CN101550134A - Method for preparing 2-[1H-pyrazole-5-radical]-4H-3, 1-benzoxazine-4-ketone compound - Google Patents
Method for preparing 2-[1H-pyrazole-5-radical]-4H-3, 1-benzoxazine-4-ketone compound Download PDFInfo
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Abstract
The invention provides a method for preparing a 2-[1H- pyrazole-5-base]-4H-3, 1-benzoxazine-4-ketone compound (I). 3-halo-1-(3-chlorine-2-pyridyl)-4 and 5-dihydro-1H-pyrazole-5-formic ether (III) are used as raw materials, and a target product is prepared by hydrolyzing, coupling and simultaneously carrying out an oxidation reaction. A reaction formula is presented as above, and radicals in the formula are presented in the specification. The invention also provides a compound of a general formula (II) and a preparation method thereof.
Description
Technical field
The invention belongs to the organic synthesis field, relate to a kind of preparation 2-[1H-pyrazoles-5-yl particularly]-4H-3, the method for 1-benzoxazine-4-ketone compounds.
Background technology
2-[1H-pyrazoles-5-yl]-4H-3; 1-benzoxazine-4-ketone compounds is preparation sterilant 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino) formyl radical] phenyl]-important intermediate of 1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide anthranilamides such as (Chlorantraniliprole, chlorine insect amides).Preparation 2-[1H-pyrazoles-5-yl is disclosed among WO 2004/011447A2, WO 03/015519A1 and the WO 2006/023783A1]-4H-3, the method for 1-benzoxazine-4-ketone compounds.According to prior art, 2-[1H-pyrazoles-5-yl]-4H-3,1-benzoxazine-4-ketone compounds need make through peroxidation, hydrolysis, coupling three-step reaction, and reaction formula is as follows:
In the formula:
X is selected from Cl or Br;
R
1Be selected from C
1-C
4Alkyl;
R
2, R
3Can be identical or different, be selected from H, halogen, NO respectively
2, CN, C
1-C
6Alkyl, C
1-C
6Haloalkyl, C
3-C
6Cycloalkyl, C
3-C
6Thiazolinyl, C
3-C
6Alkynyl, C
2-C
6Alkoxyalkyl, C
1-C
6Alkoxyl group, C
1-C
6Halogenated alkoxy, C
2-C
6Alkyl acyl, C
2-C
6Alkoxy acyl, C
1-C
6Alkylthio, C
1-C
6Alkyl sulphinyl or C
1-C
6Alkyl sulphonyl.
Wherein to select hydrogen peroxide, organic oxidizing agent, Potassium Persulphate, Sodium Persulfate, ammonium persulphate, potassium hydrogen persulfate, potassium permanganate or bromine respectively for use be oxygenant to oxidizing reaction.There are shortcomings such as oxidation operation is dangerous, step is long, a large amount of waste water of generation in reaction.For example, disclosed preparation method among the WO 03/016283A1, need earlier 3-halo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-manthanoate is oxidized to 3-halo-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-manthanoate, hydrolysis makes 3-halo-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-formic acid again, prepares target product then under certain carboxylic acid halides reagent effect.In the oxidation step, 3-halo-1-that every production is 1000 kilograms (3-chloro-2-pyridyl)-1H-pyrazoles-5-manthanoate, approximately need 1600 kilograms of Potassium Persulphates, 800 kilograms of the vitriol oils, 13000 liters of noxious solvent acetonitriles, produce 19000 liters of waste water in the last handling process.
Summary of the invention
The object of the present invention is to provide a kind of more easy, prepare 2-[1H-pyrazoles-5-yl more safely]-4H-3, the novel method of 1-benzoxazine-4-ketone compounds.
Because the 2-[1H-pyrazoles-5-yl that the present invention relates to]-4H-3, the preparation of 1-benzoxazine-4-ketone compounds is for importance that anthranilamides had such as sterilant chlorine insect amides, and the contriver has carried out brand-new exploration to its traditional preparation technology.In the new preparation method's process of research, unexpectedly having found can be earlier with 3-halo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-manthanoate hydrolysis makes 3-halo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-formic acid, then under SULPHURYL CHLORIDE and certain tertiary amine effect, can simultaneously the pyrazoline epoxy be turned to the pyrazoles ring, promptly carry out linked reaction and oxidizing reaction simultaneously in coupling reaction process, prepare target product.Successfully substituted the oxidizing reaction that traditional employing oxygenant carries out, simplified reactions steps, reduced pollution, and increased reaction safety, thereby finished the present invention environment.
