CN109748878A - A kind of sulfentrazone key intermediate benzene connects the preparation method of triazolinones derivative - Google Patents

A kind of sulfentrazone key intermediate benzene connects the preparation method of triazolinones derivative Download PDF

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CN109748878A
CN109748878A CN201910051722.2A CN201910051722A CN109748878A CN 109748878 A CN109748878 A CN 109748878A CN 201910051722 A CN201910051722 A CN 201910051722A CN 109748878 A CN109748878 A CN 109748878A
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benzotriazolinone
preparation
sulfentrazone
key intermediate
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钱平
张璞
施立鑫
王凤云
侯远昌
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Jiangsu Zhongqi Polytron Technologies Inc
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Jiangsu Zhongqi Polytron Technologies Inc
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Abstract

The present invention relates to organic synthesis fields, connect the preparation method of triazolinones derivative more particularly to a kind of sulfentrazone key intermediate benzene, it is specifically included in 2-(2,4 dihalogenated phenyls) -4-(difluoromethyl) -2,4- dihydro -5- methyl -3H-1,5- introducings of phenyl ring of 2,4- triazole -3- ketone introduce halogen, then again by the substrate in NaN3Or TsN3Under the conditions of, generate aryl azide chemical combination object, the azido compound again in a mild condition with PPh3Staudinger reduction reaction occurs, then hydrolysis generation benzene connects triazolinones derivative；Or benzene is obtained through catalysis reduction and connects triazolinones derivative.The preparation method that sulfentrazone key intermediate benzene provided by the invention connects triazolinones derivative is easy to industrialize, raw material is cheap and easy to get, reaction yield and quality are higher, the use for having avoided poisonous reagent methylsufonyl chloride in original synthetic route simultaneously, keeps industrialized production more safe and environment-friendly.

Description

A kind of sulfentrazone key intermediate benzene connects the preparation method of triazolinones derivative
Technical field
The present invention relates to organic synthesis fields, and in particular to it is derivative that a kind of sulfentrazone key intermediate benzene connects Triazolinones The preparation method of object.
Background technique
It is a kind of very important pesticide intermediate that the benzene that 5- bit amino replaces on phenyl ring, which connects triazolinones derivative, such as 2- (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone is exactly former porphin The core intermediate of quinoline original oxidase inhibitor sulfentrazone (A), and 2- (fluoro- 5 aminobenzene of the chloro- 2- of 4-) -4- (difluoromethyl) - 2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone is the key intermediate of another herbicide azoles humulone (B) again.
The benzene that 5- bit amino replaces connects the general synthetic route of triazolinones derivative and (is related to patent US as follows 4980480、US5468863、US5468868、US5438149、US4909831、US5756755、CN102993108、 CN1110683, CN1079963, WO199002120, US5125958, US05621112):
Reaction is before this using a large amount of dense mixed acid systems in 2- (2,4 dichlorophenyl) -4- (difluoromethyl) -2,4- dihydro -5- Methyl -3H-1,5- introducing nitryl groups of phenyl ring of 2,4- triazole -3- ketone, is then urged in the hydrogenation of precious metals pd or Pt again Amido is reduced under change, then further derivatization generates target herbicide.Wherein nitration reaction Process Impurity is obvious, nitro The purifying of isomers difficulty, and the spent acid water content that the step generates increases, and is difficult to continue to apply next batch, and cost greatly improves, It produces one ton of product and generates a large amount of spent acid, bring huge challenge to three-protection design, and utilize in catalytic reduction step Precious metals pd or Pt, high temperature and pressure operation further improve process costs.
Summary of the invention
The technical problem to be solved by the present invention is providing a kind of environment amenable sulfentrazone key intermediate benzene connects three The preparation method of oxazoline ketone derivatives.
