KR840000072B1 - Process for preparing riovel 1-substituted uracil derivatives - Google Patents

Abstract

The title compds. I (R, R1=H, Me, Et; R2=alky1, alkoxy, Br, Cl, F, haloalkyl, CN, NO2, alkylthio, OH, olkylcarbonyl, alkoxycarbonyl, haloalkoxy, cycloalkyl, ahloalkylthio, alkenyl, alkynyl; R3,R4=independently selected from R2; X=H, CN, carbamoyl; Y=0˜3) were prepd. Thus, 5-cyano1-(2,6-dimethyl-phenyl)uracil was prepd. from NCCH2CONHCO2Et by sequential treatment with HC(OEt)3-AC2O (reflux, l hr) and 2,6-Me2C6H3-NH2(refluxing EtOH9,several hrs.), followed by heating in refluxing p-cymene for ˜1.5 hrs. The activities of I were assessed against pyricularia oryzae and Xanthomonas oryzae.

Description

Manufacturing method of novel 1-substituted uracils for cocci

The present invention relates to novel 1-substituted uracils, particularly novel and substituted 1-substituted uracils, which are useful for fungal and fungal cocci, including their synthesis and intermediates, and mixtures thereof. It relates to a manufacturing method of. The 1-substituted uracils of the present invention are represented by the following structural formula (a).

Wherein R and R ¹ are each hydrogen, methyl or ethyl.

R ² is lower alkyl, lower alkoxy, bromine, chlorine, fluorine, lower haloankyl, cyano, nitro, lower alkylthio, hydroxy, lower alkylcarbonyl, lower alkoxycarbonyl, lower haloalkoxy, cycloalkyl, Cycloalkaline, lower haloalkylthio, lower alkenyl or lower alkynyl.

R ³ is hydrogen or is independently selected from the value of R ² .

R ⁴ is hydrogen or independently selected from the value of R ² .

X is hydrogen, carbamoyl or cyano.

Y is 0,1,2 or 3.

The synthesis of compounds of formula (A) (X is cyano and R ¹ is hydrogen) is summarized below.

In actual synthesis, for example, N-ethoxycarbonyl cyanoacetamide (I) is reacted with triethyl orthoformate in acetic anhydride to α-cyano-β-ethoxy-N- Toxoxycarbonyl acrylamide (II, R is hydrogen) is obtained.

Using triethyl orthoacetate and triethylorthopropionate instead of triethylorthoformate yields compounds of formula II wherein R is methyl and ethyl, respectively.

When the compound of formula (II) is flammed with substituted aniline (II ') in ethanol, β-substituted anilino compound (III) is obtained.

When heated in a high boiling solvent such as P-cymene, tetralin, ortho-dichlorobenzene, etc. which can dissolve the compound of formula (III), it is cyclized to give 5-cyano-1-substituted phenyl uracil ( Get '

Compounds of formula (I) wherein R ¹ is methyl or ethyl are obtained by, for example, alkylating with dimethyl sulfate.

Each step of the above synthesis is actually carried out by quantitative calculation in a solid state which is easy to separate by filtration in II, III and structural formula (A).

The schematic synthesis procedure is described in Senda et al., Chem. Pharm. Bull. 20 (7), 1380-1388 (1972) and East and West citations CF. Lees et al., J. Chem. Soc. (C) 1519 (1968): Senda et al., J. Org. Chem. 40 (3), 353 (1975) and Offenlegungsschrift 25 09 037 (1976). Compounds of the invention of formula (A) wherein X is hydrogen are described in Senda et al., Chem. Pharm. Bull. 22 (1), 189-195 (1974) for several hours, heating the structural (a) or (ga ') 5-cyano compound with HBr or Enders et al., Offenlegunsschrift 25 09 037 (1976 Can be obtained by heating with sulfuric acid according to the procedure in.

The compound of formula A wherein X is carbamoyl (-CONH ₂ ) can be treated with 48% HBr following the procedure of Enders et al., Supra, or by Atkinson et al., J. Chem. Soc., 4118-4123 (1956), using alkaline hydrolysis according to the procedure.

The term "lower alkyl" as used herein refers to a lower alkyl group of 1-6 carbon atoms.

"Lower alkoxy" refers to a lower alkoxy group of 1-6 carbon atoms.

"Lower alkylthio" refers to a lower alkylthio group of 1-6 carbon atoms.

The term "lower haloalkyl" refers to a lower alkyl group substituted with 1-3 bromine, chlorine or fluorine atoms.

The term "low haloalkoxy" refers to a lower alkoxy group substituted with 1-3 bromine, chlorine or fluorine atoms.

The term "lower carbonyl" refers to a lower alkylcarbonyl group of 2-7 carbon atoms.

The term "cycloalkyl" refers to a cycloalkyl group of 3-4 carbon atoms.

The term "cycloalkalkyl" refers to a cycloalkyl group of 4-5 carbon atoms.

The term "lower haloalkylthio" refers to a lower alkylthio group substituted with 1-3 bromine, chlorine or fluorine atoms.

