CN104193696A - Preparation method for novel insecticide indoxacarb - Google Patents
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Abstract
The invention discloses a preparation method for a novel insecticide indoxacarb. The preparation method comprises the following steps: taking (+)5-chlorine-1,3-dihydro-2-hydroxyl-1-oxo-2H-indene-methyl carboxylate and 4-(trifluoromethoxy)benzenaime as raw materials, protecting (+)5-chlorine-1,3-dihydro-2-hydroxyl-1-oxo-2H-indene-methyl carboxylate by virtue of fluorenylmethyl chloroformate, and carrying out cyclization to prepare 2-( fluorenylmethyl)-7-chlorinindene-[1,2-e][1,34]] oxadiazine-2,4a(3H, 5H)-dicarboxylic acid-4a-methyl ether; reacting trifluoromethoxyaniline and methylchloroformate with phosgene to prepare (chlorocarbonyl)[4-(trifluoromethoxy)phenyl] methyl carbamate; carrying out deprotection on 2-( fluorenylmethyl)-7-chlorinindene-[1,2-e][1,34]] oxadiazine-2,4a(3H, 5H)-dicarboxylic acid-4a-methyl ether in alkaline solution and then carrying out condensation reaction with (chlorocarbonyl)[4-(trifluoromethoxy)phenyl] methyl carbamate to prepare the indoxacarb. The process yield of the indoxacarb is high and the purity of the indoxacarb is good.
Description
Technical field
The present invention relates to a kind of preparation method of novel pesticide indoxacarb, be specifically related to a kind of with (+) 5-chloro-1, 3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester (formula 2) and be raw material to trifluoro-methoxyaniline (formula 7), by fluorenes methoxy dicarbonyl chloride (formula 3), protect, crucial two key intermediate 2-(the fluorene methyl)-7-chlorine indeno [1 of the reaction such as cyclization carbonylation preparation, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester (formula 5) and (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane (formula 9), by preparing the method for indoxacarb with the condensation reaction of (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane (formula 9) again after deprotection, belong to agrochemicals field.
Background technology
According to the World Food Programme's statistics, due to the invasion of various diseases, worm, crop smothering, the loss causing to farm crop, about the same in 1/3rd of the every annual cut in the world.With regard to China's Pesticidal products structural analysis, take the riskiest pesticides such as organophosphorus, carbamate as main, riskiest pesticide is own through becoming the important barrier of agricultural products in China outlet.Exploitation is efficient, low toxicity, environmentally safe green pesticide are extremely urgent.Oxadiazine insecticides is the novel pesticide being with historically new significance it is found that after pyrethrin, imidacloprid and other pesticide.
Indoxacarb (indoxacarb) is Xin Xing oxadiazine class (oxadiazine) sterilant of du pont company's exploitation, for sodium channel suppresses broad spectrum pesticide, have that insecticidal activity is high, Environmental compatibility good, low to mammalian toxicity, the advantage to birds, fish and beneficial insect safety.Be to substitute one of desirable kind of high malicious organic phosphorous insecticide, become the focus and the product that is subject to extensive concern of current research.
The preparation method who has many bibliographical information indoxacarbs, be mainly du pont company (DU PONT) patent, (1. 2. Gary D.A.et.al.Arthropodicidal oxadiazinyl of Gary D.A.et.al.Arthropodicidal carboxanilides.WO1992011249A1., thiadiazinyl and triazinyl carboxamilides.US 5462938. is .Gary D.A. 3., et.al.Arthopodicidal oxadianine intermediate US 5510505. is Gary D.A. 4., et.al.Arthropodicidal oxadiazinyl, thiadiazinyl and triazinyl carboxanilides.US5462938. is Gay D.A.et.al.Preparation of arthropodicidal oxadiazines WO 199529171A. 5.). wait document all to adopt the protection of benzyl ester, by hydrogenating reduction deprotection, again and condensation reaction prepare the method for indoxacarb.The method is used raw hydrogen, needs autoclave to react, and has the potential safety hazards such as blast, needs in process of production to be taken precautions against.
Summary of the invention
Object: for solving the deficiencies in the prior art, the invention provides a kind of method of preparing indoxacarb, with (+) 5-chloro-1, 3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester is raw material, by fluorenes methoxy dicarbonyl chloride, protect, key intermediate 2-(fluorene methyl)-7-chlorine indeno [1 is prepared in the reactions such as cyclization carbonylation, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester 5, in basic solution, by deprotection, obtain 7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester, again with by being that (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane intermediate prepared by raw material carries out condensation reaction to trifluoro-methoxyaniline, for safety life Technology, technological operation is easy, applicable batch is prepared novel pesticide indoxacarb.
