CN105017248A - Preparation method and applications of [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione compound - Google Patents
Preparation method and applications of [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione compound Download PDFInfo
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- CN105017248A CN105017248A CN201510332215.8A CN201510332215A CN105017248A CN 105017248 A CN105017248 A CN 105017248A CN 201510332215 A CN201510332215 A CN 201510332215A CN 105017248 A CN105017248 A CN 105017248A
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- Prior art keywords
- pyridine
- triazole
- formula
- thioketone
- compound
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- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- -1 pyridine-3(2H)-thione compound Chemical class 0.000 title claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 27
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- 240000008067 Cucumis sativus Species 0.000 claims abstract description 9
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 claims abstract description 9
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 8
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 241000227653 Lycopersicon Species 0.000 claims abstract 3
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000001953 recrystallisation Methods 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 241000223218 Fusarium Species 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 241000293040 Xanthomonas gardneri Species 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 5
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- 239000010813 municipal solid waste Substances 0.000 claims description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 3
- 235000015320 potassium carbonate Nutrition 0.000 claims description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 4
- 239000003513 alkali Substances 0.000 claims 1
- 239000000575 pesticide Substances 0.000 abstract description 3
- 230000002265 prevention Effects 0.000 abstract description 3
- 238000012827 research and development Methods 0.000 abstract description 2
- XAYCTBDPZIKHCW-UHFFFAOYSA-N (3-chloropyridin-2-yl)hydrazine Chemical compound NNC1=NC=CC=C1Cl XAYCTBDPZIKHCW-UHFFFAOYSA-N 0.000 abstract 1
- APGUIOQYEKPPFX-UHFFFAOYSA-N 2h-pyridine-3-thione Chemical class S=C1CN=CC=C1 APGUIOQYEKPPFX-UHFFFAOYSA-N 0.000 abstract 1
- 101100117236 Drosophila melanogaster speck gene Proteins 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 230000001580 bacterial effect Effects 0.000 abstract 1
- 238000010992 reflux Methods 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 238000000921 elemental analysis Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 9
- 238000011081 inoculation Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 240000003768 Solanum lycopersicum Species 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 230000000855 fungicidal effect Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 4
- 150000003852 triazoles Chemical class 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- 239000005758 Cyprodinil Substances 0.000 description 1
- 102100035102 E3 ubiquitin-protein ligase MYCBP2 Human genes 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101001071429 Homo sapiens Metabotropic glutamate receptor 2 Proteins 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
- 241001061127 Thione Species 0.000 description 1
- 239000005842 Thiophanate-methyl Substances 0.000 description 1
- VMFXMTJCTSYHCF-HHQUSWFZSA-N [(2r,3r,4s,5r)-5-(hexylamino)-4-hydroxy-2-(hydroxymethyl)-6-[(7-hydroxy-4-oxo-1,3a,5,6,7,7a-hexahydroimidazo[4,5-c]pyridin-2-yl)amino]oxan-3-yl] carbamate Chemical compound CCCCCCN[C@@H]1[C@H](O)[C@@H](OC(N)=O)[C@@H](CO)OC1\N=C\1NC(C(=O)NCC2O)C2N/1 VMFXMTJCTSYHCF-HHQUSWFZSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000009876 antimalignant effect Effects 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- HAORKNGNJCEJBX-UHFFFAOYSA-N cyprodinil Chemical compound N=1C(C)=CC(C2CC2)=NC=1NC1=CC=CC=C1 HAORKNGNJCEJBX-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- QGHREAKMXXNCOA-UHFFFAOYSA-N thiophanate-methyl Chemical group COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC QGHREAKMXXNCOA-UHFFFAOYSA-N 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 239000004562 water dispersible granule Substances 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The present invention discloses a [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione derivative represented by a formula (I), a preparation method and applications thereof, wherein carbon disulfide and 3-chloro-2-hydrazinopyridine are subjected to a reflux reaction to obtain a compound (II), and the compound (II), a compound (III) and an alkaline substance react to obtain the [1,2,4]triazolo[4,3-alpha]pyridine-3(2H)-thione compound. The present invention further discloses applications of the compound in prevention and control of tomato bacterial speck, cucumber wilt and tomato gray mold. The compound of the present invention is the new compound having antibacterial activity and provides foundation for research and development of new pesticides.
