CN104829598A - Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound - Google Patents
Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound Download PDFInfo
- Publication number
- CN104829598A CN104829598A CN201510277539.6A CN201510277539A CN104829598A CN 104829598 A CN104829598 A CN 104829598A CN 201510277539 A CN201510277539 A CN 201510277539A CN 104829598 A CN104829598 A CN 104829598A
- Authority
- CN
- China
- Prior art keywords
- methyl
- triazole
- quinazoline
- phenyl
- base
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 Quinazolinone compound Chemical class 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title abstract description 7
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 239000002994 raw material Substances 0.000 claims abstract description 22
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 claims abstract description 16
- 230000001580 bacterial effect Effects 0.000 claims abstract description 9
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 claims abstract description 9
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 8
- 241000207199 Citrus Species 0.000 claims abstract description 8
- 235000007164 Oryza sativa Nutrition 0.000 claims abstract description 8
- 235000020971 citrus fruits Nutrition 0.000 claims abstract description 8
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 claims abstract description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000009566 rice Nutrition 0.000 claims abstract description 8
- 244000052616 bacterial pathogen Species 0.000 claims abstract description 6
- 240000007594 Oryza sativa Species 0.000 claims abstract 3
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims description 185
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 92
- 230000015572 biosynthetic process Effects 0.000 claims description 67
- 238000003786 synthesis reaction Methods 0.000 claims description 67
- 238000002360 preparation method Methods 0.000 claims description 59
- 238000012545 processing Methods 0.000 claims description 46
- 238000001953 recrystallisation Methods 0.000 claims description 31
- 239000007787 solid Substances 0.000 claims description 26
- 241000894006 Bacteria Species 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 claims description 21
- 238000000967 suction filtration Methods 0.000 claims description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 12
- 230000000630 rising effect Effects 0.000 claims description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 235000015320 potassium carbonate Nutrition 0.000 claims description 10
- OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 claims description 8
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 241000233866 Fungi Species 0.000 claims description 6
- 241000223195 Fusarium graminearum Species 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 241001512566 Valsa mali Species 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 5
- 241000233622 Phytophthora infestans Species 0.000 claims description 5
- 241000589771 Ralstonia solanacearum Species 0.000 claims description 5
- 235000019253 formic acid Nutrition 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000010189 synthetic method Methods 0.000 claims description 4
- 230000007935 neutral effect Effects 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006178 methyl benzyl group Chemical group 0.000 claims description 2
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006502 nitrobenzyl group Chemical group 0.000 claims description 2
- XDEPVFFKOVDUNO-UHFFFAOYSA-N pentafluorobenzyl bromide Chemical compound FC1=C(F)C(F)=C(CBr)C(F)=C1F XDEPVFFKOVDUNO-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000006488 t-butyl benzyl group Chemical group 0.000 claims description 2
- 125000006493 trifluoromethyl benzyl group Chemical group 0.000 claims description 2
- 244000061176 Nicotiana tabacum Species 0.000 claims 1
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 abstract 2
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 abstract 1
- 239000005794 Hymexazol Substances 0.000 abstract 1
- 206010039509 Scab Diseases 0.000 abstract 1
- 241000209140 Triticum Species 0.000 abstract 1
- 235000021307 Triticum Nutrition 0.000 abstract 1
- KGVPNLBXJKTABS-UHFFFAOYSA-N hymexazol Chemical compound CC1=CC(O)=NO1 KGVPNLBXJKTABS-UHFFFAOYSA-N 0.000 abstract 1
- 229940102398 methyl anthranilate Drugs 0.000 abstract 1
- 229940117953 phenylisothiocyanate Drugs 0.000 abstract 1
- 244000000003 plant pathogen Species 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 239000013078 crystal Substances 0.000 description 14
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 241000196324 Embryophyta Species 0.000 description 5
- 241000209094 Oryza Species 0.000 description 5
- 230000000855 fungicidal effect Effects 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000208125 Nicotiana Species 0.000 description 4
- 239000003899 bactericide agent Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000417 fungicide Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 150000003246 quinazolines Chemical class 0.000 description 3
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- RSNWORHVUOZYLT-UHFFFAOYSA-N 5-[[(2-sulfanylidene-3h-1,3,4-thiadiazol-5-yl)amino]methylamino]-3h-1,3,4-thiadiazole-2-thione Chemical compound S1C(=S)NN=C1NCNC1=NNC(=S)S1 RSNWORHVUOZYLT-UHFFFAOYSA-N 0.000 description 2
- ZFXMPYNGDGXWSU-UHFFFAOYSA-N CBrCC1=CC=CC=C1 Chemical group CBrCC1=CC=CC=C1 ZFXMPYNGDGXWSU-UHFFFAOYSA-N 0.000 description 2
- 241000723873 Tobacco mosaic virus Species 0.000 description 2
- RHDDIGPVPZVZHJ-UHFFFAOYSA-N [F].C(C1=CC=CC=C1)Cl Chemical group [F].C(C1=CC=CC=C1)Cl RHDDIGPVPZVZHJ-UHFFFAOYSA-N 0.000 description 2
- AVPMRIWGOGRNBF-UHFFFAOYSA-N [bromo(fluoro)methyl]benzene Chemical compound FC(Br)C1=CC=CC=C1 AVPMRIWGOGRNBF-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- ZMYFCFLJBGAQRS-IRXDYDNUSA-N (2R,3S)-epoxiconazole Chemical compound C1=CC(F)=CC=C1[C@@]1(CN2N=CN=C2)[C@H](C=2C(=CC=CC=2)Cl)O1 ZMYFCFLJBGAQRS-IRXDYDNUSA-N 0.000 description 1
- 0 *c1ccc(C*C2=**=C(C*(C=*c3ccccc33)C3=O)*2C2C=CC=CC2)cc1 Chemical compound *c1ccc(C*C2=**=C(C*(C=*c3ccccc33)C3=O)*2C2C=CC=CC2)cc1 0.000 description 1
- MYYYZNVAUZVXBO-UHFFFAOYSA-N 1-(bromomethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CBr)=C1 MYYYZNVAUZVXBO-UHFFFAOYSA-N 0.000 description 1
- BBXDMCQDLOCXRA-UHFFFAOYSA-N 1-(chloromethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CCl BBXDMCQDLOCXRA-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
- DSPKXCZGSQZMRS-UHFFFAOYSA-N C(C1=CC=CC=C1)Cl.[Cl] Chemical compound C(C1=CC=CC=C1)Cl.[Cl] DSPKXCZGSQZMRS-UHFFFAOYSA-N 0.000 description 1
- MEXPXQGUYNAOCV-UHFFFAOYSA-N CCCCBrCC1=CC=CC=C1 Chemical group CCCCBrCC1=CC=CC=C1 MEXPXQGUYNAOCV-UHFFFAOYSA-N 0.000 description 1
- PJUAZXJAACRSBB-UHFFFAOYSA-N CClCC1=CC=CC=C1 Chemical compound CClCC1=CC=CC=C1 PJUAZXJAACRSBB-UHFFFAOYSA-N 0.000 description 1
- 239000005767 Epoxiconazole Substances 0.000 description 1
- JGRHGJIUEIVWFX-UHFFFAOYSA-N FC(F)(F)BrCC1=CC=CC=C1 Chemical compound FC(F)(F)BrCC1=CC=CC=C1 JGRHGJIUEIVWFX-UHFFFAOYSA-N 0.000 description 1
- 239000005656 Fenazaquin Substances 0.000 description 1
- 239000005785 Fluquinconazole Substances 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- GPLPSLWGRTUNRT-UHFFFAOYSA-N [N+](=O)([O-])ClCC1=CC=CC=C1 Chemical compound [N+](=O)([O-])ClCC1=CC=CC=C1 GPLPSLWGRTUNRT-UHFFFAOYSA-N 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- DMYHGDXADUDKCQ-UHFFFAOYSA-N fenazaquin Chemical compound C1=CC(C(C)(C)C)=CC=C1CCOC1=NC=NC2=CC=CC=C12 DMYHGDXADUDKCQ-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
- 150000003568 thioethers Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound. The quinazolinone compound for preventing and curing plant pathogens is indicated by the general formula (I). Methyl anthranilate, formamide, ethyl bromoacetate, hydrazine hydrate, phenyl isothiocyanate, substitution benzyl halide or 2-chlorine-5 chloromethyl pyridine is used as raw material and subjected to six-step reaction to synthesize the target compound. The quinazolinone compounds A7, A8 and A19 are good in inhibitory activity on rice bacterial leaf blight germs. The quinazolinone compound A19 is good in inhibitory activity on citrus canker germs. The inhibitory activity on wheat scab germs of the quinazolinone compounds A14 and A18 and the inhibitory activity on apple rotting germs of the quinazolinone compound A8 are equal to that of control chemical hymexazol.
Description
Technical field
The present invention relates to technical field of chemistry, relate in particular to a kind of containing 1,2, the preparation method of the quianzolinones of 4-triazole thioether and to bacteriums such as rice leaf spot bacteria, citrus processing and tobacco ralstonia solanacearums, the purposes that the fungies such as Valsa mali, fusarium graminearum and phytophthora infestans are inhibited.
