JPH06199840A - Nicotinic acid derivative and herbicide - Google Patents

Abstract

PURPOSE:To provide a new nicotinic acid derivative capable of controlling at extremely low dose annual or perennial weeds developing on the cultivation lands for crops such as rice, wheat, cotton and corn over the wide range from their predeveloping to growing stage. CONSTITUTION:The objective compound of formula I or formula II [A is of formula III to VIII (Y is halogen, OH, alkoxy, alkyl, acyloxy, NO2, etc.; R<4> is H or alkyl; m is O-3), etc.; R is H, OH, alkoxy, benzyloxy, phenoxy, alkylthio, phenylthio, NR<5>R<6>(R<5> and R<6> are each H, alkyl, alkoxy, phenyl, etc.), etc.; R<1> and R<2> are each H, alkoxy, halogen, alkyl, etc.; R<3> is H, OH, CN, etc.; X is halogen, alkyl, alkoxy, amino, etc.; n is 0-2; Z is CH or N; W is O, S, CH2, CO, etc.] or a salt thereof, e.g. 4-(5-chloro-2-thienyl)-2-(4,6-dimethoxypyrimidine-2- ylthio)nicotinic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel nicotinic acid derivative or a salt thereof and a herbicide containing them as an active ingredient.

[0002]

2. Description of the Related Art It is already known that nicotinic acid derivatives have herbicidal activity. For example, the expression

[0003]

[Chemical 5] A nicotinic acid derivative represented by the formula (EP 0467139 published specification) has the formula

[0004]

[Chemical 6] The nicotinic acid derivative represented by the formula (WO91 / 10653 published specification) has the formula

[0005]

[Chemical 7] Or

[0006]

[Chemical 8] The heterocyclic derivative represented by the formula (EP 0461079 published specification) further has the formula:

[0007]

[Chemical 9] It is known that a nicotinic acid derivative represented by (DE 4026177 published specification) has herbicidal activity.

[0008]

The compounds described in the above specification are not always satisfactory in terms of herbicidal effect. In addition to these, many herbicides have been developed and have contributed to labor saving of agricultural work and improvement of productivity, but they have various problems in terms of herbicidal effect and crop safety in actual use. There is.

Particularly, in the cultivation of barley, weeds belonging to the same gramineae family as barley, such as Aedes aegypti, Aedes aegypti (blackgrass) and Aedes chinensis, are controlled over a wide period from pre-emergence to development. Very few herbicides are possible. Also, few herbicides have wide selectivity between these herbicides and wheat.

[0010]

[Means for Solving the Problems] The inventors of the present invention have earnestly studied nicotinic acid derivatives for the purpose of developing compounds having excellent herbicidal activity without causing phytotoxicity to useful crops. As a result, the compound of the present invention, which is a pyrimidine and triazine derivative bound to nicotinic acid substituted with a phenyl group or a heterocycle, shows an excellent herbicidal effect not only on annual weeds but also on perennial weeds, and also on crops. The inventors have found that it is highly safe and completed the present invention.

That is, the present invention has the general formula

[0012]

[Chemical 10] Or

[0013]

[Chemical 11] [Where A is an expression

[0014]

[Chemical 12] (In the formula, Y represents a halogen atom, a hydroxyl group, an optionally substituted alkoxy group, an alkenyloxy group, an alkynyloxy group, an optionally halogen-substituted alkyl group, an acyloxy group, a benzyloxy group or a nitro group, and R ⁴ Represents a hydrogen atom or an alkyl group, m represents an integer of 0 or 1 to 3, and when m is 2 or 3, it may be a combination of different groups. Atom, hydroxyl group, optionally substituted alkoxy group, optionally substituted benzyloxy group, alkenyloxy group, alkynyloxy group, optionally substituted phenoxy group, optionally substituted phenylthio group, alkylthio group, 1- imidazolyl group, isopropylidene amino group, the formula -NR ⁵ R
⁶ (In the formula, R ⁵ and R ⁶ are the same or different and are a hydrogen atom,
An alkyl group, an alkoxy group, an optionally substituted phenyl group, an alkylsulfonyl group, and an optionally substituted phenylsulfonyl group are shown. R ⁵ and R ⁶ may form a ring together with the nitrogen atom. ) Is a group represented by R ¹ and R ²
Are the same or different and each represents a hydrogen atom, an alkoxy group, a halogen atom, an alkylamino group, a dialkylamino group, a halogen atom-substituted alkoxy group or an alkyl group, and R ³ represents a hydrogen atom, a hydroxyl group, a cyano group or an alkoxycarbonyl group. , X represents a halogen atom, an alkyl group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, an acylamino group, n represents 0 or an integer of 1 to 2, and when n is 2, a different group It may be a combination. Z represents a methine group or a nitrogen atom, W represents an oxygen atom, a sulfur atom, a methylene group, a cyanomethylene group, a carbonyl group, a 1-cyano-1-hydroxymethylene group, a formula

[0015]

[Chemical 13] (In the formula, R represents an atom or a group described above). ] The present invention relates to a nicotinic acid derivative represented by the following formula or a salt thereof, and a herbicide containing these as an active ingredient, and when W represents a cyanomethylene group, it also includes tautomers thereof. In the general formulas 10 to 13, the alkoxy group which may be substituted by R is
Alkoxy group, alkoxyalkoxy group, alkylcarbonyloxyalkoxy group, linear or branched C1-C7 alkoxy group which may be substituted with an alkylthio group, for example, methoxy group, ethoxy group, isopropoxy group, t-butoxy group. Examples thereof include a group, a methoxymethoxy group, a pivaloyloxymethoxy group, and a methylthiomethoxy group. Further, as the benzyloxy group which may be substituted, the phenoxy group which may be substituted, and the phenylthio group which may be substituted, a halogen atom, an alkyl group,
Each group which may be substituted with an alkoxy group, a nitro group or an alkoxycarbonyl group is shown.

Examples of the alkoxy group of R ¹ and R ² include linear or branched alkoxy groups having 1 to 7 carbon atoms, such as methoxy group, ethoxy group, isopropoxy group and the like.

As the halogen atom, chlorine, bromine, fluorine and iodine atoms can be mentioned.
Examples of the alkylamino group include linear or branched alkylamino groups having 1 to 3 carbon atoms, such as methylamino group and ethylamino group, and examples of the dialkylamino group include direct alkyl groups having 1 to 3 carbon atoms. Examples thereof include a chain or branched dialkylamino group, for example, a dimethylamino group, a diethylamino group, a methylethylamino group and the like. The halogen atom-substituted alkoxy group has 1 carbon atom.
Examples thereof include halogen atom-substituted alkoxy groups in which a part or all of the linear or branched alkoxy groups of to 7 are substituted with the halogen atom, for example, difluoromethoxy group, trifluoromethoxy group and the like. Examples of the alkyl group include a linear or branched alkyl group having 1 to 7 carbon atoms, such as a methyl group, an ethyl group and an isopropyl group.

The alkoxycarbonyl group for R ³ is
Examples thereof include linear or branched alkoxycarbonyl groups having 1 to 7 carbon atoms, such as methoxycarbonyl group, ethoxycarbonyl group, and isopropoxycarbonyl group.

As the alkyl group for R ^4, the same groups as described for the alkyl groups for the substituents R ¹ and R ² can be exemplified.

Examples of the alkyl group and the alkoxy group for R ⁵ and R ⁶ include the same groups as those described for the alkyl group and the alkoxy group for the substituents R ¹ and R ² . Examples of the phenyl group which may be substituted include a phenyl group which may be substituted with a halogen atom, an alkyl group, an alkoxy group or a nitro group.

