KR800001617B1 - The manufacturing method of ionene polymers - Google Patents

Abstract

Ionene polymer(I; R1,, R2= H, lower alkyl, monohydroxy substituted C1-4 alkyl, polyhydroxy substituted C3-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl substituted lower alkyl, amino lower alkyl, C3-7 alkenyl, C3-7 alkinyl; R3, R4= lower alkyl, monohydrowy substituted C1-4 alkyl, C3-7 cycloalkyl, C3-7 alkenyl, C3-7 alkinyl; n = 300-500000; m = 0, 1; z = anion; Q = ethylene, trimethylene), useful as antistatic agent, chelating agents and coagulent, was prepd. by reacting the mixt. which was composed of formaldehyde, formic acid and polymer of monomer ! (II) at 30-1000C for 100hrs.

Description

Preparation of Ionene Polymer

The present invention relates to a method for producing a novel polymer represented by the following general formula (1), and in particular, the present invention is formed by branched tertiary or quaternary nitrogen atoms, which are chain-linked through ethylene or trimethylene groups, I) and a process for producing novel polymers derived from linear oxazolines and dihydro-oxazines having no crosslinks.

''는 다음의 일반식과 같은 기군(Groups)의 결합을 표시한다.Wherein R ₁ and R ₂ are the same or different and are hydrogen; Lower alkyl; Monohydroxy-substituted C ₁ -C ₄ alkyl; Polyhydroxy-substituted C ₃ -C ₆ alkyl and polyhydroxy-substituted C ₃ -C ₆ cycloalkyl; C ₃ -C ₇ cycloalkyl; C ₃ -C ₇ cycloalkyl-substituted loweralkyl; Loweralkyl-substituted C ₃ -C ₇ cycloalkyl; Ammonium lower alkyl; Lower alkyl ammonium lower alkyl; Lower alkyl ammonium lower alkyl; Trilower alkylammono lower alkyl; Carboxyl lower alkyl; Carbo lower alkoxy lower alkyl; C ₃ -C ₇ alkenyl; C ₃ -C ₇ alkynyl; Aralkyl such as 2 (1-naphthyl) ethyl, benzyl; Carbamyl lower alkyl; Fluoroloweralkyl such as ω-trifluoroloweralkyl; Cyano lower alkyl; Guanidinolower alkyl; Carbamidino lower alkyl; N-lower alkylcarbamidino lower alkyl; Lower alkoxy lower alkyl; Lower alkylthio lower alkyl; Furanosyl; Pyranosyl, such as α-D-glucopyranosyl; And lower alkanoyl lower alkyl and the like, R ₃ and R ₄ are the same or different and lower alkyl; Monohydroxy-substituted C ₁ -C ₄ alkyl, polyhydroxy-substituted C ₃ -C ₆ alkyl and polyhydroxy-substituted C ₃ -C ₆ cycloalkyl; C ₃ -C ₇ cycloalkyl; C ₃ -C ₇ cycloalkyl; C ₃ -C ₇ substituted lower alkyl; Loweralkyl-substituted C ₃ -C ₇ cycloalkyl; Ammonium lower alkyl; Lower alkyl ammonium lower alkyl; Lower alkyl ammonium lower alkyl; Trilower alkylammono lower alkyl; Carboxy lower alkyl; Carbo lower alkoxy lower alkyl; C ₃ -C ₇ alkenyl; C ₃ -C ₇ alkynyl; Aralkyl such as 2 (1-naphthyl) ethyl; benzyl; Carbamyl lower alkyl; Fluoroloweralkyl such as ω-trifluoroloweralkyl; Cyano lower alkyl; Guanidinolower alkyl; Carbamidino lower alkyl; N-lower alkylcarbamidino loweralkyl; Lower alkoxy lower alkyl; Lower alkylthio lower alkyl; Furanosyl, pyranosyl, such as α-D-glucopyranosyl; And lower alkanoyl lower alkyl and the like, n denotes an integer such that the weight average molecular weight is 300-50,000, m denotes 0 or 1, and Z 'is equivalent or multivalent. Represents an anion, Q represents ethylene or trimethylene, and the symbol ''

'' Denotes a combination of Groups, such as the following general formula:

또는

or

In formula, Q, Z, m, R <_1> , R <_2> , R <_3> and R <_4> are as above-mentioned.

And T ₁ and T ₂ represents a terminal group (terminal groups) on the polymer, T ₁ represents a group represented by the following general formula.

T ₂ represents a fleet represented by the general formula

Or a complex compound of dihydro-1, 3-oxazinium or an anion of an initiator and Δ ² -oxazolinium.

Was above general _{formula, R 1, R 3, Z} , m and Q are as stated above, R ₅ is one or both of the selection from the same gigun but R ₁ and R ₃ as R ₁ and R ₃ It can be the same or different.

R ^* is a group derived from a solvent which affects ring opening, such as hydrogen in the case of hydrotreatment, or alkyl in the case of alcohol treatment.

The exact nature or identity of T, or the use of polymers as described below, is in fact inconvenient to the present invention.

The prefix `` lower '' used in the present invention means 1-4 carbon atoms and has a straight chain bond as described above for the alkyl group.

Where m is 1, Q is trimethylene, and when R ₁ , R ₂ , R ₃ and R ₄ are lower alkyl, the compounds obtained from these groups are known, but these compounds are prepared by the present invention. The method is also a new method.

The polymers according to the invention are not only useful as antimicrobial agents, coagulants, electrical conductive agents of paper coatings, antistatic agents, chelating agents, and bile acid binders, but also as analogous uses for weight ratios. It is effective when the amount of polymer is large and when the influence of nitrogen atoms is necessary.

In particular, the polymers according to the present invention are useful as nonabsorbable gastrointestinal bile acid binders because it is known that their binding reduces the serum concentration of serum cholesterol. It has been pointed out by all medical evidence that higher than normal serum cholesterol levels in humans (particularly so-called Fredericsson type II patients) are signs of atherosclerosis and hypercholesterolemia. Atherosclerosis is expressed due to circulatory disorders and causes some of coronary artery disease, cerebrovascular disease and peripheral vascular disease and causes death in each country.

High serum cholesterol levels in reducing the incidence of atherosclerosis are subject to various inhibitory methods. Various suppression methods include dietary restriction, special dietary therapy, inhibition of cholesterol synthesis in the body, promotion of metabolism, bile acids in the gastrointestinal tract, and at the same time, suppression of gastrointestinal absorption. Of these methods, the latter method is very well received because it does not involve physical burden or sudden severe change in the diet or lifestyle of the patient.

However, the exact method for lowering serum cholesterol concentration by bile acid binding in the stomach is not known. The mechanism of action is believed to affect cholesterol oxidation, which excretes serum cholesterol to restore the bile acid baseline. Although the mechanism of action is uncertain, the above-described methods are widely used. Uncertain but convenient, effective, nontoxic and easily tolerated binder.

Conventionally, various bile acid binders have been used, but they contain metal salts, which combine with bile acids to form insoluble precipitates, and organic bases have similar functions, and polymers have salt forming ability. However, hygroscopic precipitants show acute and chronic toxicity. Conventionally used polymers have an average daily effective dose of 40 grams for adults, so the use of non-absorbent polymers to avoid this toxicity problem has no toxic changes. Such high doses can cause some disorders of the gastrointestinal tract, discomfort and pressure, especially in the case of transverse-linked resins that are insoluble in water. Moreover, it is difficult to get rid of unpleasant smells and tastes because of the high dose.

The branched gel composition with low transverse-chain bonds expands upon absorption of water, causing relatively no frictional irritation but sometimes causing discomfort due to compression.

The water-soluble polymer conventionally proposed to be used as a bile acid binder exhibited a too high viscosity in solution to converge in the oral cavity. Moreover, since the water-soluble polymer contains the same amount of water in a dry form, it is too large to be taken. many. It is a major problem that this polymer may be degraded in the gastrointestinal tract. Therefore, although the incidence of diseases associated with hypercholesterolemia is extremely high and continues to be anomalous, the benefits obtained by treatment with conventional methods are limited.

As described above, resins conventionally proposed for use in hypercholesterolemia were incapable of binding and removing bile acids as a collection effect of chloride.

One view is that small inorganic anions can easily reach the binding site. Therefore, in order to produce more effective resins, it was necessary to separate a lot of parts that can be combined with a large amount of acid. In another view, resins need to be similar to fat to penetrate micelle products in vivo that contain bile acids similar to fats. Therefore, it is suggested that the solubility of the resin in water needs to be reduced.

Unfortunately, this notion has not improved much when the polymer is used to treat hypercholesterolemia.

On the other hand, as described below according to the present invention, it has been found that the novel polymers can bind or remove bile acids in the gastrointestinal tract and are surprisingly effective in lowering the concentration of hyperserum cholesterol.

By `` nitrogen chloride '' is meant an imino group or substituted imino group which is present in the form of a nitrogen atom, e.g. tetravalent or acid addition salts, or which has sufficient basicity to form acid and salts.

By `` linear polymer backbone '' is meant a polymer containing an acyclic group, such as a methylene or trimethylene group bonded to a nitrogen atom in a single chain.

`` Non-branching '' means a polymer in which the monomeric unit extending from the polymer backbone is not polymerized, and `` cross-linking '' usually means binding of two skeletons. Used to

The fact that the polymers according to the invention are linear skeletal and unbranched bonds is of paramount importance in understanding the improvements made by the invention. And for example, US Pat. No. 3,308,020 describes monomer units similar to the monomer units described in the present specification.