The term "lower alkenyl" refers to a lower alkenyl group of 2-4 carbon atoms.

The term "lower alkynyl" refers to a lower alkynyl group of 2-4 carbon atoms.

Compounds of structural formula (A) are useful biological agents against phytopathogens. In particular, the compounds of the present invention are useful antifungal or antibacterial agents for diseases caused by plant pathogens.

For example, during long periods of high humidity and reverse climate conditions that vary from warm to slightly cold temperatures, many plants, such as rice, tomato, pepper, cabbage, and fruits, are found in Pyicularia, xanthomonas ( Microorganisms belonging to Xanthomonas, Erwinia and the like, such as Piricularia Oryzae, Xanthomonas oryzae or Erwinia amylovora The fungal or bacterial disease caused by it is easily caught and damaged. The compounds of the present invention are effective for controlling such diseases. The compounds of the present invention can be used in or roughly on whole tissues by conventional methods of use.

The compounds of the present invention are solid and can be used in combination with a suitable solid or liquid vehicle in a conventional manner for use as an antifungal or antibacterial drug against plants.

The compounds of the present invention are used in concentrations of about 0.01-10.0% or more by weight. Suitable solid media include talc, kaolin, diatomaceous earth and diatomaceous earth, to which wetting agents and dispersants are added to form wettable powders. The wettable powder is diluted with water to the desired concentration and added to soil or plant skin.

Mixtures of the present invention comprising a compound of formula (A) have a variety of efficacy against the following diseases. Bacterial plant diseases such as Xanthomonas Canpestris of cabbage, Xanthomonas Vesicatoria of pepper, and Xanthomonas Malvacearus of cotton.

Erysiphe graminis of wheat and barley, Sphaerotheca fuliginea (e.g., gourds and cucumbers), Podosphaer Leucotricha (apples) and Uncinula nectar Fungal plant diseases such as powdery mildew, such as necator.

Puccinia recondita, Puccinia Struformis and other rusts of wheat, Puccinia hordel of barley, Puccinia struformis and other rusts: other Examples of plants include rust of coffee, apples, vegetables and ornamental plants. The compound is also used in Botrytis cinerea gray molds of tomatoes, strawberries, grapes and other plants and in the case of Collettortrichum coffeanum (berry desserts) of coffee. It is also valid for other diseases, such as disease. In addition to agriculture, they are also used as industrial antibacterial and antifungal agents, as are antifungal agents in paint films. The compounds also have properties that regulate plant growth. Active ingredients can be used as antifungal or antibacterial as they are, but for this purpose they are more conveniently used in mixtures.

The active ingredients of the mixtures of the present invention and their salts can be used in several ways. For example, they can be used directly or mixed with the medium directly on the leaves of plants, or they can be used in shrubs, trees, fruits or incubators in which they are grown, sprayed, powdered or creamed. It may be used in the form of or in the form of steam. It can be used on any part of a plant, shrub or tree. For example, it can be used on leaves, stems, branches or roots, or on soil or surrounding rice fields or on seeds before planting.

As used herein, "plant" includes seedlings, shrubs, and trees. Furthermore, the antifungal method of the present invention combines prevention and sterilization. In another aspect, therefore, the present invention provides a method for the cocci of fungi and bacteria of plants, seeds or places using the mixtures according to the invention. In another aspect, the present invention relates to Xanthomonas oryzae and pyricla by spraying on rice, its fruit or its place using a compound of formula (A) or a mixture comprising a compound of formula (A). It provides a way to overcome diseases like Pyricularia oryaze.

These mixtures include, for example, active ingredients and kaolin, bentonite, diatomaceous earth, dolomite, calcium carbide talcum, powder magnesia, fuller's earth, gypsum, hewitt's earth and dots. It may be in the form of a powder or particles containing a solid diluent such as (iii) or a medium. For example, a mixture for application to fruit may include, for example, mineral oil, to allow the mixture to adhere to the fruit. Alternatively, it can also be prepared using an organic solvent such as, for example, N-methyl pyrrolidone or dimethylform amide for fruiting. These mixtures may also be in the form of dispersible powders or particles comprising a humidifier to promote dispersion in the liquid. These powders and particles may also include fillers and suspending agents.

Liquid dispersants and emulsions dissolve the active ingredients in an organic solvent that optionally contains a humidifier, dispersant, or emulsifying agents, and then add these mixtures to water containing a humidifier, dispersant, or emulsifier. Obtained by.

Suitable organic solvents include ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methyl naphthalene, xylene, trichloroethylene, furfuryl alcohol, tetrahydrofurfuryl alcohol and glycol ethers (e.g., 2 Ethoxyethanol and 2-butoxyethanol). The mixtures used as sprays may be in the form of aerosols contained in a pressurized barrel, for example in the presence of a propellant such as fluorotrichloromethane or dichlorodifluoromethane.