As the halogen atom of Y, the substituent R
The same groups as those described for the halogen atom of ¹ and R ² can be exemplified, and the alkoxy group which may be substituted is a halogen atom, an alkoxy group, an alkoxycarbonyl group, or a dimethylcarbamoyl group which may be substituted. Examples thereof include a chain or branched alkoxy group having 1 to 7 carbon atoms, such as a methoxy group, an ethoxy group, a difluoromethoxy group, an ethoxyethoxy group, an ethoxycarbonylmethoxy group, a 1-dimethylcarbamoylethoxy group, and the like. As the alkyl group which may be substituted with halogen, a part of a linear or branched alkyl group having 1 to 7 carbon atoms, or
Examples thereof include an alkyl group which may be entirely substituted with a halogen atom, such as a methyl group, an ethyl group, an isopropyl group, a trifluoromethyl group and a chloroethyl group.

The halogen atom, the alkyl group, the alkoxy group, the alkylamino group and the dialkylamino group for X are the halogen atom, the alkyl group, the alkoxy group, the alkylamino group and the dialkylamino group for R ¹ and R ² of the substituent, respectively. Examples of the acylamino group include those having 1 to 7 carbon atoms, such as a formylamino group, an acetylamino group and a propionylamino group.

The compounds of the present invention are shown in Tables 1 to 15 and 21 to 22. The compound numbers will be referred to in the following description.

[0024]

[Table 1]

[0025]

[Table 2]

[0026]

[Table 3]

[0027]

[Table 4]

[0028]

[Table 5]

[0029]

[Table 6]

[0030]

[Table 7]

[0031]

[Table 8]

[0032]

[Table 9]

[0033]

[Table 10]

[0034]

[Table 11]

[0035]

[Table 12]

[0036]

[Table 13]

[0037]

[Table 14]

[0038]

[Table 15]

[0039]

[Table 21]

[0040]

[Table 21] (continued)

[0041]

[Table 22] The compounds of the present invention represented by the general formulas 10 and 11 are
For example, it can be manufactured according to the following manufacturing method <1> to manufacturing method <11>. However, the method is not limited to these methods. Manufacturing method <1>

[0042]

[Chemical 14] (In the formula, Q represents an oxygen atom or a sulfur atom, L represents a leaving group such as a halogen atom or an alkylsulfonyl group, and A,
X, n, R, R ¹ , R ² and Z have the same meaning as defined above. The compound represented by the general formula [V] is obtained by reacting the compound represented by the general formula [III] and the compound represented by the general formula [IV] in the presence of a base in an equivalent amount or more in a suitable solvent from room temperature to a solvent. It can be produced by reacting for 0.5 to 24 hours within the boiling point range.

Examples of the base include alkali metals such as metallic lithium, metallic sodium and metallic potassium, organic lithium reagents such as n-butyllithium and lithium diisopropylamide (LDA), and alkaline hydrides such as sodium hydride and potassium hydride. Metals, alkali metal alkoxides such as potassium t-butoxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and alkali metal hydroxides such as sodium hydroxide and potassium hydroxide can be used.

As the solvent, hydrocarbon solvents such as toluene and xylene, halogenated hydrocarbon solvents such as dichloromethane and chloroform, ether solvents such as diethyl ether, tetrahydrofuran, 1,4-dioxane, ethyl acetate and the like. The ester-based solvent, the ketone-based solvent such as acetone, the aprotic polar solvent such as N, N-dimethylformamide and dimethylsulfoxide, and acetonitrile can be used.

The compound represented by the general formula [III] is a compound of Journal of Organic Chemistry (J.Org.Chem.) 41, 2066 (197).
6 years); Australian Journal of Chemistry (Aust.J.Chem) Vol. 36 1
It can be produced according to the following method described on page 441 (1983).

[0046]

[Chemical 15] (In the formula, R ⁷ and R ⁹ are the same or different and each represents a hydrogen atom, an alkyl group or an alkoxy group, R ⁸ represents an alkyl group, L ¹ represents a halogen atom, and A is the same as defined above. Have the same meaning.) That is, the compound represented by the general formula [VI] and the acetal compound represented by the general formula [VII] are used in the presence or absence of an inorganic or organic base in the presence of an alcohol system such as methanol or ethanol. By heating in a solvent, an ether solvent such as tetrahydrofuran, an aprotic polar solvent such as N, N-dimethylformamide, or an acetonitrile solvent for 0.1 to 10 hours, the compound of the general formula [V
The compound shown in III] can be obtained. This is reacted in an acid such as polyphosphoric acid, hydrogen halide water, sulfuric acid or acetic acid at room temperature for 1 to 24 hours, or
A compound represented by the general formula [IX] can be obtained by alkoxylating a compound represented by the general formula [X] obtained by the following method with an alkali metal alkoxide such as sodium methoxide and hydrolyzing with hydrochloric acid. it can.

Further, the compound represented by the general formula [VIII] is placed in an inert solvent such as acetic acid, dichloroethane or toluene, and hydrogen bromide or hydrogen chloride gas is added in the range of 0 ° C. to the boiling point of the solvent, preferably 10 ° C. to 50 ° C. A compound represented by the general formula [X] can be obtained by reacting at ° C.

Further, as the compound represented by the general formula [XI], the compound represented by the general formula [X] can be synthesized according to the method of JP-A-1-275562.

That is, the compound represented by the general formula [X] is treated at 50 ° C. to 12 ° C. in the presence of mineral acid such as hydrochloric acid and sulfuric acid and water.
The compound represented by the general formula [XI] is reacted with thiourea at 0 ° C for 0.5 to 10 hours, treated with an alkaline substance such as sodium hydroxide and potassium hydroxide, and acidified with an acid such as hydrochloric acid. Obtainable. Manufacturing method <2>

[0050]

[Chemical 16] (In the formula, A, X, n, L, Z, R ¹ , R ² and R ⁸ have the same meanings as defined above.) The compound represented by the general formula [XIV] is represented by the general formula [XII ] And a compound represented by the general formula [XIII]
In the presence of an equivalent amount or more of base, react in an ether solvent such as tetrahydrofuran or a nonpolar solvent such as N, N-dimethylformamide at room temperature to the boiling point of the solvent for 1 to 4 hours, and then acidify Can be manufactured by.

Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal alkoxides such as potassium t-butoxide, and the like. Can be used.

The compound represented by the general formula [XIII] can be produced by the following method.

[0053]

[Chemical 17] (In the formula, R ¹ , R ² , R ⁸ , L and Z have the same meanings as defined above.) That is, the compound represented by the general formula [XVI] is represented by the general formula [XV]. The cyanoacetic acid ester and the compound represented by the general formula [IV] are used in the presence of an equivalent amount of a base or more in a suitable solvent in the range of room temperature to the boiling point of the solvent.
It can be produced by reacting for 24 hours to 24 hours.

Regarding the base and the solvent to be used, the same ones as described in the production method <1> can be used.

Further, the compound represented by the general formula [XIII] is a compound represented by the general formula [XVI], 2 equivalents of water and a catalytic amount of an inorganic salt such as sodium chloride, and an aprotic polar solvent such as dimethyl sulfoxide. It can be produced by reacting at 150 ° C for 1 to 5 hours. Manufacturing method <3>

[0056]

[Chemical 18] (In the formula, A, X, n, R, R ¹ , R ² and Z have the same meanings as defined above.) The compound represented by the general formula [XIX] is represented by the general formula [XVII]. The compound can be produced by reacting it with an organic peroxide such as metachloroperbenzoic acid in a halogenated hydrocarbon solvent such as dichloromethane or chloroform at room temperature for 0.5 to 24 hours.

