Synthesis of Unsymmetrical Phosphinic Acids RЈP(O)OHRЈЈ
2
CH2CH), 2.85 (br., 1 H, CH2CH), 3.02 (d, JP,H = 17.4 Hz, 2 H, product. Crude yield 8.84 g, 92% (Method A); 7.78 g, 81%
CH2C6H5), 3.63 (s, 3 H, OCH3), 7.21–7.27 (br., 5 H, C6H5), 9.12
(Method B). 31P NMR {1H} (80.9 MHz, CDCl3): δ = 51 ppm.
(s, 1 H, POH) ppm. 13C NMR {1H} (125.9. CDCl3): δ = 19.0
Dodecyl(2-ethoxy-2-oxoethyl)phosphinic Acid (17d): The mixture
was taken up in water (20 mL) and extracted with ethyl acetate
(3ϫ20 mL). The organic phase was dried with MgSO4, filtered,
and evaporated under reduced pressure. The product was precipi-
tated in diethyl ether. White solid; yield 6.25 g, 98% (Method B).
1
(CH3), 31.3 (d, JP,C = 94.1 Hz, CH2C6H5), 33.7 (CH), 38.0 (d,
1JP,C = 87.8 Hz, CH2CH), 52.2 (OCH3), 127.0, 128.8, 130.0, 131.6
(C6H5), 176.1 (CO) ppm. 31P NMR {1H} (80.9 MHz, CDCl3): δ =
53 ppm.
3
1H NMR (500.9 MHz, CDCl3): δ = 0.83 [t, JH,H = 6.5 Hz, 3 H,
Benzyl(2-ethoxy-2-oxoethyl)phosphinic Acid (16d): The mixture was
taken up in water(40 mL) and washed with diethyl ether
(3ϫ40 mL) and the product was extracted with ethyl acetate
(3ϫ40 mL). The organic phase was dried with MgSO4, filtered,
and evaporated under reduced pressure. Colorless oil; yield 4.16 g,
86% (Method B). 1H NMR (500.9 MHz, CDCl3): δ = 1.27 (t, 3JH,H
= 6.5 Hz, 3 H, OCH2CH3), 2.76 (d, 1JP,H = 17.5 Hz, 2 H, PCH2Ph),
CH3(CH2)10], 1.23 [m, 19 H, CH3(CH2)8, OCH2CH3], 1.33 (m, 2
H, PCH2CH2CH2), 1.55 (m, 2 H, PCH2CH2), 1.81 [m, 2 H,
1
PCH2(CH2)10], 2.91 (d, JP,H = 17.5 Hz, 2 H, PCH2CO), 4.14 (q,
3JH,H = 7.0 Hz, 2 H, OCH2CH3), 9.84 (s, 1 H, OH) ppm. 13C NMR
{1H} (125.9 MHz, CDCl3):
δ = 14.3 [CH3(CH2)10], 21.6
(OCH2CH3), 22.6 (PCH2CH2), 28.4–32.1 [CH3(CH2)7, PCH2CH2],
1
1
3
37.5 (d, JP,C = 80.5 Hz, PCH2CO), 61.7 (OCH2CH3), 166.7
3.25 (d, JP,H = 18.5 Hz, 2 H, PCH2CO), 4.18 (q, JHH = 7.5 Hz,
2 H, OCH2CH3), 7.28 (br., 5 H, C6H5) ppm. 13C NMR {1H}
(125.9 MHz, CDCl3): δ = 13.4 (OCH2CH3), 35.0 (1JP,C = 131.0 Hz,
PCH2Ph), 35.7 (1JP,C = 138.7 Hz, PCH2CO), 60.9 (OCH2CH3),
126.4–130.4 (C6H5), 165.7 (CO) ppm. 31P NMR {1H} (80.9 MHz,
CDCl3): δ = 45.7 ppm.
(CO) ppm. 31P NMR {1H} (80.9 MHz, CDCl3): δ = 51 ppm.
Dodecyl(3-methoxy-3-oxopropyl)phosphinic Acid (17e): The mixture
was taken up in water (20 mL) and extracted with ethyl acetate
(3ϫ20 mL). The organic phase was dried with MgSO4, filtered,
and evaporated under reduced pressure. The product was precipi-
tated in diethyl ether. White solid; yield 6.18 g, 97% (Method B).
