5,6-disubstituted 3-pyridylmethylamine halides, how they acquire and the ways to obtain 5-(substituted methyl)-2,3 - pyridinedicarboxylic acids

 

(57) Abstract:

Usage: as intermediates for obtaining herbicides. The inventive products: 5,6-disubstituted-3-pyridylmethylamine halides of the formula I indicated in the description, where Z and Z1, H, X Is Cl, Br or J, y and y1-OR4, R4- H, C1-C4-alkyl, Q - R, R1R2-N- or nitrogen-containing heterocycle, R, R1and R2- C1-C4-alkyl. Reagent 1: compound of formula II is specified in the description, where Z, Z1, y and y1have the above values, which are subjected to interaction with palodiruyut agent in an inert organic solvent in the presence of a radical initiator, followed by processing the resulting reaction mixture of 1 mole of trialkylamine. 3 S. and 7 C.p. f-crystals, 1 table.

The purpose of the invention is to obtain 5,6-disubstituted-3-pyridylmethylamine compounds of high purity, which are used as intermediate compounds for the 5-(substituted methyl)-2,3-pyridinedicarboxylic acid of high purity.

In addition, the invention includes a method of obtaining a 5,6-disubstituted-3-pyridylmethylamine compounds and pic is Ihalainen connections.

The invention relates to 5,6-disubstituted-3 - pyridylmethylamine compounds of the formula I

< / BR>
where Z is hydrogen, halogen;

Z1represents hydrogen, halogen, cyano and nitro;

X represents Cl, Br, J, or R3SO3;

R3represents C1-C4-alkyl or phenyl, are not necessarily substituted with one to three C1-C4-alkoxygroup, C1-C4- alkyl groups, nitro groups: cyano groups or halogen atoms;

Y and Y1each independently represents OR4, NR4R5or, if they are taken together, YY1represent-O-, -S - or;

R4and R5are each independently hydrogen, C1-C4-alkyl, does not necessarily substituted C1-C4- alkoxygroup, or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4- alkoxygroup or halogen atoms; or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4- alkoxygroup atoms or halogen;

R6represents hydrogen or C1- C4- alkyl;

Q is

< / BR>
R, R1and R2represent each independent is RR1represents a group of the formula (CH2)nnot necessarily separated by O, S, or NR10where n represents the integer 3, 4 or 5, provided that R2represents C1-C4-alkyl;

Z2represents O, S or NR10;

R10represents C1-C4-alkyl;

R11and R12are each independently hydrogen, halogen, C1-C4-alkyl or C1-C4-alkoxy, and when taken together, R11and R12may form a 5 - or 6-membered unsaturated ring, not necessarily separated by O, S, or R10and not necessarily substituted by one to three halogen atoms, C1-C4-alkyl groups or C1-C4-alkoxygroup.

The invention relates also to an efficient method of obtaining compounds of formula I in high purity and their use in a method of producing 5-(substituted methyl)-2,3-pyridinedicarboxylic acid of high purity compounds of formula II

< / BR>
where Z is hydrogen, halogen;

Z1represents hydrogen, halogen, cyano and nitro, A represents O or S;

R7represents C1-C4-alkyl, does not necessarily substituted by phenyl, does not necessarily substituted by one to three1-C4-alkyl groups or halogen atoms.

The compounds of formula I, where X represents Cl or Br, can be obtained by the reaction of derivatives of 5-methyl-2,3-pyridinedicarboxylic acid compounds of the formula III

< / BR>
where Z, Z1, Y and Y1imagine, as described above, with galoidzamyescyennykh agent in the presence of a first solvent, not necessarily in the presence of catalytic amounts of a radical initiator, preferably at a temperature of about 0-100oC with the formation of the first mixture containing the compounds of formula IV

< / BR>
where Z, Z1, Y and Y1predstavlyayte described above, and X represents Cl or Br. The number used Alojamientos agent is selected such as to minimize the formation of the product of formula IVb. Specified the first mixture is then interacts with at least 1,0 equimolar amounts of C1-C4-trialkylamine, 5 - or 6-membered unsaturated heterocyclic amine or a 5-14-membered unsaturated heterocyclic amine, not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4-alkoxygroup, or halogen atoms, in the presence of a second solvent, preferably when the temperature is s I. Way to obtain is illustrated in the following scheme I.

