Selective chlorination of 1-(2-forfinal)-4,5-dihydro-3 - methyl-5-oxo-1h-1,2,4-triazole

 

(57) Abstract:

Describes a new method of chlorination of 1-(2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole 4-position of the phenyl ring. It is that a) type of 0.8 to 1.6 molar equivalents of chlorine to a stirred suspension of 1-(2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole in a solvent selected from acetonitrile, N,N-dimethylformamide, nitromethane and nitrobenzene at a temperature in the range of temperature from ambient to 50C at such a rate that the temperature did not exceed 50C and continue stirring at 30-50C 1 - 10 h; (b) remove most by-product hydrogen chloride for 1 to 6 h by reducing the pressure in the reaction vessel so that the solvent boiling, while maintaining a temperature of 30-50C; (C) optionally, the reaction vessel is rinsed with nitrogen to reduce the concentration of hydrogen chloride in the reaction mixture to below 1%; (d) repeating stages a), b) and (C) twice; and e) produce 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1 H-1,2,4-triazole. The technical result is an increase in the yield of the target product. 3 C.p. f-crystals.

The present invention relates to the chlorination of the phenyl ring. In particular, disclosed HVL of the Il-5 - oxo-1H-1,2,4-triazole, intermediate connection upon receipt of the herbicide ethyl- -2-dichloro-5-[4-(deformity)-4,5 - dihydro-3-methyl-5-oxo-1H-1,2,4-triazole-1-yl] -4-torbenson - propanoate ("Target herbicide").

Earlier attempts to achieve efficient access to the target herbicide concentrate on the method described in Example 1 of U.S. Patent N 4818275, in which 1-(5-amino-2-fluoro-4-chlorophenyl)-4-deformity-4,5-dihydro-3-methyl - 5-oxo-1H-1,2,4-triazole is obtained from 2-foronline vomitarium way. In this method, the chlorination of the phenyl ring at the 4-position is carried out before the closure of the triazole ring by reaction of 2-fioricetonline chloride sulfuricum in p-dioxane. However, it soon became clear that this vosmiseriyny path synthesis is not satisfactory due to excessive number of stages and the low yields of the target products.

Although the effectiveness of multi-stage method for obtaining complex molecules can be improved by optimization of the output of each stage, even higher efficiency can be achieved by finding ways of synthesis with fewer stages. It is now established that the target herbicide can be obtained more efficiently with a new path that includes only six hundred then glorious to 1-(4 - chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole. At the third stage of chlorinated product will deformational with the formation of 1-(4-chloro-2-forfinal)-4-deformity-4, 5-dihydro - 3-methyl-5-oxo-1H-1,2,4-triazole. Alternatively, although this method is less preferred, 4,5-dihydro-1-(2-forfinal)-3 - methyl-5-oxo-1H-1,2,4-triazole may first be deformation, and then chlorinated. The intermediate product of the third stage nitrous with the formation of 1-(4-chloro-2-fluoro-5 - nitrophenyl)-4-deformity-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4 - triazole, which is reduced to the corresponding 1-(5-amino - 4-chloro-2-forfinal)-4-deformity-4,5-dihydro-3-methyl-5-oxo-1H - 1,2,4-triazole. At the last stage 5-aminosilane derivative is subjected to diazotization/areleaving with the formation of the target herbicide.

The present invention aims to obtain the key intermediate compound in the specified way, the product of the second stage 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo - 1H-1,2,4-triazole, which unexpectedly was obtained in good yield by chlorination 4,5-dihydro-1-(2-forfinal)-3-methyl-5 - oxo-1H-1,2,4-triazole in a new way, opened in the description and claimed in the claims. Alternatively, although less desirable, it is possible to carry out the reaction of gloriou any way it is believed that it will be difficult to implement a large-scale chlorination 4,5-dihydro-1-(2 - forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole with a good yield. Attempts to gloriavale 4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo-1H - 1,2,4-triazole chloride sulfuricum, glorieuses agent used in similar chlorination in vospitatelnom method of obtaining, failed, giving a very low outputs. For example, in one of the tests yield determined by gas chromatography (GC), was after 18 hours, only about 8 percent of the area. (In chlorination reactions described in the description, the percentage of area not represent the actual product yield, as a by-product not determined by the GC method. However, it provides an indication of the degree of reaction, i.e., percent conversion of starting material). Previous attempts to carry out the chlorination of elemental chlorine in the laboratory given the real outputs of the order of seventy percent even when using a considerable molar excess of chlorine. It was considered that the reaction is not suitable for implementation at the pilot plant.

