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Synlett 2014; 25(08): 1145-1149
DOI: 10.1055/s-0033-1341069
letter
© Georg Thieme Verlag Stuttgart · New York

Phenylphosphonic Acid as Efficient and Recyclable Catalyst in the Synthesis of α-Aminophosphonates under Solvent-Free Conditions

Mercedes Bedolla-Medrano
a   Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México   Fax: +52(777)3297997   Email: palacios@uaem.mx
,
Eugenio Hernández-Fernández
b   Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Pedro de Alba S/N, Ciudad Universitaria, 66400 San Nicolás de los Garza, Nuevo León, México
,
Mario Ordóñez*
a   Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, México   Fax: +52(777)3297997   Email: palacios@uaem.mx
› Author Affiliations
Further Information

Publication History

Received: 19 December 2013

Accepted after revision: 03 March 2014

Publication Date:
07 April 2014 (online)

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Abstract

Phenylphosphonic acid is an efficient, friendly and reusable heterogeneous catalyst for the synthesis of α-aminophosphonates through a ‘one-pot’ three-component reaction of amines, carbonyl compounds and dialkyl phosphites under solvent-free conditions. This methodology illustrates a very simple procedure, with wide applicability, extending the scope to aliphatic and aromatic amines, aliphatic and aromatic aldehydes and aliphatic ketones. It also enabled the synthesis of α-aminophosphonates in large scale, clean conversion, easy workup and purification. Excellent results were obtained in each case obtaining the desire compounds in moderate to good yields.

Key words

α-aminophosphonates - phenylphosphonic acid catalyst - solvent-free conditions - heterogeneous catalysis
 

