Production of the fluorine-containing compounds

FIELD: chemical industry; method of production of the fluorine-containing compounds.

SUBSTANCE: the invention is pertaining to the chemical industry, in particular, to the improved method of production of fluorine-containing compounds from the halogen-containing, compounds, preferably, from chlorine-containing compounds due to an exchange of halogen for fluorine at presence of the HF-additional compound of the mono- or bicyclic amine with at least two atoms of nitrogen. At that at least one atom of nitrogen is built in the cyclic system as the fluorating agent; or at presence of anhydrous hydrogen fluoride - as the fluorating agent and the indicated HF-additional compound of the mono- or bicyclic amine as the catalyst. At usage of the applicable solvents the reaction mixtures can be divided into two phases and thus to simplify the reprocessing of the products. The invention also is pertaining to the HF-additional compounds of 1.5-diazabicyclo[4.3.0]non-5-en and N,N-dialkylaminopiridin, where alkyl represents C1-C4alkyl and where the molar ratio of HF to amine makes 1:1, and to HF- additional compounds 1.8- diazabicyclo[5.4.0]undecyl-7-ene, where the molar ratio of HF to amine compounds more than 1:1.

EFFECT: the invention ensures at usage of the applicable solvents to divide the reaction mixture into two phases and thus to simplify reprocessing of the products.

17 cl, 13 ex

 

The present invention relates to a method for producing fluorinated compounds from chlorine substituted compounds due to the exchange of chlorine for fluorine, or by attaching HF on multiple carbon-carbon bonds.

Inorganic and organic fluorine-containing compounds play an important role in chemistry and engineering. Thus, in particular, inorganic foramerica acids, such as sulphuretted or sulfurylchloride are products, which in many cases is used as such, and also as intermediate products. Sulfuretted proposed to use, for example, as a catalyst in obtaining ftoruglevodorodnyh compounds. Sulfurylchloride is an intermediate product used in the preparation of sulfurylchloride. Sulfuretted can be attached to unsaturated hydrocarbons; the resulting sulfonyl fluoride suitable for use as a catalyst. Fluorine-containing carbon compounds and hydrocarbon compounds can be used in various purposes, such as pore-formers in the process of plastics, as refrigerants or solvents. Carboxylic acids and derivatives of carboxylic acids (for example, esters of carboxylic acids or esters of dicarboxylic acids), containing the bond carbon-fluorine, also is can be used as such or as intermediates in chemical synthesis. Esters triperoxonane acceptable acid, for example, as a solvent and as an intermediate product upon receipt of triptoreline. α-Fluorine-β-dicarbonyl compounds are important intermediate products used, for example, upon receipt of the esters α-tarakanovas acid (see patent application EP-A 0597329). From EP-A 0597329 and published applications DE 19942374 known the possibility of using HF adducts of amines as catalysts in the reaction of fluorination or as a fluorinating agent. In the application EP-A 1072576 offers HF adducts of the corresponding cyclic ureas and amides of phosphoric acid for use as a fluorinating agents. In JP-A-63/128086 described hydrofloric 1,8-diazabicyclo[5.4.0]undec-7-ene as a component of ink.

Based on the foregoing, the present invention was based on the task to propose new HF adducts of nitrogen-containing compounds with improved properties for use in the fluorination. This problem is solved using the proposed HF adducts used as provided in the invention purposes.

Proposed in the invention is a method of obtaining a fluorine-containing compounds of halogenated, preferably chlorinated, compounds by halogen exchange by fluorine or by attaching HF on multiple carbon-carbon links the pits is carried out in the presence of HF adduct of mono - or bicyclic amine with at least two nitrogen atoms, at least one of these nitrogen atoms embedded in a cyclic system as a catalyst or a fluorinating agent. In normal conditions the connection receive preferably in gaseous or liquid form.

According to one embodiments of the invention apply monocyclic compounds. In these cases we are talking about saturated or unsaturated 5-membered, 6-membered or 7-membered cyclic compounds in which at least one nitrogen atom is embedded in the cycle. In the cyclic system may be integrated with another nitrogen atom. Alternative or additionally, the cycle may be substituted by one or more amino groups. Preferred are dialkylamino, in which the alkyl groups can be identical or different and contain from 1 to 4 carbon atoms. The amino group can also be a saturated cyclic system, for example piperidino group. As suitable for the effective application of the representatives of monocyclic systems can be called forth dialkylaminoalkyl, dialkylaminoalkyl and dialkylaminomethyl.

According to another variant embodiment of the invention is used, as mentioned above, and bicyclic compounds. In these cases, the cyclic system can also be integrated 1, 2 or bol is e of the nitrogen atoms. These compounds can also be substituted by one or more amino groups. Preferred, as in the first embodiment, are dialkylamino, in which the alkyl groups can be identical or different and contain from 1 to 4 C-atoms or together with the nitrogen atom can form a saturated cyclic system such as, for example, piperidinyl group.

Most preferred are bicyclic amines, especially 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

From the above it is obvious that at least two of the nitrogen atom in the compounds must have basic properties and, depending on the type of relationship they are associated with two or three carbon atoms.

The above compounds with at least two atoms of nitrogen applied in the form of HF adducts. While you can get them pre-interaction of amines with hydrogen fluoride. According to another approach get them in situ feeding appropriately hydrogen fluoride in the reaction mixture.

According to another variant embodiment of the invention receive foramerica inorganic or organic acids from the corresponding anhydrides of the acids. For your preferred foramerican acids include sulfurylchloride and sulfuretted, get a cat is that you from sulfurylchloride or of a mixture of chlorine and sulfur dioxide. Similarly, you can also receive alkyl - and arialfont from the respective chlorosulfonated. Chlorogen you can fluoridate to ferrochina.

