RU2392969C1 - Method for preparing biocide agent - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical engineering, namely a method for preparing a biocide agent to be used in agriculture, veterinary science, and medicine. The method for preparing the biocide agent of polyhexamethylene guanidine hydrochloride is enabled by a reaction of dicyandiamide, ammonium chloride and hexamethylene diamine in the mole ratio 0.5:1.0:1.0 respectively at heating to 160°C, with hexamethylene diamine being preground at temperature 15-20°C, adding dicyandiamine and ammonium chloride, mixing a three-component mixture at the same temperature to completely indiscrete mass and heating up to prepare polyhexamethylene guanidine hydrochloride.

EFFECT: invention allows preparing purer product without afterpurification with using a simplified and effective method.

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Description

The invention relates to the field of organic chemistry, in particular to a method for producing polyhexamethylene guanidine hydrochloride - an effective disinfectant for use in various fields: medicine, veterinary medicine, agriculture and other sectors of the economy where biocidal preparations are required.

Polyhexamethylene guanidine was first synthesized in 1943 in the United States by 12-hour heating in an equimolar mixture of guanidine base with hexamethylene diamine at 130-180 ° C in an inert atmosphere; as a result of the reaction, the base of polyhexamethylene guanidine is formed and ammonia is released.

The disadvantage of the process is related to the difficult accessibility and thermal instability of the guanidine base, which leads to heterogeneity of the resulting polyhexamethylene guanidine, in the chain of which there are products of the destruction of guanidine.

Known methods for producing polyhexamethylene guanidine hydrochloride, which are based on the polycondensation of hexamethylene diamine with guanidine hydrochloride. Unlike the base of guanidine, guanidine hydrochloride is a stable substance, stable at high temperatures, necessary for the synthesis of polyhexamethylene guanidine hydrochloride. Guanidine hydrochloride is usually obtained by fusion of dicyandiamide with ammonium chloride according to the scheme:

Both starting materials are solid. At a temperature of 150-180 ° C, their mixture within 3 hours turns into a liquid melt of guanidine hydrochloride, which allows you to control the reaction process and establish its end. After cooling, guanidine hydrochloride solidifies in a solid crystalline mass, which is crushed and used in polycondensation with hexamethylenediamine.

Thus, the technological scheme of synthesis consists of two chemical stages:

1) a step for the synthesis of guanidine hydrochloride;

2) the stage of synthesis of polyhexamethylene guanidine hydrochloride.

A known method of obtaining a disinfectant (USSR author's certificate No. 1616898, C07C 279/00, A61L 2/16, 1990) by the interaction of hexamethylenediamine with guanidine hydrochloride.

The synthesis is as follows.

The mixture of dicyandiamide and ammonium chloride is maintained at 180 ° C for 2-2.5 hours until the mixture is completely melted. Get the reaction product - a melt of guanidine hydrochloride. The guanidine hydrochloride melt is poured into a reactor where the temperature is maintained at 180 ° C. The melt of hexamethylenediamine with a temperature of about 50 ° C is uniformly introduced into the melt of guanidine hydrochloride for 2.5 hours, after the introduction of hexamethylenediamine, the temperature is increased to 240 ° C and the reaction mass is maintained for 5 hours with continuous stirring. Get the target product with a yield of 98%.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process;

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride;

- the use of a sufficiently high synthesis temperature significantly complicates the process technology and its hardware design;

- preliminary melt of hexamethylenediamine;

- the target product is toxic due to contamination with its hexamethylenediamine, which is a toxic substance of the second hazard class.

A known method of producing a polymer of hexamethylene guanidine (USSR author's certificate No. 1808832, C08G 73/00, 1993) by the interaction of hexamethylene diamine and guanidine hydrochloride in a molar ratio (1.2-1.5): 1, respectively, for 10 hours at 150-160 ° C followed by cooling to obtain a foamy solid mass, grinding and washing with water.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process,

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride.

