TWI383973B - 用於製備２-取代-５-（１-烷硫基）烷基吡啶之方法 - Google Patents
用於製備２-取代-５-（１-烷硫基）烷基吡啶之方法 Download PDFInfo
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- TWI383973B TWI383973B TW096104611A TW96104611A TWI383973B TW I383973 B TWI383973 B TW I383973B TW 096104611 A TW096104611 A TW 096104611A TW 96104611 A TW96104611 A TW 96104611A TW I383973 B TWI383973 B TW I383973B
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- alkyl
- membered saturated
- substituted
- alkylthio
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- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 150000002576 ketones Chemical class 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- -1 alkyl vinyl ethers Chemical class 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 150000002081 enamines Chemical class 0.000 description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- LSGZGFUQRGHSSU-UHFFFAOYSA-N 1-(3-methylsulfanylbut-1-enyl)pyrrolidine Chemical compound CSC(C)C=CN1CCCC1 LSGZGFUQRGHSSU-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- NCBDFIPMWRKPDU-UHFFFAOYSA-N 3-(Methylthio)butanal Chemical compound CSC(C)CC=O NCBDFIPMWRKPDU-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- JIRXVXHPEJBVJN-UHFFFAOYSA-N n,n-dimethyl-3-methylsulfanylbut-1-en-1-amine Chemical compound CSC(C)C=CN(C)C JIRXVXHPEJBVJN-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical compound CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 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
- 238000005292 vacuum distillation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本發明係有關於用於製備2－取代－5－(1－烷硫基)烷基吡啶之方法。
本申請案申明補充美國專利暫時申請案系列號60/835,940，於2006年8月7日提申。
本發明係相關於某種新穎之2－取代－5－(1－烷硫基)烷基吡啶，及其製備流程。
該新穎之2－取代－5－(1－烷硫基)烷基吡啶可使用作為中間產物，以製備某些新穎之殺蟲劑；請見，如美國專利公開案2005/0228027。其優點為可有效及高產率地自非吡啶來源產生2－取代－5－(1－烷硫基)烷基吡啶。
本發明係相關於2－取代－5－(1－烷硫基)烷基－吡啶，及其環化製備方法。更特別的是，本發明係相關於一種製備2－取代－5－(1－烷硫基)烷基吡啶(I)之方法，
R1
與R2
獨立地代表H、C1
－C4
烷基，或R1
或R2
任一者與R3
結合代表一4－至6－元飽和環，或R1
與R2
結合而代表一3－至7－元飽和環，選擇性地經O或N原子取代；以及R3
代表C1
－C4
烷基或R3
與R1
或R2
任一者結合而代表一4－至6－元飽和環；以及R4
代表C1
－C4
烷基或C1
－C4
鹵素烷基；其包含環化一α,β－未飽和酮II
其中X代表鹵素、OR5
OSO2
R5
、SR5
、SOR5
、SO2
R5
或NR6
R7
；R5
代表氫、C1
－C8
烷基、C2
－C8
烯基、C1
－C8
芳基烷基、C1
－C8
鹵素烷基、C1
－C8
烷氧基烷基、C1
－C8
烷基胺基烷基、芳基或雜芳基；以及R6
與R7
獨立地代表氫、C1
－C8
烷基、C2
－C8
烯基、C1
－C8
芳基烷基、C1
－C8
鹵素烷基、C1
－C8
烷氧基烷基、C1