The technical scheme to solve the above technical problems is that
A kind of sulfentrazone key intermediate benzene connects the preparation method of triazolinones derivative, includes the following steps:
(1) benzene that 5 halogen atoms of phenyl ring or boric acid base group replace connects triazolinones derivative C, under the catalysis of mantoquita, With sodium azide or to Methyl benzenesulfonyl base nitrine (TsN3) under the conditions of generate corresponding aromatic yl azide D；
(2) aromatic yl azide D Staudinger reductive hydrolysis occurs under the conditions of triphenyl phosphorus obtains compound E；Or Aromatic yl azide D obtains 2- (2,4- dihalo -5- aminobenzene) -4- (difluoromethyl) -2,4- dihydro -5- first through reduction Base -3H-1,2,4- triazole -3- ketone (compound E)；
The reaction equation of above-mentioned reaction is as follows:
Preferably, the X group in above-mentioned reaction equation in compound C, D, E is selected from fluorine or chlorine；Y group choosing in compound C From bromine, iodine, B (OH)2、B(OR)2；Wherein B (OR)2In R group be selected from C1~6Alkyl.
Preferably, above-mentioned reaction further includes the preparation step that benzene connects triazolinones derivative C:
(a) 2- (2,4- phenyl-dihalide) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone exists It reacts to obtain 2- (2,4,5- phenyl trihalide) -4- (difluoromethyl) -2,4- dihydro -5- methyl-with halogenating agent under the catalysis of acid 3H-1,2,4- triazole -3- ketone；
(b) 2- (2,4,5- phenyl trihalide) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone It is reacted with lithium alkylide or directly generates corresponding format reagent under the conditions of Mg, then reacted generation benzene with boric acid ester compound and connect triazole Quinoline ketone derivatives C.
Preferably, the halogenating agent in the step (a) includes NBS, CuBr, HBr, Br2, NIS2, HI etc.；The acid is Sulfuric acid, hydrochloric acid or nitric acid.
Preferably, the boric acid ester compound in the step (b) is specifically selected from butyl borate, trimethylborate, boron Triethylenetetraminehexaacetic acid ester, boric acid tripropyl ester, tri-isopropylborate, boric acid tributyl ester or tri-isopropylborate.
Preferably, the lithium alkylide in the step (b) is selected from lithium methide, ethyl-lithium, n-propyl lithium, isopropyl lithium, positive fourth Base lithium or isobutyl group lithium.
Preferably, in the step (1) benzene connect triazolinones derivative C, sodium azide or to Methyl benzenesulfonyl base nitrine, The molar ratio of mantoquita is 1:1~2:0.1~1.
Preferably, mantoquita is selected from CuI, CuCl, CuBr, Cu in the step (1)2O、Cu(OAc)2·(H2O)2Or CuSO4。
Preferably, when the Y group is selected from bromine or iodine, the reactant in step (1) further includes L-PROLINE and alkali；Institute State benzene connect triazolinones derivative C, L-PROLINE, alkali molar ratio be 1:0.1~0.5:0.1~0.5.
Alkali used in the step (1) is selected from potassium phosphate, potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, carbonic acid One of lithium or cesium carbonate are a variety of.
Preferably, reduction step can be used catalytic hydrogenation or use LiAlH in the step (2)4、NaBH4Direct-reduction.
Preferably, when reactant is triphenyl phosphorus in the step (2), mole of aromatic yl azide D and triphenyl phosphorus Than for 1:1~3；Preferably, when the step (2) is catalytic hydrogenation, catalyst is selected from Pd/C, Raney Ni, Pd/ CaCO3、Pt/C、PtO2、Pt/Al2O3Deng；The mass ratio of the aromatic yl azide D and catalytic hydrogenation catalyst be 1:0.01~ 0.20；Further, the mass ratio of the aromatic yl azide D and catalytic hydrogenation catalyst is 1:0.03~0.08.
The Chinese name of compound, which has with structural formula, in the present invention conflicts, and is subject to structural formula.
The preparation method that sulfentrazone key intermediate benzene provided by the invention connects triazolinones derivative be easy to industrialize, Raw material is cheap and easy to get, reaction yield and quality are higher, while having avoided poisonous reagent methylsufonyl chloride in original synthetic route It uses, keeps industrialized production more safe and environment-friendly.
Specific embodiment
Illustrate the present invention below in conjunction with example, but does not limit the present invention.In the art, technical staff is the present invention Simple replacement or improvement belong in the technical solution protected of the present invention.
