CN105820133B - Polysubstituted s-triazine compound and preparation method and application thereof - Google Patents
Polysubstituted s-triazine compound and preparation method and application thereof Download PDFInfo
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- -1 Polysubstituted s-triazine compound Chemical class 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 8
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 229910052751 metal Inorganic materials 0.000 claims abstract description 6
- 239000002184 metal Substances 0.000 claims abstract description 6
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 6
- FKPUYTAEIPNGRM-UHFFFAOYSA-N 1-(diaminomethylidene)guanidine;hydron;chloride Chemical compound [Cl-].N\C([NH3+])=N/C(N)=N FKPUYTAEIPNGRM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- DMRVBCXRFYZCPR-UHFFFAOYSA-L cycloocta-1,5-diene;ruthenium(2+);dichloride Chemical group Cl[Ru]Cl.C1CC=CCCC=C1 DMRVBCXRFYZCPR-UHFFFAOYSA-L 0.000 claims description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 24
- 241000588724 Escherichia coli Species 0.000 abstract description 7
- 238000000338 in vitro Methods 0.000 abstract description 5
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 229940124350 antibacterial drug Drugs 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZZKCEDWUQUIPMK-UHFFFAOYSA-N (1E)-1-[amino(anilino)methylidene]-2-phenylguanidine hydrochloride Chemical compound Cl.C1(=CC=CC=C1)NC(=N)NC(=N)NC1=CC=CC=C1 ZZKCEDWUQUIPMK-UHFFFAOYSA-N 0.000 description 2
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229960004329 metformin hydrochloride Drugs 0.000 description 2
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 125000005504 styryl group Chemical group 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical class C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003304 ruthenium compounds Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/16—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom
- C07D251/18—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to only one ring carbon atom with nitrogen atoms directly attached to the two other ring carbon atoms, e.g. guanamines
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/66—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms
- A01N43/68—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms with two or three nitrogen atoms directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a polysubstituted s-triazine compound shown in a formula (III), which is prepared by the following steps: adding an alcohol compound shown in a formula (I), biguanide hydrochloride shown in a formula (II), a metal ruthenium catalyst and an alkaline substance into a solvent, stirring and reacting for 10-18 h at 80-130 ℃, and then carrying out post-treatment on a reaction solution to obtain a polysubstituted s-triazine compound shown in a formula (III); the method has the advantages of mild reaction conditions, easily obtained raw materials, convenient operation, low cost and wide industrial application prospect; preliminary in vitro antibacterial experiment results show that the compound has a certain inhibition effect on escherichia coli, and can be applied to preparation of antibacterial drugs and antibacterial agents.
Description
(I) technical field
The invention relates to a polysubstituted s-triazine compound and a preparation method and application thereof.
(II) background of the invention
Triazine compounds have various biological activities such as anticancer, antimalarial and weeding, and are widely applied to the fields of medicines, pesticides and the like. Wherein, the preparation of the s-triazine compound is mainly carried out by the reaction of cyanoguanidine and nitrile compound, the reaction of biguanide and ester compound, the reaction of amide and dimethyl acetal, amidine or guanidine, and the like. Has important theoretical significance and practical application value for the research of the polysubstituted s-triazine compounds and the preparation method thereof.
Disclosure of the invention
The invention aims to provide a polysubstituted s-triazine compound, and a preparation method and application thereof.
The invention adopts the following technical scheme:
a polysubstituted s-triazine compound of formula (III):
in the formula (III), the compound represented by the formula (III),
R1hydrogen or C1-C5 alkyl, preferably hydrogen or methyl;
R2is C1-C5 alkyl or C6-C10 aryl, preferably methyl or phenyl;
R3is hydrogen or C6-C10 aryl, preferably hydrogen or phenyl;
R4is C8-C15 aralkenyl or C6-C10 halogenated aryl, the C6-C10 halogenated aryl is fluorinated aryl or brominated aryl, and styryl, p-fluorophenyl or p-bromophenyl are preferred.
The invention also provides a preparation method of the polysubstituted s-triazine compound shown in the formula (III), which comprises the following steps:
adding an alcohol compound shown in a formula (I), biguanide hydrochloride shown in a formula (II), a metal ruthenium catalyst and an alkaline substance into a solvent, stirring and reacting for 10-18 h at 80-130 ℃, and then carrying out post-treatment on a reaction solution to obtain a polysubstituted s-triazine compound shown in a formula (III);
wherein,
R1hydrogen or C1-C5 alkyl, preferably hydrogen or methyl;
R2is C1-C5 alkyl or C6-C10 aryl, preferably methyl or phenyl;
R3is hydrogen or C6-C10 aryl, preferably hydrogen or phenyl;
R4is C8-C15 aralkenyl or C6-C10 halogenated aryl, the C6-C10 halogenated aryl is fluorinated aryl or brominated aryl, and styryl, p-fluorophenyl or p-bromophenyl are preferred.