The invention provides that a kind of 5-dihydro-1 h-pyrazole-5-manthanoate is a starting raw material with 3-halo-1-(3-chloro-2-pyridyl)-4, preparation 2-[1H-pyrazoles-5-yl]-4H-3, the novel method of 1-benzoxazine-4-ketone compounds, its technical scheme is as follows:
A kind of preparation 2-[1H-pyrazoles-5-yl]-4H-3, the method of 1-benzoxazine-4-ketone compounds (I) (abbreviation benzoxazinone), with 3-halo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-ethyl formate (III) (abbreviation ester) is a raw material, make the purpose product through hydrolysis, coupling simultaneous oxidation reaction, reaction formula is as follows:
In the formula:
X is selected from Cl or Br;
R
1Be selected from C
1-C
4Alkyl;
R
2, R
3Can be identical or different, be selected from H, halogen, NO respectively
2, CN, C
1-C
6Alkyl, C
1-C
6Haloalkyl, C
3-C
6Cycloalkyl, C
3-C
6Thiazolinyl, C
3-C
6Alkynyl, C
2-C
6Alkoxyalkyl, C
1-C
6Alkoxyl group, C
1-C
6Halogenated alkoxy, C
2-C
6Alkyl acyl, C
2-C
6Alkoxy acyl, C
1-C
6Alkylthio, C
1-C
6Alkyl sulphinyl or C
1-C
6Alkyl sulphonyl;
R
4Be selected from C
1-C
6Alkyl, C
1-C
6Haloalkyl, phenyl or independently be selected from C by 1 to 3
1-C
6The phenyl that alkyl or halogen replace.
Used raw material partly has commercially available or can make by oneself according to currently known methods in the reaction.For example, the instruction of the ester shown in preparation general formula (III) in can reference WO 03/016283A1 carried out, shown in the preparation general formula (IV) the instruction of anthranilic acid in can reference WO 2006/023783A1 carry out.
Preparing the carboxylic acid shown in the general formula (II) by the ester hydrolysis shown in the general formula (III) can realize by adopting following method: ester is added entry, water and alcohol (for example methyl alcohol, ethanol) mixture or water and ether (for example tetrahydrofuran (THF)) mixture, in preferably water and alcohol (for example methyl alcohol, ethanol) mixture or water and ether (for example tetrahydrofuran (THF)) mixture, again to wherein adding suitable alkali, arrive boiling temperature scope internal reaction 0.5-48 hour in-10 ℃, generate carboxylate salt, use strong acid example hydrochloric acid or sulfuric acid acidation again, generate the carboxylic acid shown in the general formula (II).Can adopt the method for well known to a person skilled in the art (comprising crystallization, extraction or distillation) to separate and obtain this carboxylic acid.The suitable alkali that reacts used comprises the oxyhydroxide of basic metal (as lithium, sodium or potassium), preferred sodium hydroxide or potassium hydroxide.The reinforced mol ratio of ester and alkali is 1 in the hydrolysis reaction: 1-5, preferred 1: 1-2.Water is 1 with the volume ratio of alcohol in water and the alcohol mixture (for example methyl alcohol, ethanol): 0.1-10, preferred 1: 0.5-1.5.The volume ratio of water and ether is 1 in water and ether (for example tetrahydrofuran (THF)) mixture: 0.1-10, preferred 1: 0.5-1.5.
By general formula (II) compound general formula (I) compound be reflected under-30 ℃ to the 50 ℃ temperature, as follows the operation:
(1) add the solution that carboxylic acid, tertiary amine and the The suitable solvent shown in the general formula (II) is made in the SULPHURYL CHLORIDE shown in the logical formula V, reinforced mol ratio is a carboxylic acid: SULPHURYL CHLORIDE: tertiary amine=1.0: 1.0-1.5: 1.0-1.5;
(2) add the anthranilic acid shown in the general formula (IV) in above-mentioned reaction solution, reinforced mol ratio is a carboxylic acid: anthranilic acid=1.0: 0.9-1.5;
(3) add and the identical tertiary amine of step (1) in reaction solution, reinforced mol ratio is a carboxylic acid: tertiary amine=1.0: 2.0-4.0 again;
More than the suitable reaction times in each step be respectively 1 minute to 120 minutes; The further preferred reaction times is 10 minutes to 90 minutes.Then,
(4) in reaction solution, add the SULPHURYL CHLORIDE shown in the logical formula V of and equivalent identical, continue to react making general formula (I) compound in 0.5 hour to 24 hours with step (1).
