Derivatives of 4-chloro-2-thiophencarboxylic acid synthesis method of 4-chloro-2-thiophencarboxylic acid (options) and how to obtain 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2 - oxindole-1-carboxamide (options)

 

(57) Abstract:

4-Chloro-2-thiencarbazone acid is obtained by interaction of 4-chloro-5-(trimethylsilyl)-thiophene with a suitable base at a temperature below -50oC for getprotobyname chlorothiophenol ring in 5-position with formation of the corresponding anion. Which is treated with carbon dioxide at a temperature below -50oC, followed by removal of the silyl group. The product is used as an intermediate connection when receiving 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide, having pharmaceutical activity. 5 s and 5 C.p. f-crystals.

4-Chloro-2-thiencarbazone acid has the structure

< / BR>
This connection is of great importance as an intermediate product in the synthesis of compounds with pharmaceutical activity, such as, for example, 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide, which was first described in U.S. patent 5047554 (Ehrgolt et al.) in example 72.

Synthesis of 4-chloro-2-thiophencarboxylic acid (for convenience hereinafter referred to as "HTCC) was first described in publication I. Iriate et al., J. Heterocyclic Chem., 13, 393 1976. It is reported that HTC obtained with a quantitative yield in the form of technical product ecoregionalization from methanol or dichloromethane has a melting point 131 - 132oC. Iriarte with co-workers in the same article reported the receipt of SDA with so pl. 125 - 126oC by saponification of the ethyl ester of 4-chlorothiophene-2-carboxylic acid in a solution of potassium hydroxide in methanol, and carboxylate was obtained by direct chlorination of the ethyl ester thiophene-2-carboxylic acid in the presence of aluminium chloride.

In the publication (Lemaire et al., J. Electroanal. Chem., 281, 293 1990) reported receiving 3-chloro-2-trimethylsilylpropyne method using Grignard reagent, when this product is used in electropolymerization to obtain poly(3-chlorothiophene). No other methods of synthesis HTCC described was not.

The authors of the present invention found that HTC can be obtained from temperature-dependent regioselective process, in which the possible reaction sites are blocked and thus prevented from receiving the products.

The invention provides a method of obtaining 4-chloro-2-thiophencarboxylic acid, including the removal of the silyl group SiR3of the compounds of formula IVa

< / BR>
in which each R group is independently chosen from C1-C6/-alkyl, benzyl and phenyl.

A variation of the above method polucheniya formula IVb

< / BR>
in which R takes the values defined previously.

More precisely, the method of obtaining 4-chloro-2-thiophencarboxylic acid includes the following stages:

1) processing 3-chlorothiophene at a temperature below about -50oC base and the subsequent processing of the organosilicon compound of the formula R3-SiX in which X is a leaving group and each R group is independently chosen from C1-C6/alkyl, benzyl and phenyl, with the formation of the compounds of formula

< / BR>
2) treatment of the product of stage (1) at a temperature below about -50oC a suitable base for the deprotonation chlorothiophenol ring in 5-position, with the formation of the corresponding anion of the formula IIa

< / BR>
3) treatment of the product of stage (2) at temperatures below -50oC carbon dioxide for education, respectively, of monocarboxylate formula IIIa

< / BR>
4) conversion of the product of stage (3) to the corresponding acid (i.e., formula IVa) and

5) removing the silyl group SiR3.

Another variant of the method for direct production of 4-chloro-2-thiophencarboxylic acid includes the following stages:

1) processing 3-chlorothiophene at a temperature below about -50oC snowkat values, previously defined, with the formation of the compounds of formula

< / BR>
2) treatment of the product of stage (1) at a temperature below about -50oC base, suitable for deprotonation 5 and 5' - positions of the two thiophene rings, with the formation of dianion formula IIb

< / BR>
3) treatment of the product of stage (2) at temperatures below -50oC carbon dioxide with formation of the corresponding formulas in primary forms IIIb

< / BR>
4) conversion of the product of stage (3) in the appropriate decollato (i.e., the compound of formula IVb); and

5) removing the silyl group SiR2.

