CN106674169A - Preparation method of carbofuran derivatives - Google Patents
Preparation method of carbofuran derivatives Download PDFInfo
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- CN106674169A CN106674169A CN201611000003.0A CN201611000003A CN106674169A CN 106674169 A CN106674169 A CN 106674169A CN 201611000003 A CN201611000003 A CN 201611000003A CN 106674169 A CN106674169 A CN 106674169A
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- carbofuran
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- derivative
- binding agent
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- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical class CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 title claims abstract description 90
- 238000002360 preparation method Methods 0.000 title claims abstract description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 81
- 238000006243 chemical reaction Methods 0.000 claims abstract description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 67
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 36
- 150000001412 amines Chemical class 0.000 claims abstract description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000000460 chlorine Substances 0.000 claims abstract description 24
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 24
- 239000002253 acid Substances 0.000 claims abstract description 22
- 239000011230 binding agent Substances 0.000 claims abstract description 21
- 238000006482 condensation reaction Methods 0.000 claims abstract description 20
- PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 17
- 239000002994 raw material Substances 0.000 claims abstract description 11
- 230000008569 process Effects 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims description 37
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical group CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 claims description 36
- 238000004073 vulcanization Methods 0.000 claims description 19
- 239000005864 Sulphur Substances 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- KTYZSBAKDACFSZ-UHFFFAOYSA-N S(Cl)Cl.[N] Chemical compound S(Cl)Cl.[N] KTYZSBAKDACFSZ-UHFFFAOYSA-N 0.000 claims description 13
- 229940000635 beta-alanine Drugs 0.000 claims description 7
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-aminopropionic acid Natural products NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims 1
- 230000002045 lasting effect Effects 0.000 claims 1
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000001988 toxicity Effects 0.000 abstract description 4
- 230000008901 benefit Effects 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 abstract 2
- 239000007810 chemical reaction solvent Substances 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 238000005987 sulfurization reaction Methods 0.000 abstract 1
- 238000005554 pickling Methods 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- JLQUFIHWVLZVTJ-UHFFFAOYSA-N carbosulfan Chemical compound CCCCN(CCCC)SN(C)C(=O)OC1=CC=CC2=C1OC(C)(C)C2 JLQUFIHWVLZVTJ-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 10
- 238000013019 agitation Methods 0.000 description 9
- 231100000053 low toxicity Toxicity 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- UJMGZPCKYHBCKU-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydrobenzofuran Chemical compound C1=CC=C2OC(C)(C)CC2=C1 UJMGZPCKYHBCKU-UHFFFAOYSA-N 0.000 description 8
- 239000006184 cosolvent Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- -1 carbosulfan Chemical class 0.000 description 7
- 239000002904 solvent Substances 0.000 description 6
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000004445 quantitative analysis Methods 0.000 description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 238000012805 post-processing Methods 0.000 description 4
- WJGPNUBJBMCRQH-UHFFFAOYSA-N 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-ol Chemical compound C1=CC(O)=C2OC(C)(C)CC2=C1 WJGPNUBJBMCRQH-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000004065 wastewater treatment Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000073 carbamate insecticide Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000005645 nematicide Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/86—Benzo [b] furans; Hydrogenated benzo [b] furans with an oxygen atom directly attached in position 7
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of carbofuran derivatives. The preparation method of the carbofuran derivatives comprises the following steps: (1) taking amine derivatives and sulfur monochloride as raw materials, adding a first acid-binding agent and a reaction solvent and performing sulfuration reaction to obtain a first intermediate disulfide, wherein the first acid-binding agent is triethylamine and the reaction solvent is chloroform or dichloromethane; (2) performing chlorination reaction on the first intermediate disulfide and chlorine which serve as raw materials to obtain a second intermediate nitrogen and sulfur chloride; (3) taking the second intermediate nitrogen and sulfur chloride and carbofuran as raw materials, adding a second acid-binding agent and performing condensation reaction to obtain the carbofuran derivatives. The preparation method has the advantages that the process is simple, and the product is low in toxicity, high in purity and high in yield.
