UA63092C2 - A method for the preparation of polyurethanes (VARIANTS) - Google Patents

Abstract

A method for the preparation of polyurethanes is performed by the interaction of hydroxyl-containing oligoethers and diisocyanates at a molar ratio of 1:2 with subsequent incorporation of organic solvent of the chain extender to the medium. As the chain extender used is 1, N-oxide 2, 3-bis(oxymethyl) quinoxaline of a mixture of 1, N-oxide 2, 3-bis-(oxymethyl) quinoxaline and dihydrazide of carboxylic acid in the presence of dianhydride of pyromellitic acid and the method is performed in the medium of dimetyl formamide, and according the second version the method is performed in the medium of acetone with addition of the КОН solution and distilled water.

Description

The invention relates to the synthesis of polymer products, namely polyurethanes obtained from isocyanates using two or more compounds containing an active hydrogen atom, intended for use in the chemical industry, and polyurethanes can be used as bactericidal hydrophilic materials in medical practice, microbiology.

There are known methods of obtaining polyurethanes through the interaction of diisocyanates, hydroxyl-containing oligoethers and macrochain extenders, as compounds with an active hydrogen atom - diols are used |1| or hydrazide derivatives (21. These polymers form strong films, but they have neither bactericidal nor hydrophilic properties.

The inclusion of ionic groups in the macrochain of polyurethanes gives polymers the ability to absorb water, that is, hydrophilicity. There is a known method of obtaining anionically active polyurethane ionomers containing ionic groups in the main macrochain ІІІ. Polymers are obtained by lengthening the isocyanate prepolymer with compounds containing an active hydrogen atom in the presence of polycarboxylic acid anhydrides using hydrazine derivatives of various structures as macrochain extenders. These polymers form strong films, are characterized by hydrophilicity, but are not bactericidal materials.

The closest to the method of obtaining the claimed polymers in terms of the required bactericidal activity is the method of obtaining polyurethanes by the interaction of hydroxyl-containing oligoethers and diisocyanates in a molar ratio of 1:2, followed by the introduction of a chain extender in the medium of dimethylformamide, which uses dihydrazides of carboxylic acids, dihydrazides of disulfonyldibenzo- 18(24)-crown-6(8) and 1,4-di-K-oxide of 2,3-bis(oxymethyl)quinoxaline in a molar ratio of 1:(0.35-0.5):(0.2- 1.0) (100 mol.bo to the number of reacting isocyanate groups) or used as macrochain extenders of dihydrazides of carboxylic acids, dihydrazides of disulfonyldibenzo-18(24)-crown-6(8) and 1,4-di-M-oxide 2,3 - bis(oxymethyl)quinoxaline in a molar ratio of 1:(0.01-1.0): (0.01-0.53 (67.5-90.0 mol. to the number of reacting isocyanate groups) with blocking of isocyanate groups, that were not reacted with 2-(p-amino-benzenesulfamido)-thiazole or monosulfamidobenzo-15(18)-crown-5(b) hydrazide (4). These polymers formed form strong films, are characterized by bactericidal properties, but do not have hydrophilicity.

The presence of biological activity in polymers is a necessary, but not sufficient factor for the use of polymers in medical practice, which requires from them not only biological activity, but also a number of other properties - steric accessibility of active centers, the ability to absorb liquid, which is mainly ensured by hydrophilicity polymers

The task that the invention is aimed at solving is a method of obtaining polyurethanes that have both bactericidal and hydrophilic properties.

To achieve the task according to the method of obtaining polyurethanes by the interaction of hydroxyl-containing oligoethers and diisocyanates in a molar ratio of 1:22 with the subsequent introduction of a chain extender into the medium of dimethylformamide according to the method claimed as an extender in the medium of dimethylformamide, 1,4-di-H-oxide 2,3 is used -bis-(oxymethyl)-quinoxaline at the rate of 35-90 mol.bo to the number of reacting isocyanate groups in the presence of pyromellitic acid dianhydride. According to the method of obtaining polyurethanes, which is proposed as an extender, 1,4-di-M-oxide of 2,3-bis(oxymethyl)quinoxaline is used in the presence of pyromellitic acid dianhydride or a mixture of 1,4-di-M-oxide of 2,3- bis-(oxymethyl)quinoxaline and carboxylic acid dihydrazide (in the molar ratio (1.7-2.8)-1| in the presence of pyromellitic acid dianhydride. According to the proposed method of obtaining polyurethanes, the process is carried out in an acetone environment, with the addition of aqueous KOH solution and distilled water.

