Use of 2,4-dihalo-6-substituted-1,3,5-triazines and derivative thereof as condensation, cross-linking, tanning, grafting and curing agents

Abstract

Use of 2,4-dihalo-6-substituted-1,3,5-triazines as condensing, cross-linking, tanning, grafting, curing agents for the production of amides, esters, thioesters, and stabilized collagen and leather, CMC (carboxymethyl cellulose), synthetic and natural polymers. The process enables to obtain non-toxic and totally free of heavy metals products characterized by Tg values between 80° C. and 100° C.

Claims

1. A method for condensing, cross-linking, tanning, grafting, or curing, comprising: (a) reacting a reagent having a carboxylic acid group with at least one primary or secondary amine, alcohol or thioalcohol in a solvent and in the presence of a 2,4,6-substituted-1,3,5-triazine of formula (I), ##STR00005## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of linear alkyl quaternary ammonium group, branched alkyl quaternary ammonium group, aryl quaternary ammonium group, and heterocyclic quaternary ammonium group, and R.sub.3 is selected from the group consisting of (C1-C4)alkoxy, (C6-C8)aryloxy, and a substituted amine of the formula NR′R″, wherein R′ and R″ are independently (C1-C4)alkyl or (C6-C8) aryl, and (b) quenching the reaction by adding water to recover a condensed, cross-linked, tanned, grafted or cured reaction product.

2. The method according to claim 1, wherein R.sub.3 is selected from the group consisting of OCH.sub.3, OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3, and OCH.sub.2CH.sub.2CH.sub.2CH.sub.3.

3. The method according to claim 1, wherein R.sub.3 is selected from the group consisting of OC.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.4CH.sub.3.

4. The method according to claim 1, wherein R.sub.3 is selected from the group consisting of N(CH.sub.3).sub.2, N(CH.sub.2CH.sub.3).sub.2, N[CH(CH.sub.3).sub.2].sub.2, N(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 and N(C.sub.6H.sub.5).sub.2.

5. The method according to claim 1, wherein the reacting step (a) is carried out at a temperature between 0° C. and 70° C. for 15 minutes to 48 hours.

6. The method according to claim 1, wherein the solvent is selected from the group consisting of an aliphatic ether, a halogenate, an alcohol, a ketone, an ester, an aromatic hydrocarbon, an aliphatic hydrocarbon, an amide, a carbonate, DMSO and water.

7. The method according to claim 1, comprising reacting collagen dispersed in water in the presence of 1-20% by weight of the 2,4,6-substituted-1,3,5-triazine of formula (I) at a temperature of 0° C. to 40° C. for 15 minutes to 48 hours, and wherein the collagen is in the form of powder, skin or liquid.

8. A method for condensation, cross-linking, tanning, grafting or curing for the production of amides, esters, thioesters, stabilized collagen, leather, and natural and synthetic polymers, comprising the steps of: (a) reacting a reagent having a carboxylic acid group with at least one primary or secondary amine, alcohol or thioalcohol in a solvent and in the presence of a 2,4,6-substituted-1,3,5-triazine of formula (I), ##STR00006## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of linear alkyl quaternary ammonium group, branched alkyl quaternary ammonium group, aryl quaternary ammonium group, and heterocyclic quaternary ammonium group, R.sub.3 is selected from the group consisting of (C1-C4)alkoxy, (C6-C8)aryloxy, and a substituted amine of the formula NR′R″, wherein R′ and R″ are independently (C1-C4)alkyl or (C6-C8) aryl, and (b) quenching the reaction by adding water.

9. The method according to claim 8, comprising reacting collagen dispersed in water in the presence of 1-20% by weight of the 2,4,6-substituted-1,3,5-triazine of formula (I) at a temperature of 0° C. to 40° C. for 15 minutes to 48 hours, and wherein the collagen is in the form of powder, skin or liquid.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) The object of the invention is the use of 2,4-dihalo-6-substituted-1,3,5-triazines, and derivatives thereof, as condensing agents, crosslinking, tanning, grafting, curing for the production of amides, esters, thioesters, collagen and stabilized leather, carboxymethylcellulose (CMC), synthetic and natural polymers.