Background technology
Along with the development of science and technology, in the application of productive life, sterilant develops into organism gradually from early stage mineral compound.Wherein some organic bactericide toxicity is comparatively large and to environment, do not meet the theme of era development, and they are protective material mostly, application exists limitation, is eliminated gradually.Systemics due to its prevention effect good, performance progressively improves, and has become the main body of modern fungicides.
China's main development protective fungicide from the fifties, has started since the seventies to develop systemic fungicide.The volume increase provide protection of sterilant to agricultural is more and more outstanding, simultaneously constantly accept by numerous peasant.China is as large agricultural country, and along with the continuous lifting of agricultural modernization, sterilant will be fast-developing.
Quinazoline derivative has excellent biological activity, is widely used at medicine and pesticide field, as anticancer, sterilization, desinsection, anti-inflammatory, antitumor, resisting tobacco mosaic virus (TMV) etc.Part quinazoline compounds is successfully developed as commercial pharmaceutical at present, as sterilant fluquinconazole, miticide fenazaquin and cancer therapy drug Iressa etc.Due to the wide application prospect that quinazoline compounds has, its molecular designing, synthesis and bioactivity research are still a pharmaceutical chemical study hotspot at present.
In numerous heterogeneous ring compound, 1,2,4-triazole derivative is subject to the favor of people due to the biological activity of its wide spectrum always.From first 1,2,4-triazole bactericidal agent---since the spirit of prestige bacterium is come out, at present oneself triazole bactericidal agent of report is ten hundreds of, more than the fast quantity of its development, is that any sterilant in the past can not be compared.Still very active for the research and development of this compounds at present, the content of research and major objective carry out suitable modification and transformation to other positions on the basis retaining triazole ring main body, improves its fungicidal activity and the object reducing its dosage to reach.
In sum, in order to find, there is high reactivity, hypotoxicity, low residue and eco-friendly new type bactericide, the principle that the present invention is spliced according to activity unit, 5 are introduced containing 1 of different thio-ether units for 3 at quinazolinone by methylene bridge, 2,4-triazole molecule, design and synthesis one class is containing 1,2, the quinazolinone analog derivative of 4-triazole heterocycle, and anti-microbial activity test has been carried out to it, to filtering out the compound with higher fungicidal activity, the initiative for new type bactericide is provided certain theoretical reference by this.
Summary of the invention
The object of the invention is to filter out the good compound of anti-microbial activity, is specially the quianzolinones containing 1,2,4-triazole thio-ether units providing and have high fungicidal activity.
The present invention is a kind of quianzolinones containing 1,2,4-triazole thio-ether units, its general structure following (
i):
Wherein: R be benzyl, neighbour// to luorobenzyl, neighbour// p-chlorobenzyl, neighbour// to trifluoromethyl benzyl ,/to methoxy-benzyl, neighbour// to methyl-benzyl, to nitrobenzyl, to t-butylbenzyl, 2,6-dichloro benzyls, PFBBR, CCMP.
Above-mentioned formula provided by the invention (
i) in compound to bacteriums such as rice leaf spot bacteria, citrus processing and tobacco ralstonia solanacearums, the fungies such as Valsa mali, fusarium graminearum and phytophthora infestans have certain inhibit activities, part of compounds shows better bacteriostatic activity, thus can be used as the effective constituent of sterilant.
One of the present invention is containing 1,2, the synthetic method of the quianzolinones of 4-triazole thioether, it is characterized in that with methyl o-aminobenzoate, methane amide, ethyl bromoacetate, hydrazine hydrate, PITC and replacement benzyl halogen or CCMP for raw material, obtain through following six steps synthesis:
The first step: the preparation of quinazoline-4-one
In there-necked flask, add methyl o-aminobenzoate successively, methane amide, formic acid, be warming up to 130 ~ 140 DEG C of back flow reaction; Stopped reaction after 6 ~ 8 h, after being cooled to room temperature, pours into reaction solution in appropriate cold water, and have a large amount of white solid to separate out, and then stir 0.5 h, suction filtration, washing, oven dry, dehydrated alcohol recrystallization obtains white fluffy solid.
Mol ratio: methyl o-aminobenzoate: methane amide: formic acid=1:5.5:1.3
Temperature of reaction: 130 ~ 140 DEG C
Reaction times: 6 ~ 8 h
The preparation of second step: 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate
Quinazoline-4-one and salt of wormwood is added in single port bottle, then add proper amount of acetone stir make it be uniformly dispersed after, slowly ethyl bromoacetate is dripped under room temperature, dropwise the reaction of rear temperature rising reflux, stopped reaction after 3 ~ 4 h, pour in frozen water by reaction solution after being cooled to room temperature, separate out a large amount of white solid, suction filtration, washing, oven dry obtain product.
Mol ratio: quinazoline-4-one: salt of wormwood: ethyl bromoacetate=1:1.5:1.5
Temperature of reaction: 70 ~ 90 DEG C
Reaction times: 3 ~ 4 h
The preparation of the 3rd step: 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide
Add 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate in single port flask, add 80% hydrazine hydrate after dehydrated alcohol is dissolved, temperature rising reflux reacts; Stopped reaction after 2 ~ 3 h, is cooled to room temperature, suction filtration, dries and obtains white solid, then use dehydrated alcohol recrystallization.
Mol ratio: 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate: hydrazine hydrate=1:5.2
Temperature of reaction: 80 ~ 100 DEG C
Reaction times: 2 ~ 3 h
The preparation of the 4th step: 2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide
Add 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide in single port flask, dehydrated alcohol, adds PITC under stirring, and temperature rising reflux reacts; Stopped reaction after 3 ~ 5 h, is cooled to room temperature, suction filtration, dries, obtains white solid.
Mol ratio: 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide: PITC=1:1
Temperature of reaction: 80 ~ 100 DEG C
Reaction times: 3 ~ 5 h
The preparation of the 5th step: 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one
2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide is added in single port flask; the solution of potassium carbonate of appropriate 5%; temperature rising reflux reacts; stopped reaction after 5 ~ 7 h, while hot suction filtration, liquid cooling to be filtered but adjusts pH value of solution to neutral with 10% hydrochloric acid afterwards; separate out a large amount of white solid; suction filtration, dry, DMF-water recrystallization obtains product.
Temperature of reaction: 100 ~ 120 DEG C
Reaction times: 5 ~ 7 h
6th step: 3-((replacement benzylthio-)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) preparation of quinazoline-4-(3H)-one
3-((4-phenyl-5-sulfydryl-4H-1 is added in single port flask, 2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one, add salt of wormwood successively after DMF is dissolved, replace benzyl halogen (or CCMP), continue stopped reaction after reaction 2 ~ 5 h under room temperature, in system, add cold water, separate out white solid, continue stirring 0.5 h, suction filtration, dry, ethanol-dichloromethane recrystallization obtains product.
Mol ratio: 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: benzyl halogen: salt of wormwood=1:1.1:3.2
Temperature of reaction: 20 ~ 25 DEG C
Reaction times: 2 ~ 5 h
Above-mentioned steps be applicable to general formula (
i) in the synthesis of all compounds.
The a series of novel structure of design and synthesis containing 1 in the present invention, 2, the quianzolinones of 4-triazole thioether, bacteriostatic activity test result shows that such compound all has certain restraining effect to plant pathogenetic bacteria and fungi, part of compounds also shows better inhibit activities, and the effective constituent that can be used as sterilant uses.
Embodiment
Embodiment one: the synthesis of compound 3-((5-(benzylthio-)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of quinazoline-4-one
9.0 g (59.54 mmol) methyl o-aminobenzoate is added successively in 100 mL there-necked flasks, 13 mL (327.3 mmol) methane amide, 3 mL (79.52 mmol) formic acid, is warming up to 130 ~ 140 DEG C of back flow reaction; Stopped reaction after 6 h, question response liquid cooling is but poured in appropriate cold water afterwards, has a large amount of white solid to separate out, then stirs 0.5 h, suction filtration, washing, oven dry, and dehydrated alcohol recrystallization obtains White Flocculus 4.10 g, yield 47.1%.
(2) preparation of 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate
0.20 g (1.37 mmol) quinazoline-4-one is added in 25 mL single port bottles, 5 mL acetone, 0.28 g (2.04 mmol) salt of wormwood, slowly drip 0.34 g (2.05 mmol) ethyl bromoacetate under room temperature, temperature rising reflux reacts, stopped reaction after 3.5 h, after being cooled to room temperature, reaction solution is poured in frozen water, separate out a large amount of white solid, suction filtration, washing, oven dry obtain white solid 0.22 g, yield 69.2%.
(3) preparation of 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide
0.40 g (1.72 mmol) 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate is added in 25 mL single port flasks, 10 mL dehydrated alcohols, add 0.5 mL (8.94 mmol) 80% hydrazine hydrate under stirring, temperature rising reflux reacts; Stopped reaction after 2 h, is chilled to room temperature, suction filtration, and dry and obtain white solid, dehydrated alcohol recrystallization obtains white solid 0.25 g, yield 66.5%.