Conventionally, the monomer obtained by the raw material and the method which were used for manufacture of a monomer has many branching bonds. Further improvised is that Gibbs et al, Journal of American Chemical Society, 57 1137 (1935) and Noguchiet al polymer (Macromolecules), 5,261 (1972) polymerize dimethylaminoethylene halides to obtain only cyclic dimers. The claim I tried to correct is corrected. Nevertheless, German Patent Nos. 1,131.694 and 1,126,396 contain the announcement.

The polymers according to the invention are prepared by nitrogen substitution and optionally quaternization of polymers obtained by polymerizing and hydrolyzing or directly reducing oxazoline or dihydro-oxazine.

For example, a suitable embodiment of the present invention relates to a method for producing a polymer represented by the following general formula (2).

''는 다음과 같은 일반식으로 표시된 기군의 하나 또는 그 이상의 기군간의 결합을 표시하고,In the food, ''

'' Indicates the union between one or more aircraft fleets represented by the following general formula,

또는

or

R ₃ , R ₄ , Z, T ₁ , T ₂ , Q, m, and n are as described above.

Another preferred embodiment of the present invention relates to a method for producing a polymer represented by the following general formula (3).

''는 다음과 같은 일반식으로 표시된 기군의 하나 또는 그 이상의 기군간의 결합을 표시하고,In the food, ''

'' Indicates the union between one or more aircraft fleets represented by the following general formula,

또는

or

R ₁ , R ₂ , Z, T ₁ , T ₂ , Q, m and n are as described above.

As described above, Z denotes a monoanion as a bar representing an anion which neutralizes the charge on the quaternized or quantized imino group. However, as is well known, Z is thought to include a polyvalent anion capable of neutralizing the charge on one or more imino groups on which one anion is charged. Z is thus an anion of an inorganic acid, as well as, for example, halides such as chlorides, hydrates, or iodides; sulfate; Bisulfide; phosphate; acetate; Ascorbic acid salts; citrate; Hydroxy citrate; lead carbonate; bicarbonate; Nicotinate; Glycinate; Taurine salts; Anions derived from organic acids such as salicylates; And physiologically nontoxic acids, in particular clofibrate and halophenate, ie 2- (P-chlorophenoxy) -2-methylfutopionic acid and 3-trifluorotomethylphenoxy- (4-chlorophenyl) acetic acid And other anions derived from salts of physiologically active acids such as salts derived from.

It is known that only some of the charged imino groups can be neutralized if such anions of physiologically active compounds neutralize quaternary or quantum imino groups. The amount of anion derived from a physiologically active compound is taken at a rate such that the amount administered in a polymer dose falls within the desired range as a physiologically active compound.

The present invention consists of preparing the desired polymer of the general formula (1) by the following six steps.

[Step 1-Polymerization]

After completion of the reaction by polymerization of Δ ² -oxazoline represented by the following general formula (4) or 5,6-dihydro-4H-1,3-oxazine of the following general formula (5) (-C = N Measured and confirmed until no double bond of-is formed) and then the polymerization mixture of formula (6) is treated with anhydrous solvents, in particular ether such as alcohol, methanol or ethyl ether, Obtain the indicated polymerization reaction mixture. The compound is filtered, washed with anhydrous solvent, and the polymer is recovered, dried and separated for use in each of the two following reactions.

Wherein R 'is hydrogen, lower alkyl, phenyl, naphthyl, or naphthylmethyl, with R' being particularly preferred.

Wherein R ¹ Q and n are as described above, and T ₃ represents a group represented by the following general formula,

Or Y ⁻ represents an anion of the reagent, A represents a group of the reagent such as methyl cleaved from hydrogen or methyl iodide, and Q and R ^* are as described above.

Polymerization of 2-R′-Δ ² -oxazolines is known and reported in Polymer Journal, 3,35 (1972). However, it has been found by the present invention that more reliable polymerization can be achieved by using trifluoromethylsulfonic acid instead of the reagents reported in the literature. In general, ^2-R'- △ 2 - oxazoline trifluoromethyl For each molar amount and using methyl sulfonic acid 0.005 to 0.1 mol, particularly ^2-R'- △ 2 - oxazoline per mole of trimethyl acid 0.01 mol fluorophenyl It is suitable to use.

Polymerization of 2-R'-5,6-dihydro-4H-1,3-oxazine is also known (Macro molecule, 6,495 (1973)).

Suitable among known reagents are methyl iodide.

In general, ^2-R'- △ 2 - oxazoline acids and 2-R'-5,6- dihydro -4H-1,3- polymerization of the oxazine acids from 1 to 100 atmospheres can be inert under an inert atmosphere, such as nitrogen, This is done by heating to 30-120 ° C. for 1-12 hours in a closed device in a solvent. In the present invention, an inert solvent refers to a solvent that does not react with a reactant, a product, or the solvent itself under reaction conditions, and a suitable solvent is dimethylformamide.

[Step 2A-Hydrolysis]

The polymer of formula (6) is hydrolyzed by reaction with an aqueous solution of an inorganic acid such as an acid solution such as hydrochloric acid, or a base such as alkali hydroxide to obtain a polymer of formula (7).

Wherein A, m, Q, Z, R ^* and n are as described above, and Z is preferably a halide.

Alkaline hydrolysis is accomplished by mixing the saturated base to 0.1N base aqueous solution and the polymer. Alkali hydroxide is suitable as the base, in particular sodium hydroxide.

Acid hydrolysis is carried out in an aqueous solution of 1-2N acid, such as aqueous hydrochloric acid or sulfuric acid. The hydrolysis is warmed for at least 3-30 hours with stirring. In order to substantially complete the hydrolysis at the expense of molecular weight, it is carried out at a temperature of 40-180 ° C. in an airtight container. If the stirring is sufficient and the theoretical amount of alkali or acid is used at least twice, the amount of the hydrolysis aqueous solution is not limited.

Base hydrolysis yields a polymer of formula (7) with m = 0 and acid hydrolysis or acidification of the base hydrolyzed polymer yields a polymer of formula (7) with m = 1. .

[Step 2B-Direct Reduction]

The acyl group of the polymer represented by the general formula (6) is directly reduced to obtain a polymer of the following general formula (8).

Wherein A, Z, Q, R ', R ^* , Z, m and n are as described above.

This reaction is preferably mixed slowly with at least molar equivalents of a chemical reducing agent, such as Diborane, dissolved in an inert solvent and dissolved in an inert solvent. Suitable solvents are mixtures with tetrahydrofuran and ethylene glycol dimethyl ether. After the addition is complete, the reaction mixture is refluxed for 1-12 hours to cool and acidify. Other reducing agents that may be used instead of diborane include aluminum hydride, lithium aluminum hydride, and lithium lithium methoxy aluminum hydride.

Alternatively, the amide group of formula (6) is alkylated with triethyloxoniumtetrafluoro borate complex salt in methylene chloride at a temperature of 25 ° C. to be converted to iminoester, and then a portion of this iminoester is zero. Sodium borohydride dissolved in ethanol at a temperature of −25 ° C. is reduced to a portion of the tertiary amine.

[2C step-reduction methylation]

In this step, the polymer of formula (6), wherein R 'is hydrogen, is heated with a mixture of formaldehyde and formic acid, each equivalent of at least one phase, then treated with an aqueous acid solution, concentrated and dried under reduced pressure, and then the polymer of formula (9) Get

In formula, R <_5> , Q, Z, R ^* , m and n are as above-mentioned.

The polymer to be methylated by reduction is added to 97-100% formic acid, in particular 38% formaldehyde, and then the reaction mixture is combusted at a temperature of 30-100 ° C. for 20-100 hours. Although the high reaction temperature is not prohibited, it is not recommended to use a high temperature due to the increase rate of pyrolysis of formic acid and the degradation of the polymer.

The reaction mixture is treated with an aqueous solution of inorganic acid, in particular hydrochloric acid, to remove excess formic acid, formaldehyde and inorganic acid by concentration under reduced pressure.

[Step 3-Direct Methylation]

Under the conditions described above in step 2C, the polymer of general formula (7) having m = 0 according to step 2A is heated and directly methylated in each one equivalent of a mixture of formaldehyde and formic acid to directly methylate Obtain a polymer.

[Step ₄ -Addition of R ₃ and R ₄ to the polymer of general formula (7)]

When R ₃ and R ₄ are the same, to obtain a polymer of the following general formula (10), the polymer of general formula (7) is reacted with an alkylating agent RX in an inert solvent at a temperature of 30-100 ° C. at m = 0 according to step 2A. The polymer of general formula (10) with m = 1 obtained by treatment with an excess of 1.5-8 equivalents, in particular 4 equivalents of, is treated with the correct 1 equivalent of base to obtain a polymer of general formula (10) with m = 0, R _{When 3} and R ₄ differ from each other to obtain a polymer of the following general formula (10), the polymer of the general formula (7) having m = 0 is treated with less than 1 equivalent of an alkylating agent and then with a base equivalent of 1 equivalent. After neutralization, the intermediate was treated with a sufficient amount of R ₄ X to complete the alkylation, and the polymer of formula (10) having m = 1 obtained by acid neutralization was treated with the correct equivalent of base to the following formula (10). To obtain a polymer.

Wherein A, Q, Z, R ^* and n are as described above, Z ^- represents X ^- and m is 0.

Both reactions are carried out in an inert solvent at a temperature of 30-100 ° C. This reaction is carried out by dissolving the polymer in an inert solvent such as alcohols, ketones, or dimethylformamide. Suitable solvents include methanol, acetone, and dimethylformamide, and suitable temperatures are 50-75 ° C.

[Step 5-4-R ₁ , R ₂ addition]

Usually, the polymer of the formula (8) according to step 2B obtained as acid addition salt (m = 1), the polymer of the formula (9) according to step 2C or 3, and the polymer of the formula (10) according to step 4 are obtained. Treatment with an equivalent of base converts to freebase form (m = 0) to afford the desired polymer.

