JPS61112057A - Production of pyridazinone derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I [R is H or lower alkyl; X is alkyl, alkoxy, alkenyloxy, lower haloalkyl, cycloalkyl, halogen, group of formula II (Y is halogen, lower alkyl, etc.; m is integer of 0-3), etc.; n is 1, 2 or 3]. EXAMPLE:2-t-Butyl-4-chloro-5-(2'-methylbenzylthio)-3(2H)-pyridaz-inone. PREPARATION:The compound of formula I can be prepared by reacting 2-t- butyl-4-chloro-5-mercapto-3(2H)-pyridazinone of formula III with the compound of formula IV in an inert solvent in the presence of a dehydrohalogenation agent. The reaction is carried out preferably by using a double-layer system comprising water and a water-insoluble solvent as the reaction solvent, in the presence of an inorganic base, while adding a phase-transfer catalyst to the system. The phase-transfer catalyst is e.g. quaternary ammonium salt.

Description

[Detailed description of the invention] The present invention is based on the general formula (■): [In the formula, [(represents a hydrogen atom or a lower alkyl group.

m is When 9m represents 0 or an integer from 1 to 3 and is 2 or 5, Y may be the same or different from each other.

) or a trimethylsilyl group, and a represents an integer of 1 to 3. When n is 2 or 3, X may be the same or different. This invention relates to a method for producing a novel pyridazinone derivative represented by the following.

The pyridazinone derivative represented by the general formula (1) obtained by the present invention (hereinafter simply referred to as the compound of the present invention) Jri+
This is a new compound that has not been described in any literature.

Pesticide 9% (useful as an active ingredient in insecticides, acaricides, nematicides and fungicides).

The present inventors have investigated various industrial methods for producing the compound (1) of the present invention represented by the general formula (1).

The following formula (II): 〇 General formula (II): [wherein, [-(alk...Rogge/atom], R, X,
and α have the same meanings as above. We have discovered a method for obtaining the compound (I) of the present invention in high yield by reacting the compound represented by When carrying out the reaction, a two-layer system of water and a water-insoluble solvent is used as a solvent, and the compound (1) of the present invention can be produced in a high yield by adding all of the phase transfer catalyst in the presence of an inorganic base. The present invention was completed by discovering a method for obtaining the above.

The method for producing the compound (1) of the present invention studied by the present inventors is shown in the following reaction formula.

[In the reaction formula, Hal, R, X, and α represent the same meanings as above. ]

In the above reaction formula, solvents include lower alcohols (e.g. methanol, ethanol, propatool, butanol, etc.), aromatic hydrocarbons (benzene, toluene, xyleph, etc.), ketones (acetone, methyl ethyl keto 7, etc.), amides ( N,N-dimethylformamide, N,N
-dimethylacetamide, etc.), -logenated hydrocarbons (methylene chloride, carbon tetrachloride, 1,2-dichromitane, etc.), esters (methyl acetate, acetate fk, etc.), ethers (tetrahydrofuran, etc.).

dioxa/etc.), acetonitrile, propionitrile,
Dimethyl sulfoxide, sulfolane, etc. can be used. Examples of dehydrogenation agents include inorganic bases (e.g. carbonate, potassium carbonate, calcium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.)
or organic bases (for example, pyridines such as pyridine 7.4-N and N-dimethylaminopyridine, metal alkoxides such as triethylamine, sodium methoxide, and sodium ethoxide). Although the molar ratio of the raw materials (II) and (Iff) can be set arbitrarily, it is practically desirable to set it to around 1:1. (,M
) or (III), the dehydrohalogenating agent may be used in an amount of 1 equivalent or more, preferably 1 to 3 equivalents. The reaction temperature can range from 0°C or lower to the boiling point of the solvent used, but the higher the reaction temperature is set, the more compounds represented by the following formula will be produced as by-products.
The yield of [) decreases and the purification operation becomes complicated.

Therefore, generally the reaction temperature is.

It is more preferable to set it slightly lower. Although the reaction time cannot be absolutely defined depending on the reaction conditions of the pond, it is generally 1 to 30 minutes.
The reaction is completed in about 8 hours.

In the reaction shown in the above reaction formula, the compound (fl) is reacted with a base such as sodium hydride, hydroxide, etc. to prepare a salt, and (, I)t- is added to react. This classification method is also possible.