Suddenly it is now established that the chlorination 4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo-1H - 1,2,4-t is bivalent gaseous chlorine and the subsequent removal of by-product hydrogen chloride between downloads, consistently provides the actual outputs 4,5-dihydro-1-(4 - chloro-2-forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole 82-87% in laboratory conditions, 75-80% or higher on the pilot plant (up to 97% conversion) at a purity of 95% or higher.

In the method according to the present invention, the total number of three molar equivalents of elemental chlorine served in the reaction mixture in three separate downloads, about one equivalent each. Usually becoming the dominant 1-(4-chloro-2-forfinal)-4,5-dihydro - 3-methyl-5-oxo-1H-1,2,4-triazole after each of the three downloads chlorine amount in percent of the area is about 50%, 75% and 97%, respectively.

The key to such high outputs is the removal of gaseous hydrogen chloride formed during chlorination, after each download one molar equivalent of chlorine. Hydrogen chloride, if he remains in the reaction mixture to stop the reaction and/or react with the solvent acetonitrile, resulting in low outputs of the product. Hydrogen chloride is removed from the reaction mixture to the extent possible, using, first, the removal of the vacuum, and then, optionally, purging with nitrogen. Decreased concentration of hydrogen chloride also the filtering and processing stages. In the preferred method according to the present invention, 4,5-dihydro-1-(2-forfinal)-3-methyl - 5-oxo-1H-1, 2,4-triazole (one equivalent) is placed in a solvent, such as acetonitrile, N,N-dimethylformamide, nitromethane or nitrobenzene, preferably acetonitrile. The concentration of this 2-tarpenring derivative in a solvent, in a weight percent 2-tarpenring derived to the volume of solvent is in the range of about 5-70%, preferably about 10-35%, and more preferably 15-25%. Solvent used may be fresh, recycled from previous cycles of the chlorination reaction, or a combination of fresh and recycled solvents. The resulting suspension is stirred during the stage of chlorination at a temperature ranging from about 0oC to about 75oC, preferably from ambient temperature (e.g., 23oC), 50oC and more preferably in the range 30oC - 40oC. When carrying out the method according to the present invention in scale pilot plants add chlorine is carried out in a closed system under vacuum of about 300 to 500 mm Hg, which helps to soften the pressure increase when adding gaseous chlorine. In the process in the laboratory is to ensure proper absorption of important feed rate of chlorine gas. In scale pilot plant reactor pressure depends on the rate of addition of gaseous chlorine in comparison with the reaction rate. It is preferable to maintain the reactor pressure below 15 psig (103,2 kPa) by the speed of adding gaseous chlorine, preferably at about 0.5 pounds/minute (0,227 kg/minute). Despite the fact that the reaction mixture is maintained at the preferred temperature interval of 0.8 to 1.6 molar equivalents, preferably from 0.9 to 1.5 molar equivalents of chlorine gas added below the surface of the reaction mixture at a speed which will maintain the reaction mixture at a temperature below the 50oC, preferably between 30oC and 40oC. the Time required to complete the first boot gaseous chlorine while maintaining the above conditions, is approximately from 10 minutes to 2 hours, preferably from 20 minutes to one hour. After the first boot, gaseous chlorine, the reaction mixture is brought to a temperature of about 30oC - 50oC, preferably 30oC - 40oC, at which it is stirred for time-keeping from one to 10 hours, preferably from three to six hours, after which the conversion of 4,5-dihydrazino methods gas chromatography, approximately 50% (% area). After the time keeping the reaction mixture is support at the preferred temperature 30oC - 40oC and placed under reduced pressure. In scale pilot plant pressure drop amounts to about 100-200 mm Hg, preferably 135-165 mm Hg. In laboratory conditions, the pressure drop amounts to about 10 to 30 mm Hg, preferably 15 to 25 mm Hg. In scale pilot plant was boiled in the above-described conditions continued for a time of from one to six hours, preferably from two to four hours, during which trace amounts of residual chlorine and about 99% by-product hydrogen chloride is distilled over. If in the reaction mixture remains more than 1% hydrogen chloride, the reaction mixture is blown with gaseous nitrogen to bring the level of hydrogen chloride to less than 1%. When conducting the reaction in the laboratory boiling in the above-described conditions continues for from about 20 minutes to two hours, preferably 30 - 50 minutes, then the reaction mixture is blown with gaseous nitrogen over a period of time of about 10 to 30 minutes, preferably 15 to 25 minutes. Upon completion of the lane is Traut with the second load of gaseous chlorine in amounts and under conditions described above. Conversion of 4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo-1H-1,2,4 - triazole, 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazole after the second load, as determined by the methods of gas chromatography, is about 75% (% area). Subsequent removal of by-product hydrogen chloride is again carried out in the above-described conditions. In the same way hold the third chlorine loading and removal of by-product hydrogen chloride. After the completion of the third load of chlorine and subsequent removal of the sand product hydrogen chloride conversion of 4,5 - dihydro-1-(2-forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole, 1-(4 - chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, as determined by the methods of gas chromatography, is about 97% (% area) or higher. After removal of the hydrogen chloride, the reaction mixture is cooled and the solid product is collected by filtration or centrifugation. In the process pilot plant reaction mixture is cooled to about 0oC - 15oC, preferably 3oC - 10oC, to maximize the deposition of any product in the solution and kept at this temperature for a period from about 30 minutes to two hours, preference is sustained fashion acetonitrile. In the process scale pilot plant outputs 1-(4-chloro-2-forfinal)-4,5 - dihydro-3-methyl-5-oxo-1H-1,2,4-triazole approximately 80% with a purity of 98-100%. With appropriate implementation on a laboratory scale receive the outputs 82 - 89% and a purity of 98 to 100%. The solvent is acetonitrile removed from the product by filtration or tsentrifugirovaniem, can be distilled for use in subsequent khlorirovaniya in this way.

