7rane derivative of the present invention is hydrolyzed in the presence of a copper catalyst in an alkaline aqueous solution to produce 2,3-dihydro-2-hydroxybenzofuran. As a result of extensive research into methods for producing derivatives, 2,3-dihydro-7-balobenzo 7 can be effectively produced in one step by allowing ♂-hydroxyquinoline uFJ form to exist in the reaction system.
Seeing that it is possible to hydrolyze ran derivatives, the gist of the present invention is to form a general formula (wherein X represents a rogen atom, Often, by hydrolyzing a 2,3-dihydro-cuhalobenzofuran derivative 4 represented by the general formula (wherein R and R' have the same meaning as the formula (where R and R' have the same meaning as the formula) In the method for producing a 3-dihydro-7-hydroxybenzofuran derivative represented by the formula (having), the reaction is carried out in alkaline water in the presence of a compound and a ?-hydroxyquinoline conductor. A method for producing a 3-dihydro-7-hydroxybenzofuran derivative is provided.

Next, let's introduce the present invention to i! 18 Explain in detail.

In the compound represented by the general formula (1) used as a raw material of the present invention, R and R' may be the same or different, and each has a hydrogen atom, a methyl group, an ethyl group, a propyl group, and an isopropyl group. , n-butyl group, crown-butyl group, 1
"Cl which may be chained or branched" such as so-butyl group
A compound that is a lower alkyl group of xc4, specifically =, 3-dihydro-7-chlorobenzofuran 1.2.
j-dihydro-2-methyl-7-chlorobenzofuran,
z, 3-sihydro-coethyl-7-chlorobenzofuran, S, 3-sihydro-11furovir-7-chlorobenzofuran, 3-dihydro-inpropyl-7-
Chlorobenzofuran, s,3-dihydro-λ-butyl-2-chlorobenzofuran, 2,3-dihydro-coynebuteru-7-chlorobenzofuran, 2,3-dihydro-
2-day ec butyl-2-chlorobenzofuran, 2.3-
dihydro-tert 7'thyl-7-chlorobenzofuran, x, 3-dihydro-, 2-dimethyl-7-chlorobenzo7rane, 2,3-dihydro-comethyl-11-ethyl-2-chlorobenzofuran, 2, 3-dihydro-mether-λ-propyl-7-chlorobenzofuran, x,3-dihydro-mether-λ-butyl-7-chlorobenzo7rane, 2.3-dihydro-,2-diethyl-7-chlorobenzofuran , 2.3-dihydro-1-etherucoflovir-7-chloropenzofuran, 2,
i-dihydro-λ-ether-punal-7-chlorobenzofuran, x, i-dihydro-2,, 2-dipropyl-7-chlorobenzofuran, 2.3-dihydro-copropyl-λ-butyl-2-chlorobenzofuran, 2, 3
-dihydro-2, Kodibutyl-? -chlorobenzofuran, among others, 2,3-dihydro-2. Kodimethel-7-chlorobenzofuran is preferred.

The compound of general formula (1) is, for example, published by Tokkai Sho! Day 76071
It can be manufactured according to the method shown in No.

Copper compounds used in the present invention include monovalent steel compounds and divalent copper compounds, specifically cuprous oxide, cupric oxide, hydroxide steel, cuprous chloride, cupric chloride, Copper compounds such as copper sulfate, steel nitrate, copper acetate, etc., and divalent copper compounds are particularly preferred.The amount of the copper compound used is preferably 0.00/~7 mol per 1 mol of the compound of general formula (1). is 0, Q
/~0.1 mole.

2,J-dihydro-7- represented by the above general formula (1)
The hydrolysis reaction of valopenzofuran is carried out in an alkaline aqueous solution. As alkali, caustic soda, caustic potash,
Examples include caustic alkalis such as calcium hydroxide, and caustic soda 1. Particularly preferred is caustic potash. The amount of alkali used is 7 to 2,3-dihydro-7-valopenzofuran.
~5 times by mole, preferably 2 to 3 times by mole. Caustic alkali is usually added to the reaction system as an alkaline aqueous solution, and once the caustic alkali aqueous solution is added, it is usually
o% by weight, preferably 0.0% by weight. /~j wound 0.