－C8
烷基胺基烷基、芳基或雜芳基，或R6
與R7
共同與N結合代表一5－或6－元飽和或未飽和環；以及R4
如先前所定義；與一烯胺III
其中R1
、R2
、R3
、R6
、R7
如先前所定義；在氨或可產生氨之試劑之存在下。
本發明之另一觀點為一種新穎之化合物，具有下式
其中R1
與R2
獨立地代表H、C1
－C4
烷基，或R1
或R2
任一者與R3
結合代表一4－至6－元飽和環，或R1
與R2
結合代表一3－至7－元飽和環，選擇性地經O或N原子取代；以及R3
代表C1
－C4
烷基或R3
與R1
或R2
任一者結合代表一4－至6－元飽和環；以及R4
代表C1
－C4
烷基或C1
－C4
鹵素烷基。
除非另有指出，術語“烷基”(包括衍生物術語如“鹵素烷基”與“芳基烷基”)，使用於此，係指直鏈、支鏈或環狀基團。因此，典型烷基為甲基、乙基、1－甲基乙基、丙基、1,1－二甲基乙基，以及環丙基。術語“烯基”，使用於此，包括直鏈、支鏈或環狀基團，並傾向於包括一或多個未飽和鍵結。術語“鹵素”包括氟、氯、溴與碘。術語“鹵素烷基”包括烷基基團經一至最大可能數目之鹵素原子取代。術語“芳基”，以及衍生物術語如“芳基烷基”，係指一苯基或萘基。術語“雜芳基”係指一5－或6－元芳環，含有一或多個雜原子，即N、O或S；這些雜芳環可與其他芳香族系統融合。
在本發明中，2－取代－5－(1－烷硫基)烷基吡啶(I)，
其中R1
與R2
獨立地代表H、C1
－C4
烷基，或R1
或R2
任一者與R3
結合代表一4－至6－元飽和環，或R1
與R2
結合代表一3－至7－元飽和環，選擇性地經O或N原子取代；以及R3
代表C1
－C4
烷基或R3
與R1
或R2
任一者結合代表一4－至6－元飽和環；以及R4
代表C1
－C4
烷基或C1
－C4
鹵素烷基係藉由環化一α,β－未飽和酮II
其中X代表鹵素，OR5
OSO2
R5
、SR5
、SOR5
、SO2
R5
或NR6
R7
；R5
代表氫、C1
－C8
烷基、C2
－C8
烯基、C1
－C8
芳基烷基、C1
－C8
鹵素烷基、C1
－C8
烷氧基烷基、C1
－C8
烷基胺基烷基、芳基或雜芳基；以及R6
與R7
獨立地代表氫、C1
－C8
烷基、C2
－C8
烯基、C1
－C8
芳基烷基、C1
－C8
鹵素烷基、C1
－C8
烷氧基烷基、C1
－C8
烷基胺基烷基、芳基或雜芳基，或R6
與R7
共同與N結合代表一5－或6－元飽和或未飽和環；以及R4
如先前所定義；與一烯胺III
其中R1
、R2
、R3
、R6
、R7
如先前所定義，而製備。
α,β－未飽和酮(II)為商業上可購得，或可製備自相對應之乙烯基受質與乙醯化試劑。一般而言，烷基乙烯基醚可以鹵素烷基醋酸酐乙醯基化，產生II類型之化合物。烯胺(III)可方便地製備自適當之經取代胺類，加成為經適當取代之醛類，在水吸收材料存在下，具備或不具備適當之溶劑。一般而言，經適當取代之3－烷硫基丙醛係與無水二取代胺，於約－20℃至約20℃反應，在乾燥劑如無水碳酸鉀存在下，產物以蒸餾分離出。
約等莫耳量之α,β－未飽和酮(II)與烯胺(III)及氨，為此方法所必須，雖然2－4倍過量之氨或氨前驅物通常為較佳。
典型可產生氨之試劑，包括，如1)一酸之銨鹽，較佳為有機酸，2)甲醯胺，或3)具酸或酸鹽之甲醯胺。可使用脂肪族或芳香有機酸之銨鹽，但為了流程之方便性，較佳為C1
－C4
烷酸之銨鹽。甲酸銨與醋酸銨為最佳。
此反應較佳引入於極性高沸點溶劑，其可與水互溶。較佳之溶劑包括醯胺如甲醯胺、二甲基甲醯胺、二甲基乙醯胺，醇類如甲醇、乙醇、異丙醇、(2－甲氧基)乙醇與烷基腈，與乙腈，為較佳。
此反應係於溫度約－20℃至約150℃下引入。通常溫度較佳為約0℃至約80℃。
產物係以一般技術分離出，如矽膠層析法或分餾法。
在典型反應中，該α,β－未飽和酮(II)與烯胺(III)係於約－5℃至約20℃，溶解於極性溶劑中，攪拌至該α,β－未飽和酮(II)與烯胺(III)被消耗。之後加入有機酸之銨鹽，混合物加熱，至反應完全。溶解於非水互溶之溶劑中，以水清洗，並選擇性地，以濃鹽水清洗，之後該2－取代－5－(1－烷硫基)烷基吡啶(I)係以真空蒸餾方法單離出。
下列範例係用於詳細說明本發明。
5－(1－甲基硫基)乙基－2－(三氟甲基)吡啶之製備
步驟1. 1－(3－甲基硫基丁－1－烯基)吡咯烷之製備
在乾燥之5000毫升(ml)圓底瓶中，其裝配有機械式攪拌器、氮氣入口、額外之漏斗，以及加熱器，注入591 g(4.27莫耳)之無水顆粒碳酸鉀，以及1428ml(17.1莫耳)之無水吡咯烷。混合物係於氮氣環境下攪拌，並以冰浴冷卻至4℃，之後加入1050ml(8.9莫耳)之3－甲基－硫基丁醛，加入速率係使溫度維持低於10℃。添加完成後，冷卻浴移除，反應回溫至室溫。之後將反應內容物經燒結玻璃過濾漏斗過濾，移除固體，該固體以200ml無水乙醚清洗。濾液於迴旋濃縮儀中真空濃縮，至所有吡咯烷移除，得1,519g之1－(3－甲基硫基丁－1－烯基)吡咯烷，為紅色液體。1
H NMR CDCl3
δ 1.36(d,3H),1.85(m,4H),2.02(s,3H),3.02(m,4H),3.26(q,1H),3.98(dd,1H),6.25(d,1H)。
步驟2. 5－(1－甲基硫基)乙基－2－(三氟甲基)吡啶之製備