In this step, it is not necessary to remove the inorganic salts by ultracentrifugation, but it is convenient to remove the inorganic salts by this. By doing so, there is an advantage in that unnecessary low molecular weight substances can be removed. Next, an aqueous solution of the polymer is concentrated under reduced pressure and dried before the quaternization reaction to obtain a polymer of the general formula (1). This quaternization reaction is completed in an inert solvent such as alcohol, ketone or dimethylformamide. Suitable solvents are methanol, acetone and dimethylformamide and the like. Usually quaternizing agents are halide-containing compounds, especially bromo compounds; Other alkylating agents such as toluenesulfonate or trichloromethylsulfonate esters may also be used. If R ₁ and R ₂ are the same, a significant excess of alkylating agent RX is used, and if R ₁ and R ₂ are different, the polymer is first treated with a limited amount of R ₁ X (equivalent to 5% -95%) to react the reaction. After completion the product is treated with excess reagent R ₂ X. If the alkylation reactivity of the reagents R ₁ X and R ₂ X are the same, the reaction is carried out in a mixture of R ₁ X and R ₂ X in a single step. R ₁ X and R ₂ X may be simple alkyl halides or may contain other functional groups not involved in the quaternization reaction. Simple examples that can be used as quaternization reagents include haloalkyl acid esters, haloalkyl acid amides, haloketones, fluoroalkyltrichloro methylsulfonates, alkylhalohydrins, aralkyl halides, and ammonioalkyl halides. And lower alkyl-substituted ammonioalkyl halides, alkoxyalkyl halides, alkylthioalkyl halides, allyl halides, and furopargilbromide.

This reaction is usually carried out by heating a solution of polymer and alkylating agent in methanol, acetone or dimethylformamide at 35-100 ° C. for 3-6 hours. In the case of special reactive alkylating agents, the reaction is carried out at a temperature of 50 ° C. The product is usually separated directly by filtration, but in some cases it is convenient to dilute the reaction mixture with several volumes of ether before filtration. The product is usually partially dried and ground to a powder and then dried under reduced pressure at a temperature of 25-60 ° C.

[Step 6-Ion Exchange]

The anion of the polymer phase of the general formula (1) obtained by the method of each step described above is generally limited to halides. All the polymers in which the anion Z ⁻ is different from the halides dissolve the polymer of the general formula (1) containing the halide anion in water, alcohol, or a mixture thereof (regardless of proportion), and the solution is subjected to an anion exchange resin phase. ) Or through a synthetic or zeolite form, the halide ions are exchanged for Z ⁻ . The ion exchange resin method, ie, the halide ions can be exchanged directly with Z ⁻ or the halide ions are first exchanged with OH ⁻ , followed by continuous ion exchange of OH ⁻ or by simple neutralization exchange to Z ⁻ .

In addition, when the precipitation of the metal halide is lower in solubility than the addition metal salt, the precipitated metal halide can be separated from the soluble polymer of the general formula (1) using a chemical exchange method.

For a simple example of this process, the polymer solution of formula (1) containing bromide reverse ion is treated with an excess of freshly precipitated chloride temperature to complete halide anion exchange, followed by the formula (1) containing chloride reverse ion (1). ), The polymer solution is separated by filtration to remove a mixture of silver chloride and silver embrittlement.

Alternatively, the polymer of general formula (1) wherein Z ⁻ is a sulfate can be treated with a solution of water-soluble calium or barium salt, and the sulfate can be replaced with nitrate to remove the precipitation of barium sulfate.

The present invention will be described in detail by way of examples.

Example 1

[Poly-[(formimino) ethylene]]

The oxazole into a solution of 44g sleepy solution and purified (精製) of dimethylformamide were dissolved in 175㎖ boron fluoride etherate 870㎎ tree of freshly distilled to a pressure reactor containing a glass liner (glass liner) device - △ ² Nitrogen was charged to heat the mixed solution at 80 ° C. for 5 hours, then diluted with methanol and filtered to obtain 30 g of a poly-[(formimino) ethylene] polymer. When the reaction conditions are heated at a temperature of 80 ° C. for 5 hours and the boron trifluoride etherate catalyst ratio is 0.01 with respect to the molar ratio of Δ ² -oxazoline, the yield of the solid polymer is in the range of at least 13.2-68%. .

Example 2

[Poly-[(formimino) ethylene]]

△ ² - A solution of the oxazoline 217g (3.06 mol) of methyl sulfonic acid 4.6g (0.03 mol) was dissolved in trifluoroacetic purified dimethylformamide 800㎖ under nitrogen volume in solution, and in a sealed tube for 90 ℃ 5 sigan After heating and stirring, the mixture was diluted with 1,200 ml of anhydrous methanol, the product was separated by filtration, washed with methanol, washed with ether, dried under reduced pressure, and 150 g of poly-[(formimino) ethylene] was obtained. Obtained.

Example 3

[Poly-[(acetimino) ethylene]]

1 g of ² -methyl-Δ ² -oxazoline was added to a Carius combustion tube, and 2 drops of boron trifluoride (48%) were added to precipitate the nitrogen sufficiently to suppress combustion and to burn the tube at 160 ° C. for 20 hours. Put it in. The resulting poly-[(acetamino) ethylene] polymer is a glassy, almost colorless resin with a melting point of 155-175 ° C., which is soluble in methylene chloride.

Example 4

[Poly-[(butyrimino) ethylene]]

In this example, a single catalyst system is used to polymerize N-acylethyleneimine and translocate to intermediate oxazoline.

10 of N-butyrylethyleneimine and 0.05 B of BF ₃ .EtO were heated in a discharge tube at 60 ° C. for 4 hours, and the resulting solid was dissolved in 100 ml of CHCl ₃ and precipitated by adding petroleum ether to CH ₃ Cl. After dissolving again and reprecipitating with petroleum ether, the precipitate was dried to give 6.3 g of a poly-[(butylimino) ethylene] polymer having a low viscosity of 0.16 and a melting point of 150 ° C. in a 1% solution of benzene.

In a similar way

N-benzoylethyleneimine

2-isopurophyll- △ ² -oxazoline

2-cyclohexyl-Δ ² -oxazoline

2-naphthyl-Δ ² -oxazoline

2-P-tolyl-Δ ² -oxazoline

The following polymer corresponding to this is obtained.

Poly-[(benzoylimino) ethylene]

Poly-[(isobutylimino) ethylene]

Poly-[(cyclohexanoylimino) ethylene]

Poly-[(naphthoylimino) ethylene]

Poly- [toluoylimino) ethylene]

Example 5

[Poly-[(benzoylimino) ethylene]]

2-phenyl-2-oxazoline (1.1322 g, 7.60 x 10 ^-3 moles) was added to a Carius combustion tube with 7.69 x 10 ^-5 moles of borontrifluoride in the form of a dimethoxyethane solution. After filling and discharging, 1 g of the pale yellow glassy polymer produced by heating the mixture at 150 ° C. for 2 hours was pulverized into fine powder, dissolved in 25 ml of methylene chloride, and the solution was added to 75 ml of η-hexane and stirred vigorously. To obtain a thick white precipitate. This material is filtered and reprecipitated twice or more by the above-described method to obtain a fine white powder. The yield of the purified poly-[(benzoylimino) ethylene] polymer is 80% and the molecular weight of this polymer is 7,500.

Example 6

Copolymerization of a Molar Equivalent Mixture of 2-phenyl-2-oxazoline with Other 2-Substituted-2-oxazolines

Molar equivalent concentrations of 2-phenyl-2-oxazoline per liter in N, N-dimethylacetamide and 2-benzyl-2-oxazoline, 2-methyl-2-oxazoline; And 2-phenyl-2-oxazolium perchlorate as the reagent at each 1.5 molar concentration of 2-isopurophyl-2-oxazoline, respectively, at 135 ° C. for about 2 hours.

The poly-[(acylimino) ethylene] copolymer produced at this time changes arbitrarily with respect to content of N-acyl group. 2-phenyl-2-oxazoline forms N-benzoyl derivatives, 2-benzyl-2-oxazoline forms N-phenylacetyl derivatives and 2-methyl analogs form N-acetyl derivatives. The components of the copolymer at any degree are influenced by the relative reaction rate of the various monomers.

The polymer thus produced is linear poly- (ethyleneimine), in which the different acyl group components are removed by hydrolysis and thus can be directly reduced as described in the following examples as well as having no effect.

Example 7

Poly- (iminoethylene)

Hydrolysis of poly-[(acylimino) ethylene] is completed by acid or base hydrolysis.

(1) A solution of 3 g of basic hydrolyzed poly-[(formimino) ethylene] and 3 g of sodium hydroxide dissolved in 35 ml of water was heated with stirring at 98 ° C. for 3 hours, and the mixture was cooled at room temperature to precipitate. The white solid was separated by filtration, washed sufficiently with water and dried under vacuum to obtain 1.6 g of poly- (iminoethylene).

(2) 1.29 g of poly-[(acetimino) ethylene] is added to 50 ml of about 1N sodium hydroxide solution. The polymer is virtually insoluble in the base at room temperature but refluxed for 26 hours to homogenize the reaction mixture. The reaction mixture is cooled to room temperature to give a gel white mass. At this point, hydrolysis is nearly 65% complete. Non-acylated poly- (iminoethylene) is purified by repeated precipitation, i.e. filtering from some acetylated poly- (iminoethylene) by adding the solution to the acid and neutralizing the filtrate.

(3) 1 g of poly [(acetimino) ethylene] is dissolved in 50 ml of 1 N sulfuric acid, and the resulting homogeneous mixture is heated under reflux for 3.5 hours to give an acetic acid odor. When acetic acid smells, the partial sample is titrated with 1N sodium hydroxide to confirm that the hydrolysis is completed by 27%, and when maintained under reflux for 21 hours, 38% of the hydrolysis is completed.

