CN105541709A - Method for preparing boscalid - Google Patents
Method for preparing boscalid Download PDFInfo
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- CN105541709A CN105541709A CN201610103719.7A CN201610103719A CN105541709A CN 105541709 A CN105541709 A CN 105541709A CN 201610103719 A CN201610103719 A CN 201610103719A CN 105541709 A CN105541709 A CN 105541709A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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Abstract
The invention relates to a method for preparing boscalid. 2-chloro-N-(2-chlorphenyl)pyridine-3-formamide and chlorophenylboronic acid are added into a reactor, a catalyst is added, a ligand 2-phosphorus dicyclohexyl-2', 6'-dimethoxy biphenyl(S-phos), alkali and a solvent/water system are used as a solvent, and the temperature is increased to 100-140 DEG C for a reaction to obtain boscalid. The method for preparing boscalid has the advantages that reaction steps are simple, operation is easy, raw materials are low in cost and easy to purchase, and the yield is high. The molar ratio of the 2-chloro-N-(2-chlorphenyl)pyridine-3-formamide to the chlorophenylboronic acid a to the catalyst to the 2-phosphorus dicyclohexyl-2' to the 6'-dimethoxy biphenyl(S-phos) to the alkali to the solvent to water is 1:(1.3-1.8):(0.01-0.07):(0.05-0.13):(1-3):(90-122):(200-244).
Description
Technical field
The present invention relates to Novel tobacco acid amide fungicides; A kind of particularly method preparing boscalid amine.
Background technology
Chinese: boscalid amine
English name: Boscalid
The chloro-N-of chemical name: 2-(4'-chlordiphenyl-2-base) niacinamide
Chemistry English name: 2-Chloro-N-(4'-Chlorobiphenyl-2-yl) Nicotinamide
Molecular formula: C
18h
12cl
2n
2o
Molecular weight: 343.21
Structural formula is as follows:
Boscalid amine is the Novel tobacco acid amide fungicides developed by German BASF, and its fungicidal spectrum is comparatively wide, to other medicament germ resistancies also relative efficiency, can be used for the multiple fungal disease of various crop as the control of gray mold, Powdery Mildew and various cankers etc.The mechanism of action of boscalid amine is unique, not easily produces cross resistance, and rain fastness is good, becomes the more and more valued nicotinamide sterilant of one.The preparation method of boscalid amine disclosed in patent EP0545099, its synthetic route is as follows:
In this method, the chloro-2 nitro biphenyl of 4'-(5) is prepared under palladium chtalyst to chlorophenylboronic acid (4) and o-chloronitrobenzene, prepare the chloro-2-phenylaniline (6) of 4'-through iron powder reducing again, the chloro-2-phenylaniline (6) of 4'-is carried out amidate action with 2-chloronicotinoyl chloride (3) or its hydrochloride and is prepared compound (1) boscalid amine.This method is for preparing the common method of boscalid amine (1), more to its report in document, but coupling reaction process generation impurity is more, and yield is relatively low, suitability for industrialized production difficulty.
Chi Huiwei carries out amidate action with adjacent Iodoaniline (7) and 2-chloronicotinoyl chloride (3) and generates the chloro-N-of 2-(2-iodophenyl) niacinamide (8), the chloro-N-of 2-(2-iodophenyl) niacinamide (8) again with to chlorophenylboronic acid through linked reaction generate boscalid amine (Chi Huiwei. the synthesis of boscalid amine and bioactivity research [J]. the agrochemical new millennium, 2008,9 (1): 39-40.).This method is with adjacent Iodoaniline for raw material, and the expensive cost of relative price is high, not easily prepares.Its synthetic route is as follows:
Summary of the invention
The present invention is directed to the deficiencies in the prior art, provide that a kind of raw material is simple and easy to get, reactions steps is few, cost is low, easy and simple to handle, yield is higher, eco-friendly preparation method.
Technical scheme of the present invention is as follows:
A kind of method preparing boscalid amine; With the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide for raw material, then generate boscalid amine with to chlorophenylboronic acid through Suzuki linked reaction.
