CN105085564B - A kind of synthetic method of pesticide Silthiopham - Google Patents
A kind of synthetic method of pesticide Silthiopham Download PDFInfo
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- CN105085564B CN105085564B CN201510305410.1A CN201510305410A CN105085564B CN 105085564 B CN105085564 B CN 105085564B CN 201510305410 A CN201510305410 A CN 201510305410A CN 105085564 B CN105085564 B CN 105085564B
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- silthiopham
- silicon substrate
- pesticide
- synthetic method
- trimethyl
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- MXMXHPPIGKYTAR-UHFFFAOYSA-N silthiofam Chemical compound CC=1SC([Si](C)(C)C)=C(C(=O)NCC=C)C=1C MXMXHPPIGKYTAR-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 239000000575 pesticide Substances 0.000 title claims abstract description 31
- 238000010189 synthetic method Methods 0.000 title claims abstract description 18
- 239000000758 substrate Substances 0.000 claims abstract description 48
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 46
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims abstract description 36
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 claims abstract description 24
- 229930192474 thiophene Natural products 0.000 claims abstract description 23
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims abstract description 22
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- XLMPYCGSRHSSSX-UHFFFAOYSA-N 3-Mercapto-2-butanone Chemical compound CC(S)C(C)=O XLMPYCGSRHSSSX-UHFFFAOYSA-N 0.000 claims abstract description 11
- KDKYADYSIPSCCQ-UHFFFAOYSA-N ethyl acetylene Natural products CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000007530 organic bases Chemical class 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 8
- 239000011261 inert gas Substances 0.000 claims abstract description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 26
- 239000002904 solvent Substances 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 8
- -1 methylchloroformate Silicon Chemical compound 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims description 5
- 235000019270 ammonium chloride Nutrition 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- BGGIUGXMWNKMCP-UHFFFAOYSA-N 2-methylpropan-2-olate;zirconium(4+) Chemical class CC(C)(C)O[Zr](OC(C)(C)C)(OC(C)(C)C)OC(C)(C)C BGGIUGXMWNKMCP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 238000005815 base catalysis Methods 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- AGTGOYRPAHLNOS-UHFFFAOYSA-N ethynyl(methyl)silane Chemical group C[SiH2]C#C AGTGOYRPAHLNOS-UHFFFAOYSA-N 0.000 claims 1
- RLJWTAURUFQFJP-UHFFFAOYSA-N propan-2-ol;titanium Chemical compound [Ti].CC(C)O.CC(C)O.CC(C)O.CC(C)O RLJWTAURUFQFJP-UHFFFAOYSA-N 0.000 claims 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N tetraisopropyl titanate Substances CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 abstract description 8
- 239000012467 final product Substances 0.000 abstract description 7
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 238000003912 environmental pollution Methods 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000011084 recovery Methods 0.000 abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- 239000010703 silicon Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical group CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241001508365 Gaeumannomyces tritici Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- BBBXUTIHNYHDOR-UHFFFAOYSA-N [Cl-].[NH4+].[Si] Chemical compound [Cl-].[NH4+].[Si] BBBXUTIHNYHDOR-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- KXRSDCFOWWZZPE-UHFFFAOYSA-N silicon;thiophene Chemical compound [Si].C=1C=CSC=1 KXRSDCFOWWZZPE-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical group C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 229940094989 trimethylsilane Drugs 0.000 description 1
Abstract
The invention belongs to technical field of organic synthesis; to solve the problems, such as that there are exchange reaction yield is low in current pesticide Silthiopham synthesis technology; the present invention provides a kind of synthetic method of pesticide Silthiopham; (1) under inert gas protection; using trimethyl silicane ethyl-acetylene as raw material, react to obtain trimethyl silicon substrate Methyl propiolate with methylchloroformate under organic base effect;(2) trimethyl silicon substrate Methyl propiolate reacts to obtain 4,5- dimethyl -2-(trimethyl silicon substrate with 3- sulfydryl -2- butanone under base catalyst effect) thiophene -3- methyl formate;(3) 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate reacts to obtain final product pesticide Silthiopham under the action of catalyst with allyl amine.Raw material used in this method is cheap and easy to get, and route is succinct, and total recovery is higher, and avoid using alpha..alpha.-dimethylethyl nitrite (t- BuONO) with the serious reagent of environmental pollutions such as thionyl chloride.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of pesticide Silthiopham efficiently synthesizes technique.
