Halogenated ester, process for its production and method for producing olkiluoto ester 3-(2-chloro-3,3,3 - cryptocom-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylic acid

 

(57) Abstract:

Describes new compounds of formula I, CF3-l-CH(OH)CH2- (CH3)2-CH2-CO2R, where X represents the group chlorine or bromine, and R represents hydrogen or alkyl containing up to 4 carbon atoms, processes for their preparation and their use as intermediates for obtaining derivatives of cyclopropane with insecticidal properties. Also describes compounds useful as intermediates in obtaining the compounds of formula I. 3 C. and 11 C.p. f-crystals.

The present invention relates to halogenated esters that are used as intermediate products for the production of insecticides, to methods for their preparation and to methods of obtaining them from insecticides.

In UK patent N 2000764 described valuable esters with insecticidal properties, including-cyano-3-phenoxybenzyl ester 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid, which is in the form of a racemate formed its isomers (Z)-1R,CIS- (S) - and (Z)-1S,CIS- (R), is a widely used commercial insecticide that have a common name according to ISO (ISO) lambda cigalotrin (lambda-cyhalothrin).

Thus, the present invention relates to a compound of the formula I

CF3-CXCl-CH(OH)CH2-C(CH3)2- CH2-CO2R,

where X is chlorine or bromine and R is hydrogen or alkyl containing up to 4 carbon atoms. Specific examples of compounds of formula I include methyl 6-bromo-6-chloro-3,3-dimethyl-5 - hydroxy-a 7,7,7-cryptolepine, ethyl 6-bromo-6-chloro-3,3-dimethyl-5 - hydroxy-a 7,7,7-cryptolepine acid, methyl ester of 6,6-dichloro-3,3-dimethyl-5-hydroxy-a 7,7,7-cryptolepine acid and ethyl ester of 6,6-dichloro-3,3-dimethyl-5-hydroxy-a 7,7,7-cryptolepine acid and the corresponding carboxylic acid.

The present invention relates also to a method for obtaining compounds of formula I, where X represents chlorine or bromine and R represents alkyl containing up to 4 carbon atoms, which lies in the interaction of the compounds of formula II

CF3-CHXCl

with the compound of the formula III

O=CH-CH2-C(CH3)2-CH2-CO2R

in the presence of a strong base and an inert solvent.

The process is conducted in the presence of a strong base, which is considered valid by the state include a lower alcoholate of alkali metals, such as sodium alcoholate or potassium containing up to 6 carbon atoms, for example, isopropyl sodium, isopropyl potassium, tert-butyl sodium or tert-butyl potassium, but you can also use other bases, such as hydrides of alkali metals, e.g. sodium hydride, amides of alkali metals, e.g. sodium amide. The process is preferably carried out at low temperatures, to avoid receiving unwanted side products. The preferred temperature is in the range from -80oC and 0oC, especially when used aprotic polar solvent. Specific examples of aprotic polar solvents that can be used in the process include amides, such as dimethylformamide, dimethylacetamide and di-n-butylacetamide, cyclic ethers, such as tetrahydrofuran, tetrahydropyran and dioxane, ethers, glycols, such as dimethyl ether of ethylene glycol and diethyl ether of ethylene glycol, and sulfoxidov, such as dimethylsulfoxide. However, you can also use other inert solvents, such as aromatic hydrocarbons, for example toluene.

The compounds of formula III can be obtained by the interaction between the family and the Foundation. Suitable oxygen donor is pyridine-N-oxide, and as a basis it is convenient to use a carbonate of an alkali metal such as sodium carbonate or potassium.

It is expected that the compounds of formula IV have not been previously described, and in accordance with the following aspect of the present invention proposed a compound of formula IV, where R is alkyl containing up to 4 carbon atoms, preferably the stands and ethyl.

The compounds of formula IV can be obtained by reacting the compounds of formula V

CH2=CH-C(CH3)2-CH2-CO2R

with hydrogen bromide in the presence of free-radical catalyst such as an organic peroxide.

