Phosphorus-Containing Dendrimers
FULL PAPER
d=2.74 (t, 3JHH =7.5 Hz, 16H; CH2-CH2-N), 3.04 (t, 3JHH =7.5 Hz, 16H;
Cp’), 150.6 (s, HC=C-CN), 156.1 (s, Ci), 162.7 ppm (s, CO); DCI-MS: m/z:
388 [M+H]+, 405 [M+NH3]+.
3
CH2-CH2-N), 3.18 (d, 3JHP =9.1 Hz, 32H; N-CH2-P), 3.31 (d, JHP
=
10.0 Hz, 12H; N-CH3), 3.72(d, 3JHP =10.5 Hz, 96H; P(O)
(OMe)), 6.68
Penta(4-formylphenoxy)chloro-cyclo(triphosphazene) (7a): To an ice-
cooled solution of hexachloro-cyclo(triphosphazene) (1.2g, 3.45 mmol) in
THF (300 mL) was added 4-hydroxybenzaldehyde sodium salt (2.6 g,
18 mmol), and the mixture was stirred at RT for 12h. The solvent was
evaporated and the residue was purified by silica-gel flash chromatogra-
phy (hexane/ethyl acetate 5:1) to give 7a as a colourless oil (1606 mg,
60%). 31P{1H} NMR (CDCl3, 121.50 MHz): d=3.5 (2d, 2JPP =88.1,
85.0 Hz, P0), 19.1 ppm (dd, 2JPP =88.1, 85.0 Hz, P’0); 1H NMR
(m, 2H; CBP2-H), 7.19 (m, 44H; CBP3-H, CBP5-H, C0 -H, C1 -H, C1 -H),
2
2
3
7.52(m, 2H; C
4-H), 7.69 ppm (m, 12H; C03-H, CH=N); 13C{1H} NMR
BP
(CDCl3, 62.90 MHz): d=32.8 (d, 2JHP =11.0 Hz, N-CH3), 33.0 (s, CH2-
CH2-N), 49.1 (dd, 1JCP =158.0 Hz, 3JCP =7.5 Hz, N-CH2-P), 50.7 (d, JCP
=
2
3
7.0 Hz, P(O)
A
=
4.5 Hz, C1 ), 121.6 (brs, C0 , CBP2), 126.1 (s, CBP or CBP5), 128.3 (s, Co3),
2
2
3
128.4 (brs, CBP6), 129.5 (m, CBP CBP or CBP5), 129.9 (s, C1 ), 132.2 (s,
4
3
3
,
4
4
2
C0 ), 136.6 (s, C1 ), 138.6 (d, 3JCP =14.0 Hz, CH=N), 147.7 (d, JCP
=
2
([D6]acetone, 300.13 MHz): d=7.12–7.30 (m, 10H; C0 -H), 7.71–7.86 (m,
9,3 Hz, CBP1), 149.0 (d, 2JCP =7.0 Hz, C1 ), 151.4 ppm (d, 2JCP =6.5 Hz,
1
3
10H; C0 -H), 9.94 ppm (3s; 5H; CHO); 13C{1H} NMR (CDCl3,
1
2
3
4
4
C0 ).
75.48 MHz): d=121.5 (m, C0 ), 131.5 (s, C0 ), 133.9 (s, C0 ), 134.0 (s, C0 ),
2
1
154.3 (d, JCP =17.1 Hz, C0 ), 190.4 (s, CHO), 190.5 ppm (s, CHO).