(4) preparation of 2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide
0.20 g (0.92 mmol) 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide is added in 25 mL single port flasks, 5 mL dehydrated alcohols, add 0.13 g (0.92 mmol) PITC under stirring, temperature rising reflux reacts; Stopped reaction after 3 h, is chilled to room temperature, suction filtration, dries, obtains white solid 0.13 g, yield 88.5%.
(5) preparation of 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
0.15 g (0.94 mmol) 2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide is added in 25 mL single port flasks; the solution of potassium carbonate of 5 mL 5%; temperature rising reflux reacts; stopped reaction after 5 h, while hot suction filtration, liquid cooling to be filtered but adjusts pH value of solution to neutral with 10% hydrochloric acid afterwards; separate out a large amount of white solid; suction filtration, dries, DMF-H
2o (5:1, v/v) recrystallization obtains white solid 0.16 g, yield 50.9%.
(6) preparation (compound number of target product 3-((5-(benzylthio-)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one
a1):
0.11g (0.33 mmol) 3-((4-phenyl-5-sulfydryl-4H-1 is added in 25 mL single port flasks, 2, 4-triazole-3-base) methyl) quinazoline-4 (3H)-one, 5 mL DMF, 0.15 g (1.08 mmol) salt of wormwood is added after being dissolved, 0.06 g (0.38 mmol) benzyl bromine, stopped reaction after stirring 2 h is continued under room temperature, appropriate cold water is added in system, separate out white solid, continue stirring 0.5 h, suction filtration, dry, ethanol-dichloromethane (10:1, v/v) white chunks crystal 0.10 g is obtained after recrystallization, yield: 71.6%, m.p. 188 ~ 190 DEG C.
IR (KBr, cm
-1)
v: 3053, 1683, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 4.41 (s, 2H), 5.17 (s, 2H), 7.09 (d,
J = 7.45 Hz, 2H), 7.23~7.25 (m, 2H), 7.26~7.28 (m, 3H), 7.40 (t,
J = 7.45 Hz, 2H), 7.46 (s, 2H), 7.69 (d,
J = 7.45 Hz, 1H), 7.75 (t,
J = 6.87 Hz, 1H), 8.13 (d,
J = 8.60 Hz, 1H), 8.14 (s, 1H);
13C NMR (CDCl
3, 125 MHz)
δ: 37.42, 39.64, 121.78, 126.74, 127.06, 127.57, 127.76, 127.88, 128.77, 129.24, 130.11, 130.57, 132.18, 134.65, 136.33, 145.79, 147.92, 151.05, 153.04, 160.31. Anal. Calcd for C
24H
19N
5OS: C, 67.74; H, 4.50; N, 16.46. Found: C, 67.79; H, 4.93; N, 16.86. MS (ESI) m/z: 426.3 ([M+H]
+), 448.3 ([M+Na]
+).
Embodiment two: the synthesis of compound 3-((5-((4-(tertiary butyl) benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((5-((4-(tertiary butyl) benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4-(3H)-one
a2):
Synthesis step and processing condition with embodiment one (6), difference be with to tertiary butyl benzyl bromine for raw material, obtain White Flocculus after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 58.0%; M.p. 175 ~ 178 DEG C.
IR (KBr, cm
-1)
v: 2962, 1685, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 1.27 (s, 9H), 4.38 (s, 2H), 5.18 (s, 2H), 7.04 (d,
J = 8.05 Hz, 2H), 7.19 (d,
J = 8.00 Hz, 2H), 7.28 (d,
J = 8.60 Hz, 2H), 7.38 (t,
J = 7.72 Hz, 2H), 7.42~7.47 (m, 2H), 7.71 (d,
J = 8.05 Hz, 1H), 7.74~7.75 (m, 1H), 8.12~8.16 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 31.35, 34.62, 37.32, 39.50, 121.76, 125.71, 126.75, 127.07, 127.56, 127.79, 128.89, 130.04, 130.51, 132.22, 133.26, 134.62, 145.72, 147.90, 150.95, 150.99, 153.24, 160.25. Anal. Calcd for C
28H
27N
5OS: C, 69.83; H, 5.65; N, 14.54. Found: C, 69.57; H, 6.01; N, 14.87. MS (ESI) m
/z: 482.4 ([M+H]
+), 504.4 ([M+Na]
+).
Embodiment three: the synthesis of compound 3-((5-((4-nitrobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((4-nitrobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a3):
Synthesis step and processing condition with embodiment one (6), difference be with to nitrobenzyl chlorine for raw material, obtain red granules shape crystal after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 50.0%; M.p. 188 ~ 190 DEG C.
IR (KBr, cm
-1)
v: 3076, 1672, 1610, 1165;
1H NMR (CDCl
3, 500 MHz)
δ: 4.46 (s, 2H), 5.14 (s, 2H), 7.18 (d,
J = 7.45 Hz, 2H), 7.50~7.45 (m, 4H), 7.53 (d,
J = 8.60 Hz, 2H), 7.70 (d,
J = 8.00 Hz, 1H), 7.75 (t,
J = 6.88 Hz, 1H), 8.14~8.11 (m, 4H);
13C NMR (CDCl
3, 125 MHz)
δ: 35.79, 39.83, 121.76, 123.91, 126.70, 126.96, 127.66, 127.80, 130.21, 130.30, 130.82, 131.96, 134.73, 144.40, 145.78, 147.44, 147.95, 151.43, 151.97, 160.39. Anal. Calcd for C
24H
18N
6O
3S: C, 61.27; H, 3.86; N, 17.86. Found: C, 60.88; H, 4.14; N, 18.06
. MS (ESI) m
/z :471.3 ([M+H]
+), 493.3 ([M+Na]
+).
Embodiment four: the synthesis of compound 3-((5-((2,6-dichloro benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((2,6-dichloro benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a4):
Synthesis step and processing condition are with embodiment one (6), and difference is with 2,6-benzyl dichloride chlorine for raw material, obtains colourless fine particle shape crystal, yield: 90.4% after ethanol-dichloromethane (5:1, v/v) recrystallization; M.p. >250 DEG C.
IR (KBr, cm
-1)
v: 2937, 1683, 1608, 1238;
1H NMR (CDCl
3, 500 MHz)
δ: 4.68 (s, 2H), 5.21 (s, 2H), 7.12 (t,
J = 8.00 Hz, 1H), 7.20 (d,
J = 7.45 Hz, 2H), 7.24~7.26 (m, 2H), 7.39~7.48 (m, 4H), 7.70 (d,
J = 7.45 Hz, 1H), 7.73~7.76 (m, 1H), 8.13 (d,
J = 8.00 Hz, 1H), 8.18 (s, 1H);
13C NMR (CDCl
3, 125 MHz)
δ: 33.62, 39.66, 121.78, 126.76, 127.06, 127.57, 127.78, 128.50, 129.62, 130.12, 130.55, 132.10, 132.24, 134.64, 136.19, 145.80, 147.93, 151.37, 152.36, 160.32. Anal. Calcd for C
24H
17Cl
2N
5OS: C, 58.30; H, 3.47; N, 14.17. Found: C, 58.12; H, 3.68; N, 14.55. MS (ESI) m
/z 494.2 ([M+H]
+), 516.2 ([M+Na]
+).
Embodiment five: the synthesis of compound 3-((5-(((perfluorophenyl) methyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((5-(((perfluorophenyl) methyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4 (3H)-one
a5):
Synthesis step and processing condition are with embodiment one (6), and difference to be with 2,3,4,5,6-five fluorobenzyl bromide, for raw material, to obtain white crystal, yield: 60.1% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 127 ~ 128 DEG C.
IR (KBr, cm
-1)
v: 3066, 1676, 1612, 1170;
1H NMR (CDCl
3, 500 MHz)
δ: 4.39 (s, 2H), 5.18 (s, 2H), 7.27 (d,
J = 6.80 Hz, 2H), 7.45~7.51 (m, 4H), 7.70 (d,
J = 8.00 Hz, 1H), 7.75 (t,
J = 7.42 Hz, 1H), 8.14 (d,
J = 8.00 Hz, 1H), 8.16 (s, 1H);
13C NMR (CDCl
3, 125 MHz)
δ: 24.04, 39.84, 121.76, 126.72, 126.97, 127.62, 127.79, 130.30, 130.84, 132.01, 134.69, 145.78, 147.96, 151.18, 151.70, 160.38. Anal. Calcd for C
24H
14F
5N
5OS: C, 55.92; H, 2.74; N, 13.59; Found: C, 55.90; H, 3.00; N, 13.94. MS (ESI) m
/z 516.3 ([M+H]
+), 538.3 ([M+Na]
+).
Embodiment six: the synthesis of compound 3-((5 – ((2-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((2-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a6):
Synthesis step and processing condition are with embodiment one (6), and difference is to take o-chloro benzyl chloride as raw material, obtains colourless granules shape crystal, yield: 72.9% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 211 ~ 213 DEG C.
