R. T. Paine et al.
FULL PAPER
7.22–7.20 (m, 1 H, H-3), 6.98 (t, JH,H = 7.8 Hz, 1 H, H-4), 6.92 588, 519, 464 cm–1. HRMS (ESI+): m/z (%) = 381.1378 [M + H+]
(br. s, 1 H, NH), 4.46 (d, JH,H = 6.3 Hz, 2 H, H-1), 4.21 (d, JH,P
(25), C21H22N2O3P requires 381.1363; 403.1193 [M + Na+] (100),
= 13.8 Hz, 2 H, H-7) ppm. 13C NMR (75.4 MHz, CDCl3, 298 K): C21H21N2NaO3P requires 403.1182; 419.0917 [M + K+] (14),
δ = 161.1 (C-12), 146.8 (C-2), 144.2 (d, JC,P = 6.5 Hz, C-6), 132.2
(d, JC,P = 2.0 Hz, C-11), 131.9 (d, JC,P = 101.8 Hz, C-8), 131.1 (d,
JC,P = 9.8 Hz, C-9), 128.6 (d, JC,P = 12.1 Hz, C-10), 127.0 (d, JC,P
C21H21KN2O3P requires 419.0921.
(E)-[(6-{[(2-Hydroxy-3-methoxybenzylidene)amino]methyl}pyridin-
2-yl)methyl]diphenylphosphine Oxide (14): To a solution of 4
(322 mg, 1.00 mmol) in CH2Cl2 (5 mL) were added PPTS (13 mg,
5 mol-%), MgSO4 (361 mg, 3 mmol) and o-vanillin (152.2 mg,
1.00 mmol). The reaction mixture was stirred (23 °C, 12 h), and
then filtered. The solvent was evaporated, and the residue was puri-
fied by flash chromatography on silica gel (CH2Cl2/MeOH, 98:2 to
96:4) to afford 14 as an orange oil, yield 202 mg (44%). 31P{1H}
NMR (121.49 MHz, CDCl3, 298 K): δ = 30.6 ppm. 1H NMR
(300 MHz, CDCl3, 298 K): δ = 8.34 (s, 1 H, H-12), 7.74–7.67 (m,
4 H, H-9), 7.49 (t, JH,H = 7.8 Hz, 1 H, H-4), 7.41–7.34 (m, 8 H,
H-5,10,11 and OH), 7.09 (d, JH,H = 7.8 Hz, 1 H, H-3), 6.93–6.77
(m, 3 H, H-16,17,18), 4.70 (s, 2 H, H-1), 3.88 (d, JH,P = 14.1 Hz,
2 H, H-7), 3.87 (s, 3 H, H-19) ppm. 13C{1H} NMR (75.4 MHz,
CDCl3, 298 K): δ = 166.7 (C-12), 157.3 (CHAr), 152.2 (d, JC,P
7.1 Hz, C-6), 151.7 (CHAr), 148.5 (CHAr), 137.2 (CHAr), 132.3 (d,
JC,P = 100.1 Hz, C-8), 131.8 (d, JC,P = 2.1 Hz, C-11), 131.2 (d, JC,P
= 9.4 Hz, C-9), 128.4 (d, JC,P = 11.8 Hz, C-9), 123.5 (d, JC,P
3.5 Hz, C-5), 123.1 (C-18), 119.9 (C-4), 118.6 (C-3), 118.1 (C-17),
114.2 (C-16), 56.1 (C-19), 53.5 (C-1), 40.9 (d, JC,P = 64.2 Hz, C-
= 4.2 Hz, C-5), 125.6 (C-4), 124.6 (C-3), 38.5 (C-1), 32.0 (d, JC,P
=
65.2 Hz, C-7) ppm. FTIR (KBr): ν = 3426, 3232, 3032, 1678, 1590,
˜
1562, 1541, 1484, 1436, 1414, 1395, 1377, 1340, 1263, 1242 (νN–O),
1229, 1173 (νP=O), 1121, 1104, 1081, 1068, 1032, 998, 982, 952, 910,
849, 817, 795, 765, 741, 711, 694, 669, 617, 598, 558, 516, 464,
429 cm–1. HRMS (ESI+): m/z (%) = 367.1219 [M + H+] (48)
C20H20N2O3P requires 367.1206; 389.1038 [M + Na+] (100),
C
20H19N2NaO3P requires 389.1026; 405.0765 [M + K+] (11),
C20H19KN2O3P requires 405.0765; 755.2161 [2M + Na+] (28),
C40H38N4NaO6P2 requires 755.2159. C20H19N2O3P (366.35): calcd.
