New Heterocyclic Mono- and Bis(α-hydroxymethyl)phosphinic Acids
C-4), 125.6 (s, C-5), 124.9 (s, C-3), 71.32–70.08 (d, JC–P = 94.4 Hz,
FULL PAPER
CH-P, J = 9.0 Hz) ppm; Diastereomer 2: δ = 8.62 (s, 2 H, py-2, py-
C-α) ppm. IR (KBr): ν˜ = 3104 (OH), 3048, 2830 (P–OH), 2691, 2Ј), 8.55–8.45 (m, 4 H, py-4, py-6), 7.92–7.88 (m, 2 H, py-5), 5.19
3
1
2
9
515, 2319 (P–H), 1463, 1403, 1316, 1250, 1182 (P=O), 1155, 1042, (d, 2 H, CH-P, J = 10.7 Hz) ppm. P NMR (121.5 MHz, D
51, 804, 738, 605, 490 cm . C H NO P (173.11): calcd. C 41.63,
6 8 3
2
O): δ
= 31.53 (s) and 29.33 (s) ppm in a ratio 1:0.8. C NMR (75.5 MHz,
2
D O): Diastereomer 1: δ = 144.9 (s, C-2, C-2Ј), 139.7 (s, C-6, C-6Ј),
–1
13
H 4.66, N 8.09; found C 41.60, H 4.71, N 7.98.
1
6
1
39.5 (s, C-3, C-3Ј), 139.0 (s, C-4, C-4Ј), 126.7 (s, C-5, C-5Ј), 68.02–
6.61 (d, JC–P = 106.4 Hz, C-α, CЈ-α) ppm; Diastereomer 2: δ =
44.6 (s, C-2, C-2Ј), 140.0 (s, C-6, C-6Ј), 139.5 (s, C-3, C-3Ј), 139.0
[
(Hydroxy)(3-pyridyl)methyl]phosphinic Acid (2b): White solid,
1
2
yield: 1.87 g (54%), m.p. 149–151 °C. H NMR (300 MHz, D O):
δ = 8.66 (s, 1 H, py-2), 8.63 (d, 1 H, J = 5.1 Hz, py-6), 8.50 (d, 1
H, J = 7.8 Hz, py-4), 7.97 (t, 1 H, J = 6.3 Hz, py-5), 7.72–5.93 (d,
(
s, C-4, C-4Ј), 126.7 (s, C-5, C-5Ј), 69.75–68.37 (d, JC–P = 104.6 Hz,
C-α, CЈ-α) ppm. IR (KBr): ν˜ = 3375 (OH), 3111, 3094 (P–OH),
3
1
1
H, JH–P = 534 Hz, P-H), 4.96 (d, 1 H, J = 9.2 Hz, CH-P) ppm. P
3
1
4
030, 2937, 2877, 2797, 2648, 1618, 1463, 1220 (P=O), 1139, 1115,
029, 848, 735, 688 cm . C12
0.81, H 4.28, N 7.93; found C 40.85, H 4.32, N 7.88.
NMR (121.5 MHz, D
2
O): δ = 24.37 (s) ppm. 13C NMR (75.5 MHz,
–
1
13 2 4
H N O P·2HCl (353.14): calcd. C
D
2
O): δ = 144.5 (s, C-6), 139.8 (s, C-2), 138.7 (s, C-4), 138.6 (d,
2
JC–P = 9.1 Hz, C-3), 126.8 (s, C-5), 70.88–69.56 (d, JC–P = 89.5 Hz,
Bis[(hydroxy)(4-pyridyl)methyl]phosphinic Acid Hydrochloride (3c):
C-α) ppm. IR (KBr): ν˜ = 3447 (OH), 3094, 3069, 2829 (P–OH),
White solid, yield: 2.54 g (36%), m.p. 250 °C (dec.). 1H NMR
2
1
C
674, 2333 (P–H), 1558, 1470, 1403, 1379, 1262, 1206, 1156 (P=O),
–
1
(300 MHz, D O): Diastereomer 1: δ = 8.65–8.62 (d, 4 H, J = 9.8 Hz,
py-2, py-6), 8.01–7.98 (d, 4 H, J = 9.9 Hz, py-3, py-5), 5.44 (d, 2
H, J = 9.36 Hz, CH-P) ppm; Diastereomer 2: δ = 8.70–8.67 (d, 4
H, J = 6.7 Hz, py-2, py-6), 7.91–7.89 (d, 4 H, J = 6.7 Hz, py-3, py-
115, 1067, 1043, 1029, 1000, 965, 837, 690 (P–C), 616, 541 cm .