Attempts to catalyze the above-described phase chlorination of a number of catalysts have not led to a significant increase in the reaction rate or not sent it further to completion. Tested catalysts include p-toluensulfonate acid, triftorbyenzola ytterbium, acetic acid, hydroxy(4 - methylbenzenesulfonate-O) period, triethylphosphite, water, sulfuric acid, 2,6-di-tert-butyl-4-METHYLPHENOL, elemental iodine, Tris [2-(2-methoxyethoxy)ethyl] amine, aluminum chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, dimethyl - aminopyridine and ferric chloride (3). He also experienced a number of key reagents in stoichiometric quantities for removal (capture) by-product hydrogen chloride. They include sodium acetate, poly (4-vaniety hydrogen, none of them did not increase significantly the reaction rate or has not sent a response in addition to stopping.

Chlorination methods described generally above, was carried out with potassium salt of 4,5-dihydro-1-(2 - forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole or 4-deformity - 4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole. Typically, these reactions will not occur as quickly as in the case of the preferred 4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo - 1H-1,2,4-triazole, although both lead to the corresponding chlorinated product. A number of chlorination reactions using 4-deformity-4,5-dihydro-1-(2-forfinal)-3-methyl-5-oxo-1,2,4 - triazole to complete reaction required an excessive amount of chlorine and a long reaction time. To increase the rate of reaction used the above catalysts, but these attempts had no effect.

Specific examples of the application of the method according to this invention is shown below.

Example 1

Obtaining 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5 - oxo-1H-1,2,4-triazole-chlorination 4,5-dihydro-1-(2-fluoro - phenyl)-3-methyl-5-oxo-1H-1,2,4-triazole

(Lab scale)