Description
Technical field
The invention belongs to preparation technique of pesticide field, and in particular to a kind of preparation method of carbofuran derivative.
Background technology
Carbofuran is broad spectrum insecticide, nematicide, with tagging and stomach poison function, it is adaptable to paddy rice, cotton, tobacco,
The preventing and treating of various pests in Soybean and Other Crops, it is also possible to use as seed treatment.With the cry of agricultural chemicals low toxicity it is increasingly high
Rise, highly toxic carbofuran disabling also has been enter into countdown, and carbofuran low toxicity derivative is very important carbamate
Insecticides kind, principal item includes carbosulfan, Benfuracard micro, and its pesticidal strong, quick-acting, residual life is short, select
Property it is strong and to higher plant low toxicity, toxicity only has 1/20th (" the chemistry conjunction of carbosulfan such as Zeng Xianze of carbofuran
Into ",《Agricultural chemicals》No.6 (1995) P12 of volume 34 turn 16), so exploitation high-quality carbofuran low toxicity derivative contains great market
Potentiality.
The synthetic method of carbofuran low toxicity derivative has a lot, mainly there is following 2 kinds：Benzofuranol method, carbofuran method, wherein
Carbofuran method is divided into carbofuran indirect method and carbofuran direct method again.Benzofuranol method mainly has：United States Patent (USP) US4264625A with
Dioxane is solvent, and with triethylamine as acid binding agent, Jing column chromatographies obtain target compound (with benzofuranol with 50% yield
Meter), the method yield is not high.Patent DE3215256A1 with toluene as solvent, with triethylamine as acid binding agent, with 86% yield
Target compound is obtained, accessory substance is severe toxicity, deep-etching gaseous hydrogen fluoride, and post processing is bothered.Carbofuran indirect method has：It is Japanese special
Sharp JP58026878 obtains target compound with carbofuran and sulfur dichloride as starting material with 79.8% yield, and yield is not high,
It is relatively costly.Patent US4413005A synthesizes a series of carbamate derivatives, yield 80% or so, by column chromatography
Product is obtained, product content is not reported, yield is not high, relatively costly.Carbofuran direct method has：BE817517A is with pyridine
Solvent and acid binding agent, discovery still has 20% carbofuran unreacted, and it is long that the method has the reaction time, target product yield and
The characteristics of content is low.With n-hexane as reaction dissolvent in patent US4329293A, triethylamine can obtain 95% as acid binding agent
Carbosulfan crude oil, but there is the risk of secure context as solvent in n-hexane.Chinese patent CN00113443.4 leads to
Crossing column chromatography can obtain the carbosulfan crude oil that content is 92%, have the shortcomings that to purify high cost and content is low.In
State's patent CN102786503A improves carbofuran in reactant liquor using cosolvent 1-METHYLPYRROLIDONE or dimethylformamide
In dissolubility, the yield of target compound carbosulfan is 97% (in terms of carbofuran), content 96%, but its need plus
Enter cosolvent cause to be difficult to recycle and lose, the trouble for post-processing and the difficulty for increasing wastewater treatment.
In these patents, Chinese patent CN102786503A is using cosolvent 1-METHYLPYRROLIDONE or dimethyl formyl
Improving dissolubility of the carbofuran in reactant liquor, yield is 97% (in terms of carbofuran) to amine, content 96%, but its need plus
Enter cosolvent cause to be difficult to recycle and lose, the trouble for post-processing and the difficulty for increasing wastewater treatment.And in other synthesis
Solubility all very littles in method due to triethylamine hydrochloride in Conventional solvents, carbofuran is by three second in condensation reaction
Amine hydrochlorate portion envelops, cause part carbofuran to fail participation reaction and cause carbofuran low toxicity derivative content and yield not
Height, therefore seriously hinder the popularization and application of the carbofuran derivative such as carbosulfan, Benfuracard micro.
The content of the invention
The technical problem to be solved in the present invention is to overcome the deficiencies in the prior art, there is provided a kind of process is simple, purity and receipts
The preparation method of the high carbofuran low toxicity derivative of rate.
