- Email: [email protected]
Structural diversity in phosphoramidate’s chemistry: Syntheses, spectroscopic and X-ray crystallography studies
Polyhedron 28 (2009) 307–321
Contents lists available at ScienceDirect
Polyhedron journal homepage: www.elsevier.com/locate/poly
Structural diversity in phosphoramidate’s chemistry: Syntheses, spectroscopic and X-ray crystallography studies Khodayar Gholivand a,*, Zahra Shariatinia b,1, Seyedeh Mahdieh Mashhadi a, Farzaneh Daeepour a, Narjes Farshidnasab a, Hamid Reza Mahzouni a, Nasrin Taheri a, Shadi Amiri a, Sheida Ansar a a b
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Department of Chemistry, Amirkabir University of Technology, P.O. Box 159163-4311, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 15 September 2008 Accepted 7 October 2008 Available online 4 December 2008 Keywords: Bisphosphoramidates Phosphoramidates NMR X-ray crystallography
a b s t r a c t Novel phosphorus compounds of bisphosphoramidate, phosphoramidate and phosphoric triamide derivatives were synthesized using the starting materials PCl5 and POCl3. The products were then characterized by 1H, 13C, 31P, 19F NMR, IR spectroscopy and CHN elemental analysis. It is noticeable that the reaction of 4-aminobenzamide with PCl5 in different molar ratios yields different products, bisphosphoramides and phosphoric triamides. Moreover, we were taken by surprise that the interaction of POCl3 with the first-type aromatic amines gave bisphosphoramidates with P–N–P linkages that exhibited 2 J(P,P) 20.0 Hz in the 31P NMR spectra. In fact, two simple one-pot pathways are presented here for the synthesis of new bisphosphoramidates, and to the best of our knowledge these are the first instances of bisphosphoramidates that have been obtained up until now. The structures of compounds I (4-OCH3– C6H4–CH2–C9H13–NH2Cl), 34 and 44 were further determined by X-ray crystallography. All of these structures produced three dimensional polymeric chains through strong- and weak hydrogen bonds. The presence of chiral aminoacidester moieties in the phosphoric triamides lead to chiral molecules that showed two sets of signals for the two groups. Interestingly, in phosphoric triamides containing cyanoacetamide moieties, the existence of aromatic amine substituents on the P atoms created central chiral phosphorus atoms, i.e. the two aromatic groups revealed two sets of peaks in the 1H and 13C NMR spectra, while compounds with aliphatic moieties did not display this effect. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Phosphorus chemistry covers a wide area of sciences, including synthesis, coordination, biomedicine and theoretical matters. Phosphoramidates, bisphosphoramidates and phosphoric triamides are some important instances of phosphorus derivatives whose chemistry plays a significant role in various parts of science. Among the phosphoramidates, N-phosphorylated aminoacids have revealed high antitumor, antiviral and anti-HIV activities [1–4]. So far the syntheses and coordination chemistry of many bisphosphoramidates have been reported, containing P–N–P bonds via multi-step reactions [5–9], but here a simple one-pot method is presented to prepare such compounds. These types of compounds are potential bidentate ligands for the coordination to the metal atoms [10,11]. There are some reports on the synthesis of bisphosphoramides containing P(O)–(CH2)n–P(O) or P(O)–N(CH3)–(binaphthyl)–N(CH3)– P(O) moieties [12], as well as the P–(CH2)n–P group [13,14]. In addition, it is expected that due to the presence of the two phosphorus atoms in their structures, they will show more anticancer,
antibacterial and enzyme inhibitory properties than phosphoramidates. Besides, the coordination chemistry of phosphoramidates [15–18], their biological applications [19–22], quantum chemical calculations on their structures [23,24], and their spectroscopic and X-ray crystal structures [25–27] are frequently studied. In the present work, following on from our previous research, we have synthesized and characterized several new phosphorus compounds of phosphoramidates, bisphosphoramidates (including P(O)NHC6H4C(O)NHP(O) and P–N–P linkages), and phosphoric triamides. It is noteworthy that two simple one-pot pathways are presented for the synthesis of the new bisphosphoramidates and, as far as we know, these are the first examples of bisphosphoramidates that have been prepared so far. Furthermore, their NMR, IR and mass spectroscopic features as well as X-ray crystal structures are discussed and compared with our previous data.
2. Experimental 2.1. X-ray measurements
* Corresponding author. Tel.: +98 2182884422; fax: +98 2182883455. E-mail address: [email protected] (K. Gholivand). 1 Tel.: +982164543298; fax: +982164543296. 0277-5387/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2008.10.057
X-ray data of compound 34 were collected on a Bruker APEX II [28] and Siemens P3/PC [29] and those of compounds I and 44 on a
308
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Bruker SMART 1000 CCD [30] single crystal diffractometer with graphite monochromated Mo Ka radiation (k = 0.71073 Å). The structures were refined with SHELXL-97 [31] by full matrix leastsquares on F2. The positions of hydrogen atoms were obtained from the difference Fourier maps. Routine Lorentz and polarization corrections were applied and an absorption correction was performed using the SADABS program for compounds I and 44 [32]. 2.2. Spectroscopic measurements 1
H, 13C and 31P spectra were recorded on a Bruker Avance DRS 500 spectrometer. 1H and 13C chemical shifts were determined relative to internal Me4Si, 31P and 19F chemical shifts relative to 85% H3PO4 and CFCl3 as external standards, respectively. The field strengths for the acquisition of 1H, 13C, 31P and 19F NMR spectra were 500.13, 125.77, 202.46 and 470.54 MHz, respectively. Infrared (IR) spectra were recorded on a Shimadzu model IR-60 spectrometer. Elemental analyses were performed using a Heraeus CHN-O-RAPID apparatus. Melting points were obtained with an electrothermal instrument. The spectroscopic data of the synthesized compounds can be found in the online Supplementary data. 2.3. Syntheses 2.3.1. N,N0 -4-Carboxyamidophenyl-bis phosphoramidic tetrachloride (1) A suspension of 16 mmol PCl5 in 40 mL CCl4 was prepared and then 4.0 mmol of 4-aminobenzamide was slowly added to the mixture at room temperature. After 24 h stirring, the temperature was raised to 80–90 °C to reflux the flask contents. After 5 h, the yellow solution was cooled to 4 °C and 16.0 mmol of formic acid was added dropwise at 5 °C to oxide the product, releasing CO and HCl. The mixture was stirred for 2 h under these conditions and then the white product was washed with CCl4 and dried under vacuum. Yield: 76%. m.p. = 115 °C. Anal. Calc. for C7H6Cl4N2O3P2: C, 22.73; H, 1.64; N, 7.57. Found: C, 22.70; H, 1.64; N, 7.56%. 31P {1H} NMR (CD3CN): d 5.44 (s), 6.69 (s). 31P NMR (202.46 MHz; CD3CN; 85% H3PO4): d 5.44 (m), 6.69 (m). 1H NMR (CD3CN): d 7.37 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.93 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.16 (d, 2J(PNH) = 11.9 Hz, 1H, NHamine), 9.41 (s, 1H, NHamide). 13C NMR (CD3CN): d 120.04 (d, 3J(P,C) = 8.9 Hz), 127.92 (d, 3J(P,C) = 10.6 Hz), 131.19 (s), 131.45 (s), 134.93 (s), 143.79 (s), 167.25 (d, 2J(P,C) = 3.5 Hz, C@O). IR (KBr, cm1): 3405 (s, mNH), 3170 (s, mNH), 3005 (s), 2835 (s, CH), 2595 (s, CH), 2350 (m), 1644 (s, C@O), 1611 (s), 1453 (s), 1272 (s), 1211 (s, mP@O), 1176 (s, mP@O), 1156 (s), 1121 (s), 1098 (s), 1071 (s), 1049 (s), 994 (s, mP–N), 964 (s, mP–N), 750 (m), 537 (m), 478 (s, mP–Cl).
trile solution to yield molecules 3–8 and 10. For the synthesis of diazaphosphole 9, a solution of 4 mmol diamine plus 4 mmol triethylamine was added to the suspension. Compounds 11–13 were synthesized in the same way, but the molar ratio of the corresponding amines to compound 2 was 4:1. 2.3.4. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -isopropyl) phosphoric triamide] (3) Yield: 61%. m.p. = 131.5 °C. Anal. Calc. for C19H38N6O3P2: C, 49.56; H, 8.32; N, 18.26. Found: C, 49.54; H, 8.31; N, 18.26%. 31P NMR (CD3OD): d 9.16 (m), 9.26 (m). 1H NMR (CD3OD): d 0.99 (d, 3 J(H,H) = 6.5 Hz, 6H, CH3), 1.00 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.01 (d, 3J(H,H) = 6.4 Hz, 6H, CH3), 1.02 (d, 3J(H,H) = 6.4 Hz, 6H, CH3), 3.43 (m, 4H CH), 7.17 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.76 (d, 3 J(H,H) = 8.7 Hz, 2H, Ar–H). 13C NMR (CD3OD): d 25.41 (d, 3 J(P,C) = 4.7 Hz, CH3), 25.56 (d, 3J(P,C) = 5.4 Hz, CH3), 25.72 (d, 3 J(P,C) = 3.4 Hz, CH3), 25.77 (d, 3J(P,C) = 2.1 Hz, CH3), 44.33 (s, CH), 44.36 (s, CH), 118.05 (d, 3J(P,C) = 7.0 Hz), 126.20 (d, 3 J(P,C) = 8.0 Hz), 129.48 (s), 130.21 (s), 148.28 (s), 159.98 (s), 170.84 (s, C@O). IR (KBr, cm1): 3315 (s, mNH), 2950 (s, mCH), 1602 (s, mC@O), 1564 (m), 1449 (s), 1419 (s), 1225 (m, mP@O), 1169 (s, mP@O), 1126 (m), 1020 (m), 927 (m, mP–N), 896 (m, mP– N), 833 (m, mP–N), 762 (m, mP–N), 638 (m), 529 (m). 2.3.5. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -isbutyl) phosphoric triamide] (4) Yield: 58%. m.p. = 193 °C. Anal. Calc. for C23H46N6O3P2: C, 53.53; H, 8.98; N, 16.27. Found: C, 53.51; H, 8.98; N, 16.26%. 31P NMR (DMSO-d6): d 9.35 (m), 10.22 (m). 1H NMR (DMSO-d6): d 0.79 (d, 3 J(H,H) = 6.4 Hz, 12H, CH3), 1.16 (d, 3J(H,H) = 6.4 Hz, 12H, CH3), 1.86 (m, 2H, CH), 1.92 (m, 2H, CH), 2.48 (m, 4H CH2), 2.68 (m, 4H, CH2), 4.24 (m, 2H, NH), 4.35 (m, 2H, NH), 7.16 (d, 3 J(H,H) = 8.5 Hz, 2H, Ar–H), 7.22 (b, 1H, NH), 7.49 (d, 3 J(H,H) = 8.5 Hz, 2H, Ar–H). 13C NMR (DMSO-d6): d 19.96 (s, CH3), 20.08 (s, CH3), 28.59 (s, CH2), 29.35 (d, 2J(P,C) = 5.6 Hz, CH2), 45.72 (s, CH), 46.75 (s, CH), 47.73 (s, CH), 48.00 (s, CH), 115.92 (d, 3J(P,C) = 6.8 Hz), 123.65 (d, 3J(P,C) = 8.2 Hz), 128.88 (s), 132.72 (s), 147.15 (s), 158.29 (s), 167.83 (s, C@O). IR (KBr, cm1): 3421 (m, mNH), 3271 (s, mNH), 2959 (s, mCH), 2671 (s, mCH), 1647 (m), 1606 (s, mC@O), 1465 (s), 1252 (m, mP@O), 1190 (s, mP@O), 1090 (s), 922 (m, mP–N), 847 (m, mP–N), 769 (w), 547 (w).
2.3.2. N-(4-Carboxy amidophenyl) phosphoramidic dichloride (2) This compound was prepared in the same way as compound 1, but the molar ratio of 4-aminobenzamide to PCl5 was 1:1. Yield: 95%. m.p. = 80 °C. Anal. Calc. for C7H7Cl2N2O2P: C, 33.23; H, 2.79; N, 28.02. Found: C, 33.22; H, 2.78; N, 28.03%. 31P NMR (DMSO-d6): d 0.14 (m). 1H NMR (DMSO-d6): d 7.38 (d, 3J(H,H) = 8.2 Hz, 2H, Ar– H), 7.93 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 9.36 (b, 3H, NHamine,amide). 13 C NMR (DMSO-d6): d 122.05 (s), 128.94 (s), 132.50 (s), 136.29 (s), 167.11 (s, C@O). IR (KBr, cm1): 3385 (s, mNH), 3185 (s, mNH), 2795 (s, mCH), 2560 (s), 1649 (s, mC@O), 1601 (s), 1577 (s), 1524 (s), 1419 (m), 1293 (m), 1209 (m, mP@O), 1176 (m), 1115 (m), 837 (m, mP–N), 758 (s), 720 (m), 556 (m), 525 (m).
2.3.6. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -diethyl) phosphoric triamide] (5) Yield: 85%. m.p. = 188 °C. Anal. Calc. for C13H46N6O3P2: C, 39.38; H, 11.69; N, 21.20. Found: C, 39.37; H, 11.68; N, 21.21%. 31P NMR (DMSO-d6): d 14.61 (m), 14.96 (m). 1H NMR (DMSO-d6): d 0.96– 1.06 (m, 24H, CH3), 2.95–3.07 (m, 16H, CH2), 7.20 (d, 3 J(H,H) = 8.6 Hz, 2H, Ar–H), 7.31 (d, 2J(PNH) = 9.1 Hz, 1H, NHamine), 7.77 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 8.91 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 13.82 (d, 3J(P,C) = 2.3 Hz, CH3), 14.01 (d, 3 J(P,C) = 2.2 Hz, CH3), 38.84 (d, 2J(P,C) = 5.0 Hz, CH2), 38.92 (d, 2 J(P,C) = 4.6 Hz, CH2), 116. 43 (d, 3J(P,C) = 6.7 Hz), 124.61 (d, 3 J(P,C) = 8.7 Hz), 129.13 (s), 131.27 (s), 147.31 (s), 158.95 (s), 167.43 (s,C@O). IR (KBr, cm1): 3345 (m, mNH), 3153 (s, mNH), 2971 (s, mC–H), 2933 (m, mC–H), 2872 (m, mC–H), 1665 (m), 1607 (s, mC@O), 1523 (m), 1437 (s), 1381 (s), 1268 (s), 1216 (s, mP@O), 1177 (s, mP@O), 1104 (m), 1063 (m), 1026 (s), 941 (m, mP–N), 916 (m, mP–N), 874 (s, mP–N), 843 (s, P–N), 792 (s, P–N), 715 (s), 660 (m), 541(s).
2.3.3. General procedure for the synthesis of compounds 3–12 A solution of 8 mmol of corresponding amines in acetonitrile was added dropwise to a suspension of 1 mmol of compound 1 at 5 °C. After 24 h stirring, the product was filtered and washed with distilled water and recrystallized from a methanol-acetoni-
2.3.7. N,N 0 -4-Carboxyamidophenyl-bis [bis (N00 ,N00 0 -cyclohexyl) phosphoric triamide] (6) Yield: 65%. m.p. = 165 °C. Anal. Calc. for C31H54N6O3P2: C, 59.98; H, 8.77; N, 13.54. Found: C, 59.97, H, 8.77; N, 13.53%. 31P NMR (DMSO-d6): d 7.36 (m), 8.08 (m). 1H NMR (DMSO-d6): d 1.16 (m,
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
24H, CH2), 1.44–1.84 (m, 16H CH2), 2.83 (m, 4H, CH), 4.07 (m, 2H, NH), 4.17 (m, 2H, NH), 7.10 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.32 (d, 2 J(PNH) = 7.6 Hz, 1H, NHamine), 7.74 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 9.27 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 23.92 (s, CH2), 24.71 (d, 3J(P,C) = 2.8 Hz, CH2), 24.80 (d, 3J(P,C) = 2.4 Hz, CH2), 24.93 (d, 3 J(P,C) = 2.6 Hz, CH2), 25.16 (d, 3J(P,C) = 3.8 Hz, CH2), 31.11 (s, CH2), 35.04 (d, 2J(P,C) = 6.1 Hz, CH), 35.21 (d, 2J(P,C) = 6.3 Hz, CH), 35.25 (d, 2J(P,C) = 7.7 Hz, CH), 35.30(d, 2J(P,C) = 7.6 Hz, CH), 49.26 (s, CH2), 49.46 (s, CH2), 116.03 (d, 3J(P,C) = 5.8 Hz), 118.12 (s), 123.80 (d, 3J(P,C) = 7.6 Hz), 124.14 (d, 3J(P,C) = 7.4 Hz), 128.84 (s), 147.26 (s), 167.71 (s, C@O). IR (KBr, cm1): 3310 (m, mNH), 2905 (s, mCH), 1618 (m, mC@O), 1598 (m), 1568 (m), 1504 (m), 1438 (m), 1302 (m), 1235 (m, mP@O), 1177 (m, mP@O), 1080 (m), 907 (m, mP–N), 832 (m, mP–N), 635 (m, mP–N), 537 (m), 407 (m). 2.3.8. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N0 00 -phenyl) phosphoric triamide] (7) Yield: 61%. m.p. = 135 °C. Anal. Calc. for C31H30N6O3P2: C, 62.41; H, 5.07; N, 14.09. Found: C, 62.40; H, 5.07; N, 14.10%. 31P NMR (DMSO-d6): d 3.42 (m), 3.74 (m). 1H NMR (DMSO-d6): d 6.9 (m, 4H, Ar–H), 7.11 (m, 4H, Ar–H), 7.14 (m, 14H, Ar–H), 7.20 (m, 4H, NHamine), 7.78 (d, 3J(H,H) = 9.0 Hz, 2H, Ar–H), 7.84 (d, 3 J(H,H) = 9.0 Hz, 2H, Ar–H), 8.04 (d, 2J(PNH) = 10.0 Hz, 1H, NHamide). 13 C NMR (DMSO-d6): d 114.08 (s), 115.94 (s), 117.64 (d, 3 J(P,C) = 6.8 Hz), 117.89 (s), 118.07 (s), 120.18 (s), 120.34 (s), 128.43 (s), 128.59 (s), 128.77 (s), 129.21 (s), 129.74 (s), 147.25 (s), 174.21 (s, C@O). IR (KBr, cm1): 3160 (m, mNH), 3035 (m, mNH), 2885 (m, mCH), 1644 (s, mC@O), 1486 (s), 1443 (m), 1382 (m), 1275 (s), 1222 (s, mP@O), 1185 (s, mP@O), 926 (s, mP–N), 741 (s, mP–N), 686 (m, mP–N), 488 (m). 2.3.9. N,N0 -4-Carboxyamidophenyl-bis (N00 -4-chlorophenyl phosphoramidic chloride) (8) Yield: 50%. m.p. = 145 °C. Anal. Calc. for C19H16Cl4N4O3P2: C, 41.33; H, 2.92; N, 10.15. Found: C, 41.34; H, 2.92; N, 10.14%. 31P NMR (CD3OD): d 2.43 (s), 3.15 (m). 1H NMR (CD3OD): d 6.76 (s, 2 H, Ar–Haniline), 6.78 (s, 2H, Ar–Haniline), 6.99 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H4-aminobenzamide), 7.01 (d, 3J(H,H) = 8.5 Hz, 2H, Ar– H4-aminobenzamide), 7.18 (s, 2H, Ar–Haniline), 7.19 (s, 2H, Ar–Haniline). 13 C NMR (CD3OD): d 114.09 (s), 115.94 (s), 117.50 (s), 117.64 (d, 3 J(P,C) = 7.2 Hz), 118.07 (s), 120.15 (s), 120.35 (s), 128.50 (s), 128.65 (s), 128.76 (s), 129.29 (s), 129.67 (s), 141.34 (s), 148.68 (s), 169.84 (s, C@O). IR (KBr, cm1): 3400 (m, mNH), 3305 (m, mNH), 3185 (m, mNH), 2885 (m, mCH), 2570 (m, mCH), 1602 (m, mC@O), 1289 (m), 1260 (m), 1235 (m, mP@O), 1174 (m, mP@O), 1076 (m), 1040 (m), 963 (m, mP–N), 925 (m, mP–N), 842 (m, mP– N), 805 (m, mP–N), 635 (w), 542 (w). 2.3.10. N,N0 -4-Carboxyamidophenyl-bis (1,3-dimethyl-1,3,2diazaphosphole) (9) Yield: 75%. m.p. = 245 °C. Anal. Calc. for C15H26N6O3P2: C, 45.00; H, 6.55; N, 20.99. Found: C, 45.02; H, 6.55; N, 20.97%. 31P NMR (DMSO-d6): d 20.03 (m), 20.16 (m). 1H NMR (DMSO-d6): d 2.58 (s, 12H, CH3), 3.24 (s, 8H, CH2), 6.15 (s, 1H, NHamine), 6.52 (d, 3 J(H,H) = 5.0 Hz, 1H, Ar–H), 6.61 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 7.38 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 7.58 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 9.37 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 30.65 (d, 2 J(P,C) = 5.0 Hz, CH3), 30.82 (d, 2J(P,C) = 4.9 Hz, CH3), 32.44 (s, CH3), 32.47 (s, CH3), 44.39 (s, CH2), 44.42 (s, CH2), 46.30 (d, 2 J(P,C) = 7.3 Hz, CH2), 46.41 (d, 2J(P,C) = 5.7 Hz, CH2), 116.13 (d, 3 J(P,C) = 6.8 Hz), 126.14 (s), 129.36 (s), 139.16 (s), 146.85 (s), 154.68 (s), 167.45 (s, C@O). IR (KBr, cm1): 3380 (m, mNH), 3190 (m, mNH), 3010 (m, mNH), 2740 (s, mCH), 2465 (m, mCH), 1656 (s, mC@O), 1626 (s), 1599 (s), 1446 (m), 1223 (m, mP@O), 1164 (m, mP@O), 1119 (m), 1076 (s), 953 (s, mP–N), 843 (m, mP–N), 801 (w), 505 (m).
309
2.3.11. N,N0 -4-Carboxyamidophenyl-[bis (N00 ,N000 -cyclopentyl) phosphoric triamide] dihydroxy phosphoramidic acid ester (10) Yield: 60%. m.p. = 170 °C. Anal. Calc. for C17H28N4O5P2: C, 47.44; H, 6.56; N, 13.02. Found: C, 47.45; H, 6.55; N, 13.01%. 31P NMR (D2O): d 8.14 (m), 8.81 (m). 1H NMR (D2O): d 1.57 (m, 8 H, CH2), 1.67 (m, 4H CH2), 1.97 (m, 4H, CH2), 3.59 (m, 2H, CH), 6.76 (d, 3 J(H,H) = 8.2 Hz, 2H, Ar–H), 7.58 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H). 13 C NMR (D2O): d 23.08 (s, CH2), 30.16 (s, CH2), 51.82 (s, CH), 114.58 (s), 120.14 (s), 121.31 (s), 128.22 (s), 129.00 (s), 150.82 (s), 172.11 (s, C@O). IR (KBr, cm1): 3370 (s, mNH), 3190 (s, mNH), 2895 (s, mCH), 1601 (s, mC@O), 1524 (m), 1415 (m), 1209 (m, mP@O), 1176 (m, mP@O), 1115 (m), 1057 (m), 837 (m, mP–N), 756 (m, mP–N), 720 (m, mP–N), 556 (m), 525 (m), 458 (m). 2.3.12. N-(4-Carboxy amidophenyl)-N0 -isobutyl-phosphoramidic chloride (11) Yield: 54%. m.p. = 178 °C. Anal. Calc. for C11H17ClN3O2P: C, 45.61; H, 5.92; N 14.50. Found: C, 45.60; H, 5.90; N, 14.51%. 31P NMR (DMSO-d6): d 0.16 (m). 1H NMR (DMSO-d6): d 0.87 (d, 3 J(H,H) = 6.5 Hz, 6H, CH3), 1.85 (m, 1H, CH), 2.58 (m, 2H, Ar CH2), 4.13 (m, 1H, NH), 6.51 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H), 6.80 (b, 1H, NH), 7.57 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H), 7.87 (b, 2H, NH2). 13C NMR (DMSO-d6): d 19.77 (s, CH3), 26.46 (s, CH), 50.80 (s, CH2), 112.45 (s), 118.21 (s), 120.89 (s), 128.44 (s), 129.07 (s), 151.64 (s), 168.09 (s, C@O). IR (KBr, cm1): 3466 (s, mNH), 3245 (s, mNH), 2965 (s, mCH), 2805 (s, mCH), 2601 (m), 1608 (s, mC@O), 1619 (s), 1399 (s), 1292 (m), 1183 (m, mP@O), 1095 (m), 850 (m, mP–N), 778 (s, mP–N), 712 (m), 503 (m), 450 (m). 2.3.13. N-(4-Carboxy amidophenyl)-N0 ,N00 -bis (cyclopentyl) phosphoric triamide (12) Yield: 70%. m.p. = 89 °C. Anal. Calc. for C17H27N4O2P: C, 58.27; H, 7.77; N, 15.99. Found: C, 58.25; H, 7.76; N, 15.98%. 31P NMR (CDCl3): d 3.54 (m). 1H NMR (CDCl3): d 1.62 (m, 8H, CH2), 1.85 (m, 4H, CH2), 2.03 (m, 4H, CH2), 3.12 (m, 2H, CH), 3.63 (m, 2H, NH), 8.35 (m, 6H, Ar–H), 9.14 (b, 1H, NH). 13C NMR (CDCl3): d 23.86 (s), 49.05 (s), 53.29 (s), 54.20 (s), 64.36 (s), 117.21 (s), 122.92 (s), 130.07 (s), 144.25 (s), 172.31 (s, C@O). IR (KBr, cm1): 3445 (m, mNH), 3310 (m, mNH), 3136 (m, mNH), 2940 (s, mCH), 2635 (m, mCH), 1690 (m), 1597 (s, mC@O), 1550 (m), 1506 (m), 1396 (m), 1214 (m), 1176 (m, mP@O), 1089 (m), 840 (m, mP–N), 771 (m, mP–N), 706 (m), 574 (m), 526 (m). 2.3.14. N-(4-Carboxy amidophenyl)-N0 ,N00 -bis (4-bromophenyl) phosphoric triamide (13) Yield: 75%. m.p. = 225 °C. Anal. Calc. for C19H17Br2N4O2P: C, 43.54; H, 3.27; N, 10.69. Found: C, 43.55; H, 3.27; N, 10.68%. 31P NMR (DMSO-d6): d 0.11 (s). 1H NMR (DMSO-d6): d 7.20 (d, 3J(H,H) = 8.5 Hz, 4H, Ar–Hbromoaniline), 7.29 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H4-aminobenzamide), 7.63 (d, 3J(H,H) = 8.6 Hz, 4H, Ar– H4-aminobenzamide), 7.84 (d, 3J(H,H) = 8.5 Hz, 4H, Ar–Hbromoaniline), 8.61–9.52 (m, 5H, NH). 13C NMR (DMSO-d6): d 116.44 (s), 118.91 (s), 124.28 (s), 128.89 (s), 129.60 (s), 132.34 (s), 133.43 (s), 140.04 (s), 167.21 (s, C@O). IR (KBr, cm1): 3402 (s, mNH), 3200 (s, mNH), 2835 (m, mCH), 2569 (s, mCH), 1586 (s, mC8O), 1538 (s), 1514 (s), 1488 (s), 1425 (s), 1405 (s), 1299 (s), 1215 (s, mP@O), 1182 (m), 1106 (m), 1071 (s), 846 (s, mP–N), 818 (s), 767 (s, mP–N), 718 (m), 671 (m), 534 (s), 489 (s), 466 (s). 2.3.15. General procedure for the synthesis of compounds 14–21 A solution of 7 mmol of the corresponding amine in acetonitrile was added dropwise to a solution of 1 mmol N-(4-X-phenyl) phosphoramidic dichloride (X = H, F, Cl, and Br) in acetonitrile at 5 °C. The flask contents were stirred for 48 h and then the precipitate was filtered, washed with water and dried in air to yield molecules 14–17. To synthesise compounds 18–21, this procedure was ap-
310
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
plied, but a solution of 4 mmol of 4-X-aniline (X = H, F, Cl, and Br) in acetonitrile was added dropwise to a solution of 1 mmol 2pyridinyl phosphoramidic dichloride in acetonitrile. 2.3.16. l1-(N-Phenyl)-N0 -phenyl phosphoramidic chloride-bis [(N00 ,N000 -phenyl) phosphoric triamide] (14) Yield: 70%. m.p. = 212 °C. Anal. Calc. for C24H23ClN4O2P2: C, 58.02; H, 4.67; N, 11.28. Found: C, 58.00; H, 4.67; N, 11.28%. 31P NMR (DMSO-d6): d 10.42 (m), 10.28 (d, 2J(P,P) = 19.7 Hz). 31P NMR (CD3OD): d 9.52 (d, 2J(P,P) = 17.5 Hz), 8.28 (d, 2 J(P,P) = 17.5 Hz). 1H NMR (DMSO-d6): d 6.72–7.20 (m, 20H, Ar– H), 7.54 (b, 1H, NH), 8.17 (d, 2J(PNH) = 8.8 Hz, 2H, NH). 13C NMR (DMSO-d6): d 117.40 (s), 119.31 (s), 120.30 (s), 122.39 (s), 126.78 (s), 128.16 (s), 128.38 (s), 128.65 (s), 129.58 (s), 133.64 (s), 141.03 (s), 142.55 (s). IR (KBr, cm1): 3375 (m, mNH), 3235 (m, mNH), 3040 (m), 2825 (s, mCH), 2585 (s), 1592 (m), 1486 (s), 1280 (m, mP@O), 1217 (s, mP@O), 1150 (m), 1072 (m), 910 (s, mP–N), 735 (s, mP–N), 685 (s), 466 (m). 2.3.17. l1-(N-4-Fluorophenyl)-N0 -4-fluorophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-fluorophenyl) phosphoric triamide] (15) Yield: 85%. m.p. = 204 °C. Anal. Calc. for C24H19ClF4N4O2P2: C, 50.68; H, 3.37; N, 9.85. Found: C, 50.67; H, 3.37; N, 9.84%. 31P NMR (DMSO-d6): d 10.23 (d, 2J(P,P) 8 19.7 Hz), 9.90 (m). 19F NMR (DMSO-d6): d 115.61 (s), 123.71 (s), 124.63 (s). 1H NMR (DMSO-d6): d 6.82–7.06 (m, 16H, Ar–H), 7.54 (b, 1H, NH), 8.15 (d, 2J(PNH) = 8.6 Hz, 2H, NH). 13C NMR (DMSO-d6): d 114.68 (d, 2J(F,C) 8 22.4 Hz), 115.07 (d, 2J(F,C) = 22.1 Hz), 115.73 (d, 2 J(F,C) = 20.5 Hz), 118.41 (dd, 3J[(F,C),(P,C)] = 7.4 Hz), 118.76 (dd, 3 J[(F,C),(P,C)] 8 7.5 Hz), 119.19 (dd, 3J[(F,C),(P,C)] = 7.6 Hz), 119.48 (d, 4J(F,C) = 2.3 Hz), 119.54 (d, 4J(F,C) = 2.5 Hz), 119.72 (d, 4 J(F,C) = 2.6 Hz), 156.69 (d, 1J(F,C) = 237.3 Hz), 161.68 (d, 1J(F,C) 8 234.9 Hz), 164.32 (d, 1J(F,C) = 239.4 Hz). IR (KBr, cm1): 3398 (m, mNH), 3220 (m, mNH), 2925 (m, mCH), 2785 (m, mCH), 1502 (s), 1383 (m), 1240 (m, mP@O), 1209 (s, mP@O), 1152 (m), 1068 (s), 968 (s, mP–N), 913 (s, mP–N), 821 (s, mP–N), 752 (m), 501 (m), 457 (m). 2.3.18. l1-(N-4-Chlorophenyl)-N0 -4-chlorophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-chlorophenyl) phosphoric triamide] (16) Yield: 81%. m.p. = 199 °C. Anal. Calc. for C24H19Cl5N4O2P2: C, 45.42; H, 3.02; N, 8.83. Found: C, 45.40; H, 3.02; N, 8.84%. 31P NMR (DMSO-d6): d 10.75 (d, 2J(P,P) 8 17.7 Hz), 10.16 (m). 1H NMR (DMSO-d6): d 7.04–7.46 (m, 16H, Ar–H), 8.15 (b, 1H, NH), 8.40 (d, 2J(PNH) 8 8.6 Hz, 2H, NH). 13C NMR (DMSO-d6): d 117.92 (s), 119.00 (d, 3J(P,C) = 7.4 Hz), 123.35 (s), 123.65 (s), 124.38 (s), 128.19 (s), 128.44 (s), 129.43 (s), 129.92 (s), 134.12 (s), 139.81 (s), 140.56 (s). IR (KBr, cm1): 3430 (m, mNH), 3210 (m, mNH), 2975 (m, mCH), 2835 (m, mCH), 1587 (m), 1484 (s), 1453 (m), 1382 (m), 1274 (m, mP@O), 1229 (m, mP@O), 1194 (s), 1091 (m), 1037 (s), 941 (s, mP–N), 821 (s, mP–N), 571 (m). 2.3.19. l1-(N-4-Bromophenyl)-N0 -4-bromophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-bromophenyl) phosphoric triamide] (17) Yield: 67%. m.p. = 196 °C. Anal. Calc. for C24H19Br4ClN4O2P2: C, 35.48; H, 2.36; N, 6.90. Found: C, 35.46; H, 2.35; N, 6.91%. 31P NMR (DMSO-d6): d 10.92 (d, 2J(P,P) = 17.7 Hz), 10.61 (m). 1H NMR (DMSO-d6): d 6.76–7.30 (m, 16H, Ar–H), 7.91 (b, 1H, NH), 8.42 (d, 2J(PNH) = 8.9 Hz, 2H, NH). 13C NMR (DMSO-d6): d 111.12 (s), 112.03 (s), 113.12 (s), 118.67 (d, 3J(P,C) = 7.4 Hz), 119.24 (d, 3 J(P,C) = 7.8 Hz), 119.37 (d, 3J(P,C) = 6.9 Hz), 131.00 (s), 131.32 (s), 131.69 (s), 140.33 (s), 141.37 (s), 142.35 (s). IR (KBr, cm 1): 3390 (m, mNH), 3190 (m, mNH), 3045 (m, mCH), 2915 (m, mCH), 2585 (m), 1503 (m), 1400 (s), 1296 (m), 1271 (m, mmP@O), 1218 (m, mP8O), 1068 (m), 1004 (m), 964 (m, mP–N), 908 (m, mP–N), 811 (m, mP– N), 532 (m), 405 (m).