Methyl 3-[Benzyl(hydroxy)phosphinoyl]propionate (16e): The mix-
ture was taken up in water (40 mL) and washed with diethyl ether
(3ϫ40 mL) and the product was extracted with ethyl acetate
(3ϫ40 mL). The organic phase was dried with MgSO4, filtered,
and evaporated under reduced pressure. Colorless oil; yield 4.18 g,
3
1H NMR (500.9 MHz, CDCl3): δ = 0.84 (t, JH,H = 6.5 Hz, 3 H,
CH3CH2), 1.21 [m, 16 H, CH3(CH2)8], 1.30 (m,
2 H,
PCH2CH2CH2), 1.57 (m, 2 H, PCH2CH2CH2), 1.85 [m, 2 H,
PCH2(CH2)10], 2.62 (m, 2 H, PCH2CH2CO), 2.94 (m, 2 H,
PCH2CH2CO), 3.66 (s, 3 H, OCH3), 10.21 (s, 1 H, OH) ppm. 13C
NMR {1H} (125.9 MHz, CDCl3): δ = 14.3 (CH3CH2), 24.2 (d, 1JPH
1
96% (Method B). H NMR (500.9 MHz, CDCl3): δ = 1.92 (m, 2
1
H, PCH2CH2), 2.50 (m, 2 H, PCH2CH2), 3.07 (d, JP,H = 17.0 Hz,
=
93.1 Hz, PCH2CH2CO), 26.5 (PCH2CH2CO), 26.5–32.1
2 H, PCH2Ph), 3.68 (s, 3 H, OCH3), 7.28 (br., 5 H, C6H5), 9.10 (s,
[P(CH2)11], 52.2 (OCH3), 173.1 (CO) ppm. 31P NMR {1H}
(80.9 MHz, CDCl3): δ = 58 ppm.
1 H, OH) ppm. 13C NMR {1H} (125.9 MHz, CDCl3): δ = 23.3
1
1
(d, JP,C = 95.6 Hz, PCH2CH2), 26.3 (PCH2CH2), 37.5 (d, JP,C
=
Benzyl(isopropyl)phosphinic Acid (18b): The mixture was taken up
in water (20 mL) and washed with diethyl ether (3ϫ20 mL) and
88.1 Hz, PCH2Ph), 52.2 (OCH3), 127.2–131.5 (C6H5), 173.0
(CO) ppm. 31P NMR {1H} (80.9 MHz, CDCl3): δ = 53 ppm.
subjected to reversed-phase column (water/methanol, 8:2). Rf
=
Benzyl(dodecyl)phosphinic Acid (17a): The mixture was taken up in
water (20 mL) and extracted with ethyl acetate (3ϫ20 mL). The
organic phase was dried with MgSO4, filtered, and evaporated un-
der reduced pressure. The product was precipitated in diethyl ether.
0.69. White solid; yield 5.17 g, 75% (Method A); 4.83 g, 70%
3
(Method B). 1H NMR (500.9 MHz, CDCl3): δ = 1.0 (d, JH,H
=
2
7.0 Hz, 6 H, CH3), 1.68 (br., 1 H, PCH), 2.97 (d, JP,H = 15.3 Hz,
2 H, PCH2), 7.18–7.25 (br., 5 H, C6H5) ppm. 13C NMR {1H}
White solid; yield 5.41 g, 88% (Method A); 5.16 g, 84%
1
(125.9 MHz, CDCl3): δ = 15.2 (CH3), 26.7 (d, JP,C = 95.4 Hz,
3
(Method B). 1H NMR (500.9 MHz, CDCl3): δ = 0.86 [t, JH,H
=
1
PCH), 34.6 (d, JP,C = 81.6 Hz, PCH2), 126.8–131.9 (C6H5) ppm.
7.5 Hz, 3 H, CH3(CH2)10], 1.23 [br., 20 H, CH3(CH2)10], 1.50 [br.,
31P NMR {1H} (80.9 MHz, CDCl3): δ = 59 ppm.