(2) Currently there are no studies or applications regarding the use of this class of compounds as condensation, crosslinking, tanning, grafting and curing agents.

(3) These compounds are easy to be synthesized and used, are stable over time (also several months in solution) compared to alternative reagents known and used with the same purpose in the state of the art. The use of the compounds according to the invention also reduces the environmental impact of the process itself, limiting the amount of solvents and reagents, time required for their preparation and use.

(4) Condensation grafting, tanning, crosslinking, curing agents used according to the invention are 2,4-dihalo-6-substituted-1,3,5-triazines of general formula I,

(5) ##STR00002##
and derivatives thereof, wherein:

(6) R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of: linear alkyl quaternary ammonium group, branched alkyl quaternary ammonium group, aryl quaternary ammonium group, heterocyclic quaternary ammonium group, Cl, Br and F.

(7) R.sub.3 is selected from the group consisting of: alkoxy (C1-C4), aryloxy (C6-C8) and substituted NR′R″ wherein R′ and R″ independently are alkyl (C1-C4) or aryl (C6-C8);

(8) In a preferred embodiment of the invention, R.sub.3 is an alkoxy (C1-C4), and, in particular, is: OCH.sub.3, OCH.sub.2CH.sub.3, OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.3, OCH.sub.2CH.sub.2CH.sub.2CH.sub.3.

(9) In another preferred embodiment of the invention, compound of general formula I, wherein R.sub.3 is a substituted tertiary amine, whose amine substituents R′ and R″ independently are alkyl (C1-C4) or aryl (C6-C8), therefore in this embodiment R.sub.3 is: N (CH.sub.3).sub.2, N(CH.sub.2CH.sub.3).sub.2, N[CH(CH.sub.3).sub.2].sub.2, N(CH.sub.2CH.sub.2CH.sub.2CH.sub.3).sub.2 and N(C.sub.6H.sub.5).sub.2 is used.

(10) In a third preferred embodiment of the invention compound of general formula I, wherein R.sub.3 is an aryloxy (C6-C8), and, in particular, is: OC.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.4CH.sub.3 is used.

(11) In a fourth preferred embodiment, R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of linear or branched alkyl, aryl or heterocyclic quaternary ammonium salt.

(12) In a further preferred embodiment R.sub.1 and R.sub.2 are independently selected from: Cl, Br and F.

(13) According to the applicant's studies in the presence of Cl, Br and F in R.sub.1 or R.sub.2, condensation, cross-linking, tanning, grafting and curing reaction requires the presence of one or more equivalents of linear or branched, aryl or heterocyclic tertiary amine. Tertiary amines are used in combination with reagent I in the case R.sub.1 and R.sub.2 are selected from: Cl, Br and F, resulting in the formation of 2,4-diammonium derivatives of 2,4-dihalo-6-substitute-1,3,5-triazine which is the activating agent for the condensation reaction.

(14) The use of tertiary amines is particularly preferred in this type of application as these do not interfere with condensation, cross-linking, tanning, grafting and curing reactions that can only be carried out from a primary or secondary amine according to the scheme:

(15) ##STR00003##

(16) Hence, according to the invention in a particularly preferred embodiment the use of derivatives of 2,4-dihalo-6-substitute-1,3,5-triazine of general formula II

(17) ##STR00004##

(18) wherein

(19) R.sub.1 and R.sub.2 are the same or different and are selected from the group consisting of: linear or branched alkyl, aryl or heterocyclic quaternary ammonium group, Y is a counterion, having charge n/a from 1 to 4, a is between 2 and 4, and n is between 2 and 4; Y is a counterion selected from: Cl, Br and F, is provided.

