CN103214400B - Preparation method of hexaflumuron - Google Patents
Preparation method of hexaflumuron Download PDFInfo
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- CN103214400B CN103214400B CN201310129728.XA CN201310129728A CN103214400B CN 103214400 B CN103214400 B CN 103214400B CN 201310129728 A CN201310129728 A CN 201310129728A CN 103214400 B CN103214400 B CN 103214400B
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- hexaflumuron
- chloro
- bis
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- oxyethyl group
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- RGNPBRKPHBKNKX-UHFFFAOYSA-N hexaflumuron Chemical compound C1=C(Cl)C(OC(F)(F)C(F)F)=C(Cl)C=C1NC(=O)NC(=O)C1=C(F)C=CC=C1F RGNPBRKPHBKNKX-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 66
- 238000006243 chemical reaction Methods 0.000 claims abstract description 49
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 claims abstract description 28
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims abstract description 28
- 239000000243 solution Substances 0.000 claims abstract description 26
- 239000007864 aqueous solution Substances 0.000 claims abstract description 23
- 238000003756 stirring Methods 0.000 claims abstract description 16
- 239000011592 zinc chloride Substances 0.000 claims abstract description 14
- 235000005074 zinc chloride Nutrition 0.000 claims abstract description 14
- QRHUZEVERIHEPT-UHFFFAOYSA-N 2,6-difluorobenzoyl chloride Chemical compound FC1=CC=CC(F)=C1C(Cl)=O QRHUZEVERIHEPT-UHFFFAOYSA-N 0.000 claims abstract description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 12
- 239000012065 filter cake Substances 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 7
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 7
- 239000007789 gas Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 3
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims description 52
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 17
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- AJSHDAOMUKXVDC-UHFFFAOYSA-N butan-1-amine;sulfuric acid Chemical compound CCCC[NH3+].OS([O-])(=O)=O AJSHDAOMUKXVDC-UHFFFAOYSA-N 0.000 claims description 3
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 claims description 3
- 235000019441 ethanol Nutrition 0.000 claims description 3
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 claims description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 3
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 23
- 238000000034 method Methods 0.000 abstract description 7
- 238000004821 distillation Methods 0.000 abstract description 4
- 238000007086 side reaction Methods 0.000 abstract description 2
- PJUKOQFWMMLIMU-UHFFFAOYSA-N [3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)phenyl]urea Chemical compound ClC=1C=C(C=C(C1OC(C(F)F)(F)F)Cl)NC(=O)N PJUKOQFWMMLIMU-UHFFFAOYSA-N 0.000 abstract 2
- 239000012295 chemical reaction liquid Substances 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 2
- 238000005406 washing Methods 0.000 abstract 2
- JIPDPVQPKLVDIU-UHFFFAOYSA-N 3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy)aniline Chemical compound NC1=CC(Cl)=C(OC(F)(F)C(F)F)C(Cl)=C1 JIPDPVQPKLVDIU-UHFFFAOYSA-N 0.000 abstract 1
- 239000003054 catalyst Substances 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 15
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 9
- 239000001110 calcium chloride Substances 0.000 description 9
- 229910001628 calcium chloride Inorganic materials 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000007791 liquid phase Substances 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 6
- 238000010907 mechanical stirring Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000010792 warming Methods 0.000 description 6
- -1 2,6-difluorobenzene acid amides Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
- 238000010298 pulverizing process Methods 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- HRYILSDLIGTCOP-UHFFFAOYSA-N N-benzoylurea Chemical class NC(=O)NC(=O)C1=CC=CC=C1 HRYILSDLIGTCOP-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 231100000004 severe toxicity Toxicity 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- AVRQBXVUUXHRMY-UHFFFAOYSA-N 2,6-difluorobenzamide Chemical compound NC(=O)C1=C(F)C=CC=C1F AVRQBXVUUXHRMY-UHFFFAOYSA-N 0.000 description 1