Technical scheme: for solving the problems of the technologies described above, the technical solution used in the present invention is:
The present invention adopts green cleaning procedure production technology; with fluorenes methoxy dicarbonyl chloride, protect; deprotection in basic solution; carry out with (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane the method that indoxacarb is prepared in condensation reaction again; solved the problems such as the former danger of hydrogenation reaction of preparing indoxacarb, and FMO reclaims use again, to safely cleaning process production techniques; for batch production novel pesticide indoxacarb provides technical guarantee, its preparation technology is as follows:
A preparation method for novel pesticide indoxacarb, comprises the following steps:
Step 1: adopt fluorenes methoxy dicarbonyl chloride to protect, in reaction flask, add hydrazine hydrate, under-10 ℃～-20 ℃ stirrings, drip the mixing solutions of fluorenes methoxy dicarbonyl chloride and tetrahydrofuran (THF), after dropwising, continue to stir 10～20min, stopped reaction, arrest reaction, separatory, get upper strata organic layer underpressure distillation to remove desolventizing, cooling, crystallization, filtration, then use re-crystallizing in ethyl acetate, filter, dry, hydrazine carboxylic acid's fluorene methyl ester;
Step 2: add (+) 5-chloro-1 in reaction flask, 3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester, hydrazine carboxylic acid's fluorene methyl ester, tosic acid and methyl alcohol, heating reflux reaction 20～30h, after reaction finishes, cooling, filtration, by recrystallizing methanol, filter, dry (+) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester;
Step 3: add diatomite in reaction flask, Vanadium Pentoxide in FLAKES, Methylal(dimethoxymethane) and 1, 2-ethylene dichloride, at room temperature stirring 30～60min makes it to mix, then [5-chloro-2 to add (+), 3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester and 1, the solution of 2-ethylene dichloride, be heated to 55～60 ℃, react 10～15 hours, after reaction finishes, filter, filter cake l, the washing of 2-ethylene dichloride, merging filtrate, under vacuum, distillation removes 1, 2-ethylene dichloride, after adding again methyl alcohol, continue precipitation, residuum adds water, cooling, filter, by recrystallizing methanol, obtain 2-(fluorene methyl)-7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester,
Step 4: add triethylamine and to trifluoro-methoxyaniline in reaction flask, under 0 ℃～5 ℃ stirrings, drip methyl-chloroformate, after dropwising, at room temperature react 18～24 hours, reaction solution is joined in dilute hydrochloric acid, regulate pH value, filtration, washing, by recrystallizing methanol, be dried to obtain 4-(trifluoromethoxy) phenylcarbamic acid methyl esters;
Step 5: add 4-[[(trifluoromethoxy in reaction flask) phenyl] amino] in methyl-formiate, glycol dimethyl ether and 60% sodium hydride, at room temperature stirring reaction is 20～24 hours, after reaction finishes, be cooled to-8 ℃～-3 ℃, drip phosgene toluene solution ,-8 ℃～-3 ℃ reactions 3～6 hours, suction filtration was removed the NaCl of excessive phosgene and reaction generation, obtain green solution (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane, standby;
Step 6: add 2-(fluorene methyl)-7-chlorine indeno [1 in reaction flask, 2-e] [1,3,4]] oxadiazine-2,4a (3H, 5H)-dicarboxylic acid-4a-methyl ester, organic solvent and catalyzer, under stirring at room, react 2～4 hours, after reaction, at 10 ℃～15 ℃, drip above-mentioned (chlorine carboxyl) [4-(trifluoromethoxy) phenyl] Urethylane, continue stirring reaction 1～2 hour, reaction finishes that rear with hydrochloric acid, to be neutralized to PH be acid, with acetic acid alcohol extraction, with dried over mgso, vacuum concentration except desolventizing, by recrystallizing methanol, filter, be dried, obtain indoxacarb.
The preparation method of described novel pesticide indoxacarb, is characterized in that: the organic solvent in described step 6 be methyl acetate, ethyl ester ethyl ester, propyl acetate, ethanol butyl ester, methylene dichloride, trichloromethane in one or more.