Also foramerica carboxylic acids can be obtained from the carboxylic acid anhydrides. Foramerica carboxylic acids or foramerica dicarboxylic acids are preferably obtained from the corresponding carboxylic acid anhydrides or acid chlorides of dicarboxylic acids with a chain length in total up to 12 C-atoms. While you may receive aliphatic and aromatic foramerican carboxylic acids. These foramerica can be also substituted by halogen atoms such as fluorine atoms and/or chlorine. Preferably get aliphatic foramerica acids containing a total of from 2 to 7, especially 2-4 carbon atoms. It is preferable to obtain acetylphenyl, divorcedivorce, chlortetracycline or triftoratsetata. With equal success can be obtained, in addition, propiolactone and propiolactone, substituted 1-5 fluorine atoms.

Proposed in the invention method can also be used to obtain a fluorine-containing compounds with C-F-bond of chlorine-containing compounds with C-Cl bond. About the translation(O)Cl group in(On)F-groups mentioned above. For example, chloralkali with 1-5 carbon atoms can p is levaditi in alkanes, substituted by fluorine and under certain conditions chlorine.

Proposed in the invention method is also effective in the implementation of the exchange reaction of chlorine for fluorine on activated carbon atoms, such as those carbon atoms that are in α-position relative to the C(O)-groups. Thus, in particular, it is possible to fluoridate substituted by chlorine ketone or diketone chlorine substituted aliphatic carbenoxolone compounds and substituted at the carbon bridge chlorine decarbonatization connection. Preferably you get a fluorine-containing derivatives of carboxylic acids, such as fluorinated foramerica carboxylic acids, esters of carboxylic acids or amides of carboxylic acids. Preferably equally get-containing alkylenes bridge connection derivatives of dicarboxylic acids or diketones, which Allenova the bridge with a length of 1 to 2 carbon atoms substituted by at least one fluorine atom. This can come from a chlorine-containing compounds or from bromodomain connections.

The method according to the invention can be successfully used to obtain the compounds described in the application EP-A 597329. We are talking about the compounds of formula (I)

A-C(O)-C(R)(F)-C(O)-A,

in which both rest And can have identical or different meanings and denote, respectively, alkyl, aryl, alkoxygroup, ar is oxygraph or amino group, a R denotes hydrogen, fluorine, alkyl or aryl.

Source material are compounds of formula (II)

A-C(O)C(X(R'))-C(O)-A,

in which

X denotes chlorine, bromine or iodine,

And has the values specified for formula (I), and

R' has the same meaning as R in formula (I), and optionally may

denote also chlorine, bromine or iodine.

The reaction is expediently carried out at temperatures in the range from 20 to 100°C. If the initial product of the formula (II) R' denotes chlorine, bromine or iodine, in this case, get α,α-debtor-β-dicarbonyl compound, i.e. the compound of formula (I)in which R represents fluorine.

In formulas (I) and (II) And may denote, for example, remotemachine or branched, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, remotemachine or branched, unsubstituted or substituted alkoxygroup, unsubstituted or substituted alloctype or unsubstituted or is substituted by an amino group of formula (III)to(V)

in which R1, R2and R3denote alkyl, preferably2-C6alkyl, or aryl, preferably phenyl. Thus R2and R3can have identical or different meanings.

If present (optional) ALK is selected and alkoxygroup substituents, such substituents can be for example, halogen atoms, preferably fluorine, chlorine and/or bromine, or nitro.

If present (optional) aryl and alloctype substituents, such substituents can be, for example, C1-C6alkyl groups, preferably methyl or ethyl, halogen atoms, preferably fluorine, chlorine and/or bromine, or nitro.

In cases where And denotes alkyl and alkoxygroup, it contains preferably 1 to 6 C-atoms, especially 1-2 C-atoms, and if a denotes aryl and alloctype, its preferred value is phenyl.

In formulas (I) and (II) R and R' can represent, for example, hydrogen, remotemachine or branched, unsubstituted or substituted C1-C12alkyl or unsubstituted or substituted phenyl. As substituents for alkyl groups may be considered, for example, halogen atoms or nitro, and substituents for aryl groups, - C1-C6alkyl groups, halogen atoms or nitro. In the formula (II) R', as mentioned above, can additionally denote chlorine, bromine or iodine, especially chlorine or bromine. The preferred value of R and R' is hydrogen or R' represents chlorine and R represents fluorine.

In the formula (II), X preferably represents chlorine or bromine. Preferably receive dialkylamide EF is the market formalnosci acid and dialkyl ethers deformiruemoi acid. In the considered cases, the alkyl is a1-C4alkyl. You can also receive, for example, 2,2-deformational acid and its derivatives, such as esters, in particular With1-C4alkalemia or akrilovye esters from the corresponding 2,2-dichloropropionanilide connections.

As already described in the posted application DE 19942374, hydroporinae adduct can be used as a fluorinating agent. In this case, it should be used in such quantity or the reaction should be carried out within such period of time to prevent dehydrocorydaline hydroporinae adduct as much as this will avoid the formation of HCl-adducts. Otherwise, it is recommended that the regeneration of hydrogen fluoride. According to the same tiled application DE 19942374 hydroporinae adduct can also be used as a catalyst. In these cases, is used as the fluorinating agent is HF is introduced into the reaction. The amount of HF in this case is preferably at least 1 mole of HF per gram-atom of exchanging chlorine. Used HF-adduct can then be regenerated by using HF. Because this approach hydroporinae adduct is used as catalyst, it is possible to work in continuous mode.