The suitable solvent is selected from aromatic hydrocarbon in the reaction, as chlorobenzene or toluene; Ester is as ethyl acetate or butylacetate; Ketone is as acetone or 2-butanone; Ether is as tetrahydrofuran (THF) or dioxane; Nitrile is as acetonitrile; Methyl halide is as methylene dichloride or chloroform.Preferred acetonitrile, ethyl acetate, acetone, tetrahydrofuran (THF) and methylene dichloride; Further preferred acetonitrile and acetone.Described tertiary amine is selected from Trimethylamine 99, triethylamine or pyridine; Described SULPHURYL CHLORIDE is selected from Methanesulfonyl chloride, ethyl chloride, third SULPHURYL CHLORIDE, benzene sulfonyl chloride, p-methyl benzene sulfonic chloride or parachloroben-zenesulfonyl chloride.
The tertiary amine that adds for the second time in the above-mentioned reaction, does not influence successful reaction yet and carries out generation with target compound even if different with the tertiary amine and the SULPHURYL CHLORIDE that add for the first time with SULPHURYL CHLORIDE (being respectively applied for third step and the 4th step reaction).But consider that from easy and simple to handle and economic angle preferably twice selects for use identical raw material to be advisable.
Preparation 2-[1H-pyrazoles of the present invention-5-yl]-4H-3, related following general formula (II) compound is not seen open before this in the method for 1-benzoxazine-4-ketone compounds (I) (abbreviation benzoxazinone):
In the formula: X is selected from Cl or Br.
This compound is the key intermediate of preparation purpose product, so the present invention also comprises compound shown in the general formula (II) and preparation method thereof.
2-[1H-pyrazoles-5-yl]-4H-3,1-benzoxazine-4-ketone compounds (I) can be used to prepare amides, especially is used for preparing general formula (VII) compound of biologically active.Reaction formula is as follows:
In the formula:
X is selected from Cl or Br;
R
2, R
3Can be identical or different, be selected from H, halogen, NO respectively
2, CN, C
1-C
6Alkyl, C
1-C
6Haloalkyl, C
3-C
6Cycloalkyl, C
3-C
6Thiazolinyl, C
3-C
6Alkynyl, C
2-C
6Alkoxyalkyl, C
1-C
6Alkoxyl group, C
1-C
6Halogenated alkoxy, C
2-C
6Alkyl acyl, C
2-C
6Alkoxy acyl, C
1-C
6Alkylthio, C
1-C
6Alkyl sulphinyl or C
1-C
6Alkyl sulphonyl;
R
5Be selected from H or CH
3
R
6Be selected from C
1-C
6Alkyl.
The method for preparing general formula (VII) compound is that general formula (I) compound is dissolved in the The suitable solvent, adds general formula (VI) compound (can be obtained by commercially available purchase) again, temperature be-10 ℃ under boiling point, reacted 0.5-48 hour, make target compound (VII).The suitable solvent is selected from methylene dichloride, chloroform, tetracol phenixin, hexane, benzene, toluene, ethyl acetate, acetonitrile, THF, dioxane, DMF or dimethyl sulfoxide (DMSO) etc.
The synthetic method that provides above, and in the definition of each general formula compound, it is as follows to compile used term General Definition:
Alkyl is meant the straight or branched form, for example groups such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, tertiary butyl, n-pentyl, isopentyl, n-hexyl.Cycloalkyl is meant and comprises the closed chain form, for example groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.Alkylhalide group is meant the group that alkyl is replaced by one or more halogen atoms.Thiazolinyl is meant the straight or branched form, the group of 1 to 2 carbon-carbon double bond is arranged, for example vinyl, propenyl, allyl group etc.Alkynyl is meant the straight or branched form, and 1 to 2 carbon carbon triple-linked group, for example ethynyl, proyl, propargyl etc. are arranged.Alkoxyl group is meant that the alkyl end is connected with the group of Sauerstoffatom, for example methoxyl group, oxyethyl group, positive propoxy, isopropoxy, tert-butoxy etc.The halogen alkoxyl group is meant that alkyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Alkylthio is meant that the alkyl end is connected with the group of sulphur atom, for example methylthio group, ethylmercapto group etc.Acyl group is meant terminal group for (CO-).Alkyl sulphinyl refers to the terminal group for (SO-) of alkyl, as methylsulfinyl.Alkyl sulphonyl refers to the terminal (SO of being of alkyl
2-) group, as methyl sulphonyl.Halogen is meant fluorine, chlorine, bromine, iodine.
