CN107721997A

CN107721997A - Thiadiazole thiazolinone compound and its preparation method and application

Info

Publication number: CN107721997A
Application number: CN201710932057.9A
Authority: CN
Inventors: 甘春芳; 董新; 黄燕敏; 崔建国; 展军颜
Original assignee: Guangxi Teachers College
Priority date: 2017-10-10
Filing date: 2017-10-10
Publication date: 2018-02-23
Anticipated expiration: 2037-10-10
Also published as: CN107721997B

Abstract

The invention discloses a kind of thiadiazole thiazolinone compound, its chemical constitution is shown below：Wherein,

Description

Thiadiazole thiazolinone compound and its preparation method and application

Technical field

The present invention relates to agriculture chemicals fungicide field, specifically a kind of thiadiazole thiazolinone compound.

Background technology

In recent years, heterocyclic compound generally has good bioactivity, is risen in the initiative of novel pesticide and R＆D process The effect that must be studied.4- thiazoline ketone compounds are a kind of five-ring heterocycles chemical combination containing nitrogen-atoms and sulphur atom Thing, 4- thiazolines ketone compounds are even more to have preferable bioactivity, and such as antibacterial, anti-inflammatory, antitumor, antiviral biology are living Property.Due to the good biological activity of 4- thiazoline ketone compounds, make such compound that there is extensive research and application value, In chemistry, medicine, pesticide field by numerous studies and application, even more indispensable one during novel pesticide exploitation and initiative Point.

Thiazole ring is also a kind of important feature in heterocyclic compound, is widely used in pesticide research and plant protection neck Domain.And 1,3,4- thiadiazoles derivatives are also because there is the bioactivity such as weeding, sterilization, desinsection, plant growth regulating extensively to be closed for it Note, it always is a focus of environment friendly agricultural research.The thiazoles agricultural chemicals reported both at home and abroad continues to bring out, such as insecticide thiophene worm Piperazine, Fluensulfone；Bactericide Guardian, thiophene fluorine bacterium amine, probenazole, diclofop-methyl thiazole；Herbicide benzene metsulfovax and remove Careless safener solution grass amine etc..

The synthesis of bis-heterocyclic compounds and bioactivity research have become an important directions of heterocyclic pesticide.Such as sterilization Agent probenazole, herbicide hydroxyl humulone, azoles Sulfometuron Methyl, pyraflufen-ethyl, pesticide imidacloprid etc. are all to have listed the double heterocycle agricultures used Medicine.Double heterocyclic pesticides can increase its bioactivity by the collective effect of two heterocycles.

The content of the invention

It is an object of the invention to solve at least the above, and provide the advantages of at least will be described later.

It is a still further object of the present invention to provide a kind of thiadiazole thiazolinone compound.

It is a further object of the present invention to provide the preparation method of above-claimed cpd.

The further object of the present invention is to provide application of the above-claimed cpd in bactericide and insecticide.

In order to realize according to object of the present invention and further advantage, there is provided a kind of thiadiazole thiazolinone chemical combination Thing, it is characterised in that its chemical constitution is shown below：

Wherein,

Preferably, the preparation method is using thiosemicarbazide as raw material, is taken off under the conditions of sulphuric acid catalysis with formic acid Water ring is combined to the first intermediate product, the second intermediate product is then synthesized with chloracetyl chloride, then be cyclized under the effect of thiocyanic acid amine The 3rd intermediate product is synthesized, reacts to obtain thiadiazole by the 3rd compound and R1 finally by Knoevenagle condensation reactions Thiazolinone compound, wherein,

First intermediate product is 2- amido-1,3,4-thiadiazoles, and its structural formula is as follows：

Second intermediate product is 2- chloro acetylaminos -1,3,4- thiadiazoles -2- acetimides, and its structural formula is as follows：

3rd intermediate product is 2- (1,3,4- thiadiazoles -2- imino groups) -4- thiazolinones, and its structural formula is as follows：

Preferably, the first intermediate product is prepared as raw material using thiosemicarbazide to specifically include：Weigh 4.98~5.08g sulphur Be added to for semicarbazides in two neck flasks of circle, add 2.7~3.3mL formic acid, stirred at room temperature to pulpous state, then by 5.6~ 6.4mL concentrated hydrochloric acids are added dropwise in the neck flask of circle two with constant pressure separatory funnel, and 25~35min is dripped off, and continues to stir, by this Two neck flasks of circle are moved on on oil bath heating magnetic stirring apparatus, 4~5h are reacted at 105~115 DEG C, TLC detection reactions are to without raw material Point, stop reaction, after being cooled to room temperature, obtain coolant, and coolant is poured into frozen water, with concentrated ammonia liquor by body in frozen water It is that pH is adjusted to 7~8, after stand at low temperature at least 12h, the white powder that price separates out obtains producing among first through filtering, washing Thing, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1；

The second intermediate product is synthesized with chloracetyl chloride to specifically include：The intermediate products of 0.95~1.05g first are weighed, add circle In two neck flasks, dimethylformamides of the 20~30mL after the processing of steaming again is added, after the first intermediate product is completely dissolved, The triethylamine of 1.5~1.65mL dryings is added, is moved on under condition of ice bath, is measured 1~1.2mL chloracetyl chlorides and leaked with constant pressure addition Bucket is added drop-wise in reaction, and 25~35min is dripped off, and room temperature atmospheric agitation reacts 3.5~4.5h, TLC detections reaction to without raw material point, Stop reaction, reactant mixture is poured into 48~52mL frozen water, seals preservative film, at least 12h is stood under the conditions of 2~4 DEG C Afterwards, through filtering, washing, dry, obtain the second intermediate product, wherein, the detecting and tracking reagent that TLC is used be dichloromethane and Methanol, its volume ratio are 10:1, with 3 washings of distillation moisture for adding up to 30mL during washing；

The intermediate product of Cyclization the 3rd specifically includes under the effect of thiocyanic acid amine：Weigh among 0.15~0.25g second Product, it is added in two neck flasks of circle, adds 22~26mL and steam dimethylformamide again to being completely dissolved, then weigh 0.08 ~0.18g ammonium thiocyanates are added in the neck flask of circle two, and 3.5~4.5h, the reaction of TLC detecting and trackings are reacted under 75~85 DEG C of oil baths To without raw material point, stopping is reacted, reactant mixture is poured into 26~34g trash ices, seals up preservative film, quiet under the conditions of 2~4 DEG C At least 12h is put, through filtering, washing, dry, obtains the 3rd intermediate product, wherein, the detecting and tracking reagent that TLC is used is two Chloromethanes and methanol, its volume ratio are 10:1, with 3 washings of distillation moisture for adding up to 10mL during washing.