In the reaction vessel of 1500 ml, equipped with a mechanical stirrer, temperaturel-5-oxo-1H-1,2,4 - triazole and 1006 ml of acetonitrile (wt.%/the amount of triazole/solvent is a fall of 19.88%). Stir mixture is blown with nitrogen for about 25 minutes, then the temperature was adjusted to 35oC. and Then for one hour below the surface of the reaction mixture bubbled chlorine gas, about 73,7 g (1,035 mole; one equiv.). After complete addition, the reaction mixture is stirred at 35oC for about six hours, during this time gas chromatographic analysis of the reaction mixture indicates that the reaction proceeded to about 50% (% area) conversion to product. While maintaining the temperature at 35oC the reaction mixture is vacuum and kept in a vacuum of about 20 mm Hg for 45 minutes to remove the by-product hydrogen chloride. Then the reaction mixture is rinsed for 20 minutes in nitrogen gas for additional removal of by-product hydrogen chloride. After removal of the hydrogen chloride, the reaction mixture was allowed to cool to ambient temperature and stirred for about 16 hours. (This period of time was necessary for the convenience and not of necessity, requires only about three hours). After this time, the second equivalent of 73.7 g (1,035 mole, one equiv.) chlorine gas bubbled below the surface re 35oC, at which it is stirred for 1.5 hours, at this time, GC analysis indicates that the reaction proceeded to about 75% (% area) conversion to product. Keeping the temperature at 35oC, the reaction mixture is again vacuum and maintained at about 20 mm Hg for 1 hour to remove the by-product hydrogen chloride. The reaction mixture is again rinsed for 20 minutes in nitrogen gas for additional removal of byproduct hydrogen chloride. After removal of the hydrogen chloride, the reaction mixture was allowed to cool to ambient temperature where it stirred for about 16 hours (again for reasons of convenience). After this time, the third equivalent of 73.7 g (1,035 mole, one equiv.) chlorine gas bubbled below the surface of the reaction mixture for one hour. After complete addition, the temperature of the reaction mixture was adjusted to 35oC, at which it again is stirred for six hours at this time, GC analysis shows that the reaction conversion in the target product was approximately 97% (% area). Maintaining the temperature at 35oC, the reaction mixture was again kept in a vacuum of about 20 mm Hg during adnominal gaseous nitrogen for additional removal of hydrogen chloride, cooled to ambient temperature and filtered, receiving the first portion 184,5 g of solid product. Distillation of the mother liquor under vacuum of about 5 mm Hg without heating gives 936.5 ml of acetonitrile (93.1% of regeneration). The second portion of 2.3 g of product are collected from the residue remaining after distillation. Two portions of the product combine, getting 186,8 g (83.5% of yield) of 1-(4 - chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole with a purity of 99.5% (weight %, determined by gas chromatography).

Example 2

Obtaining 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5 - oxo-1H-1,2,4-triazole-chlorination 4,5-dihydro-1- (2-forfinal)-3-methyl-5-oxo-1H-1,2,4-triazole

(Scale pilot plant at 50 gallons (189,25 l))

50-gallon (189,25 l) enameled reaction vessel equipped with a condenser Hasteloy and glass mixing device, load 115 pounds (52,21 kg) acetonitrile, recycled from previous experience this reaction), 47.4 lbs (21.5 kg) of fresh acetonitrile (just 162,4 lb (73,663 kg) = 94,685 liters) and 40.6 lbs (0,210 pound-mole (95,302 mol); 1 EQ. - 18,416 kg) 4,5-dihydro-1-(2-forfinal)-3-methyl - 5-oxo-1H-1,2,4-triazole (the weight. %/about-triazole/solvent is 19,46%). The mixture is then stirred and heated to 35oC. In the IOM about 300-500 mm Hg. Then chlorine gas 21.01 pound (at 9.53 kg) (0,296 pound-mole (134,225 mol); 1,41 equiv.) served in the reaction mixture below the surface with such speed (about 0.5 lb/min = 0,227 kg/min) to maintain the temperature of the reaction mixture at 40oC or less and the pressure in the reaction vessel below 15 psig (103,2 kPa). The time required to complete the supply of chlorine gas is approximately 30 minutes. After downloading chlorine loading line chlorine gas is blown with nitrogen, which causes a decrease in temperature. The temperature of the reaction mixture is slowly brought to 40oC while maintaining the pressure in the reaction vessel below 15 psig (103,2 kPa). The reaction mixture is then stirred for time-keeping three hours, after this period of time, analyze the conversion of the source material in the product and the content of by-product hydrogen chloride. For a three-hour aging time conversion of starting material into the product, as determined by the methods of gas chromatography, was approximately 50 % (% area). After this time the reaction mixture is heated under reflux for three hours at 40oC/150 mm Hg, causing the removal of by-product hydrogen chloride. Pickup is for under reflux. Then the reaction mixture is cooled to 35oC and the reaction vessel is placed under a vacuum of about 300-500 mm Hg. The second load of chlorine gas 14,01. lb (6,355 kg) (0,198 pound-moles (89,507 mol); 0,94 equiv.) then loaded into the reaction mixture in the manner described above for the first load of chlorine ( seven hours after first boot). The time required to complete a second load of chlorine gas is approximately 30 minutes. Once the download is chlorine, the reaction mixture is maintained at 40oC/ 15 psig (103,2 kPa) for three hours, as described previously. Then the reaction mixture was examined for the degree of conversion of the source material to the target product and the contents of the byproduct hydrogen chloride. During the three-hour incubation, the conversion of starting material into the product, as determined by the methods of gas chromatography, is about 75% (% area). The reaction mixture is again heated under reflux for three hours at 40oC/ 150 mm Hg to remove the by-product hydrogen chloride content less than 1%. Then the reaction mixture is adjusted to the previously described conditions and spend a third load 14,01 feet (6,355 kg) (0,198 pound-mole (89,507 mol); 0,9 shaped chlorine, the reaction mixture was again incubated at 40oC for four hours. Conversion of starting material to product in 96% (% area) or more was made for a four-hour period of exposure. The reaction mixture is again heated under reflux at 40oC/ 15 psig (103,2 kPa) for three hours to remove by-product hydrogen chloride. After heating under reflux (total reaction time: ~ 22.5 hours) the reaction mixture is cooled to 5oC for 30 minutes and stirred at this temperature for one hour. Then the reaction mixture is transferred into an appropriate centrifuge, where it rotate for 30 minutes to remove the mother liquor. The mother liquor is stored in a separate receiver for the regeneration of acetonitrile by distillation. The filter residue is washed first 35 pounds (15,89 kg) cold (0-5oC) acetonitrile loaded directly into the centrifuge. The mixture was rotated for 30 minutes to remove the leaching of acetonitrile. The second portion 35 pounds (15,89 g kg) cold acetonitrile is loaded into the reaction vessel, where it is stirred for five minutes to remove any residue of the reaction mixture. Wash acetonitrile is then transferred into a centrifuge, where the rotation is within 24 hours, getting 38,27 lb (17,37 kg) (yield 80.2 per cent) of 1-(4-chloro-2 - forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, which were of 99.9% purity (weight percent, as determined by the methods of gas chromatography).