The active ingredients also mix dry with the flame mixture to form a mixture suitable for generating smoke comprising these compounds in an enclosed space. Alternatively, the active ingredients can be used in very small capsules. For example, different mixtures may be better used for different purposes by adding appropriate additives to improve the dispersion, adhesion and rain resistance on the prescription surface. The active ingredients can be used as a mixture with fertilizers (eg fertilizers containing nitrogen, potassium or phosphorus). For example, mixtures comprising fertilizer particles incorporated by coating a compound of formula (A) would be preferred. Such particles will suitably contain up to 25% by weight of the compound of formula (A).

In another aspect, the present invention also provides a fertilizer mixture containing the compound of the general formula (A). The compounds may also be in liquid form, which are liquid dispersants or emulsions containing one or more humidifiers, dispersants, emulsifiers or suspending agents for use as a dipping agent or spray. The agents may be cationic, anionic or nonionic. Suitable cationic agents include, for example, quaternary ammonium compounds such as cetyltrimethyl ammonium bromide.

Suitable anionic agents include soaps, monoester fatty salts of sulfuric acid (e.g. sodium lauryl sulfate) and salts of sulfated aromatic compounds (e.g. sodium dodecylbenzene sulfate, sodium lignosulphate, calcium or ammonium salts, sulfated butyl naphthalene, And sodium diisopropyl sulfate and sodium triisopropyl-naphthalene sulfate). Suitable nonionic agents are those obtained by condensation of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol or by condensation with alkyl penles such as octyl or nonylphenol and octylcresol. Other nonionic agents include partial esters obtained from fatty acids and hexyl anhydrides of Ginchain, condensates of these esters with ethylene oxide, and lecithin.

Suitable suspending agents include hydrophilic colloids (eg polyvinylpyrrolidone and carboxymethyl cellulose sodium) and phyto rubbers (eg acacia rubber and tragacanth rubber). Mixtures used as liquid dispersants or emulsions are generally supplied in concentrated form containing a large amount of the active ingredients so that they can be diluted with water before use. These concentrates must withstand long periods of storage, and after storage they should be able to form liquids that remain homogeneous so that they can be used for a sufficient time with conventional spraying apparatus even when diluted with water.

These concentrates may contain the active ingredients by weight, for example 25-60%, suitably 10-85%, and up to 95% for convenience. When diluting to a liquid phase, the active ingredient may be included in various ratios according to the purpose of use, but a liquid agent containing 0.0005% or 0.01% to 10% of the active ingredient by weight is used.

The mixtures of the present invention may also contain other compounds with biological activity [eg, growth promoters such as gibberellin (e.g. GA ₂ , GA ₄ or GA ₇ ), oxins (e.g., indle acetic acid or indrevetic acid) and As well as cytokinin (e.g. kinetin, diphenylurea, benzimidazolol and benzyladenin) and other compounds with adjuvant antifungal and insecticidal effects, as well as stabilizing agents such as epoxides (e.g. epichlorohydrin) It may contain. The following examples are intended to illustrate the practice of the present invention. The temperature is shown in degrees Celsius.

Example 1

A mixture of N-ethoxycarbonylcyanoacetamide (42 g), a salt of triethylortho formic acid (40 g) and acetic anhydride (100 ml) is heated to reflux for one hour. The reaction proceeds until it is cooled, filtered and washed with ether to obtain α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide.

0.6 g of 2.6-dimethylaniline is added to α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (1.2 g) dissolved in 5 ml of boiling ethanol. After refluxing for several hours, hexane is added. After cooling, filtration and washing with ethanol and ether gives α-cyano-β- (2.6-dimethylanilino) -N-ethoxycarbonylacrylamide having a melting point of 138-140 °. A mixture of α-cyano-β- (2.6-dimethylanilino) -N-ethoxy-carbonylacrylamide (1.2 g) and about 10 ml of P-cymene is heated to reflux for 1.5 hours.

After cooling, filtration and washing with ether gives 5-cyano-1- (2.6-dimethylphenyl) uracil having a crystalline and melting point of 267-269 °. 6-ethoxy-2-methylaniline, 6-chloro-2-methyl-4-methoxyaniline, 4-fluoro-2-methylaniline, 2.6-dimethyl-4-fluoro aniline according to the above method, 3 Each of -chloro-2-methyl-6-methoxyaniline, 2-ethoxyaniline, 2- (1-propenyl) aniline and 2.6-dimethyl-4-methoxyaniline is α-cyano-β-ethoxy When the product obtained by reaction with -N-ethoxycarbonylacrylamide is cyclized, the following compounds are obtained, respectively.

5-cyano-1- (6-ethoxy-2-methylphenyl) uracil

5-cyano-1- (6-chloro-4-methoxy-2-methylphenyl) uracil

5-cyano-1- (4-fluoro-2-methylphenyl) uracil

5-cyano-1- (2,6-dimethyl-4-fluorophenyl) uracil

5-cyano-1- (3-chloro-6-methoxy-2-methylphenyl) uracil

5-cyano-1- (2-ethoxyphenyl) uracil

5-cyano-1- [2- (1-propenyl) phenyl] uracil

5-cyano-1- (2.6-dimethyl-4-methoxyphenyl) uracil

Example 2

To a warm solution of α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (14.8 g) and ethanol, P-chloro aniline (8.9 g) dissolved in ethanol immediately precipitates. The resulting mixture was stirred for 1 hour at room temperature and then filtered to afford α-cyano-β- (4-chloroanilino) -N-ethoxycarbonylacrylamide with a melting point of 177-180 °.