- ZRJSABISRHPRSB-UHFFFAOYSA-N 2,6-difluorobenzoyl isocyanate Chemical compound FC1=CC=CC(F)=C1C(=O)N=C=O ZRJSABISRHPRSB-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 241000254173 Coleoptera Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000255967 Helicoverpa zea Species 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003151 ovacidal effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
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- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a preparation method of hexaflumuron. The preparation method of hexaflumuron taking 3, 5-dichloro-4-(1,1,2,2-tetrafluoroethoxy) aniline and sodium cyanate as raw materials comprises the following steps of: (1) adding a phase transfer catalyst in an acetic acid aqueous solution, reacting for 1-12 hours at 0-80 DEG C, filtering reaction liquid to obtain filter cakes, washing and drying to obtain 3,5-dichloro-4-(1,1,2,2-tetrafluoroethoxy) phenylurea; and (2) in an organic solvent, reacting the mixture of anhydrous zinc chloride and anhydrous trichloride taken as a catalyst and 3, 5-dichloro-4-(1,1,2,2-tetrafluoroethoxy) phenylurea and 2,6-difluorobenzoyl chloride taken as raw materials for 1-24 hours at 65-150 DEG C, vacuumizing in the reaction process to remove hydrogen chloride gas, after reaction is ended, recovering the solvent through reduced pressure distillation, after cooling, adding a sodium bicarbonate solution with the mass fraction of 5%, adjusting the pH to 7-8, stirring for 30 minutes, filtering reaction liquid to obtain filter cakes, washing, drying and recrystallizing to obtain hexaflumuron. The preparation method of hexaflumuron has the advantages of being simple and reasonable in process, little in side reaction and having high safety, high reaction yield and high product purity, great industrialization potential and great social economic benefits, and can easily realize purification of products.
Description
Technical field
The present invention relates to a kind of preparation method of compound, particularly relate to a kind of preparation method of substituted benzoyl urea insect growth regulator(IGR) HEXAFLUMURON.
Background technology
HEXAFLUMURON belongs to benzoyl urea sterilant, is chitin synthesis inhibitor, has very high desinsection and ovicidal activity, and quick-acting, especially prevents and treats bollworm.Multiple Coleoptera, Diptera, Homoptera insect is prevented and treated for cotton, potato and fruit tree.
At present, the synthetic method of HEXAFLUMURON mainly contains two kinds: (1) first generates 2,6-difluoro benzoyl isocyanate by 2,6-difluorobenzamide and phosgene or oxalyl chloride, then obtained with the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) aniline reaction; (2) first generate the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenyl isocyanate by the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) aniline and phosgene or oxalyl chloride, then react with 2,6-difluorobenzene acid amides and obtain.In above method, oxalyl chloride is colourless fuming liquid, and meet water or alcohol vigorous reaction and decomposite hydrogenchloride, have stronger toxicity and corrodibility, operating environment is poor, and expensive, and production cost is higher; Although phosgene low price, production cost is lower, and due to phosgene severe toxicity, inconvenience transport and metering, exist potential safety hazard; In addition, all first above method has obtained isocyanide acyl ester compound, and this compounds is stable not, easy autohemagglutination, is difficult to store.
Guo Xi has just waited people's (triphosgene synthesis HEXAFLUMURON, organic fluorine industry, 2009 the 2nd phases, triphosgene 5-6) is adopted to replace optical self-encoding HEXAFLUMURON, result shows triphosgene and 2, both 6-difluorobenzamides react more difficult, and adopt triphosgene first with 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline synthesis 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenyl isocyanate, again with 2, the reaction of 6-difluorobenzamide can obtain HEXAFLUMURON, the method still fails to overcome intermediate 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) the easy autohemagglutination of phenyl isocyanate, by product is more, product is not easy the difficulty of purifying, in reaction process and last handling process, still have a small amount of triphosgene can decompose generation phosgene, easily cause potential safety hazard.
