CN102174031B - 1,2,3-thiadiazole-1,3,4-thiadiazole compounds and preparation method and application thereof - Google Patents

Abstract

The invention provides 1,2,3-thiadiazole-1,3,4-thiadiazole derivatives, and a preparation method and application thereof. The invention relates to 1,2,3-thiadiazole-containing heterocyclic compounds with the chemical structural general formula shown as the specification. The invention discloses the structural general formula of the compounds, a synthesizing method of the compounds, application ofthe compounds serving as pesticides, bactericides, anti-plant-virus agents and plant activating agents, and a process for preparing the pesticides, the bactericides, the anti-plant-virus agents and the plant activating agents by mixing the compounds and agriculturally acceptable adjuvants or synergists. The invention also discloses application of the compounds when the compounds are combined withcommodities of the pesticides, the bactericides, the anti-plant-virus agents and the plant activating agents in prevention and control of agricultural, forestry, horticultural and health diseases, insect pests and virus diseases, and a preparation method of the compounds.

Description

One class 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound and its production and use

Technical field

Technical scheme of the present invention relates to the heterogeneous ring compound containing 1,2-diazole, is specifically related to 1,2,3-thiadiazoles connection-1,3,4-thiadiazole derivative.

Background technology

Thiadiazoles is the important heterogeneous ring compound of a class, in current agricultural chemicals and medical research and development in occupation of consequence.Thiadiazoles comprises 1,2,3-thiadiazoles, 1,2,4-thiadiazoles, 1,3,4-thiadiazoles and 1,2,5-thiadiazoles.Wherein 1,2,3-thiadiazoles and 1,3, the 4-thiadiazole compound has biological activity widely, as 1,2,3-thiadiazole compound has anti-inflammatory, biological activity (Boschelli, et al., J.Med.Chem.1993, the 36:1802 such as expelling parasite, sterilization, weeding, anticancer, coordinate plant growth; Saad H., Indian J.Chem, 1996,35B:980; Fan Z.J., et al., J.Agric.Food Chem.2009,57:4279; Bakulev, et al., The Chemistry of 1,2,3-thiadiazole, 2004, John WIley& Sons, Inc.), in addition, 1,2,3-thiadiazoles is that in thiadiazoles, unique energy passes through to discharge N ₂and the compound of degraded, and this reaction is irreversible, and therefore, this compounds Environmental compatibility is good; 1,3,4-thiadiazole compound especially 2, the dibasic derivative of 5-, also have biological activity (Zou X.J., et al, J Agric Food Chem, 2002, the 50:3757 such as sterilization, desinsection, coordinate plant growth, weeding; Matsumoto S., et al., US:4877804,1989-10-31; Shao Yu etc., fine chemistry industry, 2010,27:696; Magnify forever and wait, CN101659660).Though not as the above two concerned degree high, 1,2,4-thiadiazoles and 1,2,5-thiadiazole compound agricultural chemicals and medical aspect application relevant report, 1,2 are also arranged, that the 4-thiadiazoles derivative has is antibiotic, anticancer, desinsection and weeding isoreactivity (Collins I., et al., WO2009037485; Peter J.S., et al., WO2008047138; Kazuo Y., et al., JP06100550; American Cyanamid Company, EP726260); 1,2,5-thiadiazoles is the important activity group of central α 2 adrenoceptor agonists tizanidines, has its derivative of bibliographical information to also have weeding activity (Bernadskii, M.I., eet al., RU2237669; Joerg S., et al., DE2919293).

Amides be also research focus, agricultural chemicals and medical aspect the application very extensive.Agricultural chemicals has acid amide fungicides, as carboxin, oxycarboxin and mebenil etc.; The amides sterilant, as Rynaxypyr, flonicamid and Flubendiamide etc.; Acetamide-group herbicides, as acetochlor, metolachlor and Butachlor technical 92 etc.; Medicine has the amides microbiotic, as penicillin, Ampicillin Trihydrate and Gepcillin etc.; The amides local anesthetic, as ropivacaine, bupivacaine and lignocaine etc.It is worthy of note especially, the benzamide that methane amide particularly replaces and Heterocyclylcarboxamderivatives are the active groups of many sterilants, amides sterilant flonicamid (the Tadaaki T. of as former as Japanese stone industry company exploitation, et al., EP580374), chemical name: N-cyanogen methyl-4-(trifluoromethyl) niacinamide; Rynaxypyr (the Philip L.G. of du pont company exploitation, et al., WO2003015518), the bromo-N-[4-chloro-2-methyl of chemical name: 3--6-[(methyl-carbamoyl) benzene]-1-(3-chloropyridine-2-yl)-1-hydrogen-pyridine-5-methane amide; The Flubendiamide (Masanori T., et al., EP1006107) of Nihon Nihyaku Co., Ltd's exploitation, the iodo-N-of chemical name: 3-(2-methylsulfonyl-1,1-dimethyl ethyl)-N-{4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl) ethyl]-o-tolyl }-phthalamide; These medicaments are all the highest compounds of current commercialization activity.Isotianil (isotianil) is that the common research and development of Bayer and Sumitomo Chemical are used for preventing and treating rice blast, it can excite the natural immunology defense of paddy rice, also has certain insecticidal activity (Assmann L., Kuhnt D., Elbe H.L.e al.WO 9924413,1999-05-20), be the activating plants agent.

In view of thiadiazole compound and amides biological activity widely, thiadiazoles group and acid amides are combined in to existing considerable report in same a part, by studying its active discovery, this combination often can reach good result.As commercial induction of resistance sterilant tiadinil (tiadinil), just have the structure of 1,2,3-Thiadiazole and benzamide concurrently.We also design synthesized a plurality of series contain 1,2, the compound of 3-thiadiazoles group and amido linkage, by activity research, find, some compounds have good sterilization, antiviral and systemic acquired resistance, especially compound N-(5-methyl isophthalic acid, the 3-thiazol-2-yl)-4-methyl isophthalic acid, 2, (patent in past is called for short N-(5-methyl-1,3-thiazole-2-yl)-4-methyl-1,2,3-thiadiazole to 3-thiadiazoles-5-methane amide, the tentative Universal Chinese character name that has now obtained the approval of pesticide standard Technical Committee is called the first thiophene and lures amine) (Fan Zhijin etc., CN101020687; CN101003533; CN101250166; CN101250167; CN101250168).The designs such as Zhan have been synthesized and have a plurality ofly been had 1,2 concurrently, and the compound of the structure of 3-Thiadiazole and benzamide, represented antitumour activity preferably.(Eur.J.Med.Chem.2009，44：4648；Bioorg.Med.Chem.2009，17：5920)。(the RU2364592 such as Pulina; RU 2364591) on 1,3,4-thiadiazoles, after introducing benzamide structure, to find, some compounds have better anti-inflammatory and analgesic effect than diclofenac, and toxicity is lower; Some compound also has certain hypoglycemic activity.Banday etc. (Chinese Chem Lett., 2008,19:1427) synthesize a series of N-2-benzoyls with good anti-microbial activity-5-and replaced-1,3,4-thiadiazoles-2-amine.Zheng etc. (Chinese Chem Lett., 2008, a series of N-ethanamides that 19:1281) design is synthesized-(5-replaces-1,3,4-thiadiazoles-2-yl)-5 FU 5 fluorouracil has shown than the better antitumour activity of 5 FU 5 fluorouracil.Varsha etc. (Med Chem Res., 2008,17:169) synthesized a series of 1,3 of hexamethylene lactan that contain, the 4-thiadiazoles derivative, part of compounds has good fungicidal activity.(the organic chemistry such as Chen little Bao, 2009,29,1096) synthesized a series of N-(5-alkyl-1,3,4-thiadiazoles-2-yl)-1-[(heteroaryl) methyl]-5-methyl isophthalic acid H-1,2,3-triazolyl-4-methane amide, part of compounds demonstrates medium weeding activity and insecticidal activity to a certain degree.Above research is all that 1,2,3-thiadiazoles or 1,3,4-thiadiazoles and two kinds of groups of acid amides are connected in same a part, and these three kinds of groups is combined in same a part and has no bibliographical information simultaneously.The invention with the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate is raw material, by 1,2,3-thiadiazoles, 1,3,4-thiadiazoles group and amido linkage are attached in same a part simultaneously, and synthetic new compound have been carried out to the evaluated biological activity of system.

Summary of the invention

Technical problem to be solved by this invention is: provide new 1,2,3-thiadiazoles connection-1,3, the synthetic method of 4-thiadiazole derivative, provide this compounds to adjust biological activity and the measuring method thereof of empty agricultural, gardening and health and forestry plant insect and the phytopathy original, the middle application of these compounds at agriculture field, gardening field, field of forestry and health field is provided simultaneously.