IR (KBr, cm
-1)
v: 3051, 1674, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 4.52 (s, 2H), 5.16 (s, 2H), 7.09~7.11 (m, 2H), 7.14~7.20 (m, 2H), 7.30~7.32 (m, 1H), 7.40~7.43 (m, 2H), 7.44~7.48 (m, 3H), 7.70 (d,
J = 8.00 Hz, 1H), 7.69~7.77 (m, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 35.02, 39.69, 121.78, 126.75, 127.03, 127.12, 127.58, 127.76, 129.38, 129.71, 130.15, 130.60, 131.61, 132.11, 134.42, 134.46, 134.66, 145.79, 147.93, 151.18, 152.95, 160.33. Anal. Calcd for C
24H
18ClN
5OS: C, 62.67; H, 3.94; N, 15.23. Found: C, 62.87; H, 4.20; N, 15.58. MS (ESI) m
/z 460.3 ([M+H]
+), 482.3 ([M+Na]
+).
Embodiment seven: the synthesis of compound 3-((5 – ((3-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5 – ((3-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a7):
Synthesis step and processing condition are with embodiment one (6), and difference is, with a bromine chloride for raw material, to obtain light yellow tabular crystal, yield: 72.9% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 150 ~ 151 DEG C.
IR (KBr, cm
-1)
v: 3051, 1682, 1610, 1168;
1H NMR (CDCl
3, 500 MHz)
δ: 4.37 (s, 2H), 5.17 (s, 2H), 7.13~7.14 (m, 2H), 7.19~7.22 (m, 3H), 7.29 (s, 1H), 7.43~7.49 (m, 4H), 7.70~7.71 (m, 1H), 7.74~7.77 (m, 1H), 8.13~8.16 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.59, 19.68, 121.77, 126.75, 127.02, 127.47, 127.59, 127.77, 128.07, 129.26, 129.98, 130.19, 130.68, 132.08, 134.48, 134.67, 138.48, 145.78, 147.93, 151.18, 152.57, 160.34. Anal. Calcd for C
24H
18ClN
5OS: C, 62.67; H, 3.94; N, 15.23. Found: C, 62.79; H,4.20; N, 15.57. MS (ESI) m
/z 460.3 ([M+H]
+), 482.3 ([M+Na]
+).
Embodiment eight: the synthesis of compound 3-((5 – ((4-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5 – ((4-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a8):
Synthesis step and processing condition with embodiment one (6), difference be with to benzyl chloride chlorine for raw material, obtain White Flocculus after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 75.8%; M.p. 145 ~ 146 DEG C.
IR (KBr, cm
-1)
v: 3061, 1676, 1610, 1172;
1H NMR (CDCl
3, 500 MHz) δ: 4.37 (s, 2H), 5.17 (s, 2H), 7.13 (d,
J = 8.00 Hz, 2H), 7.22~7.24 (m, 4H), 7.42~7.49 (m, 4H), 7.70~7.76 (m, 2H), 8.15~8.16 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.41, 39.70, 121.77, 126.74, 127.01, 127.61, 127.79, 128.88, 130.18, 130.62, 130.65, 132.10, 133.73, 134.48, 135.11, 145.78, 147.93, 151.17, 152.66, 160.34. Anal. Calcd for C
24H
18ClN
5OS: C, 62.67; H, 3.94; N, 15.23. Found: C, 62.74; H, 4.35; N, 15.46. MS (ESI) m
/z 460.3 ([M+H]
+), 482.3 ([M+Na]
+).
Embodiment nine: the synthesis of compound 3-((5 – ((2-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5 – ((2-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a9):
Synthesis step and processing condition are with embodiment one (6), and difference to be with adjacent fluorine benzyl chlorine, for raw material, to obtain colourless granules shape crystal, yield: 75.6% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 200 ~ 202 DEG C.
IR (KBr, cm
-1)
v: 3055, 1676, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 4.43 (s, 2H), 5.16 (s, 2H), 6.98 (t,
J = 9.17 Hz, 1H), 7.03 (d,
J = 7.72 Hz, 1H), 7.11~7.13 (m, 2H), 7.20~7.23 (m, 1H), 7.38~7.48 (m, 5H), 7.69 (d,
J = 7.45 Hz, 1H), 7.72~7.76 (m, 1H), 8.12~8.15 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 32.35, 39.56, 115.37, 115.55, 121.68, 123.68, 123.80, 124.22, 124.24, 126.64, 126.91, 127.47, 127.66, 129.68, 129.75, 130.05, 130.50, 131.44, 131.46, 132.03, 134.55, 145.69, 147.83, 151.07, 152.74, 159.93, 160.21, 161.90. Anal. Calcd for C
24H
18FN
5OS: C, 65.00; H, 4.09; N, 15.79. Found: C, 65.38; H, 4.34; N, 16.14. MS (ESI) m
/z: 444.3 ([M+H]
+), 466.3 ([M+Na]
+).
Embodiment ten: the synthesis of compound 3-((5 – ((3-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5 – ((3-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a10):
Synthesis step and processing condition are with embodiment one (6), and difference is, with a fluorobenzyl bromide for raw material, to obtain white needle-like crystals, yield: 90.7% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 168 ~ 169 DEG C.
IR (KBr, cm
-1)
v: 3062, 1685, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 4.39 (s, 2H), 5.16 (s, 2H), 6.93 (d,
J = 8.30 Hz, 1H), 7.02 (d,
J = 9.70 Hz, 1H), 7.08 (d,
J = 7.40 Hz, 1H), 7.14 (t,
J = 6.30 Hz, 2H), 7.19~7.23 (m, 1H), 7.43~7.48 (m, 4H), 7.69 (d,
J = 8.00 Hz, 1H), 7.75 (t,
J = 7.75 Hz, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.50, 39.56, 114.70, 114.87, 115.99, 116.16, 121.68, 124.83, 124.85, 126.65, 126.92, 127.49, 127.69, 130.09, 130.17, 130.26, 130.58, 132.01, 134.56, 138.75, 138.81, 145.68, 147.84, 151.08, 152.57, 160.24, 161.74, 163.70. Anal. Calcd for C
24H
18FN
5OS: C, 65.00; H, 4.09; N, 15.79. Found: C, 65.13; H, 4.07; N, 16.14. MS (ESI) m
/z: 444.3 ([M+H]
+), 466.3 ([M+Na]
+).
Embodiment 11: the synthesis of compound 3-((5-((4-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((4-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a11):
Synthesis step and processing condition with embodiment one (6), difference be with to fluorine benzyl chlorine for raw material, obtain white crystal after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 58.4%; M.p. 134 ~ 136 DEG C.
IR (KBr, cm
-1)
v: 3062, 1674, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 4.38 (s, 2H), 5.16 (s, 2H), 6.94 (t,
J = 8.58 Hz, 2H), 7.14 (d,
J = 7.45 Hz, 2H), 7.26~7.29 (m, 2H), 7.41~7.48 (m, 4H), 7.70 (d,
J = 7.40 Hz, 1H), 7.71~7.77 (m, 1H), 8.12~8.15 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.93, 39.71, 115.55, 115.73, 121.77, 126.73, 127.03, 127.60, 127.78, 130.17, 130.64, 130.93, 131.00, 132.14, 132.24, 134.67, 145.79, 147.93, 151.11, 152.82, 160.34, 161.40, 163.35. Anal. Calcd for C
24H
18FN
5OS: C, 65.00; H, 4.09; N, 15.79. Found: C, 65.40; H, 4.36; N, 16.20. MS (ESI) m
/z 444.3 ([M+H]
+), 466.3 ([M+Na]
+).
Embodiment 12: the synthesis of compound 3-((5-((2-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((2-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a12):
Synthesis step and processing condition are with embodiment one (6), and difference to be with adjacent methyl benzyl bromine, for raw material, to obtain yellow particle shape crystal, yield: 89.0% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 210 ~ 213 DEG C.
IR (KBr, cm
-1)
v: 3045, 1676, 1608, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 2.26 (s, 3H), 4.41 (s, 2H), 5.17 (s, 2H), 7.04 (d,
J = 8.05 Hz, 2H), 7.09 (t,
J = 8.30 Hz, 2H), 7.14 (t,
J = 7.45 Hz, 1H), 7.18 (d,
J = 7.45 Hz, 1H), 7.38 (t,
J = 7.72 Hz, 2H), 7.42~7.48 (m, 2H), 7.70 (d,
J = 8.00 Hz, 1H), 7.73~7.77 (m, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3,125 MHz)
δ: 19.12, 35.88, 39.62, 121.78, 126.35, 126.75, 127.06, 127.57, 127.76, 128.29,130.05, 130.22, 130.52, 130.67, 132.21, 133.83, 134.64, 137.21, 145.76, 147.91, 151.04, 153.12, 160.30. Anal. Calcd for C
25H
21N
5OS: C, 68.32; H, 4.82; N, 15.93.Found: C, 68.69; H, 5.09; N, 16.26. MS (ESI) m
/z 440.3 ([M+H]
+), 462.3 ([M+Na]
+).
