Derivatives of 1-methyl-5-chloropyrazole and method of production thereof

 

(57) Abstract:

The invention relates to new derivatives of 1-methyl-5-chloropyrazole General formula where R is CH2Cl, CF3, 4-CLC6H4, 3-NO2C6H4that exhibit antibacterial activity. In addition, the proposed method of obtaining derivatives of 1-methyl-5-chloropyrazole, in which R is CH3WITH2H5WITH3H7CH2CL, CF3WITH6H5, 4-ClC6H4, 3-NO2C6H4by interaction of the corresponding derivative of 2,2-dichlorodiphenylmethane formula RC(O)CH=CCl2where R has the above significance, with dimethylhydrazine when a molar ratio of 1: 2, respectively, in the environment of an organic solvent at room temperature for 0.5-12 hours Technical results: simple one-step method based on the available raw material derivatives of 1-methyl-5-chloropyrazole, including new connections, which are promising biologically active substances and valuable technical products to create medicines, dyes, insecticides. 2 c.p. f-crystals, 3 tables.

The invention relates to derivatives of 1-methyl-5-Harper (V) WITH6H5(VI), 4-l6H4(VII), 3-N02WITH6H4(VIII)

and the way they are received.

1-Methyl-3-alkyl-, aryl-, chloroalkyl-, perfluoroalkyl-5-chloropyrazole promising for the creation of medicines, dyes, fluorescent [Chemical encyclopedia. So 3. S. 1034. Moscow. B. Ross. Encyclopedia 1992] , insecticides [Fumio Suzuki, Iwakawa Isato Toshiaki, Igeei Takachi, Oguchi Tosihiko. Jp. Kokai. Tokyo Koho Jp. 06, 56,792 [94 56,792] S. A. 122 31573f], insectoacaricidal [A. F. Granov. The USP. 1999. So 68. 8. C. 773-784; A. Pawer, A. A. Patil. Indian J. Chem. 1994. 33B, R. 156], and promising biologically active compounds [D. E. Butler, N. A. De Ward. J. Org.Chem. 1971. V. 36. R. 2542-2547; Nazarinia, M., Sharifian, A., Shafiee A. J. Heterocycl. Chem. 1995. 32(2), 223-5]. So, for example, 1,3-dimethyl-5-chloropyrazole is the initial product to obtain a special preparation of a new generation of fenpyroximate [A. F. Granov. The USP. 1999. So 68. 8. C. 773-784; A. Pawer, A. A. Patil. Indian J. Chem. 1994. 33B. 156 (1994)]. 1-Methyl-3-alkyl-5-chloropyrazole are used to obtain the number of personalization, pyrazolodiazepines connection with the antidepressant and other activity or intermediates for their production [US 3823157 And (N. A. De Wald, S. Road, A. Arbor et al. ) 09.06.1974] , [DE 2423642 (Parke Davis & CO)]. 1-Methyl-3-alkyl-5-chloropyrazole involved in the acylation reaction with the aim of obtaining 4-and the

In the literature it is known from the number of claimed compounds 3-methyl-, 3-ethyl-, 3-propyl-, 3-isopropyl-, 3-butyl - 3-phenyl-1-methyl-5-chloropyrazole and there are four ways of obtaining them [Chemical encyclopedia. So 3, S. 1034. Moscow: B. Ross. Encyclopedia 1992; A. Michaelis, H. Dorn. Ber. 1907. Century 23. P. 179; Liebigs Ann. Chem. 1907. C. 352. R. 169; K. Auwers, F. Niemyer. J. Prakt. Chem., 1925, V. 110. P. 153; C. L. Habraken, J. A. Moove. J. Org.Chem. 1965. V. 30. P. 1892-1896; D. E. Butler, N. A. De Ward. J. Org.Chem. 1971. V. 36. P. 2542-2547; M. J. Fray, D. J., Bull, K. Cooper, MJ. Parry, M. H. Stefaniak. J. Med. Chem. 1995. V. 38. N 18. R. 3524-3535].

