CN104262285B - The synthetic method of agricultural insecticide indoxacarb intermediate - Google Patents
The synthetic method of agricultural insecticide indoxacarb intermediate Download PDFInfo
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- 239000005907 Indoxacarb Substances 0.000 title claims abstract description 36
- VBCVPMMZEGZULK-NRFANRHFSA-N indoxacarb Chemical compound C([C@@]1(OC2)C(=O)OC)C3=CC(Cl)=CC=C3C1=NN2C(=O)N(C(=O)OC)C1=CC=C(OC(F)(F)F)C=C1 VBCVPMMZEGZULK-NRFANRHFSA-N 0.000 title claims abstract description 36
- 239000002917 insecticide Substances 0.000 title claims abstract description 27
- 238000010189 synthetic method Methods 0.000 title claims abstract description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 90
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 claims abstract description 18
- PDJDKHIBKLIQFI-UHFFFAOYSA-N benzyl formate hydrazine Chemical compound C(=O)OCC1=CC=CC=C1.NN PDJDKHIBKLIQFI-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000002841 Lewis acid Substances 0.000 claims abstract description 10
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000011084 recovery Methods 0.000 claims abstract description 5
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- 239000006227 byproduct Substances 0.000 claims abstract description 4
- 238000002425 crystallisation Methods 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 239000013078 crystal Substances 0.000 claims abstract description 3
- 238000010792 warming Methods 0.000 claims abstract description 3
- 238000005406 washing Methods 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 4
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
- LTYMSROWYAPPGB-UHFFFAOYSA-O diphenylsulfanium Chemical compound C=1C=CC=CC=1[SH+]C1=CC=CC=C1 LTYMSROWYAPPGB-UHFFFAOYSA-O 0.000 claims description 3
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 description 12
- 239000007787 solid Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- -1 indeno (1,2-e) diazine-4a-carboxylate methyl ester Chemical compound 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 1
- QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical compound N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 description 1
- GEHMBYLTCISYNY-UHFFFAOYSA-N Ammonium sulfamate Chemical compound [NH4+].NS([O-])(=O)=O GEHMBYLTCISYNY-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000004891 diazines Chemical class 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- TWVBEFREQNKFGN-UHFFFAOYSA-N formic acid;hydrazine Chemical compound NN.OC=O TWVBEFREQNKFGN-UHFFFAOYSA-N 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
- C07D273/04—Six-membered rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses the synthetic method of a kind of agricultural insecticide indoxacarb intermediate, comprise the following steps: 1), YCW 4, lewis acid, toluene are put in reaction vessel in proportion, stirring, it is warming up to the reaction temperature of 105～110 DEG C, reacts under above-mentioned reaction temperature until reaction is carried out completely after the toluene solution of dropping diethoxymethane and interpolation hydrazine benzyl formate；The azeotropic mixture of ethanol as by-product and diethoxymethane is constantly evaporated off in course of reaction；2), reaction terminate after stop heating, be cooled to room temperature under stirring, concentration and recovery toluene under reduced pressure, concentrated solution recrystallisation solvent crystallisation by cooling at low temperatures, sucking filtration, washing, dry, obtain light yellow crystal, be target product agricultural insecticide indoxacarb intermediate.The synthetic method of the present invention has the technical advantage that yield is high.
Description
Technical field
The invention belongs to organic synthesis field, relate to the new technique for synthesizing of agricultural insecticide indoxacarb intermediate.
Background technology
Indoxacarb (structural formula is shown in formula 1), chemical name: 7-chloro-2,3,4a, 5-tetrahydrochysene-2 (methoxycarbonyl (4-Trifluoromethoxyphen-l)
Carbamoyl) indeno (1,2-e) diazine-4a-carboxylate methyl ester, common name: indoxacarb, trade name: Ammate, Avatar
Deng.This product is the diazines novel chiral insecticide of du pont company's calendar year 2001 listing, is also first business-like sodium
Carrier frequency channel break type insecticide.Indoxacarb has novel structure, and the mechanism of action is unique, and consumption is low, to nearly all lepidoptera pest
All effective, to people and animals, environment, crop, non-target organism and the beneficial organism feature such as safely, be substitute high poison, high residue and
The favourable agents of resistance insecticide, market and having a extensive future.