Further, in the reaction represented by the above reaction formula.

When using a two-layer system of water and a water-insoluble solvent as a solvent, the water-insoluble solvent may include aromatic hydrocarbons (e.g. evabenzene, toluene, xylene, etc.) and halogenated hydrocarbons (e.g. methylene chloride, carbon tetrachloride, etc.). , 1,2-dichloroethane, etc.) can be used. As the inorganic base, sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium monocarbonate, potassium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc. can be used. As a phase transfer catalyst, quaternary ammonium l, U (e.g., t-tetra-□-butylammonium bromide, tetra-α-butyla/monium hydrogen sulfate, tetramethylammonium chloride, triethylbenzyl a/monium chloride) ,
tri-ro-octylmethylammonium chloride, etc.)
or phosphonium salts (eg, tetra-α-butyl-phosphonium bromide, etc.) can be used.

It is practically desirable that the ratio of the phase transfer catalyst to (IF) or ([[[) is set to [11 mol.

According to the method of the present invention, a novel pyridazinone derivative represented by the compound (1) of the present invention, which is extremely useful as an insecticide, acaricide, nematocide, and fungicide, can be produced in high yield and with easy operation. You can get it at

Next, the present invention will be explained with specific examples and reference examples. However, the present invention is not limited to these Examples.

Example 1 2-ter7yalybutyl-4-riocI-5-(2-methylbenzylthio)-5(2H)-M.

Preparation of pyridazino/(Compound No. 1) 2-tert-butyl-4-ri-5-mer-capto-3(2Fi)-pyridazinone 1. Of and α-chloro o-Q-xylene rL67f were dissolved in diethyl ether, triethyl aban α49tf was added, and the mixture was stirred at room temperature for 4 hours. After the reaction mixture was washed with an acid, washed with an alkali, washed with water, and dried over anhydrous sodium sulfate, diethyl ether was distilled off, and the residue was washed with cold petroleum ether to obtain white needles. Yield 91.2N m, p: 138-159°C Otori [(-NMR(ODO4), δ[ppH1]
: 1.62 (at 9 5.2-tqrt-C!, Sun, In)
2.40 (!IH,s, 2'-CFl, )4.2
1 (2nd, BCF-1!-), 7.17 (4
1 Tsuru phenyl) Example 2 Preparation of 2-tert-butyl-4-chloro-5-(4'-chlorobenzylthio)-5(2p)-pyridazinone (compound 42) 2-tert-butyl-4-chloro a- 5-mercapto-5(2H)-pyridazinone 1. Of benzene 10d
Dissolve K; 4. α-Siku a.

Toluene α77t and triethylamine [149f] were added and stirred at room temperature for 4 hours. Hereinafter, white needle crystals were obtained by the same operation as in Example 1.

Yield: 91.7
0 (98,s, 2-tert, -0,H,),
421 (2KB, -dOH,-)7.52(4
H, s, 7z-nyl), 7.56 (IH, a, 6th position) Example 3 2-tert-glutyl-4-chloroo-5-(4'-phenylbenzylthio)-3(2E()- Viridazinone (
Preparation of compound 3) 2-tert-butyl-4-chloroa-5-mercapto-3(2H)-pyridazinone 1. Of and 4-7 enylbe/zyl chloride CL97'''f'fe95 N
Powdered potassium hydroxide αS dissolved in 20m ethanol
2 ff was added and stirred at room temperature for 4 hours. Ethanol was distilled off under reduced pressure, benzene was added to the residue, washed with alkaline water, washed with anhydrous sulfuric acid) After drying with IJum, benzene was distilled off under reduced pressure and the residue was washed with cold petroleum ether to form white needles. I got crystal. Yield 952X m, p, + 169 A-171℃'H-NMR (
CDOL, ), δrppml :1.61 (9[(
, 3,2-tert-0,F(,) , 4. ! 1 (
2H,s, -dcH*-)7,26~7.75 (1
OH, rn, phenyl and 6-position) Example 4 2-tert-butyl-4-chloro-5-(4'-7
α-hexyl-α-methylbenzylthio)-5(2E1
)-Preparation of pyridazinone (compound l64) 2-tert-butyl-4-chloroa-5-mercapto-5 (2H)
-Pyridazino 7tOf and 4-cyclohexyl-
α-Methylbenzyl chloride was dissolved in t11Ft-acetonitrile, 1sst of anhydrous sodium carbonate was added, and the mixture was stirred at room temperature for 5 hours. Thereafter, white needle crystals were obtained by the same operation as in Example 1 in J 3. Yield 9α6X ton, o: 157--159℃ 1 unit (-NMR (CDC4), δrppml
:1.56 (9is, 2-tart-04H,)
, 1.68(5F(,d, Ix 7.2[(Z.