As the leaving group X is using chlorine, bromine and iodine, triftorbyenzola, triptorelin, ndimethylacetamide, triptorelin, 1,2,4-triazole and imidazole, and some other groups are well known to experts in the field of chemistry. Chlorine and triftorbyenzola are the preferred groups, thanks to its wide commercial availability.

Specific examples of R groups, defined as a /C1-C6/alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and n-hexyl.

HTCC obtained by the above method is believed to be essentially pure product and imaginova in the way described earlier, the melting point of which is 131 - 132oC even after repeated recrystallization.

The invention also provides methods which are variations of the basic method/ obtain 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide (structure VIII, scheme I below), including the reaction in the presence of a base 5-fluoro-6-chloro-2-oxindole-1-carboxamide (structure VII, scheme I) with an activated form (e.g., acid chloride acid, ellimination or methyl ether) 4-chloro-2-thiophencarboxylic acid, obtained according to any of the above methods. It is preferable to use either activated allmydata obtained by the reaction of STS with carbonyl diimidazol or acid chloride, obtained by the interaction of STS with thionyl chloride. Both of these preferred activated derivatives can be obtained in a convenient manner.

A further way to obtain 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide includes the following stages:

1) interaction in the presence of a base 5-fluoro-6-chloro-2-oxindole-1-carboxamide with activated monocarboxylic acid of the formula IVc

< / BR>
where Y is chlorine, imidazol-1-yl or methyl, with education about this>2) removing the silyl group SiR3.

Another variant of the method described above, includes the following stages:

1/ interaction in the presence of a base 5-fluoro-6-chloro-2-oxindole-1-carboxamide with an activated dicarboxylic acid of the formula IVd

< / BR>
where Y takes the values defined above with the formation of the corresponding compounds of formula Vb,

< / BR>
2) removing the silyl group SiR2.

Compounds of formulas IVa and IVb, as I believe, are also new and, respectively, represent an additional object of the invention.

The chemistry of this invention with the use of silanes of the formula RSiX for simplicity, can be summarized in generalized schematic form the following form

Circuit 1

< / BR>
The specialist of this field will be clear that the use of the compounds of formula R2SiX2instead of the compounds of formula R3SiX leads, respectively, to the substitution in scheme 1 mono-derivative of the formula Ia in dimenisonal 3-chlorothiophene formula Ib, to the substitution of mono-acid of the formula IVa to decollato formula IVb and to the substitution of mono-derivative of formula Va on di-derivative of formula Vb (the structure of these derivatives is shown above).

3Si - and (-R2Si-) in the above description referred to as "blocking groups", and silyl compounds R3SiX (and R2SiX2) called "blocking reagent". Further it should be noted that when given temperature value is less than approximately -50oC and the preferred value of less than -70oC, the preferred temperature is the temperature of -78oC because it can be easily obtained using baths with a mixture of dry ice/acetone. Achievable and lower temperatures, for example -94oC, which can be achieved by cooling in a bath with a mixture of hexane with liquid nitrogen. However, this provides only marginal benefits.

3-Chlorothiophene, locked in the second position, can be obtained from the primary interaction of 3-chlorothiophene with an equivalent amount of a strong base, such as alkylate at a temperature below -50oC, preferably below -70oC, so that the deprotonation becomes regioselective and directed into the 2 position. n-Utility preferred as the base, due to its commercial availability. Anenih conditions of the reaction such as tetrahydrofuran (THF) and hexane respectively. The reaction mixture is stirred for a period of time, which can range from 30 min to several hours. The blocking reagent can be added in an equivalent amount or slight (10%) excess. After a period of time from several minutes to several hours the reaction is quenched after heating to about room temperature or lower temperature by the addition of water and/or brine. The blocked product can be extracted with a suitable organic solvent, such as ethyl acetate, in the usual way, to dry and easy to select, for example, by evaporation.

