Derivatives of nicotinic acid, the method of production thereof and herbicide composition

 

(57) Abstract:

Describes new derivatives of nicotinic acid represented by the General formula I, where a represents one of the groups of formulae A-1, A-2, a-3, a-4, where Y represents a halogen atom, a C1-C7-alkoxygroup,1-C7is an alkyl group or a nitro-group, m = 0 or represents an integer from 1 to 2, provided that when m = 2, Y can be a combination of different groups, R represents a C1-C7-alkoxygroup, C1-C7-alkoxy-C1-C7-alkoxygroup, C1-C7-halogenlampe, benzyloxy, halogensubstituted benzyloxy, C2-C7-alkenylacyl,1-C7-allylthiourea, 1-imidazolidinyl group, isopropylidenedioxy, di-C1-C7-alkylamino, di-C1-C7-alkylamino; X1-C7is an alkyl group; n = 0 or 1; Z is - CH-group, a group of the formula = CR3R4represents a fragment of formula V, where lk - C1-C7is an alkyl group, or COR-group with R4the group forms a group-C(= O)-O - with the formation of structure II, where R3represents a group selected from ON, HE, N. and COOAlk and groups A, X, lk and Z have wish also the method of obtaining the above derivative and herbicide composition based on compounds of the formula V. The compound and its salt can control annual and/or perennial of Solanki that grow on the area under such crops as rice, wheat, cotton and corn, during the period of time from the season prior to germination, before the growing season, and in very small doses. 3 S. and 4 C.p. f-crystals, 11 PL.

The present invention relates to new derivatives of nicotinic acid or their salts, and herbicides containing them as active ingredients.

It is known that derivatives of nicotinic acid have a weed-killing activity. So, for example, derivatives of nicotinic acid, represented by formula

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(published description WO 91/10653), heterocyclic derivative represented by the formula

< / BR>
(published description EP 0461079) and derivatives of nicotinic acid, represented by formula

< / BR>
(published description DE 4026177) are known to exhibit herbicide activity.

Compounds disclosed in the above published descriptions are not always in its proper degree satisfactory from the point of view of their herbicide action. Was developed a number of other herbicides to which these herbicides also have various problems, associated with herbicide action and safety for agricultural plants.

So, for example, cultivation of barley and wheat are very few herbicides can control the spread of weeds belonging to the same genus as barley and wheat, such as Alopecurus water, Alopecurus field and annual bluegrass, over a long period of time from pre-emergence, including the period of growth of these weeds. In addition, few herbicides are widely selectivity for these herbs and barley or wheat.

The authors of the present invention conducted intensive studies of derivatives of nicotinic acid to create connections that would not be cytotoxic against valuable crops and would have high herbicide activity. In the result it was found that the compounds of the present invention, which are derivatives of pyrimidine and triazine associated with nicotinic acid, a substituted phenyl group, or a heterocyclic ring, demonstrate excellent herbicide properties not only in terms of annual weeds, but also in perennial weeds and the.

Description of the invention

The present invention relates to a derivative of nicotinic acid of General formula

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where A represents one of the groups of the formula

< / BR>
(where Y represents a halogen atom,

C1-C7-alkoxygroup,

C1-C7is an alkyl group

or a nitro-group, and m = 0 or represents an integer from 1 to 2, provided that when m = 2, Y can be a combination of different groups),

R represents a

C1-C7-alkoxygroup,

C1-C7-alkoxy-C1-C7-alkoxygroup,

C1-C7-halogenlampe,

benzyloxy,

halogensubstituted benzyloxy,

C2-C7-alkenylacyl,

C1-C7-allylthiourea,

1-imidazolidinyl group

isopropylidenedioxy,

di-C1-C7-alkylamino,

di-C1-C7-acylaminoacyl;

X - C1-C7is an alkyl group (2);

n is 0 or 1; Z is CH2-group;

a group of the formula =CR3R4represents a fragment of formula

< / BR>
where Alk - C1-C7is an alkyl group,

or COR-group with R4the group forms a group-C(O)-O - with the way out the above values; each of R1and R2- C1-C7-alkoxygroup or its salt.

Preferred is a derivative of nicotinic acid, where A represents a group of formula A-4, where m=0 or 1;

Y represents a halogen atom, a C1-C7-alkoxygroup or C1-C7is an alkyl group(81, 82, 171, 172, 267);

R represents a C1-C7-alkoxygroup, C1-C7-alkoxy-C1-C7-alkoxygroup or C1-C7-halogenlampe, C1-C7-allylthiourea, benzyloxy, halogensubstituted benzyloxy, di-C1-C7-alkylamino or di-C1-C7- acylaminoacyl,

each of R1and R2represents a methoxy group, a group of the formula = CH3R4represents a fragment of formula

< / BR>
where n=0, Z is CH, or

COR-group with R4the group forms a group-C(=O)O - with the formation of compound II, where R3represents a group selected from-OH or-CN. The next aspect of the invention is a method of obtaining derivatives of nicotinic acid according to claim 1 wherein the group of formula =CR3R4represents a fragment of formula =CHCN or =CO or COR-group with R4the group forms a g that includes the interaction of the compounds of General formula (a):

< / BR>
where A represents one of the groups of the formula

< / BR>
(where Y represents a halogen atom, a C1-C7-alkoxygroup, C1-C7is an alkyl group or a nitro-group, and m=0 or represents an integer from 1 to 2, provided that when m=2, Y can be a combination of different groups; R8represents C1-C7is an alkyl group, X represents C1-C7is an alkyl group, n = 0 or represents an integer of 1, and L1represents a halogen atom)

with a compound of General formula (b):

< / BR>
(where each R1and R2represents C1-C7-alkoxygroup, and Z represents a group Metin in the presence of at least two equivalents of a base in a solvent, followed by acidification with getting the connection Icthe General formula

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which, if necessary, to obtain compounds of General formula IId (IId):

