CN1147474C - 2-氰基吡啶类化合物的制备方法 - Google Patents
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- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title abstract description 5
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical class N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 28
- 239000012190 activator Substances 0.000 claims description 19
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 14
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 11
- 239000002798 polar solvent Substances 0.000 claims description 9
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052731 fluorine Chemical group 0.000 claims description 7
- 239000011737 fluorine Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- -1 alkali metal cyanide Chemical class 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- ICAIHGOJRDCMHE-UHFFFAOYSA-O ammonium cyanide Chemical compound [NH4+].N#[C-] ICAIHGOJRDCMHE-UHFFFAOYSA-O 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910017464 nitrogen compound Inorganic materials 0.000 claims description 2
- 150000002830 nitrogen compounds Chemical class 0.000 claims description 2
- 150000003512 tertiary amines Chemical group 0.000 claims description 2
- 125000005270 trialkylamine group Chemical group 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 229910001385 heavy metal Inorganic materials 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 3
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 230000007096 poisonous effect Effects 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- 150000005759 2-chloropyridine Chemical class 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
Classifications
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- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Catalysts (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明是关于一种制备化合物(I)的方法，其中Y和n如说明书所述。
Description
[0001]本发明涉及一种制备2-氰基吡啶类化合物的新方法，2-氰基吡啶类化合物可作为中间体用于生产杀虫剂和药物。
[0002]已知有许多方法可在吡啶的2位引入氰基，这通常包括在二甲基亚砜或二甲基甲酰胺等极性溶剂中进行卤素尤其是溴或氟的取代。此外，还有许多方法从活化的吡啶N-氧化物或N-烷基吡啶开始。这些氰基化路径中，许多都用到含铜或镍的重金属试剂。例如，EP0034917在二甲基甲酰胺中，在120℃，用氰化亚铜，由2-溴吡啶制备2-氰基-3-氯-5-三氟甲基吡啶。
[0003]然而，许多现有方法存在一个或多个缺点，包括得率低，因使用重金属而产生有毒废液，以及用到难以回收的极性溶剂。而且，涉及形成吡啶N-氧化物或N-烷基吡啶的方法包括多个步骤。就放大到产业规模来说，这些缺点尤其重要。
[0004]现在，我们发明了一种可以产业规模生产2-氰基吡啶类化合物的新方法。
[0005]本发明提供了一种制备化合物(I)的方法：
该方法包括：在极性溶剂中，用活化剂和氰化物处理化合物(II)：
其中，X是卤素；
各Y相同或不同，是吸电子基团；n是1-4；