Method 1. 3-Methyl - 3-phenyl-1-methyl-5-chloropyrazole the resulting two-stage process, the first stage of which carry out processing corresponding 3-methyl-, 3-phenylpyrazole-5 phosphorus oxychloride in benzene at 140-200oC for 10 hours in a sealed tube in order to obtain 3-methyl(phenyl)-5-chloropyrazole. In the second stage the obtained chloropyrazole sequentially treated with iodine stands (4 hours in a sealed tube at 100oC) and alkali and produce 5-chloro-1-methyl-3-methyl or 3-phenylpyrazoles low outputs [A. Michaelis, H. Dorn. Ber. 1907. Century 23. P. 179; Liebigs Ann. Chem. 1907. C. 352. R. 169; K. Auwers, F. Niemyer. J. Prakt. Chem., 1925, V. 110. R. 153].

Method 2. 3-Methyl - and 3-phenylpyrazole-5 in the first stage is introduced into reaction with iodine stands at long agravat with phosphorus oxychloride at 160oWith over 8 hours of targeted products with low yield and low purity. To clean them, it takes two recrystallization [A. Michaelis, H. Dorn. Ber. 1907. Century 23. P. 179; Liebigs Ann. Chem. 1907. C. 352. R. 169; K. Auwers, F. Niemyer. J. Prakt. Chem., 1925, B. 110. P. 153].

The closest to the claimed method are the methods 3 and 4.

Method 3. The first stage is introduced into the reaction of the acyl - or benzoyloxy esters with methylhydrazine and the resulting pyrazolones-5 is treated with phosphorus oxychloride with targeted products with an admixture of isomers, and low output [A. Michaelis, H. Dorn. Ber. 1907. Century 23. P. 179; Liebigs Ann. Chem. 1907. C. 352. 169; K. Auwers, F. Niemyer. J. Prakt. Chem., 1925, V. 110. P. 153; C. L. Habraken, J. A. Moove. J. Org.Chem. 1965. V. 30. P. 1892-1896; M. J. Fray, D. J., Bull, K. Cooper, M. J. Parry, M. H. Stefaniak. J. Med. Chem. 1995. V. 38. N 18. R. 3524-3535].

Method 4. The first stage is introduced into the reaction of the methyl esters alkylaminocarbonyl acid with methylhydrazine at low temperature (0oC) and the resulting 1,3-dialkylphenols-5 boiled with phosphorus oxychloride 24 hours [D. E. Butler, H. A. De Ward. J. Org.Chem. 1971. V. 36. R. 2542-2547].

The main disadvantages of the known methods are:

1. Limited availability of 3-R-pyrazolones. While 3-methyl - and 3-phenylpyrazole available products, their receipt of the gross ester of acetic acid and the corresponding halide atilov in the presence of alkali metals potassium or sodium) are utilized in industry to obtain pyrazolones with other deputies is required to develop methods for the synthesis of the starting materials. The reaction processes of obtaining allocating esters with the participation of Chloroacetic acid chlorides of the acids, in particular monochloracetic acid, ethyl acetate and alkali metal cannot spend in developed conditions for participating in a constraint C-H1 alkyl radical. For other source esters etilatsetatom of halide atilov and ethyl acetate is also necessary to develop instructional techniques.

2. At the same time, 1-methyl-3-R-pyrazolones-5 by the reaction of methylhydrazine with alloxane esters are obtained with low yield and heterogeneous isomeric composition.

3. It should also be stressed that obtaining 1-methyl-3-acylpyrazolone-5 (II, III) reaction of methylhydrazine with methyl esters alkylaminocarbonyl acids is limited by the availability alkylarenes acids.

4. A multi-stage process. The first stage is synthesized corresponding acyloxy ester or ether alkylaminocarbonyl acid, based on them - pyrazolone, then in subsequent transformations (two stages in methods 1 and 2 and one in the m (iodine stands, dimethylsulfate and others) and a base; b) was identified in pyrazolone, and then the product is treated with phosphorus oxychloride, releasing 5-chloro-1-methyl-3-methyl - or 3-phenylpyrazoles with low yield; C) reaction of the methyl esters of alkylaminocarbonyl acids or allocating ethers with methylhydrazine get 1-methyl-3-acylpyrazolon, which is influenced by gloriouse agent.