Preferably, the 3rd intermediate product is reacted to obtain with 4- cyanobenzaldehydes by Knoevenagle condensation reactions Thiadiazole thiazolinone compound specifically includes：Weigh the intermediate products of 0.06~0.16g the 3rd, 0.11~0.21g 4- cyanogen Benzaldehyde, 0.13~0.23g anhydrous sodium acetates, add in two neck flasks of circle, add 2~4mL acetic anhydrides and 3~5mL ice Acetic acid, stirred under the conditions of 100~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to original Shots disappear, and stop reaction, are cooled to room temperature, reactant is poured into 45~55mL frozen water, seals up preservative film, be put in 2~4 DEG C Refrigerator stands at least 12h, through filtering, washing, dry, obtains the first compound, wherein, the detecting and tracking reagent that TLC is used is equal For dichloromethane and methanol, its volume ratio is 10:1, first with adding up to 30mL 3 washings of distillation moisture during washing, then use 30mL 3 washings of methanol point are added up to, the chemical structural formula of the first compound is as follows：

Wherein,

Preferably, the 3rd intermediate product is reacted to obtain with 3- hydroxy benzaldehydes by Knoevenagle condensation reactions Thiadiazole thiazolinone compound specifically includes：Weigh the intermediate products of 0.15~0.25g the 3rd, 0.19~0.29g 3- hydroxyls Benzaldehyde, 0.28~0.38g anhydrous sodium acetates, add in round-bottomed flask, add 5~7mL acetic anhydrides, 7~9mL ice vinegar Acid, stirred under the conditions of 100~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without original Shots, stop reaction, be cooled to room temperature, then reactant mixture is poured into 45~55mL frozen water, seals up preservative film, in 2~4 At least 12h is stood under the conditions of DEG C, through filtering, washing, dry, obtains second compound, wherein, the detecting and tracking examination that TLC is used Agent is dichloromethane and methanol, and its volume ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, It is as follows with 3 washings of methanol point for adding up to 30mL, the chemical structural formula of second compound again：

Wherein,

Preferably, the 3rd intermediate product and 4- fluorobenzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.15~0.25g the 3rd, 0.31~0.41g anhydrous acetic acids Sodium, 233~237 μ L 4- fluorobenzaldehydes are measured, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7~9mL ice vinegar Acid, stirred under the conditions of 100~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without original Shots, stop reaction, be cooled to room temperature, then reactant mixture is poured into 45~55mL frozen water, seals up preservative film, in 2~4 At least 12h is stood under the conditions of DEG C, through filtering, washing, dry, obtains the 3rd compound, wherein, the detecting and tracking examination that TLC is used Agent is dichloromethane and methanol, and its volume ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, It is as follows with 3 washings of methanol point for adding up to 30mL, the chemical structural formula of the 3rd compound again：

Wherein,

Preferably, the 3rd intermediate product and 4-chloro-benzaldehyde are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：The intermediate products of 0.16~0.26g the 3rd are weighed, 0.20~0.30g is to chlorobenzene first Aldehyde, 0.28~0.39g anhydrous sodium acetates, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7~9mL glacial acetic acid, 100 Stirred under the conditions of~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without raw material point, Stop reaction, be cooled to room temperature, then pour into reactant mixture in 45~55mL frozen water, stood at least under the conditions of 2~4 DEG C 12h, through filtering, washing, dry, obtain the 4th compound, wherein, the detecting and tracking reagent that TLC is used be dichloromethane and Methanol, its volume ratio are 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then with adding up to 30mL's 3 washings of methanol point, the chemical structural formula of the 4th compound are as follows：

Wherein,

Preferably, the 3rd intermediate product and 2,5- 4-dihydroxy benzaldehyde are reacted by Knoevenagle condensation reactions Thiadiazole thiazolinone compound is obtained to specifically include：The intermediate products of 0.25~0.35g the 3rd are weighed, 0.27~0.38g's 2,5- 4-dihydroxy benzaldehydes, 0.30~0.41g anhydrous sodium acetates, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7 ~9mL glacial acetic acid, stirred under the conditions of 100~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking Reaction stops reaction, is cooled to room temperature, then pours into reactant mixture in 45~55mL frozen water, in 2~4 to without raw material point At least 12h is stood under the conditions of DEG C, through filtering, washing, dry, obtains the 5th compound, wherein, the detecting and tracking examination that TLC is used Agent is dichloromethane and methanol, and its volume ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, It is as follows with 3 washings of methanol point for adding up to 30mL, the chemical structural formula of the 5th compound again：

Wherein,

Preferably, the 3rd intermediate product and 4- dimethylaminobenzaldehydes are reacted by Knoevenagle condensation reactions Thiadiazole thiazolinone compound is obtained to specifically include：The intermediate products of 0.15~0.25g the 3rd are weighed, 0.25~0.35g's 4- dimethylaminobenzaldehydes, 0.28~0.38g anhydrous sodium acetates, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7 ~9mL glacial acetic acid, stirred under the conditions of 100~110 DEG C of oil baths to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking Reaction stops reaction, is cooled to room temperature, then pours into reactant mixture in 45~55mL frozen water, seal up guarantor to without raw material point Fresh film, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtain the 6th compound, wherein, what TLC was used Detecting and tracking reagent is dichloromethane and methanol, and its volume ratio is 10:1, first with the distilled water for adding up to 30mL during washing Divide 3 washings, then it is as follows with 3 washings of methanol point for adding up to 30mL, the chemical structural formula of the 6th compound：

Wherein,

Preferably, application of the described thiadiazole thiazolinone compound in disinfectant use in agriculture.

Preferably, application of the described thiadiazole thiazolinone compound in insecticide.

The present invention can at least reach following beneficial effect：

1,3,4- thiadiazoles is synthesized one kind by the present invention using active structure splicing principle with 4- thiazolinone structures to form Bis-heterocyclic compounds with thiazole ring and thiazolinone, double heterocyclic pesticide derivatives of good activity are obtained, filter out high work Property, hypotoxicity, the few environment friendly agricultural new varieties of pollution.

This invention describes six kinds of specific thiadiazole thiazolinone compounds, preparation method step of the present invention It is few, it is simple to operate, substantial amounts of time and cost can be saved in actual production, it is good in economic efficiency.From data as can be seen that benzene There is base substitution thiadiazole thiazolinone compound good suppression to make to the growing multiplication of Alternaria solani, Pyricularia oryzae etc. With, can as pesticide intermediate be applied to different disinfectant use in agriculture manufacture and purposes.Insecticide application can also be used as simultaneously In the plantation such as rice, rape.

Further advantage, target and the feature of the present invention embodies part by following explanation, and part will also be by this The research and practice of utility model and be understood by the person skilled in the art.

Embodiment

With reference to embodiment, the present invention is described in further detail, to make those skilled in the art with reference to specification Word can be implemented according to this.

It should be noted that experimental method described in following embodiments, is conventional method unless otherwise specified, institute Reagent and material are stated, unless otherwise specified, is commercially obtained.

Specifically included Step 1: preparing the first intermediate product as raw material using thiosemicarbazide：Weigh 4.98g thiosemicarbazides It is added in two neck flasks of circle, adds 2.7mL formic acid, stirs at room temperature to pulpous state, then by 5.6mL concentrated hydrochloric acids constant pressure point Liquid funnel is added dropwise in the neck flask of circle two, and 25min is dripped off, and continues to stir, and the neck flask of circle two is moved on into oil bath heating On magnetic stirring apparatus, 4h is reacted at 105 DEG C, TLC detections reaction stops reaction, after being cooled to room temperature, obtained cold to without raw material point But liquid, and coolant is poured into frozen water, system pH is adjusted to 7~8 with concentrated ammonia liquor in frozen water, stand at low temperature at least 12h Afterwards, the white powder that price separates out obtains the first intermediate product through filtering, wash, wherein, the detecting and tracking reagent that TLC is used It is dichloromethane and methanol, its volume ratio is 10:1, i.e. V_{Dichloromethane}:V_Methanol=10:1；

First intermediate product is 2- amido-1,3,4-thiadiazoles, and it is water white transparency bulk crystals, and its structural formula is as follows：

