CN115385903A - Preparation method of cyano-substituted benzoxazine-4-one derivative - Google Patents
Preparation method of cyano-substituted benzoxazine-4-one derivative Download PDFInfo
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- CN115385903A CN115385903A CN202110568327.9A CN202110568327A CN115385903A CN 115385903 A CN115385903 A CN 115385903A CN 202110568327 A CN202110568327 A CN 202110568327A CN 115385903 A CN115385903 A CN 115385903A
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- -1 cyano-substituted benzoxazine-4-one Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims abstract description 23
- MOXMPWAWQLBNGS-UHFFFAOYSA-N 5-bromo-2-(3-chloropyridin-2-yl)pyrazole-3-carbonyl chloride Chemical compound ClC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl MOXMPWAWQLBNGS-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000003513 alkali Substances 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001348 alkyl chlorides Chemical class 0.000 claims description 2
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- IDTPZHAYLYZIDP-UHFFFAOYSA-N 2-amino-5-cyano-3-methylbenzamide Chemical compound CC1=CC(C#N)=CC(C(N)=O)=C1N IDTPZHAYLYZIDP-UHFFFAOYSA-N 0.000 description 2
- FYPIIMYXBCWBPQ-UHFFFAOYSA-N 2-amino-5-cyano-3-methylbenzoic acid Chemical compound CC1=CC(C#N)=CC(C(O)=O)=C1N FYPIIMYXBCWBPQ-UHFFFAOYSA-N 0.000 description 2
- HQNZNIJPAYTWJK-UHFFFAOYSA-N 2-amino-5-cyanobenzoic acid Chemical compound NC1=CC=C(C#N)C=C1C(O)=O HQNZNIJPAYTWJK-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- 239000005889 Cyantraniliprole Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- DVBUIBGJRQBEDP-UHFFFAOYSA-N cyantraniliprole Chemical compound CNC(=O)C1=CC(C#N)=CC(C)=C1NC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl DVBUIBGJRQBEDP-UHFFFAOYSA-N 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- HHPMPAYAWGLODN-UHFFFAOYSA-N 2-(cyanoamino)benzoic acid Chemical class OC(=O)C1=CC=CC=C1NC#N HHPMPAYAWGLODN-UHFFFAOYSA-N 0.000 description 1
- KCMMKWRPPVXDTH-UHFFFAOYSA-N 2-amino-3-chloro-5-cyanobenzoic acid Chemical compound NC1=C(Cl)C=C(C#N)C=C1C(O)=O KCMMKWRPPVXDTH-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 1
- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of a cyano-substituted benzoxazine-4-one derivative, which comprises the steps of taking 2-amino-5-cyano-3-substituted benzoic acid and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride as starting raw materials, sequentially adding alkali and sulfonyl chloride solution into an organic solvent for reaction to obtain 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one. The novel preparation method of 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one has the advantages of simple operation, high yield, low cost and less three wastes, and is suitable for industrial production.
Description
Technical Field
The invention relates to a preparation method of a cyano-substituted benzoxazine-4-one derivative, in particular to a preparation method of a 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one derivative, and belongs to the technical field of chemical synthesis.
Background
2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one derivatives are important intermediates for synthesizing bisamide type pesticide, for example, 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-8-methyl 4H-3, 1-benzoxazine-4-one is a precursor for synthesizing cyantraniliprole.
Dupont first reported a synthetic method for cyantraniliprole by condensing pyrazolecarboxylic acid with 2-amino-3-methyl-5-cyanobenzamide (WO 200662978).
There have been many reports on the synthesis of 2-amino-3-methyl-5-cyanobenzamide (WO 200662978, US2014148611, WO 200623783) in which a cyanoaminobenzoic acid derivative is obtained by reacting a haloaminobenzoic acid derivative with zinc cyanide, cuprous cyanide, sodium cyanide, or the like as a cyano source.