5. Sophisticated equipment. To obtain chloropyrazole requires special equipment as used in the reaction process, the phosphorus oxychloride is aggressive, toxic, vysokoletuchie low-boiling compound, and to the process of chlorination, high temperature and high pressure.

6. The high energy intensity of the process. For a long time all the reaction stages are carried out under heating, leads to higher costs of energy and time.

7. In addition, for the synthesis of the desired pyrazoles required isolation of pure intermediates at each stage, which significantly increases the consumption of materials, energy and intensity of the process.

8. And finally, do not exclude the possibility of obtaining different isomers, namely 1-methyl-3-R-5-chloropyrazole and 1-methyl-3-chloro-5-R-pyrazolidone described 1-methyl-3-methyl-, 3-ethyl-, 3-propyl-, 3-isopropyl-, butyl - and 3-phenyl-5-chloropyrazole. However, for 1-methyl-3-ethyl-, 3-propyl - 3-butyl-5-chloropyrazole shown only the boiling temperature, and for 1-methyl-3-isopropyl-5-chloropyrazole only the data of the spectrum of the PMR. Other physico-chemical characteristics, confirming their structure, were not known.

Known methods for producing these important, in practical terms, 5-chloropyrazole unsuitable for large-scale and industrial implementation due to their complexity, mnogostadiinost, small output of products and the complexity of their treatment.

The purpose of the invention:

1. The creation of new derivatives of 1-methyl-5-chloropyrazole, promising biologically active substances.

2. The creation of new original technology, single stage, based on available products of way to obtain 5-chloro-1-methyl-3-alkyl-, aryl-, chloroalkyl-performancerelated.

3. Improving the environment by eliminating from the process of synthesis of the desired products of aggressive reagents, temperature and pressure; due to the use in the process, and therefore, the disposal of large waste industry - 1,1-dimethylhydrazine.

Set cladrina in the medium of organic solvent: hexane, benzene, a lower alcohol, ether or acetonitrile in the ratio 1:2. The process was performed at room temperature. After the exothermic reaction allocation of target products is carried out by known methods.

The chemistry of the process is presented in scheme at the end of the text.

As a result of implementation of the process is obtained 1-methyl-3-alkyl-, chloroalkyl-, perfluoroalkyl-, aryl-5-chloropyrazole I-VIII, with a stable high output. The structure of pyrazoles proven physico-chemical methods and confirmed by elemental analysis. Physico-chemical data pyrazoles I-VIII are shown in tables 1-3, so square and t Kip. pyrazoles I and VI correspond to the literature data.

The invention is illustrated by the following examples.

Example 1. 1,3-Dimethyl-5-chloropyrazole (I).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 12.0 g (0.2 g-mol) of N,N-dimethylhydrazine in 50-100 ml of dry hexane. To the solution is slowly added dropwise 13.9 g (0.1 g-mole) 4,4-dichlorobut-3-EN-2-it. After the end of the exothermic reaction the reaction mixture was kept under stirring for 1-2 hours. Fallen in sediment Trimethylhydrazinium filtered and dried in vacuum over P2ABOUT5. /SUB>lN2.

Calculated,%: 32.58; N, 10.03; C1 32.06; N At 25.33.

IR-spectrum (in KBR), cm-1: 3200, 3100, 3005, 2700 (NH), 2950 (CH3), 1480, 1630 (C-N).

The PMR spectrum of BD3OD , M. D.: 3.41 (N3).

From the filtrate by distillation get with the release 8.36 g (64%) of the target pyrazole I. T. bales. 156-157.5oC (lit. : so Kip. 158oS, nD17.6=1.4841, d417.6= 1.1367: K. Auwers, F. Niemyer. J. Prakt. Chem., 1925, V. 110. P. 153; so bales. 153 to 155oFrom: C. L. Habraken, J. A. Moove. J. Org. Chem. 1965. V. 30. R. 1892-1896).

When carrying out the reaction of N,N-dimethylhydrazine with methyl-2,2-dichlorophenylamino when the reagent ratio 2:1 in benzene, ether, acetonitrile, lower alcohols - methanol, ethanol, isopropanol - in similar conditions obtained pyrazole (I) with the release of 63-68%.