Background technique
Take-all (Gaeumammomyces gramini) is one of serious plant disease of wheat, Silthiopham
(Silthiopham) the having to the microbial take-all of wheat total eclipse in official listing in 1999 that be Monsanto Chemicals
The seed treatment of special efficacy.But the Silthiopham synthetic method being currently known, there is reaction step more and is related to a variety of severe toxicity
The use of object and the serious reagent of environmental pollution, it is at high cost the disadvantages of.Hence it is imperative that developing a kind of high efficiency, low cost
Silthiopham synthetic method.
United States Patent (USP) US 5,486,621 reports Silthiopham N- allyl -4,5- dimethyl -2-(trimethyl for the first time
Silicon substrate) thiophene -3- formamide it is fully synthetic, they obtain 2- ammonia using 2- butanone, cyan-acetic ester and sulphur single step reaction
Then base thiophene reacts to obtain Silthiopham using several steps, this method total recovery is relatively low (about 2%), and further relates to height
Toxic agent alpha..alpha.-dimethylethyl nitrite (t- BuONO) and thionyl chloride use, great pressure is caused to environment and health.
Afterwards by continuing to optimize and improving (WO 9962915), it is using 3- sulfydryl -2- butanone and trimethyl silane substitution propine amide
One step of raw material (containing simple dehydration) obtains final product, and yield is higher, but key intermediate trimethyl silicon substrate alkynes
Amide is difficult to be synthetically prepared in high yield.The journey of nearest Henan agricultural university unravels silk south et al. and reports (CN 103044479A) one kind newly
The synthetic method of the Silthiopham of type, they have obtained 3-(trimethyl from Methyl propiolate and trim,ethylchlorosilane synthesis
Silicon substrate) Methyl propiolate, then cyclization dehydration is carried out with 3- sulfydryl -2- butanone, it finally swaps and reacts with allyl amine
Final product Silthiopham is obtained.This method relative to having reported that process route is simple, and avoid high toxicity reagent (t-
BuONO use), but some fatal defects still have, such as final step 4,5- dimethyl -2-(trimethyl silicane
Base) thiophene -3- methyl formate and allyl amine exchange reaction yield it is extremely low, even if in the reflux condition that pure allyl amine is solvent
20 hours yields are reacted under part also 10% hereinafter, therefore there is an urgent need to develop a kind of synthesis technology of green high-efficient.
Summary of the invention
To solve the problems, such as in current pesticide Silthiopham synthesis technology that there are exchange reaction yield is low, the present invention provides one
The synthetic method of pesticide Silthiopham is planted, raw material used in this method is cheap and easy to get, and route is succinct, and total recovery is higher, and
Avoid using alpha..alpha.-dimethylethyl nitrite (t- BuONO) with the serious reagent of environmental pollutions such as thionyl chloride.
What the invention is realized by the following technical scheme: a kind of synthetic method of pesticide Silthiopham is following steps:
(1) under inert gas protection, using trimethyl silicane ethyl-acetylene as raw material, organic base effect under with methylchloroformate
Reaction obtains trimethyl silicon substrate Methyl propiolate;
The organic base is a kind of in metal alkyl lithiumation object, amido lithiumation object, organic base and trimethyl silicon substrate second
The molar ratio of alkynes is 1.0 ~ 1.5:1.Preferably, metal alkyl lithiumation object is selected from butyl lithium, lithium methide, phenyl lithium, tert-butyl
It is a kind of in lithium, lithium diisopropyl amido.More preferably butyl lithium.
Chloro-carbonic acid esters and the molar ratio of trimethyl silicane ethyl-acetylene are 1.1 ~ 1.5:1.Preferably, chloro-carbonic acid esters are selected from
Methylchloroformate, it is a kind of in ethyl chloroformate.
