JPS63313743A - Substituted phenoxyalkylaldehyde dialkylacetals and production thereof - Google Patents

Abstract

NEW MATERIAL:The compound of formula I (R1-R5 are lower alkyl; m is 1 or 2; n is 1-3). EXAMPLE:2-(2,3-Dimethyl-4-ethoxyethylphenoxy)acetaldehyde ethylacetal. USE:A synthetic intermediate for a phenoxyalkylamine derivative exhibiting high activity as an insecticidal miticide. PREPARATION:The compound of formula I can be produced by reacting a Grignard reagent of formula II (X is halogen; m is 1 or 2) with a compound of formula III [R3 is alkyl; Y is halogen or R4SO3 (R4 is phenyl or alkyl); n is 1-3].

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to novel substituted phenoxyalkyl aldehyde dialkyl acetals and a method for producing the same, and more particularly, to novel substituted phenoxyalkyl aldehyde dialkyl acetals and a method for producing the same. The present invention relates to substituted phenoxyalkyl aldehyde dialkyl acetals useful as synthetic intermediates and methods for producing the same.

(Prior Art) Phenoxyalkylamine derivatives are known to exhibit high activity as insecticides and acaricides. For example, in JP-A-55-76803, phenoxyalkylamine compounds having a quinazoline ring are disclosed in JP-A-55-76803. Showa 59-3666
No. 7 discloses a phenoxyalkylamine compound having a pyrimidine ring or a pyrimidine ring fused with a cycloalkane, and JP-A-59-42387 discloses a phenoxyalkylamine compound having a chenopyrimidine ring.

Phenoxyalkylamine is one of the important raw materials for these compounds (Japanese Patent Application No. 56473/1983)
. Conventionally, the following methods have been used to synthesize phenoxyalkylamines.

It is made by applying glyoxylic acid to phenols and
After α-hydroxyacetic acid is added to the phenolic acid position, it is reduced to form phenol acetic acid, and then the acid part is reacted with the desired alcohol to form an ester, which is then reduced again to synthesize an ether part. Thereafter, an ether moiety is synthesized from the phenol moiety using a dihaloalkane, and then ammonia is reacted with the synthesized ether moiety.

0OH COOHCOOR3 [Problems to be Solved by the Invention] However, when the conventional synthesis method is used, it includes steps that are not suitable as an industrial synthesis method. In particular, the reduction process is a partial reduction, and a method using a difficult-to-handle reagent such as LiAJIH4 must be used. Moreover, in the case of phenols having an alkyl group at the 3-position, the yield of glyoxylic acid addition reaction decreases significantly due to steric hindrance, and the desired compound cannot be obtained in good yield, and furthermore, by-products are produced. There are problems such as it is not easy to separate and purify.

Therefore, an object of the present invention is to find an intermediate for easily and inexpensively synthesizing phenoxyalkylamines, and to provide a method for producing the intermediate.

[Means for Solving the Problems] As a result of intensive studies to achieve the above object, the present inventors found that when an acetal of phenoxyalkyl aldehyde is used as an intermediate, it can be easily induced into phenoxyalkylamine, Furthermore, the present invention was completed based on the knowledge that it can be synthesized from inexpensive and available raw materials.

That is, the present invention provides general formula (1): (wherein R1, R2, R3, R4 and R5 each independently represent a lower alkyl group; m represents 1 or 2; n represents 1 to 3 The present invention provides substituted phenoxyalkyl aldehyde dialkyl acetals represented by the following integer: and a method for producing the same.

In the above formula (I), the lower alkyl group has 1 to 1 carbon atoms.
5 linear or branched alkyl group, for example,
Methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, 5ee-butyl group, tert-
These include butyl group, pentyl group, etc.

In the compound represented by the above formula (I), preferably R4 is a methyl group, R5 is a methyl group at the 3-position, and m is 1. n is 2
It is a compound represented by the following formula (wherein R1-R3 have the same meanings as above).

Next, two methods of producing the compound represented by formula (I) according to the present invention will be described.

First, the first manufacturing method is the reaction shown below.

