High-polarity quaternary ammonium salt antibacterial agent and preparation method thereof

Abstract

The invention discloses a high-polarity quaternary ammonium salt antibacterial agent and a preparation method thereof, an aryl sulfonamide compound and a terminal alcohol compound containing an active leaving group are used as raw materials, heating reflux is performed in an organic solvent, nucleophilic substitution is performed, and the high-polarity quaternary ammonium salt antibacterial agent is generated. According to the synthesis method disclosed by the invention, hydroxyl groups are introduced into the molecular structure of the product and can form hydrogen bonds with other polar substances, so that the interaction force among molecules is increased, the product is firmly combined on the surface of a coating and is not easy to elute, the antibacterial effect is favorably improved, and the antibacterial life is prolonged; the method has the advantages of mild reaction conditions, simple and reliable process flow, high safety and high yield, and is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of chemical product preparation, in particular to a high-polarity quaternary ammonium salt antibacterial agent and a preparation method thereof. Background Art

[0002] After bacteria, fungi, viruses and other pathogenic microorganisms adhere to the surface of the material, they will communicate with each other through signal molecules, attract the same kind of aggregation, and form a complete biofilm structure, which will lead to persistent infection in the human body and pathological changes in body tissues. The walls and furniture in public places and medical institutions are the main places for pathogenic microorganisms such as bacteria, fungi and viruses to adhere, and their hygiene conditions are directly related to the cleanliness of the environment and people's health.

[0003] Paint antimicrobial agents are a class of chemicals that are specifically added to paint to give the coating lasting antimicrobial properties. They can effectively inhibit or kill bacteria, mold and other microorganisms attached to the surface of the paint, thereby keeping the environment clean and reducing the risk of pathogen transmission. They can be widely used in walls, floors, ceilings, etc. in medical, school and home areas to provide people with a healthier living environment. In addition, paint antimicrobial agents have stable properties, can maintain long-term antimicrobial effects, will not release harmful substances, and are environmentally friendly and healthy.

[0004] However, in the process of implementing the technical solution of the invention in the embodiments of the present application, the inventors of the present application found that the existing coating antibacterial agents have poor binding strength in the coating, are easily worn or washed off, have a short antibacterial life, and affect the antibacterial effect and antibacterial durability. Summary of the invention

[0005] The present invention can solve the above-mentioned shortcomings of the existing coating antibacterial agents by providing a high-polarity quaternary ammonium salt antibacterial agent and a preparation method thereof.

[0006] In order to solve the above technical problems, the present invention provides a high-polarity quaternary ammonium salt antibacterial agent, which at least includes a compound of the following structural formula:

[0007]

[0008] in, is phenyl, p-tolyl, 2-tolyl, 3-tolyl, 4-ethylphenyl, 4-butylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-butoxyphenyl, 2,4,6-trimethylphenyl, 2,5-xylyl, 2,4-xylyl, 4-fluorophenyl, 3-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-iodophenyl, 2,4,6-triisopropylphenyl, 2-naphthylphenyl, 2-nitrophenyl, 3-nitrophenyl or 4-nitrophenyl;

[0009] n is an integer from 0 to 12;

[0010] m is an integer from 0 to 18;

[0011] R2 is a C1-C4 straight chain alkyl group;

[0012] X is at least one of chloride, bromide, iodide, methanesulfonate, trifluoromethanesulfonate, ethylsulfonate, butylsulfonate, perfluorobutylsulfonate, benzenesulfonate, 4-fluorobenzenesulfonate, 4-chlorobenzenesulfonate, 4-bromobenzenesulfonate, camphorsulfonate, hexafluorophosphate, tetrafluoroborate or bis(trifluoromethanesulfonylimide) ion.