Embodiment 1:
2- 1. (the fluoro- 5- iodobenzene of the chloro- 2- of 4-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- The synthesis of ketone
20% oleum of 200mL is added in the round-bottomed flask of 500mL, is subsequently added into 57.4g (0.208mol) 2- (4- Chloro- 2- fluorobenzene) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, ice-water bath cooling addition 52.6g (0.208mol) elemental iodine, is vigorously stirred and is warmed to room temperature, and 10h reaction terminates.Reaction is poured into 700g ice, 1000g bis- Chloroethanes extracts in two times, then 10%K2CO3Aqueous solution, the washing of 5% sodium sulfite aqueous solution, last 500g soft water washing have Machine phase, decompression precipitation obtain 2- (the fluoro- 5- iodophenyl of the chloro- 2- of 4-) -4- (difluoro of 77.6g purity 97% to white solid is done to obtain Methyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, yield 92%, purity 97%.
2- 2. (the fluoro- 5- bromobenzene of the chloro- 2- of 4-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- The synthesis of ketone
20% oleum of 200mL is added in the round-bottomed flask of 500mL, is subsequently added into 57.4g (0.208mol) 2- (4- Chloro- 2- fluorobenzene) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, ice-water bath cooling addition 34.7g (0.216mol) bromine simple substance, is vigorously stirred and is warmed to room temperature, and 10h reaction terminates.Reaction is poured into 1000g ice, 1000g Dichloroethanes extracts in two times, then 10%K2CO3Aqueous solution, the washing of 5% sodium sulfite aqueous solution, last 500g soft water washing Organic phase, decompression precipitation obtain 2- (the fluoro- 5- bromobenzene of the chloro- 2- of 4-) -4- (two of 66.34g purity 97% to white solid is done to obtain Methyl fluoride) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, yield 90%, purity 97%.
2- 3. (the chloro- 5- iodobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone Synthesis
In the round-bottomed flask of 500mL be added 20% oleum of 200mL, be subsequently added into 61.2g (0.208mol) 2- (2, 4- chlorobenzene) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, ice-water bath cooling addition 52.6g (0.208mol) elemental iodine, is vigorously stirred and is warmed to room temperature, and 10h reaction terminates.Reaction is poured into 700g ice, bis- chloroethene of 1000g Alkane extracts in two times, then 10%K2CO3Aqueous solution, the washing of 5% sodium sulfite aqueous solution, last 500g soft water wash organic phase, Precipitation is depressurized to white solid is done to obtain, obtains 2- (2,4- bis- chloro- 5- iodophenyl) -4- (difluoromethyl)-of 80.4g purity 96% 2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone, yield 92%, purity 96%.
4. the chloro- 5- of 2,4- bis- (4- (difluoromethyl) -3- methyl -5- oxo -4,5- dihydro -1H-1,2,4- triazolyl benzene boron The synthesis of acid
2.88g (0.12mol) magnesium chips and a granule crystal iodine are added in tetra- mouthfuls of original place flasks of 500ml, is placed in 37 DEG C of water In bath.N2Under protection, 37.3g (0.10mol) 2- (2,4- bis- chloro- 5- bromophenyl) -4- (difluoromethyl) -2,4- dihydro-is added dropwise The mixed solution of 5- methyl -3H-1,2,4- triazole -3- ketone and 140mL anhydrous tetrahydro furan；After ten minutes, the color of iodine disappears, Temperature increases, and continues to add 40mL tetrahydrofuran in whipping process, adjusts rate of addition, solution temperature is made to maintain 42-45 DEG C, Rear insulated and stirred 1h is added dropwise in about 1h, obtains the solution of corresponding phenyl-magnesium-bromide grignard reagent, and reaction solution stands 10min, takes Supernatant liquor 5.00mL, it is 98% that acidimetry, which measures yield, is directly entered and reacts in next step；By grignard reagent through constant pressure addition Funnel is slowly dropped in the mixed solution of 46g (0.2mol) butyl borate and 70ml anhydrous tetrahydro furan, stirring, temperature control System is at -10 DEG C, and about 0.5h is added dropwise, insulation reaction 0.5h；It is rapidly heated to 20 DEG C, stirs 1h.It is slowly added to 100ml volume The cold hydrochloric acid that score is 4% stirs 30 minutes.Organic layer is separated, water layer extracts (200ml*3) with ether, is associated with Machine phase, is recovered under reduced pressure solvent.Water is added in concentrate, with NaOH solution tune pH to 10.Reduced steam distillation cleans, while hot mistake Filter, acidification of filtrate to pH are 2, are precipitated crystal；It filters, drying to constant weight obtains the accordingly chloro- 5- of 2,4- bis- (4- (difluoromethyl) -3- Methyl -5- oxo -4,5- dihydro -1H-1,2,4- triazolyl phenyl boric acid 28.7g, yield 85%, purity 95%.