A known method of obtaining a disinfectant (RU, application for the invention No. 98103647, C07C 279/02, A61L 2/16, 1999) by the interaction of hexamethylenediamine with guanidine hydrochloride when mixed in a molar ratio of 1: 1 at a temperature of 120 ° C for 5 hours a subsequent increase in temperature to 150 ° C and heating at this temperature for 10 hours. The process is carried out in bulk of the starting components or in the presence of a solvent. Polyethylene glycol is used as a solvent. To obtain guanidine hydrochloride, guanidine carbonate is used as a starting product, which is treated with ammonium chloride immediately before the reaction with hexamethylene diamine.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process;

- the implementation of the process in the presence of a solvent leads to a complication of technology and instrumentation and the problem of disposal of wastewater.

A known method of obtaining a disinfectant (RU, patent No. 2039735, С07С 279/02, 1995) by the interaction of hexamethylenediamine with guanidine carbonate in a molar ratio at a temperature of 135-140 ° C until completion of carbon dioxide evolution. Polyhexamethylene guanidine carbonate obtained in the form of a foamed mass is removed from the reactor and ground.

To obtain polyhexamethylene guanidine hydrochloride, the obtained polyhexamethylene guanidine carbonate is dissolved with stirring in concentrated hydrochloric acid. After complete separation of carbon dioxide, a viscous solution of polyhexamethylene guanidine hydrochloride with a concentration of ≈75% is obtained.

If necessary, carry out additional cleaning. Dissolve the salt of polyhexamethylene guanidine in water (until a solution of 20-30% concentration is obtained), add an equimolar amount of caustic alkali, separate the insoluble base, wash it three times with water and add an equimolar amount of acid. The resulting salt is dried in air or in vacuum.

The disadvantages of this method are:

- the need for preliminary preparation of an intermediate component - polyhexamethylene guanidine carbonate, which increases the staged process;

- additional purification and washing of the target product entails the formation of large volumes of wastewater and the need for their disposal.

A known method of obtaining a disinfectant (RU, patent No. 2052453, C07C 279/02, 1996) by the interaction of the guanidine salt with hexamethylenediamine.

The synthesis is as follows.

A mixture of dicyandiamide with ammonium chloride (1: 2) is heated at 180-200 ° C for 2-3 hours. After complete melting, the mixture is poured into a metal glass, to which crystalline hexamethylenediamine is added in a molar ratio (1.0-1.5): 1.0, respectively. The condensation mixture is maintained at a temperature of 160 ° C and stirring for 5 hours until a transparent, uniform, viscous melt is obtained. After that, the temperature was raised to 180 ° C and the reaction mixture was kept at this temperature for 3 hours. The resulting melt is poured to harden on a baking sheet.

Thus obtained polyhexamethylene guanidine hydrochloride may contain up to 3-5% of unreacted starting hexamethylene diamine, which is a toxic substance.

To remove the starting hexamethylene diamine, the crude salt of polyhexamethylene guanidine is dissolved in hot water to obtain a 10-40% concentration, a concentrated alkali solution is added, the base is washed three times with water, concentrated hydrochloric acid is added until the solution reaches pH 5. A viscous clear solution is obtained containing polyhexamethylene guanidine hydrochloride ≈ 75% The content of toxic hexamethylenediamine does not exceed 0.1%.

The disadvantages of this method are:

- the process proceeds in two stages, carried out in two reactors, with the formation of an intermediate product, guanidine hydrochloride;

- obtaining the latter is carried out as an independent stage in a separate reactor and requires special equipment;

- the use of a sufficiently high synthesis temperature significantly complicates the process technology and its hardware design;

- the target product contains up to 3-5% of unreacted starting hexamethylenediamine, which is a toxic substance;

- the need for purification of the target product from the starting hexamethylenediamine leads to the formation of a large volume of wastewater and the need for their disposal.

A known method of producing a disinfectant (RU, patent No. 2122866, A61L 2/16, 2/18, C07C 279/00, 1998) by the interaction of dicyandiamide with hexamethylenediamine and hexamethylenediamine dihydrochloride.