Preferably, the effect in tetrahydrofuran (THF) with organic base at -50 ~ -78 DEG C of trimethyl silicane ethyl-acetylene,
It is warmed to room temperature again and with ether extraction, dry and column chromatographic purifying obtains trimethyl after being quenched with chloro-carbonic acid ester reaction, ammonium chloride
Silicon substrate Methyl propiolate.
(2) trimethyl silicon substrate Methyl propiolate reacts to obtain 4,5- bis- with 3- sulfydryl -2- butanone under base catalyst effect
Methyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate;
The base catalyst is selected from the carbonate of alkali metal, alkali alcoholate, one of organic amine compound
Or it is several, base catalyst and trimethyl silicon substrate Methyl propiolate mole are 0.1 ~ 1.5:1.It is preferred that base catalyst is sodium methoxide,
Sodium ethoxide, sodium carbonate, it is a kind of in potassium carbonate.
Preferably, the molar ratio of 3- sulfydryl -2- butanone and trimethyl silicon substrate Methyl propiolate is 1.0 ~ 5.0:1.
Preferably, under inert gas protection by trimethyl silicon substrate Methyl propiolate and 3- sulfydryl -2- butanone, base catalysis
Under agent effect, back flow reaction 5 ~ for 24 hours, is down to room temperature in a solvent, washes, dry simultaneously to obtain 4,5- diformazan through column chromatographic purifying
Base -2-(trimethyl silicon substrate) thiophene -3- methyl formate.
(3) 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate under the action of catalyst with allyl amine
Reaction obtains final product pesticide Silthiopham.
The catalyst is selected from tri- azabicyclic of 1,5,7- [4.4.0] decyl- 5- alkene, four zirconium tert-butoxides, four isopropyl of metatitanic acid
Ester, aluminum isopropylate, indium bromide and zinc chloride, catalyst and 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- formic acid first
The molar ratio of ester is 0.1 ~ 1:1, preferred catalyst 1,5, tri- azabicyclic of 7- [4.4.0] decyl- 5- alkene (TBD).
4,5- dimethyl -2-(trimethyl the silicon substrate) molar ratio of thiophene -3- methyl formate and allyl amine is 1:1
~10。
Preferably, under inert gas protection, by 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate
Under the action of catalyst with allyl amine, heating reflux reaction is down to room temperature in solvent-free or solvent after 12 ~ 72 hours, decompression
Solvent and extra allyl amine are boiled off, residue, which is added n-hexane and is heated to reflux rear low temperature crystallization, obtains pesticide silicon thiophene bacterium
Amine.Preferred reaction time is 12~48h.
Solvent described in above-mentioned steps is selected from toluene, halogenated hydrocarbons, aromatic hydrocarbon, and alcohols is a kind of in polar non-solute
Or it is several, step (2) preferred solvent is diethoxymethane, and the preferred solvent of step (3) is toluene.
Above-mentioned room temperature is 23 DEG C ± 3 DEG C.Inert gas is preferably nitrogen, argon gas.
The present invention i.e. from cheap raw material trimethyl silicane ethyl-acetylene, byn-BuLi acts on lower and methylchloroformate
Reaction is converted into trimethyl silicon substrate Methyl propiolate, then carries out ring closure reaction with 3- sulfydryl -2- butanone and obtains 4,5- dimethyl -
2-(trimethyl silicon substrate) thiophene -3- methyl formate, finally reacts with allyl amine under the activation of catalyst and is converted into finished product
Pesticide Silthiopham.Reaction equation is as follows:
Compared with prior art, the beneficial effects of the present invention are: raw material used in this method is cheap and easy to get, route letter
Clean, yield is higher, and avoid using alpha..alpha.-dimethylethyl nitrite (t- BuONO) with the serious examination of environmental pollutions such as thionyl chloride
Agent is suitble to large-scale production.
Detailed description of the invention
Fig. 1 is 1 gained pesticide Silthiopham of embodiment1H NMR spectra;
Fig. 2 is 1 gained pesticide Silthiopham of embodiment13C NMR spectra.
Specific embodiment
Below by embodiment, invention is further described in detail.