Described novel pesticide indoxacarb, is characterized in that: the catalyzer in described step 6 is: pyridine, piperidines, triethylamine, DIPEA, N, a kind of in N-diη-propyl ethamine.
Beneficial effect: the preparation method of novel pesticide indoxacarb provided by the invention; with (+) 5-chloro-1; 3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester and be raw material to trifluoro-methoxyaniline; chloro-1 to (+) 5-by fluorenes methoxy dicarbonyl chloride, 3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester is protected, 2-is prepared in cyclization (fluorene methyl)-7-chlorine indeno [1,2-e] [1; 3; 4]] oxadiazine-2,4a (3H, 5H)-dicarboxylic acid-4a-methyl ester.By being reacted with methyl-chloroformate photoreactive gas, trifluoro-methoxyaniline is prepared into (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane.2-(fluorene methyl)-7-chlorine indeno [1; 2-e] [1,3,4]] oxadiazine-2; 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester is prepared indoxacarb with (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane condensation reaction again after deprotection in basic solution.Wherein in basic solution, after deprotection, prepare the process recovery ratio high (90%) of indoxacarb with (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane condensation; good product purity (more than 96%); this technology is safely cleaning production technology, is suitable for preparing in batches indoxacarb.Have the following advantages: 1, adopt safely cleaning technique technology of preparing, can prepare in a large number novel pesticide indoxacarb, be applicable to batch production, yield is high, and purity is good.2, adopt Fmoc protection, under alkaline condition, de-Fmoc protection, solves to adopt and makes the hidden danger that hydrogenating reduction deprotection is prepared indoxacarb.3, this Waste water yield is few, and protecting group and organic solvent are all recyclable.4, reaction temperature and, easy and simple to handle.
Embodiment
Below in conjunction with example, the present invention is illustrated:
Example one: the preparation of hydrazine carboxylic acid's fluorene methyl ester
In 500mL reaction flask, add 80% hydrazine hydrate (24.5g, 0.40mol), at-20 ℃, drip Fmoc-Cl (51.8g, 0.20mol) at tetrahydrofuran (THF) (280ml) solution, after dropwising in about 2 hours, 30min is stirred in rear continuation, and stopped reaction, pours in separating funnel, static, separate upper strata organic layer, underpressure distillation is except desolventizing, and residuum is cooling, filter, obtain hydrazine carboxylic acid's fluorene methyl ester crude product, by re-crystallizing in ethyl acetate, obtain white needle-like crystals hydrazine carboxylic acid fluorene methyl ester 32.7g.Yield: 85.7%, fusing point: 168～170 ℃.
1HNMR(DMSO)δ(ppm):4.05(s,2H),4.16-4.31(m,3H),7.31(t,2H,J＝7.3Hz),7.40(t,2H,J＝7.3Hz),7.67(d,2H,J＝7.3Hz),7.86(d,2H,J＝7.3Hz),8.36(s,1H)。
Example two: the preparation of hydrazine carboxylic acid's fluorene methyl ester
In 500mL reaction flask, add 80% hydrazine hydrate (26.8g, 0.60mol), at-10 ℃, drip Fmoc-Cl (51.8g, 0.20mol) at tetrahydrofuran (THF) (360ml) solution, after dropwising in about 2 hours, 60min is stirred in rear continuation, and stopped reaction, pours in separating funnel, static, separate upper strata organic layer, underpressure distillation is except desolventizing, and residuum is cooling, filter, obtain hydrazine carboxylic acid's fluorene methyl ester crude product, by re-crystallizing in ethyl acetate, obtain white needle-like crystals hydrazine carboxylic acid fluorene methyl ester 33.2g.Yield: 87.0%.
Example three: the preparation of (+) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester
In 500mL reaction flask, add (+) 5-chloro-1,3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester (24.1g, 0.10mol), hydrazine carboxylic acid's fluorene methyl ester (25.3g, 0.10mol), tosic acid (3.0g, 0.015mol) and methyl alcohol (250ml).Heating reflux reaction 20h, after reaction finishes,
Cooling, filtration,) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester crude product, by recrystallizing methanol, filter, after vacuum-drying white knot product solid [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester 39.5g, yield is 82.8%, fusing point: 172-174 ℃.
