Method for producing tetra (1-vinylimidazole)cabalt dichloride
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a method for preparing compendial tetra(1-vinylimidazole)cobalt dichloride (Cobazol). The method involves a reaction of 1-vinylimidazole and cobalt dichloride in the molar relation of 1-vinylimidazole: CoCl2·6H2O = 4:1 at room temperature. The process is carried out in an aqueous medium at the concentration of 1-vinylimidazole 20-45%. A cobalt dichloride salt is introduced in the form of a solid crystalline hydrate added to a ligand solution in portions. The reaction is conducted for 3-8 hours. The end product is purified by water stripping in vacuum and then air elimination.
EFFECT: invention enables considerably reducing production costs, providing higher production and ecological safety with preserving higher yield of the compendial preparation Cobazol.
The invention relates to the field of chemistry of the coordination metal complex compounds, specifically to improvements in the method of producing metal complex of Tetra-(1-vinyl-imidazole)cobalticyanide (drug kobazol"®, a trademark No. 209159, "cobazol"®, a trademark No. 209160)with gemostimuliruyuschee, immunomodulatory and antibacterial action.
We propose a new method of obtaining complex compounds of cobalticyanide with 1-vinylimidazole - Tetra(1-vinylimidazole)cobalticyanide on the basis of which the previously developed a new medicinal cobalt-organic preparation Kobazol, which is an effective stimulator of hematopoiesis wide spectrum of action, as well as immunomodulatory and antibacterial agent (VFS on substance No. 42-28-86-97 and lectora No. 42-28-87-97, RF Patent 2157813). The way to get Tetra(1-vinylimidazole)cobaltichloride, characterized in that the reaction of 1-vinylimidazole with cobalt dichloride is carried out in water, adding to the solution of 1-vinylimidazole with a concentration of 20-45% of hydrated cobalt dichloride in dry form, and achieve high yield (99%) of high-purity Pharmacopeia drug Kobazol.
The advantage of the proposed method is that it allows you to increase the efficiency of the process and, therefore, reduce the loss of reagents when an appreciable reduction in the time of synthesis. The technical result is a substantial reduction in production costs, the simplification and cheapening of the process in achieving a high yield of high-purity Pharmacopeia drug Kobazol.
Was previously briefly described the synthesis of a complex of Tetra(1-vinylimidazole)cobalticyanide exit 81% mix of ethanol solutions of 1-vinylimidazole and cobalt chloride CoCl2·6N2About at room temperature [Vol, Mr Ivanov, Dneprov, Engracia. Joh. 1979. V.49. No. 3. S-650]. In the work does not provide a specific number of used reagents and solvent (ethanol), and reaction time. The resulting complex was purified by consecutive washing it with ethanol, ether (many times) and dried in vacuum.
There is also known a method of producing Tetra(1-vinylimidazole)cobalticyanide interaction anhydrous cobalt dichloride (14.3 g, 110 mmol) in an organic solvent (solvent not specified) with 1-vinylimidazole (4 g, 42.6 mmol) at room temperature (Patent RF №2157813). In these conditions was obtained 5.36 g (yield 99%) of the target complex. In the patent there is no data about how were isolated and purified complex of cobalt dichloride, which was used in this experience a 10-fold excess. In an earlier patent (Patent RF №565506) synthesis of Tetra(1-vinylimidazole)cobalticyanide carried out by mixing 1-vinylimidazole (4 g, 426 mmol) acetone solution of dichloride cobalt (38 g, 293 mmol) at room temperature. The product was purified by recrystallization from acetone. The obvious disadvantages of this method are the high consumption of cobalt salts, the need for recrystallization of the target product, the use of large quantities of flammable organic solvent (acetone).
It was mentioned that the reaction of 1-vinylimidazole with cobalt dichloride (room temperature, 24 h) in water leads to Tetra(1-vinylimidazole)cobalticyanide low output [GOV, Essmann, Uniview, Ann, Vigoroth, Wasmachine. Complexation of 1-vinylation with the chlorides of manganese, iron, cobalt and copper. Joh. 1972. V.42. No. 3. S-599]. Mandatory details of the experiment, which is necessary to qualify this information as a way to generate (i.e. number of initial reagents and solvent, the method of isolation and purification of the target product and its output)is not specified.