(20) R.sub.3 is selected from the group consisting of: alkoxy (C1-C4), aryloxy (C6-C8) and substituted amine NR′R″ wherein R′ and R″ independently are alkyl (C1-C4) or aryl (C6-C8);

(21) According to the invention herein described, the process for the use of 2,4-dihalo-6-substituted-1,3,5-triazines and its derivatives comprises the following steps: reaction between a reagent having carboxylic acid groups with one or more primary or secondary amines, alcohols or thioalcohols, in a single step, in a solvent, in the presence, depending on the type of specific reaction, e.g.: condensation, cross-linking tanning, grafting and curing, of the respective condensation, cross-linking, tanning, grafting and curing agent I as above described; quenching the reaction by adding water and recovering the product according to standard techniques known to the field expert.

(22) The solvent is selected from the group consisting of: aliphatic ether, halogenate, alcohol, ketone, ester, aromatic or aliphatic hydrocarbon, amide, carbonate, DMSO, water.

(23) In particular, the above-specified procedure for the various types of reactions is: Condensation reaction: reaction between 1 equivalent of carboxylic acid compound and 1-3 equivalents of primary or secondary amine, alcohol or thioalcohol, in an organic solvent or water in the presence of 1-3 equivalents of condensation agent I, as above described. The reaction is carried out at a temperature ranging from 0° C. to 70° C., for a time varying between 15 min and 6 hours. Reaction times are very short and purification procedures are very simplified with respect to the state of the art (Examples 9 and 10). Cross-linking reaction: in this case the crosslinking reaction occurs between the carboxylic acid groups and primary or secondary amine groups, alcoholic or thioalcoholic groups present within the same matrix, in an organic solvent or water, in the presence of 1-20% by weight of crosslinking agent. In this case the reaction can occur in a homogeneous or heterogeneous phase depending on the nature of the treated matrix. For “homogeneous phase” in this description should be intended a reaction wherein in the same step all reagents are present; by the expression “heterogeneous phase” a reaction wherein the reagents are present in different phases is meant. The reaction is carried out at a temperature ranging from 0° C. to 70° C., for a time varying between 15 min and 6 hours (examples 3 and 4). Tanning reaction: is a particular example of cross-linking reaction. Collagen, in form of powder, skin or liquid, is dispersed in water and 1-20% by weight of tanning agent is added. In this case the reaction can occur in a homogeneous or heterogeneous phase as the nature of the treated organic matrix varies. The reaction is carried out at a variable temperature ranging from 0° C. to 40° C., for a time varying from 15 minutes to 48 hours (examples 1-2).

(24) The efficacy of the crosslinking degree obtained by the effect of 2,4-dihalo-6-substituted-1,3,5-triazines and their derivatives according to the invention is measured by DSC (Differential Scanning Calorimetry); a rise in Tg compared to non-crosslinked native collagen (Tg 60-65° C.) indicates an increase in the degree of crosslinking. In all cases, the collagen samples treated according to the invention have Tg values higher than 80° C., and in particular between 80° C. and 100° C.

(25) To date there are no available tanning agents that can provide Tg values comparable to chromium salts (about 100° C.) that are used to produce more than 85% of tanned leather in the world, although chromium (III) is a heavy metal producing carcinogenic chromium (VI) and generating a high impact on the environment due to the formation of large quantities of sludge which should be disposed of.