A mixture of 8.8 g of α-cyano-β- (4-chloro-anilino) -N-ethoxycarbonylacrylamide and 40 ml of ortho-dichlorobenbene is heated to reflux. After 2 hours crystals form and the mixture is cooled to room temperature. Filtration of the mixture yields 5-cyano-1- (4-chlorophenyl) uracil with a melting point of 236-239 °.

Example 3

To 10.0 g of α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide dissolved in about 40 ml of hot ethanol is added 6.45 g of 2.6-difluoroaniline dissolved in 15 ml of ethanol. The reaction mixture was cooled to reflux for 6 hours to obtain a white solid (12.61 g) α-cyano-β- (2.6-difluoroanilino) -N-ethoxycarbonylacrylamide. It is added again to 60 ml of tetralin and heated to reflux for 5 hours. The mixture is cooled, filtered and washed with ether to give 10.21 g of 5-cyano-1- (2.6-difluorophenyl) uracil as a white solid.

Example 4

A mixture of α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (10 g) and 45 ml of ethanol is dissolved by heating. To this was added 8.12 g of P-trifluoromethylaniline dissolved in 10 ml of ethanol and the mixture was heated to reflux for 45 minutes. The mixture was cooled and filtered to yield 14.01 g of α-cyano-β- (4-trifluoromethylanilino) -N-ethoxycarbonylacrylamide.

It is then added to 60 ml of tetralin and heated to reflux for several hours. When a precipitate is formed, the mixture is cooled, filtered and washed with ether to give 5-cyano-1- (4-trifluoromethylphenyl) uracil having a melting point of 230.5-231.5 °. According to the above method, P-methoxyaniline (0.05 ml) is reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (0.05 mol) to produce α-cyano-β- (4- Obtain methoxyanilino) -N-ethoxycarbonylacrylamide. This is added to tetralin and cyclized by heating to give 5-cyano-1- (4-methoxyphenyl) uracil having a melting point of 304.5-306.5 °.

Reaction of 3-fluoro aniline (0.05 mol) with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (0.05 mol) results in α-cyano-β- (with a melting point of 169.5-171.0 °). 3-fluoroanilino) -N-ethoxy-carbonylacrylamide is obtained. This is added to tetralin and heated to reflux to yield 5-cyano-1- (3-fluorophenyl) uracil having a melting point of 245.5-246.5 °.

2.6-dichloroaniline and α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide added to ethanol were refluxed for 3 days and hexane was added to give α-cyano-β- (2.6-dichloroanilino) -N Obtain ethoxycarbonylacrylamide. When this is added to tetralin and cyclized by heating, 5-cyano-1- (2.6-dichlorophenyl) uracil having a melting point of 273-274.5 ° is obtained.

When 2,4.6-trifluoroaniline (0.04 mol) is reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (0.04 mol) while heating under reflux in ethanol, α-cyano- (2,4,6-trichloroanilino) -N-ethoxycarbonylacrylamide is obtained. This is added to 1,2-dichlorobenzene and subjected to ring heating to reflux to give an incomplete product. Purification by chromatography on silica eluting with chloroform / acetone (3/1) gave slightly yellow crystals and 5-cyano-1- (2,4,6-trichlorophenyl) with a melting point of 245-247 °. Get uracil.

When a mixture of α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide (0.047 mol), 3,4-dichloroaniline (8.15 g) and ethanol (70 ml) is heated, the α-cyano-β- (3,4-dichloroanilino) -N-ethoxycarbonylacrylamide is obtained. This is added to tetralin and cyclized with heating overnight to give 5-cyano-1- (3,4-dichlorophenyl) uracil with a melting point of 206.5-207.5 °. In the same manner, 5-cyano-1- (3,5-dichlorophenyl) uracil is obtained by using 3,5-dichloroaniline instead of 3,4-dichloroaniline.

Example 5

2-methoxyaniline, 4-nitroaniline, 4-ethylaniline, 4-methoxy-2-methylaniline, 4- (N, N-dimethyl) aniline, 2-bromoaniline, 4- Methylaniline, 4-isopropylaniline, 4-t-butylaniline, 4-acetylaniline, 2-fluoroaniline, 2-cyanoaniline, 4-methylthioaniline, 2-fluoro-4-methylaniline, 4 -Chloro-2-fluoroaniline, 4-fluoro-2-methylaniline, 4-trifluoromethylthioaniline, 2-chloro-4-cyanoaniline, 4-chloro-2,6-difluoroaniline , 4-chloro-2-cyanoaniline, 2,4-dimethoxyaniline-2-chloro-6-methylaniline, 4-cyclopropylaniline, 2,6-dimethyl-4-t-butylaniline, 2, 4 , 6-trimethylaniline, 4-chloro-2,6-dimethylaniline, 2-trifluoromethylaniline, 3,4-methylenedioxyaniline, 4-bromo-2-fluoroaniline, 2-fluoro- 4-trifluoromethylaniline, 2-chloro-4-trifluoromethylaniline and 2-methyl Each of the 4-trifluoromethylaniline is reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide to obtain the β-anilino compound shown in the following I, respectively.