Should be clear and definite be in claim of the present invention institute restricted portion, can carry out various conversion and change.
Embodiment
The following example is used to describe in detail the preparation method of general formula shown in the present (II), (I) compound and further prepares the application example of the amides shown in the general formula (VII) by general formula (I) compound, but does not mean that restriction the present invention.
General formula (II) compound part:
Embodiment 1:3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-formic acid synthetic
In 500 milliliters reaction flask, add 3-chloro-1-(3-chloro-2-pyridyl)-4 successively, 5-dihydro-1 h-pyrazole-5-ethyl formate (15.90 grams, 50.00 mmoles), THF (100 milliliters), water (100 milliliters), sodium hydroxide (3.03 grams, 75.00 mmoles), room temperature reaction 6 hours, THF is deviate from decompression, adds entry (50 milliliters) and ethyl acetate (20 milliliters) and extracts, inorganic with hcl acidifying to pH=2, use methylene dichloride (75 milliliters * 3 times) extraction again, the anhydrous MgSO of organic phase
4Drying, the decompression precipitation gets 12.68 gram white crystalline powder, HPLC normalizing content is that 98% (analysis condition: chromatographic column is ZORBAX Eclipse XDB-C84.6 * 150mm 5 μ m, moving phase is acetonitrile: water=70: 30), m.p.57-59 ℃, yield is 95%.
1H?NMR(300MHz，CDCl
3)δ(ppm)11.608(br?s，1H)，8.090(dd，1H)，7.732(dd，1H)，6.923(dd，1H)，5.270(dd，1H)，3.602(dd，1H)，3.371(dd，1H)。
Embodiment 2:3-bromo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-formic acid synthetic
In 500 milliliters reaction flask, add 3-chloro-1-(3-chloro-2-pyridyl)-4 successively, 5-dihydro-1 h-pyrazole-5-ethyl formate (18.50 grams, 50.78 mmoles), THF (100 milliliters), water (100 milliliters), sodium hydroxide (3.06 grams, 76.17 mmoles), room temperature reaction 6 hours, THF is deviate from decompression, adds entry (50 milliliters) and ethyl acetate (20 milliliters) and extracts, inorganic with hcl acidifying to pH=2, use methylene dichloride (75 milliliters * 3 times) extraction again, the anhydrous MgSO of organic phase
4Drying, the decompression precipitation gets 15.25 gram white crystalline powder, HPLC normalizing content is that 98% (analysis condition: chromatographic column is ZORBAX Eclipse XDB-C84.6 * 150mm 5 μ m, moving phase is acetonitrile: water=70: 30), m.p.66-68 ℃, yield is 96%.
1H?NMR(300MHz，CDCl
3)δ(ppm)9.376(br?s，1H)，8.105(dd，1H)，7.750(dd，1H)，6.957(dd，1H)，5.186(dd，1H)，3.798(dd，1H)，3.422(dd，1H)。
General formula (I) compound part:
Embodiment 3:6-chloro-2-[3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-yl]-8-methyl-4H-3,1-benzoxazine-4-ketone synthetic
In 250 milliliters reaction flask, add methylsulfonyl chloride (6.02 grams, 52.57 mmole), be added dropwise to 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-formic acid (12.68 grams, 47.77 mmole), acetonitrile (50 milliliters) and triethylamine (5.31 grams, 52.57 the solution of Xing Chenging mmole), room temperature reaction 1 hour adds 2-amino-5-chloro-3-tolyl acid (8.87 grams, 47.77 mmole), reacted 30 minutes, and be added dropwise to triethylamine (10.62 grams, 105.14 mmoles), reacted 1 hour, drip methylsulfonyl chloride (6.02 grams, 52.57 mmoles), reacted 6 hours.Leave standstill, filter, filter cake is a yellow solid, and with THF (20 milliliters * 2 times) filter wash cake, filtrate decompression precipitation, column chromatography (ethyl acetate/petroleum ether=1/5) gets 7.38 gram yellow solids, and HPLC normalizing content is 95%, yield 36%.