1HNMR(CDCl
3)，δ(ppm):3.633(d,1H,J＝5.7Hz)，3.812(d,1H,J＝5.7Hz)，4.122(s,3H)，4.532(m,1H)，4.754(m,2H)，7.586-7.778(m,8H),8.108-8.105(m,3H)。
Example four: the preparation of (+) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester
In 500mL reaction flask, add (+) 5-chloro-1,3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester (24.1g, 0.10mol), hydrazine carboxylic acid's fluorene methyl ester (37.9g, 0.15mol), tosic acid (6.0g, 0.03mol) and methyl alcohol (350ml).Heating reflux reaction 30h, after reaction finishes, cooling, filtration,) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester crude product, by recrystallizing methanol, filter, after vacuum-drying white knot product solid [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester 40.2g, yield is 84.3%.
Example five: 2-(fluorene methyl)-7-chlorine indeno [1,2-e] [1,3,4]] oxadiazine-2, the preparation of 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester
Diatomite in 500mL reaction flask (10.0g), Vanadium Pentoxide in FLAKES (10.0g, 70mmol), Methylal(dimethoxymethane) (10.0ml) and 1, 2-ethylene dichloride (80ml), at room temperature stirring 60min makes it to mix, then [5-chloro-2 to add (+), 3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] (the 10.0g of hydrazine carboxylic acid's fluorene methyl ester, 23.0mmol) be dissolved in 1, in 2-ethylene dichloride (200ml) solution, be heated to 55～60 ℃, react 15 hours, after reaction finishes, filter, filter cake l, the washing of 2-ethylene dichloride, merging filtrate, under vacuum, distillation removes 1, 2-ethylene dichloride, add again methyl alcohol (100m1), continue precipitation, residuum adds water (60m1), cooling, filter, obtain 2-(fluorene methyl)-7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester crude product, by recrystallizing methanol, obtain 9.1 grams of solid phase prods, yield 80.9%, fusing point: 117-119.5 ℃.
1HNMR(CDCl3)，δ(ppm):3.583(d,1H,J＝15.5Hz)，3.815(d,1H,J＝15.5Hz)，4.033(s,3H)，4.070(s,1H)，4.450(d,2H,J＝7.2Hz)，4.675(d,2H,J＝7.2Hz)，4.450(d,2H,J＝7.2Hz)，4.864(d,1H,J＝7.2Hz),5.482(d,1H,J＝7.5Hz),7.552-8.121(m,11H)。
Example six: 2-(fluorene methyl)-7-chlorine indeno [1,2-e] [1,3,4]] oxadiazine-2, the preparation of 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester
Diatomite in 500mL reaction flask (15.0g), Vanadium Pentoxide in FLAKES (15.0g, 105mmol), Methylal(dimethoxymethane) (15.0ml) and 1, 2-ethylene dichloride (120ml), at room temperature stirring 30min makes it to mix, then [5-chloro-2 to add (+), 3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] (the 10.0g of hydrazine carboxylic acid's fluorene methyl ester, 23.0mmol) be dissolved in 1, in 2-ethylene dichloride (250ml) solution, be heated to 55～60 ℃, react 10 hours, after reaction finishes, filter, filter cake l, the washing of 2-ethylene dichloride, merging filtrate, under vacuum, distillation removes 1, 2-ethylene dichloride, add again methyl alcohol (150m1), continue precipitation, residuum adds water (100m1), cooling, filter, [5-chloro-2 to obtain (+), 3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester crude product, by recrystallizing methanol, obtain 8.4 grams of solid phase prods, yield 74.7%.
The preparation of example seven: 4-(trifluoromethoxy) phenylcarbamic acid methyl esters
In 500mL reaction flask, add triethylamine (26.9g, 0.30mol) with to trifluoro-methoxyaniline (35.5g, 0.20mol), under 0 ℃ of stirring, drip methyl-chloroformate (28.5g, 0.30mol), at room temperature react 24 hours, reaction solution is slowly joined in dilute hydrochloric acid, regulate pH=2, in solution, have a large amount of white solids to separate out, filter, washing, by recrystallizing methanol, obtains solid 4-(trifluoromethoxy) phenylcarbamic acid methyl esters 43.5g, yield 92.1%, molten point: 76-87.5 ℃.