Cyclization gives the 5-cyano-1-substituted phenyl uracil shown in II, respectively.

I

(1) α-cyano-β- (2-methoxyanilino) -N-ethoxycarbonylacrylamide

(2) α-cyano-β- (4-nitroanilino) -N-ethoxycarbonylacrylamide

(3) α-cyano-β- (4-ethylanilino) -N-ethoxycarbonylacrylamide

(4) α-cyano-β- (4-methoxy-2-methylanilino) -N-ethoxycarbonylacrylamide

(5) α-cyano-β- (4- (N, N-dimethyl) anilino) -N-ethoxycarbonylacrylamide

(6) α-cyano-β- (2-bromoanilino) -N-ethoxycarbonylacrylamide

(7) α-cyano-β- (4-methylanilino) -N-ethoxycarbonylacrylamide

(8) α-cyano-β- (4-isopropylanilino) -N-ethoxycarbonylacrylamide

(9) α-cyano-β- (4-t-butylanilino) -N-ethoxycarbonylacrylamide

(10) α-cyano-β- (4-acetylanilino) -N-ethoxycarbonylacrylamide

(11) α-cyano-β- (2-fluoroanilino) -N-ethoxycarbonylacrylamide

(12) α-cyano-β- (2-cyanoaniline) -N-ethoxycarbonylacrylamide

(13) α-cyano-β- (4-methylthioanilino) -N-ethoxycarbonylacrylamide

(14) α-cyano-β- (2-fluoro-4-methylanilino) -N-ethoxycarbonylacrylamide

(15) α-cyano-β- (4-chloro-2-fluoroanilino) -N-ethoxycarbonylacrylamide

(16) α-cyano-β- (4-fluoro-2-methylanilino) -N-ethoxycarbonylacrylamide

(17) α-cyano-β- (4-trifluoromethylthioanilino) -N-ethoxycarbonylacrylamide

(18) α-cyano-β- (2-chloro-4-cyanoanilino) -N-ethoxycarbonylacrylamide

(19) α-cyano-β- (4-chloro-2,6-difluoroanilino) -N-ethoxycarbonylacrylamide

(20) α-cyano-β- (4-chloro-2-cyanoanilino) -N-ethoxycarbonylacrylamide

(21) α-cyano-β- (2,4-dimethoxyanilino) -N-ethoxycarbonylacrylamide

(22) α-cyano-β- (2-chloro-6-methylanilino) -N-ethoxycarbonylacrylamide

(23) α-cyano-β- (4-cyclopropylanilino) -N-ethoxycarbonylacrylamide

(24) α-cyano-β- (2,6-dimethyl-4-t-butyl-anilino) -N-ethoxycarbonylacrylamide

(25) α-cyano-β- (2,4,6-trimethylanilino) -N-ethoxycarbonylacrylamide

(26) α-cyano-β- (4-chloro-2,6-dimethylanilino) -N-ethoxycarbonylacrylamide

(27) α-cyano-β- (2-trifluoromethylanilino) -N-ethoxycarbonylacrylamide

(28) α-cyano-β- (3,4-methylenedioxyanilino) -N-ethoxycarbonylacrylamide

(29) α-cyano-β- (4-bromo-2-fluoroanilino) -N-ethoxycarbonylacrylamide

(30) α-cyano-β- (2-fluoro-4-trifluoromethylanilino) -N-ethoxycarbonylacrylamide

(31) α-cyano-β- (2-chloro-4-trifluoromethylanilino) -N-ethoxycarbonylacrylamide

(32) α-cyano-β- (2-methyl-4-trifluoromethylanilino) -N-ethoxycarbonylacrylamide

(32) α-cyano-β- (2-methyl-4-trifluoromethylanilino) -N-ethoxycarbonylacrylamide

Ⅱ

(1) 5-cyano-1- (2-methoxyphenyl) uracil, melting point 2 6-238 °

(2) 5-cyano-1- (4-nitrophenyl) uracil, melting point 269-272 °

(3) 5-cyano-1- (4-ethylphenyl) uracil, melting point 223-225 °

(4) 5-cyano-1- (4-methoxy-2-methylphenyl) uracil, melting point 276-278 °

(5) 5-cyano-1- (4- (N, N-dimethyl) phenyl) uracil, melting point 309-310 °

(6) 5-cyano-1- (2-bromophenyl) uracil

(7) 5-cyano-1- (4-methylphenyl) uracil

(8) 5-cyano-1- (4-isopropylphenyl) uracil

(9) 5-cyano-1- (4-t-butylphenyl) uracil

(10) 5-cyano-1- (4-acetylphenyl) uracil

(11) 5-cyano-1- (2-fluorophenyl) uracil, melting point 275 ° (dec)