The present invention solves this technical problem adopted technical scheme: have agriculture field, gardening field, field of forestry insecticidal activity, fungicidal activity, anti-phytoviral activity, inducing plant and produce 1 of anti-disease activity, insect growth regulator activity, 2,3-thiadiazoles connection-1,3, the chemical structure of general formula of 4-thiadiazole derivative is shown in formula I, and the chemical structure of particular compound is in Table 1:

Wherein: R is selected from phenyl, the 4-methyl isophthalic acid, 2, 3-thiadiazoles-5-base, cyclobutyl, cyclohexyl, the 4-pyridyl, the 4-trifluoromethyl, 3, 6-dichloro-2-pyridyl base, the 4-ethylphenyl, 5-methyl-3-(2-chloro-phenyl-)-4-isoxazolyl, 5-methyl-3-phenyl-4-isoxazolyl, the 4-fluorophenyl, 2, 2-dimethyl-3-(2-methyl-1-propylene base)-cyclopropyl, 3-(2, 2 dichloroethylenes)-2, 2-dimethyl cyclopropyl, the 2-fluorophenyl, the 4-chloro-phenyl-, the 3-chloro-phenyl-, the 3-fluorophenyl, 3, the 5-difluorophenyl, 1-(4-fluorophenyl) methyl, the 3-trifluoromethyl, 1-(4-chloro-phenyl-) methyl, the 4-nitrophenyl, 3, the 5-3,5-dimethylphenyl, the 3-aminomethyl phenyl, the 4-p-methoxy-phenyl, the 3-nitrophenyl, 3, the 5-dichlorophenyl, the 2-trifluoromethyl, 2, the 4-dichlorophenyl, the 2-aminomethyl phenyl, the 2-p-methoxy-phenyl, the 3-p-methoxy-phenyl, the 5-methyl isophthalic acid, 2, 3-thiadiazoles-4-base, 5-ethyl-1-methyl-3-pyrazolyl.

Synthetic method and the reaction equation of N-of the present invention (5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl) amide derivatives are as follows:

Wherein: R is selected from phenyl, the 4-methyl isophthalic acid, 2, 3-thiadiazoles-5-base, cyclobutyl, cyclohexyl, the 4-pyridyl, the 4-trifluoromethyl, 3, 6-dichloro-2-pyridyl base, the 4-ethylphenyl, 5-methyl-3-(2-chloro-phenyl-)-4-isoxazolyl, 5-methyl-3-phenyl-4-isoxazolyl, the 4-fluorophenyl, 2, 2-dimethyl-3-(2-methyl-1-propylene base)-cyclopropyl, 3-(2, 2 dichloroethylenes)-2, 2-dimethyl cyclopropyl, the 2-fluorophenyl, the 4-chloro-phenyl-, the 3-chloro-phenyl-, the 3-fluorophenyl, 3, the 5-difluorophenyl, 1-(4-fluorophenyl) methyl, the 3-trifluoromethyl, 1-(4-chloro-phenyl-) methyl, the 4-nitrophenyl, 3, the 5-3,5-dimethylphenyl, the 3-aminomethyl phenyl, the 4-p-methoxy-phenyl, the 3-nitrophenyl, 3, the 5-dichlorophenyl, the 2-trifluoromethyl, 2, the 4-dichlorophenyl, the 2-aminomethyl phenyl, the 2-p-methoxy-phenyl, the 3-p-methoxy-phenyl, the 5-methyl isophthalic acid, 2, 3-thiadiazoles-4-base, 5-ethyl-1-methyl-3-pyrazolyl.

Embodiment

Enforcement of the present invention is specifically carried out according to the following steps:

A.4-methyl isophthalic acid, the preparation of 2,3-thiadiazoles-5-formyl hydrazine:

The 4-methyl isophthalic acid, the preparation of 2,3-thiadiazoles-5-formyl hydrazine is carried out with reference to the method for Chinese patent CN 100488962C; The volume of respective reaction container enlarges in proportion or dwindles.

B.1-the preparation of (4-methyl isophthalic acid, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide:

In 100 milliliters of round-bottomed flasks, add the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine 31.6 mmoles, concentrated hydrochloric acid 6.8 grams, 30 milliliters, water and dry potassium sulfocyanate 47.5 mmoles, under induction stirring, oil bath is heated to 90～100 degrees centigrade, approximately, after 1 hour, has a large amount of white solids to separate out, continue reacting by heating 3 hours, stopped reaction, cooling rear suction filtration, use respectively dilute sodium bicarbonate solution and water washing, obtain sterling white solid product, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; The amount of synthetic 1-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles.

C.2-amino-5-(4-methyl isophthalic acid, 2,3-thiadiazoles 5-yl)-1,3, the preparation of 4-thiadiazoles:

Add 1-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide 16.6 mmoles, the vitriol oil are 10 milliliters, under room temperature, stir 6 hours, then by 80 milliliters of frozen water of reaction solution impouring, ammoniacal liquor with 25% is regulated pH value to 9～10, separate out a large amount of yellow solids, standing rear suction filtration, and difference water and washing with alcohol, obtain product sterling, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; Synthetic 2-amino-5-(4-methyl isophthalic acid, 2,3-thiadiazoles 5-yl)-1,3, the amount of 4-thiadiazoles enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles.

D.1,2,3-thiadiazoles connection-1, the preparation of 3,4-thiadiazole compound:

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles 5-yl)-1,3,4-thiadiazoles 1.1-2.0 mmole, methylene dichloride 15-20 milliliter and triethylamine 2.2-4 mmole, to replace acyl chlorides 1.5-2.5 mmole and be dissolved in 5 milliliters of methylene dichloride, slowly drop under stirring at room in reaction solution, and drip and finish, continue room temperature reaction 5 hours, TLC plate monitoring raw material has reacted, and suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain product sterling, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; Synthetic 1,2,3-thiadiazoles connection-1, the amount of 3,4-thiadiazole compound enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles; Compound chemical structure is in Table 1.

E.1,2,3-thiadiazoles connection-1, the mensuration of 3,4-thiadiazole compound on the impact of pathogenic fungi growth activity:

Of the present invention 1, 2, 3-thiadiazoles connection-1, 3, the mensuration of 4-thiadiazole compound bacteriostatic activity adopts thalli growth rate assay method, detailed process is: get 5 milligrams of sample dissolution in appropriate dimethyl formamide, then with containing the medicament that a certain amount of polysorbas20 emulsifier aqueous solution is diluted to 500 ug/ml, reagent agent is respectively drawn under aseptic condition in 1 milliliter of injection culture dish, add respectively again 9 milliliters of substratum, make 50 ug/ml pastille flat boards after shaking up, do blank with the flat board that adds 1 milliliter of aqua sterilisa, cut the bacterium dish with the punch tool of 4 millimeters of diameters along the mycelia outer rim, move on the pastille flat board, being equilateral triangle puts, every processing repeats 3 times, culture dish is placed in 24 ± 1 degrees centigrade of constant incubators and cultivates, colony diameter to be contrasted expands to 2-3 centimetre of " Invest, Then Investigate " and respectively processes bacterium dish expansion diameter, average, relatively calculate relative bacteriostasis rate with blank, comprise frequently seen plants pathogenic bacteria on various agricultural for the examination bacterial classification, 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), GZ: fusarium graminearum (Gibberella zeae), PI: phytophthora infestans (Phytophthora infestans (Mont.) de Bary), PP: Botryosphaeria berengeriana f. sp (Physalosporapiricola), PS: Rhizoctonia solani Kuhn (Pallicularia sasakii), RC: Rhizoctonia cerealis (Rhizoctonia cerealis), SS: Sclerotinia sclerotiorum (Sclerotinia sclerotiorum), these pathogenic fungies can represent the kind ， of most of pathogenic bacteria of the actual generation in field in China's agriculture production take the mould azoles of Evil as the contrast medicament.

