C-H Amination of Nitro Aza-Heterocyclic Compounds by Vicarious Nucleophilic Substitution

This manuscript describes the C-H amination of a variety of nitro aza-heterocyclic compounds by Vicarious Nucleophilic Substitution (VNS) methodology with 4-amino-1,2,4-triazole (ATA). The aminated products were characterized by NMR, MS and single-crystal X-ray diffraction. Among the substrates examined, moderate to excellent yield (30-88%) and good regioselectivity (ortho/para position of the nitro) are exhibited. This protocol offers the advantages of mild conditions, short reaction time (only 2-4 h) with inexpensive, commercially available and less toxic amination reagent, no additional catalysts or reagents needed. Possible reaction mechanism was also discussed.

Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one were determined by single-crystal X-ray diffraction measurements. The 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one illustrate the nitro/nitroso conversion within VNS reaction. Additionally, 9-(8-isopropyl-2-((8-isopropyl-2-methyl-5-nitroquinolin-6-yl)methyl)-5-nitrosoquinolin-6-yl)-9H-carbazole is presented as a double VNS product. It is postulated that the potassium counterion interacts with the oxygen on the nitro group, which could influence nucleophile attack in that way.

Simple Synthesis of Dimethyl Nitrobenzhydrylphosphonates and Heteroarylnitroarylacetonitriles via Vicarious Nucleophilic Substitution (VNS) Reaction

Acetals of dimethyl phenyl- and heteroaryl-α-hydroxymethanephosphonates were deprotonated to generate carbanions, which enter the vicarious nucleophilic substitution (VNS) of hydrogen in aromatic nitro compounds to form 4-nitrobenzhydrylphosphonates and α-heteroaryl-4-nitrobenzylphosphonates. Similarly acetals of cyano­hydrins of heteroaromatic aldehydes (furfural and 2-formylthiophene) react to form heteroaryl 4-nitroarylacetonitriles. The anion of the hemiacetal of acetaldehyde is an efficient leaving group in the base-induced β-elimination step – the crucial step in the VNS reaction. The reaction selectively occurred at the para-position to the nitro group.

α-Fluorination of Nitrobenzenes and Nitropyridines via Vicarious Nucleophilic Substitution of Hydrogen

A highly selective C–H functionalization of nitrobenzenes and nitropyridines is reported using tandem vicarious nucleophilic substitution (VNS) chemistry with electrophilic fluorination using Selectfluor®. The process generates tertiary benzylic fluorides in good yield under simple, mild conditions and short reaction times.

New nitroindazolylacetonitriles: efficient synthetic access via vicarious nucleophilic substitution and tautomeric switching mediated by anions

Efficient synthesis of new N-methylnitroindazolylacetonitriles and their ability to switch between tautomeric forms in the presence of anionic species.

Metal-free Deamidative Ugi Access to Isoindolinones

A two-step isoindolone synthesis has been achieved by using an Ugi/oxidative vicarious nucleophilic substitution sequence starting from 3-nitrobenzoic acid and aromatic aldehydes. Loss of the amido group was observed as well as a further oxidative process towards hydroxyisoindolone derivatives after prolonged stirring open to the atmosphere.