1. The chlorination of 1-(2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole 4-position of the phenyl ring, wherein (a) type of 0.8 to 1.6 molar equivalents of chlorine to a stirred suspension of 1-(2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole in a solvent selected from acetonitrile, N,N-dimethylformamide, nitromethane and nitrobenzene, at a temperature in the range from ambient temperature up to 50C at such a rate that the temperature did not exceed 50C and continue stirring at 30 - 50C 1 - 10 h; (b) remove most by-product hydrogen chloride for 1 to 6 h by reducing the pressure in the reaction vessel so that the solvent boiling, while maintaining the temperature at 30 to 50C; (C) optionally, the reaction vessel is rinsed with nitrogen to reduce the concentration of hydrogen chloride in the reaction mixture to below 1%; (d) repeating stages a), (b) and (C) twice; and e) produce 1-(4-chloro-2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole.

2. The method according to p. 1, characterized in that a) add 0,9 - 1,5 mo is iatola in acetonitrile, when the weight percentage of 1-(2-forfinal)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole on the volume of acetonitrile 5 to 70% at a temperature of 30 - 40C, at such a rate that the temperature was between 35 and 40C and continue mixing for 3 to 6 h; (b) remove most by-product hydrogen chloride over a period of 2 to 4 hours by reducing the pressure in the reaction vessel so that the solvent is boiled, while maintaining the temperature at 35 - 40; carry out stage (C) - (d) as indicated above.

3. The method according to p. 2, in which stage (a) - (d) is carried out at reduced pressure.

4. The method according to p. 3, in which a reduced pressure is in the range of 300 to 500 mm Hg.

 

Same patents:

The invention relates to novel triazole compounds of the General formula (1), where a denotes a linear or branched C1-C18-alkylenes group which may comprise at least one group which is selected from O, S, CONH, COO,3-C6-cycloalkene or double or triple bond; In denotes the radical of formula (a), (b) or (C); R1denotes H, NH2WITH3-C6-cycloalkyl or1-C8-alkyl, which is not substituted or substituted OS1-C8-alkyl; R2denotes H, HE, C1-C8-alkyl, C3-6-cycloalkyl, CF3, CN, NR3R4, SR3or CO2R3where R3denotes N or C1-C8-alkyl, a R4denotes H, C1-C8-alkyl, or COR3where R3stands WITH1-C8-alkyl; Ar represents naphthyl, phenyl with 1-2 substituent selected from C1-C8-alkyl, CF3, CHF2, NO2, SR3, SO2R3where R3means1-C8-alkyl; and pyridyl, pyrimidyl or triazinyl, which have from 1 to 3 substituents selected from C1-C8-alkyl, C2-C6-alkenyl, C2-C6-quinil, halogen, CN, CF3, OR4where R43-C6-lalouche possibly condensed, phenylalkylamine or 5-membered aromatic heterocycle with 1 to 2 nitrogen atoms, which may be condensed with a benzene ring

