The dihydrate sodium salt of 3-chloro-2 - oxo-4 - hydroxy-5 - alkylamino-1,3,5-triazine, showing sporicidal activity


C07D251/26 - with only hetero atoms directly attached to ring carbon atoms

 

(57) Abstract:

The inventive product-dihydrate sodium salt of 3-chloro-2-oxo-4 - hydroxy-5 - alkylamino -1,3,5-triazine f-ly I, where R is CH3or C2H5. Reagent 1: cyanuric chloride. Reagent 2: alkylamine. Reaction conditions: aqueous or aqueous organic medium at 10 and 5C. the Alkaline hydrolysis product of amination. Reagent 3: gaseous chlorine. Reagent 4: caustic soda. The compound is well soluble in water, has high stability in aqueous solutions and has sporicidal activity. table 4. Connection structure of f-crystals I:

The invention relates to new chemical compounds, specifically to N-chloramination SIMM. triazine, which can find use as a disinfectant and sterilizing tools in various fields of national economy.

The most traditional disinfectants are hypochlorites and chloramines. Hypochlorites have a broad spectrum of antimicrobial activity, but they are not stable, especially in acidic and neutral environments, have irritating and corrosive action. In toxicity studies hypochlorites can be used for disinfection Graysville and acceptable for disinfection are monochloramine-B and sodium salt of dichloroisocyanuric acid (PA-Sol THICK). Monochloramine B contains a low percentage of active chlorine (26%). When the skin monochloramine B causes a slight allergic reaction (itching, peeling skin). In addition, the monochloramine B not active and has sporicidal action only at a concentration of 5-10% (as active chlorine). At a concentration of 0.2-0.5% (as active chlorine) aqueous solutions of monochloramine B are used for disinfection of various objects. To increase the activity of aqueous solutions of monochloramine require additional activation immediately before use by acidification or by the introduction of ammonium salts or aqueous ammonia.

However, acidification and activation of aqueous solutions of monochloramine B unstable.

The closest in structure and properties to the new chloramines are Na-salt THICK exhibiting a wide spectrum of antimicrobial action. Na-salt THICK as trichloroisocyanurate and dichloroisocyanurate acid has a high bactericidal and sporicidal activity and is far superior sporicidal activity of chloramine B, bleach and two-thirds of the basic salt of calcium hypochlorite. So spores anticaida die in 0.1% solution, and E. coli in 0.004 solutions during storage even when the pH of 6-6,6, irritates skin and mucous membranes.

The objective of the invention is the development of new water-soluble chloramines with strong resistance in the form of aqueous solutions in combination in disinfecting and sterilizing activity.

This object is achieved by new connections dihydrate sodium salt of 3-chloro-2-oxo-4-hydroxy-5-alkylamino-1,3,5-triazine of the formula

< / BR>
where R is CH3- C2H5- high stability in aqueous solutions and manifesting sporicidal activity.

New chloramines receive from the available domestic raw materials: cyanuric chloride, alkylamino chlorine.

Way to obtain is in the interaction of cyanuric chloride with alkylamines followed in aqueous or aqueous-organic medium at a temperature of 10 5aboutC and a molar ratio of 1:1, in the subsequent alkaline hydrolysis of the product of the amination, the chlorination product of hydrolysis in aqueous-alkaline medium with gaseous chlorine and the subsequent interaction of the obtained bleach with equimolar amounts of caustic soda.

P R I m e R 1. Getting dihydrate sodium salt of 3-chloro-2-oxo-4-hydroxy-5-methylchloride-1,3,5-triazine (Na-salt MGHMX).