2.3.20. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -phenyl) phosphoric triamide] (18) Yield: 70%. m.p. = 175 °C. Anal. Calc. for C22H21ClN4O2P2: C, 56.12; H, 4.50; N, 11.90. Found: C, 56.10; H, 4.51; N, 11.90%. 31P NMR (DMSO-d6): d 10.30 (m), 10.11 (d, 2J(P,P) = 20.0 Hz). 1H NMR (DMSO-d6): d 6.69 (t, 3J(H,H) 8 7.0 Hz, 1H, Ar–H), 6.75 (t, 3 J(H,H) = 7.0 Hz, 2H, Ar–H), 6.86 (d, 3J(H,H) = 7.9 Hz, 1H, Ar–H), 7.03 (m, 10H, Ar–H), 7.18 (t, 3J(H,H) = 7.0 Hz, 2H, Ar–H), 7.49 (b, 1H, NH), 8.15 (d, 2J(PNH) = 8.5 Hz, 2H, NH). 13C NMR (DMSO-d6): d 109.81 (s), 117.22 (s), 117.32 (d, 3J(P,C) = 7.7 Hz), 117.54 (s), 119.24 (s), 120.12 (s), 128.29 (s), 128.57 (s), 129.14 (s), 141.08 (s), 141.90 (s), 142.31 (s), 149.35 (s), 152.60 (s). IR (KBr, cm-1): 3375 (m, mNH), 3235 (s, mNH), 2820 (m, mCH), 1637 (s), 1593 (s), 1487 (s), 1399 (s), 1288 (m, mP@O), 1216 (s, mP@O), 1151 (m), 1063 (s), 955 (s, mP–N), 909 (m, mP–N), 743 (s, mP–N), 688 (s), 506 (m), 476 (m, mP–Cl). 2.3.21. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-fluorophenyl) phosphoric triamide] (19) Yield: 68%. m.p. = 185 °C. Anal. Calc. for C22H19ClF2N4O2P2: C, 52.14; H, 3.78; N, 11.06. Found: C, 52.12; H, 3.77; N, 11.06%. 31P NMR (CD3OD): d 9.59 (d, 2J(P,P) = 21.3 Hz), 8.32 (d, 2 J(P,P) = 21.3 Hz); dP (202.46 MHz; DMSO-d6; 85% H3PO4) 10.27 (d, 2J(P,P) = 20.0 Hz), 9.99 (m). 1H NMR (CD3OD): d 6.85–7.05 (m, 16H, Ar–H), 7.49 (b, 1H, NH), 8.13 (d, 2J(PNH) = 8.4 Hz, 2H, NH). 13 C NMR (CD3OD): d 114.49 (s), 114.66 (s), 114.98 (d, 2 J(F,C) = 22.1 Hz), 115.43 (d, 4J(F,C) = 2.5 Hz), 115.63 (s), 116.20 (s), 117.80 (s), 118.02 (s), 118.36 (dd, 3J[(F,C),(P,C)] = 7.8 Hz), 118.68 (s), 137.33 (s), 143.80 (s), 155.20 (s), 156.62 (d, 1 J(F,C) = 234.8 Hz). IR (KBr, cm1): 3390 (m, mNH), 3230 (m, mNH), 2940 (m, mCH), 1502 (s), 1463 (m), 1300 (m), 1284 (m, mP@O), 1239 (m, mP@O), 1211 (s), 1153 (m), 1069 (m), 966 (m, mP–N), 913 (s, mP–N), 821 (s, mP–N), 752 (m), 698 (m), 500 (m), 499 (m, mP–Cl). 2.3.22. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-chlorophenyl) phosphoric triamide] (20) Yield: 75%. m.p. = 213 °C. Anal. Calc. for C22H19Cl3N4O2P2: C, 48.96; H, 3.55; N, 10.38. Found: C, 48.95; H, 3.55; N, 10.37%. 31P NMR (DMSO-d6): d 10.79 (d, 2J(P,P) = 18.6 Hz), 10.49 (m). 1H NMR (DMSO-d6): d 6.75 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.00–7.14 (m, 4H, Ar–H), 7.87 (b, 1H, NH), 8.38 (d, 2J(PNH) = 9.0 Hz, 2H, NH). 13C NMR (DMSO-d6): d 109.10 (s), 117.68 (s), 118.73 (d, 3 J(P,C) = 7.9 Hz), 118.88 (d, 3J(P,C) = 7.7 Hz), 121.40 (s), 123.33 (s), 124.21 (s), 128.09 (s), 128.41 (s), 128.76 (s), 135.32 (s), 139.89 (s), 140.93 (s), 147.50 (s). IR (KBr, cm1): 3370 (m, mNH), 3195 (m, mNH), 2920 (m, mCH), 2808 (m, mCH), 1590 (m), 1485 (s), 1381 (m), 1275 (m, mP@O), 1215 (s, mP@O), 1188 (m), 1006 (m), 965 (m, mP–N), 910 (s, mP–N), 815 (s, mP–N), 650 (m), 539 (m), 480 (m, mP–Cl). 2.3.23. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-bromophenyl) phosphoric triamide] (21) Yield: 75%. m.p. = 230 °C. Anal. Calc. for C22H19Br2ClN4O2P2: C, 42.03; H, 3.05; N, 8.91. Found: C, 42.01; H, 3.05; N, 8.90%. 31P NMR (DMSO-d6): d 10.82 (d, 2J(P,P) = 18.4 Hz), 10.66 (m). 1H NMR (DMSO-d6): d 6.63 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 6.96 (m, 6H, Ar–H), 7.16 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 7.20 (d, 2 J(PNH) = 7.1 Hz, 2H, Ar–H), 7.23 (d, 3J(H,H) = 8.7 Hz, 4H, Ar–H), 7.89 (b, 1H, NH), 8.39 (d, 2J(PNH) = 8.3 Hz, 2H, NH). 13C NMR (DMSO-d6): d 112.10 (s), 117.25 (s), 117.35 (s), 119.25 (d, 3 J(P,C) = 7.8 Hz), 130.96 (s), 131.28 (s), 131.47 (s), 133.80 (s), 137.20 (s), 140.27 (s), 146.50 (s), 151.50 (s), 152.10 (s). IR (KBr, cm1): 3305 (m, mNH), 3190 (m, mNH), 2915 (m, mCH), 1624 (m), 1481 (s), 1379 (m), 1296 (m), 1272 (m, mP@O), 1215 (s, mP@O), 1110 (m), 1068 (m), 962 (s, mP–N), 911 (s, mP–N), 812 (m, mP–N), 639 (m), 570 (m), 485 (m, mP–Cl).
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
2.3.24. Phenylalanine benzylester hydrochloride (22) A solution of 6 mmol DL-phenylalanine was added to a solution of 35 mL of benzyl alcohol and the mixture was refluxed for 5 h. Then the temperature was decreased to 5 °C and 5.8 mL SOCl2 was added dropwise to the mixture to yield the product that was washed with ether. Yield: 95%. m.p. = 200 °C. Anal. Calc. for C16H18ClNO2: C, 65.86; H, 6.22; N, 4.80. Found: C, 65.85; H, 6.21; N, 4.81%. 1H NMR (D2O): d 3.21 (d, 3J(H,H) = 6.6 Hz, 2H, CH2–O), 4.39 (t, 3J(H,H) = 6.7 Hz, 1H, CH), 5.18 (d, 2J(H,H) = 11.9 Hz, 1H, CH of CH2), 5.24 (d, 2J(H,H) = 11.9 Hz, 1H, CH of CH2), 7.10 (m, 2H, Ar–H), 7.28–7.40 (m, 8H, Ar–H). 13C NMR (D2O): d 35.64 (s), 54.03 (s), 68.66 (s), 127.50 (s), 128.05 (s), 128.90 (s), 131.00 (s), 129.09 (s), 129.21 (s), 129.36 (s), 133.49 (s), 134.39 (s). IR (KBr, cm-1): 3430 (m, mNH), 3135 (m, mNH), 2990 (m, mCH), 2950 (m, mCH), 2860 (m), 1732 (s, mC@O), 1480 (s), 1439 (m), 1367 (m), 1225 (s), 1187 (m), 932 (m), 734 (s), 691 (s), 575 (m). 2.3.25. General procedure for the synthesis of compounds 23–27 A solution of 2 mmol of the corresponding aminoester plus 2 mmol of triethylamine in acetonitrile was added dropwise to a solution of 1 mmol N-(4-X-phenyl) phosphoramidic dichloride (X = CH3, Cl, and NO2) (in the case of compound 24, 1 mmol of 4-tolyl dichlorophosphate) in acetonitrile at 5 °C. The flask contents were stirred for 48 h and then the precipitate was filtered, washed with water and dried in air to yield the products. 2.3.26. N,N0 -Bis (phenylalanino)-N00 -4-methylphenyl phosphoric triamide (23) Yield: 55%. m.p. = 214 °C. Anal. Calc. C25H28N3O5P: C, 62.36; H, 5.86; N, 8.73. Found: C, 62.35; H, 5.85; N, 8.74%. 31P NMR (DMSOd6): d 0.27 (m). 1H NMR (DMSO-d6): d 2.09 (s, 3H, p-CH3), 3.38 (s, 2H, OH), 3.41 (m, 4H, CH2), 3.67 (m, 2H, CH), 5.04 (s, 2H, NHa13 C NMR (DMSO-d6): d 20.06 (s, mine), 6.44–7.32 (m, 15H, Ar–H). CH3), 55.50 (s, CH), 65.62 (s, CH2), 113.99 (s), 126.32 (s), 126.76 (s), 127.93 (s), 127.96 (s), 128.13 (s), 128.15 (s), 128.18 (s), 128.32 (s), 129.17 (s), 129.20 (s), 129.57 (s), 169.26 (s), 170.14 (s). IR (KBr, cm-1): 3420 (m, mNH), 3275 (s, mNH), 3155 (m, mNH), 3030 (s, mCH), 2855 (m, mCH), 1724 (s, mC@O), 1655 (m), 1602 (m), 1504 (m), 1443 (m), 1284 (m), 1160 (s, mP@O), 1039 (s), 910 (m, mP–N), 744 (m, mP–N), 687 (s, mP–N), 599 (m), 465 (m). 2.3.27. N,N0 -Bis (phenylalanine benzylester)-4-methylphenyl phosphoramidicacid ester (24) Yield: 50%. m.p. = 220 °C. Anal. Calc. for C39H39N2O6P: C, 70.68; H, 5.93; N, 4.23. Found: C, 70.66; H, 5.93; N, 4.22%. 31P NMR (DMSO-d6): d 0.24 (m). 1H NMR (DMSO-d6): d 2.19 (s, 3H, pCH3), 2.78 (dd, 3J(PNCH) = 7.9 Hz, 2J(H,H) = 13.0 Hz, 1H, CH), 2.85 (dd, 3J(PNCH) = 7.9 Hz, 2J(H,H) = 13.0 Hz, 1H, CH), 2.98 (dd, 2 J(H,H) = 13.6 Hz, 3J(H,H) = 8.0 Hz, 1H, CH of CH2), 3.00 (dd, 2 J(H,H) = 13.6 Hz, 3J(H,H) = 8.0 Hz, 1H, CH of CH2), 3.11 (dd, 2 J(H,H) = 13.7 Hz, 3J(H,H) = 5.6 Hz, 1H, CH of CH2), 3.14 (dd, 2 J(H,H) = 13.7 Hz, 3J(H,H) = 5.6 Hz, 1H, CH of CH2), 4.05 (dd, 3 2 J(H,H) = 6.5 Hz, J(PNH) = 13.0 Hz, 1H, NH), 4.10 (dd, 3 2 J(H,H) = 6.4 Hz, J(PNH) = 12.7 Hz, 1H, NH), 4.86 (d, 2 J(H,H) = 12.7 Hz, 2H, CH of CH2), 5.06 (d, 2J(H,H) = 12.7 Hz, 2H, CH of CH2), 6.93–7.32 (m, 24H, Ar–H). 13C NMR (DMSO-d6): d 20.19 (s, CH3), 37.00 (s), 40.35 (d, 2J(P,C) = 6.3 Hz), 53.73 (s), 56.53 (s), 65.37 (s), 66.61 (s), 119.90 (d, 3J(P,C) = 4.7 Hz), 126.22 (s), 126.93 (s), 127.81 (s), 128.02 (s), 128.13 (s), 128.19 (s), 128.21 (s), 128.30 (s), 128.32 (s), 128.40 (s), 128.41 (s), 129.05 (s), 129.15 (s), 129.34 (s), 130.25 (s), 135.02 (s), 135.29 (s), 135.78 (s), 137.22 (s), 170.16 (s, C@O), 173.15 (s, C@O). IR (KBr, cm1): 3390 (m, mNH), 3025 (m, mCH), 2855 (m, mCH), 1732 (s, mC@O), 1598 (m), 1494 (m), 1290 (m), 1205 (s, mP@O), 1150 (s), 1063 (m), 935 (m, mP–N), 907 (m), 734 (m, mP–N), 691 (s, mP–N), 594 (m), 470 (m).
311
2.3.28. N,N0 -Bis (phenylalanine benzylester)-N00 -4-nitrophenylphosphoric triamide (25) Yield: 55%. m.p. = 150 °C. Anal. Calc. for C38H37N4O7P: C, 65.89; H, 5.38; N, 8.09. Found: C, 65.90; H, 5.38; N, 8.10%. 31P NMR (DMSO-d6): d 2.04 (m). 1H NMR (DMSO-d6): d 2.85 (m, 2H, CH2), 3.09 (m, 2H, CH2), 3.21 (m, 1H, CH), 3.92 (m, 1H, NH), 4.31 (m, 1H, NH), 4.85 (m, 2H, OCH2), 5.12 (m, 2H, OCH2), 5.31 (m, 1H, CH), 7.07–7.34 (m, 22H, Ar–H), 7.92 (d, 3J(H,H) = 7.7 Hz, 2H, Ar– H), 8.31 (d, 2J(PNH) = 6.6 Hz, 1H, NH). 13C NMR (DMSO-d6): d 35.58 (s), 39.95 (s), 53.17 (s), 55.87 (s), 65.56 (s), 66.95 (s), 116.19 (d, 3J(P,C) = 8.1 Hz), 124.81 (s), 126.26 (s), 127.13 (s), 127.76 (s), 127.64 (s), 127.79 (s), 128.02 (s), 128.16 (s), 128.21 (s), 128.26 (s), 128.31 (s), 128.49 (s), 128.99 (s), 129.34 (s), 134.55 (s), 134.76 (s), 135.59 (s), 136.91 (s), 139.03 (s), 168.79 (s, C@O), 172.39 (s, C@O). IR (KBr, cm1): 3348 (m, mNH), 3255 (s, mNH), 3025 (m, mCH), 2850 (s, mCH), 1732 (s, mC@O), 1590 (s, mNO2), 1509 (s), 1484 (s), 1446 (s), 1342 (s, mNO2), 1224 (s), 1290 (m), 1187 (s, mP@O), 1109 (s), 999 (s), 960 (m, mP–N), 846 (m), 735 (m, mP–N), 689 (s, mP–N), 529 (m). 2.3.29. N-Phenylalanine benzylester-N0 -4-chlorophenylphosphoramidic chloride (26) Yield: 65%. m.p. = 146 °C. Anal. Calc. for C22H21Cl2N2O3P: C, 57.03; H, 4.57; N, 6.05. Found: C, 57.01; H, 4.56; N, 6.05%. 31P NMR (DMSO-d6): d 3.75 (m). 1H NMR (DMSO-d6): d 2.84 (m, 2H, CH2), 3.92 (m, 1H, CH), 4.86 (m, 2H, OCH2), 5.12 (m, 1H, NH), 7.00–7.29 (m, 14H, Ar–H), 7.51 (b, 1H, NH). 13C NMR (DMSO-d6): d 39.75 (s), 55.82 (s), 65.57 (s), 118.42 (d, 3J(P,C) = 6.4 Hz), 122.92 (s), 123.56 (s), 126.37 (s), 127.74 (s), 127.65 (s), 128.13 (s), 128.23 (s), 129.03 (s), 135.64 (s), 136.92 (s), 141.42 (s), 172.41 (s, C@O). IR (KBr, cm1): 3285 (s, mNH), 3255 (s, mNH), 3025 (m, mCH), 2850 (m, mCH), 1712 (s, mC@O), 1484 (s), 1442 (s), 1381 (s), 1274 (m), 1194 (s, mP@O), 1120 (s), 997 (s), 963 (m, mP–N), 911 (m), 822 (m, mP–N), 746 (m, mP–N), 692 (m, mP–N), 587 (m), 531 (m), 460 (m). 2.3.30. N,N0 -Bis (alaninethylester)-N00 -4-methylphenyl-phosphoric triamide (27) Yield: 85%. m.p. = 76 °C. Anal. Calc. for C17H28N3O5P: C, 52.98; H, 7.32; N, 10.90. Found: C, 52.99; H, 7.31; N, 10.91%. 31P NMR (DMSO-d6): d -0.23 (m). 1H NMR (DMSO-d6): d 1.20 (t, 3 J(H,H) = 7.0 Hz, 6H, CH3), 1.40 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.41 (s, 3H, p-CH3), 2.24 (m, 2H, CH), 3.97 (m, 2H, NH), 4.15 (m, 4H, CH2), 7.19 (s, 4 H, Ar–H). 13C NMR (DMSO-d6): d 13.94 (s, CH3), 15.69 (s, CH3), 20.49 (s, p-CH3), 47.86 (s, CH2), 61.64 (s, CH), 122.16 (s), 129.63 (s), 131.23 (s), 135.83 (s), 169.86 (s, C@O). IR (KBr, cm1): 3466 (s, mNH), 3245 (s, mNH), 2965 (s, mCH), 2805 (s, mCH), 2601 (m), 1608 (s), 1619 (s, mC@O), 1399 (s), 1292 (m), 1183 (m, mP@O), 1095 (m), 850 (m, mP–N), 778 (s, mP–N), 712 (m), 503 (m), 450 (m). 2.3.31. N-(2-Pyridinyl) phosphoramidic dichloride (28) A solution of 6 mmol 2-aminopyridine in acetonitrile was added dropwise to a solution of 3 mmol POCl3 in acetonitrile at 5 °C and the mixture was stirred for 8 h. Then the precipitate was filtered and the solution was evaporated under vacuum to yield the product. Yield: 77%. m.p. = 81 °C. Anal. Calc. for C5H5Cl2NOP: C, 30.49; H, 2.56; N, 7.11. Found: C, 30.50; H, 2.56; N, 7.12%. 31P NMR (DMSOd6): d 10.69 (s). 1H NMR (DMSO-d6): d 6.85 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 6.97 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 7.55 (t, 3 J(H,H) = 6.7 Hz, 1H, Ar–H), 8.10 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 9.12 (s 1H, NH). 13C NMR (DMSO-d6): d 111.38 (s), 116.65 (s), 137.96 (s), 147.47 (s), 153.67 (s). IR (KBr, cm-1): 3410 (m, mNH), 3130 (s, mNH), 2935 (m, mCH), 1591 (s), 1468 (s), 1321 (m), 1242 (m), 1214 (s, mP@O), 1149 (m), 985 (s, mP–N), 912 (s), 768 (m), 630 (m), 503 (m), 475 (m).
312
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
2.3.32. N-(2-Pyridinyl)-N0 ,N00 -bis (4-methylphenyl) phosphoric triamide (29) A solution of 8 mmol p-toluidine in acetonitrile was added dropwise to a solution of 2 mmol of compound 28 in acetonitrile at 5 °C and the mixture was stirred for 10 h. Then the precipitate was filtered and washed with water and CH2Cl2. Yield: 83%. m.p. = 204 °C. Anal. Calc. for C19H21N3OP: C, 67.44; H, 6.26; N, 12.42. Found: C, 67.45; H, 6.25; N, 12.41%. 31P NMR (DMSO-d6): d 4.08 (m). 1H NMR (DMSO-d6): d 2.13 (s, 6H, CH3), 6.81 (t, 3J(H,H) 8 7.0 Hz, 1H, Ar–H), 6.92 (d, 3J(H,H) = 8.3 Hz, 2H, Ar–Hp-toluidine), 7.03 (d, 3J(H,H) = 8.3 Hz, 2H, Ar–H), 7.54 (t, 3J(H,H) = 7.0 Hz, 1H, Ar–H), 7.64 (d, 2J(PNH) = 7.0 Hz, 2H, NH), 8.32 (b, 1H, NH). 13C NMR (DMSO-d6): d 20.14 (s, CH3), 111.17 (d, 2J(P,C) = 5.5 Hz), 115.94 (s), 117.55 (d, 3J(P,C) = 7.2 Hz), 128.75 (s), 129.04 (s), 137.63 (s), 139.02 (s), 147.52 (s), 154.64 (s). IR (KBr, cm1): 3215 (m, mNH), 3025 (m, mNH), 2910 (m, mCH), 1594 (m), 1505 (s), 1461 (m), 1389 (s), 1302 (s), 1288 (s), 1220 (m), 1183 (s, mP@O), 966 (s, mP–N), 804 (s, mP–N), 768 (m), 635 (m), 583 (m), 485 (m). MS (20 eV, EI): m/z (%): 352 (100) M+, 259 (7) [(4-CH3– C6H4NH)2P(O)]+, 246 (73) [(4-CH3–C6H4NH)P(O)(2-C5H4N–NH)]+, 153 (3) [(4-CH3–C6H4NH)P(O)]+, 140 (7) [(2-C5H4N–NH)P(O)]+, 106 (66) [4-CH3–C6H4NH]+, 93 (17) [2-C5H4N–NH]+. 2.3.33. N-[1-(4-methoxybenzyl)-decahydro-isoquinolinyl)] phosphoramidic dichloride (30) A solution of 3 mmol N-[1-(4-methoxybenzyl)-decahydro-isoquinoline)] plus 3 mmol of triethylamine in acetonitrile was added dropwise to a solution of 3 mmol POCl3 in acetonitrile at 5 °C and the mixture was stirred for 12 h. Then the precipitate was filtered and washed with water and diethylether. Yield: 52%. Anal. Calc. for C17H22Cl2NO2P: C, 54.56; H, 5.93; N, 3.74. Found: C, 54.55; H, 5.92; N, 3.75%. 31P NMR (DMSO-d6): d 0.26 (m). 1H NMR (DMSO-d6): d 1.36 (m, 2H, CH2), 1.64 (m, 2H, CH2), 1.78 (m, 1H, CH), 1.93 (s, 3H, CH3), 2.05 (m, 1H, CH), 2.23 (m, 1H, CH), 2.90 (m, 2H, CH2), 3.09 (m, 2H, CH2), 3.77 (s, 4H, CH2), 6.89 (d, 3J(H,H) = 8.6 Hz), 7.31 (d, 3J(H,H) = 8.6 Hz), 7.31 (d, 3J(H,H) = 8.6 Hz). 13C NMR (DMSO-d6): d 21.85 (s), 22.09 (s), 25.85 (s), 26.19 (s), 29.34 (s), 35.37 (s), 38.35 (s), 55.00 (s), 56.30 (s), 113.92 (s), 125.35 (s), 127.95 (s), 128.39 (s), 130.54 (s), 158.19 (s). IR (KBr, cm1): 3440 (w, mNH), 2925 (s, mCH), 2770 (s, mCH), 2600 (m), 1602 (m), 1503 (s), 1452 (s), 1418 (m), 1297 (m), 1242 (s, mP@O), 1176 (m), 1031 (m), 828 (m, mP–N), 784 (m), 570 (m). 2.3.34. N-[1-(4-methoxybenzyl)-decahydro-isoquinolinyl)] (phenyl) phosphoramidic chloride (31) A solution of 3 mmol N-[1-(4-methoxybenzyl)-decahydro-isoquinoline)] plus 3 mmol of triethylamine in acetonitrile was added dropwise to a solution of 3 mmol phenyl phosphorodichloridate in acetonitrile at 5 °C and the mixture was stirred for 18 h. Then the precipitate was filtered and washed with water and ethylacetate. Yield: 63%. Anal. Calc. for C23H27ClNO2P: C, 66.42; H, 6.54; N, 3.37. Found: C, 66.43; H, 6.54; N, 3.36%. 31P NMR (DMSO-d6): d 6.57 (m). 1H NMR (DMSO-d6): d 1.42 (m, 2H, CH2), 1.64 (m, 2H, CH2), 1.79 (m, 1H, CH), 1.93 (s, 3H, OCH3), 2.07 (d, 3J(H,H) = 6.3 Hz, 1H, CH), 2.15 (m, 1H, CH), 2.77 (m, 1H, CH), 2.78 (m, H, CH), 3.09 (m, 2H, CH2), 4.36 (m, 4H, CH2), 6.89 (d, 3J(H,H) = 8.4 Hz, 2H, Ar– 3 J(H,H) = 8.4 Hz, 2H, Ar–H), 7.36 (dd, H), 7.26 (d, 3 J(PCCH) = 13.4 Hz, 3J(H,H) = 7.4 Hz, 2H, Ar–H), 7.43 (t, 3 J(H,H) = 8.4 Hz, 1H, Ar–H), 7.65 (d, 3J(H,H) = 7.4 Hz, 2H, Ar–H). 13 C NMR (DMSO-d6): d 21.81 (s), 22.05 (s), 25.88 (s), 26.18 (s), 29.28 (s), 35.42 (s), 38.23 (s), 54.96 (s), 56.18 (s), 113.90 (s), 125.38 (s), 127.56 (d, 3J(P,C) = 7.2 Hz), 127.76 (d, 1J(P,C) = 28.8 Hz), 128.30 (s), 130.33 (s), 130.47 (s), 130.68 (s), 130.73 (d, 3 J(P,C) = 4.9 Hz), 158.16 (s). IR (KBr, cm-1): 3435 (m, mNH), 2910 (s, mCH), 2798 (s, CH), 1503 (s), 1426 (s), 1240 (s, mP@O), 1177 (m), 965 (s, mP–N), 699 (m), 526 (s).
