2-氯-3-乙基吡啶的合成工艺研究
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摘要
2-氯-3-乙基吡啶是一种重要的医药中间体,本文对其合成工艺进行研究与优化,并设计了一种新的合成方法。目标产物以2-氯烟醛为原料,经Witting反应和还原反应制得,其结构经~1H-NMR、~(13)C-NMR证实,总收率为61.6%。该方法原料廉价易得,操作简单,路线较短且收率和纯度均较高,易于实现工业化生产。
2-Chloro-3-ethylpyridine is an important pharmaceutical intermediate.The synthesis of 2-chloro-3-ethylpyridine was studied and optimized to design a novel synthesis method in this paper.2-chloro-nicotinaldehyde was used as a starting material to give the target product via witting reaction and reduction reaction.The structures of 2-chloro-3-ethylpyridine was confirmed by MS,~1H NMR,~(13)C NMR and the total yield of the product was 61.6%.It was easy to achieve industrial production because of the cheap and accessible raw materials,simple operation,higher yield and purity and shorter synthetic routes.
2-Chloro-3-ethylpyridine is an important pharmaceutical intermediate.The synthesis of 2-chloro-3-ethylpyridine was studied and optimized to design a novel synthesis method in this paper.2-chloro-nicotinaldehyde was used as a starting material to give the target product via witting reaction and reduction reaction.The structures of 2-chloro-3-ethylpyridine was confirmed by MS,~1H NMR,~(13)C NMR and the total yield of the product was 61.6%.It was easy to achieve industrial production because of the cheap and accessible raw materials,simple operation,higher yield and purity and shorter synthetic routes.
引文
[1]杨维清,马梦林,张园园.3,6-二氯-2-氨基吡啶合成新方法[J].化学研究与应用,2014(7):1 161-1 165.
[2]Shaw E,Bernstein J,Losee K,et al.Analogs of aspergillicacid.IV.substituted 2-bromopyridine-N-oxides and their conversion to cyclic thiohydroxamicacids1[J].J Am Chem Soc,1950,72(10):4 362-4 364.
[3]Zaslowsky J A.Process for the preparation of 2-chloropyridine[P].US:3153044,1964-05-01.
[4]Friis N,Fr S L P O.Process for the preparation of 2,3,5,6-tetrachloropyridine[P].US:5591857 A,1997-01-07.
[5]Dietsche T J,Love J.Preparation of polychlorinated pyridines from 2,4-dichloro-6-(trichloro methyl)pyridine[P].US:4227001,1980-10-07.
[6]宋杰.2-氯吡啶的用途与合成[J].广州化学,2002,27(4):35-42.
[7]吕金魁,魏荣宝,梁娅,等.新型烟用香料3-乙基吡啶的合成[J].天津理工大学学报,1995(2):71-75.
[8]Sakamoto T,Nagata H,Kondo Y,et al.Reductive amination of ethynylpyridines with sodium cyanoborohydride.[J].Chem Pharm Bull,1984,32(12):4 866-4 872.
[9]Jiang P P,Yang X J.A quick,mild and efficient bromination using a CFBSA/KBrsystem[J].RSC Adv,2016,6(93):90 031-90 034.
[10]Wybon C C D,Mensch C,Hollanders K,et al.Zn-catalyzed tert-butyl nicotinate-directed amide cleavage as a biomimic of metallo-exopeptidase activity.[J].ACS Catal,2018,8(1):203-218.
[11]Keigo T,Eiichi Y,Naoaki W.Pyridine derivative substituted with heterocycle and phosphonoamino and antifungal agent containing the same[P].EP:2141171(A1),2010-01-06.
[12]Plas H C V D,Wozniak M,Veldhuizen A V.ChemInform abstract:Didehydrohetarenes.partxxxix.on the reaction of 2-,3-and 4-bromo(chloro)-1,8-naphthyridine with potassium amide in liquid ammonia[J].Chem inform,1978,97(5):130-135.
[13]Jacobs R,Orr M,Wring S,et al.Boron-containing small molecules as anti-protozoal agents[P].US:20110207702 A1,2011-08-25.
[14]Lafaye K,Nicolas L,Guérinot A,et al.Lewis Basicity Modulation of N-Heterocycles:a key for successful cross-metathesis[J].Cheminform,2015,46(12):4 972-4 975.
[15]Wang G,Beigelman L,Truong A,et al.Compounds for the treatment of paramyxovirus viral infections[P].US:20170283429,2017-10-05.
[16]Yoshida S,Ohishi T,Matsui T,et al.Identification of a novel GPR119 agonist,AS1269574,with in vitro and in vivo glucose-stimulated insulin secretion[J].Biochem Biophys Res Commun,2010,400(3):437-441.
[2]Shaw E,Bernstein J,Losee K,et al.Analogs of aspergillicacid.IV.substituted 2-bromopyridine-N-oxides and their conversion to cyclic thiohydroxamicacids1[J].J Am Chem Soc,1950,72(10):4 362-4 364.
[3]Zaslowsky J A.Process for the preparation of 2-chloropyridine[P].US:3153044,1964-05-01.
[4]Friis N,Fr S L P O.Process for the preparation of 2,3,5,6-tetrachloropyridine[P].US:5591857 A,1997-01-07.
[5]Dietsche T J,Love J.Preparation of polychlorinated pyridines from 2,4-dichloro-6-(trichloro methyl)pyridine[P].US:4227001,1980-10-07.
[6]宋杰.2-氯吡啶的用途与合成[J].广州化学,2002,27(4):35-42.
[7]吕金魁,魏荣宝,梁娅,等.新型烟用香料3-乙基吡啶的合成[J].天津理工大学学报,1995(2):71-75.
[8]Sakamoto T,Nagata H,Kondo Y,et al.Reductive amination of ethynylpyridines with sodium cyanoborohydride.[J].Chem Pharm Bull,1984,32(12):4 866-4 872.
[9]Jiang P P,Yang X J.A quick,mild and efficient bromination using a CFBSA/KBrsystem[J].RSC Adv,2016,6(93):90 031-90 034.
[10]Wybon C C D,Mensch C,Hollanders K,et al.Zn-catalyzed tert-butyl nicotinate-directed amide cleavage as a biomimic of metallo-exopeptidase activity.[J].ACS Catal,2018,8(1):203-218.
[11]Keigo T,Eiichi Y,Naoaki W.Pyridine derivative substituted with heterocycle and phosphonoamino and antifungal agent containing the same[P].EP:2141171(A1),2010-01-06.
[12]Plas H C V D,Wozniak M,Veldhuizen A V.ChemInform abstract:Didehydrohetarenes.partxxxix.on the reaction of 2-,3-and 4-bromo(chloro)-1,8-naphthyridine with potassium amide in liquid ammonia[J].Chem inform,1978,97(5):130-135.
[13]Jacobs R,Orr M,Wring S,et al.Boron-containing small molecules as anti-protozoal agents[P].US:20110207702 A1,2011-08-25.
[14]Lafaye K,Nicolas L,Guérinot A,et al.Lewis Basicity Modulation of N-Heterocycles:a key for successful cross-metathesis[J].Cheminform,2015,46(12):4 972-4 975.
[15]Wang G,Beigelman L,Truong A,et al.Compounds for the treatment of paramyxovirus viral infections[P].US:20170283429,2017-10-05.
[16]Yoshida S,Ohishi T,Matsui T,et al.Identification of a novel GPR119 agonist,AS1269574,with in vitro and in vivo glucose-stimulated insulin secretion[J].Biochem Biophys Res Commun,2010,400(3):437-441.