The mechanism of the reaction of nicotinic acid 1-oxide with acetic anhydride.

The m-CPBA–NH3(g) System: A Safe and Scalable Alternative for the Manufacture of (Substituted) Pyridine and Quinoline N-Oxides

“…7 Moreover, N-oxide derivatives of substituted pyridines serve as key raw materials for the synthesis of rabeprazole, an antiulcer drug, 8 and lansoprazole, a proton pump inhibitor. 9 The 2-and 4-substituted pyridine and quinoline N-oxides have a high demand in drug development 10 and are synthesized by Polonovski rearrangement in the presence of acetic anhydride 11 or trifluoroacetic acid. 12,13 Several reagents are used for N-oxidation of heterocycles, such as peracetic acid/AcOH, 14 perbenzoic acid, 15 monoperphthalic acid, 16 H 2 O 2 /AcOH, 17 H 2 O 2 /[Mn(TDCPP)Cl], 18 H 2 O 2 /MTO, BTSP/HOReO 3 , 19,20 and dimethyl dioxirane.…”

“…Moreover, N -oxide derivatives of substituted pyridines serve as key raw materials for the synthesis of rabeprazole, an antiulcer drug, and lansoprazole, a proton pump inhibitor . The 2- and 4-substituted pyridine and quinoline N -oxides have a high demand in drug development and are synthesized by Polonovski rearrangement in the presence of acetic anhydride or trifluoroacetic acid. , …”

A General and Efficient Synthesis of 2‐Pyridones, 2‐Quinolinones, and 1‐Isoquinolinones from Azine N‐Oxides

“…Traditionally, 2‐pyridones (i.e., 3 ) are prepared by treating N ‐oxides in refluxing acetic anhydride (Scheme A, 1 → 3 ), but an extra hydrolysis step is required. Although this method is useful, the yields are low because of the harsh reaction conditions and poor regioselectivity (C2 vs. C4) . In addition, the exposure of N ‐oxides to prolonged heating and high temperatures can cause safety concerns with regard to thermal stability and the risk of exothermic degradation.…”

Preparation of Pyridine N-oxide Derivatives in Microreactor

“…[18] Another very important application of the N-oxide intermediate is the preparation of 2-hydroxypyridine derivatives, which can be synthesized with Polonovski rearrangement in the presence of TFAA or with Ac 2 O at high temperature. [19,20] The 2-hydroxypyridines can be further functionalized into different 2-substituted pyridine derivatives. [21][22][23][24][25][26] N-oxidants Different N-oxidants are well known in the literature for heteroatom oxidation.…”

“…[20] Besides TFAA, other anhydrides can be used. [44,45] The 2-hydroxy pyridine is produced from pyridine N-oxide at 130°C in batch and 33% conversion is can be achieved.…”