Synthesis of polyfunctional stable nitrile oxides of the thiophene series and their relative reactivities in 1,3-dipolar cycloaddition with styrene

Exploration of Unimolecular and Bimolecular Pathways for Nitrile N‐Oxide Isomerization to Isocyanate Through Global Reaction Route Mapping Techniques

“…In the ring closure of the diradical intermediate, the substituent R of nitrile N ‐oxides approaches each other. This can explain that the dimerization can be prevented by the introduction of a bulky substituent to R, such as 2,6‐dimethoxyphenyl, thereby preventing rotation. Additionally, the furoxanes are decomposed to nitrile N ‐oxides by the flash vacuum thermolysis method (600 °C, 10 –3 Torr), indicating that further isomerization of furoxanes to isocyanates does not occur.…”

“…The important reaction pathways among the exhaustive ones were calculated with the realistic nitrile N ‐oxide, 2,6‐dimethoxybenzonitrile oxide (Ar–CNO), with increasing calculation complexity at the ωB97X‐D/6‐311G(d,p) level using the Gaussian 16 program . It is known that Ar–CNO resists dimerization . The optimized molecular structures were verified by vibrational analysis; the equilibrium structures did not have imaginary frequencies and each transition state structure had only one imaginary frequency corresponding to the reaction coordinate.…”

“…On the other hand, a nitrile N ‐oxide, as a reagent for a 1,3‐dipolar cycloaddition reaction, is inactivated by its thermal isomerization to the corresponding isocyanate, and its dimerization to the furoxane, as shown in Scheme . Although a method of suppressing this dimerization reaction has been reported, the issue of inactivation of nitrile N ‐oxides as substrates for click reactions due to isomerization has not been solved.…”