CN104910208B - Quaternary phosphonium salt type halogen amine antiseptic and preparation method thereof - Google Patents
Quaternary phosphonium salt type halogen amine antiseptic and preparation method thereof Download PDFInfo
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- 150000004714 phosphonium salts Chemical group 0.000 title claims abstract description 40
- 230000002421 anti-septic effect Effects 0.000 title claims abstract description 27
- -1 halogen amine Chemical class 0.000 title claims abstract description 26
- 229910052736 halogen Inorganic materials 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims description 26
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 16
- 239000000243 solution Substances 0.000 claims description 15
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 11
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 10
- 238000005660 chlorination reaction Methods 0.000 claims description 10
- 229940091173 hydantoin Drugs 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 230000031709 bromination Effects 0.000 claims description 5
- 238000005893 bromination reaction Methods 0.000 claims description 5
- 238000005342 ion exchange Methods 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 239000003957 anion exchange resin Substances 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 241000370738 Chlorion Species 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 2
- 150000003003 phosphines Chemical class 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 8
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 230000036541 health Effects 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 150000003384 small molecules Chemical class 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 230000010148 water-pollination Effects 0.000 abstract description 2
- 235000021393 food security Nutrition 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000001954 sterilising effect Effects 0.000 description 7
- 238000004659 sterilization and disinfection Methods 0.000 description 7
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
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- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical class BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- 241000486679 Antitype Species 0.000 description 1
- GMJCOCRMAWKBAL-UHFFFAOYSA-N CC(C)(C(N(CCC[N-](C)(C)C)C1=O)=O)N1Cl Chemical compound CC(C)(C(N(CCC[N-](C)(C)C)C1=O)=O)N1Cl GMJCOCRMAWKBAL-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
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- 229940125782 compound 2 Drugs 0.000 description 1
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- 229910001431 copper ion Inorganic materials 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002242 deionisation method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
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- 230000004060 metabolic process Effects 0.000 description 1
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- 150000002989 phenols Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The present invention discloses a kind of small molecule quaternary phosphonium salt type halogen amine antiseptic and preparation method thereof.Quaternary phosphonium salt group and halogen amine groups are incorporated into same molecule by antiseptic of the present invention by chemical covalent bonds, both solved the problem of halogen amine molecule hydrophily is bad, halogen amine unit, two kinds of respective advantages of antiseptic of quaternary phosphonium salt unit are remained again.Not only bactericidal effect is good and with low cost for this kind of antiseptic, technological process is simple.Suitable for numerous areas such as health care, food security, environmental protection.
Description
Technical field
The present invention relates to antibacterial agent, class quaternary phosphonium salt type halogen amine antibacterial moleucles and preparation method thereof are related specifically to,
Belong to antimicrobial technology field.
Background technology
With the progress of epoch and science and technology, people are to environment and healthy requirement also more and more higher.Antiseptic is used as one kind
Pathogenic bacteria, the effective means of virus are resisted, health care, food processing, clothes processing, environmental improvement has been widely used in
Etc. all many-sides.
Antiseptic refers to that a class can kill microorganism or suppress growth of microorganism the chemical substance of breeding, to bacterium,
Fungi, spore etc. all with certain inactivation or suppress its effect grown.Its function is divided into two kinds of antibacterial and sterilization, and antibacterial is
To delay the growth for hindering microorganism, sterilization is directly to kill microorganism.Both the above function can with target strain, use
It is concentration, different from the condition such as bacterium time of contact, temperature, humidity and mutually convert, have no tight lattice and define.
The huge number that antiseptic is included, is broadly divided into inorganic, organic, natural three major types.Although inorganic antiseptic
Have the advantages that heat-resist, persistence is strong, continuity is high and security is good, but there is also shortcomings, such as copper ion easily makes
Material changes colour, and silver ion type antiseptic is expensive, and anti-mold effect is bad, and addition is larger.Disadvantages mentioned above causes tradition
The development space of inorganic antiseptic is more narrow.Although natural antimicrobial agent has preferable biocompatibility, but it is present
Raw material sources are limited, difficulty of processing is big, high temperature easy in inactivation the shortcomings of, greatly limit its application.Organic antiseptic bag
It is various containing species, such as guanidine, phenols, halogen substitution class, quaternary ammonium salt quaternary phosphonium salt class, wherein many all have raw material inexpensively easy
, easily preparation, sterilization of high efficiency, lasting effect the features such as, just more and more by it is found that and being used.
Quaternary phosphonium salt structure is similar to quaternary ammonium salt, but because season phosphine ionic radius is big compared with quaternary ammonium ion, so the pole of quaternary phosphonium salt
Change effect is stronger, has stronger sucking action to the negative electrical charge on Membranes surface, therefore its bactericidal effect is more preferable than quaternary ammonium salt.But
It is that, if be used for a long time, microorganism drug resistance problems can be produced, while having also contributed to this kind of antimicrobial molecule in the environment secondary
Pollution problem.