The ♂-hydroxygynoline derivatives which can be used in the present invention have the general formula (where R1, R2, R", R', R5 and , alkyl group, aryl group, cycloalkyl group, aralkyl group,
Hydroxyl group, alkoxy group, amino group, alkylamino group, sulfo group, alkylsulfonyl group, nitro group,
(Indicates halogen atom, carboxyl group, phosphono group, etc.)
It is expressed as In general formula (1111), R1, R2,
R8, R4, R5 and R6 may preferably be the same or different, and are hydrogen atoms, C1 to Cta linear or optionally branched alkyl groups, C6 to 010 aryl groups, 06 to CIO cyclo Alkyl group, 07-coo aralkyl group, hydroxyl group, at""-'coo linear or optionally branched alkoxy group, ami7 group,
01 to C5 optionally linear or branched alkylamino group, sulfo group, q to CIO optionally linear or branched alkylsulfonyl group, nitro group, halogen atom,
Represents a carboxyl group, a phosphono group, especially a hydrogen atom,
Preferred are alkyl groups of self to cB, nitro groups, sulfo groups, norogen atoms, hydroxyl groups, and carboxyl groups.
Specific compounds of /-hydroxyquinoline derivatives include r-hydroxyquinoline, cometeru? -Hydroxyquinoline! - nitro r-hydroxyquinoline,
! -Sulfo r-hydrooxyquinoline, r,y-cycloru! -hydroxyquinoline, -carboxyl, ?
-dihydroxyquinoline, etc., especially ? -Hydroxyquinoline is preferred. these,! -Hydroxyquinoline derivatives can be used alone or in the presence of two or more kinds in a reaction system.

! -Hydroxyquinoline conductor forms a complex with a copper compound as a catalyst in a certain stoichiometric relationship in the reaction system, and
The generated complex and copper compound and! - Since there is an equilibrium relationship between hydroxyquinoline derivatives, the amount of t-hydroxyquinoline derivative used is 0.07 to 100% relative to the copper compound.
It is preferably 7 to 50 times the mole amount.

In addition, in the present invention, the copper plating stand v! Instead of adding J catalyst and r-hydroxyquinoline derivative to the reaction system individually, a copper complex formed from a copper compound and male-hydroxyquinoline g4 is added in the same manner. (15'jJ)
/ :l fCyo') It may be added to the H-producing reaction system.

The hydrolysis reaction of the present invention is usually carried out at a temperature of 0 to 300°C, preferably 750 to 220°C, under self-generated pressure at the reaction temperature or under pressure in an inert gas atmosphere such as nitrogen. 2~2! Under pressure of 0. ! ~2
It is carried out for 0 hours, preferably 7 to 10 hours.

In the method of the present invention, the reaction system is a heterogeneous system consisting of an aqueous layer and an organic layer, and is it a catalyst? The copper complex of -hydroxyquinoline is a soluble or partially insoluble solid in the reaction system, and the starting material, 2,3-dihydro-7-valobenzofuran derivative, is added to the organic layer, and the product, 2,3- dihydro-7-
Hydroquine benzofuran derivatives exist in the aqueous layer as alkaline salts. Therefore, after the reaction is completed, the complex can be precipitated by cooling, etc., if necessary, and then the complex can be precipitated by -! -Separate the copper complex of the hydroxyquinoline derivative, recover the unreacted starting material by layer separation, neutralize the aqueous layer, and recover the product by extraction, distillation, etc., or neutralize the reaction solution with mineral acid, etc. The raw materials and products are separated by extractive distillation, etc., and the aqueous layer is purified by conventional means such as alkali neutralization, filtration, extraction, and distillation to remove the copper complex of the pr-hydroxyquinoline derivative and excess chlorine. It is also possible to separate and recover the 84 -hydroxyquinolines and reuse them.

〔Example〕

Next, the present invention will be explained in detail with reference to examples, but the present invention is not limited to the following examples unless it exceeds the gist thereof.

Example/In a pressurized SUS reactor? Dissolve 2,3 tons of 5% caustic soda in 10θd of water, then dissolve ♂-hydroxyquinoline/
, '46? is added to this alkaline aqueous solution and dissolved.

Copper sulfate! Water salt 0. ．． 2! The above is an aqueous solution of Of dissolved in water < wl? - Submerged in an alkaline aqueous solution of hydroxyquinoline with stirring and continued stirring for O, S hours, then =, 3-dihydro-z, -1-dimethyl-7-chlorobenzofuran L6
jf was added to the inside of the reactor.

After replacing with nitrogen, adjust the temperature of the reactor to 00'' to 207℃, immerse it in a Shisein bath, and heat and stir for 4 hours. After the reaction is complete, cool it and dilute the reaction solution with 3% dihydrochloric acid, !d. Neutralize and liberate the six oils from benzene/θdtetrahydrofuran (hereinafter TH
(abbreviated as F) was extracted with a mixed solvent of 10 d, and the extract was distilled after eluting the solvent and distilled under a vacuum of 3 Hg.
A 3-dihydro-,2-dimethyl-7-hydroxybenzofuran soluble fraction (elution temperature J'j, ?g°C) 2,r2f was obtained. This dissolved content was determined by gas chromatography, and the conversion rate of the raw material was 97%.
The yield of 2,2-dimethyl-7-hydroxybenzofuran was 76%. On the other hand, the extracted residual water layer was mixed with caustic powder 1.3
! Neutralized and generated with f! - Do not filter and recover the copper complex of hydroxyquinoline. P liquid! ! pH with dihydrochloric acid/,/d
Neutralize and release with t~7 box! -Hydroxyquinoline was recovered by extraction and distillation.

