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.

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

References and Notes

1a Allen MC. Fuhrer W. Tuck B. Wade R. Wood JM. J. Med. Chem.  1989,  32:  1652 

1b Patel DV. Rielly-Gauvin K. Ryono DE. Tetrahedron Lett.  1990,  31:  5587 

1c Stowasser B. Budt KH. Li JQ. Peyman A. Ruppert D. Tetrahedron Lett.  1992,  33:  6625 

2 Kafarski P. Lejczak B. Phosphorus, Sulfur Silicon Relat. Elem.  1991,  63:  1993 

3a Baylis EK. Campbell CD. Dingwall JG. J. Chem. Soc., Perkin Trans. 1  1984,  2845 

3b Atherton FR. Hassal CH. Lambert RW. J. Med. Chem.  1986,  29:  29 

4 Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 

5a Engel R. Chem. Rev.  1977,  77:  349 

5b Hiratake J. Oda J. Biosci. Biotechnol. Biochem.  1997,  61:  211 

5c Schug KA. Lindner W. Chem. Rev.  2005,  105:  67 

5d Moonen K. Laureyn I. Stevens CV. Chem. Rev.  2004,  104:  6177 

5e Palacios F. Alonso C. De Los Santos JM. Curr. Org. Chem.  2004,  8:  1481 

6 Hafez EA. Elnagdi MH. Elagamey AGA.
El-Taweel FMAA. Heterocycles  1987,  26:  903 

7 Hiramoto J. Nasuhara A. Michiloshi K. Kato T. Kikugawa K. Mutat. Res.  1997,  395:  47 

8 Bianchi G. Tava A. Agric. Biol. Chem.  1987,  51:  2001 

9a Elagamey AGA. El-Taweel FMAA. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.  1990,  29:  885 

9b Bloxham J. Dell CP. Smith CW. Heterocycles  1994,  38:  399 

10a Dömling A. Curr. Opin. Chem. Biol.  2000,  4:  318 

10b Dömling A. Curr. Opin. Chem. Biol.  2002,  6:  306 

10c Ugi I. Werner B. Dömling A. Molecules  2003,  8:  53 

10d Weber L. Drug Discovery Today  2002,  7:  143 

10e Orru RVA. Greef M. Synthesis  2003,  1471 

10f Bienayme H. Hulme C. Oddon G. Schmitt P. Chem. Eur. J.  2000,  6:  3321 

10g Dömling A. Chem. Rev.  2006,  106:  17 

10h Zhu J. Bienayme H. Multicomponent Reactions   Wiley-VCH; Weinheim: 2005. 

11a Frost CG. Chauhan KK. J. Chem. Soc., Perkin Trans. 1  2000,  3015 

11b Fringuelli F. Piermatti O. Pizzo F. Vaccaro L. Curr. Org. Chem.  2003,  7:  7 

11c Frost CG. Hartley JP. Mini-Rev. Org. Chem.  2004,  1:  1 

12a Shanthi G. Perumal PT. Synlett  2008,  2791 

12b Shanthi G. Perumal PT. Tetrahedron Lett.  2007,  48:  6785 

12c Shanthi G. Perumal PT. Tetrahedron Lett.  2008,  49:  7139 

12d Shanthi G. Subbulakshmi G. Perumal PT. Tetrahedron  2007,  63:  2057 

12e Babu G. Nagarajan R. Natarajan R. Perumal PT. Synthesis  2000,  661 

12f Babu G. Perumal PT. Aldrichimica Acta  2000,  33:  16 

12g Babu G. Perumal PT. Tetrahedron  1998,  54:  1627 

12h Babu G. Perumal PT. Tetrahedron Lett.  1997,  38:  5025 

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.

15 Bhuyan PJ. Deb ML. Tetrahedron Lett.  2005,  46:  6453