Description
Technical field
The present invention relates to a kind of triazole class compounds containing the pyridine i.e. preparation method of [1,2,4] triazole [4,3-a] pyridine-3 (2H)-thioketone and application thereof.
Background technology
Effectively crop yield can be increased using of agriculture Pesticides.No matter be in medical treatment, in agriculture or industrial nitrogenous medicine, triazole class compounds is all an important class, and this compounds often shows the activity that the activity of anti-malignant cell proliferation, anti-convulsant activity, fungicidal activity, antitumour activity and suppression P-glycoprotein regulate.Equally, this compounds also shows good fungicidal activity.Some of them have been developed becomes commercialization agricultural chemicals, such as, and fluorine ether azoles, hydroxyl bacterium azoles, prothioconazoles etc.Also mention this compounds in many reports and have multiple different application, such as, to the PAM activity, anti-convulsant activity, anti-microbial activity, weeding activity etc. of mGlu2 acceptor, therefore [1,2,4] triazole [4,3-
a] synthesis of pyridine compounds and their has considerable value.
Summary of the invention
The object of the invention is to provide one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone and application thereof.
[1,2,4] of the present invention triazole [4,3-
a] pyridine-3 (2
h)-thioketone, its structural formula as shown in the formula (I):
In formula (I): R is phenmethyl, 3,4-dichloro benzyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenmethyl, acetonitrile-base, 4-itrile group phenmethyl, 3-itrile group phenmethyl, (6-chloropyridine-3-base) methyl, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that concrete steps are as follows:
1) dithiocarbonic anhydride and 3-chloride-2-hydrazinopyridine are joined in CEM micro-wave diminishing pot carry out microwave radiation reaction, be poured into by reaction mixture after reaction terminates in water after forming precipitation and filter, thick product recrystallization obtains compound (II) as shown in the formula (II);
2) in organic solvent, react under the compound (III) shown in the compound (II) shown in formula (II), formula (III) and alkaline matter microwave radiation, after reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography, shown in acquisition formula (I) [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketone,
，
R in formula (I) is identical with the R in formula (III), and R is phenmethyl, and 3,4-dichloro benzyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenmethyl, acetonitrile-base, 4-itrile group phenmethyl, 3-itrile group phenmethyl, (6-chloropyridine-3-base) methyl, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that the recrystallization solvent of thick product recrystallization in step 1) is one or more in sherwood oil, ethyl acetate, normal hexane or ethanol.
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that in step 1), 3-chloride-2-hydrazinopyridine is 1:2.0 ~ 4.0 with the ratio of the amount of substance of thiocarbamide,
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) described in organic solvent be one or more in DMF, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane or acetone.
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) described in alkaline matter be one or more in salt of wormwood, sodium bicarbonate, sodium hydroxide, potassium hydroxide or sodium hydride.
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) ratio of the amount of substance of Chinese style (II) compound, formula (III) and alkaline matter is 1:1.0 ~ 1.5:1.0 ~ 1.5,
Described one [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) in organic solvent volume consumption count 3-9ml/mmol with the amount of substance of formula (II) compound,
Building-up process of the present invention is as follows:
。
Described [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketone is preparing the application prevented and treated in bacterial spot of tomato, cucumber fusarium axysporum, graw mold of tomato sterilant.
Compared with prior art, beneficial effect of the present invention is mainly reflected in: the invention provides a kind of 8-chloro-[1,2,4] triazole [4,3-
a] pyridine-3 (2
hits preparation method of)-40 thione derivatives and intermediate and application, this compound is the new compound with fungicidal activity, for the research and development of novel pesticide provide the foundation.
Embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
Triazole class compounds (I) containing pyridine of the present invention can synthesize in the following manner:
By dithiocarbonic anhydride (30mmol), 3-chloride-2-hydrazinopyridine (143 mg, 1mmol) back flow reaction 30 hours Radiation works.Be spin-dried for by mixture after end, then wash to obtain thick product, thick product in ethanol recrystallization obtains formula (II).DMF (5 mL), formula (II) (1mmol), RCH2Cl (1.1 mmol) and salt of wormwood (0.05 g, 1.2mmol) are reacted 24 hours at ambient temperature.After reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography.Obtained formula (I).
