CN101891708B - Diacylhydrazine compounds containing 4-methyl-1,2,3-thiadiazole groups, preparation method and application thereof - Google Patents

Diacylhydrazine compounds containing 4-methyl-1,2,3-thiadiazole groups, preparation method and application thereof Download PDF

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CN101891708B
CN101891708B CN201010187048XA CN201010187048A CN101891708B CN 101891708 B CN101891708 B CN 101891708B CN 201010187048X A CN201010187048X A CN 201010187048XA CN 201010187048 A CN201010187048 A CN 201010187048A CN 101891708 B CN101891708 B CN 101891708B
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milliliters
thiadiazoles
methyl isophthalic
isophthalic acid
phenyl
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CN101891708A (en
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范志金
王唤
付一峰
杨知昆
米娜
王守信
左翔
郑琴香
国丹丹
赵晖
张海科
范谦
杨维清
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Nankai University
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Abstract

The invention provides diacylhydrazine derivatives containing 1,2,3-thiadiazole groups, a preparation method and application thereof, and relates to heterocyclic compounds containing 1,2,3-thiadiazole, which have chemical structural general formulas shown in a graph I, a graph II, a graph III, a graph IV, a graph V and a graph VI. The invention discloses the structural general formulas, a synthesizing method, application in pesticide, fungicide, antiphytovirucide and plant activator of the compounds, and a process for preparing the pesticide, the fungicide, the antiphytovirucide and the plant activator by mixing the compounds and agriculturally accepted auxiliaries or synergist, and further discloses application and a preparation method for combining the compounds with commodity pesticide, the fungicide, the antiphytovirucide and the plant activator in controlling diseases, insect pests, virus diseases of agriculture, forestry and gardening.

Description

A kind of 4-methyl isophthalic acid that contains, 2, the bishydrazide compounds of 3-thiadiazoles group
Technical field
Technical scheme of the present invention relates to the heterogeneous ring compound that contains 1,2-diazole, is specifically related to contain the 4-methyl isophthalic acid; 2, the bishydrazide verivate of 3-thiadiazoles group more specifically relates to N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl radical)-the N '-tertiary butyl-N '-substituted formyl hydrazine class compound, N-(4-methyl isophthalic acid, 2; 3-thiadiazoles-5-formyl radical)-and the N-tertiary butyl-N '-substituted formyl hydrazine class compound, the N '-tertiary butyl-N '-substituted formacyl-N-substituted formacyl-N-4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine compounds, the N '-tertiary butyl-N-substituted formacyl-N-4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl hydrazine compounds, the N '-tertiary butyl-N '-(4-methyl isophthalic acid, 2; 3-thiadiazoles-5-formyl radical)-and N-substituted formacyl-N-4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine compounds and two-[(N '-tertiary butyl-N '-substituted formacyl)-N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl hydrazine)] compounds.
Background technology
Bishydrazide compounds obtained at aspects such as agricultural chemicals, bio-medical material, electroluminescent, selectivity identification and liquid crystal materials widespread use (Gao Wei, etc. chemical industry progress, 2009,28 (5): 882-889).At pesticide field, triazolo pyrimidine thioether bishydrazide compounds have the activity that suppresses the test plant growth (Xia Bo, etc. Chinese agricultural chemicals, 2007,6:48-51); Tertiary butyl bishydrazide compound is one big type of insect growth regulator(IGR), and this type medicament is a target of attack with the distinctive system of growing of insect, utilizes the hormone substance that different steps produced in the insect growth process, grows normally with interference insect.U.S. Rohm-Hass company reported first in 1988 the N-tertiary butyl bishydrazide compounds RH-5849 of synthetic have corresponding plan moulting hormone effect (Wing.Science.1988; 241:467); And successfully with its be developed as commercial pesticide species press down the food hydrazine (Feng Jian. modern agricultural chemicals; 2004,3 (2): 4-8).Subsequently, the said firm is guide's active structure with RH-5849 again, utilize in the pesticide molecule design etc. row's principle and roughly the same the synthetic method it has been carried out structural modification, successfully developed RH-5992 (Heller again; Et al., Brighton Crop.Prot.Conf., Pests&Dis., 1992; 1:59), RH-2485 (Le, et al., Brighton Crop.Prot.Conf., Pests&Dis.; 1996,2:481), RH-0345 (Cowles, et al.; J.Econ.Entomol., 1996,89:1556) three kinds of commercialization kinds.The nineties in 20th century, Japanese scientist has reported the progress of bishydrazide compounds successively, with N-tertiary butyl bishydrazide or be first guide structure with two acylhydrazines only; Conversion two ends acyl group contains phenyl ring, heterocycle, the fused heterocycle with different substituents; Nippon Kayaku Co.Ltd and Sankyo Co.Ltd have developed jointly two aromatic hydrazide kind compound ANS-118 (Yanagi et al., BrightonCrop.Prot.Conf., the Pests&Dis. that contains benzheterocycle; 2000,2:27).N-tertiary butyl bishydrazide compounds becomes another type of commercial insect growth regulator(IGR) after neotonin and chitin synthesis inhibitor, is widely used in the control of insect.China's Jiangsu pesticide research cumarone introduced in the structure of bishydrazide developed furans worm hydrazides; This compound shows very high insecticidal activity to lepidoptera pest armyworm and beet armyworm; Obtain China's novel pesticide and registered (Zhang Xiangning temporarily; Deng. Agricultural University Of Nanjing's journal, 2005,28 (4): 135-139).
Figure DEST_PATH_RE-GSB00000275544900011
The general structure of bishydrazide sterilant
China is very active in the initiative research in this field; Small ring compound is introduced in the bishydrazide molecule synthetic Trimetylene bishydrazide compound as 1; 1 '-ethyl dicarboxylate's gem-dimethyl Trimetylene bishydrazide has better insecticidal activity (Su Jiangtao to the broad bean aphid; Deng. agricultural chemicals, 2006,45 (11): 737-738); The N-tertiary butyl-N-substituted benzoyl hydrazides (or contain on the phenyl ring amino bishydrazide compound) have good larvicidal activity (the hair light of spring, etc. organic chemistry, 2006,26 (1): 60-64); That the verivate of heterocycle bishydrazide compound such as chroman also has is synthetic (Huang Zhiqiang, etc. organic chemistry, 2009,29 (6): 891-897); Fused heterocycle and contain the activity that the ferrocene substituted aryl also can improve compound; Contain the bishydrazide compounds of trifluoro ethoxy on the phenyl ring and do not contain the N-tertiary butyl and also show biological activity (Cui Zining in various degree; Deng. organic chemistry, 2007,27 (10): 1300-1304).Relatively more outstanding is; The yellow profit autumn of Nankai University and the people of Wangqing County teach seminar with finding that new compound shows mosquito larvae and the good biological activity of small cabbage moth (Sun Ranfeng in N-S-N or the N-S-S-N key introducing bishydrazide structure; Et al.J.Agric.FoodChem.; 2009,57 (9): 3661-3668), part of compounds has good DEVELOPMENT PROSPECT.
Many bibliographical informations the composition optimizes and the biological activity of aryl class bishydrazide lead compound, but with 1,2,3-thiadiazoles active structure fragment is introduced structure in the bishydrazide molecule and is derived and biological activity report very few (200910069470.2).Because 1,2, the 3-thiadiazoles heterocyclic compounds has wide biological activity, like (Boschelli, et al., J.Med.Chem.1993,36:1802 such as anti-inflammatory, expelling parasite, weeding, coordinate plant growth; Saad H., Indian J.Chem, 1996,35B:980; Bakulev, et al., The Chemistry of 1,2,3-thiadiazole, 2004, John Wiley Sons, Inc.), the first thiophene lures amine (Fan Zhijin etc., CN1810808A; Fan Zhijin etc., CN2020667A), diazosulfide (BTH) and tiadinil (TDL) all be 1,2, the verivate of 3-thiadiazoles (Ni Changchun, world's agricultural chemicals, 2007,29 (1): 18-23).Based on above-mentioned document analysis and patent investigation; Novelty of the present invention be lead compound with existing two aromatic hydrazide kind insect growth regulator(IGR)s; Principle and means according to the design of agricultural chemicals such as structure activity relationship and bioisostere, active substructure splicing; Existing two aromatic hydrazide kind insect growth regulator(IGR)s are carried out further composition optimizes, and a series of 4-of containing methyl isophthalic acids, 2 have been synthesized in design; The bishydrazide compounds of 3-thiadiazoles-N-tertiary butyl; And the synthetic new compound carried out the evaluated biological activity of system, the biological activity of these compounds all has comparatively significantly than the positive control compound and improves, the present invention for efficient, the eco-friendly novel pesticide molecular designing of low toxicity synthetic and exploitation provides the candidate compound.
Summary of the invention
Technical problem to be solved by this invention is: the new 4-methyl isophthalic acid that contains is provided; 2; The compound method of the bishydrazide verivate of 3-thiadiazoles group; Provide biological activity that this compounds suppresses agricultural, gardening and forestry pathogenic fungi, insect and plant virus and the growth of regulating insect, inducing plant to produce the purposes of anti-disease activity and the working method of these medicaments, provide simultaneously the use of these compounds and commercially available agricultural chemical breed combination in agriculture field and gardening field and field of forestry application and with agricultural on the complete processing and the working method of acceptable auxiliary agent or synergistic agent combined preparation sterilant, desinsection and sterilant and desinsection and Antiphytoviral medicament and desinsection and plant activator compsn.
The present invention solves this technical problem the technical scheme that is adopted: what have that agriculture field, gardening field, field of forestry insecticidal activity, fungicidal activity, anti-phytoviral activity and inducing plant produce anti-disease activity or insect growth regulator activity contains the 4-methyl isophthalic acid; 2, the chemical structure of general formula of the bishydrazide verivate of 3-thiadiazoles group is suc as formula shown in I, formula II, formula III, formula IV, formula V and the formula VI:
Figure GSA00000123738900021
Figure GSA00000123738900031
Wherein, R 1, R 2, R 3, R 4, R 5Be respectively and be selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl; Q is arylidene or inferior fatty group.
The 4-methyl isophthalic acid that contains of the present invention, 2, the compound method of the bishydrazide derivative I of 3-thiadiazoles group is following:
Wherein: R 1For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl.
The 4-methyl isophthalic acid that contains of the present invention, 2, the compound method of the bishydrazide derivative I I of 3-thiadiazoles group is following:
Figure GSA00000123738900033
Wherein: R 2For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl.
The 4-methyl isophthalic acid that contains of the present invention, 2, the compound method of the bishydrazide derivative III of 3-thiadiazoles group is following:
Figure GSA00000123738900041
Wherein: R 3For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl.
The 4-methyl isophthalic acid that contains of the present invention, 2, the compound method of the bishydrazide derivative I V of 3-thiadiazoles group is following:
Figure GSA00000123738900042
Wherein: R 4For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl.
The 4-methyl isophthalic acid that contains of the present invention, 2, the compound method of the bishydrazide verivate V of 3-thiadiazoles group is following:
Wherein: R 5For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2; 3-thiadiazolyl group, 2-furyl, 2-methyl-2-(4-chloro-phenyl-)-1-propyl group, trichloromethyl, chrysanthemum acyl group, dichloro chrysanthemum acyl group, 4-fluorobenzene ethyl, 2; 6-dichlorophenyl, methyl, propyl group, heptyl, 3; 5-dichlorophenyl, 3; 5-dimethyl-, 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-base, 2; 4-dimethyl--1-phenylpyrazole-3-base, cyclohexyl, 2-fluorobenzene ethyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base, 2-fluorobenzene ethyl.
Of the present inventionly contain 1,2, the compound method of the bishydrazide verivate VI of 3-thiadiazoles reactive group is following:
Figure GSA00000123738900052
Wherein: Q is arylidene or inferior fatty group, like
Figure GSA00000123738900053
etc.
Specifically be divided into following steps:
A. the preparation of substituted formyl chlorine:
The replacement formic acid that in 50 milliliters of round-bottomed flasks, adds 2 mmoles adds the sulfur oxychloride of 12 mmoles again, with reaction mixture with oil bath reflux 3-4 hour, air distillation remove behind the intact sulfur oxychloride of unreacted substituted formyl chlorine, the sealing preservation is subsequent use; The amount of substituted formyl chlorine preparation enlarges by corresponding proportion or dwindles.
The preparation of B.N-(substituted formacyl)-N '-tertiary butyl hydrazine:
In 100 milliliters of round-bottomed flasks, add 15 mmole tertiary butyl hydrazonium salt hydrochlorates; Add 40 milliliters of methylene dichloride and 5 ml waters and 30 mmole sodium hydroxide again; Slowly drip 20 milliliters of dichloromethane solutions of 15 mmole substituted formyl chlorine down in the cooling of induction stirring and ice bath, dropwise afterwards room temperature reaction 3 hours, the stopped reaction afterreaction mixes useless water washing; Tell organic layer; Behind the anhydrous magnesium sulfate drying, removal of solvent under reduced pressure obtains N-(substituted formacyl)-N '-tertiary butyl hydrazine, and product need not to be further purified the reaction that directly is used for next step; The amount of N-(substituted formacyl)-N '-tertiary butyl hydrazine preparation enlarges by corresponding proportion or dwindles.
C.4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl chloride:
With the 4-methyl isophthalic acid of 9.66 gram (0.067 mole) synthetic or purchase, 2,3-thiadiazoles-5-formic acid and 29 milliliters of thionyl chlorides join in 100 milliliters of three mouthfuls of round-bottomed flasks; 80 degrees centigrade of following reflux 6 hours remove excessive thionyl chloride under reduced pressure, and underpressure distillation is collected 94-96 degree centigrade cut and got faint yellow product 9.25 grams under 2000Pa; Column chromatography purification, productive rate: 85%, midbody 4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl chloride sealing is kept in the moisture eliminator subsequent use, the 4-methyl isophthalic acid; 2, the amount of 3-thiadiazoles-5-formyl chloride preparation enlarges by corresponding proportion or dwindles.
The preparation of D.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine:
In 1000 milliliters of round-bottomed flasks, add 0.4 mole of tertiary butyl hydrazonium salt hydrochlorate, add 450 milliliters of methylene dichloride and 100 ml waters and 0.6 molar sodium hydroxide again, under induction stirring and ice bath cooling, slowly drip 0.4 mole of 4-methyl isophthalic acid; 2,50 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride dropwise the back room temperature reaction 5 hours; The stopped reaction afterreaction mixes useless water washing, tells organic layer, behind the anhydrous magnesium sulfate drying; Removal of solvent under reduced pressure obtains N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine, product need not to be further purified the reaction that directly is used for next step; The amount of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine preparation enlarges by corresponding proportion or dwindles.