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide with join in reactor to chlorophenylboronic acid, add catalyzer, part 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl (S-Phos), alkali, solvent/water system is solvent, is warming up to 100 ~ 140 DEG C, obtains boscalid amine.
Described alkali is one in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, potassiumphosphate or its mixture.
Described catalyzer is palladium, Palladous chloride or palladium charcoal.
Described solvent is selected from the one in tetrahydrofuran (THF), toluene, N, N-methylacetamide.
Described starting material mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: catalyzer: 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl: alkali: solvent: water=1:(1.3 ~ 1.8): (0.01 ~ 0.07): (0.05 ~ 0.13): (1 ~ 3): (90 ~ 122): (200 ~ 244).In said ratio, preferred raw material system is the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl: salt of wormwood: N,N-dimethylacetamide: water=1:(1.3 ~ 1.8): (0.01 ~ 0.07): (0.05 ~ 0.13): (1 ~ 3): (90 ~ 122): (200 ~ 244).
The chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide adopts customary preparation methods, or the method that the embodiment of the present invention exemplifies.
Synthetic route raw material of the present invention is simple and easy to get, easy and simple to handle, environmentally friendly, is applicable to suitability for industrialized production.Reaction scheme is as follows:
In boscalid amine preparation method provided by the invention: preferred catalyst palladium, alkali is salt of wormwood, and N,N-dimethylacetamide/water body is solvent.
Temperature of reaction described in aforesaid method is: 100 ~ 140 DEG C, preferably 130 ~ 140 DEG C.
Preferred method is described in detail as follows:
The chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide with join in reactor to chlorophenylboronic acid, add catalyst acetic acid palladium, part S-Phos, alkali is salt of wormwood, N, N-N,N-DIMETHYLACETAMIDE/water body is solvent, be warming up to 130 ~ 140 DEG C of reactions to raw material reaction completely after, reaction solution is stirred and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression is down to room temperature after steaming most of solvent, add methylene dichloride and water, layering extracts, aqueous phase uses dichloromethane extraction twice again, merge organic phase, water washing, organic phase anhydrous magnesium sulfate drying, suction filtration, filtrate steaming removal solvent obtains product as light yellow solid, the light yellow solid obtained obtains white solid boscalid amine with dehydrated alcohol recrystallization again.Reacting optimum mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N,N-dimethylacetamide: water=1:1.5:0.04:0.09:2:106:222.Optimal reaction temperature is 130 DEG C.
Adopt the present invention to prepare the method for boscalid amine, have that reactions steps is short, simple to operate, material cost is low compared to original production process and be easy to buy, yield advantages of higher.
Specific embodiments
Following embodiment only for further illustrating the present invention, but does not limit the present invention.
The preparation of the chloro-N-of embodiment 12-(2-chloro-phenyl-) pyridine-3-carboxamide
Ortho-Chloro aniline 12.8g and 2-chloronicotinoyl chloride hydrochloride 23g is joined in reaction flask, add 1,2-ethylene dichloride 500mL, (mol ratio is triethylamine 30g: Ortho-Chloro aniline: 2-chloronicotinoyl chloride hydrochloride: 1,2-ethylene dichloride: triethylamine=1:1.2:55:3), stir and be warming up to back flow reaction 2h.It is complete that TLC detects raw material reaction, stops heating, stirs and be down to room temperature (15 DEG C), separate out solid, filter, with 1,2-ethylene dichloride washing leaching cake, filtrate decompression is steamed and is desolventized, and obtains buff white solid, adds 100mL re-crystallizing in ethyl acetate, suction filtration, drying, obtains the chloro-N-of white solid 2-(2-chloro-phenyl-) pyridine-3-carboxamide 25.5g, yield 95.50%.