Specifically included Step 2: synthesizing the second intermediate product with chloracetyl chloride：The intermediate products of 0.95g first are weighed, are added In two neck flasks of circle, dimethylformamides of the 20mL after the processing of steaming again is added, after the first intermediate product is completely dissolved, then The triethylamine that 1.5mL is dried is added, is moved on under condition of ice bath, is measured 1mL chloracetyl chlorides and be added drop-wise to reaction with constant pressure funnel In, 25min is dripped off, and room temperature atmospheric agitation reaction 3.5h, TLC detection reaction stops reaction, by reactant mixture to without raw material point Pour into 48mL frozen water, seal preservative film, after at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtain the Two intermediate products, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, washing When with the washing of distillation moisture 3 times for adding up to 30mL；

Second intermediate product is 2- chloro acetylaminos -1,3, and 4- thiadiazoles -2- acetimides, it is white powder, and it is tied Structure formula is as follows：

Step 3: the intermediate product of Cyclization the 3rd specifically includes under the effect of thiocyanic acid amine：Weigh among 0.15g second Product, it is added in two neck flasks of circle, adds 22mL and steam dimethylformamide again to being completely dissolved, then weigh 0.08g sulphur Ammonium cyanate is added in the neck flask of circle two, and 3.5h is reacted under 75 DEG C of oil baths, and TLC detecting and trackings react to without raw material point, stopped anti- Should, reactant mixture is poured into 26g trash ices, seals up preservative film, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing Wash, dry, obtain the 3rd intermediate product, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, its volume Than being 10:1, with 3 washings of distillation moisture for adding up to 10mL during washing.

3rd intermediate product is 2- (1,3,4- thiadiazoles -2- imino groups) -4- thiazolinones, and it is white powder, and it is tied Structure formula is as follows：

Step 4: the 3rd intermediate product and 4- cyanobenzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.06g the 3rd, 0.11g 4- cyanobenzaldehydes, 0.13g Anhydrous sodium acetate, add circle two neck flasks in, add 2mL acetic anhydrides and 3mL glacial acetic acid, stirred under the conditions of 100 DEG C of oil baths to It is completely dissolved, continues to react 5.5h, TLC detecting and trackings react to raw material point and disappeared, and stop reaction, are cooled to room temperature, will react Thing is poured into 45mL frozen water, seals up preservative film, is put in 2~4 DEG C of refrigerators and is stood at least 12h, through filtering, washing, drying, obtains the One compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, during washing 3 washings of distillation moisture for adding up to 30mL are first used, then divide 3 washings, the change of the first compound with the methanol for adding up to 30mL It is as follows to learn structural formula：

Wherein,

Step 1: Step 2: step 3 is in the same manner as in Example 1, the dosage and experiment parameter of each material are also identical, difference It is：

Step 4: the 3rd intermediate product and 3- hydroxy benzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.15g the 3rd, 0.19g 3- hydroxy benzaldehydes, 0.28g Anhydrous sodium acetate, add in round-bottomed flask, add 5mL acetic anhydrides, 7mL glacial acetic acid, stirred under the conditions of 100 DEG C of oil baths to complete Dissolving, continue to react 5.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then will react mixed Compound is poured into 45mL frozen water, seals up preservative film, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, is obtained Second compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, washing Shi Xianyong adds up to 30mL 3 washings of distillation moisture, then divides 3 washings with the methanol for adding up to 30mL, second compound Chemical structural formula is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4- fluorobenzaldehydes are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：The intermediate products of 0.15g the 3rd are weighed, 0.31g anhydrous sodium acetates, measure 233 μ L's 4- fluorobenzaldehydes, add in two neck flasks of circle, add 5mL acetic anhydrides, 7mL glacial acetic acid, stirred under the conditions of 100 DEG C of oil baths to complete Fully dissolved, continue to react 5.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then will react Mixture is poured into 45mL frozen water, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains the 3rd chemical combination Thing, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with total during washing 30mL 3 washings of distillation moisture are calculated as, then divide 3 washings, the chemical constitution of the 3rd compound with the methanol for adding up to 30mL Formula is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4-chloro-benzaldehyde are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：Weigh the intermediate products of 0.16g the 3rd, 0.20g 4-chloro-benzaldehydes, the anhydrous second of 0.28g Sour sodium, adds in two neck flasks of circle, adds 5mL acetic anhydrides, 7mL glacial acetic acid, is stirred under the conditions of 100 DEG C of oil baths to completely molten Solution, continue to react 5.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then mix reaction Thing is poured into 45mL frozen water, seals up preservative film, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, is dried, and obtains the Four compounds, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, during washing 3 washings of distillation moisture for adding up to 30mL are first used, then divide 3 washings, the change of the 4th compound with the methanol for adding up to 30mL It is as follows to learn structural formula：

Wherein,

Step 4: the 3rd intermediate product and 2,5- 4-dihydroxy benzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.25g the 3rd, 0.27g 2,5- dihydroxy benzenes first Aldehyde, 0.30g anhydrous sodium acetates, add in two neck flasks of circle, 5mL acetic anhydrides, 7mL glacial acetic acid are added, under the conditions of 100 DEG C of oil baths Stirring continues to react 5.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, so to being completely dissolved Reactant mixture is poured into 45mL frozen water afterwards, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, is obtained 5th compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, washing Shi Xianyong adds up to 30mL 3 washings of distillation moisture, then divides 3 washings with the methanol for adding up to 30mL, the 5th compound Chemical structural formula is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4- dimethylaminobenzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.15g the 3rd, 0.25g 4- Dimethylaminobenzene first Aldehyde, 0.28g anhydrous sodium acetates, add in two neck flasks of circle, add 5mL acetic anhydrides, 7mL glacial acetic acid, 100~110 DEG C of oil baths Under the conditions of stir to being completely dissolved, continue to react 5.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room Temperature, then reactant mixture is poured into 45mL frozen water, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, The 6th compound is obtained, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, 3 washings of distillation moisture for adding up to 30mL are first used during washing, then divide 3 washings, the 6th chemical combination with the methanol for adding up to 30mL The chemical structural formula of thing is as follows：

Wherein,

Specifically included Step 1: preparing the first intermediate product as raw material using thiosemicarbazide：Weigh 5.028g (55.17mmol) white plates thiosemicarbazide, which is added to 50mL, to be justified in two neck flasks, adds 3mL (74.30mmol) formic acid, Stirring to pulpous state, be then added dropwise to 6mL concentrated hydrochloric acids in the neck flask of circle two with constant pressure separatory funnel at room temperature, 30min is dripped off, Continue to stir, the neck flask of circle two is moved on on oil bath heating magnetic stirring apparatus, 4~5h, TLC detections are reacted at 110 DEG C Reaction is reacted to without raw material point, stopping, after being cooled to room temperature, obtains coolant, and coolant is poured into frozen water, in frozen water System pH is adjusted to 7~8 with concentrated ammonia liquor, after stand at low temperature at least 12h, the white powder that price separates out obtains through filtering, washing To the first intermediate product, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, That is V_{Dichloromethane}:V_Methanol=10:1；

The quality of first intermediate product is 4.286g, yield：76.82%, its structural characterization data is as follows：

IR(KBr)ν/cm-1:3284,3102,1619,1504,1018,682；1H NMR(300MHz,DMSO-d6)δ: 7.20 (2H, s ,-NH2), 8.56 (1H, s, N=CH-S)；13C NMR(75MHz,DMSO-d6)δ:143.07(2-C),168.73 (4-C)；HR-EI-MS m/z:102.0122 [M+H]+, (calcd for C2H4N3S, 102.0126).