The method for synthesizing the cyano-substituted benzoxazine-4-one derivative mainly comprises two methods, namely under the action of tertiary amine, methanesulfonyl chloride, pyrazolecarboxylic acid corresponding to the formula (2) and 2-amino-5-cyanobenzoic acid of the formula (1) react to prepare the cyano-substituted benzoxazine-4-one derivative; secondly, the isatoic anhydride with the corresponding structure reacts with pyrazole acyl chloride shown in the formula (2) in pyridine or pyridine acetonitrile solvent to prepare the compound.
The research and development of the two methods show that the method has the problems of low yield, difficult treatment of a large amount of three wastes caused by excessive use of organic base and unsuitability for industrial production.
Therefore, a low-cost, safe and efficient synthetic method for synthesizing the cyano-substituted benzoxazine-4-one derivative is needed.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a preparation method of cyano-substituted benzoxazine-4-one derivative shown as formula 3 aiming at the defects in the prior art, wherein the method takes a 2-amino-5-cyanobenzoic acid derivative and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride as raw materials to directly cyclize to obtain a target product, and has high synthesis yield and small three-waste generation amount.
In order to achieve the purpose, the invention adopts the following technical scheme:
a preparation method of cyano-substituted benzoxazine-4-one derivatives comprises the following steps:
taking 2-amino-5-cyano-3-substituted benzoic acid shown in a formula 1 and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 as starting materials, and sequentially adding alkali and a sulfonyl chloride solution into an organic solvent to react to obtain 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one shown in the formula 3; the chemical reaction formula is as follows:
wherein: r1 is Me or Cl.
In the above technical scheme, the preparation method specifically comprises the following steps:
placing 2-amino-5-cyano-3-substituted benzoic acid shown in a formula 1 and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in a formula 2 in a reaction container, adding an organic solvent, adding an alkali, cooling, dropwise adding a sulfonyl chloride solution into the system at a low temperature, heating after dropwise adding, carrying out cyclization reaction on the compound shown in the formula 1 and the compound shown in the formula 2, cooling after the cyclization reaction is finished, adding water into the system, stirring, sequentially filtering, washing and drying to obtain 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one shown in the formula 3.
In the above technical scheme, the feeding molar ratio of the 2-amino-5-cyano-3-substituted benzoic acid shown in formula 1 to the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in formula 2 is 1-2: 1.
in the technical scheme, the organic solvent is any one of or a mixture of two or more of a ketone solvent, an ester solvent, a benzene solvent, a chlorinated alkane solvent, an amide solvent, an ether solvent and a nitrile solvent; the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 to the organic solvent is 1.5-6.
In the above technical solution, the ketone solvent is preferably any one of acetone, methyl ethyl ketone, and butanone, or a mixture of two or more thereof; the ester solvent is preferably one or a mixture of two or more of ethyl acetate, butyl acetate and isopropyl acetate; the benzene solvent is preferably any one of toluene, p-xylene, m-xylene and mesitylene, or a mixture of two or more of the toluene, the p-xylene, the m-xylene and the mesitylene; the chloroalkane solvent is preferably any one of dichloromethane, dichloroethane and chloroform, or a mixture of two or more of the dichloromethane, the dichloroethane and the chloroform; the amide solvent is preferably any one, two or more of N, N-dimethylformamide and N, N-diethylacetamide; the ether solvent is preferably any one or a mixture of two or more of diethyl ether, tetrahydrofuran and methyltetrahydrofuran; the nitrile solvent is preferably acetonitrile; the organic solvent is preferably acetonitrile.
In the technical scheme, the alkali is organic alkali and/or inorganic alkali, the organic alkali is any one of, a mixture of two or more of triethylamine, diethylamine, diisopropylethylamine, pyridine, 3-methylpyridine, 2-methylpyridine and 2, 6-dimethylpyridine, and the inorganic alkali is any one of, a mixture of two or more of liquid alkali, potassium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate; the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 to the alkali is 1.5-6.
In the above technical scheme, the alkali is preferably 3-methylpyridine.
In the above technical solution, the feeding molar ratio of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride represented by formula 2 to the base is preferably 1.