The preparation of embodiment 2 boscalid amine
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide 14g, to chlorophenylboronic acid 12g, salt of wormwood 13.8g, palladium 0.55g and S-Phos part 2g directly joins in reaction flask, add N, (mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N for N-N,N-DIMETHYLACETAMIDE 398mL and 200mL water, N-N,N-DIMETHYLACETAMIDE: water=1:1.5:0.04:0.09:2:106:222), stirring is warming up to 130 DEG C, to raw material complete reaction, stopped reaction.Reaction solution stirs and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression steams most of solvent, residue 1/4, be down to room temperature, add 300mL methylene dichloride and 300mL water, layering extracts, aqueous phase 100mL dichloromethane extraction twice, merge organic phase, add 200mL water washing, separatory, organic phase adds anhydrous magnesium sulfate drying, suction filtration, filter cake 50mL washed with dichloromethane, obtain light yellow filtrate, filtrate steaming removal solvent obtains product as light yellow solid, with 25mL dehydrated alcohol recrystallization, suction filtration, dry white solid boscalid amine 14.37g, yield 83.79%.
The preparation of embodiment 3 boscalid amine
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide 14g, to chlorophenylboronic acid 10.2g, salt of wormwood 6.9g, palladium 0.11g and S-Phos ligand 1 g directly joins in reaction flask, add N, (mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N for N-N,N-DIMETHYLACETAMIDE 340mL and 180mL water, N-N,N-DIMETHYLACETAMIDE: water=1:1.3:0.01:0.05:1:90:200), stirring is warming up to 100 DEG C, to raw material complete reaction, stopped reaction.Reaction solution stirs and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression steams most of solvent, residue 1/4, be down to room temperature, add 300mL methylene dichloride and 300mL water, layering extracts, aqueous phase 100mL dichloromethane extraction twice, merge organic phase, add 200mL water washing, separatory, organic phase adds anhydrous magnesium sulfate drying, suction filtration, filter cake 50mL washed with dichloromethane, obtain light yellow filtrate, filtrate steaming removal solvent obtains product as light yellow solid, with 25mL dehydrated alcohol recrystallization, suction filtration, dry white solid boscalid amine 10.89g, yield 63.51%.
The preparation of embodiment 4 boscalid amine
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide 14g, to chlorophenylboronic acid 14g, salt of wormwood 20.7g, palladium 0.78g and S-Phos part 2.6g directly joins in reaction flask, add N, (mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N for N-N,N-DIMETHYLACETAMIDE 460mL and 220mL water, N-N,N-DIMETHYLACETAMIDE: water=1:1.8:0.07:0.13:3:122:244), stirring is warming up to 140 DEG C, to raw material complete reaction, stopped reaction.Reaction solution stirs and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression steams most of solvent, residue 1/4, be down to room temperature, add 300mL methylene dichloride and 300mL water, layering extracts, aqueous phase 100mL dichloromethane extraction twice, merge organic phase, add 200mL water washing, separatory, organic phase adds anhydrous magnesium sulfate drying, suction filtration, filter cake 50mL washed with dichloromethane, obtain light yellow filtrate, filtrate steaming removal solvent obtains product as light yellow solid, with 25mL dehydrated alcohol recrystallization, suction filtration, dry white solid boscalid amine 14.35g, yield 83.64%.
The preparation of embodiment 5 boscalid amine
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide 14g, to chlorophenylboronic acid 12.5g, salt of wormwood 10.3g, palladium 0.33g and S-Phos part 2g directly joins in reaction flask, add N, (mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N for N-N,N-DIMETHYLACETAMIDE 410mL and 188mL water, N-N,N-DIMETHYLACETAMIDE: water=1:1.6:0.03:0.1:1.5:108:209), stirring is warming up to 135 DEG C, to raw material complete reaction, stopped reaction.Reaction solution stirs and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression steams most of solvent, residue 1/4, be down to room temperature, add 300mL methylene dichloride and 300mL water, layering extracts, aqueous phase 100mL dichloromethane extraction twice, merge organic phase, add 200mL water washing, separatory, organic phase adds anhydrous magnesium sulfate drying, suction filtration, filter cake 50mL washed with dichloromethane, obtain light yellow filtrate, filtrate steaming removal solvent obtains product as light yellow solid, with 25mL dehydrated alcohol recrystallization, suction filtration, dry white solid boscalid amine 13.96g, yield 81.37%.
