Recent Advances in N‐Hyrdoxypthalimide: As a Free Radical Initiator and its Applications

Abstract

N‐Hydroxypthalimide (NHPI) has become a powerful and versatile organocatalyst, it has been known to catalyze various free‐radical processes leading to the wide range of organic transformations. Primarily, phthalimido‐N‐oxyl (PINO) radical formed from NHPI is highly efficient abstraction species for carrying out radical chain reactions. In this review, we have discussed about the most important and successful reactions from last six years, with their plausible reaction mechanisms. This review broadly covers the type of bond formation such as carbon‐carbon, carbon‐oxygen and carbon‐nitrogen bond formations. We have also highlighted various types of reaction strategies where in combination with divergent reagent systems it helps to construct different types of molecules which further find applications in the synthesis of complex set of biologically active molecule. NHPI catalyzed oxidation reactions of different class of organic compounds are also reviewed.

A Mechanistic Investigation of the N-Hydroxyphthalimide Catalyzed Benzylic Oxidation Mediated by Sodium Chlorite

“…Exposure of the alcohol 16 to standard reaction conditions (NaClO 2 1.5 equiv, NHPI 1 10 mol %, AcOH 1.0 equiv, MeCN/ H 2 O (2:1), 50 °C) showed some conversion to fluorenone 11; however, the reaction was considerably slower. Conversion of fluorenol 16 reached just 14% after 90 min and 94% after 24 h. In addition, the oxidation of fluorene 10 in the presence of 18 OH 2 (10% v/v) led to ketone 11 (98%) with no isotope incorporation. To support this observation, stirring a sample of fluorenone 11 with acetic acid (1.0 equiv) in 2:1 MeCN/ 18 OH 2 for 2 h at 50 °C showed no incorporation of the heavy atom by LCMS analysis.…”

“…Since the first report by Cohn in 1880, N -hydroxyphthalimide (NHPI) 1 has been developed as a robust and versatile organocatalyst for a broad variety of C–C, C–O, C–N, and C–S bond forming reactions. − Of specific note in the chemistry of this molecule is the conversion of 1 to the phthalimide- N -oxyl (PINO) radical 2 , a compound that is stable enough to function as a catalytically active species within many transformations. Abstraction of a hydrogen atom from organic substrates by 2 regenerates NHPI 1 and forms a reactive carbon centered radical that can participate in clean and efficient bond forming processes. − …”

Overlooked interaction between redox-mediator and bisphenol-A in permanganate oxidation

“…The toxicity of TEMPO, ABNO, and PTIO hinders their application in real aquatic environments. NHPI with lower toxicity has a similar cyclic transformation to TEMPO ( Scheme 1 ) [ 26 , 27 ]. Besides, NHPI can be easily loaded onto heterogeneous materials (e.g., metal-organic frameworks, porous polymers, and high-surface-area carbons) [ 28 ]; thus, it might be superior to the reported nitroxides-RMs (i.e., HBT [ 11 ], TEMPO [ 13 ], ABNO [ 17 ], and PTIO [ 18 ]).…”

Porous Aromatic Framework Covalently Embedded with N‐Hydroxyphthalimide as Metal‐free Heterogeneous Catalyst for Highly Efficient and Selective Aerobic Oxidation

“…[3] In particular, the N-hydroxyphthalimide (NHPI) has emerged as a low-cost but very efficient organic radicalprecursor catalyst for establishing prominent selective oxidation systems. [19][20][21][22][23][24] However, most of the NHPI-involved catalysis is homogeneous which inevitably suffers from the disabilities to complete removal and easy-purification, etc. With the urgent demands and requirements for green and sustainable industrial applications, the construction of heterogeneous catalysts from NHPI has attracted great attention and gradually sprouted recently.…”

“…In the past few decades, catalytic oxidation reactions have developed from the inexpensive but hazardous inorganic catalysts, precious metal complexes to organic free radicals, and from the homogeneous to heterogeneous catalysis [3] . In particular, the N ‐hydroxyphthalimide (NHPI) has emerged as a low‐cost but very efficient organic radical‐precursor catalyst for establishing prominent selective oxidation systems [19–24] . However, most of the NHPI‐involved catalysis is homogeneous which inevitably suffers from the disabilities to complete removal and easy‐purification, etc.…”