As diisocyanates are used: aliphatic diisocyanate, for example 1,6-hexamethylene diisocyanate, or aromatic diisocyanates, for example 4,4-diphenylmethane diisocyanate, 2,4(2,6)-toluene-ylene diisocyanate

As polyesters, simple polyesters are used, for example, oligooxytetramethylene glycol MM1000, 2000, or complex polyesters, for example, oligodiethylene glycol adipinate MM800.

Dihydrazides of aliphatic or aromatic carboxylic acids, such as iso- and terephthalic and adipic acids, are used as dihydrazides of carboxylic acids.

The composition of polymers is given in table. 1.

The achievement of the set task can be explained by the synergistic effect of the biologically active center in the composition of 1,4-di-H-oxide of 2,3-bis-(oxymethyl)quinoxaline. and ionic groups (in the composition of pyromellitic acid dianhydride|), which are introduced into the structure of the macrochain. The introduction of ionic groups into the composition of rigid blocks of polyurethanes leads to the restructuring of the physical network of intermolecular hydrogen bonds. At the same time, the supramolecular structure of polymers changes significantly. Structural modification of polyurethanes makes it possible to regulate the supramolecular organization, which in turn, it allows to vary the place of localization and the availability of the biologically active center.The possibility of varying the properties of polymers within wide limits: mechanical and especially hydrophilic - from weak swelling to dissolution, ensures the use of polymers in various fields of medical practice.

The essence of the invention is explained by the following examples.

Example 1

A mixture of 100 g (0.1 mol) of dry oligooxytetramethylene glycol (OTMG) (molecular weight 1000) and 34.8 g (02 mol) of freshly distilled toluene diisocyanate (TDIC (a mixture of isomers in the ratio 35:65)) is heated in a 3-neck reactor at with constant stirring and a temperature of (85245)"C for 2 hours to the content of isocyanate groups (5.6:20.2)95. After the end of the reaction, the macrodiisocyanate is cooled to a temperature of (5555)"C and with stirring, 7.63 (0.035 mol) of pyromellitic acid dianhydride in 50 ml of dry dimethylformamide, mixed to a homogeneous mass. Then slowly add 15.54 g (0.07 mol) of finely ground 1,4-di-)-oxide of 2,3-bis(oxymethyl)quinoxaline ( 0OXI in 100 ml of dry dimethylformamide. The reaction mixture is stirred for 3 hours at a temperature of (60522) C. Then 200 ml of dry dimethylformamide is added, mixed until homogeneous, and 6.79 g (0.035 mol) of isophthalic acid dihydrazide in 140 ml of dry dimethylformamide is slowly added Stir for 2 hours at room temperature temperature.

A solution of the polymer in dimethylformamide is obtained, capable of forming strong elastic films.

Example 2

To 41.19 g of polymer in 124 ml of dimethylformamide, synthesized according to example 1, slowly add 18.25 ml of 0.5 N aqueous KOH solution with vigorous stirring. An ionomer solution capable of forming strong elastic films is obtained.

Example C

A mixture of 200 g (0.1 mol) of dry oligooxytetramethylene glycol (molecular weight 2000) and 50 g (0.2 mol) of freshly distilled 4,4"-diphenylmethanediisocyanate IDFMDI is heated in a 3-neck reactor with constant stirring and a temperature of 807"C for 10 minutes to the content of isocyanate groups (5,750,1)95. After the end of the reaction, the macrodiisocyanate is cooled to a temperature of (5525)"C and, with stirring, 7.63 g (0.035 mol) of pyromellitic acid dianhydride is added to 50 ml of dry dimethylformamide, mixed to a homogeneous mass. Then slowly add 15.54 g (0.07 mol) carefully crushed 1,4-di-BI-oxide, 2,3-bis(oxymethyl)quinone-saline in 100 ml of dimethylformamide. The reaction mixture is stirred for 3 hours at a temperature of 6022"C. Then add 200 ml of dry dimethylformamide, mix until homogenous and slowly add 6.09 g (0.035 mol) of adipic acid dihydrazide IDGADKI in 180 ml of dry dimethylformamide. Stir for 2 hours at room temperature and slowly add 70 ml of a 0.5N aqueous solution.