所述活化剂是含亲核叔氮的化合物，该活化剂不是化合物(I)和(II)，氰化物原料是氢氰酸，碱金属氰化物，碱土金属氰化物或可含取代的氰化铵。
[0006]吸电子基团例如卤素，卤代烷基，硝基，氰基，烷氧基羰基和烷基磺酰基。
[0007]本发明中，卤素代表氟、氯或溴原子，优选氯。
[0008]卤代烷基表示一卤代或多卤代的C1-6烷基。例如，所述C1-6烷基部分可以是甲基，乙基，正丙基或异丙基，优选甲基。优选被氯或氟一取代或多取代的C1-6烷基。更好的是三氟甲基。
[0009]Y优选卤素或卤代烷基(以三氟甲基为佳)。X优选氯。
[0010]化合物(II)优选2，3-二氯-5-三氟甲基吡啶。
[0011]本发明方法可高得率地制备2-氰基吡啶类化合物，该方法避免了许多现有方法的缺点。尤其是，本发明不需要化学计量的铜或镍等重金属氰化物，这些重金属氰化物若以产业规模应用会产生难以回收的有毒废液。本发明方法产生的废液易于处理。而且，本发明方法不需要制备活化的吡啶N-氧化物或N-烷基吡啶就可获得高转化率，而所述制备是许多现有方法的前提条件。
[0012]所述氰化物以氰化钠或氰化钾为宜，尤其是氰化钠。氰化物的用量一般约为1.0-2.5摩尔当量，以1.4-1.6摩尔当量为宜。
[0013]极性溶剂被发现可获得最佳效果。典型的可用的极性溶剂包括二甲基甲酰胺，二甲基亚砜，乙酸正丁酯等酯，正丁醚等醚，乙基甲基酮等酮，和乙腈或丙腈等腈。优选的溶剂是乙腈和丙腈，优选丙腈。尤其好的是水可混溶性极性溶剂。我们发现，在这些优选溶剂中，无需无水条件即可实现高转化率。若采用水溶性氰化物，可用水作为助溶剂。
[0014]“亲核叔氮”指所含氮原子不连接任何氢原子且呈亲核性的基团。许多叔氮亲核基团都可用作活化剂，具体为叔胺，例如三乙胺等三烷基胺；或可含取代的吡啶，例如4-吡咯烷基吡啶，尤其是二烷基氨基吡啶，特别是二甲基氨基吡啶，例如4-二甲基氨基吡啶；或N-烷基咪唑；或N-烷基三唑。最好的活化剂是4-二甲基氨基吡啶。
[0015]活化剂用量一般符合化学计量(0.9-1.5摩尔当量，以0.9-1.1摩尔当量为佳)，虽然，有时略低的用量也可以(一般为0.05-0.2摩尔当量)。然而，当X是氯时(尤其是大规模生产时)，仅使用催化量的活化剂，会造成化合物(I)的得率低。
[0016]对X是氟的化合物来说，催化量(一般约0.15-0.2摩尔当量)的叔氮亲核试剂就已足够。
[0017]反应条件一般包括：在合适的反应器中混合所有反应物，在20-150℃，以75-100℃为佳，搅拌。
[0018]本发明的优选实施方式包括：(a)在合适的反应器中混合化合物(II)、活化剂和极性溶剂(以丙腈为佳)，在约20-150℃，以75-100℃为佳，搅拌；然后，(b)用金属氰化物(以氰化钠为佳)的水溶液处理生成的反应混合物，在0-90℃，以20-30℃为佳，搅拌。
[0019]本发明的另一特征是，活化剂循环使用。在使用水可混溶性溶剂时，这尤其方便：先用水小心地洗去所有未反应的金属氰化物，然后用酸的稀水溶液萃取反应混合物中的活化剂。
[0020]因此，本发明提供了一种高得率制备2-氰基吡啶类化合物的方法。由于反应采用低温至中温，只需简单而廉价的反应器和下游处理设备即可。而且，由于活化剂可循环使用，而且，反应物容易获得，该方法成本低廉。此外，本发明方法产生的废液容易处理。
[0021]现有方法一般需用氰化物取代溴或氟。这些底物通常很贵。我们的方法得率高，所用是相对便宜的氯代化合物。所以，化合物(II)最好是2-氯吡啶类，尤其是2，3-二氯-5-三氟甲基吡啶。然而，本发明方法也适用于X是溴或氟的情形。
[0022]以下实施例将进一步描述本发明。
实施例1显示改变反应条件对于底物2，3-二氯-5-三氟甲基吡啶氰化成3-氯-2-氰基-5-三氟甲基吡啶的影响。表1中，Me代表甲基，Et代表乙基。实施例2显示改变底物，保持反应条件不变，对于转化率的影响。用FID(火焰离子化检测器)由GC计算转化率。
实施例1
按表1中的比例，将2，3-二氯-5-三氟甲基吡啶(II)，氰化物，活化剂4-二甲基氨基吡啶(4-DMAP)((II)重量的10％)和溶剂加入一圆底烧瓶。反应条件如见表1。
表1
| 实施例 | 溶剂 | 催化剂 | 氰化物 | 氰化物/II摩尔比 | 反应条件 | ％转化率 |
| 1 | EtCN | 4-DMAP | NaCN | 1.5 | 98℃，10.5小时 | 92 |
| 2 | MeCN | 4-DMAP | KCN | 1.5 | 84℃，10小时 | 84 |
| 3 | MeCN | 4-DMAP | NaCN | 1.5 | 82℃，21小时 | 75 |
| 4 | 甘醇二甲醚 | 4-DMAP | NaCN | 1.5 | 85℃，4小时 | 60 |
| 5 | EtCN | 4-DMAP | Bu4NCN | 1.0 | 98℃，4小时 | 40 |
实施例2
将化合物(II)，丙腈(4.7mmol(II)/100ml丙腈)，氰化钠(与化合物(II)的摩尔比为1.5)，4-二甲基氨基吡啶(与化合物(II)的摩尔比为0.186)，水(丙腈的5％v/v)加入一圆底烧瓶，90-100℃搅拌10-12小时。
表2
| 实施例 | 底物 | 反应时间 | 转化率％ |
| 6 | 3-Cl-2-F-5-CF3-吡啶 | 9小时 | 92 |
| 7 | 2-Cl-4，5-二CF3-吡啶 | 9小时 | 49 |
| 8 | 3-Cl-2-Br-5-CF3-吡啶 | 10小时 | 51 |
实施例3
