JPS5848559B2 - Satsukin Seika Gobutsu no Seizou Hohou - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of furancarboxamide derivatives having fungicidal activity and to certain novel compounds within this class of compounds.

In particular, the present invention provides the following steps: (a) a solid heterogeneous acid catalyst;
erogeneous acid catalyst
(b) converting the furanic acid ester formed into the corresponding carboxamide compound, in the presence of (R1 represents an alkyl group of C1.) , wherein R represents an optionally substituted alkyl, cycloalkyl, or aryl.

Examples of solid heterogeneous acid catalysts used in step (a) above include acidic clays and ion exchange resins.

The montmorillonite material commercially available from Sidchem ie-Munchen under code number K10 is particularly suitable as the acidic clay.

Preferably step (a) is carried out in an aromatic hydrocarbon solvent such as benzene or toluene.

According to the invention, by using a solid heterogeneous acid catalyst in step (a), for example J, Amer. C hem.
Soc. 70, pp. 739-741 (1948), a surprisingly high yield of the cyclized compound can be obtained compared to the case of using concentrated sulfuric acid (the yield is 18% in the method of the above-mentioned document). , yields of more than 70% are obtained with the method of the invention).

Furthermore, the solid acid can be easily removed from the reaction mixture by filtration and used again in subsequent reactions (in concentrated sulfuric acid, it is diluted with the water produced by the reaction and cannot be recycled). , and its disposal will not cause any environmental problems.

Furthermore, the solid acid does not corrode equipment and is less expensive than concentrated sulfuric acid.

Step (b) can be carried out by any method known in the art for converting carboxylic acid esters into carboxyamides.

The method includes reacting the furoate ester or reactive derivative thereof with an amine of formula RNH2.

The reactive derivative is a free acid, an acid . . . ride, etc. that responds to the furoate ester.

The following two methods have been found to be particularly suitable: 1. Furocarponic acid ester with a strong base and formula RNH
React with amine of 2.

The strong base is preferably an alkali metal hydride, such as sodium hydride, and the reaction is preferably carried out in a polar neutral solvent such as dimethyl sulfoxide.

2. The ester is hydrolyzed to the corresponding acid to form the corresponding amine salt of the acid, and the amine salt is treated with an acid catalyst,
Dehydration is preferably carried out in the presence of the solid heterogeneous acid catalyst described above.

The production method of the present invention is particularly applicable to the compound of formula (1) in which R is CI
up to 2 alkyl groups, such as methyl, ethyl, provyl, improvil, butyl, isophthyl, S-butyl,
Suitable for producing compounds which are t-7'' tyl, pentyl, hexyl, octyl, decyl, dodecyl or cyclohexyl or phenyl groups.

The starting material, a compound of formula
Any known method such as reacting a salt of acetoacetate of OCH2COOR1 ■ with a haloacetone compound of the formula HalCH COCH3 IV2 (where Hal represents chlorine or bromine) in the presence of an alkali metal iodide, preferably potassium iodide. It can be manufactured according to the method.

The acetoacetate of 2m (where Rl represents a methyl group) is obtained by reacting methyl acetate with sodium metal,
It can be produced in good yield using a new method in which methanol formed during the reaction is adsorbed onto a molecular sieve with a pore size of 4 to 5.

This sodium salt of methyl acetoacetate can be used for the production of the compound of formula (1) or can be converted by hydrolysis to crude methyl acetoacetate, which is purified by distillation.

The preferred molecular sieve used in the above method is code number 4A (Union Carbide).
) and has a pore diameter of 4mm.

The present invention also provides that R is an alkyl group, preferably methyl, ethyl, probyl, isopropyl, butyl, inftyl,
C1 such as S-butyl, t-butyl, pentyl, hexyl, octyl, decyl or dodecyl.

Furancarboxamide compounds of formula 1, which represent alkyl groups, are also included within the scope of the present invention as new compounds.

Since these novel compounds are useful as fungicides, the present invention also includes fungicidal compositions containing the novel compounds of the present invention together with a carrier and/or a surfactant.