The chemical structural formula (YCW) of formula 1 indoxacarb
Indoxacarb is a baroque diazines compound, containing a chiral centre in structure, there is R and S two different
Structure body, the most only S isomer is active, and R isomer does not has activity.It is public that presently commercially available commercialization indoxacarb is mainly Du Pont
The safety hit (ee=50%) of department and triumphant grace (essence indoxacarb, ee=100%).Owing to the compound patent of indoxacarb will be in April, 2015
Expiring, the most domestic pesticide enterprise increasingly payes attention to optimization and the innovation of its synthesis technique.
Patent WO09211249 and WO9319045 once disclosed 2-(benzyl)-7-chlorine indeno [1,2-e] [1,3,4] diazine
The synthesis technique of-2,4a (3H, 5H)-dicarboxylic acids-4a-methyl ester (YCW-5).But it is low that the major defect of this technique is reaction yield,
Raw material easily resolves into 5-chloro-2,3-dihydro-2-hydroxyl-1-oxo-1H-indenes-2-carboxylate methyl ester (structural formula is shown in formula 2).
The structural formula of formula 2 5-chloro-2,3-dihydro-2-hydroxyl-1-oxo-1H-indenes-2-carboxylate methyl ester
The present invention is (synthetic route is shown in formula 3) on the basis of early stage literature survey and indoxacarb synthesising process research, primary study and
Optimizing cyclization (YCW-5) reaction, it is the committed step of synthesis indoxacarb (YCW).But the method according to reported in literature
When carrying out cyclization, yield is on the low side, and when main cause is cyclization, raw material hydrazone (YCW-4) easily resolves into 5-chloro-2,3-dihydro-2-hydroxyl
-1-oxo-1H-indenes-2-carboxylate methyl ester (YCW-3), the reaction temperature of the method is 80-85 DEG C.The industry is highly desirable can be effective
Solve the problems referred to above；Therefore the synthetic method of agricultural insecticide indoxacarb intermediate of the present invention is devised.
The synthetic route of formula 3 indoxacarb
Summary of the invention
The technical problem to be solved in the present invention is to provide 2-(the benzyl)-7-chlorine indeno that a kind of efficiency is high and operation is safe
[1,2-e] [1,3,4] diazine-2, the new synthesis process of 4a (3H, 5H)-dicarboxylic acids-4a-methyl ester (YCW-5), with applicable industrialization
Produce.
In order to solve above-mentioned technical problem, the present invention provides the synthetic method of a kind of agricultural insecticide indoxacarb intermediate (YCW-5),
Comprise the following steps:
1), by (5-chloro-2,3-dihydro-2-hydroxyl-2-methoxycarbonyl group-1H-indenes-subunit) hydrazine carboxylic acid's benzyl esters (YCW-4), Louis
This acid, toluene put in reaction vessel in proportion, and stirring is warming up to the reaction temperature of 105～110 DEG C (preferably 106～108 DEG C)
Degree, reacts until reaction is carried out after the toluene solution of dropping diethoxymethane and interpolation hydrazine benzyl formate under above-mentioned reaction temperature
Completely；The azeotropic mixture of ethanol as by-product and diethoxymethane is constantly evaporated off in course of reaction；
Described hydrazine benzyl formate is 0.1～1:1 (preferably 0.15～0.55:1) with the mol ratio of YCW-4；Lewis acid and YCW-4
Mol ratio be 0.02～0.2:1 (preferably 0.1:1)；The mol ratio of diethoxymethane and YCW-4 is 3～10:1 (preferably
It is 4.6～4.7:1)；
Remarks illustrate: ethanol is the by-product that reaction produces；After generation, reaction there is adverse influence, so to be evaporated off；
2), reaction terminate after stop heating, be cooled to room temperature under stirring, concentration and recovery toluene under reduced pressure, concentrated solution knot
Brilliant solvent crystallisation by cooling at low temperatures, sucking filtration, washing, dry, obtain light yellow crystal, be target product--agricultural insecticidal
Agent indoxacarb intermediate.
The improvement of synthetic method as the agricultural insecticide indoxacarb intermediate of the present invention: the toluene solution of described diethoxymethane
Drip at twice, add hydrazine benzyl formate first after dropping, carry out secondary dropping the most again；Second time dropping
After under reaction temperature reaction until reaction carries out completely.
Remarks illustrate:
It is said that in general, dropping first accounts for the toluene solution of the diethoxymethane of total amount 2/3；Second time drips remaining diethoxy
The toluene solution of methylmethane.
