PAPER
Synthesis of Bis(1-diethoxyphosphorylalkyl)amines
3065
31P NMR (101 MHz, CDCl3, H3PO4): d = 23.36/23.68 (68:32).
Anal. Calcd for C22H31F2NP2O6: C, 55.8; H, 6.5; N, 3.0. Found: C,
55.7; H, 6.4; N, 3.1.
Anal. Calcd for C22H33NP2O6: C, 56.3; H, 7.1; N, 3.0. Found: C,
56.2; H, 7.1; N, 2.8.
Bis(1-diethoxyphosphoryl-m-nitrophenylmethyl)amine (2g)
Yield: 69%; colorless oil.
Bis(1-diethoxyphosphoryl-p-methoxyphenylmethyl)amine (2b)
Yield: 71%; colorless oil.
1H NMR (250 MHz, CDCl3, TMS): d = 1.14-1.35 (m, 12 H), 3.82-
4.23 (m, 11 H), 7.40-7.70 (m, 4 H), 8.05-8.41 (m, 4 H).
1H NMR (250 MHz, CDCl3, TMS): d = 1.14 (t, J = 7.1 Hz, 6 H),
1.29 (t, J = 7.1, 6 H), 1.69 (br, 1 H, NH), 3.68-4.35 (m, 16 H), 6.87
(d, J = 8.5 Hz, 4 H), 7.22 (d, J = 8.5 Hz, 4 H).
13C NMR (62.9 MHz, CDCl3, TMS): d = 148.5, 136.9, 134.7, 129.8,
123.4, 123.3, 62.8-63.7 (c), 57.3 (dd, JPC = 154.5, 16.6 Hz), 55.1,
16.0-16.5 (c).
13C NMR (62.9 MHz, CDCl3, TMS): d = 159.4, 129.9, 125.9, 113.8,
62.4-62.8 (c), 56.4 (dd, JPC = 156.7, 17.9 Hz), 55.1, 16.1-16.3 (c).
31P NMR (101 MHz, CDCl3, H3PO4): d = 21.04/21.58 (88:12).
31P NMR (101 MHz, CDCl3, H3PO4): d = 23.78/24.00 (72:28).
Anal. Calcd for C22H31N3P2O10: C, 47.2; H, 5.5; N, 7.5. Found: C,
47.0; H, 5.3; N, 7.4.
Anal. Calcd for C24H37NP2O8: C, 54.4; H, 7.0; N, 2.6. Found: C,
54.3; H, 7.1; N, 2.7.
Bis(1-diethoxyphosphoryl-b-naphthylmethyl)amine (2h)
Yield: 67%; colorless oil.
Bis(1-diethoxyphosphoryl-p-chlorophenylmethyl)amine (2c)
Yield: 72%; colorless oil.
1H NMR (250 MHz, CDCl3, TMS): d = 1.10 (t, J = 7.0 Hz, 6 H),
1.31 (t, J = 7.0, 6 H), 3.03 (br, 1 H, NH), 3.70-4.57 (m, 10 H), 7.35-
7.92 (m, 14 H).
1H NMR (250 MHz, CDCl3, TMS): d = 1.15 (t, J = 7.1 Hz, 6 H),
1.29 (t, J = 7.1 Hz, 6 H), 2.19 (br, 1 H, NH), 3.65-4.35 (m, 10 H),
7.23 (d, J = 8.25 Hz, 4 H), 7.33 (d, J = 8.25 Hz, 4 H).
13C NMR (62.9 MHz, CDCl3, TMS): d = 133.3, 132.0, 131.9, 128.4,
127.9, 127.7, 126.2, 62.8-63.1 (c), 57.7 (dd, JPC = 155.1, 17.8 Hz),
16.1-16.3 (c).
13C NMR (62.9 MHz, CDCl3, TMS): d = 134.1, 132.9, 130.1, 128.9,
62.9-63.2 (c), 56.9 (dd, JPC = 155.4, 17.6 Hz), 16.3-16.4 (c).
31P NMR (101 MHz, CDCl3, H3PO4): d = 23.27/23.60 (63:37).
31P NMR (101 MHz, CDCl3, H3PO4): d = 22.53/22.90 (79:21).
Anal. Calcd for C30H37NP2O6: C, 63.3; H, 6.5; N, 2.5. Found: C,
63.2; H, 6.5; N, 2.5.
Anal. Calcd for C22H31Cl2NP2O6: C, 52.2; H, 6.1; N, 2.7. Found: C,
52.3; H, 5.9; N, 2.6.
Bis(1-diethoxyphosphoryl-p-fluorophenylmethyl)amine (2d)
Yield: 85%; colorless oil.
Acknowledgment
The Institute for Advanced Studies in Basic Sciences (IASBS) is
thanked for supporting this work.