In some cases, it may be obtained as a mixture with an intermediate represented by the general formula [XVIII]. In this case, it is isolated and purified by recrystallization with a suitable solvent or silica gel column chromatography. can do. Manufacturing method <4>

[0058]

[Chemical 19] (In the formula, A, X, n, R ¹ , R ² and Z have the same meanings as defined above.) The compound represented by the general formula [XX] is a compound represented by the general formula [XIX]. In the presence of an equivalent amount or more of base in water or a suitable solvent containing water in the range of room temperature to the boiling point of the solvent of 0.5.
It can be produced by reacting for 24 hours to 24 hours and then acidifying.

As the base, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide can be used.

As the solvent, hydrocarbon solvents such as toluene, alcohol solvents such as methanol and ethanol, ether solvents such as ethyl ether and tetrahydrofuran, ketone solvents such as acetone and methyl ethyl ketone, N, N-dimethylformamide. An aprotic polar solvent such as the above can be used. Manufacturing method <5>

[0061]

[Chemical 20] (In the formula, R ¹⁰ represents an optionally substituted alkyl group, an optionally substituted benzyl group, an alkenyl group or an alkynyl group, and A, X, n, R ¹ , R ² , Z and L are defined above. The compound represented by the general formula [XXII] is the compound represented by the general formula [XXI] in the presence of an equivalent amount or more of a base in a suitable solvent. It can be produced by reacting with the compound shown in the range of 0 ° C. to the boiling point of a solvent for 0.5 to 24 hours.

Regarding the base and the solvent to be used, the same ones as described in the production method <1> can be used. Manufacturing method <6>

[0063]

[Chemical 21] (In the formula, A, X, n, R ¹ , R ² and Z have the same meanings as described above.) The compound represented by the general formula [XXIII] is a compound represented by the general formula [XX]. In an alcohol solvent such as ethanol,
It can be produced by reduction with a reducing agent such as NaBH ₄ at 0 ° C. to room temperature. Manufacturing method <7>

[0064]

[Chemical formula 22] (In the formula, M represents 1 equivalent of a cation of an alkali metal, alkaline earth metal, ammonium or organic ammonium ion, and A, X, n, R ¹ , R ² and Z have the same meaning as defined above. The compound represented by the general formula [XXIV] is the compound represented by the general formula [XX] together with an equal amount of a base in a suitable solvent in the range of room temperature to the boiling point of the solvent for 0.5 hours to 24 hours. It can be produced by reacting for a time.

Examples of the base include alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal alkoxides such as sodium methylate and sodium ethylate, and alkali metal hydroxides such as sodium hydroxide and calcium hydroxide. And alkaline earth metal hydroxides,
Alkali metal carbonates such as sodium carbonate and calcium carbonate, alkaline earth metal carbonates, ammonia and organic amines such as isopropylamine can be used.

As the solvent, hydrocarbon solvents such as toluene and xylene, alcohol solvents such as methanol and ethanol, ether solvents such as diethyl ether and tetrahydrofuran, and nonpolar protic solvents such as N, N-dimethylformamide. In addition, acetonitrile, water, etc. can be used. Manufacturing method <8>

[0067]

[Chemical formula 23] (In the formula, A, X, n, Q, Z, R ¹ , R ² and R ¹⁰ have the same meanings as defined above.) The compound represented by the general formula [XXVI] is represented by the general formula [XXV ] In the presence of a base represented by the above) in the presence of water or an appropriate solvent containing water in the range of room temperature to the boiling point of the solvent.
It can be produced by reacting for 5 to 24 hours and then acidifying.

Regarding the base and the solvent, the production method <4
The same as those described above can be used. Manufacturing method <9>

[0069]

[Chemical formula 24] (In the formula, A, X, n, Q, R ¹ , R ² , Z and M have the same meanings as defined above.) The compound represented by the general formula [XXVII] is XXVI)
It can be produced by reacting the compound represented by the formula (1) with an equivalent amount of a base in a suitable solvent at room temperature to the boiling point of the solvent for 0.5 to 24 hours.

As the base and the solvent, the same ones as described in the production method <7> can be used. Manufacturing method <10>

[0071]

[Chemical 25] (In the formula, A, X, n, Q, R ¹ , R ² , Z, R ¹⁰ and L have the same meanings as defined above.) The compound represented by the general formula [XXV] has the general formula The compound represented by [XXVI] is reacted with the compound represented by the general formula [XXI] in the presence of an equal amount or more of a base in a suitable solvent for 0.5 to 24 hours in the range of 0 ° C. to the boiling point of the solvent. It can be manufactured by

The base and solvent used may be the same as those described in the production method <1>. Manufacturing method <11>

[0073]

[Chemical formula 26] (In the formula, E represents a halogen atom, a 1-imidazolyl group, a substituted amidinooxy group, A, X, n, Q, R ¹ , R ² , R, Z
Has the same meaning as defined above. The compound represented by the general formula [V] is obtained by mixing the compound represented by the general formula [XXVI] with an equal amount or more of a condensing agent in a suitable solvent in the range of -10 ° C to the boiling point of the solvent for 0.5 hours to 24 hours. By reacting for a time, an intermediate compound represented by the general formula [XXVII] can be obtained. This is isolated or without isolation in a suitable solvent together with a compound of the formula [XXVIII] in an amount equal to or more than the amount of the compound in the range of -10 ° C to the boiling point of the solvent for 0.5 to 24 hours. By reacting, a compound represented by the general formula [V] can be obtained.

As the condensing agent, thionyl chloride, oxalic acid dichloride, chlorocarbonic acid ester, carbonyldiimidazole, carbodiimides and the like can be used.

Regarding the base and the solvent to be used, the same ones as described in the production method <1> can be used.

Next, synthetic examples of novel intermediate compounds of the general formulas [VIII], [IX], [X], and [XI] will be described as reference examples.

Reference Example 1 Methyl 2-cyano-5-N, N-dimethylamino-3
Synthesis of-(2-thienyl) -2,4-pentadienate (Intermediate No. 334) 400 g of 2-acetylthiophene, methyl cyanoacetate 3
14 g of ammonium acetate and 48.8 g of ammonium acetate were dissolved in 153 ml of acetic acid and 1.5 l of toluene, and the mixture was heated under reflux for 8 hours while dehydrating. The reaction solution was washed well with water and then dried over anhydrous magnesium sulfate. The solvent was distilled off, and vacuum distillation (b.
p.110-140 ° C / 0.05mmHg), 263.4
g of methyl 2-cyano-3- (2-thienyl) crotonate was obtained. (40% yield) then 38.9 g of methyl
2-cyano-3- (2-thienyl) crotonate and 3
3.4 g of N, N-dimethylformamide dimethyl acetal was dissolved in 600 ml of methanol and heated under reflux for 30 minutes. The solvent was concentrated, and the obtained oily substance was crystallized from methanol to obtain 40 g of the desired product. (Yield 44%) Melting point: 140-143 ° C

