We are grateful to the Science and Engineering Research Board (SERB), India for financial
support (CRG/2022/004763) and the Indian Institute of Technology Hyderabad for providing
facilities.
This report outlines an intramolecular oxidative annulation process involving N-substituted
o-amino phenylacetylene, performed under electrochemical conditions, which yields substituted
quinoline in an undivided cell at room temperature. The reaction features mild conditions,
requiring neither external oxidants nor metals, and achieves yields that range from
good to excellent. Moreover, the synthetic potential of quinoline has been demonstrated
resulting in the synthesis of substituted polycyclic isoindolinone and (aza-)isoindolinone
compounds.
9
Soares RR,
da Silva JM. F,
Carlos BC,
da Fonseca CC,
de Souza LS. A,
Lopes FV,
de Paula Dias RM,
Moreira PO. L,
Abramo C,
Viana GH. R,
de Pila Varotti F,
da Silva AD,
Scopel KK. G.
Bioorg. Med. Chem. Lett. 2015; 25: 2308
22General Procedure for Electrochemical Quinoline Synthesis Into the undivided cell were taken N-substituted o-amino phenylacetylene 1a, KI (1 equiv), 5 mL of DMF–H2O (99:1). The mixture was stirred under constant current (10 mA) with a C anode and
a C cathode in an undivided cell at room temperature for 6 h. After the completion
of reaction as monitored on TLC, the reaction was quenched with cold water and extracted
with EtOAc. The combined organic layer was dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The product was purified by flash column chromatography
using PE and EtOAc as solvent as eluent.Compound 2: 84% yield, yellow solid, mp 124–126 °C. 1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.6 Hz, 1 H), 7.87–7.81 (m, 3 H), 7.75 (t, J = 1.7 Hz, 1 H), 7.64 (ddd, J = 8.7, 6.0, 1.1 Hz, 2 H), 7.57–7.38 (m, 6 H), 3.91 (q, J = 7.1 Hz, 2 H), 0.86 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 195.46, 166.74, 155.93, 148.13, 147.48, 141.97, 136.58, 134.56, 134.52, 131.96,
130.21, 129.75, 129.16, 129.06, 128.94, 128.40, 126.95, 125.96, 123.36, 123.27, 62.16,
13.35. IR (neat): 3062, 2982, 1722, 1672, 1581 cm–1. HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H18ClNO3: 416.1048; found: 416.1060.
27General Procedure for the Synthesis of IsoindolinoneInto the RB were taken substituted quinoline 2aa, 2ad, 2ae, or 2af and hydrazine hydrate (5 equiv). To this EtOH was added and kept under reflux. The
reaction was stirred for 12–24 h. After completion of the reaction as monitored on
TLC, it was quenched with water and extracted with EtOAc. The combined organic layer
was dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The product was purified by flash column chromatography
using PE and EtOAc as eluent.
Compound 2aa: 71% yield, yellow solid, mp 252–254 °C. 1H NMR (600 MHz, DMSO): δ = 8.15 (d, J = 8.4 Hz, 1 H), 7.97 (dd, J = 6.5, 2.9 Hz, 2 H), 7.91–7.81 (m, 2 H), 7.60–7.56 (m, 1 H), 7.51 (ddd, J = 15.4, 8.3, 3.6 Hz, 5 H), 7.18 (t, J = 8.9 Hz, 2 H), 4.38 (s, 2 H). 13C NMR (150 MHz, DMSO): δ = 163.66, 162.71, 161.09, 160.45, 155.02, 154.93, 149.02,
141.50, 137.42, 134.99, 131.66, 130.40, 129.17, 128.68, 127.63, 127.45, 124.46, 120.27,
120.03, 115.36, 115.21, 88.41. IR (neat): 3399, 3060, 2920, 1720, 1656, 1570 cm–1. HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H16FN3O2: 386.1300; found: 386.1271.
28General Procedure for the Synthesis of (Aza-)Isoindolinone
Into the RB were taken substituted quinoline 2ab, 2ac, or 2ag and hydroxylamine hydrochloride (10 equiv). To this, Et3N (10 equiv) was added followed by addition of ethanol under reflux conditions. The
reaction was stirred for 12 h. After completion of the reaction as monitored on TLC,
it was quenched with water and extracted with EtOAc. The combined organic layer was
dried with anhydrous Na2SO4, filtered, and concentrated in vacuo. The product was purified by flash column chromatography
using PE and EtOAc as eluent.Compound 2ab: 79% yield, white solid, mp 210–212 °C. 1H NMR (400 MHz, DMSO): δ = 9.98 (s, 1 H), 8.16 (d, J = 8.5 Hz, 1 H), 7.90 (dt, J = 15.0, 10.4 Hz, 5 H), 7.63–7.41 (m, 8 H). 13C NMR (100 MHz, DMSO): δ = 161.54, 154.81, 153.48, 149.08, 137.29, 137.23, 133.14,
131.88, 131.47, 130.37, 130.02, 129.28, 128.78, 128.54, 128.47, 127.87, 127.57, 124.31,
120.09, 119.37, 88.11. IR (neat): 3450, 3063, 2922, 1705, 1618, 1564 cm–1. HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H15ClN2O3: 403.0844; found: 403.0827.
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