C 65.57, H 5.23, N 7.65; found C 65.02, H 5.17, N 7.54.
N-({6-[(Diphenylphosphoryl)methyl]pyridin-2-yl}methyl)acetamide
(12): To a solution of 4 (322 mg, 1.00 mmol) in chloroform (5 mL,
0 °C) was added acetic anhydride (0.11 mL, 1.2 mmol). The re-
sulting deep-red solution was stirred (23 °C, 16 h) and then washed
with saturated aqueous ammonium chloride (25 mL). The aqueous
layer was extracted with chloroform (3ϫ 20 mL), and the com-
bined organic layers were washed with brine (15 mL), dried
(MgSO4), filtered, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel
(CH2Cl2/MeOH, 95:5) to give 12 as an orange oil, yield 185 mg
(51%). 31P{1H} NMR (121.49 MHz, CDCl3, 298 K): δ = 31.0 ppm.
1H NMR (300 MHz, CDCl3, 298 K): δ = 7.68–7.61 (m, 4 H, H-9),
7.41–7.30 (m, 7 H, H-4,10,11), 7.10 (d, JH,H = 7.5 Hz, 1 H, H-5),
6.92 (d, JH,H = 7.5 Hz, 1 H, H-3), 6.81 (br. s, 1 H, NH), 4.26 (d,
JH,H = 1.3 Hz, 2 H, H-1), 3.82 (d, JH,P = 14.4 Hz, 2 H, H-7), 1.87
(s, 3 H, H-13) ppm. 13C NMR (75.4 MHz, CDCl3, 298 K): δ =
170.0 (C-12), 156.0 (C-2), 151.7 (d, JC,P = 7.8 Hz, C-6), 137.0 (C-
=
=
7) ppm. FTIR (KBr): ν = 3424, 3056, 1631 (νC=N), 1590, 1574,
˜
1457, 1437, 1317, 1254, 1192 (νP=O), 1120, 1103, 1080, 996, 911,
832, 783, 734, 695, 644, 522 cm–1. HRMS (ESI+): m/z (%) =
457.1685 [M + H+] (51), C27H26N2O3P requires 457.1676; 479.1491
[M + Na+] (24), C27H25N2NaO3P requires 479.1495.
(E)-2-[(Diphenylphosphoryl)methyl]-6-{[(4-hydroxy-3-methoxybenz-
ylidene)amino]methyl}pyridine 1-Oxide (15): To a solution of 5
(338 mg, 1.00 mmol) in CH2Cl2 (5 mL) were added PPTS (13 mg,
5 mol-%), MgSO4 (361 mg, 3 mmol) and vanillin (167.4 mg,
1.1 mmol). The reaction mixture was stirred (23 °C, 12 h), filtered,
and the solvent was evaporated. The residue was purified by flash
chromatography on silica gel (CH2Cl2/MeOH, 100:0 to 96:4) to
afford 15 as an orange foam, yield 267 mg (56%). 31P{1H} NMR
4), 132.2 (d, JC,P = 100.4 Hz, C-8), 131.8 (C-11), 131.0 (d, JC,P
9.3 Hz, C-9), 128.4 (d, JC,P = 11.8 Hz, C-10), 123.3 (d, JC,P
=
=
3.9 Hz, C-3), 119.8 (C-5), 44.2 (C-1), 40.4 (d, JC,P = 64.8 Hz, C-7),
23.0 (C-13) ppm. FTIR (KBr): ν = 3262, 3057, 1666 (νC=O), 1591,
˜
1
(121.49 MHz, CDCl3, 298 K): δ = 32.8 ppm. H NMR (300 MHz,
1574, 1485, 1454, 1437, 1370, 1285, 1189 (νP=O), 1120, 1070, 1027,
995, 923, 831, 720, 694, 643, 606, 521 cm–1. HRMS (ESI+): m/z
(%) = 365.1414 [M + H+] (51), C21H22N2O2P requires 365.1413;
387.1234 [M + Na+] (100), C21H21N2NaO2P requires 387.1233;
751.2592 [2M + Na+] (16), C42H42N4NaO4P2 requires 751.2573.