Generally virtually complete hydrolysis can be achieved as described above, but is accomplished by carrying out at a temperature of 120 ° C. or higher in a closed tube.

Poly-[(acylamino) ethylene] is reduced to N-alkyl and N-aralkyl derivatives without prior hydrolysis with free bases. The reducing agent selected is Diborane as in the following examples, and may also be used as lithium aluminum hydride, lithium trimethoxyaluminum hydride.

Example 8

Poly-[(ethylimino) ethylene]

100 ml of tetrahydrofuran over 15 minutes in 200 ml (334 mmol) of a solution of diborane 1.67 M dissolved in tetrahydrofuran in a 500 ml flask equipped with a reflux condenser, dropping funnel, and magnetic stirring rod and maintained in a nitrogen atmosphere. 17 g (200 mmole / monomer unit) of poly-[(acetimino) ethylene] dissolved in the solution was added (the temperature during the addition was maintained at about 0 ° C.), and the reaction mixture was kept under reflux for 6 hours, and the mixture was After cooling to room temperature, 50 ml of 6M hydrochloric acid is slowly added through a dropping funnel. Since hydrogen is released (15.51, 0.6 mol) from the hydrolysis of the amine-borane complex salt, tetrahydrofuran is distilled off at atmospheric pressure. Next, sodium hydroxide is added to precipitate poly-[(ethylimino) ethylene].

By reacting each polymer obtained in Example 4 by a similar method, each of the following polymers was produced.

Poly-[(benzylimino) ethylene];

Poly-[(isobutylimino) ethylene];

Poly-[(naphthylmethylimino) ethylene];

Example 9

Poly-[(methylimino) ethylene hydrochloride]

2.5 g of poly- (iminoethylene) was slowly added to 12 g of 90% formic acid, 5.5 g of 38% aqueous formaldehyde was added thereto, and the mixture was heated and cooled at 100 DEG C for 72 hours, followed by 5.5 ml of concentrated hydrochloric acid, Concentration and drying of this mixed solution under reduced pressure yields 5 g of poly-[(methylimino) ethylene] hydrochloride.

Example 10

Poly-[(dimethylimino) ethylenechloride]

500 mg (5.4 mmoles) of poly-[(methylimino) ethylene hydrochloride] were dissolved in 50 ml of methanol containing 291 mg (5.4 mmoles) of sodium methoxide, and the solution was cooled in an acetone-dry ice bath. After condensing 10 g of methyl chloride in solution, the mixture was heated in a closed tube at 80 ° C. for 5 hours, concentrated to dryness under reduced pressure, the product was dissolved in 3 ml of anhydrous methanol, filtered, the solution was concentrated to dryness, and the product was methanol. It is dissolved in, filtered and concentrated to dryness several times. Concentration of the filtrate under reduced pressure yielded 400 mg of poly-[(dimethylimino) ethylene] chloride.

Example 11

Poly-[(dimethylimino) ethylene bromide]

A 860 mg (20 mmol equivalent) solution of poly- (iminoethylene) dissolved in 30 ml of methanol was treated with 9.5 g (100 mmoles) of methyl bromide at 50 ° C. for 3 hours, and the reaction mixture was concentrated to dryness under reduced pressure. After treating with 1.08 g (20 mmoles) of sodium methoxide dissolved in 10 ml of methanol, the residue was dissolved in 30 ml of anhydrous methanol, and treated with 9.5 g (100 mmoles) of methyl bromide. The solution was heated and concentrated at 50 DEG C for 3 hours. After dissolving the product in water, the solution was ultrafiltered through a VM ₂ Diaflo ultrafilter, and the residue was concentrated under reduced pressure to yield 2.8 g of poly-[(dimethylimino) ethylenebromide]. .

Example 12

Poly-[(dimethylimino) ethylenemethosulfate]

0.5 g of poly-[(methylimino) ethylene hydrochloride] was dissolved in 50 ml of methanol containing 0.29 g of sodium methoxide, the solution was concentrated to about 20 ml, and 0.7 g of dimethyl sulfate was added. The solution is poured into a large amount of acetone by heating for a time or the product is precipitated by evaporation of methanol and washing with acetone. The product is dried at ambient temperature under reduced pressure.

Example 13

Poly-[{(2-hydroxyethyl) methylimino} ethylenechloride

According to the method of Example 10, instead of 10 g of methyl chloride, 15.8 g of ethylenechlorohydrin is used. The mixture is heated at 80 ° C. for 5-7 hours and then extracted under reduced pressure to remove the solvent and excess reagent to afford poly-[{(2-hydroxyethyl) methylimino} ethylenechloride} as a residue.

By a similar method, equivalent amounts of furophilene chlorohydrin or secondary-furophilene chlorohydrin are used in place of ethylenechlorohydrin, respectively, to give poly-[{(1-methyl-2-hydroxyethyl) methylimino}. Ethylene chloride] and poly-[{(2-hydroxyfurophyll) methylimino} ethylenechloride] are obtained.

Example 14

Poly-[(2-hydroxyethylimido) ethylene]

0.5 g of poly- (iminoethylene) of Example 7 was dissolved in 50 ml of methanol, heated with 0.35 g of ethylene oxide in a closed tube under nitrogen atmosphere for 3 hours at 60 DEG C, and extracted under reduced pressure to excess solvent and excess. When the epoxide of is removed, poly-[(2-hydroxyethylimino) ethylene] is obtained as a residue.

Example 15

Poly-[{(2-hydroxybutyl) -2-hydroxyethylimino} ethylene bromide]

The poly-[(2-hydroxyethylimino) ethylene] obtained in the above-described example was dissolved in 50 ml of acetone containing 20 g of 2-hydroxybutyl bromide, and the mixed solution was kept in a closed tube for 6-8 hours. The product is recovered by heating at 80-90 ° C. and then removing the solvent and excess reagent under reduced pressure as described above. Poly-[{(2-hydroxybutyl) -2-hydroxyethylimino} ethylene bromide] is obtained as a residue.

Example 19

Poly-[(methylimino) ethylene hydrochloride]

A mixture of 25 g of poly- (formiminoethylene), 504 g of 97-100% formic acid, and 38% aqueous formaldehyde solution (formalin) was heated at 100 ° C. for 60 hours, and the reaction mixture was cooled and 210 ml of concentrated hydrochloric acid was added thereto. The mixture was concentrated to dryness at 50 ° C. under reduced pressure, the product was washed with methanol and then with ether and dried to give 34.6 g of poly-[(methylimino) ethylene hydrochloride].

Example 17

Poly-[(methylimino) ethylene]

17.55 g of sodium methoxide was dissolved in 400 ml of water to prepare a solution containing 0.325 mol of sodium hydroxide. 28.6 g of poly-[(methylimino) ethylene hydrochloride] was added thereto, followed by water to add 500 ml of the total amount of the solution. The solution is then desalted and a product having a molecular weight of less than 1,000 is also removed using an Amicon filter chamber equipped with a UM ₂ Diafloultrafilter. Then, the solution was concentrated to dryness at 50 ° C. under reduced pressure to yield 16 g of poly-[(methylimino) ethylene].

Example 18

Poly-[(dimethylimino) ethylene bromide]

A solution of 21.7 g of poly-[(methylimino) ethylene] dissolved in 130 ml of anhydrous methanol was cooled and 364 g (3.8 mol) of condensed methyl bromide was added thereto, and the mixture was placed in a glass-finished pressure reactor. After heating at 50 DEG C for 5 hours to cool the mixture, the product was separated by filtration, washed with ether and dried under reduced pressure to obtain 58 g of poly-[(dimethylimino) ethylene bromide].

Example 19

Poly-[(dimethylimino) ethylenechloride]

A solution of 58 g of poly-[(dimethylimino) ethylene bromide] dissolved in 3 liters of water was placed in a 770 ml column of 200-400 mesh AG1-X8 quaternary ammonium chloride resin (1,078 equivalents of Cl ^_ ). After slowly passing through, 4,200 mL of the effluent was collected and concentrated and dried under reduced pressure at 50-55 ° C. to obtain 37 g of poly-[(dimethylimino) ethylene chloride.

Example 20

Preparation of Poly-[(dimethylimino) ethyleneiscorbate]

5.0 g of poly-[(dimethylimino) ethylene chloride] was dissolved in 75 ml of distilled water and 100 g (0.5 mol Cl ^- exchange capacity) of polystyrene resin in which the benzene ring was substituted with 4-methotrimethyl ammonium hydroxide (BiORad AG 1 × 8). The effluent (450 ml) of the six-column volume containing poly-[(dimethylimino) ethylene hydroxide] was recovered by passing through the bottom of the column containing the Concentrated to 150ml, cooled to 15 ℃, neutralized with 8.8g (0.05mol) of ascorbic acid (USP), and whitened to neutralize the clear neutralized solution by shell-freezing. A solid is obtained.

The conversion of other polymers according to the invention to ascorbic acid salts in a similar manner or the use of other acids containing physiologically acceptable anions instead of ascorbic acid yields other salts as described above.

Example 21

5,6-dihydro-4H-1,3-oxazine

A mixture of 94 g of tert-butylisonitrile, 85 g (1.13 mol) of freshly distilled 3-aminofuropanol, and 7.4 g (0.055 mol) of silver cyanide was stirred at 90 ° C. for 16 hours under nitrogen atmosphere to distill the product to 45 mm. The mixture is separated from the reaction mixture, purified by repeated classification.