A solution of the polymer in dimethylformamide is obtained, capable of forming strong elastic films.

Example 4

A mixture of 100 g (0.1 mol) of dry oligooxytetramethylene glycol (molecular weight 1000) and 33.6 g (0.2 mol) of freshly distilled hexamethylene diisocyanate (HMDII is heated in a 3-neck reactor with constant stirring for 2 hours at 80"С to the content of isocyanate groups 5.84-0.2 95. After the end of the reaction, the macrodiisocyanate is cooled to a temperature of (4545)"C and, with stirring, add 7.3 (0.035 mol) of pyromellitic acid dianhydride IDAPKIA in 100 ml of dry acetone, stir to then slowly add 15.54 g (0.07 mol) of finely ground 2,3-bis(oxymethyl)quinoxaline 1,4-di-M-oxide.

The reaction mixture is stirred for 4 hours at 557C. The resulting viscous mass is diluted with 350 ml of acetone and with vigorous stirring at 55-607C, 70 ml of 0.5N aqueous KOH solution and 400 ml of distilled water are added.

The obtained transparent yellow solution is stirred for 30 minutes and the acetone is driven off in a vacuum.

An aqueous solution of the polymer with a pH of 8.2 is stable for more than 4 months.

To obtain the films, the polymer solution is poured onto a Teflon substrate and dried for 1 day at room temperature, and then at 60"C to a constant weight.

Example 5

1.526 g (0.007 mol) of pyromellitic acid dianhydride in 20 ml of dry acetone is added to 26.72 g (0.02 mol) of the prepolymer obtained as described in example 1, cooled to a temperature of (45245)"C, and mixed until homogenous and add 3.108 g (0.0014 mol) of finely ground 1,4-di-M-oxide of 2,3-bis(oxymethyl)quinoxaline. The reaction mixture is stirred for 4 hours at 56"C. Then 1.358 g (0.007 mol) of isophthalic acid dihydrazide IDHIFKI is added and stirred for another 2 hours at a temperature of 5570.

The resulting viscous mass is diluted with 90 ml of acetone and with vigorous stirring, 14 ml of 0.5 N aqueous KOH solution and 90 ml of distilled water are added. After that, it is stirred for 30 minutes and the acetone is driven off in a vacuum.

An aqueous solution of a yellow polymer with a pH of 8.3 is obtained, stable for more than 4 months, capable of forming strong elastic films.

Example 6

The synthesis is carried out similarly to example 2 with the use of terephthalic acid dihydrazide IDTFC|I instead of

DGIFK.

Example 7

A mixture of 80 g (0.1 mol) of dry oligoethylene glycol adipinate (ODGA)| (molecular weight 800) and 33.6 g (02 mol) of freshly distilled hexamethylene diisocyanate are heated in a 3-well reactor with constant stirring for 20 minutes at a temperature of 80°C until the content of isocyanate groups (7.1-0.1)95 . 7.63 (0.035 mol) of pyromellitic acid dianhydride in 100 ml of dry acetone are added to the formed prepolymer cooled to a temperature of 50"C, mixed to a homogeneous mass and 15.54 g (0.7 mol) of finely ground 1,4-di -M-oxide of 2,3-bis(oxymethyl)quinoxaline. The reaction mixture is stirred for 4 hours at 56"C. Then 6.79 g (0.035 mol) of isophthalic acid dihydrazide is added and stirred for another 2 hours at a temperature of 5670.

The resulting viscous mass is diluted with 330 ml of acetone, and with vigorous stirring, 70 ml of 0.5 N aqueous KOH solution and 360 ml of distilled water are added. Stir for 30 minutes and drive off the acetone in a vacuum.

An aqueous solution of a yellow polymer with a pH of 8.2 is obtained, stable for more than 4 months, capable of forming a film.