At the same time, the present invention provides an effective bactericidal dose for areas where grains are damaged or have already been damaged by fungi, the seeds of such grains, the soil of the cultivation area of such grains, or the land on which grains are already grown. The present invention also provides a method for controlling damage to crops caused by such fungi by applying the novel compound or a composition containing the same.

The fungicidal furanylupoxiamide compound of the present invention is effective against powdery mildew of cucumber.
( E rysiphe cichoracearu
m) and powdery mildew of barley (Erysiphe g.
It is particularly effective in the systematic extermination of P. raminis).

In this respect, the compound of the present invention is disclosed in British Patent No. 1 303844.
Known 2-methyl-, 2,4-dimethyl-, and 2,4-dimethyl-, as shown in the specifications of No.
It is even better than 5-trimethyl-N-alkylfluamide compounds (see Example 10 below).

As used herein, "carrier" means any compound with which the active compound is mixed or formulated to facilitate the application of the active compound to the plants, seeds or other objects to be treated. A solid or fluid substance, natural or synthetic, inorganic or organic, which facilitates its storage, transportation or handling.

Surfactants may be either emulsifiers or dispersants or wetting agents, and may be ionic or nonionic.

Any carrier material or surfactant commonly used in the formulation of insecticides can be used for the compositions of the present invention; British Patent No. 12329 filed by a person
This is as shown in the specification of No. 30.

The composition of the present invention comprises hydrophilic powder, dust,
It can be formulated into granules, solutions, emulsified concentrates, emulsions, suspended concentrates and aerosols.

Hydrophilic powders usually contain 25, 50 or 75% by weight of active compound and, in addition to the solid carrier, 3 to 10% by weight.
dispersant and optionally 0 to 10% by weight of various stabilizers and/or other additives such as penetrants and fixing agents.

The dust is formulated into a dust formulation having a composition similar to that of the hydrophilic powder, except that it usually does not contain a dispersant, and generally contains an additional amount of solids, so as to give a composition containing from 10% to 10% by weight of the active ingredient. It is diluted with a carrier at the point of application.

Granules are usually 10-100BS mesh (1.676-
0.152 m) and manufactured by bulk accumulation or impregnation methods.

Typically, the granules contain % to 25% by weight of active ingredient and 0 to 10% by weight of additives such as stabilizers, slow-release modifiers and binders.

Emulsifying concentrates usually contain a co-solvent in addition to the solvent, if necessary, and contain 10-50 W/V% of the active ingredient, 2-2
It contains 0 W/V% emulsifier and 0.20 W/V% suitable additives such as stabilizers, penetrants, preservatives.

Suspension concentrates are formulated to provide a stable, non-sedimenting, well-flowing product and are typically 10-75% by weight.
active ingredient, 0.5-15% by weight dispersant, 0.1-1
0% by weight of suspending agents such as protective colloids and liquefaction agents, 0
- 10% by weight of suitable additives such as defoamers, preservatives, stabilizers, penetrants and fixing agents, and as a carrier water or an organic solvent which does not substantially dissolve the active ingredient; Contains.

Certain organic or inorganic salts may be dissolved as anti-settling or water anti-icing agents.

Aqueous dispersions and emulsions obtained by diluting the hydrophilic powder or concentrate of the present invention with water are also included within the scope of the present invention.

Such emulsions may be either water-in-water or water-in-oil, and may be of a thick mayonnaise-like consistency.

The compositions according to the invention may also contain other substances, such as compounds having insecticidal, especially insecticidal, acaricidal, herbicidal or fungicidal properties.

The invention is further illustrated by the following examples.

Example 1 Preparation of Methyl Acetoacetate Metallic sodium (34.7 f?, 1.51 mol) and methyl acetate (850 mJ) were heated together under reflux conditions until all the sodium metal was dissolved.

The refluxing solvent was passed through a molecular sieve (4A Union Carbide, 150f) before being refluxed into the reactor.
was passed to.