F. of the present invention 1,2,3-thiadiazoles connection-1, the mensuration of 3,4-thiadiazole compound inducing anti-disease activity:

Of the present invention 1,2,3-thiadiazoles connection-1, the active screening method of 3,4-thiadiazole compound evoking tobacco resisting tobacco mosaic virus (TMV) is as follows: the mensuration of in vitro directly antiviral activity adopts half leaf method to carry out, it is the common cigarette that seedling age is consistent that live body is induced, 3 basins are one group, cigarette seedling respectively at inoculation pre-treatment in first 7 days, processing mode comprises: spray test compound solution 2 to 3 times, each 10 milliliters, or soil treatment, each 10 milliliters, the 7th day frictional inoculation TMV on the tobacco leaf newly grown, after the cigarette seedling is placed under its growth optimal temperature and illumination and cultivates 3 days, check incidence, comprehensive scab number is calculated as follows out the inducing anti-disease toxic effect fruit of test compound to TMV, 3 repetitions are established in each processing, 2 kinds of contrast minute blank and the contrasts of standard chemicals treatment, select the induced resistance of plant activiator contrast medicament that tiadinil (TDL) (purity is greater than 99.5%) is standard, the positive control medicament that the Ningnanmycin of take is antiviral activity, reference literature Fan Z.J. simultaneously, et al.J.Agric.Food Chem., 2010,58 (5): 2630-2636 and Zuo X., et al.J.Agric.Food Chem., 2010,58 (5): the method that 2755-2762 describes is carried out the biological activity of compound to protection, passivation, treatment and the withered spot of half leaf of tobacco mosaic virus (TMV).

$R=\frac{\mathrm{CK}-I}{\mathrm{CK}}\×100$

Wherein, R is the effect of new compound to Resistance In Tobacco TMV, unit: %

The average withered spot number that CK is clear water contrast blade, unit: individual

The average withered spot number that I is the chemicals treatment rear blade, unit: individual;

G. of the present invention 1,2,3-thiadiazoles connection-1, the mensuration of 3,4-thiadiazole compound to the small cabbage moth insecticidal activity:

Of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound is as follows 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 ug/ml carries out, get former medicine sample and first use a small amount of acetone solution, then, with 0.5 ‰ Triton-100 aqueous solution dilutions, the 0.5 ‰ Triton-100 aqueous solution are contrast, each concentration repeats for 3 times, 10 examination worms of each re-treatment; Get fresh free of contamination cabbage leaves, soaked for 10 seconds in liquid, after indoor drying (approximately 2 hours), put into the culture dish of 9 centimetres of diameters, small cabbage moth 2 instar larvaes that access size respectively is basically identical, tighten and be placed in small cabbage moth constant temperature insectary with bungee, 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 fluorine pyridine urea.

H. of the present invention 1,2,3-thiadiazoles connection-1, the mensuration of 3,4-thiadiazole compound to the mosquito larvae insecticidal activity:

Of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound is as follows to the screening method of mosquito larvae insecticidal activity: culex pipiens pallens (Culex pipiens pallens), the normal population of indoor feeding; Take test compound approximately 2 milligrams in the penicillin medicine bottle, add 10 milliliters of acetone, the mother liquor that sample is mixed with 200 ug/ml is dissolved in vibration; Get 2.5 milliliters of mother liquors in 100 ml beakers that fill 87.5 ml waters, choose mosquito larvae at the beginning of 10 4 ages, pour in the lump in beaker together with 10 milliliters of feeding liquids, its liquor strength is 5 ug/ml; The solution with water of 5 ug/ml can be diluted to the liquid of 2 ug/ml.It is 25 degrees centigrade of cultivations that the solution of handling well is put into to indoor maintenance temperature together with the beaker of mosquito larvae, and check result after 24 hours, till observing all larvae pupations; The aqueous solution that contains 1 milliliter of acetone of take is blank; Add a small amount of mosquito feed and sucking-off tumbler every day, and the moisture evaporated in supplementary beaker (5 milliliters/day), until mosquito larvae is all dead or pupate; Most larvas pupated in 8 days; With the positive contrast of fluorine pyridine urea.

The invention has the beneficial effects as follows: the present invention is to 1,2,3-thiadiazoles connection-1,3, that the 4-thiadiazole compound has carried out is antibacterial, the mensuration of inducing anti-disease activity and anti-phytoviral activity and insecticidal activity, this compounds can be used for the control of disease, insect pest and the virus disease in agriculture field, field of forestry, gardening field, can, for the preparation of sterilant, antiviral agent, activating plants agent, sterilant, also can comprise with the agricultural chemicals of commodity that sterilant, sterilant, anti-plant virus agent, activating plants agent are used in combination.

The present invention will more specifically describe 1 by specific preparation and biological activity determination embodiment, 2,3-thiadiazoles connection-1,3, synthetic and biological activity and the application thereof of 4-thiadiazole compound, but described embodiment is only for illustrating the present invention, unrestricted the present invention, especially its biological activity only illustrate, and unrestricted this patent, embodiment is as follows:

Embodiment 1

Preparation and the Structural Identification of compound WSX-9:1-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide

In 100 milliliters of round-bottomed flasks, add the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine (5 grams, 31.6 mmole), concentrated hydrochloric acid (6.8 gram), water (30 milliliters) and dry potassium sulfocyanate (4.6 grams, 47.5 mmole), under induction stirring, the oil bath heating is 90～100 degrees centigrade, approximately, after 1 hour, has a large amount of white solids to separate out, continue reacting by heating 3 hours, stopped reaction, cooling rear suction filtration, and use respectively dilute sodium bicarbonate solution and water washing, obtain pure white solid product, yield 85% after oven dry; Fusing point: 183-185 degree centigrade; Carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-dd ₆), chemical shift: 12.45 (s, 1H, CONH), 9.03 (s, 1H, CSNH), 7.68 (s, 2H, NH ₂), 2.93 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 2

Compound WSX-10:2-amino-5-(4-methyl isophthalic acid, 2,3-thiadiazoles 5-yl)-1,3, the preparation of 4-thiadiazoles and Structural Identification

Add 1-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide (3.6 grams, 16.6 mmoles), the vitriol oil (10 milliliters), under room temperature, stir 6 hours, then by 80 milliliters of frozen water of reaction solution impouring, the ammoniacal liquor with 25% is regulated pH value to 9～10, separates out a large amount of yellow solids, standing rear suction filtration, and difference water and washing with alcohol, obtain pure product, yield 90% after oven dry; Fusing point: 246-248 degree centigrade; Carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 7.87 (s, 2H, NH ₂), 2.85 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 3

Compound WSX-59:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-4 methyl isophthalic acids, the preparation of 2,3-thiobizole formanide and Structural Identification

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.21 gram, 1.1 mmole), methylene dichloride (15 milliliters) and triethylamine (0.22 gram, 2.2 mmole), by the 4-methyl isophthalic acid, 2, 3-thiadiazoles-5-formyl chloride (0.27 gram, 1.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 5 hours, TLC plate monitoring raw material has reacted, suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 60%, fusing point: 240 degrees centigrade (decomposition), carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 7.71 (s, 1H, NH), 2.97 (s, 3H, thiadiazolyl-CH ₃), 2.91 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 4

Compound WSX-64:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of cyclohexyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.4 gram, 2 mmoles), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by cyclohexyl formyl chloride (0.44 gram, 3 mmoles) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, separate out a large amount of light yellow solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 65%, fusing point: 246-247 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 12.93 (s, 1H, NH), 2.94 (s, 3H, thiadiazolyl-CH ₃), 2.55-2.63 (m, 1H, cyclohexyl-H), 1.19-1.88 (m, 10H, cyclohexyl-H).

Embodiment 5

Compound WSX-65:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of cyclobutylmethyl acid amides

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.4 gram, 2 mmoles), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by cyclobutylmethyl acyl chlorides (0.35 gram, 3 mmoles) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, separate out a large amount of brown solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 73%, fusing point: 218-219 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 12.89 (s, 1H, NH), 3.43-3.47 (m, 1H, cyclobutyl-H), 2.95 (s, 3H, thiadiazolyl-CH ₃), 1.84-2.29 (m, 6H, cyclobutyl-H).

Embodiment 6

Compound WSX-66:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-pyridinyl carboxamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.4 gram, 2 mmoles), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by pyridine-4-formyl chloride (0.42 gram, 3 mmoles) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 4 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 54%, fusing point: 245 degrees centigrade (decomposition), carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.95 (s, 1H, NH), 8.93 (d, 2H, J=5.6Hz, pyridyl-H), 8.10 (d, 2H, J=5.6Hz, pyridyl-H), 3.05 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 7

Compound WSX-133:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-trifluoromethyl benzamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.4 gram, 2 mmoles), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), will be to trifluoromethyl benzoyl chloride (0.62 gram, 3 mmoles) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, separate out a large amount of white solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 60%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.79 (s, 1H, NH), 8.33 (d, 2H, J=7.6Hz, Ph-H), 7.97 (d, 2H, J=8.0Hz, Ph-H), 2.99 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 8

Compound WSX-135:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-3, preparation and the Structural Identification of 6-dichloro-2-pyridyl base methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 3, 6-dichloropyridine-2-formyl chloride (0.56, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, separate out a large amount of light brown solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 52%, fusing point: 218-220 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.90 (s, 1H, NH), 8.27 (d, 1H, J=8.8Hz, pyridyl-H), 7.86 (d, 1H, J=8.8Hz, pyridyl-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 9

Compound WSX-136:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-ethylphenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by p-ethylbenzoyl chloride (0.45 gram, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 67%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.45 (s, 1H, NH), 8.09 (d, 2H, J=8.0Hz, Ph-H), 7.43 (d, 2H, J=8.0Hz, Ph-H), 2.97 (s, 3H, thiadiazolyl-CH ₃) 2.70 (q, 2H, J=7.6Hz, CH ₂), 1.22 (t, 3H, J=7.6Hz, CH ₂ cH ₃ ).