Specifically included Step 2: synthesizing the second intermediate product with chloracetyl chloride：Weigh in 1.001g (9.898mmol) first Between product, add 100mL justify two neck flasks in, add 25mL through steaming again processing after dimethylformamide, treat among first After product is completely dissolved, the triethylamine that 1.645mL (11.878mmol) is dried is added, moves on under condition of ice bath, measures 1.12mL (14.875mmol) chloracetyl chloride is added drop-wise in reaction with constant pressure funnel, and 30min is dripped off, and room temperature atmospheric agitation is anti- 4h is answered, TLC detections reaction stops reaction, reactant mixture is poured into 50mL frozen water, seals preservative film, in 2 to without raw material point After at least 12h is stood under the conditions of~4 DEG C, through filtering, washing, dry, the second intermediate product is obtained, wherein, the detection that TLC is used It is dichloromethane and methanol to track reagent, and its volume ratio is 10:1, i.e. V_{Dichloromethane}:V_Methanol=10:1, with adding up to during washing 30mL 3 washings of distillation moisture；

The quality of second intermediate product is 1.212g, yield：69.18%, its structural characterization data is as follows：

IR(KBr)ν/cm^-1:3409,3104,3070,2992,2935,2895,2818,2718,2222,1741,1711, 1591,1447,1220,1167,1135,1055,1015,908,858.¹H NMR(300MHz,DMSO-d₆)δ:12.95(s, 1H ,-NH-), 9.22 (s, 1H, N=CH-S), 4.46 (s, 2H, CO-CH₂-Cl).¹³C NMR(75MHz,DMSO-d₆)δ: 170.86,163.81,154.40,47.80.HR-EI-MS m/z:177.9838[M+H]⁺(calcd for C₄H₆ClN₃OS, 177.9842).

Step 3: the intermediate product of Cyclization the 3rd specifically includes under the effect of thiocyanic acid amine：Weigh 0.203g (1.147mmol) second intermediate product, it is added to 100mL and justifies in two neck flasks, add 25mL and steam dimethylformamide again extremely It is completely dissolved, then weighs 0.131g (1.721mmol) ammonium thiocyanate and add in the neck flask of circle two, reacted under 80 DEG C of oil baths 4h, TLC detecting and tracking react to without raw material point, stopping and react, reactant mixture is poured into 30g trash ices, seals up preservative film, in At least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains the 3rd intermediate product, wherein, the detection that TLC is used It is dichloromethane and methanol to track reagent, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, with adding up to during washing 10mL 3 washings of distillation moisture.

The quality of 3rd intermediate product is 0.187g, yield：81.66%, its structural characterization data is as follows：

m.p.：194-195 DEG C, IR (KBr)/cm^-1:3409,3104,2718,2222,1711,1591,1454,1447, 1407,1285,1167,1135,1015,908,818；¹H NMR(300MHz,DMSO-d₆)δ:12.30(s,1H,-NH-),9.30 (s, 1H, N=CH-S), 4.10 (s, 2H, CO-CH₂-S).¹³C NMR(75MHz,DMSO-d₆)δ:174.55,170.72, 166.45,151.64,36.02.HR-EI-MS m/z:200.9906[M+H]⁺(calcd for C₅H₅N₄OS₂,200.9905).

Step 4: the 3rd intermediate product and 4- cyanobenzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.110g (0.550mmol) the 3rd, 0.155g The 4- cyanobenzaldehydes of (1.182mmol), 0.182g (2.219mmol) anhydrous sodium acetate, add 100mL and justify in two neck flasks, Add 3mL acetic anhydrides and 4mL glacial acetic acid, stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continue react 6h, TLC detection with Track reacts to raw material point and disappeared, and stops reaction, is cooled to room temperature, reactant is poured into 50mL frozen water, seals up preservative film, is put in 2~4 DEG C of refrigerators stand at least 12h, through filtering, washing, dry, obtain the first compound, wherein, the detecting and tracking that TLC is used Reagent is dichloromethane and methanol, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first with adding up to during washing 30mL 3 washings of distillation moisture, then divide 3 washings with the methanol for adding up to 30mL, the chemical structural formula of the first compound is such as Under：

Wherein,

First compound is white powder, quality 0.065g, yield：35.91%, its structural characterization data is as follows：

m.p.：m.p.：250-252℃；IR(KBr)ν/cm^-1:3411,3124,2918,2820,1713,1581,1486, 1399,1267,1088,1008,846；¹H NMR(300MHz,DMSO-d₆)δ：9.37 (s, 1H, N=CH-S), 7.80 (s, H, ), NH 7.82 (s, 1H, HC=C), 7.82-8.02 (m, 4H, Ph-H)¹³C NMR(75MHz,DMSO-d₆)δ:169.54, 167.18,158.77,151.75,135.35,132.24,130.98,127.57,125.57,124.89,123.60.

Step 1: Step 2: step 3 is in the same manner as in Example 7, the dosage and experiment parameter of each material are also identical, difference It is：

Step 4: the 3rd intermediate product and 3- hydroxy benzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.200g (1.000mmol) the 3rd, 0.244g The 3- hydroxy benzaldehydes of (1.998mmol), 0.328g (3.999mmol) anhydrous sodium acetate, add in 100mL round-bottomed flasks, then 6mL acetic anhydrides, 7mL glacial acetic acid are added, is stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continues to react 6h, TLC detecting and trackings Reaction is reacted to without raw material point, stopping, being cooled to room temperature, then pour into 50mL frozen water reactant mixture, seal up preservative film, At least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains second compound, wherein, the detection that TLC is used It is dichloromethane and methanol to track reagent, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first with amounting to during washing For the 30mL washing of distillation moisture 3 times, then washed for 3 times with the methanol point for adding up to 30mL, the chemical structural formula of second compound It is as follows：

Wherein,

Second compound is white powder 0.121g, yield：37.81%, its structural characterization data is as follows：

m.p.：174-175℃；IR(KBr)ν/cm^-1:3434,3124,3082,2962,2915,2828,1761,1713, 1576,1481,1242,1030,1013,903,813,729,659；¹H NMR(300MHz,DMSO-d₆)δ:9.83 (s, 1H, N= ), CH-S 7.99 (s, 1H), 7.60-7.69 (m, 2H, Ph-H), 7.49 (m, 1H, Ph-H), 7.32-7.36 (m, 1H ,=CH- Ph).¹³C NMR(75MHz,DMSO-d₆)δ:183.64,172.52,164.18,137.67,133.66,133.54,131.45, 130.99,125.08,119.08,113.05,112.43.