Hexamethylene diamine dihydrochloride is prepared from hexamethylene diamine and hydrochloric acid in the same reactor as the polycondensation.

The synthesis is as follows.

Ground hexamethylenediamine is introduced into the reactor, with a working stirrer, 36% hydrochloric acid is added in portions. The heating is turned on, the mixture is heated to 120 ° C and the water supplied with hydrochloric acid is distilled off. Under stirring, dicyandiamide and hexamethylenediamine are added in portions to the reactor. After the introduction of the components is completed, the mixture is heated to 150 ° C and maintained for 5 hours with stirring. The melt is heated to 170 ° C and maintained at this temperature for 5 hours with stirring until the completion of the cessation of ammonia evolution. The melt is cooled to 50-40 ° C and reprecipitated with an aqueous solution of sodium or potassium salt.

The disadvantages of this method are as follows:

- the need for preliminary preparation of an intermediate component - hexamethylenediamine dihydrochloride, which increases the staged process;

- purification of the target product leads to the formation of large volumes of wastewater and the need for their disposal.

A known method of producing a disinfectant (RU, patent No. 2170743, C08G 73/00, A61L 2/16, 2001) by melt condensation of hexamethylenediamine and hexamethylene diguanidine dihydrochloride for 1-2 hours at 180-200 ° C with a molar ratio of 1: 1.2, respectively.

To obtain hexamethylenediguanidine dihydrochloride, guanidine hydrochloride is condensed with hexamethylene diamine in a melt at 200 ° C for 1 hour in a molar ratio of 2: 1, respectively. The cooled melt is crystallized from a HCl solution, the product is washed with ethyl alcohol, and dried.

The yield of polyhexamethylene guanidine hydrochloride is 98.2%.

The disadvantages of this method are:

- the need for preliminary preparation of intermediate components - guanidine hydrochloride and hexamethylene diguanidine dihydrochloride, which increases the staged process;

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride;

- crystallization from a solution with hydrochloric acid, washing with ethyl alcohol and drying of the intermediate product complicate the technological scheme and apparatus design of the process;

- crystallization and washing of the intermediate product leads to the formation of large volumes of wastewater and the need for their disposal.

A known method of producing a disinfectant (RU, patent No. 2172748, C08G 73/00, A61L 2/16, 2001) by the interaction of hexamethylenediamine with guanidine hydrochloride.

The synthesis is as follows.

Hexamethylenediamine and guanidine hydrochloride are charged into the reactor in a molar ratio of 1: 1, heating is turned on at a temperature of 120 ° C, and after the hexamethylene diamine is melted, stirrers are launched. Then the temperature is increased to 150 ° C, kept for 5 hours, again raised to 180 ° C and kept for 1 hour. The crude polyhexamethylene guanidine hydrochloride is obtained. The polymer is completely dissolved in water and purified with sodium chloride, dried and granulated.

The synthesis of guanidine hydrochloride from dicyandiamide and ammonium chloride in a molar ratio of 1: 2, respectively, is carried out in the same reactor at a temperature of 200 ° C with stirring. After the reaction mixture is completely melted, it is fed to granulation and guanidine hydrochloride granulate is obtained.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process;

- the need to purify the product using sodium chloride leads to the formation of large volumes of wastewater and the need for their disposal.

A known method for producing polyhexamethylene guanidine hydrochloride (RU, Patent No. 2191606, A61L 2/16, C07C 279/00, 2002) by treating with guanidine carbonate 36% hydrochloric acid, followed by adding pre-molten hexamethylene diamine in stoichiometric amount and further polycondensation at boiling temperature 102-107 ° C and normal pressure without distillation of water to achieve a reduced polymer viscosity of 0.03-0.08. A concentrated (about 70%) solution of polyhexamethylene guanidihydrochloride is obtained.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process;

- the need for preliminary melting of the second component - hexamethylenediamine, which complicates the technological scheme of the process.