The invention relates to 2-[1',2',4'-triazole-3'-roximation] anilides formula I

< / BR>
in which the index and the substituents have the following meanings:

n means 0, 1, 2, 3 or 4, where the substituents R1may be different if n is greater than 1;

X represents a direct bond, O, or NRa;

Rameans hydrogen, alkyl, alkenyl, quinil, cycloalkyl or cycloalkenyl;

R1means nitro, cyano, halogen, optionally substituted alkyl, alkenyl, quinil, alkoxy, alkenylacyl, alkyloxy or

if n is 2, additionally represents associated with two adjacent ring atoms optionally substituted by a bridge containing three or four members from the group containing 3 or 4 carbon atoms, 1-3 carbon atoms and 1 or 2 nitrogen atom, oxygen and/or sulphur, and this bridge together with the ring to which it is linked, may form a partially unsaturated or aromatic radical;

R2means hydrogen, nitro, cyano, halogen, C1-C4alkyl, C1-C4halogenated, C1-C4alkoxy, C1-C4alkylthio or C1-C4alkoxycarbonyl; R3means optionally substituted is which, together with the carbon atoms may contain one to three heteroatoms as members of a cycle of the following: oxygen, sulfur and nitrogen, or an optionally substituted single or dual core aromatic radical, which together with the carbon atoms may contain as members of the cycle from one to four nitrogen atoms or one or two nitrogen atom and one oxygen atom or sulfur or one oxygen atom or sulfur;

R4means hydrogen, optionally substituted alkyl, alkenyl, quinil, cycloalkyl, cycloalkenyl, alkylaryl or alkoxycarbonyl;

R5means alkyl, alkenyl, quinil, cycloalkyl or cycloalkenyl or if X is NRaadditionally represents a hydrogen

The invention relates to new nitrogen-containing heterocyclic compounds possessing biological activity, in particular fungicidal activity, and more particularly to a derivative triazolyl, the way they are received and fungicidal tool

-methoxykynuramine acids" target="_blank">

The invention relates to a method of producing methylamino- methoxykynuramine acids of the formula I, where Y represents a C-organic radical through reaction of Pinner interaction achilleid formula II with an alcohol and subsequent interaction of the formed in the Pinner reaction of ester of the formula (IV) with hydroxylamine to obtain the oxime of the formula V by methylation of the oxime of the formula V to oximoula ether of the formula VI or b) somethingitaliano obtaining oximoula ester of formula VI, followed by interaction oximoula ester of formula VI with methylamine, characterized in that in the reaction of Pinner used alcohol of the formula III R-OH, boiling point above 75C

The invention relates to the production technology of heterocyclic substances, in particular to the production technology, morpholine 3-methyl-1,2,4-triazolyl-5-thioacetate used in medicine and veterinary medicine

The invention relates to new derivatives thiocarbonic acid having biological activity, in particular to substituted aromatic Amida thiocarbonic acid and the herbicide agent containing them

The invention relates to substituted derivative asalaam, which is an effective anti-Helicobacter tools that can be used as monotherapy for eradication of Helicobacter pylori and related species

The invention relates to cyclic Amida substituted in-the position of different aryl groups, agricultural suitable salts and their mixtures, and their use as fungicides systemic or selective action

The invention relates to new chemical compounds having valuable properties, in particular to new derivatives of sulfonamidophenylhydrazine

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention relates to new substituted benzoylketones of the general formula (I): , all possible tautomeric forms and possible salts that can represent active substance as a component of herbicide agent. In the formula (I) A means (C1-C4)-alkyl; R1 means cyclo-(C3-C6)-alkyl; R2 means hydrogen atom (H), cyano-group (CN); R3 means hydrogen atom (H), halogen atom, CF3, (C1-C4)-alkylsulfonyl; R4 means halogen atom; X means groups: or wherein R5 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, (C1-C4)-alkylthio-group, di-(C1-C6-alkyl)-amino-group; R6 means (C1-C4)-alkyl, (C1-C4)-alkoxy-group, cyclo-(C3-C6)-alkyl; n = 0 or 1 including all possible tautomeric forms and possible salts. Compounds of the formula (I) elicit herbicide activity and can be used in herbicide composition.