The compounds of formula I can be converted into cyhalothrin acid (in the form of its Olkiluoto ether) using a simple two-stage process. According to another aspect of the present invention provides a method of obtaining Olkiluoto ester 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid, which comprises (a) processing the compounds of formula I dehydration agent with obtaining the compounds of formula VI

CF3-CXCl-CH=CH-C(CH3)2-CH2-CO2

Preferred dehydrating agent for use in stage (a) is axilary phosphorus, and the process is preferably carried out in a suitable solvent, such as pyridine base, such as lutidine. The base used in stage (b) is preferably an alcoholate of an alkali metal, and the process can be carried out in a suitable solvent or diluent, such as, for example, polar aprotic solvent, such as dimethylformamide, or an excess of the alcohol corresponding to the alcoholate of an alkali metal. Tert-butylate sodium or potassium are the preferred bases, and preferably, the reaction is carried out in dimethylformamide. Can also be applied to other grounds, such as amides of alkali metals, for example sodium amide, or disilicide alkali metals, for example disilicate sodium, preferably in the presence of catalytic amounts of alcohol, such as tert-butanol. Particularly preferred technique for use in stage (b) is carrying out the reaction in the presence of an aromatic hydrocarbon solvent such as toluene or xylene, in the circumstances in which the tert-butanol is removed by distillation.

Far is rmula I, in the following examples, which are illustrative in relation to various aspects of the invention.

Example 1. This example shows how to obtain methyl(5-bromo-3,3-dimethylpent-4-enoate).

Methyl(3,3-dimethylpentane) (50.0 g) was dissolved in carbon tetrachloride (500 cm3) and heated to 60oC in nitrogen atmosphere. One portion add benzoyl peroxide (2,44 t), and the mixture is stirred for 10 minutes, after which through steklofil enter the stream of gaseous bromoiodide within 45 minutes. The reaction mixture is blown with nitrogen and incubated at ambient temperature for 72 hours. The mixture is then heated to 50oC, add the next portion of benzoyl peroxide (2,44 g) and within 15 minutes introducing gaseous bromovalerate to complete the reaction. After removal of the remainder of bromoiodide by ozonation of nitrogen, the reaction mixture was concentrated by removing the solvent by evaporation under reduced pressure. The remaining liquid phase is purified by distillation to obtain methyl(5-bromo-3,3-dimethylbutanoate) as a colourless liquid, T square 80oC/267 PA, yield 80%.

H1NMR (M. D. ): 3,70 (3H, s, OMe); 3,40 (2H, m, CH2Br); 2,25 (2H, s, CH2CO2

A mixture of methyl(5-bromo-3,3-dimethylbutanoate) (5.0 g), pyridine-N-oxide (4,49 g), sodium bicarbonate (3.77 g) and toluene (30 cm3) heated at boiling temperature under vigorous stirring for 14 hours. After cooling the mixture to ambient temperature, add water (20 cm3, a saturated solution of ammonium carbonate (20 cm3) and toluene (50 cm3) and the aqueous phase is separated and extracted with toluene (3 x 75 cm3). Toluene extracts are added to the main organic phase and all of the organic phase, dried over anhydrous magnesium sulfate, concentrated by evaporation of the more volatile components under reduced pressure. The residual liquid is purified by means of distillation in Kugeler (130oC/pressure water pump), which gives methyl(3,3-dimethyl-5-oxopentanoate output to 63%.

H1NMR (M. D. ): 9,85 (1H, m, CHO); the 3.65 (3H, s, OMe); of 2.50 (2H, m, CH2CHO); 2,40 (2H, s, CH2CO2Me); to 1.15 (6H, s, CMe2).

Example 3. This example shows how to obtain methyl(6,6-dichloro-3,3-dimethyl-5-hydroxy-a 7,7,7-cryptolepine).

To a stirred mixture of methyl(3,3-dimethyl-5-oxopentanoate) (1.0 g), 1,1-dichloro-2,2,2-triptorelin (1.06 g) and anhydrous tetrahydrofuran (10 cm3), the temperature to which the solution in dimethylformamide), after which the mixture continued to stir at -78oC over the next 60 minutes. The reaction is quenched with saturated ammonium chloride at low temperature and allow the mixture to warm to ambient temperature. After adding water (20 cm3and separation of the organic phase the aqueous phase is extracted with diisopropyl ether (3 x 30 cm3) and the extracts combined with the organic phase, which was washed with saturated salt solution (2 x 10 cm3) and dried over anhydrous magnesium sulfate. After removal of volatile components by evaporation under reduced pressure the residual oil purified via column chromatography (column with silica gel, elwira a mixture of 9:1 (by volume) of hexane and ethyl acetate) to obtain methyl(6,6-dichloro-3,3-dimethyl-5-hydroxy-a 7,7,7-Cryptor-heptanoate) as a colourless oil (yield 56%).