Reference Example 2 Synthesis of methyl 2-hydroxy-4- (2-thienyl) nicotinate (Intermediate No. 381) A solution of 120 g of methyl 2-bromo-4- (2-thienyl) nicotinate in 500 ml of methanol was cooled in an ice-water bath. 28% sodium methoxide solution 86 with stirring
g was added dropwise over about 30 minutes. After that, the mixture was stirred at room temperature for 8 hours and then heated under reflux for 6 hours. After returning to room temperature, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the obtained crystals were washed with n-hexane to give 88 g (yield 88%) of methyl 2-methoxy-4- (2-thienyl) nicotinate. Got Melting point: 85-88 [deg.] C. This methyl 2-methoxy-4- (2-thienyl)
A solution of nicotinate (87.7 g) in methanol (300 ml) was added dropwise with stirring at room temperature while adding 6 N-hydrochloric acid (200 ml) in about 20 minutes, and the mixture was heated under reflux for 1 hour. After returning to room temperature, the reaction solution was poured into water and the precipitated crystals were collected by filtration, washed with ethyl ether, and dried under reduced pressure to give 64.7 g (yield 78%) of methyl.
2-Hydroxy-4- (2-thienyl) nicotinate was obtained. Melting point: 207 to 211 ° C

Reference Example 3 Synthesis of methyl 2-bromo-4- (5-chloro-2-thienyl) nicotinate (Intermediate No. 360) Methyl 2-cyano-5-N, N-dimethylamino-3
4 (4g) of-(5-chloro-2-thienyl) -2,4-pentadieneate was dissolved in 300ml of acetic acid and cooled to 25% under ice cooling.
146 g of hydrobromic acetic acid solution was added dropwise. Then, the mixture was stirred at room temperature for 6 hours, poured into water, and extracted with ethyl acetate. After thoroughly washing with water, it was dried over anhydrous magnesium sulfate and the solvent was distilled off to obtain 35 g of the desired product. (Yield 78.3
%) Refractive index: 1.6408

Reference Example 4 Synthesis of 2-mercapto-4- (3-thienyl) nicotinic acid (Intermediate No. 382) 4-Bromo-4- (3-thienyl) nicotinic acid 43.7 g, thiourea 15.0 g, 5 %
A mixture of 60 ml of hydrochloric acid and 80 ml of acetic acid was heated and stirred at 100 ° C. for 2 hours. After returning to room temperature, pour in ice water and gradually add 200 ml of 50% aqueous sodium hydroxide solution to room temperature for 30 minutes.
Stir for minutes. The pH was adjusted to 2 with concentrated hydrochloric acid, and the precipitated crystals were collected by filtration, washed with water, and dried under reduced pressure to give 29.4 g (yield 80
%) Of 2-mercapto-4- (3-thienyl) nicotinic acid. Melting point: 212 to 214.5 ° C. Specific examples of the intermediates thus obtained are shown in Tables 16 and 2 below.
0 and Table 23.

[0081]

[Table 16]

[0082]

[Table 17]

[0083]

[Table 18]

[0084]

[Table 19]

[0085]

[Table 20]

[0086]

[Table 20] (continued)

[0087]

[Table 23]

[0088]

EXAMPLES Next, the production method of the compound of the present invention will be specifically described with reference to examples. Example 1 Preparation of 4- (5-chloro-2-thienyl) -2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinic acid (Compound No. 32) 2-Bromo-4- (5-chloro-2) -Thienyl) nicotinic acid 7.4 g and thiourea 4.0 g were weighed and 5% HCl
Water (15 ml) and acetic acid (90 ml) were added and the mixture was stirred at 100 ° C. for 2 hours. The reaction mixture was poured into water, 100 ml of 50% aqueous sodium hydroxide was added, and the mixture was stirred at room temperature for 30 minutes. 20% HCl
The mixture was acidified with. The precipitated crystals were filtered, washed with water and dried.

Next, the obtained crude crystals, 10.0 g of 4,6-dimethoxy-2-methylsulfonylpyrimidine and 3.8 g of potassium hydroxide were weighed, 100 ml of N, N-dimethylformamide and 50 ml of water were added, and the mixture was heated to 90 ° C. And stirred for 6 hours.
The mixture was poured into water, washed twice with ethyl acetate, acidified with 10% HCl, extracted with 200 ml of ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. The crystals obtained by distilling off the solvent were recrystallized from methyl alcohol to obtain 3.16 g (29.5%) of the desired product as yellow crystals. Melting point: 176
~ 180 ° C

Example 2 2- (4,6-dimethoxypyrimidin-2-ylthio)
Preparation of 4- (2-thienyl) nicotinic acid (Compound No. 1) Methyl 2- (4,6-dimethoxypyrimidin-2-ylthio) -4- (2-thienyl) nicotinate 2.55 g
Was weighed, 50 ml of dimethyl sulfoxide was added, and the mixture was stirred at 60 ° C. To this, 6.5 ml of 2N aqueous sodium hydroxide was added dropwise, and the mixture was further stirred at 60 ° C. for 30 minutes. The aqueous layer, which was poured into water and washed twice with ethyl acetate, was acidified with 10% HCl,
It was extracted with 300 ml of ethyl acetate. After washing with saturated saline,
It was dried over anhydrous magnesium sulfate. After the solvent was distilled off, the obtained crystals were washed with methanol and isopropyl ether to obtain 1.52 g (61.8%) of the target product as pale yellow granular crystals. Melting point: 168-169 ° C

Example 3 Preparation of methyl 2- [1-cyano- (4,6-dimethoxypyrimidin-2-yl) methyl] -4- (3-pyridyl) nicotinate (Compound No. 127) 60% sodium hydride 1 0.9 g was weighed, 100 ml of N, N-dimethylformamide was added, and the mixture was stirred under ice cooling. To this, 4.6-dimethoxypyrimidin-2-ylacetonitrile (4.49 g) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was ice-cooled again and methyl 2-bromo-4-
7.0 g of (3-pyridyl) nicotinate was added, and the mixture was stirred at 80 ° C. for 3 hours. This was poured into water and acidified with 20% HCl, and the precipitated crystals were filtered, washed with isopropyl ether and dried under reduced pressure to obtain 4.8 g of the desired product as orange crystals (yield 57.8%). Melting point:> 300 ° C

Example 4 7-Cyano-7- (4,6-dimethoxypyrimidine-2
-Yl) -4- (2-thienyl) furo [3,4-b] pyridin-5 (7H) one (Compound No. 264) Methyl 2- [1-cyano- (4,6-dimethoxypyrimidine-2 1.01 g of -yl) methyl] -4- (2-thienyl) nicotinate was weighed, 50 ml of chloroform was added, and the mixture was stirred at -10 ° C. To this was added 0.75 g of 70% metachloroperbenzoic acid and the mixture was stirred at room temperature for 30 minutes. This was washed with saturated sodium thiosulfate and water, and dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/2) to give the desired product as yellow crystals.
40 g (yield 41.0%) was obtained. Melting point: 187-18
8.5 ° C

Example 5 7- (4,6-dimethoxypyrimidin-2-yl) -4
-(2-Furyl) -7-hydroxyfuro [3,4-b]
Preparation of Pyridine-5 (7H) one (Compound No. 288) 7-Cyano-7- (4,6-dimethoxypyrimidine-2
-Yl) -4- (2-furyl) furo [3,4-b] pyridin-5 (7H) one 0.42 g was weighed, 14 ml of tetrahydrofuran was added, and the mixture was stirred under ice cooling. To this, 14 ml of 0.25N aqueous sodium hydroxide was added dropwise, and the mixture was stirred at room temperature for 30 minutes. 10% of the water layer was poured into water and washed twice with ethyl acetate.
The mixture was acidified with HCl, extracted with 100 ml of ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate.
After the solvent was distilled off, the obtained crystals were washed with methyl alcohol to obtain 0.40 g (yield 94.6%) of the desired product as yellow crystals. Melting point: 198-204 ° C