The preparation of E.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-the formyl radical)-N '-tertiary butyl-N '-substituted formyl hydrazine class compound I:
Get 0.1 mmole N-(4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.1 mmole substituted formyl chlorine down; Dropwise the back and continued stirring reaction 4 hours in room temperature, after reaction finished, the reaction mixture water was given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying filters the back removal of solvent under reduced pressure, and crude product is with Virahol or re-crystallizing in ethyl acetate; Obtain N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl radical)-the N '-tertiary butyl-N '-substituted formyl hydrazine class compound I, carry out fusing point with 1The mensuration of H NMR is confirmed its chemical structure, and the amount of compound I preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound I is seen table 1.
The preparation of F.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-the formyl radical)-N-tertiary butyl-N '-substituted formyl hydrazine class compound II:
Getting 0.1 mmole N-(substituted formacyl)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join then in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.12 mmole triethylamine; The ice bath cooling slowly drips 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride down; Dropwise the back and continued stirring reaction 4 hours in room temperature, after reaction finished, the reaction mixture water was given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, and filters the back removal of solvent under reduced pressure, and crude product is with Virahol or re-crystallizing in ethyl acetate; Obtain N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl radical)-the N-tertiary butyl-N '-substituted formyl hydrazine class compound II, carry out fusing point with 1The mensuration of H NMR is confirmed its chemical structure, and the amount of compound I I preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound I I is seen table 1.
G.N '-the tertiary butyl-N '-substituted formacyl-N-substituted formacyl-N-4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl hydrazine derivative III
In 100 milliliters of round-bottomed flasks, add 0.1 mmole N '-tertiary butyl-4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine; 0.2 the triethylamine of mmole, 20 milliliters of methylene dichloride stirring and dissolving slowly drip 10 milliliters of dichloromethane solutions that are dissolved with 0.1 mmole substituted formyl chlorine then under condition of ice bath; Dropwised in 1 hour; Naturally heat up stirring at room 5 hours, saturated NaHCO 3Solution extraction, anhydrous Na 2SO 4Dry; Filter; The decompression precipitation, (eluent is 60-90 degree centigrade a sherwood oil: ETHYLE ACETATE volume ratio 3: 1) get the product N '-tertiary butyl-N '-substituted formacyl-N-substituted formacyl-N-4-methyl isophthalic acid, 2 with 200-300 order silica gel column chromatography; 3-thiadiazoles-5-formyl hydrazine derivative III, carry out fusing point with 1The mensuration of H NMR is confirmed its chemical structure, and the amount of compound III preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound III is seen table 1.
H.N '-the tertiary butyl-N-substituted formacyl-N-4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl hydrazine derivative I V
In 100 milliliters of round-bottomed flasks, add 0.1 mmole N-(substituted formacyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling slowly drips 0.1 mmole 4-methyl isophthalic acid down; 2,20 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride dropwised in 1 hour; Naturally heat up; Continue stirring reaction 4 hours in room temperature, after reaction finishes, filter the back removal of solvent under reduced pressure; (eluent is 60-90 degree centigrade a sherwood oil to crude product: ETHYLE ACETATE volume ratio 3: 1) get N '-tertiary butyl N-substituted formacyl-N-4-methyl isophthalic acid with 200-300 order silica gel column chromatography; 2,3-thiadiazoles-5-formyl hydrazine derivative I V, carry out fusing point with 1The mensuration of HNMR is confirmed its chemical structure, and the amount of compound IV preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound IV is seen table 1.
I.N '-the tertiary butyl-N '-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N-substituted formacyl-N-4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl hydrazine verivate V
In 100 milliliters of round-bottomed flasks, add 4.54 mmole N-(substituted formacyl)-N '-tertiary butyl hydrazines and be dissolved in 20 milliliters of methylene dichloride, add acid binding agent 6.8 mmole triethylamines then, the ice bath cooling slowly drips 6.8 mmole 4-methyl isophthalic acids down; 2,20 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride dropwised in 1 hour; Naturally heat up, continued stirring reaction 4 hours, after reaction finishes in room temperature; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying 60-90 degree centigrade sherwood oil: methylene dichloride mixed solvent recrystallization gets N '-tertiary butyl N '-(4-methyl isophthalic acid, 2; 3-thiadiazoles-5-formyl radical)-N-substituted formacyl-N-4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl hydrazine verivate V, carry out fusing point with 1The mensuration of HNMR is confirmed its chemical structure, and the amount of compound V preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound IV is seen table 1.
J. the preparation of two-[(N '-tertiary butyl-N '-substituted formacyl)-N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine)] verivate VI
In 100 milliliters of round-bottomed flasks, add 7 mmole N '-tertiary butyl-4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine, the triethylamine of 8 mmoles; 20 milliliters of methylene dichloride stirring and dissolving slowly drip under condition of ice bath then and are dissolved with 3.5 mmoles to 5 milliliters of the dichloromethane solutions of substituted dimethyl acyl chlorides, dropwise; Naturally heat up, stirring at room 4 hours, the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, that sherwood oil and methylene dichloride recrystallization get product is two-[(N '-tertiary butyl-N '-substituted formacyl) N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl hydrazine)] verivate VI, measure fusing point with 1HNMR confirms chemical structure, and the amount of compound VI preparation enlarges by corresponding proportion or dwindles; The chemical structure of compound IV is seen table 1.
K. the 4-methyl isophthalic acid that contains of the present invention, 2, the bishydrazide verivate of 3-thiadiazoles group is to the mensuration of small cabbage moth insecticidal activity:
The 4-methyl isophthalic acid that contains of the present invention, 2, the bishydrazide verivate of 3-thiadiazoles group is following to the screening method of the insecticidal activity of small cabbage moth: adopt the blade medicine embrane method; The solution that sample to be tested is mixed with 200 mcg/ml carries out; Get former medicine sample earlier with the small amount of acetone dissolving, then with the dilution of the 0.5 ‰ Triton-100 aqueous solution, the 0.5 ‰ Triton-100 aqueous solution are contrast; Each concentration repeats for 3 times, 10 examinations of each re-treatment worm; Get fresh free of contamination cabbage leaves, in soup, soaked for 10 seconds, after indoor drying (about 2 hours); Put into the petridish of 9 centimetres of diameters; Insert small cabbage moth 2 instar larvaes of big or small basically identical respectively, tighten with bungee and be placed in the small cabbage moth constant temperature insectary check result after 96 hours or 120 hours; Touch polypide with little writing brush or tweezers, can not coordinated movement as death; With the positive contrast of worm hydrazides.
L. the 4-methyl isophthalic acid that contains of the present invention, 2, the bishydrazide verivate of 3-thiadiazoles group is to the mensuration of mosquito larvae insecticidal activity:
The 4-methyl isophthalic acid that contains of the present invention, 2, the bishydrazide verivate of 3-thiadiazoles group is following to the screening method of the insecticidal activity of mosquito larvae: culex pipiens pallens (Culex pipiens pallens), the normal population of indoor feeding; Take by weighing test compound about 2 milligrams in the Synnematin B medicine bottle, add 10 milliliters of acetone, vibration dissolving sample is mixed with the mother liquor of 200 mcg/ml; Pipette 1 milliliter of mother liquor in 100 ml beakers that fill 99 ml waters, choose mosquito larvae at the beginning of 10 4 ages, pour in the lump in the beaker together with 10 milliliters of feeding liquids, the concentration of its soup is 2 mcg/ml.It is 25 degrees centigrade of cultivations that the solution of handling well is put into indoor maintenance temperature together with the beaker of mosquito larvae, and check result after 24 hours observes till all larvae pupations.With the aqueous solution that contains 1 milliliter of acetone is blank; Add a small amount of mosquito feed and sucking-off tumbler every day, and moisture evaporated (5 milliliters/day) in the additional beaker, all dead or pupate up to mosquito larvae; Most larvas generally pupated in 8 days; With the positive contrast of worm hydrazides.
M. contain the 4-methyl isophthalic acid, 2, the mensuration that the bishydrazide verivate of 3-thiadiazoles group influences the pathogenic fungi growth activity:
The 4-methyl isophthalic acid that contains of the present invention, 2, the mensuration of the bishydrazide verivate bacteriostatic activity of 3-thiadiazoles group adopts thalli growth rate assay method; Detailed process is: get 5 milligrams of sample dissolution in an amount of N, with containing the medicament that a certain amount of polysorbas20 emulsifier aqueous solution is diluted to 500 mcg/ml, will supply the reagent agent under aseptic condition, respectively to draw in 1 milliliter of injection petridish then; Add 9 milliliters of substratum more respectively, it is dull and stereotyped to process 50 mcg/ml pastilles after shaking up, and does blank with the flat board that adds 1 milliliter of aqua sterilisa; Punch tool with 4 millimeters of diameters cuts the bacterium dish along the mycelia outer rim; Move on the pastille flat board, be equilateral triangle and put, every processing repetition 3 times; Petridish is placed in the 24+1 degree centigrade of constant incubator cultivates; Colony diameter to be contrasted expands to 2-3 centimetre of " Invest, Then Investigate " and respectively handles bacterium dish expansion diameter, averages, and relatively calculates relative bacteriostasis rate with blank; Supply the examination bacterial classification to comprise frequently seen plants pathogenic bacteria on the various agricultural, its title and code name comprise AS: tomato early blight bacterium (Alternaria solani); BC: botrytis cinerea pers (Botrytis cinerea); CA: peanut Cercospora bacteria (Cercospora arachidicola); CB: sugar beet leaf spot bacteria (Cercospora beticola); CL: watermelon anthrax bacteria: (Colletotrichum lagenarium); FO: cucumber fusarium axysporum (Fusarium oxysporum); GZ: fusarium graminearum (Gibberella zeae); PG: rice blast fungus (Phyricularia grisea (Cooke) Sacc.); PI: phytophthora infestans (Phytophthora infestans (Mont.) de Bary); PP: ring rot of apple bacterium (Physalospora piricola); PS: Rhizoctonia solani Kuhn (Pellicularia sasakii); RS: dry thread Pyrenomycetes (Rhizoctonia solani kuhn), these bacterial classifications have good representativeness, can represent the kind of most of pathogenic bacteria that the field takes place in the agriculture prodn.
N. the 4-methyl isophthalic acid that contains of the present invention, 2, the mensuration of the derivative induced anti-disease activity of bishydrazide of 3-thiadiazoles group:
The 4-methyl isophthalic acid that contains of the present invention, 2, the active screening method of the derivative induced tobacco resisting tobacco mosaic virus of the bishydrazide of 3-thiadiazoles group (TMV) is:
(1). standard plant activator: selecting tiadinil (TDL) (purity is greater than 99.5%) is the plant activator of standard;
(2). contain the 4-methyl isophthalic acid, 2, the active screening method of the anti-TMV of the derivative induced tobacco of bishydrazide of 3-thiadiazoles group: the mensuration of the direct antiviral activity that exsomatizes adopts half leaf method to carry out; It is the common cigarette that seedling age is consistent that live body is induced, and 3 basins are one group, respectively at the cigarette seedling of inoculation pre-treatment in preceding 7 days; Processing mode comprises: spray test compound solution 2 to 3 times, and each 10 milliliters, or soil treating; Each 10 milliliters, the 7th day frictional inoculation TMV on the tobacco leaf that newly grows places its growth optimal temperature and the following cultivation of illumination after 3 days the cigarette seedling; The inspection incidence; Comprehensive scab number is calculated as follows out the inducing anti-disease toxic effect fruit of test compound to TMV, and 3 repetitions are established in each processing, and water and TDL are selected in blank and the contrast of standard medicament respectively:
R = CK - I CK × 100
Wherein, R is the induce effect of new compound to the anti-TMV of tobacco, unit: %
CK is the average withered spot number of clear water contrast blade, unit: individual
I is for inducing the average withered spot number of handling rear blade, unit: individual through compound.
The invention has the beneficial effects as follows: the present invention is to containing the 4-methyl isophthalic acid; 2; The bishydrazide of 3-thiadiazoles group has carried out the optimization of first guide structure; And the synthetic new compound carried out the mensuration of desinsection, antibacterial and inducing anti-disease activity and anti-phytoviral activity, this compounds can be used for disease, insect pest and the virus disease control in agriculture field, field of forestry, gardening field.
The present invention will and use the formulation of complete processing and selection more specifically to explain as embodiment with the commercially available agricultural chemical combination through specific preparation and biological activity determination to contain the 4-methyl isophthalic acid; 2; Synthetic and the biological activity and the application thereof of the bishydrazide verivate of 3-thiadiazoles group, unrestricted the present invention, especially its biological activity and complete processing only illustrate but said embodiment only is used for bright specifically the present invention; And unrestricted this patent, embodiment is following:
Embodiment 1:4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl chloride
With the 4-methyl isophthalic acid of 9.66 gram (0.067 mole) synthetic or purchase, 2,3-thiadiazoles-5-formic acid and 29 milliliters of thionyl chlorides join in 100 milliliters of three mouthfuls of round-bottomed flasks; 80 degrees centigrade of following reflux 6 hours remove excessive thionyl chloride under reduced pressure, underpressure distillation collect 2000Pa; Cut under 94-96 degree centigrade gets weak yellow liquid 9.25 gram column chromatography purifications, productive rate: 85%, and midbody 4-methyl isophthalic acid; 2, the 3-thiadiazoles-sealing of 5-formyl chloride is kept in the moisture eliminator subsequent use.
The preparation of embodiment 2:N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine
In 1000 milliliters of round-bottomed flasks, add 400 mmole tertiary butyl hydrazonium salt hydrochlorates, add 450 milliliters of methylene dichloride and 100 ml waters and 600 mmole sodium hydroxide again, under induction stirring and ice bath cooling, slowly drip 400 mmole 4-methyl isophthalic acids; 2,50 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride dropwise the back room temperature reaction 5 hours; The stopped reaction afterreaction mixes useless water washing; Tell organic layer, behind the anhydrous magnesium sulfate drying, removal of solvent under reduced pressure obtains N-(4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formyl radical)-and N '-tertiary butyl hydrazine, product need not purifying can directly be used for next step reaction, carries out next step reaction behind the also available ethyl alcohol recrystallization.
Embodiment 3: replace the preparation of acyl chlorides
The substituted carboxylic acid that in 50 milliliters of round-bottomed flasks, adds 0.2 mole adds 1.2 moles sulfur oxychloride again, and with oil bath reflux 3-4 hour, air distillation must replace acyl chlorides after removing the intact sulfur oxychloride of unreacted with reaction mixture, and the sealing preservation is subsequent use.
The preparation of embodiment 4:N-(substituted formacyl)-N '-tertiary butyl hydrazine
In 100 milliliters of round-bottomed flasks, add 15 mmole tertiary butyl hydrazonium salt hydrochlorates; Add 30 milliliters of methylene dichloride and 5 ml waters and 3 mmole sodium hydroxide again, slowly drip 20 milliliters of dichloromethane solutions of 15 mmole substituted formyl chlorine down, dropwise afterwards room temperature reaction 3 hours in the cooling of induction stirring and ice bath; The stopped reaction afterreaction mixes useless water washing; Tell organic layer, behind the anhydrous magnesium sulfate drying, removal of solvent under reduced pressure obtains N-(substituted formacyl)-N '-tertiary butyl hydrazine; Product need not purifying can directly be used for next step reaction, carries out next step reaction behind the also available ethyl alcohol recrystallization.