A known method of producing a disinfectant (RU, patent No. 2223791, A61L 2/18, С07С 279/08, 277/08, 2004) by melt condensation of hexamethylenediamine and hexamethylene diguanidine dihydrochloride for 1-2 hours at 180-200 ° C at a molar ratio of 1: 1.2, respectively. The hot reaction mixture is poured onto a Teflon pan, cooled, and ground.

Hexamethyleneiguanidine dihydrochloride is obtained by melt condensation of hexamethylene diamine and guanidine hydrochloride at 180-200 ° C for 1-2 hours and a molar ratio of 1: 2, respectively.

The disadvantages of the method are:

- the need for preliminary synthesis of one of the components - hexamethylenediguanidine dihydrochloride, which increases the staged process;

- the resulting dihydrochloride is too toxic and corrosive;

- the need for preliminary synthesis of the starting component - guanidine hydrochloride, which increases the staged process;

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride.

A known method of obtaining a disinfectant (RU, patent No. 2258696, C07C 279/00, A61L 2/16, 2005) by thermal polycondensation of hexamethylene diamine with guanidine hydrochloride.

The synthesis is as follows.

A mixture of dicyandiamide and ammonium chloride in a molar ratio of 1: 2, respectively, is heated at a temperature of 200 ° C until complete melting. In this case, guanidine hydrochloride is formed. The molten guanidine hydrochloride is poured into a metal glass, crystalline hexamethylenediamine is added to it with stirring in a molar ratio of 1: 1, respectively. The temperature of the reaction mixture decreases to 100 ° C and the intensive evolution of ammonia begins. The temperature is increased to 165 ° C and thermostatted with stirring at this temperature until the evolution of ammonia ceases and a transparent, uniform, viscous melt of polyhexamethylene guanidine hydrochloride is obtained.

The disadvantages of this method are:

- the need for preliminary synthesis of one of the components - guanidine hydrochloride, which increases the staged process;

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride.

A known method of producing a disinfectant (AT Patent No. 406163, C08G 73/02, 2000) by reacting hexamethylenediamine with guanidine hydrochloride in a molar ratio of 1: 1 for 5 hours at a temperature of 120 ° C in a solvent (polyethylene glycol) or in bulk. Then the temperature is raised to 150 ° C and maintained at this temperature for 10 hours. Guanidine hydrochloride is prepared from guanidine carbonate by treatment with hydrochloric acid or ammonium chloride.

The disadvantages of this method are:

- the need for pre-synthesis of one of the components of guanidine hydrochloride, which increases the staged process;

- the synthesis in a solvent leads to the formation of large volumes of wastewater and the need for their disposal.

The closest in technical essence and the achieved result is a method of obtaining a disinfectant (RU, patent No. 2165268, A61L 2/16, C08G 73/00, 2001, prototype) by the interaction of hexamethylenediamine with guanidine salt when heated.

The synthesis is as follows.

Ammonium chloride and dicyandiamide were charged into the reactor in a ratio of 2: 1, the mixture was stirred and heated to 160 ° C, and kept at this temperature for about 5 hours. The hexamethylenediamine molten at 50-60 ° C in a molar ratio of 1: 1 is introduced into the obtained guanidine hydrochloride melt. At the same time, the temperature of the mixture decreases to 120-130 ° C, the release of ammonia begins. The polycondensation reaction is carried out with stepwise heating: at the first stage, the reaction mass is maintained at 130 ° C for 3 hours, at the second stage at 150 ° C for 7 hours, at the third stage at 180 ° C for 2 hours at constant stirring. The reaction mass is cooled to 80 ° C, the product is saponified and washed.

The disadvantages of this method are as follows:

- the need for preliminary preparation of an intermediate component - guanidine hydrochloride, which increases the staged process;

- due to the increased corrosion activity of the reaction medium, special equipment is required to obtain guanidine hydrochloride;

- preliminary melt of hexamethylenediamine;

- washing the target product leads to the formation of large volumes of wastewater and the need for their disposal.