2-Blocked 3-chlorothiophene can then be used in the reaction in a suitable dry solvent such as THF, with a base (in an equivalent amount or slight excess) at a temperature of less than -50oC, preferably less than -70oC, for the selective deprotonation of the remaining non-carbon atom adjacent to the sulfur atom in the thiophene series. After that, while maintaining the temperature below -50oC gaseous carbon dioxide can be used for processing deprotonated intermediate product, resulting in a gain of 4-chloro-5-blocked-2-thiophenecarboxylate the governmental nucleophilic properties, than a blocking group that is already attached to thiophene cycle. Bases that can be used at this stage include Nitidulidae, which can be obtained in situ by reaction alkyllithium derived from di-alkylamino. For example, n-utility can be processed at a temperature of approximately 0oC in THF prior to the introduction of a 2-blocked-3-chlorothiophene obtained at the previous stage, the equivalent number of dialkylamino, such as Diisopropylamine, with the formation of diisopropylamide lithium. After this, the temperature may be lowered to less than -50oC and held the accession of carbon dioxide. Carboxylate turned into acid by quenching the reaction with an aqueous solution of an acid, for example aqueous hydrochloric acid. The organic fraction can be separated, the aqueous layer can be extracted (e.g., ethyl acetate) followed by acid secretion.

The blocking group at this point it can be removed by treatment of the product with fluoride with the formation in the reaction of 4-chloro-2-thiophencarboxylic acid. After this, the acid can be activated and put into interaction with 5-fluoro-6-chloro-2-oxindole-1-carboxamide (also called "carboxamide predecessor"), with picturesto.

In another method, the blocking group should not be deleted and blocked acid can be activated to react directly with carboxamidine precursor to obtain the corresponding blocked product (Va) or (Vb) with pharmaceutical properties.

In any case, the blocking group can be removed by treatment with a fluorine anion, with the ultimate pharmaceutically active product is isolated by the quenching of the reaction with an aqueous solution (e.g., hydrochloric) acid. Source type anion of fluorine does not play an important role and can be used by different reagents containing the anion of fluorine, including fluorides of alkali metals (for example, fluorides of sodium, potassium, lithium and cesium), fluorides of alkaline-earth metals (for example, fluoride, magnesium and calcium), fluorohydrogen as in free (HF) and in the bound form (for example, in the form of hydrohloride pyridine) and fluoride Tetra-lower alkyl-ammonium. Fluoride Tetra-lower alkyl-ammonium are preferred, and most preferred fluoride, Tetra-n-butylamine due to its light commercial availability. For intensification of the reaction can be used an excess of fluoride, for example, 2 to 3 equivalent.

The Way The/P> The following examples illustrate various aspects of the invention, without any limitation of its scope. In the above examples, the Yarm obtained appliances brand Brooker AM u Brooker AM. For H1The PMR spectra were used frequencies from 250 MHz or 300 MHz,13C NMR spectra were obtained at 62,5 MHz or 75 MHz.

Example 1A. 2-Trimethylsilyl-3-chlorothiophene

< / BR>
To 3-chlorothiophene (5.0 g, 42,16 mmol), dissolved in 50 ml of tetrahydrofuran under stirring at a temperature of -72oC (cooling bath: acetone/dry ice) for 15 min add to 16.8 ml of 2.5 M aqueous solution of utility in hexane. During the addition the temperature of the reaction mass retain below -70oC. after addition of n-utillity a white precipitate is formed. After stirring for 40 min at -70oC to the resulting reaction mixture slowly over 5 min add 5,88 ml of chlorotrimethylsilane. After adding the solution quickly becomes transparent, and then again becomes cloudy due to the formation of lithium chloride which is a by-product. After 10 min the reaction solution was heated to 0oC and add 5 ml of water and then 25 ml of brine for quenching the reaction. The aqueous solution is extracted with ethyl is,0 g connection specified in the title, in the form of a clear oil.

Physical properties: mass spectrum /EIMS/ m/z = 192 M++2,14%/, 190 /M+, 36%/, 177 /M++2-CH3, 41%/, 175 /M+-CH3, 100%/; PMR /CDCl3/ 7,49 /1H, d, J = 4,7 Hz/ 7,07 /1H, d, J = 4,7 Hz/ and 0.46 /9H, s/;13C NMR /CDCl3/ 132,0; 130,2; to 130.1; 129,8 and a-0.7.