Embodiment 1
(1) preparation of trimethyl silicon substrate Methyl propiolate:
Under nitrogen protection, trimethyl silicane ethyl-acetylene (5.6 mL, 40.0 mmol) are added in dry THF, be cooled to-
78 DEG C, n-BuLi (27.6 mL, 44.0 mmol) are slowly added into system, and stirring 30 minutes at this temperature, so
After be warmed to room temperature, and methylchloroformate (3.4 mL, 44.0 mmol) are added, are followed by stirring for reaction 2.5 hours.Reaction is mixed
It closes object and pours into ammonium chloride solution to quench the reaction, and ether extraction is added, organic phase water and brine It and with anhydrous sulphur
Sour sodium is dry.It is removed in vacuum solvent, gained crude product obtains yellow oil product three with column chromatographic purifying (5% EtOAc/PE)
Methylsilyl Methyl propiolate 5.9 g (yield: 95.0%).
(2) 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate preparation:
Under nitrogen protection, by trimethyl silicon substrate Methyl propiolate (3 g, 19.2mmol) and 3- sulfydryl -2- butanone (2.4
G, 23.0 mol) it is added in dry toluene, sodium methoxide (1.0 g, 19.2 mmol) then are added, reaction system heats back
Reaction system is down to room temperature by stream reaction 10 hours, distillation water washing is added, and (2 × 20 ml) is extracted with ethyl acetate, has
Machine is mutually dry with anhydrous sodium sulfate, solvent is removed in vacuum, gained crude product column chromatographic purifying obtains yellow oil product 4,5-
Dimethyl -2-(trimethyl silicon substrate) 4.1 g (yield: 88.3%) of thiophene -3- methyl formate.
(3) preparation of final product pesticide Silthiopham:
Under nitrogen protection, 4,5- dimethyl -2-(trimethyl silicon substrate is added into reaction flask) thiophene -3- methyl formate (1.0
G, 4.1 mmol) and allyl amine (1.2 g, 20.5 mmol), add tri- azabicyclic of 1,5,7- of catalyst
[4.4.0] decyl- 5- alkene (TBD, 0.17 g, 1.2 mmol), reaction mixture is heated to reflux after 48h and is down to room temperature, vacuum
Extra allyl amine is pumped, residue is added n-hexane and is heated to reflux 2h, and reaction system is cooling, and yellow solid, mistake is precipitated
0.68 g (yield: 62.3%) of yellow powder pesticide Silthiopham is dried to obtain after filter.
1H-NMR (CDCl3, 400MHz), δ =5.89-5.94 (m, 1H), 5.68 (br, s, 1H), 5.27
(d, J= 16.8 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 4.06 (t, J= 5.6 Hz, 2H), 2.34
(s, 3H). 2.16 (s, 3H), 0.31 (s, 9H). 13C-NMR (CDCl3, 100MHz), δ =167.0, 144.7,
138.5, 134.6, 133.0, 132.3, 116.4, 41.6, 12.5, 11.9, -0.6。
Gained pesticide Silthiopham1H NMR spectra as shown in Figure 1,13C NMR spectra is as shown in Figure 2.
Embodiment 2
(1) preparation of trimethyl silicon substrate Methyl propiolate:
Under nitrogen protection, trimethyl silicane ethyl-acetylene (5.6 mL, 40.0 mmol) are added in dry tetrahydrofuran,
It is cooled to -50 DEG C, lithium methide (37.6 mL, 60.0 mmol) is slowly added into system, and stirs 30 minutes at this temperature,
Then it is warmed to room temperature, and methylchloroformate (4.0 mL, 52.0 mmol) is added, be followed by stirring for reaction 2.5 hours.It will reaction
Mixture pours into ammonium chloride solution to quench the reaction, and ether extraction is added, organic phase water and brine It and with anhydrous
Sodium sulphate is dry.It is removed in vacuum solvent, gained crude product obtains yellow oil product with column chromatographic purifying (5% EtOAc/PE)
5.8 g (yield: 93.0%) of trimethyl silicon substrate Methyl propiolate.