=1.4485Usually sorting twice is enough to obtain a pure product. In this way, 44 g of pure 5,6-dihydro-4H-1,3-oxazine is obtained and stored on molecular sieve 4A under nitrogen. Boiling point 58 degrees Celsius / 58mm

= 1.4485

Example 22

Poly-[(formimino) trimethylene]

In 140 mL of purified dimethylformamide, 44 g of 5,6-dihydro-4H-1,3-oxazine was placed in a solution pressurized tube, and 1.52 g of urethane-methane was added to 1.52 g (0.011 mol) to charge the device with nitrogen. After sealing, the mixture was heated at 80 ° C. for 5 hours to cool the mixture, diluted with 10 times the volume of ether, and the product was separated by filtration. The product was washed with ether and dried under reduced pressure at 75 ° C. to obtain poly-((formimino). ) Trimethylene] 40 g is obtained.

Melting point 111-112 ℃

Example 23

Poly-[(methylimino) trimethylene hydrochloride]

A mixture of 53 g of poly- (formimino trimethylene), 1,320 g of 97-100% formic acid, and 308 g of 38% formaldehyde aqueous solution was heated at 100 ° C. for 120 hours, and the mixture was cooled and 650 ml of concentrated hydrochloric acid was added thereto. The mixture was concentrated to dryness at 50 ° C. under reduced pressure, softened with 400 ml of methanol, the residue was filtered off, washed with ether and dried under reduced pressure to obtain 67 g of poly-[(methylimino) trimethylene hydrochloride]. Lose.

Example 24

Poly-[(methylimino) trimethylene]

A solution of 67 g (630 mmol equivalent) of poly-[(methylimino) trimethylene hydrochloride] dissolved in 600 ml of water was treated with 39 g (0.72 mol) of sodium methoxide. This treatment is an easy way to prepare a precisely defined solution of sodium hydroxide, which is exactly the same amount as the standard solution of sodium hydroxide. The solution was desalted and a polymer having a molecular weight of 1,000 or less was removed using an Amicon filter chamber equipped with a DM2 diaflo filter, and then the solution was concentrated to dryness at 50 ° C. under reduced pressure. Mino) trimethylene] 45 g is obtained.

Example 25

Poly-[(dimethylimino) trimethylene bromide]

A solution of 14 g of poly-[(methylimino) trimethylene and 76 g (0.8 mole) of bromomethane dissolved in 90 ml of methanol was heated in a closed reactor at 50 ° C. for 5 hours, and the product was filtered off and washed with methanol. Then washed with ether and dried under reduced pressure to give 28 g of poly-[(dimethylimino) trimethylene bromide].

Example 26

Poly-[(dimethylimino) trimethylene chloride]

A cylindrical tube containing 1,000 ml of Dowex 1- × 2 (Cl ^- Cycle) resin (0.8 mol) in a solution of 28 g (milliliter equivalents) of poly-[(dimethylimino) trimethylene bromide dissolved in 400 ml of water. After passing through the column slowly, pass the water through the cylinder tube until the solution is passed and tested for nitrate as negative. The total amount of effluent was concentrated to dryness and the product dried under reduced pressure to afford 17.2 g of poly-[(dimethyl amino) trimethylene chloride)].

Example 27

Poly-[{methyl- (3-hydroxyfurophyll) imino} trimethylene bromide]

A solution of 142 mg (2 milliequivalents) of poly-[(methylimino) trimethylene] dissolved in 5 ml of purified dimethyl formamide and 1.12 g (8 mmoles) of 3-bromo-furopanol at 75 ° C. for 24 hours Heat, the product is filtered off, washed with acetone and dried under reduced pressure to give 330 mg of poly-[{methyl- (3-hydroxyfurophyll) imino} trimethylene bromide].

Example 28

Poly-[{methyl- (3-hydroxyfurophyll) imino} trimethylene chloride]

9 ml of Dowex1-x2 ion exchange resin (72 mmolesCl ⁻ ) in a solution of 315 mg (1.5 mmol) of poly-[{methyl- (3-hydroxyfurophyll) imino} trimethylene bromide dissolved in 16 ml of water After passing slowly through a column containing, the mixture was passed through water until the test for chloride ions of the effluent was negative, and the mixed effluent was concentrated to dryness at 50 ° C. under reduced pressure to obtain poly-[{methyl- 230 mg of 3 (-hydroxyfurophyll) imino} trimethylene chloride] is obtained.

Example 29

A polymer of formula (3) wherein R ₁ = 3-hydroxyfurophyll and R ₂ = CH ₃ (optionally distributed as a ratio of 5:95)

A solution of 462 mg (6 milliequivalents) of poly-[(methylimino) trimethylene] dissolved in 12 ml of dimethylformamide and 41 mg (300 μmol) of 3-bromofuranol was heated at 75 ° C. for 24 hours After cooling the mixture, 2.9 g (30 mmoles) of methyl bromide was added, the reaction mixture was heated at 50 ° C. for 3 hours, and the product was separated by concentrating the reaction mixture under reduced pressure, washed with ether, and dried under reduced pressure. Likewise, bromide reverse ions are exchanged by chloride ions in a conventional manner using ion exchange resins.

Example 30

A polymer of formula (3) wherein R ₁ = 3-hydroxyfurophyll and R ₂ = CH ₃ (optionally distributed as a 50:50 ratio)

A solution of 213 mg (3 milliequivalents) of poly-[(methylimino) trimethylene] and 209 mg (1.5 mmoles) of 3-bromofuropanol was heated at 75 ° C. for 24 hours and the reaction mixture was cooled to give methyl bromide 1.5 After adding g, the reaction mixture was heated at 50 ° C. for 3 hours and operated in the same manner as described above.

Example 31

Polymer of formula (3) wherein R ₁ = 3-hydroxyfurophyll and R = CH ₃ (optionally distributed as a ratio of 95: 5)

A solution of 142 mg (2 milliequivalents) of poly-[(methylimino) trimethylene] and 264 mg (1.9 mmoles) of 3-bromofuropanol was heated for 16 hours at 75 ° C., and the reaction mixture was cooled down. After adding 1 g of methyl bromide, the mixed solution was heated at 50 ° C. for 12 hours, and then the reaction mixture was operated in the same manner as described above.

Example 32

Poly-[{methyl- (3-methoxyfurophyll) imino} trimethylene chloride]

A solution of 284 mg (4 mmol equivalent) of poly-[(methylimino) trimethylene] and 2.45 g (16 mmoles) of methoxyfurophyll bromide dissolved in 15 ml of dimethylformamide was heated at 75 ° C. for 16 hours. The filtrate was washed with ether, dried under reduced pressure, the product was dissolved in 25 ml of water and the bromide reverse ion was exchanged for chloride by ion exchange as described above. This method yields 450 mg of poly-[{methyl- (3-methoxyfurophyll) imino} trimethylene chloride].

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 5-methoxyfurophyll and methyl distributed in a ratio of 5: 95-95: 5, respectively, is basically the same as described above. [(Methylimino) trimethylene] is treated with a limited amount of 3-methoxy furophyll and then with excess methyl bromide.

Example 33

Poly-[{methyl- (3-methylthiofurophyll) imino} trimethylene chloride]

A solution of 426 mg (6 mmol equivalent) of poly-[(methylimino) trimethylene and 4.06 g of 3-methylthiofurophyll bromide dissolved in 15 ml of dimethylformamide was heated at 75 ° C. for 24 hours, and the product was filtered. Separated, dissolved in 30 ml of water, passed through a column containing 45 ml of Dowex × 1- × 2 ion exchange resin (36 mmoles chloride ion), and the aqueous effluent was concentrated to give poly-[{methyl- ( 3-methylthiofurophyll) imino} trimethylene chloride] 650 mg is obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 3-methylthiofurophyll and methyl distributed in a ratio in the range of 5: 95-95: 5, respectively, is basically the same as described above. -[(Methylimino) trimethylene] is treated with a limited amount of 3-methylthiofurophyll bromide followed by excess methyl bromide.

Example 34

Poly-[{methyl- (3-ammoniafurophyll) imino trimethylene dichloride]

A solution of 568 mg of poly-[(methylimino) trimethylene] and 3-phthalimidofurophyl bromide dissolved in 25 ml of dimethylformamide was heated at 75 ° C. for 18 hours, the product was filtered off, and then methanol 10 The solution was suspended in ㎖, treated with 1 g of anhydrous hydrazine at 50 ° C. for 3 hours, concentrated under reduced pressure, acidified with dilute hydrochloric acid, softened with ether, filtered off, and the product was dissolved in water to dissolve Dowex 1- × 2 ions. The aqueous effluent is concentrated after passing through a 45 ml cylinder containing 36 mmoles of exchange resin chloride ions to give poly-[{methyl- (3-ammoniofurophyll) imino} trimethylene dichloride].

Alternatively, 568 mg (8 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 20 ml of dimethylformamide and 6.3 g (40 mmoles) of 1-bromo-3-chlorofuropane were prepared at 75 ° C. The reaction mixture was heated under reduced pressure for 18 hours, the reaction mixture was concentrated under reduced pressure, heated with 30 ml of liquid ammonia for 5 hours at 50 ° C. to evaporate ammonia, and the product was subjected to a Dowex 1- × 2 ion exchange resin in a chloride ion stage. It is passed through a 45 mL cylindrical tube containing to convert into a form containing chloride ions.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 3-ammoniofurophyll and methyl distributed in a ratio in the range of 5: 95-95: 5, respectively, is basically as described above, and poly -[(Methylimino) trimethylene] is reacted with a limited amount of 3-phthalimidofurophyll bromide or 1-bromo-3-chloro furopane followed by excess methyl bromide.