In the above technical solution, the sulfonyl chloride solution refers to sulfonyl chloride or a solution obtained by dissolving sulfonyl chloride in a solvent; the sulfonyl chloride is any one of methanesulfonyl chloride, propanesulfonyl chloride and benzenesulfonyl chloride, preferably methanesulfonyl chloride; the solvent is any one or a mixture of two or more of ketone solvents, ester solvents, benzene solvents, chlorinated alkane solvents, amide solvents, ether solvents and nitrile solvents (the specific type is the same as that of the organic solvent).
In the technical scheme, the mass concentration of the solute sulfonyl chloride in the sulfonyl chloride solution is 10-100%; in the sulfonyl chloride solution, the charging molar ratio of the solute sulfonyl chloride to 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in formula 2 is 0 to 5, preferably 1.25.
In the technical scheme, the temperature for dripping the sulfonyl chloride solution is-20-60 ℃, and preferably-5-10 ℃.
In the technical scheme, the cyclization reaction is carried out at the temperature of 5-60 ℃ and preferably at the temperature of 25 ℃; the reaction time is 0.1-24 h.
In the above technical scheme, the cooling is carried out by adding water into the system, stirring, cooling to-10-30 ℃, preferably 0-5 ℃.
The invention has the technical effects that: the novel preparation method of the 2- [ 3-bromine-1- (3-chlorine-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-ketone has the advantages of simple operation, high yield, low cost and less three wastes, and is suitable for industrial production.
Detailed Description
The following detailed description of the embodiments of the present invention is provided, but the present invention is not limited to the following description:
the invention will now be illustrated with reference to specific examples:
example 1
A preparation method of 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-ketone comprises the following steps:
20g (113.6 mmol) of 2-amino-5-cyano-3-methylbenzoic acid and 36.3g (113.6 mmol) of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride are placed in a flask, 100g of acetonitrile is added, 37.0g of 3-methylpyridine is added, the temperature is reduced to 0-5 ℃, acetonitrile (20 g) solution containing 19.5g of methanesulfonyl chloride is added dropwise, after the dropwise addition is finished, the temperature is increased to 25 ℃, stirring is carried out for 3H, then the temperature is reduced to 0-5 ℃, 50g of water is added, stirring is carried out for 0.5H, filtering is carried out, a filter cake is washed by using glacial acetonitrile, and drying is carried out to obtain 45.6g of a target product, wherein the yield is 91%.
Example 2
A preparation method of 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-ketone comprises the following steps:
100g (568.2 mmol) of 2-amino-5-cyano-3-methylbenzoic acid and 181.5g (568.2 mmol) of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride are placed in a flask, 500g of acetonitrile is added, 185g of 3-methylpyridine is added, the temperature is reduced to 0-5 ℃, acetonitrile (100 g) solution containing 97.5g of methanesulfonyl chloride is added dropwise, after the dropwise addition is finished, the temperature is increased to 25 ℃, stirring is carried out for 3 hours, then the temperature is reduced to 0-5 ℃, 250g of water is added, stirring is carried out for 0.5 hour, filtering is carried out, a filter cake is washed by using glacial acetonitrile, and drying is carried out to obtain 230.8g of a target product, wherein the yield is 92%.
Example 3
A preparation method of 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazol-5-yl ] -6-cyano-8-chloro-4H-3, 1-benzoxazine-4-one comprises the following steps:
30g (152.7 mmol) of 2-amino-3-chloro-5-cyanobenzoic acid and 48.8g (152.7 mmol) of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride are placed in a flask, 120g of acetonitrile is added, 49.7g of 3-methylpyridine is added, the temperature is reduced to 0-5 ℃, 30g of acetonitrile solution containing 26.2g of methanesulfonyl chloride is added dropwise, after the dropwise addition, the temperature is raised to 25 ℃ and stirred for 3H, then the temperature is reduced to 0-5 ℃, 60g of water is added, stirring is carried out for 0.5H, filtering is carried out, a filter cake is washed with glacial acetonitrile, and drying is carried out to obtain 62.8g of a target product, wherein the yield is 89%.