2.3.35. N-Cyanoacetyl-phosphoramidic dichloride (32) A solution of 5 mmol of cyanoacetamide in CCl4 was added slowly to a mixture of 3 mmol PCl5 in CCl4 at 5 °C and the mixture was refluxed for 10 h. Then the orange precipitate that formed was filtered and washed with CCl4 and dried under vacuum. Yield: 55%. Anal. Calc. for C3H3Cl2N2O2P: C, 17.93; H, 1.50; N, 13.94. Found: C, 17.92; H, 1.51; N, 13.95%. 31P NMR (DMSO-d6): d 0.56 (d, 2 J(PNH) = 6.1 Hz). 1H NMR (DMSO-d6): d 3.77 (s, 2H, CH2), 9.44 (d, 2J(PNH) = 6.1 Hz). 13C NMR (DMSO-d6): d 26.62 (d, 3 J(P,C) = 10.5 Hz, CH2), 115.56 (d, 4J(P,C) = 1.6 Hz, C„N), 164.04 (s, C@O). IR (KBr, cm1): 3190 (s, mNH), 2985 (s), 1710 (s, mC@O), 1452 (s, mC„N), 1265 (s, mP@O), 1153 (m), 982 (m, mP–N), 663 (m), 580 (s), 526 (m). 2.3.36. N-Cyanoacetyl-N0 -benzyl phosphoramidic chloride (33) A solution of 2 mmol benzylamine in acetonitrile was added dropwise to a solution of 1 mmol of compound 32 in acetonitrile at 5 °C and the mixture was stirred for 15 h. Then the precipitate was filtered and the solvent was evaporated to give the product that was washed with water and n-heptane. Yield: 63%. Anal. Calc. for C10H11ClN3O2P: C, 44.22; H, 4.08; N, 15.47. Found: C, 44.21; H, 4.09; N, 15.46%. 31P NMR (DMSO-d6): d 1.16 (s). 1H NMR (DMSOd6): d 3.58 (s, 2H, CH2 of amide), 3.59 (s, Ar–CH2), 3.98 (m, 1H, NHamine), 7.29–7.474 (m, 5H, Ar–H), 9.46 (b, 2H, NHamide). 13C NMR (DMSO-d6): d 25.49 (s, CH2 of amide), 42.22 (s, Ar–CH2), 116.31 (s, C„N), 128.91 (s), 128.54 (s), 128.91 (s), 134.25 (s), 165.93 (s, C@O). IR (KBr, cm1): 3355 (m, mNH), 3080 (s, mNH), 2980 (s), 1711 (s), 1677 (s, mC@O), 1400 (s, mC„N), 1212 (s, mP@O), 1101 (s), 980 (s, mP–N), 926 (m, mP–N), 608 (m), 497 (m, mP–Cl). 2.3.37. General procedure for the synthesis of compounds 34–45 A solution of 8 mmol of the corresponding amine in acetonitrile was added dropwise to a solution of 2 mmol of compound 32 in acetonitrile at 5 °C and the mixture was stirred for 24 h. Then the precipitate tha formed was filtered and washed with water and n-hexane. Compound 45 was synthesized in the same way, but 8 mmol of amine was added to 2 mmol of N-trifluoroacetyl phosphoramidic dichloride. 2.3.38. N-Cyanoacetyl-N0 ,N00 -dibenzyl phosphoric triamide (34) Yield: 56%. Anal. Calc. for C17H19N4O2P: C, 59.64; H, 5.59; N, 16.37. Found: C, 59.65; H, 5.60; N, 16.38%. 31P NMR (DMSO-d6): d 7.49 (m). 1H NMR (DMSO-d6): d 3.67 (s, 2H, CH2 of amide), 4.20 (dd, 3J(PNCH) = 11.5 Hz, 3J(H,H) = 7.4 Hz, 2H, Ar–CH2), 5.04 (m, 2H, NHamine), 7.19–7.34 (m, 10H, Ar–H), 9.25 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.67 (d, 3J(P,C) = 8.7 Hz, CH2 of amide), 43.80 (s, Ar–CH2), 115.58 (s, C„N), 126.59 (s), 127.25 (s), 128.07 (s), 128.64 (s), 128.82 (s), 140.91 (d, 3J(P,C) = 5.7 Hz, Cipso), 164.47 (s, C@O). IR (KBr, cm1): 3305 (m, mNH), 3100 (m, mNH), 2975 (s), 1692 (m, mC@O), 1476 (m, mC„N), 1446 (m), 1159 (s, mP@O), 932 (m, mP–N), 880 (m, mP–N), 798 (s), 546 (m). 2.3.39. N-Cyanoacetyl-N0 ,N00 -bis (a-phenylethyl) phosphoric triamide (35) Yield: 52%. Anal. Calc. for C19H23N4O2P: C, 61.61; H, 6.26; N, 15.13. Found: C, 61.60; H, 6.25; N, 15.13%. 31P NMR (DMSO-d6): d 4.02 (m). 1H NMR (DMSO-d6): d 1.33 (d, 3J(H,H) = 7.2 Hz, 3H, CH3), 1.34 (d, 3J(H,H) = 7.2 Hz, 3H, CH3), 3.40 (m, 2H, CH2 of amide), 4.27 (m, 2H, NHamine), 4.57 (m, 1H, CH), 4.93 (m, 1H, CH), 7.16–7.45 (m, 10H, Ar–H), 8.86 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 25.25 (d, 3J(P,C) 8 5.0 Hz, CH3), 25.34 (d, 3J(P,C) = 5.1 Hz, CH3), 26.51 (d, 3 J(P,C) 8 8.8 Hz, CH2), 49.77 (s, CH), 50.10 (s, CH), 115.49 (s, C„N), 125.92 (s), 126.04 (s), 126.34 (s), 126.39 (s), 126.66 (s), 128.00 (s), 128.65 (s), 146.00 (d, 3J(P,C) = 5.7 Hz, Cipso), 146.15 (d, 3 J(P,C) = 5.4 Hz, Cipso), 164.10 (s, C@O). IR (KBr, cm1): 3255 (s, mNH), 2250 (m), 1672 (m, mC@O), 1440 (s, mC„N), 1416 (s), 1328
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
(m), 1188 (s, mP@O), 1111 (m), 1037 (m), 953 (m, mP–N), 633 (m, mP–N), 503 (m). 2.3.40. N-Cyanoacetyl-N0 ,N00 -bis (2-chlorobenzyl) phosphoric triamide (36) Yield: 64%. Anal. Calc. for C17H17Cl2N4O2P: C, 49.65; H, 4.17; N, 13.62. Found: C, 49.64; H, 4.16; N, 13.61%. 31P NMR (DMSO-d6): d 7.38 (m). 1H NMR (DMSO-d6): d 3.73 (s, 2H, CH2 of amide), 4.15 (ddd, 3J(PNCH) = 11.0 Hz, 3J(H,H) = 7.2 Hz, 2J(H,H) = 14.5 Hz, 2H, Ar–CH2), 5.23 (dd, 3J(H,H) = 7.2 Hz, 2J(PNH) 8 10.1 Hz, 2H, NHamine), 7.19–7.62 (m, 10H, Ar–H), 9.26 (s, 1H, NHamide). 13C NMR (DMSOd6): d 26.75 (d, 3J(P,C) = 8.9 Hz, CH2 of amide), 41.43 (s, Ar–CH2), 115.55 (s, C„N), 126.98 (s), 128.25 (s), 128.86 (s), 129.47 (s), 131.52 (s), 138.00 (s), 164.64 (s, C@O). IR (KBr, cm1): 3255 (m, mNH), 2915 (m), 1678 (s, mC@O), 1457 (s, mC„N), 1432 (s), 1184 (s, mP@O), 1082 (m), 1037 (m), 868 (m, mP–N), 741 (m, mP–N), 503 (m), 413 (m). 2.3.41. N-Cyanoacetyl-N0 ,N00 -bis (cyclopentyl) phosphoric triamide (37) Yield: 64%. Anal. Calc. for C13H23N4O2P: C, 52.34; H, 7.77; N, 18.78. Found: C, 52.35; H, 7.78; N, 18.77%. 31P NMR (DMSO-d6): d 6.13 (m). 1H NMR (DMSO-d6): d 1.38 (m, 8H, CH2), 1.58 (m, 4H, CH2), 1.71 (m, 4H, CH2), 3.37 (m, 2H, CH), 3.74 (m, 2H, CH2 of amide), 4.23 (m, 2H, NHamine), 9.13 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 22.76 (s, CH2), 22.88 (s, CH2), 26.58 (d, 3 J(P,C) = 8.7 Hz, CH2 of amide), 33.97 (d, 3J(P,C) = 5.1 Hz, CH2), 34.14 (d, 2J(P,C) = 6.5 Hz, CH), 51.97 (s, CH2), 115.64 (s, C„N), 164.16 (s, C@O). IR (KBr, cm1): 3390 (s, mNH), 3090 (m, mCH), 2920 (s, mCH), 1694 (s, mC@O), 1478 (s, mC„N), 1155 (s, mP@O), 1105 (m), 977 (m, mP–N), 926 (m, mP–N), 899 (m, mP–N), 565 (m), 461 (m). 2.3.42. N-Cyanoacetyl-N0 ,N00 -bis (cyclohexyl) phosphoric triamide (38) Yield: 58%. Anal. Calc. for C15H27N4O2P: C, 55.20; H, 8.34; N, 17.17. Found: C, 55.20; H, 8.33; N, 17.17%. 31P NMR (DMSO-d6): d 4.32 (m). 1H NMR (DMSO-d6): d 1.09 (m, 10H, CH2), 1.48 (m, 2H, CH2), 1.74 (m, 8H, CH2), 2.85 (m, 2H, CH), 3.73 (m, 2H, CH2 of amide), 4.14 (m, 2H, NHamine), 8.50 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 21.11 (s), 24.55 (d, 3J(P,C) = 6.6 Hz), 24.73 (d, 3 J(P,C) = 4.0 Hz), 27.36 (s, CH2 of amide), 31.85 (s), 34.84 (d, 2 J(P,C) = 4.1 Hz, CH), 35.03 (d, 2J(P,C) = 6.6 Hz, CH), 40.19 (s), 40.22 (s), 115.46 (s, C„N), 167.26 (s, C@O). IR (KBr, cm1): 3305 (m, mNH), 2925 (s, mCH), 1692 (m, mC@O), 1476 (m, mC„N), 1159 (m, mP8O), 1114 (m), 932 (m, mP–N), 868 (m, mP–N), 736 (m, mP– N), 471 (m). 2.3.43. N-Cyanoacetyl-N0 ,N00 -bis (4-methylpiperidinyl) phosphoric triamide (39) Yield: 72%. Anal. Calc. for C15H27N4O2P: C, 55.20; H, 8.34; N, 17.17. Found: C, 55.19; H, 8.35; N, 17.16%. 31P NMR (DMSO-d6): d 10.12 (m). 1H NMR (DMSO-d6): d 0.88 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.00 (m, 4H, CH2), 1.43 (m, 2H, CH), 1.54 (m, 4H, CH2), 2.55 (m, 4H, CH2), 3.36 (m, 4H, CH2), 3.84 (s, 2H, CH2), 9.12 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 21.98 (s), 26.77 (d, 3J(P,C) 8 8.6 Hz, CH2 of amide), 130.40 (s), 33.99 (s), 34.06 (d, 3J(P,C) = 8.6 Hz, CH2), 34.10 (d, 3 J(P,C) = 5.3 Hz, CH2), 44.05 (d, 3J(P,C) = 2.6 Hz, CH2), 44.32 (d, 3 J(P,C) = 2.8 Hz, CH2), 115.63 (d, 4J(P,C) = 1.3 Hz, C„N), 164.46 (s, C@O). IR (KBr, cm1): 3430 (w, mNH), 3100 (m, mNH), 2950 (s), 2465 (s), 1639 (s, mC@O), 1631 (m), 1583 (m), 1212 (s, mP=O), 1063 (s), 968 (m, mP–N), 772 (m, mP–N), 538 (m). 2.3.44. N-Cyanoacetyl-N0 ,N00 -bis (4-fluorophenyl) phosphoric triamide (40) Yield: 56%. Anal. Calc. for C15H13F2N4O2P: C, 51.44; H, 3.74; N, 16.00. Found: C, 51.45; H, 3.75; N, 16.00%. 31P NMR (DMSO-d6): d
313
-5.92 (s). 1H NMR (DMSO-d6): d 3.72 (s, 2H, CH2 of amide), 6.75 (m, 2H, Ar–H), 6.95 (m, 4H, Ar–H), 7.05 (m, 2H, Ar–H), 7.58 (s, 2H, NHamine), 9.50 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.41 (s, CH2 of amide), 115.00 (d, 2J(F,C) = 22.0 Hz), 115.41 (d, 2 J(F,C) = 22.1 Hz), 115.63 (s, C„N), 117.23 (dd, 3J[(F,C), (P,C)] = 7.4 Hz), 118.46 (dd, 3J[(F,C), (P,C)] = 7.5 Hz), 138.40 (s), 1 J(F,C) = 232.0 Hz), 156.43 (d, 141.08 (s), 155.92 (d, 1 J(F,C) = 235.0 Hz), 163.94 (s, C@O). IR (KBr, cm-1): 3415 (m, mNH), 3285 (m, mCH), 3155 (m, mCH), 2960 (m, mCH), 1671 (s, mC@O), 1500 (s, mC„N), 1441 (s), 1201 (s, mP@O), 1065 (s), 941 (m, mP–N), 825 (m, mP–N), 500 (m), 481 (m). 2.3.45. N-Cyanoacetyl-N0 ,N00 -bis (4-chlorophenyl) phosphoric triamide (41) Yield: 60%. Anal. Calc. for C15H13Cl2N4O2P: C, 47.02; H, 3.42; N, 14.62. Found: C, 47.00; H, 3.42; N, 14.61%. 31P NMR (DMSO-d6): d 5.91 (s). 1H NMR (DMSO-d6): d 3.74 (s, 2H, CH2 of amide), 6.70 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.07 (d, 3J(H,H) = 9.7 Hz, 2H, Ar– H), 7.09 (d, 3J(H,H) = 9.7 Hz, 2H, Ar–H), 7.17 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.88 (s, 2H, NHamine), 9.62 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.52 (d, 3J(P,C) = 9.8 Hz, CH2 of amide), 115.53 (s, C„N), 116.92 (s), 118.70 (d, 3J(P,C) = 7.5 Hz), 121.13 (s), 123.58 (s), 128.39 (s), 128.67 (s), 140.90 (s), 144.76 (s), 163.99 (s, C@O). IR (KBr, cm1): 3415 (m, mNH), 3270 (m, mCH), 3125 (m, mCH), 2930 (s, mCH), 1671 (s, mC@O), 1483 (s, mC„N), 1451 (s), 1389 (m), 1295 (m), 1187 (s, mP@O), 1051 (s), 940 (m, mP–N), 817 (m, mP–N), 532 (m). 2.3.46. N-Cyanoacetyl-N0 ,N00 -bis (4-bromophenyl) phosphoric triamide (42) Yield: 63%. Anal. Calc. for C15H13Br2N4O2P: C, 38.16; H, 2.78; N, 11.87. Found: C, 38.15; H, 2.77; N, 11.88%. 31P NMR (DMSO-d6): d 6.01 (s). 1H NMR (DMSO-d6): d 3.74 (s, 2H, CH2 of amide), 6.68 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.01 (d, 3J(H,H) = 8.1 Hz, 2H, Ar– H), 7.22 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.29 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.90 (s, 2H, NHamine), 9.63 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.57 (d, 3J(P,C) = 9.8 Hz, CH2 of amide), 109.16 (s), 111.38 (s), 115.56 (s, C„N), 117.83 (s), 119.23 (d, 3J(P,C) = 7.4 Hz), 131.30 (s), 131.59 (s), 141.36 (s), 144.63 (s), 164.04 (s, C@O). IR (KBr, cm1): 3345 (m, mNH), 3260 (s, mNH), 3120 (s, mCH), 2835 (s, mCH), 2590 (s), 1670 (s, mC@O), 1478 (s, mC„N), 1452 (s), 1187 (s, mP@O), 1051 (s), 1005 (m), 938 (m, mP–N), 813 (m, mP– N), 577 (m), 527 (m), 485 (m). 2.3.47. N-Cyanoacetyl-N0 ,N00 -bis (4-butylphenyl) phosphoric triamide (43) Yield: 66%. Anal. Calc. for C23H23N4O2P: C, 65.99; H, 5.54; N, 13.39. Found: C, 66.00; H, 5.55; N, 13.40%. 31P NMR (DMSO-d6): d 7.09 (m). 1H NMR (DMSO-d6): d 0.86 (t, 3J(H,H) = 7.4 Hz, 6H, CH3), 1.27 (m, 4H, CH2), 1.46 (m, 4H, CH2), 2.43 (m, 2H, CH2), 2.47 (m, 2H, CH2), 3.72 (s, 2H, CH2 of amide), 6.78 (d, 3 J(H,H) = 8.1 Hz, 2H, Ar–H), 6.92 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 6.95 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 7.00 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.37 (b, 2H, NHamine), 9.45 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 13.68 (s), 13.71 (s), 21.59 (s), 21.64 (s), 26.37 (d, 3 J(P,C) = 9.6 Hz, CH2 of amide), 33.16 (s), 33.33 (s), 34.02 (s), 34.09 (s), 115.59 (s, C„N), 117.17 (d, 3J(P,C) = 6.5 Hz), 119.66 (s), 128.26 (s), 129.03 (s), 133.34 (s), 135.63 (s), 137.44 (s), 139.52 (s), 164.12 (s, C@O). IR (KBr, cm1): 3354 (m, mNH), 3260 (m, mNH), 3010 (m, mCH), 2840 (s, mCH), 2580 (s), 1669 (s, mC@O), 1504 (s), 1457 (s, mC„N), 1193 (s, mP@O), 1060 (s), 925 (m, mP– N), 815 (m, mP–N), 535 (m). 2.3.48. N-Cyanoacetyl-N0 ,N00 -bis (furfuryl) phosphoric triamide (44) Yield: 60%. Anal. Calc. for C13H15N4O2P: C, 53.79; H, 5.21; N, 19.30. Found: C, 53.80; H, 5.20; N, 19.30%. 31P NMR (DMSO-d6): d
314
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
7.67 (m). 1H NMR (DMSO-d6): d 3.71 (s, 2H, CH2 of amide), 3.95 (m, 4H, Ar–CH2), 4.98 (m, 2H, NHamine), 6.22 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 6.36 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 7.53 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 9.30 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.60 (d, 3 J(P,C) = 8.6 Hz, CH2 of amide), 37.06 (s, Ar–CH2), 106.31 (s), 110.34 (s), 115.52 (s, C„N), 141.82 (s), 153.95 (d, 3J(P,C) = 6.6 Hz), 164.38 (s, C@O). IR (KBr, cm1): 3295 (s, mNH), 3095 (m, mCH), 2910 (m, mCH), 1686 (s, mC@O), 1470 (s, mC„N), 1150 (s, mP@O), 1067 (m), 924 (m, mP–N), 877 (m, mP–N), 748 (m, mP–N), 564 (m).
have been obtained up until now in such a simple one-step reaction. The 31P{1H} NMR spectrum of compound 1 displays two singlet peaks for the two phosphorus atoms, at 5.44 and 6.69 ppm, and the substitution of different cyclic and acyclic aliphatic amines for the chlorine atoms shifts the d (31P) downfield, while substitution with phenyl groups leads to upfield shifts. The d (31P) in this series varies between 3.42 and 3.74 ppm (in 7 containing an aromatic aniline moiety) to 20.03, 20.16 ppm (in 9 containing a heterocyclic aliphatic diazaphosphole ring). The 1H NMR spectrum of 3 displayed four doublet signals for the four types of CH3 groups of isopropyl moieties due to the fact that the carbon atom of the CH group in the iso-propyl substituent is prochiral, and so the two methyl groups bonded to this group are different and show two signals in both the 1H and 13C NMR spectra. The 13C NMR spectra of compounds 1 and 3–10 displayed six separate signals for the aromatic carbon atoms of the 4-aminobenzamide group and 2 J(P,C@O) = 3.5 Hz for the C@O group in 1, while this constant was zero for the other compounds. Compound 6, with cyclohexyl substituents, displayed 12 peaks in the aliphatic region of the 13C NMR spectrum, with four 3J(P,C) coupling constants for CH2 groups, four singlet signals for CH2 groups and four 2J(P,C) coupling constants for the CH groups. These results indicate that due to the different spatial orientation of the aliphatic six-membered rings, the four CH groups of the four cyclohexyl groups are different, but other related carbon atoms on one side of the molecule are equal to each other while being unequal to their related carbon atoms on the other side. The 13C NMR spectrum of bis diazaphosphole 9 displayed two 2J(P,C) = 5.0, 4.9 Hz for the CH3 groups, two 2J(P,C) = 7.3, 5.7 Hz for CH2 moieties, two singlets for CH3 as well as two singlets for CH2 groups. A reason for this may be that for the phosphorus and carbon atoms a simple splitting is seen on one side of the molecule, while for the carbon atoms on the other side no coupling is observed. According to the Karplus relationship between the 3J(P,X), X = H, C coupling constant and the P–N–C–X torsion angle [33], this is due to the P–N–C–H torsion angle values. The 13C NMR spectrum of 10 showed three signals in the aliphatic region for the cyclopentyl moieties and the proton integrals in the 1H NMR spectrum indicate that only two cyclopentyl groups are connected to one of the phosphorus atoms, while for
2.3.49. N-Trifluoroacetyl-N0 ,N00 -bis (4-methyl phenyl) phosphoric triamide (45) Yield: 78%. Anal. Calc. for C16H17F3N3O2P: C, 51.76; H, 4.62; N, 11.32. Found: C, 51.77; H, 4.62; N, 11.33%. 31P NMR (CD3CN): d 5.38 (m). 1H NMR (CD3CN): d 2.26 (s, 6H, CH3), 6.53 (d, 2 J(PNH) = 9.9 Hz, 2H, NHaromatic), 7.04 (d, 3J(H,H) = 8.4 Hz, 2H, Ar– H), 7.07 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 9.48 (b, 1H, NHamide). 13C NMR (CD3CN): d 20.64 (s, CF3), 119.94 (d, 3J(P,C) = 6.9 Hz), 130.73 (s), 132.99 (s), 137.89 (s), 167.42 (s, C@O). IR (KBr, cm1): 3419 (s, mNH), 3279 (s, mNH), 2924 (m, mCH), 1724 (s, mC@O), 1616 (s), 1517 (s), 1459 (s), 1309 (s), 1282 (m), 1208 (s), 1175 (s, mP@O), 966 (m, mP–N), 815 (m, mP–N), 596 (m), 474 (m). 3. Results and discussion 3.1. Spectroscopic study In this work a number of new phosphoramidate derivatives of bisphosphoramidates and phosphoric triamides were synthesized using PCl5 and POCl3 as starting materials, Schemes 1 and 2. Here, the spectroscopic features of these compounds are studied. 3.1.1. Bisphosphoramidates 1, 3–10 The syntheses of the bisphosphoramidates 1 and 3–10 (containing the (O)P–NH–C6H4–C(O)NH–P(O) linkage) were performed by the reaction of PCl5 with 4-aminobenzamide in a 1:4 molar ratio to initially yield the bisphosphoramide Cl2P(O)NHC6H4C(O)NHP(O)Cl2 (1) that was used as an intermediate to react with different amines to give molecules 3–10, Scheme 1. As far as we know, these compounds are the first examples of bisphosphoramidates that
C
O P R1 R2
H2N
P N H
O
O
O
O
C X
NH2
R4
C
P
PCl5
R3
R1 R2
N H
O
O NH2
C N H
X
NH2
R1 = R2 =R3 = R4= Cl (1), NH-CH(CH3)2 (3), NH-CH 2CH(CH3)2 (4), N( C2H5)2 (5), NH- C6H11 (6), NH- C6H5 (7), R1 = R3= Cl; R2 = R4= 4-Cl-C6H4-NH (8), R1 = R2 =R3 = R4= (CH3)N-(CH2)2-N(CH3) (9), R1 = R2= NH-C5H9; R3 = R4= OH (10)
H2N
C
P R2
O C
O R1
O
NH2
N H
(2), R1 = R2 = Cl R1 = Cl; R2 = NH-CH2-CH(CH3)2 (11), R1 = R2 = NH-C5H9 (12), R1 = R2 = 4-Br-C6H4-NH (13)
(32), X = CN-CH2; R1 = R2 = Cl X = CN-CH2; R1 = Cl, R2 = NHCH2C6H5 (33), X = CN-CH2; R1 = R2 = Cl NHCH2C6H5 (34), NHCH(CH3)(C6H5) (35), NHCH2(2-Cl-C6H4) (36), NHC5H9 (37), NHC6H11 (38), 4-CH3-C5H9N (39), 4-F-C6H4-NH (40), 4-Cl-C6H4-NH (41), (42), 4-Br-C6H4-NH (43), 4-Bun-C6H4-NH NH-CH2-C4H3O (44), X = CF3; R1 = R2 = 4-CH3-C6H4-NH (45)
Scheme 1. Preparation pathway for compounds using PCl5 as a starting compound.
315
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
NO2
O P
N H
HN Cl
O
HN
O
P
P
O
HN
O
HN
O
HN
O
HN
O
CH3
O
(25)
O
O
(24)
(26)
CH3
O CH3
O
O
P
HO
N H
HN
P
O
N H
HN HN
X
OH
P
O
HN
O
Y
R1
O
R2 Y
(27)
(23) OCH3
O
O P
HN
P
N
X Cl
HN
NH
O P
HN
NH2
X
OCH3
H2C
X
POCl3
Cl
H2C N
X X
X
X
HN
O
O
P
P
N
N
N X
O
H3C H2N Cl
O
X
N
P
N
H3C
NH2
P
N H
N NH H
N H
Cl
HN
NH
X = Cl (30), C6H5 (31)
NH2
X = H (14), F (15), Cl (16), Br (17)
Cl
N
(28) H3C X
X = H (18), F (19), Cl (20), Br (21)
(29)
Scheme 2. Preparation pathway for compounds using POCl3 as a starting compound.
the other phosphorus atom the two cyclopentyl substituents are replaced by OH groups. This is probably due to the acquisition of the NMR spectra in D2O solvent, and hence hydrolysis of the molecule occurs. A comparison of d (31P) in compounds 4 and 11 revealed that in the bisphosphoramide 4 the P atom is far more deshielded than in the phosphoric triamide 11. The IR spectra indicated two m (P@O) for the two P@O bonds and a m (C@O) in each compound. The 2J(PNHamine) coupling constant for compounds 1, 5 and 6 are 11.9, 9.1 and 7.6 Hz, respectively, and the corresponding m (P–N) values are 994, 941 and
907 cm1. These data reveal that the more the m (P–N) value increases, i.e., a shorter P–N bond with more s character in the nitrogen hybridization, the more the 2J(PNHamine) coupling constant is enhanced. 3.1.2. Bisphosphoramidates 14–21 The bisphosphoramidates 14–21 (containing the (O)P–N–P(O) linkage) were prepared by the reaction of POCl3 with different first-type aromatic amines, Scheme 2. To our knowledge, this is the first attempt that has been made to obtain these types of
316
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
compounds using time-dependent reactions. That is, the synthesis procedure of these molecules is similar to that of phosphoric triamides, but these compounds are obtained after 48 h stirring and if the reaction mixture was allowed to stir for about one or two weeks, the corresponding phosphoric triamides would be yielded. In fact, these compounds are kinetically stable products of the reaction and are not stable with time. Thus after a relatively long time they convert to their related thermodynamically stable phosphoric triamides. The 2J(P,P) coupling constants observed in the 31P{1H} NMR spectra are about 20 Hz. The two phosphorus atoms are not connected directly to each other, because the 1 J(P,P) coupling constants in other similar compounds are reported to be about 200 Hz [34]. The 2J(P,P) coupling constant in compound 14 was measured as 19.7 Hz in DMSO-d6 and it decreased to 17.5 Hz in the solvent CD3OD, probably due to the different hydrogen bonding interactions in this solvent. The 31P NMR spectra of compounds 14 and 18 (containing the anilinium substituent) indicated two signals, the upfield one of them being a multiplet and the other being only a doublet peak. This trend is reverse for compounds 15–17 and 19–21, including para-haloanilinium groups. It is clear that the doublet peak is related to the P1 atom and the multiplet peak to the P2 atom (Scheme 3), and the reason for the reduced splitting of P1 with the NH group of the aromatic amine may be described by the resonance interaction in Scheme 3. The downfield shift of d (31P) for the P2 atom in compounds containing para-haloanilinium groups is related to the electron withdrawing nature of the electronegative halogen atoms in comparison with the inert H atom. Comparison of d (31P) in compounds 14–17 and also in 19–21 revealed that the shielding of the P1 and P2 atoms decreases with the decreasing halogen electronegativity from F to Cl to Br (i.e., from 15 to 17 and from 19 to 21). The shielding of the phosphorus atoms in compounds 14 and 18 containing anilinium moieties are greater than that of compounds containing 4-fluoroanilinium groups, and the shielding order is Br > Cl > H > F. The reason for the greater shielding of the P atoms in compounds with 4-Cl and 4-Br substituents relative to the H substituent can be explained by the electron release of the halogens through resonance. The 13C NMR spectra of 15 and 19 indicate 1–4J(F,C) coupling constants as well as 3J(P,C) coupling constants. The IR spectra revealed two m(P@O) frequencies for the two P@O bonds and we can relate the smaller m(P@O) to the weaker P@O bond and vice versa. In molecules 14 and 18, the upfield signal is related to P2 and in compounds 15–17 and 19–21, it is related to P1. 3.1.3. Phosphoramidates and phosphoric triamides The phosphoramidates 2 and 11–13 were prepared by the reaction of PCl5 with 4-aminobenzamide in a 1:1 molar ratio and we may judge that the P–N bond is formed from the anilinium NH2 group not from the amidic C(O)NH2. This is because stronger P–N bonds always have been observed for P–Namine compared to P–Namide in our other synthesized compounds, and also the C(O) group causes weakening of the P–N bond via resonance interactions. A
O
O P2
HN
NH
comparison of d (31P) in these molecules indicated that substitution of aliphatic electron donor amines with the chlorine atoms of 2 leads to a more positive P atom (in 11 and 12), while the aromatic 4-bromoaniline (in 13) had the opposite effect. In the 13C NMR spectra of these compounds four singlet signals were observed for the benzamidic ring, while in their related bisphosphoramidates six different signals were obtained for the six carbon atoms of the ring. Replacement of an amine group by a chlorine atom gives a m (P–N) value indicating a stronger P–N bond and a m(C@O) value indicating a weaker C@O bond. For the synthesis of compounds 23–26, first the hydrochloride salt of the phenylalanine benzylester was obtained for subsequent reaction with an RP(O)Cl2 intermediate, where R = amine or phenol. Phosphoric triamides of this type have shown antitumor, antiviral and anti-HIV properties [1–4] and for this reason we have been interested in studying such molecules. In the case of compound 23, it is concluded from the 1H and 13C NMR spectra that the phenylalanine benzylester is hydrolyzed and the phenylalanine is connected to the phosphorus atom. The 1H and 13C NMR spectra of molecules 23–26 displayed two unequivalent aminoester (or aminoacid) moieties, probably owing to the presence of chiral CH groups as well as the spatial hinderance caused by these two huge substituents. However, this is not observed in the 1H and 13C NMR spectra of 29 that also contain two chiral aminoester groups. Therefore, the chirality of these moieties is not the reason for the difference between these groups in compounds 23–26, but it is the various spatial orientations of the aminoester/aminoacid groups (the huge groups are far away from each other due to the repulsion) which result in the creation of a central chiral phosphorus atom. The 31P NMR spectra exhibited an upfield shift for d (31P) in compounds including electron donor groups such as p-tolyl (24), while it is shifted downfield with electronegative 4-nitroanilinium or 4-chloroanilinium groups (25 and 26). Both compounds 23 and 27 contain a p-toluidinium substituent and their difference is the replacement of the aminoacid groups in 23 with aminoester groups (27). The d (31P) in 23 is upfield, and the P@O bond shows a weaker m(P@O), whereas the C@O bond has a stronger m(C@O) relative to those of 27. The d (31P) in compound 28 is upfield relative to that of 29, perhaps due to the greater electron donation of the two chlorine atoms via resonance in comparison to the two p-toluidinium groups. A huge amino group is bonded to the phosphorus atom in molecules 30 and 31. This kind of amine group has indicated possible clinical applications [35–37] and significant importance in medicine. Our attempts to obtain a single crystal of compound 30 in a methanol/acetonitrile mixture resulted in structure I, which is most likely a hydrolyzed product of 30 in the solution (perhaps the P–N bond of this giant amino group is labile due to steric repulsion). The d (31P) of 30 is at a much higher field relative to that of 31. Therefore, it could be concluded that the phenyl ring plays an important role as an electron withdrawing group in compound 31.