Need to control temperature when dripping the toluene solution of diethoxymethane and cannot be below 92 DEG C, therefore dropping mode is intermittent dropping,
That is, when temperature is less than 92 DEG C, dropping is stopped；When temperature recovery to 92 DEG C, recover dropping.Therefore, the time dripped first
It is about 2～2.6 hours, adds hydrazine benzyl formate first after dropping and react 1～1.5 hour；Second time dropping diethoxymethane
Time of toluene solution be about 1～1.3 hour；React until reaction carries out completely after second time dropping under reaction temperature,
That is, this course of reaction is followed the tracks of with thin layer chromatography (TLC), and YCW-4 reaction is reaction end completely；Therefore the response time is about
2～2.5 hours.
The decomposition amount of YCW-4 is between 10%-50%, and the amount of the hydrazine benzyl formate of addition can be decomposed generation by the YCW-4 measured
The amount of YCW-3 determines, in order to cost-effective, the hydrazine benzyl formate of addition has only to the amount of skipping over, therefore, and general hydrazine formic acid
Benzyl ester is 0.15～0.55:1 with the mol ratio of YCW-4.
The further of synthetic method as the agricultural insecticide indoxacarb intermediate of the present invention is improved:
Lewis acid is boron trifluoride, phosphorus pentoxide, sulfur trioxide, p-methyl benzenesulfonic acid or diphenylsulfonium pyrovinic acid ammonium.
Preferred Lewis acids is p-methyl benzenesulfonic acid, diphenylsulfonium pyrovinic acid ammonium.Most preferably lewis acid is p-methyl benzenesulfonic acid.
The further improvement of synthetic method as the agricultural insecticide indoxacarb intermediate of the present invention: described step 2) in crystallization
Solvent is the lower alcohol containing 1～4 carbon atom.
The further improvement of synthetic method as the agricultural insecticide indoxacarb intermediate of the present invention: described contain 1～4 carbon atom
Lower alcohol be methanol, ethanol, isopropanol, n-butyl alcohol or isobutanol.Preferably methanol.
The further improvement of synthetic method as the agricultural insecticide indoxacarb intermediate of the present invention: at room temperature, by YCW-4,
Lewis acid, toluene put in reaction vessel in proportion.
Generally room temperature is 15～25 DEG C.
In the present invention, step 2) carry out with reference to documents below: Wang Min. at the beginning of the synthetic route of new and effective insecticide indoxacarb
Visit [D]. Beijing: China Agricultural University, 2007.Stephen F M, Gary D A, Rafael S, et al.The discovery of
indoxacarb:oxadiazine as a new class of pyrazoline-type insecticides.Pest Management
Science,2001,57:153-164.
In the present invention, step 1) in reaction used by solvent be toluene.The amount ranges of toluene is YCW-4 at a temperature of visual response
Dissolubility depending on, i.e. its consumption minimum want YCW-4 can be made to dissolve.Therefore, it is however generally that, in the reaction temperature of the present invention
Under, the toluene of the YCW-4 adapted 50～60mL of every 0.026mol.
Diethoxymethane in the toluene solution of diethoxymethane: the volume ratio of toluene is 1:2～4 (preferably 1:3)
Step 2) in the amount ranges of recrystallisation solvent be at a reflux temperature, consumption when YCW-5 can be completely dissolved.Point
From recovered solvent---during toluene can produce in lower batch with recycled.
In sum, the agricultural insecticide indoxacarb intermediate of the present invention, i.e. 2-(benzyl)-7-chlorine indeno [1,2-e] [1,3,4]
Diazine-2, the synthesis of 4a (3H, 5H)-dicarboxylic acids-4a-methyl ester (YCW-5) is with YCW-4 as raw material, lewis acidic
Under catalysis, generate YCW-5 with diethoxymethane generation condensation reaction.
Synthesis route is as follows:
The preparation method of the YCW-5 of the present invention, production suitable for industrialized, react raw materials used and reagent and be commercially available.Product
Yield is more than 80%, content more than 95%.
The present invention relates to the preparation method of YCW-5, have the advantages that addition hydrazine benzyl formate in course of reaction,
Reaction can not only be quickly finished, and effectively inhibit the decomposition of YCW-4.
In sum, the present invention, by optimizing technique, improves appropriate interpolation hydrazine formic acid benzyl in reaction temperature, especially course of reaction
Ester, have found factor and the preferred process parameter affecting ring-closure reaction, significantly reduces the decomposition of YCW-4, improve cyclization anti-
Answering and the overall yield of the former medicine of indoxacarb, the industrialization for this project lays a solid foundation.