Embodiment 5: the synthetic and structure of target compound YZK-6-32 is identified (I-1)
Getting 0.02 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.03 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.02 mole of Benzoyl chloride 99min. down; After dropwising, room temperature continued to stir after 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 2.83%, fusing point: 200-202 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.15 (s, 1H, NH), 7.29-7.37 (m, 5H, ArH), 2.51 (s, 3H, thiadiazolyl-CH 3), 1.56 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 319.1223 (M+H) +
Embodiment 6: the synthetic and structure of target compound YZK-6-40 is identified (I-2)
Getting 0.004 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.006 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.004 mole of 2-methyl benzoyl chloride down; After dropwising, room temperature continued to stir after 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 32.34%, fusing point: 194-196 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 7.94 (s, 1H, NH), 7.06-7.24 (m, 4H, ArH), 2.92 (s, 3H, ArCH 3), 2.50 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 333.1380 (M+H) +
Embodiment 7: the synthetic and structure of target compound YZK-6-42 is identified (I-3)
Getting 0.005 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.015 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.005 mole of 3-methyl benzoyl chloride down; After dropwising, room temperature continued to stir after 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, re-crystallizing in ethyl acetate obtains product; Yield: 43.32%, fusing point: 195-196 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 7.77 (s, 1H, NH), 7.11-7.33 (m, 4H, ArH), 2.92 (s, 3H, ArCH 3), 2.57 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 333.1380 (M+H) +
Embodiment 8: the synthetic and structure of target compound YZK-6-45 is identified (I-4)
Getting 0.005 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.015 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.005 mole of 4-methyl benzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, re-crystallizing in ethyl acetate obtains product; Yield: 43.92%, fusing point: 208-210 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 7.77 (s, 1H, NH), 7.11-7.33 (m, 4H, ArH), 2.92 (s, 3H, ArCH 3), 2.57 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 333.1380 (M+H) +
Embodiment 9: the synthetic and structure of target compound YZK-7-42 is identified (I-5)
Getting 0.0071 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0075 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0075 mole of 2-methoxy benzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, re-crystallizing in ethyl acetate obtains product; Yield: 43.82%, fusing point: 228-230 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 8.27 (s, 1H, NH), 6.86-7.40 (m, 4H, ArH), 3.91 (s, 3H, OCH 3), 2.59 (s, 3H, thiadiazolyl-CH 3), 1.59 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 371.1148 (M+Na) +
Embodiment 10: the synthetic and structure of target compound ZQX-2-18 is identified (I-6)
In 50 milliliters of round-bottomed flasks, add 1.5 gram N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazines; 0.77 the triethylamine of gram, 30 milliliters of methylene dichloride stirring and dissolving slowly drip 15 milliliters of dichloromethane solutions that are dissolved with 1.21 gram 3-methoxy benzoyl chlorides then under condition of ice bath; Dropwised in 1 hour, and heated up stirring at room 5 hours naturally; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; The decompression precipitation, (eluent is 60-90 degree centigrade a sherwood oil: ETHYLE ACETATE volume ratio 3: 1), obtain white solid 0.50 gram with 200-300 order silica gel column chromatography; Yield 22.95%, fusing point: 166-167 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 1.558 (s, 9H, CH 3), 2.560 (s, 3H, CH 3), 3.765 (s, 3H, CH 3), 6.880-6.915 (m, 3H, ArH), 7.200 (t, 1H, J=8.0Hz, Ph), 8.082 (s, 1H, NH), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 349.1329 (M+H) +
Embodiment 11: the synthetic and structure of target compound YZK-6-41 is identified (I-7)
Getting 0.0082 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0247 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0082 mole of 4-methoxy benzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, re-crystallizing in ethyl acetate obtains product; Yield: 46%, fusing point: 176-177 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.09 (s, 1H, NH), 6.78-7.37 (m, 4H, ArH), 3.79 (s, 3H, OCH 3), 2.58 (s, 3H, thiadiazolyl-CH 3), 1.55 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 371.1148 (M+Na) +
Embodiment 12: the synthetic and structure of target compound YZK-7-35 is identified (I-8)
Getting 0.0091 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.01 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.1 mmole 2-chloro-benzoyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate obtains product, yield: 52.95% 1H NMR (solvent: CDCl 3, chemical shift): 8.02 (s, 1H, NH), 7.22-7.39 (m, 4H, ArH), 2.59 (s, 3H, thiadiazolyl-CH 3), 1.59 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 351.0688 (M-H) -
Embodiment 13: the synthetic and structure of target compound YZK-7-38 is identified (I-9)
Getting 0.007 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0074 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0074 mole of 3-chloro-benzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 45.65%, fusing point: 202-204 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 7.95 (s, 1H, NH), 7.27-7.38 (m, 4H, ArH), 2.61 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 351.0688 (M-H) -
Embodiment 14: the synthetic and structure of target compound YZK-7-45 is identified (I-10)
Getting 0.0047 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0047 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0047 mole of 4-chloro-benzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 56.68%, fusing point: 194-197 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.00 (s, 1H, NH), 7.34-7.53 (m, 4H, ArH), 2.59 (s, 3H, thiadiazolyl-CH 3), 1.56 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 353.0833 (M+H) +
Embodiment 15: the synthetic and structure of target compound YZK-7-15 is identified (I-11)
Getting 0.005 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.01 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0055 mole of 2-fluorobenzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 43.24%, fusing point: 125-128 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 8.10 (s, 1H, NH), 6.99-7.52 (m, 4H, ArH), 2.58 (s, 3H, thiadiazolyl-CH 3), 1.58 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 337.1129 (M+H) +
Embodiment 16: the synthetic and structure of target compound YZK-7-19-5 is identified (I-12)
Getting 0.1 mmole N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.1 mmole 3-fluorobenzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 56%, fusing point: 199-200 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.45 (s, 1H, NH), 7.06-7.29 (m, 4H, ArH), 2.57 (s, 3H, thiadiazolyl-CH 3), 1.55 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 17: the synthetic and structure of target compound YZK-6-37 is identified (I-13)
Getting 0.02 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.03 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.02 mole of 4-fluorobenzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 1.34%, fusing point: 204-207 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 7.64 (s, 1H, NH), 7.04-7.64 (m, 4H, ArH), 2.62 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 337.1129 (M+H) +
Embodiment 18: the synthetic and structure of target compound WH-2-34 is identified (I-14)
Get 0.013 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.028 mmole triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.014 mmole 2-trifluoromethyl benzoyl chloride, after dropwising, room temperature continues to stir after 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; The Virahol recrystallization obtains the product column chromatography purification, productive rate: 23.49%, and fusing point: 173-175 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.77 (s, 1H, NH), 7.11-7.33 (m, 4H, ArH), 2.69 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), the 1H NMR data presentation of this compound is consistent with its chemical structure; HR MS (m/z): 409.0917 (M+Na) +
Embodiment 19: the synthetic and structure of target compound WH-2-35 is identified (I-15)
Getting 0.016 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.034 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.017 mole of 3-trifluoromethyl benzoyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; The Virahol recrystallization obtains the product column chromatography purification, productive rate: 10%, and fusing point: 165-168 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.77 (s, 1H, NH), 7.11-7.33 (m, 4H, ArH), 2.69 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HRMS (m/z): 409.0917 (M+Na) +
Embodiment 20: the synthetic and structure of target compound WH-3-18 is identified (I-16)
Getting 0.0080 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0080 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0096 mole of 4-trifluorobenzoyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate obtains the product column chromatography purification, productive rate: 33.44%, and fusing point: 186-189 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.121 (s, 1H, NH), 7.57 (d, 2H, ArH), 7.49 (d, 2H, ArH), 2.69 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HRMS (m/z): 409.0917 (M +Na) +
Embodiment 21: the synthetic and structure of target compound YZK-7-50-1 is identified (I-17)
Getting 0.0071 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0078 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0078 mole of 2-nitrobenzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 19.52%, fusing point: 119-123 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 3.81 (s, 1H, NH), 7.52-7.529 (m, 4H, ArH), 2.99 (s, 3H, thiadiazolyl-CH 3), 1.20 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 364.1074 (M+H) +
Embodiment 22: the synthetic and structure of target compound YZK-7-48 is identified (I-18)
Getting 0.008 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0088 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0088 mole of 3-nitrobenzoyl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 44.72%, fusing point: 202-205 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.04 (s, 1H, NH), 7.54-8.25 (m, 4H, ArH), 2.63 (s, 3H, thiadiazolyl-CH 3), 1.61 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 364.1074 (M+H) +
Embodiment 23: the synthetic and structure of target compound WH-2-33 is identified (I-19)
Get 0.0057 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.113 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0057 mole of 4-nitrobenzoyl chloride down; After dripping, room temperature continued to stir after 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and the Virahol recrystallization obtains the product column chromatography purification; Productive rate: 18.31%, fusing point: 99-101 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.28 (d, 1H, ArH), 8.20 (d, 1H, ArH), 5.29 (s, 1H, NH), 2.69 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 24: the synthetic and structure of target compound YZK-7-11 is identified (I-20)
Get 0.01 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.02 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.01 mole of 4-ethylamino benzonitrile acyl chlorides down; After dripping, room temperature continued to stir after 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying spends the night, and removal of solvent under reduced pressure behind the suction filtration, re-crystallizing in ethyl acetate obtain the product column chromatography purification; Productive rate: 26%, fusing point: 176-178 degree centigrade; HR MS (m/z): 347.1536 (M+H) +
Embodiment 25: the synthetic and structure of target compound YZK-6-36 is identified (I-21)
Getting 0.02 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.03 mole of triethylamine then, the ice bath cooling slowly drips 0.02 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 2.35%, HR MS (m/z): 341.0849.
Embodiment 26: the synthetic and structure of target compound YZK-6-39 is identified (I-22)
Getting 0.004 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.006 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.004 mole of furans-2-formyl chloride, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 15%, fusing point: 124-128 degree centigrade; HR MS (m/z): (M+H) +: 309.1016.
Embodiment 27: the synthetic and structure of target compound YZK-7-3 is identified (I-23)
Getting 0.008 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.024 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.008 mole of 2-(4-chloro-phenyl-)-3-methyl-butyryl chloride, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 30.37%, fusing point: 182-185 degree centigrade; HR MS (m/z): (M+Na) +: 431.1279.
Embodiment 28: the synthetic and structure of target compound YZK-7-6 is identified (I-24)
Getting 0.01 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.03 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.01 mole of trichoroacetic chloride, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 40.50%, fusing point: 48-50 degree centigrade.
Embodiment 29: the synthetic and structure of target compound YZK-7-16 is identified (I-25)
Getting 0.005 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.01 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0053 mole of chrysanthemum acyl chlorides, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 49.45%, HR MS (m/z): (M+Na) +: 387.1825.
Embodiment 30: the synthetic and structure of target compound YZK-7-17 is identified (I-26)
Getting 0.005 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.01 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0053 mole of dichloro chrysanthemum acyl chlorides, after dropwising, room temperature continues to stir after 5 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate, yield: 60.32%, HR MS (m/z): (M+Na) +: 405.0913.
Embodiment 31: the synthetic and structure of target compound WH-5-28 is identified (I-27)
Get 0.0023 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0023 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0046 mole of 4-fluorobenzene acetyl acyl chlorides, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 64.35% 1H NMR (solvent: DMSO, chemical shift): 7.623 (s, 1H, NH), 7.083 (t, 2H, ArH), 7.001 (t, 2H, ArH), 3.597 (s, 2H, CH 2) 2.947 (s, 3H, thiadiazolyl-CH 3), 1.479 (s, 9H, C (CH 3) 3), HR MS (m/z): (M+Na) +: 373.1105.