Example 6 Preparation of methyl 2- (4,6-dimethoxypyrimidin-2-ylcarbonyl) -4- (2-furyl) nicotinate (Compound No. 101) 7- (4,6-Dimethoxypyrimidine-2- Ill) -4
-(2-Furyl) -7-hydroxyfuro [3,4-b]
Pyridine-5 (7H) one (2.1 g) was weighed, N, N-dimethylformamide (50 ml) and potassium carbonate (0.82 g) were added, and the mixture was stirred at room temperature. 0.8 g of methyl iodide was added dropwise to this, and the mixture was stirred at room temperature overnight, poured into water and 200 ml of ethyl acetate.
The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. After evaporating the solvent, the residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/3) to give 1.1 g of the desired product as brown crystals.
(Yield 50.7%) was obtained. Melting point: 135-140 ° C

Example 7 7- (4,6-dimethoxypyrimidin-2-yl) -4
-(2-thienyl) furo [3,4-b] pyridine-5
Production of (7H) one (Compound No. 266) 7- (4,6-Dimethoxypyrimidin-2-yl) -7
-Hydroxy-4- (2-thienyl) furo [3,4-
b] Pyridine-5 (7H) one (0.7 g) was dissolved in ethyl alcohol (30 ml), and NaBH _{4 (} 0.07 g) was added with stirring under ice cooling. After stirring this for 30 minutes at room temperature, ethyl alcohol was distilled off under reduced pressure. The mixture was acidified with 10% HCl, extracted with 200 ml of ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/2) to give the desired compound (0.1).
35 g (yield 52.0%) was obtained. Melting point: 120-123
℃

Example 8 Preparation of methyl 2- (4,6-dimethoxypyrimidin-2-yloxy) -4- (2-thienyl) nicotinate (Compound No. 7) Methyl 2-hydroxy-4- (2-thienyl) nicotinate 64.7 g and 4,6-dimethoxy-2-methylsulfonylpyrimidine 66.0 g and potassium carbonate 50 g were weighed. To this was added 500 ml of dimethyl sulfoxide, and the mixture was stirred at 100 ° C. for 1.5 hours. The reaction mixture was poured into water, extracted with 1 l of ethyl acetate, washed with saturated saline and then dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/5) to obtain 1.8 g of the desired product (yield 1.8%). Melting point: 113-1
15 ° C

Example 9 Preparation of 2- (4,6-dimethoxypyrimidin-2-yloxy) -4- (2-thienyl) nicotinic acid (Compound No. 6) Methyl 2- (4,6-dimethoxypyrimidine-2- Iloxy) -4- (2-thienyl) nicotinate 1.5 g
Dimethyl sulfoxide (20 ml) was added to the mixture, and 2N aqueous sodium hydroxide (4.1 g) was added dropwise with stirring at 60 ° C. After the dropping, the mixture was further stirred at 60 ° C. for 0.5 hours. It was poured into water and washed twice with ethyl acetate. The aqueous layer was adjusted to pH 2 with 10% HCl, extracted with 200 ml of ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained solid was recrystallized with methanol to obtain 0.6 g (yield 41.1%) of the desired product as a colorless crystal. Melting point: 184-187 ° C

Example 10 Preparation of 1-t-butylcarbonyloxyethyl 4- (5-chloro-2-thienyl) -2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinate (Compound No. 35) 4- 0.2 g of (5-chloro-2-thienyl) -2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinic acid
Then, 0.1 g of potassium carbonate was weighed and 50 ml of N, N-dimethylformamide was added. Under ice-cooling stirring, 0.1 g of 1-t-butylcarbonyloxy-1-chloroethane was added dropwise. After the dropping, the mixture was stirred overnight at room temperature. The mixture was poured into water, extracted with 100 ml of ethyl acetate, washed with saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/3) to give 0.21 g (yield: 80.0%) of the desired product as a yellow oily substance. Obtained. Refractive index: 1.5
740

Example 11 Sodium 2- (4,6-dimethoxypyrimidine-2
-Ylcarbonyl) -4- (2-thienyl) nicotinate (Compound No. 233) 7- (4,6-dimethoxypyrimidin-2-yl) -4
-(2-thienyl) -7-hydroxyfuro [3,4-
b] Pyridine-5 (7H) one 0.4 g was added to benzene 100
It was dissolved in ml, and 60% sodium hydride (0.05 g) was added under ice cooling. Then, the mixture was stirred at room temperature for 24 hours, and the precipitated crystals were washed well with benzene to give 0.4 g of the desired product (yield 97
%) Was obtained. Melting point:> 300 ° C

Example 12 Sodium 2- (4,6-dimethoxypyrimidine-2
Preparation of -ylthio) -6-methyl-4- (2-thienyl) nicotinate (Compound No. 234) 2- (4,6-dimethoxypyrimidin-2-ylthio)
-6-Methyl-4- (2-thienyl) nicotinic acid 0.6
5 g was dissolved in 20 ml of tetrahydrofuran, 0.07 g of 60% sodium hydride was added, and the mixture was stirred at room temperature for 2 hours. The precipitated crystals were collected by filtration to give 0.45 g of the desired product (yield 6
5.5%). Melting point: 232-237 ° C

Example 13 Preparation of methyl 2- [1-cyano-1- (4,6-dimethoxypyrimidin-2-yl) methyl] -4-phenylnicotinate (Compound No. 163) 60% sodium hydride 3. 2 g was washed with n-hexane and 100 ml of N, N-dimethylformamide was added.
While cooling with ice, 6 g of 4,6-dimethoxypyrimidin-2-ylacetonitrile was gradually added and stirred for 30 minutes, 10 g of methyl 2-bromo-4-phenylnicotinate was added thereto, and the mixture was stirred at 80 ° C. for 2 hours. . The reaction solution was poured into ice water, adjusted to pH 2-3 with diluted hydrochloric acid, and the precipitated crystals were collected by filtration and washed well with toluene and ethyl acetate. The obtained crystals were dried to obtain 5 g of the desired product (yield 38%). Melting point: 198-199 ° C

Example 14 Methyl 2- [1-cyano-1-hydroxy-1-
(4,6-dimethoxypyrimidin-2-yl) methyl]
Preparation of 4-phenylnicotinate (Compound No. 20
0) Methyl 2- [cyano (4,6-dimethoxypyrimidin-2-yl) methyl] -4-phenylnicotinate 3.
9 g was suspended in 50 ml chloroform and 3 g of 70% metachloroperbenzoic acid was added. The mixture was stirred at room temperature for 30 minutes, washed well with an aqueous sodium hydrogen sulfite solution, a saturated aqueous sodium hydrogen carbonate solution, and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off, and the residue was crystallized with a mixed solvent of isopropyl ether and ethyl acetate to obtain 2.9 g of the desired product.
(Yield 73%) was obtained. Melting point: 126-129 ° C

Example 15 7-Cyano-7- (4,6-dimethoxypyrimidine-2
-Yl) -4-phenylfuro [3,4-b] pyridine-
Preparation of 5 (7H) one (Compound No. 305) Methyl 2- [cyano (4,6-dimethoxypyrimidin-2-yl) methyl] -4-phenylnicotinate 1 g
Was suspended in 20 ml of dichloromethane, 0.8 g of 70% metachloroperbenzoic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed well with a sodium hydrogensulfite aqueous solution, a saturated sodium hydrogencarbonate aqueous solution and a saturated saline solution, dried and the solvent was distilled off. The crude product obtained was treated with ethanol 2
It was dissolved in 0 ml, 0.5 ml of concentrated hydrochloric acid was added, and the mixture was stirred at 40 ° C. for 30 minutes. Ethanol was distilled off, ice water was added, and the precipitated crystals were recrystallized with ethanol to give 0.31 g of the desired product (yield 31
%) Was obtained. Melting point: 196-198 ° C