< / BR>
The above method is especially effective for producing compounds of formula I, where

Z represents hydrogen;

Z1represents hydrogen;

X represents Cl or Br;

Y and Y1each independently represents OR4;

R4represents C1-C4-alkyl;

R, R1and R2are each independently methyl or ethyl, or R and R1taken together with the nitrogen atom to which they are attached with the formation of the pyridine ring, provided that R2not present.

Preferred compounds of formula I obtained according to the method of the invention are dimethyl ether [(5,6-dicarboxy-3 - pyridyl)methyl]trimethylammonium, diethyl ether [(5,6-dicarboxy-3-pyridyl)methyl]trimethylammonium, dimethyl ether [(5,6-dicarboxy-3-pyridyl)methyl]pyridineboronic, dimethyl ether 1-[(5,6-dicarboxy-3-pyridyl)methyl]-4-methylpyridinium, dimethyl ether 1-[(5,6-dicarboxy-3-pyridyl)methyl]pyridineboronic, dimethyl ether 1-[(5,6-dicarboxy-3-pyridyl)methyl]pyridineboronic, dimethyl ether 1-[(5,6-dicarboxy-3-pyridyl)methyl] hyalinized, dimethyl ether 1-[(5,6-dicarboxy-is d, dimethyl 3-[(5,6-dicarboxy-3-pyridylmethyl)-4-methyl] thiazolidine, dimethyl ether 1-[(5,6-dicarboxy-3-pyridyl)methyl] -3 - methylimidazolidine and dimethyl 1-[(5,6-dicarboxy-3-pyridyl)methyl]benzothiazolinone.

The compounds of formula I can be isolated by filtration or extraction with water in the form of compounds of high purity.

Amines that can be used for implementing the method, are alkali, 5-6-membered saturated, and 5-14 membered unsaturated heterocyclic amines, not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4-alkoxygroup or halogen atoms.

Preferred amines are C1-C4-trialkylamine, 5-6-membered saturated heterocyclic amines and 5-14 membered unsaturated heterocyclic amines, in which the heterocyclic ring contains one to three nitrogen atoms, and may not necessarily include sulfur or oxygen within the ring system.

Preferred amines include alkylamines followed, trimethylamine and triethylamine, heterocyclic saturated amines, including pyridine, pikolines, pyrazine, pyridazine, triazine, quinoline, isoquinolines, imidazoles, benzothiazole, or C1-C4-alkoxygroup, and unsaturated heterocyclic amines, such as pyrrolidine, piperidine, piperazine, morpholines, thiazolidine and thiomorpholine.

The number halogenous agent depends both on the type of reaction (periodic or continuous), and the procedure of recycling used to return unreacted starting materials. Usually for continuous process use from 0.3 to 0.8 morrnah equivalents halogenous agent, and for the continuous reaction initially require even smaller amounts of halogen.

Ganoderma agents that can be used for implementing the method include N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, bromine, chlorine, tert-butylhypochlorite, sulfurylchloride, sulfanilamide, N-chlorosuccinimide etc. Preferred calodromini agents are chlorine, bromine, N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin and sulfurylchloride. Radical initiators suitable for use in the method of the invention include 2,2'-azobisisobutyronitrile, 2,2'-azobis-(2-methylbutyronitrile), 2,2'-azobis-(2,4-dimethylpentanenitrile), 1,1'-azobis-(cyclohexanecarbonitrile), organic and inorganic peroxides, such as is with 2,2'-azobisisobutyronitrile and 2,2'-azobis-(2-methylbutyronitrile). Among the C1-C4-trialkylamines that can be used in the method of the invention, using trimethylamine and triethylamine.