Example 1b. 4-Chloro-5-trimethylsilyl-2-thiencarbazone acid

< / BR>
A small amount (4 mg) diphenyloxazole acid are dissolved in 50 ml of tetrahydrofuran and stirred at room temperature. To the resulting solution was slowly added dropwise n-utility in the form of a 2.5 M aqueous solution in hexane until then, until the solution acquires a yellow color from the resulting dianion di-phenylacetic acid. This sequence provides a dry solution. Then the solution is cooled to a temperature of -72oC (acetone/dry ice). At this temperature, add to 4.62 ml (11,542 mmol) of 2.5 M aqueous solution of utility in hexane followed by the addition of 1.76 ml (12,592 mmol) Diisopropylamine. For the formation of sitedisability reaction solution was heated to 0oC (ice bath) for 20 min and again cooled to -72oC. To the cooled reaction solution was added 2.0 g (10,493 mmol) of 2-trimethylsilyl-3-chloro who Finance the temperature of the reaction support below -70oC. After 30 min the reaction through the yellow reaction solution was slowly passed gaseous carbon dioxide, maintaining the temperature of the reaction mixture below -55oC. the Total processing time of the reaction solution with carbon dioxide is 10 minutes After that, the solution is quickly heated to 0oC and the reaction quenched with 50 ml of IN hydrochloric acid, resulting in the allocation of a certain amount of gas. In the process of adding the acid solution, the reaction solution is heated to room temperature, then add 50 ml of brine. The organic fraction was separated and the aqueous portion extracted with ethyl acetate (2 x 50 ml). The organic extracts are combined, washed with brine (1 x 50 ml), dried sodium sulfate, filtered and evaporated, the result is 3 grams of white solids. Recrystallization of the technical product from heptane results in 1,67 g specified in the title of the pure product as a white crystalline substance, so pl. 206 - 210oC.

Physical properties: mass spectrum /LSIMS/ m/z = 237 (M + H++ 2,12%), 235 (M + H+10%); PMR (CDCl3) 7,74 (1H, s) and 0.41 (9H, s);13C NMR (CDCl3+ CD3OD) 163,1; 141,2; 137,8; 134,7; 131,6 and to 1.4.

Example 1c. 4-Chloro-2-thiencarbazone sour is wound with 0.3 ml of water and cooled to -50oC (ice/brine). 2.5 ml 1M aqueous solution of fluoride, Tetra-n-butylamine slowly added to the reaction solution. After 4 h the reaction solution is transferred into 50 ml of 5% aqueous sodium bicarbonate solution. The resulting reaction solution was placed in a separating funnel and washed with ethyl acetate (2 x 25 ml). The alkaline aqueous solution is acidified with concentrated hydrochloric acid to pH 2 and extracted with ethyl acetate (3 x 30 ml). The organic fraction is dried with sodium sulfate, filtered and evaporated to obtain 216 mg of product as a white solid. After recrystallization from warm heptane obtain 85 mg of pure crystalline product, so pl. 138oC.

Physical properties: mass spectrum (EIMS) m/z = 164 (M++ 2,30%) and 162 (M+, 100%); PMR (CDCl3) 10,9 (1H, ush. with replaceable), 7,74 (1H, d, J = 1,5 Hz) and the 7.43 (1H, d, J = 1,5 Hz);13C NMR (CDCl3) 166,1; 134,6; 133,2; 128,3 and 126,5.