(2) 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate preparation:
Under nitrogen protection, by trimethyl silicon substrate Methyl propiolate (3 g, 19.2mmol) and 3- sulfydryl -2- butanone (2.4
G, 23.0 mol) it is added in dry diethoxymethane, sodium methoxide (1.0 g, 19.2 mmol) then are added, reactant
It is heating reflux reaction 24 hours, reaction system is down to room temperature, distillation water washing is added, and be extracted with ethyl acetate (2 × 20
Ml), organic phase is dry with anhydrous sodium sulfate, solvent is removed in vacuum, gained crude product column chromatographic purifying obtains yellow oily
Product 4,5- dimethyl -2-(trimethyl silicon substrate) 4.0 g (yield: 86.0%) of thiophene -3- methyl formate.
(3) preparation of final product pesticide Silthiopham:
Under nitrogen protection, 4,5- dimethyl -2-(trimethyl silicon substrate is added into reaction flask) thiophene -3- methyl formate (1.0
G, 4.1 mmol), 15 mL toluene and allyl amine (0.24 g, 4.1 mmol) add the 1 of catalyst, 5,7- tri- nitrogen
Miscellaneous two ring [4.4.0] decyl- 5- alkene (TBD, 0.17 g, 1.2 mmol) cools down after reaction mixture is heated to reflux 48h, vacuum
It pumps solvent (toluene and extra allyl amine), residue is added n-hexane and is heated to reflux 2h, and reaction system is cooling, analysis
Yellow solid out is dried to obtain 0.55 g (yield: 50.4%) of yellow powder pesticide Silthiopham after filtering.
1H-NMR (CDCl3, 400MHz), δ =5.89-5.94 (m, 1H), 5.68 (br, s, 1H), 5.27
(d, J= 16.8 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 4.06 (t, J= 5.6 Hz, 2H), 2.34
(s, 3H). 2.16 (s, 3H), 0.31 (s, 9H). 13C-NMR (CDCl3, 100MHz), δ =167.0, 144.7,
138.5, 134.6, 133.0, 132.3, 116.4, 41.6, 12.5, 11.9, -0.6。
Embodiment 3
(1) preparation of trimethyl silicon substrate Methyl propiolate:
Under nitrogen protection, trimethyl silicane ethyl-acetylene (5.6 mL, 40.0 mmol) are added in dry THF, be cooled to-
60 DEG C, phenyl lithium (26.7 mL, 40.0 mmol) are slowly added into system, and stirring 30 minutes at this temperature, then
It is warmed to room temperature, and methylchloroformate (4.7 mL, 60.0 mmol) is added, be followed by stirring for reaction 2.5 hours.Reaction is mixed
Object pours into ammonium chloride solution to quench the reaction, and ether extraction, organic phase water and brine It is added and uses anhydrous slufuric acid
Sodium is dry.It is removed in vacuum solvent, gained crude product obtains yellow oil product front three with column chromatographic purifying (5% EtOAc/PE)
5.7 g (yield: 92.0%) of base silicon substrate Methyl propiolate.
(2) 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate preparation:
Under nitrogen protection, by trimethyl silicon substrate Methyl propiolate (3 g, 19.2mmol) and 3- sulfydryl -2- butanone (2.4
G, 23.0 mol) it is added in dry toluene, sodium ethoxide (1.3 g, 19.2 mmol) then are added, reaction system heats back
Reaction system is down to room temperature by stream reaction 5 hours, distillation water washing is added, and (2 × 20 ml) is extracted with ethyl acetate, has
Machine is mutually dry with anhydrous sodium sulfate, solvent is removed in vacuum, gained crude product column chromatographic purifying obtains yellow oil product 4,5-
Dimethyl -2-(trimethyl silicon substrate) 3.9 g (yield: 83.8%) of thiophene -3- methyl formate.
(3) preparation of final product pesticide Silthiopham:
Under nitrogen protection, 4,5- dimethyl -2-(trimethyl silicon substrate is added into reaction flask) thiophene -3- methyl formate (1.0
G, 4.1 mmol), 15 mL toluene and allyl amine (1.8 g, 30.8 mmol) add four zirconium tert-butoxides of catalytic amount
(0.16 g, 0.41 mmol), reaction mixture is heated to reflux after 48h cooling, and vacuum pumps solvent (toluene and extra
Allyl amine), residue is added n-hexane and is heated to reflux 2h, and reaction system is cooling, and yellow solid is precipitated, dry after filtering
Obtain 0.62 g (yield: 56.8%) of yellow powder pesticide Silthiopham.