Solvents that can be used for implementing the method include halogenated hydrocarbons such as dichloroethane, carbon tetrachloride and the like, halogenated aromatic hydrocarbons, such as chlorobenzene, dichlorobenzene and the like, nitrobenzene, acetic acid, water and alcohols, such as methanol, ethanol, n-propanol and the like, and also mixtures of the aforementioned solvents. Preferred first solvents include chlorobenzene, dichlorobenzene, carbon tetrachloride and mixtures of chlorobenzene and methanol. Preferred second solvents include methanol, ethanol, chlorobenzene.

Another way to get some compounds of formula I are shown on the flowsheet II.

< / BR>
where Z, Z1, R3, Y and Y1represent substituents as described above for formula I.

Similarly, other compounds of formula I can be obtained by the reaction presented in scheme III.

< / BR>
where Z, Z1, R3, Y and Y1represent substituents as described above for compounds is C R, R1or R2can C1-C4-alkyl radicals, which are connected to the polymer and can be obtained by passing the compounds of formulas IV through ion-exchange resin containing amine substituents. Mainly the compounds of formula IVb and IVc does not interact with the resin and removed. Ammonialike compounds of high purity interact further with the formation of compounds of formula II.

The compounds of formula I are intermediate compounds in the production method of the compounds 5-(substituted methyl)-2,3-pyridinedicarboxylic acid of formula II with a high purity. The compounds of formula II can be obtained by the interaction of the 5,6-disubstituted-3 - pyridylmethylamine compounds of formula I, as described above, c is at least 1 mol of alkoxide or alkylsulfides the compounds of formula V

R7A-M+(V)

where R7and-are as described above for compounds of formula II, and M+represents alkali metal such as sodium or potassium,

in the presence of organic solvents, preferably at a temperature of 0-110oC with the formation of the first mixture, which then interacts with 2 mol of aqueous base, preferably at the Auteuil with the formation of 5-(substituted methyl)-2,3-pyridinedicarboxylic acid compounds of formula II.

Way to obtain is illustrated in scheme IV.

< / BR>
The above-described method is especially effective for producing compounds of formula II high purity, where Z and Z1represent hydrogen, A is O or S, and R7represents C1-C4-alkyl. A preferred compound of formula II obtained by the method of the invention is 5-methoxymethyl-2,3-pyridinedicarboxylate acid.

The compounds of formula II can be isolated by filtration or by extraction with an appropriate solvent. In the process of allocating the appropriate extraction solvents include tetrahydrofuran, and alcohols, is not miscible with water, by themselves or in a mixture with toluene.

Aqueous solutions of bases suitable for implementing the method, include aqueous solutions of sodium hydroxide, aqueous solutions of potassium hydroxide and the like. Acids that can be used in the process include mineral acids such as sulfuric acid, hydrochloric acid, and the like.

Organic solvents that can be used for implementing the method include acetonitrile, tetrahydrofuran, aromatic hydrocarbons, R7HE alcohols where R7the submitted the t alcohols, the corresponding R7in the formula II, as described above, such as methanol and ethanol.

The corresponding diesters of compounds of formula II can be prepared by the reactions shown in scheme V:

< / BR>
where Z, Z1, R7, A, Q and X and M are as described above, and R4represents C1-C4-alkyl, does not necessarily substituted C1-C4-alkoxy, or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4-alkoxy groups, halogen, or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups, C1-C4-alkoxy groups or halogen atoms.

The compounds of formula II high purity are used as initial substances for obtaining herbicide 2-(2-imidazolin-2-yl)pyridinium compounds having the structural formula VI

< / BR>
where R8represents C1-C4-alkyl;

R9represents C1-C4-alkyl or C3-C6-cycloalkyl; and, if R8and R9taken together with the carbon to which they are attached, they may represent C3-C6-cycloalkyl, not necessarily replaced by stands;

Z represents hydrogen or halogen;

ecstasy C1-C4-alkyl, does not necessarily substituted by phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups or halogen atoms, or phenyl, does not necessarily substituted with one to three C1-C4-alkyl groups or halogen atoms, and when R8and R9represent different substituents, their optical isomers.