Compound 5g: To
a vigorously stirred solution of 5d (269 mg,
Compound 7b: To a mixture of 7 (92mg, 237 mmol) and 7a (184 mg,
237 mmol) in THF (10 mL) was added cesium carbonate (155 mg,
475 mmol), and the mixture was allowed to stir at RT for 12h. The reac-
tion mixture was centrifuged, filtered and evaporated. The residue was
purified by silica-gel flash chromatography (pentane/ethyl acetate 1:1) to
give 7b as an orange oil (227 mg, 85%). 31P{1H} NMR (CDCl3,
81.02MHz): d=10.9 ppm (brs); 1H NMR ([D6]acetone, 200.13 MHz):
d=1.74 (m, 4H; CH2-CH2-CH2-N), 2.64 (m, 6H; CH2-CH2-CH2-N, HN-
CH2-CH2), 3.31 (m, 6H; CH2-CH2-CH2-N, HN-CH2-CH2), 7.03–7.20 (m,
0.593 mmol) in dry acetonitrile (5 mL) was added at 08C, under a dry
argon atmosphere, bromotrimethylsilane (326 mL, 2.470 mmol) and the
mixture was allowed to stir at RT for 12h. The reaction mixture was
evaporated and the residue was diluted in methanol (2mL). The result-
ing mixture was stirred at RT for 1 h and evaporated. After a second
methanolysis conducted as above, the residue was washed with water to
afford 5 f as a white solid. The sodium monosalt form was obtained by
adding aqueous sodium hydroxide (0.1966n, 4.810 mL) to a suspension
of 5 f in water (1 mL). The clear solution was then lyophilised to give 5g
2
as
a
white powder (230 mg, 90%). 31P{1H} NMR (D2O/CD3CN,
14H; Cm-H, Co-H, C0 -H), 7.63–7.87 ppm (m; 13H; Co’-H, HC=C-CN,
3
C0 -H), 9.98 ppm (s; 3H; CHO), 9.99 ppm (s; 2H; CHO); 13C{1H} NMR
202.54 MHz): d=7.6 (s, PO3HNa), 10.7 (brd, 2JPP =88.7 Hz, P0), 25.3
(brt, 2JPP =88.7 Hz, P’0), 64.0 ppm (s, P1); 1H NMR (D2O/CD3CN,
200.13 MHz): d=3.51 (brs, 16H; CH2-CH2-N), 3.67 (brm, 12H; N-CH3),
4.02(brd, 2JHP =11.9 Hz, 32H; N-CH2-P), 4.10 (brs, 16H; CH2-CH2-N),
(CDCl3, 62.90 MHz): d=21.2 (s, CH2-CH2-CH2-N), 28.0 (s, CH2-CH2-
CH2-N), 35.0 (s, CH2-CH2-NH), 41.4 (s, CH2-CH2-NH), 50.1 (s, CH2-CH2-
CH2-N), 92.9 (s, C-CN), 118.5 (s, CN), 119.5 (s, Cm’), 120.8 (s, Co), 121.3
2
(s, C0 ), 130.0 (s, Cm), 131.1 (s, Co’), 131.4 (2s, C03), 133.6 (s, Ci’), 133.7 (s,
6.94 (brm, 2H; CBP2-H), 7.53 (m, 24H; C0 -H, C1 -H), 7.69 (m, 16H; C1 -
2
2
3
4
1
H), 7.80–7.99 (m, 4H; CBP3-H, CBP5-H), 8.11 (brm, 8H; C0 -H), 8.12ppm
3
C0 ), 136.4 (s, Cp), 147.2(s, C p’), 148.8 (s, Ci), 152.4 (s, C0 ), 154.6 (brs,
HC=C-CN), 162.6 (s, CO), 190.5 (2s, CHO), 190.6 ppm (s, CHO).