1H-NMR (CDCl3, 400MHz), δ =5.89-5.94 (m, 1H), 5.68 (br, s, 1H), 5.27
(d, J= 16.8 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 4.06 (t, J= 5.6 Hz, 2H), 2.34
(s, 3H). 2.16 (s, 3H), 0.31 (s, 9H). 13C-NMR (CDCl3, 100MHz), δ =167.0, 144.7,
138.5, 134.6, 133.0, 132.3, 116.4, 41.6, 12.5, 11.9, -0.6。
Claims (9)
1. a kind of synthetic method of pesticide Silthiopham, which is characterized in that the synthetic method is following steps: (1) lazy
Property gas shield under, using trimethyl silicane ethyl-acetylene as raw material, organic base effect under react to obtain trimethyl with methylchloroformate
Silicon substrate Methyl propiolate;
(2) trimethyl silicon substrate Methyl propiolate reacts to obtain 4,5- dimethyl-with 3- sulfydryl -2- butanone under base catalyst effect
2-(trimethyl silicon substrate) thiophene -3- methyl formate;
(3) under inert gas protection, by 4,5- dimethyl -2-(trimethyl silicon substrate) thiophene -3- methyl formate and allyl amine
Under the action of catalyst, heating reflux reaction is down to room temperature after 12 ~ 72 hours, and vacuum pumps extra allyl amine, residue
N-hexane is added to crystallize to obtain pesticide Silthiopham,
The catalyst is selected from tri- azabicyclic of 1,5,7- [4.4.0] decyl- 5- alkene, four zirconium tert-butoxides, tetraisopropyl titanate, three
Aluminium isopropoxide, indium bromide and zinc chloride,
Reaction structure formula is as follows:
。
2. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that described in step (1)
Organic base it is a kind of in metal alkyl lithiumation object, amido lithiumation object, the molar ratio of organic base and trimethyl silicane ethyl-acetylene is
1.0 ~ 1.5:1.
3. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that chloro-carbonic acid esters and three
The molar ratio of methylsilyl acetylene is 1.1 ~ 1.5:1.
4. a kind of synthetic method of pesticide Silthiopham according to claim 1 or 2 or 3, which is characterized in that step (1)
Trimethyl silicane ethyl-acetylene acts at -50 ~ -78 DEG C with organic base in tetrahydrofuran, then at room temperature with chloro-carbonic acid esters
Reaction, ammonium chloride is extracted after being quenched with ether, dry and column chromatographic purifying obtains trimethyl silicon substrate Methyl propiolate.
5. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that described in step (2)
Base catalyst be selected from alkali metal carbonate, alkali alcoholate, one or more of organic amine compound, base catalysis
Agent and trimethyl silicon substrate Methyl propiolate mole are 0.1 ~ 1.5:1.
6. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that 3- mercapto in step (2)
The molar ratio of base -2- butanone and trimethyl silicon substrate Methyl propiolate is 1.0 ~ 5.0:1.
7. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that catalysis in step (3)
Agent and 4,5- dimethyl -2-(trimethyl silicon substrate) molar ratio of thiophene -3- methyl formate is 0.1 ~ 1:1.
8. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that described in step (3)
4,5- dimethyl -2-(trimethyl silicon substrate) molar ratio of thiophene -3- methyl formate and allyl amine is 1:1 ~ 10.
9. a kind of synthetic method of pesticide Silthiopham according to claim 1, which is characterized in that be added in step (3)
Solvent is reacted, and solvent is selected from toluene, halogenated hydrocarbons, aromatic hydrocarbon, and alcohols is one or more of in polar non-solute.
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"Synthesis of Carbamates and Ureas Using Zr(IV)-Catalyzed Exchange Processes";Chong Han等;《Org. Lett.》;20070315;第9卷(第8期);第1517-1520页 |
A convenient aminolysis of esters catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene(TBD) under solvent-free conditions";Cyrille Sabot等;《Tetrahedron Letters》;20070330;第48卷;第3863-3866页 |
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