CN104003949A - Preparing method of carfentrazone - Google Patents
Preparing method of carfentrazone Download PDFInfo
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- CN104003949A CN104003949A CN201410124861.0A CN201410124861A CN104003949A CN 104003949 A CN104003949 A CN 104003949A CN 201410124861 A CN201410124861 A CN 201410124861A CN 104003949 A CN104003949 A CN 104003949A
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- propionic acid
- acid amide
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- 0 C*(C)(C)C(C(*)CC(C(O)=*CCF)=[C@]=C(*1)C1N(*1)N=C(C)N(*)C1O)=O Chemical compound C*(C)(C)C(C(*)CC(C(O)=*CCF)=[C@]=C(*1)C1N(*1)N=C(C)N(*)C1O)=O 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
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Abstract
The invention relates to the field of compound preparation, and particularly discloses a preparing method of carfentrazone. According to the method, 1-(5-amino-4-chloro-2-fluorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4,-triazole-5-ketone (hereinafter referred to as substituted aniline) and acrylamide are used as raw materials; 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole-1-yl]-4-fluorophenyl}propanamide (hereinafter referred to as substituted benzenepropanamide) is obtained through diazo arylation of amino groups; the substituted benzenepropanamide takes an esterification reaction with ethanol under the existence of sulfuric acid; and the carfentrazone is obtained. The preparing method has the advantages that the process is simple; the reaction conditions are mild; the odor of the raw materials and the odor in production environment are small; the product yield is high; and the industrial production can be favorably achieved.
Description
(1) technical field
The present invention relates to compound preparation field, particularly a kind of preparation method of azoles humulone.
(2) background technology
Azoles humulone (having another name called carfentrazone, carfentrazoneethyl) chemical name is the chloro-3-of 2-{ the chloro-5-of 2-(4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazole-1-yl)-4-fluorophenyl } propionic acid amide ethyl ester, molecular formula: C
15h
14cL
2f
3n
3o
3, be the triazolineone weedicide with following structure:
。
The main preparation methods of azoles humulone has now: method one (WO1990002120, CN1031307C, US5125958) take acetonitrile as solvent, the cupric chloride of molar weight, with nitrite tert-butyl, be that diazo reagent carries out diazotization to the amino intermediate of 5-, then react with excessive acrylamide ethyl ester the azoles humulone obtaining.Method two (WO1997007107, CN1068594, US05621112) in aqueous acetone solution, take cuprous chloride as catalyzer, to be diazo reagent carry out diazotization and react and obtain azoles humulone with excessive acrylamide ethyl ester simultaneously the amino intermediate salt hydrochlorate of 5-Sodium Nitrite.Method three (WO1999019308; CN1159301C) utilize the intermediate of 5-position halo to react with chain acid alkyl ester under the existence of palladium catalyst, the propionic acid amide alkane ester that has ethanoyl is obtained to target product with clorox chlorination obtain azoles humulone on the α position obtaining.Method four (CN201110058827.4) be take vinylformic acid as raw material synthetic intermediate substituted benzene propionic acid, refining rear esterification synthesis of high content azoles humulone.
Method one and method two all belong to Meerwein arylation reaction (Meerwein arylation), all relate to diazotization reaction, as everyone knows, diazotization reaction exists more side reaction, the for example thermolysis of diazonium salt, halo (Sandmeyer reaction), coupling etc., will bring more impurity like this, and target product is a kind of liquid of thickness, is difficult to obtain by the refining way of routine the product of high-content; Method three has been used expensive palladium catalyst on the one hand, has equally on the other hand refining problem; Easily polymerization of method tetrapropylene acid, smell is large, and production environment is poor.Raw material propylene acid/ethyl propenoate that above-mentioned four kinds of methods are used all belongs to the liquid of irritant smell, and volatile, production environment is poor.
(3) summary of the invention
The present invention is in order to make up the deficiencies in the prior art, provides that a kind of raw material smell is little, the preparation method of product yield and the azoles humulone that purity is high, production environment is good.
The present invention is achieved through the following technical solutions:
A preparation method for azoles humulone, with 1-(the chloro-2-fluorophenyl of 5-amino-4-)-4-difluoromethyl-3-methyl isophthalic acid H-1,2,4 ,-triazole-5-ketone, substituted aniline is raw material, comprises the steps:
(1) by 1 mole of substituted aniline in organic solvent after stirring and dissolving, at 0-5 ℃, pass into 1-4 mole of hydrogenchloride, and to add successively 1-12 mol propylene acid amides, 0.01-0.10 mole cuprous chloride and 1-2 molar mass percentage concentration be 40% sodium nitrite in aqueous solution, after reaction finishes, slough organic solvent, suction filtration, suction filtration thing is used respectively pickling, washing, alkali cleaning, hot water wash, obtains crude product substituted benzene propionic acid amide; Crude product substituted benzene propionic acid amide is added to benzene class/alkane solvents, with hot water wash twice, crystallisation by cooling, suction filtration, obtain the substituted benzene propionic acid amide of purifying;
(2) by 1 mole of substituted benzene propionic acid amide, 4-20 mole ethanol under 0.5-0.6 mol sulfuric acid exists, under reflux conditions, carry out esterification, after reaction finishes, add alkaloid compound to adjust PH to neutral, filter, after precipitation, obtain product azoles humulone.