To solve above-mentioned technical problem, the present invention is employed the following technical solutions：
A kind of preparation method of carbofuran derivative, comprises the following steps：
(1) with amine derivative and sulfur monochloride as raw material, the first acid binding agent and reaction dissolvent are added, carry out vulcanization reaction,
Obtain disulphide；First acid binding agent is triethylamine；The reaction dissolvent is chloroform or dichloromethane；
(2) chlorination reaction is carried out as raw material with disulphide and chlorine, obtains nitrogen sulphur chloride；
(3) with nitrogen sulphur chloride and carbofuran as raw material, the second acid binding agent is added, carries out condensation reaction, obtain carbofuran
Derivative.
The preparation method of above-mentioned carbofuran derivative, it is preferred that the amine derivative, sulfur monochloride, the first acid binding agent,
The mol ratio of chlorine, carbofuran and the second acid binding agent is 1.0: 0.5~0.55: 1.0~1.1: 0.5~0.55: 0.93~0.95:
2~2.2.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (1), the amine derivative is two just
Butylamine or N- isopropyls-Beta-alanine ethyl ester.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (1), the reaction dissolvent spreads out with amine
Biological volume ratio is 10~20: 1.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (1), the reaction dissolvent spreads out with amine
Biological volume ratio is 15: 1.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (1), the vulcanization reaction temperature is 0
DEG C~10 DEG C, the reaction time is 1.5h~2h.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (2), the chlorination reaction it is concrete
Process is：5 DEG C~10 DEG C, continue under stirring condition, chlorine to be passed through in the solution after vulcanization reaction, chlorine is passed through the time and is
1h~1.5h；Chlorine is passed through after finishing reaction 2h~3h at 0 DEG C~30 DEG C.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (2), when the amine derivative is two
During n-butylamine, the disulphide is double sulphur things of di-n-butylamine base two；When the amine derivative is N- isopropyls-Beta-alanine second
During ester, the disulphide is double N- isopropyls-sulphur things of Beta-alanine ethoxycarbonyl two.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (3), second acid binding agent is three
Ethamine, the detailed process of the condensation reaction is：By carbofuran add chlorination reaction after solution in, 5 DEG C~10 DEG C, continue
Under stirring condition, then triethylamine is added dropwise, 4h~6h is stirred at 10 DEG C~30 DEG C after completion of dropping.
The preparation method of above-mentioned carbofuran derivative, it is preferred that in the step (3), when the disulphide is double
During two sulphur thing of di-n-butylamine base, the nitrogen sulphur chloride is di-n-butylamine base sulfur chloride；When the disulphide is double N- isopropyls
During base-two sulphur thing of Beta-alanine ethoxycarbonyl, the nitrogen sulphur chloride is N- isopropyls-N- sulfur chlorides-Beta-alanine ethyl ester.
The carbofuran derivative is preferably carbosulfan or Benfuracard micro.
The present invention with amine derivative as raw material, with triethylamine as acid binding agent, with chloroform or dichloromethane as reaction dissolvent with
There is vulcanization reaction and synthesize the first intermediate disulphide in sulfur monochloride, disulphide occurs again chlorination reaction synthesis the with chlorine
Two intermediate nitrogen sulphur chlorides, finally in the presence of acid binding agent there is condensation reaction in nitrogen sulphur chloride and carbofuran, and condensation is anti-
Cosolvent is not needed during answering, you can obtain content >=96%, the carbofuran low toxicity derivative of yield >=98%.
Specifically, amine derivative is di-n-butylamine or N- isopropyls-Beta-alanine ethyl ester, when amine derivative is di-n-butylamine
When, disulphide is double sulphur things of di-n-butylamine base two, and nitrogen sulphur chloride is di-n-butylamine base sulfur chloride, and the product of gained is fourth sulphur
Carbofuran；When amine derivative is N- isopropyls-Beta-alanine ethyl ester, disulphide is double N- isopropyls-Beta-alanine ethoxycarbonyies
Two sulphur things, nitrogen sulphur chloride is N- isopropyls-N- sulfur chlorides-Beta-alanine ethyl ester, and the product of gained is Benfuracard micro.Chemistry
Reaction equation is as follows：
Work as R1For CH (CH3)2When, R2For CH2CH2COOC2H5, the product of gained is Benfuracard micro；Work as R1For C4H9When, R2
For C4H9, the product of gained is carbosulfan.