Listed well-known ways of getting Kobazol have significant shortcomings. This is either the use of flammable, toxic solvents, or not a high yield of target product, which leads to low efficiency of the process and, as a consequence of the high production costs.
We propose a new simple and cheap way to get pharmacopoeial Koba the Ola high yield (up to 99%).
The technical object of the present invention is simpler, cheaper and safer get the Pharmacopoeia Kobazol at room temperature (20-25°C) as due to the exclusion of organic solvents and changes in the conditions of complex formation, and due to the more complete extraction of the resulting product from the reaction mixture.
The problem is solved by the use in the synthesis of Tetra(1-vinylimidazole)cobalticyanide aqueous solutions of 1-vinylimidazole with a concentration of 20-45%, at a molar ratio of 1-vinylimidazole: CoCl2·6H2O, is equal to 4:1. The use of aqueous solutions of 1-vinylimidazole specified concentration provides a high reaction rate. In addition, in each of the above methods for producing complex Tetra(1-vinylimidazole)cobalticyanide reaction has introduced pre-dissolved in an organic solvent or in water salt dichloride cobalt (anhydrous or hydrated). In our proposed method, the salt enters the reaction in solid form, which also provides a high reaction rate due to the greater concentration of the source. The reaction is carried out at room temperature for 3-8 hours. This method provides almost complete release of the formed complex (Kobazol) in the form of sediment on the next filtering which leads to obtain the desired product in high yield (90%). Applying the same procedure of distillation of water at the stage of selection of the target product allows you to achieve a practically quantitative yield of Kobazol (99%).
Further increasing the concentration of aqueous solutions of 1-vinylimidazole significantly hampers the process due to the increased viscosity of the reaction mixture and lengthens the duration of the synthesis, 8 a.m. to 12 p.m.
Physico-chemical parameters of selected samples of the preparation meet these specifications by VFS to the substance of Kobazol (No. 42-28-86-97).
The following non-limiting examples illustrate the present invention:
Example 1. To a solution of 1-vinylimidazole (1.58 g, 16.8 mmol) in water (6.3 ml, which corresponds to a concentration of 1-vinylimidazole 20%) at 20-25°C and stirring was added in small portions CoCl2·6H2O (1.00 g, 4.2 mmol). The reaction mixture is stirred for 3 hours the precipitate lilac is filtered off (the filtrate 5.5 g), dried in vacuum (2-3 mm Hg) and obtain 1.43 g (68%) of the complex of Tetra(1-vinylimidazole)cobalticyanide with TPL 161-162°C. Found, %: C, 47.82; H, 4.48; Cl 14.33; Co 11.73; N 22.27; C20H24Cl2CoN8Calculated, % C, 47.49; H, 4.98; Cl 14.00; Co at 11.64; N 22.13.
Example 2. To a solution of 1-vinylimidazole (1.58 g, 16.8 mmol) in water (4.0 ml, the concentration of 1-vinylimidazole 28%) at 20-25°C and stirring was added in small portions CoCl2·6H2O (1.00 is, 4.2 mmol). The reaction mixture is stirred for 4 hours the precipitate is filtered off (the filtrate 3 g), dried in vacuum (2-3 mm Hg) and obtain 1.71 g (82%) of the complex of Tetra(1-vinylimidazole)cobalticyanide with TPL 161-162°C. Found, %: C 48.10; N, 5.20; Cl 14.16; 11.26; N 21.97. C20H24Cl2CoN8. Calculated, % 47.49; N, 4.98; Cl 14.00; Co at 11.64; N 22.13.
Example 3. To a solution of 1-vinylimidazole (1.58 g, 16.8 mmol) in water (1.9 ml, the concentration of 1-vinylimidazole 45%) at 20-25°C and stirring was added in small portions CoCl2·6H2O (1.00 g, 4.2 mmol). The reaction mixture is stirred for 8 hours the precipitate is filtered off (the filtrate 1.2 g), dried in vacuum (2-3 mm Hg) and obtain 1.92 g (90%) of the complex of Tetra(1-vinylimidazole)cobalticyanide in the form of a powder lilac with TPL 161-162°C. Found, %: C 47.70; H, 5.01; Cl 14.24; 11.69; N 21.92. C20H24Cl2CoN8. Calculated, % 47.49; N, 4.98; N 22.13; Cl 14.00. Co at 11.64.