Embodiment 10

Compound WSX-137:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 5-methyl-3-(2-chloro-phenyl-)-4-isoxazolyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 5-methyl-3-(2-chloro-phenyl-)-isoxazoles-4-formyl chloride (0.69 gram, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 76%, fusing point: 121-123 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.44 (s, 1H, NH), 7.52-7.63 (m, 4H, Ph-H), 2.92 (s, 3H, thiadiazolyl-CH ₃), 2.75 (s, 3H, isoxazolyl-CH ₃).

Embodiment 11

Compound WSX-139:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 5-methyl-3-phenyl-4-isoxazolyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 5-methyl-3-phenyl-isoxazole azoles-4-formyl chloride (0.55 gram, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, separate out a large amount of white solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 78%, fusing point: 248-250 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.19 (s, 1H, NH), 7.64 (d, 2H, J=6.4Hz, Ph-H), 7.51-7.56 (m, 3H, Ph-H), 2.74 (s, 3H, thiadiazolyl-CH ₃), 2.65 (s, 3H, isoxazolyl-CH ₃).

Embodiment 12

Compound WSX-140:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-fluorophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), will be to fluorobenzoyl chloride (0.43 gram, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, separate out a large amount of white solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 83%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.57 (s, 1H, NH), 8.24 (q, 2H, J=8.4Hz, Ph-H), 7.45 (t, 2H, J=8.6Hz, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 13

Compound WSX-141:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-2, preparation and the Structural Identification of 2-dimethyl-3-(2-methyl-1-propylene base)-cyclopropyl carboxamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 2, 2-dimethyl-3-(2-methyl-1-propylene base)-cyclopropyl formyl chloride (0.5 gram, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 75%, fusing point: 208-209 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.18 (s, 1H, NH), 5.02 (d, 1H, J=7.6Hz, CH=C), 2.94 (s, 3H, thiadiazolyl-CH ₃), 2.13-2.16 (m, 1H, cHcH=C), 1.83 (d, 1H, J=5.6Hz, CHC=O), 1.71 (s, 3H, CH=CH cH ₃ ), 1.67 (s, 3H, CH=CH cH ₃ ), 1.23 (s, 3H, cyclopropyl-CH ₃), 1.18 (s, 3H, cyclopropyl-CH ₃).

Embodiment 14

Compound WSX-148:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-3-(2,2 dichloroethylene)-2, preparation and the Structural Identification of 2-dimethyl cyclopropyl carboxamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.35 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 3-(2, 2 dichloroethylenes)-2, 2-dimethyl cyclopropyl formyl chloride (0.61 gram, 2.7 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 70%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.18 (s, 1H, NH), 6.31 (dd, 1H, J=8.8Hz, J=95.2Hz, CH=C), 2.94 (s, 3H, thiadiazolyl-CH ₃), 2.19-2.33 (m, 2H, 2cyclopropyl-H), 1.23-1.29 (m, 6H, 2cyclopropyl-CH ₃).

Embodiment 15

Compound WSX-152 (the former WSX-24 that is numbered): N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of phenyl formamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.25 gram, 1.3 mmole), methylene dichloride (20 milliliters) and triethylamine (0.25 gram, 2.5 mmole), by Benzoyl chloride (0.26 gram, 1.9 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 87%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.31 (s, 1H, NH), 8.17 (d, 2H, J=7.6Hz, Ph-H), 7.71 (t, 1H, J=7.4Hz, Ph-H), 7.60 (t, 2H, J=7.6Hz, Ph-H), 2.99 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 16

Compound WSX-158:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 2-fluorophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by o-fluoro-benzoyl chloride (0.4 gram, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continuing 8 hours TLC plate monitoring raw materials of room temperature reaction has reacted, separate out a large amount of white solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 83%, fusing point: 200-202 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.64 (s, 1H, NH), 7.83 (s, 1H, Ph-H), 7.01 (s, 1H, Ph-H), 7.41-7.46 (m, 2H, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 17

Compound WSX-160:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-chloro-phenyl-methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles 5-yl)-1,3,4-thiadiazoles (0.3 gram, 1.5 mmoles), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by parachlorobenzoyl chloride (0.44 gram, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, separate out a large amount of white solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product, yield 78% after oven dry; Fusing point:>250 degrees centigrade; Carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.64 (s, 1H, NH), 8.17 (d, 2H, J=8.4Hz, Ph-H), 7.69 (d, 2H, J=8.4Hz, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 18

Compound WSX-162:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-chloro-phenyl-methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by m-chlorobenzoyl chloride (0.44 gram, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 90%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.60 (s, 1H, NH), 8.18 (s, 1H, Ph-H), 8.06 (d, 1H, J=8.0Hz, Ph-H), 7.74 (d, 1H, J=8.0Hz, Ph-H), (7.60 t, 1H, J=8.0Hz, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 19

Compound WSX-164:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-fluorophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), fluorobenzoyl chloride (0.4 gram between inciting somebody to action, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 94%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.61 (s, 1H, NH), 7.95-8.00 (m, 2H, Ph-H), 7.65 (q, 1H, J=7.8Hz, Ph-H), 7.56 (s, 1H, J=8.2Hz, Ph-H), 2.96 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 20

Compound ZHJF-10:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-3, preparation and the Structural Identification of 5-difluorophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by 3, 5-difluoro benzoyl chloride (0.4 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 78%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.77 (s, 1H, NH), 7.92 (s, 2H, Ph-H), 7.70 (s, 1H, Ph-H), 3.01 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 21

Compound ZHJF-11:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 1-(4-fluorophenyl) methylformamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), will be to fluorophenyl phenyllacetyl chloride (0.38 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, suction filtration obtains pale solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 64%, fusing point: 245-246 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.26 (s, 1H, NH), 7.38 (q, 2H, J=8.2Hz, Ph-H), 7.17 (t, 2H, J=8.8Hz, Ph-H), 2.92 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 22

Compound ZHJF-17:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-trifluoromethyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by m-trifluoromethyl benzoyl chloride (0.48 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains the near-white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 59%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.77 (s, 1H, NH), 8.53 (s, 1H, Ph-H), 8.40 (d, 1H, J=7.6Hz, Ph-H), 8.06 (d, 1H, J=7.6Hz, Ph-H), (7.84 t, 1H, J=8.0Hz, Ph-H), 2.97 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 23

Compound ZHJF-19:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 1-(4-chloro-phenyl-) methylformamide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by rubigan phenyllacetyl chloride (0.43 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 62%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.29 (s, 1H, NH), 7.39 (q, 4H, J=8.2Hz, Ph-H), 3.91 (s, 2H, CH ₂), 2.91 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 24

Compound ZHJF-24:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-nitrophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by paranitrobenzoyl chloride (0.43 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 58%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.89 (s, 1H, NH), 8.38 (q, 4H, J=8.8Hz, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 25

Compound ZHJF-25:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-3, preparation and the Structural Identification of 5-3,5-dimethylphenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by 3, 5-dimethyl benzoyl chloride (0.39 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 83%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.39 (s, 1H, NH), 7.79 (s, 2H, Ph-H), 7.34 (s, 1H, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃), 2.37 (s, 6H, 2ph-CH ₃).

Embodiment 26

Compound ZHJF-27:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-aminomethyl phenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by m-methyl benzoyl formyl chloride (0.36 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 84%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.44 (s, 1H, NH), 7.98 (s, 1H, Ph-H), 7.94 (d, 1H, J=7.2Hz, Ph-H), 7.45-7.52 (m, 2H, Ph-H), 2.97 (s, 3H, thiadiazolyl-CH ₃), 2.41 (s, 3H, ph-CH ₃).