oncol and refrigerator, put 73,6 g (0.4 mol) of cyanuric chloride dissolved in 400 ml of acetone. At a temperature of 10 5aboutWith added 13 g (0.4 mol) of methylamine (or the appropriate amount of the aqueous solution) and then under stirring at the same temperature was added 300 ml of an aqueous solution containing of 21.2 g (0.2 mol) sodium carbonate or 13 g (0.4 mol) of methylamine taken as an acceptor of hydrogen chloride. The reaction is complete at pH 7. The reaction mass is diluted with water in the ratio 1:2. The obtained precipitate was separated by filtration, wring out and transferred in the form of a wet paste or powder flask 1000 ml Add to the flask 600 ml of 50% aqueous sodium hydroxide solution, stirred and incubated the mixture for a period of not more than one hour at a temperature of 90 5aboutC, then cooled to room temperature (20 5aboutC) and transferred into a flask XLERATOR equipped with a mixer with stopper, thermometer, bubbler and drain tube. In charator put an additional 300 and 10% aqueous sodium hydroxide solution and serves chlorine gas for 2-3 hours, keeping the temperature 25 5aboutC. during the chlorination reaction mass is dissolved, then the solution stands out sediment, while the pH in the reaction mass changes from in a drying Cabinet at a temperature of 40 50aboutC.

Get up to 50 g of a white powder with a yield up to 70% in terms of cyanuric chloride. The resulting powder 3-chloro-2-oxo-4-oxymetholone-1,3,5-triazine. Then in a round bottom flask with a capacity of 250 ml, equipped with a stirrer with stopper, thermometer, dropping funnel and air refrigerator, placed 42 g (0.2 mol) of chloramine MAGICK in 35 ml of water and with stirring was added dropwise 15 ml of an aqueous solution containing 8 g (0.2 mol) sodium hydroxide at room temperature for 0.5 hours the precipitate is separated, press on the filter and dried in air. From the filtrate allocate an additional amount of product. Total yield dihydrate sodium salt of 3-chloro-2-oxo-4-hydroxy-5-methylchloride-1,3,5-triazine (Na-salt MAGICK) is 43.5 g, which in terms of cyanuric chloride is 82%

Calculated With 17,85; N 2,66; N 20,82; Cl 26,36; Na 8,55; Clact52,72.

C4H3N4Cl2NaO2.2H2O

Found, 18,23; 18,13; N 2,41; 2,44; N 19.93 Per; 20,25; Cl 25,84; 26,08; Na 8,53; 8,54; Clact52,47; 52,16.

P R I m m e R 2. Getting dihydrate sodium salt of 3-chloro-2-oxo-4-hydroxy-5-ethylchloride-1,3,5-triazine (Na-salt ECHECK).

In a round bottom flask is placed 73,6 g (0.4 mol) of cyanuric chloride dissolved in 400 ml of acetone. is the target), then add 300 ml of an aqueous solution containing of 21.2 g (0.2 mol) sodium carbonate or 18 g (0.4 mol) of ethylamine, taken as an acceptor of hydrogen chloride. The reaction is complete at pH 7. The reaction mass is diluted with water in the ratio 1:2 and the formed precipitate was separated by filtration, wring out and paste or dried product is transferred into a round bottom flask with a capacity of 1000 ml flask additionally placed 600 ml of 5% aqueous sodium hydroxide solution and incubated the reaction mixture for a period of not more than one hour at a temperature of 90 5aboutC.

The hydrolysis product is cooled to 25 5aboutWith optionally placed in a reaction flask of 300 ml of 10% aqueous sodium hydroxide solution and glorious gaseous chlorine in 2-3 hours, keeping the temperature 25 5aboutC, while the pH in the reaction mass changes from 12 to 3. The formed precipitate was separated by filtration, slightly washed with water, squeezed and dried. Get white powder with a yield up to 70% in terms of cyanuric chloride. The resulting powder 3-chloro-2-oxo-4-hydroxy-5-ethylchloride-1,3,5-triazine (chloramine ECHECK) with a content of active chlorine 49 0,5% Then in a round bottom flask with a capacity of 250 ml is placed 45 g (0.2 mol) of chloramine ECHECK in 30 ml of water and when premesis is of 0.5 hours The obtained precipitate was separated by filtration, squeezed and dried in the air or at a temperature of 40-50aboutWith in a drying Cabinet. From the filtrate additionally produce chloramines. The total yield of Na-salt ECHECK is 40 g, which in terms of cyanuric chloride up to 70%

Calculated With 21,21; N 3,18; N 19,80; Cl 25,06; Na 8,13; Clact50,12.