After 2 hours, excess methyl acetate was removed under reduced pressure and the residue was dissolved in an ice/water mixture (500 Tl) containing acetic acid (128P).
dissolved in.

The aqueous mixture was saturated with sodium chloride and extracted with chloroform (2×250ml).

The extract was washed with saturated potassium carbonate solution (50 mA'), dried and the solvent was removed under reduced pressure.

Distillation of the residue gave the desired product.

(149.5P, 85.5%, b.p, 60-62℃)
.

Example 2 Preparation of ethyl acetonyl acetoacetate Sodium metal (34,5r, 1.5 mol) in dry ethyl acetate (480rnl) is mixed with dry ethyl acetoacetate (195P, 1.5 mol), This mixture was heated under reflux conditions until all the sodium metal was dissolved.

The solvent was then removed under reduced pressure and the residue was dissolved in dry acetone (750 mJ).

Potassium iodide powder (3.0P) was added to this solution,
Next, this product is chloroacetone (148P, 1.
The mixture was heated under reflux conditions while adding chicken for 10 minutes.

This acetone was distilled off at normal pressure, and the residue was water (60%
0 mJ).

The organic phase was separated and the aqueous phase was diluted with methylene chloride (50
0ya7).

The separated organic phase and this extract phase were combined and the solvent was removed, resulting in a crude product that could be used in the reaction of Example 3 without further purification.

Example 3 Production of ethyl 2,5-dimethylfuran-3-carboxylate Ethyl acetonylacetoacetate (91.4P
) and acidic montmorillonite clay (K 1 0-Siidchemie, 5.) in toluene (120 mj?).
Of) is a Dean End Stark trap for water collection (
Dean and Stark trap).

9. Once 7 ml of water has been collected, the mixture is cooled, filtered, and the P solution is distilled to give ethyl-2.
5-dimethylfuran-3-carboxylate was obtained (60i, 71.5%, b, p, 9092 °C/1 1
mmHg).

When the above reaction was repeated using benzene as a solvent, the desired product was obtained with a yield of 76%.

Example 4?・Production of 5-dimethylfuran-3-N-butylcarpoxyamide 2.Ethyl 5-dimethylfuran-3-carboxylate (8
．． 4f, 0.05 mol), n-butylamine (3.65
? , 0.05 mol) and sodium hydride ( 1.2
P, 0.05 mol) is dimethylsulfoxide (2
Stirred in 5TILO for 3 days at room temperature.

The mixture was then poured into water, acidified with hydrochloric acid and extracted with chloroform (2X5QmJ).

The extract was washed with 5% sodium bicarbonate solution, dried and evaporated.

The residue was purified by chromatography on silica gel with methylene chloride as eluent, resulting in the desired product as an oil (Rf(CHCl3)0.75
) was obtained in 67% yield.

Theoretical value calculated as analytical value C1H1NO2: C67.7; H8,8; N7.2% Experimental value;
C6 7.3; H8.9; N7.1%Example 5 Preparation of 2,5-dimethylfuran-31N-phenylcarboxamide In dimethyl sulfoxide, 2,5-dimethylfuran-
Methyl 3-carboxylate (7.7 g, 0.05 mole), aniline (4.65 g, 0.05 mole) and sodium hydride (1.

21, 0.05 mol) was heated at room temperature for 24 hours.

This mixture was then poured into water (200 mQ), the solid formed was collected, and 5% hydrochloric acid (100 mQ, water 100 mQ) was poured into water.
mJ and then dried.

The product with m, p, 9 0-9 2°C was obtained in 86% yield.

Example 6 Preparation of 2,5-dimethylfuran-3-N-cyclohexyl-rupoxylamide 2,5-dimethylfuran-3
-Carboxylic acid (141, 0.1 mol) and cyclohexylamine (12P, 0.121 mol) were mixed.

Acidic montmorillonite clay (K10-Siid
Chemie, 10? ) was added to the solution and the mixture was heated under reflux conditions for 18 hours.

The solvent was then removed by distillation and the residue was heated such that the temperature rose from 145°C to 180°C in 6 hours.