Embodiment 1
3-(benzylthio)-8-chloro-[1,2,4] triazole [4,3-
a] yield 87%, m.p.140-141 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.29 (s, 2H, SCH
2), 6.62 (t,
j=7.0Hz, 1H, Py-H), 7.09-7.11 (m, 2H, Ar-H), 7.15-7.16 (m, 3H, Py-H and Ar-H), 7.27 (s, 1H, Ar-H), 7.62 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
13h
10clN
3s:found C 56.74, H 3.76, N 15.43; Calcd. C, 56.62; H, 3.66; N, 15.24.
Embodiment 2
The chloro-3-of 8-((3,4-dichloro benzyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
productive rate 81%, m.p.152-153 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.30 (s, 2H, SCH
2), 6.75 (t,
j=7.0Hz, 1H, Py-H), 7.02 (d,
j=6.2Hz, 1H, Py-H), 7.33 (d,
j=6.5Hz, 1H, Py-H). Elemental analysis for C
13h
8cl
3n
3s:found C 45.44, H 2.53, N 11.98; Calcd. C, 45.30; H, 2.34; N, 12.19.
Embodiment 3
(Z)-methyl 2-(2-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) phenyl)-2-(methoxy imino) acetic ester
productive rate 77%, m.p.155-156 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 3.77 (s, 3H, OCH
3), 3.89 (s, 3H, OCH
3), 4.10 (s, 2H, SCH
2), 6.53 (t,
j=7.0Hz, 1H, Py-H), 6.66 (d,
j=7.0Hz, 1H, Ar-H), 6.90 (d,
j=7.5Hz, 1H, Ar-H), 7.13 (d,
j=7.5Hz, 1H, Ar-H), 7.19 (t,
j=7.5Hz, 1H, Ar-H), 7.25 (d,
j=7.0Hz, 1H, Py-H), 7.71 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
17h
15clN
4o
3s:found C 52.33, H 3.97, N 14.45; Calcd. C, 52.24; H, 3.87; N, 14.33
Embodiment 4
2-((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) acetonitrile
productive rate 68%, m.p.200-201 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 3.90 (s, 2H, SCH
2), 7.00 (t,
j=7.0Hz, 1H, Py-H), 7.48 (d,
j=7.2Hz, 1H, Py-H), 7.24-7.28 (m, 2H, Ar-H), 7.31 (d,
j=6.5Hz, 1H, Py-H), 7.31 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
8h
5clN
4s:found C 42.97, H 2.31, N 24.99; Calcd. C, 42.77; H, 2.24; N, 24.94.
Embodiment 5
4-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) benzonitrile
productive rate 76%, m.p.194-195 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.50 (s, 2H, SCH
2), 6.89 (t,
j=7.0Hz, 1H, Py-H), 7.40 (d,
j=8.1Hz, 1H, Ar-H), 7.45 (d,
j=6.5Hz, 1H, Py-H), 7.54 (d,
j=8.1Hz, 1H, Ar-H), 7.82 (d,
j=6.8Hz, 1H, Py-H). Elemental analysis for C
14h
9clN
4s:found C 55.89, H 2.97, N 18.87; Calcd. C, 55.91; H, 3.02; N, 18.63.
Embodiment 6
The chloro-3-of 8-(((6-chloropyridine-3-base) methyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
productive rate 82%, m.p.150-151 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.40 (s, 2H, SCH
2), 6.81 (t,
j=7.0Hz, 1H, Py-H), 7.18 (d,
j=8.2Hz, 1H, Py-H), 7.34 (d,
j=7.2Hz, 1H, Py-H), 7.58 (dd,
j=2.5,2.5Hz, 1H, Py-H), 7.78 (d,
j=6.9Hz, 1H, Py-H), 8.31 (d,
j=2.3Hz, 1H, Py-H). Elemental analysis for C
12h
8cl
2n
4s:found C 46.42, H 2.75, N 17.96; Calcd. C, 46.32; H, 2.59; N, 18.00.
Embodiment 7
The chloro-3-of 8-((3-fluorophenyl) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
productive rate 81%, m.p.99-100 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.30 (s, 2H, SCH
2), 6.69 (t,
j=7.0Hz, 1H, Py-H), 6.85-6.91 (m, 2H, Ar-H), 6.93 (d,
j=1.6Hz, 1H, Ar-H), 7.09-7.13 (m, 1H, Ar-H), 7.27 (d,
j=7.2Hz, 1H, Py-H), 7.71 (d,
j=7.5Hz, 1H, Py-H). Elemental analysis for C
13h
9clFN
3s:found C 53.22, H 2.97, N 14.51; Calcd. C, 53.15; H, 3.09; N, 14.30.