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(where A, Xn, R1, R2or Z have the previously indicated values) is treated with an organic peroxide in a solvent, and then the obtained compound (IId) if necessary, to obtain the compounds IIe General formula (IIe):

< / BR>
(where A, Xn, R1, R2or Z have the previously indicated values) was treated at present the value of compound I of the General formula (g):

< / BR>
(where A, Xn, R1, R2, R10or Z have the previously indicated values), the compound of General formula (IIe) is subjected to interaction with the compound represented by General formula (f):

R10L1< / BR>
(where R10represents C1-C7-alkoxy-C1-C7is an alkyl group, a C1-C7-halogenation group, C1-C7is an alkyl group, optionally substituted with halogen benzyl group, a C2-C7-alkenylphenol group, and L1represents a halogen atom), or to obtain compound I represented by the General formula (i):

< / BR>
(where A, Xn, R, R1, R2or Z have the previously indicated values) the compound of General formula (IIe) is subjected to interaction with the compound of General formula (h):

RH, (h)

where R is referred to in paragraph 1 values, in the presence of a condensing agent in a solvent.

Another aspect of the invention is a herbicide composition containing a derivative of nicotinic acid as the active ingredient and additives target, the difference is that as the specified active ingredient contains a connection on p. 1 or its salt in an effective amount.

Method (1)

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(where A, X, n, Z, R1and R2have the previously indicated meanings, L1represents a halogen atom, and R8represents alkyl group).

The connection represented by the General formula (V) can be obtained by the interaction of the compounds represented by the General formula (III) with the compound represented by the General formula (IV) in the presence of at least two equivalents of a base such ethereal solvent like tetrahydrofuran, or in such a nonpolar solvent like N,N-dimethylformamide, at a temperature in the range from room temperature to the boiling temperature of the solvent for from 1 to 4 hours, followed by acidification.

As a basis you can use such hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide, such hydrides of alkali metals as sodium hydride or potassium hydride, or alkoxides of alkali metals, such as tert.-piperonyl potassium.

Compounds represented by the General formula (III) can be obtained in accordance with the method, a may be the same or different, represents a hydrogen atom, alkyl group, or alkoxygroup, and R8L1and A have the previously indicated values).

In particular, the compound represented by the General formula (VIII) can be obtained by heating the compound represented by the General formula (VI), and acetal compounds represented by the General formula (VII) in the presence (or absence) of an inorganic or organic base such alcoholic solvent like methanol or ethanol, then ether solvent as tetrahydrofuran, in such aprotic polar solvent like N,N-dimethylformamide or acetonitrile, in the course of from 0.1 to 10 hours.

The connection represented by the General formula (IX) can be obtained by interaction of the compounds represented by the General formula (VIII), in acetic acid or in such an inert solvent as dichloromethane or toluene, with hydrogen bromide or hydrogen chloride (gaseous state) at a temperature in the range of 0oC to the boiling point of the solvent, preferably from 10oC to 50oC.

The connection represented by the General formula (IV) can be obtained as follows:

< / BR>
(where R1, R2, R8and Z have the previously indicated the PA).

So, the connection represented by the General formula (XII) can be obtained by interacting complex cyanoxantha ether represented by the General formula (X) with the compound represented by the General formula (XI) in the presence of at least an equivalent amount of base in a suitable solvent at a temperature in the range from room temperature to the boiling temperature of the solvent for 1 to 24 hours.

As a basis you can use such alkali metals as metallic lithium, metallic sodium or metallic potassium, such organic lithium reagents like n-utility or sitedisability (LDA), such hydrides of alkali metals as sodium hydride or potassium hydride, such alkoxides of alkali metals, such as tert.-piperonyl potassium, carbonates such alkali metals as sodium carbonate or potassium carbonate, or hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide.

As a solvent it is possible to use hydrocarbon solvents such as toluene or xylene, such halogenated hydrocarbons like dichloromethane or chloroform, such ethereal solvents, such as diethyl ether, tetrahydrofuran or 1,4-d is ton solvents, as N,N-dimethylformamide or dimethyl sulfoxide or acetonitrile.

The connection represented by the General formula (IV) can be obtained by interaction of the compounds represented by the General formula (XII) with two equivalents of water and a catalytic amount of inorganic salts such as sodium chloride, in such aprotic polar solvent like dimethyl sulfoxide, at a temperature of 150oC for 1 to 5 hours.

Method (2)

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(where A, X, n, R, R1, R2and Z have the previously indicated values).

The connection represented by the General formula (XV) can be obtained by interacting compounds represented by the General formula (XIII) with an organic peroxide, such as meta-chloroperbenzoic acid in a halogenated hydrocarbon solvent such as dichloromethane or chloroform, at room temperature for from 0.5 to 24 hours.

The connection represented by the General formula (XV), sometimes get mixed with the compound represented by the General formula (XIV). In this case, it is possible to isolate and purify by recrystallization from a suitable solvent or by chromatography on a column of silica gel.

Method (3)

As a basis you can use such hydroxides of alkaline metals such as sodium hydroxide or potassium hydroxide.

As a solvent it is possible to use hydrocarbon solvents such as toluene, alcohol such solvents as methanol or ethanol, such ethereal solvents, such as ethyl ether or tetrahydrofuran, such katonya solvents, such as acetone, methyl ethyl ketone, or an aprotic polar solvents, such as N,N-dimethylformamide.

Method (4)

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where R10represents optionally substituted alkyl group, optionally substituted benzyl group, a group alkenyl or alkylamino group, and where A, X, n, R1, R2Z and L1have these values.

The connection represented by the General formula (XVIII) can be obtained by interacting compounds Ave is in the presence, at least an equivalent amount of a base at a temperature in the range of 0oC to the boiling temperature of the solvent for from 0.5 to 24 hours. As the base and solvent can be used the same compounds that have been shown in the production method of compound (XII), in method (1).