According to another variant of osushestvlyaetsya HF added by nucleophilic or electrophilic double or triple carbon-carbon bonds. The preferred starting material for these purposes are unsaturated aliphatic hydrocarbon compounds, which may be substituted by one or more halogen atoms. For preferred compounds include those with2-C4chain. The most preferred compounds substituted by at least one atom of chlorine or fluorine. HF can, for example, be attached to hexaferrite order to obtain 1,1,1,2,3,3,3-Heptafluoropropane, and at his accession to panafcortelone get pentaverate.

Proposed in the invention, the method can be carried out, which also preferably, and without the use of solvents. This approach is suitable, in particular, for the reason that it provides a more simple processing of products and avoids the danger of interaction, such as possible side reactions with the solvent. However, the method can be carried out and by other means, namely: in the course of the reaction or preferably after conversion to add a solvent, initiating the formation of two phases, one of which contains the solvent and the organic compound, and the other contains amine-HF-adduct, which allows a simple way to distinguish organic compounds from their mixtures with amine-HF-adducts. It is also obvious that the method allows to separate mixtures, provided the two or more organic compounds. This variant of the method with the formation of the phases described in more detail below.

A mixture of amine-HF-adducts and organic compounds are formed, for example, when the fluorination reactions, when such a reaction fluoridation injected hydrogen fluoride and/or when the amine-HF-adduct is used as a fluorinating agent is not so much that his consumption was full, so I would place the presence of amine Cl-adduct (it is, obviously, about the reaction of the exchange of chlorine for fluorine). Appropriate mechanisms for the implementation of such approach is described, for example, in the tiled application DE 19942374 and in the patent application German P 10104663.4.

Preferably the method with the formation of two phases used for the separation of certain organic compounds, which are substituted by at least one fluorine atom. Using this method can be divided, for example, substituted by at least one fluorine atom hydrocarbons, cycloaliphatic hydrocarbons, aromatic hydrocarbons, esters, thioesters or ketones.

Special advantages of the method provides, obviously, the separation of organic compounds, divide that by conventional methods such as distillation directly from the mixture with the amine-HF adducts or by aqueous processing, it is not possible at all or could only with great difficulty. This refers, the particular to compounds having a boiling point above 50°and thermally unstable compounds, which under the action of temperature, for example above 50°S, susceptible to decomposition. However, under all conditions the efficiency of the method is not subject to doubt, since according to the invention the amine-HF-adduct when the processing is not hydrolyzed.

Another object of the present invention are new hydroporinae adducts 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and in the case of DBU, provided that the molar ratio of HF and amine exceeds 1:1. These compounds preferably have the following formula:

DBN·(HF)x,

where x is equal to 1 or denotes 1<x≤9;

DBU·(HF)y,

where denotes 1<y≤9.

The object of the invention is also HF adducts of N-dialkylaminoalkyl, the alkyl is a1-C4alkyl, first of all adducts, where the molar ratio of HF and amine is greater than 1:1, preferably equal to or less than 9; the most preferred HF adducts, where alkyl represents methyl.

Proposed in the invention, the method allows for the exchange reaction of chlorine for fluorine with high yields, especially in the case of diketones and diesters.

Below the invention is explained in more detail on the example of the x, which do not limit its scope.

Examples 1-6

The exchange of chlorine for fluorine in complex diesters

The overall reaction equation:

CH3-CH2-Soo-CHCl-COO-CH2-CH3+Amin×HF→

CH3-CH2-Soo-CHF-COO-CH2-CH3+Amin×HCl

Experiments on fluoridation using DBU and DBN-HP/linecomplete without solvents

Example 1

The initial mixture

of 0.15 mol of diethyl ether 2-hormonology acid29,3 g
of 0.3 mole of 1,5-diazabicyclo[4.3.0]non-5-ene ×1,73 HFof 54.4 g

Methodology

In a 100-ml flask of the APF (polyformaldehyde) with reflux condenser (water cooling) pre-placed linecomplete, after which was added diethyl ether of hormonology acid and the mixture was kept under stirring in an oil bath at 80°C. after 1, 3, 6 and 12 h were taken, respectively, of the sample solution, which hydrolyzed, dried with sodium sulfate and analyzed by GC (gas chromatography). After 12 h 91,23% of educt turned into diethyl ether of formalnosci acid. The selective action was quantitative.

Example 2

The initial mixture

of 0.15 mole of diethyl EPE is hormonology acid 29,3 g
of 0.3 mole of 1,8-diazabicyclo[5.4.0]undec-7-ene ×1,37 HFof 56.5 g

Methodology

In a 100-ml flask of the APF with a reflux condenser (water cooling) pre-placed linecomplete, after which was added diethyl ether of hormonology acid and the mixture was kept under stirring in an oil bath at 80°C. after 1, 3, 6, 12, 18 and 24 h were taken, respectively, of the sample solution, which hydrolyzed, dried with sodium sulfate and analyzed by GC. After 24 h 72,5% of the educt turned into diethyl ether of formalnosci acid. The selective action was quantitative,

Example 3

The initial mixture

of 0.10 mol of diethyl ether 2-hormonology acid19.5 g
of 0.05 mole of 1,5-diazabicyclo[4.3.0]non-5-ene ×2,93 HF8.8 g

Methodology

In a 100-ml flask of the APF with a reflux condenser (water cooling) pre-placed linecomplete, after which was added diethyl ether of hormonology acid and the mixture was kept under stirring in an oil bath at 80°C. during the reaction the color of the solution changed from light orange to dark red. After 1, 3, 6, 12 and 18 h were taken according to the government, samples of the solution are hydrolyzed, dried with sodium sulfate and analyzed by GC. After 18 h 21.8% of educt turned in quantitative selectivity of action in diethyl ether formalnosci acid.