In the preparation method of the invention, the ratio of the alcohol compound shown in the formula (I) to the biguanide hydrochloride shown in the formula (II), the metal ruthenium catalyst and the alkaline substance is 1: 0.5-1.5: 0.01-0.04: 1.0 to 3.0.
The solvent is ether, preferably 1, 4-dioxane. The volume dosage of the solvent is recommended to be 10-50 mL/g based on the mass of the alcohol compound shown in the formula (I).
The metal ruthenium catalyst is a divalent ruthenium compound, preferably 1, 5-cyclooctadiene ruthenium dichloride.
The base is an organic base, preferably potassium tert-butoxide.
The post-treatment can adopt the following method: after the reaction is finished, adding water (the volume of water is 1.0-3.0 times of the volume of the reaction solution generally), extracting with ethyl acetate, collecting an organic layer, drying with anhydrous sodium sulfate, filtering, concentrating the filtrate, and performing column chromatography separation on the obtained concentrate by using dichloromethane: the volume ratio of methanol is 50:1 as eluent, collecting the eluent containing the target compound, evaporating the solvent under reduced pressure, and drying to obtain the target compound shown in formula (III).
The polysubstituted s-triazine compound has a certain inhibition effect on escherichia coli, and has an application prospect in preparation of antibacterial drugs and antibacterial agents.
The method has the advantages that the reaction condition of the process is mild, the raw materials are easy to obtain, the operation is convenient, the cost is low, and the method has wide industrial application prospect; preliminary in vitro antibacterial experiment results show that the compound has a certain inhibition effect on escherichia coli and has corresponding practical value.
(IV) detailed description of the preferred embodiments
The present invention is further illustrated by the following specific examples, but the scope of the invention is not limited thereto.
Example 1: preparation of Compound (III-1)
1, 5-diphenylbiguanide hydrochloride (0.1653g, 0.9954mmol), p-fluorobenzyl alcohol (0.1342g, 1.0642mmol), 1, 5-cyclooctadiene ruthenium dichloride (0.0056g, 0.02mmol), potassium tert-butoxide (0.2250g, 2.0052mmol), 1, 4-dioxane (4mL) were added to a reaction vessel and stirred in a 100 ℃ oil bath for reaction for 15 hours; after completion of the reaction, water (10mL) was added, extraction was performed with ethyl acetate (10mL × 3), organic layers were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and the resulting concentrate was subjected to column chromatography, wherein R was collected as an eluent, dichloromethane: methanol: 50:1(V: V)fThe eluate (TLC monitoring, eluent and developing agent) having a value of 0.3 to 0.35 was distilled under reduced pressure and dried to obtain 0.2012g of the objective compound (III-1) in a yield of 55%.
1H NMR(500MHz,CDCl3)δ8.46(m,2H),7.63(d,J＝7.6Hz,4H),7.53(br,2H),7.37(t,J＝7.6Hz,4H),7.21–7.09(m,4H).
Example 2:
the reaction temperature was changed to 80 ℃ and the same operations as in example 1 were carried out to finally obtain 0.1463g of the objective compound (III-1) in a yield of 40%.
Example 3:
the reaction temperature was changed to 130 ℃ and the other operations were carried out in the same manner as in example 1 to obtain 0.106g of the objective compound (III-1) with a yield of 29%.
Example 4:
the same procedures as in example 1 were repeated except for changing the amount of 1, 5-cyclooctadiene ruthenium dichloride to 0.0115g and 0.04mmol to finally obtain 0.1975g of the objective compound (III-1) in a yield of 54%.
Example 5:
the same procedures used in example 1 were repeated except for changing the amount of 1, 5-cyclooctadiene ruthenium dichloride to 0.0027g and 0.01mmol, to finally obtain 0.1609g of the objective compound (III-1) in 44% yield.
Example 6:
the same operation as in example 1 was carried out except for changing the amount of potassium tert-butoxide to 0.3369g and 3.0mmol, thereby obtaining 0.1829g of the objective compound (III-1) with a yield of 50%.
Example 7:
the same operation as in example 1 was carried out except for changing the amount of potassium tert-butoxide to 0.1136g and 1.0mmol, thereby obtaining 0.03658g of the objective compound (III-1) in a yield of 10%.