The present invention is with 1-(the chloro-2-fluorophenyl of 5-amino-4-)-4-difluoromethyl-3-methyl isophthalic acid H-1,2,4,-triazole-5-ketone (hereinafter to be referred as substituted aniline) and acrylamide are raw material, by amino diazonium arylation, obtain the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide (hereinafter to be referred as substituted benzene propionic acid amide), substituted benzene propionic acid amide carries out esterification with ethanol and the azoles humulone that obtains under sulfuric acid exists.
The molecular structural formula of substituted aniline is:
.
Reaction equation of the present invention is:
（1）
；
（2）
。
More excellent technical scheme of the present invention is:
In step (1), organic solvent is acetone or acetonitrile, and the weight ratio of organic solvent and substituted aniline is 4-10:1; Benzene class/alkane solvents is benzene,toluene,xylene, normal hexane or cyclohexane solvent.
In step (2), basic cpd is volatile salt, sodium bicarbonate, salt of wormwood, saleratus or triethylamine.
The beneficial effect that the present invention compared with prior art has is:
(1) raw material propylene acid amides is solid, not volatile;
(2) the intermediate substituted benzene propionic acid amide of solid state can pass through solvent recrystallization, and content can reach more than 98%;
(3) utilize the intermediate substituted benzene propionic acid amide of high-content and ethanol under sulfuric acid catalysis, to carry out esterification, through aftertreatment, can obtain the azoles humulone of high-content.
Technique of the present invention is simple, and reaction conditions is gentle, and raw material and production environment smell are little, and product yield and purity are high, are conducive to suitability for industrialized production.
(4) accompanying drawing explanation
Below in conjunction with accompanying drawing, the present invention is further illustrated.
Fig. 1 is the nucleus magnetic resonance figure of intermediate substituted benzene propionic acid amide of the present invention.
(5) embodiment
Example below further for example understands features more of the present invention, but the present invention applies for the content of protection and the restriction that scope is not subject to following embodiment.
Implement the preparation of the chloro-3-of 1:2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide
In reaction flask, drop into 1-(the chloro-2-fluorophenyl of 5-amino-4-)-4-difluoromethyl-3-methyl isophthalic acid H-1,2,4,292 grams of-triazole-5-ketone, after 1200 grams of stirring and dissolving of acetone, be controlled at 0-5 ℃, pass into 89 grams of hydrogenchloride, and add according to this 419 grams of acrylamides, 3 grams of cuprous chlorides, drip 201 grams of 40% sodium nitrite in aqueous solution, add and continue stirring reaction 0.5 hour, solvent is sloughed in decompression, filters, use respectively 400g 5% hydrochloric acid, 200g water, 400g 5% aqueous sodium hydroxide solution, 400g hot wash, obtain intermediate substituted benzene propionic acid amide crude product.By 1200ml toluene rising temperature for dissolving for intermediate substituted benzene propionic acid amide crude product, with 800g hot water, divide 2 washings, then concentrated organic layer under reduced pressure, crystallisation by cooling, suction filtration, dries, and obtains the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4 of 233 grams, 5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide (being called for short substituted benzene propionic acid amide), white solid, content 99.0%, yield 62%.
Implement the preparation of the chloro-3-of 2:2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide
In reaction flask, drop into 1-(the chloro-2-fluorophenyl of 5-amino-4-)-4-difluoromethyl-3-methyl isophthalic acid H-1,2,4,292 grams of-triazole-5-ketone, after 1200 grams of stirring and dissolving of acetonitrile, be controlled at 0-5 ℃, pass into 89 grams of hydrogenchloride, and add according to this 209 grams of acrylamides, 6 grams of cuprous chlorides, drip 201 grams of 40% sodium nitrite in aqueous solution, add and continue stirring reaction 0.5 hour, solvent is sloughed in decompression, filters, use respectively 400g 5% hydrochloric acid, 200g water, 400g 5% aqueous sodium hydroxide solution, 400g hot wash, obtain intermediate substituted benzene propionic acid amide crude product.By 1200ml normal hexane rising temperature for dissolving for intermediate substituted benzene propionic acid amide crude product, with 800g hot water, divide 2 washings, then concentrated organic layer under reduced pressure, crystallisation by cooling, suction filtration, dries, and obtains the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4 of 197 grams, 5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide (being called for short substituted benzene propionic acid amide), white solid, content 98.7%, yield 52.3%.The nucleus magnetic resonance of intermediate substituted benzene propionic acid amide is shown in Fig. 1.