Method (5)

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(where A, X, n, R1, R2and Z have the previously indicated values).

The connection represented by the General formula (XIX) can be obtained by restoring the connection represented by the General formula (XVI), thereby regenerating agent, such as sodium borohydride, in which the alcohol solvent as ethanol, at a temperature in the range of 0oC to room temperature.

Method (6)

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(where M represents an equivalent amount of cation of an alkali metal, alkaline earth metal, ammonium or organic ammonium ion, and A, X, n, R1, R2and Z have the previously indicated values).

The connection represented by the General formula (XX) can be obtained by interaction of the compounds represented by the General formula (XVI) with an equivalent amount of base in a suitable solvent at a temperature in the range from room temperature to temperaturesof such hydrides of alkali metals, as sodium hydride or potassium hydride, alkoxides such alkali metals as sodium methoxide or ethoxide sodium, such hydroxides of alkali metals or alkaline earth metals, such as sodium hydroxide or calcium hydroxide, such carbonates of alkaline or alkaline earth metals, such as sodium carbonate or calcium carbonate, ammonia, or organic amines such as Isopropylamine.

As a solvent it is possible to use hydrocarbon solvents such as toluene or xylene, alcohol such solvents as diethyl ether or tetrahydrofuran, such non-polar proton solvents, such as N, N-dimethylformamide, or such other solvents, such as acetonitrile or water.

Method (7)

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(where E represents a halogen atom, 1-imidazolidinyl group or substituted amidinothiourea, and A, X, n, R1, R2, R and Z have the previously indicated values).

The connection represented by the General formula (XXIII) can be obtained by interaction of the compounds represented by the General formula (XVI), with at least an equivalent amount of the condensing agent in a suitable solvent in the temperature range from -10oC to the boiling point of the solvent in t the following allocation (or allocations), interacting obtained intermediate compound with a compound represented by the General formula (XXII) in the presence of at least an equivalent amount of base in a suitable solvent at a temperature in the range -10oC to the boiling temperature of the solvent for from 0.5 to 24 hours.

As the condensing agent can be used thionyl chloride, oxalidales, complex chlorocarbonyl ether, carbonyldiimidazole or carbodiimide.

With regard to the base and the solvent to be used as the basis it is possible to use alkali metals such as metallic lithium, metallic sodium or metallic potassium, such organic compounds of lithium, such as n-utility or sitedisability (LDA), such hydrides of alkali metals as sodium hydride or potassium hydride, such alkoxides of alkali metals, such as tert.-piperonyl potassium, carbonates such alkali metals as sodium carbonate or potassium carbonate, hydroxides such alkali metals as sodium hydroxide or potassium hydroxide, or organic amines such as triethylamine or N,N-dimethylaminopyridine.

As a solvent, you can use the ate, as dichloromethane or chloroform, such ethereal solvents, such as diethyl ether, tetrahydrofuran or 1,4-dioxane, an ester such solvents as ethyl acetate, a ketone such solvents as acetone, such aprotic polar solvents, such as N,N-dimethylformamide or dimethylsulfoxide, or such other solvents, such as acetonitrile.

Method (8)

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(where A, R1, R2, R10, L, L1X, Z and n have the previously indicated values).

The connection represented by the General formula (XXVI) can be obtained by interaction of the compounds represented by the General formula (XXV) with a compound represented by the General formula (XXVII), in such polar solvents as N,N-dimethylformamide, in the presence of base - tert.-butoxide potassium at a temperature in the temperature range of 0oC to the boiling temperature of the solvent for a period of time from 0.5 to 24 hours.

The connection represented by the General formula (XXV) can be obtained by interaction of the compounds represented by the General formula (XXIV), with ethylacetoacetate in the presence of copper acetate and ethoxide sodium in alcohol for esterification.

Method (9)

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(where A, X, R10, R1R is about to receive, interacting compounds represented by the General formula (XXVI), with such organic peroxide, as a meta-chloroperbenzoic acid, in such a halogenated hydrocarbon solvent like dichloromethane or chloroform, at room temperature over a period of time from 0.5 to 24 hours.

The method (10)

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(where A, X, R10, R1, R2, Z and n have the previously indicated values).

Compounds represented by the General formula (XXIX) can be obtained by reaction of the compound represented by the General formula (XXVIII) in the presence of a base in a suitable solvent at a temperature in the range of 0oC to the boiling temperature of the solvent for a period of time from 0.5 to 24 hours.

As a basis you can use such alkali metals as metallic lithium, metallic sodium or metallic potassium, such hydrides of alkali metals as sodium hydride or potassium hydride, hydroxides such alkali metals as sodium hydroxide or potassium hydroxide, such alkoxides of alkali metals, such as tert.-piperonyl potassium, carbonates such alkali metals as sodium carbonate or potassium carbonate.

The solvent can be the s, as dichloromethane or chloroform, such ethereal solvents, such as diethyl ether, tetrahydrofuran or 1,4-dioxane, an ester such solvents as ethyl acetate, such katonya solvents, such as acetone, such aprotic polar solvents, such as N,N-dimethylformamide or dimethylsulfoxide, or such other solvents, such as acetonitrile.

The examples of the preparation of new intermediates of the General formulae (VIII) and (IX) below in the reference examples.

Reference example 1

Obtaining methyl-2-cyano-5-N, N-dimethylamino-3-(2-thienyl)-2,4-pentadienoic (intermediate compound N 275)

400 g of 2-acetylthiophene, 314 g of medicinehat.ca and to 48.8 g of ammonium acetate dissolved in a mixture of 153 ml of acetic acid and 1.5 l of toluene, and the resulting reactive solution is refluxed for 8 hours with removing water. The reaction solution was washed with a sufficient amount of water, dried over anhydrous magnesium sulfate. After removal of the solvent by distillation carry out vacuum distillation (i.e. boiling 110-140oC/0.05 mm RT. Art. ) obtaining 263,4 g of methyl 2-cyano-3-(2-thienyl)crotonate (yield 40%).

