Facile, high-yield, regioselective synthesis of ortho-nitro derivatives of hydroxy heterocycles using cerium (IV) ammonium nitrate

Abstract

A series of hydroxy heterocycles with two different unsubstituted ortho sites undergo exclusive regioselective nitration with the CAN/NaHCO 3 reagent at the less hindered ortho site. Neither dinitro nor oxidized products were observed. The hydroxy heterocycles studied include: some derivatives of 7-hydroxycoumarins, sesamol, 2,3-dihydrobenzo[b]furan-3-one, 6-hydroxy-1,3-benzoxathiol, 5-hydroxybenzothiazol, 5-hydroxyindole, 7-benzofuranol, and (5-isoxazolyl)phenols. A mechanism is proposed in which an initial oxidation of the phenol to a radical cation by CAN occurs. Another molecule of CAN subsequently reacts with the phenolic radical cation to give an radical adduct from which an NO 2 radical is transferred to the less hindered carbon via a tight ion-radical pair yielding the Wheland complex that furnishes the nitrophenol after proton loss.

Copper-Assisted Direct Nitration of Cyclic Ketones with Ceric Ammonium Nitrate for the Synthesis of Tertiary α-Nitro-α-substituted Scaffolds

“…Initially, we selected commercially available 2-phenylcyclohexanone as a model substrate to test our designed nitration using CAN as a multifunctional reagent. However, competitive side reactions needed to be suppressed, such as the nitration of the C­(sp 2 )–H bond on the phenyl ring, the formation of benzyl nitrates, the cleavage of the C–C bond at the ketone α-position, and the self-coupling of 2-phenylcyclohexanone . After some attempts, to our delight, the desired product 2a was isolated in 43% yield when the reaction was performed in 1,2-dichloroethane (DCE) at 80 °C for 12 h (entry 1).…”

Rate Enhancement in CAN-Promoted Pd(PPh3)2Cl2-Catalyzed Oxidative Cyclization: Synthesis of 2-Ketofuran-4-carboxylate Esters

“…Surprisingly, substrates 6 (Scheme ) underwent both oxidative cyclization and C-6 nitration on the 3,4-dimethoxyaryloyl rings to produce furans 7 . A brief scope of this conversion was shown with substrates 6a , 6d , 6k , and 6l .…”

Intramolecular Dehydrogenative Coupling of 2,3-Diaryl Acrylic Compounds: Access to Substituted Phenanthrenes

“…Also other less reactive substrates such as toluene, halobenzene, and benzene did not afford the coupled product under the above-mentioned optimized conditions (Scheme ). Substrates with two and three methoxy groups at the aryl ring gave the corresponding nitro products ( 8b and 8c ) in place of a biaryl compound (Scheme ).…”