Article

Highly Regioselective N -2 Arylation of 4,5-Dibromo-1,2,3-triazole: Efficient Synthesis of 2-Aryltriazoles

Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, USA.
Organic Letters (Impact Factor: 6.14). 01/2009; 11(21):5026-5028. DOI: 10.1021/ol9019875

ABSTRACT Reaction of 4,5-dibromo-1,2,3-triazole with electron-deficient aromatic halides in the presence of potassium carbonate in DMF produces the corresponding 2-aryl-4,5-dibromotriazoles with high regioselectivity. Subsequent debromination of these triazoles by hydrogenation furnishes 2-aryltriazoles in excellent yields. Overall, this two-step process provides an efficient access to 2-aryl-1,2,3-triazoles.

0 Bookmarks
 · 
43 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: 1,2,3-Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper-catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1-substituted 1,2,3-triazoles. However, only a few methods are available for the selective preparation of 2-substituted 1,2,3-triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2-aryl-1,2,3-triazoles. Our strategy involves a three-step synthesis under continuous-flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2-substituted 1,2,3-triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3-triazoles.
    Chemistry - A European Journal 07/2014; · 5.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Disclosed herein is a general catalytic system for the intermolecular anti-Markovnikov hydroamination of alkenes. By using an organocatalytic photoredox system, α- and β-substituted styrenes as well as aliphatic alkenes undergo anti-Markovnikov hydroamination. Heterocyclic amines were also successfully employed as nitrogen nucleophiles, thus providing a direct route to heterocyclic motifs common in medicinal agents.
    Angewandte Chemie International Edition 04/2014; · 11.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rhodium-catalyzed, highly N(2) - and N(1) -selective coupling of benzotriazoles with allenes is reported. The exceptionally high N(2) and N(1) selectivities were achieved by using a rhodium(I)/DPEphos and rhodium(I)/JoSPOphos catalyst, respectively. This method permits the atom-economic synthesis of valuable branched N(2) - and N(1) -allylated benzotriazole derivatives and allows for preliminary studies of their reactivity.
    Angewandte Chemie International Edition in English 05/2014; · 13.45 Impact Factor