Embodiment 13: the synthesis of compound 3-((5-((3-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((3-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a13):
Synthesis step and processing condition are with embodiment one (6), and difference to be with a methyl benzyl bromine, for raw material, to obtain yellow solid, yield: 69.8% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 146 ~ 148 DEG C.
IR (KBr, cm
-1)
v: 3035, 1683, 1610, 1178;
1H NMR (CDCl
3, 500 MHz)
δ: 2.28 (s, 3H), 4.37 (s, 2H), 5.17 (s, 2H), 7.03~7.10 (m, 5H), 7.14 (t,
J = 7.72 Hz, 1H), 7.40 (t,
J = 7.42 Hz, 2H), 7.44~7.47 (m, 2H), 7.69 (d,
J = 8.00 Hz, 1H), 7.75 (t,
J = 6.88 Hz, 1H), 8.12~8.15 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 21.37, 37.42, 39.63, 121.76, 126.26, 126.75, 127.08, 127.57, 127.75, 128.66, 129.93, 130.09, 130.55, 132.20, 133.12, 134.65, 136.08, 138.49, 145.80, 147.90, 151.00, 153.16, 160.32. Anal. Calcd for C
25H
21N
5OS: C, 68.32;H, 4.82;N, 15.93. Found: C, 68.66; H, 5.19; N, 16.32. MS (ESI) m
/z 440.3 ([M+H]
+), 462.3 ([M+Na]
+).
Embodiment 14: the synthesis of compound 3-((5-((4-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((4-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a14):
Synthesis step and processing condition with embodiment one (6), difference be with to methyl benzyl chlorine for raw material, obtain white plates crystal after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 83.7%; M.p. 153 ~ 154 DEG C.
IR (KBr, cm
-1)
v: 3059, 1687, 1610, 1172;
1H NMR (CDCl
3, 500 MHz)
δ: 2.28 (s, 3H), 4.37 (s, 2H), 5.18 (s, 2H), 7.04~7.07 (m, 4H), 7.16 (d,
J = 8.00 Hz, 2H), 7.39 (t,
J = 7.75 Hz, 2H), 7.43~7.48 (m, 2H), 7.70 (d,
J = 7.40 Hz, 1H), 7.75 (t,
J = 6.88 Hz, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 21.21, 37.23, 39.54, 121.77, 126.75, 127.06, 127.56, 127.77, 129.14, 129.43, 130.07, 130.53, 132.20, 133.24, 136.63, 137.69, 145.76, 147.90, 150.99, 153.19, 160.27. Anal. Calcd for C
25H
21N
5OS: C, 68.32; H, 4.82; N, 15.93. Found: C, 68.60; H, 5.23; N, 16.30. MS (ESI) m
/z 440.3 ([M+H]
+), 462.3 ([M+Na]
+).
Embodiment 15: the synthesis of compound 3-((5-((3-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((3-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a15)
Synthesis step and processing condition are with embodiment one (6), and difference to be with meta-methoxy benzyl chlorine, for raw material, to obtain white granular crystal, yield: 92.0% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 162 ~ 164 DEG C.IR (KBr, cm
-1)
v: 3001, 1683, 1610, 1153;
1H NMR (CDCl
3, 500 MHz)
δ: 3.74 (s, 3H),4.37 (s, 2H), 5.17 (s, 2H), 7.76~7.78 (m, 1H), 6.81 (s, 1H), 6.85 (d,
J = 8.00 Hz, 1H), 7.09 (d,
J = 8.00 Hz, 2H), 7.17 (t,
J = 7.72 Hz, 1H), 7.39~7.48 (m, 4H), 7.69 (d,
J = 7.45 Hz, 1H), 7.73~7.76 (m, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 37.45, 39.62, 55.31, 113.68, 114.46, 121.47, 121.76, 126.74, 127.06, 127.56, 127.75, 129.76, 130.08, 130.54, 132.17, 134.64, 137.72, 145.77, 147.91, 151.03, 152.99, 159.78, 160.30. Anal. Calcd for C
25H
21N
5O
2S: C, 65.92; H, 4.65; N, 15.37. Found: C, 66.30; H, 4.67; N, 15.75. MS (ESI) m
/z 456.3 ([M+H]
+), 478.3 ([M+Na]
+).
Embodiment 16: the synthesis of compound 3-((5-((4-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) preparation (compound number of target product 3-((5-((4-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one
a16)
Synthesis step and processing condition are with embodiment one (6), and difference is to take p-methoxybenzyl chloride as raw material, obtains colourless granules shape crystal, yield: 70.1% after ethanol-dichloromethane (10:1, v/v) recrystallization; M.p. 151 ~ 153 DEG C.IR (KBr, cm
-1)
v: 3051, 1683, 1612, 1165;
1H NMR (CDCl
3, 500 MHz)
δ: 3.75 (s, 3H), 4.36 (s, 2H), 5.17 (s, 2H), 6.78 (d,
J = 8.55 Hz, 2H), 7.10 (d,
J= 8.00 Hz, 2H), 7.20 (d,
J = 9.20 Hz, 2H), 7.39~7.48 (m, 4H), 7.69 (d,
J = 7.45 Hz, 1H), 7.76~7.76 (m, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.94, 39.59, 55.37, 114.10, 121.77, 126.75, 127.06, 127.56, 127.76, 128.24, 130.10, 130.47, 130.54, 132.22, 134.63, 145.77, 147.92, 150.96, 153.21, 159.28, 160.30. Anal. Calcd for C
25H
21N
5O
2S: C, 65.92; H, 4.65; N, 15.37. Found: C, 66.17; H, 5.04; N, 15.76. MS (ESI) m
/z 456.3 ([M+H]
+), 478.3 ([M+Na]
+).
Embodiment 17: the synthesis of compound 3-((4-phenyl-5-((2-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((4-phenyl-5-((2-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4 (3H)-one
a17)
Synthesis step and processing condition are with embodiment one (6), difference to be with o-trifluoromethyl benzyl chlorine, for raw material, to obtain white fluffy solid after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 92.7%, m.p. 180 ~ 181 DEG C.IR (KBr, cm
-1)
v: 3051, 1683, 1612, 1165;
1H NMR (CDCl
3, 500 MHz)
δ: 4.62 (s, 2H), 5.17 (s, 2H), 7.14~7.15 (m, 2H), 7.35 (t,
J = 7.75 Hz, 1H), 7.41~7.49 (m, 5H), 7.60 (d,
J = 7.45 Hz, 1H), 7.66~7.71 (m, 2H), 7.74~7.77 (m, 1H), 8.13~8.16 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 33.31, 39.64, 121.79, 123.08, 125.18, 126.26, 126.30, 126.74, 127.00, 127.60, 127.78, 130.20, 130.67, 132.05, 132.30, 132.37, 134.68, 135.30, 145.80, 147.95, 151.30, 153.02, 160.37. Anal. Calcd for C
25H
18F
3N
5OS: C, 60.84; H, 3.68; N, 14.19. Found: C, 60.47; H, 4.05; N, 14.21. MS (ESI) m
/z 494.3 ([M+H]
+), 516.3 ([M+Na]
+).
Embodiment 18: the synthesis of compound 3-((4-phenyl-5-((3-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((4-phenyl-5-((3-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4 (3H)-one
a18):
Synthesis step and processing condition are with embodiment one (6), and difference is, with m-trifluoromethyl benzyl bromine for raw material, to obtain white plates crystal, yield: 86.7% after dehydrated alcohol-methylene dichloride (10:1, v/v) recrystallization; M.p. 116 ~ 119 DEG C.IR (KBr, cm
-1)
v: 3051, 1683, 1612, 1165;
1H NMR (CDCl
3, 500 MHz)
δ: 4.44 (s, 2H), 5.15 (s, 2H), 7.10~7.12 (m, 2H), 7.38 (t,
J = 7.72 Hz, 1H), 7.41~7.54 (m, 7H), 7.70 (d,
J = 8.05 Hz, 1H), 7.74~7.77 (m, 1H), 8.12~8.14 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.61, 39.70, 121.76, 122.89, 124.65, 124.70, 125.87, 125.91, 126.73, 126.98, 127.60, 127.78, 129.22, 130.22, 130.72, 131.16, 132.05, 132.74, 134.68, 137.61, 145.77, 147.94, 151.25, 152.38, 160.34. Anal. Calcd for C
25H
18F
3N
5OS: C, 60.84; H, 3.68; N, 14.19. Found: C, 61.13; H, 4.06; N, 14.58. MS(ESI) m
/z 494.3 ([M+H]
+), 516.3 ([M+Na]
+).
Embodiment 19: the synthesis of compound 3-((4-phenyl-5-((4-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((4-phenyl-5-((4-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4 (3H)-one
a19):
Synthesis step and processing condition with embodiment one (6), difference be with to trifluoromethyl benzyl bromine for raw material, obtain White Flocculus after ethanol-dichloromethane (10:1, v/v) recrystallization, yield: 67.9%; M.p. 98 ~ 101 DEG C.