H1NMR (M. D.): 4,50 (1H, d, OH); to 4.28 (1H, m, CHOH); to 3.73 (3H, s, OMe); 2,48 (2H, d[ab], CH2CO2Me); of 1.95 (2H, m, CH3); to 1.15 (3H, s, CMe2); 1,09 (3H, s, CMe2).

Mass spectrum: 279 (M-OMe); 257 (M-[Cl+H2O].

IR-spectrum: 1710, 3400 cm-1(user.).

Example 4. This example shows how to obtain methyl(6,6-dichloro-3,3-dimethyl-a 7,7,7-cryptogam-4-enoate).

The phosphorus oxychloride (10 is enoate) (5.49 g) of 3,5-lutidine (50 cm3), the temperature of which is supported 0oC. the Resulting mixture is heated at 100oC for 30 minutes and then cooled to ambient temperature in nitrogen atmosphere and then poured into stirred mixture of ice and water (300 cm3). The mixture is extracted with ethyl acetate (2 x 150 cm3), diethyl ether (3 x 150 cm3and, finally, ethyl acetate (150 cm3). The volume of the combined extracts is reduced to about 400 cm3by evaporating some of the solvent under reduced pressure, and then washed with diluted (3.5 M) hydrochloric acid. The washing water is extracted with diethyl ether (3 x 50 cm3and combine the extracts with organic phase. After washing the combined organic phases with saturated salt solution and dried over anhydrous magnesium sulfate the solvent is removed by evaporation under reduced pressure and the residual oil is purified by means of distillation in Kugeler (123oC/133 PA) which gives methyl(6,6-dichloro-3,3-dimethyl-a 7,7,7-cryptogam-4-ENOAT) as a pale yellow oil (2.86 g, 52% yield) together with a number formed by allylic rearrangement of isomer - methyl(4,6-dichloro-3,3-dimethyl-a 7,7,7-cryptogam-5-enoate).

/P>Mass spectrum: 257 (M-Cl); 219 (M-CH2CO2Me).

IR-spectrum: 1750 cm-1.

Example 5. This example illustrates obtaining the ethyl ester of 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid.

Mix a solution of ethyl(6,6-dichloro-3,3-dimethyl-a 7,7,7 - cryptogam-4-enoate) (0.1 g) in dimethylformamide (10 ml) is cooled to -25oC in nitrogen atmosphere and added dropwise tert-butyl sodium (0.1 ml of a 42% solution in dimethylformamide). After 30 minutes, add five drops of a solution of tert-butyl sodium, and the mixture is stirred for another 15 minutes, then the reaction quenched with a saturated solution of ammonium chloride (2 ml) for 10 minutes. Add water (40 ml) and extracted with a mixture of hexane (3 x 40 ml), the combined extracts washed with saturated salt solution (20 ml) and dried over anhydrous sodium sulfate. The dried solution is filtered and concentrated by evaporation under reduced pressure, giving ethyl ester 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclo-propenylboronic acid in the form of a mixture of isomers.

Example 6. This example illustrates the obtaining of the methyl ester of 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid.

Example 7. This example illustrates the obtaining of the methyl ester of 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid conditions, when tert-butanol is removed by azeotropic distillation with toluene.

Tert-butyl sodium (2.5 g) is quickly added to a mixture of methyl(6,6-dichloro-3,3-dimethyl-a 7,7,7-cryptogam-4-enoate) (5,55 g, the concentration of 91%) and toluene (50 cm3), the temperature of which support equal 40oC at atmospheric pressure. The resulting mixture is stirred, while the pressure is reduced to 5333 PA, and maintained at this pressure for 2 hours, after which the pressure returned to atmospheric and the mixture is quenched with acetic acid (4.0 cm3). The study mixture using quantitative gas chromatographic analysis shows that the desired product (CIS-Z-isomers) is present in the amount of 75%.