The preparation of embodiment 6 boscalid amine
By chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide 14g, to chlorophenylboronic acid 10.2g, salt of wormwood 15g, palladium 0.67g and S-Phos ligand 1 .4g directly joins in reaction flask, add N, (mol ratio is N-N,N-DIMETHYLACETAMIDE 418mL and water 207mL: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: S-Phos: salt of wormwood: N, N-N,N-DIMETHYLACETAMIDE: water=1:1.3:0.06:0.07:2.2:110:230), stirring is warming up to 120 DEG C, to raw material complete reaction, stopped reaction.Reaction solution stirs and is cooled to 50 DEG C, suction filtration, filter cake retains, filtrate decompression steams most of solvent, residue 1/4, be down to room temperature, add 300mL methylene dichloride and 300mL water, layering extracts, aqueous phase 100mL dichloromethane extraction twice, merge organic phase, add 200mL water washing, separatory, organic phase adds anhydrous magnesium sulfate drying, suction filtration, filter cake 50mL washed with dichloromethane, obtain light yellow filtrate, filtrate steaming removal solvent obtains product as light yellow solid, with 25mL dehydrated alcohol recrystallization, suction filtration, dry white solid boscalid amine 12.56g, yield 73.21%.
Claims (8)
1. prepare the method for boscalid amine for one kind; It is characterized in that with the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide for raw material, then generate boscalid amine with to chlorophenylboronic acid through Suzuki linked reaction.
2. the method for claim 1, it is characterized in that chloro-for 2-N-(2-chloro-phenyl-) pyridine-3-carboxamide and join in reactor to chlorophenylboronic acid, add catalyzer, part 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl, alkali, solvent/water system is solvent, be warming up to 100 ~ 140 DEG C, obtain boscalid amine.
3. the method as described in claim 1,2, is characterized in that alkali is one in sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, potassiumphosphate or its mixture.
4. the method as described in claim 1,2, is characterized in that catalyzer is palladium, Palladous chloride or palladium charcoal, is preferably palladium.
5. the method as described in claim 1,2, it is characterized in that solvent is selected from the one in tetrahydrofuran (THF), toluene, N, N-methylacetamide, preferred solvent is N, N-methylacetamide.
6. method as claimed in claim 2, it is characterized in that described starting material mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: catalyzer: 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl: alkali: solvent: water=1:(1.3 ~ 1.8): (0.01 ~ 0.07): (0.05 ~ 0.13): (1 ~ 3): (90 ~ 122): (200 ~ 244).
7. method as claimed in claim 6, it is characterized in that described starting material mol ratio is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl: salt of wormwood: N,N-dimethylacetamide: water=1:(1.3 ~ 1.8): (0.01 ~ 0.07): (0.05 ~ 0.13): (1 ~ 3): (90 ~ 122): (200 ~ 244).
8. the method as described in claim 2,3,4 or 5, it is characterized in that described optimal seeking of raw and processed materials proportioning is: the chloro-N-of 2-(2-chloro-phenyl-) pyridine-3-carboxamide: to chlorophenylboronic acid: palladium: 2-dicyclohexyl phosphine-2', 6'-dimethoxy-biphenyl: salt of wormwood: N,N-dimethylacetamide: water=1:1.5:0.04:0.09:2:106:222.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109476603A (en) * | 2016-08-04 | 2019-03-15 | 江苏龙灯化学有限公司 | The method for preparing Boscalid |
| CN113880759A (en) * | 2021-10-22 | 2022-01-04 | 江苏七洲绿色科技研究院有限公司 | Preparation method of boscalid |
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| CN105085389A (en) * | 2015-09-08 | 2015-11-25 | 利民化工股份有限公司 | Preparation method of boscalid |
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2016
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| CN104725303A (en) * | 2015-02-02 | 2015-06-24 | 西安近代化学研究所 | Synthetic method of 2-chloro-N-(4'-chlorodiphenyl-2-yl) nicotinamide |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109476603A (en) * | 2016-08-04 | 2019-03-15 | 江苏龙灯化学有限公司 | The method for preparing Boscalid |
| CN113880759A (en) * | 2021-10-22 | 2022-01-04 | 江苏七洲绿色科技研究院有限公司 | Preparation method of boscalid |
| CN113880759B (en) * | 2021-10-22 | 2023-09-05 | 江苏七洲绿色科技研究院有限公司 | Preparation method of boscalid |
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