EFFECT: valuable properties of compounds.

3 cl, 1 sch, 3 tbl, 13 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes substituted benzoylcyclohexanediones of the general formula (I):

wherein m = 0 or 1; n = 0 or 1; A means a single bond or alkanediyl (alkylene) with 1-4 carbon atoms; R1 means hydrogen atom or unsubstituted alkyl with from 1 to 6 carbon atoms; R2 means methyl; R3 means hydrogen atom, nitro-, cyano-group, halogen atom, alkyl with from 1 to 4 carbon atoms substituted with halogen atom, alkoxy-group with from 1 to 4 carbon atoms or alkyl sulfonyl with from 1 to 4 carbon atoms; R4 means nitro-group, halogen atom, unsubstituted alkyl with from 1 to 4 carbon atoms of that substituted with halogen atom; Z means heterocycle, and herbicide agent based on thereof. Also, invention describes substituted derivatives of benzoic acid of the general formula (III):

wherein values n, A, R3, R4 and Z are given above. These compounds represent the parent substances used for preparing compound of the formula (I). Compounds of the formula (I) elicit high and selective herbicide activity.

EFFECT: valuable properties of compounds.

7 cl, 8 tbl, 7 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: substituted benzoylisoxazols of general formula I are described, wherein R1 is cycloalkyl; R2 is hydrogen, alkoxycarbonyl; R3 is halogen, substituted alkyl, alkoxyl; R4 is halogen, alkoxil; Z is substituted 5-membered saturated or unsaturated heterocycle having 1-3 nitrogen atoms and additionally including one oxogroup (C=O). Also disclosed is herbicidal agents, containing compounds of formula I.

EFFECT: effective suppression of weeds in such cultures as maize and wheat.

16 cl, 6 tbl, 4 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to novel retinoid compounds of the structural formula (I) or their pharmaceutically acceptable salts and pharmaceutical compositions possessing agonistic activity with respect to retinoid receptors and comprising indicated compounds wherein n = 1; d = 0 or 1; B means -CR7=CR8-, -CH2O- wherein R7 and R8 each means independently hydrogen atom; X means phenyl optionally substituted with halogen atom, or 5-membered heteroaryl comprising sulfur atom (S) as a heteroatom; R1 means -C(=O)-R9 wherein R9 means alkyl, hydroxyl, amino-, heteroaryloxy-group comprising oxygen atom (O) or 6-membered heterocyclyl comprising nitrogen atom (N) as a heteroatom; R2 means: (a) -(CR10R11)m-Yp-R12; m means a whole number from 1 to 10; p means 0 or 1; R10 and R11 mean hydrogen atom; Y means -O-, -S- or -NR13-; R13 means hydrogen atom; R12 means hydrogen atom, alkyl, cycloalkyl, phenyl, 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heteroarylalkyl comprising atoms N, S, O as a heteroatom, heteroalkyl comprising atoms N, S, O as a heteroatom, 5- or 6-membered heterocyclyl comprising atoms N, S, O as a heteroatom, or 5- or 6-membered heterocyclylalkyl comprising atoms N, S, O as a heteroatom under condition that when p means 0 then R12 doesn't mean hydrogen atom or alkyl; (b) 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (c) -Z-L wherein Z means -CR14=CR15-, -C≡C-, -C(=O) or -S-; R14 and R15 mean hydrogen atom; L means 5- or 6-membered heteroaryl comprising atoms N, S, O as a heteroatom; (d) -CR14=CR15-L1 wherein L1 means -S(O)2R17 or -SO2NR18R19 wherein R17 means alkyl; R18 and R19 mean hydrogen atom; each R3 means independently hydrogen atom, hydroxyl or oxo-group; t means 1 or 2.

EFFECT: valuable medicinal properties of compounds and compositions.

59 cl, 10 tbl, 54 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1,2,4-triazolone-3- representing the parent component used in the creature of energy-saturated materials - gun powders, fuels, explosive substances, blowing agents. Method involves interaction of acetone semicarbazone with formic acid in the presence of 96% sulfuric acid as the reaction activating agent in the mole ratio of reagents = 1:(4.5-5.5):(0.35-0.45), respectively, at temperature 107-110°C for 12 h. Method provides simplifying the process and to enhance the yield of the end product.

EFFECT: improved method of synthesis.

1 tbl, 1 ex

FIELD: herbicides, agriculture.