(brs, 4H; CH=N); 13C{1H} NMR (D2O/CD3CN, 75.48 MHz): d=29.5 (s,
CH2-CH2-N), 33.1 (d, 2JCP =10.5 Hz, N-CH3), 52.8 (brd, 1JCP =133.4 Hz,
Compound 7c: To an ice-cooled solution of dichlorothiophospho(N-
G
N-CH2-P), 58.3 (brs, CH2-CH2-N), 121.5 (s, CBP2), 121.7 (s, C0 ), 122.0
2
methyl)hydrazide (0.3 mmol) in chloroform (1.5 mL) was added 7b
(100 mg, 0.05 mmol) and the mixture was stirred at RT for 1 h. Upon the
evaporation of the solvent, the residue was diluted in the minimum of di-
chloromethane and precipitated by the addition of a large amount of
pentane. This purification step was repeated three times to give 7c as an
orange solid (87 mg, 90%). 31P{1H} NMR (CDCl3, 81.02MHz): d=10.9
(brs, N3P3), 66.3 ppm (s, P1); 31P{1H} NMR (CDCl3, 202.55 MHz): d=8.4
(s, N3P3), 62.6 (s, P1), 62.7 (s, P1), 62.8 ppm (s, P1); 1H NMR (CDCl3,
500.33 MHz): d=1.98 (tt, 3JHH =6.3, 5.8 Hz, 4H; CH2-CH2-CH2-N), 2.76
(t, 3JHH =6.3 Hz, 4H; CH2-CH2-CH2-N), 2.86 (t, 3JHH =7.2Hz, 2H; HN-
(brs, C1 ), 127.4 (s, CBP or CBP5), 128.5 (s, CBP6), 128.9 (s, C0 ), 130.6 (m,
2
3
3
CBP4, CBP or CBP5), 130.9 (brs, C1 ), 133.2(s, C 4), 134.4 (s, C1 ), 140.4
3
3
4
0
(brs, CH=N), 147.7 (brs, CBP1), 149.9 (d, 2JCP =6.0 Hz, C1 ), 151.4 ppm
1
1
(brs, C0 ).
2-Cyano-N-[2-(4-hydroxyphenyl)ethyl]acetamide (6): To
a solution of
ethyl cyanoacetate (1.00 g, 8.84 mmol) in DMF was added tyramine
(1.28 g, 9.33 mmol), and the mixture was stirred at 1108C for 4 h and at
RT for 12h. The reaction mixture was diluted in an acidic aqueous solu-
tion (pH 3, 50 mL) and was extracted with ethyl acetate (150 mL). The
organic phase was dried over magnesium sulfate, filtered and evaporated
to give a viscous brown solid that was co-evaporated with toluene until
complete removal of DMF. Finally, the residue was washed with dichloro-
CH2-CH2), 3.34 (t, 3JHH =5.8 Hz, 4H; CH2-CH2-CH2-N), 3.59 (m, 2H;
3
HN-CH2-CH2), 3.50 (2d, 3JHP =14.0 Hz, 6H; N-CH3), 3.51 (d, JHP
=
3
14.0 Hz, 9H; N-CH3), 6.26 (t, 3JHH =5.8 Hz, 1H NH), 6.95 (d, JHH
=
2
8.3 Hz, 2H; Co-H), 7.00 (d, 3JHH =8.6 Hz, 4H; C0 -H), 7.04–7.09 (m, 8H;
methane to afford
6
as
a
brown solid (1120 mg, 65%). 1H NMR
2
3
C0 -H, Cm-H), 7.44 (s, 2H; Co’-H), 7.60 (d, 3JHH =8.6 Hz, 10H; C0 -H),
7.64 (s, 3H; CH=N), 7.68 (s, 2H; CH=N), 7.99 ppm (s, 1H; HC=C-CN);
13C{1H} NMR (CDCl3, 125.82 MHz): d=21.1 (s, CH2-CH2-CH2-N), 27.6
(s, CH2-CH2-CH2-N), 32.0 (d, 2JCP =12.9 Hz, N-CH3), 35.2(s, CH2-CH2-
NH), 41.6 (s, CH2-CH2-NH), 50.1 (s, CH2-CH2-CH2-N), 92.8 (s, C-CN),
3
([D6]acetone, 200.13 MHz): d=2.71 (t, JHH =6.7 Hz, 2H; CH2-CH2-NH),
3.41 (t, 3JHH =6.7 Hz, 2H; HN-CH2-CH2), 3.56 (s, 2H; CH2-CN), 6.74–
7.08 (m, 4H; Harom), 7.52(brs, 1H; OH), 8.12 ppm (brs, 1H; NH);
13C{1H} NMR ([D6]acetone, 50.32MHz): d=26.1 (s, CH2-CN), 35.1 (s,
CH2-CH2-NH), 42.3 (s, HN-CH2), 116.0 (s, Co, CN), 130.4 (s, Cm, Cp),
156.6 (s, Ci), 162.7 ppm (s, CO).