Example 4:

The initial mixture

of 0.10 mol of diethyl ether 2-hormonology acid19.5 g
of 0.05 mole of 1,8-diazabicyclo[5.4.0]undec-7-ene ×3,09 HF10.7 g

Methodology

In a 100-ml flask of the APF with a reflux condenser (water cooling) pre-placed linecomplete, after which was added diethyl ether of hormonology acid and the mixture was kept under stirring in an oil bath at 80°C. after 1, 3 and 6 h were taken, respectively, of the sample solution, which hydrolyzed, dried with sodium sulfate and analyzed by GC. After 6 h of 4.1% of the educt turned into diethyl ether of formalnosci acid.

Example 5 (comparative) without the use of solvent

The initial mixture

a 0.23 mol of diethyl ether 2-hormonology acid53,1 g
0,16 mol of triethylamine ×2,72 HF24,6 g

Methodology

In 100-ml m ogogoro flask with reflux condenser (water cooling) pre-placed diethyl ether of hormonology acid, then under stirring was added dropwise triethyleneamine. The solution is kept at 100°C in an oil bath. After 3 and 6 h were taken, respectively, of the sample solution, which hydrolyzed, dried with sodium sulfate and analyzed by GC. After 6 h of 3.3% of the educt turned into diethyl ether of formalnosci acid.

Example 6

Comparative experience in the presence of a solvent using triethylamine ×HF-complex

The initial mixture

the 0.375 mol of diethyl ether 2-hormonology acid73,125 g
of 0.5 mol of triethylamine ×2,72 HF
of 0.25 mol of triethylamine
125 ml of acetonitrile

Methodology

In a 100-ml flask of the APF with a reflux condenser (water cooling) pre-placed linecomplete and added first, acetonitrile, and then diethyl ether of hormonology acid and the mixture under stirring was kept in an oil bath at 80°C. after 1, 3, 6, 12, 18 and 24 h were taken, respectively, of the sample solution, which hydrolyzed, dried with sodium sulfate and analyzed by GC. After 24 h 66,02% of educt turned into diethyl ether of formalnosci is islote.

Examples 7-11

Getting foramerican acid

SO2Cl2+Amin×HF→SO2F2+HCl

Methodology (identical for all examples in obtaining foramerican acid)

In a 100-ml flask of the APF, equipped with reflux condenser and addition funnel, pre-placed linecomplete. In the reflux condenser by using the device type Kryomat served chilled to -30°With saline. For recovery of the reaction product to the refrigerator was plugged in steel cylinder (approximately 300 ml) with immersion pipe and an output device for gas pre-cooled in a Dewar with/methanol to -78°C. At room temperature in an oily light yellow solution slowly and with vigorous stirring introduced SO2Cl2. Shortly after the start of this operation was observed gas evolution. Upon completion of adding dropwise, under the flask was established oil bath with a temperature of 100°and to fully uninstall formed SO2F2within 1 h, kept at cooling and for 1 h without cooling.

Example 7

The initial mixture

of 0.20 mole of sulfurylchloride SO2Cl226,99 g
0,24 mol of 1,5-diazabicyclo[4.3.0]non-5-ene ×2,67 HF 42,50 g

Results

As a result by the above General methodology experience failed to allocate 57,70% SO2F2and of 35.27% SO2FCl in terms of the quantity used of the educt.

Example 8

The initial mixture

of 0.20 mole of sulfurylchloride SO2Cl226,99 g
to 0.127 mole of 1,5-diazabicyclo[4.3.0]non-5-ene ×7,19 HF42,50 g

Results

As a result by the above General methodology experience failed to allocate 90,65% SO2F20.34% SO2FCl in terms of the quantity used of the educt.

Example 9

The initial mixture

of 0.20 mole of sulfurylchloride SO2Cl226,99 g
0,253 mole of 1,8-diazabicyclo[5.4.0]undec-7-ene ×5,58 HF40,90 g

Results

As a result by the above General methodology experience was found to be 0.04% of SO2F2and 69,87% SO2FCl in terms of the quantity used of the educt.

Example 10 (comparative)

The initial mixture

of 0.20 mole of sulfurylchloride SO2Cl226,99 g
of 0.21 mol of pyridine ×2,93 HF28,0 g

Results

As a result by the above General methodology experience failed to allocate 5,03% SO2F2and 28,12% SO2FCl in terms of the quantity used of the educt.

Example 11

The initial mixture

of 0.15 mol of sulfurylchloride So2Cl220,25 g
0,16 mol of 4-dimethylaminopyridine ×2,93 HF28,90 g

Results

As a result by the above General methodology experience failed to allocate 16,40% SO2F2and 21,76% SO2FCl in terms of the quantity used of the educt.

Example 12

Getting diethyl ether mooftormetilnoy acid by extraction with ethyl ether triperoxonane acid

(EtO)C(O)-CHCl-C(O)(OEt)×(EtO)C(O)-CHF-C(O)(OEt)

to 0.1 mol of diethyl ether 2-hormonology acid were subjected to interaction with 0.2 mole of 1,5-diazabicyclo[4.3.0]non-5-ene ×1,4 HF at 80°C for 6 hours. After cooling, to the reaction mixture were added ethyl ether triperoxonane acid. Which resulted in formation of two phases. The phase containing the product and the solvent was separated and the ethyl ester triperoxonane acid with the aim to highlight the desired product were released. At a concentration of from 25 to 70 mol.% observed separation of phases.