Embodiment 27

Compound ZHJF-30:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 4-p-methoxy-phenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by anisoyl chloride (0.39 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 64%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.33 (s, 1H, NH), 8.17 (d, 2H, J=8.4Hz, Ph-H), 7.12 (d, 2H, J=8.4Hz, Ph-H), 3.87 (s, 3H, OCH ₃), 2.97 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 28

Compound ZHJF-32:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-nitrophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.8 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by m-nitrobenzoyl chloride (0.43 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 57%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.91 (s, 1H, NH), 9.01 (s, 1H, Ph-H), 8.54 (t, 2H, J=8.8Hz, Ph-H), 7.88-7.92 (m, 1H, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 29

Compound ZHJF-35:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-3, preparation and the Structural Identification of 5-dichlorophenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by 3, 5-dichlorobenzoyl chloride (0.48 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 80%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.71 (s, 1H, NH), 7.85 (s, 1H, Ph-H), 7.79 (d, 1H, J=8.4Hz, Ph-H), 7.63 (q, 1H, J=8.4Hz, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 30

Compound WSX-233:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 2-trifluoromethyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by o-trifluoromethyl Benzoyl chloride (0.48 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 86%, fusing point: 189-190 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.78 (s, 1H, NH), 7.71-7.94 (m, 4H, Ph-H), 2.99 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 31

Compound WSX-238:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 2,4 dichloro benzene base methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by 2, 4-dichlorobenzoyl chloride (0.52 gram, 2.5 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 77%, fusing point: 216-217 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.74 (s, 1H, NH), 7.83 (s, 1H, Ph-H), 7.01 (s, 1H, Ph-H), 7.41-7.46 (m, 2H, Ph-H), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 32

Compound WSX-251:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 2-aminomethyl phenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by o-methyl-benzene formyl chloride (0.36 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 90%, fusing point: 201-203 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 12.79 (s, 1H, NH), 7.80 (d, 1H, J=7.6Hz, Ph-H), 7.48 (t, 1H, J=7.6Hz, Ph-H), 7.26 (t, 2H, J=8.4Hz, Ph-H), 2.96 (s, 3H, thiadiazolyl-CH ₃), 2.43 (s, 3H, ph-CH ₃).

Embodiment 33

Compound WSX-254:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 2-p-methoxy-phenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.4 gram, 4 mmoles), by o-methoxy benzoyl chloride (0.39 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 72%, fusing point: 232-233 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 12.82 (s, 1H, NH), 7.69 (d, 1H, J=7.6Hz, Ph-H), (7.61 t, 1H, J=8.0Hz, Ph-H), 7.24 (d, 1H, J=8.2Hz, Ph-H), (7.12 t, 1H, J=7.4Hz, Ph-H), 2.98 (s, 3H, OCH ₃), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 34

Compound WSX-263:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 3-p-methoxy-phenyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.27 gram, 1.4 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 2.8 mmole), by meta-methoxy Benzoyl chloride (0.34 gram, 2 mmoles) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 10 hours, TLC plate monitoring raw material has reacted, suction filtration obtains light yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 70%, fusing point>250 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.52 (s, 1H, NH), 7.74 (s, 2H, Ph-H), 7.50 (t, 1H, J=8.0Hz, Ph-H), 7.25 (t, 1H, J=8.4Hz, Ph-H), 3.86 (s, 3H, OCH ₃), 2.98 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 35

Compound WSX-265:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-the 5-methyl isophthalic acid, preparation and the Structural Identification of 2,3-thiadiazoles-4-base methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by the 5-methyl isophthalic acid, 2, 3-thiadiazoles-4-formyl chloride (0.37 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 6 hours, TLC plate monitoring raw material has reacted, suction filtration obtains white solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 85%, fusing point:>250 degrees centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.93 (s, 1H, NH), 3.00 (s, 3H, thiadiazolyl-CH ₃), 2.96 (s, 3H, thiadiazolyl-CH ₃).

Embodiment 36

Compound WSX-270:N-[5-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-yl)-1,3,4-thiadiazoles-2-yl]-preparation and the Structural Identification of 5-ethyl-1-methyl-3-pyrazolyl methane amide

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2, 3-thiadiazoles 5-yl)-1, 3, 4-thiadiazoles (0.3 gram, 1.5 mmole), methylene dichloride (20 milliliters) and triethylamine (0.3 gram, 3 mmoles), by 5-ethyl-1-methylpyrazole-3-formyl chloride (0.4 gram, 2.3 mmole) be dissolved in methylene dichloride (5 milliliters), under stirring at room, slowly drop in reaction solution, drip and finish, continue room temperature reaction 8 hours, TLC plate monitoring raw material has reacted, separate out a large amount of yellow solids after mother liquor is concentrated, suction filtration, use respectively dilute hydrochloric acid, water and methanol wash, obtain pure product after oven dry, yield 74%, fusing point: 179-181 degree centigrade, carry out ¹the mensuration of HNMR, ¹hNMR (solvent: DMSO-d ₆), chemical shift: 13.09 (s, 1H, NH), 6.88 (s, 1H, pyrazolyl-H), 3.88 (s, 3H, NCH ₃), 2.96 (s, 3H, thiadiazolyl-CH ₃), 2.69 (q, 2H, J=7.0Hz, CH ₂), 1.24 (t, 3H, J=7.0Hz, C H ₂ cH ₃ ).

Embodiment 37

Of the present invention 1,2,3-thiadiazoles connection-1, the bacteriostatic activity of 3,4-thiadiazole compound:

Title and the code name of the frequently seen plants pathogenic fungi of the present invention's test comprise AS: tomato early blight bacterium (Alternaria solani); BC: botrytis cinerea pers (Botrytis cinerea); CA: peanut Cercospora bacteria (Cercospora arachidicola); GZ: fusarium graminearum (Gibberella zeae); PI: phytophthora infestans (Phytophthora infestans (Mont.) de Bary); PP: Botryosphaeria berengeriana f. sp (Physalosporapiricola); PS: Rhizoctonia solani Kuhn (Pellicularia sasakii); RC: Rhizoctonia cerealis (Rhizoctonia cerealis); SS: Sclerotinia sclerotiorum (Sclerotinia sclerotiorum), these bacterial classifications have good representativeness, can represent the kind of most of pathogenic bacteria that in agriculture production, field occurs.Thalli growth rate method measurement result is in Table 2, table 2 shows, the synthetic part of compounds of the present invention has germicidal action in various degree to the growth of the part pathogenic fungi measured: when 50 ug/ml, and compound WSX-59, WSX-140, WSX-141, WSX-238, WSX-270, ZHJF-24 and the ZHJF-32 fungicidal activity to SS; The fungicidal activity of compound WSX-137 to AS; The fungicidal activity of compound WSX-141 to CA; Compound WSX-139, WSX-251 and the ZHJF-35 fungicidal activity to PP; The fungicidal activity of compound WSX-139 to BC; Compound WSX-59, WSX-137 and the WSX-270 fungicidal activity to RC; Compound WSX-133, WSX-135 and WSX-136 all are greater than 60% to the fungicidal activity of PS.Have no the similar compound report with fungicidal activity, the present invention has found the fungicidal activity of this compounds first.The commercial three azoles fungicide Evil mould azoles different from the compounds of this invention structure are when 50 ug/ml, and fungicidal activity is 100%.

Embodiment 38: of the present invention 1,2, and 3-thiadiazoles connection-1, the insecticidal activity of 3,4-thiadiazole compound

Bioassay results is in Table 2, table 2 shows, the major part 1 that the present invention synthesizes, 2,3-thiadiazoles connection-1,3,4-thiadiazole compound has good insecticidal activity, activity for small cabbage moth: when 200 ug/ml, the insecticidal activity of compound WSX-64 and WSX-152 (WSX-24) is respectively 46.15% and 76.92%; When 400 ug/ml, the insecticidal activity of compound WSX-141 and ZHJF-10 is respectively 100% and 97.37%.Up till now, have no the report of the compound insecticidal activity of homogeneous structure, owing to there is no commercial 1,2,3-thiadiazoles connection-1, the kind of 3,4-thiadiazoles, adopt the medicament fluorine pyridine urea contrast of other structure types, it is when 400 ug/ml and 200 ug/ml, and insecticidal activity is 100%.When 5 ug/ml, compound WSX-65, WSX-136, WSX-141, WSX-160, WSX-162, WSX-164, ZHJF-11, ZHJF-19, ZHJF-25, ZHJF-27, ZHJF-30, ZHJF-35, WSX-254 and WSX-263 are greater than 60% to the insecticidal activity of mosquito larvae; Up till now, have no the report of the compound insecticidal activity of homogeneous structure, owing to there is no commercial 1,2,3-thiadiazoles connection-1, the kind of 3,4-thiadiazoles, adopt the medicament fluorine pyridine urea contrast of other structure types, fluorine pyridine urea is when 5 ug/ml, and insecticidal activity is 100%.The present invention has found the insecticidal activity of this compounds first.