(26) The Tg values obtained according to the invention described herein by derivatives of I are a result of great value and innovation for the production of leather and for the collagen stabilization in general. In addition, as these reagents do not leave any traces in the final product, they enable to obtain highly stabilized, non-toxic, totally metal free leather and collagen. Grafting reaction: reaction between a polymer having carboxylic acid groups, primary or secondary amines, alcohol or thioalcohol (in solution or solid) dispersed in a solvent or water and one or more carboxylic acids, primary or secondary amines, alcohols, thioalcohols in variable stoichiometry depending on the nature of the treated matrix. To this mixture, 0.1-3 equivalents of grafting agent I are added to the moles of acid, primary or secondary amines, alcohol, thioalcohol are added. In this case the reaction can occur in a homogeneous or heterogeneous phase as the nature of the treated matrix varies. The reaction is carried out at a temperature ranging from 0° C. to 70° C., for a time varying from 1 to 48 hours. Carboxylic acids, primary or secondary amines, alcohols and thioalcohols can be chosen to provide peculiar characteristics to the final polymers such as anti-fungal, anti-vegetative, anti-mould properties (examples 7 and 8). The grafting procedure of the present invention allows to modify the characteristics of polymers in a simple way, at high yield, and improved to the state of the art. Curing reaction: reaction between a polymer having more carboxylic acid groups and one or more polymers having more primary or secondary amino groups, alcoholic, thioalcoholic in stoichiometry depending on the nature of the treated polymers. To this mixture is added 0.1-3 equivalents of curing agent I to the moles of acid, primary or secondary amine, alcohol, thioalcohol are added. In this case, the reaction can occur in a homogeneous or heterogeneous phase, depending on the nature of the polymeric matrix treated. The reaction is carried out at a temperature ranging from 0° C. to 70° C., for a time varying between 15 min and 48 hours (examples 5 and 6).

(27) In the condensation, crosslinking, tanning, grafting and curing reactions in the presence of I, in the particular embodiment wherein R.sub.1═R.sub.2═Cl, Br or F, the condensation reagent I is used in combination with one or more tertiary amines that can be added to the reaction mixture simultaneously, or in succession, producing species of general formula II. Alternatively, reagents I and tertiary amines may be premixed in a solvent or water at a temperature between 0° C. and 50° C. for a time ranging from 15 minutes to 1 hour and then to be used for the reaction.

(28) Based on the results obtained for the condensation, crosslinking, tanning, grafting and curing reactions it is evident that the combined use of the reagents I wherein R.sub.1═R.sub.2═Cl, Br or F and a tertiary amine according to the invention (see examples): (i) provides conversions, performances and characteristics equal to or greater than those obtained by the use of reagent I having R.sub.2 and R.sub.3 other than a halogen; (ii) may be formulated in the presence of different tertiary amines, and accordingly, depending on the type of application, one may choose the one available at the most advantageous market price; (iii) has no problem of activity related to the nature of the solvent.

(29) The effectiveness of the process according to the invention has been tested in various condensation reactions between a carboxylic acid and an amine, alcohol or thioalcohol, as widely described in the examples of the experimental section.

(30) Experimental Part

(31) The invention will now be below described with particular reference to some non limitative examples.

Example 1. Collagen Tanning in the Presence of the Derivative I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═N-ethylmorpholine

(32) In a becker equipped with magnetic stirrer, 250 mg of collagen in powder were suspended in 20 ml of water and 31 mg (0.075 mmoles) of I. After 4 hours at room temperature the suspension was filtered and collagen analyzed by DSC (Tg=84° C.)

Example 2. Collagen Tanning in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═Cl and N-methylmorpholine

(33) In a becker equipped with magnetic stirring, 250 mg of powdered collagen were suspended in 20 mL of water, 12-50 mg (0.075-0.35 mmol) of I and 7.6-35.4 mg (0.075-0.35 mmol) of N-methylmorpholine. After 4 hours at room temperature, the suspension was filtered and collagen analyzed by DSC, providing Tg=82-90° C. at varying the moles of reagents employed.

Example 3. CMC Cross-Linking in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═N-methylmorpholine

(34) In a magnetically stirred balloon 280 mg of CMC (carboxylation degree c=0.7) were dissolved in 25 ml of water and 20 mg (0.05 mmoles) of I. After 24 hours at r.t., the CMC was filtered, washed and characterized by FT-IR: 3200, 1750-1735, 1602, 1020 cm.sup.−1.