Example 35

Poly-[{methyl- (3-methylammoniofurophyll) imino} trimethylene dichloride]

A solution of 710 mg of poly-[(methylimino) trimethylene] and 8 g of 1-bromo-3-chlorofurophan dissolved in 30 ml of dimethyl formamide was heated at 75 ° C. for 16 hours, and the mixture was dried under reduced pressure. Concentrated and suspended in 10 ml of methanol, treated with 3 g of methylamine at 50 ° C. in a sealed tube, and the reaction mixture was concentrated under reduced pressure and dissolved in water, followed by a 50 ml column containing Dowex 1- × 2 ion exchange resin. Passing through the clearance, the desired product is obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 3-methylammoniofurophyll and methyl distributed in a ratio in the range of 5: 95-95: 5, respectively, is basically as described above. Poly-[(methylimino) trimethylene] is first reacted with a limited amount of 1-bromo-3-chlorofuropane followed by excess methyl bromide.

Example 36

Poly-[{methyl- (3-dimethylammoniofurophyll) imino} trimethylene dichloride]

A solution of 710 mg of poly-[(methylimino) trimethylene] and 7.9 g of 1-bromo-3-chlorofurophan dissolved in 35 ml of dimethylformamide was heated at 75 ° C. for 16 hours. The mixture was concentrated under reduced pressure, suspended in 10 ml of methanol, treated with 2.3 g (50 mmoles) of dimethylamino at 50 ° C. in a sealed tube, and then the reaction mixture was concentrated under reduced pressure and dissolved in water to give DOWEX 1- × 2 ion exchange. Passing through a 50 ml cylinder containing resin (40 mmoles of chloride ions) yields poly-[{methyl- (3-dimethylammoniofurophyll) imino} trimethylene dichloride].

Alternatively, a solution of 710 mg (10 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 35 ml of dimethylformamide was added to 6.6 g of 3-dimethylaminofurophyll bromide at 50 ° C. for 6 hours. 10 mmoles), the product was filtered off, dissolved in water, and passed through a 50 ml cylinder containing Dowex 1- × 2 ion exchange resin (4 mmoles of chloride ions) to obtain the same 3-dimethylammonium protophil as described above. Obtained.

The process for preparing the polymer of formula (3) wherein R ₁ and R ₂ are 3-dimethyl ammoniofurophyll and methyl distributed in a ratio in the range of 5: 95-95: 5, respectively, is essentially as described above, Poly-[(methylimino) trimethylene] is first treated with a limited amount of 1-bromo-3-chlorofurophane or 3-dimethylfurophane bromide followed by excess methyl bromide.

Example 37

Poly-[{methyl- (3-trimethylammoniofurophyll) imino} trimethylene dibromide

A solution of 710 mg (10 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 40 ml of purified dimethylformamide and 10.4 g (40 mmoles) of 3-bromo-furophyltrimethylammonium bromide at 75 ° C Heated for 12 hours, the product was filtered off, washed with acetone and dried under reduced pressure to yield 1.8 g of poly-[{methyl- (3-trimethylammoniofurophyll) imino} trimethylene dibromide].

Example 38

Poly-[{methyl- (3-trimethylammonium furophyll) imino} trimethylene chloride]

A solution of 1.66 g of poly-[{methyl- (3-trimethylammoniofurophyll) imino} trimethylene dibromide dissolved in 85 ml of water was placed in a chloride ion stage with 50 ml of Dowex 1- × 2 resin ( 40 mmoels) is passed slowly through a tube containing water, and then through water until no chloride ions are detected in the effluent. The mixed effluent was concentrated at 50 ° C. to give 1.1 g of poly-[{methyl- (3-trimethylammoniofurophyll) imino} trimethylene dichloride.

The method of synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 3-trimethyl ammoniofurophyll and methyl distributed in a ratio in the range of 5: 95-95: 5, respectively, is described in detail in Example 37. And poly-[(methylimino) trimethylene] with a limited amount of 3-bromofurophylltrimethylammonium bromide followed by methyl bromide.

Example 39

Poly-[{methyl- (carboethoxymethyl) imino} trimethylene chloride]

A solution of 1 g (14 milliequivalents) of poly-[(methylimino) trimethylene] and 8.8 g (56 mmoles) of ethyl α-bromo acetate dissolved in 20 ml of dimethylformamide was heated at 50 ° C. for 12 hours. The mixture was diluted with 5-fold ether, the product was isolated by filtration, the product was dissolved in water and passed through a 75 ml cylinder containing Dowex 1- × 2 ion exchange resin (60 mmoles of chloride ions). Concentration under reduced pressure affords poly-[{methyl- (carboethoxymethyl) imino} -trimethylene chloride].

Example 40

Poly-[{methyl- (carboxyatomethyl) imino} trimethylene]

A solution of 500 mg (7 mmol equivalent) of poly-[(methyl imino) trimethylene] and 4.4 g (28 mmoles) of ethyl α-bromoacetate dissolved in 10 ml of purified dimethylformamide was heated at 50 ° C. for 12 hours. The reaction mixture was concentrated to dryness under reduced pressure, and the residue was treated with 28 ml of 1 N sodium hydroxide overnight. Then, 21 ml of 1 N hydrochloric acid was added to the mixture, and the solution was desalted in an amicon filter unit equipped with an UM2 diaflo filter. When the solution was concentrated to dryness at 50 ° C, 650 mg of poly-[{methyl- (carboxyatomethyl) imino} trimethylene] was obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are carboxy atomethyl and methyl distributed in the ratio of 5: 95-95: 5, respectively, is basically the same as described above, and poly- [ (Methylimino) trimethylene] is reacted with a limited amount of ethyl-α-bromo acetate followed by methyl bromide.

Example 41

Poly-[{methyl- (carbaylmethyl) imino} trimethylene chloride]

A solution of 355 mg of poly-[(methylimino) trimethylene and 3.5 g (25 mmoles) of 2-bromoacetamide dissolved in 10 ml of dimethylformamide was heated at 60 ° C. for 15 hours, and the product was The filtrate was dissolved in water and then passed through a 25 ml cylinder containing Dowex 1- × 2 ion exchange resin (20 mmoles of chloride ions) to give poly-[{methyl- (carbamylmethyl] imino} trimethylene chloride] Is obtained.

The method of synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are carbamylmethyl and methyl distributed in the ratio of 95: 5-5: 95, respectively, is basically as described above, and poly-[( Methylimino) trimethylene] is treated with a limited amount of 2-bromoacetamide followed by excess methyl bromide.

Example 42

Poly-[{methyl- (3-N ² -methylcarbamidinofurophyll) imino} trimethylene chloride hydrochloride]

710 mg of poly-[(methylimino) trimethylene dissolved in 50 ml of dimethylformamide (10 mmol equivalent) and 12.5 g (40 mmoles of 4-bromo-N ² -methyl-N-benzyloxycarbonyl butyramidine) ) Is heated at 75 ° C. for 16 hours, and the mixture is concentrated under reduced pressure to extract the product with water. The aqueous solution was acidified to pH 3 with hydrochloric acid, hydrotreated on a 5% palladium / carbon catalyst, filtered and passed through a 100 ml cylinder containing Dowex1-x2 ion exchange resin (chloride 80 mmoles) containing chloride reverse ion. The desired product is obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are each distributed in a ratio in the range of 95: 5-5: 95 and 3-N ² -methylcarbamidinofurophyll and methyl is essentially as described above. Poly-[(methylimino) trimethylene) is first treated with a limited amount of 4-bromo-N ² -methyl-N-benzyloxycarbonyl butyramidine followed by excess methyl bromide do.

Example 43

Poly-[{methyl- (3-guanidinofurophyll) imino trimethylene chloride hydrochloride

A solution of 355 mg (5 mmol equivalent) of poly-[(methylimino) trimethylene and N'-3-bromofurophyl-N ³ -nitroguanidine dissolved in 15 ml of dimethyl formamide was stirred at 75 DEG C for 16 hours. The mixture is heated and concentrated under reduced pressure to extract the product with water. The aqueous solution was acidified to pH 3 with hydrochloric acid, hydrogenated in the presence of 100 mg of active platinum, and the solution was filtered and passed through a 50 ml cylinder containing Dowex1-x2 ion exchange resin (40 mmoles of chloride). The desired product to contain is obtained.

The process for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 3-guadinoprotropil and methyl distributed in the ratio of 95: 5-5: 95, respectively, is basically as described above and poly- [(Methylimino) trimethylene] is first treated with a limited amount of N'-3-bromofurophyll-N ³ -nitroguanidine followed by excess methyl bromide.

Example 44

Poly-[{methyl- (2-oxofurophyll) imino} trimethylene chloride

A solution of 335 mg (5 milliliter equivalents) of poly-[(methylimino) trimethylene] and 2.3 g (25 mmoles) of chlorofuropanone was heated at 50 ° C. for 16 hours, and the product was filtered off to soften with ether. After drying under reduced pressure.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 2-oxofurophyll and methyl distributed in the ratio of 95: 5-5: 95, respectively, is basically as described above, and poly- [(Methylimino) trimethylene] is first treated with a limited amount of chlorofuropanol-2 and then with excess methyl bromide.

Treatment of the product with Dowex1-x2 for the chloride ion stage yields a product containing chloride ions in particular.

Example 45

Poly-[{methyl- (benzyl) imino} trimethylene chloride]

A solution of 710 mg (10 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 15 ml of dimethylformamide and 6.8 g (40 mmoles) of benzyl bromide was heated at 50 ° C. for 16 hours, and the product was dried under reduced pressure. The reaction mixture is concentrated, separated, extracted with water, and the aqueous solution is passed through a 25 ml cylinder containing Dowex1-x2 ion exchange resin (40 mmoles of chloride ions) to give the desired product containing chloride reverse ions.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are benzyl and methyl, respectively, is as described above, wherein poly-[(methylimino) trimethylene] is first reacted with a limited amount of benzyl bromide Then react with excess benzylbromide.