SUBSTANCE: herbicide composition is prepared as emulsion concentrate that is characterized by the presence of carfetrazon-ethyl, 2,4-D 2-ethylhexyl ester and organic solvent in the following content of components per 1 l of solvent: carfetrazon-ethyl, 2-50 g/l; 2,4-dichlorophenoxyacetic acid (2,4-D) 2-ethylhexyl ester, 400-700 g/l. Xylene is used as an organic solvent. For control of weeds the above said composition is taken in the dose 0.5-0.6 l/ha that is diluted and cereal crops are sprayed in bushing out phase and maize - in phase of 3-5 leaves. Invention provides decreasing consumption dose of herbicides.

EFFECT: valuable properties of herbicide.

2 cl, 2 tbl

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention relates to novel substituted arylketones of the general formula (I): wherein n = 1; A means alkanediyl (alkylene) comprising from 1 to 6 carbon atoms; R1 means one of the following groups: ; R6 means -OH; R7 means hydrogen atom (H); R8 means H, (C1-C6)-alkyl substituted if necessary with (C1-C6)-alkoxyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group; R9 means -OH; R2 means H, halogen atom, (C1-C4)-alkylsulfonyl group, (C1-C6)-alkyl substituted if necessary with halogen atom; R3 means halogen atom, (C1-C4)-alkylthio-group, (C1-C4)-alkylsulfonyl; R4 means one of the following heterocyclic groups: wherein a dotted bond represents a simple bond of double bond; Q means oxygen atom; R14 means H, (C1-C6)-alkyl substituted if necessary with (C1-C4)-alkoxyl, (C1-C6)-alkoxy-, (C1-C6)-alkylthio-group or (C3-C6)-cycloalkyl; R15 means H, (C1-C6)-alkyl substituted if necessary with (C1-C4)-alkoxyl, (C1-C6)-alkoxy- (C1-C6)-alkylthio-group and wherein separate radicals R14 and R15 bound by similar heterocyclic groups can be similar or different within the limits of above given definition and involving all possible tautomeric forms of compounds of the general formula (I) and possible salts or adducts of acids and bases of the general formula (I). Compounds of the formula (I) can be used as herbicide agent.

EFFECT: valuable property of compounds.

5 cl, 8 tbl, 14 ex

FIELD: organic chemistry, agriculture.

SUBSTANCE: invention relates to fluoroalkoxyphenylsulphonylamino(thio)carbonyl triazolynes of general formula I wherein n = 2 or 3; Q1 is sulfur or oxygen; Q2 is oxygen; R1 is methyl, optionally substituted with fluorine, C2-C4-alkyl, C1-C4-alkoxy; R2 is F, Cl, Br, methyl, optionally substituted with methoxy, C2-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, di-C1-C2-flkylamino, C3-C6-cycloalkyl, C3-C6-cycloalkylmethoxy; R3 is C1-C3-alkyl, C1-C3-alcoxy, C3-C6-cycloalkyl, except for certain compounds wherein n = 2; R1 is methyl; Q1 is oxygen; R2 is C1-C3-alkoxy or methyl; R3 is methyl or cyclopropyl, or salts thereof and herbicidal agent based on the same.

EFFECT: compounds with good compatibility with cultural plants and improved herbicidal activity.

5 cl, 3 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: novel compounds of formulas , , , , , , (designation of all groups are given in invention formula) are used for treatment of different metabolic diseases, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver, cachexia, obesity, atherosclerosis and arteriosclerosis.

EFFECT: using compounds as biologically active agent and creating pharmaceutical compositions based on said compounds.

124 cl, 52 ex, 17 tbl, 2 dwg

FIELD: chemistry, pharmacology.

SUBSTANCE: described is compound of formula (I) , where X1 - group R5O, X2 is selected from group, including O, S, and NR7, R1 and R2 each is independently selected from group including hydrogen and halogen, R3 and R4 stand for hydrogen, R5 stands for phenyl, which optionally includes substituent, selected from halogen, R7 stands for C1-C6alkyl, as well as its acid-additive salts. Also described is pharmaceutical composition, containing therapeutically efficient amount of formula (I) compound or its acid-additive salt, in mixture with at least one pharmaceuticaly acceptable carrier or diluent.

EFFECT: obtaining compound possessing inhibiting activity with respect to reverse HIV tannscriptase.

10 cl, 2 tbl, 23 ex

Up!