Detailed description of the invention
Following example are used for further describing the present invention, but the present invention is only limitted to absolutely not this.
Embodiment 1, the synthetic method of a kind of agricultural insecticide indoxacarb intermediate, follow the steps below successively:
1) in the 250mL four-hole bottle have fractionating device, 10gYCW-4 (0.026mol), 0.45g, are added to toluene sulphur
Acid (0.0026mol), 50mL toluene (through Non-aqueous processing), be heated to reflux there is drop formation to thorn shape dephlegmator, now four mouthfuls
Temperature T in bottlelIt is 108 DEG C, stings shape post tip temperature T2When being 106 DEG C, start intermittence dropping by 10mL diethoxy
Methane (0.08mol) and the mixed liquor of 30mL toluene composition, during dropping, the reflux temperature of reactant liquor can reduce, when thorn shape
Post tip temperature T2During less than 92 DEG C, stop dropping, start to separate partially liq to thorn shape post tip temperature T2Go back up to 92 DEG C,
Stop distillation procedure, continue dropping, so circulate operation, in 2h after dropping, check reaction condition by TLC, estimation
Raw material decomposes the amount of the YCW-3 produced, and after adding the hydrazine benzyl formate reaction 1h of appropriate (0.0143mol), then adds two
Ethoxy methane 5ml, dropping in toluene 15ml, 1h (dropping control mode is ibid) is complete.In 106～108 DEG C of insulations to instead
Should carry out completely (about 2 hours).
2), reaction terminate after stop heating, be cooled to room temperature, after concentration brown viscous liquid, add 30mL methanol carry out
Recrystallization, has solid to separate out, sucking filtration, and cold methanol washs, and dries to obtain faint yellow solid 8.45g (content >=95%), with YCW-4
The rate of collecting is 83%.
Embodiment 2: the synthetic method of a kind of agricultural insecticide indoxacarb intermediate, follows the steps below successively:
1), in the 250mL four-hole bottle have fractionating device, 10g YCW-4 (0.026mol), 0.83g diphenyl three are added
Methyl fluoride ichthyodin (0.0026mol), 50mL toluene (through Non-aqueous processing), be heated to reflux there is drop formation to thorn type reflux column,
Now temperature T in four-hole bottlelIt is 108 DEG C, stings shape post tip temperature T2When being 106 DEG C, start intermittence dropping by 10mL
Diethoxymethane and the mixed liquor of 30mL toluene composition, during dropping, the reflux temperature of reactant liquor can reduce, when thorn shape post
Tip temperature T2During less than 92 DEG C, stop dropping, start to separate partially liq to thorn shape post tip temperature T2Go back up to 92 DEG C,
Stop distillation procedure, continue dropping, so circulate operation, in 2h after dropping, check reaction condition by TLC, estimation
Raw material decomposes the amount of the YCW-3 produced, and after adding the hydrazine benzyl formate reaction 1h of appropriate (0.0143mol), then adds two
Ethoxy methane 5ml, dropping in toluene 15ml, 1h (dropping control mode is ibid) is complete.In 106～108 DEG C of insulations to instead
Should carry out completely (about 2 hours).
2), reaction terminate after stop heating, be cooled to room temperature, after concentration brown viscous liquid, add 30mL methanol carry out
Recrystallization, has solid to separate out, sucking filtration, and cold methanol washs, and dries to obtain faint yellow solid 7.32g (content >=95%), with YCW-4
The rate of collecting is 71%.
The use (but the response time of 1h still retains) of " hydrazine benzyl formate " in comparative example 1-1, cancellation embodiment 1, remaining etc.
It is same as embodiment 1.Final faint yellow solid 5.8g, with the YCW-4 rate of collecting for 58%.
In comparative example 1-2, change embodiment 1, the consumption of " hydrazine benzyl formate " makes 0.006mol into；Remaining is equal to embodiment 1.
Final faint yellow solid 8.4g, with the YCW-4 rate of collecting for 84%.
In comparative example 1-3, change embodiment 1, the consumption of " hydrazine benzyl formate " is 0.020mol；Remaining is equal to embodiment 1.
Final faint yellow solid 8.3g, with the YCW-4 rate of collecting for 83%.
Comparative example 2, by embodiment 1 step 1) in reaction temperature informed by 106～108 DEG C of documents made into described in above-mentioned formula 3
Temperature 80-85 DEG C；Remaining is with embodiment 1.Final faint yellow solid 5.4g, with the YCW-4 rate of collecting for 54%.