IR (KBr, cm
-1)
v: 3051, 1683, 1612, 1165;
1H NMR (CDCl
3, 500 MHz)
δ: 4.28 (s, 2H), 5.15 (s, 2H), 7.10~7.13 (m, 2H), 7.41~7.44 (m, 4H), 7.45~7.48 (m, 2H), 7.52 (d,
J = 8.05 Hz, 2H), 7.70 (d,
J = 6.90 Hz, 1H), 7.73~7.77 (m, 1H), 8.12~8.15 (m, 2H);
13C NMR (CDCl
3, 125 MHz)
δ: 36.42, 39.72, 121.76, 125.66, 125.69, 126.72, 126.97, 127.62, 127.80, 129.59, 130.21, 130.70, 131.06, 132.04, 134.69, 140.82, 145.75, 147.94, 151.28, 152.39, 160.36. Anal. Calcd for C
25H
18F
3N
5OS: C, 60.84; H, 3.68; N, 14.19. Found: C, 60.58; H, 4.02; N, 14.52. MS(ESI) m
/z: 494.3 ([M+H]
+),516.3 ([M+Na]
+).
Embodiment 20: compound 3-((5-(((6-chloropyridine-3-base) methyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) synthesis of quinazoline-4 (3H)-one:
(1) preparation of intermediate 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: synthesis step and processing condition are with embodiment one (1 ~ 5);
(2) target product 3-((5-(((6-chloropyridine-3-base) methyl) sulfenyl)-phenyl-4H-1,2,4-triazole-3-base) methyl) preparation (compound number of quinazoline-4 (3H)-one
a20):
Synthesis step and processing condition are with embodiment one (6), and difference is to take CCMP as raw material, obtains brown solid, yield: 80.7% after ethanol-dichloromethane (4:1, v/v) recrystallization; M.p. 132 ~ 134 DEG C.
IR (KBr, cm
-1)
v: 3064, 1683, 1608, 1165;
1H NMR (CDCl
3, 500 MHz) δ: 4.37 (s, 2H), 5.15 (s, 2H), 7.18~7.23 (m, 3H), 7.45~7.52 (m, 4H), 7.69~7.77 (m, 3H), 8.13~8.15 (m, 2H), 8.34 (d,
J = 2.30 Hz, 1H);
13C NMR (CDCl
3, 125 MHz)
δ: 32.88, 39.78, 121.76, 124.23, 126.74, 126.94, 127.64, 127.80, 130.32, 130.83, 131.90, 131.93, 134.71, 139.79, 145.77, 147.96, 150.08, 150.82, 151.42, 151.99, 160.40. Anal. Calcd for C
23H
17ClN
6OS: C, 59.93; H, 3.72; N, 18.23. Found: C, 59.57; H, 3.85; N, 18.41. MS(ESI) m
/z 461.3 ([M+H]
+), 483.3 ([M+Na]
+).
As can be seen from bacteriostatic activity test experiments below, dislike mould spirit, bismerthiazol and epoxiconazole for positive control drug with commercialization sterilant, formula of the present invention (
i) represented by compound to bacteriums such as rice leaf spot bacteria, citrus processing, tobacco ralstonia solanacearums, the fungies such as fusarium graminearum, Valsa mali, phytophthora infestans all show certain inhibit activities, especially compound
a19show good water resistant rice bacterial leaf spot pathogenic bacteria and citrus processing activity, compound
a14with
a18suitable with the mould spirit of evil to the inhibit activities of gibberella saubinetii.
Embodiment 21: anti-fungal activity of plant pathogenic experiment (suppressing mycelial growth rate method)
Adopt and suppress mycelial growth rate method, with formula (
i) compound carried out the test of anti-mycotic activity to fusarium graminearum, Valsa mali, phytophthora infestans, sample concentration is 50
μg/mL.The tested medicament of precise 5 mg, dissolves with 1 mL DMSO, and add 9 mL 0.1% tween 20 solution and be settled to 10 mL, joined by the medicament prepared in 90 mL PDA substratum (40 ~ 50 DEG C), fully shake up, being namely made into concentration is 50
μg/mL sample, is poured in the culture dish after sterilizing, arranges three repetitions, arranges blank simultaneously.With tested bacterial classification for screening object, with 4 mm punch tool, some bacterium cakes are made in normal for growth bacterium colony punching for subsequent use, with inoculating needle bacterium cake moved and receive dull and stereotyped central authorities, every ware connects a bacterium cake, be placed in 27 DEG C of constant incubators to cultivate 24 ~ 72 hours, check bacterial plaque diameter, each bacterium colony measures 2 times by right-angled intersection method.
Represent the size of bacterium colony with its mean number, bacteriostasis rate calculation formula is as follows:
Bacteriostasis rate=(contrast bacterial plaque diameter-sample bacterial plaque diameter)/(contrast bacterial plaque diameter-0.4) × 100%
Table 1 be formula (
i) in compound to the Antibacterial Activity result of subject plant fungi.
Embodiment 22: anti-plant pathogenetic bacteria activity experiment (opacity method)
Adopting opacity method, with rice leaf spot bacteria, citrus processing and tobacco ralstonia solanacearum for tested object, with commercialization sterilant Thiodiazole-copper and bismerthiazol for positive control medicament, is 200 at sample concentration
μg/mL and 100
μunder g/mL concentration, to formula (
i) compound carried out in vitro Antibacterial activity screening.
It is 200 and 100 that medicament and contrast medicament are configured to concentration respectively
μg/mL, and it is joined respectively in the test tube of NB liquid nutrient medium, measure OD value, this value is aseptic culture medium OD value.Then access tested bacterial classification, at 28 DEG C, 180 rpm constant-temperature table shaking culture 24 ~ 48 h, the bacterium liquid of each concentration is measured OD value on spectrophotometer, this value is the OD value containing bacterium culture medium.
Correction OD value=containing bacterium culture medium OD value-aseptic culture medium OD value.
Bacteriostasis rate=(after correcting the rear sample cultivation base OD value of control medium OD value-correction)/correct rear control medium OD value × 100%
Table 2 be formula (
i) in compound to subject plant bacterium Antibacterial Activity result.
When compound of the present invention uses as sterilant, can by carrier that compound of the present invention and other plant protection allow and mixing diluents, be modulated into normally used various formulation whereby, as mixture, granule, aqueous emulsion etc. use, also can be as used in combination in sterilant, Insecticides (tech) & Herbicides (tech), plant-growth regulator etc. or simultaneously and use with other agricultural chemicals.
Claims (9)
1. the quianzolinones containing 1,2,4-triazole thioether, it is characterized in that general formula be following formula (
i):
Wherein: R be benzyl, neighbour// to luorobenzyl, neighbour// p-chlorobenzyl, neighbour// to trifluoromethyl benzyl ,/to methoxy-benzyl, neighbour// to methyl-benzyl, to nitrobenzyl, to t-butylbenzyl, 2,6-dichloro benzyls, PFBBR, CCMP.
2. compound according to claim 1, is characterized in that the compound of partial synthesis is as follows:
a1: 3-((5-(benzylthio-)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a2: 3-((5-((4-(tertiary butyl) benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a3: 3-((5-((4-nitrobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a4: 3-((5-((2,6-dichloro benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a5: 3-((5-(((perfluorophenyl) methyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a6: 3-((5-((2-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a7: 3-((5-((3-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a8: 3-((5-((4-chlorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a9: 3-((5-((2-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a10: 3-((5-((3-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a11: 3-((5-((4-luorobenzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a12: 3-((5-((2-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a13: 3-((5-((3-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a14: 3-((5-((4-methyl-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a15: 3-((5-((3-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a16: 3-((5-((4-methoxy-benzyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a17: 3-((4-phenyl-5-((2-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a18: 3-((4-phenyl-5-((3-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a19: 3-((4-phenyl-5-((4-(trifluoromethyl) benzyl) sulfenyl)-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one;
a20: 3-((5-(((6-chloropyridine-3-base) methyl) sulfenyl)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4 (3H)-one.