N R
Cl
HN
P2
HN
NH
R
X X X
OH
O
P1
X = H, F, Cl, Br R = 4-X-C6H4, C5H4N
X
Scheme 3. The resonance interaction in bisphosphoramidates 14–21.
N R
P1
Cl
N R
317
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
The 31P NMR spectra of the phosphoramidates 32–44, containing the cyanoacetamide substituent, demonstrated that substitution of the chlorine atoms in compound 32 by aliphatic amino groups result in deshielded phosphorus atoms, while replacing with aromatic amino groups of the formula 4-X–C6H4NH, X = F, Cl, Br, (CH2)3CH3, leads to much more shielded phosphorus atoms. The connection of p-butylaniline to the phosphorus atom causes its shielding, and the d (31P) is the most upfield in this series. Also, the d (31P) of the p-haloanilinium substituents becomes more positive on decreasing the halogen electronegativity. d (31P) changed in the order of Br > Cl > F > (CH2)3CH3 for compounds 40–43. An interesting feature in the 1H and 13C NMR spectra of compounds 40–43, having p-substituted anilinium substituents, is that the two aromatic groups are different and present two sets of signals in the spectra, whereas when aliphatic amino groups are replaced by the two Cl atoms in 32, they are equal. This characteristic was not seen in the spectra of compound 45. The 13C NMR spectra of 32–44 revealed that the 2J(P,C) coupling constant, i.e., the coupling of the amidic CH2 carbon atom with the P atom, is decreased from 10.5 Hz (in 32) to about 8.9 Hz (in 33– 44). Therefore, replacement of the chlorine atoms by different amino groups reduces the 2J(P,C) coupling constant. Compound 35 contains a-phenylethyl substituents that have a chiral carbon
1
H3C
atom at the CH groups, leading to the appearance of two sets of peaks in its 1H and 13C NMR spectra. The 13C NMR spectrum of compound 37 exhibited five signals for the five carbon atoms of the two aliphatic cyclopentyl moieties owing to the fact that the two aliphatic rings are equal, but the five carbon atoms of the ring are different. The 13C NMR spectra of compounds 38 and 39 display eight separate signals for the aliphatic carbon atoms of the cyclohexyl and 4-methylpiperidinyl groups due to the fact that the two aliphatic groups are not equal. A 4J(P,C) coupling constant of 1.6 Hz was observed for the splitting of the C„N carbon atom with the phosphorus atom in 32, but this coupling did not occur in molecules 33–44. The mass spectrum of compound 29 indicates ionic fragments corresponding to this molecule as well as a base peak at m/z = 352 (100%). There are also some peaks at m/z > 352 related to dimerization of the ionic fragments [38]. The following rearrangements are proposed for the mechanism of the dimerizations (Scheme 4(1 and 2)). (a) The P–N bond of the aminopyridinium group is broken, an aminopyridine group is released and a P@N bond is formed. Then, conjugation of the two similar fragments, i.e. a cycloaddition reaction, will yield the diazadiphosphetidine i with m/z = 516. (b) If a ptoluidine group is separated from the molecule and the resulting
H3C
O H3C
O
P N H
N H
NH
CH3
N
H3C
NH2
N
CH3
O
P N H
O
O
P
P N N
HN
CH3
NH
P
+
N H
N
N
CH3 H3C
H3C
i , m/z = 516
m/z = 258 NH2
CH3 O
O
N
CH3
O
N N H
N
N N
CH3
O
N P
N
P
P HN
NH
P
+
N H
N CH3 H3C
ii , m/z = 490
m/z = 246
2
H3C
O
O
P
P
CH3
P
P
N N
HN
N
HN
NH
CH3
O
O
H3C
.
.
N
H3C
NH
O
O
P
P N
HN
NH
NH
NH
CH3
NH HN N
CH3 H3C
CH3
H3C
m/z = 516
i O
O
N
N
N N
H3C
NH
N
.
O N
HN NH
NH
N
P
P
NH HN
NH
H3C
CH3 H3C
H3C
N
O
N
P
P HN
NH
.
O
O
N
P
P HN
CH3
H3C
CH3
ii
Scheme 4. The proposed fragmentation mechanism of compound 29 in the mass spectrum.
CH3
m/z = 597
CH3
318
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
N(2)–C(1)–C(8A)–C(4A) and N(20 )–C(10 )–C(80 A)–C(40 A) are 6.6(3)° and 8.7(3)° (also, compare the torsion angles N(2)–C(1)–C(9)– C(10), N(20 )–C(10 )–C(90 )–C(100 ) and C(14)–C(13)–O(1)–C(16), C(140 )–C(130 )–O(10 )–C(160 ) that are 68.0(3)°, 61.0(3)° and 11.4(4)°, 1.8(4)°, respectively). This phenomenon was observed for some of our previously reported structures [17,18,23]. Although there is a C@C double bond between the two unsaturated sixmembered rings, they are not planar and show a puckered shape. The C(5)–C(10) and C(50 )–C(100 ) carbon atoms of the phenyl ring as well as their corresponding hydrogen atoms in compound 34 revealed disorder in the structure that can be described by free rotation along the C(4)–N(3) bond, causing uncertainty in the determination of the carbon and hydrogen locations of the phenyl ring. The P@O bond lengths in molecules 34 and 44 are 1.483(16) and 1.491(15) Å, which are larger than the normal P@O bond length (1.450 Å) [40]. The P atoms have slightly distorted tetrahedral configurations, e.g. the surrounding angles around the P atoms of the two symmetrically different molecules in compound 34 are in the range 103.16(10)–117.34(10)°. The P–Namide bond lengths are longer than the P–Namine bond lengths because of the interaction of the Namide atom with the p resonance system of the C@O group, which results in a shorter C–Namide bond length, i.e., 1.687(19) > 1.616(19), 1.620(2) (in 34), and 1.685(17) > 1.622(18), 1.621(18) Å (in 44). All of these P–N bonds are shorter than the typical P–N single bond length (1.770 Å) [40]. The nitrogen envi-
similar fragments are bonded to each other, another diazadiphosphetidine (ii) is obtained with m/z = 490. (c) If one of the P–N bonds in the cyclic diazadiphosphetidines i breaks then an aminopyridinium radical cation is bonded to it, a bisphosphoramidate with m/z = 516 could be produced. (d) If one of the P–N bonds in the diazadiphosphetidine ii breaks then a p-toluidinum radical cation is bonded to it, a bisphosphoramidate with m/z = 597 is obtained. This fragmentation pathway is also proposed for the mass spectrum of compound (C5H4N–NH)2P(O)[N(CH3)(C6H11)] [39] in which there are some molecular ion peaks at m/z greater than the base peak, and a similar mechanism could be considered for its fragmentation (Scheme 5(1 and 2)). 3.2. X-ray crystallography Single crystals of compounds I (4-OCH3–C6H4–CH2–C9H13– NH2Cl), 34 and 44 were obtained from a solution of methanol/chloroform or methanol/acetonitrile/water at room temperature. The crystallographic data and the details of the X-ray analysis of these compounds are represented in Table 1, and selected bond lengths and angles are given in Table 2. Hydrogen bonding data of these structures are presented in Table 3. Molecular structures (ortep views) have been shown in Figs. 1–3. There are two symmetrically independent molecules in the crystalline lattice of compound I due to the differences in the related torsion angles of these two conformers. The torsion angles
1
N
P
N
O
N H
NH
CH3
N H
N
N
P
P N N
P
P N H
N HN
+
N
N
O
N
N
O
O
N
O H3C
NH N
N N
NH
m/z = 258
i , m/z = 464
NH2 N
O
O O
O
N
N
P
P N
N
N
N
N N
H3C
CH3
N CH3
CH3
ii , m/z = 502
m/z = 251
2
N N
N
+
P
P
O
O
N
N
P
P N N
HN
. O
O
N
.
N
HN
N
O
O
P
P NH
NH
NH
N
N
HN
P
P
NH N
CH3
N
N
N
NH
N
N
N
CH3
N
N
m/z = 577
i
O
O
P
P N N
N H3C
ii
O
P
P N
N N
H3C
N CH3
N
O
.
N
.
O
NH
P
NH
H3C
P N
N
N
O
NH
N HN
CH3
CH3 N
H3C
CH3
m/z = 596
Scheme 5. The proposed fragmentation mechanism of compound (C5H4N–NH)2P(O)[N(CH3)(C6H11)] in the mass spectrum.
319
K. Gholivand et al. / Polyhedron 28 (2009) 307–321 Table 1 Crystallographic data for compounds I, 34 and 44.
Empirical formula Formula weight Temperature (K) Wavelength (Å) Crystal system, space group Unit cell dimensions a (Å) b (Å) c (Å) a (°) b (°) c (°) V (Å3) Z, Dcalc (Mg m3) Absorption coefficient (mm1) F(0 0 0) Crystal size (mm) h Range for data collection (°) Limiting indices Reflections collected/unique Rint Completeness to h (%) Absorption correction Maximum and minimum transmission Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices R indices (all data) Absolute structure parameter Largest difference in peak and hole (e Å3)
I
34
44
C17H24ClNO 293.82 293(2) 0.71073 triclinic, P 1
C17H19N4O2P 342.33 293(2) 0.71073 triclinic, P 1
C13H15N4O4P 322.26 120(2) 0.71073 triclinic, P 1
8.0732(10) 9.3318(11) 11.8945(14) 88.970(5) 75.950(5) 73.436(5) 831.95(17) 2, 1.173 0.226 316 0.25 0.25 0.20 1.77–26.03 9 6 h 6 9; 11 6 k 6 11; 14 6 l 6 14 6914/6011 0.0134 98.6 semi-empirical from equivalents 0.954 and 0.948 full-matrix least-squares on F2 6011/3/361 1.022 R1 = 0.0377, wR2 = 0.0798 R1 = 0.0489, wR2 = 0.0842 0.02(5) 0.210 and 0.110
5.1799(10) 12.799(3) 14.177(3) 71.44(3) 84.98(3) 85.71(3) 886.5(4) 2, 1.282 0.172 360 0.40 0.30 0.25 2.60–27.06 0 6 h 6 6; 16 6 k 6 16; 18 6 l 6 18 4297/3868 0.0193 99.4 none full-matrix least-squares on F2 3868/41/199 1.012 R1 = 0.0496, wR2 = 0.1208 R1 = 0.0743, wR2 = 0.1265
4.9743(5) 10.6382(10) 14.5630(14) 81.395(2) 81.346(2) 81.013(2) 746.21(13) 2, 1.434 0.208 336 0.43 0.08 0.07 1.95–28.03 6 6 h 6 6; 14 6 k 6 13; 19 6 l 6 19 7801/3610 0.0331 99.7 semi-empirical from equivalents 0.986 and 0.904 full-matrix least-squares on F2 3610/0/199 1.040 R1 = 0.0511, wR2 = 0.1202 R1 = 0.0710, wR2 = 0.1334
0.364 and 0.474
0.426 and 0.407
Table 2 Selected bond lengths (Å) and angles (°) for compounds I, 34 and 44. I
34
44
C(1)–C(8A) C(1)–N(2) C(1)–C(9) C(1)–H(1A) C(3)–N(2) N(2)–H(2A) N(2)–H(2B) C(3)–C(4) C(4)–C(4A) C(10 )–C(80 A) C(10 )–N(20 ) C(10 )–C(90 ) C(10 )–H(10 A) C(30 )–N(20 ) N(20 )–H(20 A)
1.500(3) 1.502(3) 1.554(3) 0.980 1.483(3) 0.961 0.920 1.514(4) 1.493(4) 1.520(4) 1.501(3) 1.537(3) 0.980 1.489(3) 0.996
P(1)–O(1) P(1)–N(1) P(1)–N(2) P(1)–N(3) O(2)–C(1) N(1)–C(1) N(1)–H(1N) N(2)–C(11) N(3)–C(4) N(4)–C(3) C(4)–C(5) C(4)–C(50 ) C(5)–C(6) C(50 )–C(60 ) C(50 )–C(100 )
1.483(16) 1.687(19) 1.616(19) 1.620(2) 1.212(2) 1.355(3) 0.870 1.460(3) 1.477(3) 1.133(3) 1.496 1.460(7) 1.3900 1.343(9) 1.345(10)
P(1)–O(1) P(1)–N(1) P(1)–N(2) P(1)–N(3) O(2)–C(1) O(3)–C(5) O(3)–C(8) O(4)–C(10) O(4)–C(13) N(1)–C(1) N(1)–H(1A) N(2)–C(4) N(3)–C(9) N(4)–C(3) C(1)–C(2)
1.4914(15) 1.6846(17) 1.6218(18) 1.6208(18) 1.223(2) 1.370(3) 1.375(3) 1.367(3) 1.371(3) 1.356(3) 0.880 1.467(3) 1.465(3) 1.149(3) 1.525(3)
C(8A)–C(1)–N(2) C(8A)–C(1)–C(9) N(2)–C(1)–C(9) C(8A)–C(1)–H(1A) N(2)–C(1)–H(1A) C(9)–C(1)–H(1A) C(3)–N(2)–C(1) C(3)–N(2)–H(2A) C(1)–N(2)–H(2A) C(3)–N(2)–H(2B) C(1)–N(2)–H(2B) C(80 A)–C(10 )–N(20 ) C(80 A)–C(10 )–C(90 ) N(20 )–C(10 )–C(90 ) C(80 A)–C(10 )–H(10 A) N(20 )–C(10 )–H(10 A) C(90 )–C(10 )–H(10 A)
112.10(19) 113.44(19) 107.56(18) 107.80 107.80 107.80 113.22(18) 107.80 110.10 111.80 109.10 110.93(18) 113.20(2) 108.70(2) 107.90 107.90 107.90
O(1)–P(1)–N(1) O(1)–P(1)–N(2) O(1)–P(1)–N(3) N(2)–P(1)–N(1) N(3)–P(1)–N(1) N(3)–P(1)–N(2) C(1)–N(1)–P(1) C(1)–N(1)–H(1N) P(1)–N(1)–H(1N) C(11)–N(2)–P(1) C(11)–N(2)–H(2N) P(1)–N(2)–H(2N) C(4)–N(3)–P(1) C(4)–N(3)–H(3N) P(1)–N(3)–H(3N) O(2)–C(1)–N(1) O(2)–C(1)–C(2)
106.00(9) 109.71(10) 117.34(10) 113.04(10) 103.16(10) 107.58(10) 125.01(14) 114.80 120.00 128.27(15) 115.90 115.90 121.41(15) 114.30 123.40 123.70(2) 122.10(2)
O(1)–P(1)–N(1) O(1)–P(1)–N(2) O(1)–P(1)–N(3) N(2)–P(1)–N(1) N(3)–P(1)–N(1) N(3)–P(1)–N(2) C(1)–N(1)–P(1) C(1)–N(1)–H(1A) P(1)–N(1)–H(1A) C(4)–N(2)–P(1) C(4)–N(2)–H(2A) P(1)–N(2)–H(2A) N(1)–C(1)–C(2) O(2)–C(1)–C(2) O(2)–C(1)–N(1) C(6)–C(5)–O(3) C(11)–C(10)–O(4)
105.72(9) 108.09(9) 119.51(9) 114.33(9) 102.54(9) 106.89(9) 123.40(14) 118.30 118.30 129.36(15) 115.30 115.30 115.53(17) 121.63(18) 122.84(18) 109.90(2) 109.90(2)
ronment is nearly planar. In compound 34, the angles C(1)–N(1)– P(1), C(1)–N(1)–H(1N) and P(1)–N(1)–H(1N) are 125.01(14),
114.8° and 120.0°, respectively, with an average of 119.94°. The sum of the surrounding angles around the N(2) and N(3) atoms
320
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Table 3 Hydrogen bonds for compounds I, 34 and 44 (Å, °) Compound
d(H A) 0
0
d(D–H)
d(H A)
d(D A)
\DHA
I
N(2 )–H(2 A) Cl(1)#1 N(2)–H(2A) Cl(1)#1 N(2)–H(2B) Cl(2)#4 N(20 )–H(20 B) Cl(2)#1
1.00 0.96 0.92 0.90
2.16 2.18 2.15 2.19
3.160(19) 3.130(19) 3.034(2) 3.035(2)
178 172 160 155
34
N(1)–H(1N) O(1)#5 N(2)–H(2N) O(2)#3 N(3)–H(3N) O(1)#2
0.87 0.86 0.87
1.97 2.17 2.33
2.833(2) 2.946(2) 3.178(3)
174 151 166
44
N(1)–H(1A) O(1)#6 N(2)–H(2A) O(2)#7 N(3)–H(3A) O(1)#8
0.88 0.88 0.88
1.89 2.11 2.08
2.764(2) 2.889(2) 2.959(2)
174 147 177
Symmetry transformations used to generate equivalent atoms: (#1) x, y, z, (#2) x + 1, y, z, (#3) x 1, y, z, (#4) x + 1, y 1, z, (#5) x, y + 1, z + 2, (#6) x, y + 1, z + 1, (#7) x 1, y, z, (#8) x + 1, y, z.
are 360.07° and 359.11°, respectively. Similar results were obtained for the nitrogen atoms in the structure of 44, which indicate sp2 hybridization for the nitrogen atoms, although because of the repulsion and steric effects, some angles were either greater or smaller than 120°. It is noticeable that the P@O and C@O bonds indicate an anti configuration with respect to each other in compounds 34 and 44, which is in agreement with our previously reported results [17,18,25–27]. The two symmetrically independent molecules of I are connected to each other through two intermolecular N(2)– H(2A) Cl(1) and N(20 )–H(20 A) Cl(1) hydrogen bonds and each of these independent molecules is linked to its symmetrically independent molecules via intermolecular N(2)–H(2B) Cl(2) and N(20 )–H(20 B) Cl(2) hydrogen bonds. Considering the weak intermolecular C–H O and C–H Cl hydrogen bonds, this creates a three dimensional polymeric chain in the crystalline lattice. Intermolecular N(1)–H(1N) O(1) hydrogen bonds between the two adjacent molecules in compound 34 create a non-centrosymmetric dimer (because of the disorder in one molecule, the dimer is not centrosymmetric). This dimer is connected to similar dimers by intermolecular N(2)–H(2N) O(2) and N(3)–H(3N) O(1) hydrogen bonds. Beside these H-bonds, there are also weak intermolecular hydrogen bonds such as C(16)–H(16A) O(2), and all of them produce a three dimensional network. The intermolecular N(2)– H(2A) O(2) and N(3)–H(3A) O(1) hydrogen bonds in the structure of 44 connect the neighboring molecules to each other to
Fig. 2. Molecular structure and atom labelling scheme for C„N–CH2C(O)NHP(O)(NHCH2C6H5)2, compound 34 (30% probability ellipsoids).
construct a linear chain. The molecules in this polymeric chain are linked to other molecules through intermolecular N(1)– H(1A) O(1) hydrogen bonds. Repetition of the H-bonds generates a one dimensional polymeric chain. If weak intermolecular C– H O and C–H N hydrogen bonds [like C(12)–H(12A) O(2), C(2)–H(2B) N(4) and C(13)–H(13A) N(4)] are taken into account, a 3-D polymeric chain is obtained. 4. Conclusion Using PCl5 and POCl3 as starting materials, a number of novel phosphorus derivatives of bisphosphoramidates, phosphoramidates and phosphoric triamides were synthesized. The reaction of 4-aminobenzamide with PCl5 in different molar ratios yielded different products, bisphosphoramides and phosphoric triamides. Furthermore, the interaction of POCl3 with first-type aromatic
Fig. 1. Molecular structure and atom labelling scheme for 4-OCH3–C6H4–CH2–C9H13–NH2Cl, compound I (50% probability ellipsoids).
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Fig. 3. Molecular structure and atom labelling scheme for C„N–CH2C(O)NHP(O)(NHCH2C4H3O)2, compound 44 (50% probability ellipsoids) that shows two conformers in the crystal lattice.
amines gave bisphosphoramidates with a P–N–P linkage that demonstrated 2J(P,P) 20.0 Hz in the 31P NMR spectra. Indeed, two simple one-pot pathways are presented here for the synthesis of the new bisphosphoramidates that are, to our knowledge, the first examples of bisphosphoramidates that have been obtained so far. The X-ray crystal structures of compounds I (4-OCH3–C6H4–CH2– C9H13–NH2Cl), 34 and 44 were further investigated and all of these structures displayed three dimensional polymeric chains through strong- and weak hydrogen bonds. The presence of chiral aminoacidester moieties in the phosphoric triamides lead to chiral molecules which showed two sets of signals for the two groups. Acknowledgement We wish to thank the Research Council of Tarbiat Modares University for the financial support of this work. Appendix A. Supplementary data CCDC 604118, 604115 and 678082 contain the supplementary crystallographic data for (C17H24ClNO), (C17H19N4O2P) and (C13H15N4O4P). These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: [email protected]. Crystallographic data for the structures of I, 34 and 44. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.poly.2008.10.057. References [1] N.-H. Nam, Y. Kim, Y.-J. You, D.-H. Hong, H.-M. Kim, B.-Z. Ahn, Bioorg. Med. Chem. 11 (2005) 1021.
321
[2] T.K. Venkatachalam, P. Samuel, F.M. Ucken, Bioorg. Med. Chem. 13 (2005) 1763. [3] C. Mc Guigan, J.-C. Thiery, F. Daverio, W.G. Jiang, G. Davis, M. Mason, Bioorg. Med. Chem. 13 (2005) 3219. [4] A.-L. Villard, G. Coussot, I. Lefebvre, P. Augustijns, A.-M. Aubertin, G. Gosselin, S. Peyrottes, C. Périgaud, Bioorg. Med. Chem. 16 (2008) 7321. [5] I. Ghesner, A. Soran, C. Silvestru, J.E. Drake, Polyhedron 22 (2003) 3395. [6] M. Ghesner, A. Silvestru, C. Silvestru, J.E. Drake, M.B. Hursthouse, M.E. Light, Inorg. Chim. Acta 358 (2005) 3724. [7] C. Silvestru, J.E. Drake, Coord. Chem. Rev. 223 (2001) 117. [8] K. He, Z. Zhou, L. Wang, K. Li, G. Zhao, Q. Zhao, C. Tang, Tetrahedron 60 (2004) 10505. [9] M.S. Balakrishna, S.S. Krishnamurthy, H. Manohar, Organometallics 10 (1991) 2522. [10] O. Bumbu, A. Silvestru, C. Silvestru, J.E. Drake, M.B. Hursthouse, M.E. Light, J. Organomet. Chem. 687 (2003) 118. [11] I. Ghesner, L. Opris, G. Balazs, H.J. Breunig, J.E. Drake, A. Silvestru, C. Silvestru, J. Organomet. Chem. 642 (2002) 113. [12] S.E. Denmark, J. Fu, M.J. Lawler, J. Org. Chem. 71 (2006) 1523. [13] P.K. Baker, M.G.B. Drew, D.S. Moore, J. Organomet. Chem. 664 (2002) 45. [14] T. Appleby, J.D. Woollins, Coord. Chem. Rev. 235 (2002) 121. [15] E.A. Trush, V.A. Ovchynnikov, K.V. Domasevitch, J.S. Wiatekkozlowska, V.Y. Zub, V.M. Amirkhanov, Z. Naturforsch. 57b (2002) 746. [16] V.V. Skopenko, V.M. Amirkhanov, T. Yu. Silva, I.S. Vasilchenko, E.L. Anpilov, A.D. Garnovski, Russ. Chem. Rev. 73 (2004) 737. [17] K. Gholivand, Z. Shariatinia, M. Pourayoubi, Polyhedron 25 (2006) 711. [18] K. Gholivand, Z. Shariatinia, J. Organomet. Chem. 691 (2006) 4215. [19] T.L. Lassiter, R.S. Marshall, L.C. Jackson, D.L. Hunter, J.T. Vu, S. Padilla, Toxicology 186 (2003) 241. [20] O.I. Guliy, O.V. Ignatov, O.E. Makarov, V.V. Ignatov, Biosens. Bioelectron. 18 (2003) 1005. [21] K. Kaur, S.A. Adediran, J.K. Lan Martin, R.F. Pratt, Biochemistry 42 (2003) 1529. [22] K. Gholivand, Z. Shariatinia, K. Khajeh, H. Naderi-Manesh, J. Enzyme Inhib. Med. Chem. 21 (2006) 31. [23] (a) K. Gholivand, C.O. Della Vedovab, A. Anaraki Firooza, A. Madani Alizadehgana, M.C. Michelinic, R. Pis Diez, J. Mol. Struct. 750 (2005) 64; (b) K. Gholivand, Z. Shariatinia, M. Pourayoubi, Z. Naturforsch. 60b (2005) 67. [24] M.A.M. Forgeron, M. Gee, R.E. Wasylishen, J. Phys. Chem. A 108 (2004) 4895. [25] K. Gholivand, M. Pourayoubi, Z. Shariatinia, H. Mostaanzadeh, Polyhedron 24 (2005) 655. [26] K. Gholivand, Z. Shariatinia, Struct. Chem. 18 (2007) 95. [27] K. Gholivand, Z. Shariatinia, M. Pourayoubi, Z. Anorg. Allg. Chem. 631 (2005) 961. [28] Bruker, Programs APEX II, Version 2.0-1; SAINT, Version 7.23A; SADABS, Version 2004/1; XPREP, Version 2005/2; SHELXTL, Version 6.1. Bruker AXS Inc., Madison, WI, USA, 2005. [29] Siemens P3 and XDISK. Release 4.1. Siemens AXS, Madison, Wisconsin, USA, 1989. [30] Bruker, SMART. Bruker Molecular Analysis Research Tool, v. 5.059. Bruker AXS, Madison, Wisconsin, USA, 1998. [31] G.M. Sheldrick, Programs SHELXS97 (crystal structure solution) and SHELXL97 (crystal structure refinement), University of Gottingen, Germany, 1997. [32] G.M. Sheldrick, SADABS v. 2.01, Bruker/Siemens area detector absorption correction program. Bruker AXS, Madison, WI, USA, 1998. [33] H.-O. Kalinowski, S. Berger, S. Braun, Carbon-13 NMR Spectroscopy, Wiley, 1991, p. 527. [34] R.L. Keiter, J.W. Benson, E.A. Keiter, T.A. Harris, M.W. Hayner, L.L. Mosimann, E.E. Karch, C.A. Boecker, D.M. Olson, J. VanderVeen, D.E. Brandt, Organometallics 16 (1997) 2246. [35] L. Aluisio, B. Lord, A.J. Barbier, I.C. Fraser, S.J. Wilson, J. Boggs, L.K. Dvorak, M.A. Letavic, B.E. Maryanoff, N.I. Carruthers, P. Bonaventure, T.W. Lovenberg, Eur. J. Pharmacol. 587 (2008) 141. [36] N. Vasdev, F.J. LaRonde, J.R. Woodgett, A. Garcia, E.A. Rubie, J.H. Meyer, S. Houle, A.A. Wilson, Bioorg. Med. Chem. 16 (2008) 5277. [37] X.-H. Liu, P. Cui, B.-A. Song, P.S. Bhadury, H.-L. Zhu, S.-F. Wang, Bioorg. Med. Chem. 16 (2008) 4075. [38] E.A.V. Ebsworth, D.W.H. Rankin, S. Cradock, Structural Methods in Inorganic Chemistry, 2nd ed., Blackwell Scientific Publication, 1991. [39] K. Gholivand, C.O. Della Ve´dova, M.F. Erben, H.R. Mahzouni, Z. Shariatinia, S. Amiri, J. Mol. Struct. 874 (2008) 178. [40] D.E.C. Corbridge, Phosphorus, an Outline of its Chemistry, Biochemistry and Technology, 5th ed., Elsevier, The Netherlands, 1995, p. 55.