Embodiment 32: the synthetic and structure of target compound WH-2-32 is identified (I-28)
Getting 0.0134 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0268 mole of triethylamine then, the ice bath cooling slowly drips 0.0134 mole 2 down; 5 milliliters of dichloromethane solutions of 6-dichlorobenzoyl chloride, after dropwising, room temperature continues to stir after 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; The Virahol recrystallization obtains the white products column chromatography purification, productive rate: 14.64%, and fusing point: 118-119 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.77 (s, 1H, NH), 7.11-7.33 (m, 3H, ArH), 2.69 (s, 3Hthiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), the 1H NMR data presentation of this compound is consistent with its chemical structure; HR MS (m/z): 387.0444 (M+H) +
Embodiment 33: the synthetic and structure of target compound WH-3-15 is identified (I-31)
Get 0.0103 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0052 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0052 mole of positive capryl(yl)chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio; Productive rate: 20%, liquid 1H NMR (solvent: CDCl 3, chemical shift): 9.104 (s, 1H, NH), 2.938 (s, 3H, thiadiazolyl-CH 3), 2.278 (s, 3H ,-CH 3) 1.445 (s, 9H, C (CH 3) 3), 1.211 (m, 7H ,-CH), 0.846 (m, 5H ,-CH), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 363.1825 (M+Na) +
Embodiment 34: the synthetic and structure of target compound WH-3-21 is identified (I-32)
Get 0.0140 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0140 mole of triethylamine, the ice bath cooling drips 0.0157 mole 3 down; 5 milliliters of dichloromethane solutions of 5-dichlorobenzoyl chloride, after dripping off, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 19.34%, fusing point: 149-152 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 8.236 (s, 1H, NH), 7.364 (m, 1H, ArH), 7.276 (s, 1H, ArH), 7.272 (s, 1H, ArH), 2.69 (s, 3H, thiadiazolyl-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HRMS (m/z): 409.0263 (M+Na) +
Embodiment 35: the synthetic and structure of target compound WH-3-25 is identified (I-33)
Get 0.01 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.01 mole of triethylamine then, the ice bath cooling slowly drips 0.0119 mole 3 down; 5 milliliters of dichloromethane solutions of 5-dimethyl benzoyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 17.29%, fusing point: 197-200 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 7.854 (s, 1H, NH), 6.988-6.972 (m, 3H, ArH), 2.578 (s, 3H, thiadiazolyl-CH 3), 2.256 (s, 6H ,-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 369.1356 (M+Na) +
Embodiment 36: the synthetic and structure of target compound WH-4-18 is identified (I-34)
Getting 0.001 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.001 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.00105 mole of 3-(2-chloro-phenyl-)-5-methyl-isoxazole-4-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 18%, fusing point: 78-81 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 7.572-7.119 (m, 4H, ArH), 6.542 (1H ,-NH), 2.661 (s, 3Hthiadiazolyl-CH 3), 2.655 (s, 3H ,-CH 3), 1.365 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 456.0869 (M+Na) +
Embodiment 37: the synthetic and structure of target compound WH-4-30 is identified (I-35)
Getting 0.0038 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0045 mole of triethylamine then, the ice bath cooling slowly drips 0.0045 mole 2 down; 5 milliliters of dichloromethane solutions of 4-dimethyl--1-phenylpyrazole-3-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 15%, fusing point: 220-224 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 7.712 (s, 1H, NH), 7.472-7.287 (m, 5H, ArH), 2.578 (s, 3H, thiadiazolyl-CH 3), 2.350 (s, 3H ,-CH 3), 2.302 (s, 3H ,-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 38: the synthetic and structure of target compound WH-4-37 is identified (I-36)
Getting 0.0078 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0078 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0117 mole of cyclohexyl formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 35%, fusing point: 162-164 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.712 (s, 1H, NH), 2.578 (s, 3H, thiadiazolyl-CH 3), 2.302 (s, 3H ,-CH 3), 1.57 (s, 9H, C (CH 3) 3), 1.82-1,60 (m, 11H,
Figure GSA00000123738900161
), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 325.1693 (M+H) +
Embodiment 39: the synthetic and structure of target compound WH-5-11 is identified (I-37)
Get 0.0023 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0023 mole of triethylamine then, the ice bath cooling slowly drips 0.0035 mole 3 down; 5 milliliters of dichloromethane solutions of 6-dichloropyridine-2-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 3: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 35%, fusing point: 162-164 degree centigrade; 1H NMR (solvent: DMSO, chemical shift): 8.087 (d, 1H, Pyridine-H), 7.619 (d, 1H, Pyridine-H), 2.529 (s, 3H, thiadiazolyl-CH 3), 1.526 (s, 9H, C (CH 3) 3), HR MS (m/z): 410.0216 (M+Na) +
Embodiment 40: the synthetic and structure of target compound WSX-44 is identified (I-38)
Get 0.0037 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0045 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0037 mole of 5-ethyl-1-methylpyrazole-3-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 3: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 46%, fusing point: 147-148 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 8.527 (S, 1H, NH), 6.601 (s, 1H ,-CH=), 3.634 (s, 3H ,-CH 3), 2.867 (s, 3H, thiadiazolyl-CH 3), 2.540 (q, 2H, CH 2), 1.574 (s, 9H, C (CH 3) 3), 1.236 (s, 3H ,-CH 3), HR MS (m/z): 351.1598 (M+H) +
Embodiment 41: the synthetic and structure of target compound WH-4-40 is identified (I-39)
Getting 0.0084 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0084 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.0169 mole of o-fluorobenzene chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio; Re-crystallizing in ethyl acetate, productive rate: 33% 1H NMR (solvent: CDCl 3, chemical shift): 11.179 (s, 1H, NH), 7.299-7.113 (m, 4H, Ph), 2.857 (s, 3H, thiadiazolyl-CH 3), 2.504 (s, 2H, CH 2), 1.394 (s, 9H, C (CH 3) 3).
Embodiment 42: the synthetic and structure of target compound YZK-7-29 is identified (II-2)
Get 0.1 mmole N-(2-methyl benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 13.03%, fusing point: 145-147 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 5.74 (s, 1H, NH), 7.24-7.43 (m, 4H, ArH), 2.85 (s, 3H, ArCH 3), 2.41 (s, 3H, thiadiazolyl-CH 3), 1.21 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 333.1380 (M+H) +
Embodiment 43: the synthetic and structure of target compound WH-4-6 is identified (II-3)
Get 0.0096 mole of N-(3-methyl benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0096 mole of triethylamine then; The ice bath cooling slowly drips 0.0192 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 6: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 30%; Fusing point: 142-145 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.565 (s, 1H, NH), 7.080 (m, 4H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 2.352 (s, 3H ,-CH 3), 1.579 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 333.1380 (M+H) +
Embodiment 44: the synthetic and structure of target compound YZK-6-48 is identified (II-4)
Get 0.1 mmole N-(4-methyl benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 6.02%, fusing point: 143-144 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 7.31-7.80 (m, 4H, ArH), 5.74 (s, 1H, NH), 2.92 (s, 3H, ArCH 3), 2.46 (s, 3H, thiadiazolyl-CH 3), 1.18 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 333.1380 (M+H) +
Embodiment 45: the synthetic and structure of target compound YZK-7-44 is identified (II-5)
Get 0.1 mmole N-(2-anisoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 34.85%, fusing point: 141-142 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 9.52 (s, 1H, NH), 6.70-8.02 (m, 4H, ArH), 4.01 (s, 3H, OCH 3), 2.86 (s, 3H, thiadiazolyl-CH 3), 1.59 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 371.1148 (M+Na) +
Embodiment 46: the synthetic and structure of target compound ZQX-2-20-b is identified (II-6)
In 100 milliliters of round-bottomed flasks, add 2.9 gram tertiary butyl hydrazonium salt hydrochlorates, 1.0 gram NaOH, 30 milliliters methylene dichloride, 1 ml water stirs.Under condition of ice bath, slowly drip 15 milliliters of dichloromethane solutions that contain 1.98 gram 3-methoxy benzoyl chlorides; Finished in 30 minutes, stirring at room 5 hours is told organic layer; With water washing 2 times; With anhydrous sodium sulfate drying 12 hours, suction filtration, rotary evaporation obtained the 2.2 gram midbody N '-tertiary butyl-N-(3-methoxybenzoyl hydrazine).
In 100 milliliters of round-bottomed flasks, add the 0.0099 mole of N '-tertiary butyl-N-(3-methoxybenzoyl hydrazine), 0.1060 triethylamine that rubs, 40 milliliters of methylene dichloride stirring and dissolving; Under condition of ice bath, slowly drip then and be dissolved with the 0.0110 4-methyl isophthalic acid that rubs, 2,20 milliliters of the dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; Dropwised in 1 hour, and heated up stirring at room 5 hours naturally; The decompression precipitation, (eluent is 60-90 degree centigrade a sherwood oil: ETHYLE ACETATE volume ratio 2: 1), obtain white solid 0.70 gram with 200-300 order silica gel column chromatography; Yield 20.29%, fusing point: 151-152 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 1.591 (s, 9H, CH 3), 2.809 (s, 3H, CH 3), 3809 (s, 3H, CH 3), 7.060-7.325 (m, 4H, ArH), 8.127 (s, 1H, NH); This compound 1The HNMR data presentation is consistent with its chemical structure, HRMS (m/z): 349.1329 (M+H) +
Embodiment 47: the synthetic and structure of target compound WH-4-7 is identified (II-7)
Get 0.0104 mole of N-(4-anisoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0104 mole of triethylamine then, the ice bath cooling down; Slowly drip 0.0208 mole of 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration obtains crude product; Methylene dichloride and sherwood oil recrystallization, productive rate: 30%, fusing point: 135-137 degree centigrade; HR MS (m/z): 349.1329 (M+H) +
Embodiment 48: the synthetic and structure of target compound YZK-7-34 is identified (II-8)
Get 0.1 mmole N-(2-chlorobenzene formacyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 20.36%, fusing point: 165-169 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.15 (s, 1H, NH), 7.11-7.40 (m, 4H, ArH), 2.80 (s, 3H, thiadiazolyl-CH 3), 1.62 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 353.0833 (M+H) +
Embodiment 49: the synthetic and structure of target compound YZK-7-39 is identified (II-9)
Get 0.1 mmole N-(3-chlorobenzene formacyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 40.49%, fusing point: 138-142 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 8.33 (s, 1H, NH), 7.33-7.59 (m, 4H, ArH), 2.79 (s, 3H, thiadiazolyl-CH 3), 1.59 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure.
Embodiment 50: the synthetic and structure of target compound YZK-7-46 is identified (II-10)
Get 0.1 mmole N-(4-chlorobenzene formacyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 54.87%, fusing point: 137-139 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.50 (s, 1H, NH), 7.37-7.56 (m, 4H, ArH), 2.76 (s, 3H, thiadiazolyl-CH 3), 1.58 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 353.0833 (M+H) +
Embodiment 51: the synthetic and structure of target compound YZK-7-19-1 is identified (II-11)
Get 0.1 mmole N-(2-fluoro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 7.51%, fusing point: 109-109 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 8.44 (s, 1H, NH), 7.12-7.92 (m, 4H, ArH), 2.84 (s, 3H, thiadiazolyl-CH 3), 1.60 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 337.1129 (M+H) +
Embodiment 52: the synthetic and structure of target compound YZK-7-31 is identified (II-12)
Get 0.1 mmole N-(3-fluoro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 63.33%, fusing point: 212-213 degree centigrade 1H NMR (solvent: CDCl 3, chemical shift): 8.59 (s, 1H, NH), 7.22-7.40 (m, 4H, ArH), 2.76 (s, 3H, thiadiazolyl-CH 3), 1.58 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 337.1129 (M+H) +
Embodiment 53: the synthetic and structure of target compound WH-3-43-B is identified (II-13)
Get 0.0133 mole of N-(4-fluoro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0133 mole of triethylamine then; The ice bath cooling slowly drips 0.0139 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, fusing point: 162-164 degree centigrade, productive rate: 30%; 1H NMR (solvent: CDCl 3, chemical shift): 8.565 (s, 1H, NH), 7.635 (d, 2H, ArH), 7.080 (d, 2H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.579 (s, 9H, CH 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 337.1129 (M+H) +
Embodiment 54: the synthetic and structure of target compound WH-3-32 is identified (II-14)
Get 0.0057 mole of N-(2-trifluoromethyl benzoyl-)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0057 mole of triethylamine then; The ice bath cooling slowly drips 0.0060 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and ETHYLE ACETATE volume ratio 5: 1 and sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 20%, fusing point: 198-199 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.094 (s, 1H, NH), 7.117 (m, 4H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3) 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 55: the synthetic and structure of target compound WH-3-33 is identified (II-15)
Get 0.0088 mole of N-(3-trifluoromethyl benzoyl-)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0088 mole of triethylamine then; The ice bath cooling slowly drips 0.0093 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Obtain white solid yield 28.24%, fusing point: 200-203 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.554 (s, 1H, NH), 7.887 (s, 1H, ArH), 7.775 (q, 2H, ArH), 7.558 (t, 1H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 387.1097 (M+H) +
Embodiment 56: the synthetic and structure of target compound WH-3-22 is identified (II-16)
Get 0.01535 mole of N-(4-trifluoromethyl benzoyl-)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add 50 milliliters of round-bottomed flasks, add acid binding agent 0.01535 mole of triethylamine; The ice bath cooling slowly drips 0.01842 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure; Sherwood oil and ETHYLE ACETATE and methylene chloride volume be than 5: 1: 1 column chromatography purifications, productive rate: 46.28%, and fusing point: 149-151 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.485 (s, 1H, NH), 7.688 (m, 4H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 387.1097 (M+H) +
Embodiment 57: the synthetic and structure of target compound WH-4-12 is identified (II-17)
Get 0.0059 mole of N-(2-nitro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0062 mole of triethylamine then; The ice bath cooling slowly drips 0.0062 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 4: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 25%, fusing point: 193-195 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.229 (s, 1H, ArH), 8.026 (s, 1H, ArH), 7.564-7.530 (m, 2H, ArH), 6.397 (s, 1H, NH), 2.560 (s, 3H, CH 3), 1.558 (s, 9H ,-C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure; HRMS (m/z): 364.1074 (M+H) +
Embodiment 58: the synthetic and structure of target compound YZK-7-49 is identified (II-18)
Get 0.1 mmole N-(3-nitro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 53.65%, fusing point: 167-176 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 9.05 (s, 1H, NH), 7.64-8.46 (m, 4H, ArH), 2.78 (s, 3H, thiadiazolyl-CH 3), 1.61 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 364.1074 (M+H) +
Embodiment 59: the synthetic and structure of target compound YZK-6-50 is identified (II-19)
Get 0.1 mmole N-(4-nitro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling down; Slowly drip 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, and re-crystallizing in ethyl acetate obtains product; Yield: 20.23%, fusing point: 152-155 degree centigrade 1HNMR (solvent: CDCl 3, chemical shift): 8.78 (s, 1H, NH), 7.76-8.25 (m, 4H, ArH), 2.77 (s, 3H, thiadiazolyl-CH 3), 1.59 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure, HR MS (m/z): 364.1074 (M+H) +
Embodiment 60: the synthetic and structure of target compound YZK-7-33 is identified (II-20)
Get 0.01 mole of N-(4-ethylamino benzonitrile acyl group)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.015 mole of triethylamine then; The ice bath cooling slowly drips 0.015 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate obtains product, yield: 10.41%, and HR MS (m/z): 347.1536 (M+H) +
Embodiment 61: the synthetic and structure of target compound YZK-7-4 is identified (II-23)