1H?NMR(300MHz，CDCl
3)δ(ppm)8.562(dd，1H)，7.99-7.96(m，2H)，7.52-7.48(m，2H)，7.171(s，1H)，1.804(s，3H)。
Embodiment 4:2-[3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-ketone synthetic
In the reaction flask of 250mL, add methylsulfonyl chloride (6.19 grams, 53.98 mmole), be added dropwise to 3-bromo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-formic acid (15.25 grams, 49.07 mmole), acetonitrile (50 milliliters) and triethylamine (5.46 grams, 53.98 the solution of Xing Chenging mmole), room temperature reaction 1 hour adds 2-amino-5-chloro-3-tolyl acid (9.11 grams, 49.07 mmole), reacted 30 minutes, and be added dropwise to triethylamine (10.91 grams, 107.96 mmoles), reacted 1 hour, drip methylsulfonyl chloride (6.19 grams, 53.98 mmoles), reacted 6 hours.Leave standstill, filter, filter cake is a yellow solid, and with THF (20 milliliters * 2 times) filter wash cake, filtrate decompression precipitation, column chromatography (ethyl acetate/petroleum ether=1/5) gets 8.13 gram yellow solids, and HPLC normalizing content is 96%, yield 35%.
1H?NMR(300MHz，CDCl
3)δ(ppm)8.562(dd，1H)，7.99-7.95(m，2H)，7.52-7.48(m，2H)，7.256(s，1H)，1.800(s，3H)。
General formula (I) compound applying portion
Embodiment 5:3-chloro-N-[4-chloro-2-methyl-6-[(methylamino) formyl radical] phenyl]-synthetic (benzoxazinone with embodiment 3 preparations is a raw material) of 1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide
In 125 milliliters reaction flask, add 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-yl]-8-methyl-4H-3,1-benzoxazine-4-ketone (6.00 grams, 13.98 mmoles) and THF (60 milliliters) are added dropwise to methylamine (4.05 grams, 32.66 mmole), room temperature reaction is 2 hours.Decompression precipitation, column chromatography (ethyl acetate/petroleum ether=1/5) get 3.40 gram white solids, and HPLC normalizing content is 95%, yield 52%.
1H?NMR(300MHz，CDCl
3)δ(ppm)10.111(s，1H)，8.458(dd，1H)，7.853(dd，1H)，7.380(dd，1H)，7.214(d，1H)，7.190(d，1H)，7.066(s，1H)，6.238(br?d，1H)，2.941(d，3H)，2.160(s，3H)。
Embodiment 6:3-bromo-N-[4-chloro-2-methyl-6-[(methylamino) formyl radical] phenyl]-synthetic (benzoxazinone with embodiment 4 preparations is a raw material) of 1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-methane amide
In 125 milliliters reaction flask, add 2-[3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazoles-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-ketone (7.00 grams, 15.17 mmoles) and THF (60 milliliters) are added dropwise to methylamine (4.03 grams, 32.50 mmole), room temperature reaction is 2 hours.Decompression precipitation, column chromatography (ethyl acetate/petroleum ether=1/5) get 5.20 gram white solids, and HPLC normalizing content is 97%, yield 68%.
1H?NMR(300MHz，CDCl
3)δ(ppm)10.098(s，1H)，8.463(dd，1H)，7.853(dd，1H)，7.382(dd，1H)，7.240(d，1H)，7.210(d，1H)，7.121(s，1H)，6.177(br?d，1H)，2.952(d，3H)，2.173(s，3H)。
Claims (6)
1, a kind of preparation 2-[1H-pyrazoles-5-yl]-4H-3, the method of 1-benzoxazine-4-ketone compounds, it is characterized in that: with 3-halo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1 h-pyrazole-5-manthanoate (III) is a raw material, make the purpose product through hydrolysis, coupling simultaneous oxidation reaction, reaction formula is as follows:
In the formula:
X is selected from Cl or Br;
R
1Be selected from C
1-C
4Alkyl;
R
2, R
3Can be identical or different, be selected from H, halogen, NO respectively
2, CN, C
1-C
6Alkyl, C
1-C
6Haloalkyl, C
3-C
6Cycloalkyl, C
3-C
6Thiazolinyl, C
3-C
6Alkynyl, C
2-C
6Alkoxyalkyl, C
1-C
6Alkoxyl group, C
1-C
6Halogenated alkoxy, C
2-C
6Alkyl acyl, C
2-C
6Alkoxy acyl, C
1-C
6Alkylthio, C
1-C
6Alkyl sulphinyl or C
1-C
6Alkyl sulphonyl;
R
4Be selected from C
1-C
6Alkyl, C
1-C
6Haloalkyl, phenyl or independently be selected from C by 1 to 3
1-C
6The phenyl that alkyl or halogen replace.