[0013] In order to solve the above technical problems, the present invention also provides a method for preparing a high-polarity quaternary ammonium salt antibacterial agent, which uses an aryl sulfonamide compound and a terminal alcohol compound containing an active leaving group as raw materials, heats and refluxes in an organic solvent, and performs a nucleophilic substitution reaction. After the reaction, the high-polarity quaternary ammonium salt antibacterial agent is obtained by cooling, filtering, washing, and drying. The reaction formula is as follows:

[0014]

[0015] In a preferred embodiment of the present invention, it is characterized in that the molar ratio of the arylsulfonamide compound to the terminal alcohol compound containing an active leaving group is 1:1-1.2.

[0016] In a preferred embodiment of the present invention, the temperature of the heating reflux is 60-120°C.

[0017] In a preferred embodiment of the present invention, the temperature of the heating reflux is 80-100°C.

[0018] In a preferred embodiment of the present invention, the organic solvent includes at least one of benzene, toluene, xylene, chlorobenzene, methanol, ethanol, n-propanol, isopropanol, n-butanol, cyclohexanol, acetonitrile, acetone, ethyl acetate, propyl acetate, butyl acetate, petroleum ether, ethylene glycol dimethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, cyclohexanone or toluene cyclohexanone.

[0019] In a preferred embodiment of the present invention, the organic solvent includes at least one of ethyl acetate, butyl acetate or ethylene glycol dibutyl ether.

[0020] In a preferred embodiment of the present invention, the sulfonyl group in the arylsulfonamide compound includes benzenesulfonyl, p-toluenesulfonyl, 2-toluenesulfonyl, 3-toluenesulfonyl, 4-ethylbenzenesulfonyl, 4-butylbenzenesulfonyl, 4-methoxybenzenesulfonyl, 4-ethoxybenzenesulfonyl, 4-isopropoxybenzenesulfonyl, 4-butoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2,5-dimethylbenzenesulfonyl, 2, At least one of 4-xylenesulfonyl, 4-fluorobenzenesulfonyl, 3-fluorobenzenesulfonyl, 2-fluorobenzenesulfonyl, 4-chlorobenzenesulfonyl, 3-chlorobenzenesulfonyl, 2-chlorobenzenesulfonyl, 4-bromobenzenesulfonyl, 3-bromobenzenesulfonyl, 2-bromobenzenesulfonyl, 4-iodobenzenesulfonyl, 2,4,6-triisopropylbenzenesulfonyl, 2-naphthalenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl and 4-nitrobenzenesulfonyl.

[0021] The invention has the beneficial effects of: a high-polarity quaternary ammonium salt antibacterial agent and a preparation method thereof, using an aromatic sulfonamide compound and a terminal alcohol compound containing an active leaving group as raw materials, introducing a hydroxyl group into the molecular structure of the product, and being able to form hydrogen bonds with other polar substances, thereby increasing the interaction force between molecules, achieving firm bonding on the coating surface, not being easy to elute, being beneficial to improving the antibacterial effect, and extending the antibacterial life; the invention has mild reaction conditions, a simple and reliable process flow, high safety, high yield, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The present invention discloses a method for preparing a highly polar quaternary ammonium salt antibacterial agent, and shows a nuclear magnetic resonance spectrum of N-(2-(benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(12-hydroxydodecyl)-1-ammonium bromide prepared in a preferred embodiment 1. DETAILED DESCRIPTION

[0023] The preferred embodiments of the present invention are described in detail below in conjunction with the accompanying drawings so that the advantages and features of the present invention can be more easily understood by those skilled in the art, thereby making a clearer and more definite definition of the protection scope of the present invention.

[0024] The invention discloses a high-polarity quaternary ammonium salt antibacterial agent and a preparation method thereof. Specifically, the preparation method uses an aryl sulfonamide compound and a terminal alcohol compound containing an active leaving group as raw materials, and heats and refluxes them in an organic solvent at a molar ratio of 1:1-1.2 under the condition of 60-120 DEG C, preferably 80-100 DEG C, to generate a nucleophilic substitution reaction to generate a high-polarity aryl sulfonamide quaternary ammonium salt. After the reaction, the high-polarity quaternary ammonium salt is obtained through cooling, suction filtration, organic solvent washing and drying.

