Scope of tetrazolo[1,5- a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

Abstract

The conversion of tetrazolo[1,5-a]quinoxalines to 1,2,3-triazoloquinoxalines and triazoloimidazoquinoxalines under typical conditions of a CuAAC reaction has been investigated. Derivatives of the novel compound class of triazoloimidazoquinoxalines (TIQ) and rhenium(I) triazoloquinoxaline complexes as well as a new TIQ rhenium complex were synthesized. As a result, a small 1,2,3-triazoloquinoxaline library was obtained and the method could be expanded towards 4-substituted tetrazoloquinoxalines. The compatibility of various aliphatic and aromatic alkynes towards the reaction was investigated and the denitrogenative annulation towards imidazoloquinoxalines could be observed as a competing reaction depending on the alkyne concentration and the substitutions at the quinoxaline.

Keywords: CuAAC; click reaction; denitrogenative annulation; imidazole; metal complexes; quinoxaline; tetrazole; triazole.

Scheme 1

Reactions of tetrazoloquinoxalines 1 to 1,2,3-triazoloquinoxalines 3 via CuAAC and denitrogenative annulation to imidazo[1,2-a]quinoxalines 2 catalyzed by an iron porphyrin catalyst 5 in combination with Zn. The scheme includes all quinoxaline-based derivatives that were obtained by these procedures so far [–12].

Scheme 2

Synthesis of tetrazolo[1,5-a]quinoxalines. Reaction conditions: (a) 9, THF or 4 M HCl, 70–110 °C, 2–3 h; (b) POCl₃, 100 °C, 2–4 h, yields over two steps are given above; (c) NaN₃, DMF, 60–80 °C, 2–26 h; (d) H₂NNH_2·H₂O, EtOH, 25 °C, 21 h; (e) NaNO₂, AcOH/H₂O, 0 °C, 3 h; (f) diverse conditions, see Supporting Information File 1 for details.

Scheme 3

Synthesis of 1,2,3-triazole-substituted quinoxalines via CuAAC from tetrazolo[1,5-a]quinoxaline (11a). ^aSynthesis of 14j* from 14j = Et₂NH, K₂CO₃, DMF, 70 °C, 1 d.

Scheme 4

Mechanism of CuAAC vs denitrogenative annulation.

Scheme 5

Synthesis of bis(tetrazolo)[1,5-a:5',1'-c]quinoxaline (24) and conversion to triazoloimidazoquinoxalines (TIQs): 2.5 equiv hexyne, 10 mol % (CuOTf)₂·C₆H₆ (7), toluene, 100 °C, 4 h to 3 d. ORTEP diagram of triazoloimidazoquinoxaline 25b with the thermal ellipsoids shown at 50% probability.

Scheme 6

Synthesis of rhenium tricarbonyl complexes 27a–d and ORTEP diagrams of the resulting molecular structures with the thermal ellipsoids shown at 50% probability.

Scheme 7

Synthesis of rhenium tricarbonyl complex 29 and ORTEP diagram of the resulting molecular structure with the thermal ellipsoids shown at 50% probability.

Scheme 8

Synthesis of a TIQ rhenium complex and ORTEP diagram of the obtained product 30 with the thermal ellipsoids shown at 50% probability.

Figure 1

UV–vis absorption spectra of the obtained metal complexes (18 µM solutions) in acetonitrile at 20 °C.

Figure 2

Cyclic voltammetry traces for rhenium complexes 27a–d, 29 and 30: 0.5 mM in MeCN solution with 0.1 M Bu₄NPF₆ under nitrogen at 25 °C, recorded at 0.1 V/s at a glassy carbon electrode and referenced to the saturated calomel electrode (SCE) using Fc/Fc⁺ as an internal standard (0.46 V vs SCE [12]).