Summary of the invention
The object of the invention is the deficiency that prior art poor stability, the easy autohemagglutination of intermediate, by product are more, product is not easily purified in order to solve, a kind of technique advantages of simple be provided, security is high, side reaction is few, product is easily purified, reaction yield and the high HEXAFLUMURON preparation method of product purity.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is as follows:
A preparation method for HEXAFLUMURON, described preparation method comprises the following steps:
(1) in the acetic acid aqueous solution of massfraction 20-60%, add 3 shown in formula I, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline and 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phase-transfer catalyst of aniline quality 1-5%, under agitation condition, drip the Zassol aqueous solution of massfraction 5-30%, 1-12h is reacted at 0-80 DEG C, then the reaction solution water of 1-3 times of volume dilutes, filter after being cooled to 0-5 DEG C, filter cake washes with water to neutrality, 3 shown in formula II is obtained after drying, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea,
(2) obtain with step (1) 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, 6-difluoro benzoyl chloride is raw material, in organic solvent, add 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, the Zinc Chloride Anhydrous of 6-difluoro benzoyl chloride total mass 5-30% and aluminum trichloride (anhydrous) mixture are catalyzer, 1-24h is reacted at 65-150 DEG C, vacuumize the hydrogen chloride gas got rid of and generate with water pump in reaction process, reaction terminates through vacuum distillation recovered solvent, after cooling, slowly add the sodium hydrogen carbonate solution of massfraction 5%, regulate pH to 7-8, stir 30min, filter, filter cake is washed with water to neutrality, the HEXAFLUMURON shown in formula III is obtained again with 80-95% ethyl alcohol recrystallization.
As preferably, the phase-transfer catalyst described in step (1) is one of following: benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, tetrabutylammonium chloride, 4-butyl ammonium hydrogen sulfate, tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride.
As preferably, in step (1) in acetic acid solution in contained acetic acid and Zassol solution contained by the mol ratio of Zassol be the mol ratio of the chloro-4-of 1-4:1,3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) aniline and Zassol be 1:1.05-1.5.
Further, in step (1) in acetic acid solution in contained acetic acid and Zassol solution contained by the mol ratio of Zassol be 1.5-2.5:1.
As preferably, in step (2) catalyzer by the ratio of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) 5:1 in mass ratio mix pulverize obtained.
As preferably, organic solvent described in step (2) is one of following: chlorobenzene, benzene,toluene,xylene, tetrahydrofuran (THF), 2-methyltetrahydrofuran.
As preferably, in step (2), 2,6-difluoro benzoyl chlorides and the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea mol ratio are 1-1.25:1.
Further, in step (2), 2,6-difluoro benzoyl chlorides and the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea mol ratio are 1.02-1.1:1.
As preferably, in step (1), acetic acid aqueous solution massfraction is 30-50%; The massfraction of the Zassol aqueous solution dripped is 10 ~ 20%; 2-5h is reacted under 30-50 DEG C of condition.
As preferably, in step (2), the consumption of catalyzer is the 5-15% of the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea and 2,6-difluoro benzoyl chloride total mass, under 90-120 DEG C of condition, react 6-10h.
The present invention compared with prior art, has following beneficial effect:
(1) under the effect of phase-transfer catalyst, Zassol and the chloro-4-(1 of 3,5-bis-is used, 1,2,2-tetrafluoro oxyethyl group) aniline is Material synthesis 3, the chloro-4-of 5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea, reaction conditions is gentle, and yield is high, because Zassol is obtained by urea and sodium carbonate, cheap, good stability, be decomposed into volatile salt, sodium carbonate and urea in the hot water, to people, animal, fish safety.
(2) be Material synthesis HEXAFLUMURON with the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea and 2,6-difluoro benzoyl chloride, technique is simple, and by product is few, and product is easy to purify.
The present invention effectively avoids and adopts the oxalyl chloride of severe toxicity or phosgene to be raw material, and main raw material used is cheap and easy to get, and security is high, and the production process three wastes are few, and the purity of product is high, has larger implementary value and economic results in society.
(4) embodiment
Below in conjunction with specific embodiment, the present invention is described further, and in following each embodiment, agents useful for same is commercial analytical pure, and instrument and equipment are all commercial conventional instrument and equipment, and unless specifically indicated, in embodiment, each solution is the aqueous solution.