Similarly derived pyrazoles II-VIII. The yield and physico-chemical properties of the target products are shown in tables 1-3.

Example 2. 1,3-Dimethyl-5-chloropyrazole (I).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel was dissolved 12.0 g (0.2 g-mol) of N,N-dimethylhydrazine in 50-100 ml of ethanol. To the solution is slowly added dropwise 13.9 g (0.1 g-mole) 4,4-dichlorobut-3-EN-2-it. After the end of the exothermic reaction the reaction mixture is maintained at lane is hydrazinehydrate water. The ether solution is dried and distilled. Get with the release of 64% (8,40 d) target pyrazole I.

Similarly derived pyrazoles II-VIII.

Example 3. 1,3-Dimethyl-5-chloropyrazole (I).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 12.0 g (0.2 g-mol) of N,N-dimethylhydrazine in 50-100 ml of ethanol. To the solution is slowly added dropwise 13.9 g (0.1 g-mole) 4,4-dichlorobut-3-EN-2-it. After the end of the exothermic reaction the reaction mixture was kept under stirring 0.5 hours. The alcohol is distilled off in a vacuum or evaporated. The residue is diluted with ether and washed from trimethylacetylchloride water. The ether solution is dried and distilled. Get off exit 63% (8,39 g) target pyrazole I.

Similarly derived pyrazoles II-VIII.

Example 4. Obtain 1-methyl-3-phenyl-5-chloropyrazole (VI).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 12.0 g (0.2 g-mol) of N,N-dimethylhydrazine in 50-100 ml of dry ether. To the solution slowly, preventing overheating of the reaction mixture, was added dropwise 20.2 g (0.1 g-mole) of 1-phenyl-3,3-dichloroprop-2-EN-1-it. Thus, there is a self heating and precipitation of trimethylacetylchloride. After okonchan tigertailz filtered and dried in vacuum over P205. The output of salt 87%.

From the filtrate after removal of the ether produce the target product. Further purification it is carried out by recrystallization from petroleum ether or hexane. Yield 60% (5.46 g). So pl. 61-62oWith (lit.: 60-62oC, A. Michaelis, H. Dorn. Ber. 1907. Century 23. P. 169).

When carrying out the reaction of N,N-dimethylhydrazine with phenyl-2,2-dichlorophenylamino when the reagent ratio 2:1 in benzene, hexane, acetonitrile, lower alcohols - methanol, isopropanol-in similar conditions obtained pyrazole VI with the release of 60-63%.

Similarly pyrazoles obtained I-V, VII, VIII.

Example 5. Obtain 1-methyl-3-phenyl-5-chloropyrazole (VI).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 12.0 g (0.2 g-mol) of N,N-dimethylhydrazine in 50-100 ml of dry ether. To the solution slowly, preventing overheating of the reaction mixture, was added dropwise 20.2 g (0.1 g-mole) of 1-phenyl-3,3-dichloroprop-2-EN-1-it. Thus, there is a self heating and precipitation of trimethylacetylchloride. After the end of the exothermic reaction the mixture is kept for 0.5 hour and precipitated in the sediment Trimethylhydrazinium filtered and dried in vacuum over P205. The output of salt 84%.

Similarly, when carrying out the process over a period of 0.5 hours received pyrazoles II-V, VII, VIII.

Example 6. Obtain 1-methyl-3-ethyl-5-chloropyrazole (II).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 7.54 g (0.125 g-mol) of N,N-dimethylhydrazine in 50-100 ml of methanol. To the solution slowly, preventing overheating of the reaction mixture, was added dropwise 8.72 g (0.0627 g-mole) 4,4-dichlorine-3-EN-2-it. After the end of the exothermic reaction the reaction mixture was kept under stirring 0.5-2 hours. The solvent is removed in vacuum. Trimethylhydrazinium chloride is separated from the target product, washing the residue with cold water and extragere pyrazole boiling petroleum ether or hexane. The output of salt 80%.

The organic solution dispersed. The output of the pyrazole II 71% (6.4 g). So Kip. 186oC. [lit.: so Kip. 82-83o(28 mm RT.article): D. E. Butler, H. A. De Ward. J. Org. Chem. 1971. V. 36. R. 2542-2547); other physical and chemical characteristics in the work are not given).