Example 8:
the reaction time was changed to 18 hours, and the other operations were carried out in the same manner as in example 1 to finally obtain 0.1829g of the objective compound (III-1) in a yield of 50%.
Example 9:
the reaction time was changed to 10 hours, and the other operations were carried out in the same manner as in example 1 to finally obtain 0.1280g of the objective compound (III-1) in a yield of 35%.
Example 10:
the same operation as in example 1 was carried out except that the amount of metformin hydrochloride was changed to 0.2478g and 1.5mmol, to finally obtain 0.0915g of the objective compound (III-1) in a yield of 25%.
Example 11:
0.1793g of the objective compound (III-1) was obtained in 49% yield by the same operation as in example 1 except that the amount of benzyl alcohol was changed to 0.1622g and 1.5 mmol.
Example 12: preparation of Compound (III-2)
By following the same procedure as in example 1 except for changing p-fluorobenzyl alcohol to p-bromobenzyl alcohol (0.1874g, 0.9977mmol), 0.2276g of the objective compound (III-2) was obtained in a yield of 56%.
1H NMR(500MHz,CDCl3)：δ8.30(d,J＝8.5Hz,2H),7.67(d,J＝7.8Hz,4H),7.66–7.58(d,J＝8.5Hz,2H),7.40(t,J＝7.8Hz,4H),7.21(br,2H),7.17–7.10(m,2H).
Example 13: preparation of Compound (III-3)
By following the same procedure as in example 1 except for changing p-fluorobenzyl alcohol to cinnamyl alcohol (0.1399g, 1.0125mmol) and changing 1, 5-diphenylbiguanide hydrochloride to metformin hydrochloride (0.1653g, 0.9954mmol), 0.0635g of the objective compound (III-3) was obtained in a yield of 23%.
1H NMR(500MHz,CDCl3)δ7.95(d,J＝15.9Hz,1H),7.63–7.58(m,2H),7.41–7.31(m,3H),6.85(d,J＝15.9Hz,1H),5.23(s,2H),3.26(s,3H),3.15(s,3H).
Example 14: in vitro bacteriostatic activity test on escherichia coli (e.coli, Ec)
The in vitro bacteriostatic action of the target compound on escherichia coli (e.coli, Ec) at a concentration of 10mg/mL was investigated by a diffusion method (a perforation method).
The method comprises the following steps: 6 holes are symmetrically punched on the plate coated with the bacteria liquid by a sterilized puncher in a cross way, 100 mu L of sample dimethyl sulfoxide solution with the mass concentration of 10mg/mL is respectively added by a sterile micro syringe, and ampicillin is used as a reference substance. The culture dish was placed in a constant temperature (28 ℃) incubator for 24 hours, and was taken out to observe whether or not the bacteriostatic action was present, and the results are shown in table 1.
TABLE 1 in vitro antibacterial Activity of the Compound concentration 10mg/mL
| Test number | Compound (I) | Ec |
| 1 | (III-1) | + |
| 2 | (III-2) | + |
| 3 | (III-3) | ++ |
| Reference substance | Ampicillin | +++ |
Claims (4)
1. A preparation method of a polysubstituted s-triazine compound shown in a formula (III) comprises the following steps:
adding an alcohol compound shown in a formula (I), biguanide hydrochloride shown in a formula (II), a metal ruthenium catalyst and an alkaline substance into a solvent, stirring and reacting for 10-18 h at 80-130 ℃, and then carrying out post-treatment on a reaction solution to obtain a polysubstituted s-triazine compound shown in a formula (III);
the ratio of the alcohol compound shown in the formula (I) to the biguanide hydrochloride shown in the formula (II), the metal ruthenium catalyst and the alkaline substance is 1: 0.5-1.5: 0.01-0.04: 1.0 to 3.0;
wherein,
R1hydrogen or C1-C5 alkyl;
R2is C1-C5 alkyl or C6-C10 aryl;
R3hydrogen or C6-C10 aryl;
R4is C8-C15 aryl alkenyl or C6-C10 halogenated aryl.
2. The process according to claim 1, wherein the solvent is 1, 4-dioxane; the volume dosage of the solvent is 10-50 mL/g based on the mass of the alcohol compound shown in the formula (I).
3. The process according to claim 1, wherein the ruthenium metal catalyst is 1, 5-cyclooctadiene ruthenium dichloride.
4. The method of claim 1, wherein the base is potassium tert-butoxide.
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| CN107129498B (en) * | 2017-03-22 | 2019-04-09 | 浙江工业大学 | Imidazoles arone compounds and the preparation method and application thereof |
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