Compared with prior art, it is an advantage of the current invention that：
1st, the preparation method of carbofuran derivative of the invention, is synthesized in the middle of first in amine derivative and sulfur monochloride
Body disulphide and the second intermediate nitrogen sulphur chloride and carbofuran occur all produce hydrochloric acid and triethylamine shape during condensation reaction
Into triethylamine hydrochloride, and solubility of the triethylamine hydrochloride in Conventional solvents is very poor that whole reaction mass can be caused to become viscous
It is thick to be difficult to fully agitation and cause reaction incomplete, especially in the condensation reaction because being that (carbofuran is solid to solid-liquid two phase reaction
Add) cause carbofuran to be wrapped up by triethylamine hydrochloride, it is impossible to and fully (di-n-butylamine base sulfur chloride or N- are different with the second intermediate
Propyl group-N- sulfur chlorides-Beta-alanine ethyl ester) reaction, cause carbofuran derivative content and yield obtained by reacting it is not high, grams hundred
Prestige residual is higher to cause final products toxicity higher.And this patent vulcanization reaction and condensation reaction are all using chloroform or dichloromethane
For reaction dissolvent, triethylamine hydrochloride has good solubility in chloroform or dichloromethane compare other organic solvents, it is to avoid
Amine derivative and sulfur monochloride reaction cause reaction incomplete because reaction mass is sticky, and carbofuran quilt during condensation reaction
Triethylamine hydrochloride parcel can not fully participate in the shortcoming of condensation reaction, it is to avoid (cosolvent adds inevitable for the addition of cosolvent
Bring cosolvent to be difficult to recycle and lose, the trouble for post-processing and the difficulty for increasing wastewater treatment).Fourth obtained by the present invention
Product content >=96% of the carbofuran low toxicity derivative such as Carbosulfan, Benfuracard micro, product yield >=98%, carbofuran<
0.1%, toxicity is low, and popularizing application prospect is wide, with larger practical value and economic results in society.
2nd, the preparation method of carbofuran derivative of the invention, further, has been carried out excellent to the parameter in preparation process
Change, amine derivative: sulfur monochloride: triethylamine: chlorine: carbofuran: the molar feed ratio of triethylamine is defined to 1.0: 0.5~0.55
: 1.0~1.1: 0.5~0.55: 0.93~0.95: 2~2.2, in vulcanization reaction, reaction dissolvent volumetric usage is defined to raw material two
10~20 times of n-butylamine or N- isopropyls-Beta-alanine ethyl ester volume, in chlorination reaction, reaction temperature is limited to 0~30 DEG C,
2~3 hours reaction time.After completion of the reaction washing, pickling, wash as again reduced pressure concentration obtains brown-red oil after neutrality.With
High performance liquid chromatography quantitative analysis, yield >=98% (in terms of carbofuran).Because carbofuran derivative is the oil of heat endurance difference
Shape thing is difficult to follow-up purification operations, and the optimization that the present invention passes through above parameter is generated in course of reaction without byproduct, from
And improve the present invention yield and content, while remain carbofuran amount also minimize.
Specific embodiment
Below in conjunction with concrete preferred embodiment, the invention will be further described, but not thereby limiting the invention
Protection domain.