  • References and Notes

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  • 24 In a typical experiment, to a mixture of aldehyde or ketone (2.0 mmol) and benzylamine (2.0 mmol) was added the phenylphosphonic acid (5; 10 mol%). The reaction mixture was stirred at r.t. for 20 min. After this time, dimethyl phosphite (2.1 mmol) was added and the reaction mixture was stirred at 50 °C for the specific period of time (see Tables 1–3), and the progress of the reaction was monitored by TLC. The crude was directly subjected to silica gel flash chromatography eluting with EtOAc, obtaining the pure α-aminophosphonates. 1H NMR, 13C NMR, 31P NMR, and HRMS data for some newly obtained α-aminophosphonates are as follows. Compound 6g: yellow liquid. 1H NMR (400 MHz, CDCl3): δ = 3.48 [d, J = 10.5 Hz, 3 H, (MeO)2P], 3.52 (AB system, J = 13.3 Hz, 1 H, Bn), 3.78 (AB system, J = 13.3 Hz, 1 H, Bn), 3.79 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.89 (d, J = 20.1 Hz, 1 H, CHP), 6.63 (ddd, J = 8.0, 2.0, 2.0 Hz, 1 H, HAr), 6.77 (d, J = 8.0 Hz, 1 H, HAr), 7.11 (dd, J = 2.0, 2.0 Hz, 1 H, HAr), 7.20–7.31 (m, 5 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 50.8 (d, J = 17.6 Hz, Bn), 53.8 [d, J = 7.1 Hz, (MeO)2P], 54.1 [d, J = 7.6 Hz, (MeO)2P], 58.2 (d, J = 157.8 Hz, CHP), 114.7 (d, J = 5.0 Hz), 115.1, 121.0 (d, J = 8.1 Hz), 126.0, 127.2, 128.4 (2 × C), 139.0, 145.0 (2 × C). 31P NMR (161.9 MHz, CDCl3): δ = 26.62. HRMS (FAB+): m/z [M + H]+ calcd for C16H21NO5P: 338.1157; found: 338.1159. Compound 6k: white solid; mp 94–96 °C. 1H NMR (400 MHz, CDCl3): δ = 2.44 (br s, 1 H, NH), 3.58 (AB system, J = 13.3 Hz, 1 H, Bn), 3.58 [d, J = 10.5 Hz, 3 H, (MeO)2P], 3.75 [d, J HP = 10.6 Hz, 3 H, (MeO)2P], 3.84 (AB system, J = 13.3 Hz, 1 H, Bn), 4.10 (d, J = 20.2 Hz, 1 H, CHP), 7.22–7.36 (m, 6 H, HAr), 7.40–7.52 (m, 4 H, HAr), 7.59–7.64 (m, 4 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 51.3 (d, J = 17.4 Hz, Bn), 53.6 [d, J = 6.6 Hz, (MeO)2P], 53.9 [d, J = 6.6 Hz, (MeO)2P], 59.1 (d, J = 154.3 Hz, CHP), 127.1, 127.3, 127.4, 127.5, 128.5 (d, J = 6.7 Hz), 128.9, 129.1 (d, J = 5.5 Hz), 134.6, 139.3, 140.7, 140.9, 141.0. 31P NMR (161.9 MHz, CDCl3): δ = 23.05. HRMS (FAB+): m/z [M + H]+ calcd for C22H25NO3P: 382.1572; found: 382.1588. Compound 6l: colorless liquid. 1H NMR (400 MHz, CDCl3): δ = 2.17 (br s, 1 H, NH), 3.52 (AB system, J = 13.3 Hz, 1 H, Bn), 3.58 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.74 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.80 (AB system, J = 13.3 Hz, 1 H, Bn), 3.93 (s, 3 H, MeO), 4.13 (d, J = 20.7 Hz, 1 H, CHP), 7.21–7.36 (m, 5 H, HAr), 7.52 (AA′BB′ system, J = 8.3, 2.2 Hz, 2 H, HAr), 8.06 (AA′BB′ system, J = 8.3 Hz, 2 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 51.5 (d, J = 17.3 Hz, Bn), 52.3 (MeO2C), 53.7 [d, J = 6.9 Hz, (MeO)2P], 54.0 [d, J = 6.9 Hz, (MeO)2P], 59.4 (d, J = 152.8 Hz, CHP), 127.5, 128.5, 128.7, 128.8 (d, J = 5.9 Hz), 130.0, 130.1, 138.9, 141.1, 166.9. 