Example 4. CMC Cross-Linking in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.2.═R.SUB.3.═Cl and N-ethylmorpholine

(35) In a magnetically stirred balloon 280 mg of CMC (c=0.7), 25 ml of water, 12-50 mg (0.075-0.35 mmoles) of I and 8.6-40.3 mg (0.075-0.35 mmoles) of N-ethylmorpholine were added. After 24 hours, the CMC was filtered, washed and characterized by FT-IR.

Example 5. Curing of CMC/Chitosan in the Presence of I Having R.SUB.3.═N(CH.SUB.2.CH.SUB.3.).SUB.2., R.SUB.1.═R.SUB.2.═N-methylpyrrolidinium

(36) In a magnetically stirred balloon, 50 mL of water, 1 g of CMC (c=0.7), 250 mg of chitosan and 50 mg (0.13 mmoles) of I were introduced. After 24 hours, the product was filtered, washed and characterized by FT-IR: 3200.3000, 1750-1735, 1602, 1020, 890 cm.sup.−1.

Example 6. Curing of CMC/Chitosan in the Presence of I Having R.SUB.3.═N(CH.SUB.2.CH.SUB.3.).SUB.2., R.SUB.1.═R.SUB.2.═Cl and N-methylpyrrolidine

(37) In a magnetically stirred balloon, 50 mL of water, 1 g of CMC=0.7), 250 mg of chitosan, 13.5-63 mg (0.075-0.35 mmoles) of I and 6.3-30.0 mg (0.075-0.35 mmoles) of N-methylpyrrolidine were added. After 24 hours, the product was filtered, washed and characterized by FT-IR.

Example 7. Polyacrylic Acid Grafting with Taurine in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═N-trimethylammonium

(38) In a balloon equipped with magnetic stirrer, 600 mg of polyacrylic acid, 500 mg of taurine (3.8 mmoles), 15 mL water and 630 mg (2.1 mmoles) of I. After 24 hours, the obtained white solid was filtered, washed, dried and characterized by NMR. 1H NMR (300 MHz, DMSO D6, ppm) δ: 4.36 (1H, s), 4.23 (2H, s)

Example 8. Polyacrylic Acid Grafting with Taurine in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═Cl and N-trimethylamine

(39) In a balloon equipped with magnetic stirrer, 600 mg of polyacrylic acid, 500 mg of taurine (3.8 mmoles), 15 mL of water, 270-450 mg (1.5-2.5 mmoles) of I and 89.0-147.5 mg (1.5-2.5 mmoles) of N-trimethylamine. After 24 hours, the obtained solid is filtered, washed, dried and characterized by NMR.

Example 9. Condensation of Benzoic Acid in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═N-trimethylammonium

(40) In a balloon equipped with magnetic stirring, 146 mg (1.2 mmol) of phenylethylamine, 147 mg (1.2 mmol) of benzoic acid, 6 mL of methanol and 230 mg (0.6 mmol) of I were added. After 3 hours at a temperature between 0° C. and 50° C., the solvent was removed and the solid residue was dissolved in diethyl ether (30 mL), was washed with an aqueous solution of Na.sub.2CO.sub.3, then with a 1N solution of HCl, made anhydrous with MgSO.sub.4 and filtered. The solution was dehydrated to obtain a white solid (yield 92%, purity 95%). H NMR (300 MHz, CDCl.sub.3, ppm) δ: 7.8-7.2 (10H, m), 6.20 (1H, s broad), 3.71 (2H, q), 2.95 (2H, t).

Example 10. Condensation of Benzoic Acid and Phenylethylamine in the Presence of I Having R.SUB.3.═OCH.SUB.3., R.SUB.1.═R.SUB.2.═Cl and N-methylmorpholine

(41) In a balloon equipped with magnetic stirring, 146 mg (1.2 mmol) of phenylethylamine, 147 mg (1.2 mmol) of benzoic acid, 4 mL of methanol, 108-180 mg (0.6-1.0 mmol) of I and 60.6-101.5 mg (0.6-1.0 mmol) of N-methyl morpholine were added. After 1 hour, the reaction mixture was treated as described in Example 9 (yield 95% purity 93%).