Embodiment 3: the preparation of azoles humulone
In reaction flask, drop into the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2 that 90 grams of examples 1 obtain, 4-triazol-1-yl]-4-fluorophenyl } propionic acid amide, 108 grams of ethanol, 12.6 grams of vitriol oils, back flow reaction 6 hours, cooling, adds 10g anhydrous sodium carbonate, filter, mother liquor steams after ethanol, obtains product azoles humulone, and outward appearance is faint yellow transparent thick liquid, content 95.7%, yield 95.6%.
Embodiment 4: the preparation of azoles humulone
In reaction flask, drop into the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2 that 90 grams of examples 1 obtain, 4-triazol-1-yl]-4-fluorophenyl } propionic acid amide, 108 grams of ethanol, 12.6 grams of vitriol oils, back flow reaction 6 hours, cooling, adds 2.4g triethylamine, filter, mother liquor steams after ethanol, obtains product azoles humulone, and outward appearance is faint yellow transparent thick liquid, content 95.2%, yield 96.1%.
Claims (5)
1. the preparation method of an azoles humulone, with 1-(the chloro-2-fluorophenyl of 5-amino-4-)-4-difluoromethyl-3-methyl isophthalic acid H-1, 2, 4,-triazole-5-ketone, be that substituted aniline is raw material, it is characterized by, comprise the steps: (1) by 1 mole of substituted aniline in organic solvent after stirring and dissolving, at 0-5 ℃, pass into 1-4 mole of hydrogenchloride, and add successively 1-12 mol propylene acid amides, 0.01-0.10 mole of cuprous chloride and 1-2 molar mass percentage concentration are 40% sodium nitrite in aqueous solution, after reaction finishes, slough organic solvent, suction filtration, suction filtration thing is used respectively pickling, washing, alkali cleaning, hot water wash, obtain crude product substituted benzene propionic acid amide, crude product substituted benzene propionic acid amide is added to benzene class/alkane solvents, with hot water wash twice, crystallisation by cooling, suction filtration, obtain the substituted benzene propionic acid amide of purifying, (2) by 1 mole of substituted benzene propionic acid amide, 4-20 mole ethanol under 0.5-0.6 mol sulfuric acid exists, under reflux conditions, carry out esterification, after reaction finishes, add alkaloid compound to adjust PH to neutral, filter, after precipitation, obtain product azoles humulone.
2. the preparation method of azoles humulone according to claim 1, it is characterized in that: in step (1), substituted benzene propionic acid amide is the chloro-3-of 2-{ the chloro-5-[4-of 2-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxygen-1H-1,2,4-triazol-1-yl]-4-fluorophenyl } propionic acid amide.
3. the preparation method of azoles humulone according to claim 1, is characterized in that: in step (1), organic solvent is acetone or acetonitrile, and the weight ratio of organic solvent and substituted aniline is 4-10:1.
4. the preparation method of azoles humulone according to claim 1, is characterized in that: in step (1), benzene class/alkane solvents is benzene,toluene,xylene, normal hexane or cyclohexane solvent.
5. the preparation method of azoles humulone according to claim 1, is characterized in that: in step (2), basic cpd is volatile salt, sodium bicarbonate, salt of wormwood, saleratus or triethylamine.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410124861.0A CN104003949A (en) | 2014-03-31 | 2014-03-31 | Preparing method of carfentrazone |
| CN201510103138.9A CN104926740B (en) | 2014-03-31 | 2015-03-10 | A kind of preparation method of azoles humulone |
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| CN201410124861.0A CN104003949A (en) | 2014-03-31 | 2014-03-31 | Preparing method of carfentrazone |
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| CN201510103138.9A Active CN104926740B (en) | 2014-03-31 | 2015-03-10 | A kind of preparation method of azoles humulone |
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Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1331463C (en) * | 1988-08-31 | 1994-08-16 | Kathleen Megan Poss | Herbicidal triazolinones |
| DE69626525T2 (en) * | 1995-08-21 | 2004-02-19 | Fmc Corp. | METHOD FOR PRODUCING THE HERBICIDE ALPHA-2-DICHLORO-5- [4- (DIFLUOROMETHYL) -4,5-DIHYDRO-3-METHYL-5-OXO-1H-1,2,4-TRIAZOL-1-YL] -4 -FLUOROPHENYLPROPANSÄUREETHYLESTER |
| US5621112A (en) * | 1996-07-18 | 1997-04-15 | Fmc Corporation | Process for the preparation of the herbicide ethyl α-2-dichloro-5-[4-(Difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate |
| JP2001519418A (en) * | 1997-10-16 | 2001-10-23 | エフ エム シー コーポレーション | Preparation method and intermediate of triazoline herbicide |
| CN102174026B (en) * | 2011-03-11 | 2012-12-05 | 浙江省诸暨合力化学对外贸易有限公司 | Preparation method of carfentrazone-ethyl |
| CN103450100A (en) * | 2013-09-05 | 2013-12-18 | 南京工业大学 | Method for synthesizing carfentrazone-ethyl |
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- 2014-03-31 CN CN201410124861.0A patent/CN104003949A/en active Pending
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| CN104926740B (en) | 2017-09-19 |
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Application publication date: 20140827 |