Example 8. This PR is th acid conditions, when tert-butanol is removed by azeotropic distillation with xylene.

Using the method of the previous example, except that instead of toluene used xylene (50 cm3), and a reduced pressure is 2667 PA and incubated for 2.5 hours. During this period additionally add xylene, in order to maintain a constant volume. Study of the reaction mixture shows that the desired product (CIS-Z-isomers) was obtained with a yield of 75%.

1. Halogenated ester of formula I

CF3- CXCl - CH(OH) CH2- C(CH3)2- CH2- CO2R,

where X is chlorine or bromine and R is hydrogen or alkyl containing up to 4 carbon atoms.

2. Connection on p. 1, where X is chlorine, R is methyl.

3. The method of obtaining the compounds of formula I on p. 1, where X represents chlorine or bromine, R represents alkyl containing up to 4 carbon atoms, which consists in the fact that the compound of formula II

CF3- CHXCl

subjected to interaction with the compound of the formula III

O = CH - CH2- C(CH3)3- CH2- CO2R,

the values of X and R described above, in the presence of a strong base and inercooler alkali metal.

5. The method according to p. 4, wherein the strong base is a tert-butyl sodium or potassium.

6. The method according to p. 3, characterized in that the process is carried out in the temperature range from - 80oWith 0oC.

7. The method according to p. 3, characterized in that the compound of formula III is obtained by an additional stage of the interaction of the compounds of formula IV

BrCH2- CH2- C(CH3)2- CH2- CO2R

with the oxygen donor and the Foundation.

8. The method according to p. 7, wherein the oxygen donor is a pyridine-N-oxide and the base is a carbonate of an alkali metal.

9. The method according to p. 7, characterized in that the compound of formula IV is obtained by an additional stage of the interaction of the compounds of formula V

CH2= CH - C(CH3)2- CH2- CO2R

with hydrogen bromide in the presence of free-radical catalyst.

10. The method according to p. 9, wherein the free-radical catalyst is an organic peroxide.

11. The method of obtaining Olkiluoto ester 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid, characterized in that it included the CF3- CXCl - CH = CH - C(CH3)2- CH2- CO2R

(b) treatment of compounds of formula VI, at least one molar equivalent of a base in an inert solvent and isolation of complex Olkiluoto ester 3-(2-chloro-3,3,3-Cryptocom-1-EN-1-yl)-2,2-dimethylcyclopropanecarboxylic acid from the reaction mixture.

12. The method according to p. 11, wherein the dehydrating agent is phosphorus oxychloride.

13. The method according to p. 11, characterized in that the base used in stage (b) is an alcoholate of an alkali metal.

14. The method according to p. 12, wherein the alcoholate of an alkali metal is a tert-butyl sodium or potassium.

 

Same patents:

The invention relates to a new process for the preparation of esters cyclopropanecarbonyl acid of the formula I

< / BR>
where R is the ester residue, split in neutral or acid medium and which WITH1-18the alkyl possibly substituted with halogen or benzyl radical, possibly substituted on the tops of the aromatic ring by one or more halogen atoms, or a radical of formula (a) -(g),

< / BR>
where R2Is h or methyl;

R3- aryl;

R4- CN, N.;

R5- fluorine, chlorine, bromine or hydrogen;

R6, R7, R8, R9is hydrogen or methyl;

S/1 symbolizes tetrahedrite

The invention relates to a new method of obtaining some of esters of cyclopropane used in the synthesis of important pesticides

The invention relates to new chemical product, particularly, to pentafluorobenzyl 1R, 3S-2,2-dimethyl-3(2-chlorpro - penyl)-cyclopropanecarboxylate formula I

in the form of indivisible mixture of isomers Ia and IB in the ratio from 1: 2 to 1: 4

The invention relates to a new method of obtaining some of esters of cyclopropane used in the synthesis of important pesticides