Example 16 7- (4,6-dimethoxypyrimidin-2-yl) -7
-Hydroxy-4- (4-chlorophenyl) furo [3,
Preparation of 4-b] pyridin-5 (7H) one (Compound No. 309) Methyl 2- [cyano- (4,6-dimethoxypyrimidin-2-yl) methyl] -4- (4-chlorophenyl)
Dissolve 2.2 g of nicotinate in 50 ml of chloroform,
Add 1.07 g of 0% metachloroperbenzoic acid, and add 1 at room temperature.
Stir for hours. The reaction mixture was washed well with saturated aqueous sodium hydrogen sulfite solution, saturated sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off and the obtained crude product was dissolved in 30 ml of tetrahydrofuran.
30 ml of an aqueous solution in which 0.7 g of sodium hydroxide was dissolved was added, and the mixture was stirred at room temperature for 2 hours. Pour the reaction solution into ice water,
The pH was adjusted to 2-3 with dilute hydrochloric acid and extracted with ethyl acetate. After thoroughly washing with water, it was dried over anhydrous magnesium sulfate. The solvent was distilled off, and the obtained crude crystals were thoroughly washed with ethanol to obtain 1.5 g of the desired product (yield 75%). Melting point: 228-
231 ° C

Example 17 7- (4,6-dimethoxypyrimidin-2-yl) -4
-Preparation of phenylfuro [3,4-b] pyridin-5 (7H) one (Compound No. 307) 7- (4,6-dimethoxypyrimidin-2-yl) -7
1 g of -hydroxy-4-phenylfuro [3,4-b] pyridin-5 (7H) one was dissolved in 30 ml of ethanol,
At room temperature 0.1 g NaBH ₄ was added. The mixture was stirred at room temperature for 6 hours, ethanol was distilled off, ice water was added, and diluted hydrochloric acid was added to p.
It was made H2 to 3 and extracted with ethyl acetate. After washing well with water, it was dried over anhydrous magnesium sulfate and the solvent was distilled off. The obtained crude product was purified by silica gel column chromatography to obtain 0.7 g of the desired product (yield 73%). Melting point: 151 to 153.5 ° C

Example 18 Benzyl 2- (4,6-dimethoxypyrimidine-2-
Ilcarbonyl) -4-phenylnicotinate (Compound No. 165) 7- (4,6-dimethoxypyrimidin-2-yl) -7
0.5 g of -hydroxy-4-phenylfuro [3,4-b] pyridin-5 (7H) one was dissolved in 10 ml of N, N-dimethylformamide, 0.2 g of potassium carbonate was added, and the mixture was stirred well. At room temperature, add 0.23 g of benzyl bromide dropwise,
Stirred overnight. The reaction solution was poured into ice water, extracted with ethyl acetate, washed well with water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained crude crystals were washed with isopropyl ether to obtain 0.5 g of the desired product (yield 80%). Melting point: 124-126 ° C

Example 19 Preparation of 4- (4-allyloxyphenyl) -2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinic acid (Compound No. 210) 4- (4-allyloxyphenyl) -2 -Mercaptonicotinic acid (100 g), 4,6-dimethoxy-2-methylsulfonylpyrimidine (84 g) and potassium carbonate (144 g) were weighed, dimethyl sulfoxide (500 ml) was added, and the mixture was stirred at 80 ° C for 2 hours. The reaction solution is returned to room temperature and methyl iodide 8 is added.
0 g was added dropwise, and the mixture was stirred for 30 minutes. Pour into water 1 l of ethyl acetate
The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/5) to give methyl 4- (4-allyloxyphenyl) -2- (4,6-dimethoxy). Pyrimidin-2-ylthio) nicotinate 26.0 g (yield 17%)
Got To 3.0 g of this methyl nicotinate, 100 ml of dimethyl sulfoxide was added, 5.2 ml of 2N aqueous sodium hydroxide was added dropwise under stirring at 60 ° C., and the mixture was stirred at 60 ° C. for 0.5 hours. The mixture was poured into ice water, acidified with 10% HCl, extracted with 300 ml of ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was recrystallized from methanol to obtain 1.5 g of the desired product as colorless crystals.
(Yield 54.3%) was obtained. Melting point: 170-172 ° C

Example 20 Preparation of 4- (4-hydroxyphenyl) -2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinic acid (Compound No. 207) 4- (4-allyloxyphenyl) -2- (4,6-Dimethoxypyrimidin-2-ylthio) nicotinic acid 1.9
g, 0.5 g of formic acid, and 0.3 g of tetrakistriphenylphosphine palladium were weighed, 50 ml of tetrahydrofuran was added, and the mixture was stirred at 60 ° C. for 12 hours. The solvent was distilled off and the residue was crystallized from methanol to give 1.0 g of the desired product (yield 58.1).
%) Was obtained. Melting point: 207 to 210 ° C

Example 21 4- [4- (N, N-dimethylpropionamide-2-
Oxy) phenyl] -2- (4,6-dimethoxypyridin-2-ylthio) nicotinic acid (Compound No. 21
5) methyl 4- (4-hydroxyphenyl) -2- (4,
3.5 g of 6-dimethoxypyrimidin-2-ylthio) nicotinate, 2.0 g of N, N-dimethyl-2-chloropropionamide and 3.0 g of potassium carbonate were weighed, 100 ml of N, N-dimethylformamide was added, and the temperature was adjusted to 80 ° C. Stir for 1 hour. The mixture was cooled to room temperature, poured into water, extracted with 200 ml of ethyl acetate, washed with water and saturated saline, and dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/2). To 4.2 g of this compound was added 100 ml of dimethyl sulfoxide, 9.0 g of 2N aqueous sodium hydroxide was added dropwise with stirring at 60 ° C., and the mixture was stirred for 3 hours. After pouring in water and washing twice with ethyl acetate, the aqueous layer was acidified with 10% HCl and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate, the solvent was distilled off, and the obtained crystals were recrystallized from methyl alcohol to obtain 0.9 g of the desired product (yield 21.2%). Melting point: 188-191 ° C

Example 22 4- (4-ethoxyethoxyphenyl) -2- (4,6)
Preparation of -dimethoxypyrimidin-2-ylthio) nicotinic acid (Compound No. 212) Methyl 4- (4-hydroxyphenyl) -2- (4,
2.0 g of 6-dimethoxypyrimidin-2-ylthio) nicotinate and 1.92 of 2-bromoethyl ethyl ether.
g, 0.83 g of potassium carbonate were weighed, 50 ml of N, N-dimethylformamide was added, and the mixture was stirred at 80 ° C. for 1 hour. The mixture was cooled to room temperature, poured into water, extracted with 200 ml of ethyl acetate, washed with water and saturated saline, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/4). Dimethyl sulfoxide 8 was added to 1.45 g of this compound.
0 ml was added, and the mixture was stirred at 60 ° C., and 3.7 g of 2N aqueous sodium hydroxide
Was added dropwise and stirred for 3 hours. The mixture was poured into water, washed twice with ethyl acetate, the aqueous layer was acidified with 10% HCl, extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was recrystallized from methyl alcohol to obtain 0.6 g of the desired product (yield 42.6%).
Melting point: 114-115 ° C

