A One-Pot Approach to 2-(N-Substituted Amino)-1,4-naphthoquinones with Use of Nitro Compounds and 1,4-Naphthoquinones in Water

Abstract

A one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones from 1,4-naphthoquinones and nitro compounds in water has been developed. This method features mild reaction conditions and provides aromatic nitro compounds with various functional groups such as halogens, methylthio, ester, amide, even allyl, propargyl, and heterocycles, as well as aliphatic nitro compounds that are well tolerated. This method can be scaled up and we conducted further transformation of the obtained 2-(N-substituted amino)-1,4-naphthoquinones to synthesize carbazolequinone derivatives.

Key words

amines - 1,4-naphthoquinones - nitro compounds - one-pot reactions - reactions in water - carbazolequinones

• References and Notes

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• 27 Typical Procedure: Preparation of 2-(Phenylamino)naphthalene-1,4-dione (3aa) ²⁵To a solution of 1,4-naphthoquinone (0.3 mmol, 1 equiv), nitrobenzene (0.36 mmol, 1.2 equiv), Zn(OAc)₂ ·2H₂O (0.06 mmol, 20 mol%), Zn (1.5 mmol, 5 equiv) in H₂O (0.6 mL) was added AcOH (4.5 mmol, 15 equiv). The resulting mixture was stirred for 5 h at rt. Then, the reaction mixture was diluted with water, filtered to remove the residual Zn dust, extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine, dried with Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was then purified by column chromatography (petroleum ether/EtOAc 5:1) on silica gel to afford the desired product as red solid (yield: 93%), mp 184–187 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.21–8.03 (m, 2 H), 7.84–7.70 (m, 1 H), 7.73–7.61 (m, 1 H), 7.57 (s, 1 H), 7.43 (t, J = 7.9 Hz, 2 H), 7.26 (t, J = 7.4 Hz, 3 H), 7.21 (d, J = 7.3 Hz, 1 H), 6.42 (s, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 183.92, 182.05, 144.69, 137.41, 134.91, 133.18, 132.34, 130.34, 129.68, 126.51, 126.14, 125.60, 122.58, 103.36.
• 28 Reaction on Gram ScaleTo a solution of 1,4-naphthoquinone (1a) (2.3 g, 15 mmol, 1 equiv), 1-methoxy-4-nitrobenzene (2c) (18 mmol, 1.2 equiv), Zn(OAc)₂ ·2H₂O (3 mmol, 20 mol%), Zn (75 mmol, 5 equiv) in H₂O (30 mL) was added AcOH (0.2 mol, 15 equiv). The resulting mixture was stirred for 5 h at rt. Then, the reaction mixture was diluted with water and extracted with EtOAc (3×80 mL). The combined organic layers were washed with brine, dried with Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was then purified by column chromatography (petroleum ether/EtOAc 5:1) on silica gel to afford the desired product 3ac (yield: 2.9 g, 71%).
• 29 Synthesis of 2-Methoxy-5H-benzo[b]carbazole-6,11-dione (4ac) ²⁶To a solution of 2-(4-methoxyphenylamino)naphthalene-1,4-dione (3ac) (0.13 g, 0.5 mmol, 1 equiv) in DMF (2.0 mL) were added Pd(OAc)₂ (0.1 mmol, 0.2 equiv) and Cu(OAc)₂ (1.25 mmol, 2.5 equiv). The resulting mixture was stirred for 24 h at 120 °C. Then, the reaction mixture was cooled to rt, diluted with water and extracted with EtOAc (3×20 mL). The combined organic layers were washed with water, brine, dried with Na₂SO₄, filtered, and concentrated under reduced pressure. The resulting crude product was then purified by column chromatography (petroleum ether/EtOAc 1:1) on silica gel to afford the desired product 4ac as a yellow solid (yield: 90.1 mg, 65%), mp 300–305 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.00 (s, 1 H), 8.08 (t, J = 7.3 Hz, 2 H), 7.81 (d, J = 19.1 Hz, 2 H), 7.59 (d, J = 2.1 Hz, 1 H), 7.47 (d, J = 9.0 Hz, 1 H), 7.07 (dd, J = 9.0, 2.3 Hz, 1 H), 3.84 (s, 3 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 180.06, 177.02, 156.76, 136.82, 133.98, 133.25, 132.96, 132.55, 125.83, 124.65, 118.24, 116.82, 114.80, 101.91, 55.20.