Embodiment 39: of the present invention 1,2, and 3-thiadiazoles connection-1, the antiviral activity of 3,4-thiadiazole compound

Bioassay results shows, the major part 1 that the present invention synthesizes, 2,3-thiadiazoles connection-1,3,4-thiadiazole compound has good activity of resisting tobacco mosaic virus, and the withered spot method of half leaf of all compounds is measured activity and all is less than 30%, but the inactivate activity of all compounds is all more than 60%, and the inactivate activity of corresponding control compound Ningnanmycin is 50%; The therapeutic activity of compound of the present invention is also below 30%, but the activity of the anti-TMV of evoking tobacco of compound WSX-64, WSX-65, WSX-136, WSX-141, WSX-152, WSX-160, WSX-162, WSX-164, ZHJF-10, ZHJF-11, ZHJF-19, ZHJF-25, ZHJF-27, ZHJF-30, ZHJF-35, WSX-254 and WSX-263 all is greater than 55%, and the induced activity of corresponding control compound Ningnanmycin is 40%.Up till now, have no the compound of homogeneous structure to the inactivate activity of TMV and the activity report of the anti-TMV of evoking tobacco, the present invention has found the antiviral activity of this compounds first.

Embodiment 40

Of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound and insecticide composition prepare desinsection, disease-resistant and desinsection, the application of activating plants agent in preventing and treating agricultural, forestry, gardening plant disease, insect pest

Of the present invention 1,2,3-thiadiazoles connection-1,3, the total quality percentage composition of 4-thiadiazole compound in composition is 1%-90%, of the present invention 1,2,3-thiadiazoles connection-1, the ratio of 3,4-thiadiazole compound and commercially available agricultural chemical is mass percent 1%: 99% to 99%: 1%, can directly be watered rear spraying, comprise the upper acceptable solvent of agricultural and emulsifying agent and solubility promoter and synergistic agent etc. in its preparation, the formulation of composition processing is selected from wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse any one in dense dose, seed treatment emulsion, aqueous emulsion, large granula, granule, microemulsion, oil-suspending agent, finish, the seed with coated pesticidal, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules, 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, the east mole cricket, rice thrips, onion thrips, greenhouse thrips, haplothrips aculeatus, Mai Jian manages 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, Didesmococcus koreanus Borchs, pear lace bug, the banana lace bug, thin corner piece stinkbug, Orius minutus, 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, the apple Spilonota lechriaspis, brown belt length leaf roller, Adoxophyes cyrtosema, striped rice borer, bean-pod borer, Pyrausta nubilalis (Hubern)., yellow rice borer, Oeobia undalis, Cnaphalocrocis medinali(rice leaf roller), the 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 point diamond drill, black cutworm, large cutworm, yellow cutworm, steal poison moth, gypsymoth, palaearctic sweet potato, greenish brown hawk moth, the straight burr rice hesperiidae, pelopidas mathias, the oranges and tangerines swallowtail butterfly, Common Mormon, small white, pyrameis indica, the yellow a kind of butterfly harmful to crop plants of ramie, the beans blister beetle, the 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, gold edge buprestid beetle, tenebrio molitor, dark mealworm, red flour beetle, confused flour beetle, the verdigris different beetle, H. parallela, holotrichia oblita, mulberry borer, longicorn beetle, nadezhdiella cantori, pink neck longicorn, large 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, the yellowish leukorrhea ichneumon wasp, armyworm white star ichneumon wasp, corn earworm is hanged the cocoon ichneumon wasp, 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, the melon trypetid, the latent fly of wheat leaf ash, Americal rice leaf miner, the black fly of diving of beans stalk, frit fly, plant fly, onion fly, the radish fly, full skirt chases after posts fly, Pyrausta nubilalis (Hubern). is strict posts fly, armyworm lacks Agricultural pests such as must posting fly, forestry pest, gardening pest insect and sanitary insect pest, controlling mode also comprises double controlling simultaneously, of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound can mix use with one or more in the sterilant of lower group: Chlorpyrifos 94, the inferior Nong in ground, acetamiprid, Affirm (Merck Co.), milbemectin, Avrmectin, pleocidin, fenvalerate, efficient fenvalerate, Cypermethrin, effective cypermethrin, lambda-cyhalothrin, Deltamethrin, Fenvalerate, the Beta-cyfloxylate, cyfloxylate, the Lambda-lambda-cyhalothrin, Permanone, permethrin, esbiothrin, cyhalothrin, bifenthrin, permethrin, ether chrysanthemum ester, flumethrin, fluvalinate, Provado, acetamiprid, Ti304, imidaclothiz, thiacloprid, Diacloden, clothianidin, MTI-446, clothianadin, Da Tenan, diflubenzuron, young urea goes out, Teflubenzuron, deinsectization is grand, HEXAFLUMURON, flufenoxuron, the pyridine worm is grand, lufenuron, the poisonous insect urea, penfluron, Noviflumuron, flucycloxuron, Novaluron, fluorine pyridine urea, Bay sir 6874, piperazine worm urea, Bistrifluron, furan tebufenozide, the worm hydrazides, chlorine worm hydrazides, methoxyfenozide, ring worm hydrazides, Rogor, omethoate, SD-1750, acephate, triazophos, Resitox, pyridaphenthione, isazofos, Ro 7-5050, SevinCarbaryl, Aphox, meta-tolyl-N-methylcarbamate (MTMC), isoprocarb, cartap, fenobucarb, leaf disperses, carbaryl, benfuracarb, carbosulfan, cartap, bromopropylate, hexythiazox, fenpyroximate, pyridaben, clofentezine, propargite, diafenthiuron, benfuracarb, pymetrozine, spiral shell mite ester, spiral shell worm ester, spiral shell worm ethyl ester, butene-fipronil, azocyclotin, Buprofezin, ethoprophos, ethiprole, the desinsection list, disosultap, Flubendiamide, chlorantraniliprole or tebufenpyrad, bromothalonil, pyrazinones, second mite azoles, tebufenpyrad, the young ketone of rattling away, Nylar, emaricin etc., the prevention effect of combination medicament is good, and drug effect is played stably, because compound of the present invention has good fungicidal activity and the long-living activity to the pathogenic fungi resistance of inducing plant, therefore, combination medicament also has good preventive effect to Plant diseases in the control insect pest of the plant, can also improve the immunological competence of plant, therefore, this based composition not only has the effect of desinsection, also there is sterilization and improve via plant immunity to obtain the effect of disease resistance and virus disease, composition can prepare sterilant, sterilant, antiviral agent and sterilant, activating plants agent, and its drug effect is played stably.

Embodiment 41

Of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound and sterilant combination preparation sterilization, the application of activating plants agent in preventing and treating agricultural, forestry, gardening plant virus disease