Step 4: the 3rd intermediate product and 4- fluorobenzaldehydes are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：Weigh the intermediate products of 0.201g (1.005mmol) the 3rd, 0.328g (3.999mmol) anhydrous sodium acetate, 215 μ L (2.004mmol) 4- fluorobenzaldehydes are measured, added in 100mL round-bottomed flasks, then 6mL acetic anhydrides, 8mL glacial acetic acid are added, is stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continues to react 6h, TLC detecting and trackings Reaction is reacted to without raw material point, stopping, being cooled to room temperature, then pour into 50mL frozen water reactant mixture, seal up preservative film, At least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains the 3rd compound, wherein, the detection that TLC is used It is dichloromethane and methanol to track reagent, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first with amounting to during washing For the 30mL washing of distillation moisture 3 times, then washed for 3 times with the methanol point for adding up to 30mL, the chemical structural formula of the 3rd compound It is as follows：

Wherein,

3rd compound is yellowish-brown powder, quality 0.19g, yield：59.94%, its structural characterization data is as follows：

m.p.：182-184℃.IR(KBr)ν/cm^-1:3411,3124,2918,2820,1713,1581,1486,1447, 1399,1329,1202,1162,1088,1053,1008,881,726,517；¹H NMR(300MHz,DMSO-d₆)δ:9.84(s, 1H, N=CH-S), 8.03 (s, 1H ,=CH-Ph), 7.83 (dd, J=9.0,6.0Hz, 2H, Ph-H), 7.48 (t, J=18, 9.0Hz,2H,Ph-H).¹³C NMR(75MHz,DMSO-d₆)δ:183.57,164.41,163.43,162.08,159.06, 156.81,133.81,133.69,130.09,117.41,117.12.

Step 4: the 3rd intermediate product and 4-chloro-benzaldehyde are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：Weigh the intermediate products of 0.208g (1.040mmo) the 3rd, 0.25g (2.047mmol) 4-chloro-benzaldehyde, 0.337g (4.108mmol) anhydrous sodium acetate, add 100mL round-bottomed flasks in, add 6mL acetic anhydrides, 8mL glacial acetic acid, being stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continue to react 6h, TLC detecting and trackings are reacted to without raw material point, Stop reaction, be cooled to room temperature, then reactant mixture is poured into 50mL frozen water, seals up preservative film, under the conditions of 2~4 DEG C At least 12h is stood, through filtering, washing, dry, obtains the 4th compound, wherein, the detecting and tracking reagent that TLC is used is two Chloromethanes and methanol, its volume ratio are 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first with the distilled water for adding up to 30mL during washing Divide 3 washings, then it is as follows with 3 washings of methanol point for adding up to 30mL, the chemical structural formula of the 4th compound：

Wherein,

4th compound is white powder, quality 0.15g, yield：43.52%, its structural characterization data is as follows：

m.p.：242-243℃.IR(KBr)ν/cm^-1:3424,3129,3082,2962,2915,1716,1579,1449, 1397,1332,1267,1212,1053,921,818,763；¹H NMR(300MHz,DMSO-d₆)δ:9.84 (s, 1H, N=CH- ), S 8.00 (s, 1H ,=CH-Ph), 7.76 (m, 2H, Ph-H), 7.70 (s, 1H, Ph-H), 7.62-7.64 (m, 2H, Ph-H)¹³C NMR(75MHz,DMSO-d₆)δ:183.57,164.35,163.31,159.11,156.77,136.24,135.07,132.79, 130.11,129.84,122.16.

Step 4: the 3rd intermediate product and 2,5- 4-dihydroxy benzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.202g (1.010mmol) the 3rd, 0.277g 2, the 5- 4-dihydroxy benzaldehydes of (1.513mmol), 0.329g (4.011mmol) anhydrous sodium acetate, add 100mL and justify two neck flasks In, 6mL acetic anhydrides, 8mL glacial acetic acid are added, is stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continues to react 6h, TLC detections Tracking reaction stops reaction, is cooled to room temperature, then pours into reactant mixture in 50mL frozen water, seal up guarantor to without raw material point Fresh film, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtain the 5th compound, wherein, what TLC was used Detecting and tracking reagent is dichloromethane and methanol, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first use during washing 30mL 3 washings of distillation moisture are added up to, then are tied with 3 washings of methanol point for adding up to 30mL, the chemistry of the 5th compound Structure formula is as follows：

Wherein,

5th compound is white powder, quality 0.126g, yield：38.99%, m.p.：208-209℃.Its structure Characterize data is as follows：

IR(KBr)ν/cm^-1:3299,3096,2783,2745,2666,1614,1509,1442,1400,1376,1331, 1216,1050,1140,1018,886,785；¹H NMR(300MHz,DMSO-d₆)δ:10.06(s,1H,-NH),9.84(s, 1H) 9.39 (s, 1H, N=CH-S), 7.60 (s, 1H, Ph-H), 7.42 (s, 1H, Ph-H), 7.39 (s, 1H, Ph-H), 7.36 (m, 1H ,=CH-Ph)¹³C NMR(75MHz,DMSO-d₆)δ：169.63,169.50,164.19,158.38,152.61, 148.59,147.28,128.26,127.10,125.70,125.37,121.73.

Step 4: the 3rd intermediate product and 4- dimethylaminobenzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.20g (1.020mmol) the 3rd, 0.302g The 4- dimethylaminobenzaldehydes of (2.024mmol), 0.328g (3.999mmol) anhydrous sodium acetate, add 100mL and justify two neck flasks In, 6mL acetic anhydrides, 8mL glacial acetic acid are added, is stirred under the conditions of 105 DEG C of oil baths to being completely dissolved, continues to react 6h, TLC detections Tracking reaction stops reaction, is cooled to room temperature, then pours into reactant mixture in 50mL frozen water, seal up guarantor to without raw material point Fresh film, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtain the 6th compound, wherein, what TLC was used Detecting and tracking reagent is dichloromethane and methanol, and its volume ratio is 10:1, i.e. V_{Dichloromethane}：V_Methanol=10:1, first use during washing 30mL 3 washings of distillation moisture are added up to, then are tied with 3 washings of methanol point for adding up to 30mL, the chemistry of the 6th compound Structure formula is as follows：

Wherein,

6th compound is orange red powder, quality 0.201g, yield：59.52%,

Its structural characterization data is as follows：

m.p.：246-248 DEG C, 1H NMR (300MHz, DMSO-d6) δ：12.70 (s, 1H ,-NH), 7.67 (s, 1H ,= CH-Ph),7.52(s,2H,Ph-H),6.84(m,2H,Ph-H),3.04(s,6H,-CH3).

Specifically included Step 1: preparing the first intermediate product as raw material using thiosemicarbazide：Weigh 5.08g thiosemicarbazides It is added in two neck flasks of circle, adds 3.3mL formic acid, stirs at room temperature to pulpous state, then by 6.4mL concentrated hydrochloric acids constant pressure point Liquid funnel is added dropwise in the neck flask of circle two, and 35min is dripped off, and continues to stir, and the neck flask of circle two is moved on into oil bath heating On magnetic stirring apparatus, 5h is reacted at 115 DEG C, TLC detections reaction stops reaction, after being cooled to room temperature, obtained cold to without raw material point But liquid, and coolant is poured into frozen water, system pH is adjusted to 7~8 with concentrated ammonia liquor in frozen water, stand at low temperature at least 12h Afterwards, the white powder that price separates out obtains the first intermediate product through filtering, wash, wherein, the detecting and tracking reagent that TLC is used It is dichloromethane and methanol, its volume ratio is 10:1, i.e. V_{Dichloromethane}:V_Methanol=10:1；