Get 0.005 mole of N-(2-(4-chloro-phenyl-)-3-methyl-butyryl radicals)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.015 mole of triethylamine then; The ice bath cooling slowly drips 0.005 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous magnesium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Re-crystallizing in ethyl acetate obtains product, yield: 32.36%, and HR MS (m/z): 409.1460 (M+H) +
Embodiment 62: the synthetic and structure of target compound WH-3-10 is identified (II-25)
Get 0.0204 mole of freshly prepd N-(chrysanthemum acyl group)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add 50 milliliters of round-bottomed flasks, add acid binding agent 0.0306 mole of triethylamine then; The ice bath cooling slowly drips 0.0306 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 6: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 10%, fusing point: 153-155 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 4.846 (s, 1H, NH), 2.818 (d, 3H, thiadiazolyl-CH 3), 1.701 (s, 3H ,-CH 3), 1.660 (s, 3H ,-CH 3), 1.570 (s, 3H ,-CH 3), 1.541 (s, 3H ,-CH 3), 1.528 (s, 9H, C (CH 3) 3), 1.125 (s, 1H ,-CH), 1.027 (s, 1H ,-CH), 0.748 (s, 1H ,-CH), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 387.1825 (M+Na) +
Embodiment 63: the synthetic and structure of target compound WH-3-14 is identified (II-26)
Get 0.0197 mole of freshly prepd N-(dichloro chrysanthemum acyl group)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0197 mole of triethylamine then; The ice bath cooling slowly drips 0.0207 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 6: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 35.13%, fusing point: 146-148 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.527 (s, 1H, NH), 5.597 (m, 1H ,=CH), 2.806 (d, 3H, thiadiazolyl-CH 3), 2.235 (m, 1H ,-CH), 1.534 (s, 9H, C (CH 3) 3), 1.240 (t, 2H ,-CH 2), 1.162 (t, 2H ,-CH 3), 1.072 (s, 1H ,-CH), 0.762 (s, 1H ,-CH), 0.070 (s, 2H ,-CH), this compound 1H NMR data presentation is consistent with its chemical structure; HRMS (m/z): 427.0722 (M+Na) +
Embodiment 64: the synthetic and structure of target compound WSX-54 is identified (II-27)
Get 0.0013 mole of freshly prepd N-(4-fluorophenethyl acyl group)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.002 mole of triethylamine then; The ice bath cooling slowly drips 0.0015 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 6: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 54%, fusing point: 200-202 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.621 (m, 2H, ArH), 7.092 (t, 2H, ArH), 2.788 (d, 3H, thiadiazolyl-CH 3), 2.174 (s, 2H ,-CH 2), 1.586 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 65: the synthetic and structure of target compound WH-3-42 is identified (II-28)
Get 0.0062 mole of N-(2,6-dichloro-benzoyl base)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0062 mole of triethylamine then; The ice bath cooling slowly drips 0.0065 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 22.43%, fusing point: 195-198 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 7.445-7.305 (m, 3H, ArH), 5.567 (s, 1H, NH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.236 (s, 9H, CH 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 409.0263 (M+Na) +
Embodiment 66: the synthetic and structure of target compound WH-2-39 is identified (II-29)
Get 0.0047 mole of N-ethanoyl-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0094 mole of triethylamine then; The ice bath cooling slowly drips 0.0045 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; The re-crystallizing in ethyl acetate column chromatography purification, productive rate: 33.81%, fusing point: 76-78 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 5.543 (s, 1H, NH), 3.028 (s, 3H ,-CH 3), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 279.0886 (M+Na) +
Embodiment 67: the synthetic and structure of target compound WH-2-44 is identified (II-30)
Get 0.0109 mole of N-butyryl radicals-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0217 mole of triethylamine then; The ice bath cooling slowly drips 0.0217 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 3: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 27.50%, fusing point: 75-78 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 5.596 (s, 1H, NH), 3.051 (m, 1H ,-CH), 3.026 (s, 3H, thiadiazolyl-CH 3), 2.845 (m, 1H ,-CH), 1.762 (m, 2H ,-CH 2), 1.071 (s, 9H, C (CH 3) 3), 1.020 (t, 3H ,-CH 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 285.1380 (M+H) +
Embodiment 68: the synthetic and structure of target compound WH-4-14 is identified (II-31)
Get 0.0293 mole of N-capryloyl-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0323 mole of triethylamine then; The ice bath cooling slowly drips 0.0323 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and ETHYLE ACETATE volume ratio 4: 1, productive rate: 33% 1H NMR (solvent: CDCl 3, chemical shift): 7.890 (s, 1H, NH), 2.787 (s, 3H, thiadiazolyl-CH 3), 2.026 (m, 2H ,-CH 2), 1.509 (s, 9H ,-C (CH 3) 3), 1.258-1.103 (m, 10H ,-CH 2), 0.857 (t, 3H, CH 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 341.2006 (M+H) +
Embodiment 69: the synthetic and structure of target compound WH-3-23 is identified (II-32)
Getting 0.01169 mole of N-(3,5-dichloro-benzoyl base)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0123 mole of triethylamine then, the ice bath cooling slowly drips 0.0100 mole of 4-methyl isophthalic acid down; 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride are after dropwising; Stirring at room 4 hours, reaction mixture water are given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying; Removal of solvent under reduced pressure obtains the white mass column chromatography purification behind the suction filtration, productive rate: 49.73%, and fusing point: 228-231 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 8.163 (s, 1H, NH), 7.540-7.531 (t, 1H, ArH), 7.446 (d, 2H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.558 (s, 9H, C (CH 3) 3), the 1H NMR data presentation of this compound is consistent with its chemical structure; HR MS (m/z): 387.0444 (M+H) +
Embodiment 70: the synthetic and structure of target compound WH-3-27 is identified (II-33)
Get 0.0144 mole of N-(3, the 5-dimethylbenzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0144 mole of triethylamine then; The ice bath cooling slowly drips 0.0150 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 13.43%, fusing point: 182-185 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.094 (s, 1H, NH), 7.117 (m, 3H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 2.314 (s, 6H ,-CH 3), 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 347.1536 (M+H) +
Embodiment 71: the synthetic and structure of target compound WH-4-42 is identified (II-36)
Get 0.0029 mole of N-(cyclohexylcarbonyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0057 mole of triethylamine then, the ice bath cooling down; Slowly drip 0.0057 mole of 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration, sherwood oil and methylene dichloride recrystallization; Fusing point: 182-185 degree centigrade, productive rate: 25% 1H NMR (solvent: CDCl 3, chemical shift): 7.712 (s, 1H, NH), 2.578 (s, 3H, thiadiazolyl-CH 3), 2.302 (s, 3H ,-CH 3), 1.57 (s, 9H, C (CH 3) 3), 1.82-1.60 (m, 11H,
Figure GSA00000123738900231
), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 325.1693 (M+H) +
Embodiment 72: the synthetic and structure of target compound WSX-50 is identified (II-38)
Get 0.0144 mole of N-(1 methyl-5-ethyl pyrazoles-3-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0144 mole of triethylamine then; The ice bath cooling slowly drips 0.0150 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 13.43%, fusing point: 182-185 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 8.094 (s, 1H, NH), 7.117 (m, 3H, ArH), 2.623 (s, 3H, thiadiazolyl-CH 3), 2.314 (s, 6H ,-CH 3), 1.558 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 347.1536 (M+H) +
Embodiment 73: the synthetic and structure of target compound WH-2-36 is identified (III-1)
Getting 0.01 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.02 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.01 mole of Acetyl Chloride 98Min., after dropwising, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 3: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, productive rate: 48.93%, fusing point: 113-114 degree centigrade; 1H NMR (solvent: CDCl 3, chemical shift): 2.69 (s, 3H, thiadiazolyl-CH 3), 2.587 (s, 3H ,-CH 3), 2.029 (s, 3H ,-CH 3), 1.57 (s, 9H, C (CH 3) 3), this compound 1The HNMR data presentation is consistent with its chemical structure; HRMS (m/z): 321.0992 (M+Na) +
Embodiment 74: the synthetic and structure of target compound WH-2-43 is identified (III-2)
Getting 0.009 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride, joins in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.0054 mole of triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.027 mole of butyryl chloride down; After dropwising, room temperature continues to stir 4 hours, and the reaction mixture water is given a baby a bath on the third day after its birth inferior; Anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration, sherwood oil and 3: 1 column chromatography purifications of ETHYLE ACETATE volume ratio; Productive rate: 45.76%, liquid 1H NMR (solvent: CDCl 3, chemical shift): 2.936 (s, 3H, thiadiazolyl-CH 3), 2.849 (s, 2H ,-CH), 2.157 (m, 1H ,-CH), 2.049 (m, 1H ,-CH), 1.714 (m, 4H ,-CH2), 1.348 (s, 9H, C (CH 3) 3), 1.021 (t, 3H ,-CH 3), 0.928 (t, 3H ,-CH 3), this compound 1H NMR data presentation is consistent with its chemical structure.
Embodiment 75: target compound: the synthetic and structure of ZQX-2-20-a is identified (IV-1)
In 100 milliliters of round-bottomed flasks, add 0.0099 N-(3-the anisoyl)-N '-tertiary butyl hydrazine that rubs, 0.1060 triethylamine that rubs, 40 milliliters of methylene dichloride stirring and dissolving; Under condition of ice bath, slowly drip then and be dissolved with the 0.0110 4-methyl isophthalic acid that rubs, 2,20 milliliters of the dichloromethane solutions of 3-thiadiazoles-5-formyl chloride; Dropwised in 1 hour, and heated up stirring at room 5 hours naturally; The decompression precipitation, (eluent is 60-90 degree centigrade a sherwood oil: ETHYLE ACETATE volume ratio 3: 1), obtain white solid 0.42 gram with 200-300 order silica gel column chromatography; Yield 12.17%, fusing point: 127-128 degree centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 1.189 (s, 9H, CH 3), 2.910 (s, 3H, CH 3), 3.871 (s, 3H, CH 3), 5.702 (s, 1H, NH), 7.166-7.442 (m, 4H, ArH), this compound 1H NMR data presentation is consistent with its chemical structure, HR MS (m/z): 349.1329 (M+H) +
Embodiment 76: the synthetic and structure of target compound WH-3-43-A is identified (IV-2)
Get 0.0133 mole of N-(4-fluoro benzoyl)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride, add in 50 milliliters of round-bottomed flasks, add acid binding agent 0.0133 mole of triethylamine then; The ice bath cooling slowly drips 0.0139 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, stirring at room 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and 5: 1 column chromatography purifications of ETHYLE ACETATE volume ratio, fusing point: 168-171 degree centigrade, productive rate: 10%; 1H NMR (solvent: CDCl 3, chemical shift): 7.922-7.887 (q, 2H, ArH), 7.221-7.179 (t, 2H, ArH), 5.743 (s, 1H, NH), 2.623 (s, 3H, thiadiazolyl-CH 3), 1.579 (s, 9H, C (CH 3) 3), this compound 1H NMR data presentation is consistent with its chemical structure; HR MS (m/z): 337.1129 (M+H) +
Embodiment 77: the synthetic and structure of target compound WH-5-16 is identified (V-1)
N-(3,6-dichloropyridine-2-formyl radical)-N '-tertiary butyl hydrazine of getting 0.00454 mole of preparation is dissolved in 20 milliliters of methylene dichloride, adds in 50 milliliters of round-bottomed flasks, adds acid binding agent 0.0068 mole of triethylamine then; The ice bath cooling slowly drips 0.0068 mole of 4-methyl isophthalic acid, 2 down; 5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, anhydrous sodium sulfate drying, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and methylene dichloride mixed solvent recrystallization, productive rate: 30% 1HNMR (solvent: CDCl 3, chemical shift): 7.557 (d, 1H, ArH), 7.209 (d, 1H, ArH), 2.795 (s, 3H, thiadiazolyl-CH 3), 2.590 (s, 3H ,-CH 3), 1.645 (s, 9H, C (CH 3) 3), HR MS (m/z): 536.0103 (M+Na) +
Embodiment 78: the synthetic and structure of target compound WSX-40 is identified (VI-1)
Get 0.007 mole of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine and be dissolved in 20 milliliters of methylene dichloride; Add in 100 milliliters of round-bottomed flasks, add acid binding agent 0.008 mole of triethylamine then, the ice bath cooling down; Slowly drip 5 milliliters of dichloromethane solutions of 0.0035 mole of p-phthaloyl chloride, after dripping, room temperature continues to stir 4 hours; The reaction mixture water is given a baby a bath on the third day after its birth inferior, and anhydrous sodium sulfate drying spends the night, removal of solvent under reduced pressure behind the suction filtration; Sherwood oil and methylene dichloride recrystallization get product, productive rate: 21%, and fusing point is greater than 250 degrees centigrade; 1HNMR (solvent: CDCl 3, chemical shift): 11.058 (s, 1H, NH), 11.011 (s, 1H, NH), 7.407 (s, 2H, ArH), 2.391 (s, 6H, thiadiazolyl-CH 3), 1.464 (s, 18H, C (CH 3) 3), HR MS (m/z): 581.1724 (M+Na) +
Embodiment 79: the 4-methyl isophthalic acid that contains of the present invention, 2, the insecticidal activity of the bishydrazide verivate of 3-thiadiazoles group
Bioassay results is seen table 2; Table 2 shows; Synthetic major part of the present invention contains the 4-methyl isophthalic acid; 2; The bishydrazide compounds of 3-thiadiazoles group has excellent insecticidal activity, and as far as the activity of small cabbage moth: when 400 mcg/ml, the insecticidal activity of the positive control medicament worm hydrazides of the insecticidal activity of compound I-5, I-7, I-18, I-23, I-27, I-34, I-35, I-36, I-39, II-7, II-10, II-14, II-36 and IV-1, IV-2, V-1, VI-1 and homogeneous structure quite or be higher than the insecticidal activity of positive control medicament worm hydrazides; When 200 mcg/ml, the insecticidal activity of the positive control medicament worm hydrazides of the insecticidal activity of compound I-4, I-6, I-7, I-8, I-10, I-11, I-12, I-14, I-15, I-20, I-21, I-22, I-24, I-25, I-26, I-32, I-38, II-2, II-3, II-4, II-5, II-8, II-9, II-12, II-15, II-16, II-17, II-18, II-19, II-23, II-29, II-38 and III-1, III-2 and homogeneous structure quite or be higher than the insecticidal activity of positive control medicament worm hydrazides; As far as mosquito larvae; When 2 mcg/ml, the insecticidal activity of the positive control medicament worm hydrazides of the insecticidal activity of compound I-1, I-10, I-15, I-22, I-31, I-38 and II-2, II-13, II-15, II-16, II-20, II-25, II-28, II-31 and homogeneous structure quite or be higher than the insecticidal activity of positive control medicament worm hydrazides.The activity of part of compounds has reached 100%, and is outstanding especially, is significantly higher than the positive control medicament.
Embodiment 80: the 4-methyl isophthalic acid that contains of the present invention, 2, the bacteriostatic activity of the bishydrazide verivate of 3-thiadiazoles group
The title and the code name of frequently seen plants pathogenic fungi comprise AS on the agricultural of the present invention's test: tomato early blight bacterium (Alternaria solani); BC: botrytis cinerea pers (Botrytis cinerea); CA: peanut Cercospora bacteria (Cercosporaarachidicola); CB: sugar beet leaf spot bacteria (Cercospora beticola); CL: watermelon anthrax bacteria: (Colletotrichumlagenarium); FO: cucumber fusarium axysporum (Fusarium oxysporum); GZ: fusarium graminearum (Gibberella zeae); PG: rice blast fungus (Phyricularia grisea (Cooke) Sacc.); PI: phytophthora infestans (Phytophthorainfestans (Mont.) de Bary); PP: ring rot of apple bacterium (Physalospora piricola); PS: Rhizoctonia solani Kuhn (Pellicularia sasakii); RS: dry thread Pyrenomycetes (Rhizoctonia solani kuhn), these bacterial classifications can be represented the kind of most of pathogenic bacteria that the field takes place in the agriculture prodn.Thalli growth rate method is measured the result and is seen table 2; Table 2 shows; Major part of the present invention contains the 4-methyl isophthalic acid; 2, the bishydrazide compound of 3-thiadiazoles group has restraining effect in various degree to the growth of most of pathogenic fungi of mensuration, and its bacteriostatic activity is significantly higher than the bacteriostatic activity of positive control medicament worm hydrazides.