Bioassay results shows, of the present invention all 1,2,3-thiadiazoles connection-1, and 3,4-thiadiazole compound and existing sterilant are as diazosulfide, tiadinil, tisocromide, the first thiophene lures amine, isotianil, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-sodium formiate, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate, 5-brooethyl-1,2,3-thiadiazoles-4-ethyl formate, 5-iodomethyl-1,2,3-thiadiazoles-4-ethyl formate, 4-methyl-5-brooethyl-1,2, the 3-thiadiazoles, 4-methyl-5-iodomethyl-1,2, the 3-thiadiazoles, 5,5-dibromo methyl isophthalic acid, 2,3-thiadiazoles-4-ethyl formate, 4-brooethyl-1,2,3-thiadiazoles-5-ethyl formate, 4-iodomethyl-1,2,3-thiadiazoles-5-ethyl formate, 4-brooethyl-5-methyl isophthalic acid, 2,3-thiadiazoles, 4-iodomethyl-5-methyl isophthalic acid, 2,3-thiadiazoles, 4,4-dibromo methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate, the DL-beta-aminobutyric acid, virazole, antofine, Ningnanmycin or Whitfield's ointment, frost urea cyanogen, thiram, ziram, zinc manganese ethylenebisdithiocarbamate, phosethyl Al, thiophanate_methyl, m-tetrachlorophthalodinitrile, the enemy can be loose, procymidone, fenpropidin, thiophanate methyl, thiophanate, Metalaxyl-M, Whitfield's ointment, flumorph, dimethomorph, efficient metaxanin, efficient M 9834, two chlorine zarilamids, flusulfamide, the first flusulfamide, thiophene fluorine bacterium amine, fultolanil, tecloftalam, ring propionyl bacterium amine, cyflufenamid, fenhexamid, zarilamid, Silthiopham, furametpyr, the pyrrole metsulfovax, mandipropamid, zoxamide, fenfuram, carboxin, chlozolinate, RP-26019, Azoxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, SSF 126, orysastrobin, ZEN 90160, Strobilurin, oxime bacterium ester, enostroburin, alkene oxime amine, oxygen ring azoles, bromuconazole, SN-108266, difenoconazole, alkene azoles alcohol, efficient alkene azoles alcohol, epoxiconazole, RH-7592, fluquinconazole, fluzilazol, flutriafol, own azoles alcohol, imibenconazole, plant the bacterium azoles, metconazole, nitrile bacterium azoles, Topaze, Wocosin 50TK, prothioconazoles, simeconazoles, tebuconazole, tertraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, fuberidazole, imazalil, efficient imazalil, prochloraz, fluorine bacterium azoles, cyazofamid, fenamidone, the Evil imidazoles, pefurazoate, famoxadone, SYP-Z048, hymexazo, the spirit of Evil frost, Guardian, etridiazole, octhilinone, benthiozole, dodemorph, fenpropimorph, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyrifenox, ring pyridine bacterium amine, boscalid amine, fluopicolide, pyridine bacterium amine, cyprodinil, the fluorine mepanipyrim, ferimzone, mepanipyrim, phonetic mould amine, fenarimol, nuarimol, chinomethionate, dithianon, ethoxyquin, hydroxyquinoline, the third oxygen quinoline, benzene oxygen quinoline, the mould prestige of second, iprovalicarb, the benzene metsulfovax, Propamocarb, methasulfocarb, edifenphos, iprobenfos, pyrazophos, tolclofosmethyl, miewensu, kasugamycin, polyoxin, Polyoxin, validamycin, jingganmycin, Streptomycin sulphate, metaxanin, furalaxyl, M 9834, ofurace, mebenil, derosal, F-1991, thiophanate_methyl, triazolone, bupirimate, dimethirimol, the phonetic phenol of second, Difolatan, Vancide 89, Phaltan, Vinclozoline, fluoromide, dimetachlone, m-tetrachlorophthalodinitrile, isoprothiolane, Kitazine, bismerthiazol, quintozene, zinc manganese ethylenebisdithiocarbamate, zinc 1,2-propylene bisdithiocarbamate, fosetylaluminium, sulphur, Bordeaux mixture, copper sulfate, copper oxychloride, Red copper oxide, copper hydroxide, metrafenone, pencycuron, diclomezin, phthalide, pyroquilon, volution bacterium amine, tricyclazole, triforine, the pyridine of many fruits, the hot salt of biguanides, iminoctadine, dicloran, the benzene flusulfamide, the toluene flusulfamide, K-281, fenaminosulf, oxolinic acide, probenazole, bronopol, methyl iodide, metamsodium, enemy's line ester, dazomet, dichloroisopropyl ether, lythidathion, cadusafos, fensulfothion, thionazin, fenamiphos, ethoprophos, dichlofenthion, isazofos, fosthietan, oxamyl, aldicarb, carbofuran, sulfuryl fluoride, dichloropropylene, dichloro-isonicotinic acid, other known any any one or multiple combination can be used as in sterilant such as allyl isothiazole is used, of the present invention 1,2,3-thiadiazoles connection-1,3, the total quality percentage composition of 4-thiadiazole compound in composition is 1%-90%, of the present invention 1,2,3-thiadiazoles connection-1, the ratio of 3,4-thiadiazole compound and commercially available agricultural chemical is mass percent 1%: 99% to 99%: 1%, the prevention effect of medicament is good, and these compositions have certain synergism and summation action, does not find to have the composition of antagonistic action, above-mentioned composition can be used for the control of agricultural plants disease and gardening plant disease, controlling object comprises that more than 20 of the Achylas, Aphanomyces, pythium, phytophthora, Sclerospora, Plasmopara, Pseudoperonospora, Peronospora of Oomycete etc. belong to the diseases that produce, as other diseases of plurality of cereals crop, cash crop, gardening plant and the forestry plants such as seedling blight of rice, tomato root maize ear rot, the late blight of potato, black shank, millet Powdery Mildew, downy mildew of garpe, downy mildew of lettuce, cucumber downy mildew, cucumber anthracnose etc., because compound of the present invention has good fungicidal activity and inducing anti-disease activity, therefore, this based composition, when carrying out disease control, can improve the immunizing power of plant, the system that plant is produced pathogenic fungi obtains disease resistance, and this based composition can prepare the activating plants agent, the formulation of composition processing is selected from wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse any one in dense dose, seed treatment emulsion, aqueous emulsion, large granula, granule, microemulsion, oil-suspending agent, finish, the seed with coated pesticidal, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules.

The applicable crop of these compositions comprises that cereal (comprises paddy, wheat, barley, oat, corn, millet, Chinese sorghum etc.), tuber crops (comprise sweet potato, potato, cassava etc.), beans (comprises soybean, broad bean, pea, mung bean, red bean etc.) and fiber (cotton, crudefiber crop, silkworm and mulberry etc.), oil plant (peanut, rape, sesame, soybean, Sunflower Receptacle etc.), sugar material (beet, sugarcane etc.), beverage (tealeaves, coffee, cocoa etc.), hobby (tobacco leaf etc.), medicinal (ginseng, the bulb of fritillary etc.), the torrid zone (rubber, coconut, oil palm, sisal hemp etc.) food crop and the fruit such as, flowers, oil plant, sugar material and cotton, fiber crops, tea, tobacco, cash crop and the 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, the garden crops such as seedling and other garden crops are as tobacco (flue-cured tobacco, 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.), potato, wheat, corn, paddy rice, peanut, fruit tree, (apple, banana, citrus, peach, papaya), flowers (as orchid), potted landscape etc.

Embodiment 42

Of the present invention 1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound prepares antiviral agent, the application of activating plants agent in preventing and treating agricultural, forestry, gardening plant virus disease with the antiviral agent combination

1,2,3-thiadiazoles connection-1,3,4-thiadiazole compound and existing Antiphytoviral medicament diazosulfide, tiadinil, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-sodium formiate, the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate, 5-brooethyl-1,2,3-thiadiazoles-4-ethyl formate, 5-iodomethyl-1,2,3-thiadiazoles-4-ethyl formate, 4-methyl-5-brooethyl-1,2, the 3-thiadiazoles, 4-methyl-5-iodomethyl-1,2, the 3-thiadiazoles, 5,5-dibromo methyl isophthalic acid, 2,3-thiadiazoles-4-ethyl formate, 4-brooethyl-1,2,3-thiadiazoles-5-ethyl formate, 4-iodomethyl-1,2,3-thiadiazoles-5-ethyl formate, 4-brooethyl-5-methyl isophthalic acid, 2,3-thiadiazoles, 4-iodomethyl-5-methyl isophthalic acid, 2,3-thiadiazoles, 4,4-dibromo methyl isophthalic acid, 2,3-thiadiazoles-5-ethyl formate, the DL-beta-aminobutyric acid, virazole, antofine, Ningnanmycin, tisocromide, the first thiophene lures amine, isotianil or Whitfield's ointment, cytosintetidemycin, dichloro-isonicotinic acid, any one or multiple compounds combination in allyl isothiazole, the energy inducing plant produces the resistance of viral diseases of plants and the anti-TMV of the resistance of fungal disease, especially evoking tobacco or, for directly preventing and treating the activity of TMV, the applicable plant staple crop of inducing comprises these compositions: paddy, wheat, barley, oat, corn, millet, Chinese sorghum, sweet potato, potato, cassava, soybean, broad bean, pea, pea-pods, mung bean, red bean, cotton, crudefiber crop, silkworm and mulberry, peanut, rape, sesame, soybean, Sunflower Receptacle, beet, sugarcane, tealeaves, coffee, cocoa, tobacco leaf, tobacco, flue-cured tobacco, ginseng, the bulb of fritillary, rubber, coconut, oil palm, sisal hemp, fruit, flowers, oil plant, the sugar material, cotton, fiber crops, tea, Chinese medicinal materials, the plantation melon, really, tea, silkworm and mulberry, vegetables, various wild vegetable, bamboo shoots, flowers and ornamental plant, hops, medicinal material, pepper, seedling, garden crop, air-curing of tobacco leaves, suncured tabacco, vegetables, tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tube, beet, rape, green onion, garlic, watermelon, muskmelon, hami melon, pawpaw, potato, paddy rice, peanut, fruit tree, apple, banana, citrus, peach, papaya, orchid, potted landscape etc., virus disease comprises tobacco mosaic virus disease, various melon virus diseases, various solanaceous vegetables virus diseases, the beans virus disease, the Cruciferae virus disease, the grain and oil crop virus disease, cotton virus disease and various fruit tree virus diseases etc., wherein endanger serious mainly containing: tobacco virus, peppery pimento virus disease, tomato virus disease, Chinese cabbage virus disease, Virus Diseases of Rice comprises rice dwarf virus disease, yellow dwart, stripe virus disease, the fern leaf of tomato viral disease, pepper mosaic virus disease viral disease and tobacco veinal necrosis virus disease, maize dwarf mosaic, cauliflower mosaic virus, the oranges and tangerines virus disease, cymbidium mosaic virus, cybidium ring spot virus etc., the use of these compositions makes the immunizing power of crop self be improved, and has induced plant to produce the control to viral diseases of plants, also can produce the direct prevention effect of virus disease, be green eco-friendly novel pesticide formulation, therefore, these compositions can be preparation and the application of activating plants agent for Antiphytoviral medicament and inducing plant Antiphytoviral medicament.Of the present invention 1,2,3-thiadiazoles connection-1,3, the total quality percentage composition of 4-thiadiazole compound in composition is 1%-90%, of the present invention 1,2,3-thiadiazoles connection-1, the ratio of 3,4-thiadiazole compound and commercially available agricultural chemical is mass percent 1%: 99% to 99%: 1%; The formulation of composition processing is selected from wettable powder, sustained release dosage, pulvis, micro-capsule suspension, can disperse any one in dense dose, seed treatment emulsion, aqueous emulsion, large granula, granule, microemulsion, oil-suspending agent, finish, the seed with coated pesticidal, suspended emulsion agent, water-soluble granule, soluble thick agent, water-dispersible granules; All show addition or synergism between these compositions, when keeping fungicidal activity, the antiviral activity of its antiviral activity or inducing plant all is greater than the effect that any one compound is used separately; Find no the composition of antagonistic action, the drug effect lasting period of composition is long.