Example 13

Getting dieti the new ether deformiruemoi acid by extraction with ethyl ether triperoxonane acid

(EtO)C(O)-CCl2-C(O)(OEt)×(EtO)C(O)-CF2-C(O)(OEt)

Analogously to example 1 and 0.6 mole of 1,8-diazabicyclo[5.4.0]undec-7-ene ×1,9 HF were subjected to interaction with the 0.15 mol of the ether dichlormethane acid. After adding ethyl ether triperoxonane acid formed, the phases were separated and provided the desired product.

Experiments using different extractants

When using isopropyl ether triperoxonane acid, trifluorotrichloroethane, hexane and cyclohexane are also effectively managed to separate the phases. After phase separation, the solvent was separated by a single equilibrium by distillation, and the product was purified by distillation to a high degree of purity.

1. A method of obtaining a fluorine-containing compounds of halogenated, preferably chlorinated, compounds by halogen exchange on fluoride in the presence of HF adduct of mono - or bicyclic amine with at least two nitrogen atoms, at least one nitrogen atom embedded in a cyclic system, as a fluorinating agent, or in the presence of hydrogen fluoride as the fluorinating agent and the specified HF adduct of mono - or bicyclic amine as a catalyst.

2. The method according to claim 1, in which use HF adduct of mono - or bicyclic compound with two nitrogen atoms, where one or both of the nitrogen atom is embedded in clichesque system.

3. The method according to claim 1 or 2, characterized in that as a mono - or bicyclic compound is used as a compound selected from the group comprising aminosilane pyridine and bicyclic amines.

4. The method according to claim 3, wherein the mono - or bicyclic compound selected from the group comprising Diisobutylene, diazobicyclo and dialkylaminoalkyl.

5. The method according to claim 1, characterized in that the inorganic or organic foramerica acids obtained from the corresponding acid chlorides of the acids.

6. The method according to claim 5, characterized in that sulfurylchloride or sulfurylchloride.

7. The method according to claim 1, characterized in that the fluorine-containing compounds with C-F-bond derived from chlorine-containing compounds with C-Cl bond.

8. The method according to claim 7, characterized in that get fluorinated carbon or hydrocarbon compounds.

9. The method according to claim 7, characterized in that get fluorinated derivatives of carboxylic acids or foramerica carboxylic acids.

10. The method according to claim 9, characterized in that get associated alkilinity bridge derivatives of dicarboxylic acids substituted in Allenova the bridge at least one fluorine atom.

11. The method according to claim 10, characterized in that the esters of mono - or deformiruemoi acid.

12. The method according to claim 1, characterized in that the HF-ADDY is mono - or bicyclic compounds used as catalyst, and hydrogen fluoride is used as a fluorinating agent.

13. The method according to claim 1, characterized in that the used HF adducts of mono - or bicyclic compounds are subjected to using hydrogen fluoride recycling.

14. The method according to claim 1, characterized in that get substituted by at least one fluorine atom of an organic compound, thereby forming a mixture of amine-NR-adducts and substituted or substituted by at least one atom of fluorine compounds, and add the solvent, whereby formation of two liquid phases, one phase contains an organic solvent and (s) connection (s), and the other phase contains the amine-HF-adduct.

15. HF adducts 1,5-diazabicyclo[4.3.0]non-5-ene and N,N-dialkylaminoalkyl, where alkyl represents a C1-C4alkyl and where the molar ratio of HF to amine is 1:1, and HF adducts of 1,8-diazabicyclo[5.4.0]undec-7-ene, where the molar ratio of HF to amine is greater than 1:1.

16. HF adducts under item 15, where the molar ratio of HF to amine is greater than 1:1, preferably equal to or less than 9.

17. HF adducts indicated in paragraph 15, where the alkyl is a methyl.



 

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8 cl, 7 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a compound and to all its enantiomeric and diastereomeric forms and pharmaceutically acceptable salts that are able to prevent extracellular release of inflammatory cytokines. Proposed compounds have the formula (I): wherein R represents: (a) -OR3 or (b) -NR4aR4b; R3 represents unsubstituted or substituted phenyl wherein substitutes are: (i) halogen atom; (ii) (C1-C6)-alkyl; (iii) trifluoromethyl; (iv) trichloromethyl; (v) tribromomethyl; (vi) cyano-group, and (vii) (C1-C6)-alkoxy-group; each R4a and Rb represents independently: (a) hydrogen atom or (b) -[C(R5aR5b)]xR6 wherein index x = 0-5; each R5a and R5b represents independently hydrogen atom, linear or branched (C1-C4)-alkyl, (C3-C7)-cyclic alkyl; R6 represents -OR7 or (C1-C4)-alkyl; R7 represents hydrogen atom or (C1-C4)-alkyl; R1 represents halogen-substituted phenyl; each among links R2a and R2b is chosen independently from the groups consisting of: (a) hydrogen atom; (b) -O(CH2)jR8; (c) -(CH2)jCO2R10; (d) -(CH2)jCON(R10)2; (e) a double bond when R2a and one R2b are chosen with formation of a double bond; (f) a ring when one R2a and one R2b are chosen with formation a ring and indicated ring is chosen from the group consisting of: (i) benzene and (ii) dioxalane; each R8 and R10 represents independently hydrogen atom or (C1-C4)-alkyl; j represents index from 0 to 5; m represents index from 1 to 3; n represents index from 1 to 3, and m + n = 4. Also, invention relates to a pharmaceutical composition based on abovementioned compounds that inhibits extracellular release of inflammatory cytokines, and a method for regulation of extracellular release of inflammatory cytokines.

EFFECT: valuable medicinal properties of compounds.