The halogen atom with positive charge has strong oxidizing property in halogen amine molecule, after being contacted with thalline, can aoxidize thalline thin
The a series of receptors of intracellular, so as to suppress or even destroy the metabolic process and enzymatic system of thalline, so as to cause thalline dead.
Because intramolecular contains strong oxidizing property halogen atom, so halogen amine antiseptic will not typically make thalline produce drug resistance.
The content of the invention
The purpose of the present invention is to prepare a kind of antibacterial agent：Using chemical synthesis strategy by halogen amine groups and quaternary phosphonium salt base
Group is incorporated into same small molecule, is on the one hand solved the problem of halogen amine antiseptic is water-soluble bad, is on the other hand obtained activity
Higher antimicrobial molecule；It is a further object of the present invention to provide the preparation method of above-mentioned quaternary phosphonium salt type halogen amine antiseptic.
The present invention concrete technical scheme be：A kind of quaternary phosphonium salt type halogen amine antiseptic that the present invention is provided, with followingization
Learn structural formula：
Wherein, n is selected from 2~10 integer, and A is selected from aliphatic three-level base phosphine or aromatic series three-level base phosphine.
Further, in the above-mentioned technical solutions, described aliphatic three-level base phosphine contains three C1~C18Alkyl chain and
One phosphorus atoms.
Further, in the above-mentioned technical solutions, the aromatic series three-level base phosphine contains three phenyl and a phosphorus atoms.
Present invention also offers the preparation method of above-mentioned quaternary phosphonium salt type halogen amine antiseptic, including 3- (n- alkylhalide groups) -5,5-
Preparation, the preparation of glycolylurea base quaternary phosphonium salt, the chlorination of the ion exchange and quaternary phosphonium salt of glycolylurea base quaternary phosphonium salt of DMH are several
Step：
(1) synthesis of 3- (n- alkylhalide groups) -5,5- DMHs：
First 5,5- DMHs are dissolved in acetone, potassium carbonate is added, 0.5h are heated to reflux, then add into mixture
Alkylene dihalide, continues the 4~12h that flows back, and is cooled to room temperature, and bromine alkyl can be obtained by removing to concentrate under vacuum after inorganic salts
Glycolylurea compound, pillar layer separation can further improve purity；
(2) synthesis of quaternary phosphonium salt：
By the bromine alkylated hydantoin of gained in (1) because compound is dissolved in appropriate acetonitrile, after dissolving fully, add equimolar amounts fat
Race's three-level base phosphine or aromatic series three-level base phosphine, are heated to reflux 12~24h, and being cooled to removing solvent under room temperature, vacuum condition can obtain
Bromination quaternary phosphonium salt type hydantoin-based compound；
(3) ion exchange of quaternary phosphonium salt：
Bromination quaternary phosphonium salt type hydantoin-based compound NaOH obtained by step (2), NaCl solution are pre-processed, then will be described
Quaternary phosphonium salt is configured to saturated solution, crosses chlorion type anion exchange resin, collects and is concentrated under relative leacheate, vacuum condition,
It can obtain chlorination quaternary phosphonium salt type hydantoin-based compound；
(4) chlorination of quaternary phosphonium salt：
It is 4 by obtained chlorination quaternary phosphonium salt type hydantoin-based compound volume ratio in (3)：1 tertiary butanol aqueous solution (tertiary fourth
Alcohol:Water=4:1) it is completely dissolved, 12~24h of stirring under the conditions of t-butyl hypochlorate, normal temperature lucifuge is added under the conditions of lucifuge, will
Reacted mixed solution concentration obtains generalformulaⅰcompound.
Further, in the above-mentioned technical solutions, in step (1), the mol ratio of potassium carbonate and 5,5- DMH is 3
~5:1.
Further, in the above-mentioned technical solutions, in step (1), mole of alkylene dihalide and 5,5- DMH
Than for 2~4:1.
Further, in the above-mentioned technical solutions, in step (4), t-butyl hypochlorate and chlorination quaternary phosphonium salt type glycolylurea class
The mol ratio of compound is 3~5:1.
Further, in the above-mentioned technical solutions, alkylene dihalide structural formula described in step (1) is X1—(CH2)n—
X1, wherein X1Selected from I, Br or Cl, n is selected from 2~10 integer.
Invention beneficial effect
Although Halamine antibacterial agent sterilization speed is exceedingly fast, halogen amines be usually by acid amides chlorination or bromination,
Therefore its hydrophily is poorer than acid amides, so as to limit its use scope.This kind of new quaternary phosphonium salt type halogen amine antiseptic was both effectively solved
The problem of traditional halogen amine antiseptic of having determined is water-soluble bad, remains the anti-type antiseptic sterilization speed of halogen amine fast, renewable, anti-again
Bacterium spectrum is wide, the advantages of be not likely to produce drug resistance.