When carrying out the reaction of N,N-dimethylhydrazine with 4,4-dichlorine-3-EN-2-one when the reagent ratio 2: 1 in ether, benzene, hexane, acetonitrile, lower alcohols - ethanol, isopropanol - in similar conditions also Polo-methyl-3-propyl-5-chloropyrazole (III).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 12.0 g (0.2 g-mole) N,N-dimethylhydrazine in 50-100 ml of isopropanol. To the solution slowly, preventing overheating of the reaction mixture, was added dropwise 16.7 g (0.1 g-mole) 1,1-dialogex-1-EN-3-one. After the end of the exothermic reaction the reaction mixture was kept under stirring 0.5-2 hours. The solvent is removed in vacuum. Trimethylhydrazinium separated from the target product, washing the precipitate with cold water or extragere pyrazole boiling petroleum ether or hexane. The output of salt 80%.

The output of the pyrazole 76.9% (13 g). So Kip. 67o(7 mm RT.CT.) [lit.: so Kip. 78-79o(10 mm RT.article): D. E. Butler, H. A. De Ward. J. Org.Chem. 1971. V. 36. R. 2542-2547); other physical and chemical characteristics in the work are not given).

Similarly derived pyrazoles I, II, IV-VIII.

When carrying out the reaction of N,N-dimethylhydrazine with propyl-2,2-dichlorophenylamino when the reagent ratio 2:1 in ether, benzene, hexane, acetonitrile, lower alcohols - methanol, ethanol under similar conditions obtained pyrazole (III) with the release of 60-63%.

Example 8. Obtain 1-methyl-3-chloromethyl-5-chloropyrazole (IV).

In a three-neck flask, equipped with MERALCO is. the solution slowly, preventing overheating of the reaction mixture, was added dropwise 17.3 g (0.1 g-mole) 1,4,4-trichlorobut-3-EN-2-it. After the end of the exothermic reaction the reaction mixture was kept under stirring 0.5-2 hours. Fallen in sediment Trimethylhydrazinium separated from the desired product by filtration. The output of salt 80%. The filtrate is evaporated, the residue of pyrazole washed with cold water and recrystallized from petroleum ether or hexane.

The output of the pyrazole 76.9% (13 g). So pl. 33-33.5oC.

Similarly derived pyrazoles I-III, V-VIII.

When carrying out the reaction of N,N-dimethylhydrazine with chloromethyl-2,2-dichlorophenylamino when the reagent ratio 2:1 in ether, hexane, acetonitrile, lower alcohols - methanol, ethanol, isopropanol - in similar conditions obtained pyrazole IV with access 76-83%.

Example 9. 1-Methyl-3-trifluoromethyl-5-chloropyrazole (V).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 7.44 g (0.1238 g-mol) of N,N-dimethylhydrazine in 40-50 ml of dry acetonitrile. To the solution is slowly added dropwise 10.97 g (0.0619 g-mol) of 1,1,1-Cryptor-4,4-dichlorobut-3-EN-2-it. Thus, there is a self heating and precipitation of trimethylhydrazine. Fallen in sediment Trimethylhydrazinium was filtered and dried in vacuum over P2ABOUT5. The output of salt 80%. From the filtrate after removal of the solvents emit with the release of 56.4% (5.46 g) target pyrazole.

Similarly derived pyrazoles I-IV, VI-VIII.

When carrying out the reaction of N,N-dimethylhydrazine with trifluoromethyl-2,2-dichlorophenylamino when the reagent ratio 2:1 in ether, hexane, benzene, lower alcohols - methanol, ethanol, isopropanol - in similar conditions obtained pyrazole (V) output 58-60%.

Example 10. 1-Methyl-3-(4-chlorophenyl)-5-chloropyrazole (VII).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 4.6 g (0.02 g-mole) 4-chlorophenyl-2,2-dichloroaniline in 50 ml of dry ether to the solution is added 2.4 g (0.04 g-mole) N, N-dimethylhydrazine. After the end of the exothermic reaction the mixture is stirred for another 2 hours. Fallen in sediment Trimethylhydrazinium filtered off and dried over P2O5. The output of salt 80%. From the filtrate after removal of the solvent allocate exit 89% (3.9 g) target pyrazole.