-OH,), 1.02-2.72 (IE,
m, 7 chlorohexyl).

a, s 4(IF(, q, Ix7.2Hz, -s?
[(-)7.01-7.40 (4H, m, phenyl)
, 7.51 (IE (, s, 6th place) implementation fi5 2-tert-butyl-4-ri arose + (4/
-trimethylsilylbenzylthio)-5(2EI)-pyridazino/(Compound A5) Preparation of 2-tert-butyl-4-chloroo-5-mercapto-3(2[()-pyridazinone 1.Of and 4-trimethyl/rilbe / fg solution of 1.0t of dichloride to 715ml of 1.2-dichloroethyltriethylamine (
L49ff was added and stirred at room temperature for 5 hours. Thereafter, white needle crystals were obtained by the same operation as in Example 1. Yield 8a4
Xl,p: 99.6~101.4℃"Fl-N
MR (CDOL, ), δ [”pp However]: Cl3
7 (9[(,s, -di(Of(,), ),
1.65 (9H,s, 2-tert-C,H,)4.
25 (2B, s, -dc days, -L 7.26~
7.65 (4HIm, 7x knee k) 767 (IH,s
, 6th position) Example 6 2-tert-butyl-4-chloro-5-(4'-(
p-)lifluoromethoxy)-benzylthio]-5(2
Preparation of H)-pyridazinone (compound 46) 2-tert-butyl-4-chloro-5-mercapto-3 (2 days)-pyridazinone 1.02 and 4-(p-
1.5 Of trifluoromethylphenoxy)-benzyl bromide was dissolved in acetone, 8fi of anhydrous potassium carbonate was added, and the mixture was stirred at room temperature for 5 hours. White needle crystals were obtained by the same operation as in Example 3. Yield 9 (
L7X tun, p: 15:l~15S5℃'H-N
MR (CDC4), δl”poml: 1.60 (
9F(,8,2-tart,-C,H,), 4.22
(2E(,s, -dcH,-)&92~7.60
(9H,m, phenyl and 6-position) Example 7 2-tert-butyl-4-rioo-5-bucine; (4'-4ael;-butylbenzylthio)-5(2H
)-Preparation of pyridazinone (compound muff) 2-tert-butyl-4-chloroa-5-mercapto-5 (2[()
-Viridazinone 1. Of and p-tert-butylbenzyl chloride [L88F to benzene! #L, 2
% sodium hydroxide aqueous solution 112F and tetra-Ω-butylammonium bromide 1L07f were added to 50%
The mixture was stirred at ℃ for 1.5 hours. After the benzene layer was washed with water and dried over anhydrous sodium sulfate, the benzene was distilled off under reduced pressure and the residue was washed with cold petroleum ether to obtain white needle crystals. Yield 9 & 4X m, p,: 111 to 112°C '[-]-NMR (ODO4), δ [ppm]: 1.
29 (9F(,s, 4'-tqrt-c, H,)
, 1.60 (9E(ea, 2-i6rt-01
11(@)4.21 (2H,s, -5cH,-L
7.52 (4) 11 m, 7z nil) 7, 61
(1 μs, 6th position) Example day 2-tert-butyl-4-ri alow 5-[4'-(
p-riaabenzoyl)-benzylthio]-5(2F!
)-Preparation of pyridazinone (compound 8) 2-tert-butyl-4-chloro-5-mercapto-5(2H)-pyridazinone 1. Of Oyo (F 4-
(p-riaabenzoyl)-benzyl bromide t43
Dissolve in rt-L2-dichloroethane and 2N hydroxide)
IJum water fg solution and 1L06ft of triethylbenzylammonium chloride were added, and the mixture was stirred at room temperature for 5 hours.