2
3
119.5 (s, CN), 120.8 (s, Cm’), 121.2 (s, Co), 121.4 (brs, C0 ), 128.6 (s, C0 ),
129.8 (s, Cm), 131.1 (s, Co’), 131.2(s, C i’), 131,3 (s, C0 ), 135.8 (s, Cp), 140.7
(m, CH=N), 147.2(s, C p’), 151.7 (m, C0 , Ci), 152.4 (s, HC=C-CN),
4
1
2-Cyano-N-[2-(4-hydroxyphenyl)ethyl]-3-(2,3,6,7-tetrahydro-1H,5H-3-for-
mylbenzo(ij)quinolizine)acrylamide (7): A mixture of 2,3,6,7-tetrahydro-
162.6 ppm (s, CO).
1H,5H-3-formylbenzo(ij)quinolizine
(formyljulolidine[29]
)
(130 mg,
Compound 7d: To a solution of 7c (100 mg, 0.052mmol) in THF (5 mL)
0.646 mmol), 6 (198 mg, 0.969 mmol), triethylamine (360 mL, 2.580 mmol)
and THF (14 mL) was heated under reflux for 18 h. The solvent was
evaporated and the residue was purified by silica-gel chromatography (di-
chloromethane/methanol 98:2) to give 7 as an orange solid (160 mg,
67%). 1H NMR ([D6]DMSO, 500.33 MHz): d=1.86 (m, 4H; CH2-CH2-
CH2-N), 2.64 (m, 6H; CH2-CH2-CH2-N, HN-CH2-CH2), 3.31 (m, 6H;
CH2-CH2-CH2-N, HN-CH2-CH2), 6.66–7.01 (m, 4H; Cm-H, Co-H), 7.42(s,
2H; Co’-H), 7.79 (s, 1H; HC=C-CN), 7.97 (t, 3JHH =7.5 Hz, 1H; NH),
9.18 ppm (s, 1H; OH); 13C{1H} NMR ([D6]DMSO, 125.81 MHz): d=21.1
(s, CH2-CH2-CH2-N), 27.6 (s, CH2-CH2-CH2-N), 34.8 (s, CH2-CH2-NH),
42.0 (s, CH2-NH), 49.8 (s, CH2-CH2-CH2-N), 95.2(s, C-CN), 115.6 (s, Co),
119.0 (s, CN), 120.9 (s, Cm’), 129.9 (s, Cm, Cp, Ci’), 130.6 (s, Co’), 147.1 (s,
were added the tyramine-based aza-bis(dimethyl) phosphonate TamBP
G
derivative (198 mg, 0.520 mmol) and cesium carbonate (339 mg,
1.04 mmol) and the mixture was allowed to stir at RT for 12h. The reac-
tion mixture was centrifuged, filtered and evaporated. The residue was
diluted in the minimum of THF and precipitated by the addition of a
large amount of pentane. This purification step was repeated three times
to yield 7d as an orange solid (195 mg, 70%). 31P{1H} NMR (CDCl3,
202.55 MHz): d=8.5 (s, N3P3), 27.0 (2s, PO3Me2), 27.2 (s, PO3Me2), 62.3
(brs, P1), 62.4 ppm (s, P1); 1H NMR (CDCl3, 500.33 MHz): d=1.93 (m,
3
4H; CH2-CH2-CH2-N), 2.69 (m, 4H; CH2-CH2-CH2-N), 2.72 (brt, JHH
=
6.6 Hz, 20H; Ph-CH2-CH2-N), 2.84 (m, 2H; HN-CH2-CH2), 3.01 (t,
3JHH =6.6 Hz, 20H; Ph-CH2-CH2-N), 3.16 (d, 2JHP =9.0 Hz, 24H; N-CH2-
Chem. Eur. J. 2008, 14, 4836 – 4850
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4847