10 cl, 9 tbl, 11 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to bicyclic heterocyclic substituted phenyloxazolidinones that represent compounds of the formula (I): wherein R is taken from the group consisting of -OH, O-heteroaryl, -N3, -OSO2R'', -NR'''R'''', or the formula: wherein: (ii) R'' represents direct or branched alkyl comprising up to 5 carbon atoms; (iii) R''' and R'''' are taken independently from the group consisting of hydrogen atom (H), -CO2-R1, -CO-R1, -CS-R1 and -SO2-R4 wherein R1 is taken among the group consisting of cycloalkyl comprising from 3 to 6 carbon atoms and direct or branched alkyl comprising up to 6 carbon atoms; R4 is taken from direct or branched alkyl comprising up to 4 carbon atoms; and R4a represents -CN or -NO2; R4b represents -SR4c, amino-group, -NHR4c or -NR4cR4d wherein R4c and R4d are taken independently from hydrogen atom (H) or alkyl; X represents from 0 to 4 members taken independently from the group consisting of halogen atom; and Y represents radical of the formula (II): or (III): wherein R5, R6, R7 and R8 represent independently hydrogen atom (H), or R and R6 and/or R7 and R8 form in common oxo-group; R9 and R10 represent independently hydrogen atom (H); A, B, C and D are taken from carbon atom (C) and nitrogen atom (N) to form phenyl ring or 5-6-membered heteroaromatic ring wherein the indicated heteroaromatic ring comprises from 1 to 4 members taken from the group consisting of nitrogen atom (N); Z is taken from alkyl, heteroaryl comprising nitrogen atom (N); and m represents 0 or 1. These compounds are useful as antibacterial agents and can be used for treatment of patient with the state caused the bacterial infection or with the bacterial infection caused by S. aureus and E. faecium.

EFFECT: valuable medicinal properties of compounds.

45 cl, 1 tbl, 50 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds of the formula (1): and its salts wherein X means unsubstituted monocyclic (5-6-membered) ring system comprising nitrogen atom (N); or X means condensed bicyclic (9-12-membered) ring system comprising N-atom that can be substituted with substitute -SO2-phenyl; Z represents hydrogen atom (H) or means a condensed bicyclic (9-12-membered) unsubstituted or substituted ring system comprising at least one heteroatom, N-atom; Ar represents unsubstituted phenyl ring; each among L1, L2 and L3 represents independently a bond, -CO, -SO2 or -CH2 wherein at least one among L2 and L3 must involve -CO or -SO2; L2 and L3 can represent can represent independently -CONH or -CONHCH2 also; n = 0, 1 or 2; each R1 and R2 represents independently hydrogen atom (H) or a direct (C1-C6)-alkyl chain; Y comprises at least one substituted or unsubstituted phenyl ring or 5-6-membered heteroaromatic ring comprising at least one N-atom as a heteroatom; wherein optional substituted are chosen among the group consisting of halogen atom, alkyl, -COOH, -OH or -NH2; or Y represents 6,7-dihydropyrrolo[3,4-b]pyridine-5-one; wherein ring nitrogen atom can be oxidized optionally. Also, invention relates to a pharmaceutical composition used in treatment states regulated by chemokine CXCR4 or CCR5 receptors based on these compounds. Invention provides preparing new compounds and medicinal agents based on thereof for aims in treatment of HIV- and FIV-infected patients.

EFFECT: valuable medicinal properties of compounds and composition.

15 cl, 57 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new amide derivatives of carboxylic acid that are antagonists of NMDA receptors of the formula (I): , wherein one radical among R1, R2, R3 and R4 represents -OH or NH2-group and others are hydrogen atoms; or two adjacent groups R1, R2, R3 and R4 in this case in common with one or more similar or different additional heteroatoms and -CH= and/or -CH2-groups form 5-6-membvered homo- or heterocyclic ring but preferably pyrrole, pyrazole, imidazole, oxazole, oxooxazolidine or 3-oxo-1,4-oxazine ring; two other groups among R1, R2, R3 and R4 radicals represent hydrogen atoms; R5 and R6 in common with nitrogen atom between them form saturated or unsaturated 4-6-membered heterocyclic ring that is substituted with phenoxy-, phenyl-[(C1-C4)-alkoxy]-, phenoxy-[(C1-C4)-alkyl]-, benzoyl-group optionally substituted in aromatic ring with one or more halogen atoms, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; X and Y mean independently oxygen, nitrogen atom or group -CH=, and to their salts formed with acids and bases. Also, invention relates to a method for preparing compounds of the formula (I) and pharmaceutical compositions showing activity as selective antagonists of NR2B receptor based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of the following diseases: chronic neurodegenerative diseases, chronic painful states, bacterial and viral infections.

EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.

11 cl, 2 tbl, 27 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to 5-aminoalkylpyrazolo[4,3-d]pyrimidines of the general formula (I): wherein R1 and R2 are similar or different and represent independently of one another (C1-C8)-alkyl group; R3 and R4 are similar or different and represent independently of one another (C1-C8)-alkoxy-group or halogen atom; R5 and R6 can be similar or different and represent independently of one another hydrogen atom, linear or branched (C1-C8)-alkyl group that can be substituted with one or more hydroxyl groups, (C1-C8)-alkoxy-, amino-, mono-(C1-C8)-alkyl-amino-, di-[(C1-C8)-alkyl]-amino-, N-morpholino- or pyridyl groups or in common with nitrogen atom to which they are bound form unsaturated heterocyclic ring that comprises optionally one or more additional atoms of nitrogen and/or oxygen and substituted with one or more hydroxyl, (C1-C8)-alkylol, (C1-C6)-oligohydroxyalkyl, amino-, mono-[(C1-C8)-alkyl]-amino- or di-[(C1-C8)-alkyl]-amino-groups. Proposed compounds inhibit activity of cGMP-phosphodiesterase and can be used in treatment of states of cardiovascular system and for treatment in potency disturbances. Also, invention relates to a medicinal preparation used for inhibition of activity of cGMP-phosphodiesterase based on indicated compounds, a method for preparing compounds of the formula (I) and a method for preparing the medicinal preparation.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.