Contents lists available at ScienceDirect
Polyhedron journal homepage: www.elsevier.com/locate/poly
Structural diversity in phosphoramidate’s chemistry: Syntheses, spectroscopic and X-ray crystallography studies Khodayar Gholivand a,*, Zahra Shariatinia b,1, Seyedeh Mahdieh Mashhadi a, Farzaneh Daeepour a, Narjes Farshidnasab a, Hamid Reza Mahzouni a, Nasrin Taheri a, Shadi Amiri a, Sheida Ansar a a b
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran Department of Chemistry, Amirkabir University of Technology, P.O. Box 159163-4311, Tehran, Iran
a r t i c l e
i n f o
Article history: Received 15 September 2008 Accepted 7 October 2008 Available online 4 December 2008 Keywords: Bisphosphoramidates Phosphoramidates NMR X-ray crystallography
a b s t r a c t Novel phosphorus compounds of bisphosphoramidate, phosphoramidate and phosphoric triamide derivatives were synthesized using the starting materials PCl5 and POCl3. The products were then characterized by 1H, 13C, 31P, 19F NMR, IR spectroscopy and CHN elemental analysis. It is noticeable that the reaction of 4-aminobenzamide with PCl5 in different molar ratios yields different products, bisphosphoramides and phosphoric triamides. Moreover, we were taken by surprise that the interaction of POCl3 with the first-type aromatic amines gave bisphosphoramidates with P–N–P linkages that exhibited 2 J(P,P) 20.0 Hz in the 31P NMR spectra. In fact, two simple one-pot pathways are presented here for the synthesis of new bisphosphoramidates, and to the best of our knowledge these are the first instances of bisphosphoramidates that have been obtained up until now. The structures of compounds I (4-OCH3– C6H4–CH2–C9H13–NH2Cl), 34 and 44 were further determined by X-ray crystallography. All of these structures produced three dimensional polymeric chains through strong- and weak hydrogen bonds. The presence of chiral aminoacidester moieties in the phosphoric triamides lead to chiral molecules that showed two sets of signals for the two groups. Interestingly, in phosphoric triamides containing cyanoacetamide moieties, the existence of aromatic amine substituents on the P atoms created central chiral phosphorus atoms, i.e. the two aromatic groups revealed two sets of peaks in the 1H and 13C NMR spectra, while compounds with aliphatic moieties did not display this effect. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Phosphorus chemistry covers a wide area of sciences, including synthesis, coordination, biomedicine and theoretical matters. Phosphoramidates, bisphosphoramidates and phosphoric triamides are some important instances of phosphorus derivatives whose chemistry plays a significant role in various parts of science. Among the phosphoramidates, N-phosphorylated aminoacids have revealed high antitumor, antiviral and anti-HIV activities [1–4]. So far the syntheses and coordination chemistry of many bisphosphoramidates have been reported, containing P–N–P bonds via multi-step reactions [5–9], but here a simple one-pot method is presented to prepare such compounds. These types of compounds are potential bidentate ligands for the coordination to the metal atoms [10,11]. There are some reports on the synthesis of bisphosphoramides containing P(O)–(CH2)n–P(O) or P(O)–N(CH3)–(binaphthyl)–N(CH3)– P(O) moieties [12], as well as the P–(CH2)n–P group [13,14]. In addition, it is expected that due to the presence of the two phosphorus atoms in their structures, they will show more anticancer,
antibacterial and enzyme inhibitory properties than phosphoramidates. Besides, the coordination chemistry of phosphoramidates [15–18], their biological applications [19–22], quantum chemical calculations on their structures [23,24], and their spectroscopic and X-ray crystal structures [25–27] are frequently studied. In the present work, following on from our previous research, we have synthesized and characterized several new phosphorus compounds of phosphoramidates, bisphosphoramidates (including P(O)NHC6H4C(O)NHP(O) and P–N–P linkages), and phosphoric triamides. It is noteworthy that two simple one-pot pathways are presented for the synthesis of the new bisphosphoramidates and, as far as we know, these are the first examples of bisphosphoramidates that have been prepared so far. Furthermore, their NMR, IR and mass spectroscopic features as well as X-ray crystal structures are discussed and compared with our previous data.
2. Experimental 2.1. X-ray measurements
* Corresponding author. Tel.: +98 2182884422; fax: +98 2182883455. E-mail address: [email protected] (K. Gholivand). 1 Tel.: +982164543298; fax: +982164543296. 0277-5387/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2008.10.057
X-ray data of compound 34 were collected on a Bruker APEX II [28] and Siemens P3/PC [29] and those of compounds I and 44 on a
308
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Bruker SMART 1000 CCD [30] single crystal diffractometer with graphite monochromated Mo Ka radiation (k = 0.71073 Å). The structures were refined with SHELXL-97 [31] by full matrix leastsquares on F2. The positions of hydrogen atoms were obtained from the difference Fourier maps. Routine Lorentz and polarization corrections were applied and an absorption correction was performed using the SADABS program for compounds I and 44 [32]. 2.2. Spectroscopic measurements 1
H, 13C and 31P spectra were recorded on a Bruker Avance DRS 500 spectrometer. 1H and 13C chemical shifts were determined relative to internal Me4Si, 31P and 19F chemical shifts relative to 85% H3PO4 and CFCl3 as external standards, respectively. The field strengths for the acquisition of 1H, 13C, 31P and 19F NMR spectra were 500.13, 125.77, 202.46 and 470.54 MHz, respectively. Infrared (IR) spectra were recorded on a Shimadzu model IR-60 spectrometer. Elemental analyses were performed using a Heraeus CHN-O-RAPID apparatus. Melting points were obtained with an electrothermal instrument. The spectroscopic data of the synthesized compounds can be found in the online Supplementary data. 2.3. Syntheses 2.3.1. N,N0 -4-Carboxyamidophenyl-bis phosphoramidic tetrachloride (1) A suspension of 16 mmol PCl5 in 40 mL CCl4 was prepared and then 4.0 mmol of 4-aminobenzamide was slowly added to the mixture at room temperature. After 24 h stirring, the temperature was raised to 80–90 °C to reflux the flask contents. After 5 h, the yellow solution was cooled to 4 °C and 16.0 mmol of formic acid was added dropwise at 5 °C to oxide the product, releasing CO and HCl. The mixture was stirred for 2 h under these conditions and then the white product was washed with CCl4 and dried under vacuum. Yield: 76%. m.p. = 115 °C. Anal. Calc. for C7H6Cl4N2O3P2: C, 22.73; H, 1.64; N, 7.57. Found: C, 22.70; H, 1.64; N, 7.56%. 31P {1H} NMR (CD3CN): d 5.44 (s), 6.69 (s). 31P NMR (202.46 MHz; CD3CN; 85% H3PO4): d 5.44 (m), 6.69 (m). 1H NMR (CD3CN): d 7.37 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.93 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.16 (d, 2J(PNH) = 11.9 Hz, 1H, NHamine), 9.41 (s, 1H, NHamide). 13C NMR (CD3CN): d 120.04 (d, 3J(P,C) = 8.9 Hz), 127.92 (d, 3J(P,C) = 10.6 Hz), 131.19 (s), 131.45 (s), 134.93 (s), 143.79 (s), 167.25 (d, 2J(P,C) = 3.5 Hz, C@O). IR (KBr, cm1): 3405 (s, mNH), 3170 (s, mNH), 3005 (s), 2835 (s, CH), 2595 (s, CH), 2350 (m), 1644 (s, C@O), 1611 (s), 1453 (s), 1272 (s), 1211 (s, mP@O), 1176 (s, mP@O), 1156 (s), 1121 (s), 1098 (s), 1071 (s), 1049 (s), 994 (s, mP–N), 964 (s, mP–N), 750 (m), 537 (m), 478 (s, mP–Cl).
trile solution to yield molecules 3–8 and 10. For the synthesis of diazaphosphole 9, a solution of 4 mmol diamine plus 4 mmol triethylamine was added to the suspension. Compounds 11–13 were synthesized in the same way, but the molar ratio of the corresponding amines to compound 2 was 4:1. 2.3.4. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -isopropyl) phosphoric triamide] (3) Yield: 61%. m.p. = 131.5 °C. Anal. Calc. for C19H38N6O3P2: C, 49.56; H, 8.32; N, 18.26. Found: C, 49.54; H, 8.31; N, 18.26%. 31P NMR (CD3OD): d 9.16 (m), 9.26 (m). 1H NMR (CD3OD): d 0.99 (d, 3 J(H,H) = 6.5 Hz, 6H, CH3), 1.00 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.01 (d, 3J(H,H) = 6.4 Hz, 6H, CH3), 1.02 (d, 3J(H,H) = 6.4 Hz, 6H, CH3), 3.43 (m, 4H CH), 7.17 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.76 (d, 3 J(H,H) = 8.7 Hz, 2H, Ar–H). 13C NMR (CD3OD): d 25.41 (d, 3 J(P,C) = 4.7 Hz, CH3), 25.56 (d, 3J(P,C) = 5.4 Hz, CH3), 25.72 (d, 3 J(P,C) = 3.4 Hz, CH3), 25.77 (d, 3J(P,C) = 2.1 Hz, CH3), 44.33 (s, CH), 44.36 (s, CH), 118.05 (d, 3J(P,C) = 7.0 Hz), 126.20 (d, 3 J(P,C) = 8.0 Hz), 129.48 (s), 130.21 (s), 148.28 (s), 159.98 (s), 170.84 (s, C@O). IR (KBr, cm1): 3315 (s, mNH), 2950 (s, mCH), 1602 (s, mC@O), 1564 (m), 1449 (s), 1419 (s), 1225 (m, mP@O), 1169 (s, mP@O), 1126 (m), 1020 (m), 927 (m, mP–N), 896 (m, mP– N), 833 (m, mP–N), 762 (m, mP–N), 638 (m), 529 (m). 2.3.5. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -isbutyl) phosphoric triamide] (4) Yield: 58%. m.p. = 193 °C. Anal. Calc. for C23H46N6O3P2: C, 53.53; H, 8.98; N, 16.27. Found: C, 53.51; H, 8.98; N, 16.26%. 31P NMR (DMSO-d6): d 9.35 (m), 10.22 (m). 1H NMR (DMSO-d6): d 0.79 (d, 3 J(H,H) = 6.4 Hz, 12H, CH3), 1.16 (d, 3J(H,H) = 6.4 Hz, 12H, CH3), 1.86 (m, 2H, CH), 1.92 (m, 2H, CH), 2.48 (m, 4H CH2), 2.68 (m, 4H, CH2), 4.24 (m, 2H, NH), 4.35 (m, 2H, NH), 7.16 (d, 3 J(H,H) = 8.5 Hz, 2H, Ar–H), 7.22 (b, 1H, NH), 7.49 (d, 3 J(H,H) = 8.5 Hz, 2H, Ar–H). 13C NMR (DMSO-d6): d 19.96 (s, CH3), 20.08 (s, CH3), 28.59 (s, CH2), 29.35 (d, 2J(P,C) = 5.6 Hz, CH2), 45.72 (s, CH), 46.75 (s, CH), 47.73 (s, CH), 48.00 (s, CH), 115.92 (d, 3J(P,C) = 6.8 Hz), 123.65 (d, 3J(P,C) = 8.2 Hz), 128.88 (s), 132.72 (s), 147.15 (s), 158.29 (s), 167.83 (s, C@O). IR (KBr, cm1): 3421 (m, mNH), 3271 (s, mNH), 2959 (s, mCH), 2671 (s, mCH), 1647 (m), 1606 (s, mC@O), 1465 (s), 1252 (m, mP@O), 1190 (s, mP@O), 1090 (s), 922 (m, mP–N), 847 (m, mP–N), 769 (w), 547 (w).
2.3.2. N-(4-Carboxy amidophenyl) phosphoramidic dichloride (2) This compound was prepared in the same way as compound 1, but the molar ratio of 4-aminobenzamide to PCl5 was 1:1. Yield: 95%. m.p. = 80 °C. Anal. Calc. for C7H7Cl2N2O2P: C, 33.23; H, 2.79; N, 28.02. Found: C, 33.22; H, 2.78; N, 28.03%. 31P NMR (DMSO-d6): d 0.14 (m). 1H NMR (DMSO-d6): d 7.38 (d, 3J(H,H) = 8.2 Hz, 2H, Ar– H), 7.93 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 9.36 (b, 3H, NHamine,amide). 13 C NMR (DMSO-d6): d 122.05 (s), 128.94 (s), 132.50 (s), 136.29 (s), 167.11 (s, C@O). IR (KBr, cm1): 3385 (s, mNH), 3185 (s, mNH), 2795 (s, mCH), 2560 (s), 1649 (s, mC@O), 1601 (s), 1577 (s), 1524 (s), 1419 (m), 1293 (m), 1209 (m, mP@O), 1176 (m), 1115 (m), 837 (m, mP–N), 758 (s), 720 (m), 556 (m), 525 (m).
2.3.6. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N000 -diethyl) phosphoric triamide] (5) Yield: 85%. m.p. = 188 °C. Anal. Calc. for C13H46N6O3P2: C, 39.38; H, 11.69; N, 21.20. Found: C, 39.37; H, 11.68; N, 21.21%. 31P NMR (DMSO-d6): d 14.61 (m), 14.96 (m). 1H NMR (DMSO-d6): d 0.96– 1.06 (m, 24H, CH3), 2.95–3.07 (m, 16H, CH2), 7.20 (d, 3 J(H,H) = 8.6 Hz, 2H, Ar–H), 7.31 (d, 2J(PNH) = 9.1 Hz, 1H, NHamine), 7.77 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 8.91 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 13.82 (d, 3J(P,C) = 2.3 Hz, CH3), 14.01 (d, 3 J(P,C) = 2.2 Hz, CH3), 38.84 (d, 2J(P,C) = 5.0 Hz, CH2), 38.92 (d, 2 J(P,C) = 4.6 Hz, CH2), 116. 43 (d, 3J(P,C) = 6.7 Hz), 124.61 (d, 3 J(P,C) = 8.7 Hz), 129.13 (s), 131.27 (s), 147.31 (s), 158.95 (s), 167.43 (s,C@O). IR (KBr, cm1): 3345 (m, mNH), 3153 (s, mNH), 2971 (s, mC–H), 2933 (m, mC–H), 2872 (m, mC–H), 1665 (m), 1607 (s, mC@O), 1523 (m), 1437 (s), 1381 (s), 1268 (s), 1216 (s, mP@O), 1177 (s, mP@O), 1104 (m), 1063 (m), 1026 (s), 941 (m, mP–N), 916 (m, mP–N), 874 (s, mP–N), 843 (s, P–N), 792 (s, P–N), 715 (s), 660 (m), 541(s).
2.3.3. General procedure for the synthesis of compounds 3–12 A solution of 8 mmol of corresponding amines in acetonitrile was added dropwise to a suspension of 1 mmol of compound 1 at 5 °C. After 24 h stirring, the product was filtered and washed with distilled water and recrystallized from a methanol-acetoni-
2.3.7. N,N 0 -4-Carboxyamidophenyl-bis [bis (N00 ,N00 0 -cyclohexyl) phosphoric triamide] (6) Yield: 65%. m.p. = 165 °C. Anal. Calc. for C31H54N6O3P2: C, 59.98; H, 8.77; N, 13.54. Found: C, 59.97, H, 8.77; N, 13.53%. 31P NMR (DMSO-d6): d 7.36 (m), 8.08 (m). 1H NMR (DMSO-d6): d 1.16 (m,
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
24H, CH2), 1.44–1.84 (m, 16H CH2), 2.83 (m, 4H, CH), 4.07 (m, 2H, NH), 4.17 (m, 2H, NH), 7.10 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 7.32 (d, 2 J(PNH) = 7.6 Hz, 1H, NHamine), 7.74 (d, 3J(H,H) = 8.7 Hz, 2H, Ar–H), 9.27 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 23.92 (s, CH2), 24.71 (d, 3J(P,C) = 2.8 Hz, CH2), 24.80 (d, 3J(P,C) = 2.4 Hz, CH2), 24.93 (d, 3 J(P,C) = 2.6 Hz, CH2), 25.16 (d, 3J(P,C) = 3.8 Hz, CH2), 31.11 (s, CH2), 35.04 (d, 2J(P,C) = 6.1 Hz, CH), 35.21 (d, 2J(P,C) = 6.3 Hz, CH), 35.25 (d, 2J(P,C) = 7.7 Hz, CH), 35.30(d, 2J(P,C) = 7.6 Hz, CH), 49.26 (s, CH2), 49.46 (s, CH2), 116.03 (d, 3J(P,C) = 5.8 Hz), 118.12 (s), 123.80 (d, 3J(P,C) = 7.6 Hz), 124.14 (d, 3J(P,C) = 7.4 Hz), 128.84 (s), 147.26 (s), 167.71 (s, C@O). IR (KBr, cm1): 3310 (m, mNH), 2905 (s, mCH), 1618 (m, mC@O), 1598 (m), 1568 (m), 1504 (m), 1438 (m), 1302 (m), 1235 (m, mP@O), 1177 (m, mP@O), 1080 (m), 907 (m, mP–N), 832 (m, mP–N), 635 (m, mP–N), 537 (m), 407 (m). 2.3.8. N,N0 -4-Carboxyamidophenyl-bis [bis (N00 ,N0 00 -phenyl) phosphoric triamide] (7) Yield: 61%. m.p. = 135 °C. Anal. Calc. for C31H30N6O3P2: C, 62.41; H, 5.07; N, 14.09. Found: C, 62.40; H, 5.07; N, 14.10%. 31P NMR (DMSO-d6): d 3.42 (m), 3.74 (m). 1H NMR (DMSO-d6): d 6.9 (m, 4H, Ar–H), 7.11 (m, 4H, Ar–H), 7.14 (m, 14H, Ar–H), 7.20 (m, 4H, NHamine), 7.78 (d, 3J(H,H) = 9.0 Hz, 2H, Ar–H), 7.84 (d, 3 J(H,H) = 9.0 Hz, 2H, Ar–H), 8.04 (d, 2J(PNH) = 10.0 Hz, 1H, NHamide). 13 C NMR (DMSO-d6): d 114.08 (s), 115.94 (s), 117.64 (d, 3 J(P,C) = 6.8 Hz), 117.89 (s), 118.07 (s), 120.18 (s), 120.34 (s), 128.43 (s), 128.59 (s), 128.77 (s), 129.21 (s), 129.74 (s), 147.25 (s), 174.21 (s, C@O). IR (KBr, cm1): 3160 (m, mNH), 3035 (m, mNH), 2885 (m, mCH), 1644 (s, mC@O), 1486 (s), 1443 (m), 1382 (m), 1275 (s), 1222 (s, mP@O), 1185 (s, mP@O), 926 (s, mP–N), 741 (s, mP–N), 686 (m, mP–N), 488 (m). 2.3.9. N,N0 -4-Carboxyamidophenyl-bis (N00 -4-chlorophenyl phosphoramidic chloride) (8) Yield: 50%. m.p. = 145 °C. Anal. Calc. for C19H16Cl4N4O3P2: C, 41.33; H, 2.92; N, 10.15. Found: C, 41.34; H, 2.92; N, 10.14%. 31P NMR (CD3OD): d 2.43 (s), 3.15 (m). 1H NMR (CD3OD): d 6.76 (s, 2 H, Ar–Haniline), 6.78 (s, 2H, Ar–Haniline), 6.99 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H4-aminobenzamide), 7.01 (d, 3J(H,H) = 8.5 Hz, 2H, Ar– H4-aminobenzamide), 7.18 (s, 2H, Ar–Haniline), 7.19 (s, 2H, Ar–Haniline). 13 C NMR (CD3OD): d 114.09 (s), 115.94 (s), 117.50 (s), 117.64 (d, 3 J(P,C) = 7.2 Hz), 118.07 (s), 120.15 (s), 120.35 (s), 128.50 (s), 128.65 (s), 128.76 (s), 129.29 (s), 129.67 (s), 141.34 (s), 148.68 (s), 169.84 (s, C@O). IR (KBr, cm1): 3400 (m, mNH), 3305 (m, mNH), 3185 (m, mNH), 2885 (m, mCH), 2570 (m, mCH), 1602 (m, mC@O), 1289 (m), 1260 (m), 1235 (m, mP@O), 1174 (m, mP@O), 1076 (m), 1040 (m), 963 (m, mP–N), 925 (m, mP–N), 842 (m, mP– N), 805 (m, mP–N), 635 (w), 542 (w). 2.3.10. N,N0 -4-Carboxyamidophenyl-bis (1,3-dimethyl-1,3,2diazaphosphole) (9) Yield: 75%. m.p. = 245 °C. Anal. Calc. for C15H26N6O3P2: C, 45.00; H, 6.55; N, 20.99. Found: C, 45.02; H, 6.55; N, 20.97%. 31P NMR (DMSO-d6): d 20.03 (m), 20.16 (m). 1H NMR (DMSO-d6): d 2.58 (s, 12H, CH3), 3.24 (s, 8H, CH2), 6.15 (s, 1H, NHamine), 6.52 (d, 3 J(H,H) = 5.0 Hz, 1H, Ar–H), 6.61 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 7.38 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 7.58 (d, 3J(H,H) = 5.0 Hz, 1H, Ar–H), 9.37 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 30.65 (d, 2 J(P,C) = 5.0 Hz, CH3), 30.82 (d, 2J(P,C) = 4.9 Hz, CH3), 32.44 (s, CH3), 32.47 (s, CH3), 44.39 (s, CH2), 44.42 (s, CH2), 46.30 (d, 2 J(P,C) = 7.3 Hz, CH2), 46.41 (d, 2J(P,C) = 5.7 Hz, CH2), 116.13 (d, 3 J(P,C) = 6.8 Hz), 126.14 (s), 129.36 (s), 139.16 (s), 146.85 (s), 154.68 (s), 167.45 (s, C@O). IR (KBr, cm1): 3380 (m, mNH), 3190 (m, mNH), 3010 (m, mNH), 2740 (s, mCH), 2465 (m, mCH), 1656 (s, mC@O), 1626 (s), 1599 (s), 1446 (m), 1223 (m, mP@O), 1164 (m, mP@O), 1119 (m), 1076 (s), 953 (s, mP–N), 843 (m, mP–N), 801 (w), 505 (m).
309
2.3.11. N,N0 -4-Carboxyamidophenyl-[bis (N00 ,N000 -cyclopentyl) phosphoric triamide] dihydroxy phosphoramidic acid ester (10) Yield: 60%. m.p. = 170 °C. Anal. Calc. for C17H28N4O5P2: C, 47.44; H, 6.56; N, 13.02. Found: C, 47.45; H, 6.55; N, 13.01%. 31P NMR (D2O): d 8.14 (m), 8.81 (m). 1H NMR (D2O): d 1.57 (m, 8 H, CH2), 1.67 (m, 4H CH2), 1.97 (m, 4H, CH2), 3.59 (m, 2H, CH), 6.76 (d, 3 J(H,H) = 8.2 Hz, 2H, Ar–H), 7.58 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H). 13 C NMR (D2O): d 23.08 (s, CH2), 30.16 (s, CH2), 51.82 (s, CH), 114.58 (s), 120.14 (s), 121.31 (s), 128.22 (s), 129.00 (s), 150.82 (s), 172.11 (s, C@O). IR (KBr, cm1): 3370 (s, mNH), 3190 (s, mNH), 2895 (s, mCH), 1601 (s, mC@O), 1524 (m), 1415 (m), 1209 (m, mP@O), 1176 (m, mP@O), 1115 (m), 1057 (m), 837 (m, mP–N), 756 (m, mP–N), 720 (m, mP–N), 556 (m), 525 (m), 458 (m). 2.3.12. N-(4-Carboxy amidophenyl)-N0 -isobutyl-phosphoramidic chloride (11) Yield: 54%. m.p. = 178 °C. Anal. Calc. for C11H17ClN3O2P: C, 45.61; H, 5.92; N 14.50. Found: C, 45.60; H, 5.90; N, 14.51%. 31P NMR (DMSO-d6): d 0.16 (m). 1H NMR (DMSO-d6): d 0.87 (d, 3 J(H,H) = 6.5 Hz, 6H, CH3), 1.85 (m, 1H, CH), 2.58 (m, 2H, Ar CH2), 4.13 (m, 1H, NH), 6.51 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H), 6.80 (b, 1H, NH), 7.57 (d, 3J(H,H) = 8.5 Hz, 2H, Ar–H), 7.87 (b, 2H, NH2). 13C NMR (DMSO-d6): d 19.77 (s, CH3), 26.46 (s, CH), 50.80 (s, CH2), 112.45 (s), 118.21 (s), 120.89 (s), 128.44 (s), 129.07 (s), 151.64 (s), 168.09 (s, C@O). IR (KBr, cm1): 3466 (s, mNH), 3245 (s, mNH), 2965 (s, mCH), 2805 (s, mCH), 2601 (m), 1608 (s, mC@O), 1619 (s), 1399 (s), 1292 (m), 1183 (m, mP@O), 1095 (m), 850 (m, mP–N), 778 (s, mP–N), 712 (m), 503 (m), 450 (m). 2.3.13. N-(4-Carboxy amidophenyl)-N0 ,N00 -bis (cyclopentyl) phosphoric triamide (12) Yield: 70%. m.p. = 89 °C. Anal. Calc. for C17H27N4O2P: C, 58.27; H, 7.77; N, 15.99. Found: C, 58.25; H, 7.76; N, 15.98%. 31P NMR (CDCl3): d 3.54 (m). 1H NMR (CDCl3): d 1.62 (m, 8H, CH2), 1.85 (m, 4H, CH2), 2.03 (m, 4H, CH2), 3.12 (m, 2H, CH), 3.63 (m, 2H, NH), 8.35 (m, 6H, Ar–H), 9.14 (b, 1H, NH). 13C NMR (CDCl3): d 23.86 (s), 49.05 (s), 53.29 (s), 54.20 (s), 64.36 (s), 117.21 (s), 122.92 (s), 130.07 (s), 144.25 (s), 172.31 (s, C@O). IR (KBr, cm1): 3445 (m, mNH), 3310 (m, mNH), 3136 (m, mNH), 2940 (s, mCH), 2635 (m, mCH), 1690 (m), 1597 (s, mC@O), 1550 (m), 1506 (m), 1396 (m), 1214 (m), 1176 (m, mP@O), 1089 (m), 840 (m, mP–N), 771 (m, mP–N), 706 (m), 574 (m), 526 (m). 2.3.14. N-(4-Carboxy amidophenyl)-N0 ,N00 -bis (4-bromophenyl) phosphoric triamide (13) Yield: 75%. m.p. = 225 °C. Anal. Calc. for C19H17Br2N4O2P: C, 43.54; H, 3.27; N, 10.69. Found: C, 43.55; H, 3.27; N, 10.68%. 31P NMR (DMSO-d6): d 0.11 (s). 1H NMR (DMSO-d6): d 7.20 (d, 3J(H,H) = 8.5 Hz, 4H, Ar–Hbromoaniline), 7.29 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H4-aminobenzamide), 7.63 (d, 3J(H,H) = 8.6 Hz, 4H, Ar– H4-aminobenzamide), 7.84 (d, 3J(H,H) = 8.5 Hz, 4H, Ar–Hbromoaniline), 8.61–9.52 (m, 5H, NH). 13C NMR (DMSO-d6): d 116.44 (s), 118.91 (s), 124.28 (s), 128.89 (s), 129.60 (s), 132.34 (s), 133.43 (s), 140.04 (s), 167.21 (s, C@O). IR (KBr, cm1): 3402 (s, mNH), 3200 (s, mNH), 2835 (m, mCH), 2569 (s, mCH), 1586 (s, mC8O), 1538 (s), 1514 (s), 1488 (s), 1425 (s), 1405 (s), 1299 (s), 1215 (s, mP@O), 1182 (m), 1106 (m), 1071 (s), 846 (s, mP–N), 818 (s), 767 (s, mP–N), 718 (m), 671 (m), 534 (s), 489 (s), 466 (s). 2.3.15. General procedure for the synthesis of compounds 14–21 A solution of 7 mmol of the corresponding amine in acetonitrile was added dropwise to a solution of 1 mmol N-(4-X-phenyl) phosphoramidic dichloride (X = H, F, Cl, and Br) in acetonitrile at 5 °C. The flask contents were stirred for 48 h and then the precipitate was filtered, washed with water and dried in air to yield molecules 14–17. To synthesise compounds 18–21, this procedure was ap-
310
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
plied, but a solution of 4 mmol of 4-X-aniline (X = H, F, Cl, and Br) in acetonitrile was added dropwise to a solution of 1 mmol 2pyridinyl phosphoramidic dichloride in acetonitrile. 2.3.16. l1-(N-Phenyl)-N0 -phenyl phosphoramidic chloride-bis [(N00 ,N000 -phenyl) phosphoric triamide] (14) Yield: 70%. m.p. = 212 °C. Anal. Calc. for C24H23ClN4O2P2: C, 58.02; H, 4.67; N, 11.28. Found: C, 58.00; H, 4.67; N, 11.28%. 31P NMR (DMSO-d6): d 10.42 (m), 10.28 (d, 2J(P,P) = 19.7 Hz). 31P NMR (CD3OD): d 9.52 (d, 2J(P,P) = 17.5 Hz), 8.28 (d, 2 J(P,P) = 17.5 Hz). 1H NMR (DMSO-d6): d 6.72–7.20 (m, 20H, Ar– H), 7.54 (b, 1H, NH), 8.17 (d, 2J(PNH) = 8.8 Hz, 2H, NH). 13C NMR (DMSO-d6): d 117.40 (s), 119.31 (s), 120.30 (s), 122.39 (s), 126.78 (s), 128.16 (s), 128.38 (s), 128.65 (s), 129.58 (s), 133.64 (s), 141.03 (s), 142.55 (s). IR (KBr, cm1): 3375 (m, mNH), 3235 (m, mNH), 3040 (m), 2825 (s, mCH), 2585 (s), 1592 (m), 1486 (s), 1280 (m, mP@O), 1217 (s, mP@O), 1150 (m), 1072 (m), 910 (s, mP–N), 735 (s, mP–N), 685 (s), 466 (m). 2.3.17. l1-(N-4-Fluorophenyl)-N0 -4-fluorophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-fluorophenyl) phosphoric triamide] (15) Yield: 85%. m.p. = 204 °C. Anal. Calc. for C24H19ClF4N4O2P2: C, 50.68; H, 3.37; N, 9.85. Found: C, 50.67; H, 3.37; N, 9.84%. 31P NMR (DMSO-d6): d 10.23 (d, 2J(P,P) 8 19.7 Hz), 9.90 (m). 19F NMR (DMSO-d6): d 115.61 (s), 123.71 (s), 124.63 (s). 1H NMR (DMSO-d6): d 6.82–7.06 (m, 16H, Ar–H), 7.54 (b, 1H, NH), 8.15 (d, 2J(PNH) = 8.6 Hz, 2H, NH). 13C NMR (DMSO-d6): d 114.68 (d, 2J(F,C) 8 22.4 Hz), 115.07 (d, 2J(F,C) = 22.1 Hz), 115.73 (d, 2 J(F,C) = 20.5 Hz), 118.41 (dd, 3J[(F,C),(P,C)] = 7.4 Hz), 118.76 (dd, 3 J[(F,C),(P,C)] 8 7.5 Hz), 119.19 (dd, 3J[(F,C),(P,C)] = 7.6 Hz), 119.48 (d, 4J(F,C) = 2.3 Hz), 119.54 (d, 4J(F,C) = 2.5 Hz), 119.72 (d, 4 J(F,C) = 2.6 Hz), 156.69 (d, 1J(F,C) = 237.3 Hz), 161.68 (d, 1J(F,C) 8 234.9 Hz), 164.32 (d, 1J(F,C) = 239.4 Hz). IR (KBr, cm1): 3398 (m, mNH), 3220 (m, mNH), 2925 (m, mCH), 2785 (m, mCH), 1502 (s), 1383 (m), 1240 (m, mP@O), 1209 (s, mP@O), 1152 (m), 1068 (s), 968 (s, mP–N), 913 (s, mP–N), 821 (s, mP–N), 752 (m), 501 (m), 457 (m). 2.3.18. l1-(N-4-Chlorophenyl)-N0 -4-chlorophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-chlorophenyl) phosphoric triamide] (16) Yield: 81%. m.p. = 199 °C. Anal. Calc. for C24H19Cl5N4O2P2: C, 45.42; H, 3.02; N, 8.83. Found: C, 45.40; H, 3.02; N, 8.84%. 31P NMR (DMSO-d6): d 10.75 (d, 2J(P,P) 8 17.7 Hz), 10.16 (m). 1H NMR (DMSO-d6): d 7.04–7.46 (m, 16H, Ar–H), 8.15 (b, 1H, NH), 8.40 (d, 2J(PNH) 8 8.6 Hz, 2H, NH). 13C NMR (DMSO-d6): d 117.92 (s), 119.00 (d, 3J(P,C) = 7.4 Hz), 123.35 (s), 123.65 (s), 124.38 (s), 128.19 (s), 128.44 (s), 129.43 (s), 129.92 (s), 134.12 (s), 139.81 (s), 140.56 (s). IR (KBr, cm1): 3430 (m, mNH), 3210 (m, mNH), 2975 (m, mCH), 2835 (m, mCH), 1587 (m), 1484 (s), 1453 (m), 1382 (m), 1274 (m, mP@O), 1229 (m, mP@O), 1194 (s), 1091 (m), 1037 (s), 941 (s, mP–N), 821 (s, mP–N), 571 (m). 2.3.19. l1-(N-4-Bromophenyl)-N0 -4-bromophenyl phosphoramidic chloride-bis [(N00 ,N000 -4-bromophenyl) phosphoric triamide] (17) Yield: 67%. m.p. = 196 °C. Anal. Calc. for C24H19Br4ClN4O2P2: C, 35.48; H, 2.36; N, 6.90. Found: C, 35.46; H, 2.35; N, 6.91%. 31P NMR (DMSO-d6): d 10.92 (d, 2J(P,P) = 17.7 Hz), 10.61 (m). 1H NMR (DMSO-d6): d 6.76–7.30 (m, 16H, Ar–H), 7.91 (b, 1H, NH), 8.42 (d, 2J(PNH) = 8.9 Hz, 2H, NH). 13C NMR (DMSO-d6): d 111.12 (s), 112.03 (s), 113.12 (s), 118.67 (d, 3J(P,C) = 7.4 Hz), 119.24 (d, 3 J(P,C) = 7.8 Hz), 119.37 (d, 3J(P,C) = 6.9 Hz), 131.00 (s), 131.32 (s), 131.69 (s), 140.33 (s), 141.37 (s), 142.35 (s). IR (KBr, cm 1): 3390 (m, mNH), 3190 (m, mNH), 3045 (m, mCH), 2915 (m, mCH), 2585 (m), 1503 (m), 1400 (s), 1296 (m), 1271 (m, mmP@O), 1218 (m, mP8O), 1068 (m), 1004 (m), 964 (m, mP–N), 908 (m, mP–N), 811 (m, mP– N), 532 (m), 405 (m).
