Metal-free Cross-Dehydrogenative Coupling of HN-azoles with α-C(sp³)-H Amides via C–H Activation and Its Mechanistic and Application Studies

Abstract

A metal-free one step coupling reaction between various N-azole rings and diverse α-C(sp)-H containing amides has been developed under oxidative reaction conditions. Commercially available tetrabutyl ammonium iodide (TBAI) in the presence of terbutylhydroperoxide (TBHP), under neat reaction condition, efficiently catalyzed the coupling. Various azole types, such as 1H-benzotriazoles, 1H-1,2,3-triazoles, 1H-1,2,4-triazoles, 1H-tetrazoles, 1H-pyrazoles, and 1H-benzimidazoles, and α-C(sp)-H containing amides, such as N,N-dimethylacetamide, N,N-dimethylbenzamide, N-methylacetamide, N,N-diethylacetamide, N-methylpyrrolidine, and pyrrolidine-2-one, were successfully employed for the coupling. A series of designed and controlled experiments were also performed in order to study the involvement of the different intermediates. Based on the evidence, a plausible mechanism is also proposed. These novel, simple, rapid, attractive, and straightforward transformations open the way of the construction of novel highly functionalized N-azoles via direct covalent N-H bond transformations onto N-C bonds. This approach allows to the synthesis of complex molecules requiring number of steps using classical synthetic ways. In addition, the range of α-C(sp)-H containing amide substrates is virtually unlimited highlighting the potential value of this simple system for the construction of complex heterocyclic molecules, such as fused azoles derivatives.

On Water Cu@g‐C3N4 Catalyzed Synthesis of NH‐1,2,3‐Triazoles via [2+3] Cycloadditions of Nitroolefins/Alkynes and Sodium Azide

“…Again, NH ‐1,2,3‐triazole is one of the important class of 1,2,3‐triazoles with numerous applications. Particularly, these moieties can further be modified synthetically with alkyl/aryl/acyl‐functionality with choice to yield N2‐substituted 1,2,3‐triazoles . Few pharmaceutically active drugs containing NH ‐1,2,3‐triazole scaffold were shown in Figure …”

Intermolecular CDC amination of remote and proximal unactivated Csp3–H bonds through intrinsic substrate reactivity – expanding towards a traceless directing group

“…A nitrogen centered radical (NCR) is generated by reacting tetrazole with a combination of iodide and peroxide or tert -butyl hydroperoxide (TBHP)/tetrabutylammonium iodide (TBAI). 17 a , b In the absence of any other radical coupling partners, the generated NCR abstracts a methyl (–CH 3 ) group from the TBHP giving a N 2 -methylated tetrazole exclusively. 17 a Taking cues from this and the non-directed remote C sp 3 –H bond functionalization strategies, 6–8,9 a particularly Wu's and Tang's trifluorothiomethylation, 9 b , c we envisaged the incorporation of N-heterocycles (tetrazoles) at an unactivated remote methylene C sp 3 –H position.…”

Bio‐waste Derived Catalytic Approach Towards NH‐1,2,3‐Triazole Synthesis

“…Within the category of 1,2,3‐triazoles, NH‐1,2,3‐triazole is an important class of compounds with distinct application in pharmaceuticals and synthetic organic chemistry. NH‐1,2,3‐triazoles which can be synthetically modified by incorporation of aryl, alkyl or acyl functionalization, have been particularly useful in formation of N 2 ‐substituted‐1,2,3‐triazoles [11–13] . Moreover, many pharmaceutically active molecules contain NH‐1,2,3‐triazole motif as an integral part [14–18] .…”

“…NH-1,2,3triazoles which can be synthetically modified by incorporation of aryl, alkyl or acyl functionalization, have been particularly useful in formation of N 2 -substituted-1,2,3-triazoles. [11][12][13] Moreover, many pharmaceutically active molecules contain NH-1,2,3-triazole motif as an integral part. [14][15][16][17][18] Compared to direct synthesis of substituted triazoles, NH-1,2,3-triazole synthesis is much complex.…”