The content of HEXAFLUMURON adopts high performance liquid chromatography to detect, and concrete testing conditions is as follows: Lichrospher C18 post, 4.6mm × 250mm; Column temperature: room temperature; Moving phase: acetonitrile-water (volume ratio is 68:32); Flow velocity: 1ml/min; Determined wavelength: 254nm.
Fusing point detects: adopt melting point apparatus (WRS-3, Shanghai precision instrumentation company limited).
Embodiment 1
A preparation method for HEXAFLUMURON, described preparation method comprises the following steps:
Step (1): by 7.8g(0.12mol) Zassol is dissolved in 148.2ml water the Zassol aqueous solution being configured to 5%, by 7.14g(0.12mol) acetic acid is dissolved in 28.56ml water the acetic acid aqueous solution being configured to 20%, mechanical stirring is being housed, in the 500ml there-necked flask of constant pressure funnel and thermometer, add the above-mentioned acetic acid aqueous solution configured successively, 0.278g benzyltriethylammoinium chloride, add 27.803g(0.1mol again) 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline, stir the above-mentioned Zassol aqueous solution configured of lower slowly dropping, namely off-white color solid is had to separate out, after dropwising, continue at 0 DEG C of reaction 12h, stopped reaction, reaction solution is slowly poured in the beaker that 176.7ml water is housed under agitation condition and dilute, be cooled to 0 DEG C, filter, filter cake is washed with water to neutrality, vacuum-drying obtains off-white color solid 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea 27.74g, the yield that step (1) is reacted is 86.4%,
Step (2): by 2, 6-difluoro benzoyl chloride 16.85g(0.1mol) be dissolved in the toluene that 25ml uses Calcium Chloride Powder Anhydrous dried in advance for subsequent use, Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) in mass ratio 5:1 mix rear pulverizing, seal for subsequent use, the add-on of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) is reactant 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, 5% of 6-difluoro benzoyl chloride total mass, mechanical stirring is being housed, reflux condensing tube (suitable for reading connect Calcium Chloride Powder Anhydrous drying tube), in the 250ml four-hole boiling flask of constant pressure funnel and thermometer, add 3 successively, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea 32.10g(0.1mol), the toluene stirring and dissolving that 100ml uses Calcium Chloride Powder Anhydrous dried in advance, add 2.45g Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) mixture, be warming up to 40 DEG C, slow dropping is above-mentioned configure 2, the toluene solution of 6-difluoro benzoyl chloride, after dropwising, be warming up to 105 DEG C of stirring reaction 12h, eliminating hydrogen chloride gas is vacuumized with water pump in reaction process, after stopped reaction, toluene solvant is reclaimed in underpressure distillation, then cool, slowly add the sodium hydrogen carbonate solution of massfraction 5% again, regulate reaction solution pH to 7.0, stir 30min, filter, filter cake is washed with water to the neutral solid obtaining pinkish, obtained solid phase prod is put in 500ml single port flask, add ethanolic soln and 2g gac that 400ml massfraction is 80%, reflux 30min, filtered while hot, filtrate is cooled to 0 DEG C, separate out solid, filter, vacuum-drying obtains white solid 37.14g, i.e. product HEXAFLUMURON, reaction yield 80.5%, product fusing point: 202-204 DEG C, it is 98.6% that efficient liquid phase chromatographic analysis obtains content.