1HNMR(CDCl
3)，δ(ppm):3.787(s,3H)，6.739(s,1H)，7.160(d,2H,J＝8.7Hz)，7.407(d,2H,J＝8.7Hz)。
The preparation of example eight: 4-(trifluoromethoxy) phenylcarbamic acid methyl esters
In 500mL reaction flask, add triethylamine (17.9g, 0.20mol) and to trifluoro-methoxyaniline (35.5g, 0.20mol), under 0 ℃ of stirring, drip methyl-chloroformate (19.0g, 0.20mol), at room temperature react 18 hours, reaction solution is slowly joined in dilute hydrochloric acid, regulate pH=2, in solution, have a large amount of white solids to separate out, filter, washing, by recrystallizing methanol, obtain solid 4-(trifluoromethoxy) phenylcarbamic acid methyl esters 42.0g, yield 89.3.
Example nine: the preparation of (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane
In 500mL reaction flask, add 4-[[(trifluoromethoxy) phenyl] amino] methyl-formiate (23.3g, 0.10mol) be dissolved in glycol dimethyl ether (100ml), then add 60% sodium hydride (0.80g, 0.20mol), reaction mixture at room temperature reacts 24h, and now reaction solution is white thickness oar liquid.With cryosel, bathe and be cooled to-8 ℃, drip phosgene toluene solution (containing phosgene 0.20mol), react 6 hours at-8 ℃, suction filtration is removed excessive phosgene and is reacted the NaCl producing, and obtains green solution standby.
Example ten: the preparation of indoxacarb
In 500mL reaction flask, add, under nitrogen protection, add 2-(fluorene methyl)-7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester (37.8g, 0.09mol), ethyl acetate (300m1) and piperidines (12.6g, 0.15mol), under stirring at room, react 4 hours, after reaction, at 10 ℃, drip (chlorine carboxyl) [4-(trifluoromethoxy) phenyl] Urethylane of above-mentioned example nine preparations, continue stirring reaction 2 hours, reaction finishes that rear with hydrochloric acid, to be neutralized to PH be acid, use acetic acid alcohol extraction, by dried over mgso, vacuum concentration removes desolventizing and obtains indoxacarb crude product, by recrystallizing methanol, filter, dry, obtain white solid indoxacarb 36.2g, fusing point is 89～91 ℃, yield 76.2%.
1HNMR(CDCl
3)，δ(ppm)：3.252(d,1H,J＝13.5Hz)，3.498(d,1H,J＝13.5Hz)，3.683(s.3H),3.724(s,3H),5.219(d,1H,J＝9.9Hz)，5.722(d,1H,J＝10.2Hz),7.217-7.401(m,6H)，7.531(d,1H,J＝7.8Hz)。
Example 11: the preparation of (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane
In 500mL reaction flask, add 4-[[(trifluoromethoxy) phenyl] amino] methyl-formiate (23.3g, 0.10mol) be dissolved in glycol dimethyl ether (100ml), then add 60% sodium hydride (0.40g, 0.10mol), reaction mixture at room temperature reacts 20h, and now reaction solution is white thickness oar liquid.With cryosel, bathe and be cooled to-3 ℃, drip phosgene toluene solution (containing phosgene 0.10mol), at-3 ℃, react 3h, suction filtration is removed excessive phosgene and is reacted the NaCl producing, and obtains green solution standby.
Example 12: the preparation of indoxacarb
In 500mL reaction flask, add, under nitrogen protection, add 2-(fluorene methyl)-7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester (37.8g, 0.09mol), ethyl acetate (200m1) and piperidines (8.4g, 0.10mol), under stirring at room, react 2 hours, after reaction, at 15 ℃, drip (chlorine carboxyl) [4-(trifluoromethoxy) phenyl] Urethylane of above-mentioned example nine preparations, continue stirring reaction 1 hour, reaction finishes that rear with hydrochloric acid, to be neutralized to PH be acid, use acetic acid alcohol extraction, by dried over mgso, vacuum concentration removes desolventizing and obtains indoxacarb crude product, by recrystallizing methanol, filter, dry, obtain white solid indoxacarb 32.1g, fusing point is 137～140 ℃, yield 67.6%.
Below with preferred embodiment, disclose the present invention, so it is not intended to limiting the invention, and all employings are equal to replaces or technical scheme that equivalent transformation mode obtains, within all dropping on protection scope of the present invention.