Then of 38.9 g of methyl 2-cyano-3-/2-thienyl/crotonate and 33.4 g of N,N-dimethylformamid minutes. The solution is concentrated and the resulting oily substance is crystallized from methanol to obtain 40 g of target compound (yield 44%). So melting 140-143oC.

Comparative example 2

Obtain methyl 2-bromo-4-(5-chloro-2-thienyl)nicotinate (intermediate compound N 283)

44,6 g of methyl 2-cyano-5-N,N-dimethylamino-3-(5-chloro-2-thienyl)-2,4-pentadienoic dissolved in 300 ml of acetic acid was added dropwise and 146 g of a 25% solution of hydrogen bromide in acetic acid under ice cooling. Then the reaction solution was stirred at room temperature for 6 hours, then poured into water and extracted with ethyl acetate. The extract obtained was washed with a sufficient amount of water and dried over anhydrous magnesium sulfate, and the solvent is distilled off to obtain 35 g of target compound (yield 78,3%). Refractive index: 1,6408.

Specific examples of the intermediate compounds obtained in a similar way, are shown in tables 4 and 5 (see the end of the description).

The preferred embodiment of the invention

Next, methods of producing compounds of the present invention will be specifically presented with links to examples.

Example 1

Obtaining methyl-2-[-cyano-/4,6-d is then added 100 ml of N,N-dimethylformamide. The resulting mixture was stirred under ice cooling. Then add of 4.49 g of 4,6-dimethoxypyrimidine-2-ylacetonitrile, and the reaction solution was stirred at room temperature for 30 minutes. This mixed reaction solution was cooled again with ice, and added 7.0 g of methyl 2-bromo-4-(3-pyridyl)nicotinate. The mixed reaction solution was stirred at 80oC for 3 hours and then poured into water and acidified with 20% hydrochloric acid. Precipitated precipitated crystals are filtered off, washed with isopropyl ether and dried in vacuo to obtain 4.8 g (yield of 57.8%) of target compound in the form of orange crystals. So melting more than 300oC.

Example 2

Getting 7-cyano-7-(4,6-dimethoxypyrimidine-2-yl)-4-(2-thienyl-furo[3,4-b]pyridine-5(7H)she (compound N 208)

1.01 g of methyl 2-[-cyano-(4,6-dimethoxypyrimidine-2-yl)- methyl]-4-(2-thienyl)nicotinate weighed, and add 50 ml of chloroform. Then the resulting mixture was stirred at -10oC. Add 0.75 g of 70% meta-chloroperbenzoic acid, and the resulting mixture was stirred at room temperature for 30 minutes. The resulting mixture was washed with saturated thiosulfonate sodium and dried over anhydrous magnesium sulfate. The solvent is distilled off, and the hexane = 1/2) to obtain 0.40 g of target compound /output 41,0%/ in the form of yellow crystals. So melting point 187-188,5oC.

Example 3

Getting 7-/4,6-dimethoxypyrimidine-2-yl/-4-/2-furyl/-7-hydroxyfuran[3,4-b]pyridine-5/7/she (compound N 229)

Beat at 0.42 g of 7-cyano-7-(4,6-dimethoxypyrimidine-2-yl)-4-/2-furyl/furo[3,4-b] pyridine-5/7/it and add 14 ml of tetrahydrofuran. The resulting mixture is stirred while cooling with ice. Added dropwise 14 ml of 0.25 N. aqueous sodium hydroxide solution, and the resulting mixture was stirred at room temperature for 30 minutes. This mixture was poured into water, and the aqueous layer was washed twice with ethyl acetate, acidified with 10% hydrochloric acid and extracted with 100 ml of ethyl acetate. The extract obtained was washed with saturated aqueous sodium chloride and then dried over anhydrous magnesium sulfate. The solvent is distilled off and the resulting crystals are washed with methyl alcohol to obtain 0.40 g (yield of 94.6%) of target compound as yellow crystals. So melting 198-204oC.

Example 4

Obtaining methyl-2-(4,6-dimethoxypyrimidine-2-ylcarbonyl)-4-(2-furyl)nicotinate (compound N 38)

2.1 g of 7-(4,6-dimethoxypyrimidine-2-yl)-4-(2-furyl-7 - hydroxyfuran[3,4-b] pyridine-5(7H)it is weighed and added to 50 ml of N,N-dimethylformamide and 0.82 g of potassium carbonate. The resulting mixture was stirred at room throughout the night, then poured into water and extracted with 200 ml of ethyl acetate. The extract obtained was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is distilled off and the residue is purified on a chromatographic column with silica gel (manifested solvent: ethyl acetate/hexane = 1/3) to obtain 1.1 g (yield 50,7%) of target compound in the form of brown crystals. So melting 135-140oC.

Example 5

Obtain 7-(4,6-dimethoxypyrimidine-2-yl)-4-(2-thienyl)furo[3,4-b] pyridine-5-(7H)she (compound N 210)

0.7 g of 7-(4,6-dimethoxypyrimidine-2-yl)-7-hydroxy-4-(2-thienyl)furo[3,4-b] pyridine-5(7H)it is dissolved in 30 ml of ethanol, and this solution is stirred while cooling with ice, added 0.07 g of sodium borohydride. The resulting mixture was stirred at room temperature for 30 minutes, and then the ethanol is removed by distillation in vacuum. The residue is acidified with 10% hydrochloric acid and extracted with 200 ml of ethyl acetate. The extract obtained was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is distilled off and the obtained residue is purified on a chromatographic column with silica gel (manifesting solvent: ethyl acetate/what>Obtain sodium 2-(4,6-dimethoxypyrimidine-2-ylcarbonyl)-4-(2-thienyl)nicotinate (compound N 96)

0.4 g of 7-(4,6-dimethoxypyrimidine-2-yl)-4-(2-thienyl)-7 - hydroxyfuran[3,4-b]pyridine-5/7H/she dissolved in 100 ml of benzene and cooled with ice add 0.05 g of 60% sodium hydride. Then the resulting mixture was stirred at room temperature for one day, and fell in precipitate crystals thoroughly washed with benzene to obtain 0.4 g (yield 97%) of target compound. So melting more than 300oC.