Embodiment 1：
Benfuracard micro, chemical name N- [2,3- dihydro -2,2- dimethyl benzofuran -7- base oxygen carbonyl (methyl) ammonia
Sulfenyl]-N- isopropyls-Beta-alanine ethyl ester preparation
79.5g (0.5mol, 83mL) N- isopropyls-Beta-alanine ethyl ester is added in the 2L reaction bulbs with stirring,
0.9L dichloromethane and 50.5g (0.5mol) triethylamine, are cooled to 5 DEG C.33.7g (0.25mol) chlorine is added dropwise under agitation
Change sulphur, vulcanization reaction is carried out at 5 DEG C after 1 hour drop finishes, react 1.5 hours.After completion of the reaction washing, pickling, be washed to
Dichloromethane layer (the double N- isopropyls-sulphur things of Beta-alanine ethoxycarbonyl two of the first intermediate vulcanization reaction product are isolated after neutrality
In being dissolved in methylene chloride).Then dichloromethane layer is cooled into 5 DEG C, stirs in lower 1 hour and be passed through 17.8g (0.25mol)
Chlorine, be passed through after finishing carries out chlorination reaction at 20 DEG C, reacts 2 hours, adds 105g (0.465mol) carbofuran, cools down
To 5 DEG C, stirring is lower to be added dropwise 101g (1mol) triethylamine, and drop finishes carries out condensation reaction at 20 DEG C, stirs 4 hours, has reacted
After finishing successively washing, pickling, be washed to after neutrality and isolate reduced pressure concentration after dichloromethane layer and obtain brown-red oil 194.7g,
Jing high performance liquid chromatography quantitative analyses, content is 96.2%, and yield is 98.1% (in terms of carbofuran).
Embodiment 2
Benfuracard micro, chemical name N- [2,3- dihydro -2,2- dimethyl benzofuran -7- base oxygen carbonyl (methyl) ammonia
Sulfenyl]-N- isopropyls-Beta-alanine ethyl ester preparation
79.5g (0.5mol, 83mL) N- isopropyls-Beta-alanine ethyl ester is added in the 2L reaction bulbs with stirring,
1.25L dichloromethane and 50.5g (0.5mol) triethylamine, are cooled to 5 DEG C.33.7g (0.25mol) chlorine is added dropwise under agitation
Change sulphur, vulcanization reaction is carried out at 5 DEG C after 1 hour drop finishes, react 1.5 hours.After completion of the reaction washing, pickling, be washed to
Dichloromethane layer is isolated after neutrality.Then dichloromethane layer is cooled into 5 DEG C, stirs in lower 1 hour and be passed through 17.8g
(0.25mol) chlorine, be passed through after finishing carries out chlorination reaction at 20 DEG C, reacts 2 hours, adds 105g (0.465mol) gram
Budweiser, is cooled to 5 DEG C, and stirring is lower to be added dropwise 101g (1mol) triethylamine, and drop finishes carries out condensation reaction at 20 DEG C, and stirring 4 is little
When, after completion of the reaction successively washing, pickling, be washed to after neutrality and isolate reduced pressure concentration after dichloromethane layer and obtain bronzing oily
Thing 194.7g, Jing high performance liquid chromatography quantitative analysis, content is 96.3%, and yield is 98.2% (in terms of carbofuran).
Embodiment 3
Benfuracard micro, chemical name N- [2,3- dihydro -2,2- dimethyl benzofuran -7- base oxygen carbonyl (methyl) ammonia
Sulfenyl]-N- isopropyls-Beta-alanine ethyl ester preparation
79.5g (0.5mol, 83mL) N- isopropyls-Beta-alanine ethyl ester is added in the 2L reaction bulbs with stirring,
0.9L chloroforms and 50.5g (0.5mol) triethylamine, are cooled to 5 DEG C.33.7g (0.25mol) sulfur monochloride is added dropwise under agitation,
Vulcanization reaction is carried out at 5 DEG C after 1 hour drop finishes, is reacted 1.5 hours.After completion of the reaction washing, pickling, be washed to after neutrality
Isolate chloroform layer.Then chloroform layer is cooled into 5 DEG C, stirs in lower 1 hour and be passed through 17.8g (0.25mol) chlorine, be passed through
Chlorination reaction is carried out after finishing at 20 DEG C, is reacted 2 hours, add 105g (0.465mol) carbofuran, be cooled to 5 DEG C, stirring
Lower dropwise addition 101g (1mol) triethylamine, drop finishes carries out condensation reaction at 20 DEG C, stirs 4 hours, after completion of the reaction water successively
Wash, pickling, be washed to after neutrality and isolate reduced pressure concentration after chloroform layer and obtain brown-red oil 194.7g, Jing high performance liquid chromatography
Quantitative analysis, content is 96.5%, and yield is 98.4% (in terms of carbofuran).