Similarly derived pyrazoles I-VI, VIII.

When carrying out the reaction of 4-chlorophenyl-2,2-dichloroaniline with N,N-dimethylamide ropanol - similar conditions obtained pyrazole (VII) with the release of 86-92%.

Example 11. 1-Methyl-3-(3-nitrophenyl)-5-chloropyrazole (VIII).

In a three-neck flask equipped with stirrer, reflux condenser and addition funnel, dissolved 4.8 g (0.02 g-mol) 3-nitrophenyl-2,2-dichloroaniline in 50 ml of dry ether to the solution is added 2.4 g (0.04 g-mole) N,N-dimethylhydrazine. After the end of the exothermic reaction the mixture is stirred for another 2 hours. Fallen in sediment Trimethylhydrazinium filtered off and dried over P2ABOUT5. The output of salt 86%. From the filtrate after removal of the solvent allocate exit 87% (4.0 g) target pyrazole.

Similarly derived pyrazoles I-VII.

When carrying out the reaction of 3-nitrophenyl-2,2-dichloroaniline with N,N-dimethylhydrazine in the reagent ratio 2:1 in acetonitrile, hexane, benzene, lower alcohols - methanol, ethanol, isopropanol - in similar conditions obtained pyrazole (VIII) with the release of 86-92%.

Thus, the obtained 1-methyl-3-alkyl-, aryl-, chloroalkyl-, perfluoroalkyl-5-chloropyrazole I-VIII, including previously unknown (IV-VII, VIII) high purity and good yields and developed a new method to produce 1-methyl-3-alkyl-, aryl-, perfluoroalkyl -, chlorine and biological activity of 1-methyl-3-(4-chlorophenyl)-5-chloropyrazole (VII) (code VM-1-01), 1-methyl-3-(3-nitrophenyl)-5-chloropyrazole (VIII) (code VM-2-01), 1-methyl-3-chloromethyl-5-chloropyrazole (IV) (code VM-3-01) and 1-methyl-3-trifluoromethyl-5-chloropyrazole (V) (code VM-05-01). The tests were carried out on 11 Museum strains of bacteria and bacilli. High antibacterial activity showed drugs VM-2-01 against P. mirabilis in the dose of 4 mg cm-3-01 against P. aeruginosa, B. subtilis, B. anthracoides.

Toxicity was determined after intragastric administration of drugs outbred white mice weighing 20-22, the Highest toxicity showed the connection VM-3-01, LD50which was 400 mg/kg, which corresponds to the qualification of second class of toxic substances. Connection VM-1-01 and VM-2-01 at this dose is not toxic, they are not toxic dose is 4 times greater, which allows them to be classified as low-toxic compounds. The exact value of the dose LD50it was not determined due to insufficient number of substances.

New chemical compounds, 1-methyl-3-aryl-, chloroalkyl-, perfluoroalkyl-5-chloropyrazole (IV, V, VII, VIII) can find purpose as intermediates for the synthesis of new derivatives of pyrazole - technically valuable products and biologically active compounds, are promising for the creation of antibiotics.

The proposed CSP is Il-, arylketones and N, N-dimethyl hydrazine in a molar ratio of reactants of 1:2 is new and differs from the known methods.

1. To date 1,1-dimethylhydrazine was not used to obtain pyrazoles. It is known that reactions of carbonyl compounds including unsaturated, 1,1-dimethylhydrazone obtained corresponding hydrazones [Y. P. Kitaev, B. I. Buzykin. The hydrazones. Moscow: Nauka, 1974].

2. The reaction of 1,1-dimethylhydrazine with the closest analogs of 2,2-dichlorophenylamino - 2,2-dibromobiphenyl(thienyl)ketones [Century. N.Elokhin, A. S. Nachmanovitch, L. I. Larina, O. C. Shishkin, V. N. The Bäumer, C. A. Lopyrev. Synthesis of 1-[1-bromo-2-benzoyl(2-thenoyl)vinyl] -1,1-dimethylhydrazinium of 1-bromo-2-benzoyl(2-thenoyl)acetylenes and 1,1-dimethylhydrazine. WPI. Russian Academy of Sciences. Ser. chem. 1999. 8. P. 1536-1538] observed the formation of Quaternary salts dimethyl - 1-[1-bromo-2-benzoyl(2-thenoyl)vinyl]-1,1-dimethylhydrazinium.