1H NMR (250 MHz, CDCl3, TMS): d = 1.04 (t, J = 7.0 Hz, 6 H),
1.18 (t, J = 7.0 Hz, 6 H), 2.82 (br, 1 H, NH), 3.57-4.22 (m, 10 H),
6.80-6.97 (m, 4 H), 7.10-7.22 (m, 4 H).
13C NMR (62.9 MHz, CDCl3, TMS): d = 162.0 (d, JCF = 246.5 Hz),
130.4, 115.7, 115.3, 62.6-63.0 (c), 56.6 (dd, JPC = 156.6, 17.6 Hz),
16.1-16.3 (c).
References
(1) (a) Engel, R. Chem. Rev. 1977, 77, 349. (b) Hiratake, J.;
Oda, J. Biosci. Biotechnol. Biochem. 1997, 61, 211.
(c) Schug, K. A.; Lindner, W. Chem. Rev. 2005, 105, 64.
(d) Moonen, K.; Laureyn, I.; Stevens, C. V. Chem. Rev.
2004, 104, 6177. (e) Palacios, F.; Alonso, C.; de los Santos,
J. M. Curr. Org. Chem. 2004, 8, 1481.
31P NMR (101 MHz, CDCl3, H3PO4): d = 22.30/22.67 (73:27).
Anal. Calcd for C22H31F2NP2O6: C, 55.8; H, 6.5; N, 3.0. Found: C,
55.7; H, 6.5; N, 3.2.
(2) Dingwall, J. G.; Campell, C. D.; Baylis, E. K. UK Pat. Appl.,
1542938, 1979; Chem. Abstr., 1979, 88, 105559j.
(3) Kafarski, P.; Lejczak, B.; Tyka, R.; Koba, L.; Pliszczak, E.;
Wieczorek, P. J. Plant Growth Regul. 1995, 14, 199.
(4) Ishiguri, Y.; Yamada, Y.; Kato, T.; Sasaki, M.; Mukai, K.
Eur. Pat. Appl., EP 82301905, 1982; Chem. Abstr., 1983, 98,
102686u.
(5) (a) Gancarz, R.; Chakraborty, S. Synthesis 1977, 625.
(b) Giannousi, P. P.; Bartlett, P. A. J. Med. Chem. 1987, 30,
1603. (c) Maier, L.; Lea, P. J. Phosphorus Sulfur 1983, 17,
1. (d) Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J.
Chem. Soc., Perkin Trans. 1. 1984, 2445. (e) Hilderbrand,
R. L. In The Role of Phosphonates in Living Systems; CRC
Press: Boca Raton F1, 1982.
Bis(1-diethoxyphosphoryl-p-methylphenylmethyl)amine (2e)
Yield: 65%; colorless oil.
1H NMR (250 MHz, CDCl3, TMS): d = 1.04 (t, J = 7.1 Hz, 6 H),
1.19 (t, J = 7.1, 6 H), 2.24 (s, 6 H), 2.85 (br, 1 H, NH), 3.60-4.25
(m, 10 H), 6.95-7.15 (m, 8 H).
13C NMR (62.9 MHz, CDCl3, TMS): d = 137.7, 131.1, 129.2, 128.7,
62.4-62.9 (c), 57.0 (dd, JPC = 156.0, 18.2 Hz), 21.1, 16.1-16.3 (c).
31P NMR (101 MHz, CDCl3, H3PO4): d = 23.69/23.97 (86:14).
Anal. Calcd for C24H37NP2O6: C, 57.9; H, 7.4; N, 2.8. Found: C,
57.7; H, 7.6; N, 2.9.
Bis(1-diethoxyphosphoryl-m-fluorophenylmethyl)amine (2f)
Yield: 61%; colorless oil.
(6) Atherton, F. R.; Hassal, C. H.; Lambert, R. W. J. Med.
Chem. 1987, 30, 1603.
(7) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M.
J. Med. Chem. 1989, 32, 1652.
1H NMR (250 MHz, CDCl3, TMS): d = 1.11 (t, J = 7.0 Hz, 6 H),
1.24 (t, J = 7.0 Hz, 6 H), 2.92 (br, 1 H, NH), 3.65-4.25 (m, 10 H),
6.85-7.09 (m, 6 H), 7.15-7.32 (m, 2 H).
(8) Hassal, C. H. In Antibiotics, Vol VI; Hahn, F. E., Ed.;
Springer Verlag: Berlin, 1983, 1–11.
(9) Kukhar, V. P.; Hudson, H. R. In Aminophosphonic and
Aminophosphinic Acids; John Wiley & Sons: Chichester,
2000.
13C NMR (62.9 MHz, CDCl3, TMS): d = 162.9 (d, JCF = 246.8 Hz),
137.1, 130.1, 124.5, 115.7, 115.3, 62.9-63.2 (c), 57.2 (dd, JPC
155.1, 17.4 Hz), 16.1-16.3 (c).
=
31P NMR (101 MHz, CDCl3, H3PO4): d = 21.71/22.17 (89:11).
Synthesis 2006, No. 18, 3063–3066 © Thieme Stuttgart · New York