Embodiment 4
Benfuracard micro, chemical name N- [2,3- dihydro -2,2- dimethyl benzofuran -7- base oxygen carbonyl (methyl) ammonia
Sulfenyl]-N- isopropyls-Beta-alanine ethyl ester preparation
79.5g (0.5mol, 83mL) N- isopropyls-Beta-alanine ethyl ester is added in the 2L reaction bulbs with stirring,
1.25L chloroforms and 50.5g (0.5mol) triethylamine, are cooled to 5 DEG C.33.7g (0.25mol) monochlor(in)ate is added dropwise under agitation
Sulphur, after 1 hour drop finishes vulcanization reaction is carried out at 5 DEG C, is reacted 1.5 hours.After completion of the reaction washing, pickling, be washed to
Chloroform layer is isolated after property.Then chloroform layer is cooled into 5 DEG C, stirs in lower 1 hour and be passed through 17.8g (0.25mol) chlorine, led to
Enter and carry out chlorination reaction at 20 DEG C after finishing, react 2 hours, add 105g (0.465mol) carbofuran, be cooled to 5 DEG C,
Stirring is lower to be added dropwise 101g (1mol) triethylamine, and drop finishes carries out condensation reaction at 20 DEG C, stirs 4 hours, after completion of the reaction according to
Secondary washing, pickling, it is washed to after neutrality and isolates reduced pressure concentration after chloroform layer and obtain brown-red oil 194.7g, Jing efficient liquid phases
Chromatographic quantitative analysis, content is 96.6%, and yield is 98.5% (in terms of carbofuran).
Embodiment 5
Carbosulfan, chemical name 2,3- dihydro -2,2- dimethyl benzofuran -7- bases (dibutylamine sulfidomethyl ammonia
Base) formic acid esters preparation
With stirring 2L reaction bulbs in add 64.5g (0.5mol, 84mL) di-n-butylamine, 0.9L dichloromethane and
50.5g (0.5mol) triethylamine, is cooled to 5 DEG C.33.8g (0.25mol) sulfur monochloride is added dropwise under agitation, is finished in 1 hour drop
Carry out vulcanization reaction at 5 DEG C afterwards, react 1 hour.After completion of the reaction washing, pickling, be washed to after neutrality and isolate dichloromethane
Alkane layer (the double sulphur things of di-n-butylamine base two of the first intermediate vulcanization reaction product are dissolved in methylene chloride).Then by dichloromethane
Alkane layer is cooled under 5 DEG C, stirring and is passed through 17.8g (0.25mol) chlorine, and be passed through after finishing carries out chlorination reaction at 20 DEG C, instead
Answer 2 hours.105g (0.465mol) carbofuran is added, 5 DEG C are cooled to, stirring is lower to be added dropwise 101g (1mol) triethylamine, and drop finishes
Carry out condensation reaction at 20 DEG C, stir 4 hours, after completion of the reaction successively washing, pickling, be washed to after neutrality and isolate two
Chloromethanes layer, reduced pressure concentration obtains brown-red oil 180.5g, Jing high performance liquid chromatography quantitative analyses, and purity is 96.1%, receives
Rate is 98.0% (in terms of carbofuran).
