P. Servin et al. / Tetrahedron Letters 48 (2007) 579–583
583
Nature Biotechnol. 2005, 23, 1517; (c) Caminade, A. M.;
then left to evaporate in an evaporating dish. The product
was washed six times with MeOH giving 0.131 g of 2-G1
(yield 39.7%) as a poorly soluble white powder. 31P {1H}
´
Padie, C.; Laurent, R.; Maraval, A.; Majoral, J. P. Sensors
2006, 6, 901.
1
´
4. (a) Wooley, K. L.; Hawker, C. J.; Frechet, J. M. J. J. Am.
NMR (81 MHz, DMSO-d6): 11.28 (s, P0) ppm. H NMR
Chem. Soc. 1991, 113, 4252; (b) Miller, T. M.; Neenan, T.
X.; Zayas, R.; Bair, H. E. J. Am. Chem. Soc. 1992, 114,
1018; (c) Xu, Z. F.; Kahr, M.; Walker, K. L.; Wilkins, C.
L.; Moore, J. S. J. Am. Chem. Soc. 1994, 116, 4537; (d)
Maraval, V.; Laurent, R.; Donnadieu, B.; Mauzac, M.;
Caminade, A. M.; Majoral, J. P. J. Am. Chem. Soc. 2000,
122, 2499.
(200 MHz, DMSO-d6): 7.85 (br s, 12H, C21H), 8.27 (br s,
6H, C41H), 9.96 (br s, 12H, CHO) ppm. 13C {1H} NMR
(50 MHz, DMSO-d6): 124.88 (s, C21), 127.94 (s, C14), 138.31
(s, C31), 150.26 (s, C11), 191.24 (s, CHO) ppm. IR (KBr):
1699 (mCO) cmꢀ1. MS (FAB): 1030 [M+H]+. Synthesis of
the second generation 2-G2. A solution of the phosphor-
hydrazide 3 in CHCl3 (11 mL of a 0.23 M solution) was
added to powdered 2-G1 (0.131 g, 0.126 mmol). The
resulting mixture was stirred overnight at rt then precip-
itated into a pentane/ether (5:1) mixture. After filtration,
the resulting powder was solubilized in a minimum
amount of THF then precipitated with pentane/ether; this
process was repeated 3 times. Dendrimer 2-G2 was isolated
in 77% yield (0.288 g). 31P {1H} NMR (81 MHz, CDCl3):
10.48 (s, P0), 65.16 (s, P2) ppm. 1H NMR (250 MHz,
5. (a) Kawaguchi, T.; Walker, K. L.; Wilkins, C. L.; Moore,
J. S. J. Am. Chem. Soc. 1995, 117, 2159; (b) Chang, H. T.;
Chen, C. T.; Kondo, T.; Siuzdak, G.; Sharpless, K. B.
Angew. Chem., Int. Ed. 1996, 35, 182; (c) Ashton, P. R.;
Anderson, D. W.; Brown, C. L.; Shipway, A. N.;
Stoddart, J. F.; Tolley, M. S. Chem. Eur. J. 1998, 4, 781.
´
6. (a) Spindler, R.; Frechet, J. M. J. J. Chem. Soc., Perkin
Trans 1 1993, 913; (b) Xu, Z.; Moore, J. S. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1354; (c) Zeng, F. W.; Zimmerman,
S. C. J. Am. Chem. Soc. 1996, 118, 5326; (d) Deb, S. K.;
Maddux, T. M.; Yu, L. P. J. Am. Chem. Soc. 1997, 119,
9079; (e) Ishida, Y.; Jikei, M.; Kakimoto, M. Macromole-
cules 2000, 33, 3202.
3
CDCl3): 3.41 (d, JHP = 13.5 Hz, 36H, CH3NP2), 7.46 (s,
12H, C21H), 7.56 (s, 12H, CH@N), 7.76 (s, 6H, C41H) ppm.
13C {1H} NMR (75 MHz, CDCl3): 32.05 (d,
2JCP = 12.8 Hz, CH3NP2), 120.16 (s, C12), 122.97 (s, C41),
136.38 (s, C31),139.74 (d, 3JCP = 9.4 Hz, CH@N), 151.18 (s,
C11) ppm. MS (IS, MeOH): 2960.3 [M+H]+. Synthesis of
the third generation 2-G3. Powdered sodium salt 1 (0.239 g,
1.37 mmol) was added to a solution of the second
generation dendrimer 2-G2 (0.157 g, 0.528 lmol) in THF
(6 mL). The reaction was left stirring for 5 days at rt while
monitoring by 31P NMR. This mixture was then centri-
fuged and the solution was evaporated to dryness. The
resulting powder was solubilized in a minimum amount of
THF then precipitated with pentane/ether. Dendrimer 2-
G3 was isolated in 46.8% yield (0.142 g). 31P {1H} NMR
7. (a) Brauge, L.; Magro, G.; Caminade, A. M.; Majoral, J.
P. J. Am. Chem. Soc. 2001, 123, 6698, correction: J. Am.
Chem. Soc. 2001, 123, 8446.; (b) Maraval, V.; Caminade,
A. M.; Majoral, J. P.; Blais, J. C. Angew. Chem., Int. Ed.
2003, 42, 1822; (c) Maraval, V.; Pyzowski, J.; Caminade,
A. M.; Majoral, J. P. J. Org. Chem. 2003, 68, 6043.
8. (a) Launay, N.; Caminade, A. M.; Lahana, R.; Majoral, J.
