SU504801A1 - The method of producing polyureas - Google Patents

Description

one

This invention relates to the synthesis of optically active polyureas based on natural L-diaminocarboxylic acids and, in particular, polyureas, the main chain of which includes lysine and / or ornithine residues.

A known method for producing polyureas by the migratory copolymerization of diisocyanates with an amine component, for example with a diamine.

The use as an amino component in the polyaddition reaction of diamines, which are different in nature from the corresponding diisocyanates, does not allow the use of the polyurea obtained by a known method for medical purposes due to the toxicity of most aliphatic and aromatic diamines.

The proposed method provides for obtaining polyureas that are optically active and homogeneous in composition, which creates favorable prerequisites for their use in medicine, for example, as biologically active absorbable coatings for wounds and burns, as well as a suture material that can be absorbed in the body in a short time.

According to the proposed method, polyureas are obtained by migratory copolymerization of diisocyanates with an amine component, which is used as trimethylsilyl derivatives of alkyl esters of L-diaminocarboxylic acids of the general formula

(CH3) s-31-YH (CH2) „- CH-NH-51 (CH3) s,

I

sooh

where n is 3 or 4 and X is an alkyl radical.

The trimethylsilyl group is removed with absolute ethyl alcohol during the reaction.

The use of trimethylsilyl derivatives of alkyl ethers of L-diamnnocarboxylic acids as the amino component in the polyaddition reaction makes it possible to obtain optically active polyurea homogeneous in composition. Such amines are easy to purify by non-distillation under reduced pressure, which allows the polymerization reaction to be carried out with highly pure reagents. The original monomers are stable when stored and the temperature is from -15 to 0 ° C.

As diisocyanates, diisocyanates obtained by reacting trimethylsilyl derivatives of alkyl esters of L-ornithine or L-lysis with phosgene at temperatures from -50 to -20 ° C for 30-40 minutes are used.

The polyurea reaction is carried out in aprotic solvents such as N-methylpyrrolidone, dimethylacetamide (DMAA), dimethyl sulfoxide (DMS), etc. The reaction temperature can vary from -10 to 80 ° C, but it is preferable to perform the process at room temperature at which the reaction rate is quite high and the possibility of side reactions occurring at elevated temperatures is excluded.

Measured viscosity of a 0.5% polymer solution in LCA, melting point, angle of rotation of plane-polarized light (0.5% solution in LCA) are measured.

The table shows the physico-chemical parameters of polymers and copolymers based on alkyl esters of L-lysine and L-ornithine, obtained by the interaction of equimolecular amounts of diisocyanates and trimethylsilyl derivatives of alkyl esters of L-lysine and L-ornithine.

The polyureas form transparent, colorless, quite elastic films and fibers.

The advantage of the proposed method in comparison with the known method is the production of polyureas by a universal method, simple to implement, ensuring the preparation of an optically active polymer based on L-diaminocarboxylic acids,

This method eliminates the possibility of side reactions and allows obtaining polymers of satisfactory purity and with a good yield.

Example 1. In a reaction vessel equipped with a stirrer, a thermometer, a nozzle to determine the expiration time of the solution and a system for passing a gas, dry argon is flushed for 1 hour. Then, 1.6098 g (0.0053 mol) of trimethylsilyl derivative of L-ornithine ethyl ester in 4.0 ml of DMS is introduced into the reaction vessel. With vigorous stirring, 0.615 ml of absolute ethanol is added to the mixture, and the temperature of the solution rises to 36 ° C. Thereafter, 1.1257 g (0.0053 mol) of L-ornithine ethyl ester diisocyanate in 4.0 ml of DMS is introduced into the reaction vessel, the temperature of the solution rises to 75 ° C, and the viscosity of the solution gradually increases. The reaction time is 60 hours at 25 ° C.

The polymer solution is colorless or slightly yellowish liquid. The polymer is planted in a mixture of acetone-hexane in the ratio of 1: 1.

The white fiber polymer is filtered, washed with acetone and dried to constant weight.

Polymer yield 87%; m.p. 203 ° C; + 19.0; viscosity 0.34.

Calculated,%: C 51.5; H 7.5; N 14.9.

Found,%: C 50.76; H 7.58; N 14.38.

The polymer forms sufficiently elastic transparent films from solution in LCA. The films, washed from traces of the solvent and dried to constant weight, are placed in the rabbit muscle pocket. In 22 days the films dissolve and break up into fragments.

Example 2. The conditions of exp.meite are similar to example 1, and trimethylsilylethyl lysine is taken as the ammonium ion in the polymeric reaction.

Polymer yield 74%; m.p. 209 ° C; a + 23.0 ° {0.5% solution in DMS); 0.31 is given viscosity.

Example 3. The process is carried out as in Example 1, but L-lysine ethyl ester diisocyanate is used in the migration copolymerization reaction.

Polymer yield 73% of theoretical; m.p. 165 ° C; +21.0, reduced viscosity 0.27 {0.5% solution in LCA).

Example 4. The process is carried out as in Example 1, but L-cystine ethyl ester diisocyanate and L-cystine ethyl ester trimethylsilyl derivative are used in the migration copolymerization reaction.

The polymer is a white powder, soluble in sulfuric and trifluoroacetic acids and in fluorinated ketones.

Polymer yield 70% of theoretical; m.p. 235 ° С, reduced viscosity 0.04 (0.5% solution in trifluoroacetic acid).

Example 5. The process is carried out as described in Example 4, but L-lysine ethyl ester diisocyanate is used in the migration copolymerization reaction.

The copolymer is a slightly yellow powder.

The output of copolymer 88% of theoretical; m.p. 0.15 given viscosity (0.5% solution in LCA).

Example 6. In a three-necked flask equipped with a stirrer, a gas inlet tube and a carbon chloride tube, 3.5008 g (0.010987 mol) of ethyl No., №-bis-) trimethylsilyl) -L-lysine in 7.0 ml of absolute DMAA, and with vigorous stirring, 0.92 ml (0.023 mol) of methanol, and then 2.4857 g (0.01098 mol) of N% no-bis- (carbonyl) -L-lysine ethyl ether in 5 ml of absolute DMA, while the temperature of the mixture rises sharply and the viscosity of the mixture rises very quickly. After 35 minutes after mixing the components, a jelly is formed, m.p. 170 ° C MO +15.67; the viscosity of a 0.5% solution in formic acid is 1.28, a 0.5% solution in DMC-0.64. Strength at stretching, kg / cm 124 Relative elongation,% 327 Modulus of elasticity,

KG / CM21.8-103

M 250000

The film dissolves in the rabbit muscle pocket in 22 days.

Example 7. The process is carried out according to Example 5, except that L-lysine propyl ether diisocyanate is used in the polyaddition reaction.

Polymer yield 98%; m.p. 146 ° C, Hg + + 17.3. The reduced viscosity is 0.72 (0.5% solution in LCA).

Claims (1)

Invention Formula The method of obtaining polyureas by migrating copolymerization of diisocyanates with a.MHHi-ibiM component in an organic solvent medium, differs from 1a in that, in order to obtain a homogeneous composition and optically active end product, trimethylsilyl derivatives of alkyl ethers of L-diaminocarboxylic are used as the amine component acids.