氮气氛下，将丙腈(656ml)，2，3-二氯-5-三氟甲基吡啶(87.5g)和4-二甲基氨基吡啶(52g)加热回流5小时。冷却该混合物，15℃时，加入氰化钠(30g)的水(110ml)溶液。15℃搅拌5小时后，反应完成，加入水(250ml)，溶解其中的无机盐。有机相用水洗涤，然后用2N HCl萃取，用以去除4-二甲基氨基吡啶。40℃真空蒸馏，去除丙腈，得产物3-氯-2-氰基-5-三氟甲基吡啶73g，得率：84％。
实施例4
用30分钟，向反应器中加入氰化钠(73.5g)的水(150ml)溶液，丙腈(500ml)，4-二甲基氨基吡啶(16g)和3-氯-2-氟-5-三氟甲基吡啶(149.3g)。20℃搅拌5小时，分离出上层有机相，用水洗涤。用丙腈萃取下层水相，与有机相合并，45℃真空蒸馏去除溶剂，得3-氯-2-氰基-5-三氟甲基吡啶73g，得率：83％。
Claims (9)
1.一种制备化合物(I)的方法；
该方法包括：在极性溶剂中，用活化剂和氰化物处理化合物(II)，
其中，X是氯或氟；
各Y相同或不同，是选自卤素、卤代烷基、硝基、氰基、烷氧基羰基或烷基磺酰基的吸电子基团；n是1-4；
所述活化剂是含亲核叔氮的化合物，该活化剂不是化合物(I)和(II)，所述氰化物是氢氰酸，碱金属氰化物，碱土金属氰化物或可含取代的氰化铵。
2.根据权利要求1所述的方法，包括：
(a)在合适的反应器中混合化合物(II)、活化剂和极性溶剂，在75-100℃搅拌；然后，(b)用金属氰化物的水溶液处理生成的反应混合物，在0-90℃，以20-30℃为佳。
3.根据权利要求1或2所述的方法，所述活化剂是叔胺，选自三烷基胺，可含取代的吡啶，N-烷基咪唑和N-烷基三唑。
4.根据权利要求3所述的方法，所述活化剂是4-二甲基氨基吡啶。
5.根据权利要求1所述的方法，所述氰化物是氰化钠或氰化钾。
6.根据权利要求1所述的方法，所述极性溶剂是乙腈或丙腈。
7.根据权利要求1所述的方法，其中的活化剂循环使用。
8.根据权利要求1所述的方法，其中的X是氯。
9.根据权利要求1所述的方法，所述化合物(II)是2，3-二氯-5-三氟甲基吡啶。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9920959.5A GB9920959D0 (en) | 1999-09-07 | 1999-09-07 | Novel process |
| GB9920959.5 | 1999-09-07 |
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| CN1372550A CN1372550A (zh) | 2002-10-02 |
| CN1147474C true CN1147474C (zh) | 2004-04-28 |
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| CNB008124655A Expired - Lifetime CN1147474C (zh) | 1999-09-07 | 2000-08-30 | 2-氰基吡啶类化合物的制备方法 |
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| US (1) | US6699993B1 (zh) |
| EP (1) | EP1210331B1 (zh) |
| JP (1) | JP4764586B2 (zh) |
| KR (1) | KR100714146B1 (zh) |
| CN (1) | CN1147474C (zh) |
| AT (1) | ATE446952T1 (zh) |
| AU (1) | AU781641B2 (zh) |
| BR (1) | BR0013799B1 (zh) |
| CA (1) | CA2381176A1 (zh) |
| DE (1) | DE60043228D1 (zh) |
| GB (1) | GB9920959D0 (zh) |
| HK (1) | HK1048814A1 (zh) |
| HU (1) | HUP0202865A3 (zh) |
| IL (2) | IL148161A0 (zh) |
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| PL (1) | PL353926A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2002213948B2 (en) | 2000-08-25 | 2006-08-17 | Bayer Cropscience S.A. | Process for the preparation of 2-aminoethylpyridines |
| JP2012508717A (ja) * | 2008-11-13 | 2012-04-12 | バイエル・クロップサイエンス・アーゲー | 殺真菌剤としての置換（ピリジル）−アジニルアミン誘導体 |
| CN106905231A (zh) * | 2015-12-23 | 2017-06-30 | 联化科技股份有限公司 | 3-氯-5-三氟甲基吡啶类化合物及中间体的制备方法 |
| CN106117131B (zh) * | 2016-06-29 | 2018-09-04 | 天津市均凯化工科技有限公司 | 一种制备2-氨基-3-氯-5-三氟甲基吡啶的方法 |
| CN106349159B (zh) * | 2016-08-29 | 2019-03-22 | 山东省联合农药工业有限公司 | 一种3-氯-2-氰基-5-三氟甲基吡啶的制备方法 |