Specific embodiment
The features of the present invention is further illustrated below by embodiment, but the protection domain of this patent is not limited by embodiment
System.
Embodiment 1
First 5,5- DMHs 4g (about 31.2mmol) is added in 500mL single-necked flasks, 200mL third is added
Ketone, flask is placed in oil bath and preheated.After after solid dissolving, about 17g K are added2CO3(about 123.2mmol), add 40~
1,3- dibromopropanes 18.9g (about 9.6mL, 93.7mmol) is added after 50mL acetone, backflow 0.5h into reactor, continues to add
Heat backflow is stayed overnight.Washed for several times with 100mL moisture, reacted mixture is removed after inorganic salt impurities, removed under vacuum condition
Solvent is removed, crude product is obtained, pillar layer separation can further improve its purity, and yield is about 85%, product structure such as following formula institute
Show：
First 3.0g (about 12.1mmol) compound 1 is dissolved in about 50mL acetonitriles, N is passed through into reactor2By air
Discharge, then injects tributylphosphine 1.6g (about 2mL, 8.0mmol) into reactor with syringe, is heated to reflux after about 48h
Stop reaction, then concentration removes solvent under vacuum, then through column chromatography purified product.The reaction yield is more than
95%, product structure is shown below：
This experiment use for 201 × 7 type anion exchange resin, before ion exchange, first resin is located in advance
Reason.Processing method is：First by saturated aqueous common salt, take its volume to be approximately equal to twice of processed resin volume, immersion 18~
Then 20h filters out saline solution, is rinsed only with deionized water, until discharge water is without yellow；Then 4~8h is soaked with 5%HCl,
Acid solution is filtered out, is rinsed with deionized water to neutrality；4~8h is soaked with 2%~4%NaOH solution again, alkali lye is filtered out, uses deionization
Water rinses stand-by to neutrality.By the anion exchange in resin it is Cl with saturated aqueous common salt—, then resin is washed with deionized water
To neutrality, then compound 2 is dissolved in water as a small amount of as possible, slow transitting through will make under anion exchange resin, vacuum condition
For solvent water it is cleared after obtain chlorion type tributyl quaternary phosphonium salt, its structure is as follows：
2.0g compounds 3 (about 5.0mmol) first are dissolved in into 20mL tertiary butanol aqueous solutions, and (volume ratio of the tert-butyl alcohol and water is
4:1) in, lucifuge under t-butyl hypochlorate 2.2g (about 2.3mL, 19.8mmol), normal temperature is added dropwise and is stirred overnight.Reaction solution is existed
Concentration removes solvent and unnecessary t-butyl hypochlorate under vacuum condition, you can obtain the quaternary phosphonium salt type halogen amine described in claim 1
Antiseptic.Its yield is more than 95%, and nuclear-magnetism characterize data is：
1H NMR(D2O, 500MHz, δ) 3.60 (t, J=6.75Hz, 2H), 2.05-2.14 (m, 8H), 1.77-1.87 (m,
2H), 1.27-1.49 (m, 12H), 1.40 (s, 6H), 0.82 (t, J=7.25Hz, 9H)；13C NMR(D2O,126MHz,δ)
177.0,155.6,66.4,39.8,23.3,22.7,21.0,19.7,17.7,15.7,12.6.
Structure is shown below：
Embodiment 2
5,5- DMHs 3.2g (about 25.3mmol) is dissolved in about 200mL acetone, it is to be dissolved completely backward anti-
Answer and K is added in device2CO313.8g (about 101.2mmol), is heated to reflux after 0.5h adding 1,12- dibromos 12 into reactor
Alkane 24.9g (about 75.9mmol), reaction is stopped after continuing backflow about 24h.Remove after inorganic salt impurities, it is dense under vacuum
Contracting removes solvent, compound 17 can be obtained after being purified through column chromatography, its yield is more than 70%, and structure is shown below：
2.5g compounds 5 (about 6.7mmol) are dissolved in 40mL acetonitriles.It is to be dissolved completely after, be passed through into reactor
N2By the complete emptying of air.Tributylphosphine 1.2g (about 1.5mL, 6.0mmol) is injected into reactor again, continues to be heated to reflux
Stop reaction after 48h.Reaction solution is concentrated to removing solvent under vacuum, compound 6 is can obtain through column chromatography purification,
Its yield is more than 80%, and structure is shown below：
Compound 7 is what compound 6 was obtained after ion exchange, and its structure is shown below：
Compound 7
1.5g (about 2.8mmol) compound 7 is dissolved in the 15mL tertiary butanol aqueous solutions (volume ratio of the tert-butyl alcohol and water
For 4:1) in, t-butyl hypochlorate 1.2g (about 1.3mL, 11.2mmol), normal temperature are added dropwise in completely backward reactor to be dissolved
Stop concentration of reaction solution under reaction, vacuum condition under the conditions of lucifuge after stir about 24h, remove solvent and the tertiary fourth of unnecessary hypochlorous acid
Compound 8 is obtained after ester, the reaction yield is more than 95%, nuclear-magnetism characterize data is：
1H NMR(D2O, 500MHz, δ) 3.44 (t, J=6.75Hz, 2H), 2.05-2.17 (m, 8H), 1.12-1.56 (m,
32H), 1.37 (s, 6H), 0.85 (t, J=7.25Hz, 9H)；13C NMR(D2O,126MHz,δ)175.6,155.0,66.0,
39.5,30.3,29.7,29.3,29.3,29.0,28.5,27.6,26.3,23.5,23.0,21.6,21.1,21.0,18.2,
17.8,12.9.