Example 7

Obtaining methyl-2-[-cyano-/4,6-dimethoxypyrimidine-2-yl/-methyl]-4-phenyldiamine (compound N 60)

3.2 g of 60% sodium hydride was washed with n-hexane, and add 100 ml of N, N-dimethylformamide. Then gradually add 6 g of 4,6-dimethoxypyrimidine-2-ylacetonitrile under ice cooling, and the mixture was stirred for 30 minutes. Then add 10 g of 2-bromo-4-phenyldiamine, and the resulting solution was stirred at 80oC for 2 hours. The reaction solution was poured into ice water and adjusted to pH 2-3 with diluted hydrochloric acid. Precipitated precipitated crystals are collected by filtration and washed successively with toluene and ethyl acetate. Thus obtained crystals are dried to obtain 5 is hydroxy-1-(4,6 - dimethoxypyrimidine-2-yl/methyl]-4-phenyldiamine (compound # 95)

of 3.9 g of methyl 2-[-cyano-(4,6-dimethoxypyrimidine-2-yl)methyl] -4-phenyldiamine suspended in 50 ml of chloroform, and add 3 g of a 70% metallocarboranes acid. This suspension is stirred at room temperature for 30 minutes, then washed thoroughly with an aqueous solution of sodium sulfite, saturated aqueous sodium bicarbonate and dried over anhydrous magnesium sulfate. The solvent is distilled off and the resulting residue is crystallized from a mixture of solvents: isopropyl ether and ethyl acetate to obtain 2.9 g (yield 73%) of target compound. So melting 126-129oC.

Example 9

Getting 7-cyano-7-(4,6-dimethoxypyrimidine-2-yl)-4-phenylfuro[3,4-b]pyridine-5-(7H)she (compound N 244)

1 g of methyl 2-[-cyano-/4,6-dimethoxypyrimidine-2-yl/ methyl]-4-phenyldiamine suspended in 20 ml of dichloromethane, and to this add 0.8 g of 70% meta-chloroperbenzoic acid. The suspension of the reaction mixture is stirred at room temperature for 2 hours, then washed with a sufficient amount of an aqueous solution of sodium bisulfite, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and then dried. The solvent is then distilled off. The crude product was dissolved in 20 ml etano is for 30 minutes. The ethanol is distilled off and to the residue is added ice-cold water. Precipitated precipitated crystals are recrystallized from ethanol to obtain 0.31 g (yield 31%) of target compound. So melting point 196-198oC.

Example 10

Obtain 7-(4,6-dimethoxypyrimidine-2-yl/-7-hydroxy-4-(4-chlorophenyl)furo[3,4-b]pyridine-5(7H)she (compound N 248)

2.2 g of methyl 2-[-cyano-(4,6-dimethoxypyrimidine-2-yl)- methyl]-4-(4-chlorophenyl)nicotinate was dissolved in 50 ml of chloroform, and to this added 1.07 g of 70% meta-chloroperbenzoic acid. The resulting reaction solution was stirred at room temperature for 1 hour, then well washed with a saturated aqueous solution of sodium bisulfite, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and then dried over anhydrous sodium sulfate. The solvent is distilled off, the resulting crude product is dissolved in 30 ml of tetrahydrofuran. To this add 30 ml of an aqueous solution of 0.7 g of sodium hydroxide, and the resulting reaction solution was stirred at room temperature for 2 hours. The reaction solution was poured into ice water, the pH adjusted to 2-3 with diluted hydrochloric acid and extracted with ethyl acetate. The extract obtained was washed with sufficient amounts of crude crystals are washed with a sufficient amount of ethanol to obtain 1.5 g (yield 75%) of target compound. So melting 228-231oC.

Example 11

Obtain 7-(4,6-dimethoxypyrimidine-2-yl)-4-phenylfuro[3,4-b] pyridine-5(7H)she (compound No. 246)

1 g of 7-(4,6-dimethoxypyrimidine-2-yl)-7-hydroxy-4-phenylfuro[3,4-b]pyridine-5(7H)it is dissolved in 30 ml of ethanol, and to this add 0.1 g of sodium borohydride at room temperature. The resulting mixture was stirred at room temperature for 6 hours, and the ethanol is distilled off. To the residue is added ice water, and the pH of the resulting mixture was adjusted to 2-3 with diluted hydrochloric acid, and then extracted with ethyl acetate. The extract obtained was washed with a sufficient amount of water and dried over anhydrous magnesium sulfate and then the solvent is distilled off. The crude product is purified on a chromatographic column with silica gel to obtain 0.7 g (yield 73%) of target compound. So melting 151-153,5oC.

Example 12

Getting benzyl-2-(4,6-dimethoxypyrimidine-2-ylcarbonyl)-4-phenyldiamine (compound No. 62)

0.5 g of 6-(4,6-dimethoxypyrimidine-2-yl)-7-hydroxy-4-phenylfuro[3,4-b]pyridine-5(6H)it is dissolved in 10 ml of N,N-dimethylformamide, and to this add 0.2 g of potassium carbonate. Then intensively stirred reaction solution, and thereto was added dropwise to 0.23 g benzylbromide at room temp is stragiht with ethyl acetate. The extract obtained was washed with a sufficient amount of water, and then dried over anhydrous magnesium sulfate. The solvent is distilled off and the resulting crude crystal was washed with isopropyl ether to obtain 0.5 g (yield 80%) of target compound. So melting point 124-126oC.