Example 4. To a solution of 1-vinylimidazole (1.58 g, 16.8 mmol) in water (1.9 ml, the concentration of 1-vinylimidazole 45%) at 20-25°C and stirring was added in small portions CoCl2·6H2O (1.00 g, 4.2 mmol). The reaction mixture is stirred for 8 hours At the end of the reaction the reaction mixture is distilled water under vacuum (2-3 mm Hg). The residue is dried in vacuum (2-3 mm Hg) and obtain 2.11 g (99%) of the complex of Tetra(1-vinylimidazole)cobalticyanide in the form of p the Rosca lilac with TPL 161-162°C. Found, %: 47.50; H 4.93; Cl 14.49; 11.43; N 21.62;. C20H24Cl2CoN8. Calculated, % 47.49; N, 4.98; Cl 14.00; Co at 11.64; N 22.13;
Infrared spectra obtained by this technique the sample Kobazol identical position and intensities of the bands with absorption bands of the spectrum of the control sample.
Thus, it was found that the complex of Tetra(1-vinylimidazole)cobalticyanide (Kobazol) can be obtained much more simple, economical and safe method compared to previously known methods. Implementation of the proposed method on an industrial scale will exclude from the process flammable organic solvents (ethanol, acetone, ether), to eliminate stage washing of the final product with organic solvents, which leads to the inevitable contamination of the product with trace amounts of these solvents and reduces its pharmacopoeial quality. This Pharmacopoeia purity of Kobazol and its high output is achieved at a significant cost reduction, time saving and improving industrial and environmental safety.
1. GOV, Essmann, Uniview, Ann, Vigoroth, Wasmachine. Complexation of 1-vinylation with the chlorides of manganese, iron, cobalt and copper. Joh. 1972. V.42. No. 3. S-599.
2. Val is s, Mr Ivanov, Dneprov, Engracia. Complexation of cobalt chloride(II) with N-vinylimidazole. Joh. 1979. V.49. S-650.
3. RF patent №2157813. The means with erythropoeisis stimulating, immunomodulatory and antibacterial effect. (C07F 15/06, A61K 31/4164, A61P 7/06, A61P 37/02, A61P 31/04) Bakalova L.V., Domnina Y.S., Trofimov B.A., Kulinich, S., Kolesnikov, Tareeva E.V. // BI. 2000. No. 29.
4. RF patent №565506. Tetra-(1-vinylimidazole)-cobaltichloride as a stimulator of erythropoiesis. (C07F 15/06, C07D 233/58) Voronkov, M.G., Skvortsova GG, Domnina Y.S., Ivlev, Y., Lazarev D.N., Yanovsky S.M., Kugushev S.A., Alekhin E.K., Tropinina E.N. // BI 1996.10.11.
The method of obtaining pharmacopoeial Tetra(1-vinylimidazole)cobalticyanide (Kobazol) interaction of 1-vinylimidazole with cobalt dichloride in a molar ratio of 1-vinylimidazole: CoCl2·6N2O=4:1 at room temperature, wherein the process is carried out in aqueous medium at a concentration of 1-vinylimidazole 20-45%, and a salt of cobalt dichloride is injected in the form of solid hydrated, adding portions to a solution of the ligand, the reaction is carried out within 3-8 h, purification of the finished product is carried out by distillation of the water in vacuum with subsequent degassing.
SUBSTANCE: invention relates to a cobalt complex with a modified phthalocyanine ligand which is covalently bonded with silica gel and has the following general formula: , where: R=Cl, NHAlk, NAlk2, n = 5-7, M = Co. Also disclosed is a method for valence isomerisation of quadricyclane in norbornadiene in the presence of the complex.
EFFECT: invention enables to obtain a cobalt complex with a modified phthalocyanine ligand, which can be used as a heterogeneous catalyst having high activity and high stability.
3 cl, 1 tbl, 29 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine and chemical-pharmaceutical industry, namely industrial chemistry, and concerns a method for preparing octa-4,5-carboxyphthalocyanine sodium salt (a substance of the preparation teraphthal).