From the basic principles of chemistry, can know, 1,2,3-thiadiazoles connection-1,3, the 4-thiadiazole compound can be degraded and produces the 4-methyl isophthalic acid in plant with after the water molecules effect, 2,3-thiadiazoles-5-formic acid, also confirm that by relevant software prediction and test compound of the present invention can produce the 4-methyl isophthalic acid in the degraded of plant materials intracellular metabolite, 2,3-thiadiazoles-5-formic acid, bibliographical information confirms: 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formic acid has inducing plant and produces the resistance to the phytopathy original, can be used in the control of Plant diseases and viral diseases of plants.Therefore, these compositions have rationale for the preparation of Antiphytoviral medicament and inducing plant Antiphytoviral medicament.

Embodiment 43

Of the present invention 1,2,3-thiadiazoles connection-1, complete processing and the stability of 3,4-thiadiazole compound and commercially available agricultural chemical compound preparation

Of the present invention 1, 2, 3-thiadiazoles connection-1, 3, the mixed preparation complete processing of 4-thiadiazole compound and commercially available agricultural chemical is in Table 4, table 4 is visible, most medicament all can be processed according to the method for statement, the main component of liquid preparation is effective constituent and solubility promoter and tensio-active agent and synergistic agent, antifreezing agent, stablizer, other the component etc. such as thickening material or permeate agent, the composition of solid preparation mainly includes the effect composition, the upper acceptable adjuvant component of other agriculturals such as tensio-active agent and filler, preparation to processing carries out cold storage test, liquid preparation is placed 1 week without Precipitation at 0 ± 2 degree centigrade, solid preparation is placed 2 weeks at 54 ± 2 degrees centigrade, caking phenomenon does not appear in medicament, all preparations store the medicament drug effect of placement front and back without significant difference, mix the rate of decomposition of effective constituent in 5%, the medicament qualified stability is described.

Table 1 the present invention synthesize 1,2,3-thiadiazoles connection-1, the chemical structure of 3,4-thiadiazole compound

Table 2 the present invention synthesize 1,2,3-thiadiazoles connection-1, the fungicidal activity of 3,4-thiadiazole compound (%)

The measurement result that in table, data are 50 ug/ml

Table 31,2,3-thiadiazoles connection-1, the insecticidal activity of 3,4-thiadiazole compound (%)

Table 41,2,3-thiadiazoles connection-1,3,4-thiadiazole compound mixes the working method of using preparation with commercially available agricultural chemical

Claims (1)

1. join-1 containing 2,3-thiadiazoles, the synthetic method of 3,4-thiadiazole compound, its total synthetic route is as follows:

Wherein: R is selected from phenyl, the 4-methyl isophthalic acid, 2, 3-thiadiazoles-5-base, cyclobutyl, cyclohexyl, the 4-pyridyl, the 4-trifluoromethyl, 3, 6-dichloro-2-pyridyl base, the 4-ethylphenyl, 5-methyl-3-(2-chloro-phenyl-)-4-isoxazolyl, 5-methyl-3-phenyl-4-isoxazolyl, the 4-fluorophenyl, 2, 2-dimethyl-3-(2-methyl-1-propylene base)-cyclopropyl, 3-(2, 2 dichloroethylenes)-2, 2-dimethyl cyclopropyl, the 2-fluorophenyl, the 4-chloro-phenyl-, the 3-chloro-phenyl-, the 3-fluorophenyl, 3, the 5-difluorophenyl, 1-(4-fluorophenyl) methyl, the 3-trifluoromethyl, 1-(4-chloro-phenyl-) methyl, the 4-nitrophenyl, 3, the 5-3,5-dimethylphenyl, the 3-aminomethyl phenyl, the 4-p-methoxy-phenyl, the 3-nitrophenyl, 3, the 5-dichlorophenyl, the 2-trifluoromethyl, 2, the 4-dichlorophenyl, the 2-aminomethyl phenyl, the 2-p-methoxy-phenyl, the 3-p-methoxy-phenyl, the 5-methyl isophthalic acid, 2, 3-thiadiazoles-4-base, 5-ethyl-1-methyl-3-pyrazolyl,

Concrete steps are as follows:

A.4-methyl isophthalic acid, the preparation of 2,3-thiadiazoles-5-formyl hydrazine:

By 6.9 gram 4-methyl isophthalic acids, 2,3-thiadiazoles-5-ethyl formate and 44 mmole hydrazine hydrates join in 50 milliliters of there-necked flasks, reflux 10 hours, then stirred overnight at room temperature, reaction system yellowly solid, add 40 milliliters of sherwood oils to wash away the complete ester of unreacted, suction filtration, dry yellow solid 4.9 grams that obtain, yield 77.5%, the consumption of this compound enlarges in proportion or dwindles;

B.1-the preparation of (4-methyl isophthalic acid, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide:

In 100 milliliters of round-bottomed flasks, add the 4-methyl isophthalic acid, 2,3-thiadiazoles-5-formyl hydrazine 31.6 mmoles, concentrated hydrochloric acid 6.8 grams, 30 milliliters, water and dry potassium sulfocyanate 47.5 mmoles, under induction stirring, oil bath is heated to 90～100 degrees centigrade, approximately, after 1 hour, has a large amount of white solids to separate out, continue reacting by heating 3 hours, stopped reaction, cooling rear suction filtration, use respectively dilute sodium bicarbonate solution and water washing, obtain product sterling, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; The amount of synthetic 1-(4-methyl isophthalic acid, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles;

C.2-amino-5-(4-methyl isophthalic acid, 2,3-thiadiazoles 5-yl)-1,3, the preparation of 4-thiadiazoles:

Add 1-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles-5-carbonyl) thiosemicarbazide 16.6 mmoles, the vitriol oil are 10 milliliters, under room temperature, stir 6 hours, then by 80 milliliters of frozen water of reaction solution impouring, ammoniacal liquor with 25% is regulated pH value to 9～10, separate out a large amount of yellow solids, standing rear suction filtration, and difference water and washing with alcohol, obtain product sterling, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; Synthetic 2-amino-5-(4-methyl isophthalic acid, 2,3-thiadiazoles 5-yl)-1,3, the amount of 4-thiadiazoles enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles;

D.1,2,3-thiadiazoles connection-1, the preparation of 3,4-thiadiazole compound:

Add 2-amino-5-(4-methyl isophthalic acid in 100 milliliters of round-bottomed flasks, 2,3-thiadiazoles 5-yl)-1,3,4-thiadiazoles 1.1-2.0 mmole, methylene dichloride 15-20 milliliter and triethylamine 2.2-4 mmole, to replace acyl chlorides 1.5-2.5 mmole and be dissolved in 5 milliliters of methylene dichloride, slowly drop under stirring at room in reaction solution, and drip and finish, continue room temperature reaction 5 hours, TLC plate monitoring raw material has reacted, and suction filtration obtains yellow solid, suction filtration after mother liquor is concentrated, combining solid, use respectively dilute hydrochloric acid, water and methanol wash, obtain product sterling, calculated yield after oven dry; Carry out fusing point and ¹the mensuration of HNMR; Synthetic 1,2,3-thiadiazoles connection-1, the amount of 3,4-thiadiazole compound enlarges or dwindles by corresponding proportion; The volume of respective reaction container enlarges in proportion or dwindles.