4.04 – Pyrazoles and their Benzo Derivatives

Cycloaddition reactions have figured prominently in both synthetic and mechanistic organic chemistry.1,2 Current understanding of the underlying principles in this area has grown from a fruitful interplay between theory and experiment.3 The monumental work of Huisgen and coworkers in the early 1960s led to the general concept of 1,3-dipolar cycloaddition.4–7 Few reactions rival this process in the number of bonds that undergo transformation during the reaction, producing products considerably more complex than the reactants. Over the years this reaction has developed into a generally useful method of five-membered heterocyclic ring synthesis, since many 1,3-dipolar species are readily available and react with a wide variety of dipolarophiles. 1,3-Dipolar cycloadditions are bimolecular in nature and involve the addition of a 1,3-dipole (1) to a multiple π-bond system (2) leading to five-membered heterocycles (3; equation 1).

4.9 – Intermolecular 1,3-Dipolar Cycloadditions

Diazo groups have broad and tunable reactivity. That and other attributes endow diazo compounds with the potential to be valuable reagents for chemical biologists. The presence of diazo groups in natural products underscores their metabolic stability and anticipates their utility in a biological context. The chemoselectivity of diazo groups, even in the presence of azido groups, presents many opportunities. Already, diazo compounds have served as chemical probes and elicited novel modifications of proteins and nucleic acids. Here, we review advances that have facilitated the chemical synthesis of diazo compounds, and we highlight applications of diazo compounds in the detection and modification of biomolecules.

Diazo Compounds: Versatile Tools for Chemical Biology.

Publisher Summary The 1,2,3-triazolines were first discovered during their studies on the action of organic azides on quinones. Triazolines have assumed considerable importance as intermediates in a number of organic syntheses and recently as a new class of potential anticonvulsant drugs. This chapter presents a comprehensive, unified survey of the methods of synthesis and reactions of Δ 2 -1,2,3-Triazolines. The chemistry of mono-, bi-, and polycyclic triazolines, and that of spiro- and bistriazolines, is considered. A brief account of the chemistry of Δ 3 - and Δ 4 -1,2,3-triazolines is given. Triazoline aromatization to triazoles is achieved by oxidation, isomerization reactions, and elimination of stable molecular fragments, all of which require the presence of free hydrogen at position 4 and/or 5 of the triazoline ring. The aromatization reaction affords a selective, synthetic route for the preparation of triazoles of definitive structure, in as much as azide addition to acetylenes is not regioselective.

Sabine Vass

Papers

Reactivity sequences of dipolarophiles towards diazocarbonyl compounds - MO perturbation treatment