(12) 5-cyano-1- (2-cyanophenyl) uracil, melting point 269-275 °

(13) 5-cyano-1- (4-methylthiophenyl) uracil

(14) 5-cyano-1- (2-fluoro-4-methylphenyl) uracil

(15) 5-cyano-1- (4-chloro-2-fluorophenyl) uracil

(16) 5-cyano-1- (4-fluoro-2-methylphenyl) uracil

(17) 5-cyano-1- (4-trifluoromethylthiophenyl) uracil

(18) 5-cyano-1- (2-chloro-4-cyanophenyl) uracil

(19) 5-cyano-1- (4-chloro-2,6-difluorophenyl) uracil

(20) 5-cyano-1- (4-chloro-2-cyanophenyl) uracil

(21) 5-cyano-1- (2,4-dimethoxyphenyl) uracil, melting point 285 ° (dec)

(22) 5-cyano-1- (2-chloro-6-methylphenyl) uracil

(23) 5-cyano-1- (4-cyclopropylphenyl) uracil

(24) 5-cyano-1- (2,6-dimethyl-4-t-butylphenyl) uracil

(25) 5-cyano-1- (2,4,6-trimethylphenyl) uracil, melting point 276-277 °

(26) 5-cyano-1- (4-chloro-2,6-dimethylphenyl) uracil

(27) 5-cyano-1- (2-trifluoromethylphenyl) uracil, melting point 258-259 °

(28) 5-cyano-1- (3,4-methylenedioxyphenyl) uracil

(29) 5-cyano-1- (4-bromo-2-fluorophenyl) uracil

(30) 5-cyano-1- (2-fluoro-4-trifluoromethylphenyl) uracil

(31) 5-cyano-1- (2-chloro-4-trifluoromethylphenyl) uracil

(32) 5-cyano-1- (2-methyl-4-triflumethylofenal) uracil

Example 6

Α-cyano-β-ethoxy-N-ethoxycarbonylcrotonamide (0.05 mol) is reacted with 2,6-dimethylaniline (0.05 mol) in hot ethanol according to the method of Example 1 No-β- (2,6-dimethylanilino) -N-ethoxycarbonyl crotonamide is obtained.

This was added to tetralin and heated to cyclize to give 5-cyano-1- (2,6-dimethylphenyl) 6-methyluracil having a melting point of 302-303 °.

Example 7

Add dimethyl sulfate (0.1 mol) slowly while stirring a mixture of 5-cyano-1- (2,6-dimethylphenyl) uracil (0.1 mol) and 80 ml of 5% sodium hydroxide solution.

The reaction mixture is stirred for 2 hours, filtered, washed and dried to afford 5-cyano-1- (2,6-dimethylphenyl) -3-methyluracil with a melting point of 198.2-199.5 °. 5-cyano-3,6-dimethyl-1- (2,6-dimethylphenyl) uracil was prepared from 5-cyano-1- (2,6-dimethylphenyl) -6-methyluracil according to the above method. Get

Example 8

Ten grams of α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide is dissolved by heating to 50 ° in 50 ml of ethanol. 5.32 g of 2-methylaniline added to 20 ml of ethanol was added thereto and stirred at reflux for 4 hours while stirring.

When cooled, crystals form and the mixture is filtered and washed with ether to give 11.36 g of α-cyano-β- (2-methylanilino) -N-ethoxycarbonylacrylamide. It is dissolved in tetralin and heated to reflux for 3 hours.

After cooling, filtration and washing with ether gives 5-cyano-1- (2-methylphenyl) uracil having a melting point of 251.5-252.5 °. The procedure was repeated using 0.05 mol of 4-cyanoaniline instead of 2-methylaniline to give 10.43 of 5-cyano-1- (4-cyanophenyl) uracil with a melting point of 324-326 ° (dec). g get Repeating the above procedure using 6.83 g of 4-methoxy-2-methylaniline instead of 2-methylaniline results in 5-cyano-1- (4-methoxy-2-methylphenyl having a melting point of 276.5-277.5 °. Get uracil.

Example 9

A mixture of 5-cyano-1- (2,6-dimethylphenyl) uracil (0.01 mol) and 30 ml of 48% HBr is heated to reflux for about 10 hours. After cooling, the solid product is filtered, washed with water and dried to obtain 1- (2,6-dimethylphenyl) uracil.

Hydrolysis of 5-cyano-3-methyl1- (2,6-dimethylphenyl) uracil according to the above method yields 1- (2,6-dimethylphenylmethyl) -3-uracil.

Example 10

A mixture of 5-cyano-1- (2,6-dimethylphenyl) uracil (0.01 mol) and 50 ml of 48% HBr is heated to reflux for 2 hours. After cooling, the solid reaction product is filtered, washed with water and dried to obtain 5-carbamoyl-1- (2,6-dimethylphenyl) uracil having a melting point of 315 ° (dec).