Thereafter, pale yellow needle crystals were obtained by the same operation as in Example F. Yield 7 a9X ton, p: 177-178°C 'H-NMR (ODot, ), δ[ppm]: 16
3 (9H,s, 2-tert-048,) , 4
．． 55 (21'1.s, -8(W,-)7.30
~795 (9H, m, phenyl and 6-position) Example 1
Compounds produced according to any of methods 1 to 8 are listed in Table 1.

Table 1 [However, in Table 1, 1M represents a methyl group, 1gt represents an ethyl group, Bu represents a butyl group, n represents normal, and t
indicates 7 years. ] Next, for reference, the insecticidal, acaricidal, nematocidal, and bactericidal tests of the compound (1) of the present invention are shown below.

Reference Example 1 Insecticidal test against adult house flies An acetone solution 1- of the compound of the present invention, 1 o o ppm1llf, was dropped onto a 91-shear area so as to spread evenly, and after the acetone was completely evaporated at room temperature, 10 adult house flies were added. , I covered the hole with plastic i1k. This petri dish was housed in a constant temperature room at 25° C., and the mortality rate after 48 hours was calculated using the following formula. The test was conducted in two sections. The results are shown in Table 2.

Mortality rate Mortality rate (X)"[x1" Reference example 27 Insecticidal test against Culex pipiens larvae After putting 200 d of water bath solution containing the compound of the present invention at a concentration of 10 ppm into a waist-high petri dish with a diameter of 97 m and a height of 63 cm, Culex pipiens entangled. Larva 1
0 animals were released.

This waist-high petri dish was housed in a thermostatic chamber at 25° C., and the mortality rate after 96 hours was calculated using the following formula.

The test was conducted in two sections.

The results are shown in Table 2.

Reference Example 3 Contact insecticidal test against diamondback moth A leaf of Citrus lanternis was immersed in a water emulsion of the compound of the present invention at a concentration of 10QOppm for about 10 seconds, air-dried, and then placed in a petri dish. The insects were released and housed in a thermostatic chamber at 25°C with a lid with holes, and the mortality rate after 96 hours was calculated using the following formula. The test was conducted in two sections. The results are shown in Table 2.

Reference Example 4 Contact Insecticidal Test with Tentula Nijekuyahoshitento Krff Tomato leaves were immersed in a water emulsion of the present invention compound at a concentration of 11,000 pp for about 10 seconds, air-dried, and placed in a petri dish, and in this, the leaves of Tomato leaves were immersed in a water emulsion of the compound of the present invention at a concentration of 11,000 pp. All 10 instar larvae were released per shear V.

The animals were placed in a 25C thermostatic chamber with a perforated lid, and the mortality rate after 96 hours was calculated using the following formula.

The test was conducted in two sections. result? Shown in Table 2.

Reference Example 5 Acaricidal Efficacy Test against Red Spider Mites A green bean leaf was cut into a circle with a diameter of 1.5 mm using a leaf punch, and placed on moist paper on a styrene cup with a diameter of 7. Add 1 Kanzawa spider mite larva per leaf to this.
0 animals were vaccinated. Half a day after inoculation, 1,000 doses of the compound of the present invention
A solution prepared by adding a spreading agent to a water emulsion with a concentration of ppm was sprayed at 2 parts per styrene cup using a rotary scattering tower, and the death rate after 96 hours was calculated using the formula in "af:F". The test was conducted in two sections.

The results are shown in Table 2.

Reference Example 6 Acaricidal efficacy test against Zukan spider mites Using a leaf punch, leaves of Unshu Baka were 1.5 cm in diameter.
It was cut out into a circular shape and placed on a wet door paper on a styrene cup with a diameter of 7α. This was inoculated with 10 ξ. spider mite larvae per leaf.

After one and a half days, a 10 Q Oppma water emulsion of the compound of the present invention with a spreading agent added was added to each styrene cup.
What is the mortality rate of insects after 96 hours of spraying using a rotary spray tower? It was calculated using the calculation formula below. The test was conducted in two sections.

The results are shown in Table 2.

Reference example) Insecticidal test against black leafhopper A rice mold leaf was immersed in a 1000 ppm concentrated emulsion of the compound of the present invention for about 10 seconds, and the molded rice leaf was placed in a glass cylinder to test its resistance to organophosphorus insecticides. Released 10 adult leafhoppers.