3. according to described in claim 1 or 2 containing 1,2, the synthetic method of the quianzolinones of 4-triazole thioether, it is characterized in that with methyl o-aminobenzoate, methane amide, ethyl bromoacetate, hydrazine hydrate, PITC and replacement benzyl halogen or CCMP for raw material, obtain through following six steps synthesis:
。
4. the synthetic method of the quianzolinones containing 1,2,4-triazole thioether as claimed in claim 1 or 2, is characterized in that synthesis step and processing condition are:
The first step: the preparation of quinazoline-4-one
In there-necked flask, add methyl o-aminobenzoate successively, methane amide, formic acid, be warming up to 130 ~ 140 DEG C of back flow reaction; Stopped reaction after 6 ~ 8 h, after being cooled to room temperature, pours into reaction solution in appropriate cold water, and have a large amount of white solid to separate out, then stir 0.5 h, suction filtration, washing, oven dry, dehydrated alcohol recrystallization obtains white fluffy solid;
Mol ratio: methyl o-aminobenzoate: methane amide: formic acid=1:5.5:1.3
Temperature of reaction: 130 ~ 140 DEG C
Reaction times: 6 ~ 8 h
The preparation of second step: 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate
Quinazoline-4-one is added in single port bottle, salt of wormwood, then add proper amount of acetone stir make it be uniformly dispersed after, slowly ethyl bromoacetate is dripped under room temperature, dropwise the reaction of rear temperature rising reflux, stopped reaction after 3 ~ 4 h, pours in frozen water by reaction solution after being cooled to room temperature, separate out a large amount of white solid, suction filtration, washing, oven dry obtain product;
Mol ratio: quinazoline-4-one: salt of wormwood: ethyl bromoacetate=1:1.5:1.5
Temperature of reaction: 70 ~ 90 DEG C
Reaction times: 3 ~ 4 h
The preparation of the 3rd step: 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide
Add 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate in single port flask, add 80% hydrazine hydrate after dehydrated alcohol is dissolved, temperature rising reflux reacts; Stopped reaction after 2 ~ 3 h, is chilled to room temperature, suction filtration, dries and obtains white solid, then use dehydrated alcohol recrystallization;
Mol ratio: 2-(4-oxoquinazolin-3-(4H)-Ji) ethyl acetate: hydrazine hydrate=1:5.2
Temperature of reaction: 80 ~ 100 DEG C
Reaction times: 2 ~ 3 h
The preparation of the 4th step: 2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide
Add 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide in single port flask, dehydrated alcohol, adds PITC under stirring, and temperature rising reflux reacts; Stopped reaction after 3 ~ 5 h, is cooled to room temperature, suction filtration, dries, obtains white solid;
Mol ratio: 2-(4-oxoquinazolin-3-(4H)-Ji) acethydrazide: PITC=1:1
Temperature of reaction: 80 ~ 100 DEG C
Reaction times: 3 ~ 5 h
The preparation of the 5th step: 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one
2-(2-(4-oxoquinazolin-3-(4H)-Ji) ethanoyl)-N-phenyl amide base thiocarbamide is added in single port flask, the solution of potassium carbonate of appropriate 5%, temperature rising reflux reacts, stopped reaction after 5 ~ 7 h, while hot suction filtration, liquid cooling to be filtered but adjusts pH value of solution to neutral with 10% hydrochloric acid afterwards, separate out a large amount of white solid, suction filtration, dry, DMF-water recrystallization obtains product;
Temperature of reaction: 100 ~ 120 DEG C
Reaction times: 5 ~ 7 h
6th step: 3-((replacement benzylthio-)-4-phenyl-4H-1,2,4-triazole-3-base) methyl) preparation of quinazoline-4-(3H)-one
3-((4-phenyl-5-sulfydryl-4H-1 is added in single port flask, 2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one, add salt of wormwood successively after DMF is dissolved, replace benzyl halogen or CCMP, continue stopped reaction after reaction 2 ~ 5 h under room temperature, in system, add cold water, separate out white solid, continue stirring 0.5 h, suction filtration, dry, ethanol-dichloromethane recrystallization obtains product;
Mol ratio: 3-((4-phenyl-5-sulfydryl-4H-1,2,4-triazole-3-base) methyl) quinazoline-4-(3H)-one: benzyl halogen: salt of wormwood=1:1.1:3.2
Temperature of reaction: 20 ~ 25 DEG C
Reaction times: 2 ~ 5 h
Above-mentioned steps be applicable to general formula (
i) in the synthesis of all compounds.
5. the application of a kind of quianzolinones containing 1,2,4-triazole thioether as claimed in claim 1 or 2, is characterized in that, for the preparation of medicine and the medicament of control phytopathogen.
6. as claimed in claim 1 or 2 a kind of containing 1,2, the application of the quianzolinones of 4-triazole thioether, it is characterized in that, for the preparation of water prevention rice bacterial leaf spot pathogenic bacteria, citrus processing, tobacco ralstonia solanacearum bacterium, the medicine of Valsa mali, fusarium graminearum, phytophthora infestans fungi and medicament.
7. the application of a kind of quianzolinones containing 1,2,4-triazole thioether as claimed in claim 2, is characterized in that, compound
a7,
a8with
a19to rice leaf spot bacteria, there is good inhibit activities,
a19to citrus processing, there is good inhibit activities.
8. the application of a kind of quianzolinones containing 1,2,4-triazole thioether as claimed in claim 2, is characterized in that, compound
a14with
a18to the inhibit activities of fusarium graminearum, to dislike mould spirit suitable with contrasting medicament.
9. the application of a kind of quianzolinones containing 1,2,4-triazole thioether as claimed in claim 2, is characterized in that, compound
a8to the inhibit activities of Valsa mali, to dislike mould spirit suitable with contrasting medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510277539.6A CN104829598B (en) | 2015-05-27 | 2015-05-27 | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510277539.6A CN104829598B (en) | 2015-05-27 | 2015-05-27 | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104829598A true CN104829598A (en) | 2015-08-12 |
| CN104829598B CN104829598B (en) | 2017-05-10 |
Family
ID=53807839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510277539.6A Active CN104829598B (en) | 2015-05-27 | 2015-05-27 | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104829598B (en) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105145109A (en) * | 2015-10-26 | 2015-12-16 | 赤峰蒙鼎生物科技有限公司 | Greenhouse tomato overwintering cultivation method suitable for north alpine regions |
| CN105272611A (en) * | 2015-10-26 | 2016-01-27 | 赤峰蒙鼎生物科技有限公司 | Formula and production method of culture substrate for horticultural crops |
| CN105524047A (en) * | 2015-12-27 | 2016-04-27 | 贵州大学 | Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base |
| CN105859693A (en) * | 2016-03-01 | 2016-08-17 | 浙江工业大学 | 4-phenyl-3-((4,6-dimethylpyrimidin-2-yl thio)methyl)-5-benzylthio triazole compounds and application thereof |
| CN105859692A (en) * | 2016-03-01 | 2016-08-17 | 浙江工业大学 | Thioether compounds containing pyrimidine, thiadiazole ring and amide structures and application thereof |
| RU2668212C1 (en) * | 2017-11-14 | 2018-09-27 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский химико-технологический университет имени Д.И. Менделеева" (РХТУ им. Д.И. Менделеева) | N4-substituted 3-alkylsulphanyl-5-(1,2,4-triazole-1-ylmethyl)-1,2,4-triazoles, method for production thereof, fungicide and growth regulatory composition on their basis |
| CN109265448A (en) * | 2018-11-15 | 2019-01-25 | 三峡大学 | TMSIM N imidazole acetyldihydro quinoxaline derivatives of the one kind containing tert-butyl, synthetic method and its as the application on fungicide |
| CN109400589A (en) * | 2018-12-07 | 2019-03-01 | 湖北文理学院 | A kind of quinoxaline fungicide, preparation method and applications |
| CN109400588A (en) * | 2018-12-07 | 2019-03-01 | 湖北文理学院 | One kind quinoxaline containing flutrimazole fungicide, preparation method and applications |
| CN109721559A (en) * | 2019-01-28 | 2019-05-07 | 贵州大学 | A kind of 1,4- pentadiene -3- ketones derivant, the Preparation method and use of Sulfide-containing Hindered triazole |
| CN110330487A (en) * | 2019-07-31 | 2019-10-15 | 西南大学 | Quinazolone thiazolium compounds and its preparation method and application |
| CN110447651A (en) * | 2019-09-18 | 2019-11-15 | 兰州大学 | A kind of quianzolinones and the application in preparation or prevention and treatment agricultural plant disease |
| CN112239464A (en) * | 2019-07-19 | 2021-01-19 | 南京农业大学 | Quinazoline-4 (3H) -ketone derivative containing 1,3, 4-oxadiazole, preparation method and application |
| RU2757808C1 (en) * | 2020-04-30 | 2021-10-21 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский химико-технологический университет имени Д.И. Менделеева" (РХТУ им. Д.И. Менделеева) | 2-alkylthio-5-(1h-1,2,4,-triazole-1-ilmethyl)-1,3,4-thiadiazoles, method for production thereof and fungicidal compositions based thereon |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104086508A (en) * | 2014-07-25 | 2014-10-08 | 贵州大学 | 1, 3, 4-thiadiazole amide derivatives containing nitrogen heterocyclic ring as well as preparation methods and applications of 1, 3, 4-thiadiazole amide derivatives containing nitrogen heterocyclic rings |