Example 11

A mixture of 5-cyano-1- (2,6-dimethylphenyl) uracil (0.01 mol) and 50 ml of NaOH (2.5N) is heated at about 90 ° for 2 hours. After cooling a little dil HCl is added and the product precipitates. The precipitate obtained by filtration of the mixture is washed with water to give 5-carbamoyl-1- (2,6-dimethylphenyl) uracil.

Example 12

A solution of α-cyano-β-ethoxy-N-ethoxycarbonyl acrylamide (0.05 mol) and 2,6-dimethylaniline (0.05 mol) added to 75 ml of ethanol was confirmed by thin membrane chromatography. Reflux for several hours until 6-dimethylaniline is gone.

Cooling (no precipitation is formed) and adding the hexane (approx. 400 ml) and filtering the mixture gives 10.52 g of α-cyano-β- (2,6-dimethylanilino) -N-ethoxycarbonylacrylamide (melting point) 138-140 °). This is added to ortho-dichlorobenzene and cyclized with heating for 4 hours to give 5-cyano-1- (2,6-dimethylphenyl) uracil.

Example 13

According to the above method, each of the aniline compounds shown in III below is reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide to obtain corresponding β-anilino compounds, respectively. Cyclization of this yields the corresponding 5-cyano-1-substituted phenyl uracil shown in IV below.

Ⅲ

2-chloro-4-methylaniline 3,4-dimethoxyaniline

4-chloro-2-methylaniline 4-n-butylaniline

2-chloroaniline 3-chloroaniline

3,5-dimethoxyaniline 2-chloro-5-trifluoromethylaniline

6-chloro-2-methylaniline 3-chloro-2-methylaniline

3-acetylaniline 2-isopropylaniline

4-chloro-3-trifluoromethylaniline 3-methylaniline

2-chloro-5-nitroaniline 3-trifluoromethylaniline

3-chloro-4-fluoroaniline 4-hydroxy-2-methylaniline

2,3-dichloroaniline 4-fluoroaniline

5-methyl-2-nitroaniline 2,4-difluoroaniline

2-methylthioaniline

Ⅳ

5-cyano-1- (2-chloro-4-methylphenyl) uracil, melting point 249-250 °

5-cyano-1- (4-chloro-2-methylphenyl) uracil, melting point 230-231 °

5-cyano-1- (2-chlorophenyl) uracil, melting point 260-262 °

5-cyano-1- (3,5-dimethoxyphenyl) uracil, melting point 236-238 °

5-cyano-1- (6-chloro-2-methylphenyl) uracil, melting point 241-243 °

5-cyano-1- (3-acetylphenyl) uracil, melting point 270-271 °

5-cyano-1- (4-chloro-3-trifluoromethylphenyl) uracil, melting point 231-232 °

5-cyano-1- (2-chloro-5-nitrophenyl) uracil, melting point 244 ° (dec)

5-cyano-1- (3-chloro-4-fluorophenyl) uracil, melting point 193-196 °

5-cyano-1- (2,3-dichlorophenyl) uracil, melting point 235-240 °

5-cyano-1- (5-methyl-2-nitrophenyl) uracil, melting point 295-300 ° (dec)

5-cyano-1- (2-methylthiophenyl) uracil, melting point 215-219 °

5-cyano-1- (3,4-dimethoxyphenyl) uracil, melting point 222-225 °

-부틸페닐)우라실, 융해점 181-183°5-cyano-1- (4-

Butylphenyl) uracil, melting point 181-183 °

5-cyano-1- (3-chlorophenyl) uracil, melting point 228-231 °

5-cyano-1- (2-chloro-5-trifluoromethylphenyl) uracil, melting point 170-170 °

5-cyano-1- (3-chloro-2-methylphenyl) uracil, melting point 225 °

5-cyano-1- (2-isopropylphenyl) uracil, melting point 153-156 °

5-cyano-1- (3-methylphenyl) uracil, melting point 235-237 °

5-cyano- (3-trifluoromethylphenyl) uracil, melting point 155-157 °

5-cyano-1- (4-hydroxy-2-methylphenyl) uracil, melting point 292-294 °

5-cyano-1- (4-fluorophenyl) uracil, melting point 224-226 °

5-cyano-1- (2,4-difluorophenyl) uracil, melting point 216-219 °

Example 14

According to the above method, aniline and 4-bromoaniline are reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide and cyclized, respectively, to give 5-cyano-1-phenyluracil (melting point 290). °) and 5-cyano-1- (4-bromophenyl) uracil, (melting point 257-260 °). The two compounds are described in Atkinson et al., J. Chem. Soc. 4118-4123 (1956) and Senda et al., Chem Pharm. Bull 22 (1) and 189-195 (1974), respectively.

Example 15

According to the above method, each of the anilino compounds and the like shown in V below is reacted with α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide to cyclize to obtain the corresponding uracil compound shown in VI below.