Embodiment 2:
1. 2- (the fluoro- 5- iodobenzene of the chloro- 2- of 4-) -4- (difluoromethyl) -2,4- dihydro -5- is added in the reaction flask of 1L size Methyl -3H-1,2,4- triazole -3- ketone 40.5g (0.1mol), sodium azide 7.8g (0.12mol), 1.9g CuI (0.01mol), L-PROLINE 1.9g (0.01mol), 0.4g NaOH (0.01mol), nitrogen are replaced three times, and 300mL DMSO, inertia is then added The lower 60 DEG C of oil bath heatings of atmosphere, TLC plate track reaction process, and reaction terminates, is reduced to room temperature, reaction solution is added dropwise to 1L In water, it is precipitated white solid product, a small amount of water washing, solid drying to constant weight product 29.3g, yield 92%, purity 97%.
2. 2- (the fluoro- 5- bromobenzene of the chloro- 2- of 4-) -4- (difluoromethyl) -2,4- dihydro -5- is added in the reaction flask of 1L size Methyl -3H-1,2,4- triazole -3- ketone 35.6g (0.1mol), sodium azide 13g (0.2mol), 1.9g CuI (0.01mol), L- Proline 9.5g (0.05mol), 2.0g NaOH (0.05mol), nitrogen are replaced three times, and 300mL DMSO is then added.Indifferent gas The lower 60 DEG C of oil bath heatings of body atmosphere, TLC plate track reaction process, and reaction terminates, is reduced to room temperature, reaction solution is added dropwise to 1L water In, it is precipitated white solid product, a small amount of water washing, solid drying to constant weight product 28.0g, yield 88%, purity 96%.
2- 3. (5- azido -2,4 dichloro benzene) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole - The synthesis of 3- ketone
2- (the chloro- 5- iodophenyl of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- is added in the reaction flask of 1L size Methyl -3H-1,2,4- triazole -3- ketone 42.0g (0.1mol), sodium azide 7.8g (0.12mol), 1.9g CuI (0.01mol), L-PROLINE 1.9g (0.01mol), 0.4g NaOH (0.01mol), nitrogen are replaced three times, and 300mL DMSO, inertia is then added The lower 60 DEG C of oil bath heatings of atmosphere, TLC plate track reaction process, and reaction terminates, is reduced to room temperature, reaction solution is added dropwise to 1L In water, it is precipitated white solid product, a small amount of water washing, solid drying to constant weight product 30.8g, yield 92%, purity 97%.
4. the NaN in the reaction flask for being equipped with blender, thermometer, drying tube378g (1.2mol), copper sulphate 16g (0.1mol), 2,4- bis- chloro- 5- (4- (difluoromethyl) -3- methyl -5- oxo -4,5- dihydro -1H-1,2,4- triazolyl benzene boron 1000g methanol is added in sour 33.78g (0.1mol), is vigorously stirred 6h at room temperature, and TLC monitors reaction process, and reaction terminates, precipitation 600g toluene dissolution filter is added, washs organic phase with massive laundering, precipitation obtains 2- (5- azido -2,4- dichloro-benzenes) -4- (difluoro Methyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone 30.48g, purity 96%, yield 91%.
Embodiment 3:
2- 1. (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- The synthesis of ketone
In the reaction flask for being equipped with blender, thermometer, reflux condensing tube, it is added 2- (5- azido -2,4- dichloro-benzenes) - 4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone 46.9g (0.14mol), THF- water (10: 1.5mL), it stirs lower room temperature and triphenylphosphine 41g (0.16mol) is added, reaction is stirred at room temperature for 24 hours, is concentrated under reduced pressure.Residue passes through Column chromatography purifying, does eluent with chloroform-methanol (18:1), obtains 2- (2,4- bis- chloro- 5- aminobenzene) -4- (difluoromethyl) -2, 4- dihydro -5- methyl -3H-1,2,4- triazole -3- ketone solid 39.8g, yield 92%, purity 98%.