Example 2a. 5-fluoro-6-chloro-2,3-dihydro-3-[hydroxy-2-(4-chloro-5 - trimethylsilylethynyl)methylene]-2-oxo-1H-indol-1-carboxamid

< / BR>
375 mg (1,60 mmol) 4-chloro-5-trimethylsilyl-2-thiophencarboxylic acid combined with 5 ml of thionyl chloride and heated to boiling. After 1.5 h the reaction is finished. The flask is cooled slowly to room temperature and the excess t is t in 5 ml of N,N'-dimethylformamide and slowly added to 15 ml of a solution of 5-fluoro-6-chloro-2,3-dihydro-2-oxo-1H-indole-1-carboxamide (500 mg, 2,24 mmol) and 4-(N,N-dimethylamino)pyridine (708 mg, 5.8 mmol) in N,N-dimethylformamide at a temperature of 0oC and stirring. After 1 h the reaction solution is transferred into 30 ml of 1 N-Noah hydrochloric acid, the resulting product is precipitated in the form of sediment chestnut color. Technical product is filtered and recrystallized from warm acetic acid to obtain 307 mg (609 mmol) specified in the title of the pure compounds in the form of a solid crystalline substance is yellow, so pl. 200oC.

Physical properties: mass spectrum /LSIMS/ m/z = 470 (M - H++ Na + 4,4%), 468 (M - H++ Na + 2,16%), 466 (M - H++ Na 21%), 448 (M++ 4,17%), 446 (M+2,74%), 444 (M+, 100%), 405 (M+- CONH + 4.8 PERCENT), 403 (M+- CONH + 2,28%) and 401 (M+- CONH, 39%); PMR (DMSO-d6) (1H, exchangeable), 8,51 (1H, s), 8,11 (1H, d, J = 7,3 Hz), of 7.96 (1H, JM-F= to 11.0 Hz), 7,30 (1H, exchangeable), 6,21 (1H, exchangeable) and 0.37 (9H, s).

Example 2b. 5-fluoro-6-chloro-2,3-dihydro-3-[hydroxy-2-(4-chloranil)- methylene]-2-oxo-1H-indol-1-carboxamid

< / BR>
50 mg (0.11 mmol) of 5-fluoro-6-chloro-2,3-dihydro-3-[hydroxy-2-(4-chloro-5 - trimethylsilylethynyl)methylene] -2-oxo-1H-indole-1-carboxamide are dissolved in 2 ml of tetrahydrofuran and cooled to 5oC. Small of 0.56 ml aliquot of 1M aqueous solution of fluoride, Tetra-butylamine dobavlyu add 0.25 ml of water. After another 30 min the reaction is quenched by adding 5 ml of 1N hydrochloric acid. The contents of the reaction flask was poured into 15 ml of water, resulting in precipitation of the product from the reaction solution as a precipitate. After filtration receive 25 ml of the product specified in the title, in the form of a solid yellow color, after recrystallization from acetic acid to obtain crystalline product, so pl. 234 - 237oC.

Physical properties: PMR (DMSO - d6) 9,10 (1H, exchangeable), 8,69 (1H, d, J = 1,5 Hz), 8,10 (1H, d, JH-F= 7,4 Hz), of 8.06 (1H, d, JH-F= to 11.4 Hz), the 7.65 (1H, d, J = 1,5 Hz) and 7,26 (1H, exchangeable).

Example 3a. Obtaining bis(3-chlorothiophene-2-yl)-dimethylsilane.

< / BR>
To 3-chlorothiophene (5.0 g, 42,16 mmol) dissolved in tetrahydrofuran with stirring in a bath (acetone/dry ice) at a temperature of -72oC add to 16.8 ml of 2.5 M solution of n-utility in hexane for 15 minutes the reaction Temperature support - 70oC during the whole time of adding. As soon as Appendix h-utility ends, a precipitate may form. After stirring at -70oC for 40 min, slowly add 2,81 ml of dichlorodimethylsilane within 5 minutes After complete addition, the solution immediately becomes transparent with subsequent pouvait to 0oC. Add 5 ml of water and then 25 ml of brine at 0oC to terminate the reaction. Then extracted with an aqueous solution with ethyl acetate (2 x 30 ml). The organic extract is dried (Na2SO4), filtered and evaporated to obtain the connection specified in the header.

Example 3b. Obtaining bis(5-carboxy-3-chlorothiophene-2-yl) dimethylsilane

< / BR>
The specified connection receive according to the method of example 1B, is used instead of 2-trimethylsilyl-3-chlorothiophene, the product obtained in example 3a.