Example 46

Poly-[{methyl- (1-furophen-3-yl) imino} trimethylene chloride]

A solution of 426 mg (6 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 12 ml of dimethylformamide and 3.7 (30 mmoles) of 3.7 (30 mmoles) of 3-bromo furophen-1 (allyl bromide) After heating for 16 hours at 占 폚, the product was separated by filtration and dissolved in water, and the aqueous solution was passed through a 40 ml cylinder containing Dowex1-x2 ion exchange resin (32 mmoles of chloride ions), and the effluent was concentrated under reduced pressure. The desired product containing counter ions is obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 1-furophen-3-yl and methyl distributed in the ratio of 95: 5-5: 95, respectively, is as described above, and poly -[(Methylimino) trimethylene] is reacted with a limited amount of 3-bromopuropen-1 and then with excess methyl bromide.

Example 47

Poly-[{methyl- (1-furopin-3-yl) imino} trimethylene chloride]

A solution of 710 mg (10 mmol equivalent) of poly-[(methylimino) trimethylene] dissolved in 12 ml of dimethylformamide and 3.6 g (30 mmoles) of 3-bromofuropine-1 (furopargyl bromide) After heating for 16 hours at ℃, the product was filtered off, dissolved in water and passed through a 40 ml cylinder containing Dowex 1-x2 ion exchange resin (Cl ^- 32 mmoles) to obtain the desired product containing chloride reverse ion. Lose.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are each distributed in the ratio of 5: 95-95: 5 in the range of R ₁ = 1-furopin-3-yl and R ₂ = CH ₃ As described above, poly-[(methylimino) trimethylene] is first treated with a limited amount of furargyl bromide followed by excess methyl bromide.

Example 48

Poly-[{methyl- (2,2,2-trifluoroethyl) imino} trimethylene chloride]

A solution of 355 mg (5 mmol equivalent) of poly-[(methylimino) trimethylene and 6.2 g (22 mmoles) of 2,2,2-trifluoroethyl trichloromethylsulfonate dissolved in 15 ml of dimethylformamide was added. Heat 16 ° C. for 16 hours, dilute the reaction mixture with ether, filter the product off, dissolve the product in water and pass it through a 25 ml cylinder containing Dowex 1-X2 ion exchange resin (Cl ^-20 mmoles). Concentration of the effluent under reduced pressure yields the desired product containing chloride counterions.

The process for preparing the polymer of the general formula (3) wherein R ₁ and R ₂ are 2,2,2-trifluoroethyl and methyl distributed in the ratio of 95: 5-5: 95 respectively is as described above. , Poly-[(methylimino) trimethylene] is first treated with a limited amount of 2,2,2-trifluoroethyl trichloromethylsulfonate followed by excess methyl bromide.

Example 49

Poly-[{methyl- (1-α-D-glucopyranosyl) imino} trimethylene chloride]

A solution of 535 mg (5 milliliter equivalents) of poly-[(methylimino) trimethylene and 10.3 g (25 mmoles) of tetra-0-acetyl-α-D-glucopyranosyl bromide dissolved in 25 ml of dimethylformamide was heated to 50 ° C. After heating for 16 hours, the product was diluted with ether, separated and filtered. The product was dissolved in 5 ml of water, and 2 ml of 10% hydrochloric acid was added to prevent overnight, and the solution was diluted with 100 ml of water to obtain UM-2 diaflohan. After passing through an amicon filter chamber equipped with a filter, 800 ml of the filtrate was concentrated to a volume of 50 ml, and then passed through a 25 ml cylinder containing Dowex1-X2 ion exchange resin (Cl ^-20 mmoles) to concentrate the effluent. The desired product containing chloride counterion is obtained.

The method for synthesizing the polymer of the general formula (3) wherein R ₁ and R ₂ are 1-α-D-glucopyranosyl and methyl distributed in the ratio of 95: 5-5: 95, respectively, is as described above and poly -[(Methylimino) trimethylene] is first treated with a limited amount of tetra-0-acetyl-α-D-glucopyranosyl bromide followed by excess methyl bromide.

By changing the poly-[(methylimino) ethylene] together by the method described in Examples 27-49, a quaternary polymer can be obtained, as described in Example 50 below. Instead of poly-[(methyleneimino) trimethylene] the equivalent of milli equivalents of poly-[(methylimino) ethylene] is used.

Example 50

Poly-[{methyl- (2-trimethylammonioethyl) imino} ethylene dibromide]

A solution of 50 mg (10 milliequivalents) of poly-[(methylimino) ethylene] dissolved in 40 ml of dimethylformamide and 9.9 g (40 mmoles) of 2-bromoethyltrimethylammonium bromide was heated at 75 ° C. for 12 hours. The mixture was cooled and then diluted with a 5-fold volume of ether, and the product was separated by filtration and dried under reduced pressure.

The polymer according to the present invention is effective in lowering blood levels of cholesterol even with a small amount of underwear. Therefore, the formulation which was not available previously can be formulated freely.

The polymer according to the present invention can be used as a fine powder or mixed with a solid carrier such as colloidal silica, starch, sucrose, talc, lactose, cellulose or protein powders such as modified cellulose, powdered milk and soy flour. It is appropriate. Formulation with such carriers is preferably made in unit doses into tablets, capsules, or silver foils or bags containing normal doses, and may contain vitamins and minerals. The contents of these formulations can also be readily added to beverages such as juices or other beverages. The unit composition may contain 10-99% by weight of the polymer. The remainder uses excipients, carriers, flavors, flow agents, and the like.

As such a unit amount, the active polymer may contain up to 0.1 g-10 g in powder packaging. Moreover, it can be prepared with aqueous solution or suspension, and it is good to set it as a sweetener or a flavoring agent. If necessary, the polymer may be mixed with various excipients such as safflower oil or corn oil to prepare for internal use, and may also be made into capsules.

As described above, the bile acid-binding polymer is preferably divided into several daily doses before meals and before bedtime. By taking in this way, the contact time of resin becomes maximum when the concentration of bile acid in intestine is the highest.

The polymers according to the invention can be used as single agents or in combination with triglyceride synthesis inhibitors or other bile acid binders for special treatment as needed. In addition, as described above, the polymer according to the present invention forms salts with acids of crofibrate and halophenate, which salts are effective for the treatment of cardiovascular diseases. The following examples can be used in the application of the polymers according to the invention as details of the dosage form. Further components used as carriers in the composition of the polymers according to the present invention may have a pharmacological action and include tocampfil floranthrone; Taurine; And other anti-biliary agents nicotinic acid such as glycine; Low cholesterin agents such as 3,3 ', D isomer of 5-triyo-dotyronine, thyroxine-like compounds such as sodium L-thyroxine and sodium D-thyroxine; Triyo-dotiropurion; Napoxidine hydrochloride, 5-methylpyrazole-3-carboxylic acid and 3-methyl-5-isoxazolecarboxylic acid; Stool softeners such as poloxalchol and dioctyl sodium, sulfosuccinate and the like, as well as unsaturated fatty acids such as linoleic acid, arachidonic acid and linolenic acid; Edible vegetable oils such as corn oil and safflower oil.

[Example of Zippo Agent]

Linearly unbranched and non-horizontal-chain bonded poly-[(dimethylimino) ethylene chloride) (molecular weight: about 20,000) as a fine powder, mixed with 1% by weight of lactose powder, and then put into a paper bag 0.55 g of the above-mentioned mixture in an aluminum bag is filled in each bag and sealed to prevent wet solidification. Poly-[(2-hydroxyethyl methyliminoethylene chloride] or other polymers according to the invention instead of poly-[(dimethylimino) ethylene chloride] and having a molecular weight ranging from about 1500-50,000 and higher and generally about It can be used as an excess of 1,500 as a polymer having a single average molecular weight or replaced with a mixture having several molecular weights.

[Hard Capsule Example]

Poly-[(dimethylimino) ethylene chloride] containing 1% by weight of lactose mal as described above is filled into hard capsules of suitable size. Alternatively, a dry filling capsule is prepared using the following ingredients.

Poly-[{trimethylammonioethyl) methylimino} ethylene chloride] 300 mg

Corn Starch 150mg

Cabb-o-sil (silica anhydride) 5 mg

Dry filled capsules are also prepared using other novel polymers according to the invention as described above. If the capsule is to be made less effective, reduce the size of the capsule, add corn starch, or use other diluents. If small amounts of active ingredient are used, increase the number of doses of the capsule.

[Tablet example]

The dry mixture is prepared as follows.

[ingredient :]

1 kg poly-[(dimethylimino) ethylene chloride]

30g per book

10g colloidal silica

Carbowax-4000 30g

Direct tableting to contain 250 mg of ionene polymer per tablet yields 4,000 tablets. In addition, tablets are tableted with the following tablets per tablet.

Poly-[(dimethylimino) ethylene chloride] 300 mg polyvinylpyrrolidone 10 mg

Corn starch 30 mg magnesium stearate 3 mg

After making into tablets as described above, the plastic film is coated by known methods to prevent moisture.

As another method, it coats as enteric skin as needed. Such coating can be made by a known method using fats, fatty acids, waxes and mixtures thereof, shellec, ammonium shelle and cellulose phthalate.

Instead of poly-[(dimethylimino) ethylene chloride] any of the polymers according to the invention can be used. As other binders, dextrose, lactose, methylcellulose, natural and synthetic rubber, etc. may be used instead of sugar, and talc may be used instead of calcium stearate or magnesium. Various non-toxic desiccants which can be easily used can be used in place of colloidal silica.