2.3.20. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -phenyl) phosphoric triamide] (18) Yield: 70%. m.p. = 175 °C. Anal. Calc. for C22H21ClN4O2P2: C, 56.12; H, 4.50; N, 11.90. Found: C, 56.10; H, 4.51; N, 11.90%. 31P NMR (DMSO-d6): d 10.30 (m), 10.11 (d, 2J(P,P) = 20.0 Hz). 1H NMR (DMSO-d6): d 6.69 (t, 3J(H,H) 8 7.0 Hz, 1H, Ar–H), 6.75 (t, 3 J(H,H) = 7.0 Hz, 2H, Ar–H), 6.86 (d, 3J(H,H) = 7.9 Hz, 1H, Ar–H), 7.03 (m, 10H, Ar–H), 7.18 (t, 3J(H,H) = 7.0 Hz, 2H, Ar–H), 7.49 (b, 1H, NH), 8.15 (d, 2J(PNH) = 8.5 Hz, 2H, NH). 13C NMR (DMSO-d6): d 109.81 (s), 117.22 (s), 117.32 (d, 3J(P,C) = 7.7 Hz), 117.54 (s), 119.24 (s), 120.12 (s), 128.29 (s), 128.57 (s), 129.14 (s), 141.08 (s), 141.90 (s), 142.31 (s), 149.35 (s), 152.60 (s). IR (KBr, cm-1): 3375 (m, mNH), 3235 (s, mNH), 2820 (m, mCH), 1637 (s), 1593 (s), 1487 (s), 1399 (s), 1288 (m, mP@O), 1216 (s, mP@O), 1151 (m), 1063 (s), 955 (s, mP–N), 909 (m, mP–N), 743 (s, mP–N), 688 (s), 506 (m), 476 (m, mP–Cl). 2.3.21. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-fluorophenyl) phosphoric triamide] (19) Yield: 68%. m.p. = 185 °C. Anal. Calc. for C22H19ClF2N4O2P2: C, 52.14; H, 3.78; N, 11.06. Found: C, 52.12; H, 3.77; N, 11.06%. 31P NMR (CD3OD): d 9.59 (d, 2J(P,P) = 21.3 Hz), 8.32 (d, 2 J(P,P) = 21.3 Hz); dP (202.46 MHz; DMSO-d6; 85% H3PO4) 10.27 (d, 2J(P,P) = 20.0 Hz), 9.99 (m). 1H NMR (CD3OD): d 6.85–7.05 (m, 16H, Ar–H), 7.49 (b, 1H, NH), 8.13 (d, 2J(PNH) = 8.4 Hz, 2H, NH). 13 C NMR (CD3OD): d 114.49 (s), 114.66 (s), 114.98 (d, 2 J(F,C) = 22.1 Hz), 115.43 (d, 4J(F,C) = 2.5 Hz), 115.63 (s), 116.20 (s), 117.80 (s), 118.02 (s), 118.36 (dd, 3J[(F,C),(P,C)] = 7.8 Hz), 118.68 (s), 137.33 (s), 143.80 (s), 155.20 (s), 156.62 (d, 1 J(F,C) = 234.8 Hz). IR (KBr, cm1): 3390 (m, mNH), 3230 (m, mNH), 2940 (m, mCH), 1502 (s), 1463 (m), 1300 (m), 1284 (m, mP@O), 1239 (m, mP@O), 1211 (s), 1153 (m), 1069 (m), 966 (m, mP–N), 913 (s, mP–N), 821 (s, mP–N), 752 (m), 698 (m), 500 (m), 499 (m, mP–Cl). 2.3.22. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-chlorophenyl) phosphoric triamide] (20) Yield: 75%. m.p. = 213 °C. Anal. Calc. for C22H19Cl3N4O2P2: C, 48.96; H, 3.55; N, 10.38. Found: C, 48.95; H, 3.55; N, 10.37%. 31P NMR (DMSO-d6): d 10.79 (d, 2J(P,P) = 18.6 Hz), 10.49 (m). 1H NMR (DMSO-d6): d 6.75 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.00–7.14 (m, 4H, Ar–H), 7.87 (b, 1H, NH), 8.38 (d, 2J(PNH) = 9.0 Hz, 2H, NH). 13C NMR (DMSO-d6): d 109.10 (s), 117.68 (s), 118.73 (d, 3 J(P,C) = 7.9 Hz), 118.88 (d, 3J(P,C) = 7.7 Hz), 121.40 (s), 123.33 (s), 124.21 (s), 128.09 (s), 128.41 (s), 128.76 (s), 135.32 (s), 139.89 (s), 140.93 (s), 147.50 (s). IR (KBr, cm1): 3370 (m, mNH), 3195 (m, mNH), 2920 (m, mCH), 2808 (m, mCH), 1590 (m), 1485 (s), 1381 (m), 1275 (m, mP@O), 1215 (s, mP@O), 1188 (m), 1006 (m), 965 (m, mP–N), 910 (s, mP–N), 815 (s, mP–N), 650 (m), 539 (m), 480 (m, mP–Cl). 2.3.23. l1-(N-2-Pyridinyl)-N0 -2-pyridinyl phosphoramidic chloride-bis [(N00 ,N000 -4-bromophenyl) phosphoric triamide] (21) Yield: 75%. m.p. = 230 °C. Anal. Calc. for C22H19Br2ClN4O2P2: C, 42.03; H, 3.05; N, 8.91. Found: C, 42.01; H, 3.05; N, 8.90%. 31P NMR (DMSO-d6): d 10.82 (d, 2J(P,P) = 18.4 Hz), 10.66 (m). 1H NMR (DMSO-d6): d 6.63 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 6.96 (m, 6H, Ar–H), 7.16 (d, 3J(H,H) = 8.6 Hz, 2H, Ar–H), 7.20 (d, 2 J(PNH) = 7.1 Hz, 2H, Ar–H), 7.23 (d, 3J(H,H) = 8.7 Hz, 4H, Ar–H), 7.89 (b, 1H, NH), 8.39 (d, 2J(PNH) = 8.3 Hz, 2H, NH). 13C NMR (DMSO-d6): d 112.10 (s), 117.25 (s), 117.35 (s), 119.25 (d, 3 J(P,C) = 7.8 Hz), 130.96 (s), 131.28 (s), 131.47 (s), 133.80 (s), 137.20 (s), 140.27 (s), 146.50 (s), 151.50 (s), 152.10 (s). IR (KBr, cm1): 3305 (m, mNH), 3190 (m, mNH), 2915 (m, mCH), 1624 (m), 1481 (s), 1379 (m), 1296 (m), 1272 (m, mP@O), 1215 (s, mP@O), 1110 (m), 1068 (m), 962 (s, mP–N), 911 (s, mP–N), 812 (m, mP–N), 639 (m), 570 (m), 485 (m, mP–Cl).
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
2.3.24. Phenylalanine benzylester hydrochloride (22) A solution of 6 mmol DL-phenylalanine was added to a solution of 35 mL of benzyl alcohol and the mixture was refluxed for 5 h. Then the temperature was decreased to 5 °C and 5.8 mL SOCl2 was added dropwise to the mixture to yield the product that was washed with ether. Yield: 95%. m.p. = 200 °C. Anal. Calc. for C16H18ClNO2: C, 65.86; H, 6.22; N, 4.80. Found: C, 65.85; H, 6.21; N, 4.81%. 1H NMR (D2O): d 3.21 (d, 3J(H,H) = 6.6 Hz, 2H, CH2–O), 4.39 (t, 3J(H,H) = 6.7 Hz, 1H, CH), 5.18 (d, 2J(H,H) = 11.9 Hz, 1H, CH of CH2), 5.24 (d, 2J(H,H) = 11.9 Hz, 1H, CH of CH2), 7.10 (m, 2H, Ar–H), 7.28–7.40 (m, 8H, Ar–H). 13C NMR (D2O): d 35.64 (s), 54.03 (s), 68.66 (s), 127.50 (s), 128.05 (s), 128.90 (s), 131.00 (s), 129.09 (s), 129.21 (s), 129.36 (s), 133.49 (s), 134.39 (s). IR (KBr, cm-1): 3430 (m, mNH), 3135 (m, mNH), 2990 (m, mCH), 2950 (m, mCH), 2860 (m), 1732 (s, mC@O), 1480 (s), 1439 (m), 1367 (m), 1225 (s), 1187 (m), 932 (m), 734 (s), 691 (s), 575 (m). 2.3.25. General procedure for the synthesis of compounds 23–27 A solution of 2 mmol of the corresponding aminoester plus 2 mmol of triethylamine in acetonitrile was added dropwise to a solution of 1 mmol N-(4-X-phenyl) phosphoramidic dichloride (X = CH3, Cl, and NO2) (in the case of compound 24, 1 mmol of 4-tolyl dichlorophosphate) in acetonitrile at 5 °C. The flask contents were stirred for 48 h and then the precipitate was filtered, washed with water and dried in air to yield the products. 2.3.26. N,N0 -Bis (phenylalanino)-N00 -4-methylphenyl phosphoric triamide (23) Yield: 55%. m.p. = 214 °C. Anal. Calc. C25H28N3O5P: C, 62.36; H, 5.86; N, 8.73. Found: C, 62.35; H, 5.85; N, 8.74%. 31P NMR (DMSOd6): d 0.27 (m). 1H NMR (DMSO-d6): d 2.09 (s, 3H, p-CH3), 3.38 (s, 2H, OH), 3.41 (m, 4H, CH2), 3.67 (m, 2H, CH), 5.04 (s, 2H, NHa13 C NMR (DMSO-d6): d 20.06 (s, mine), 6.44–7.32 (m, 15H, Ar–H). CH3), 55.50 (s, CH), 65.62 (s, CH2), 113.99 (s), 126.32 (s), 126.76 (s), 127.93 (s), 127.96 (s), 128.13 (s), 128.15 (s), 128.18 (s), 128.32 (s), 129.17 (s), 129.20 (s), 129.57 (s), 169.26 (s), 170.14 (s). IR (KBr, cm-1): 3420 (m, mNH), 3275 (s, mNH), 3155 (m, mNH), 3030 (s, mCH), 2855 (m, mCH), 1724 (s, mC@O), 1655 (m), 1602 (m), 1504 (m), 1443 (m), 1284 (m), 1160 (s, mP@O), 1039 (s), 910 (m, mP–N), 744 (m, mP–N), 687 (s, mP–N), 599 (m), 465 (m). 2.3.27. N,N0 -Bis (phenylalanine benzylester)-4-methylphenyl phosphoramidicacid ester (24) Yield: 50%. m.p. = 220 °C. Anal. Calc. for C39H39N2O6P: C, 70.68; H, 5.93; N, 4.23. Found: C, 70.66; H, 5.93; N, 4.22%. 31P NMR (DMSO-d6): d 0.24 (m). 1H NMR (DMSO-d6): d 2.19 (s, 3H, pCH3), 2.78 (dd, 3J(PNCH) = 7.9 Hz, 2J(H,H) = 13.0 Hz, 1H, CH), 2.85 (dd, 3J(PNCH) = 7.9 Hz, 2J(H,H) = 13.0 Hz, 1H, CH), 2.98 (dd, 2 J(H,H) = 13.6 Hz, 3J(H,H) = 8.0 Hz, 1H, CH of CH2), 3.00 (dd, 2 J(H,H) = 13.6 Hz, 3J(H,H) = 8.0 Hz, 1H, CH of CH2), 3.11 (dd, 2 J(H,H) = 13.7 Hz, 3J(H,H) = 5.6 Hz, 1H, CH of CH2), 3.14 (dd, 2 J(H,H) = 13.7 Hz, 3J(H,H) = 5.6 Hz, 1H, CH of CH2), 4.05 (dd, 3 2 J(H,H) = 6.5 Hz, J(PNH) = 13.0 Hz, 1H, NH), 4.10 (dd, 3 2 J(H,H) = 6.4 Hz, J(PNH) = 12.7 Hz, 1H, NH), 4.86 (d, 2 J(H,H) = 12.7 Hz, 2H, CH of CH2), 5.06 (d, 2J(H,H) = 12.7 Hz, 2H, CH of CH2), 6.93–7.32 (m, 24H, Ar–H). 13C NMR (DMSO-d6): d 20.19 (s, CH3), 37.00 (s), 40.35 (d, 2J(P,C) = 6.3 Hz), 53.73 (s), 56.53 (s), 65.37 (s), 66.61 (s), 119.90 (d, 3J(P,C) = 4.7 Hz), 126.22 (s), 126.93 (s), 127.81 (s), 128.02 (s), 128.13 (s), 128.19 (s), 128.21 (s), 128.30 (s), 128.32 (s), 128.40 (s), 128.41 (s), 129.05 (s), 129.15 (s), 129.34 (s), 130.25 (s), 135.02 (s), 135.29 (s), 135.78 (s), 137.22 (s), 170.16 (s, C@O), 173.15 (s, C@O). IR (KBr, cm1): 3390 (m, mNH), 3025 (m, mCH), 2855 (m, mCH), 1732 (s, mC@O), 1598 (m), 1494 (m), 1290 (m), 1205 (s, mP@O), 1150 (s), 1063 (m), 935 (m, mP–N), 907 (m), 734 (m, mP–N), 691 (s, mP–N), 594 (m), 470 (m).
311
2.3.28. N,N0 -Bis (phenylalanine benzylester)-N00 -4-nitrophenylphosphoric triamide (25) Yield: 55%. m.p. = 150 °C. Anal. Calc. for C38H37N4O7P: C, 65.89; H, 5.38; N, 8.09. Found: C, 65.90; H, 5.38; N, 8.10%. 31P NMR (DMSO-d6): d 2.04 (m). 1H NMR (DMSO-d6): d 2.85 (m, 2H, CH2), 3.09 (m, 2H, CH2), 3.21 (m, 1H, CH), 3.92 (m, 1H, NH), 4.31 (m, 1H, NH), 4.85 (m, 2H, OCH2), 5.12 (m, 2H, OCH2), 5.31 (m, 1H, CH), 7.07–7.34 (m, 22H, Ar–H), 7.92 (d, 3J(H,H) = 7.7 Hz, 2H, Ar– H), 8.31 (d, 2J(PNH) = 6.6 Hz, 1H, NH). 13C NMR (DMSO-d6): d 35.58 (s), 39.95 (s), 53.17 (s), 55.87 (s), 65.56 (s), 66.95 (s), 116.19 (d, 3J(P,C) = 8.1 Hz), 124.81 (s), 126.26 (s), 127.13 (s), 127.76 (s), 127.64 (s), 127.79 (s), 128.02 (s), 128.16 (s), 128.21 (s), 128.26 (s), 128.31 (s), 128.49 (s), 128.99 (s), 129.34 (s), 134.55 (s), 134.76 (s), 135.59 (s), 136.91 (s), 139.03 (s), 168.79 (s, C@O), 172.39 (s, C@O). IR (KBr, cm1): 3348 (m, mNH), 3255 (s, mNH), 3025 (m, mCH), 2850 (s, mCH), 1732 (s, mC@O), 1590 (s, mNO2), 1509 (s), 1484 (s), 1446 (s), 1342 (s, mNO2), 1224 (s), 1290 (m), 1187 (s, mP@O), 1109 (s), 999 (s), 960 (m, mP–N), 846 (m), 735 (m, mP–N), 689 (s, mP–N), 529 (m). 2.3.29. N-Phenylalanine benzylester-N0 -4-chlorophenylphosphoramidic chloride (26) Yield: 65%. m.p. = 146 °C. Anal. Calc. for C22H21Cl2N2O3P: C, 57.03; H, 4.57; N, 6.05. Found: C, 57.01; H, 4.56; N, 6.05%. 31P NMR (DMSO-d6): d 3.75 (m). 1H NMR (DMSO-d6): d 2.84 (m, 2H, CH2), 3.92 (m, 1H, CH), 4.86 (m, 2H, OCH2), 5.12 (m, 1H, NH), 7.00–7.29 (m, 14H, Ar–H), 7.51 (b, 1H, NH). 13C NMR (DMSO-d6): d 39.75 (s), 55.82 (s), 65.57 (s), 118.42 (d, 3J(P,C) = 6.4 Hz), 122.92 (s), 123.56 (s), 126.37 (s), 127.74 (s), 127.65 (s), 128.13 (s), 128.23 (s), 129.03 (s), 135.64 (s), 136.92 (s), 141.42 (s), 172.41 (s, C@O). IR (KBr, cm1): 3285 (s, mNH), 3255 (s, mNH), 3025 (m, mCH), 2850 (m, mCH), 1712 (s, mC@O), 1484 (s), 1442 (s), 1381 (s), 1274 (m), 1194 (s, mP@O), 1120 (s), 997 (s), 963 (m, mP–N), 911 (m), 822 (m, mP–N), 746 (m, mP–N), 692 (m, mP–N), 587 (m), 531 (m), 460 (m). 2.3.30. N,N0 -Bis (alaninethylester)-N00 -4-methylphenyl-phosphoric triamide (27) Yield: 85%. m.p. = 76 °C. Anal. Calc. for C17H28N3O5P: C, 52.98; H, 7.32; N, 10.90. Found: C, 52.99; H, 7.31; N, 10.91%. 31P NMR (DMSO-d6): d -0.23 (m). 1H NMR (DMSO-d6): d 1.20 (t, 3 J(H,H) = 7.0 Hz, 6H, CH3), 1.40 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.41 (s, 3H, p-CH3), 2.24 (m, 2H, CH), 3.97 (m, 2H, NH), 4.15 (m, 4H, CH2), 7.19 (s, 4 H, Ar–H). 13C NMR (DMSO-d6): d 13.94 (s, CH3), 15.69 (s, CH3), 20.49 (s, p-CH3), 47.86 (s, CH2), 61.64 (s, CH), 122.16 (s), 129.63 (s), 131.23 (s), 135.83 (s), 169.86 (s, C@O). IR (KBr, cm1): 3466 (s, mNH), 3245 (s, mNH), 2965 (s, mCH), 2805 (s, mCH), 2601 (m), 1608 (s), 1619 (s, mC@O), 1399 (s), 1292 (m), 1183 (m, mP@O), 1095 (m), 850 (m, mP–N), 778 (s, mP–N), 712 (m), 503 (m), 450 (m). 2.3.31. N-(2-Pyridinyl) phosphoramidic dichloride (28) A solution of 6 mmol 2-aminopyridine in acetonitrile was added dropwise to a solution of 3 mmol POCl3 in acetonitrile at 5 °C and the mixture was stirred for 8 h. Then the precipitate was filtered and the solution was evaporated under vacuum to yield the product. Yield: 77%. m.p. = 81 °C. Anal. Calc. for C5H5Cl2NOP: C, 30.49; H, 2.56; N, 7.11. Found: C, 30.50; H, 2.56; N, 7.12%. 31P NMR (DMSOd6): d 10.69 (s). 1H NMR (DMSO-d6): d 6.85 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 6.97 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 7.55 (t, 3 J(H,H) = 6.7 Hz, 1H, Ar–H), 8.10 (d, 3J(H,H) = 6.7 Hz, 1H, Ar–H), 9.12 (s 1H, NH). 13C NMR (DMSO-d6): d 111.38 (s), 116.65 (s), 137.96 (s), 147.47 (s), 153.67 (s). IR (KBr, cm-1): 3410 (m, mNH), 3130 (s, mNH), 2935 (m, mCH), 1591 (s), 1468 (s), 1321 (m), 1242 (m), 1214 (s, mP@O), 1149 (m), 985 (s, mP–N), 912 (s), 768 (m), 630 (m), 503 (m), 475 (m).
312
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
2.3.32. N-(2-Pyridinyl)-N0 ,N00 -bis (4-methylphenyl) phosphoric triamide (29) A solution of 8 mmol p-toluidine in acetonitrile was added dropwise to a solution of 2 mmol of compound 28 in acetonitrile at 5 °C and the mixture was stirred for 10 h. Then the precipitate was filtered and washed with water and CH2Cl2. Yield: 83%. m.p. = 204 °C. Anal. Calc. for C19H21N3OP: C, 67.44; H, 6.26; N, 12.42. Found: C, 67.45; H, 6.25; N, 12.41%. 31P NMR (DMSO-d6): d 4.08 (m). 1H NMR (DMSO-d6): d 2.13 (s, 6H, CH3), 6.81 (t, 3J(H,H) 8 7.0 Hz, 1H, Ar–H), 6.92 (d, 3J(H,H) = 8.3 Hz, 2H, Ar–Hp-toluidine), 7.03 (d, 3J(H,H) = 8.3 Hz, 2H, Ar–H), 7.54 (t, 3J(H,H) = 7.0 Hz, 1H, Ar–H), 7.64 (d, 2J(PNH) = 7.0 Hz, 2H, NH), 8.32 (b, 1H, NH). 13C NMR (DMSO-d6): d 20.14 (s, CH3), 111.17 (d, 2J(P,C) = 5.5 Hz), 115.94 (s), 117.55 (d, 3J(P,C) = 7.2 Hz), 128.75 (s), 129.04 (s), 137.63 (s), 139.02 (s), 147.52 (s), 154.64 (s). IR (KBr, cm1): 3215 (m, mNH), 3025 (m, mNH), 2910 (m, mCH), 1594 (m), 1505 (s), 1461 (m), 1389 (s), 1302 (s), 1288 (s), 1220 (m), 1183 (s, mP@O), 966 (s, mP–N), 804 (s, mP–N), 768 (m), 635 (m), 583 (m), 485 (m). MS (20 eV, EI): m/z (%): 352 (100) M+, 259 (7) [(4-CH3– C6H4NH)2P(O)]+, 246 (73) [(4-CH3–C6H4NH)P(O)(2-C5H4N–NH)]+, 153 (3) [(4-CH3–C6H4NH)P(O)]+, 140 (7) [(2-C5H4N–NH)P(O)]+, 106 (66) [4-CH3–C6H4NH]+, 93 (17) [2-C5H4N–NH]+. 2.3.33. N-[1-(4-methoxybenzyl)-decahydro-isoquinolinyl)] phosphoramidic dichloride (30) A solution of 3 mmol N-[1-(4-methoxybenzyl)-decahydro-isoquinoline)] plus 3 mmol of triethylamine in acetonitrile was added dropwise to a solution of 3 mmol POCl3 in acetonitrile at 5 °C and the mixture was stirred for 12 h. Then the precipitate was filtered and washed with water and diethylether. Yield: 52%. Anal. Calc. for C17H22Cl2NO2P: C, 54.56; H, 5.93; N, 3.74. Found: C, 54.55; H, 5.92; N, 3.75%. 31P NMR (DMSO-d6): d 0.26 (m). 1H NMR (DMSO-d6): d 1.36 (m, 2H, CH2), 1.64 (m, 2H, CH2), 1.78 (m, 1H, CH), 1.93 (s, 3H, CH3), 2.05 (m, 1H, CH), 2.23 (m, 1H, CH), 2.90 (m, 2H, CH2), 3.09 (m, 2H, CH2), 3.77 (s, 4H, CH2), 6.89 (d, 3J(H,H) = 8.6 Hz), 7.31 (d, 3J(H,H) = 8.6 Hz), 7.31 (d, 3J(H,H) = 8.6 Hz). 13C NMR (DMSO-d6): d 21.85 (s), 22.09 (s), 25.85 (s), 26.19 (s), 29.34 (s), 35.37 (s), 38.35 (s), 55.00 (s), 56.30 (s), 113.92 (s), 125.35 (s), 127.95 (s), 128.39 (s), 130.54 (s), 158.19 (s). IR (KBr, cm1): 3440 (w, mNH), 2925 (s, mCH), 2770 (s, mCH), 2600 (m), 1602 (m), 1503 (s), 1452 (s), 1418 (m), 1297 (m), 1242 (s, mP@O), 1176 (m), 1031 (m), 828 (m, mP–N), 784 (m), 570 (m). 2.3.34. N-[1-(4-methoxybenzyl)-decahydro-isoquinolinyl)] (phenyl) phosphoramidic chloride (31) A solution of 3 mmol N-[1-(4-methoxybenzyl)-decahydro-isoquinoline)] plus 3 mmol of triethylamine in acetonitrile was added dropwise to a solution of 3 mmol phenyl phosphorodichloridate in acetonitrile at 5 °C and the mixture was stirred for 18 h. Then the precipitate was filtered and washed with water and ethylacetate. Yield: 63%. Anal. Calc. for C23H27ClNO2P: C, 66.42; H, 6.54; N, 3.37. Found: C, 66.43; H, 6.54; N, 3.36%. 31P NMR (DMSO-d6): d 6.57 (m). 1H NMR (DMSO-d6): d 1.42 (m, 2H, CH2), 1.64 (m, 2H, CH2), 1.79 (m, 1H, CH), 1.93 (s, 3H, OCH3), 2.07 (d, 3J(H,H) = 6.3 Hz, 1H, CH), 2.15 (m, 1H, CH), 2.77 (m, 1H, CH), 2.78 (m, H, CH), 3.09 (m, 2H, CH2), 4.36 (m, 4H, CH2), 6.89 (d, 3J(H,H) = 8.4 Hz, 2H, Ar– 3 J(H,H) = 8.4 Hz, 2H, Ar–H), 7.36 (dd, H), 7.26 (d, 3 J(PCCH) = 13.4 Hz, 3J(H,H) = 7.4 Hz, 2H, Ar–H), 7.43 (t, 3 J(H,H) = 8.4 Hz, 1H, Ar–H), 7.65 (d, 3J(H,H) = 7.4 Hz, 2H, Ar–H). 13 C NMR (DMSO-d6): d 21.81 (s), 22.05 (s), 25.88 (s), 26.18 (s), 29.28 (s), 35.42 (s), 38.23 (s), 54.96 (s), 56.18 (s), 113.90 (s), 125.38 (s), 127.56 (d, 3J(P,C) = 7.2 Hz), 127.76 (d, 1J(P,C) = 28.8 Hz), 128.30 (s), 130.33 (s), 130.47 (s), 130.68 (s), 130.73 (d, 3 J(P,C) = 4.9 Hz), 158.16 (s). IR (KBr, cm-1): 3435 (m, mNH), 2910 (s, mCH), 2798 (s, CH), 1503 (s), 1426 (s), 1240 (s, mP@O), 1177 (m), 965 (s, mP–N), 699 (m), 526 (s).