Embodiment 6
Carbosulfan, chemical name 2,3- dihydro -2,2- dimethyl benzofuran -7- bases (dibutylamine sulfidomethyl ammonia
Base) formic acid esters preparation
With stirring 2L reaction bulbs in add 64.5g (0.5mol, 84mL) di-n-butylamine, 1.25L dichloromethane with
And 50.5g (0.5mol) triethylamine, it is cooled to 5 DEG C.33.8g (0.25mol) sulfur monochloride is added dropwise under agitation, is dripped at 1 hour
Vulcanization reaction is carried out after finishing at 5 DEG C, is reacted 1 hour.After completion of the reaction washing, pickling, be washed to after neutrality and isolate dichloro
Methane layer.Then dichloromethane layer is cooled under 5 DEG C, stirring and is passed through 17.8g (0.25mol) chlorine, be passed through after finishing 20
Chlorination reaction is carried out at DEG C, is reacted 2 hours, add 105g (0.465mol) carbofuran, be cooled to 5 DEG C, stirring is lower to be added dropwise
101g (1mol) triethylamine, drop finishes carries out condensation reaction at 20 DEG C, stirs 5 hours, washing, acid successively after completion of the reaction
Wash, be washed to after neutrality and isolate dichloromethane layer, reduced pressure concentration obtains brown-red oil 180.5g, Jing high performance liquid chromatography
Quantitative analysis, purity is 96.3%, and yield is 98.2% (in terms of carbofuran).
Embodiment 7
Carbosulfan, chemical name 2,3- dihydro -2,2- dimethyl benzofuran -7- bases (dibutylamine sulfidomethyl ammonia
Base) formic acid esters preparation
With stirring 2L reaction bulbs in add 64.5g (0.5mol, 84mL) di-n-butylamine, 0.9L chloroforms and
50.5g (0.5mol) triethylamine, is cooled to 5 DEG C.33.8g (0.25mol) sulfur monochloride is added dropwise under agitation, is finished in 1 hour drop
Carry out vulcanization reaction at 5 DEG C afterwards, react 1 hour.After completion of the reaction washing, pickling, be washed to after neutrality and isolate chloroform layer.
Then chloroform layer is cooled under 5 DEG C, stirring and is passed through 17.8g (0.25mol) chlorine, be passed through after finishing carries out chlorination at 20 DEG C
Reaction, reacts 2 hours, adds 105g (0.465mol) carbofuran, is cooled to 5 DEG C, and stirring is lower to be added dropwise 101g (1mol) three second
Amine, drop finishes carries out condensation reaction at 20 DEG C, stirs 6 hours, after completion of the reaction successively washing, pickling, be washed to after neutrality
Chloroform layer is isolated, reduced pressure concentration obtains brown-red oil 180.6g, Jing high performance liquid chromatography quantitative analyses, and purity is
96.4%, yield is 98.4% (in terms of carbofuran).
Embodiment 8
Carbosulfan, chemical name 2,3- dihydro -2,2- dimethyl benzofuran -7- bases (dibutylamine sulfidomethyl ammonia
Base) formic acid esters preparation
With stirring 2L reaction bulbs in add 64.5g (0.5mol, 84mL) di-n-butylamine, 1.25L chloroforms and
50.5g (0.5mol) triethylamine, is cooled to 5 DEG C.33.8g (0.25mol) sulfur monochloride is added dropwise under agitation, is finished in 1 hour drop
Carry out vulcanization reaction at 5 DEG C afterwards, react 1 hour.After completion of the reaction washing, pickling, be washed to after neutrality and isolate chloroform layer.
Then chloroform layer is cooled under 5 DEG C, stirring and is passed through 17.8g (0.25mol) chlorine, be passed through after finishing carries out chlorination at 20 DEG C
Reaction, reacts 2 hours, adds 105g (0.465mol) carbofuran, is cooled to 5 DEG C, and stirring is lower to be added dropwise 101g (1mol) three second
Amine, drop finishes carries out condensation reaction at 20 DEG C, stirs 6 hours, after completion of the reaction successively washing, pickling, be washed to after neutrality
Chloroform layer is isolated, reduced pressure concentration obtains brown-red oil 180.7g, Jing high performance liquid chromatography quantitative analyses, and purity is
96.5%, yield is 98.5% (in terms of carbofuran).