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to an improved method for synthesis of 2,2-chloro- or dibromophenylacetic acid alkyl ester of the formula (I): wherein X means Cl or Br; n can be a whole number from 1 to 5; R means hydrogen atom, (C1-C8)-alkyl, aryl, heteroaryl, (C1-C8)-alkaoxy, aryloxy group or halogen atom; R1 means (C1-C8)-alkyl. Method involves interaction of 2,2-dichloro- or dibromophenylacetonitrile of the formula (II): wherein X, n and R are given above in 0.8-2 moles of water per 1 mole of nitrile of the formula (II) with 1-8 moles of alcohol of the formula (III): R1OH (III) wherein R1 is given above per 1 mole of nitrile of the formula (II) in the presence of from 1 to 3 moles of HCl or HBr per 1 mole of nitrile of the formula (II) in the presence if necessary of an inert solvent under conditions of this reaction, at reaction temperature from 30 to 60°C. Then method involves heating to temperature 60-100°C and keeping at this temperature. After termination of reaction the reaction mixture is cooled to temperature from 20 to 40°C, diluted with water and the corresponding 2,2-dichloro- or dibromophenylacetic acid alkyl ester of the formula (I) is isolated. Also, invention relates to a method for synthesis of 2,2-dichloro- or dibromophenylacetic acid alkyl ester of the formula (I): wherein X means Cl or Br; n can mean a whole number from 1 to 5; R means hydrogen atom, (C1-C8)-alkyl, aryl, heteroaryl, (C1-C8)-alkoxy, aryl oxy group or halogen atom; R1 means (C1-C8)-alkyl wherein in the first step of synthesis a possibly substituted benzyl cyanide of the formula (IV): wherein n and R are given above is subjected for interaction with chlorine in the presence of the catalytic amount of gaseous hydrogen chloride or with brominating agent to yield the corresponding nitrile of the formula (II): wherein n, X and R are given above, and formed exhausting gas HCl or HBr is used in the second step for conversion of nitrile of the formula (II) to corresponding 2,2-dichloro- or dibromophenylacetic acid alkyl ester of the formula (I). Conversion to the corresponding 2,2-dichloro- or dibromophenylacetic acid alkyl ester of the formula (I) at the second step occurs in 0.8-2 moles of water per 1 mole of nitrile of the formula (II), 1-8 moles of alcohol of the formula (III): R1OH (III) wherein R1 is given above per 1 mole of nitrile of the formula (II) in the presence of HCl or HBr as a gas exhausting from the first step taken in the amount 1-3 moles per 1 mole of nitrile of the formula (II), and if necessary in the presence of a solvent, at the reaction conversion from 30 to 60°C. Then the process involves heating to temperature 60-100°C and keeping at this temperature, and after termination of reaction the reaction mixture is cooled to temperature from 20 to 40°C and diluted with water. Methods provide preparing the end products with high yields and high purity.

EFFECT: improved methods of synthesis.

10 cl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.

EFFECT: higher clinical effectiveness.

61 cl, 4 tbl, 16 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: in general formula

groups Zi (Z1, Z2 and Z3) independently on each other represent branched or non-branched alkyl groups or groups of structure Ri(A(CR1R2)ci(CR3R4)c'i)di, where respective indices ci and c'i independently on each other represents 0-6, and di=0-5, where Ri represents branched or non-branched fluorine-containing alkyl radical, R1-R4 independently on each other represent hydrogen or branched or non-branched C1-4alkyl group, ci and c'i are not simultaneously 0, and A=O, Y1 represents anionic polar group, selected from SO3, SO3, PO32 and PO32 , and Y2 represents hydrogen atom, X represents cation, selected from H+, alkali metal cation or NR4+, where R=H+ or C1-C6-alkyl, and all R can be identical or different, and, at least, one of groups Zi represents group of structure Ri(A(CR1R2)ci(CR3R4)c'i)di.

EFFECT: claimed invention relates to compounds of formula (I), containing fluorinated terminal groups, to based on them composition, their application as surface-active substances and to methods of obtaining claimed compounds.