R20(II) (m)
R20 (I) In this reaction, examples of the halogen atom of X in compound (II) include chlorine, bromine, and iodine. When Y in compound (III) is a halogen atom,
and when Y represents R45o, a group, R4 is a phenyl group or a phenyl group substituted with a lower alkyl group such as a methyl group or an ethyl group, such as a P-)lyl group, etc. , or a lower alkyl group. The lower argyl group has the same meaning as the lower alkyl group described above. Compound (m) is 2.0 to i per 1 mole of compound (II),
Use omol.

This reaction can be carried out under the same conditions as the usual Grignard reaction. That is, under anhydrous conditions, using tetrahydrofuran (THF) or an ether such as diethyl ether, methyl ethyl ether, or dipropyl ether as a solvent, the reaction temperature is 70 to -10°C, and the reaction time is 0.5 to 5 hours. be.

It is also effective to coexist Cu" ions in this reaction system. For example, CuC1, CuBr, Cu OCOCR3, etc. are added in an amount of 10 to 3 mol% relative to the substrate (compound II).

It is also effective to coexist P(OEt)3,
Add 3 to 1 mol per 1 mol of substrate (compound II).

Next, the steps of the second method for producing the compound represented by formula (I) of the present invention are shown below.

(First step) (Second step) The first step in the R3Z/salt basic reaction is to react the Grignard reagent (compound II) with the alkylene oxide represented by (IV). The alkylene oxide represented by (IV) is preferably ethylene oxide. (I
V) is used in an amount of 1.5 to 0.9 mol, preferably 1.2 to 1.0 mol, per 1 mol of (IT). Alkylene oxide (IV) can be dissolved in a reaction solvent and added dropwise to the reaction system, or if it is a gas, it can be introduced into the reaction system as it is. At that time, the introduction is 3
The reaction is carried out in 0 minutes to 2 hours, and is completed in 1 to 3 hours after introduction. The reaction temperature was -10-1o.

°C1 is preferably 20 to 50 °C. Since this step is also a Grignard reaction, the other reaction conditions can be carried out under normal Grignard reaction conditions as in the first production method.

In the second step, without isolating and purifying the compound (V) obtained in the first step, in the presence of water, a phase transfer catalyst and a base were added to form a two-phase system with dialkyl sulfuric acid [(R3) 280
41 or an alkyl chloride (R3Z) to obtain the desired compound (I). Dialkyl sulfate is
It is used in an amount of 0.5 mol or more, preferably 0.6 to 1.2 mol, per 1 mol of the substrate (compound V). In the case of halogenated alkyl, it is used in an amount of 100 to 1 mol, preferably 10 to 1 mol, per 1 mol of the substrate.

As the base, for example, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide is used, and the base is 1 mol or more, preferably 1.2 to 1 mol per 1 mol of the substrate (compound V).
2.4 mol is used. As phase transfer catalysts, tetraalkyl or benzyltrialkyl quaternary ammonium salts can be used, the alkyl being methyl, ethyl, butyl and the like. The salt form is hydrochloride,
Examples include bromate, iodate, sulfate, and the like. These phase transfer catalysts have a ratio of 0.5 to
20 mol % is used, preferably 2 to 10 mol %. As the reaction solvent, benzene or toluene is used instead of the solvent used up to the first step. The reaction temperature is -1
The temperature is 0 to 1500 C1, preferably 30 to 100 C, and the reaction time is 1 to 6 hours.

Compound (II), which is a common raw material compound in the first production method and the second production method, can be synthesized, for example, as follows.

In the above formula, when R4 and R5 are methyl groups and R5 is substituted at the 5-position, the raw material is 2,3-xylenol, which is industrially available at low cost.

The substituted phenoxyalkyl aldehyde dialkyl acecool (I) of the present invention can be easily derived into the corresponding phenoxyalkyl amine by hydrolysis under acidic conditions, and can also be used as an insecticide and acaricide as described above. Since it is possible to synthesize phenoxyalkylamine derivatives with high activity as a compound, it can be said to have high value as a synthetic intermediate.