Specifically included Step 2: synthesizing the second intermediate product with chloracetyl chloride：The intermediate products of 1.05g first are weighed, are added In two neck flasks of circle, dimethylformamides of the 30mL after the processing of steaming again is added, after the first intermediate product is completely dissolved, then The triethylamine that 1.65mL is dried is added, is moved on under condition of ice bath, is measured 1.2mL chloracetyl chlorides and be added drop-wise to instead with constant pressure funnel Ying Zhong, 35min are dripped off, and room temperature atmospheric agitation reaction 4.5h, TLC detection reaction stops reaction, reaction is mixed to without raw material point Thing is poured into 52mL frozen water, seals preservative film, after at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, is obtained Second intermediate product, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, wash With 3 washings of distillation moisture for adding up to 30mL when washing；

Step 3: the intermediate product of Cyclization the 3rd specifically includes under the effect of thiocyanic acid amine：Weigh among 0.25g second Product, it is added in two neck flasks of circle, adds 26mL and steam dimethylformamide again to being completely dissolved, then weigh 0.18g sulphur Ammonium cyanate is added in the neck flask of circle two, and 4.5h is reacted under 85 DEG C of oil baths, and TLC detecting and trackings react to without raw material point, stopped anti- Should, reactant mixture is poured into 34g trash ices, seals up preservative film, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing Wash, dry, obtain the 3rd intermediate product, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, its volume Than being 10:1, with 3 washings of distillation moisture for adding up to 10mL during washing.

Step 4: the 3rd intermediate product and 4- cyanobenzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.16g the 3rd, 0.21g 4- cyanobenzaldehydes, 0.23g Anhydrous sodium acetate, add circle two neck flasks in, add 4mL acetic anhydrides and 5mL glacial acetic acid, stirred under the conditions of 110 DEG C of oil baths to It is completely dissolved, continues to react 6.5h, TLC detecting and trackings react to raw material point and disappeared, and stop reaction, are cooled to room temperature, will react Thing is poured into 55mL frozen water, is put in 2~4 DEG C of refrigerators and is stood at least 12h, through filtering, washing, dry, obtains the first compound, its In, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with adding up to during washing 30mL 3 washings of distillation moisture, then divide 3 washings with the methanol for adding up to 30mL, the chemical structural formula of the first compound is such as Under：

Wherein,

Step 1: Step 2: step 3 is identical with embodiment 13, the dosage and experiment parameter of each material are also identical, area It is not：

Step 4: the 3rd intermediate product and 3- hydroxy benzaldehydes are reacted to obtain thiophene by Knoevenagle condensation reactions Diazoles thiazolinone compound specifically includes：Weigh the intermediate products of 0.25g the 3rd, 0.29g 3- hydroxy benzaldehydes, 0.38g Anhydrous sodium acetate, add in round-bottomed flask, add 7mL acetic anhydrides, 9mL glacial acetic acid, stirred under the conditions of 110 DEG C of oil baths to complete Dissolving, continue to react 6.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then will react mixed Compound is poured into 55mL frozen water, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains second compound, Wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with amounting to during washing For the 30mL washing of distillation moisture 3 times, then washed for 3 times with the methanol point for adding up to 30mL, the chemical structural formula of second compound It is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4- fluorobenzaldehydes are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：The intermediate products of 0.25g the 3rd are weighed, 0.41g anhydrous sodium acetates, measure 237 μ L's 4- fluorobenzaldehydes, add in two neck flasks of circle, add 7mL acetic anhydrides, 9mL glacial acetic acid, stirred under the conditions of 110 DEG C of oil baths to complete Fully dissolved, continue to react 6.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then will react Mixture is poured into 55mL frozen water, seals up preservative film, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, is obtained To the 3rd compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, wash 3 washings of distillation moisture for adding up to 30mL are first used when washing, then divide 3 washings, the 3rd compound with the methanol for adding up to 30mL Chemical structural formula it is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4-chloro-benzaldehyde are reacted to obtain thiophene two by Knoevenagle condensation reactions Azole thiazolinone compound specifically includes：Weigh the intermediate products of 0.26g the 3rd, 0.30g 4-chloro-benzaldehydes, the anhydrous second of 0.39g Sour sodium, adds in two neck flasks of circle, adds 7mL acetic anhydrides, 9mL glacial acetic acid, is stirred under the conditions of 110 DEG C of oil baths to completely molten Solution, continue to react 6.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, then mix reaction Thing is poured into 55mL frozen water, and at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, obtains the 4th compound, its In, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with adding up to during washing 30mL 3 washings of distillation moisture, then divide 3 washings with the methanol for adding up to 30mL, the chemical structural formula of the 4th compound is such as Under：

Wherein,

Step 4: the 3rd intermediate product and 2,5- 4-dihydroxy benzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.35g the 3rd, 0.38g 2,5- dihydroxy benzenes first Aldehyde, 0.41g anhydrous sodium acetates, add in two neck flasks of circle, 7mL acetic anhydrides, 9mL glacial acetic acid are added, under the conditions of 110 DEG C of oil baths Stirring continues to react 6.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, so to being completely dissolved Reactant mixture is poured into 55mL frozen water afterwards, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, is obtained 5th compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, washing Shi Xianyong adds up to 30mL 3 washings of distillation moisture, then divides 3 washings with the methanol for adding up to 30mL, the 5th compound Chemical structural formula is as follows：

Wherein,

Step 4: the 3rd intermediate product and 4- dimethylaminobenzaldehydes are reacted by Knoevenagle condensation reactions Specifically included to thiadiazole thiazolinone compound：Weigh the intermediate products of 0.25g the 3rd, 0.35g 4- Dimethylaminobenzene first Aldehyde, 0.38g anhydrous sodium acetates, add in two neck flasks of circle, 7mL acetic anhydrides, 9mL glacial acetic acid are added, under the conditions of 110 DEG C of oil baths Stirring continues to react 6.5h, TLC detecting and trackings react to without raw material point, stop reaction, be cooled to room temperature, so to being completely dissolved Reactant mixture is poured into afterwards and stands at least 12h in 55mL frozen water under the conditions of 2~4 DEG C, through filtering, washing, is dried, obtains the Six compounds, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, during washing 3 washings of distillation moisture for adding up to 30mL are first used, then divide 3 washings, the change of the 6th compound with the methanol for adding up to 30mL It is as follows to learn structural formula：

Wherein,

The phenyl prepared in 7-12 of the embodiment of the present invention is taken to substitute thiadiazole thiazolinone compound to be configured to try respectively Agent carries out sterilization test to certain plants bacterium or fungi and carries out insecticidal test to certain plants disease and insect, the results are shown in Table 1 He Table 2.

First, sterilization test

S1, by the first compound, second compound made from 7-12 of the embodiment of the present invention, the 3rd compound, the 4th chemical combination Thing, the 5th compound, the 6th compound are separately added into proper amount of methanol (analysis is pure) and are completely dissolved sample, are made into the to be measured of 500g/L Solution.Blank group (solution to be measured for being added without any compound of embodiment 6-10 preparations) is set simultaneously.Take what is prepared 500g/L solution 1.5mL to be measured add 13.5mL potato dextrose agars and are well mixed, and are configured to 50g/L PDA test fine jades Fat liquid, pour into disposable sterilized culture dish, at room temperature after cooled and solidified, obtain agar plates, stand-by, agar culture herein Ware includes the first compound, second compound, the agar plates that the 3rd compound, the 4th compound, the 5th compound are formed And the agar plates that blank group is formed.