Comparative Example/The reaction was carried out in the same manner as in Example/ except that monohydroxyquinoline was removed. As a result, the raw material 3-dihydro-2,,2-dimethyl-7-chlorobenzofuran was almost recovered. and the hydrolysis reaction product 2,3
It was found that -dihydro-2,2-dimethyl-7-hydroxybenzo7rane has a very large effect on the skin.

Comparative Example Magnetically stirred autoclave J (-1 of 4tP)
3-dihydro-2,2-dimethyl-7-chlorobenzofuran! J polyaqueous solution of 2F sodium hydroxide and 0.
/! ? Cuprous oxide was charged and heated at 720 to 200°C for a period of time. As a result, almost no 3-dihydro-2,2-dimethyl-2-hydroxybenzofuran was produced, as in Comparative Example. I hadn't.

Example: In a SUS crack pressure reactor, 0.1 liter of caustic acid was dissolved in 109 td of water, and then! -Hydroxyquinoline 0.220f was added and dissolved in this alkaline aqueous solution.

Suboxide steel 0.072 f above! - Added to an alkaline aqueous solution of hydroxyquinoline and continued stirring at room temperature for 03 hours, then added 2,3-dihydro-2,2-dimethyl-2-chlorobenzofuran L64tf, replaced the inside of the reactor with nitrogen, and carried out the reaction. A vessel/? The temperature was adjusted to θ~/r/T:, and the mixture was immersed in an oil bath and heated and stirred for 3 hours.

After the reaction is completed, the reaction solution is cooled and 1! After neutralization with dihydrochloric acid, extraction was performed with a mixed solvent of benzene/OD, THF' 10d, and the extract was quantified by gas chromatography. Conversion rate is 7! The selectivity for excellent 2,3-dihydro-2-dimethyl-7-hydroxybenzofuran was 77%.

Example 3 In a pressurized SUS reactor, lt% caustic powder/7tf was dissolved in 100d of water, and then 11 methyl! - Add hydroxyquinoline o3oot to this alkaline aqueous solution and dissolve. Copper sulfate trihydrate 0.2! Dissolve Ot in 1 m of water and add the aqueous solution to the above 2-methyl-! - Added dropwise to an alkaline aqueous solution of hydroxyquinoline and stirred at room temperature for θ, j hours. After 9 hours, 3.64 tf of 2,3-dihydro-2,2-dimethyl-7-chlorobenzofuran was added, and the inside of the reactor was heated with nitrogen. The temperature of the reactor was adjusted to 100 to 207°C, and the reactor was immersed in an oil bath and heated and stirred for 3 hours.

After the reaction is complete, cool the reaction solution and step 3! Thihydrochloric acid! - and then extracted with a mixed solvent of benzene 10d% THFloffij, and the extract was quantified by gas chromatography. ,3-dihydro-11,-1dimethyl-7-hydroxybenzofuran has a selectivity of 16
It was %.

Examples 4t-7 In Example 3? -Changing the type of hydroxyquinoline derivative to the compound listed in Table 1, ? -Hydroxyquinoline derivative/copper sulfate; 2,! (Mole ratio) Execute in exactly the same manner except for 9.

The results are shown in Table-/.

〔Effect of the invention〕

According to the present invention, s,3-dihydro-7-
When producing hydroxybenzofuran derivatives, the presence of r-hydroxyquinoline derivatives in the reaction system significantly improves the conversion rate, making it possible to obtain the target compound in a high yield in one step.Applicant: Mitsubishi Kasei Kogyo Co., Ltd. Agent Patent Attorney Hase - (7 others)

Claims (2)

[Claims] (1) General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼……(I) (In the formula, X represents a halogen atom, R and R' may be the same or different, and a hydrogen atom or a lower alkyl By hydrolyzing 2,3-dihydro-7-halobenzofuran represented by I) has the same meaning as the formula)
A method for producing a 2,3-dihydro-7-hydroxybenzofuran derivative represented by 2,3-dihydro-7, characterized in that the reaction is carried out in an alkaline aqueous solution in the presence of a copper compound and an 8-hydroxyquinoline derivative. −
Method for producing hydroxybenzofuran derivatives (2) The method according to claim 1, characterized in that in general formula (I), X is a chlorine atom.