| CN112390747A (zh) * | 2020-11-03 | 2021-02-23 | 内蒙古佳瑞米精细化工有限公司 | 2-氰基-3-氯-5-三氟甲基吡啶与丁二腈的联合制备方法 |
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| GB1601761A (en) * | 1978-02-07 | 1981-11-04 | May M A | Swimming pool accessory |
| EP0034917B1 (en) * | 1980-02-21 | 1984-08-08 | Ishihara Sangyo Kaisha Ltd. | 2-substituted-5-trifluoromethylpyridines and a process for producing the same |
| JPS56118065A (en) * | 1980-02-21 | 1981-09-16 | Ishihara Sangyo Kaisha Ltd | 5-trifluoromethylpyridine-2-carboxylic acid, its salt, and their preparation |
| JPS56118066A (en) * | 1980-02-21 | 1981-09-16 | Ishihara Sangyo Kaisha Ltd | 2-cyano-3-halogeno-5-trifluoromethylpyridine and its preparation |
| US4766219A (en) * | 1985-06-03 | 1988-08-23 | The Dow Chemical Company | Preparation of 2-cyano-6-chloropyridine compounds |
| US4776219A (en) * | 1987-04-06 | 1988-10-11 | Jaromir Friedrich | Pressure transducer |
| US4829164A (en) | 1987-11-02 | 1989-05-09 | Western Pacific Industries Inc. | Counter |
| NZ242290A (en) * | 1991-04-15 | 1994-12-22 | Zeneca Ltd | Pyridyl and pyrimidinyl substituted oxime-o-benzyl ether derivatives; preparatory processes, fungicidal compositions and an intermediate |
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Also Published As
| Publication number | Publication date |
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| JP4764586B2 (ja) | 2011-09-07 |
| DE60043228D1 (de) | 2009-12-10 |
| IL148161A (en) | 2006-12-31 |
| HUP0202865A3 (en) | 2005-01-28 |
| EP1210331B1 (en) | 2009-10-28 |
| GB9920959D0 (en) | 1999-11-10 |
| PL353926A1 (en) | 2003-12-15 |
| IL148161A0 (en) | 2002-09-12 |
| KR100714146B1 (ko) | 2007-05-02 |
| RU2222530C2 (ru) | 2004-01-27 |
| HUP0202865A2 (hu) | 2002-12-28 |
| BR0013799A (pt) | 2002-05-21 |
| MXPA02001945A (es) | 2002-08-20 |
| EP1210331A1 (en) | 2002-06-05 |
| JP2003508520A (ja) | 2003-03-04 |
| BR0013799B1 (pt) | 2011-07-12 |
| CA2381176A1 (en) | 2001-03-15 |
| CN1372550A (zh) | 2002-10-02 |
| KR20020021409A (ko) | 2002-03-20 |
| AU781641B2 (en) | 2005-06-02 |
| ZA200200938B (en) | 2003-07-30 |
| US6699993B1 (en) | 2004-03-02 |
| HK1048814A1 (en) | 2003-04-17 |
| AU7420200A (en) | 2001-04-10 |
| WO2001017970A1 (en) | 2001-03-15 |
| TWI274054B (en) | 2007-02-21 |
| ATE446952T1 (de) | 2009-11-15 |
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