Embodiment 81: the 4-methyl isophthalic acid that contains of the present invention, 2, the effect of the derivative induced tobacco resisting tobacco mosaic virus of bishydrazide of 3-thiadiazoles group
The result of the determination test of induced activity shows; The plant inducing anti-disease activator BTH of standard and tiadinil can produce the resistance to TMV by evoking tobacco; Major part of the present invention contains the 4-methyl isophthalic acid; 2, the bishydrazide verivate of 3-thiadiazoles group has the activity of the anti-TMV of evoking tobacco preferably, and the induce effect of part of compounds when 100 mcg/ml are irritated 10 milliliters of roots reached 85%.Be because above-claimed cpd has become to have the 4-methyl isophthalic acid of inducing anti-disease cytotoxic activity at the tobacco vivo degradation, 2,3-thiadiazoles-5-formic acid is seen from chemical structure, C=O in the 5-position all can be by water molecules or OH in plant materials for all compounds of the present invention -The ion attack, thus hydrolysis goes out the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid, consistent with the meta-bolites of TDL.Therefore, compound of the present invention has Antiphytoviral and inducing plant and produces the effect that viral diseases of plants is produced resistance.
Embodiment 82: the 4-methyl isophthalic acid that contains of the present invention, and 2, the bishydrazide verivate of 3-thiadiazoles group and antiviral agent are combined in the application in control agricultural and forestry and the gardening plant virus disease
Contain the 4-methyl isophthalic acid; 2; The bishydrazide verivate of 3-thiadiazoles group and existing Antiphytoviral medicament diazosulfide, tiadinil, 4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formic acid, 4-methyl isophthalic acid; 2; 3-thiadiazoles-5-sodium formiate, 4-methyl isophthalic acid; 2,3-thiadiazoles-5-ethyl formate, DL-beta-aminobutyric acid, virazole, antofine, Ningnanmycin, tisocromide, first thiophene lure that any 1 or 2 compound combinations can be used for preventing and treating Agricultural pests such as Asiatic migrotory locust, clouding car locust, Chinese rice grasshopper, Patanga japonica (l.Bol.), single thorn mole cricket, east mole cricket, rice thrips, onion thrips, greenhouse thrips, haplothrips aculeatus, Mai Jian pipe thrips, Trialeurodes vaporariorum Westwood, Bemisia tabaci, rice green leafhopper, green leaf hopper, chlorita biguttula, spot clothing plant hopper, brown paddy plant hopper, white backed planthopper, small brown rice planthopper, the flat angle of sugarcane plant hopper, cotten aphid, green bugs, grain aphid, black peach aphid, kaoliang aphid, radish aphid, icerya purchasi, Pseudaulacaspis pentagona, unaspis shield kuwana, san jose scale, wax insect, ceroplastes rubens, the hard a red-spotted lizard of Korea's ball, pear lace bug, banana lace bug, thin corner piece stinkbug, little minute pirate bugs, slender rice bug, paddy fly, niphe elongata, scotinophora lurida, Nezara viridula smaragdula Fabricius., green plant bug, alfalfa plant bug, black striped plant bug, chrysopa septempunctata, beautiful Chrysopa, Chinese green lacewing, rain moth, casemaking clothes moth, cnidocampa flavescens walker, brown slug moth, thosea siensis, gelechiid, pink bollworm, brachmia triannuella, small cabbage moth, small heart-eating peach worm, eating-core bean worm, small heart-eating peach worm, apple Spilonota lechriaspis, brown belt length leaf roller in amine or Whitfield's ointment, cytosintetidemycin, dichloro-isonicotinic acid, the allyl isothiazole, intend smaller apple leaf roller, striped rice borer, bean-pod borer, Pyrausta nubilalis (Hubern)., yellow rice borer, Oeobia undalis, Cnaphalocrocis medinali(rice leaf roller), bar snout moth's larva, the wild snout moth's larva of lap leaf, dichocrocis punctiferalis, armyworm, prodenia litura, rice green caterpillar, anomis flava, beet armyworm, pink rice borer, bollworm, ancient cooking vessel selects diamond drill, black cutworm, big cutworm, yellow cutworm, robber poison moth, gypsymoth, palaearctic sweet potato, greenish brown hawk moth, straight burr rice hesperiidae, pelopidas mathias, oranges and tangerines swallowtail butterfly, Common Mormon, small white, pyrameis indica, the yellow a kind of butterfly harmful to crop plants of ramie, beans blister beetle, Venus ground beetle, wrinkle sheath ground beetle, wheat head ground beetle, pleonomus canaliculatus, Agriotes subrittatus Motschulsky, khapra beetle, attagenus piceus, the little buprestid beetle of oranges and tangerines, golden edge buprestid beetle, tenebrio molitor, dark mealworm, red flour beetle, confused flour beetle, verdigris different beetle, black dull cockchafer, holotrichia oblita, mulberry borer, longicorn beetle, nadezhdiella cantori, pink neck longicorn, big daikon leaf beetle, daicon leaf beetle, aulacophora femoralis, Phyllotreta striolata, Callosobruchus chinensis, pea weevil, broad bean weevil, sitophilus zea-mais, rice weevil, dolerus tritici, pear fruit sawfly, yellowish leukorrhea ichneumon wasp, armyworm white star ichneumon wasp, the outstanding cocoon ichneumon wasp of corn earworm, bollworm tooth lip ichneumon wasp, snout moth's larva stain wart ichneumon wasp, mosquito, fly, horsefly, wheat midge, contarinia tritici, pachydiplosis oryzae, citrus fruit fly, melon trypetid, wheat leaf ash are dived fly, Americal rice leaf miner, the black fly of diving of beans stalk, frit fly, kind fly, onion fly, radish fly, full skirt chase after and post that fly, Pyrausta nubilalis (Hubern). are strictly posted fly, armyworm is scarce must post fly etc.; Inducing plant produces the resistance to virus disease and fungal disease simultaneously; The anti-TMV of evoking tobacco or be used for directly preventing and treating TMV, can be used for inducing paddy, wheat, barley, oat, corn, Chinese sorghum, sweet potato, yam, cassava, soybean, broad bean, pea, mung bean, red bean, cotton, silkworm and mulberry, peanut, rape, sesame, Sunflower Receptacle, beet, sugarcane, coffee, cocoa, genseng, the bulb of fritillary, rubber, coconut, oil palm, sisal hemp, tobacco, melon, really, agricultural plants, gardening plant, economic plants, forestry plants such as tea, wild vegetable, bamboo shoots, hops, pepper produce the control to insect especially infection insect and virus disease.Above-mentionedly contain 1; 2; The bishydrazide verivate of 3-thiadiazoles group and the ratio of commodity antiviral agent in compsn are 1%: 99% to 99%: 1%, and the formulation of compsn processing is selected from wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse in dense dose, seed treatment emulsion, aqueous emulsion, big granula, granule, microemulsion, oil-suspending agent, finish, the seed with coated pesticidal, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules any one; All show summation action or synergism between these compsns, when keeping insecticidal activity, the effect that the effect of its antiviral activity is all used separately greater than any one compound, the result of all mensuration is all greater than 80%; Do not have to find to have the compsn of antagonistic action, the drug effect lasting period of compsn has all surpassed 21 days.
The staple crop that these compsns are suitable for comprise cereal crop (comprising paddy, wheat, barley, oat, corn, millet, Chinese sorghum etc.), tuber crops (comprising sweet potato, yam, cassava etc.), legume crop (comprising soybean, broad bean, pea, mung bean, red bean etc.) and fibre crops (cotton, crudefiber crop, silkworm and mulberry etc.), oil crops (peanut, rape, sesame, soybean, Sunflower Receptacle etc.), sugar crop (beet, sugarcane etc.), beverage crops (tealeaves, coffee, cocoa etc.), hobby crop (tobacco leaf etc.), medicinal crop (genseng, the bulb of fritillary etc.), tropical crops (rubber, coconut, oil palm, the sisal hemp etc.) food crop of etc.ing and fruit, flowers, oil plant, sugared expect and cash crop such as cotton, fiber crops, tea, tobacco, Chinese medicinal materials and plant melon, really, tea, silkworm and mulberry, vegetables (containing various wild vegetable etc.), bamboo shoots, flowers and garden crop such as tobacco (flue-cured tobaccos such as ornamental plant, hops, medicinal material, pepper, seedling and other garden crops; Air-curing of tobacco leaves, suncured tabacco), vegetables, (tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tube, beet, rape, green onion, garlic etc.), melon (watermelon, muskmelon, hami melon, pawpaw etc.), beans (soybean, broad bean, pea-pods etc.), yam, wheat, corn, paddy rice, peanut, fruit tree, (apple, banana, citrus, peach, papaya), flowers (like orchid), potted landscape etc.; Virus disease comprises tobacco mosaic virus disease, various melon virus disease, various solanberry viroid disease, beans virus disease, Cruciferae virus disease, grain and oil crop virus disease, cotton virus disease and various fruit tree virus diseases etc., wherein endangers serious mainly containing: tobacco virus, peppery pimento virus disease, tomato virus disease, Chinese cabbage virus disease, paddy rice virus disease comprise rice dwarf virus disease, BYDV, stripe virus disease, fern leaf of tomato viral disease, chilli pepper mosaic virus disease and tobacco veinal necrosis virus disease, corn short mosaic disease, cauliflower mosaic virus, oranges and tangerines virus disease, cymbidium mosaic virus, cybidium ring spot virus etc.
Embodiment 83: the 4-methyl isophthalic acid that contains of the present invention, 2, the application in the bishydrazide verivate of 3-thiadiazoles group and sterilant combination control agricultural and forestry and the gardening plant disease
Bioassay results showed that all of the present invention, with 4 - methyl-1, 2,3 - thiadiazole group dihydrazide derivative with existing fungicides such as benzo-thiadiazole, thiazole amine acid bacteria, thiophene amide, amine induced a thiophene 4 - methyl-1, 2,3 - thiadiazole-5 - carboxylic acid 4 - methyl-1, 2,3 - thiadiazole-5 - Sodium 4 - methyl- -1,2,3 - thiadiazole-5 - carboxylic acid ethyl ester, DL-β-aminobutyric acid, ribavirin, An Tuofen, Ningnanmycin, thiophene amide, amine or acid induced a thiophene, cream urea cyanide, thiram, ziram, mancozeb, fosetyl, thiophanate-methyl, chlorothalonil, the enemy can be loose, procymidone, Fenpropidine, thiophanate, thiophanate, fine A Cream Spirit, salicylic acid, flumorph, Dimethomorph, efficient metalaxyl, efficient Benalaxyl, double cypermethrin bacteria amine, flusulfamide, A flusulfamide, thiophene bacteria amine fluoride, fluorine amide, leaf dry phthalocyanine, cyclopropane amino acid bacteria, cyflufenamid, cycloalkyl amine acid bacteria, cyano bacteria amine, amine silica thiabendazole, furosemide topiramate amine bacteria, penthiopyrad, diacetylene amine acid bacteria, zoxamide, methyl furosemide amide, carboxin, B strains Lee, iprodione, azoxystrobin, Kresoxim amines, fluoxastrobin, kresoxim, phenoxy bacteria amines, amine oxime ether bacteria, picoxystrobin, pyraclostrobin esters, trifloxystrobin, enestroburin, allyl amine oxime bacteria, oxygen propiconazole, bromuconazole, cyproconazole, difenoconazole azole, Diniconazole, efficient diniconazole, Epoxiconazole, nitrile benzene yl, fluoro quinazoline, flusilazole, flutriafol, hexaconazole, imines yl, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole , tebuconazole, PTFE ether, triazole alcohol, sterilization azole, Bitertanol, thiabendazole, fuberidazole, imazalil, efficient imazalil, prochloraz, triflumizole, cyanide Cream azole, imidazole cycloheximide, evil imidazole, pefurazoate, Famoxadone, pyridine bacteria oxazole, hymexazol oxadixyl, thiophene pyraclostrobin, earth benomyl, Xin thiazone, benzoth thiocyanate, ten Ring morpholine, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, piperidine oxime plaque, bacteria amine piperidine ring, boscalid, fluorine boscalid, piperidine amine bacteria , cyprodinil, mepanipyrim fluorine, ferimzone, mepanipyrim, pyrimethanil, fenarimol, nuarimol, Chinomethionate, dithianon, ethoxyquin hydroxyquinoline , propoxyphene quinoline, phenoxy quinoline, diethofencarb, isopropyl bacteria amines, benzene thiabendazole amines Propamocarb, sulfur bacteria Granville, edifenphos, iprobenfos, topiramate bacteria phosphorus, methyl standing dead phosphorus, blasticidin, kasugamycin, polymyxin, Polyoxin, validamycin, Jinggangmycin, streptomycin, metalaxyl, furalaxyl, Benalaxyl, furosemide amide, mepronil , carbendazim, benomyl, thiophanate-methyl, triadimefon, ethirimol sulfonate, dimethyl ethyl phenol, ethirimol, captafol, captan, folpet, vinclozolin Lee, chlorofluorocarbons sclerotia Lee, Dimetachlone, chlorothalonil, Isoprothiolane, kitazine, leaf blight, PCNB, mancozeb, Propineb, fosetyl-aluminum, sulfur , Bordeaux mixture, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, benzene cycloheximide, Pencycuron, da cycloheximide, tetrachlorophthalide, pyroquilon, Spiro bacteria amines, Tricyclazole, triforine, more fruit, piperidine, Iminoctadine salts, biguanides octylamine, Dicloran,? benzene flusulfamide, toluene flusulfamide, indole ester, Fenaminosulf, oxolinic acid, allyl benzene, thiazole, bromine nitrate alcohol, methyl iodide, metam sodium, the enemy lines esters, dazomet, dichloro-isopropyl ether, Fosthiazate, Cadusafos, fensulfothion, insects fenamiphos, fenamiphos, Ethoprophos, in addition to line phosphorus, chlorine triazophos, carbosulfan cyclophosphamide, oxamyl, aldicarb, carbofuran, sulfuryl fluoride, dichloropropene, dichloro-isonicotinic acid, allyl isothiazolin any other known as a fungicide in any a combination of one or two; the present invention with 4 - methyl-1, 2,3 - thiadiazole group dihydrazide derivative of the mass in the composition ratio is 1% -90%, pharmaceutical control effect is good, these compositions have a certain synergy and additive effect is not found to have antagonistic effects composition; said composition can be used for agricultural and horticultural plant disease plant disease control, prevention and treatment of objects including Oomycetes Achlya genus Aphanomyces spp, Pythium, Phytophthora, referring Terrier spp, Plasmopara genus false downy mildew genus Peronospora spp more than twenty genera of pathogens or viruses that cause food crops , cash crops, horticultural and forestry plants produce overflow pus, dark pink, white, rust powder, cotton mildew, downy mildew, scab, leaf, cancer, purpura, leaf burn, leaf blight, wilting, Physalospora, gum, ulcers, angular spots, yellow wilt, mosaic, brown spots, decay, perforation, leaves, fruit drop, falling branches and other symptoms of the disease, the containing 1,2,3 - thiadiazole group Diacylhydrazine derivatives and commodity sterilization agent in the composition ratio of 1%: 99% to 99%: 1%, the composition processing of the dosage form is selected wettable powders, sustained-release agent, powder, microcapsule suspensions, dispersible concentrate agent emulsion for seed treatment , water, emulsions, large grain, granules, micro-emulsions, oil suspensions, oil, seed coated with a pesticide, suspension emulsion, a water-soluble granule, soluble concentrate agent, water dispersible granules in any one.