7 cl, 15 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of β-carboline of the general formula (I)

showing properties of phosphodiesterase V inhibitor (PDE V). In the general formula (I) R1 means hydrogen atom; n = 0; X is taken among the group consisting of oxygen (O), sulfur (S) atoms and NRD; R2 is taken among the following group: phenyl (that can be optionally substituted with 1-3 RB), 6-membered nitrogen-containing heteroaryl and 5-6-membered heterocycloalkyl comprising 1-2 oxygen atoms and condensed with benzene ring (optionally substituted with 1-3 RB); R4 is taken among the group consisting of hydrogen atom, carboxy-group. (C1-C6)-alkylcarbonyl, di-[C1-C8)-alkyl]-aminoalkoxycarbonyl, di-[(C1-C8)-alkyl]-amino-(C1-C8)-alkylaminocarbonyl; a = a whole number from 0 to 1; Y is taken among the group consisting of -CH2, -C(O); Z is taken among the group consisting of -CH2, -CHOH, and -C(O) under condition that when Z represents -CHOH or -C(O) then X represents -NH; is taken among the group consisting of naphthyl, 5-6-membered heteroaryl comprising 1-3 heteroatoms taken among nitrogen, oxygen and/or sulfur atoms possibly condensed with benzene ring; m = a whole number from 0 to 2; R3 is taken independently among the group consisting of halogen atom, nitro-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, trifluorophenyl, phenyl (optionally substituted with 1-3 RB), phenylsulfonyl, naphthyl, (C1-C8)-aralkyl, 5-6-membered heteroaryl comprising 1-3 nitrogen atoms in the ring (optionally substituted with 1-3 RB). Also, invention relates to a pharmaceutical composition, a method for its preparing and methods for inhibition of phosphodiesterase V activity (PDE V), and for increase of the cGMP concentration.

EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.

14 cl, 11 sch, 7 tbl, 13 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention describes phenyl-substituted heterocyclic 1,3-ketoenols of the formula (I): wherein R1 and R3 mean independently of one another ethyl or (C1-C2)-alkoxy-group; Q means the group of the formula (Q1): or (Q2): wherein R4 and R5 in common with atoms to which they are joined form 5-7-membered cycle that can comprise additionally anellated alkylene chain consisting of 2-6 carbon atoms that, in turn, can comprise two heteroatoms taken among oxygen atom, and indicated cycle can be substituted with halogen atom, hydroxy-group, (C1-C6)-alkoxy-group, (C1-C6)-alkoxy-(C1-C6)-alkoxy-group, (C1-C4)-alkylcarbonyloxy-group, hydroxy-(C1-C4)-alkoxy-group, hydroxycarbonyl-(C1-C2)-alkoxy-group, methoxycarbonyl-(C1-C2)-alkoxy-group, methoxyimino-, methoxyethoxyethoxy-group; R6 and R7 means (C1-C10)-alkyl; R8 means hydrogen atom; X means oxygen atom; R20 means (C1-C10)-alkyl, and also agronomically acceptable salts and isomers of these compounds. Also, invention describes a method for preparing compounds of the formula (I), herbicide agent and a method for control of weed growth based on compounds of the formula (I). Invention provides preparing compounds possessing the herbicide activity.

EFFECT: improved preparing method, valuable properties of compounds and agents.

5 cl, 28 tbl, 5 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to heterocyclic compounds of general formula I with PGl2 receptor agonist activity. In formula R1 and R2 represent independently optionally substituted phenyl; Y represents N, N-O or CR5; Z represents N or CR6; A represents NR7; D represents alkylene or alkenylene; or A and D may together form divalent group; E represents phenylene or direct bond, or D and E may together form divalent group; G represents O, S, SO, SO2; R3 and R4 represent hydrogen atom or alkyl; Q represents carboxyl, alkoxycarboxyl, tetrazolyl, carbamoyl or -CONH-SO-R10 group. Prostaglandin I2(PGl2) is potent inhibitor of platelet aggregation and may be effectively used in treatment of vascular diseases, arteriosclerosis, hypertension, etc.

EFFECT: new compounds and drugs for platelet aggregation inhibition and treatment of vascular and other diseases.

15 cl, 3 tbl, 109 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, herbicides, agriculture.

SUBSTANCE: invention elates to novel derivatives of uracil of the formula [I] possessing herbicide activity, a herbicide composition based on thereof and to a method for control of weeds. In derivatives of uracil of the formula [I] the group Q-R3 represents a substituted group taken among:

wherein a heterocyclic ring can be substituted with at least a substitute of a single species taken among the group involving halogen atom, (C1-C6)-alkyl-(C1-C6)-alkoxy; Y represents oxygen, sulfur atom, imino-group or (C1-C3)-alkylimino-group; R1 represents (C1-C3)-halogenalkyl; R2 represents (C1-C3)-alkyl; R3 represents OR7, SR8 or N(R9)R10; X1 represents halogen atom, cyano-group, thiocarbamoyl or nitro-group; X2 represents hydrogen or halogen atom wherein each among R7, R8 and R10 represents independently carboxy-(C1-C6)-alkyl and other substitutes given in the invention claim; R9 represents hydrogen atom or (C1-C6)-alkyl. Also, invention relates to intermediate compounds used in preparing uracil derivatives.