Example 13

Obtain sodium 2-(4,6-dimethoxypyrimidine-2-ylcarbonyl)-4-(4-chlorophenyl)nicotinate (compound N 97)

0.4 g of 7-(4,6-dimethoxypyrimidine-2-yl)-4-(4-chlorophenyl)-7 - hydroxyfuran[3,4-b] pyridine-5-(7H)-she dissolved in 100 ml of toluene, and then to this add 0.05 g of 60% sodium hydride. The resulting mixture was stirred at room temperature for one day. Precipitated precipitated crystals are collected by filtration and washed with a sufficient amount of acetone to obtain 0.25 g (yield 60%) of target compound. Melting point 263-267oC.

Example 14

Getting 2-(4,6-dimethoxypyridine-2-ylcarbonyl)-3-(imidazol-1-ylcarbonyl)-4-phenylpyridine (compound No. 112)

1.5 g of 7-(4,6-dimethoxypyridine-2-yl)-7-hydroxy-4-phenylfuro[3,4-b]pyridine-5(7H)it was dissolved in 20 ml of tetrahydrofuran, and to this add 0.6 g of N,N-carbonyldiimidazole. After stirring at room temperature for 2 days the reaction solution was poured into water, and ek is the Ulfat magnesium. The solvent is distilled off and the resulting residue is recrystallized from isopropyl ether to obtain 1.3 g (yield of 76.5%) of target compound. So melting point 126-128oC.

Example 15

Getting ethyl-4-(5-chlorothiophene-2-yl)-2-[(4,6-dimethoxypyridine-2-yl)--ethoxycarbonylmethyl)nicotinate with the release of 50%.

Then, 2.9 g of tert.-butoxide potassium is added to 50 ml of N,N-dimethylformamide. To the mixture was added dropwise to 8.9 g of ethyl-4-(5-chlorothiophene-2-yl)-(-ethoxycarbonylmethyl)nicotinate dissolved in N,N-dimethylformamide at -10oC, and the resulting reaction solution was stirred at room temperature for 1 hour. To this add 5.6 g of 4,6-dimethoxy-2-methylsulfonylamino, and the reaction solution is stirred at a temperature of from 60oC to 80oC for 8 hours. After completion of the reaction, the reaction solution was poured into water and adjusted to pH 4-5 and extracted with ethyl acetate. The extract obtained was washed with water and dried over anhydrous magnesium sulfate. The ethyl acetate is distilled off and the residue is purified on a chromatographic column with silica gel (hexane: ethyl acetate 5:1) to obtain 2.7 g (yield 23%) of target compound. So melting 127-132oC.

Example 16

S-ethyl-2-(4,6-dimethoxypyrimidine-2-and is-4-(4-chlorophenyl)furo[3,4-b] pyridine-5(7H)it was dissolved in 20 ml of dichloromethane, and then to this solution was added to 0.29 g of 3-(3-dimethylaminopropyl)-1-ethylcarbodiimide and 0.09 g of N,N-dimethylformamide. The resulting mixture was stirred at room temperature for 30 minutes. Then to this add 0.08 g of ethyl mercaptan, and the reaction mixture was stirred at room temperature for 2 hours. The reaction solution is washed thoroughly with water and dried over anhydrous magnesium sulfate. The solvent is distilled off and the resulting residue is crystallized from diisopropyl ether to obtain 0.45 g (yield 81%) of target compound. So melting point 205-207oC.

Example 17

Getting ethyl-4-/5-chlorothiophene-2-yl/-2-[/4,6-dimethoxypyrimidine-2-yl/ - hydroxymethyl]nicotinate (compound No. 102)

1.0 g ethyl-4-/5-chlorothiophene-2-yl/-2-[/4,6-dimethoxypyrimidine-2-yl/ - hydroxymethyl/nicotinate was dissolved in 10 ml of tetrahydrofuran, and under ice cooling added 0.08 g of 60% sodium hydride. After stirring at room temperature for 1 hour, the reaction solution was poured into ice water and extracted with ethyl acetate. The extract obtained was washed with a sufficient amount of saturated aqueous solution of sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent is distilled, and obtained mperature melting 150-156oC.

The herbicides of the present invention include derivatives of nicotinic acid of General formula (I) or (II) as the active ingredient.

For use as an active ingredient of a herbicide compound of the present invention can be used by itself. However, it can be used in the form of such compositions, as dusty, wettable powders, emulsifiable concentrate, microgranules or granules, mixing it with a carrier, a surface-active agent, a dispersant or adjuvant, which is usually used to prepare compositions.

Carriers that can be used in such compositions may be, for example, solid carriers, such as siclet (zeeklite), talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, calcium carbonate, slaked lime, siliceous sand, ammonium sulfate or urea, or such liquid carriers as isopropyl alcohol, xylene, cyclohexanone or methylnaphthalene.

As surface-active agents or dispersants can specify such metal salts alkylbenzenesulfonic acids as metal salts dinaftiletilena acid, salt of ester of sulfuric acid is polyoxyethylenesorbitan. The adjuvant can be, for example, carboxymethylcellulose, polyethylene glycol or the Arabian gum. In the practical application of herbicide may be diluted to the desired concentration before use or it can be applied directly.

The herbicides of the present invention can be used for application to foliage, soil or water surface. The ratio of the blending of the active ingredient are selected in accordance with necessity. However, in the case Farrukh Dustov or granules proportion of the active ingredient is chosen appropriately in the range from 0.01 to 10 wt.%, preferably from 0.05 to 5 wt.%. In the case of emulsifiable concentrates or wettable powders, the proportion is chosen appropriately in the range from 1 to 50 wt.% preferably, from 5 to 30 wt.%.