Example 23 t-Butylcarbonyloxymethyl 4- (3-allyloxy) phenyl-2- (4,6-dimethoxypyrimidin-2-ylthio) nicotinate (Compound No. 216) 4- (3-allyloxy) -2 35.6 g of-(4,6-dimethoxypyrimidin-2-ylthio) nicotinic acid was added to N,
It was dissolved in 200 ml of N-dimethylformamide, 20 g of potassium carbonate and 15.2 g of t-butylcarbonyloxymethyl chloride were added, and the mixture was stirred at room temperature for 8 hours. This was poured into water, extracted with 500 ml of ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / hexane = 1/4) to obtain 36.47 g (yield: 80.8%) of the target product as pale yellow crystals. Melting point: 10
8 ~ 111 ℃

Example 24 Sodium 2- (4,6-dimethoxypyrimidine-2
Preparation of 4-ylcarbonyl) -4- (4-chlorophenyl) nicotinate (Compound No. 236) 7- (4,6-dimethoxypyrimidin-2-yl) -4
-(4-chlorophenyl) -7-hydroxyfuro [3,
4-b] Pyridin-5- (7H) one (0.4 g) was dissolved in 100 ml of toluene, and 60% of sodium hydride (0.4%) was added thereto.
05 g was added, and the mixture was stirred overnight at room temperature. The precipitated crystals were collected by filtration, washed well with acetone, and the desired product was 0.25 g.
(Yield 60%) was obtained. Melting point: 263-267 ° C

Example 25 S-Methyl-4- (4-benzyloxyphenyl) -2
Preparation of-(4,6-dimethoxypyrimidin-2-ylthio) thionicotinate (Compound No. 242) 4- (4-benzyloxyphenyl) -2- (4,6-
Dimethoxypyrimidin-2-ylthio) nicotinic acid 3.
2 g was dissolved in 20 ml of tetrahydrofuran, 1.1 g of 1,1'-carbonyldiimidazole was added, and the mixture was stirred at room temperature for 24 hours. The solvent was distilled off, water was added, the mixture was extracted with ethyl acetate, washed well with water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained residue was crystallized with isopropyl ether to obtain 2.6 g of an acyl imidazole product.
(Yield 70%) Next, 0.5 g of this acyl imidazole compound was dissolved in 10 ml of N, N-dimethylformamide to give 15%.
0.45 g of methyl mercaptan sodium salt aqueous solution was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into water, extracted with ethyl acetate, washed well with water, and then dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by silica gel column chromatography to obtain 0.3 g of the desired product.
(Yield 62.5%) was obtained. Melting point: 143-144 ° C

The herbicide of the present invention has the general formula 10 or 1
The nicotinic acid derivative represented by 1 is used as an active ingredient.

In order to use the compound of the present invention as a herbicide, the compound of the present invention may be used as it is, but a carrier, a surfactant, a dispersant, an auxiliary agent or the like which is generally used for formulation is blended. It can also be used by formulating into a powder, a wettable powder, an emulsion, a fine granule or a granule.

[0116] As the carrier used for formulation,
For example Sieglite, talc, bentonite, clay,
Examples thereof include solid carriers such as kaolin, diatomaceous earth, white carbon, vermiculite, calcium carbonate, slaked lime, silica sand, ammonium sulfate and urea, and liquid carriers such as isopropyl alcohol, xylene, cyclohexinosan and methylnaphthalene.

Examples of the surfactant and dispersant include alkylbenzene sulfonic acid metal salt, dinaphthylmethane disulfonic acid metal salt, alcohol sulfate ester salt, alkylaryl sulfonate, lignin sulfonate, polyoxyethylene glycol ether, and polyoxyethylene glycol ether. Examples thereof include oxyethylene alkyl aryl ether and polyoxyethylene sorbitan monoalkylate. Examples of the auxiliary agent include carboxymethyl cellulose, polyethylene glycol, gum arabic and the like. Before use, dilute to an appropriate concentration and spray or apply directly.

The herbicide of the present invention can be used by foliage application, soil application or water application. The blending ratio of the active ingredient is appropriately selected according to need, but in the case of powder or granule, it is appropriately selected from the range of 0.01 to 10% (weight), preferably 0.05 to 5% (weight). Is good. When used as an emulsion or wettable powder, 1-50%
(Weight), preferably 5 to 30% (weight).

The application rate of the herbicide of the present invention varies depending on the kind of compound used, target weeds, development tendency, environmental conditions and dosage form used, but when it is used as it is as in powder and granules, The active ingredient may be appropriately selected from the range of 0.1 g to 5 kg, preferably 1 g to 1 kg per 10 ares. When it is used in a liquid state such as an emulsion or a wettable powder, it may be appropriately selected from the range of 0.1 to 50,000 ppm, preferably 10 to 10,000 ppm.

The compound of the present invention may be mixed with insecticides, fungicides, other herbicides, plant growth regulators, fertilizers and the like, if necessary.

Next, the formulation method will be specifically described with reference to representative formulation examples. The types and compounding ratios of the compounds and additives are not limited to these, and can be changed in a wide range. In the following description, “part” means part by weight.

Formulation Example 1 Wettable powder 10 parts of Compound No. 305, 0.5 parts of polyoxyethylene octyl phenyl ether, 0.5 part of sodium salt of β-naphthalenesulfonic acid formalin condensate, 20 parts of diatomaceous earth, clay 69 parts of are mixed and ground to obtain a wettable powder.

Formulation Example 2 Wettable Powder 10 parts of Compound No. 63, 0.5 parts of polyoxyethylene octyl phenyl ether, 0.5 part of sodium salt of β-naphthalenesulfonic acid formalin condensate, 20 parts of diatomaceous earth, white 5 parts of carbon and 64 parts of clay are mixed and ground to obtain a wettable powder.

Formulation Example 3 Wettable powder 10 parts of Compound No. 32, 0.5 parts of polyoxyethylene octyl phenyl ether, 0.5 part of sodium salt of β-naphthalenesulfonic acid formalin condensate, 20 parts of diatomaceous earth, white 5 parts of carbon, 6 of calcium carbonate
4 parts are mixed and ground to obtain a wettable powder. Formulation Example 4 Emulsion To 30 parts of Compound No. 34 was added 60 parts of an equal mixture of xylene and isophorone, 10 parts of a mixture of a surfactant polyoxyethylene sorbitan alkylate, a polyoxyethylene alkylaryl polymer and an alkylaryl sulfonate. An emulsion is obtained by thoroughly stirring.

Formulation Example 5 Granules 10 parts of Compound No. 307, 80 parts of a filler which mixes talc and bentonite in a ratio of 1: 3, 5 parts of white carbon, surfactant polyoxyethylene sorbitan alkylate, poly 5 of mixtures of oxyethylene alkylaryl polymers and alkylaryl sulfonates
10 parts of water was added to the parts, and the mixture was thoroughly kneaded to form a paste, which was extruded through a sieve hole having a diameter of 0.7 mm, dried, and then cut into a length of 0.5 to 1 mm to obtain granules.