2, according to the described preparation method of claim 1, it is characterized in that: the carboxylic acid shown in the general formula (II),
In the formula: X is selected from Cl or Br.
3, according to the described preparation method of claim 2, it is characterized in that: the ester shown in the general formula (III) is added in entry, water and alcohol mixture or water and the ether mixture, again to wherein adding alkali-metal oxyhydroxide, arriving boiling temperature scope internal reaction 0.5-48 hour in-10 ℃, generate carboxylate salt, generate the carboxylic acid shown in the general formula (II) after the acidifying; The reinforced mol ratio of ester and alkali is 1: 1-5.
4, according to the described preparation method of claim 1, it is characterized in that: by general formula (II) compound general formula (I) compound be reflected under-30 ℃ to the 50 ℃ temperature, as follows the operation,
(1) add the solution that carboxylic acid, tertiary amine and the The suitable solvent shown in the general formula (II) is made in the SULPHURYL CHLORIDE shown in the logical formula V, reinforced mol ratio is a carboxylic acid: SULPHURYL CHLORIDE: tertiary amine=1.0: 1.0-1.5: 1.0-1.5;
(2) add the anthranilic acid shown in the general formula (IV) in above-mentioned reaction solution, reinforced mol ratio is a carboxylic acid: anthranilic acid=1.0: 0.9-1.5;
(3) add and the identical tertiary amine of step (1) in reaction solution, reinforced mol ratio is a carboxylic acid: tertiary amine=1.0: 2.0-4.0 again;
More than the suitable reaction times in each step be respectively 1 minute to 120 minutes; Then,
(4) in reaction solution, add the SULPHURYL CHLORIDE shown in the logical formula V of and equivalent identical, continue to react making general formula (I) compound in 0.5 hour to 24 hours with step (1);
The suitable solvent is selected from chlorobenzene, toluene, ethyl acetate, butylacetate, acetone, 2-butanone, tetrahydrofuran (THF), dioxane, acetonitrile, methylene dichloride or chloroform in the reaction; Described tertiary amine is selected from Trimethylamine 99, triethylamine or pyridine; Described SULPHURYL CHLORIDE is selected from Methanesulfonyl chloride, ethyl chloride, third SULPHURYL CHLORIDE, benzene sulfonyl chloride, p-methyl benzene sulfonic chloride or parachloroben-zenesulfonyl chloride.
5, according to the described preparation method of claim 4, it is characterized in that: described SULPHURYL CHLORIDE is selected from Methanesulfonyl chloride, third SULPHURYL CHLORIDE or benzene sulfonyl chloride; The suitable solvent is selected from acetonitrile, ethyl acetate, acetone, tetrahydrofuran (THF) or methylene dichloride.
6, according to the described preparation method of claim 5, it is characterized in that: described SULPHURYL CHLORIDE is selected from Methanesulfonyl chloride; The suitable solvent is selected from acetonitrile or acetone.
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| Publication number | Priority date | Publication date | Assignee | Title |
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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 |
| CN110835331A (en) * | 2018-08-15 | 2020-02-25 | 海利尔药业集团股份有限公司 | Preparation method of substituted salicylamide compound with insecticidal activity |
| CN114341126A (en) * | 2019-08-19 | 2022-04-12 | Fmc公司 | Process for preparing carboxylic acid derivatives of 3-halo-4, 5-dihydro-1H-pyrazole |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN110835331A (en) * | 2018-08-15 | 2020-02-25 | 海利尔药业集团股份有限公司 | Preparation method of substituted salicylamide compound with insecticidal activity |
| CN114341126A (en) * | 2019-08-19 | 2022-04-12 | Fmc公司 | Process for preparing carboxylic acid derivatives of 3-halo-4, 5-dihydro-1H-pyrazole |
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