2.3.35. N-Cyanoacetyl-phosphoramidic dichloride (32) A solution of 5 mmol of cyanoacetamide in CCl4 was added slowly to a mixture of 3 mmol PCl5 in CCl4 at 5 °C and the mixture was refluxed for 10 h. Then the orange precipitate that formed was filtered and washed with CCl4 and dried under vacuum. Yield: 55%. Anal. Calc. for C3H3Cl2N2O2P: C, 17.93; H, 1.50; N, 13.94. Found: C, 17.92; H, 1.51; N, 13.95%. 31P NMR (DMSO-d6): d 0.56 (d, 2 J(PNH) = 6.1 Hz). 1H NMR (DMSO-d6): d 3.77 (s, 2H, CH2), 9.44 (d, 2J(PNH) = 6.1 Hz). 13C NMR (DMSO-d6): d 26.62 (d, 3 J(P,C) = 10.5 Hz, CH2), 115.56 (d, 4J(P,C) = 1.6 Hz, C„N), 164.04 (s, C@O). IR (KBr, cm1): 3190 (s, mNH), 2985 (s), 1710 (s, mC@O), 1452 (s, mC„N), 1265 (s, mP@O), 1153 (m), 982 (m, mP–N), 663 (m), 580 (s), 526 (m). 2.3.36. N-Cyanoacetyl-N0 -benzyl phosphoramidic chloride (33) A solution of 2 mmol benzylamine in acetonitrile was added dropwise to a solution of 1 mmol of compound 32 in acetonitrile at 5 °C and the mixture was stirred for 15 h. Then the precipitate was filtered and the solvent was evaporated to give the product that was washed with water and n-heptane. Yield: 63%. Anal. Calc. for C10H11ClN3O2P: C, 44.22; H, 4.08; N, 15.47. Found: C, 44.21; H, 4.09; N, 15.46%. 31P NMR (DMSO-d6): d 1.16 (s). 1H NMR (DMSOd6): d 3.58 (s, 2H, CH2 of amide), 3.59 (s, Ar–CH2), 3.98 (m, 1H, NHamine), 7.29–7.474 (m, 5H, Ar–H), 9.46 (b, 2H, NHamide). 13C NMR (DMSO-d6): d 25.49 (s, CH2 of amide), 42.22 (s, Ar–CH2), 116.31 (s, C„N), 128.91 (s), 128.54 (s), 128.91 (s), 134.25 (s), 165.93 (s, C@O). IR (KBr, cm1): 3355 (m, mNH), 3080 (s, mNH), 2980 (s), 1711 (s), 1677 (s, mC@O), 1400 (s, mC„N), 1212 (s, mP@O), 1101 (s), 980 (s, mP–N), 926 (m, mP–N), 608 (m), 497 (m, mP–Cl). 2.3.37. General procedure for the synthesis of compounds 34–45 A solution of 8 mmol of the corresponding amine in acetonitrile was added dropwise to a solution of 2 mmol of compound 32 in acetonitrile at 5 °C and the mixture was stirred for 24 h. Then the precipitate tha formed was filtered and washed with water and n-hexane. Compound 45 was synthesized in the same way, but 8 mmol of amine was added to 2 mmol of N-trifluoroacetyl phosphoramidic dichloride. 2.3.38. N-Cyanoacetyl-N0 ,N00 -dibenzyl phosphoric triamide (34) Yield: 56%. Anal. Calc. for C17H19N4O2P: C, 59.64; H, 5.59; N, 16.37. Found: C, 59.65; H, 5.60; N, 16.38%. 31P NMR (DMSO-d6): d 7.49 (m). 1H NMR (DMSO-d6): d 3.67 (s, 2H, CH2 of amide), 4.20 (dd, 3J(PNCH) = 11.5 Hz, 3J(H,H) = 7.4 Hz, 2H, Ar–CH2), 5.04 (m, 2H, NHamine), 7.19–7.34 (m, 10H, Ar–H), 9.25 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.67 (d, 3J(P,C) = 8.7 Hz, CH2 of amide), 43.80 (s, Ar–CH2), 115.58 (s, C„N), 126.59 (s), 127.25 (s), 128.07 (s), 128.64 (s), 128.82 (s), 140.91 (d, 3J(P,C) = 5.7 Hz, Cipso), 164.47 (s, C@O). IR (KBr, cm1): 3305 (m, mNH), 3100 (m, mNH), 2975 (s), 1692 (m, mC@O), 1476 (m, mC„N), 1446 (m), 1159 (s, mP@O), 932 (m, mP–N), 880 (m, mP–N), 798 (s), 546 (m). 2.3.39. N-Cyanoacetyl-N0 ,N00 -bis (a-phenylethyl) phosphoric triamide (35) Yield: 52%. Anal. Calc. for C19H23N4O2P: C, 61.61; H, 6.26; N, 15.13. Found: C, 61.60; H, 6.25; N, 15.13%. 31P NMR (DMSO-d6): d 4.02 (m). 1H NMR (DMSO-d6): d 1.33 (d, 3J(H,H) = 7.2 Hz, 3H, CH3), 1.34 (d, 3J(H,H) = 7.2 Hz, 3H, CH3), 3.40 (m, 2H, CH2 of amide), 4.27 (m, 2H, NHamine), 4.57 (m, 1H, CH), 4.93 (m, 1H, CH), 7.16–7.45 (m, 10H, Ar–H), 8.86 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 25.25 (d, 3J(P,C) 8 5.0 Hz, CH3), 25.34 (d, 3J(P,C) = 5.1 Hz, CH3), 26.51 (d, 3 J(P,C) 8 8.8 Hz, CH2), 49.77 (s, CH), 50.10 (s, CH), 115.49 (s, C„N), 125.92 (s), 126.04 (s), 126.34 (s), 126.39 (s), 126.66 (s), 128.00 (s), 128.65 (s), 146.00 (d, 3J(P,C) = 5.7 Hz, Cipso), 146.15 (d, 3 J(P,C) = 5.4 Hz, Cipso), 164.10 (s, C@O). IR (KBr, cm1): 3255 (s, mNH), 2250 (m), 1672 (m, mC@O), 1440 (s, mC„N), 1416 (s), 1328
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
(m), 1188 (s, mP@O), 1111 (m), 1037 (m), 953 (m, mP–N), 633 (m, mP–N), 503 (m). 2.3.40. N-Cyanoacetyl-N0 ,N00 -bis (2-chlorobenzyl) phosphoric triamide (36) Yield: 64%. Anal. Calc. for C17H17Cl2N4O2P: C, 49.65; H, 4.17; N, 13.62. Found: C, 49.64; H, 4.16; N, 13.61%. 31P NMR (DMSO-d6): d 7.38 (m). 1H NMR (DMSO-d6): d 3.73 (s, 2H, CH2 of amide), 4.15 (ddd, 3J(PNCH) = 11.0 Hz, 3J(H,H) = 7.2 Hz, 2J(H,H) = 14.5 Hz, 2H, Ar–CH2), 5.23 (dd, 3J(H,H) = 7.2 Hz, 2J(PNH) 8 10.1 Hz, 2H, NHamine), 7.19–7.62 (m, 10H, Ar–H), 9.26 (s, 1H, NHamide). 13C NMR (DMSOd6): d 26.75 (d, 3J(P,C) = 8.9 Hz, CH2 of amide), 41.43 (s, Ar–CH2), 115.55 (s, C„N), 126.98 (s), 128.25 (s), 128.86 (s), 129.47 (s), 131.52 (s), 138.00 (s), 164.64 (s, C@O). IR (KBr, cm1): 3255 (m, mNH), 2915 (m), 1678 (s, mC@O), 1457 (s, mC„N), 1432 (s), 1184 (s, mP@O), 1082 (m), 1037 (m), 868 (m, mP–N), 741 (m, mP–N), 503 (m), 413 (m). 2.3.41. N-Cyanoacetyl-N0 ,N00 -bis (cyclopentyl) phosphoric triamide (37) Yield: 64%. Anal. Calc. for C13H23N4O2P: C, 52.34; H, 7.77; N, 18.78. Found: C, 52.35; H, 7.78; N, 18.77%. 31P NMR (DMSO-d6): d 6.13 (m). 1H NMR (DMSO-d6): d 1.38 (m, 8H, CH2), 1.58 (m, 4H, CH2), 1.71 (m, 4H, CH2), 3.37 (m, 2H, CH), 3.74 (m, 2H, CH2 of amide), 4.23 (m, 2H, NHamine), 9.13 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 22.76 (s, CH2), 22.88 (s, CH2), 26.58 (d, 3 J(P,C) = 8.7 Hz, CH2 of amide), 33.97 (d, 3J(P,C) = 5.1 Hz, CH2), 34.14 (d, 2J(P,C) = 6.5 Hz, CH), 51.97 (s, CH2), 115.64 (s, C„N), 164.16 (s, C@O). IR (KBr, cm1): 3390 (s, mNH), 3090 (m, mCH), 2920 (s, mCH), 1694 (s, mC@O), 1478 (s, mC„N), 1155 (s, mP@O), 1105 (m), 977 (m, mP–N), 926 (m, mP–N), 899 (m, mP–N), 565 (m), 461 (m). 2.3.42. N-Cyanoacetyl-N0 ,N00 -bis (cyclohexyl) phosphoric triamide (38) Yield: 58%. Anal. Calc. for C15H27N4O2P: C, 55.20; H, 8.34; N, 17.17. Found: C, 55.20; H, 8.33; N, 17.17%. 31P NMR (DMSO-d6): d 4.32 (m). 1H NMR (DMSO-d6): d 1.09 (m, 10H, CH2), 1.48 (m, 2H, CH2), 1.74 (m, 8H, CH2), 2.85 (m, 2H, CH), 3.73 (m, 2H, CH2 of amide), 4.14 (m, 2H, NHamine), 8.50 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 21.11 (s), 24.55 (d, 3J(P,C) = 6.6 Hz), 24.73 (d, 3 J(P,C) = 4.0 Hz), 27.36 (s, CH2 of amide), 31.85 (s), 34.84 (d, 2 J(P,C) = 4.1 Hz, CH), 35.03 (d, 2J(P,C) = 6.6 Hz, CH), 40.19 (s), 40.22 (s), 115.46 (s, C„N), 167.26 (s, C@O). IR (KBr, cm1): 3305 (m, mNH), 2925 (s, mCH), 1692 (m, mC@O), 1476 (m, mC„N), 1159 (m, mP8O), 1114 (m), 932 (m, mP–N), 868 (m, mP–N), 736 (m, mP– N), 471 (m). 2.3.43. N-Cyanoacetyl-N0 ,N00 -bis (4-methylpiperidinyl) phosphoric triamide (39) Yield: 72%. Anal. Calc. for C15H27N4O2P: C, 55.20; H, 8.34; N, 17.17. Found: C, 55.19; H, 8.35; N, 17.16%. 31P NMR (DMSO-d6): d 10.12 (m). 1H NMR (DMSO-d6): d 0.88 (d, 3J(H,H) = 6.5 Hz, 6H, CH3), 1.00 (m, 4H, CH2), 1.43 (m, 2H, CH), 1.54 (m, 4H, CH2), 2.55 (m, 4H, CH2), 3.36 (m, 4H, CH2), 3.84 (s, 2H, CH2), 9.12 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 21.98 (s), 26.77 (d, 3J(P,C) 8 8.6 Hz, CH2 of amide), 130.40 (s), 33.99 (s), 34.06 (d, 3J(P,C) = 8.6 Hz, CH2), 34.10 (d, 3 J(P,C) = 5.3 Hz, CH2), 44.05 (d, 3J(P,C) = 2.6 Hz, CH2), 44.32 (d, 3 J(P,C) = 2.8 Hz, CH2), 115.63 (d, 4J(P,C) = 1.3 Hz, C„N), 164.46 (s, C@O). IR (KBr, cm1): 3430 (w, mNH), 3100 (m, mNH), 2950 (s), 2465 (s), 1639 (s, mC@O), 1631 (m), 1583 (m), 1212 (s, mP=O), 1063 (s), 968 (m, mP–N), 772 (m, mP–N), 538 (m). 2.3.44. N-Cyanoacetyl-N0 ,N00 -bis (4-fluorophenyl) phosphoric triamide (40) Yield: 56%. Anal. Calc. for C15H13F2N4O2P: C, 51.44; H, 3.74; N, 16.00. Found: C, 51.45; H, 3.75; N, 16.00%. 31P NMR (DMSO-d6): d
313
-5.92 (s). 1H NMR (DMSO-d6): d 3.72 (s, 2H, CH2 of amide), 6.75 (m, 2H, Ar–H), 6.95 (m, 4H, Ar–H), 7.05 (m, 2H, Ar–H), 7.58 (s, 2H, NHamine), 9.50 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.41 (s, CH2 of amide), 115.00 (d, 2J(F,C) = 22.0 Hz), 115.41 (d, 2 J(F,C) = 22.1 Hz), 115.63 (s, C„N), 117.23 (dd, 3J[(F,C), (P,C)] = 7.4 Hz), 118.46 (dd, 3J[(F,C), (P,C)] = 7.5 Hz), 138.40 (s), 1 J(F,C) = 232.0 Hz), 156.43 (d, 141.08 (s), 155.92 (d, 1 J(F,C) = 235.0 Hz), 163.94 (s, C@O). IR (KBr, cm-1): 3415 (m, mNH), 3285 (m, mCH), 3155 (m, mCH), 2960 (m, mCH), 1671 (s, mC@O), 1500 (s, mC„N), 1441 (s), 1201 (s, mP@O), 1065 (s), 941 (m, mP–N), 825 (m, mP–N), 500 (m), 481 (m). 2.3.45. N-Cyanoacetyl-N0 ,N00 -bis (4-chlorophenyl) phosphoric triamide (41) Yield: 60%. Anal. Calc. for C15H13Cl2N4O2P: C, 47.02; H, 3.42; N, 14.62. Found: C, 47.00; H, 3.42; N, 14.61%. 31P NMR (DMSO-d6): d 5.91 (s). 1H NMR (DMSO-d6): d 3.74 (s, 2H, CH2 of amide), 6.70 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.07 (d, 3J(H,H) = 9.7 Hz, 2H, Ar– H), 7.09 (d, 3J(H,H) = 9.7 Hz, 2H, Ar–H), 7.17 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.88 (s, 2H, NHamine), 9.62 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.52 (d, 3J(P,C) = 9.8 Hz, CH2 of amide), 115.53 (s, C„N), 116.92 (s), 118.70 (d, 3J(P,C) = 7.5 Hz), 121.13 (s), 123.58 (s), 128.39 (s), 128.67 (s), 140.90 (s), 144.76 (s), 163.99 (s, C@O). IR (KBr, cm1): 3415 (m, mNH), 3270 (m, mCH), 3125 (m, mCH), 2930 (s, mCH), 1671 (s, mC@O), 1483 (s, mC„N), 1451 (s), 1389 (m), 1295 (m), 1187 (s, mP@O), 1051 (s), 940 (m, mP–N), 817 (m, mP–N), 532 (m). 2.3.46. N-Cyanoacetyl-N0 ,N00 -bis (4-bromophenyl) phosphoric triamide (42) Yield: 63%. Anal. Calc. for C15H13Br2N4O2P: C, 38.16; H, 2.78; N, 11.87. Found: C, 38.15; H, 2.77; N, 11.88%. 31P NMR (DMSO-d6): d 6.01 (s). 1H NMR (DMSO-d6): d 3.74 (s, 2H, CH2 of amide), 6.68 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.01 (d, 3J(H,H) = 8.1 Hz, 2H, Ar– H), 7.22 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.29 (d, 3J(H,H) = 8.2 Hz, 2H, Ar–H), 7.90 (s, 2H, NHamine), 9.63 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.57 (d, 3J(P,C) = 9.8 Hz, CH2 of amide), 109.16 (s), 111.38 (s), 115.56 (s, C„N), 117.83 (s), 119.23 (d, 3J(P,C) = 7.4 Hz), 131.30 (s), 131.59 (s), 141.36 (s), 144.63 (s), 164.04 (s, C@O). IR (KBr, cm1): 3345 (m, mNH), 3260 (s, mNH), 3120 (s, mCH), 2835 (s, mCH), 2590 (s), 1670 (s, mC@O), 1478 (s, mC„N), 1452 (s), 1187 (s, mP@O), 1051 (s), 1005 (m), 938 (m, mP–N), 813 (m, mP– N), 577 (m), 527 (m), 485 (m). 2.3.47. N-Cyanoacetyl-N0 ,N00 -bis (4-butylphenyl) phosphoric triamide (43) Yield: 66%. Anal. Calc. for C23H23N4O2P: C, 65.99; H, 5.54; N, 13.39. Found: C, 66.00; H, 5.55; N, 13.40%. 31P NMR (DMSO-d6): d 7.09 (m). 1H NMR (DMSO-d6): d 0.86 (t, 3J(H,H) = 7.4 Hz, 6H, CH3), 1.27 (m, 4H, CH2), 1.46 (m, 4H, CH2), 2.43 (m, 2H, CH2), 2.47 (m, 2H, CH2), 3.72 (s, 2H, CH2 of amide), 6.78 (d, 3 J(H,H) = 8.1 Hz, 2H, Ar–H), 6.92 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 6.95 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 7.00 (d, 3J(H,H) = 8.1 Hz, 2H, Ar–H), 7.37 (b, 2H, NHamine), 9.45 (b, 1H, NHamide). 13C NMR (DMSO-d6): d 13.68 (s), 13.71 (s), 21.59 (s), 21.64 (s), 26.37 (d, 3 J(P,C) = 9.6 Hz, CH2 of amide), 33.16 (s), 33.33 (s), 34.02 (s), 34.09 (s), 115.59 (s, C„N), 117.17 (d, 3J(P,C) = 6.5 Hz), 119.66 (s), 128.26 (s), 129.03 (s), 133.34 (s), 135.63 (s), 137.44 (s), 139.52 (s), 164.12 (s, C@O). IR (KBr, cm1): 3354 (m, mNH), 3260 (m, mNH), 3010 (m, mCH), 2840 (s, mCH), 2580 (s), 1669 (s, mC@O), 1504 (s), 1457 (s, mC„N), 1193 (s, mP@O), 1060 (s), 925 (m, mP– N), 815 (m, mP–N), 535 (m). 2.3.48. N-Cyanoacetyl-N0 ,N00 -bis (furfuryl) phosphoric triamide (44) Yield: 60%. Anal. Calc. for C13H15N4O2P: C, 53.79; H, 5.21; N, 19.30. Found: C, 53.80; H, 5.20; N, 19.30%. 31P NMR (DMSO-d6): d
314
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
7.67 (m). 1H NMR (DMSO-d6): d 3.71 (s, 2H, CH2 of amide), 3.95 (m, 4H, Ar–CH2), 4.98 (m, 2H, NHamine), 6.22 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 6.36 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 7.53 (d, 3J(H,H) = 6.5 Hz, 2H, Ar–H), 9.30 (s, 1H, NHamide). 13C NMR (DMSO-d6): d 26.60 (d, 3 J(P,C) = 8.6 Hz, CH2 of amide), 37.06 (s, Ar–CH2), 106.31 (s), 110.34 (s), 115.52 (s, C„N), 141.82 (s), 153.95 (d, 3J(P,C) = 6.6 Hz), 164.38 (s, C@O). IR (KBr, cm1): 3295 (s, mNH), 3095 (m, mCH), 2910 (m, mCH), 1686 (s, mC@O), 1470 (s, mC„N), 1150 (s, mP@O), 1067 (m), 924 (m, mP–N), 877 (m, mP–N), 748 (m, mP–N), 564 (m).
have been obtained up until now in such a simple one-step reaction. The 31P{1H} NMR spectrum of compound 1 displays two singlet peaks for the two phosphorus atoms, at 5.44 and 6.69 ppm, and the substitution of different cyclic and acyclic aliphatic amines for the chlorine atoms shifts the d (31P) downfield, while substitution with phenyl groups leads to upfield shifts. The d (31P) in this series varies between 3.42 and 3.74 ppm (in 7 containing an aromatic aniline moiety) to 20.03, 20.16 ppm (in 9 containing a heterocyclic aliphatic diazaphosphole ring). The 1H NMR spectrum of 3 displayed four doublet signals for the four types of CH3 groups of isopropyl moieties due to the fact that the carbon atom of the CH group in the iso-propyl substituent is prochiral, and so the two methyl groups bonded to this group are different and show two signals in both the 1H and 13C NMR spectra. The 13C NMR spectra of compounds 1 and 3–10 displayed six separate signals for the aromatic carbon atoms of the 4-aminobenzamide group and 2 J(P,C@O) = 3.5 Hz for the C@O group in 1, while this constant was zero for the other compounds. Compound 6, with cyclohexyl substituents, displayed 12 peaks in the aliphatic region of the 13C NMR spectrum, with four 3J(P,C) coupling constants for CH2 groups, four singlet signals for CH2 groups and four 2J(P,C) coupling constants for the CH groups. These results indicate that due to the different spatial orientation of the aliphatic six-membered rings, the four CH groups of the four cyclohexyl groups are different, but other related carbon atoms on one side of the molecule are equal to each other while being unequal to their related carbon atoms on the other side. The 13C NMR spectrum of bis diazaphosphole 9 displayed two 2J(P,C) = 5.0, 4.9 Hz for the CH3 groups, two 2J(P,C) = 7.3, 5.7 Hz for CH2 moieties, two singlets for CH3 as well as two singlets for CH2 groups. A reason for this may be that for the phosphorus and carbon atoms a simple splitting is seen on one side of the molecule, while for the carbon atoms on the other side no coupling is observed. According to the Karplus relationship between the 3J(P,X), X = H, C coupling constant and the P–N–C–X torsion angle [33], this is due to the P–N–C–H torsion angle values. The 13C NMR spectrum of 10 showed three signals in the aliphatic region for the cyclopentyl moieties and the proton integrals in the 1H NMR spectrum indicate that only two cyclopentyl groups are connected to one of the phosphorus atoms, while for
2.3.49. N-Trifluoroacetyl-N0 ,N00 -bis (4-methyl phenyl) phosphoric triamide (45) Yield: 78%. Anal. Calc. for C16H17F3N3O2P: C, 51.76; H, 4.62; N, 11.32. Found: C, 51.77; H, 4.62; N, 11.33%. 31P NMR (CD3CN): d 5.38 (m). 1H NMR (CD3CN): d 2.26 (s, 6H, CH3), 6.53 (d, 2 J(PNH) = 9.9 Hz, 2H, NHaromatic), 7.04 (d, 3J(H,H) = 8.4 Hz, 2H, Ar– H), 7.07 (d, 3J(H,H) = 8.4 Hz, 2H, Ar–H), 9.48 (b, 1H, NHamide). 13C NMR (CD3CN): d 20.64 (s, CF3), 119.94 (d, 3J(P,C) = 6.9 Hz), 130.73 (s), 132.99 (s), 137.89 (s), 167.42 (s, C@O). IR (KBr, cm1): 3419 (s, mNH), 3279 (s, mNH), 2924 (m, mCH), 1724 (s, mC@O), 1616 (s), 1517 (s), 1459 (s), 1309 (s), 1282 (m), 1208 (s), 1175 (s, mP@O), 966 (m, mP–N), 815 (m, mP–N), 596 (m), 474 (m). 3. Results and discussion 3.1. Spectroscopic study In this work a number of new phosphoramidate derivatives of bisphosphoramidates and phosphoric triamides were synthesized using PCl5 and POCl3 as starting materials, Schemes 1 and 2. Here, the spectroscopic features of these compounds are studied. 3.1.1. Bisphosphoramidates 1, 3–10 The syntheses of the bisphosphoramidates 1 and 3–10 (containing the (O)P–NH–C6H4–C(O)NH–P(O) linkage) were performed by the reaction of PCl5 with 4-aminobenzamide in a 1:4 molar ratio to initially yield the bisphosphoramide Cl2P(O)NHC6H4C(O)NHP(O)Cl2 (1) that was used as an intermediate to react with different amines to give molecules 3–10, Scheme 1. As far as we know, these compounds are the first examples of bisphosphoramidates that
C
O P R1 R2
H2N
P N H
O
O
O
O
C X
NH2
R4
C
P
PCl5
R3
R1 R2
N H
O
O NH2
C N H
X
NH2
R1 = R2 =R3 = R4= Cl (1), NH-CH(CH3)2 (3), NH-CH 2CH(CH3)2 (4), N( C2H5)2 (5), NH- C6H11 (6), NH- C6H5 (7), R1 = R3= Cl; R2 = R4= 4-Cl-C6H4-NH (8), R1 = R2 =R3 = R4= (CH3)N-(CH2)2-N(CH3) (9), R1 = R2= NH-C5H9; R3 = R4= OH (10)
H2N
C
P R2
O C
O R1
O
NH2
N H
(2), R1 = R2 = Cl R1 = Cl; R2 = NH-CH2-CH(CH3)2 (11), R1 = R2 = NH-C5H9 (12), R1 = R2 = 4-Br-C6H4-NH (13)
(32), X = CN-CH2; R1 = R2 = Cl X = CN-CH2; R1 = Cl, R2 = NHCH2C6H5 (33), X = CN-CH2; R1 = R2 = Cl NHCH2C6H5 (34), NHCH(CH3)(C6H5) (35), NHCH2(2-Cl-C6H4) (36), NHC5H9 (37), NHC6H11 (38), 4-CH3-C5H9N (39), 4-F-C6H4-NH (40), 4-Cl-C6H4-NH (41), (42), 4-Br-C6H4-NH (43), 4-Bun-C6H4-NH NH-CH2-C4H3O (44), X = CF3; R1 = R2 = 4-CH3-C6H4-NH (45)
Scheme 1. Preparation pathway for compounds using PCl5 as a starting compound.
315
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
NO2
O P
N H
HN Cl
O
HN
O
P
P
O
HN
O
HN
O
HN
O
HN
O
CH3
O
(25)
O
O
(24)
(26)
CH3
O CH3
O
O
P
HO
N H
HN
P
O
N H
HN HN
X
OH
P
O
HN
O
Y
R1
O
R2 Y
(27)
(23) OCH3
O
O P
HN
P
N
X Cl
HN
NH
O P
HN
NH2
X
OCH3
H2C
X
POCl3
Cl
H2C N
X X
X
X
HN
O
O
P
P
N
N
N X
O
H3C H2N Cl
O
X
N
P
N
H3C
NH2
P
N H
N NH H
N H
Cl
HN
NH
X = Cl (30), C6H5 (31)
NH2
X = H (14), F (15), Cl (16), Br (17)
Cl
N
(28) H3C X
X = H (18), F (19), Cl (20), Br (21)
(29)
Scheme 2. Preparation pathway for compounds using POCl3 as a starting compound.
the other phosphorus atom the two cyclopentyl substituents are replaced by OH groups. This is probably due to the acquisition of the NMR spectra in D2O solvent, and hence hydrolysis of the molecule occurs. A comparison of d (31P) in compounds 4 and 11 revealed that in the bisphosphoramide 4 the P atom is far more deshielded than in the phosphoric triamide 11. The IR spectra indicated two m (P@O) for the two P@O bonds and a m (C@O) in each compound. The 2J(PNHamine) coupling constant for compounds 1, 5 and 6 are 11.9, 9.1 and 7.6 Hz, respectively, and the corresponding m (P–N) values are 994, 941 and
907 cm1. These data reveal that the more the m (P–N) value increases, i.e., a shorter P–N bond with more s character in the nitrogen hybridization, the more the 2J(PNHamine) coupling constant is enhanced. 3.1.2. Bisphosphoramidates 14–21 The bisphosphoramidates 14–21 (containing the (O)P–N–P(O) linkage) were prepared by the reaction of POCl3 with different first-type aromatic amines, Scheme 2. To our knowledge, this is the first attempt that has been made to obtain these types of
316
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
compounds using time-dependent reactions. That is, the synthesis procedure of these molecules is similar to that of phosphoric triamides, but these compounds are obtained after 48 h stirring and if the reaction mixture was allowed to stir for about one or two weeks, the corresponding phosphoric triamides would be yielded. In fact, these compounds are kinetically stable products of the reaction and are not stable with time. Thus after a relatively long time they convert to their related thermodynamically stable phosphoric triamides. The 2J(P,P) coupling constants observed in the 31P{1H} NMR spectra are about 20 Hz. The two phosphorus atoms are not connected directly to each other, because the 1 J(P,P) coupling constants in other similar compounds are reported to be about 200 Hz [34]. The 2J(P,P) coupling constant in compound 14 was measured as 19.7 Hz in DMSO-d6 and it decreased to 17.5 Hz in the solvent CD3OD, probably due to the different hydrogen bonding interactions in this solvent. The 31P NMR spectra of compounds 14 and 18 (containing the anilinium substituent) indicated two signals, the upfield one of them being a multiplet and the other being only a doublet peak. This trend is reverse for compounds 15–17 and 19–21, including para-haloanilinium groups. It is clear that the doublet peak is related to the P1 atom and the multiplet peak to the P2 atom (Scheme 3), and the reason for the reduced splitting of P1 with the NH group of the aromatic amine may be described by the resonance interaction in Scheme 3. The downfield shift of d (31P) for the P2 atom in compounds containing para-haloanilinium groups is related to the electron withdrawing nature of the electronegative halogen atoms in comparison with the inert H atom. Comparison of d (31P) in compounds 14–17 and also in 19–21 revealed that the shielding of the P1 and P2 atoms decreases with the decreasing halogen electronegativity from F to Cl to Br (i.e., from 15 to 17 and from 19 to 21). The shielding of the phosphorus atoms in compounds 14 and 18 containing anilinium moieties are greater than that of compounds containing 4-fluoroanilinium groups, and the shielding order is Br > Cl > H > F. The reason for the greater shielding of the P atoms in compounds with 4-Cl and 4-Br substituents relative to the H substituent can be explained by the electron release of the halogens through resonance. The 13C NMR spectra of 15 and 19 indicate 1–4J(F,C) coupling constants as well as 3J(P,C) coupling constants. The IR spectra revealed two m(P@O) frequencies for the two P@O bonds and we can relate the smaller m(P@O) to the weaker P@O bond and vice versa. In molecules 14 and 18, the upfield signal is related to P2 and in compounds 15–17 and 19–21, it is related to P1. 3.1.3. Phosphoramidates and phosphoric triamides The phosphoramidates 2 and 11–13 were prepared by the reaction of PCl5 with 4-aminobenzamide in a 1:1 molar ratio and we may judge that the P–N bond is formed from the anilinium NH2 group not from the amidic C(O)NH2. This is because stronger P–N bonds always have been observed for P–Namine compared to P–Namide in our other synthesized compounds, and also the C(O) group causes weakening of the P–N bond via resonance interactions. A
O
O P2
HN
NH
comparison of d (31P) in these molecules indicated that substitution of aliphatic electron donor amines with the chlorine atoms of 2 leads to a more positive P atom (in 11 and 12), while the aromatic 4-bromoaniline (in 13) had the opposite effect. In the 13C NMR spectra of these compounds four singlet signals were observed for the benzamidic ring, while in their related bisphosphoramidates six different signals were obtained for the six carbon atoms of the ring. Replacement of an amine group by a chlorine atom gives a m (P–N) value indicating a stronger P–N bond and a m(C@O) value indicating a weaker C@O bond. For the synthesis of compounds 23–26, first the hydrochloride salt of the phenylalanine benzylester was obtained for subsequent reaction with an RP(O)Cl2 intermediate, where R = amine or phenol. Phosphoric triamides of this type have shown antitumor, antiviral and anti-HIV properties [1–4] and for this reason we have been interested in studying such molecules. In the case of compound 23, it is concluded from the 1H and 13C NMR spectra that the phenylalanine benzylester is hydrolyzed and the phenylalanine is connected to the phosphorus atom. The 1H and 13C NMR spectra of molecules 23–26 displayed two unequivalent aminoester (or aminoacid) moieties, probably owing to the presence of chiral CH groups as well as the spatial hinderance caused by these two huge substituents. However, this is not observed in the 1H and 13C NMR spectra of 29 that also contain two chiral aminoester groups. Therefore, the chirality of these moieties is not the reason for the difference between these groups in compounds 23–26, but it is the various spatial orientations of the aminoester/aminoacid groups (the huge groups are far away from each other due to the repulsion) which result in the creation of a central chiral phosphorus atom. The 31P NMR spectra exhibited an upfield shift for d (31P) in compounds including electron donor groups such as p-tolyl (24), while it is shifted downfield with electronegative 4-nitroanilinium or 4-chloroanilinium groups (25 and 26). Both compounds 23 and 27 contain a p-toluidinium substituent and their difference is the replacement of the aminoacid groups in 23 with aminoester groups (27). The d (31P) in 23 is upfield, and the P@O bond shows a weaker m(P@O), whereas the C@O bond has a stronger m(C@O) relative to those of 27. The d (31P) in compound 28 is upfield relative to that of 29, perhaps due to the greater electron donation of the two chlorine atoms via resonance in comparison to the two p-toluidinium groups. A huge amino group is bonded to the phosphorus atom in molecules 30 and 31. This kind of amine group has indicated possible clinical applications [35–37] and significant importance in medicine. Our attempts to obtain a single crystal of compound 30 in a methanol/acetonitrile mixture resulted in structure I, which is most likely a hydrolyzed product of 30 in the solution (perhaps the P–N bond of this giant amino group is labile due to steric repulsion). The d (31P) of 30 is at a much higher field relative to that of 31. Therefore, it could be concluded that the phenyl ring plays an important role as an electron withdrawing group in compound 31.
