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

Abstract

Mechanisms of the unimolecular and bimolecular isomerization of nitrile N‐oxide to isocyanate were investigated by quantum chemical calculations using the global reaction route mapping (GRRM) technique, which consists of the anharmonic downward distortion following (ADDF) and multi‐component artificial force induced reaction (AFIR) methods, which can exhaustively search reaction paths. In the unimolecular isomerization, isomerization paths of nitrile N‐oxide to isocyanate were exhaustively explored by the ADDF method. The energetically lowest path for 2,6‐dimethoxybenzonitrile oxide (Ar–CNO) isomerization was via oxazirine intermediate formation, which was the rate‐determining step with an activation free energy of 56.8 kcal mol–1. The high activation free energy indicates that the isomerization hardly proceeds as a thermal unimolecular reaction. Next, the bimolecular isomerization paths of Ar–CNO were explored for diradical addition, [3+2] and [3+3] cycloadditions, and self‐catalyzed isomerization through the AFIR method. The diradical addition was the energetically lowest path with an activation free energy of 55.4 kcal mol–1. Although the bimolecular isomerization was energetically favorable than the unimolecular isomerization, its activation free energy was still high for the reaction to proceed under thermal conditions. Exhaustive path searching for these unimolecular and bimolecular isomerizations suggest that these reactions are catalyzed by acid or base.

From Humorous Post to Detailed Quantum-Chemical Study: Isocyanate Synthesis Revisited

“…[17] Thus, chemically unreliable barriers exceeding 50 and sometimes even 80 kcal/mol were obtained. [18][19][20][21] In 1977, fascinatingly illogical isomerization from nitrile oxides to isocyanate under relatively mild conditions was demonstrated, but remained almost unnoticed (see Figure 2). [14] Authors speculated that the reaction proceeds through the 1,3-dipolar cycloaddition (Huisgen reaction), and thus isomerization is an oxygen exchange, with SO 2 playing an atypical role of a catalyst.…”

CHNO – Formylnitrene, Cyanic, Isocyanic, Fulminic, and Isofulminic Acids and their Interrelationships at DFT and CASPT2 Levels of Theory

“…Global reaction route mapping consisting of anharmonic downward distortion following and multicomponent artificial force induced reaction methods were employed with the wB97-XD functional combined with the 6-31G(d,p) basis set to map the relationships between the HCNO isomers. 62 The nitrene HC(O)N and oxazirine c-HC(ON) were considered as separate entities with a large energy separation (52 kcal/mol), the oxazirine being of the lowest energy, and a high barrier between them (114 kcal/mol from the nitrene), but the nitrene calculated this way was not an energy minimum. Optimization caused it to collapse into the oxazirine.…”

From a humorous post to a detailed quantum-chemical study: isocyanate synthesis revisited

“…16 Thus, chemically unreliable barriers exceeding 50 and sometimes even 80 kcal mol À1 were obtained. [17][18][19][20] In 1977, fascinatingly illogical isomerization from nitrile oxides to isocyanate under relatively mild conditions was demonstrated, but remained almost unnoticed (see Fig. 2).…”

“…15 Since the development of computational chemistry, numerous studies have aimed to explain the nitrile-oxide-to-isocyanate isomerization; however, usually, the objects were “spherical molecules in a vacuum.” 16 Thus, chemically unreliable barriers exceeding 50 and sometimes even 80 kcal mol −1 were obtained. 17–20 In 1977, fascinatingly illogical isomerization from nitrile oxides to isocyanate under relatively mild conditions was demonstrated, but remained almost unnoticed (see Fig. 2).…”