Example 8 (control)

To 33.4 g (0.025 mol) of the prepolymer obtained as described in example 1, cooled to a temperature of (6022)"C, add 70 ml of dry dimethylformamide, mix until homogeneous, and slowly add 3.89 g (0.0175 mol) of finely ground of 1,4-di-M-oxide of 2,3-bis(oxymethyl)quinoxaline in 80 ml of dimethylformamide.

Stir at a temperature of (60522)"C for 3 hours.

A polymer solution capable of forming films is obtained.

Polymers obtained by the claimed method have high activity against pathogenic bacteria, which are the most frequent causative factors of hospital and postoperative infections: E. coli, E. coli,

KiIebzieiia rp.. Rgetsa, aegpidiposa, Rgoieiv mycYidagiv (table. 2) and hydrophilicity, the sign of which is water absorption from 40 to 30095 (table. 3).

The polymer obtained according to example 8 has no biological activity, although its composition contains 1,4-di-M-oxy2,3-bis(oxymethyl)quinoxaline, which does not contain dianhydridepyromellitic acid.

The subject of the invention can be widely used as protective coatings and impregnation compositions for preventive and therapeutic purposes and as a matrix for creating transdermal therapeutic systems in medical practice, microbiology.

Sources of information: 1. JH Saunders, KK Frisch. Chemistry of polyurethanes. M.: Chemistry, 470 p. (1968). 2. Synthesis and study of elastic polyurea urethanes and polyurethane semicarbazides / A.P. Grekov,

V.P. Tkach, V.V. Medvedeva, V.V. Myshko, N.M. Shchepetkina // Synthesis and physical chemistry of polymers. Vip. 7, p. 88-92 (1970).

Z. As. USSR 979387 C 08 (18/32, 18/08. Method of obtaining anionic polyurethane ionomers dispersible in water (1982). 4. Pat. of Ukraine 14952А C 0802; 18/ 02, A 23 BE 1/08, EE 61.) 1/00 (1997). Polyurethanes with antimicrobial properties and the method of their production (Prototypes.

Table 1

Composition of polymers

Poikla KON, 8 GOoomol! 101010 Imol| | moth! | mole| And mole | mole

DFMDI otTMg dpFk | 045 |soh| 0 | - otTMg doFK

GMDI otMg DGADK

GMDI otmg | 1 |dapk| 035) - | - |soh| about | at

GMDI otTMg dpFk | 040 |ooh| 06 | 06 6 | gMDI otTMg dgtFK gMDI ODHA doFK 8 | gmdi om"| 1: HER - | - ,| - | - |ooh| ov | - amm2000

Table 2

Bactericidal activity of polyurethanes"

An example of a test culture

Kiervyvga rp. Antibacterial activity: (-) absent; (x) moderate; (i) satisfactory; (і---) high; (і---і) very high.

Table C

Indicators of mechanical properties and hydrophilicity of polyurethanes

Example 171117 777112о81 77717116 37 | 77771125 776 17777520170 | m | "6 Du KgfI

Claims (2)

1. The method of obtaining polyurethanes by the interaction of hydroxyl-containing oligoethers and diisocyanates in a molar ratio of 1:22 with the subsequent introduction into the medium of an organic solvent of an elongated chain, which is characterized by the fact that 1,4-di-M-oxide 2,3-bis( oxymethyl)quinoxaline or a mixture of 1,4-di-M-oxide 2,3-bis-(oxymethyl)quinoxaline and carboxylic acid dihydrazide |in the molar ratio (1,7-2,8)-1| from the calculation of 35-90 mol. o to the number of reacting isocyanate groups in the presence of pyromellitic acid dianhydride and the method is carried out in the medium of dimethylformamide. 2. The method of obtaining polyurethanes by the interaction of hydroxyl-containing oligoethers and diisocyanates in a molar ratio of 1:2 with the subsequent introduction of an elongated chain into the medium of an organic solvent, which is characterized by the fact that 1,4-di-M-oxide 2,3-bis( oxymethyl)quinoxaline or a mixture of 1,4-di-M-oxide of 2.,3-bis-(oxymethyl)quinoxaline and carboxylic acid dihydrazide |in the molar ratio (1,7-2,8)-1| 13 calculation 35-90 mol. to the number of reacting isocyanate groups in the presence of pyromellitic acid dianhydride, and the method is carried out in an acetone medium with the addition of a solution of KOH II and distilled water.