Claims (3)
1. a preparation method for novel pesticide indoxacarb, comprises the following steps:
step 1:adopt fluorenes methoxy dicarbonyl chloride to protect, in reaction flask, add hydrazine hydrate, under-10 ℃～-20 ℃ stirrings, drip the mixing solutions of fluorenes methoxy dicarbonyl chloride and tetrahydrofuran (THF), after dropwising, continue to stir 10～20 min, stopped reaction, arrest reaction, separatory, get upper strata organic layer underpressure distillation to remove desolventizing, cooling, crystallization, filtration, then use re-crystallizing in ethyl acetate, filter, dry, hydrazine carboxylic acid's fluorene methyl ester;
step 2:in reaction flask, add (+) 5-chloro-1,3-dihydro-2-hydroxyl-1-oxo-2H-indenes-2-carboxylate methyl ester, hydrazine carboxylic acid's fluorene methyl ester, tosic acid and methyl alcohol, heating reflux reaction 20～30h, after reaction finishes, cooling, filtration, by recrystallizing methanol, filter, dry (+) [5-chloro-2,3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester;
step 3:in reaction flask, add diatomite, Vanadium Pentoxide in FLAKES, Methylal(dimethoxymethane) and 1, 2-ethylene dichloride, at room temperature stirring 30～60min makes it to mix, then [5-chloro-2 to add (+), 3--hydrogen-2-hydroxyl-2-methoxy carboxyl-1H-indenes-subunit] hydrazine carboxylic acid's fluorene methyl ester and 1, the solution of 2-ethylene dichloride, be heated to 55～60 ℃, react 10～15 hours, after reaction finishes, filter, filter cake l, the washing of 2-ethylene dichloride, merging filtrate, under vacuum, distillation removes 1, 2-ethylene dichloride, after adding again methyl alcohol, continue precipitation, residuum adds water, cooling, filter, by recrystallizing methanol, obtain 2-(fluorene methyl)-7-chlorine indeno [1, 2-e] [1, 3, 4]] oxadiazine-2, 4a (3H, 5H)-dicarboxylic acid-4a-methyl ester,
step 4:in reaction flask, add triethylamine and to trifluoro-methoxyaniline, under 0 ℃～5 ℃ stirrings, drip methyl-chloroformate, after dropwising, at room temperature react 18～24 hours, reaction solution is joined in dilute hydrochloric acid, regulate pH value, filtration, washing, by recrystallizing methanol, be dried to obtain 4-(trifluoromethoxy) phenylcarbamic acid methyl esters;
step 5:in reaction flask, add 4-[[(trifluoromethoxy) phenyl] amino] in methyl-formiate, glycol dimethyl ether and 60% sodium hydride, at room temperature stirring reaction is 20～24 hours, after reaction finishes, be cooled to-8 ℃～-3 ℃, drip phosgene toluene solution ,-8 ℃～-3 ℃ reactions 3～6 hours, suction filtration was removed the NaCl of excessive phosgene and reaction generation, obtain green solution (chloroformyl) [4-(trifluoromethoxy) phenyl] Urethylane, standby;
step 6:in reaction flask, add 2-(fluorene methyl)-7-chlorine indeno [1,2-e] [1,3,4]] oxadiazine-2,4a (3H, 5H)-dicarboxylic acid-4a-methyl ester, organic solvent and catalyzer, under stirring at room, react 2～4 hours, after reaction, at 10 ℃～15 ℃, drip above-mentioned (chlorine carboxyl) [4-(trifluoromethoxy) phenyl] Urethylane, continue stirring reaction 1～2 hour, reaction finishes that rear with hydrochloric acid, to be neutralized to PH be acid, with acetic acid alcohol extraction, with dried over mgso, vacuum concentration except desolventizing, by recrystallizing methanol, filter, be dried, obtain indoxacarb.
2. the preparation method of novel pesticide indoxacarb according to claim 1, is characterized in that: the organic solvent in described step 6 be methyl acetate, ethyl ester ethyl ester, propyl acetate, ethanol butyl ester, methylene dichloride, trichloromethane in one or more.
3. novel pesticide indoxacarb according to claim 1 and 2, is characterized in that: the catalyzer in described step 6 is: pyridine, piperidines, triethylamine, DIPEA, N, a kind of in N-diη-propyl ethamine.
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| CN109704994A (en) * | 2018-12-26 | 2019-05-03 | 山东华阳农药化工集团有限公司 | A kind of improved method synthesizing indoxacarb intermediate chloroformyl [4- (trifluoromethoxy) phenyl] methyl carbamate |
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