[Example] Example 1 (1) Synthesis of 2,3-dimethyl-4-bromophenol 2,3-xylenol 196g (1,6moJlj
) was dissolved in a mixed solvent of 1.4 grams of acetic acid and 0.2 Fl of methanol, and the solution was cooled to -4°C. Next, 140 g (1-,76 moJ1) of bromine was added dropwise to this solution over 1.5 hours. The same temperature was maintained at -4°C to 5°C. After the addition, stirring was continued for 1 hour at room temperature. After the reaction is complete,
The reaction solution was added to 8 g of water and extracted 4 times with 1.8 g of toluene. After washing with water, it was dried over anhydrous magnesium sulfate, and after concentration, hexane was added to obtain 275 g of the desired product as crystals. Yield 80%.

(2) Synthesis of 2-(2,3-dimethyl-4-bromophenoxy)acetaldehyde diethylacetal 2,3-dimethyl-4-bromophenol log (50 mmou) obtained in (1), 1 g (56 mmou) of bromoacetaldehyde diethylacetal ) was added to dimethylformamide (DMF) at 80°C, stirred vigorously, and
The reaction was carried out at 00°C for 6 hours. After cooling the reaction solution, water 2
00- was added and extracted with benzene 100-. After washing the extract with water, it was dried over anhydrous magnesium sulfate and concentrated to obtain 12.1 g of the target product. Yield 76%.

(3) Synthesis of 2-(2,3-dimethyl-4-ethoxyethylphenoxy)acetaldehyde diethyl acecool (according to the first production method) Compound 6 obtained in (2)
．． 3g (19 mmo), magnesium 0,6 (2
6 mmou) was added to dry THF 50+n/ and vigorous stirring was continued at room temperature under nitrogen atmosphere. After 1 hour, the reaction temperature was raised to a THF reflux state, and a solution of 5.3 g (21 mmou) of ethoxyethanol sulfonic acid ester in THF (20 WJ) was added dropwise over 30 minutes. The reaction was continued at the same temperature for 30 minutes after the dropwise addition. After the reaction was completed, the reaction solution was cooled, added to 100% of water, and 100% of chloroform was added.
! Extracted with. The extract was washed with water, dried over anhydrous magnesium sulfate, and concentrated to obtain the target product 2.525-71, 49
00 g was obtained. Yield 42%. J IH-NMR spectral data of product [τ(CDCl
2)] was as follows.

3.04 (2H, w), 3.45 (2H, w), 5
．． 15 (IH, t), 6.02 (2H, w), 6.18
~6.36 (8H, m), 7.77 (3H, s), 7.80 (3H, s), 8
．． 70-8.82 (9H, m) Furthermore, mass spectrum data shows that m/z310.
Peaks were observed at 219, 135, and 103, and the structure was confirmed.

Example 2 Synthesis of 2-(2,3-dimethyl-4-ethoxyethylphenoxy)acetaldehyde diethyl acecool (second
9.5 g (30 mm) of the compound obtained in Example 1 (2)
ou), 1.0 g (41 mmol) of magnesium was added to 50 - of dry THF, and vigorous stirring was continued at room temperature under a nitrogen atmosphere. After 1.5 hours, ethylene oxide 1
, 45g (33IIlmo) of THF solution 20- was added dropwise over 1 hour. After the dropwise addition, stirring was continued at room temperature for 2 hours.

After that, THF was distilled off, 50% of benzene was added, and 10% of water was added.
0- was added and washed with water. Diethyl sulfate 5 in benzene solution
．． 2g (33mmofL), sodium hydroxide 1.9
2 g (48 oJlj) of 54 aqueous solution and 0.5 g (1.8 mmou) of tetrabutylammonium chloride were added, and the reaction was continued at 40°C for 5 hours. After the reaction was completed, the benzene layer was concentrated to obtain 7.0 g of the target product. Accommodation 25°71
．． 4900 rate 75%. IH-NMR spectral data of np product [τ(CD
Cu3)] were as follows.