2- 2. (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- Compound 1- (the chloro- 5- azido of 2,4- bis-) -4- difluoromethyl -4,5- dihydro -3- first is added in the synthesis of ketone in hydrogenation apparatus Base -5- oxygen -1H-1,2,4- triazole 60.3g (0.18mol), methanol 400mL, 5%Pd/C catalyst 1.8g lead to after nitrogen displacement Enter hydrogen to be reacted, normal pressure is passed through hydrogen reaction 10h.With nitrogen replacing hydrogen, catalyst is filtered off.Precipitation obtains gray object production Product 53.4g, yield 96%, purity 97%.
2- 3. (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- Compound 1- (the chloro- 5- azido of 2,4- bis-) -4- difluoromethyl -4,5- dihydro -3- first is added in the synthesis of ketone in hydrogenation apparatus Base -5- oxygen -1H-1,2,4- triazole 60.3g (0.18mol), methanol 400mL, Ranney Ni catalyst 5g lead to after nitrogen displacement Enter hydrogen to be reacted, 1MPa is passed through hydrogen reaction 10h.With nitrogen replacing hydrogen, catalyst is filtered off.Precipitation obtains gray object production Product 51.72g, yield 88%, purity 98%.
2- 4. (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- The synthesis of ketone
Compound 1- (the chloro- 5- azido of 2,4- bis-) -4- difluoromethyl -4,5- dihydro -3- first is added in hydrogenation apparatus Base -5- oxygen -1H-1,2,4- triazole 60.3g (0.18mol), methanol 400mL, 5%Pd/C catalyst 1.8g lead to after nitrogen displacement Enter hydrogen to be reacted, normal pressure is passed through hydrogen reaction 10h.With nitrogen replacing hydrogen, catalyst is filtered off.Precipitation obtains gray object production Product 51.72g, yield 93%, purity 97%.
2- 5. (the chloro- 5- aminobenzene of 2,4- bis-) -4- (difluoromethyl) -2,4- dihydro -5- methyl -3H-1,2,4- triazole -3- The synthesis of ketone
Compound 1- (the chloro- 5- azido of 2,4- bis-) -4- difluoromethyl -4,5- dihydro -3- first is added in hydrogenation apparatus Base -5- oxygen -1H-1,2,4- triazole 60.3g (0.18mol), methanol 400mL, Pd/CaCO3Catalyst 3g is passed through after nitrogen displacement Hydrogen is reacted, and after 0.5MPa is passed through hydrogen reaction 10h, with nitrogen replacing hydrogen, filters off catalyst；Precipitation obtains gray object Product 50.05g, yield 90%, purity 96%.
1H NMR(600MHz,CDCl3),d 2.46(s,3H,CH3),4.19(s,2H,NH2),6.82(s,1H,ArH), 7.05 (t, 1H, J=58.2Hz, CHF2),7.40(s,1H,ArH).EI-MS,m/z 307.9(M)+.
Intermediate and product in the various embodiments described above, through mass spectrum and hydrogen spectrum confirmation.
What has been described above is only a preferred embodiment of the present invention, it is noted that for those of ordinary skill in the art For, without departing from the concept of the premise of the invention, various modifications and improvements can be made, these belong to the present invention Protection scope.