After cooling, the raw material was chromatographed on silica gel using chloroform as eluent to obtain the desired product m, p, 104. ．． 5-106°C was obtained with a yield of 45%.

Example 7 Preparation of 2,5-dimethylfuran-3-N-propylupoxyamide Using excess thionyl chloride, 2,5-dimethylfuran-
The 3-carboxylic acid was converted to the acid chloride.

This acid chloride (32 g) in dry ether (10 m0) was added over 5 minutes to a solution of probylamine (3.1') in pyridine (25 m0).

The mixture was kept at 0° C. for 3 hours, followed by a further 16 hours.
Maintained at room temperature.

This solution, remaining in ether, was then distilled under reduced pressure to obtain an oil.

The ether solution was washed thoroughly with water, 5% hydrochloric acid, water, 5% sodium bicarbonate, and water.

Removal of the ether gave the desired product as a brown oil.

Analysis value C10H15NO2 and calculation Theoretical value: C66.3; H8.3: N7.7% Experimental value: C65.4; H8.1; N7.5% Example 8 Same as Example 4-7 Other compounds were prepared by the method and their physical properties and analytical values are shown in Table 1.

Example 9 Fungicidal activity A young cucumber tree with two leaves is called perl
ite)/soil mixture into a 9 cm diameter plastic pot and 7 days after transplanting, the mixture in this pot was injected with a solution 5 containing 250 ppm of the test compound.
0ml was added.

24 hours after application, this young tree was treated with E rys iph.
ec i choracearum (cucumber powdery mildew)
dew) was inoculated.

This young tree was then placed under constant temperature (22-30°C) and constant humidity conditions.

Bacterial growth was observed after 10-13 days.

The test results are shown in Table 2, where the number 2 indicates that the bacterial killing rate is 80% or more, the number 1 indicates a 50-80% killing rate, and the number O indicates that the killing rate is 80% or more. Mortality rate 5
This indicates that it is 0% or less.

Example 10 Comparative example regarding fungicidal activity In this experiment, 2.
The bactericidal activity of 5-dimethylfuran N-S-butylcarboxamide is higher than that of 2-methylfuran N-S-butylcarboxamide, 2,4-dimethylfuran N-S-butylcarboxamide, and 2,4,5-trimethylfuran N. The bactericidal activity of -S-butylcarboxamide was compared.

(a) Cucumber powdery mildew The test method was similar to that described in Example 9.

The infection rate of the fungus was observed after 11 days (b) Barley powdery mildew (1) Pre-emergence test J ohn placed in a 9 cm plastic pot
Innes compost was soaked with 50,771 liters of solution containing 250 ppm of each compound.

Twenty grains of dog oat (var, Suttan) were planted in each pot and covered with soil.

E rysiphe was applied to seedlings that germinated 7 days after sowing the seeds.
graminis was inoculated and then incubated in a greenhouse for 20
The cells were incubated at ℃ for 7 days.

The killing rate of bacteria was observed in two cases.

(11) Post-germination test In this test, barley seedlings aged 8 days in α pots were treated with solution 5Q containing 250 ppm of each compound.
Soaked in m7.

Two days after spraying the fungicide, these seedlings became E. grami.
Nis was inoculated and the bacterial infection rate was observed after an additional 7 days.

jtu%) The test results are shown in Table 3, and from the table X, it is clear that the 2,5-dimethylfuran derivative of the present invention has a bactericidal effect superior to other compounds similar to the compound. It should be obvious.

Claims (1)

[Claims] 1(a) A compound of the formula: (wherein Rl represents an alkyl group having 1 to 6 carbon atoms) is cyclized in the presence of a solid heterogeneous acid catalyst, and (b) thus comprising the steps of reacting the furoate ester or reactive derivative thereof formed with an amine of the formula RNH2, in which R is an optionally substituted alkyl, cycloalkyl or aryl (which may also be represented by alkyl, cycloalkyl or aryl)
A method for producing a furancarboxamide derivative.