P. Angew. Chem., Int. Ed. Engl. 1994, 33, 1589; (b)
Launay, N.; Caminade, A. M.; Majoral, J. P. J. Am.
Chem. Soc. 1995, 117, 3282; (c) Launay, N.; Caminade, A.
M.; Majoral, J. P. J. Organomet. Chem. 1997, 529, 51.
9. Lartigue, M. L.; Donnadieu, B.; Galliot, C.; Caminade, A.
M.; Majoral, J. P.; Fayet, J. P. Macromolecules 1997, 30,
7335.
1
(81 MHz, DMSO-d6): 10.42 (s, P0), 66.38 (s, P2) ppm. H
3
NMR (200 MHz, DMSO-d6): 3.25 (br d, JHP = 8.9 Hz,
36H, CH3NP2), 7.42 (s, 12H, C21H), 7.70 (s, 12H, CH@N),
7.78 (br s, 54H, C23H, C14H), 8.14 (s, 24H, C43H), 9.89 (s,
48H, CHO) ppm. 13C {1H} NMR (50 MHz, DMSO-d6):
10. This compound was synthesized in two steps from 5-
2
hydroxydiethylisophthalate by
a
modification of the
32.65 (d, JCP = 11.5 Hz, CH3NP2), 119.72 (s, C21), 120.73
published procedure.15 The first step is the reduction of
the esters to the corresponding alcohols by LiAlH4 as
published. We modified as follows the second step. A
mixture of 3,5-bis(hydroxymethyl)phenol obtained in the
first step (0.250 g, 1.6 mmol) and MnO2 (1.11 g,
12.8 mmol) in 20 mL of THF/CH2Cl2 (1:9) was refluxed
under stirring for 2 days. The progress of the reaction was
supervised by thin layer chromatography (pentane/ethyl-
acetate 2:1). 5-hydroxy isophthaldehyde was isolated after
column chromatography with the same solvent conditions
as a white powder (yield: 62%). 1H NMR (250 MHz,
CDCl3): 7.48 (s, 2H, C2H), 7.78 (s, 1H, C4H), 9.92 (s, 2H,
CHO) ppm. 13C {1H} NMR (63 MHz, CDCl3/CD3CN):
121.04 (s, C2), 123.23 (s, C4), 138.53 (s, C3), 158.38 (s, C1),
(s, C41), 126.07 (s, C23), 127.67 (s, C34), 136.41 (s, C31), 138.00
3
(s, C33), 140.46 (br d, JCP = 13.3 Hz, CH@N), 150.64
(d, 2JCP = 7.0 Hz, C31), 150.8 (s, C11), 191.09 (s, CHO) ppm.
IR (KBr): 1699 (mCO) cmꢀ1. MS (Maldi-Tof): 5712
[M+Na]+. Synthesis of the fourth generation 2-G4. A
solution of the phosphorhydrazide 3 in CHCl3 (3.15 mL of
a
0.24 M solution) was added to powdered 2-G3
(0.083 g,14.5 lmol). The resulting mixture was stirred
overnight at rt then precipitated into a pentane/ether
(5:1) mixture. After filtration, the resulting powder was
solubilized in a minimum amount of THF then precipi-
tated with pentane/ether; this process was repeated twice.
Dendrimer 2-G4 was isolated in 28.8% yield (0.056 g). 31P
{1H} NMR (203 MHz, CDCl3): 7.17 (s, P0), 62.04 (br s,
191.33 (s, CHO) ppm. IR (KBr): 1687, 1701 (mCO) cmꢀ1
.
P2, P4) ppm. H NMR (200 MHz, CDCl3/CD3CN): 2.8–
1
The sodium salt of this compound (1) was obtained by
adding a solution of 5-hydroxyisophthaldehyde (1.205 g,
7.9 mmol) in THF (20 mL) to a suspension of NaH
(0.187 g, 7.8 mmol) in THF (6 mL) cooled by an ice bath.
The mixture was left stirring overnight, then the solvent
was eliminated via a filtering canula. The crude product
was washed with four portions of THF. Compound 1 was
isolated as an orange powder in 73% yield. It was used for
the synthesis of dendrimers without characterization, due
to its very poor solubility.
3.4 (br m, 180H, CH3N), 6.9–8.1 (br m, 150H, aromatics
and CH@N), ppm. 13C {1H} NMR (126 MHz, CDCl3/
CD3CN): 32.23 (br s, CH3NP4), 33.32 (br s, CH3NP2),
120.87 (br s, C12, C32), 123.47 (s, C14, C34), 136.53 (br s, C13,
C33), 140.06 (br s, CH@N), 150.96 (br s, C11, C13Þ ppm.
12. Leclaire, J.; Coppel, Y.; Caminade, A. M.; Majoral, J. P.
J. Am. Chem. Soc. 2004, 126, 2304.
13. Blais, J. C.; Turrin, C. O.; Caminade, A. M.; Majoral, J. P.
Anal. Chem. 2000, 72, 5097.
14. De Gennes, P. G.; Hervet, H. J. Phys. Lett. 1983, 44,
351.
11. Synthesis of the first generation 2-G1. Powdered sodium
salt 1 (0.443 g, 2.54 mmol) was added to a solution of
N3P3Cl6 (0.11 g, 0.32 mmol) in DMSO (4.5 mL). The
reaction was stirred at room temperature (rt) for 2 days,
15. Star, A.; Liu, Y.; Grant, K.; Ridvan, L.; Stoddart, J. F.;
Steuerman, D. W.; Diehl, M. R.; Boukai, A.; Heath, J. R.
Macromolecules 2003, 36, 553.