14 cl, 2 dwg, 15 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved process for the preparation of compounds of formula . The process involves the conversion of the compound of formula into a compound of formula (I) in the presence of at least one base and in the presence of at least one polymerisation inhibitor, selected from 2,2,6,6-tetramethylpiperidine-N-oxyl, sulphur, p-benzoquinone, 4-tert-butylpyrocatechol, phenothiazine, di-tert-butylhydroxytoluene or mixtures of these polymerisation inhibitors. In the compounds of formulas (I) and (II) R1 and R2 are identical or different and, independently of one another, represent hydrogen, C1-C15-alkyl, C6-C24-aryl,or C1-C15-alkoxy, R3 is C1-C15-alkoxy, and X in formula (II) represents Cl, Br, I or pseudohalogen.

EFFECT: invention provides the process for the production of compounds with good yields and high purities.

14 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to chemistry of organofluoric compounds, in particular to method of obtaining methyl-2-fluoroacrylate (methyl ether of 2-fluoroacrylic acid). Methyl-2-fluoroacrylate is obtained by interaction of methyl ether of fluorodichloracetic acid, chloromethyl ether of trifluoroacetic acid and zinc in polar aprotic solvent such as dimethylformamide, N-methylpyrrolidone, N,N-dimethylurea or N,N-dimethylpropyleneurea, with simultaneous distillation of target product under reduced pressure.

EFFECT: output of target product constitutes 50-60%.

1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to fluorine-containing acrylic acid esters, in particular to a novel monomer - (perfluoro-2-trichloromethylisopropyl)acrylate, and polymer made therefrom - (perfluoro-2-trichloromethylisopropyl)acrylate, which can be most effectively used for making light-conducting strands and coatings of optical waveguides. Monomer (I) is obtained from hexafluoroacetone and acryloyl chloride. Reaction of hexafluoroacetone with sodium trichloroacetate in dimethyl formamide produces 1,1,1-trichloro-3,3,3-trifluoro-2-(trifluoromethyl)propan-2-ol, acylation of which in presence of triethylamine in a medium of acetonitrile yields desired perfluoro-2-trichloromethylisopropylacrylate with output of 75 %, wherein purity of produced monomer is 99.9 %.

EFFECT: polymer is obtained through radical polymerisation of said monomer in presence of a polymerisation initiator.

5 cl, 1 dwg, 1 tbl

FIELD: organic chemistry, in particular stereoselective method for production of dihydroxyesters and derivatives thereof.

SUBSTANCE: disclosed is method for production of compound having formula 1, wherein R and R' represent optionally substituted hydrocarbon groups; X represents hydrocarbon linker group. Claimed method includes either stereoselective ketogroup reducing to dihydroketo precursor followed by selective etherification of primary hydroxyl or selective etherification of primary dihydroketo precursor hydroxyl followed by stereoselective ketogroup reducing.

EFFECT: compounds useful in production of pharmaceutical compositions.

19 cl, 1 tbl, 4 ex

FIELD: biologically active substances.

SUBSTANCE: invention relates to improved method of obtaining total amount of phenol acid including following steps: (a) multi-rooted sage is extracted with water and filtered; (b) filtrate is placed in polyamide column and washed with water to neutral reaction, wash water is removed, and polyamide column is eluted with weak aqueous alkali solution, and obtained fractions are connected; (c) alkali fractions obtained in step (b) are acidified and placed in absorption column with macroporous resin, column is washed to neutral state, wash water is removed, column is eluted with aqueous or anhydrous lower alcohol, eluent is collected, evaporated at reduced pressure to remove alcohol, and dried. Yield of final product exceeds 4% based on amount of crude drug and content of total amount of phenol acid exceeds 80%. Thus obtained total amount of phenol acid can be used as drug for prevention and treatment of brain vessel diseases.

EFFECT: enlarged resource of vegetable material for preparation of vascular drugs.

15 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method for synthesis of alkyl(meth)acrylates which are used in synthesis of polymers and copolymers with other polymerisable compounds, involving a step for re-esterification of alkyl ester of α-hydroxycarboxylic acid with (meth)acrylic acid, accompanied by formation of alkyl(meth)acrylates and α-hydroxycarboxylic acid, and a step for dehydration of α-hydroxycarboxylic acid, accompanied by formation of (meth)acrylic acid.

EFFECT: method enables to obtain a product with high selectivity.

