Acid‐Catalyzed Rearrangements of 3‐Aryloxirane‐2‐Carboxamides: Novel DFT Mechanistic Insights

Abstract

Efficient synthesis of 3‐arylquinolin‐2(1H)‐ones and N‐(2‐carboxyaryl)‐oxalamides from protic acid‐catalyzed rearrangements of 3‐aryloxirane‐2‐carboxamides was achieved recently but not well understood. In contrast to the classical Meinwald rearrangement, extensive DFT calculations reveal that the proximal aryl and amide groups have strong synergetic effects to control the amide‐aided and aryl‐directed oxirane‐opening and further rearrangement sequences. The ortho‐nitro substituent of the proximal aryl is directly involved in a nucleophilic oxirane ring‐opening, the amide C=O is an important proton shuttle for facile H‐shifts, while the N‐aryl may act as a potential ring‐closing site via Friedel‐Crafts alkylation. The mechanistic insights are useful for rational design of novel synthesis by changing the aryl and amide functional groups proximal to the oxirane ring.

Three-Dimensional Large-Scale Fused Silica Microfluidic Chips Enabled by Hybrid Laser Microfabrication for Continuous-Flow UV Photochemical Synthesis

“…Regarding superior optical transmission properties of fused silica ranging from 200 nm to 3500 nm, on-chip UV photochemical synthesis using the same glass chip was performed. Cycloaddition reactions are reliable and effective in the synthesis of polycyclic compounds which are important for pharmaceutical engineering [31][32][33] and fine chemical engineering [34,35]. These reactions are usually driven by heat or light.…”

Divergent Synthesis of 3-(Indol-2-yl)quinoxalin-2-ones and 4-(Benzimidazol-2-yl)-3-methyl(aryl)cinnolines via Polyphosphoric Acid (PPA)-Mediated Intramolecular Rearrangements of 3-(Methyl/aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones

“…To gain mechanstic insights, extensive DFT calculations were carried out at the PW6B95-D3/def2-QZVP + COSMO-RS // TPSS-D3/def2-TZVP + COSMO level in acetic acid solution . The final Gibbs free energies (at 298 K and 1 M concentration) in solution are used in our discussion.…”

Synthesis and Mechanistic Insights of the Formation of 3-Hydroxyquinolin-2-ones including Viridicatin from 2-Chloro-N,3-diaryloxirane-2-carboxamides under Acid-Catalyzed Rearrangements

“…According to our previous experience with anilides of arylglycidic acids ( N ,3-diaryl-3-oxirine-2-carboxamides), the direction of acid-catalyzed rearrangements and the structure of the resulting products are sensitive to small changes in the structures of these compounds. For example, the acid-catalyzed rearrangement of N ,3-diaryloxrine-2-carboxamides, which do not contain ortho -nitro groups in the aryl fragment of the epoxy ring, proceeds with the formation of the corresponding 3-arylquinoline-2­(1 H )-ones regardless of the nature of the substituents in the aryl fragments, , and the rearrangement of 3-(2-nitrophenyl)­oxirane-2-carboxamides ( N ,3-diaryloxirane-2-carboxamides with an ortho -nitro group in the aryl fragment at the epoxy ring) proceeds with the formation of N -(2-carboxyphenyl)­oxalamides. , …”

“…According to our previous experience with anilides of arylglycidic acids (N, 3-diaryl-3-oxirine-2-carboxamides), the direction of acid-catalyzed rearrangements and the structure of the resulting products are sensitive to small changes in the structures of these compounds. For example, the acid-catalyzed rearrangement of N,3-diaryloxrine-2-carboxamides, which do not contain ortho-nitro groups in the aryl fragment of the epoxy ring, proceeds with the formation of the corresponding 3-arylquinoline-2(1H)-ones regardless of the nature of the substituents in the aryl fragments, 24,25 and the rearrangement of 3-(2-nitrophenyl)oxirane-2-carboxamides (N,3-diaryloxirane-2-carboxamides with an ortho-nitro group in the aryl fragment at the epoxy ring) proceeds with the formation of N-(2-carboxyphenyl)oxalamides. 25,26 The question therefore arises: is the pathway shown in Scheme 2 the only route leading to 4-arylquinolin-2(1H)-ones 4 from anilides of arylchloroglycidic acids 5, or are there alternative options for the formation of 4-arylquinolinones 4? To answer this question, we investigated the reaction of the formation of 4-arylquinolin-2(1H)-ones 4 from chloroxiranocarboxamides 5 in more detail under various cyclization conditions by changing the reaction conditions and substituents in the aryl groups at the epoxy ring and in the anilide fragment.…”