Embodiment 2
Step (1): by 15.6g(0.24mol) Zassol is dissolved in 88.4ml water the Zassol aqueous solution being configured to 15%, by 30g(0.5mol) acetic acid is dissolved in 45ml water the acetic acid aqueous solution being configured to 40%, mechanical stirring is being housed, in the 500ml there-necked flask of constant pressure funnel and thermometer, add the above-mentioned acetic acid aqueous solution configured successively, 2.78g Tetrabutyl amonium bromide, add 55.606g(0.2mol) 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline, under stirring, the above-mentioned Zassol aqueous solution configured of slow dropping, namely off-white color solid is had to separate out, dropwise rear continuation at 80 DEG C of reaction 1h, stopped reaction, under agitation condition, reaction solution is slowly poured in the beaker that 400ml water is housed, dilution is cooled to 5 DEG C, filter, filter cake is washed with water to neutrality, drying obtains off-white color solid 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea product 58.11g, step (1) reaction yield is 90.5%,
Step (2) is by 2, 6-difluoro benzoyl chloride 21.068g(0.125mol) be dissolved in the dimethylbenzene that 25ml uses Calcium Chloride Powder Anhydrous dried in advance for subsequent use, Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) in mass ratio 5:1 mix rear pulverizing, seal for subsequent use, the add-on of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) is reactant 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, 30% of 6-difluoro benzoyl chloride total mass, mechanical stirring is being housed, reflux condensing tube (suitable for reading connect Calcium Chloride Powder Anhydrous drying tube), in the 250ml four-hole boiling flask of constant pressure funnel and thermometer, add 3 successively, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea 32.10g(0.1mol), the dimethylbenzene stirring and dissolving that 100ml uses Calcium Chloride Powder Anhydrous dried in advance, add 15.95g Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) mixture, be warming up to 40 DEG C, slow dropping is above-mentioned configure 2, the xylene solution of 6-difluoro benzoyl chloride, after dropwising, be warming up to 150 DEG C of stirring reaction 1h, eliminating hydrogen chloride gas is vacuumized with water pump in reaction process, after stopped reaction, xylene solvent is reclaimed in underpressure distillation, then cool, slowly add the sodium hydrogen carbonate solution that massfraction is 5% again, regulate reaction solution pH to 8.0, stir 30min, filter, filter cake is washed with water to the neutral solid obtaining pinkish, obtained solid phase prod is put in 500ml single port flask, add ethanolic soln and 2g gac that 400ml massfraction is 95%, reflux 30min, filtered while hot, filtrate is cooled to 5 DEG C, separate out solid, filter, dry, obtain white solid 37.61g, i.e. product HEXAFLUMURON, reaction yield 82.0%, product fusing point: 202.5-204 DEG C, efficient liquid phase chromatographic analysis obtains content 99.0%.
Embodiment 3
Step (1): by 19.5g(0.3mol) Zassol is dissolved in 45.5ml water the Zassol aqueous solution being configured to 30%, by 30g(0.5mol) acetic acid is dissolved in 20ml water the acetic acid aqueous solution being configured to 60%, mechanical stirring is being housed, in the 500ml there-necked flask of constant pressure funnel and thermometer, add the above-mentioned acetic acid aqueous solution configured successively, 1.39g tetrabutylammonium chloride, add 55.61g(0.2mol) 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline, stir the above-mentioned Zassol aqueous solution configured of lower slowly dropping, namely off-white color solid is had to separate out, dropwise and continue at 40 DEG C of reaction 6h, stopped reaction, reaction solution is slowly poured in the beaker that 150ml water is housed under stirring and dilute, be cooled to 2.5 DEG C, filter, filter cake is washed with water to neutrality, drying obtains off-white color solid 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea product 59.68g, step (1) reaction yield is 92.95%,
Step (2): by 2, 6-difluoro benzoyl chloride 18.54g(0.11mol) be dissolved in the benzene that 25ml uses Calcium Chloride Powder Anhydrous dried in advance for subsequent use, Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) in mass ratio 5:1 mix rear pulverizing, seal for subsequent use, the add-on of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) is reactant 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, 15% of 6-difluoro benzoyl chloride total mass, mechanical stirring is being housed, reflux condensing tube (suitable for reading connect Calcium Chloride Powder Anhydrous drying tube), in the 250ml four-hole boiling flask of constant pressure funnel and thermometer, add 3 successively, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea 32.10g(0.1mol), the benzene stirring and dissolving that 100ml uses Calcium Chloride Powder Anhydrous dried in advance, add 7.6g Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) mixture, be warming up to 40 DEG C, slow dropping is above-mentioned configure 2, the benzole soln of 6-difluoro benzoyl chloride, stirring reaction 24h at being warming up to 65 DEG C after dropwising, eliminating hydrogen chloride gas is vacuumized with water pump in reaction process, after stopped reaction, benzene solvent is reclaimed in underpressure distillation, then cool, slowly add the sodium hydrogen carbonate solution that massfraction is 5% again, regulate pH to 7.5, stir 30min, filter, filter cake is washed with water to the neutral solid obtaining pinkish, obtained solid phase prod is put in 500ml single port flask, add ethanolic soln and 2g gac that 400ml massfraction is 85%, reflux 30min, filtered while hot, filtrate is cooled to 2.5 DEG C, separate out solid, filter, dry, obtain white solid 39.89g, i.e. product HEXAFLUMURON, reaction yield 86.5%, product fusing point: 202.7-204 DEG C, efficient liquid phase chromatographic analysis obtains content 99.1%.