Product structure is shown below：
Antibacterial test：
Sterilization experiment is with 0.57 × 106CFU Escherichia coli ATCC 25922 is target strain, season prepared by method described above
Phosphonium salt type halogen amine antiseptic is that the solution (active chlorine content is 20ppm) of compound 4 is killed to it, as a result 5min it
Interior, Escherichia coli ATCC 25922 is all killed.And it has been reported that the compound 9 crossed can only be killed under similarity condition in 5min
Dead 90.6% Escherichia coli.
Then with 1.66 × 106CFU Escherichia coli ATCC 25922 is target strain, is 20ppm's with active chlorine content
Solution compared for the bactericidal effect of the quaternary phosphonium salt type halogen amine antiseptic of different carbon chain lengths.As a result find compound 4 in 5min
The Escherichia coli of kill 95.96%, and compound 8 kills 99.33% Escherichia coli in same time.Pass through sterilization experiment
Prove, it is best with the bactericidal effect of compound 8 in the quaternary phosphonium salt type halogen amine antiseptic of synthesized different carbon chain lengths.
Claims (5)
1. a kind of quaternary phosphonium salt type halogen amine antiseptic, it is characterised in that with formula：
2. the preparation method of quaternary phosphonium salt type halogen amine antiseptic as claimed in claim 1, it is characterised in that comprise the following steps：
(1) synthesis of 3- (n- bromines alkyl) -5,5- DMHs：
First 5,5- DMHs are dissolved in acetone, potassium carbonate is added, is heated to reflux 0.5h, then add into mixture dihalo-
For alkane, continue the 4~12h that flows back, be cooled to room temperature, remove after inorganic salts concentration under vacuum can obtain bromine alkylated hydantoin because
Compound, pillar layer separation can further improve purity；
(2) synthesis of quaternary phosphonium salt：
By the bromine alkylated hydantoin of gained in (1) because compound is dissolved in appropriate acetonitrile, after dissolving fully, add equimolar amounts tributyl
Phosphine, is heated to reflux 12~24h, and bromination quaternary phosphonium salt type hydantoin-based compound can be obtained by being cooled to removing solvent under room temperature, vacuum condition；
(3) ion exchange of quaternary phosphonium salt：
Bromination quaternary phosphonium salt type hydantoin-based compound NaOH obtained by step (2), NaCl solution are pre-processed, then by the season phosphine
Salt is configured to saturated solution, crosses chlorion type anion exchange resin, collects and is concentrated under relative leacheate, vacuum condition, can be obtained
To chlorination quaternary phosphonium salt type hydantoin-based compound；
(4) chlorination of quaternary phosphonium salt：
It is 4 by obtained chlorination quaternary phosphonium salt type hydantoin-based compound volume ratio in (3):1 tertiary butanol aqueous solution is completely dissolved,
12~24h of stirring under the conditions of t-butyl hypochlorate, normal temperature lucifuge is added under the conditions of lucifuge, reacted mixed solution is concentrated
Obtain compound in claim 1；
Alkylene dihalide structural formula described in step (1) is X1—(CH2)n—X1, wherein X13 or 12 are selected from selected from Br, n.
3. preparation method according to claim 2, it is characterised in that：In step (1), potassium carbonate and 5,5- DMH
Mol ratio be 3~5:1.
4. preparation method according to claim 2, it is characterised in that：In step (1), alkylene dihalide and 5,5- dimethyl
The mol ratio of glycolylurea is 2~4:1.
5. preparation method according to claim 2, it is characterised in that：In step (4), t-butyl hypochlorate and chlorination season phosphine
The mol ratio of salt form hydantoin-based compound is 3~5:1.
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