N R
Cl
HN
P2
HN
NH
R
X X X
OH
O
P1
X = H, F, Cl, Br R = 4-X-C6H4, C5H4N
X
Scheme 3. The resonance interaction in bisphosphoramidates 14–21.
N R
P1
Cl
N R
317
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
The 31P NMR spectra of the phosphoramidates 32–44, containing the cyanoacetamide substituent, demonstrated that substitution of the chlorine atoms in compound 32 by aliphatic amino groups result in deshielded phosphorus atoms, while replacing with aromatic amino groups of the formula 4-X–C6H4NH, X = F, Cl, Br, (CH2)3CH3, leads to much more shielded phosphorus atoms. The connection of p-butylaniline to the phosphorus atom causes its shielding, and the d (31P) is the most upfield in this series. Also, the d (31P) of the p-haloanilinium substituents becomes more positive on decreasing the halogen electronegativity. d (31P) changed in the order of Br > Cl > F > (CH2)3CH3 for compounds 40–43. An interesting feature in the 1H and 13C NMR spectra of compounds 40–43, having p-substituted anilinium substituents, is that the two aromatic groups are different and present two sets of signals in the spectra, whereas when aliphatic amino groups are replaced by the two Cl atoms in 32, they are equal. This characteristic was not seen in the spectra of compound 45. The 13C NMR spectra of 32–44 revealed that the 2J(P,C) coupling constant, i.e., the coupling of the amidic CH2 carbon atom with the P atom, is decreased from 10.5 Hz (in 32) to about 8.9 Hz (in 33– 44). Therefore, replacement of the chlorine atoms by different amino groups reduces the 2J(P,C) coupling constant. Compound 35 contains a-phenylethyl substituents that have a chiral carbon
1
H3C
atom at the CH groups, leading to the appearance of two sets of peaks in its 1H and 13C NMR spectra. The 13C NMR spectrum of compound 37 exhibited five signals for the five carbon atoms of the two aliphatic cyclopentyl moieties owing to the fact that the two aliphatic rings are equal, but the five carbon atoms of the ring are different. The 13C NMR spectra of compounds 38 and 39 display eight separate signals for the aliphatic carbon atoms of the cyclohexyl and 4-methylpiperidinyl groups due to the fact that the two aliphatic groups are not equal. A 4J(P,C) coupling constant of 1.6 Hz was observed for the splitting of the C„N carbon atom with the phosphorus atom in 32, but this coupling did not occur in molecules 33–44. The mass spectrum of compound 29 indicates ionic fragments corresponding to this molecule as well as a base peak at m/z = 352 (100%). There are also some peaks at m/z > 352 related to dimerization of the ionic fragments [38]. The following rearrangements are proposed for the mechanism of the dimerizations (Scheme 4(1 and 2)). (a) The P–N bond of the aminopyridinium group is broken, an aminopyridine group is released and a P@N bond is formed. Then, conjugation of the two similar fragments, i.e. a cycloaddition reaction, will yield the diazadiphosphetidine i with m/z = 516. (b) If a ptoluidine group is separated from the molecule and the resulting
H3C
O H3C
O
P N H
N H
NH
CH3
N
H3C
NH2
N
CH3
O
P N H
O
O
P
P N N
HN
CH3
NH
P
+
N H
N
N
CH3 H3C
H3C
i , m/z = 516
m/z = 258 NH2
CH3 O
O
N
CH3
O
N N H
N
N N
CH3
O
N P
N
P
P HN
NH
P
+
N H
N CH3 H3C
ii , m/z = 490
m/z = 246
2
H3C
O
O
P
P
CH3
P
P
N N
HN
N
HN
NH
CH3
O
O
H3C
.
.
N
H3C
NH
O
O
P
P N
HN
NH
NH
NH
CH3
NH HN N
CH3 H3C
CH3
H3C
m/z = 516
i O
O
N
N
N N
H3C
NH
N
.
O N
HN NH
NH
N
P
P
NH HN
NH
H3C
CH3 H3C
H3C
N
O
N
P
P HN
NH
.
O
O
N
P
P HN
CH3
H3C
CH3
ii
Scheme 4. The proposed fragmentation mechanism of compound 29 in the mass spectrum.
CH3
m/z = 597
CH3
318
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
N(2)–C(1)–C(8A)–C(4A) and N(20 )–C(10 )–C(80 A)–C(40 A) are 6.6(3)° and 8.7(3)° (also, compare the torsion angles N(2)–C(1)–C(9)– C(10), N(20 )–C(10 )–C(90 )–C(100 ) and C(14)–C(13)–O(1)–C(16), C(140 )–C(130 )–O(10 )–C(160 ) that are 68.0(3)°, 61.0(3)° and 11.4(4)°, 1.8(4)°, respectively). This phenomenon was observed for some of our previously reported structures [17,18,23]. Although there is a C@C double bond between the two unsaturated sixmembered rings, they are not planar and show a puckered shape. The C(5)–C(10) and C(50 )–C(100 ) carbon atoms of the phenyl ring as well as their corresponding hydrogen atoms in compound 34 revealed disorder in the structure that can be described by free rotation along the C(4)–N(3) bond, causing uncertainty in the determination of the carbon and hydrogen locations of the phenyl ring. The P@O bond lengths in molecules 34 and 44 are 1.483(16) and 1.491(15) Å, which are larger than the normal P@O bond length (1.450 Å) [40]. The P atoms have slightly distorted tetrahedral configurations, e.g. the surrounding angles around the P atoms of the two symmetrically different molecules in compound 34 are in the range 103.16(10)–117.34(10)°. The P–Namide bond lengths are longer than the P–Namine bond lengths because of the interaction of the Namide atom with the p resonance system of the C@O group, which results in a shorter C–Namide bond length, i.e., 1.687(19) > 1.616(19), 1.620(2) (in 34), and 1.685(17) > 1.622(18), 1.621(18) Å (in 44). All of these P–N bonds are shorter than the typical P–N single bond length (1.770 Å) [40]. The nitrogen envi-
similar fragments are bonded to each other, another diazadiphosphetidine (ii) is obtained with m/z = 490. (c) If one of the P–N bonds in the cyclic diazadiphosphetidines i breaks then an aminopyridinium radical cation is bonded to it, a bisphosphoramidate with m/z = 516 could be produced. (d) If one of the P–N bonds in the diazadiphosphetidine ii breaks then a p-toluidinum radical cation is bonded to it, a bisphosphoramidate with m/z = 597 is obtained. This fragmentation pathway is also proposed for the mass spectrum of compound (C5H4N–NH)2P(O)[N(CH3)(C6H11)] [39] in which there are some molecular ion peaks at m/z greater than the base peak, and a similar mechanism could be considered for its fragmentation (Scheme 5(1 and 2)). 3.2. X-ray crystallography Single crystals of compounds I (4-OCH3–C6H4–CH2–C9H13– NH2Cl), 34 and 44 were obtained from a solution of methanol/chloroform or methanol/acetonitrile/water at room temperature. The crystallographic data and the details of the X-ray analysis of these compounds are represented in Table 1, and selected bond lengths and angles are given in Table 2. Hydrogen bonding data of these structures are presented in Table 3. Molecular structures (ortep views) have been shown in Figs. 1–3. There are two symmetrically independent molecules in the crystalline lattice of compound I due to the differences in the related torsion angles of these two conformers. The torsion angles
1
N
P
N
O
N H
NH
CH3
N H
N
N
P
P N N
P
P N H
N HN
+
N
N
O
N
N
O
O
N
O H3C
NH N
N N
NH
m/z = 258
i , m/z = 464
NH2 N
O
O O
O
N
N
P
P N
N
N
N
N N
H3C
CH3
N CH3
CH3
ii , m/z = 502
m/z = 251
2
N N
N
+
P
P
O
O
N
N
P
P N N
HN
. O
O
N
.
N
HN
N
O
O
P
P NH
NH
NH
N
N
HN
P
P
NH N
CH3
N
N
N
NH
N
N
N
CH3
N
N
m/z = 577
i
O
O
P
P N N
N H3C
ii
O
P
P N
N N
H3C
N CH3
N
O
.
N
.
O
NH
P
NH
H3C
P N
N
N
O
NH
N HN
CH3
CH3 N
H3C
CH3
m/z = 596
Scheme 5. The proposed fragmentation mechanism of compound (C5H4N–NH)2P(O)[N(CH3)(C6H11)] in the mass spectrum.
319
K. Gholivand et al. / Polyhedron 28 (2009) 307–321 Table 1 Crystallographic data for compounds I, 34 and 44.
Empirical formula Formula weight Temperature (K) Wavelength (Å) Crystal system, space group Unit cell dimensions a (Å) b (Å) c (Å) a (°) b (°) c (°) V (Å3) Z, Dcalc (Mg m3) Absorption coefficient (mm1) F(0 0 0) Crystal size (mm) h Range for data collection (°) Limiting indices Reflections collected/unique Rint Completeness to h (%) Absorption correction Maximum and minimum transmission Refinement method Data/restraints/parameters Goodness-of-fit on F2 Final R indices R indices (all data) Absolute structure parameter Largest difference in peak and hole (e Å3)
I
34
44
C17H24ClNO 293.82 293(2) 0.71073 triclinic, P 1
C17H19N4O2P 342.33 293(2) 0.71073 triclinic, P 1
C13H15N4O4P 322.26 120(2) 0.71073 triclinic, P 1
8.0732(10) 9.3318(11) 11.8945(14) 88.970(5) 75.950(5) 73.436(5) 831.95(17) 2, 1.173 0.226 316 0.25 0.25 0.20 1.77–26.03 9 6 h 6 9; 11 6 k 6 11; 14 6 l 6 14 6914/6011 0.0134 98.6 semi-empirical from equivalents 0.954 and 0.948 full-matrix least-squares on F2 6011/3/361 1.022 R1 = 0.0377, wR2 = 0.0798 R1 = 0.0489, wR2 = 0.0842 0.02(5) 0.210 and 0.110
5.1799(10) 12.799(3) 14.177(3) 71.44(3) 84.98(3) 85.71(3) 886.5(4) 2, 1.282 0.172 360 0.40 0.30 0.25 2.60–27.06 0 6 h 6 6; 16 6 k 6 16; 18 6 l 6 18 4297/3868 0.0193 99.4 none full-matrix least-squares on F2 3868/41/199 1.012 R1 = 0.0496, wR2 = 0.1208 R1 = 0.0743, wR2 = 0.1265
4.9743(5) 10.6382(10) 14.5630(14) 81.395(2) 81.346(2) 81.013(2) 746.21(13) 2, 1.434 0.208 336 0.43 0.08 0.07 1.95–28.03 6 6 h 6 6; 14 6 k 6 13; 19 6 l 6 19 7801/3610 0.0331 99.7 semi-empirical from equivalents 0.986 and 0.904 full-matrix least-squares on F2 3610/0/199 1.040 R1 = 0.0511, wR2 = 0.1202 R1 = 0.0710, wR2 = 0.1334
0.364 and 0.474
0.426 and 0.407
Table 2 Selected bond lengths (Å) and angles (°) for compounds I, 34 and 44. I
34
44
C(1)–C(8A) C(1)–N(2) C(1)–C(9) C(1)–H(1A) C(3)–N(2) N(2)–H(2A) N(2)–H(2B) C(3)–C(4) C(4)–C(4A) C(10 )–C(80 A) C(10 )–N(20 ) C(10 )–C(90 ) C(10 )–H(10 A) C(30 )–N(20 ) N(20 )–H(20 A)
1.500(3) 1.502(3) 1.554(3) 0.980 1.483(3) 0.961 0.920 1.514(4) 1.493(4) 1.520(4) 1.501(3) 1.537(3) 0.980 1.489(3) 0.996
P(1)–O(1) P(1)–N(1) P(1)–N(2) P(1)–N(3) O(2)–C(1) N(1)–C(1) N(1)–H(1N) N(2)–C(11) N(3)–C(4) N(4)–C(3) C(4)–C(5) C(4)–C(50 ) C(5)–C(6) C(50 )–C(60 ) C(50 )–C(100 )
1.483(16) 1.687(19) 1.616(19) 1.620(2) 1.212(2) 1.355(3) 0.870 1.460(3) 1.477(3) 1.133(3) 1.496 1.460(7) 1.3900 1.343(9) 1.345(10)
P(1)–O(1) P(1)–N(1) P(1)–N(2) P(1)–N(3) O(2)–C(1) O(3)–C(5) O(3)–C(8) O(4)–C(10) O(4)–C(13) N(1)–C(1) N(1)–H(1A) N(2)–C(4) N(3)–C(9) N(4)–C(3) C(1)–C(2)
1.4914(15) 1.6846(17) 1.6218(18) 1.6208(18) 1.223(2) 1.370(3) 1.375(3) 1.367(3) 1.371(3) 1.356(3) 0.880 1.467(3) 1.465(3) 1.149(3) 1.525(3)
C(8A)–C(1)–N(2) C(8A)–C(1)–C(9) N(2)–C(1)–C(9) C(8A)–C(1)–H(1A) N(2)–C(1)–H(1A) C(9)–C(1)–H(1A) C(3)–N(2)–C(1) C(3)–N(2)–H(2A) C(1)–N(2)–H(2A) C(3)–N(2)–H(2B) C(1)–N(2)–H(2B) C(80 A)–C(10 )–N(20 ) C(80 A)–C(10 )–C(90 ) N(20 )–C(10 )–C(90 ) C(80 A)–C(10 )–H(10 A) N(20 )–C(10 )–H(10 A) C(90 )–C(10 )–H(10 A)
112.10(19) 113.44(19) 107.56(18) 107.80 107.80 107.80 113.22(18) 107.80 110.10 111.80 109.10 110.93(18) 113.20(2) 108.70(2) 107.90 107.90 107.90
O(1)–P(1)–N(1) O(1)–P(1)–N(2) O(1)–P(1)–N(3) N(2)–P(1)–N(1) N(3)–P(1)–N(1) N(3)–P(1)–N(2) C(1)–N(1)–P(1) C(1)–N(1)–H(1N) P(1)–N(1)–H(1N) C(11)–N(2)–P(1) C(11)–N(2)–H(2N) P(1)–N(2)–H(2N) C(4)–N(3)–P(1) C(4)–N(3)–H(3N) P(1)–N(3)–H(3N) O(2)–C(1)–N(1) O(2)–C(1)–C(2)
106.00(9) 109.71(10) 117.34(10) 113.04(10) 103.16(10) 107.58(10) 125.01(14) 114.80 120.00 128.27(15) 115.90 115.90 121.41(15) 114.30 123.40 123.70(2) 122.10(2)
O(1)–P(1)–N(1) O(1)–P(1)–N(2) O(1)–P(1)–N(3) N(2)–P(1)–N(1) N(3)–P(1)–N(1) N(3)–P(1)–N(2) C(1)–N(1)–P(1) C(1)–N(1)–H(1A) P(1)–N(1)–H(1A) C(4)–N(2)–P(1) C(4)–N(2)–H(2A) P(1)–N(2)–H(2A) N(1)–C(1)–C(2) O(2)–C(1)–C(2) O(2)–C(1)–N(1) C(6)–C(5)–O(3) C(11)–C(10)–O(4)
105.72(9) 108.09(9) 119.51(9) 114.33(9) 102.54(9) 106.89(9) 123.40(14) 118.30 118.30 129.36(15) 115.30 115.30 115.53(17) 121.63(18) 122.84(18) 109.90(2) 109.90(2)
ronment is nearly planar. In compound 34, the angles C(1)–N(1)– P(1), C(1)–N(1)–H(1N) and P(1)–N(1)–H(1N) are 125.01(14),
114.8° and 120.0°, respectively, with an average of 119.94°. The sum of the surrounding angles around the N(2) and N(3) atoms
320
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Table 3 Hydrogen bonds for compounds I, 34 and 44 (Å, °) Compound
d(H A) 0
0
d(D–H)
d(H A)
d(D A)
\DHA
I
N(2 )–H(2 A) Cl(1)#1 N(2)–H(2A) Cl(1)#1 N(2)–H(2B) Cl(2)#4 N(20 )–H(20 B) Cl(2)#1
1.00 0.96 0.92 0.90
2.16 2.18 2.15 2.19
3.160(19) 3.130(19) 3.034(2) 3.035(2)
178 172 160 155
34
N(1)–H(1N) O(1)#5 N(2)–H(2N) O(2)#3 N(3)–H(3N) O(1)#2
0.87 0.86 0.87
1.97 2.17 2.33
2.833(2) 2.946(2) 3.178(3)
174 151 166
44
N(1)–H(1A) O(1)#6 N(2)–H(2A) O(2)#7 N(3)–H(3A) O(1)#8
0.88 0.88 0.88
1.89 2.11 2.08
2.764(2) 2.889(2) 2.959(2)
174 147 177
Symmetry transformations used to generate equivalent atoms: (#1) x, y, z, (#2) x + 1, y, z, (#3) x 1, y, z, (#4) x + 1, y 1, z, (#5) x, y + 1, z + 2, (#6) x, y + 1, z + 1, (#7) x 1, y, z, (#8) x + 1, y, z.
are 360.07° and 359.11°, respectively. Similar results were obtained for the nitrogen atoms in the structure of 44, which indicate sp2 hybridization for the nitrogen atoms, although because of the repulsion and steric effects, some angles were either greater or smaller than 120°. It is noticeable that the P@O and C@O bonds indicate an anti configuration with respect to each other in compounds 34 and 44, which is in agreement with our previously reported results [17,18,25–27]. The two symmetrically independent molecules of I are connected to each other through two intermolecular N(2)– H(2A) Cl(1) and N(20 )–H(20 A) Cl(1) hydrogen bonds and each of these independent molecules is linked to its symmetrically independent molecules via intermolecular N(2)–H(2B) Cl(2) and N(20 )–H(20 B) Cl(2) hydrogen bonds. Considering the weak intermolecular C–H O and C–H Cl hydrogen bonds, this creates a three dimensional polymeric chain in the crystalline lattice. Intermolecular N(1)–H(1N) O(1) hydrogen bonds between the two adjacent molecules in compound 34 create a non-centrosymmetric dimer (because of the disorder in one molecule, the dimer is not centrosymmetric). This dimer is connected to similar dimers by intermolecular N(2)–H(2N) O(2) and N(3)–H(3N) O(1) hydrogen bonds. Beside these H-bonds, there are also weak intermolecular hydrogen bonds such as C(16)–H(16A) O(2), and all of them produce a three dimensional network. The intermolecular N(2)– H(2A) O(2) and N(3)–H(3A) O(1) hydrogen bonds in the structure of 44 connect the neighboring molecules to each other to
Fig. 2. Molecular structure and atom labelling scheme for C„N–CH2C(O)NHP(O)(NHCH2C6H5)2, compound 34 (30% probability ellipsoids).
construct a linear chain. The molecules in this polymeric chain are linked to other molecules through intermolecular N(1)– H(1A) O(1) hydrogen bonds. Repetition of the H-bonds generates a one dimensional polymeric chain. If weak intermolecular C– H O and C–H N hydrogen bonds [like C(12)–H(12A) O(2), C(2)–H(2B) N(4) and C(13)–H(13A) N(4)] are taken into account, a 3-D polymeric chain is obtained. 4. Conclusion Using PCl5 and POCl3 as starting materials, a number of novel phosphorus derivatives of bisphosphoramidates, phosphoramidates and phosphoric triamides were synthesized. The reaction of 4-aminobenzamide with PCl5 in different molar ratios yielded different products, bisphosphoramides and phosphoric triamides. Furthermore, the interaction of POCl3 with first-type aromatic
Fig. 1. Molecular structure and atom labelling scheme for 4-OCH3–C6H4–CH2–C9H13–NH2Cl, compound I (50% probability ellipsoids).
K. Gholivand et al. / Polyhedron 28 (2009) 307–321
Fig. 3. Molecular structure and atom labelling scheme for C„N–CH2C(O)NHP(O)(NHCH2C4H3O)2, compound 44 (50% probability ellipsoids) that shows two conformers in the crystal lattice.
amines gave bisphosphoramidates with a P–N–P linkage that demonstrated 2J(P,P) 20.0 Hz in the 31P NMR spectra. Indeed, two simple one-pot pathways are presented here for the synthesis of the new bisphosphoramidates that are, to our knowledge, the first examples of bisphosphoramidates that have been obtained so far. The X-ray crystal structures of compounds I (4-OCH3–C6H4–CH2– C9H13–NH2Cl), 34 and 44 were further investigated and all of these structures displayed three dimensional polymeric chains through strong- and weak hydrogen bonds. The presence of chiral aminoacidester moieties in the phosphoric triamides lead to chiral molecules which showed two sets of signals for the two groups. Acknowledgement We wish to thank the Research Council of Tarbiat Modares University for the financial support of this work. Appendix A. Supplementary data CCDC 604118, 604115 and 678082 contain the supplementary crystallographic data for (C17H24ClNO), (C17H19N4O2P) and (C13H15N4O4P). These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: [email protected]. Crystallographic data for the structures of I, 34 and 44. Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.poly.2008.10.057. References [1] N.-H. Nam, Y. Kim, Y.-J. You, D.-H. Hong, H.-M. Kim, B.-Z. Ahn, Bioorg. Med. Chem. 11 (2005) 1021.
321
[2] T.K. Venkatachalam, P. Samuel, F.M. Ucken, Bioorg. Med. Chem. 13 (2005) 1763. [3] C. Mc Guigan, J.-C. Thiery, F. Daverio, W.G. Jiang, G. Davis, M. Mason, Bioorg. Med. Chem. 13 (2005) 3219. [4] A.-L. Villard, G. Coussot, I. Lefebvre, P. Augustijns, A.-M. Aubertin, G. Gosselin, S. Peyrottes, C. Périgaud, Bioorg. Med. Chem. 16 (2008) 7321. [5] I. Ghesner, A. Soran, C. Silvestru, J.E. Drake, Polyhedron 22 (2003) 3395. [6] M. Ghesner, A. Silvestru, C. Silvestru, J.E. Drake, M.B. Hursthouse, M.E. Light, Inorg. Chim. Acta 358 (2005) 3724. [7] C. Silvestru, J.E. Drake, Coord. Chem. Rev. 223 (2001) 117. [8] K. He, Z. Zhou, L. Wang, K. Li, G. Zhao, Q. Zhao, C. Tang, Tetrahedron 60 (2004) 10505. [9] M.S. Balakrishna, S.S. Krishnamurthy, H. Manohar, Organometallics 10 (1991) 2522. [10] O. Bumbu, A. Silvestru, C. Silvestru, J.E. Drake, M.B. Hursthouse, M.E. Light, J. Organomet. Chem. 687 (2003) 118. [11] I. Ghesner, L. Opris, G. Balazs, H.J. Breunig, J.E. Drake, A. Silvestru, C. Silvestru, J. Organomet. Chem. 642 (2002) 113. [12] S.E. Denmark, J. Fu, M.J. Lawler, J. Org. Chem. 71 (2006) 1523. [13] P.K. Baker, M.G.B. Drew, D.S. Moore, J. Organomet. Chem. 664 (2002) 45. [14] T. Appleby, J.D. Woollins, Coord. Chem. Rev. 235 (2002) 121. [15] E.A. Trush, V.A. Ovchynnikov, K.V. Domasevitch, J.S. Wiatekkozlowska, V.Y. Zub, V.M. Amirkhanov, Z. Naturforsch. 57b (2002) 746. [16] V.V. Skopenko, V.M. Amirkhanov, T. Yu. Silva, I.S. Vasilchenko, E.L. Anpilov, A.D. Garnovski, Russ. Chem. Rev. 73 (2004) 737. [17] K. Gholivand, Z. Shariatinia, M. Pourayoubi, Polyhedron 25 (2006) 711. [18] K. Gholivand, Z. Shariatinia, J. Organomet. Chem. 691 (2006) 4215. [19] T.L. Lassiter, R.S. Marshall, L.C. Jackson, D.L. Hunter, J.T. Vu, S. Padilla, Toxicology 186 (2003) 241. [20] O.I. Guliy, O.V. Ignatov, O.E. Makarov, V.V. Ignatov, Biosens. Bioelectron. 18 (2003) 1005. [21] K. Kaur, S.A. Adediran, J.K. Lan Martin, R.F. Pratt, Biochemistry 42 (2003) 1529. [22] K. Gholivand, Z. Shariatinia, K. Khajeh, H. Naderi-Manesh, J. Enzyme Inhib. Med. Chem. 21 (2006) 31. [23] (a) K. Gholivand, C.O. Della Vedovab, A. Anaraki Firooza, A. Madani Alizadehgana, M.C. Michelinic, R. Pis Diez, J. Mol. Struct. 750 (2005) 64; (b) K. Gholivand, Z. Shariatinia, M. Pourayoubi, Z. Naturforsch. 60b (2005) 67. [24] M.A.M. Forgeron, M. Gee, R.E. Wasylishen, J. Phys. Chem. A 108 (2004) 4895. [25] K. Gholivand, M. Pourayoubi, Z. Shariatinia, H. Mostaanzadeh, Polyhedron 24 (2005) 655. [26] K. Gholivand, Z. Shariatinia, Struct. Chem. 18 (2007) 95. [27] K. Gholivand, Z. Shariatinia, M. Pourayoubi, Z. Anorg. Allg. Chem. 631 (2005) 961. [28] Bruker, Programs APEX II, Version 2.0-1; SAINT, Version 7.23A; SADABS, Version 2004/1; XPREP, Version 2005/2; SHELXTL, Version 6.1. Bruker AXS Inc., Madison, WI, USA, 2005. [29] Siemens P3 and XDISK. Release 4.1. Siemens AXS, Madison, Wisconsin, USA, 1989. [30] Bruker, SMART. Bruker Molecular Analysis Research Tool, v. 5.059. Bruker AXS, Madison, Wisconsin, USA, 1998. [31] G.M. Sheldrick, Programs SHELXS97 (crystal structure solution) and SHELXL97 (crystal structure refinement), University of Gottingen, Germany, 1997. [32] G.M. Sheldrick, SADABS v. 2.01, Bruker/Siemens area detector absorption correction program. Bruker AXS, Madison, WI, USA, 1998. [33] H.-O. Kalinowski, S. Berger, S. Braun, Carbon-13 NMR Spectroscopy, Wiley, 1991, p. 527. [34] R.L. Keiter, J.W. Benson, E.A. Keiter, T.A. Harris, M.W. Hayner, L.L. Mosimann, E.E. Karch, C.A. Boecker, D.M. Olson, J. VanderVeen, D.E. Brandt, Organometallics 16 (1997) 2246. [35] L. Aluisio, B. Lord, A.J. Barbier, I.C. Fraser, S.J. Wilson, J. Boggs, L.K. Dvorak, M.A. Letavic, B.E. Maryanoff, N.I. Carruthers, P. Bonaventure, T.W. Lovenberg, Eur. J. Pharmacol. 587 (2008) 141. [36] N. Vasdev, F.J. LaRonde, J.R. Woodgett, A. Garcia, E.A. Rubie, J.H. Meyer, S. Houle, A.A. Wilson, Bioorg. Med. Chem. 16 (2008) 5277. [37] X.-H. Liu, P. Cui, B.-A. Song, P.S. Bhadury, H.-L. Zhu, S.-F. Wang, Bioorg. Med. Chem. 16 (2008) 4075. [38] E.A.V. Ebsworth, D.W.H. Rankin, S. Cradock, Structural Methods in Inorganic Chemistry, 2nd ed., Blackwell Scientific Publication, 1991. [39] K. Gholivand, C.O. Della Ve´dova, M.F. Erben, H.R. Mahzouni, Z. Shariatinia, S. Amiri, J. Mol. Struct. 874 (2008) 178. [40] D.E.C. Corbridge, Phosphorus, an Outline of its Chemistry, Biochemistry and Technology, 5th ed., Elsevier, The Netherlands, 1995, p. 55.