Embodiment 4
Step (1): elementary operation is with the step (1) of embodiment 2, difference is: the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) addition of aniline is 63.55g(0.228mol), i.e. Zassol and the chloro-4-(1 of 3,5-bis-, 1,2,2-tetrafluoro oxyethyl group) mol ratio of aniline is 1.05:1, the yield of step (1) is 88.2%;
Step (2): elementary operation is with the step (2) of embodiment 2, and step (2) product HEXAFLUMURON reaction yield 82.0%, product fusing point: 202.5-204 DEG C, efficient liquid phase chromatographic analysis obtains content 99.0%.
Embodiment 5
Step (1): elementary operation is with the step (1) of embodiment 2, and difference is: after dripping Zassol solution, in 60 DEG C of reaction 2h, the yield of step (1) is 91.5%;
Step (2): elementary operation is with the step (2) of embodiment 2, and step (2) product HEXAFLUMURON reaction yield 82.0%, product fusing point: 202.5-204 DEG C, efficient liquid phase chromatographic analysis obtains content 99.0%.
Embodiment 6
Step (1): elementary operation is with the step (1) of embodiment 3, and the reaction yield of step (1) is 92.95%;
Step (2): elementary operation is with the step (2) of embodiment 3, and difference is: the chloro-4-(1 of 3,5-bis-, 1,2,2-tetrafluoro oxyethyl group) addition of phenylurea is 29.43g(0.0917mol), i.e. 2,6-difluoro benzoyl chlorides and the chloro-4-(1 of 3,5-bis-, 1,2,2-tetrafluoro oxyethyl group) mol ratio of phenylurea is 1.2:1, the reaction yield of step (2) is 87.0%, product fusing point: 202.7-204.0 DEG C, efficient liquid phase chromatographic analysis obtains content 99.1%.
Embodiment 7
Step (1): elementary operation is with the step (1) of embodiment 3, and the reaction yield of step (1) is 92.95%;
Step (2): elementary operation is with the step (2) of embodiment 3, difference is: the add-on of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) is reactant 3, the chloro-4-(1 of 5-bis-, 1,2,2-tetrafluoro oxyethyl group) phenylurea and 2,20% of 6-difluoro benzoyl chloride total mass, the reaction yield of step (2) is 86.0%, and product fusing point: 202.2-204 DEG C, efficient liquid phase chromatographic analysis obtains content 98.9%.
Embodiment 8
Step (1), elementary operation is with the step (1) of embodiment 1, and the reaction yield of step (1) is 86.4%;
Step (2), elementary operation is with the step (2) of embodiment 1, and difference is: 2, after 6-difluorobenzoyl chlorine solution dropwises, the reaction times is 4h, and the reaction yield of step (2) is 78.6%, product fusing point: 202.0-204.0 DEG C, efficient liquid phase chromatographic analysis obtains content 98.6%.
The present invention is not restricted to the described embodiments; describe in above-described embodiment and specification sheets just in order to principle of the present invention is described; without departing from the spirit and scope of the present invention; the present invention also has the changes and improvements of various unsubstantiality; if phase-transfer catalyst can also be 4-butyl ammonium hydrogen sulfate, tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride; organic solvent can also be chlorobenzene, tetrahydrofuran (THF), 2-methyltetrahydrofuran, and these all fall in the scope of protection of present invention.