EFFECT: method provides preparing high-purity octa-4,5-carboxyphthalocyanine sodium salt free from residual low-molecular impurities, oligomer products and residual chlorides, reducing the labour content of production, and increasing yield.
SUBSTANCE: invention discloses an alkylation composition which is characterised by that it contains a cobalt complex, as well as a method for detoxification of a harmful compound, characterised by that a harmful compound containing at least one element selected from a group comprising arsenic, antimony and selenium is detoxified through alkylation in the presence of the disclosed composition.
EFFECT: obtaining novel compounds.
27 cl, 10 ex, 11 tbl
SUBSTANCE: invention relates to stable complexes consisting of metal oxides - iron, cobalt or alloys thereof in form of nanoparticles and bifunctional compounds, where the bifunctional compounds are selected from thiols, carboxylic acids, hydroxamic acids, phosphoric esters or salts thereof, having an aliphatic chain containing a second functional group in the terminal position ω, which can be used in certain novel hydrophilic plates and fibres, as well as a method of producing complexes. The method involves reaction of dispersion of said nanoparticles in an organic solvent with a suitable binder. The mixture is stirred for several hours at low temperature and the obtained product is then cooled and separated by centrifuging, and can then be cleaned via repeated dispersion in a suitable solvent and repeated deposition.
EFFECT: novel complexes with improved solubility in water-alcohol medium are obtained.
13 cl, 3 dwg, 9 ex
SUBSTANCE: invention relates to a method of producing bis(3,6-di(tert-butyl)benzosemiquinolates-1,2) of cobalt (II) or manganese (II) or nickel (II), of general formula: M(SQ)2 , where: SQ is 3,6-di(tert-butyl)benzoquinolate-1,2, and M = Mn(II) or Co(II) or Ni(II). The method is characterised by that a disubstituted salt of an alkali metal salt and 3,6-di(tert-butyl) pyrocatechol-1,2 is obtained, followed by reaction thereof with 3,6-di(tert-butyl)benzoquinoline-1,2. The formed 3,6-di(tert-butyl)benzosemiquinolate-1,2 of the alkali metal reacts with a Co(II) or Mn(II) or Ni(II) halide in an inert atmosphere in tetrahydrofuran.
EFFECT: simple synthesis of bis-semiquinolates of metals.
4 cl, 5 ex
FIELD: information technology.
SUBSTANCE: article with an image includes a substrate having a masked or concealed protective image on at least part thereof, which reflects less than 50% of radiation at wavelength 800-900 nm. The protective image contains an infrared radiation absorbing compound selected from:
or salt or polymer thereof, where M is a metal selected from iron, cobalt, nickel, aluminium, scandium, chromium, vanadium, titanium, manganese and lanthanide. R1 is selected from hydrogen, phosphonate, sulphonate, nitro, halogen, cyano, thiocyano, thioalkyl, thioaryl, alkyl, alkoxy, aryl, aryloxy, amine, substituted amines and substituted aryl. One of R2 and R3 is oxygen and the other is NO; n is a number corresponding to half the coordination number of metal M; each of L and L' independently denotes a ligand which forms a complex with metal M, and y is a number which corresponds to the coordination number of metal M. The infrared radiation absorbing compound does not form an intensely coloured protective image, and the protective image is pale, colourless or tinted. The invention also discloses a method of making the article with the image, using the compound and a method of authenticating the said article.
EFFECT: obtaining a protective image which can reflect less than half the light at 800-900 nm, and a protective image which is not intensely coloured.
14 cl, 35 ex, 4 tbl
SUBSTANCE: invention relates to novel derivatives of 1-allylimidazole with metal salts , where R denotes allyl, E denotes a metal, e.g. Zn (II) or Co (II), An denotes chlorine or acetate, n equals 2.
EFFECT: novel 1-allylimidazole derivatives having antihypoxic activity are obtained.
1 cl, 7 tbl, 2 ex
SUBSTANCE: described is a novel compound - 1-acetyl-5,10-dioxy-5,10-dihydro-2H-anthra[2,3-D][1,2,3]triazole-7,8-dicarboxylic acid of formula , which can be used as a starting compound in synthesis of metal complexes of tetra[4,5]([6,7]1-acetyl-2H-naphtho[2,3-D][1,2,3]triazole-5,8-dione)phthalocyanine.