Mainly the compounds of formula VI obtained from compounds of formula II obtained by the method of the invention are unexpectedly cleaner than the compounds of formula VI obtained by the method previously known.

The invention is not limited to the above examples, except for the parts defined in the claims. The term "NMR" refers to nuclear magnetic resonance, and the term "HPLC (GHSD)" refers to liquid chromatography high pressure.

Example 1. Getting [(5,6-dicarboxy-3 - pyridyl)methyl] trimethylammonium dimethyl ester using N-bromosuccinimide

< / BR>
A mixture of dimethyl 5-methyl-2,3-pyridinedicarboxylate (533 g, 2.5 mol) in chlorobenzene (2,440 ml) is heated to 85oC in nitrogen atmosphere. A mixture of N-bromosuccinimide (356 g, 2.0 mol) and 2,2-azobisisobutyronitrile (12.5 g, 0,076 mol) are added to the reaction with the SUP>oC for 1 hour, cooled to room temperature overnight and diluted with water. The organic layer is separated, diluted with methanol, cooled to 10oC, and add anhydrous trimethylamine (180 ml, 1.8 mol). The reaction mixture is stirred at 5-10oC for 3 hours, filtered to obtain a solid residue. The solid residue is dried overnight in a vacuum to obtain the product mentioned in the title as a white solid (429 g, so pl. 200-208oC with decomposition).

Repeat the procedure above, but replace diethyl-5-methyl-2,3-pyridinedicarboxylate and receive diethyl ether [(5,6-dicarboxy-3-pyridyl)methyl] trimethylammonium in the form of a white solid (so pl. 156-161oC with decomposition).

Example 2. Getting diethyl ether [(5,6-dicarboxy-3 - pyridyl)methyl] ammoniumbromide using 1,3-dibromo-5,5 - dimethylhydantoin

< / BR>
A mixture of dimethyl-5-methyl-2,3-pyridinedicarboxylate (104,5 g, 0.5 mol) in chlorobenzene (470 ml) is heated to 85oC in nitrogen atmosphere. A mixture of 1,3-dibromo-5,5-dimethylhydantoin (71,5 g, 0.25 mol) and 2,2-azobisisobutyronitrile (2.5 g, 0.015 mol) is added to the reaction mixture for 30 minutes at 80-90oC. After the addition of raybaut with water and dried. Dried organic mixture is diluted with methanol, cooled to 10oC? and add anhydrous trimethylamine (17,4 g, 0.29 mol). The reaction mixture was stirred at 10-36oC overnight, filtered to obtain a solid product. The solid residue is washed with chlorobenzene and dried in vacuo to obtain the product mentioned in the title, in the form of a white solid (74,4 g, so square - 200-208oC with decomposition).

Example 3. Getting 5-(methoxymethyl)-2,3-pyridinedicarboxylic acid

< / BR>
A mixture of 25% sodium methoxide in methanol (270 g, 1.25 mol) and dimethyl ether [(5,6-dicarboxy-3-pyridyl)methyl]trimethylammonium (347 g, 1.00 mol) in methanol (650 ml) is heated under reflux for 1 hour in nitrogen atmosphere. Water (1 l) and sodium hydroxide (80,0 g, 2.0 mol) is added and the reaction mixture is distilled until the temperature of the reactor 100-105oC. the Reaction mixture is cooled to room temperature, treated with sulfuric acid to achieve a pH from 1.5 to 2.0 and filtered to obtain a solid residue. The solid residue is washed with water, dried in vacuum to obtain compound indicated in the title, in the form of a white solid product (so pl. 161-162oC), which is pure bol < / BR>
A mixture of dimethyl-5-methyl-2,3-pyridinedicarboxylate (30 g, 0,143 mol), N-bromosuccinimide (32 g, 0.18 mol) and 2,2-azobisisobutyronitrile (0.9 g, 0,0055 mol) in carbon tetrachloride (200 ml) is heated at 80oC for 1.5 hours. Additionally add 2,2-azobisisobutyronitrile (0.9 g, 0,0055 mol) and the reaction mixture heated under reflux for 2 hours, cooled to room temperature and filtered. The filter cake was washed with carbon tetrachloride. The filtrate and wash water are combined washed with water and concentrated in vacuo to obtain oil. Oil according to Ehud contains 57% of the product specified in title, 16% dimethyl-5-methyl-2,3-pyridinedicarboxylate.