EFFECT: improved preparing method, valuable properties of compounds.

40 cl, 16 sch, 12 tbl, 65 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:

; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.

EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of carboxylic acids of the formula: wherein Y is taken independently in each case among the group comprising C(O), N, CR1, C(R2)(R3), NR5, CH; q means a whole number from 3 to 10; A is taken among the group comprising NR6; E is taken among the group comprising NR7; J is taken among the group comprising O; T is taken among the group comprising (CH2)b wherein b = 0; M is taken among the group comprising C(R9)(R10), (CH2)u wherein u means a whole number from 0 to 3; L is taken among the group comprising NR11 and (CH2)n wherein n means 0; X is taken among the group comprising CO2H, tetrazolyl; W is taken among the group comprising C, CR15 and N; R1, R2, R3 and R15 are taken independently among th group comprising hydrogen atom, halogen atom, hydroxyl, alkyl, alkoxy-group, -CF3, amino-group, -NHC(O)N(C1-C3-alkyl)-C(O)NH-(C1-C3-alkyl), -NHC(O)NH-(C1-C6-alkyl), alkylamino-, alkoxyalkoxy-group, aryl, aryloxy-, arylamino-group, heterocyclyl, heterocyclylalkyl, heterocyclylamino-group wherein heteroatom is taken among N atom or O atom, -NHSO2-(C1-C3-alkyl), aryloxyalkyl; R4 is taken among the group comprising hydrogen atom, aryl, aralkyl, benzofuranyl, dihydrobenzofuranyl, dihydroindenyl, alkyl, benzodioxolyl, dihydrobenzodioxynyl, furyl, naphthyl, quinolinyl, isoquinolinyl, pyridinyl, indolyl, thienyl, biphenyl, 2-oxo-2,3-dihydro-1H-benzimidazolyl, pyrimidinyl and carbazolyl. Other values of radicals are given in the claimed invention. Also, invention relates to pharmaceutical composition used for inhibition binding α4β1-integrin in mammal based on these compounds. Invention provides preparing new compounds and pharmaceutical composition based on thereof in aims for treatment or prophylaxis of diseases associated with α4β1-integrin.

EFFECT: improved method for inhibition, valuable medicinal properties of compounds.

33 cl, 7 tbl, 42 ex

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

The invention relates to new compounds of the formula (I)

in which Ar1means pyrazole which may be substituted by one or more groups R1, R2or R3; Ar2means naphthyl, tetrahydronaphthyl, each of which is optionally substituted by 0-1 groups R2; X means5-C8cycloalkenyl, phenyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, furan, pyridinoyl, pyrazolyl, pyridinyl, optionally substituted by a hydroxy-group or1-C4alkoxygroup, piperidinyl; Y represents a bond or a saturated branched or unbranched1-C4the carbon chain, with one methylene group is optionally replaced with NH, or and Y is optionally independently substituted by oxopropoxy; Z means morpholine, group, pyridinyl, furanyl, tetrahydrofuranyl, thiomorpholine, pentamethylbenzene, pentamethylbenzene, secondary or tertiary amine, the nitrogen atom of the amino group covalently linked to the following groups selected from a range that includes the C1-C3alkyl and C1-C5alkoxyalkyl; R1means31-C6alkyl which is optionally partially or fully galogenidov, halogen; R3means phenyl, pyrimidinyl, pyrazolyl, which is substituted by one branched or unbranched1-C6the alkyl, and pyridinyl, optionally substituted C1-C3alkoxygroup or amino group, W denotes O and its pharmaceutically acceptable salts

The invention relates to new derivatives of 1,3-diaryl-2-pyridin-2-yl-3-(pyridine-2-ylamino)propanol of the formula (I)

where Z denotes-NH-(C1-C16-alkyl)-(C=O)-; -(C=O)-(C1-C16-alkyl)-(C=O)-;

-(C=O)-phenyl-(C=O)-; AND1AND2AND3AND4denote independently of each amino-acid residue, E represents-SO2-R4and-CO-R4; R1- phenyl, thiazolyl, oxazolyl, thienyl, thiophenyl and others, R2- N., HE, CH2HE, OMe; R3Is h, F, methyl, OMe; R4denotes -(C5-C16-alkyl), -(C0-C16-alkylen)-R5, -(C=O)-(C0-C16-alkylen)-R5, -(C=O)-(C0-C16-alkylene)-NH-R5and others, R5denotes-COO-R6, -(C=O)-R6-(C1-C6-alkylen)-R7, phenyl, naphthyl and others, R6denotes H, -(C1-C6) alkyl; R7denotes H, -(C1-C7-cycloalkyl, phenyl, naphthyl and others, l, q, m, n, o, p denote 0 or 1, and l+q+m+n+o+p is greater than or equal to 1, and their pharmaceutically acceptable salts

FIELD: industrial organic synthesis.

SUBSTANCE: invention relates to a method for preparation of multivalent carbonyl compounds and to a novel polyvalent carbonyl compound, which may be useful, for example, as intermediate in production of various fluorinated compounds. Polyvalent carbonyl compound is prepared through economically advantageous way from inexpensive substances and with no need of using any complex synthesis stage. In particular, polyvalent alcohol, including alcohols with at least two structures selected from primary, secondary, and tertiary structures, is brought into reaction with acid halide to form polyvalent ester, which is then fluorinated in liquid phase to form perfluorinated polyvalent ester, in which ester bonds, provided by reaction with primary and secondary alcohols, are further cleaved.

EFFECT: expanded synthetic possibilities in organofluoric compound area.

8 cl, 3 dwg, 2 ex

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