CDCl3, 298 K): δ = 8.29 (s, 1 H, H-12), 7.89–7.84 (m, 4 H, H-9),
7.82–7.74 (m, 1 H, H-5), 7.46–7.43 (m, 9 H, H-10,11,14,17,18),
7.17–7.15 (m, 1 H, H-4), 6.96 (d, JH,H = 8.1 Hz, 1 H, H-3), 4.82
(s, 2 H, H-1), 4.30 (d, JH,P = 13.8 Hz, 2 H, H-7), 3.91 (s, 3 H, H-
19) ppm. 13C{1H} NMR (125 MHz, CDCl3, 298 K): δ = 164.6 (C-
12), 150.5 (C-2), 149.8 (C-15), 147.8 (C-13), 143.4 (d, JC,P = 5.9 Hz,
C-6), 132.1 (C-11), 131.7 (d, JC,P = 100.1 Hz, C-8), 130.8 (d, JC,P
= 9.5 Hz, C-9), 128.5 (d, JC,P = 11.9 Hz, C-10), 127.9 (C-16), 125.3
(C-5), 124.2 (C-4), 124.2 (C-18), 122.9 (C-17), 114.9 (C-3), 108.9
(C-14), 59.1 (C-1), 55.8 (C-19), 31.4 (d, JC,P = 66.3 Hz, C-7) ppm.
2-(Acetamidomethyl)-6-[(diphenylphosphoryl)methyl]pyridine 1-Ox-
ide (13): To a solution of 12 (161 mg, 0.442 mmol) in CH2Cl2
(7 mL) was added m-chloroperoxybenzoic acid (77 wt.-%, 148 mg,
0.66 mmol). The mixture was stirred (23 °C, 12 h) and then washed
with an aqueous solution of NaOH (2 m, 3ϫ 10 mL). The organic
phase was dried (MgSO4), filtered, and the solvent was removed
by vacuum evaporation to give 13 as an orange oil, yield 115 mg
(69%). 31P{1H} NMR (121.49 MHz, CDCl3, 298 K): δ = 30.8 ppm.
1H NMR (300 MHz, CDCl3, 298 K): δ = 7.76–7.69 (m, 4 H, H-9),
7.56 (d, JH,H = 7.8 Hz, 1 H, H-5), 7.41–7.31 (m, 6 H, H-10,11),
7.12 (d, JH,H = 7.5 Hz, 1 H, H-3), 7.04–6.98 (m, 2 H, H-4 and
NH), 4.35 (d, JH,H = 6.0 Hz, 2 H, H-1), 4.15 (d, JH,P = 14.1 Hz, 2
FTIR (KBr): ν = 3055, 1676 (νC=N), 1643, 1591, 1514, 1487, 1437,
˜
1407, 1287, 1263, 1246 (νN–O), 1175 (νP=O), 1158, 1129, 997, 851,
820, 784, 721, 695, 554, 517 cm–1. HRMS (ESI+): m/z (%) =
473.1620 [M + H+] (40), C27H26N2O4P requires 473.1625; 495.1432
[M + Na+] (17), C27H25N2NaO4P requires 495.1444.
(E)-2-[(Benzylideneamino)methyl]-6-[(diphenylphosphoryl)methyl]-
H, H-7), 1.84 (s, 3 H, H-13) ppm. 13C NMR (75.4 MHz, CDCl3, pyridine 1-Oxide (16): To a solution of 5 (100 mg, 0.30 mmol) in
298 K): δ = 170.2 (C-12), 147.5 (C-2), 143.9 (d, JC,P = 6.2 Hz, C-
CH2Cl2 (5 mL) were added molecular sieves (4 Å) (150 mg) and
benzaldehyde (0.03 mL, 0.3 mmol). The reaction mixture was
stirred (23 °C, 14 h), filtered, and the solvent was evaporated. The
residue was purified by flash chromatography on silica gel (CH2Cl2/
MeOH, 100:0 to 98:2) to afford 16, yield 80.0 mg (63%); off-yellow
solid; m.p.174–176 °C. X-ray quality single crystals were obtained
by slow evaporation of a MeOH/CH2Cl2 solution (23 °C). 31P{1H}
6), 132.1 (C-11), 131.9 (d, JC,P = 101.6 Hz, C-8), 130.8 (d, JC,P
9.8 Hz, C-9), 128.5 (d, JC,P = 12.1 Hz, C-10), 126.4 (d, JC,P
4.1 Hz, C-5), 125.3 (C-4), 124.2 (C-3), 39.8 (C-1), 31.5 (d, JC,P
=
=
=
65.6 Hz, C-7), 23.1 (C-13) ppm. FTIR (KBr): ν = 3260, 3056, 1669
˜
(νC=O), 1590, 1545, 1489, 1437, 1415, 1371, 1346, 1243 (νN–O), 1184
(νP=O), 1119, 1071, 1028, 997, 922, 848, 819, 784, 724, 694, 644,
3142
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Eur. J. Org. Chem. 2014, 3132–3148