Indium Trichloride Catalyzed One-Pot Synthesis of New (2-Amino-3-cyano-4H-chromen-4-yl) Phosphonic Acid Diethyl Ester

Abstract

A one-pot synthesis of new (2-amino-3-cyano-4H-chromen-4-yl) phosphonic acid diethyl ester was achieved in good yields by indium trichloride catalyzed three-component reaction of salicylaldehyde and malononitrile with triethyl phosphite.

Key words

chromenes - salicylaldehyde - triethyl phosphite - malononitrile - three-component

References and Notes

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13

(2-Amino-3-cyano-4 H -chromen-4-yl) Phosphonic Acid Diethyl Ester (4a, Table 1, Entry 1); Typical Procedure
To a stirred mixture of salicylaldehyde (1 mmol) and malononitrile (1 mmol) in EtOH, triethyl phosphite, and InCl₃ (20 mol%) was added. The reaction mixture was stirred at r.t. for the appropriate time (Table  [¹] ). After complete conversion as indicated by TLC, the mixture was poured into ice and extracted with EtOAc. The organic extracts were washed with brine solution, dried over Na₂SO₄, and concentrated under vacuum to yield pure product 4a.

14

(2-Amino-3-cyano-4 H -chromen-4-yl) Phosphonic Acid Diethyl Ester (4a, Table 1, Entry 1)
White solid; mp 140-142 ˚C. IR (KBr): ν_max = 3349, 3167, 2189, 1648, 1422, 1233, 1030 cm^-¹. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 1.09 (t, 3 H, J = 6.9 Hz), 1.14 (t, 3 H, J = 6.85 Hz), 3.87 (m, 4 H), 4.04 (d, 1 H, ^² J _PH = 17.6 Hz), 6.97 (d, 1 H, J = 8.4 Hz), 7.10 (t, 1 H, J = 6.85 Hz), 7.14 (br s, 2 H, NH₂, D₂O exchangeable), 7.22 (m, 2 H). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 16.1, 16.2, 34.5 (d, ^¹ J _CP = 144.0 Hz), 47.3 (d, ^² J _CP = 7.5 Hz), 62.1 (d, ^² J _CP = 7.5 Hz), 62.2 (d, ^² J _CP = 6.75 Hz), 115.9, 117.7, 120.1, 124.2, 128.8, 129.4, 149.9, 162.6. ^³¹P NMR (202.5 MHz, DMSO-d ₆): δ = 23.17. MS: m/z = 308 [M⁺]. Anal. Calcd (%) for C₁₄H₁₇N₂O₄P: C, 54.55; H, 5.56; N, 9.09. Found: C, 54.50; H, 5.52; N, 9.03.
(2-Amino-6-bromo-3-cyano-4 H -chromene-4-yl) Phosphonic Acid Diethyl Ester (4f, Table 1, Entry 6)
White solid; mp 180-182 ˚C. IR (KBr): ν_max = 3353, 3156, 2190, 1655, 1417, 1241, 1040 cm^-¹. ^¹H NMR (300 MHz, DMSO-d ₆): δ = 1.13 (m, 6 H), 3.91 (m, 4 H), 4.17 (d, 1 H, ^² J _PH = 18.0 Hz), 6.99 (d, 1 H, J = 8.7 Hz), 7.26 (br s, 2 H, NH₂, D₂O exchangeable), 7.44 (m, 2 H). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 16.1, 16.2, 34.1 (d, ^¹ J _CP = 144.0 Hz), 47.0 (d, ^² J _CP = 7.5 Hz), 62.2 (d, ^² J _CP = 7.5 Hz), 62.4 (d, ^² J _CP = 7.5 Hz), 115.6, 118.1, 119.8, 120.4, 131.4, 131.8, 149.2, 162.3. ^³¹P NMR (202.5 MHz, DMSO-d ₆): δ = 22.64. MS: m/z = 387 [M⁺], 389 [M + 2]. Anal. Calcd (%) for C₁₄H₁₆BrN₂O₄P: C, 43.43; H, 4.17; N, 7.24. Found: C, 43.38; H, 4.11; N, 7.20.