The Boekelheide Rearrangement of Pyrimidine N‐oxides as a Case Study of Closed or Open Shell Reactions ‐ Experimental and Computational Evidence for the Participation of Radical Intermediates

• Published in: Chemistry : a European journal Vol. 29; no. 26; pp. e202204015 - n/a
• Main Authors: Kurzawa, Timon, Zimmer, Reinhold, Würthwein, Ernst‐Ulrich, Reissig, Hans‐Ulrich
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 08.05.2023; Wiley Subscription Services, Inc
• Subjects: Acetic anhydride; Acidic oxides; Carboxylic acids; Case studies; Chemistry; Chemistry, Multidisciplinary; heterocycles; Hydrogen atoms; Intermediates; Ion pairs; Methyl radicals; Physical Sciences; quantum chemical calculations; Quantum chemistry; radicals; reaction mechanism; rearrangement; Science & Technology; Solvents; QUADRATIC CONFIGURATION-INTERACTION; 3-COMPONENT SYNTHESIS; radicals; MECHANISM; PYRIDINE; ALKOXYALLENES; BETA-KETOENAMIDES; COUPLED-CLUSTER SINGLES; reaction mechanism; heterocycles; quantum chemical calculations; CHEMISTRY; HETEROAROMATICS; DERIVATIVES; rearrangement
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202204015

In a case study, the acetic anhydride‐promoted reaction of a model pyrimidine N‐oxide to the corresponding 4‐acetoxymethyl‐substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin‐4‐yl)methyl radical is one of the key species of the rearrangement. This interpretation was supported by the fact that rearrangements performed in solvents which can easily lose hydrogen atoms, afford considerable quantities of products incorporating the solvent. With TEMPO the key radical could be trapped. Other carboxylic acid anhydrides confirm the conclusion that the Boekelheide rearrangement of the model pyrimidine N‐oxide proceeds, at least in part, via radical intermediates. The high level closed and open shell quantum chemical calculations show that concerted [3,3]‐sigmatropic rearrangements or stepwise processes, either via ion pairs or via radicals, are energetically feasible. Heterocycles: The rearrangement of a model pyrimidine N‐oxide with carboxylic acid anhydrides provides the acyloxymethyl‐substituted compounds as major products. In addition, other compounds derived from radical intermediates are formed in considerable amounts under certain conditions. By comprehensive experimental and quantum‐chemical calculations, a rationale for the apparently competing mechanisms is proposed. The pathways via closed shell and open shell intermediates are compared.