[0025] The reaction formula is as follows:

[0026]

[0027] Specifically, the sulfonyl group in the arylsulfonamide compound includes benzenesulfonyl, p-toluenesulfonyl, 2-toluenesulfonyl, 3-toluenesulfonyl, 4-ethylbenzenesulfonyl, 4-butylbenzenesulfonyl, 4-methoxybenzenesulfonyl, 4-ethoxybenzenesulfonyl, 4-isopropoxybenzenesulfonyl, 4-butoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2,5-xylenesulfonyl, 2,4-xylenesulfonyl, At least one of sulfonyl, 4-fluorobenzenesulfonyl, 3-fluorobenzenesulfonyl, 2-fluorobenzenesulfonyl, 4-chlorobenzenesulfonyl, 3-chlorobenzenesulfonyl, 2-chlorobenzenesulfonyl, 4-bromobenzenesulfonyl, 3-bromobenzenesulfonyl, 2-bromobenzenesulfonyl, 4-iodobenzenesulfonyl, 2,4,6-triisopropylbenzenesulfonyl, 2-naphthalenesulfonyl, 2-nitrobenzenesulfonyl, 3-nitrobenzenesulfonyl or 4-nitrobenzenesulfonyl.

[0028] The n is an integer of 0-12; m is an integer of 0-18; and R2 is a C1-C4 straight chain alkyl group.

[0029] The X is at least one of chloride, bromide, iodide, methanesulfonate, trifluoromethanesulfonate, ethylsulfonate, butylsulfonate, perfluorobutylsulfonate, benzenesulfonate, 4-fluorobenzenesulfonate, 4-chlorobenzenesulfonate, 4-bromobenzenesulfonate, camphorsulfonate, hexafluorophosphate, tetrafluoroborate or bis(trifluoromethanesulfonylimide) ion.

[0030] The organic solvent includes at least one of benzene, toluene, xylene, chlorobenzene, methanol, ethanol, n-propanol, isopropanol, n-butanol, cyclohexanol, acetonitrile, acetone, ethyl acetate, propyl acetate, butyl acetate, petroleum ether, ethylene glycol dimethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, cyclohexanone or toluene cyclohexanone; preferably ethyl acetate, butyl acetate or ethylene glycol dibutyl ether.

[0031] The reaction process of the present invention is described in detail below through specific examples.

[0032] Example 1

[0033] Synthesis of N-(2-(Benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(12-hydroxydodecyl)-1-ammonium bromide

[0034]

[0035] Weigh 2.3 g of N-(2-(dimethylamino)ethyl)benzenesulfonamide and 3.2 g of 12-bromo-1-dodecanol, dissolve in 20 ml of acetonitrile, and heat under reflux for 4 hours; slowly cool and crystallize, filter, wash with acetonitrile, and vacuum dry to obtain 4.7 g of solid product N-(2-(benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(12-hydroxydodecyl)-1-ammonium bromide, with a yield of 95%.

[0036] 1H (NMR, d6-DMSO): δ8.12 (s, 1H), 7.88 (m, 2H), 7.68 (m, 3H), 4.34 (s, 1H), 3.4 0(m, 4H), 3.21(m, 2H), 3.06(s, 6H), 1.65(m, 2H), 1.42(m, 2H), 1.28(m, 18H).

[0037] Example 2

[0038] Synthesis of N-(2-(2,4,6-trimethylbenzenesulfonylamino)ethyl)-N,N-dimethyl-1-(12-hydroxydodecyl)-1-ammonium bromide

[0039]

[0040] Weigh 2.9 g of N-(3-(dimethylamino)propyl)-2,4,6-trimethylbenzenesulfonamide and 3.2 g of 12-bromo-1-dodecanol, dissolve in 20 ml of ethyl acetate, and heat under reflux for 3 hours; slowly cool and crystallize, filter, wash with ethyl acetate, and vacuum dry to obtain 5.3 g of solid product N-(2-(2,4,6-trimethylbenzenesulfonylamino)ethyl)-N,N-dimethyl-1-(12-hydroxydodecyl)-1-ammonium bromide, with a yield of 96%.