S2, uniform, the vigorous test strain of growth is chosen, a diameter of 7mm agar blocks are set to by strain is tested with card punch It is stand-by.Test agar block is tipped upside down in cultured agar plates, it is permanent to be placed in 28.0 DEG C of temperature, the constant temperature of humidity 60% Wet incubator culture 72h.

S3, test strain is taken out, (crossing method measures 2 times, is averaged with vernier caliper measurement colony growth diameter Value), record experimental result.

Wherein, a diameter of 7mm of original bacteria cake, the blank control colony diameter after culture is reference, and colony diameter is smaller, Fungistatic effect is better, more big not have bacteriostasis then.

Bacteriostasis rate EB=[(blank control colony growth diameter-chemicals treatment colony growth diameter)/(blank control bacterium colonies Growth diameter)] × 100%, and experimental results are the mean value calculation inhibiting rate of 3 bacterium colony test diameters.

Meanwhile the step of according to above-mentioned S1, S2, S3, kitazine, Yekuzuo, pyrazoles Fluoxastrobin are each configured to solution And corresponding agar plates are obtained, calculate the inhibiting rate each for testing strain.

Testing strain includes early blight of tomato germ, banana blight germ, cucumber fusarium axysporum germ, rice blast pathogen.

The bactericidal activity of table 1

It can be obtained by table 1, the thiadiazole thiazolinone compound prepared in embodiment 9-11, as a kind of brand-newization The thiazoline ketone compounds of structure are learned, there is good inhibiting rate for early blight of tomato, can reach 65.04%, height In kitazine and Yekuzuo；Also there is preferable inhibiting rate for banana blight, cucumber fusarium axysporum germ, all higher than kitazine And Yekuzuo.Also, the 3rd compound prepared by embodiments of the invention 10 reaches for the inhibiting rate of rice blast pathogen 86.96%, higher than kitazine, Yekuzuo, although slightly below pyraclostrobin for the inhibiting rate of rice blast, make by embodiment 10 The method of standby 3rd compound is simple relative to pyrazoles Fluoxastrobin operating procedure is prepared, and is not related to hydrogenation reduction, to equipment It is required that low, accessory substance is few, and three waste discharge is few, green.

2nd, insecticidal test

By the first compound made from 7-12 of the embodiment of the present invention, second compound, the 3rd compound, the 4th compound, 5th compound, the 6th compound, and Buprofezin commonly used in the prior art, 1,2,3- thiadiazoles join -1,3,4- thiadiazoles Class compound is configured to the reagent that concentration is 500ppm respectively, while sets the blank control for not spraying any reagent.

Using diamondback moth, aphid, tetranychid, rice field brown paddy plant hopper as target, determination of activity is carried out.

(1) to the assay method of diamondback moth：Rape leaf is broken into diameter 1cm blade with card punch, spraying treatment Pressure is 15psi (about 1.05kg/cm²), each leave dual sides spraying, spouting liquid 0.5ml.After drying in the shade on each blade 20 first 2 age diamondback moth worms are accessed, 25 DEG C is then placed in, cultivates in the observation ward of relative humidity 60~70%, after 72 hours, investigate Survival borer population, calculates the death rate.

(2) to the assay method of aphid：Diameter 6cm culture dishes are taken, one layer of filter paper is covered at ware bottom, and appropriate running water is added dropwise and protects It is wet.From clip suitable size (diameter about 2cm) on the apple leaf of culture aphid and with the Apple Leaves of 20 aphids, remove Alatae and the aphid of face of blade, blade back are placed in culture dish upwards.The pressure of spraying treatment is that 15psi (is roughly equal to 1.05kg/ cm²), spouting liquid 0.5ml, 25 DEG C are put into after processing, is cultivated in the observation ward of relative humidity 6~70%, investigates and deposits after 48 hours Borer population living, calculates the death rate.

(3) to the assay method of tetranychid：Peanut leaf is taken, tetranychid 20, the pressure of spraying treatment are inoculated with every blade For 15psi (about 1.05kg/cm²), each leave dual sides spraying, spouting liquid 0.5ml.It is then placed in 25 DEG C, relative humidity Cultivated in 60~70% observation ward, after 72 hours, investigation survival borer population, calculate the death rate.

(4) to the assay method of rice field brown paddy plant hopper：In the multiple culturing room of area identical after rice cultivation, launch respectively 100 brown paddy plant hoppers, the reagent that spray is prepared respectively two days later, spouting liquid 10ml, after 72 hours, investigation survival borer population, Calculate the death rate.

Investigation result is as shown in table 2 below.

The insecticidal activity of table 2

As shown in Table 2, the thiadiazole thiazolinone compound prepared in embodiment 7-12, as a kind of brand-new chemistry knot The thiazoline ketone compounds of structure, there is good fragmentation effect for diamondback moth, aphid, tetranychid, rice field brown paddy plant hopper, and it is right Observation is tracked after administration in the rice planted in culturing room, and rice seedling growth is normal, any key feelings does not occur Condition.

Although embodiment of the present invention is disclosed as above, it is not restricted in specification and embodiment listed With it can be applied to various suitable the field of the invention completely, can be easily for those skilled in the art Other modification is realized, therefore under the universal limited without departing substantially from claim and equivalency range, it is of the invention and unlimited In specific details.

Claims

1. a kind of thiadiazole thiazolinone compound, it is characterised in that its chemical constitution is shown below：

Wherein,

A kind of 2. preparation method of thiadiazole thiazolinone compound as claimed in claim 1, it is characterised in that the system Preparation Method is using thiosemicarbazide as raw material, and the first intermediate product is synthesized with formic acid cyclodehydration under the conditions of sulphuric acid catalysis, Then the second intermediate product, then the intermediate product of Cyclization the 3rd under the effect of thiocyanic acid amine are synthesized with chloracetyl chloride, is finally led to Knoevenagle condensation reactions are crossed to react to obtain thiadiazole thiazolinone compound by the 3rd compound and R1, wherein,

3. the preparation method of thiadiazole thiazolinone compound as claimed in claim 2, it is characterised in that with sulfo-amino Urea is that raw material the first intermediate product of preparation specifically includes：4.98~5.08g thiosemicarbazides are weighed to be added in two neck flasks of circle, 2.7~3.3mL formic acid is added, stirs to pulpous state, then drips 5.6~6.4mL concentrated hydrochloric acids constant pressure separatory funnel at room temperature Add in the neck flask of circle two, 25~35min is dripped off, and continues to stir, and the neck flask of circle two is moved on into oil bath heating magnetic force On agitator, 4~5h is reacted at 105~115 DEG C, TLC detections reaction stops reaction, after being cooled to room temperature, obtained to without raw material point Pour into frozen water, adjusted system pH to 7~8 with concentrated ammonia liquor in frozen water, stand at low temperature is at least to coolant, and by coolant After 12h, the white powder that price separates out obtains the first intermediate product through filtering, wash, wherein, the detecting and tracking examination that TLC is used Agent is dichloromethane and methanol, and its volume ratio is 10:1；

The second intermediate product is synthesized with chloracetyl chloride to specifically include：The intermediate products of 0.95~1.05g first are weighed, add two necks of circle In flask, dimethylformamides of the 20~30mL after the processing of steaming again is added, after the first intermediate product is completely dissolved, then is added Enter the triethylamine of 1.5~1.65mL dryings, move on under condition of ice bath, measure 1~1.2mL chloracetyl chlorides and dripped with constant pressure funnel It is added in reaction, 25~35min is dripped off, and room temperature atmospheric agitation reacts 3.5~4.5h, and TLC detections reaction stops to without raw material point Reaction, reactant mixture is poured into 48~52mL frozen water, seals preservative film, after at least 12h is stood under the conditions of 2~4 DEG C, warp Filter, washing, dry, obtain the second intermediate product, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, Its volume ratio is 10:1, with 3 washings of distillation moisture for adding up to 30mL during washing；