3. From the known properties of 2,2-dichlorophenylamino should not evident that their interaction with dimethyl may lead to pyrazoles. It is known that the monosubstituted hydrazines (phenyl-, 2,4-dinitrophenylhydrazine) by reaction with 2,2-dichloroisocyanuric s. Chemical Reviews. 1966. V. 66. N 2. 161-197; A. N. Mirkova, G. G. Levkovskaya, M. G. Voronkov. WPI. THE USSR ACADEMY OF SCIENCES. Ser. chem. 1981. Vol. 6. C. 1349-1353].

As a result of implementation of the present invention are achieved the following benefits:

1. Derived new chemical compounds, derivatives of 1-methyl-5-chloropyrazole, promising biologically active substances and technically valuable products, intermediates for their synthesis.

2. The proposed method is simple to perform, requires no special equipment, pressure, heat, expensive solvents.

3. The selection of target products of high purity is easily known techniques.

4. The process is stable and well played.

5. The single-stage process.

6. Formed simultaneously with the target products Trimethylhydrazinium - crystalline, water-soluble Quaternary salt of dimethyl, of which dimethyl may be regenerated at the same time Trimethylhydrazinium may find further application in other processes, as well as in agriculture, because it is a system of soil fungicide.

7. The method is based on the available raw material: 2,2-dichlorovinyl the situation atilov, chloride vinylidene and aluminum chloride, to obtain the alkyl-, aryl-, chloroalkyl, perftorgeksilsilanami with a good yield [A. S. Atavin, A. N. Mirkova, G. G. Levkovskaya. W ORH.1994. T. 9. 3. C. 318-321; A. E. Pohland, W. R. Benson. Chem. Reviews. 1966. V. 66. N 2. R. 161-197].

8. Products are formed one isomeric composition.

Thus, a number of new derivatives of 1-methyl-5-chloropyrazole and proposed a new one-step method for the synthesis of derivatives of 1-methyl-5-chloropyrazole, based on available and large industrial raw materials that do not require special equipment, catalysts, simple in execution, which can be easily implemented on an industrial scale.

1. Derivatives of 1-methyl-5-chloropyrazole General formula

< / BR>
where R is CH2Cl, CF3, 4-lC6H4, 3-NO2C6H4.

2. The method of obtaining derivatives of 1-methyl-5-chloropyrazole formula

< / BR>
where R is CH3WITH2H5WITH3H7CH2CL,CF3WITH6H5, 4-lC6H4, 3-NO2C6H4, characterized in that the corresponding derivative of 2,2-dichloroaniline formula

RC(O)CH=CCl2,

where R is wytestone in the environment of an organic solvent at room temperature for 0.5 - 12 o'clock

 

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The invention relates to medicine, namely to surgery, and is intended for antibacterial protection anastomoses in the bowel resections

The invention relates to new derivatives of benzoxazinone General formula (I), where R1means N or carboxyethyl, R2represents hydrogen or alkyl, and R3is a different derivatively of amino acids, dipeptides and hydrazones acid groups, respectively, their conjugates with active substances, such as residues from a number of penicillin

The invention relates to pharmaceutical industry and relates to drugs used in obstetric practice for the treatment and prevention of infectious and inflammatory diseases and dysbacteriosis
The invention relates to medicine, specifically to a pharmaceutical composition having antimicrobial activity comprising as active principle an effective amount sulfalena and targeted supplements, which are used potato starch and/or corn, oxypropylation, magnesium stearate and/or calcium

The invention relates to organic chemistry and relates to pharmacologically active substances, namely new 1-isopropyl-2-formyl-3-aminopyrrolidine possessing anti-inflammatory, analgesic, antipireticescoe and antihypoxic activity with low toxicity, does not irritate the gastrointestinal tract and not oppressive blood

The invention relates to medicine, namely to drugs with antitumor activity
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