I covered it with a perforated plastic lid. This cylinder fc
The specimens were placed in a constant temperature room at 25° C., and the dead insect count after 96 hours was calculated using the following formula. The test was conducted in two sections. The results are shown in Table 2.

Reference Example 8 Nematicidal efficacy test against Nematode Nematode Contaminated soil with Nematode Nematode was placed on a sterol cag with a diameter of 8. A water emulsion of the compound of the present invention at a concentration of I Q Q Oorv was prepared, a spreading agent was added, and the mixture was sprinkled onto the soil at a rate of 50 d per styrene cup. After 48 hours, tomato seedlings of the indicator crop were transplanted. After 30 days of transplantation, the roots of the tomato plants were washed with water and an examination for Nekop parasitism was conducted according to the following criteria. The test was conducted in two sections. The results are shown in Table 2.

Nekop parasitism index 0: No nekkuk observed 1: Nekkub slightly observed 2: Nekkub is moderately observed 5: Nekkop is observed in large numbers 4: Nekokub is observed in extremely large numbers Reference example 9 Cucumber downy mildew control test 2 A water emulsion I (100%
0 ppm)' i Sprayed 20 times per pot. This Kieu I
A spore suspension of the downy mildew fungus (15 spores per field of view at 150x magnification) was sprayed and inoculated in a greenhouse for one day.

Chie cucumbers inoculated with spores of downy mildew fungus are grown at 25°C.
The plants were placed in a room with a relative humidity of 100X for 24 hours, and then transferred to a greenhouse to wait for the onset of disease. Seven days after inoculation, the degree of disease was investigated according to the following criteria. The results are shown in Table 3 - Summer.

0: No inoculated leaves develop disease 1: Inoculated leaves below 5X develop disease 2: Inoculated leaves 6-2ON develop disease 5: Inoculated leaves 21-50X develop disease 4: Inoculated leaves 51-9ON develop disease 5: Inoculated Aqueous emulsion (1000 ppm) of the compound of the present invention adjusted to a specified concentration using Kitame cucumber (variety: Sumo Hanshiro) grown in pots for 2 weeks (Cucumber Powdery Mildew Control Test)
- per pot #720 - sprayed. This Powdery mildew fungus was placed in a greenhouse for one day, and a spore suspension (15
Inoculation was performed by spraying 25 spores per field of view with OIII.

This plant was placed in a greenhouse at a temperature of -25 to 50°C and waited for the onset of disease. Ten days after inoculation, the degree of disease was investigated according to the following criteria. The results are shown in Table 3-■.

0: Inoculated leaves do not develop disease at all 1: Disease occurs on 5X or less of inoculated leaves 2: 6-20X of inoculated leaves develop disease 3: Disease occurs on 21-50X leaves 4: 51-90X of inoculated leaves develop disease 5: Disease occurs in 90X or more of the apical leaves. 4 2 Table Table 3-I Table 3-■ As is clear from the above results, the compound of the present invention.

It is a new compound that is extremely useful as an insecticide, acaricide, nematocide, and fungicide.

Claims (2)

[Claims] (1) The following formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) 2-tert-butyl-4-chloro-5-
Mercapto-3(2H)-pyridazinone and general formula (I
II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(III) [In the formula, Hal is a halogen atom, R is a hydrogen atom or a lower alkyl group, and X is a linear or branched chain having 1 to 6 carbon atoms. Alkyl group, linear or branched alkoxy group having 1 to 6 carbon atoms, alkenyloxy group having 3 to 6 carbon atoms, lower haloalkyl group, cycloalkyl group having 3 to 6 carbon atoms, halogen atom, ▲ mathematical formula, chemical formula, There are tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, Y is a halogen atom, lower alkyl group, or lower haloalkyl group, m is 0 or 1 (When m is 2 or 3, X may be the same or different.) or a trimethylsilyl group, and a represents an integer of 1 to 3. When a is 2 or 3, X may be the same or different. ] in the presence of a dehydrohalogenating agent,
General formula (I) characterized by the reaction being carried out in a solvent inert to the reaction: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R, X, and a have the same meanings as above. represent. ]
A method for producing a pyridazinone derivative represented by (2) In claim 1, the general formula (
A method for producing a pyridazinone derivative represented by I).