Claims (10)

1.一种甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于包括如下步骤：1. a preparation method of sulfentrazone key intermediate benzotriazolinone derivative, is characterized in that comprising the steps: (1)苯环5位卤原子或者硼酸基团取代的苯连三唑啉酮衍生物C，在铜盐的催化下，与叠氮化钠或者对甲基苯磺酰基叠氮条件下生成相应芳基叠氮化物D；(1) The benzotriazolinone derivative C substituted by the halogen atom at the 5th position of the benzene ring or the boronic acid group, under the catalysis of copper salt, generates the corresponding reaction with sodium azide or p-methylbenzenesulfonyl azide. Arylazide D; (2)芳基叠氮化物D在三苯基磷条件下发生Staudinger还原水解得到化合物E；或芳基叠氮化物D经还原得到得到2-(2,4-二卤代-5-氨基苯)-4-(二氟甲基)-2,4-二氢-5-甲基-3H-1,2,4-三唑-3-酮；(2) Staudinger reductive hydrolysis of arylazide D under the condition of triphenylphosphorus to obtain compound E; or reduction of arylazide D to obtain 2-(2,4-dihalo-5-aminobenzene )-4-(difluoromethyl)-2,4-dihydro-5-methyl-3H-1,2,4-triazol-3-one; 上述反应的反应式如下：The reaction formula of the above reaction is as follows: 2.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述反应中化合物C、D、E中的X基团选自氟或氯；化合物C中的Y基团选自溴、碘、B(OH)2、B(OR)2；其中B(OR)2中的R基团选自C1～6烷基。2. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, in described reaction, the X group in compound C, D, E is selected from fluorine or chlorine; the Y group in compound C is selected from bromine, iodine, B(OH) 2 , B(OR) 2 ; wherein the R group in B(OR) 2 is selected from C 1-6 alkyl. 3.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述反应还包括苯连三唑啉酮衍生物C的制备步骤：3. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, described reaction also comprises the preparation step of benzotriazolinone derivative C: (a)2-(2,4-二卤代苯)-4-(二氟甲基)-2,4-二氢-5-甲基-3H-1,2,4-三唑-3-酮在酸的催化下与卤代试剂反应得到2-(2,4,5-三卤代苯)-4-(二氟甲基)-2,4-二氢-5-甲基-3H-1,2,4-三唑-3-酮；(a) 2-(2,4-Dihalobenzene)-4-(difluoromethyl)-2,4-dihydro-5-methyl-3H-1,2,4-triazole-3- Ketones react with halogenated reagents under the catalysis of acids to give 2-(2,4,5-trihalobenzene)-4-(difluoromethyl)-2,4-dihydro-5-methyl-3H- 1,2,4-triazol-3-one; (b)2-(2,4,5-三卤代苯)-4-(二氟甲基)-2,4-二氢-5-甲基-3H-1,2,4-三唑-3-酮与烷基锂反应或在Mg条件下直接生成相应格式试剂，再与硼酸酯化合物反应生成苯连三唑啉酮衍生物C。(b) 2-(2,4,5-Trihalobenzene)-4-(difluoromethyl)-2,4-dihydro-5-methyl-3H-1,2,4-triazole- The 3-ketone reacts with alkyl lithium or directly generates the corresponding Grignard reagent under the condition of Mg, and then reacts with the boronate compound to generate the benzotriazolinone derivative C. 4.如权利要求3所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，步骤(a)中的卤代试剂包括NBS、CuBr、HBr、Br2、NIS2、HI；所述酸为硫酸、盐酸或硝酸。4. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 3, is characterized in that, the halogenated reagent in step (a) comprises NBS, CuBr, HBr, Br 2 , NIS 2 , HI; the acid is sulfuric acid, hydrochloric acid or nitric acid. 5.如权利要求3所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述步骤(b)中的硼酸酯化合物选自硼酸三丁酯、硼酸三甲酯、硼酸三乙酯、硼酸三丙基酯、硼酸三异丙基酯、硼酸三丁基酯或硼酸三异丙基酯。5. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 3, is characterized in that, the borate compound in described step (b) is selected from tributyl borate , trimethyl borate, triethyl borate, tripropyl borate, triisopropyl borate, tributyl borate or triisopropyl borate. 6.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述步骤(1)中苯连三唑啉酮衍生物C、叠氮化钠或对甲基苯磺酰基叠氮、铜盐的摩尔比为1：1～2：0.1～1。6. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, in described step (1), benzotriazolinone derivative C, stack The molar ratio of sodium nitride or p-toluenesulfonyl azide and copper salt is 1:1-2:0.1-1. 7.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述步骤(1)中铜盐选自CuI、CuCl、CuBr、Cu2O、Cu(OAc)2(H2O)2或CuSO4。7. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, in described step (1), copper salt is selected from CuI, CuCl, CuBr, Cu 2 O, Cu(OAc) 2 (H 2 O) 2 or CuSO 4 . 8.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，当所述Y基团选自溴或碘时，步骤(1)中的反应物还包括L-脯氨酸和碱；所述苯连三唑啉酮衍生物C、L-脯氨酸、碱的摩尔比为1：0.1～0.5：0.1～0.5。8. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, when described Y group is selected from bromine or iodine, in step (1) The reactant also includes L-proline and base; the molar ratio of the benzotriazolinone derivative C, L-proline and base is 1:0.1-0.5:0.1-0.5. 9.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，步骤(1)中使用的碱选自磷酸钾、碳酸钾、碳酸钠、氢氧化钠、氢氧化钾、碳酸锂或碳酸铯中的一种或多种。9. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, the alkali used in step (1) is selected from potassium phosphate, salt of wormwood, sodium carbonate , one or more of sodium hydroxide, potassium hydroxide, lithium carbonate or cesium carbonate. 10.如权利要求1所述的甲磺草胺关键中间体苯连三唑啉酮衍生物的制备方法，其特征在于，所述步骤(2)中反应物为三苯基磷时，芳基叠氮化物D与三苯基磷的摩尔比为1：1～3；所述步骤(2)为催化氢化反应时，催化剂选自Pd/C、Raney Ni、Pd/CaCO3、Pt/C、PtO2、Pt/Al2O3；所述芳基叠氮化物D与催化氢化催化剂的质量比为1：0.01～0.20。10. the preparation method of sulfentrazone key intermediate benzotriazolinone derivative as claimed in claim 1, is characterized in that, in described step (2), when reactant is triphenylphosphine, aryl The molar ratio of azide D to triphenylphosphorus is 1:1 to 3; when the step (2) is a catalytic hydrogenation reaction, the catalyst is selected from Pd/C, Raney Ni, Pd/CaCO 3 , Pt/C, PtO 2 , Pt/Al 2 O 3 ; the mass ratio of the arylazide D to the catalytic hydrogenation catalyst is 1:0.01-0.20.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114149342A (en) * 2021-11-02 2022-03-08 浙大宁波理工学院 N- (2, 4-dichloro-5-hydrazinophenyl) acetamide compound and synthesis method thereof
CN115703746A (en) * 2021-08-04 2023-02-17 北京颖泰嘉和生物科技股份有限公司 Preparation method of 1,2,4-triazol-3-one derivatives

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101910143A (en) * 2008-01-18 2010-12-08 卫材R&D管理有限公司 Fused Aminodihydrothiazine Derivatives
CN103819418A (en) * 2014-01-14 2014-05-28 泸州东方农化有限公司 Method for synthesizing carfentrazone-ethyl and carfentrazone-ethyl intermediate
WO2014099768A1 (en) * 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. C6-azaspiro iminothiadiazine dioxides as bace inhibitors
CN103951627A (en) * 2014-05-06 2014-07-30 泸州东方农化有限公司 Method for synthesizing sulfentrazone midbody and sulfentrazone

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101910143A (en) * 2008-01-18 2010-12-08 卫材R&D管理有限公司 Fused Aminodihydrothiazine Derivatives
WO2014099768A1 (en) * 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. C6-azaspiro iminothiadiazine dioxides as bace inhibitors
CN103819418A (en) * 2014-01-14 2014-05-28 泸州东方农化有限公司 Method for synthesizing carfentrazone-ethyl and carfentrazone-ethyl intermediate
CN103951627A (en) * 2014-05-06 2014-07-30 泸州东方农化有限公司 Method for synthesizing sulfentrazone midbody and sulfentrazone

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ROMAIN EYCHENNE，ET AL.: "Rhenium Complexes Based on an N2O Tridentate Click Scaffold:From Synthesis, Structural and Theoretical Characterization to a Radiolabelling Study", 《EUR. J. INORG. CHEM.》 *
S. YU. BUKHVALOVA，ET AL.: "Synthesis of Polymethoxy-Substituted Triazolobenzoxazepines", 《RUSSIAN JOURNAL OF ORGANIC CHEMISTRY》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115703746A (en) * 2021-08-04 2023-02-17 北京颖泰嘉和生物科技股份有限公司 Preparation method of 1,2,4-triazol-3-one derivatives
CN114149342A (en) * 2021-11-02 2022-03-08 浙大宁波理工学院 N- (2, 4-dichloro-5-hydrazinophenyl) acetamide compound and synthesis method thereof

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