Example 5. Getting dimethyl ether [(5,6-carboxy-3 - pyridyl)methyl] pyridinylamino

< / BR>
The mixture of oil obtained in example 6 (32,0 g), and pyridine (9.2 grams, 0.12 mole) in absolute methanol is heated under reflux for 2 hours in nitrogen atmosphere, cooled to room temperature and filtered. The filter cake is washed with ethanol and dried in vacuum at 50oC to obtain specified in the connection name in the form of a solid product (18,1 g), which is more pure than 99% according to analysed in ethanol using anhydrous trimethylamine

< / BR>
The mixture of oils obtained according to the method of example 6 (100 g) in absolute ethanol is cooled to 5oC in nitrogen atmosphere. Add anhydrous trimethylamine (16 g, 0.27 mol) and the reaction mixture is stirred for 3 hours at 5oC and filtered. The filter cake is washed with ethanol and dried in air to obtain specified in the connection name in the form of a white solid product (49,1 g).

Example 7. Getting dimethyl-5-(methoxymethyl)-2,3-pyridinedicarboxylate

< / BR>
A mixture of 25% sodium methoxide in methanol (320 g, 1.5 mol) and [(5,6-dicarboxy-3-pyridyl)methyl] trimethylammonium, dimethyl ether (160 g, 0.5 mol) in methanol (650 ml) is heated under reflux for 6 hours in nitrogen atmosphere. The reaction mixture is cooled to 5oC, and add acetic acid (90 g) and water (200 ml). The methanol is removed in vacuo, water is added, and the mixture is extracted with methylene chloride. The combined organic extracts are washed sequentially with 5% sodium bicarbonate solution and water and concentrated in vacuo to obtain specified in the product name in the form of a transparent liquid (83,2 g), which identify data1H-NMR spectral analysis.

Following tilby ether [(5,6-dicarboxy-3-pyridyl)methyl] trimethylammonium, get a product that is listed in the title, in the form of a transparent liquid.

Example 8. Getting 5-(methoxymethyl)-2,3-pyridinedicarboxylic acid

< / BR>
A mixture of dimethyl-5-(methoxymethyl)-2,3-pyridinedicarboxylate (60,0 g, 0.25 mol) and 50% aqueous solution hydroxynitrile (50.0 g, to 0.63 mol) in water heated at 90-110oC for 2 hours in nitrogen atmosphere, at the same time fending off the methanol and water. The reaction mixture is cooled to 10oC, treated with sulfuric acid, bringing the pH to 2, and filtered to obtain a solid residue. The solid residue washed with water and dried in vacuum to obtain specified in the connection name in the form of a white solid product (44,3 g, so pl. is 161-162oC).

Example 9. Getting dimethyl ether 2,3-pyridinedicarboxylic acid and 5-(aromatic amine)bromide

< / BR>
In a 250 ml flask in nitrogen atmosphere add solvent specified in the table (or 100 ml of absolute ethanol, 200 ml of a mixture of 50/50 methanol/chlorobenzene), and 30 g of crude product dimethyl ether 5-monobromodiphenyl-2,3-dicarboxylic acid (actually 57% according to GHVD) and 0.1 mol of aromatic amine indicated in the table. The mixture is heated under reflux and maintained for approximately 5 charature, and suspended in approximately 100 ml of an organic solvent, identified as "Suspendresume solvent" in the table. The mixture was then filtered, and the filter cake washed with about 50 ml of a suspending solvent. The resulting crystalline solid is dried in vacuum at 50oC. Then determine the melting point and structure identify according to the1H-NMR,13C-NMR and12C-ATPI-NMR spectra.