3.04 (2H, w), 3.45 (2H, w), 5.
15 (IH, t), 6.02 (2H, w), 6, 18
~6, 36 (8H, m), 7.77 (3H, s),
7.80 (3H, s), 8.70~8.82 (9H,
m) Furthermore, the mass spectrum data is m/z310.2
Peaks were observed at 19, 135, and 103.

Example 3 Synthesis of 2-(2,3-dimethyl-4-ethoxyethylphenoxy)acetaldehyde dimethyl acetal 10 g (50 mmou) of 2,3-dimethyl-4-bromophenol obtained in Example 1 (1), bromo Acetaldehyde dimethyl acetal 9,5g (56m
moJL), potassium iodide 0.8g (5mmou
), 6.9 g of potassium carbonate (65 mmojD in DMF
In addition to 80 mJ, the mixture was stirred vigorously and the reaction was carried out in a reflux state for 4 hours. After cooling the reaction solution, 200% of water was added and extracted with 100% of benzene. The extract was washed with a 12N aqueous sodium hydroxide solution to remove unreacted raw materials. The benzene solution was dried over anhydrous magnesium sulfate, and benzene was distilled off under reduced pressure. Dry THF 50. +J was added to this concentrate, and magnesium 1.15g (50
mmo) was added thereto, and vigorous stirring was continued at room temperature under a nitrogen atmosphere. After 2 hours, ethylene oxide 2 was added to the reaction solution.
, 2g (50m+mol) of THF solution (20WJ)
was added dropwise over 1 hour. After the dropwise addition, stirring was continued at room temperature for 2 hours.

After the reaction was completed, THF was distilled off, 75% of benzene was added, and 100% of water was added for washing. Add 6.2 g (40 mmouJL) of diethyl sulfate to the benzene solution, and add 2.6 g (65 mmou) of sodium hydroxide in an aqueous solution (8.2 g (40 mmouJL)).
/), tetrabutylammonium bromide 0.5g
(1.6 mmoJl) was added and the reaction was continued at 40°C for 5 hours. After the reaction is completed, the benzene layer is concentrated to obtain the desired product 6.
2g was obtained. Yield 24°71.4964 Rate 44%. IH-NMR spectral data of nD product ([τ(CDC
u3)] were as follows.

2.79 (3H, t), 3.75 (IH, w), 3
．． 34 (IH, w), 5.22 (IH, t), 6.03
(2H, w), 6.40-6.59 (IOH, m), 7.12 (2H
, t), 7.77 (3H, s), 7.82 (3H, s) Furthermore, from the mass spectrum data, m / z282.2
A peak was observed at 23.135, confirming the structure.

[Effect of the Invention J According to the present invention, a novel intermediate in phenoxyalkylamine synthesis can be provided. Furthermore, phenoxyalkylamine derivatives, which are useful compounds, can be produced using inexpensive raw material compounds.

Claims (4)

[Claims] (1) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2, R_3, R_4 and R_5
each independently represents a lower alkyl group; m represents 1 or 2; n represents an integer of 1 to 3). (2) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2 and R_3 each independently represent a lower alkyl group) The compound according to claim 1, represented by the following: . (3) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1, R_2, R_4 and R_5 each independently represent a lower alkyl group; X represents a halogen atom; m is 1 or 2) and the Grignard reagent represented by the general formula: Y-(CH_2)-_nO-R_3 [wherein, R_3 represents a lower alkyl group; Y is a halogen atom or R_4SO_3 (wherein, R_4 is substituted or unsubstituted phenyl group or lower alkyl group)
Represents a group represented by , and n represents an integer of 1 to 3] A general formula characterized by reacting a compound represented by: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2, R_3, R_4, R_5, m
and n has the same meaning as above). (4) General formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2, R_4 and R_5 each independently represent a lower alkyl group; X represents a halogen atom; m is 1 or 2) and the general formula: ▲Mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, n represents an integer from 1 to 3) After reacting with the alkylene oxide shown by ( R
_3)_2SO_4 or R_3Z (in both formulas, R_3
represents a lower alkyl group, and Z represents a halogen atom. , R_5m and n have the same meanings as above).