NO P (173.11): calcd. C 41.63, H 4.66, N 8.09; found C 41.56,
H 4.79, N 8.01.
2
6
H
8
3
[(Hydroxy)(4-pyridyl)methyl]phosphinic Acid (2c): White solid,
31
5
), 5.34 (d, 2 H, J = 13.9 Hz, CH-P) ppm. P NMR (121.5 MHz,
1
yield: 1.55 g (45%), m.p. 174–176 °C. H NMR (300 MHz, D
δ = 8.64 (d, 2 H, J = 6.6 Hz, py-2, py-6), 7.96 (d, 2 H, J = 6.0 Hz,
py-3, py-5), 7.75–5.95 (d, 1 H, JH–P = 541 Hz, P–H), 5.08 (d, 1 H,
J = 12.6 Hz, CH–P) ppm. P NMR (121.5 MHz, D
(
2
O):
13
D
(
(
2
O): δ = 31.3 (s) and 29.4 (s) ppm in a ratio 1:0.7. C NMR
75.5 MHz, D O): Diastereomer 1: δ = 160.8 (s, C-4, C-4Ј), 140.3
s, C-2, C-2Ј, C-6, C-6Ј), 124.9 (s, C-3, C-3Ј, C-5, C-5Ј), 71.37–
2
31
2
O): δ = 23.87
7
1
0.03 (d, JC–P = 101.2 Hz, C-α, CЈ-α) ppm; Diastereomer 2: δ =
60.5 (s, C-4, C-4Ј), 141.1 (s, C-2, C-2Ј, C-6, C-6Ј), 125.7 (s, C-3,
s) ppm. 13C NMR (75.5 MHz, D
24.72 (d, JC–P = 2.8 Hz, C-4), 124.23 (s, C-3, C-5), 73.64–72.40
O): δ = 140.26 (s, C-2, C-6),
2
2
1
(
C-3Ј, C-5, C-5Ј), 74.68–73.34 (d, JC–P = 100.9 Hz, C-α, CЈ-α) ppm.
IR (KBr): ν˜ = 3226 (OH), 3100, 3080, 3063 (P–OH), 2938, 2848,
d, JC–P = 93.4 Hz, C-α) ppm. IR (KBr): ν˜ = 3099 (OH), 2823 (P–
OH), 2671, 2377, 2308 (P–H), 2141, 2050, 1524, 1497, 1383, 1362,
1
5
1
1
630, 1618, 1505, 1493, 1408, 1367, 1347, 1334, 1269, 1237 (P=O),
198, 1184, 1144, 1100, 1062, 1026, 1005, 954, 834, 811, 756 cm .
276, 1213, 1193 (P=O), 1145, 1052, 988, 955, 842, 747, 693, 633,
–1
–1
6 8 3
44 cm . C H NO P (173.11): calcd. C 41.63, H 4.66, N 8.09;
12 13 2 4
C H N O P·2HCl (353.14): calcd. C 40.81, H 4.28, N 7.93; found
C 40.70, H 4.32, N 7.91.
found C 41.61, H 4.68, N 8.03.
[
(Hydroxy)(4-imidazolyl)methyl]phosphinic Acid (2d): White solid,
Bis[(hydroxy)(4-imidazolyl)methyl]phosphinic Acid Hydrochloride
1
1
yield: 1.78 g (55%), m.p. 119–121 °C. H NMR (300 MHz, D
δ = 8.62 (s, 1 H, imidazole-2), 7.79–5.98 (d, 1 H, JH–P = 545 Hz,
P–H), 7.37 (s, 1 H, imidazole-5), 4.82 (d, 1 H, J = 10.0 Hz, CH-P) azole-2), 7.31–7.28 (m, 2 H, imidazole-5), 5.16 (d, 2 H, J = 8.3 Hz,
2
O):
(3d): White solid, yield: 87%, m.p. 218–222 °C.
H NMR
(300 MHz, D O): Diastereomer 1: δ = 8.55–8.52 (m, 2 H, imid-
2
31
13
ppm. P NMR (121.5 MHz, D
2
O): δ = 23.36 (s) ppm. C NMR CH-P) ppm; Diastereomer 2: δ = 8.55–8.52 (m, 2 H, imidazole-2),
(
75.5 MHz, D O): δ = 133.83 (s, C-2), 129.61 (s, C-5), 116.33 (d, 7.31–7.28 (m, 2 H, imidazole-5), 5.06 (d, 2 H, J = 9.6 Hz, CH-P)
2
2
31
J
C–P = 5.7 Hz, C-4), 65.13–63.72 (d, JC–P = 106.3 Hz, C-α) ppm.