EFFECT: possibility of use as dyes or catalysts.
1 cl, 3 ex, 4 dwg, 1 dwg
SUBSTANCE: invention relates to tetra[4,5]([6,7]1-acetyl-2H-naphtho[2,3-D][1,2,3]triazole-5,8-dione)phthalocyanines of copper and cobalt of formula , where M denotes Cu and Co.
EFFECT: invention enables to obtain novel derivatives of phthalocyanines which can be used as dyes, as well as catalysts for various processes.
2 ex, 6 dwg
SUBSTANCE: invention relates to tetra-(5-acetylamino-7-heptyloxy)anthraquinonoporphyrazines of copper and cobalt of formula .
EFFECT: obtained compounds can be used as dyes and catalysts.
4 ex, 5 dwg,
SUBSTANCE: invention relates to veterinary science. A method involves in the fact that intramuscular injections of ferroglucinum 150 mg twice every four days are combined with crezacin 4 mg/kg a day of fed-on plan in the morning for 5 days and intramuscular injections of gamavit 0.03 ml/kg once a day in the morning for 5 days.
EFFECT: method enables normalising spontaneous erythrocyte aggregation in piglets, sanitising seed stock, reducing death loss, providing higher weight gain and high-quality meat products.
SUBSTANCE: invention relates to veterinary science. A method involves the use of intramuscular injections of ferroglucinum 75 mg at 15 mg of iron per 1 kg of calf's body weight, once in a combination with feeding of glycopine 6.0 mg/day in the morning for 6 days starting simultaneously with injections of ferroglucinum 75.
EFFECT: method is high-effective in correction of blood antithrombin III activity.
1 dwg, 3 ex
FIELD: veterinary medicine.
SUBSTANCE: calves are injected intramuscularly as a single dose the solution of ferroglucine-75 on the basis of 15 mg of iron per 1 kg of live weight of a calf, and glicopin is fed 6.0 mg/day in the morning for 6 days, starting simultaneously with the injection of ferroglucine-75.
EFFECT: method enables to normalise the antioxidant activity of the liquid part of the blood of newborn calves with iron deficiency anemia, to increase the reactivity of the animal organism, to reduce the risk of thrombotic complications, promotes normal growth and development of calves.
SUBSTANCE: invention relates to field of veterinary. Method includes introduction of ferroglucinum-75 solution in dose 15 mg of iron per 1 kg of live weight of calf body, one time, intramuscularly and drinking of glicopin in dose 6.0 mg/day is the morning during 6 days, starting simultaneously with injection of ferroglucinum.
EFFECT: method makes it possible to stably normalise thrombotic hemostasis in newborn calves with iron-deficient anemia, ensures long-time support of thrombotic hemostasis in optimal mode of functioning, excludes risk of thrombotic complications and assists normal growth and development of calves.
SUBSTANCE: invention relates to field of veterinary. Method includes introduction of ferroglucinum-75 in dose 15 mg of iron per 1 kg of live weight of calf intramuscularly, one time and drinking of glicopin in dose 6.0 mg/day is the morning during 6 days, starting simultaneously with injection of ferroglucinum.
EFFECT: claimed method makes it possible to avoid vascular complications in newborn calves with iron-deficient anemia, make the herd healthier, reduce murrain, increase volume and quality of obtained meat and milk production, obtain healthy offspring from the animals.
