Handling Hazards Using Continuous Flow Chemistry: Synthesis of N1-Aryl-[1,2,3]-triazoles from Anilines via Telescoped Three-Step Diazotization, Azidodediazotization, and [3+2] Dipolar Cycloaddition Processes

被引:36
作者
Teci, Matthieu [1 ]
Tilley, Michael [1 ]
McGuire, Michael A. [2 ]
Organ, Michael G. [1 ,3 ,4 ]
机构
[1] York Univ, Dept Chem, 4700 Keele St, Toronto, ON M3J 1P3, Canada
[2] GlaxoSmithKline Pharmaceut Inc, 709 Swedeland Rd,POB 1539,UMW 2810, King Of Prussia, PA 19406 USA
[3] Univ Ottawa, CCRI, Ottawa, ON K1N 6N5, Canada
[4] Univ Ottawa, Dept Chem, Ottawa, ON K1N 6N5, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
anilines; diazotization; triazoles; click chemistry; dipolar cycloaddition; flow; AZIDE-ALKYNE CYCLOADDITION; ORGANIC-SYNTHESIS MACOS; MULTICOMPONENT CLICK SYNTHESIS; 1,4-DISUBSTITUTED 1,2,3-TRIAZOLES; COPPER NANOPARTICLES; MULTISTEP SYNTHESIS; REACTOR TECHNOLOGY; CHEMICAL-SYNTHESIS; NATURAL-PRODUCTS; PROCESS WINDOWS;
D O I
10.1021/acs.oprd.6b00292
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
The conversion of commercially available anilines into triazole products was realized using a telescoped three-reactor flow diazotization, azidodediazotization, and [3 + 2] dipolar cycloaddition process. The diazotization azidodediazotization sequence was accelerated by means of an ultrasonic bath resulting in a degassed, segmented effluent. An automated continuous flow unit controlled by custom software created in-house was used to collect the aryl azide stream and restore it to a continuous column of the reagent. When combined with a variety of dipolarophiles, 1-aryl-[1,2,3]-triazoles were thus assembled by either copper catalyzed alkyne azide cycloaddition (CuAAC) or Huisgen cycloaddition reactions.
引用
收藏
页码:1967 / 1973
页数:7
相关论文
共 101 条
[1]   The Development of a General Strategy for the Synthesis of Tyramine-Based Natural Products by Using Continuous Flow Techniques [J].
Achanta, Srinivas ;
Liautard, Virginie ;
Paugh, Robert ;
Organ, Michael G. .
CHEMISTRY-A EUROPEAN JOURNAL, 2010, 16 (43) :12797-12800
[2]   Click Chemistry: 1,2,3-Triazoles as Pharmacophores [J].
Agalave, Sandip G. ;
Maujan, Suleman R. ;
Pore, Vandana S. .
CHEMISTRY-AN ASIAN JOURNAL, 2011, 6 (10) :2696-2718
[3]   An efficient one-pot strategy for the highly regioselective metal-free synthesis of 1,4-disubstituted-1,2,3-triazoles [J].
Ali, Akbar ;
Correa, Arlene G. ;
Alves, Diego ;
Zukerman-Schpector, Julio ;
Westermann, Bernhard ;
Ferreira, Marco A. B. ;
Paixao, Marcio W. .
CHEMICAL COMMUNICATIONS, 2014, 50 (80) :11926-11929
[4]   Multicomponent Click Synthesis of 1,2,3-Triazoles from Epoxides in Water Catalyzed by Copper Nanoparticles on Activated Carbons [J].
Alonso, Francisco ;
Moglie, Yanina ;
Radivoy, Gabriel ;
Yus, Miguel .
JOURNAL OF ORGANIC CHEMISTRY, 2011, 76 (20) :8394-8405
[5]   Multicomponent Synthesis of 1,2,3-Triazoles in Water Catalyzed by Copper Nanoparticles on Activated Carbon [J].
Alonso, Francisco ;
Moglie, Yanina ;
Radivoy, Gabriel ;
Yus, Miguel .
ADVANCED SYNTHESIS & CATALYSIS, 2010, 352 (18) :3208-3214
[6]   Efficient conversion of aromatic amines into azides: A one-pot synthesis of triazole linkages [J].
Barral, Karine ;
Moorhouse, Adam D. ;
Moses, John E. .
ORGANIC LETTERS, 2007, 9 (09) :1809-1811
[7]  
Baumann M, 2015, ORG BIOMOL CHEM, V13, P4231, DOI [10.1039/C5OB00245A, 10.1039/c5ob00245a]
[8]   An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals [J].
Baumann, Marcus ;
Baxendale, Ian R. ;
Ley, Steven V. ;
Nikbin, Nikzad .
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 2011, 7 :442-495
[9]   Multistep Synthesis Using Modular Flow Reactors: Bestmann-Ohira Reagent for the Formation of Alkynes and Triazoles [J].
Baxendale, Ian R. ;
Ley, Steven V. ;
Mansfield, Andrew C. ;
Smith, Christopher D. .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (22) :4017-4021
[10]  
BAXTER CA, 2011, J ORG PROCESS RES DE, V15, P367, DOI DOI 10.1021/OP1002853