2
ppm. P NMR (121.5 MHz, D O): δ = 30.2 (s) and 28.8 (s) ppm
1
3
IR (KBr): ν˜ = 3357 (OH), 3125 (P–OH), 2853, 2614, 2375, 1313,
1
C
2
in a ratio 1:0.9. C NMR (75.5 MHz, D O): Diastereomer 1: δ =
2
–
1
271 (P=O), 1147, 1019, 967, 817, 658, 623, 547, 462 cm .
P (162.08): calcd. C 29.64, H 4.35, N 17.28; found C
9.55, H 4.41, N 17.20.
133.6 (s, C-2, C-2Ј), 130.6 (s, C-4, C-4Ј), 116.6 (s, C-5, C-5Ј), 63.71–
4
H
7
N
2
O
3
62.24 (d, JC–P = 110.7 Hz, C-α, CЈ-α) ppm. Diastereomer 2: δ =
133.6 (s, C-2, C-2Ј), 130.2 (s, C-4, C-4Ј), 116.5 (s, C-5, C-5Ј), 62.48–
6
1.00 (d, JC–P = 111.6 Hz, C-α, CЈ-α) ppm. IR (KBr): ν˜ = 3347
General Procedure for the Preparation of Heterocyclic Bis(α-hy-
droxymethyl)phosphinic Acids 3a–d: Hypophosphorous acid (50%
aqueous solution, 1.32 g, 20 mmol) was mixed with the appropriate
heterocyclic aldehyde (40 mmol) and diluted with aqueous HCl
(
OH), 3125, 3029 (P–OH), 2855, 2616, 1312 (P=O), 1220, 1145,
–
1
1
8 11 4 4
096, 1023, 818, 658, 624 cm . C H N O P·2HCl (331.09): calcd.
C 29.02, H 3.96, N 16.92; found C 28.91, H 4.00, N 16.87.
Potentiometric Studies of CuII Complexes: Both protonation and
stability constants were determined by pH-metric titration of 1.8–
2
concentration in the samples was 3ϫx 10 molL and the molar
ratio of metal ion: ligand varied from 1:2 to 1:6. Initial solutions
were titrated with sodium hydroxide solutions delivered by a
(1 , 40 mmol, 40 mL). The resulting homogeneous mixture was
heated at reflux for 2 h. The solvent was then evaporated under
reduced pressure, and the residue was dissolved in methanol
3
.0 cm samples at 25 °C over the pH range 2.5–10.5. The ligand
–
3
–1
(10 mL) and placed in the refrigerator for crystallization. The sepa-
rated products, bis(α-hydroxymethyl)phosphinic acids 3a–d, were
collected by filtration, washed with cold MeOH, and dried on air.
All products gave satisfactory spectroscopic data in accordance
with the assigned structures.
0
.25 mL micrometer syringe previously calibrated by the weight ti-
trations of standard materials. The purities and exact concentration
of the ligand solutions were determined by the method of Gran.
pH-Metric titrations were performed in 0.1 KNO solutions by
using MOLSPIN automatic titration system with Russell
CMAW711 semi-combined electrode calibrated with H concentra-
[
16]
Bis[(hydroxy)(2-pyridyl)methyl]phosphinic Acid Hydrochloride (3a):
3
White solid, yield: 2.1 g (30%), m.p. 160 °C (dec.) (ref.[ 148–
9b
1
ture.
50 °C). All spectroscopic data are in agreement with the litera-
+
[
9b]
[17]
tion with the use of HNO
3
.
The method SUPERQUAD was
used for stability constants and calculation of protonation con-
Bis[(hydroxy)(3-pyridyl)methyl]phosphinic Acid, Hydrochloride (3b):
White solid, yield: 4.0 g (57%), m.p. 237–240 °C. H NMR
stants.[
18]
1
(300 MHz, D
2
O): Diastereomer 1: δ = 8.65 (s, 2 H, py-2, py-2Ј),
Spectroscopic Studies of CuII Complexes: The absorption spectra
8.55–8.45 (m, 4 H, py-4, py-6), 7.90 (m, 2 H, py-5), 5.33 (d, 2 H,
were recorded with Beckman DU 650 spectrometer and thermo-
Eur. J. Org. Chem. 2007, 3539–3546
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3545