1
-Hydroxymethylene-1,1-bis(phosphonic acids) from Acid Anhydrides
SHORT COMMUNICATION
C. At this stage, 31P, H and 13C NMR spectra of the crude silyl-
1
°
[
1]
ated intermediate were performed in CDCl
anol was then added to the residue and the solution was stirred for
1
3
3
. Twenty mL of meth-
L. Widler, K. A. Jaeggi, M. Glatt, K. Muller, R. Bachmann,
M. Bisping, A. R. Born, R. Cortesi, G. Guiglia, H. Jeker, R.
Klein, U. Ramseier, J. Schmid, G. Schreiber, Y. Seltenmeyer, J.
R. Green, J. Med. Chem. 2002, 45, 3721.
E. Gumienna-Kontecka, J. Jezierska, M. Lecouvey, Y. Leroux,
H. Kozlowski, J. Inorg. Biochem. 2002, 89, 13.
E. Gumienna-Kontecka, R. Silvagni, R. Lipinski, M. Lecou-
vey, F. Cesare Marincola, G. Crisponi, V. M. Nurchi, Y. Ler-
oux, H. Kozlowski, Inorg. Chim. Acta 2002, 339, 111.
H. Khadrahoui, H. Gillier, D. El Manouni, Y. Leroux, A. Neu-
man, T. Prang e´ , J. P. Silvestre, N. Q. Dao, Phosphorus, Sulfur
Silicon Relat. Elem. 1997, 127, 67.
M. Dyba, M. Jezowska-Bojczuk, E. Kiss, T. Kiss, H. Kozlow-
ski, J. Chem. Soc., Dalton Trans. 1996, 6, 1119.
M. Dyba, H. Kozlowski, A. Tlalka, Y. Leroux, D. El Manouni,
Pol. J. Chem. 1998, 72, 1148.
R. G. Russell, P. I. Croucher, M. J. Rogers, Osteoporos. Int.
999, 9, 66.
R. G. Russell, M. J. Rogers, J. C. Frith, S. P. Luckman, F. P.
Coxon, H. L. Benford, P. I. Croucher, C. Shipman, H. A. Fle-
isch, J. Bone Miner. Res. 1999, 14, 53.
H. Fleisch, Prog. Mol. Subcell. Biol. 1999, 23, 197.
J. R. Green, Semin. Oncol. 2002, 29, 3.
P. Clezardin, P. Fournier, S. Boissier, O. Peyruchaud, Curr.
Med. Chem. 2003, 10, 173.
T. Yoneda, A. Sasaki, C. Dunstan, P. J. Williams, F. Bauss, Y.
A. De Clerck, G. R. Mundy, J. Clin. Invest. 1997, 99, 2509.
S. Boissier, M. Ferreras, O. Peyruchaud, S. Magnetto, F. H.
Ebetino, M. Colombel, P. Delmas, J. M. Delaisse, P. Clezardin,
Cancer Res. 2000, 60, 2949.
J. E. Brown, R. E. Coleman, Breast Cancer Res. 2002, 4, 24.
P. Fournier, S. Boissier, S. Filleur, J. Guglielmi, F. Cabon, M.
Colombel, P. Clezardin, Cancer Res. 2002, 62, 6538.
Y. Hamma-Kourbali, M. Di Benedetto, D. Ledoux, O. Oudar,
Y. Leroux, M. Lecouvey, M. Kraemer, Biochem. Biophys. Res.
Commun. 2003, 310, 816.
J. Wood, K. Bonjean, S. Ruetz, A. Bellahcene, L. Devy, J. M.
Foidart, V. Castronovo, J. R. Green, J. Pharmacol. Exp. Ther.