Claims (8)
1. a preparation method for HEXAFLUMURON, is characterized in that, described preparation method comprises the following steps:
(1) in the acetic acid aqueous solution of massfraction 20-60%, add 3 shown in formula I, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) aniline and 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phase-transfer catalyst of aniline quality 1-5%, under agitation condition, drip the Zassol aqueous solution of massfraction 5-30%, 1-12h is reacted at 0-80 DEG C, then the reaction solution water of 1-3 times of volume dilutes, filter after being cooled to 0-5 DEG C, filter cake washes with water to neutrality, 3 shown in formula II is obtained after drying, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea,
(2) obtain with step (1) 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, 6-difluoro benzoyl chloride is raw material, in organic solvent, add 3, the chloro-4-(1 of 5-bis-, 1, 2, 2-tetrafluoro oxyethyl group) phenylurea and 2, the catalyzer of 6-difluoro benzoyl chloride total mass 5-30%, 1-24h is reacted at 65-150 DEG C, vacuumize the hydrogen chloride gas got rid of and generate with water pump in reaction process, reaction terminates through vacuum distillation recovered solvent, after cooling, slowly add the sodium hydrogen carbonate solution of massfraction 5%, regulate pH to 7-8, stir 30min, filter, filter cake is washed with water to neutrality, the HEXAFLUMURON shown in formula III is obtained again with 80-95% ethyl alcohol recrystallization, described catalyzer by the ratio of Zinc Chloride Anhydrous and aluminum trichloride (anhydrous) 5:1 in mass ratio mix pulverize obtained,
Phase-transfer catalyst described in step (1) is one of following: benzyltriethylammoinium chloride, Tetrabutyl amonium bromide, tetrabutylammonium chloride, 4-butyl ammonium hydrogen sulfate, tri-n-octyl methyl ammonium chloride, Dodecyl trimethyl ammonium chloride, tetradecyl trimethyl ammonium chloride.
2. the preparation method of a kind of HEXAFLUMURON according to claim 1, it is characterized in that, in step (1) in acetic acid aqueous solution in contained acetic acid and Zassol solution contained by the mol ratio of Zassol be 1-4:1,3, the chloro-4-(1 of 5-bis-, 1,2,2-tetrafluoro oxyethyl group) mol ratio of aniline and Zassol is 1:1.05-1.5.
3. the preparation method of a kind of HEXAFLUMURON according to claim 2, is characterized in that, in step (1) in acetic acid solution in contained acetic acid and Zassol solution contained by the mol ratio of Zassol be 1.5-2.5:1.
4. the preparation method of a kind of HEXAFLUMURON according to claim 1 or 2 or 3, is characterized in that, organic solvent described in step (2) is one of following: chlorobenzene, benzene,toluene,xylene, tetrahydrofuran (THF), 2-methyltetrahydrofuran.
5. the preparation method of a kind of HEXAFLUMURON according to claim 1 or 2 or 3, is characterized in that, in step (2), the mol ratio of 2,6-difluoro benzoyl chlorides and the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea is 1-1.25:1.
6. the preparation method of a kind of HEXAFLUMURON according to claim 5, is characterized in that, in step (2), the mol ratio of 2,6-difluoro benzoyl chlorides and the chloro-4-of 3,5-bis-(1,1,2,2-tetrafluoro oxyethyl group) phenylurea is 1.02-1.1:1.
7. the preparation method of a kind of HEXAFLUMURON according to claim 1, is characterized in that, in step (1), acetic acid aqueous solution massfraction is 30-50%; The massfraction of the Zassol aqueous solution dripped is 10-20%; 2-5h is reacted under 30-50 DEG C of condition.
8. the preparation method of a kind of HEXAFLUMURON according to claim 1, it is characterized in that, in step (2), the consumption of catalyzer is 3, the chloro-4-(1 of 5-bis-, 1,2,2-tetrafluoro oxyethyl group) phenylurea and 2, the 5-15% of 6-difluoro benzoyl chloride total mass, reacts 6-10h under 90-120 DEG C of condition.
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