1. 5,6-Disubstituted 3-pyridylmethylamine halides of the formula I

< / BR>
where Z and Z1hydrogen;

X is Cl, Br or J;

Y and Y1OR4< / BR>
R4hydrogen, C1-C4-alkyl;

Q -

< / BR>
< / BR>
< / BR>
< / BR>
or

< / BR>
R, R1and R2WITH1WITH4-alkyl;

Z2S or NR10;

R10WITH1WITH4-alkyl;

R11and R12hydrogen, C1WITH4-alkyl, or R11and R12together may form a six-membered unsaturated or saturated ring.

2. Connection on p. 1, where Z and Z1hydrogen;

X is Cl or Br;

Y and Y1OR4;

R4WITH1WITH4-alkyl;

Q -

< / BR>
or

< / BR>
where R, R1and R2each R12can form a six-membered unsaturated or saturated ring.

3. Connection on p. 2, selected from the group consisting of dimethyl ether [(5,6 - dicarboxy-3-pyridyl)methyl] ammonium chloride, diethyl ether [(5,6 - dicarboxy-3-pyridyl)methyl] ammonium bromide, dimethyl ether [(5,6 - dicarboxy-3-pyridyl)methyl] pyridine bromide and dimethyl 1-[(5,6-dicarboxy-3-pyridyl)methyl]skinline bromide.

4. The method of obtaining compounds of formula I on p. 1, characterized in that the derivative of 5-methyl-2,3-pyridinedicarboxylic acid of General formula II

< / BR>
where Z, Z1, Y and Y1have the values listed in paragraph 1,

subjected to interaction with palodiruyut agent in an inert organic solvent in the presence of a radical initiator, followed by processing the resulting reaction mixture by at least one mole, s1WITH4-trialkylamine or 5 - or 6-membered unsaturated heterocyclic amine in an inert organic solvent.

5. The method according to p. 4, characterized in that gaodirelwe agent is used in amount of at least 0,3 mol per 1 mol pyridine derivative of the formula II, the radical initiator in catalic the soup of carbon tetrachloride, chlorobenzene and mixtures thereof, and treating the reaction mixture with the amine are in the environment of a solvent selected from the group consisting of chlorobenzene, methanol, ethanol and mixtures thereof.

6. The method according to p. 4, characterized in that gaodirelwe agent selected from the group consisting of N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, chlorine, bromine, sulfanilamide and Sulfuryl-chloride, a radical initiator selected from the group consisting of 2,2,-azobisisobutyronitrile, 2,2,-azobis(2 - methylbutyronitrile), 2,2,-azobis(2,4-dimethylpentanenitrile) and 1,1-azobis (cyclohexane-carbonitrile) and (C1-C4-trialkylamine selected from the group consisting of trimethylamine and triethylamine.

7. The method of obtaining 5-(substituted methyl)-2,3-pyridinedicarboxylic acid formula

< / BR>
where Z and Z1hydrogen;

R7WITH1WITH4-alkyl,

wherein the 5,6-disubstituted 3-pyridylmethylamine halide of the formula I

< / BR>
where Z and Z1have the above values;

X, Y, Y1and Q are defined for compounds of formula I on p. 1,

subjected to interaction with at least one molar equivalent of the alkoxide of the formula R7ABOUT-M+,

where R7has Pusey treatment of the resulting reaction mixture of at least two molar equivalents of an aqueous solution of the base and bringing the acid pH of the resulting reaction mixture to a value below 2.5.

8. The method according to p. 7, characterized in that the substrate is selected from the group consisting of sodium hydroxide and potassium hydroxide, an acid selected from the group consisting of sulfuric and hydrochloric acids, alkoxide R7OHM is chosen from the group consisting of methylate and ethylate alkali metal, and treatment of compounds of formula I alkoxide is carried out at 20 110oWith and processing the resulting reaction mixture for 20 120oC.