在乾燥之5000毫升(ml)圓底瓶中，其裝配有磁性攪拌器、氮氣入口、額外之漏斗，以及加熱器，注入654ml(4.59莫耳)之4－乙氧基－1,1,1－三氟－丁－3－烯－2－酮與1000ml之無水乙腈。該溶液冷卻至5℃，加入786g(4.59莫耳)之1－(3－甲基硫基丁－1－烯基)吡咯烷，加入速率係使溫度維持低於10℃。添加完成後，冷卻浴移除。反應於室溫下攪拌1.5小時，之後530g(6.88莫耳)之醋酸銨部分地加入，反應於80℃加熱15小時。冷卻後，反應於迴旋濃縮儀中真空濃縮，移除乙腈，殘餘物溶解於3公升之乙醚中。醚類萃取物以3×100ml水清洗，移除醋酸銨，以無水硫酸鎂乾燥、過濾，並於迴旋濃縮儀中真空濃縮。粗產物經Kugelrohr蒸餾，於0.3mmHg下。於85－110℃蒸餾出之產物經收集，得599g如標題化合物5－(1－甲基硫基)乙基－2－(三氟甲基)吡啶，為黃色油狀物。1
H NMR CDCl3
δ 1.62(d,3H),1.95(s,3H),3.93(q,1H),7.67(d,1H),7.90(dd,1H),8.67(d,1H)。
5－(1－甲基硫基)乙基－2－(三氟甲基)吡啶之製備
步驟1.N,N
－二甲基－(3－甲基硫基丁－1－烯基)胺之製備
在乾燥之50ml圓底瓶中，裝配有磁性攪拌子，加入3－甲基硫基丁醛(2.04g,17.2mmol)、碳酸鉀(1.19g,8.6mmol)，以及無水乙腈(5ml)。錐形瓶配置有3－通活塞，氣體可在家用真空度下排出。二甲基胺(過量)係引入該系統，經由連接在活塞上之氣球，所得之磁性攪拌懸浮液係置於水浴中，緩和明顯的放熱反應。氣球重新灌入二甲基胺，反應於室溫下攪拌90分鐘，期間採樣進行GC分析，顯示醛類起始物質完全消耗掉。反應經過濾，溶劑以迴旋濃縮移除，得粗N,N
－二甲基－(3－甲基硫基－丁－1－烯基)胺，為淡黃色液體(2.45g)。1
H NMR CDCl3 1.35(d,3H),2.00(s,3H),2.60(s,6H),3.24(m,1H),4.06(dd,1H),5.97(dd,1H)。
步驟2. 5－(1－甲基硫基)乙基－2－(三氟甲基) 啶之製備
該N,N
－二甲基－(3－甲基硫基丁－1－烯基)胺(2.45g,17.0mmol)係溶於無水乙 (10ml)中，於室溫下滴加入4－乙氧基－1,1,1－三氟－丁－3－烯－2－酮(2.90g,17.2mmol)，歷時10分鐘，淡橘色溶液於室溫下攪拌16小時。所得之葡萄酒色(burgundy)溶液係加入醋酸銨(1.33g,17.2mmol)，反應加熱至回流，並攪拌1小時。反應冷卻至室溫，以乙醚(150ml)稀釋，以水清洗(3×50ml)，以濃鹽水清洗(50ml)，以硫酸鈉乾燥、過濾，溶劑於迴旋濃縮儀中真空移除。所得之棕色液體係經由快速層析純化(SiO2
，20% EtOAc/己烷)，得5－(1－甲基硫基)乙基－2－(三氟甲基) 啶，為橘色液體(1.67g,44%)。1
H NMR CDCl3 1.62(d,3H),1.95(s,3H),3.93(q,1H),7.67(d,1H),7.90(dd,1H),8.67(d,1H)。
Claims (3)
- 一種製備2-取代-5-(1-烷硫基)烷基吡啶(I)之方法，
- 如申請專利範圍第1項之方法，其中R1 與R2 獨立地代表H或甲基，R3 代表甲基，以及R4 代表三氟甲基。
- 如申請專利範圍第1項之方法，其中該可產生氨之試劑為一有機酸之銨鹽。
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| TWI381811B (zh) * | 2006-06-23 | 2013-01-11 | Dow Agrosciences Llc | 用以防治可抵抗一般殺蟲劑之昆蟲的方法 |
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| TWI387585B (zh) * | 2006-09-01 | 2013-03-01 | Dow Agrosciences Llc | 殺蟲性之ｎ-取代（雜芳基）烷基烴基硫亞胺 |
| WO2008027539A1 (en) * | 2006-09-01 | 2008-03-06 | Dow Agrosciences Llc | Insecticidal n-substituted (2- sudstituted-1,3-thiazol) alkyl sulfoximines |
| TWI383970B (zh) * | 2006-11-08 | 2013-02-01 | Dow Agrosciences Llc | 多取代的吡啶基磺醯亞胺及其作為殺蟲劑之用途 |
| TWI395736B (zh) * | 2006-11-08 | 2013-05-11 | Dow Agrosciences Llc | 作為殺蟲劑之雜芳基（取代的）烷基ｎ-取代的磺醯亞胺（二） |
| US7709648B2 (en) * | 2007-02-09 | 2010-05-04 | Dow Agrosciences Llc | Process for the preparation of 2-substituted-5-(1-alkylthio)alkylpyridines |
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