Utilize similar method to confirm; The 4-methyl isophthalic acid that contains of the present invention; 2, the combination between the bishydrazide compound of 3-thiadiazoles group and the above-mentioned commodity sterilant can be used for the disease of inducing disease-resistant indigenous bacteria of agricultural crops and forestry plant and gardening plant and plant pathogenic fungi to cause.These crops comprise: cereal crop (comprise paddy; Wheat; Barley; Oat; Corn; Millet; Chinese sorghum etc.); Tuber crops (comprise sweet potato; Yam; Cassava etc.); Legume crop (comprises soybean; Broad bean; Pea; Mung bean; Red bean etc.) fibre crops (cotton; Crudefiber crop; Silkworm and mulberry etc.); Oil crops (peanut; Rape; Sesame; Soybean; Sunflower Receptacle etc.); Sugar crop (beet; Sugarcane etc.); Beverage crops (tealeaves; Coffee; Cocoa etc.); Hobby crop (tobacco leaf etc.); Medicinal crop (genseng; The bulb of fritillary etc.); Tropical crops (rubber; Coconut; Oil palm; Sisal hemp etc.) food crop and fruit such as; Flowers; Oil plant; Sugar material and cotton; Fiber crops; Tea; Tobacco; Cash crop and plantation melons such as Chinese medicinal materials; Really; Tea; Silkworm and mulberry; Vegetables (containing various wild vegetable etc.); Bamboo shoots; Flowers and ornamental plant; Hops; Medicinal material; Pepper; Garden crops such as seedling and other garden crops.
Embodiment 84: the 4-methyl isophthalic acid that contains of the present invention, 2, the application in the bishydrazide verivate of 3-thiadiazoles group and sterilant combination control agricultural and forestry and the gardening plant insect pest
Of the present invention all contain the 4-methyl isophthalic acid; 2; The bishydrazide verivate of 3-thiadiazoles group and the mass ratio of commodity insecticides are classified 1%: 99% to 99%: 1% as; Spray after can directly converting water; Comprise agricultural in its preparation and go up acceptable solvent and emulsifying agent and solubility promoter and synergistic agent etc., the formulation that compsn is processed is selected from wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse dense dose, seed treatment emulsion, aqueous emulsion, any one in granula, granule, microemulsion, oil-suspending agent, finish, the seed with coated pesticidal, suspended emulsion agent, water-soluble granule, soluble thick agent, the water-dispersible granules greatly; The insect pest that can prevent and treat mainly contains red spider, Asiatic migrotory locust, clouding car locust, Chinese rice grasshopper, Patanga japonica (l.Bol.), single thorn mole cricket, east mole cricket, rice thrips, onion thrips, greenhouse thrips, haplothrips aculeatus, Mai Jian pipe thrips, Trialeurodes vaporariorum Westwood, Bemisia tabaci, rice green leafhopper, green leaf hopper, chlorita biguttula, spot clothing plant hopper, brown paddy plant hopper, white backed planthopper, small brown rice planthopper, the flat angle of sugarcane plant hopper, cotten aphid, green bugs, grain aphid, black peach aphid, kaoliang aphid, radish aphid, icerya purchasi, Pseudaulacaspis pentagona, unaspis shield kuwana, san jose scale, wax insect, ceroplastes rubens, the hard a red-spotted lizard of Korea's ball, pear lace bug, banana lace bug, thin corner piece stinkbug, little minute pirate bugs, slender rice bug, paddy fly, niphe elongata, scotinophora lurida, Nezara viridula smaragdula Fabricius., green plant bug, alfalfa plant bug, black striped plant bug, chrysopa septempunctata, beautiful Chrysopa, Chinese green lacewing, rain moth, casemaking clothes moth, cnidocampa flavescens walker, brown slug moth, thosea siensis, gelechiid, pink bollworm, brachmia triannuella, small cabbage moth, small heart-eating peach worm, eating-core bean worm, small heart-eating peach worm, apple Spilonota lechriaspis, brown belt length leaf roller, intends smaller apple leaf roller, striped rice borer, bean-pod borer, Pyrausta nubilalis (Hubern)., yellow rice borer, Oeobia undalis, Cnaphalocrocis medinali(rice leaf roller), bar snout moth's larva, the wild snout moth's larva of lap leaf, dichocrocis punctiferalis, armyworm, prodenia litura, rice green caterpillar, anomis flava, beet armyworm, pink rice borer, bollworm, ancient cooking vessel selects diamond drill, black cutworm, big cutworm, yellow cutworm, robber poison moth, gypsymoth, palaearctic sweet potato, greenish brown hawk moth, straight burr rice hesperiidae, pelopidas mathias, oranges and tangerines swallowtail butterfly, Common Mormon, small white, pyrameis indica, the yellow a kind of butterfly harmful to crop plants of ramie, beans blister beetle, Venus ground beetle, wrinkle sheath ground beetle, wheat head ground beetle, pleonomus canaliculatus, Agriotes subrittatus Motschulsky, khapra beetle, attagenus piceus, the little buprestid beetle of oranges and tangerines, golden edge buprestid beetle, tenebrio molitor, dark mealworm, red flour beetle, confused flour beetle, verdigris different beetle, black dull cockchafer, holotrichia oblita, mulberry borer, longicorn beetle, nadezhdiella cantori, pink neck longicorn, big daikon leaf beetle, daicon leaf beetle, aulacophora femoralis, Phyllotreta striolata, Callosobruchus chinensis, pea weevil, broad bean weevil, sitophilus zea-mais, rice weevil, dolerus tritici, pear fruit sawfly, yellowish leukorrhea ichneumon wasp, armyworm white star ichneumon wasp, the outstanding cocoon ichneumon wasp of corn earworm, bollworm tooth lip ichneumon wasp, snout moth's larva stain wart ichneumon wasp, mosquito, fly, horsefly, wheat midge, contarinia tritici, pachydiplosis oryzae, citrus fruit fly, melon trypetid, wheat leaf ash are dived fly, Americal rice leaf miner, the black fly of diving of beans stalk, frit fly, kind fly, onion fly, radish fly, full skirt chase after and post that fly, Pyrausta nubilalis (Hubern). are strictly posted fly, armyworm lacks Agricultural pests, forestry pest, gardening pest insect and sanitary insect pests such as must posting fly, and the controlling mode while also comprises double controlling; The 4-methyl isophthalic acid that contains of the present invention; 2; The bishydrazide compound of 3-thiadiazoles group can with the sterilant of following group in one or more mixes uses: Chlorpyrifos 94, inferior Nong, acetamiprid, Affirm (Merck Co.), more visit that rhzomorph, Avrmectin, pleocidin, fenvalerate, efficient fenvalerate, PP-383, beta_cypermethrin, lambda-cyhalothrin, Deltamethrin, Fenvalerate, Beta-FCR-1272, FCR-1272, Lambda-lambda-cyhalothrin, Permanone, permethrin, esbiothrin, cyhalothrin, bifenthrin, WL 43479, ether chrysanthemum ester, flumethrin, fluvalinate, Provado, acetamiprid, Ti304, imidaclothiz, thiophene worm quinoline, thiophene worm piperazine, thiophene worm amine, MTI-446, clothianadin, Da Tenan, diflubenzuron, the young urea that goes out, Teflubenzuron, deinsectization swell, fluorine bell urea, WL 115110, pyridine worm swell, Acarus tritici urea, poisonous insect urea, penfluron, Noviflumuron, flucycloxuron, Novaluron, fluorine pyridine urea, Bay sir 6874, piperazine worm urea, Bistrifluron, furans worm hydrazides, worm hydrazides, chlorine worm hydrazides, methoxyfenozide, ring worm hydrazides, Rogor, omethoate, SD-1750, acephate, triazophos, Resitox, pyridaphenthione, isazofos, Ro 7-5050, SevinCarbaryl, PP-062, MTMC, isoprocarb, cartap, fenobucarb, leaf disperse, carbaryl, benfuracarb, carbosulfan, cartap, bromopropylate, hexythiazox, azoles mite ester, pyridaben, four mite piperazines, alkynes mite spy, butyl ether urea, benfuracarb, pyrrole aphid ketone, spiral shell mite ester, spiral shell worm ester, spiral shell worm ethyl ester, butene-fipronil, azocyclotin, PP618, ethoprophos, fluorine worm nitrile, desinsection list, disosultap, Flubendiamide, chlorine insect amide or tebufenpyrad, bromothalonil, pyrazine ketone, second mite azoles, tebufenpyrad, the young ketone of rattling away, pyrrole propyl ether, emaricin etc.; The preventive effect of combination medicament is good, and drug effect is played stably.
Embodiment 85: the 4-methyl isophthalic acid that contains of the present invention, 2, the bishydrazide verivate of 3-thiadiazoles group and the complete processing and the stability of commercially available agricultural chemical compound preparation
The 4-methyl isophthalic acid that contains of the present invention; 2, the bishydrazide verivate of 3-thiadiazoles group and the mixed preparation complete processing of commercially available agricultural chemical are seen table 3, and table 3 is visible; Most medicament all can be processed according to the method for statement; The main component of liquid preparation is other a component etc. of effective constituent and solubility promoter and tensio-active agent and synergistic agent, antifreezing agent, stablizer, thickening material or permeate agent etc., and the composition of solid preparation mainly includes imitates other agriculturals such as composition, tensio-active agent and filler and go up acceptable adjuvant components, and the preparation of processing is carried out cold storage test; Liquid preparation is placed 1 week not have to precipitate at 0 ± 2 degree centigrade and is separated out; Solid preparation placed for 2 weeks at 54 ± 2 degrees centigrade, and caking phenomenon does not appear in medicament, and the medicament drug effect that all preparations store before and after placing does not have significant difference; The rate of decomposition of mixing effective constituent is explained the medicament qualified stability in 5%.
Table 1 synthetic of the present invention contains the 4-methyl isophthalic acid, and 2, the chemical structure of the bishydrazide verivate of 3-thiadiazoles group
Table 1 synthetic of the present invention contains the 4-methyl isophthalic acid, and 2, the chemical structure (continuing) of the bishydrazide verivate of 3-thiadiazoles group
Table 1 synthetic of the present invention contains the 4-methyl isophthalic acid, and 2, the chemical structure (continuing) of the bishydrazide verivate of 3-thiadiazoles group
The biological activity determination result (%) of the compound among table 3 the present invention
Numbering Test code number AS CA GZ PP BC RC PS SS PI PXL2 PXL4 ?M2
I-1 YZK-6-32 43.48 58.33 18.75 17.50 63.16 56.67 41.03 91.49 86.96 0 - ?100
I-2 YZK-6-40 47.83 52.78 33.33 25.00 47.37 60.00 17.95 100.00 34.78 7.70 - ?20
I-3 YZK-6-42 39.13 52.78 29.17 20.00 21.05 63.33 26.92 100.00 26.09 0 - ?20
I-4 YZK-6-45 34.78 50.00 31.25 30.00 5.26 53.33 32.05 97.87 13.04 14.60 - ?10
I-5 YZK-7-42 16.67 14.29 20.45 50.00 17.39 30.61 1.18 79.17 14.29 - 30.00 ?10
I-6 ZQX-2-18 23.81 21.05 32.50 52.00 60.00 63.16 49.02 34.21 37.50 36.84 - ?20
I-7 YZK-6-41 43.48 58.33 33.33 15.00 21.05 58.33 34.62 95.74 26.09 25.00 - ?10
I-8 YZK-7-35 22.22 21.43 22.73 8.00 30.43 20.41 0 50.00 42.86 78.90 - ?10
I-9 YZK-7-38 27.78 7.14 20.45 40.00 26.09 32.65 2.35 58.33 28.57 0.0 - ?30
I-10 * YZK-7-45 33.33 21.43 22.73 34.00 52.17 36.73 29.41 29.17 38.10 25.00 - ?100
I-11 YZK-7-15 50.00 14.29 70.00 28.57 38.30 53.97 28.92 36.67 32.00 17.10 - ?10
I-12 YZK-7-19-5 36.36 4.76 72.00 40.00 57.45 47.62 19.28 43.33 44.00 26.30 - ?10
I-13 YZK-6-37 30.43 55.56 33.33 62.50 42.11 58.33 17.95 97.87 26.09 2.40 - ?10
I-14 WH-2-34 33.33 36.84 22.50 44.00 56.00 47.37 47.06 30.26 58.33 15.00 - ?10
I-15 WH-2-35 28.57 52.63 15.00 34.00 20.00 84.21 37.25 30.26 54.17 45.90 - ?40
I-16 WH-3-18 33.33 31.58 15.00 44.00 68.00 52.63 33.33 26.32 62.50 5.00 - ?30
I-17 YZK-7-50-1 38.89 28.57 27.27 52.00 60.87 40.82 0 54.17 52.38 - 45.00 ?10
I-18 YZK-7-48 39.13 50.00 31.25 72.50 63.16 65.00 23.08 100.00 69.57 - 22.50 ?30
I-19 WH-2-33 42.86 26.32 37.50 58.00 60.00 60.53 37.25 34.21 37.50 5.00 - ?10
I-20 YZK-7-11 16.67 28.57 20.45 24.00 47.83 48.98 36.47 47.92 4.76 69.70 - ?10
I-21 YZK-6-36 39.13 58.33 29.17 15.00 31.58 63.33 3.85 97.87 26.09 33.30 - ?20
I-22 YZK-6-39 34.78 58.33 27.08 40.00 31.58 63.33 47.44 100.00 21.74 14.30 - ?40
I-23 YZK-7-3 45.45 16.67 70.00 37.14 40.43 39.68 56.63 26.67 12.00 - 84.62 ?30
I-24 YZK-7-6 50.00 35.71 36.36 4.00 69.57 61.22 47.06 93.75 28.57 55.6 - ?20
I-25 YZK-7-16 42.86 0 0 58.97 18.18 54.84 36.62 36.36 9.52 50.00 - ?20
I-26 YZK-7-17 54.55 28.57 84.00 50.00 51.06 71.43 32.53 16.67 48.00 42.50 - ?0
I-27 WH-5-28 0 0 7.69 18.42 37.93 13.16 7.04 44.19 2.00 ? 22.50 ?20
I-28 WH-2-32 52.38 36.84 25.00 38.00 40.00 47.37 50.98 32.89 41.67 0 - ?-