002, 302, 1055.
h. After solvent removal in vacuo, the residue was washed with
ϫ 50 mL of diethyl ether to remove traces of H PO . Lyophilis-
3
3
[
[
2]
3]
ation then yielded 0.64 g (71%) of a white powder. M.p. 202 °C. IR
O): ν˜ ϭ 3397 (OϪH), 1752 (CϭO), 1602, 1465 (CϭC), 1266,
(D
2
Ϫ1
1
2
1109, 911, 766, 695, 557 cm . H NMR (D O, 500.6 MHz, 298 K):
3
3
δ ϭ 7.94 (d,
J
H
H,H ϭ 7.5 Hz, 1 H, C
6
H
4
, H4), 7.89 (d,
H,H
J ϭ
3
7
7
.5 Hz, 1 H, C
.67 (dd, 3
H,H ϭ 7.5 Hz, 1 H, C
O, 50.3 MHz, 298 K): δ ϭ 173.5 (OϭC,C3), 148.9 (C
38.3 (C , C7a), 134.0 (C , C6), 128.5 (C , C4), 128.3
, C4a), 128.2 (C , C5), 126.7 (C , C7), 107.6 (d, JC,P
96.8 Hz, PϪCϪOH, C1) ppm. P NMR{ H} (D
98 K): δ ϭ 9.08 (s) ppm. [M Ϫ H]: 228.5. C
6
4
, H7), 7.84 (dd, JH,H ϭ 7.5 Hz, C , 1 H, H6),
6
13
H
4
[4]
1
J
6
H
4
, H5) ppm. C NMR{ H}
, C7a),
(D
2
6 4
H
[
[
[
5]
6]
7]
1
6
H
4
6
H
4
6
H
4
(C
6
H
4
6
H
4
6
H
4
1
ϭ
31
1
2
2
O, 200.7 MHz,
8
7 6
H O P (230.1): calcd.
C 41.76, H 3.07, P 13.46; found C 41.31, H 3.46, P 13.23.
1
1
[8]
Silylated Intermediate 2g: H NMR (CDCl
3
, 500.6 MHz, 298 K):
δ ϭ 7.69 (d, 3
3
J
H,H ϭ 7.5 Hz, 1 H, C
6
H
4
, H4), 7.62 (d,
, H7), 7.57 (dd, JH,H ϭ 7.5 Hz, C , 1 H, H6),
H,H ϭ 7.5 Hz, C , 1 H, H5), 0.15 (s,3 H, SiCH ),
), Ϫ0.18 (s, 3 H, SiCH
, 125.9 MHz, 298 K): δ ϭ 167.9 (OϭC, C3), 146.9 (C
C7a), 134.7 (C , C6), 131.3 (C , C4), 127.3 (C , C4a), 125.4
, C5), 125.3 (C , C7), 102.9 (d, JC,P ϭ 228.9 Hz,
PϪCϪOH, C1), 1.5, 1.2, 0.9 (SiCH
) ppm. 13C NMR DEPT 135
Mode: δ ϭ 134.7 (C , C6), 131.3 (C , C4), 125.4 (C , C5),
25.3 (C , C7), 1.5, 1.2, 0.9 (SiCH
) ppm. 31P NMR{ H}
CDCl3, 200.7 MHz, 298 K): δ ϭ Ϫ6.06 (s) ppm.
H,H
J ϭ
3
7.5 Hz, 1 H, C
6
H
4
6 4
H
[9]
.47 (dd, 3
7
J
6
H
4
3
[
[
10]
11]
) ppm. 13C NMR{ H}
1
Ϫ0.13 (s,3 H, SiCH
CDCl
3
3
(
3
6 4
H ,
6
H
4
6
H
4
6
H
4
[12]
[13]
(C
6
H
4
6 4
H
3
6
H
4
6
H
4
6 4
H
1
1
(
6
H
4
3
[
[
14]
15]
Synthesis of (3-Oxo-1-phosphono-1,3-dihydroisobenzofuran-1-yl)-
phosphonic Acid (3h): To a solution of tris(trimethylsilyl) phosphite
[16]
(2.4 g, 8 mmol) in 5 mL THF was added, in a 25 mL round bottom
flask under N , phthalic anhydride (0.59 g, 4 mmol) at room tem-
2
[17]
perature. The resulting mixture was stirred for 12 h at 50 °C, and
the reaction was monitored by 31P NMR spectroscopy. The volatile
2
fractions were evaporated under vacuum (0.1 Torr) at 50 °C.