The above examples are only for illustrating the technical concept and features of the present invention, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. A preparation method of cyano-substituted benzoxazine-4-one derivatives is characterized by comprising the following steps:
taking 2-amino-5-cyano-3-substituted benzoic acid shown in a formula 1 and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 as starting materials, and sequentially adding alkali and a sulfonyl chloride solution into an organic solvent to react to obtain 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one shown in the formula 3;
the reaction formula is shown as follows:
wherein: r1 is Me or Cl.
2. The preparation method according to claim 1, wherein the preparation method specifically comprises the steps of: placing 2-amino-5-cyano-3-substituted benzoic acid shown in a formula 1 and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in a formula 2 in a reaction container, adding an organic solvent, adding alkali, cooling, dropwise adding a sulfonyl chloride solution into the system under a low temperature condition, heating after dropwise adding is finished, carrying out cyclization reaction on the compound shown in the formula 1 and the compound shown in the formula 2, cooling after the cyclization reaction is finished, adding water into the system, stirring, filtering, washing and drying in sequence to obtain 2- [ 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-yl ] -6-cyano-4H-3, 1-benzoxazine-4-one shown in the formula 3.
3. The method according to claim 2, wherein the molar ratio of 2-amino-5-cyano-3-substituted benzoic acid represented by formula 1 to 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride represented by formula 2 is 1 to 2:1.
4. the method according to claim 2, wherein the organic solvent is any one of, or a mixture of two or more of, a ketone solvent, an ester solvent, a benzene solvent, a chloroalkane solvent, an amide solvent, an ether solvent, and a nitrile solvent; the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 to the organic solvent is 1.5-6.
5. The preparation method of claim 2, wherein the base is an organic base and/or an inorganic base, the organic base is any one of triethylamine, diethylamine, diisopropylethylamine, pyridine, 3-methylpyridine, 2, 6-dimethylpyridine, or a mixture of two or more thereof, and the inorganic base is any one of liquid base, potassium hydroxide, sodium carbonate, potassium carbonate, or sodium bicarbonate, or a mixture of two or more thereof; the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 to the alkali is 1.5-6.
6. The preparation method according to claim 2, wherein the sulfonyl chloride solution is a solution obtained by dissolving sulfonyl chloride or sulfonyl chloride in a solvent; the sulfonyl chloride is any one of methanesulfonyl chloride, propanesulfonyl chloride and benzenesulfonyl chloride; the solvent is any one of or a mixture of two or more of a ketone solvent, an ester solvent, a benzene solvent, a chlorinated alkane solvent, an amide solvent, an ether solvent and a nitrile solvent.
7. The preparation method according to claim 2, characterized in that the mass concentration of the solute sulfonyl chloride in the sulfonyl chloride solution is 10-100%; in the sulfonyl chloride solution, the charging molar ratio of the solute sulfonyl chloride to the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl chloride shown in the formula 2 is 0-5.
8. The production method according to claim 2, wherein the temperature at which the sulfuryl chloride solution is dropped is-20 ℃ to 60 ℃.
9. The process according to claim 2, wherein the cyclization reaction is carried out at a temperature of 5 ℃ to 60 ℃ for 0.1 to 24 hours.
10. The preparation method according to claim 2, wherein the temperature is reduced by adding water into the system and stirring, and the temperature is reduced to-10-30 ℃.
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| CN110835330A (en) * | 2018-08-15 | 2020-02-25 | 海利尔药业集团股份有限公司 | Preparation method of substituted pyrazole amide compound with insecticidal activity |
| US20200109152A1 (en) * | 2017-05-26 | 2020-04-09 | Zhejiang Zhuji United Chemicals Co., Ltd. | Preparation method and application of isoxazinone compounds |
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| CN110835330A (en) * | 2018-08-15 | 2020-02-25 | 海利尔药业集团股份有限公司 | Preparation method of substituted pyrazole amide compound with insecticidal activity |
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