Example 3c. Getting 4-chloro-2-thiophene carboxylic acid

< / BR>
The specified connection get in crystalline form by the method of example 1c, using instead 4-chloro-3-trimethylsilyl-2 - thiophene carboxylic acid, the product obtained in example 3b.

Example 4. Getting 5-fluoro-6-chloro-2,3-dihydro-3-[hydroxy-2-(4-chloranil)methylene]-2-oxo-1H-indole-1-carboxamide.

The specified product is obtained according to the methods of examples 2a and 2b, using a 1/2 molar equivalent (0.8 mmol) of the compound obtained in Example 3b instead of 375 mg (1,60 mmol) 4-chloro-5-trimethylsilyl-2-thiophene carboxylic acid.

1. Derivatives of 4-chloro-2-thiophencarboxylic acid of General formula I

< / BR>
where R is independently selected from C1< / BR>
2. The way to obtain 4-chloro-2-thiophencarboxylic acid, characterized in that the compounds of formula IVa

< / BR>
where each group R is independently selected from C1- C6-alkyl, benzyl, phenyl,

remove the silyl group-SiR3.

3. The way to obtain 4-chloro-2-thiophencarboxylic acid, characterized in that compounds IVb

< / BR>
where R is independently selected from C1- C6-alkyl, benzyl, phenyl,

remove the silyl group-SiR2-.

4. The method according to p. 2, characterized in that a) 3-chlorothiophene process at a temperature below about -50oC base with subsequent interaction with the organosilicon compound of the formula

R3SiX,

where X is a leaving group,

each R group is independently selected from C1- C6-alkyl, benzyl and phenyl,

with the formation of the compounds of formula

< / BR>
b) process the product of stage (a) at a temperature below approximately -50oC a suitable base for the deprotonation chlorothiophenol cycle in the 5-position with formation of the corresponding anion of the formula IIa

< / BR>
c) treat the product of stage (b) at a temperature below -50oC carbon dioxide with the formation of appropriate, ) remove the silyl group-SiR3.

5. The method according to p. 4, wherein R can be methyl, X is chlorine or triftorbyenzola and process on each of the stages (a) - (c) at a temperature below -70oC.

6. The method according to p. 3, characterized in that a) 3-chlorothiophene process at a temperature below about -50oC base with subsequent interaction with the organosilicon compound of the formula

R2SiX2,

where X is a leaving group,

each R group is independently selected from C1- C6-alkyl, benzyl and phenyl,

with the formation of the compounds of formula Ib

< / BR>
b) process the product of stage (a) at a temperature below approximately -50oC base, suitable for deprotonation in 5 - and 5'-positions in both thiophene cycles, with the formation of dianion formula IIb

< / BR>
c) treat the product of stage (b) at a temperature below -50oC carbon dioxide with formation of the corresponding formulas in primary forms IIIb

< / BR>
d) turn the product of the formula IIIb in the appropriate decollato and (e) removing the silyl group-SiR2-.

7. The method according to p. 6, characterized in that R can take values methyl, X is chlorine or tryptose obtain 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide, characterized in that 5-fluoro-6-chloro-2-oxindole-1-carboxamide subjected to interaction in the presence of a base with 4-chloro-2-thiophencarboxylic acid obtained according to the methods under item 4 or 5.

9. The method according to p. 8, characterized in that a) 5-fluoro-6-chloro-2-oxindole-1-carboxamide subjected to interaction in the presence of a base with a monocarboxylic acid of the formula IVa, specified in paragraph 2, to obtain 5-fluoro-6-chloro-3-(4-chloro-3-triple-substituted silyl-2-thenoyl)-2-oxindole-1-carboxamide, (b) remove the silyl group-SiR3of the product of stage a).

10. The way to obtain 5-fluoro-6-chloro-3-(4-chloro-2-thenoyl)-2-oxindole-1-carboxamide, characterized in that a) 5-fluoro-6-chloro-2-oxindole-1-carboxamide subjected to interaction in the presence of a base with a dicarboxylic acid of the formula IVb, specified in paragraph 3, b) remove the silyl group-SiR2- from the product of stage (a).