Twenty mL of methanol was then added to the residue and the
solution was stirred for 1 h. After solvent removal in vacuo, the
residue was washed with 3 ϫ 50 mL of diethyl ether to remove
[
[
18]
19]
M. Lecouvey, Y. Leroux, Heteroat. Chem. 2000, 11, 556.
J. M. Benech, D. El Manouni, Y. Leroux, Phosphorus, Sulfur
Silicon Relat. Elem. 1996, 113, 295.
I. Mallard, J. M. Benech, M. Lecouvey, Y. Leroux, Phosphorus,
Sulfur Silicon Relat. Elem. 2000, 162, 15.
K. Kanaan, R. Burgada, Phosphorus Sulfur 1988, 37, 217.
C. E. McKenna, M. T. Higa, N. H. Cheung, M. C. McKenna,
Tetrahedron Lett. 1977, 2, 155.
S. J. Fitch, K. Moedritzer, J. Am. Chem. Soc. 1962, 84, 1876.
D. A. Nicholson, H. Vaughn, J. Org. Chem. 1971, 36, 3843.
R. Ruel, J. P. Bouvier, R. N. Young, J. Org. Chem. 1995, 60,
[20]
traces of H
powder. M.p. Ͼ 260 °C. IR (D
609, 1596, 1470 (CϭC), 1295, 1106, 948, 755, 695 cm . H NMR
3
PO
3
. Lyophilisation then yielded 1.2 g (97%) of a white
O): ν˜ ϭ 3418 (OϪH), 1752 (CϭO),
[21]
[22]
2
Ϫ1
1
1
3
2 6 4
(D O, 500.6 MHz, 298 K): δ ϭ 7.76 (d, JH,H ϭ 7.3 Hz, 1 H, C H ,
3
3
[23]
[24]
H4), 7.70 (dd, JH,H ϭ 7.3 Hz, 1 H, C
6
H
4
, H6), 7.63 (d, JH,H
, H7), 7.56 (dd, JH,H ϭ 7.3 Hz, 1 H, C , H5)
O, 125.9 MHz, 298 K): δ ϭ 176.5 (OϭC,
, C7a), 138.4 (C , C6), 133.0 (C , C4), 129.0
, C4a), 127.2 (C , C5), 127.1 (C , C7), 89.5 (t, JC,P
41.0 Hz, PϪCϪP, C1) ppm. P NMR{ H} (D
98 K): δ ϭ 9.02 (s) ppm. [M Ϫ H]: 292.4. C
ϭ
3
7
.3 Hz, 1 H, C
6
H
4
1
6 4
H
[
[
[
25]
26]
27]
13
ppm. C NMR{ H} (D
C3), 148.6 (C
2
5209.
6
H
4
6
H
4
6 4
H
M. Lecouvey, I. Mallard, T. Bailly, R. Brugada, Y. Leroux,
Tetrahedron Lett. 2001, 42, 8475.
D. V. Griffiths, P. Duncanson, Phosphorus, Sulfur Silicon Relat.
Elem. 2002, 177, 2213.
R. N. Jones, C. L. Angell, T. Ito, R. J. D. Smith, Can. J. Chem.
(C
6
H
4
6
H
4
6
H
4
ϭ
31
1
1
2
2
O, 200.7 MHz,
8 8 2
H O P (294.1): calcd.
8
C 32.67, H 2.74, P 21.06; found C 33.01, H 3.12, P 21.41.
[28]
1
959, 37, 2007.
[
29]
B. B. V. Soma Sekhar, W. G. Bentrude, Tetrahedron Lett. 1999,
Acknowledgments
40, 1087.
We express our thanks to Dr. F. Taran from Service de Marquage
Mol e´ culaire et de Chimie Bio-organique, CEA, Saclay, France, for
the mass spectrum analysis.
[30]
R. Niemi, P. Turhanen, J. Vepsalainen, H. Taipale, T. Jarvinen,
Eur. J. Pharm. Sci. 2000, 11, 173.
Received January 27, 2004
Eur. J. Org. Chem. 2004, 2983Ϫ2987
www.eurjoc.org
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2987