Doses of the herbicides of the present invention vary depending on the type of connection, weeds, the growth of which needs to be controlled, method of germination, environmental conditions, and type of composition. However, in the case Farrukh Dustov or pellets, which are used as they are, the dose of the active ingredient is chosen appropriately in the range of from 0.1 g to 5 kg, preferably from 1 g to 1 kg, 10 ar. If emulge ybiraut in the range of from 0.1 to 50 000 frequent. per million, preferably from 10 to 10,000 frequent. per million

Further, the compounds of the present invention can be used in combination with insecticides, fungicides, other herbicides, agents, controlling the growth of plants, fertilizers, etc. in accordance with need.

Next, a method of producing compositions will be described with reference to typical examples of compositions. Connections, types of additives and the ratio of mixing is not limited to these specific examples and can vary in a wide interval. In the following description, the term "parts" refers to "weight parts".

Example composition 1. Wettable powder

With 10 parts of the compound N 244 mix 0.5 parts polyoxyethyleneglycol ether, 0.5 parts of sodium salt of condensate naphtalenesulfonic acid and formalin, 20 parts of diatomaceous earth and 69 parts of clay, and the resulting mixture is pulverized to obtain a wettable powder.

Example composition 2. Wettable powder

With 10 parts of compound 105 N mix 0.5 parts polyoxyethyleneglycol ether, 0.5 parts of sodium salt of condensate naphtalenesulfonic acid and formalin, 20 parts of diatomaceous earth, 5 parts of white carbon black, and 64 parts of clay, and pososhok

With 10 parts of compound No. 3 is mixed with 0.5 part polyoxyethyleneglycol ether, 0.5 parts of sodium salt of condensate naphtalenesulfonic acid and formalin, 20 parts of diatomaceous earth, 5 parts of white carbon black, and 64 parts of calcium carbonate, and the resulting mixture is pulverized to obtain a wettable powder.

Example of composition 4. Emulsifiable concentrate

To 30 parts of the compound N 245 added 60 parts of a mixture containing equal amounts of xylene and isophorone, and 10 parts of a mixture of surface-active agents containing polyoxyethylenesorbitan, polyoxyethyleneglycol polymer and alkylarylsulfonate, and the resulting mixture was thoroughly stirred to obtain emulsifiable concentrate.

Example of composition 5. Granules

10 parts of compound No. 246, 80 parts which increases the amount of agent containing a mixture of 1: 3 talc and bentonite, 5 parts of white carbon black, 5 parts of a mixture of surface-active agents containing polyoxyethylenesorbitan, polyoxyethyleneglycol polymer and alkylarylsulfonate, and 10 parts of water are mixed and thoroughly kneaded to obtain a paste, which ekstragiruyut through a sieve with a diameter of cells of 0.7 mm Extruded product is dried, and then cut on the stair weed-killing activity against various weeds, which create problems in elevated areas, such as broad-leaved weeds such as Veronica Asherah, Hungarian chamomile, shepherd's purse, water pepper, sirica hybrid, white pigweed, limnocharis, brisket prickly, hempsesbania, morning glory blue and Xanthium strumarium L. such annual and perennial sedge weeds as sedge purple, yellow sedge, rice flat sedge, cyperus breviflius and grassy weeds, as millet, chicken, Alopecurus water, annual bluegrass, sorghum, Alopecurus wild oats, in a wide range of processing time, from season to germination before the growing season. Compounds of the present invention can control annual weeds such rice as millet, chicken, syt small-flowered and monochoria and perennial weeds of rice plantations, such as the Japanese arrowheads, arrowheads, flat sedge, water chestnuts, reed and narrow-leaved aquatic plants.

Further, the compounds of the present invention is highly safe, especially for such crops as wheat and barley.

Further herbicide action of the compounds of the present invention will be illustrated with reference to test examples.

Sample test 1 (Tyr> fill with soil from the rice fields. After compaction and leveling of the soil in pots sown the seeds of millet, chicken (Ec), monochoria (Mo) and bulrush (Sc) and the pots are immersed under water to a depth of 3 see the next day, wettable powders, prepared in accordance with example compositions 1, diluted with water and put a drip on the water surface. The dose is 100 g of active ingredient per 10 ar. Then plants grown in the greenhouse, and evaluation of herbicide action performed on the 21st day after application in accordance with the standards, as indicated in table 6 (see the end of the description). The results are shown in table 7 (see below).

Sample test 2 (test for herbicide efficacy in the treatment of soil from upland fields)

Plastic pots (120 cm2fill with soil from upland fields. In pots sown the seeds of millet, chicken (Ec), water pepper (Po), chirici hybrid (Am), Marie white (CH) and rice flat sedge (Ch), and then sprinkled them with soil. Wettable powders are prepared in accordance with example compositions 1, diluted with water and applied evenly to the soil surface using a small spray at a dose of 100 l (10 ar), which corresponds to the application of antecedent exercise on the 21st day after application in accordance with the scale of assessments shown in table 6. The results are shown in table 8 (see the end of the description).

Sample test 3 (test for herbicide efficacy in the treatment of soil from the fields on the elevated sections)

Plastic pots (120 cm2fill with soil from upland fields. In pots sown the seeds of millet, chicken (Ec), water pepper (Po), chirici hybrid (Am), Marie white (CH) and rice flat sedge (Ci), and then sprinkled them with soil. Plants grown in the greenhouse for 2 weeks. Then wettable powder prepared in accordance with example compositions 1, diluted with water and applied on the entire foliage of the plants using a small spray at a dose of 100 l /10 ar (1000 m2), which corresponds to adding 100 g of active ingredient per 10 ar (1000 m2). Then plants grown in the greenhouse, and evaluation of herbicide effectiveness of exercise on the 14th day after the treatment in accordance with the scale of assessments, as given in table 6. The results are shown in table 9 (see at the end of the description).

