Advances in Organic Synthesis: Volume 11

Atta-ur-Rahman

• Publisher: Bentham Science Publishers
• Year: 2018
• ISBN:
  9781681087474
• Topic: Physical Sciences
• Subtopic: Organic Chemistry

Advances in Organic Synthesis is a book series devoted to the latest advances in synthetic approaches towards challenging structures. The series presents comprehensive reviews written by eminent authorities on different synthetic approaches to selected ta

Synthesis and Applications of 1,2,3-Triazoles

Elżbieta Wojaczyńska^{*, 1}, Jacek Wojaczyński²

¹ Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland

² Faculty of Chemistry, University of Wrocław, Wrocław, Poland

Abstract

The chapter is devoted to the recent developments in the synthesis of 1,2,3-triazoles and their selected applications. Since the introduction of a classic Huisgen reaction which involved thermal 1,3-dipolar cycloaddition of alkynes to azides, its catalytic modifications have been elaborated, allowing the regioselective preparation of 1,4- and 1,5-disubstituted derivatives in copper(I)- or ruthenium(II)-catalyzed cyclizations (click reactions). Most of the other synthetic pathways generally also utilize organic azides or sodium azide, although methods based on other starting materials (e.g. hydrazine derivatives) are also of importance. A special attention is paid to the preparation of chiral triazole derivatives. Various applications of triazoles are also discussed, with a focus on their use as isosteres of biological functionalities, sensors for ions and neutral molecules, in catalysis and in construction of supramolecular assemblies.

Keywords: Alkyne, Azide, Bioisostere, Chemosensor, Click Reaction, CuAAC Reaction, Cyclization, Heterocyclic Compound, Multicomponent Reaction, Nitrogen Heterocycle, N-Tosylhydrazone, RuAAC Reaction, Supramolecular Chemistry, 1,3-Dipolar Cycloaddition, 1,2,3-Triazole.

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^* Corresponding author Elżbieta Wojaczyńska: Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland; Tel: [phone]; Fax: [phone]; E-mail: [email protected]

INTRODUCTION

1,2,3-Triazole, a five-membered diunsaturated heterocycle containing three nitrogen atoms at adjacent positions, ranks among the most important scaffolds used for the construction of bioactive molecules and functional materials. Three tautomeric forms of this compound are found in various derivatives: 1H-1,2,3-triazole, which can bear substituents at 1, 4, and 5 positions, 2H-1,2,3-triazole, with the possible 2,4,5-substitution pattern, and relatively rare 4H-1,2,3-triazole in which stabilization due to delocalization takes place only for certain 4,4,5-substituted rings (Fig. 1).

Fig. (1))
Tautomers of 1,2,3-triazole (from left to right): 1H-1,2,3-triazole, 2H-1,2,3-triazole, and 4H-1,2,3-triazole and their possible substitution patterns.

The story of this heterocycle begins in 1888 with works of Hans von Pechmann (1850-1902), a former assistant of Adolph von Baeyer and a professor of universities in Munich (1886-95) and Tübingen (1895-1902). The name of this brilliant synthetic organic chemist [1] is now associated with his discovery of diazomethane, first (accidental) preparation of polyethylene, syntheses of 1,2-diketones, ketoaldehydes, ketoacids and development of a new route to coumarins (Pechmann condensation). He is also commemorated in the protocol of preparation of pyrazoles (Pechman synthesis). Von Pechmann succeeded in the synthesis of substituted 1,2,3-triazoles from diacetyl (butane-2,3-dione) derivatives, e.g. di(phenylhydrazone) (Fig. 2), and properly identified them as containing a trinitrogen five-membered heterocycle [2, 3]. He was also able to obtain a parent compound [4]. Later, various routes to triazole derivatives have been introduced. In 1893, Arthur Michael (1853-1942), an American chemist, reported the isolation of a product prepared by heating acetylene diester derivative with phenyl azide (Fig. 3) [5]. Michael, known for the discovery of the reaction which now bears his name, studied in Germany with Robert Bunsen and August Wilhelm von Hofmann, in France with Charles Adolphe Wurtz and Russia with Dmitri Mendeleev, and returned to the United States in 1880 to become a professor of chemistry at Tufts College in Medford, Massachusetts.

Fig. (2))
Von Pechmann’s syntheses of 1,2,3-triazole derivatives [2, 3].

The use of acetylene and hydrogen azide for the preparation of unsubstituted 1,2,3-triazole (Fig. 4) was later described by Otto Dimroth (1872-1940) and Gustav Fester (1886–1963) [6]. Dimroth, a pupil and coworker of Johannes Thiele and Adolf von Baeyer at the University of Munich, worked also with von Pechmann and succeeded him as the Professor at the University of Tübingen. He was later connected with the Universities of Greifswald and Würzburg. The versatility of the cycloaddition has been recognized and the idea has been further developed by Rolf Huisgen (born 1920) [7]. Huisgen prepared his doctorate under the supervision of Heinrich Otto Wieland at the University of Munich in 1943 and worked at his Alma Mater until the retirement in 1988, with a short period at the University of Tübingen (1949-1952). His works on diazoalkanes led him to a general concept of 1,3-cycloaddition conceived in the late 50s. He summarized the idea in two reviews, published in Angewandte in 1963, in which the directions of further research were ...