Finally, in addition it is also necessary to be only several specific embodiments of the present invention it is noted that listed above.Obviously, the present invention is not
It is limited to above example, it is also possible to have many deformation.Those of ordinary skill in the art directly can lead from present disclosure
The all deformation gone out or associate, are all considered as protection scope of the present invention.
Claims (5)
1. the synthetic method of agricultural insecticide indoxacarb intermediate, is characterized in that comprising the following steps:
1), YCW-4, lewis acid, toluene are put in reaction vessel in proportion, stirring, be warming up to 105～110 DEG C anti-
Answering temperature, reacting under above-mentioned reaction temperature until reacting after the toluene solution of dropping diethoxymethane and interpolation hydrazine benzyl formate
Carry out completely；The azeotropic mixture of ethanol as by-product and diethoxymethane is constantly evaporated off in course of reaction；
Described YCW-4 is (5-chloro-2,3-dihydro-2-hydroxyl-2-methoxycarbonyl group-1H-indenes-subunit) hydrazine carboxylic acid's benzyl esters；
Described hydrazine benzyl formate is 0.1～1:1 with the mol ratio of YCW-4；Lewis acid is 0.02～0.2 with the mol ratio of YCW-4:
1；Diethoxymethane is 3～10:1 with the mol ratio of YCW-4；
The toluene solution of described diethoxymethane drips at twice, adds hydrazine benzyl formate first, then after dropping
Carry out secondary dropping again；React under reaction temperature until reaction is carried out completely after second time dropping；Dropping diethoxy
Need to control temperature during the toluene solution of methylmethane and cannot be below 92 DEG C, dropping mode be intermittent dropping, when temperature is less than 92 DEG C,
Stop dropping；When temperature recovery to 92 DEG C, recover dropping；
2), reaction terminate after stop heating, be cooled to room temperature under stirring, concentration and recovery toluene under reduced pressure, concentrated solution knot
Brilliant solvent crystallisation by cooling at low temperatures, sucking filtration, washing, dry, obtain light yellow crystal, be target product--agricultural insecticidal
Agent indoxacarb intermediate；Its structural formula is as follows:
The synthetic method of agricultural insecticide indoxacarb intermediate the most according to claim 1, is characterized in that:
Described lewis acid is boron trifluoride, phosphorus pentoxide, sulfur trioxide, p-methyl benzenesulfonic acid or diphenylsulfonium pyrovinic acid
Ammonium.
The synthetic method of agricultural insecticide indoxacarb intermediate the most according to claim 2, is characterized in that: described step 2)
In recrystallisation solvent be the lower alcohol containing 1～4 carbon atom.
The synthetic method of agricultural insecticide indoxacarb intermediate the most according to claim 3, is characterized in that: described contain 1～4
The lower alcohol of individual carbon atom is methanol, ethanol, isopropanol, n-butyl alcohol or isobutanol.
The synthetic method of agricultural insecticide indoxacarb intermediate the most according to claim 4, is characterized in that: at room temperature, will
YCW-4, lewis acid, toluene put in reaction vessel in proportion.
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| CN106397351B (en) * | 2016-08-31 | 2018-10-30 | 京博农化科技股份有限公司 | A kind of preparation method of indoxacarb intermediate |
| CN109701655B (en) * | 2018-06-08 | 2019-11-19 | 京博农化科技有限公司 | A kind of preparation method of S body indoxacarb |
| CN109651288A (en) * | 2018-12-29 | 2019-04-19 | 京博农化科技有限公司 | A kind of preparation method of indoxacarb intermediate |
| CN110527646B (en) * | 2019-08-20 | 2021-05-11 | 浙江工业大学 | Tropical bacillus WZZ018 and application thereof |
| CN113607833B (en) * | 2021-07-08 | 2023-10-31 | 山东京博农化科技股份有限公司 | Content analysis method of indoxacarb intermediate |
| CN113607836B (en) * | 2021-07-23 | 2023-10-31 | 山东京博农化科技股份有限公司 | Analysis method for content of indoxacarb key intermediate |
| CN114957158A (en) * | 2022-05-31 | 2022-08-30 | 浙江禾本科技股份有限公司 | Method for preparing indoxacarb intermediate |
| CN115974808B (en) * | 2022-12-21 | 2024-03-12 | 大连奇凯医药科技有限公司 | Preparation method of 2-benzyl-7-chloro [1,2-e ] indeno [1,3,4] oxadiazine dimethyl ester |
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