Study of the Addition Mechanism of 1H-Indazole and Its 4-, 5-, 6-, and 7-Nitro Derivatives to Formaldehyde in Aqueous Hydrochloric Acid Solutions

Abstract

The reaction of NH -indazoles with formaldehyde in aqueous hydrochloric acid has been experimentally studied by solution and solid-state nuclear magnetic resonance (NMR) and crystallography. The mechanism of the formation of N 1 -CH 2 OH derivatives was determined. For the first time, 2-substituted derivatives have been characterized by multinuclear NMR. Theoretically, calculations with gauge-invariant atomic orbitals (GIAOs) at the Becke three-parameter (exchange) Lee–Yang–Parr B3LYP/6-311++G(d,p) level have provided a sound basis for the experimental observations. The first X-ray structures of four (1 H -indazol-1-yl)methanol derivatives are reported.

A theoretical study of dynamic processes observed in trimethylsilyl-1H-pyrazoles: prototropy and silylotropy

“…a reference [39]; b reference [36]; c pure liquid: references [22,40] In the case of compound 1 in CD 3 OD at low temperature (-90 ºC), only H3, H5 and SiMe 3 were reported to appear at 7.70, 7.56 and 0, 21 ppm, respectively. The data of Table 1 were analyzed statistically using the calculated mean values; with regard to CDCl 3 , the other solvents (CCl 4 , CD 3 OD and "neat liquid") do not modify the values in a significant way; on the other hand, the NH proton of compound 1 differs significantly from the GIAO calculated value in the gas phase 9.06 vs. 12.97 and 14.58 ppm), a well-known fact [41]. In the following equation, NH variable corresponds to these differences but statistically calculated.…”

DFT Study on Mechanism of Ni–Al Bimetallic-Catalyzed C–H Cyclization to Construct Tricyclic Imidazoles: Roles of NHC Ligand and AlMe3

“…Tricyclic imidazoles and their 7-membered ring derivatives, as one of the most important classes of structural motifs, − are widely present in numerous biologically active material molecules. Owing to their significance, the synthesis of tricyclic imidazoles and their 7-membered ring derivatives − has attracted widespread attention, and extensive effort has been devoted to the development of new methodologies. − Among a large number of strategies, direct construction of a 7-membered ring via C7–H cyclization of benzimidazoles with alkenes would provide a more straightforward, atom- and step-economic access to tricyclic imidazoles from more easily accessible substrates.…”

Design and Synthesis of Indazole–Indole Hybrid via tert-Butyl Nitrite Mediated Cascade Diazotization/Isomerization/Cyclization

“…However, we also studied the electronic effects of p -NO 2 on the aryl ring of the 2-alkenyl aniline moiety, which could directly affect the diazonium-assisted cyclization. It was observed that these compounds underwent smooth cycloisomerization reactions in 76% and 80% yields with nonseparable tautomeric forms of 1 H- and 2 H -indazoles in 3:1 and 6:1 ratios (Scheme , 5k , 5n ) . There was no such steric influence of the ortho -phenyl group on the aryl ring of the 2-alkenyl aniline moiety (Scheme , 5f ).…”