Embodiment 8
The chloro-3-of 8-((2-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
productive rate 79%, m.p.152-153 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.42 (s, 2H, SCH
2), 6.67 (t,
j=7.0Hz, 1H, Py-H), 6.97 (d,
j=4.0Hz, 2H, Ar-H), 7.13-7.17 (m, 1H, Ar-H), 7.27-7.29 (m, 1H, Ar-H), 7.34 (d,
j=7.9Hz, 1H, Py-H), 7.72 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
13h
9cl
2n
3s:found C 50.46, H 2.90, N 13.64; Calcd. C, 50.33; H, 2.92; N, 13.55.
Embodiment 9
3-((4-bromophenyl) sulfenyl)-8-chloro-[1,2,4] triazole [4,3-
a] pyridine
productive rate 89%, m.p.168-169 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.42 (s, 2H, SCH
2), 6.72 (t,
j=6.9Hz, 1H, Py-H), 7.04 (d,
j=7.8Hz, 2H, Ar-H), 7.28-7.33 (m, 3H, Ar-H and Py-H), 7.69 (d,
j=6.9Hz, 1H, Py-H). Elemental analysis for C
13h
9brClN
3s:found C 44.33, H2.61, N 11.68; Calcd. C, 44.03; H, 2.56; N, 11.85.
Embodiment 10
3-(((8-chloro-[1,2,4] triazole [4,3-
a] pyridin-3-yl) sulfenyl) methyl) benzonitrile
productive rate 83%, m.p.186-187 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.44 (s, 2H, SCH
2), 6.82 (t,
j=6.9Hz, 1H, Py-H), 7.31-7.37 (m, 2H, Ar-H), 7.47 (d,
j=7.8Hz, 1H, Ar-H), 7.51 (d,
j=7.8Hz, 1H, Py-H), 7.61 (s, 1H, Ar-H), 7.80 (d,
j=6.7Hz, 1H, Py-H). Elemental analysis for C
14h
9clN
4s:found C 55.89, H 2.88, N 18.86; Calcd. C, 55.91; H, 3.02; N, 18.63.
Embodiment 11
The chloro-3-of 8-((4-chloro-phenyl-) sulfenyl)-[1,2,4] triazole [4,3-
a] pyridine
productive rate 81%, m.p.162-163 DEG C;
1h NMR (CDCl
3, 400 MHz), δ: 4.28 (s, 2H, SCH
2), 6.69 (t,
j=7.0Hz, 1H, Py-H), 7.06 (d,
j=8.4Hz, 2H, Ar-H), 7.14 (d,
j=8.4Hz, 2H, Ar-H), 7.29 (d,
j=7.7Hz, 1H, Py-H), 7.67 (d,
j=7.4Hz, 1H, Py-H). Elemental analysis for C
13h
9cl
2n
3s:found C 50.13, H 3.05, N 13.71; Calcd. C, 50.33; H, 2.92; Cl, 22.86; N, 13.55.
Embodiment 12
Fungicidal activity is tested
Subjects: bacterial spot of tomato, cucumber fusarium axysporum, graw mold of tomato.
Test method: adopt pot experiment method.Respectively by cucumber seeds and tomato seeds after 50 DEG C are soaked, be seeded in after vernalization in pot for growing seedlings, wait to grow to 2 true leaves for test.
Medicament prepares: for reagent: get it filled and be made into 100ppm, get 89 kinds of each 5mg of compound, add 10% POLYSORBATE 80 again after adding acetone solution, finally adds water and fully dissolves.Because 100ppm is that 100mg/L is so amount of water=5mg*1000/100mg=50ml, because of final content≤1% of organic solvent so the amount=50ml*1%=0.5ml(adding acetone dissolves), be 0.1% so tween 0.05 ml should be had in 50 ml water because of the final content of tween, that is: 10% tween 0.05 ml. should be added
Contrast medicament: 3% Zhongshengmycin WP → 800 times liquid 0.01g medicine+8ml water
75% thiophanate methyl WP → 1000 times liquid 0.01g medicine+15ml water
50% cyprodinil water dispersible granule → 1000 times liquid 0.01g medicine+15ml water
Application method: bacterial spot of tomato and graw mold of tomato experiment in, when tomato seedling grows two panels compound leaf, with watering can by reagent agent with contrast medicament evenly spray confession try on plant.