SUBSTANCE: present invention provides water-soluble iron-carbohydrate derivative complexes which are suitable for the therapy of iron deficiency states, and the preparation thereof, medicaments comprising them, and the use thereof in the prophylaxis or therapy of iron deficiency states. The medicaments are suitable in particular for parenteral administration. A water-soluble iron-carbohydrate derivative complex obtained from the reaction of an aqueous iron (III) salt solution and (b) an aqueous solution of the product of the oxidation and subsequent derivatization of one or more maltodextrins, wherein the oxidation is carried out with an aqueous hypochlorite solution at a pH value in the alkaline range, wherein when one maltodextrin is used its dextrose equivalent is from 5 to 20 and when a mixture of a plurality of maltodextrins is used the dextrose equivalent of the mixture is from 5 to 20 and the dextrose equivalent of the individual maltodextrins in the mixture is from 2 to 40, and the subsequent derivatization is carried out with a suitable reagent. The process for the preparation of the iron-carbohydrate complex, wherein one or more maltodextrins is oxidized in aqueous solution, at an alkaline pH value, with an aqueous hypochlorite solution, the subsequent derivatization is carried out with a suitable reagent, and the resulting solution is reacted with the aqueous solution of an iron (III) salt, wherein when one maltodextrin is used its dextrose equivalent is from 5 to 20 and when a mixture of a plurality of maltodextrins is used the dextrose equivalent of the mixture is from 5 to 20 and the dextrose equivalent of the individual maltodextrins in the mixture is from 2 to 40.
EFFECT: most derivatised maltodextrin ligands exhibit increased stability towards enzymatic degradation by amylase as compared with underivatised maltodextrin, which can promote retarded and uniform degradation of the iron-maltodextrin derivative complexes according to the invention in the body.
15 cl, 11 tbl, 45 ex
SUBSTANCE: invention refers to binuclear cation nitrosyl iron complexes with natural aliphatic thiolyls with general formula [Fe2(SR)2(NO)4]SO4 where R is aliphatic ligands of natural origin.
Also there is proposed method for production of binuclear cation nitrosyl iron complex, nitrogen monoxide donor, inductor of tumor cells apoptosis, application binuclear cation nitrosyl iron complex, pharmaceutical composition and set used for treatment of oncology diseased. The technical result is EFFECT: production of binuclear cation nitrosyl iron complex possessing cytotoxic, apoptotic and NO-donor activity.
15 cl, 2 ex, 4 tbl, 7 dwg
SUBSTANCE: invention refers to binuclear nitrosyl iron complexes with benzazeheterocyclic derivatives with general formula [Fe2(SR)2(NO)4] where R is And where X is NH, S, R1 is lower alkyl. Also there is proposed method for its production, nitrogen monoxide donor, application as oncology drug and for production of oncology drug, pharmaceutical composition and set used for treatment of oncology diseased.
EFFECT: production of binuclear nitrosyl iron complex that is used as an oncology drug with increased effectiveness and decreased toxicity.
15 cl, 3 ex, 4 tbl, 3 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of medicine and chemical-pharmaceutical industry, in particular, to medication, applied in case of myocardial infarction and operations on heart in conditions of artificial blood circulation. Water-soluble composition for intravenous introduction, contains ingredients with the following component ratio in wt %: D-glucose 23.40-28.60; potassium chloride 0.14-0.16; potassium salt of L-asparaginic acid 0.81-0.99; semi-magnesium salt of L-asparagenic acid (magnesium L-aspartate) 0.72-0.88; human insulin genetically engineered (in IU/l) 54.00-66.00; dinitrosyl complex of iron (II) with glutathione 0.19-0.23; water for injections - remaining part, with solution pH 7.4±0.1 at 22°C.
EFFECT: application of composition ensures limitation of myocardial infraction size, recovery of metabolic condition of heart at reperfusion, reduces injury of membranes of post-ischemic cardiomyocytes with smaller haemodinamics disorders as compared with traditionally applied medications.
2 dwg, 7 tbl, 4 ex
SUBSTANCE: invention relates to use of a tetranitrosyl complex of iron with thiophenol of formula [Fe2(SC6H5)2(NO)4] as an anti-tumour medicinal agent in order to prepare a medicinal agent for treating oncological diseases. The invention also relates to a pharmaceutical composition and a set containing said complex.
EFFECT: invention ensures high efficiency of treatment.
8 cl, 1 tbl, 1 ex
FIELD: pharmaceutical engineering; medical engineering.
SUBSTANCE: method involves carrying out nuclear magnetic resonance tomography of human or animal blood circulation system containing chelating ion complexes of bivalent and valence three paramagnetic metals of (I)X-L-Y formula, where X is the polyamide carbonyl ligand residue and Y is the gallic acid derivative, .
EFFECT: high accuracy of diagnosis.