C5H5N4O2Cl2Na 2.H2O

Found, 21,40; 21,79; N 3,48; To 3.64; N 19,59; 19,65; Cl 24,80; 25,00; Na 8,20; Of 7.90; Clact49,85; 50,25.

Physico-chemical properties of new chloramines are presented in table.1-3.

New chloramines, well dissolved in aqueous media, have a high resistance in long-term storage compared to Na-salt THICK.

The data presented in the table.3 show that the new chloramines significantly superior in durability in aqueous solutions structural analogue (prototype).

Aqueous solutions of monochloramine B (one of the most acceptable and known disinfectants) is stable for 15 days in accordance with the "guidelines on the use of chloramine for disinfection purposes" N 1359-75 from 21.10.75 year. However, aqueous solutions of monochloramine B activated amine compounds is whether MDCK and Na-salt of ADHCA.

Assessment of irritating properties hold when applied to the bare skin of rabbits powders of salts or their aqueous solutions (2-4% active chlorine) when three-time applications (for the relevant procedure. Methods for determining the toxicity and hazards of chemicals. Ed. by I. C. of Spackage. M. Medicine, 1970).

The tests were carried out in comparison with the Na-salt of dichloroisocyanuric acid (THICK). Triple coating on the bare skin of rabbits new chloramines in the form of powder or in an aqueous solution, does not lead to any change in the skin, while the Na-salt THICK in aqueous solution with a concentration of 2% (as active chlorine) causing redness of the skin after the first application.

Thus, the assessment of the inventive compounds showed that they do not have a pronounced irritant effect on bare skin.

P R I m e R 4. The definition of sporicidal activity of new chloramines.

Antimicrobial activity and disinfectant properties of sodium salts of alkylchlorosilanes acids evaluated in accordance with the methods recommended in the "Instructions to determine the bactericidal properties of new disinfectants" N 739-68. The quality of the detergent and 4% chloramine B, activated ammonium sulfate. Pre-cooked cambric test objects by size h mm containerbase spore suspension culture B. anthrcoides. After 20 minutes of exposure at room temperature of the test object remove excess slurry and dried them in thermostat at 37aboutC for 20 min In freshly prepared 4% solutions of the studied substances were immersed in 2 of the test object at each exposure. For comparison sporicidal action took subjects in the practice of 6% hydrogen peroxide, 0.5% detergent and 4% chloramine B, activated ammonium sulfate. To control contamination spore culture two contaminated test object immersed in tap water for a maximum period of exposure.

After various exposures (from 15 to 150 min) test objects to neutralize the chlorine washed in 0.5% sodium hyposulphite and tap water. Sowing the test object (test and control) were produced in the broth of Hottinger at pH of 7.2, followed by incubation at a temperature of 37aboutC. analysis was carried out daily for 7 days. To study changes in the activity sporicidal action 4% solutions of the studied drugs was performed EN the NCA efficiency sporicidal action standard and declare chlorine-containing substances are presented in table.4.

The table shows that among the freshly prepared solutions of the most effective is 4% activated chloramine B. the Claimed preparations Na-salt MDHC and Na-salt ETHIC without activation have sporicidal action is similar to that of 6% hydrogen peroxide. However, after 1-day storage in a dissolved state, all drugs both standard and claimed, gave almost the same effect. It should be emphasized that the claimed drug activity will be maintained for not less than one month of storage, as stored content of active chlorine constant during this time, while activated chloramine B and hydrogen peroxide activity in time is significantly reduced.

Thus, the tests showed that the new claimed chloramines Na-salt MTHCA and Na-salt ADHC have a high resistance in the form of aqueous solutions, do not irritate bare skin and exhibit high sporicidal activity no additional activity of aqueous solutions.

The dihydrate sodium salt of 3-chloro-2-oxo-4-hydroxy-5-alkylamino-1,3,5-triazine of General formula

< / BR>
where R is CH3or C2H5,

showing sporicidal activity.

 

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