[0126]

INDUSTRIAL APPLICABILITY The compound of the present invention is a variety of weeds that are problematic in the field, such as, for example, Scutellaria baicalensis, Chamomile, Rhododendron, Stinkweed, Aoyuyu, Shiroza, Abutilon, Staghorn deer, American hemlock, Nematoda,
In addition to broad-leaved weeds such as Ona fir, perennial and first-year cyperaceae weeds such as pearl nutsedges, yellow sedges, medusas, cyperaceae, Kogomegayatsu, etc. Excellent herbicidal effect over a wide range of growing season.
Further, it is possible to control annual weeds such as pearl millet, Pleurotus cornucopiae, and eels that occur in paddy fields, and perennial weeds such as Urikawa, Omodaka, Mizugaya-tsuri, Kurogwai, Firefly, and Hera modaka.

On the other hand, the compound of the present invention exhibits a high safety especially for crops such as wheat and barley.

Next, the effects of the compound of the present invention will be described with reference to test examples.

Test Example 1 (Test for herbicidal effect by treatment of paddy soil) Paddy soil was filled in a 100 cm ² plastic pot,
After scraping, Tainubie (Ec), Konagi (Mo) and Firefly (Sc)
Each seedling was sown and flooded to a depth of 3 cm. The next day, the wettable powder prepared according to Formulation Example 1 was diluted with water and added dropwise to the water surface. The application rate was 100 g per 10 ares of the active ingredient. After that, it was grown in a greenhouse, and on the 21st day after the treatment,
The herbicidal effect was investigated according to The results are shown in Table 25.

[0130]

[Table 24]

[0131]

[Table 25]

[0132]

[Table 25] (continued)

Test Example 2 (Herbicidal effect test by treatment of upland soil) A 120 cm ² plastic pot was filled with upland soil, and a edible millet (Ec), Acanthuridae (Po), Aobiyu (Am), Shiroza
(Ch) and Kogomegayatsuri (Ci) were sown and covered with soil. A wettable powder prepared according to Formulation Example 1 was diluted with water, and 1
100 l per 10 ares was evenly sprayed on the soil surface with a small sprayer so that the active ingredient was 0 g per 0 ares. Then, it was grown in a greenhouse, and the herbicidal effect was investigated on the 21st day of treatment according to the criteria in Table 24. The results are shown in Table 26.
Shown in.

[0134]

[Table 26]

[0135]

[Table 26] (continued)

Test Example 3 (Herbicidal effect test by field foliage treatment) A 120 cm ² plastic pot was filled with field soil, and edible millet (Ec), Stinkweed (Po), Aubiyu (Am), Shiroza
(Ch), various seeds of Kogomegayatsuri (Ci) are sowed and grown in a greenhouse for 2 weeks, and then the wettable powder prepared according to Formulation Example 1 is diluted with water so that the active ingredient becomes 100 g per 10 ares. In addition, 100 liters per 10 ares were foliage-sprayed over the whole plant with a small sprayer. After that, the plants were grown in a greenhouse, and on the 14th day of treatment, the herbicidal effect was investigated according to the criteria in Table 24. The results are shown in Table 27.

[0137]

[Table 27]

[0138]

[Table 27] (continued)

Test Example 4 (Crop Selectivity Test by Upland Soil Treatment) A 600 cm ² plastic pot was filled with upland soil, and wheat (Tr), blackgrass (Al), red-footed pod (Po), aobyu (Am), and white chylosa ( Ch) seeds were sown and covered with soil. The next day, a predetermined amount of active ingredient (ai, g / 10a) of the wettable powder prepared according to Formulation Example 1 was diluted with water, and 100 l per 10 ares was evenly sprayed on the soil surface with a small sprayer. Then, it was grown in a greenhouse and 21 days after the treatment, the herbicidal effect was investigated according to the criteria shown in Table 24. The test results including the comparison agent are shown in Table 28.

[0140]

[Table 28]

[0141]

[Table 28] (continued)

Test Example 5 (Crop Selectivity Test by Field Stem / Leaf Treatment) A 600 cm ² plastic pot was filled with field soil, and wheat (Tr), black grass (Al), Streaked sardine (Po), Aoyu (Am), Shiroza ( Ch) seeds were sown and grown in a greenhouse for 2 weeks, then the prescribed amount of active ingredient (ai, g / 10a) of the wettable powder prepared according to Formulation Example 1 was diluted with water to give 10 per 10 ares.
0 l was sprayed on the whole plant from above the plant with a small sprayer. After that, it was grown in a greenhouse and on the 14th day of the treatment, Table 2
The herbicidal effect was investigated according to the criteria of 4. The results including the comparison agent are shown in Table 29.

[0143]

[Table 29]

[0144]

[Table 29] (continued)

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical display location A01N 43/60 43/66 9159-4H 43/76 Z 9159-4H 43/78 B 9159-4H C07D 401/14 239 7602-4C 405/14 239 7602-4C 409/14 239 7602-4C 413/14 239 7602-4C 417/14 213 9051-4C 491/048 7019-4C (72) Inventor Yoshihiro Ito Shizuoka 408, Shioshinda, Fukuda-cho, Iwata-gun 1 Kei Research Institute Co., Ltd. (72) Inventor Nobuyuki Oba 1-408, Shioita, Fukuda-cho, Iwata-gun Shizuoka Kai Research Institute (72) Inventor Nobuhide Wada 1 Shioshinta, Fukuda-cho, Iwata-gun, Shizuoka Prefecture 1 408, Kain Lab Co., Ltd. (72) Inventor Shigehiko Tachikawa 3-57 Anzai, Shizuoka City, Shizuoka Prefecture (72) Inventor Takeshige Miyazawa Ogasa-gun, Shizuoka Prefecture Big 9 at 1205 Iwaname, Higashimachi

Claims (2)

[Claims] 1. A general formula: Or [Wherein A is the formula: (In the formula, Y represents a halogen atom, a hydroxyl group, an optionally substituted alkoxy group, an alkenyloxy group, an alkynyloxy group, an optionally halogen-substituted alkyl group, an acyloxy group, a benzyloxy group or a nitro group, and R ⁴ Represents a hydrogen atom or an alkyl group, m represents an integer of 0 or 1 to 3, and when m is 2 or 3, it may be a combination of different groups. Atom, hydroxyl group, optionally substituted alkoxy group, optionally substituted benzyloxy group, alkenyloxy group, alkynyloxy group, optionally substituted phenoxy group, optionally substituted phenylthio group, alkylthio group, 1- imidazolyl group, isopropylidene amino group, the formula -NR ⁵ R
⁶ (In the formula, R ⁵ and R ⁶ are the same or different and are a hydrogen atom,
An alkyl group, an alkoxy group, an optionally substituted phenyl group, an alkylsulfonyl group, and an optionally substituted phenylsulfonyl group are shown. R ⁵ and R ⁶ may form a ring together with the nitrogen atom. ) Is a group represented by R ¹ and R ²
Are the same or different and each represents a hydrogen atom, an alkoxy group, a halogen atom, an alkylamino group, a dialkylamino group, a halogen atom-substituted alkoxy group or an alkyl group, and R ³ represents a hydrogen atom, a hydroxyl group, a cyano group or an alkoxycarbonyl group. , X represents a halogen atom, an alkyl group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, an acylamino group, n represents 0 or an integer of 1 to 2, and when n is 2, a different group It may be a combination. Z represents a methine group or a nitrogen atom, W represents an oxygen atom, a sulfur atom, a methylene group, a cyanomethylene group, a carbonyl group, a 1-cyano-1-hydroxymethylene group, or a compound represented by the formula: (In the formula, R represents an atom or a group described above). ] The nicotinic acid derivative or its salt represented by these. 2. A herbicide containing the nicotinic acid derivative according to claim 1 or a salt thereof as an active ingredient.