 

Same patents:
The invention relates to chemical technology of organic polymers, and in particular to methods of obtaining,-deoxypyridoxine (MHI) polydimethylsiloxane linear structure containing a hydroxyl group at the terminal silicon atoms, with a viscosity of 10,000 Centistokes and above

The invention relates to the chemistry of organosilicon compounds, in particular to methods for fenilatsetilenov, and can be used to obtain polyphenylsiloxane resins, varnishes and enamels, widely used in national economy

The invention relates to crasneanscki chemistry, and in particular to a method for producing N, N'-bis(3-trialkylsilyl)thiocarbamide and N,N'-bis(3-trialanderror)thiocarbamide (X3Si(CH2)3NH/2C=S, where (I) X = C2H5(II) X = OS2H5

The invention relates to the field of production of organosilicon compounds containing organic radical at the silicon atom highly reactive vinyl groups: acrylic and methacryloyl

,

where R is H; CH3

The invention relates to the chemistry of organosilicon compounds, in particular to methods for fenilatsetilenov and can be used to obtain polyphenylsiloxane resins, varnishes and enamels, widely used in national economy

The invention relates to the chemistry of organosilicon compounds, namely to new ways of getting tetramethylsilane (CH3)4Si, which are widely used in organic and Organoelement synthesis and for the production of carbon fiber gas separation membranes such as hollow fibers with a high degree of separation of oxygen and nitrogen, as stereospecific polymerization catalyst and an internal standard in NMR
The invention relates to methods of producing organosilicon compounds, in particular to methods for hexamethyldisiloxane, and can be applied in the main production process for the synthesis of hexamethyldisiloxane, as well as waste hexamethyldisilazane purity

The invention relates to new benzothiophen-2-carboxamide-S,S-dioxides having valuable properties, in particular to derive benzothiophen-2-carboxamide - S,S-dioxide of the General formula I

< / BR>
where

R1unbranched or branched alkyl with 1 to 20 carbon atoms, unbranched or branched halogenated, cianelli, oxyalkyl, alkoxyalkyl or alkoxycarbonyl with 1 to 8 carbon atoms in each alkyl part, unbranched or branched alkenyl with 2 to 12 carbon atoms, unbranched or branched quinil with 2 to 12 carbon atoms or unsubstituted or once to six times substituted by alkyl cyclohexyl or cyclohexylmethyl, unsubstituted or once to fivefold substituted in the phenyl part of the same or different substituents phenyl, phenylalkyl or phenylalkyl with 1 to 12 carbon atoms in each unbranched or branched alkyl or alkenylphenol part, moreover, as substituents of the phenyl can be called a halogen atom, hydroxyl, cyano, formylamino, unbranched or branched alkyl, alkoxygroup with 1 to 4 carbon atoms, unbranched or branched girsvetlana or branched, dialkylamino, alkylsulphonyl, alkylcarboxylic, alkoxycarbonyl, aminocarbonyl, N-alkylaminocarbonyl, N,N-dialkylaminoalkyl, formylamino, alifornian;

R2a hydrogen atom or an unbranched or branched alkyl with 1 to 18 carbon atoms, unsubstituted or singly or multiply substituted by identical or different substituents from the group comprising hydroxyl group, a halogen atom, a cyano;

R1and R2together with the nitrogen atom to which they relate, signify unsubstituted or singly or multiply substituted, saturated five - to semicolony a heterocycle, which may contain in addition to the nitrogen atom, an oxygen atom and a Deputy may be alkoxycarbonyl with 1 to 4 carbon atoms;

R3, R4, R5and R6independently from each other mean a hydrogen atom, halogen atom, alkoxygroup with 1 to 6 carbon atoms

The invention relates to new derivatives of arylsulfonamides having, in particular, valuable pharmacological properties, more particularly to a derivative of arylsulfonamides General formula (I)

< / BR>
where R1benzyl, thienyl, chloranil, tetramethylene pentamethylbenzyl, phenyl, unsubstituted or monosubstituted by a halogen atom, a nitro-group, stands, metaxylem or trifluoromethyl, phenyl, disubstituted by chlorine atoms or methoxypropane,