In cucumber fusarium axysporum experiment, cucumber seeds is soaked in after respectively will processing 2h and carries out inoculation process.
Inoculation method:
Bacterial spot of tomato adopts the inoculation of bacteria suspension spray method: cultured bacterial spot of tomato bacterium is converted distilled water diluting and becomes 3 × 10
7cfu/ml bacteria suspension, uses watering can spray inoculation.After inoculation, moisturizing is cultivated.
Graw mold of tomato adopts plays mycelium inoculation inoculation: by filtered through gauze, liquid nutrient medium and bacterium block are separated, with crusher, the bacterium block of the substratum with a small amount of liquid is smashed, to mix with the bacterium block smashed with the liquid nutrient medium filtered again and be made into certain density solution, and with spectrophotometric determination solution transmittance (λ=630nm, OD=9.8).
Cucumber fusarium axysporum adopts the inoculation of Baconic method for soaking seed: will in PD substratum cultured cucumber fusarium axysporum filtered through gauze mycelia, regulate spore concentration to 1 × 10
6cfu/ml soaks seed.
After clear water is fully fallen ill, carry out Disease investigation, and calculate disease index and prevention effect.
In formula: EF: prevention effect relatively; CK: the final average disease index in check plot; PT: the final average disease index in treatment zone.
Fungicidal activity testing experiment result is as shown in table 1.
the fungicidal activity (% preventive effect) of each compound under table 1 100ppm
。
Claims (8)
1. one kind [1,2,4] triazole [4,3-a] pyridine-3 (2H)-thioketone, is characterized in that its structural formula as shown in the formula (I):
In formula (I): R is phenmethyl, 3,4-dichloro benzyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenmethyl, acetonitrile-base, 4-itrile group phenmethyl, 3-itrile group phenmethyl, (6-chloropyridine-3-base) methyl, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
2. one kind [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that concrete steps are as follows:
1) dithiocarbonic anhydride and 3-chloride-2-hydrazinopyridine are carried out back flow reaction, be poured into by reaction mixture after reaction terminates in water after forming precipitation and filter, thick product recrystallization obtains compound (II) as shown in the formula (II);
2) in organic solvent, by the compound (III) shown in the compound (II) shown in formula (II), formula (III) and alkali substance reaction, after reaction terminates, poured into by mixture in trash ice after forming precipitation and filter, recrystallization is collected, and crude product carries out purifying by column chromatography, shown in acquisition formula (I) [1,2,4] triazole [4,3-
a] pyridine-3 (2
h)-thioketone,
，
R in formula (I) is identical with the R in formula (III), and R is phenmethyl, and 3,4-dichloro benzyl, 2-(1-methoxyimino-2-methoxyl group-2-oxoethyl) phenmethyl, acetonitrile-base, 4-itrile group phenmethyl, 3-itrile group phenmethyl, (6-chloropyridine-3-base) methyl, 3-fluorophenyl, 4-bromophenyl, 4-chloro-phenyl-, 2-chloro-phenyl-.
3. one according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that the recrystallization solvent of thick product recrystallization in step 1) is one or more in sherwood oil, ethyl acetate, normal hexane or ethanol.
4. one according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that in step 1), 3-chloride-2-hydrazinopyridine is 1:2.0 ~ 4.0 with the ratio of the amount of substance of thiocarbamide,
One according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) described in organic solvent be one or more in DMF, tetrahydrofuran (THF), Isosorbide-5-Nitrae-dioxane or acetone.
5. one according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) described in alkaline matter be one or more in salt of wormwood, sodium bicarbonate, sodium hydroxide, potassium hydroxide or sodium hydride.
6. one according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) ratio of the amount of substance of Chinese style (II) compound, formula (III) and alkaline matter is 1:1.0 ~ 1.5:1.0 ~ 1.5.
7. one according to claim 2 [1,2,4] triazole [4,3-
a] pyridine-3 (2
hthe preparation method of)-thioketone, is characterized in that step 2) in organic solvent volume consumption count 3-9ml/mmol with the amount of substance of formula (II) compound.
8. [1,2,4] triazole [4,3-as claimed in claim 1
a] pyridine-3 (2
h)-thioketone is preparing the application prevented and treated in bacterial spot of tomato, cucumber fusarium axysporum, graw mold of tomato sterilant.
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