Common features for the proposed method and prototype are the starting components and heating of the reaction mixture to 160 ° C.

Distinctive features are operations related to the fact that the crystalline starting components are mixed at a temperature of 15-25 ° C and the three-component mixture is heated without a preliminary step for producing guanidine hydrochloride.

The aim of the invention is to obtain a cleaner product without additional purification, expanding the arsenal and simplifying effective technologies for its production.

This goal is achieved by the fact that the crushed mixture of dicyandiamide (DCDA), hexamethylene diamine (HMDA) and ammonium chloride in a molar ratio of 0.5: 1.0: 1.0, respectively, is placed in the reactor and the three-component mixture is slowly heated with stirring to 160 ° C and maintained at this temperature until the evolution of ammonia ceases. The resulting melt is poured onto a baking sheet. Upon cooling, the melt turns into a crystalline product.

The practical implementation of the invention is illustrated by the following examples.

Example 1. 29.05 g (0.25 mol) of hexamethylenediamine are charged into a grinder-mixer, ground at a temperature of 20 ° C, then 10.50 g (0.125 mol) of dicyandiamide and 13.37 g (0.25 mol) of chloride are added ammonium The mixture is stirred until homogeneous and transferred to a reaction flask. Turn on the heat. Heating is controlled by the rate of ammonia evolution (ammonia must not pass through an acid trap). The ternary mixture is heated to 160 ° C and maintained at this temperature until the evolution of ammonia ceases. At the end of the process, the reaction mass is poured onto a baking sheet, where the product crystallizes into a glassy mass upon cooling. Get 44.2 g of polyhexamethylene guanidine hydrochloride with a basic substance content of 98% wt.

Example 2. 29.05 g (0.25 moles) of hexamethylenediamine are loaded into a grinder-mixer and ground at a temperature of 15 ° C. A further decrease in temperature is not economically feasible. 10.50 g (0.125 mol) of dicyandiamide and 13.37 g (0.25 mol) of ammonium chloride are added. Stir until smooth. Further, the process is carried out analogously to example 1. Receive 44.3 g of a product with a basic substance content of 98.1% wt.

Example 3. 29.05 g (0.25 moles) of hexamethylenediamine are loaded into a grinder-mixer and ground at a temperature of 25 ° C. 10.50 g (0.125 mol) of dicyandiamide and 13.37 g (0.25 mol) of ammonium chloride are added. Stir until smooth. An increase in temperature above 25 ° C leads to a premature onset of the reaction. Next, the process is carried out analogously to example 1. Get 44.1 g of product with a basic substance content of 97.9% wt.

Found,%: C - 47.54; H, 9.22; N, 23.40; Cl - 19.88

Calculated,%: C - 47.32; H - 9.01; N, 23.66; Сl - 20.00

The results of infrared spectroscopy confirm that the resulting product is polyhexamethylene guanidine hydrochloride (drawing).

The advantages of the proposed method are:

- mixing of all components of the condensation at room temperature;

- the absence of a stage for producing guanidine hydrochloride;

- obtaining a cleaner product without additional purification;

- the implementation of the technological process in one stage, in one reactor;

- high reactivity of the initial mixture of three components;

- the absence in the process of solvents, cleaning and washing the target product and, accordingly, the disposal of large volumes of wastewater.

The result, along with the simplification of the process technology, is the expansion of the arsenal of effective technologies for producing biocidal agents.

Claims (1)

A method of obtaining a biocidal agent of polyhexamethylene guanidine hydrochloride by the interaction of dicyandiamide, ammonium chloride and hexamethylene diamine in a molar ratio of 0.5: 1.0: 1.0, respectively, when heated to 160 ° C, characterized in that hexamethylene diamine is preliminarily ground at a temperature of 15-20 ° C, add dicyandiamine and ammonium chloride, then the three-component mixture is stirred at the same temperature to a homogeneous mass and heated to obtain polyhexamethylene guanidine hydrochloride.

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