22 cl, 2 tbl, 2 dwg, 38 ex

FIELD: medicine.

SUBSTANCE: invention relates to applications of compound 11-deoxyprostaglandin of general formula (IV) for obtaining composition for treatment of central nervous system disorder and for obtaining composition for protection of endothelial cells of brain vessels, to pharmaceutical composition based on said compounds, to method of treating central nervous system disorder, as well as to method of treating central nervous system disorder, as well as to compounds of general formula (IV) or their pharmaceutically acceptable salts, esters or amides, on condition that compound is not 11-desoexy-13,14-dihydro-15-keto-16,16-difluor- PGE1. , where L represnts hydroxy, lower alkanoyloxy or oxo; A represents -COOH or its pharmaceutically acceptable salt, ester or amide; B represents -CH2-CH2 or -CH=CH-; Z represents , or , where R4 and R5 represent hydrogen or hydroxy. R4 and R5 cannot represent hydroxy simultaneously; X1 and X2 represent similar or different halogen atoms; R1 represents saturated or unsaturated bivalent lower or middle aliphatic hydrocarbon; R2 represents single bond or lower alkylene and R3 represents linear lower alkyl.

EFFECT: increase of treatment efficiency.

14 cl, 7 ex, 6 tbl, 20 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to an improved continuous method of producing esters of alpha-hydroxy carboxylic acids, in which an amide of alpha-hydroxy carboxylic acid reacts with alcohol as the starting components in the presence of a catalyst to obtain a mixture of products containing esters of alpha-hydroxy carboxylic acids, ammonia, unreacted amide of alpha-hydroxy carboxylic acid, as well as alcohol and a catalyst, in which a) streams of starting components containing amide of alpha-hydroxy carboxylic acid, alcohol and catalyst as the starting components are fed into a high-pressure reactor; b) the streams of starting components react with each other in the high-pressure reactor at pressure from 1 bar to 100 bar; c) the mixture of products obtained at step b), which contains esters of alpha-hydroxy carboxylic acids, unreacted amide of alpha-hydroxy carboxylic acid and catalyst, is removed from the high-pressure reactor; and d) alcohol and ammonia content in the mixture of products is reduced, where ammonia is removed by distillation under pressure which is constantly kept higher than 1 bar without recourse to additional cleaning agents. The continuous method is especially expedient when used on an industrial scale.

EFFECT: improved continuous method of producing esters of alpha-hydroxy carboxylic acids.

30 cl, 12 ex, 2 tbl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds, represented by the following formula (I) and their pharmaceutically acceptable salts, where values for groups R1, R4-R6, Ra, m, n, Y, X are determined in the invention formula. Said compounds are used as preparations for enhancing growth of axons and prevention of diseases associated with histone diacetases, in particular tumours or diseases associated with cell proliferation.

EFFECT: compounds in accordance with the claimed invention can be used as anti-cancer, antidiabetic agents and anti-neurodegenerative agents in case of diseases such as Alzheimer's disease, Huntington's disease, spinocerebral ataxia and spinal muscular atrophy in people.

18 cl, 44 dwg, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to improved method of obtaining polyols, which includes the following stages: a) oxidation of unsaturated natural fats, unsaturated natural fatty acids and/or esters of fatty acids with dinitrogen oxide; b) interaction of the product, obtained at stage a), with hydrating reagent in presence of catalyst, which contains, at least, one transition metal from groups from 6 to 11; c) interaction of the reaction product from stage b) with alkylene oxides in presence of multimetalcyanide catalyst. Invention also relates to method of obtaining polyurethanes, which includes oxidation of unsaturated natural fats, unsaturated natural fatty acids and/or esters of fatty acids with dinitrogen oxide, interaction of the obtained product with hydrating reagent in presence of catalyst, which contains, at least, one transition metal from groups from 6 to 11, interaction of the reaction product with alkylene oxides in presence of multimetalcyanide catalyst with obtaining polyols, interaction of polyisocyanates with polyols as compounds, which have two hydrogen atoms, reactionable with respect to isocyanate groups.

EFFECT: simple methods make it possible to obtain wide spectrum of products without application of expensive initial reagents.

10 cl, 8 ex

Up!