The above is only the preferred embodiment of the present invention, and protection scope of the present invention is not limited merely to above-mentioned enforcement
Example.All technical schemes belonged under thinking of the present invention belong to protection scope of the present invention.It is noted that for the art
Those of ordinary skill for, improvements and modifications under the premise without departing from the principles of the invention, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of carbofuran derivative, comprises the following steps：
(1) with amine derivative and sulfur monochloride as raw material, the first acid binding agent and reaction dissolvent are added, carries out vulcanization reaction, obtained
Disulphide；First acid binding agent is triethylamine；The reaction dissolvent is chloroform or dichloromethane；
(2) chlorination reaction is carried out as raw material with disulphide and chlorine, obtains nitrogen sulphur chloride；
(3) with nitrogen sulphur chloride and carbofuran as raw material, the second acid binding agent is added, carries out condensation reaction, obtained carbofuran and derive
Thing.
2. the preparation method of carbofuran derivative according to claim 1, it is characterised in that the amine derivative, a chlorine
Change sulphur, the first acid binding agent, chlorine, the mol ratio of carbofuran and the second acid binding agent be 1.0: 0.5~0.55: 1.0~1.1: 0.5~
0.55: 0.93~0.95: 2~2.2.
3. the preparation method of carbofuran derivative according to claim 1 and 2, it is characterised in that in the step (1),
The amine derivative is di-n-butylamine or N- isopropyls-Beta-alanine ethyl ester.
4. the preparation method of carbofuran derivative according to claim 3, it is characterised in that described in the step (1)
Reaction dissolvent is 10~20: 1 with the volume ratio of amine derivative.
5. the preparation method of carbofuran derivative according to claim 4, it is characterised in that described in the step (1)
Reaction dissolvent is 15: 1 with the volume ratio of amine derivative.
6. the preparation method of carbofuran derivative according to claim 5, it is characterised in that described in the step (1)
Vulcanization reaction temperature is 0 DEG C~10 DEG C, and the reaction time is 1.5h~2h.
7. the preparation method of carbofuran derivative according to claim 3, it is characterised in that described in the step (2)
The detailed process of chlorination reaction is：Under 5 DEG C~10 DEG C, lasting stirring condition, chlorine is passed through in the solution after vulcanization reaction,
Chlorine is passed through the time for 1h~1.5h；Chlorine is passed through after finishing reaction 2h~3h at 0 DEG C~30 DEG C.
8. the preparation method of carbofuran derivative according to claim 7, it is characterised in that in the step (2), work as institute
State amine derivative for di-n-butylamine when, the disulphide is double sulphur things of di-n-butylamine base two；When the amine derivative is that N- is different
During propyl group-Beta-alanine ethyl ester, the disulphide is double N- isopropyls-sulphur things of Beta-alanine ethoxycarbonyl two.
9. the preparation method of carbofuran derivative according to claim 3, it is characterised in that described in the step (3)
Second acid binding agent is triethylamine, and the detailed process of the condensation reaction is：Carbofuran is added in the solution after chlorination reaction,
5 DEG C~10 DEG C, continue under stirring condition, then triethylamine to be added dropwise, stir 4h~6h at 10 DEG C~30 DEG C after completion of dropping.
10. the preparation method of carbofuran derivative according to claim 9, it is characterised in that in the step (3), when
When the disulphide is double di-n-butylamine two sulphur things of base, the nitrogen sulphur chloride is di-n-butylamine base sulfur chloride；When described two
Sulfide for double N- isopropyls-two sulphur thing of Beta-alanine ethoxycarbonyl when, the nitrogen sulphur chloride be N- isopropyl-N- sulfur chlorides-
Beta-alanine ethyl ester.
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|---|---|---|---|---|
| CN111138330A (en) * | 2019-12-25 | 2020-05-12 | 湖南海利常德农药化工有限公司 | Synthesis method of bis-di-n-butylamine disulfide |
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| CN111138330A (en) * | 2019-12-25 | 2020-05-12 | 湖南海利常德农药化工有限公司 | Synthesis method of bis-di-n-butylamine disulfide |
| CN111138330B (en) * | 2019-12-25 | 2021-12-17 | 湖南海利常德农药化工有限公司 | Synthesis method of bis-di-n-butylamine disulfide |
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