9. The method of obtaining 5- (substituted methyl)-2,3-pyridinedicarboxylic acid formula

< / BR>
where Z and Z1hydrogen;

R7WITH1WITH4alkyl,

characterized in that 5-methyl-2,3-pyridineboronic acid formula

< / BR>
where Z and Z1have the above values;

Y and Y1have the meanings given for compounds of formula I on p. 1,

subjected to interaction with palodiruyut agent in an inert organic solvent in the presence of a radical initiator, followed by processing the resulting reaction mixture by at least one mole, s1WITH4-trialkylamine or 5 - or 6-membered unsaturated heterocyclic amine in an inert organic solvent, the resulting connection UP>-M+< / BR>
where R7WITH1WITH4-alkyl;

M is alkali metal,

in an inert organic solvent followed by treatment of the resulting reaction mixture of at least two molar equivalents of an aqueous solution of the base and bringing the acid pH of the resulting reaction mixture to a value below 2.5.

10. The method according to p. 9, characterized in that gaodirelwe agent is used in amount of at least 0,3 mol per 1 mol pyridine derivative of the formula II, the radical initiator in catalytic quantities and gaodirelwe agent selected from the group consisting of N-bromosuccinimide, 1,3-dibromo-5,5-dimethylhydantoin, chlorine, bromine, sulfanilamide and sulfurylchloride; radical initiator selected from the group consisting of 2,2'-azobisisobutyronitrile, 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis (2,4-dimethylpentanenitrile) and 1,1-azobis(cyclohexanecarbonitrile), WITH1- C4-trialkylamine selected from the group consisting of trimethylamine and triethylamine, the base is selected from the group consisting of sodium hydroxide and potassium hydroxide, an acid selected from the group consisting of sulfuric and hydrochloric acids, and gorodilova of compound (II) is carried out at 0-Neu mixture for 20 120oC.

 

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FIELD: organic chemistry, chemical technology, fungicides.

SUBSTANCE: invention describes derivative of benzoylpyridine of the formula (I) or its salt:

wherein X represents halogen atom, (C1-C6)-alkoxy-group optionally substituted with a substitute taken among halogen atom, phenyl, methoxy-, methylthio-, dimethylamino-group, vinyl or ethynyl; phenoxy-group, (C3-C6)-cycloalkoxy-group, hydroxyl group, (C1-C6)-alkyl group, (C2-C6)-alkenyl group, CF3, (C1-C6)-alkylthio-group, (C1-C6)-alkoxycarbonyl group, (C1-C6)-dialkylaminocarbonyl group, (C1-C6)-alkylcarbonyloxy-group, (C1-C6)-alkylcarbonyl group, amino-group, (C1-C4)-alkylamino-group or di-(C1-C4)-alkylamino-group; n represents 1, 2, 3 or 4; R1 represents (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group, (C1-C6)-alkoxy-group optionally substituted with phenyl, phenoxy-group, (C3-C10)-cycloalkyloxy-group or hydroxyl group; m = 1, 2 or 3 under condition that if m = 2 then R2 can form ring -OCH2O- (with exception when pyridine ring is substituted with benzoyl group at 2-position; pyridine ring is substituted with (C1-C6)-alkoxy-group, hydroxyl group or benzyloxy-group; n = 1; m = 1 or 2). Also, invention describes fungicide comprising compound of the formula (I) or it salt as an active component, methods for preparing derivatives of benzoylpyridine, phenylpyridylmethanol that is an intermediate compounds used for synthesis of compound of the formula (I). Invention provides fungicide properties of compound of the formula (I) or its salt.

EFFECT: improved method for preparing, valuable properties of compounds.

17 cl, 36 tbl, 4 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing tetrachloropicolinic acid. Method involves interaction of 2-cyanopyridine with chlorine in presence of catalysts wherein phosphorus chlorides are used in the amount 2-60 weight % of the initial load of 2-cyanopyridine, and phosphorus oxychlorides also. The chlorination process is carried out in the melt at temperature 120-200°C and under pressure up to 0.6 MPa followed by dosing the reaction mass into a mixture of water with sulfuric acid, and then hydrolysis is carried out in the presence of phosphoric acid formed after hydrolysis of phosphorus chlorides. The end product is isolated by the known procedures. Method provides simplifying the process by using the standard equipment, improving ecological indices and reducing energy consumptions.