Sample test 4 (test for selectivity in relation to cultural plants during cultivation of the fields on the elevated sections)

Plastic pots with a surface of 600 cm2fill p hybrid (Am) and Mary white (CH), then sprinkled the soil. The next day, wettable powders containing a predetermined quantity of active ingredient (active ingredient, g /10, ar (1000 m2), obtained in accordance with example compositions 1, diluted with water and evenly applied on the soil surface using a small spray at a dose of 100 l / 10, ar. Then plants grown in the greenhouse, and assessment of herbicide efficacy perform at the 21st day after application in accordance with the scale of assessments, as given in table 6. The results (including the results obtained for the comparative compounds), are presented in table 10 (see the end of the description).

Example test 5 (test for selectivity in respect of cultivated plants in the processing of foliage plants on upland soils)

Plastic pots with a surface of 600 cm2fill with soil. In them sow seeds of wheat (Tg), Alopecurus field (Al), water pepper (Po), chirici hybrid (Am) and Mary white (CH), after which the plants are grown in a greenhouse for 2 weeks. Wettable powders containing a predetermined amount of active ingredient (active ingredient, g/10, ar (1000 m2), obtained in accordance with example composition of 100 l/10, ar. Then plants grown in the greenhouse, and evaluation of herbicide effectiveness of exercise on the 14th day after the treatment in accordance with the scale of assessments, as given in table 6. The results, including the results for the comparative compounds shown in table 11 at the end of the description.

1. A derivative of nicotinic acid represented by the General formula I

< / BR>
where A represents one of the groups of formulae A-1, A-2, A-3 and A-4

< / BR>
< / BR>
where Y represents a halogen atom, a C1- C7-alkoxygroup, C1- C7is an alkyl group or a nitro-group;

m = 0 or represents an integer from 1 to 2, provided that when m = 2, Y can be a combination of different groups;

R represents a C1- C7-alkoxygroup, C1- C7-alkoxy-C1- C7-alkoxygroup, C1- C7-halogenlampe, benzyloxy, halogensubstituted benzyloxy, C2- C7-alkenylacyl, C1- C7-allylthiourea, 1-imidazolidinyl group, isopropylidenedioxy, di-C1- C7-alkylamino, di-C1- C7-acylaminoacyl;

X - C1- C7is an alkyl group;

n is 0 or 1;

Z is-CH-group;

the 7is an alkyl group,

or COR-group with R4the group forms a group-C(=O)-O-,

with the formation of structure II

< / BR>
where R3represents a group selected from CN, OH, H and COOAlk and groups A, X, Alk and Z have the above meanings;

R1and R2each C1- C7-alkoxygroup,

or its salt.

2. Connection on p. 1, wherein A in the General formula I or II is of formula A - 1 or formula A - 2.

3. Connection on p. 1, wherein A in the General formula I or II is of formula A - 3.

4. Connection on p. 1, wherein A in the General formula I or II is of formula A - 4.

5. A derivative of nicotinic acid on p. 1, where A represents a group of formula A - 4, where m = 0 or 1; Y represents a halogen atom, a C1- C7-alkoxygroup or C1- C7is an alkyl group; R represents a C1- C7-alkoxygroup, C1- C7-alkoxy-C1- C7-alkoxygroup or C1- C7-halogenlampe, C1- C7-allylthiourea, benzyloxy, halogensubstituted benzyloxy, di-C1- C7-alkylamino or di-C1- C7-acylaminoacyl; R1and R2
< / BR>
n = 0, Z is CH, or COR-group with R4the group forms a group-C(= O)-O-, with the formation of compound II, where R3represents a group selected from-OH or-CN.

6. The method of obtaining derivatives of nicotinic acid on p. 1, where the group of formula = CR3R4represents a fragment of formula =CH CN or =CO or COR-group with R4the group forms a group-C(=O)-O-, =CO with formation of compounds of formula II, where R3represents a group OH or CN, wherein involves reacting compounds of General formula a

< / BR>
where A represents one of the groups of the formula

< / BR>
< / BR>
where Y represents a halogen atom, a C1- C7-alkoxygroup, C1- C7is an alkyl group or a nitro-group;

m = 0 or represents an integer from 1 to 2, provided that when m = 2, Y can be a combination of different groups;

R8represents C1- C7is an alkyl group;

X represents C1- C7is an alkyl group;

n = 0 or represents an integer of 1;

L1represents a halogen atom,

with a compound of General formula b

< / BR>
where each R1and R2represents C1- C7-alkoxygroup;

Z represents a group IU the receiving obtaining compounds IC General formula

< / BR>
which, if necessary, to obtain compounds of General formula (IId)

< / BR>
where A, Xn, R1, R2or Z have the previously indicated meanings,

treated with an organic peroxide in a solvent and then the resulting compound IId, if necessary, to obtain compounds of General formula IIe

< / BR>
where A, Xn, R1, R2or Z have the previously indicated meanings, is treated in the presence of a base with water or aqueous solvent, followed by acidification and then, if necessary, to obtain compounds of General formula I g

< / BR>
where A, Xn, R1, R2, R10or Z have the previously indicated meanings,

the compound of General formula IIe is subjected to interaction with the compound represented by the General formula f

R10L1,

where R10represents C1- C7-alkoxy-C1- C7is an alkyl group, a C1- C7-halogenation group, C1- C7is an alkyl group, optionally substituted with halogen benzyl group, a C2- C7-alkenylphenol group;

L1represents a halogen atom,

or to obtain compound I represented by the General formula i

< / BR>
where A, Xn, R, R
RH,

where R is specified in paragraph 1 value,

in the presence of a condensing agent in a solvent.

7. Herbicide composition containing a derivative of nicotinic acid as the active ingredient and additives target, characterized in that, as specified active ingredient contains a connection on p. 1 or its salt in an effective amount.

 

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< / BR>
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< / BR>
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and their physiological acceptable salts

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< / BR>
where A is hydrogen or lower alkoxy,

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provided that E does not mean hydrogen or hydroxide, when G is phenyl, and their salts with inorganic acids
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