[0041] 1H (NMR, d6-DMSO): δ7.57 (s, 1H), 7.08 (s, 2H), 4.37 (s, 1H), 3.20 (m, 4H), 2.97 (s, 6 H), 2.78 (m, 2H), 2.52 (s, 6H), 2.29 (s, 3H), 1.62 (m, 2H), 1.41 (m, 4H), 1.27 (m, 18H).

[0042] Example 3

[0043] Synthesis of N-(2-(Benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(3-hydroxypropyl)-1-bis(trifluoromethanesulfonylimide)ammonium

[0044]

[0045] 2.3 g of N-(2-(dimethylamino)ethyl)benzenesulfonamide and 1.7 g of 3-bromo-1-propanol were weighed and dissolved in 20 ml of ethyl acetate, and heated under reflux for 2 hours; 3.5 g of lithium bis(trifluoromethanesulfonyl imide) and 15 ml of purified water were added, and the mixture was vigorously stirred for 1 hour. The mixture was slowly cooled for crystallization, filtered, washed with ethyl acetate, and vacuum dried to obtain 5.2 g of a solid product, N-(2-(benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(3-hydroxypropyl)-1-bis(trifluoromethanesulfonyl imide)ammonium, with a yield of 92%.

[0046] The elemental analysis was performed on the fully dried samples. The theoretical value of elemental analysis (C 15 H 23 F6N3O7S3): C 31.75; H 4.09; N 7.40; elemental analysis measured values: C 31.78; H 4.05; N 7.38.

[0047] Example 4

[0048] Synthesis of N-(2-(Benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(6-hydroxyhexyl)-1-p-toluenesulfonate ammonium

[0049]

[0050] Weigh 2.4 g of N-(3-(dimethylamino)propyl)-benzenesulfonamide and 3.0 g of 4-methylbenzenesulfonic acid-6-hydroxyhexyl ester and dissolve them in 20 ml of butyl acetate. Heat and reflux for 4 hours; slowly cool and crystallize, filter, wash with petroleum ether, and vacuum dry to obtain 4.7 g of solid product N-(2-(benzenesulfonylamino)ethyl)-N,N-dimethyl-1-(6-hydroxyhexyl)-1-toluenesulfonate ammonium, with a yield of 91%.

[0051] The elemental analysis was performed on the fully dried samples. The theoretical value of elemental analysis (C 24 H 38 N2O6S2): C 56.01; H 7.44; N 5.44; Elemental analysis found: C 56.06; H 7.42; N 5.41.

[0052] Example 5

[0053] Synthesis of N-(2-(2,4,6-trimethylbenzenesulfonylamino)ethyl)-N,N-dimethyl-1-(3-hydroxypropyl)-1-trimethylammonium sulfonate

[0054]

[0055] Weigh 2.9 g of N-(3-(dimethylamino)propyl)-2,4,6-trimethylbenzenesulfonamide and 2.3 g of 3-hydroxypropyl trifluoromethanesulfonate, dissolve in 20 ml of ethyl acetate, and heat under reflux for 1 hour; slowly cool and crystallize, filter, wash with ethyl acetate, and vacuum dry to obtain 4.6 g of solid product N-(2-(2,4,6-trimethylbenzenesulfonylamino)ethyl)-N,N-dimethyl-1-(3-hydroxypropyl)-1-trimethylammoniumsulfonate, with a yield of 94%.

[0056] 1H (NMR, d6-DMSO): δ7.62 (s, 1H), 7.12 (s, 2H), 4.23 (s, 1H), 3.92 (m, 2H), 3.78 (m, 2H), 3. 61 (m, 2H), 3.37 (s, 6H), 3.07 (m, 2H), 2.64 (s, 6H), 2.21 (s, 3H), 2.06 (m, 2H), 1.89 (m, 2H).

[0057] The invention introduces a hydroxyl group into the structure of the synthesized target compound, which can form hydrogen bonds with other polar substances, thereby increasing the interaction force between molecules. The high-polarity quaternary ammonium salt antibacterial agent prepared by the invention can be firmly bonded to the coating surface and is not easy to be eluted, which is beneficial to improving the antibacterial effect and extending the antibacterial life.