-
2015
- 2015-05-27 CN CN201510277539.6A patent/CN104829598B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104086508A (en) * | 2014-07-25 | 2014-10-08 | 贵州大学 | 1, 3, 4-thiadiazole amide derivatives containing nitrogen heterocyclic ring as well as preparation methods and applications of 1, 3, 4-thiadiazole amide derivatives containing nitrogen heterocyclic rings |
Non-Patent Citations (3)
| Title |
|---|
| 刘军虎等: "含1,2,4-三唑席夫碱的新型喹唑啉类化合物的合成及其抗菌活性研究", 《有机化学》 * |
| 林选福等: "2-苄硫（砜）基-5-甲基-7-取代苄氧基-1,2,4-三唑并[1,5-a]嘧啶类衍生物的合成及抑菌活性研究", 《有机化学》 * |
| 鲍小平等: "2-苄硫基-5-甲基-1，2，4-三唑并[1,5-a]嘧啶-7-氧乙酰腙类衍生物的合成及其抑菌活性", 《合成化学》 * |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105145109A (en) * | 2015-10-26 | 2015-12-16 | 赤峰蒙鼎生物科技有限公司 | Greenhouse tomato overwintering cultivation method suitable for north alpine regions |
| CN105272611A (en) * | 2015-10-26 | 2016-01-27 | 赤峰蒙鼎生物科技有限公司 | Formula and production method of culture substrate for horticultural crops |
| CN105145109B (en) * | 2015-10-26 | 2017-09-29 | 赤峰和润农业高新科技产业开发有限公司 | A kind of greenhouse tomato method of overwintering cultivation suitable for cold area in north |
| CN105272611B (en) * | 2015-10-26 | 2019-01-11 | 赤峰和润农业高新科技产业开发有限公司 | A kind of formula and its production method of garden crop cultivation matrix |
| CN105524047A (en) * | 2015-12-27 | 2016-04-27 | 贵州大学 | Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base |
| CN105859693A (en) * | 2016-03-01 | 2016-08-17 | 浙江工业大学 | 4-phenyl-3-((4,6-dimethylpyrimidin-2-yl thio)methyl)-5-benzylthio triazole compounds and application thereof |
| CN105859692A (en) * | 2016-03-01 | 2016-08-17 | 浙江工业大学 | Thioether compounds containing pyrimidine, thiadiazole ring and amide structures and application thereof |
| CN105859692B (en) * | 2016-03-01 | 2018-02-27 | 浙江工业大学 | A kind of thio-ether type compounds and its application containing pyrimidine, Thiadiazole and amide structure |
| CN105859693B (en) * | 2016-03-01 | 2018-06-26 | 浙江工业大学 | A kind of 4- phenyl -3- ((4,6- dimethyl pyrimidine -2- bases are thio) methyl) -5- benzylthios triazole class compounds and its application |
| RU2668212C1 (en) * | 2017-11-14 | 2018-09-27 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский химико-технологический университет имени Д.И. Менделеева" (РХТУ им. Д.И. Менделеева) | N4-substituted 3-alkylsulphanyl-5-(1,2,4-triazole-1-ylmethyl)-1,2,4-triazoles, method for production thereof, fungicide and growth regulatory composition on their basis |
| CN109265448A (en) * | 2018-11-15 | 2019-01-25 | 三峡大学 | TMSIM N imidazole acetyldihydro quinoxaline derivatives of the one kind containing tert-butyl, synthetic method and its as the application on fungicide |
| CN109265448B (en) * | 2018-11-15 | 2020-09-15 | 三峡大学 | Tert-butyl-containing N-imidazole acetyl dihydroquinoxaline derivative, synthesis method and application thereof as bactericide |
| CN109400589A (en) * | 2018-12-07 | 2019-03-01 | 湖北文理学院 | A kind of quinoxaline fungicide, preparation method and applications |
| CN109400588A (en) * | 2018-12-07 | 2019-03-01 | 湖北文理学院 | One kind quinoxaline containing flutrimazole fungicide, preparation method and applications |
| CN109721559A (en) * | 2019-01-28 | 2019-05-07 | 贵州大学 | A kind of 1,4- pentadiene -3- ketones derivant, the Preparation method and use of Sulfide-containing Hindered triazole |
| CN109721559B (en) * | 2019-01-28 | 2022-02-15 | 贵州大学 | 1, 4-pentadiene-3-ketone derivative containing thioether triazole, preparation method and application |
| CN112239464A (en) * | 2019-07-19 | 2021-01-19 | 南京农业大学 | Quinazoline-4 (3H) -ketone derivative containing 1,3, 4-oxadiazole, preparation method and application |
| CN112239464B (en) * | 2019-07-19 | 2022-09-16 | 南京农业大学 | Quinazoline-4 (3H) -ketone derivative containing 1,3, 4-oxadiazole, preparation method and application |
| CN110330487A (en) * | 2019-07-31 | 2019-10-15 | 西南大学 | Quinazolone thiazolium compounds and its preparation method and application |
| CN110447651A (en) * | 2019-09-18 | 2019-11-15 | 兰州大学 | A kind of quianzolinones and the application in preparation or prevention and treatment agricultural plant disease |
| RU2757808C1 (en) * | 2020-04-30 | 2021-10-21 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский химико-технологический университет имени Д.И. Менделеева" (РХТУ им. Д.И. Менделеева) | 2-alkylthio-5-(1h-1,2,4,-triazole-1-ilmethyl)-1,3,4-thiadiazoles, method for production thereof and fungicidal compositions based thereon |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104829598B (en) | 2017-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104829598B (en) | Quinazolinone compound containing 1, 2, 4-triazole thioether and synthesizing method and application of quinazolinone compound | |
| CN104829608B (en) | A kind of cumarin thiazole indolone type compound and its preparation method and purposes | |
| CA2534405A1 (en) | Halogenated quinazolinyl nitrofurans as antibacterial agents | |
| Szulczyk et al. | Design and synthesis of novel 1H-tetrazol-5-amine based potent antimicrobial agents: DNA topoisomerase IV and gyrase affinity evaluation supported by molecular docking studies | |
| CN112645897B (en) | Thiazole derivative and preparation method and application thereof | |
| CN103554038A (en) | Polyhalogenated benzonitrile quinazolone compounds, preparation method and use thereof | |
| CN109810029A (en) | 2- replaces ethylamine basic ring alkyl sulfonyl amine compounds and its preparation method and application | |
| CN105418505B (en) | Pyrazol acid amide compounds and its preparation method and purposes | |
| CN108358896A (en) | A kind of compound and preparation method being used to prepare prevention crop pathogenic bacteria drug | |
| CN104892602B (en) | The hydazone derivative of a kind of 1,2,4-triazole [4,3-a] pyridine ring and preparation and application thereof | |
| CN105524047A (en) | Synthetic method and application of quinazolinone compounds containing 1,2,4-triazolethione Schiff base | |
| CN111285814B (en) | Quinazolinone compound containing hydrazone structural unit or stereoisomer thereof, or salt or solvate thereof | |
| CN103980209B (en) | A kind of 4-N-replaces-5-chloro-quinazoline compounds and preparation method and application | |
| CN102391193B (en) | 1,2,4-triazole derivative and preparation method and use thereof | |
| CN106117180B (en) | A kind of substituted pyridine connection pyrazoles bishydrazide compounds and its preparation method and application | |
| CN107973807A (en) | A kind of triazol benzothiazole derivant and its preparation method and application | |
| Alafeefy | Synthesis and antimicrobial activity of some new quinazolin-4 (3 H)-one derivatives | |
| CN109851611B (en) | Sulfadiazine compound and preparation method and application thereof | |
| CN102850341A (en) | Thiadiazole compound, preparation method and applications thereof | |
| CN102603553A (en) | Compound with collaborative antifungal effect and application thereof in pharmaceuticals | |
| CN104829534A (en) | Preparation method of dihydro-pyrazole morpholine derivatives containing naphthalene nucleus frameworks and application of dihydro-pyrazole morpholine derivatives to preparation of antitumor drugs | |
| CN105130981A (en) | Berberine benzimidazole compounds, and preparation method and application thereof | |
| CN105924435B (en) | A kind of substituted pyrazoles acetamides and its preparation method and application | |
| Sharma et al. | Synthesis, characterization and biological evaluation of some imidazole bearing thiazolidin-4-ones as possible antimicrobial and anthelmintic agents | |
| CN100436455C (en) | Substitute 2,3-dihydrogen thiazole [4,5-d] pyrimidine-7(6H)- ketone (imines) having weed removal active and preparation thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210903 Address after: 300304 room 1-2050, Block E, No. 6, Huafeng Road, Huaming high tech Industrial Zone, Dongli District, Tianjin Patentee after: Zhongzhi online Co.,Ltd. Address before: 550025 science and Technology Department, Guizhou University, Huaxi District, Guizhou, Guiyang Patentee before: Guizhou University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221019 Address after: Room 107, Building 6, No. 91, Fahuasi Street, Dongcheng District, Beijing 100062 Patentee after: Beijing Legend Yousheng Culture Media Co.,Ltd. Address before: 300304 room 1-2050, Block E, No. 6, Huafeng Road, Huaming high tech Industrial Zone, Dongli District, Tianjin Patentee before: Zhongzhi online Co.,Ltd. |
|
| EE01 | Entry into force of recordation of patent licensing contract | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20150812 Assignee: TIANJIN ZHONGCHENG JIAYI BIOTECHNOLOGY Co.,Ltd. Assignor: Beijing Legend Yousheng Culture Media Co.,Ltd. Contract record no.: X2024980001861 Denomination of invention: A quinazolinone compound containing 1,2,4-triazolyl sulfide and its synthesis method and application Granted publication date: 20170510 License type: Common License Record date: 20240201 |