The intermediate product of Cyclization the 3rd specifically includes under the effect of thiocyanic acid amine：The intermediate products of 0.15~0.25g second are weighed, It is added in two neck flasks of circle, adds 22~26mL and steam dimethylformamide again to being completely dissolved, then weigh 0.08~ 0.18g ammonium thiocyanates are added in the neck flask of circle two, under 75~85 DEG C of oil baths react 3.5~4.5h, TLC detecting and trackings react to Without raw material point, stop reaction, reactant mixture is poured into 26~34g trash ices, seals up preservative film, is stood under the conditions of 2~4 DEG C At least 12h, through filtering, washing, dry, the 3rd intermediate product is obtained, wherein, the detecting and tracking reagent that TLC is used is dichloro Methane and methanol, its volume ratio are 10:1, with 3 washings of distillation moisture for adding up to 10mL during washing.

4. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through 3rd intermediate product and 4- cyanobenzaldehydes are reacted to obtain thiadiazole thiazolinone compound by Knoevenagle condensation reactions Specifically include：Weigh the intermediate products of 0.06~0.16g the 3rd, 0.11~0.21g 4- cyanobenzaldehydes, 0.13~0.23g without Water sodium acetate, add in two neck flasks of circle, add 2~4mL acetic anhydrides and 3~5mL glacial acetic acid, 100~110 DEG C of oil bath conditions Lower stirring continues reaction 5.5~6.5h, TLC detecting and tracking and reacted to raw material point disappearance, stop reaction, cooling to being completely dissolved To room temperature, reactant is poured into 45~55mL frozen water, seals up preservative film, be put in 2~4 DEG C of refrigerators and stand at least 12h, through taking out Filter, washing, dry, obtain the first compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, its body Product ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then divided 3 times with the methanol for adding up to 30mL Washing, the chemical structural formula of the first compound are as follows：

Wherein,

5. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through 3rd intermediate product and 3- hydroxy benzaldehydes are reacted to obtain thiadiazole thiazolinone compound by Knoevenagle condensation reactions Specifically include：Weigh the intermediate products of 0.15~0.25g the 3rd, 0.19~0.29g 3- hydroxy benzaldehydes, 0.28~0.38g without Water sodium acetate, add in round-bottomed flask, 5~7mL acetic anhydrides, 7~9mL glacial acetic acid are added, under the conditions of 100~110 DEG C of oil baths Stirring continues reaction 5.5~6.5h, TLC detecting and tracking and reacted to without raw material point, stop reaction, be cooled to room to being completely dissolved Temperature, then reactant mixture is poured into 45~55mL frozen water, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, Dry, obtain second compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then washed for 3 times with the methanol point for adding up to 30mL, second The chemical structural formula of compound is as follows：

Wherein,

6. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through Knoevenagle condensation reactions react the 3rd intermediate product and 4- fluorobenzaldehydes to obtain thiadiazole thiazolinone compound tool Body includes：Weigh the intermediate products of 0.15~0.25g the 3rd, 0.31~0.41g anhydrous sodium acetates, measure 233~237 μ L 4- fluorine Benzaldehyde, add in two neck flasks of circle, 5~7mL acetic anhydrides, 7~9mL glacial acetic acid are added, under the conditions of 100~110 DEG C of oil baths Stirring continues reaction 5.5~6.5h, TLC detecting and tracking and reacted to without raw material point, stop reaction, be cooled to room to being completely dissolved Temperature, then reactant mixture is poured into 45~55mL frozen water, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, Dry, obtain the 3rd compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then washed for 3 times with the methanol point for adding up to 30mL, the 3rd The chemical structural formula of compound is as follows：

Wherein,

7. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through Knoevenagle condensation reactions react the 3rd intermediate product and 4-chloro-benzaldehyde to obtain thiadiazole thiazolinone compound tool Body includes：Weigh the intermediate products of 0.16~0.26g the 3rd, 0.20~0.30g 4-chloro-benzaldehydes, 0.28~0.39g anhydrous acetic acids Sodium, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7~9mL glacial acetic acid, stirred under the conditions of 100~110 DEG C of oil baths To being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without raw material point, stop reaction, be cooled to room temperature, so Reactant mixture is poured into 45~55mL frozen water afterwards, at least 12h is stood under the conditions of 2~4 DEG C, through filtering, washing, dry, The 4th compound is obtained, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, and its volume ratio is 10:1, 3 washings of distillation moisture for adding up to 30mL are first used during washing, then divide 3 washings, the 4th chemical combination with the methanol for adding up to 30mL The chemical structural formula of thing is as follows：

Wherein,

8. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through 3rd intermediate product and 2,5- 4-dihydroxy benzaldehydes are reacted to obtain thiadiazole thiazoline assimilation by Knoevenagle condensation reactions Compound specifically includes：Weigh the intermediate products of 0.25~0.35g the 3rd, 0.27~0.38g 2,5- 4-dihydroxy benzaldehydes, 0.30~ 0.41g anhydrous sodium acetates, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7~9mL glacial acetic acid, 100~110 DEG C of oil Stirred under the conditions of bath to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without raw material point, stop reaction, Room temperature is cooled to, then pours into reactant mixture in 45~55mL frozen water, at least 12h is stood under the conditions of 2~4 DEG C, through taking out Filter, washing, dry, obtain the 5th compound, wherein, the detecting and tracking reagent that TLC is used is dichloromethane and methanol, its body Product ratio is 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then divided 3 times with the methanol for adding up to 30mL Washing, the chemical structural formula of the 5th compound are as follows：

Wherein,

9. the preparation method of thiadiazole thiazolinone compound as claimed in claim 3, it is characterised in that pass through 3rd intermediate product and 4- dimethylaminobenzaldehydes are reacted to obtain thiadiazole thiazoline assimilation by Knoevenagle condensation reactions Compound specifically includes：Weigh the intermediate products of 0.15~0.25g the 3rd, 0.25~0.35g 4- dimethylaminobenzaldehydes, 0.28~ 0.38g anhydrous sodium acetates, add in two neck flasks of circle, add 5~7mL acetic anhydrides, 7~9mL glacial acetic acid, 100~110 DEG C of oil Stirred under the conditions of bath to being completely dissolved, continue reaction 5.5~6.5h, TLC detecting and tracking and react to without raw material point, stop reaction, Be cooled to room temperature, then reactant mixture poured into 45~55mL frozen water, seals up preservative film, stood under the conditions of 2~4 DEG C to Few 12h, through filtering, washing, dry, the 6th compound is obtained, wherein, the detecting and tracking reagent that TLC is used is dichloromethane And methanol, its volume ratio are 10:1, first with 3 washings of distillation moisture for adding up to 30mL during washing, then with adding up to 30mL Points of 3 times washings of methanol, the chemical structural formula of the 6th compound is as follows：

Wherein,

10. application of the thiadiazole thiazolinone compound as claimed in claim 1 in disinfectant use in agriculture.

11. application of the thiadiazole thiazolinone compound as claimed in claim 1 in insecticide.