[0058] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A high polarity quaternary ammonium salt antibacterial agent, characterized in that: A compound comprising at least the following structural formula: in, is phenyl, p-tolyl, 2-tolyl, 3-tolyl, 4-ethylphenyl, 4-butylphenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 4-butoxyphenyl, 2,4,6-trimethylphenyl, 2,5-xylyl, 2,4-xylyl, 4-fluorophenyl, 3-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-iodophenyl, 2,4,6-triisopropylphenyl, 2-naphthylphenyl, 2-nitrophenyl, 3-nitrophenyl or 4-nitrophenyl; n is an integer from 0 to 12; m is an integer from 0 to 18; R2 is a C1-C4 straight chain alkyl group; X is at least one of chloride, bromide, iodide, methanesulfonate, trifluoromethanesulfonate, ethylsulfonate, butylsulfonate, perfluorobutylsulfonate, benzenesulfonate, 4-fluorobenzenesulfonate, 4-chlorobenzenesulfonate, 4-bromobenzenesulfonate, camphorsulfonate, hexafluorophosphate, tetrafluoroborate or bis(trifluoromethanesulfonylimide) ion.

2. A method for preparing a high-polarity quaternary ammonium salt antibacterial agent as claimed in claim 1, characterized in that: The aromatic sulfonamide compound and the terminal alcohol compound containing an active leaving group are used as raw materials, heated under reflux in an organic solvent, and a nucleophilic substitution reaction is carried out. After the reaction, the high-polarity quaternary ammonium salt antibacterial agent is obtained by cooling, filtering, washing, and drying. The reaction formula is as follows:

3. A method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 2, characterized in that: The molar ratio of the arylsulfonamide compound to the terminal alcohol compound containing an active leaving group is 1:1-1.

2.

4. The method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 2, wherein: The heating reflux temperature is 60-120°C.

5. The method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 4, characterized in that: The heating reflux temperature is 80-100°C.

6. The method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 2, characterized in that: The organic solvent includes at least one of benzene, toluene, xylene, chlorobenzene, methanol, ethanol, n-propanol, isopropanol, n-butanol, cyclohexanol, acetonitrile, acetone, ethyl acetate, propyl acetate, butyl acetate, petroleum ether, ethylene glycol dimethyl ether, ethylene glycol dibutyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, cyclohexanone or toluene cyclohexanone.

7. The method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 6, characterized in that: The organic solvent includes at least one of ethyl acetate, butyl acetate or ethylene glycol dibutyl ether.

8. A method for preparing a high-polarity quaternary ammonium salt antibacterial agent according to claim 2, characterized in that: The sulfonyl group in the arylsulfonamide compound includes benzenesulfonyl, p-toluenesulfonyl, 2-toluenesulfonyl, 3-toluenesulfonyl, 4-ethylbenzenesulfonyl, 4-butylbenzenesulfonyl, 4-methoxybenzenesulfonyl, 4-ethoxybenzenesulfonyl, 4-isopropoxybenzenesulfonyl, 4-butoxybenzenesulfonyl, 2,4,6-trimethylbenzenesulfonyl, 2,5-xylenesulfonyl, 2,4-xylenesulfonyl, The invention further comprises at least one of a 4-fluorobenzenesulfonyl group, a 3-fluorobenzenesulfonyl group, a 2-fluorobenzenesulfonyl group, a 4-chlorobenzenesulfonyl group, a 3-chlorobenzenesulfonyl group, a 2-chlorobenzenesulfonyl group, a 4-bromobenzenesulfonyl group, a 3-bromobenzenesulfonyl group, a 2-bromobenzenesulfonyl group, a 4-iodobenzenesulfonyl group, a 2,4,6-triisopropylbenzenesulfonyl group, a 2-naphthalenesulfonyl group, a 2-nitrobenzenesulfonyl group, a 3-nitrobenzenesulfonyl group or a 4-nitrobenzenesulfonyl group.

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