Oxidative Aromatization of 3,4-Dihydroquinolin-2(1H)-ones to Quinolin-2(1H)-ones Using Transition-Metal-Activated Persulfate Salts

Abstract

Inorganic persulfate salts were identified as efficient reagents for the oxidative aromatization of 3,4-dihydroquinolin-2­(1H)-ones through the activation of readily available transition metals, such as iron and copper. The feasible protocol conforming to the requirement of green chemistry was utilized in the preparation of the key intermediate (7-(4-chlorobutoxy)­quinolin-2­(1H)-one 2) of brexpiprazole in 80% isolated yield on a 100 g scale, and different quinolin-2­(1H)-one derivatives with various functional groups were demonstrated in 52–89% yields.

Divergent Total Syntheses of Yaequinolone-Related Natural Products by Late-Stage C–H Olefination

“…The combined organic extracts were washed with water three times and brine two times, dried with MgSO 4 , filtrated, and concentrated in vacuo to yield 5-ethoxy-3,4-dihydroquinolin-2­(1 H )-one as a white solid (800 mg, 98%), which was pure enough to be directly used for the next step. Its 1 H NMR data matched with those reported in the literature …”

“…Its 1 H NMR data matched with those reported in the literature. 29 1 H NMR (400 MHz): δ 7.58 (br s, 1H), 7.10 (t, J = 8.1 Hz, 1H), 6.56 (d, J = 8.2 Hz, 1H), 6.35 (d, J = 7.9 Hz, 1H), 4.05 (q, J = 7.0 Hz, 2H), 2.97 (t, J = 7.7 Hz, 2H), 2.60 (dd, J = 8.4, 6.9 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H).…”

“…Its 1 H NMR data matched with those reported in the literature. 29 1 H NMR (400 MHz): δ 7.20−7.15 (m, 1H), 6.63−6.61 (m, 2H), 4.05 (q, J = 7.0 Hz, 2H), 3.34 (s, 3H), 2.93−2.88 (m, 2H), 2.60 (t, J = 7.3 Hz, 2H), 1.42 (t, J = 7.0 Hz, 3H).…”

Sodium Persulfate (Na2S2O8)

“…The proposed mechanism for this transformation involves a transition-metal activation of persulfate salts in a single-electron transfer (SET) pathway. 3 (G) To expand the scope of application for the oxidative system Fe(OAc)2/NaI/Na2S2O8, Zhou and coworkers carried out an intramolecular dehydrogenative coupling reaction to afford pharmacologically relevant oxindazole derivatives from a variety of anilides. For the reaction optimization, different oxidants were tested, including K2S2O8, (NH4)2S2O8 and Na2S2O8, where the latter gave the best results.…”

“…1 In organic synthesis, sodium persulfate can be used as an oxidant in transition-metal-catalyzed reactions or as an oxidative species in crucial steps in metal-free reactions. 2,3 Na 2 S 2 O 8 is an inexpensive oxidant that is stable and easy to handle, making it a good reagent choice for several strategic synthetic transformations. 4 It is synthesized industrially through an electrolytic oxidation process from sodium hydrogen sulfate, 5 and recent applications for this compound are presented herein (Table 1).…”