Ⅴ

Ⅵ

Example 16

Mix the active ingredients to obtain an emulsifiable concentrate and stir the mixture until all ingredients are dissolved.

Example 17

The first three ingredients are ground together with slightly water and mixed with sodium acetate to obtain a mixture of small granules that can easily disperse in liquids such as water. The resulting mixture can be dried and filtered through English standard micromeshes (size 44-100) to obtain granules of the desired size.

Example 18

All ingredients were ground together to obtain a powder product that could easily be dispersed in a liquid.

Example 19

The solution obtained by dissolving the active ingredients in a solvent was sprayed onto the clay particles. The solution was evaporated to give a granular mixture.

Compound of Example 8 (Prepared initially) 5: 95% Doto Granules

Example 20

The following three ingredients were mixed to obtain a mixture suitable for use on fruit.

Example 21

The active ingredient was mixed with talc to obtain a spray powder.

5% compound (# 1) of Example 5, talc 95%

Example 22

The mixture obtained by grinding the following components with a bowl mill is made into water and a suspension.

Example 23

The ingredients below are mixed and ground until fully mixed to obtain a dispersible powder.

Example 24

This example illustrates the preparation of a dispersible powder.

The ingredients are mixed and ground with a grinder.

Example 25

Dispersible powder was obtained by mixing and grinding the following components.

In the examples of 16-25 the proportions of the components are shown by weight.

The substances represented by the trademarks are as follows:

LUBROL L: Condensate of nonylphenol (1 mol) and ethylene oxide (13 mol).

AROMASOL: A solvent mixture of alkylbenzenes.

DISPERSOL T AND AC: A mixture of sodium sulfate and condensate of formaldehyde and sodium naphthalene sulfone.

LUBROL APN 5: Condensate of nonylphenol (1 mol) and naphthalene oxide (5.5 mol).

CELLOF AS B600: Carboxymethyl Cellulose Sodium Thickener.

LISSAPOL NX: Condensate of nonylphenol (1 mol) and ethylene oxide (8 mol).

AEROSOL OT / B: Dioctyl sulfosuccinate sodium

PERMINAL BX: Alkyl naphthalene sulfone sodium

Example 26

The active ingredients (test compounds) were tested against various fungal diseases in the leaves of plants. The test method is as follows.

The plants were grown in small pots 4 cm in diameter with the John Innes Potting Compost (which is very appropriate). A fine sand layer is placed at the bottom of the pollen to promote the absorption of the test compound by the roots. In the soil test, the seeds were covered with weathered soil mica.

The test compound was beadmilled with an aqueous solution of Dispersol T or added to acetone / ethanol to form a solution and diluted to the desired concentration immediately before use. For leaf diseases, 100 ppm A. I suspension was sprayed onto the leaves and applied to the roots through the soil. (Spray as much as possible, and the final concentration at the root is about 40 ppm A. I for dry soil.) When spraying cereals or rusted plants, the final concentration is 0.05%. Add 20.

In most tests, test compounds were added to soil (roots) and leaves (by spraying) 1-2 days before plant inoculation. After inoculation, create a suitable environment for the plant to develop the disease and incubate until the disease is confirmed. Depending on the disease and environment, the time period between vaccination and disease identification varied from 4 to 14 days.

The disease was recorded in the following grades.

The test results are shown in Table 1 below.

TABLE I

Example 27

This example illustrates the treatment of Xanthomonas Oryzae, a bacterial disease occurring in rice according to the method of the present invention.

The test method is shown below and the results are shown in Table 2. 1-2 cotyledon rice seedlings were wetted with the test compound (10 ml) and sprayed on the leaves. After 48 hours, the tops of these leaves were inoculated by cutting them with scissors soaked in a dispersion of xanthomonas duckwood (10 ⁹ cell / ml). After 7 days at 100% humidity of 30 ° C., the disease of the seedlings was identified with a grade of 0-4.

0 indicates no cure for the disease, 1 indicates a slight cure, 2 indicates a cure, 3 indicates a good cure, and 4 indicates a cure. The results are shown in Table II below.

TABLE II

Claims (1)

Novel cocci represented by the compound represented by the following structural formula (ga) characterized in that the compound represented by the following structural formula (III) is heated and reacted in a solvent having a high boiling point such as P-cymene, tetralin, orthodichlorobenzene Method for producing 1-substituted uracils.

In the above formula R is hydrogen, methyl or ethyl. R ² is lower alkyl, lower alkoxy, bromine, chlorine, fluorine, lower haloalkyl, cyano, nitro, lower alkylthio, hydroxy, lower alkylcarbonyl, lower alkoxy carbonyl, lower haloalkoxy, cycloalkyl, Cycloalkalkyl, lower halo alkylthio, lower alkenyl or lower alkynyl. R ³ is independently selected from hydrogen or the value of R ² . R ⁴ is independently selected from hydrogen or the value of R ² . And when R is hydrogen, Y is 0,1,2 or 3, when R ² is hydrogen or bromine and Y is 1, at least one of R ³ and R ⁴ is other than hydrogen.