Other lubricants, diluents, binders, colorants, flavors and ingots use those known in the wet or dry granulation method, direct compression purification method, and spray drying method. If necessary, dry granulate the polymer particles into very small capsules to make chewable tablets:

Per tablet

Poly-[(dimethylimino) ethylene chloride)] Fine capsule 750 mg

Mannitol 300mg

Sodium Saccharin (or other artificial sweeteners) 2mg

Pepper oil 1mg

Cabo Wax-4,000 15 mg

Microcrystalline Cellulose 100mg

In addition, the polymer according to the present invention is particularly useful when used as an adsorbent of colloidal particles in liquids such as purified water and wastewater in the molecular weight range, and also adds paper feedstock during paper making operations. In this case, it can be used as a gripping aid. Moreover, the polymer according to the present invention is effective as an antibacterial and a tablet, and as a tablet, it can be used in the treatment of cotton, wool and synthetic fibers. These polymers are also used as fabric softeners and in the bonding of dye aids, in particular anionic dyes. In addition, antibacterial agents are added to nonionic and cationic detergents, cosmetics, hairsprays and similar preparations as well as viscous agents. When used in this way, the polymers according to the invention are used in the same amounts and in a similar way to conventionally known materials used for this purpose.

When the polymer according to the invention is used as a detergent or adsorbent, it is treated by adding 0.5-2 pounds of polymer per 1000 gallons of water to be dissolved or dispersed in an aqueous medium to be treated. In general, the polymers according to the invention have a molecular weight of 300-50,000 and above. Polymers of molecular weight 1,500 or less are suitable for use as adsorbents and the like, but not as bile acid binders, and the molecules of such polymers can be separated from molecules of high molecular weight by known methods. These polymers are administered orally in an effective amount of bile acid bonds. Generally, in order to lower the amount of serum cholesterol, an overdose of about 10 g may be taken as directed, but it is appropriate to take about 0.1-5.0 g once or several times. This dose is also effective for treating pruritus caused by bile. The method of administration may be administered in various forms, such as suspensions, chewing tablets or co-ting tablets or in capsules, and the treatment may be continued for a long time. In general, the dosage should be divided into daily doses and taken with meals. In order to suppress hypercholesterolemia, it is advisable to keep an eye on the amount of serum cholesterol by carefully determining the initial dose of each person with varying metabolism and dietary changes. Using the appropriate dose for the first time increases the amount of serum cholesterol until it is maintained as desired. The initial dose is satisfactory if adjusted to 2.5-100 mg / kg body weight per day, depending on the individual. Those skilled in the art also understand that in the general formula of the polymers according to the invention, when R ₁ , R ₂ , R ₃ and R ₄ are ammonium lower alkyl, lower alkyl ammonium lower alkyl, dilower alkyl ammonium lower alkyl, i.e. It will be admired that they are in the form of aminolower alkyl, lower alkylamino lower alkyl and dilower alkylamino lower alkyl, respectively.

The present invention has the subject matter of the claims, but also includes the following embodiments.

(1) a shipboard characterized in that it is formed by polymerizing a polymer formed by polymerizing a monomer unit of the following general formula (6a) with at least a molar equivalent of a chemical reducing agent and then polymerizing a weight unit of the following general formula (3a), Processes for Making Unbranched, Non-Phase-Chain-Bound Polymers

Wherein m is an integer such as 1 or 0, R ¹ is hydrogen, lower alkyl, phenyl, naphthyl, or naphthylethyl, Q is ethylene or trimethylene, and Z represents a reverse ion.

(2) The method of embodiment (1), wherein the chemical reducing agent is diborane

(3) the method of the claims using 97-100% formic acid and aqueous formaldehyde solution

(4) The following general formula is formed by heating a mixture formed by polymerizing a monomer unit of the following general formula (6b) with at least 1 equivalent of formaldehyde and formic acid, respectively, at 100-100 캜 for 100 hours. Process for producing linear, unbranched, non-horizontal-chain bonded polymers formed by polymerizing monomer units of (3b)

(5) The method of embodiment (4) using 97-100% formic acid and aqueous formaldehyde solution

(6) The method of embodiment (4), wherein Q is ethylene

(7) The method of embodiment (4), wherein Q is triethylene

(8) a second polymer formed by polymerizing the monomer units of the following general formula (6C);

(a) where R ₃ and R ₄ are the same, react in an inert solvent at a temperature of 30-100 ° C. with at least 15 equivalents of RX wherein R is R ₃ or R ₄ and X are halides or sulfonates,

(b) when R ₃ and R ₄ are different, the second polymer is first reacted with less than 1 equivalent of R ₃ X in an inert solvent and reacted with a base corresponding to the equivalent of the used R ₃ X to form a third polymer. Then, the amount of R ₃ X and R ₄ X used by reacting the above-mentioned third polymer with the R ₄ X reactant in an inert solvent is substantially the same as the equivalent of polymerizing monomer units in the above-mentioned second polymer. A process for preparing a linear, unbranched, non-horizontal-chain bonded first polymer which is then formed by polymerizing monomeric units of a generic color (3C).

'' 는 다음 일반식과 같은 기준의 결합을 표시한다.Wherein Z represents an inverse ion, Q is ethylene or trimethylene, m is an integer such as 0 or 1 and the protective ''

'' Denotes a combination of criteria such as the following general formula:

또는

or

R ₃ and R ₄ are as described above.

(9) The method of embodiment (8), wherein R ₃ and R ₄ are methyl and Q is ethylene

(10) The method of embodiment (8) wherein R ₃ and R ₄ are methyl and Q is trimethylene

(11) A second polymer formed by polymerizing the monomer units of the following general formula (6d)

(a) where R ₁ and R ₂ are the same, react with at least an equivalent amount of RX wherein R is R ₁ and X is a halide, sulfonate or sulfate;

(b) when R is different from R ₃ , the second polymer is first reacted with 5-95% of one equivalent of RX and at least one equivalent of R ₂ X

(c) A process for preparing a linear, unbranched, non-transverse-chain-linked first polymer formed by exchange with an anion Z, optionally in place of anion X on the next polymer.

'' 또는 다음과 같은 일반식의 기균의 결합을 표시한다.Wherein X is a halide, sulfate or sulfonate, Q is ethylene or methylene and the symbol '' in formula (3d)

'' Or the combination of the following organisms of the general formula:

또는

or

''는 다음과 같은 일반식의 기군결합을 표시한다.R ₃ and R ₄ are as described above, and the symbol '' in formula (6d)

'' Denotes an air force combination of the following general formula:

(12) The method of embodiment (11), wherein R ₁ and R ₂ are lower alkyl

(13) The method of embodiment (11) wherein R ₃ and R ₄ are lower alkyl

(14) R ₁ or R ₂ is ammonioalkyl; Lower alkyl ammonium lower alkyl; The method of embodiment (11), wherein the lower alkyl ammonium lower alkyl and the ammonia cation described above are trilower alkyl ammonium lower alkyls that neutralize with anions.

(15) The method of embodiment (11), wherein R ₁ or R ₂ is hydroxy-substituted lower alkyl and hydroxy-substituted cyclolower alkyl.

(16) The method of embodiment (11) wherein R ₃ and R ₄ are methyl

(17) The method of embodiment (16), wherein Q is ethylene

(18) The method of embodiment (17) wherein the first polymer described above is poly-[{methyl- (2-trimethylammonioethyl) imino} ethylenecychloride]

(19) The method of embodiment (18), wherein the first polymer described above is poly-[(dimethylimino] ethylene ascorbate]

(20) The method of embodiment (18), wherein the first polymer described above is poly-[(dimethylimino) ethylene 3-trifluoromethylphenoxy (4-chlorophenyl) acetate].

(21) The method of embodiment (16), wherein Q is trimethylene

(22) The method of embodiment (16) wherein the first polymer described above is poly-[{methyl- (3-hydroxyammoniofurophyll) imino} trimethylenechloride]

(23) The method of embodiment (16) wherein the first polymer described above is poly-[{methyl- (3-hydroxyfurophyll) imino} trimethylenechloride]

(24) The method of embodiment (16) wherein the polymer described above is poly-[{methyl- (3-methoxyfurophyll) imino} trimethylenechloride]

(25) The method of embodiment (16) wherein the first polymer described above is poly-[{methyl- (3-methylthiofurophyll) imino} trimethylenechloride]

(26) The method of embodiment (16) wherein the polymer described above is poly-[{methyl- (2-oxofurophyll) imino} trimethylenechloride]

(27) The method of embodiment (16), wherein the first polymer described above is poly-[{methyl-carboxyatomethyl) imino} trimethylene]

(28) The method of embodiment (16) wherein the polymer described above is poly-[{methyl-carbamylmethyl) imino} trimethylene chloride]

(29) The method of embodiment (11), wherein R ₁ is methyl

(30) The method of embodiment (29) wherein R ₂ is 3-trimethylammoniofurophyll halide.

(31) The method of embodiment 29, wherein R ₂ is benzyl.

(32) The method of the claims, wherein Q is ethylene.

(33) The method of the claims, wherein Q is trimethylene.

(34) The method of embodiment (11) wherein Q is trimethylene and R ₁ , R ₂ , R ₃ and R ₄ are methyl

(35) The method of embodiment (11), wherein R ₁ , R ₂ , R ₃ and R ₄ are methyl

Claims (1)

As described above in the text, a mixture obtained by mixing a polymer composed of repeating units of the monomer represented by the following general formula (11) with at least one equivalent of formaldehyde and at least one equivalent of formic acid is 100 at a temperature of 30-100 ° C. A process for preparing a linear, unbranched, non-crosslinked polymer consisting of repeating units of monomers represented by the following general formula (12), characterized by heating for a time.

Wherein Q is ethylene or trimethylene and Z is Counter-anion.