31P NMR (161.9 MHz, CDCl3): δ = 22.15. HRMS (FAB+): m/z [M + H]+ calcd for C18H23NO5P: 364.1314; found: 364.1322. Compound 6n: white solid; mp 59–62 °C. 1H NMR (400 MHz, CDCl3): δ = 2.35 (br s, 1 H, NH), 3.52 (AB system, J = 13.2 Hz, 1 H, CH2Ph), 3.61 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.74 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.79 (AB system, J = 13.2 Hz, 1 H, CH2Ph), 4.12 (d, J = 20.6 Hz, 1 H, CHP), 7.21–7.35 (m, 5 H, HAr), 7.55 (AA′BB′ system, J = 8.1, 1.4 Hz, 2 H, HAr), 7.64 (AA′BB′ system, J = 8.1 Hz, 2 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 51.5 (d, J = 17.1 Hz, CH2Ph), 53.7 [d, J = 6.9 Hz, (MeO)2P], 54.0 [d, J = 7.0 Hz, (MeO)2P], 59.3 (d, J = 153.0 Hz, CHP), 124.3 (q, J = 275.0, CF3), 125.7 (dq, J = 3.6, 3.6 Hz), 127.6, 128.5, 128.7, 129.1 (d, J = 5.9 Hz), 130.4 (dq, J = 32.2, 2.9 Hz), 138.9, 140.1 (d, J = 3.5 Hz). 31P NMR (161.9 MHz, CDCl3): δ = 24.78 (q, J = 2.5 Hz). HRMS (FAB+): m/z [M + H]+ calcd for C17H20F3NO3P: 374.1133; found: 374.1035. Compound 6p: yellow liquid. 1H NMR (400 MHz, CDCl3): δ = 2.56 (br s, 1 H, NH), 3.43 [d, J = 10.4 Hz, 3 H, (MeO)2P], 3.60 (AB system, J = 13.4 Hz, 1 H, CH2Ph), 3.74 [d, J = 10.5 Hz, 3 H, (MeO)2P], 3.82 (AB system, J = 13.4 Hz, 1 H, CH2Ph), 4.09 (d, J = 20.2 Hz, 1 H, CHP), 6.10–6.17 (m, 2 H, HAr), 6.78 (ddd, J = 4.3, 2.6, 1.8 Hz, 1 H, HAr), 7.18–7.35 (m, 5 H, HAr), 9.71 (br s, 1 H, NH-pyrrole). 13C NMR (100 MHz, CDCl3): δ = 51.2 (d, J = 16.9 Hz, CH2Ph), 52.5 (d, J = 160.4 Hz, CHP), 53.5 [d, J = 6.9 Hz, (MeO)2P], 53.9 [d, J = 7.0 Hz, (MeO)2P], 108.1, 109.5 (d, J = 9.4 Hz), 119.0, 124.8 (d, J = 5.4 Hz), 127.2, 128.4, 128.5, 139.5. 31P NMR (161.9 MHz, CDCl3): δ = 22.70. HRMS (FAB+): m/z [M + H]+ calcd for C14H20N2O3P: 295.1212; found: 295.1224. Compound 6q: yellow liquid. 1H NMR (200 MHz, CDCl3): δ = 1.94 (br s, 1 H, NH), 3.60 (AB system, J = 13.3 Hz, 1 H, Bn), 3.64 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.81 [d, J = 10.6 Hz, 3 H, (MeO)2P], 3.87 (AB system, J = 13.3 Hz, 1 H, Bn), 4.12 (d, J = 22.2 Hz, 1 H, CHP), 6.36–6.42 (m, 2 H, HAr), 7.22–7.35 (m, 5 H, HAr), 7.46 (ddd, J = 2.5, 1.8, 0.8 Hz, 1 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 51.3 (d, J = 16.4 Hz, CH2Ph), 52.7 (d, J = 162.5 Hz, CHP), 53.4 [d, J = 6.9 Hz, (MeO)2P], 53.9 [d, J = 6.8 Hz, (MeO)2P], 109.5 (d, J = 7.5 Hz), 110.6, 127.2, 128.4 (2 × C), 138.8, 142.7 (2 × C). 31P NMR (81 MHz, CDCl3): δ = 23.36. HRMS (FAB+): m/z [M + H]+ calcd for C14H19NO4P: 296.1052; found: 296.1039. Compound 6r: colorless oil. 1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 7.3 Hz, 3 H, Me), 1.31–1.43 (m, 1 H, CH2), 1.49–1.64 (m, 3 H, NH, CH2), 1.68–1.81 (m, 1 H, CH2), 2.91 (ddd, J = 12.2, 8.5, 4.6 Hz, 1 H, CHP), 3.77 [d, J = 9.9 Hz, 3 H, (MeO)2P], 3.80 [d, J = 9.9 Hz, 3 H, (MeO)2P], 3.87 (AB system, J = 13.1, 1.8 Hz, 1 H, Bn), 3.96 (AB system, J = 13.1 Hz, 1 H, Bn), 7.20–7.37 (m, 5 H, HAr). 13C NMR (100 MHz, CDCl3): δ = 14.0 (Me), 19.4 (d, J = 10.9 Hz, CH2), 32.1 (CH2), 52.3 (d, J = 5.0 Hz, CH2Ph), 52.8 [d, J = 7.6 Hz, (MeO)2P], 53.0 [d, J = 6.4 Hz, (MeO)2P], 53.7 (d, J = 149.4 Hz, CHP), 127.2, 128.5 (2 × C), 140.1. 31P NMR (161.9 MHz, CDCl3): δ = 28.35. HRMS (FAB+): m/z [M + H]+ calcd for C13H23NO3P: 272.1416; found: 272.1415.
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