EFFECT: improved preparing method.

2 cl, 6 ex

FIELD: chemical technology.

SUBSTANCE: method for preparing tetrachloropicolinic acid involves interaction of 2-cyanopyridine and chlorine in liquid phase in the melt at temperature 120-200°C under pressure up to 0.6 MPa in the presence of catalysts wherein phosphorus chlorides and oxychlorides are used in the mole ratio of 2-cyanopyridine to catalyst = 1:(0.1-1.0) followed by dissolving the reaction mixture in inert solvent, addition of water at temperature 70-80°C, decomposition of phosphorus chlorides at increased temperature to yield hydrogen chloride and phosphoric acid, separation of phosphoric acid from organic layer and the following addition of sulfuric acid to organic layer and hydrolysis of residue by heating the mixture to 120-140°C. Method provides increasing yield and purity of the end product, simplifying technology, reducing cost for its preparing.

EFFECT: improved preparing method.

2 cl, 5 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of 4-phenylpyridine of the general formula: (I) wherein R means halogen or halogen atom; R1 means -(C≡C)mR1' or -(CR'=CR'')mR1'; X means -C(O)N(R8)-, -N(R8)C(O)- or -N(R8)-(CH2)p- wherein m = 0-4 and p = 1-2; values of radicals R1', R2, R3', R3, R4, R4', R8, R' and R'' are given above, and to their pharmaceutically acceptable acid-additive salts and a medicinal agent based on thereof. New compounds are neurokinine-1 antagonists and can be used as medicinal agents in treatment of diseases mediated by neurokinine-1 receptors.

EFFECT: valuable medicinal properties of derivatives.

13 cl, 119 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to compounds inhibiting activity of hormone-sensitive lipase and represented by structure of the formula: (XXXXIVa)

and the formula (XXXXIVb): wherein R1ap and R2ap are chosen independently from (C1-C6)-alkyl, aryl wherein each (C1-C6)-alkyl and aryl can be substituted optionally with one or some substitutes chosen independently from halogen atom, (C1-C6)-alkyl under condition that if R1ap and R2ap are similar then they are not methyl or ethyl, and wherein between substitutes R1ap and R2ap can be a covalent bond optionally, and wherein R5ap, R6ap and R7ap are chosen independently from hydrogen atom and fluorine atom (F), and R4ap is chosen from hydrogen atom, sulfanyl, halogen atom, amino-, nitro-group, (C1-C6)-alkyl, heteroaryl, (C3-C8)-heterocyclyl wherein each among sulfanyl, amino-group, (C1-C6)-alkyl, heteroaryl, (C3-C8)-heterocyclyl can be substituted optionally with one or some substitutes chosen independently from hydroxy-, oxo-group, halogen atom, (C1-C6)-alkyl, aryl, heteroaryl wherein each among (C1-C6)-alkyl, aryl, heteroaryl can be substituted optionally with one or some substituted chosen independently from oxo-group, halogen atom, amino-group, (C1-C6)-alkyl, (C3-C8)-heterocyclyl wherein each among amino-group, (C1-C6)-alkyl, (C3-C8)_heterocyclyl can be substituted optionally with one or some substitutes chosen independently from oxo-group, (C1-C6)-alkyl wherein (C1-C6)-alkyl can be substituted optionally with one or some substitutes chosen independently from oxo-group under condition that R4ap is not methyl. Also, invention relates to a pharmaceutical composition and using these compounds for preparing a medicinal agent used for inhibition of lipolytic activity of hormone-sensitive lipase. Invention describes compounds that can be useful in treatment and prophylaxis of clinical disorders wherein decrease of activity of hormone-sensitive lipase is desirable.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

8 cl, 1 tbl, 602 ex

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