I-31 WH-3-15 15.00 17.65 28.89 34.85 50.00 30.00 25.00 28.95 22.22 5.26 ? ?60
I-32 WH-3-21 42.86 57.89 30.00 66.00 60.00 68.42 66.67 40.79 45.83 17.07 ? ?10
I-33 WH-3-25 33.33 47.37 25.00 54.00 60.00 39.47 35.29 26.32 54.17 10.00 ? ?30
I-34 WH-4-18 5.26 0 0 18.42 34.48 0 0 16.28 22.22 - 48.78 ?20
I-35 WH-4-30 0 0 25.00 26.67 41.18 84.00 40.82 30.26 8.33 - 35.00 ?20
I-36 WH-4-37 26.67 22.22 29.17 23.33 55.88 24.00 63.27 34.21 25.00 - 44.12 ?10
I-37 WH-5-11 0 0 11.54 21.05 20.69 18.42 0 20.93 3.70 - 12.95 ?0
I-38 WSX-44 22.22 63.64 24.39 28.13 32 41.67 28.95 16.67 16.67 12.50 ? ?40
I-39 WH-4-40 5.26 0 0 5.26 3.1 10.53 0 62.79 3.70 - 24.39 ?10
II-2 YZK-7-29 33.33 21.43 31.82 28.00 34.78 28.57 3.53 93.75 28.57 67.50 - ?100
II-3 WH-4-6 0 66.67 16.67 33.33 55.88 14.00 48.98 31.58 4.17 12.20 - ?20
II-4 YZK-6-48 34.78 58.33 27.08 22.50 26.32 55.00 29.49 95.74 0 37.00 - ?0
II-5 YZK-7-44 27.78 21.43 22.73 70.00 34.78 2.04 2.35 58.33 33.33 28.95 - ?10
II-6 ZQX-2-20-b 33.33 21.05 25.00 52.00 60.00 34.21 45.10 28.95 33.33 - 10.00 ?10
II-7 WH-4-7 26.67 33.33 41.67 33.33 26.47 18.00 59.18 23.68 20.83 - 27.50 ?10
II-8 YZK-7-34 27.78 14.29 27.27 32.00 30.43 40.82 15.29 81.25 0 23.70 - ?20
II-9 YZK-7-39 38.89 35.71 20.45 36.00 56.52 36.73 29.41 58.33 14.29 25.00 - ?0
II-10 YZK-7-46 50.00 42.86 31.82 32.00 13.04 48.98 10.59 68.75 23.81 - 42.50 ?20
II-11 YZK-7-19-1 40.91 26.19 76.00 34.29 31.91 61.90 15.66 53.33 44.00 2.40 - ?30
II-12 YZK-7-31 44.44 42.86 25.00 26.00 13.04 28.57 5.88 47.92 14.29 96.60 - ?10
II-13 WH-3-43-B 20.00 11.76 2.22 27.27 33.33 40.00 37.50 27.63 29.63 2.86 ? ?40
II-14 WH-3-32 5.26 0 2.50 26.32 24.14 18.42 0 62.79 3.70 ND 35.00 ?ND
II-15 WH-3-33 52.38 31.58 22.50 40.00 48.00 63.16 33.33 35.53 41.67 32.40 - ?100
II-16 WH-3-22 52.38 42.11 30.00 54.00 76.00 60.53 45.10 32.89 66.67 13.33 - ?40
II-17 WH-4-12 22.22 27.27 46.34 21.88 28.00 22.22 21.05 100 8.33 15.80 - ?20
The biological activity determination result (%) (continuing) of the compound among table 3 the present invention
Numbering Test code number AS CA GZ PP BC RC PS SS PI PXL2 PXL4 ?M2
II-18 YZK-7-49 44.44 50.00 20.45 32.00 30.43 46.94 24.71 68.75 14.29 34.21 - ?10
II-19 YZK-6-50 47.83 52.78 39.58 5.00 31.58 70.00 17.95 97.87 21.74 33.30 - ?30
II-20 YZK-7-33 38.89 35.71 34.09 36.00 60.87 44.90 10.59 95.83 19.05 0 - ?100
II-23 YZK-7-4 33.33 28.57 31.82 68.00 60.87 36.73 1.18 81.25 28.57 12.10 - ?10
II-25 WH-3-10 28.57 26.32 30.00 42.00 72.00 50.00 52.94 32.89 45.83 7.50 ? ?40
II-26 WH-3-14 28.57 31.58 22.50 58.00 44.00 50.00 74.51 43.42 58.33 2.80 ? ?30
II-27 WSX-54 44.44 42.86 22.73 0 17.39 53.06 8.24 68.75 33.33 6.20 - ?30
II-28 WH-3-42 33.33 26.32 37.50 30.00 64.00 34.21 49.02 43.42 29.17 4.88 ? ?40
II-29 WH-2-39 47.62 36.84 22.50 54.00 56.00 50.00 45.10 38.16 50.00 28.57 - ?0
II-30 WH-2-44 47.62 52.63 35.00 40.00 48.00 52.63 66.67 34.21 37.50 2.70 - ?20
II-31 WH-4-14 20.00 77.78 25.00 33.33 55.88 26.00 46.94 28.95 16.67 7.69 ? ?50
II-32 WH-3-23 42.86 21.05 37.50 42.00 36.00 81.58 29.41 31.58 41.67 5.13 ? ?20
II-33 WH-3-27 61.90 42.11 22.50 50.00 52.00 63.16 45.10 34.21 25.00 5.13 ? ?10
II-36 WH-4-42 13.33 33.33 54.17 36.67 41.18 14.00 55.10 31.58 20.83 - 34.15 ?30
II-38 WSX-50 27.78 36.36 12.20 37.50 28.00 41.67 23.68 41.67 16.67 15.80 ? ?20
III-1 WH-2-36 42.86 26.32 37.50 58.00 60.00 68.42 70.59 23.68 41.67 15.00 - ?30
III-2 WH-2-43 10.00 11.76 13.33 27.27 66.67 20.00 28.13 23.68 25.93 10.00 - ?10
IV-1 ZQX-2-20-a 38.10 31.58 35.00 44.00 72.00 52.63 21.57 31.58 54.17 - 25.00 ?10
IV-2 WH-3-43-A 10.00 0 0 31.82 33.33 60.00 43.75 32.89 14.81 ? 27.5 ?10
V-1 WH-5-16 15.79 0 0 31.58 44.83 15.79 0 44.19 0 ? 34.46 ?10
VI-1 WSX-40 11.11 54.55 12.20 18.75 20.00 44.44 23.68 20.83 12.50 0 28.57 ?10
CXJ ** The worm hydrazides 5.26 0 4.76 9.52 11.76 14.00 2.50 1.18 4.17 10.00 20.00 ?40
*: mosquito larvae 1 μ g/mL is 100%; 0.5 μ g/mL is 10%;
*: the worm hydrazides;
PXL2: small cabbage moth (Plutella xylostella L.) 200 μ g/mL; PXL4: small cabbage moth (Plutella xylostella L.) 400 μ g/mL; M2: mosquito larvae: 2 μ g/mL.
Table 3 contains the 4-methyl isophthalic acid, and 2, the bishydrazide verivate of 3-thiadiazoles group mixes the working method of using preparation with conventional pesticide
Liquid preparation is formed Content (%) Solid preparation is formed Content (%) Explanation
Other agricultural chemicals of compound I or II or III or IV+ ?1-90 Other agricultural chemicals of compound I or II or III or IV+ 1-90 The principle of combination is to examine synergy or consider doublely to control and lighten one's labor and practice thrift the dispenser cost
Solubility promoter ?2-8 Sodium lauryl sulphate 1-5 -
Tensio-active agent ?2-10 Zeyssatite 5-30 -
Antifreezing agent ?2-5 Sodium lignosulfonate 2-8 -
Synergistic agent ?2-8 Other agriculturals go up the acceptable auxiliary agent 1-5 -
Other agriculturals go up acceptable auxiliary agents like, stablizer, thickening material or permeate agent etc. ?1-5 Kaolin Supply 100% -
Toluene (water) Supply 100% ? ? ?

Claims (4)

1. one kind contains 2, and the bishydrazide verivate of 3-thiadiazoles group is characterized in that: have the chemical structure of general formula shown in I, II:
Figure FSB00000677850700011
Wherein: R 1For being selected from phenyl, 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 4-methyl isophthalic acid; 2,3-thiadiazoles-5-base, 2-furyl, 2-methyl isophthalic acid-(4-chloro-phenyl-)-1-propyl group, trichloromethyl,
Figure FSB00000677850700012
2,6-dichlorophenyl, heptyl, 3,5-dichlorophenyl, 3,5-3,5-dimethylphenyl, 3-(2-chloro-phenyl-)-5-methyl-isoxazole azoles-4-base, 1-phenyl-3-4-base, cyclohexyl,
2-fluorobenzene methyl, 3, the group of 6-dichloropyridine-2-base, 5-ethyl-1-methylpyrazole-3-base;
R 2For be selected from 2-aminomethyl phenyl, 3-aminomethyl phenyl, 4-aminomethyl phenyl, 2-p-methoxy-phenyl, 3-p-methoxy-phenyl, 4-p-methoxy-phenyl, 2-chloro-phenyl-, 3-chloro-phenyl-, 4-chloro-phenyl-, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-ethylphenyl, 2-methyl isophthalic acid-(4-chloro-phenyl-)-1-propyl group,
Figure FSB00000677850700013
4-fluorobenzene methyl, 2,6-dichlorophenyl, methyl, propyl group, heptyl, 3,5-dichlorophenyl, 3, the group of 5-3,5-dimethylphenyl, cyclohexyl, 5-ethyl-1-methylpyrazole-3-base.
2. claim 1 is described contains 1,2, the compound method of the bishydrazide verivate of 3-thiadiazoles group, and concrete steps are following:
A. the preparation of substituted formyl chlorine:
The replacement formic acid that in 50 milliliters of round-bottomed flasks, adds 2 mmoles adds the sulfur oxychloride of 12 mmoles again, with reaction mixture with oil bath reflux 3-4 hour, air distillation remove behind the intact sulfur oxychloride of unreacted substituted formyl chlorine, the sealing preservation is subsequent use; The amount of substituted formyl chlorine preparation enlarges by corresponding proportion or dwindles;
The preparation of B.N-(substituted formacyl)-N '-tertiary butyl hydrazine:
In 100 milliliters of round-bottomed flasks, add 15 mmole tertiary butyl hydrazonium salt hydrochlorates; Add 40 milliliters of methylene dichloride and 5 ml waters and 30 mmole sodium hydroxide again; Slowly drip 20 milliliters of dichloromethane solutions of 15 mmole substituted formyl chlorine down in the cooling of induction stirring and ice bath, dropwise afterwards room temperature reaction 3 hours, stopped reaction afterreaction mixture is used water washing; Tell organic layer; Behind the anhydrous magnesium sulfate drying, rotary evaporation remove desolvate N-(substituted formacyl)-N '-tertiary butyl hydrazine, product need not to be further purified the reaction that directly is used for next step; The amount of N-substituted formacyl-N '-tertiary butyl hydrazine preparation enlarges by corresponding proportion or dwindles;
C.4-methyl isophthalic acid, 2, the preparation of 3-thiadiazoles-5-formyl chloride:
With 0.067 mole 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid and 29 milliliters of thionyl chlorides join in 100 milliliters of three mouthfuls of round-bottomed flasks; 80 degrees centigrade of following reflux 6 hours remove excessive thionyl chloride under reduced pressure, and underpressure distillation is collected 94-96 degree centigrade cut and got faint yellow product 9.25 grams under 2000Pa; Yield 85%, midbody 4-methyl isophthalic acid, 2; The 3-thiadiazoles-sealing of 5-formyl chloride is kept in the moisture eliminator subsequent use; The 4-methyl isophthalic acid, 2, the amount of 3-thiadiazoles-5-formyl chloride preparation enlarges by corresponding proportion or dwindles;
The preparation of D.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine:
In 1000 milliliters of round-bottomed flasks, add 0.4 mole of tertiary butyl hydrazonium salt hydrochlorate, add 450 milliliters of methylene dichloride and 100 ml waters and 0.6 molar sodium hydroxide again, under induction stirring and ice bath cooling, slowly drip 0.4 mole of 4-methyl isophthalic acid; 2,50 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride dropwise the back room temperature reaction 5 hours; Stopped reaction afterreaction mixture is used water washing, tells organic layer, behind the anhydrous magnesium sulfate drying; Removal of solvent under reduced pressure gets N-(4-methyl isophthalic acid; 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine, product need not to be further purified the reaction that directly is used for next step; The amount of N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine preparation enlarges by corresponding proportion or dwindles;
The preparation of E.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-the formyl radical)-N '-tertiary butyl-N '-substituted formyl hydrazine class compound I:
Get 0.1 mmole N-(4-methyl isophthalic acid; 2; 3-thiadiazoles-5-formyl radical)-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join in 50 milliliters of round-bottomed flasks, add acid binding agent 0.12 mmole triethylamine then, the ice bath cooling slowly drips 5 milliliters of dichloromethane solutions of 0.1 mmole substituted formyl chlorine down; Dropwise the back and continued stirring reaction 4 hours in room temperature, after reaction finished, the reaction mixture water was given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night; Filter the back removal of solvent under reduced pressure, crude product gets N-(4-methyl isophthalic acid, 2 with Virahol or re-crystallizing in ethyl acetate; 3-thiadiazoles-5-formyl radical)-the N '-tertiary butyl-N '-substituted formyl hydrazine class compound I, measure fusing point with 1HNMR confirms its chemical structure, and the amount of compound I preparation enlarges by corresponding proportion or dwindles;
The preparation of F.N-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-the formyl radical)-N-tertiary butyl-N '-substituted formyl hydrazine class compound II:
Getting 0.1 mmole N-substituted formacyl-N '-tertiary butyl hydrazine is dissolved in 20 milliliters of methylene dichloride; Join then in 50 milliliters of round-bottomed flasks; Add acid binding agent 0.12 mmole triethylamine; The ice bath cooling slowly drips 0.1 mmole 4-methyl isophthalic acid, 2,5 milliliters of dichloromethane solutions of 3-thiadiazoles-5-formyl chloride down; Dropwise the back and continued stirring reaction 4 hours in room temperature, after reaction finished, the reaction mixture water was given a baby a bath on the third day after its birth inferior; Anhydrous magnesium sulfate drying spends the night; Filter the back removal of solvent under reduced pressure, crude product gets N-(4-methyl isophthalic acid, 2 with Virahol or re-crystallizing in ethyl acetate; 3-thiadiazoles-5-formyl radical)-the N-tertiary butyl-N '-substituted formyl hydrazine class compound II, measure fusing point with 1H NMR confirms its chemical structure, and the amount of compound I I preparation enlarges by corresponding proportion or dwindles.
3. an insecticide is characterized in that: contain 1,2 by claim 1 is described, the bishydrazide verivate of 3-thiadiazoles group and the agriculture acceptable assistant composition of going up.
4. a sterilant is characterized in that: contain 1,2 by claim 1 is described, the bishydrazide verivate of 3-thiadiazoles group and the agriculture acceptable assistant composition of going up.
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