Synthesis and Reactions of Homoditopic Stable Nitrile N‐Oxide as a Powerful Tool for Catalyst‐Free Constructions of Macromolecular Architectures

Abstract

Nitrile N-oxide is a highly reactive 1,3-dipole that undergoes 1,3-dipolar cycloaddition reactions to various dipolarophiles. However, the high reactivity of nitrile N-oxide leads to side reactions with nucleophiles and self-reactions, resulting in a decrease in the cycloadduct yield. The bulky substituent around nitrile N-oxide kinetically suppresses such undesirable side reactions, stabilizing nitrile N-oxide, and improving 1,3-dipolar cycloaddition efficiency. Homoditopic stable nitrile N-oxides as a ligation tool between unsaturated bonds are developed, although the challenge of the large-scale synthesis remains. Herein, the practical synthesis of a homoditopic stable nitrile N-oxide from bismaleimide is reported. Three simple steps, namely, Michael addition, oximation, and oxidation, produce the homoditopic nitrile N-oxide in 87% overall yield without purification process using column chromatography. The ligation capacity of nitrile N-oxide is discussed through polycycloadditions with several bisdipolarophiles and the cross-linking reaction of polyacrylonitrile.

Synthesis of Highly Stable and Reactive Nitrile N-Oxides and Their Application as Catalyst-Free Crosslinkers

“…Recently, a catalyst-free click reaction with nitrile N -oxides as azide substitutes for ligation has attracted a great deal of attention. , Nitrile N -oxide is a useful 1,3-dipole, which allows the [3 + 2] 1,3-dipolar cycloaddition reaction with some unsaturated bond-containing units such as alkynes, alkenes, and nitriles to produce heterocycles in the absence of a catalyst, , and such a reaction finds many potential applications in the fields of synthetic chemistry, polymer science, and materials science. − However, most nitrile N -oxides with simple structures are kinetically liable and peculiarly prone to undergo self-reactions such as isomerization, dimerization, and oligomerization to yield undesirable byproducts. − Significantly, the introduction of neighboring bulky substituents can greatly improve the stability of nitrile N -oxides. Grundmann et al prepared stable aromatic nitrile N -oxides by introducing sterically hindered substitutes to the o,o ′-positions .…”

Efficient metal-free crosslinking of common propellant binders using nitrile oxide–alkene click ligation

“…Nitrile oxide is a promising azide substitute that can perform metal-free cycloaddition reactions with unsaturated bond-containing units such as alkenes, alkynes and nitriles to yield heterocycles. [20][21][22] Primarily, nitrile oxide-alkene cycloaddition reactions have been used in polymer crosslinking. 23,24 However, most reported nitrile oxide crosslinkers are purely difunctional and are not adapted to the commonly used linear propellant binders containing two reactive end groups.…”