R2a hydrogen atom, methyl,

R3pyridyl,

R4and R5hydrogen atoms or together denote a carbon-uglerodnoi communication,

R6hydroxyl, methoxyl,

A group of the formula

< / BR>
where R7and R8a hydrogen atom or together denote a methylene or ethylene group

X N-methyl-aminogroup or sulfur atom, and the group-CHR7associated with the group-NR2-,

B a carbon-carbon bond or unbranched Allenova group with 2-4 carbon atoms,

their mixtures, isomers or individual isomers and physiologically tolerated additive salts with bases, if R6means hydroxyl, which

The invention relates to the field of chemistry of biologically active substances, which may have application in medicine

The invention relates to the field of organic chemistry and relates to a method of obtaining new derivatives of imidazole

FIELD: organic chemistry, agriculture, insecticides.

SUBSTANCE: invention relates to a substituted anilide derivative of the formula (I): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2; Z represents oxygen atom; Q means a substitute represented by any of the following formulae: Q1-Q3, Q6, Q8-Q12, Q14-Q19, Q21 and Q23 (wherein each among Y1 that can be similar or different represents halogen atom, (C1-C6)-alkyl group, and so on); Y2 represents (C1-C6)-alkyl group or halogen-(C1-C6)-alkyl group; Y3 represents (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl group or substituted phenyl group; p represents a whole number from 1 to 2; q represents a whole number from 0 or 2; r represents a whole number from 0 to 2. Also, invention proposes a chemical for control of pests of agricultural and fruit crops. The chemical comprises substituted anilide derivative of the formula (I) as an active component and represents insecticide, fungicide or acaricide. Also, invention proposes a method for addition of the chemical for control of pests of agricultural and fruits crops. Also, invention proposes aniline derivative represented by the general formula (II): wherein R1 represents hydrogen atom, (C1-C6)-alkyl group; R2 represents hydrogen atom, halogen atom or halogen-(C1-C6)-alkyl group; R3 represents hydrogen atom, halogen atom, (C1-C6)-alkyl group, hydroxyl group or (C1-C6)-alkoxy-group; t = 1; m = 0; each among X that can be similar or different represents (C2-C8)-alkyl group, hydroxy-(C1-C6)-alkyl group or (C3-C6)-cycloalkyl-(C1-C6)-alkyl group; n = 1 or 2. Invention provides the development of anilide derivative as insecticide, fungicide and acaricide against pests of agricultural and fruit crops.

EFFECT: valuable properties of compound.

5 cl, 6 tbl, 27 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to arylated amides of furan and thiophene carboxylic acids of the formulae (Ia) and (Ib) wherein W means oxygen or sulfur atom; R(1) means -C(O)OR(9) or -COR(11) wherein R(9) and R(11) mean independently of one another CxH2x-R(14) wherein x means 0, 1, 2 or 3; R(14) means phenyl, and to their pharmaceutically acceptable salts also. Also, invention describes a pharmaceutical composition and using proposed compounds a medicinal agents. Compounds can be used as anti-arrhythmic biologically active substances and especially in treatment and prophylaxis of atrium arrhythmia.

EFFECT: valuable medicinal properties of compounds and composition.

11 cl, 29 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to derivatives of aromatic dicarboxylic acids of the general formula (I):

wherein means thiophene ring that can be unsubstituted or substituted with 1 or 2 substitutes; R1 and R2 are similar or different and mean hydrogen atom, branched or unbranched (C1-C14)-alkyl group that can be unsubstituted or substituted with one or some substitutes, carbocyclic group or heterocyclic group; R1 and R2 form in common with nitrogen atom 3-6-membered cycle, and to their enantiomers, diastereoisomers, racemates and their physiologically acceptable salts. Compounds possess inhibitory effect with respect to activity of histon deacetylase. Also, invention describes a medicinal agent based on compounds of the formula (I).

EFFECT: valuable medicinal and biochemical properties of derivatives.

6 cl, 1 tbl, 18 ex

Up!