2
2 H, PCH2(CH2)10], 3.01 (d, JP,H = 20.0 Hz, 2 H, PCH2Ph), 6.92
(br., 1 H, OH), 7.24 (br., 5 H, C6H5) ppm. 13C NMR {1H}
(125.9 MHz, CDCl3): δ = 14.3 [CH3(CH2)10], 21.5 (PCH2CH2CH2),
22.8 (CH3CH2), 28.8 [d, 1JP,C = 130.6 Hz, PCH2(CH2)10], 29.5 and
Isopropyl(methyl)phosphinic Acid (18c): The mixture was taken up
in water (20 mL) and washed with diethyl ether (3ϫ20 mL) and
subjected to reversed-phase column (water/methanol, 8:2). Rf
0.76. White solid; yield 2.17 g, 89% (Method A); 2.51 g, 95%
=
2
29.8 [CH3CH2CH2(CH2)6], 30.8 (d, JP,C = 16.0 Hz, PCH2CH2),
1
3
1
(Method B). H NMR (500.9 MHz, CDCl3): δ = 1.06 (d, JH,H
=
32.1 (CH3CH2CH2), 37.3 (d, JP,C = 86.5 Hz, PCH2Ph), 126.9–
2
132.1 (C6H5) ppm. 31P NMR {1H} (80.9 MHz, CDCl3): δ =
7.0 Hz, 6 H, CH3CH), 1.30 (d, JP,H = 13.1 Hz, 3 H, PCH3), 1.76
(br., 1 H, PCH), 8.9 (s, 1 H, OH) ppm. 13C NMR {1H}
56 ppm.
1
(125.9 MHz, CDCl3): δ = 12.0 (d, JP,C = 89.6 Hz, PCH3), 15.8
(CH3CH), 29.0 (d, JP,H = 98.0 Hz, PCH) ppm. 31P NMR {1H}
1
Dodecyl(methyl)phosphinic Acid (17b): The mixture was taken up
in water (20 mL) and extracted with ethyl acetate (3ϫ20 mL). The
organic phase was dried with MgSO4, filtered, and evaporated un-
der reduced pressure. The product was precipitated in diethyl ether.
White solid; yield 4.37 g, 88% (Method A); 3.72 g, 75%
(80.9 MHz, CDCl3): δ = 53 ppm.
Methyl
3-[Hydroxy(isopropyl)phosphinoyl]-2-methylpropionate
(18d): The mixture was taken up in water (20 mL) and extracted
with ethyl acetate (3ϫ20 mL). The organic phase was dried with
MgSO4, filtered, and evaporated under reduced pressure. Yellow
oil; yield 3.16 g, 76% (Method A); 3.41 g, 82% (Method B). 1H
1
3
(Method B). H NMR (500.9 MHz, CDCl3): δ = 0.85 (t, JH,H
=
6.9 Hz, 3 H, CH3CH2), 1.22–1.37 [br., 18 H, CH3(CH2)9], 1.43 (d,
2JP,H = 16.2 Hz, 3 H, PCH3), 1.56 (br., 2 H, PCH2CH2), 1.68 (br.,
2 H, PCH2), 6.90 (br., 1 H, OH) ppm. 13C NMR {1H} (125.9 MHz,
3
NMR (500.9 MHz, CDCl3): δ = 1.11 (d, JH,H = 7.1 Hz, 6 H,
3
CH3CH), 1.30 (d, JH,H = 6.5 Hz, 3 H, PCH2CHCH3), 1.76 (t,
1
CDCl3): δ = 14.3 [CH3(CH2)10], 15.6 (d, JP,C = 101.4 Hz, PCH3),
3JH,H = 7.0 Hz, 1 H, PCH2CH), 1.93 (br., 1 H, CH3CH), 2.19 (br.,
1 H, PCH2), 2.92 (br., 1 H, PCH2), 3.65 (s, 3 H, OCH3), 8.9 (s, 1
H, OH) ppm. 13C NMR {1H} (125.9 MHz, CDCl3): δ = 15.2
1
22.4 [d, JP,C
= 106.9 Hz, PCH2(CH2)10], 29.3–32.1 [PCH2-
(CH2)10] ppm. 31P NMR {1H} (80.9 MHz, CDCl3): δ = 58 ppm.
1
Methyl 3-[Dodecyl(hydroxy)phosphinoyl]-2-methylpropionate (17c):
After several attempts at purification, we failed to obtain the pure
(CH3CH), 19.2 (PCH2CHCH3), 28.5 (d, JP,C = 93.5 Hz, PCH),
1
29.5 (d, JP,C = 87.7 Hz, PCH2), 33.6 (PCH2CH), 52.2 (OCH3),
Eur. J. Org. Chem. 2009, 6048–6054
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6053