New Journal of Chemistry
ARTICLE
DOI: 10.1039/C 062
Jou5NrnJ0al Na0Ame
gradient of ethyl acetate/hexane starting at a 1:1 ratio. This yielded the reaction) and 16.25 g of Cs CO (50 mmol, 20 eq) and dissolved
2
3
the dendrimer 4-G (2.91 g, 2.72 mmol, 75%) as a yellow oil. in 250 mL of THF. The reaction mixture was stirred overnight at
0
3
1
1
1
P{ H}ꢀNMR (101.3 MHz, CDCl , δ): 7.4 (m, N P ). HꢀNMR (250 room temperature. The mixture was centrifuged, concentrated under
MHz, CDCl , δ): 1.41 (m, 2H, C H ), 1.62 (m, 4H, C H , C H ), reduced pressure, precipitated from pentane/ether and finally put on
3
3 3
(
3)
(2)
(4)
3
2
2
2
(
6)
3
(1)
1
1
.90 (m, 1H, C H ), 2.12 (t, J = 7.4 Hz, 2H, C H CO), 2.40 (m, a small silicagel column to separate the product from the excessive
2 HH 2
(
6)
3
H, C H ), 2.73 (t,
J
= 7.0 Hz, 2H, CH Ar), 3.11 (m, 2H, amount of pꢀhydroxybenzaldehyde. This procedure yielded 5.97 g
2
2
HH
(5)
(
7)
C H S), 3.50 (m, 3H, C HꢀS, CH N), 5.81 (br s, 1H, NH), 6.82 (88%) of dendrimer 4-G in the form of a pale yellow solid.
m, 2H, C H), 7.02 (m, 2H, C H), 7.28 (m, 10H, C H), 7.80 (m,
0H, C H), 9.95 (2 s, 5H, CHO). C{ H}ꢀNMR (62.9 MHz,
2
2
1
2
3
2
31
1
1
(
1
P{ H}ꢀNMR (101.3 MHz, CDCl , δ): 8.2 (s, N P ), 60.4 (s, P ).
T
T
0
3 3 3 1
3
13
1
(3)
HꢀNMR (250 MHz, CDCl , δ): 1.38 (m, 2H, C H ), 1.57 (m, 4H,
0
3
2
(
2/4)
(3)
(2/4)
(4)
(2)
(6)
CDCl , δ): 25.3 (C H ), 28.9 (C H ), 34.6 (C H ), 35.1 C H , C H ), 1.86 (m, 1H, C H ), 2.06 (m, 2H, CH CO), 2.38 (m,
3
2
2
2
2
2
2
2
(
1)
(7)
(6)
(6)
(7)
(
(
(
(
CH Ar), 36.4 (C H CO), 38.5 (C H S), 40.3 (C H ), 40.5 1H, C H ), 2.70 (m, 2H, CH Ar), 3.06 (m, 2H, C H S), 3.36 (m,
2 2 2 2 2 2 2
(
5)
2
2
3
(5)
CH NH), 56.4 (C H), 120.7 (C ), 121.3 (C ), 129.9 (C ), 131.4 18H, C HꢀS, CH NH, P ꢀNꢀCH ), 5.98 (s, 1H, NH), 6.96 (m, 2H,
2
T
0
T
2
1
3
3
4
4
1
1
2
2
3
2
C ), 133.7 (C ), 136.6 (C ), 154.7 (C , C ), 172.8 (NCO), 190.5 C H), 7.03 (m, 12H, C H, C H), 7.34 (m, 20H, C H), 7.56 (m,
0
0
T
0
T
T
0
T
1
3
CHO).
10H, C H), 7.65 (s, 3H, CH=NꢀN), 7.67 (s, 2H, CH=NꢀN), 7.81 (m,
0
3
13
1
2
0H, C H), 9.93 (s, 10H, CHO). C{ H}ꢀNMR (62.9 MHz, CDCl ,
1 3
(
2/4)
(3)
2
δ): 25.4 (C H ), 28.8 (C H ), 32.8 (d, J = 12.8 Hz, P ꢀNꢀCH ),
Bifunctional dendrimer 5-G . A 56.7 mL 0.24 M solution of
H NNMePSCl (1.26 mmol, 5 eq.) in chloroform was added to a 50
2
2
CP
1
3
1
(
2/4)
(1)
(7)
3
(
1
1
4.6 (C H ), 35.0 (CH Ar), 36.2 (C H ), 38.4 (C H S), 40.2
2 2 2 2
2
2
(
6)
(5)
2
2
C H ), 40.5 (CH NH), 56.5 (C HꢀS), 121.0 (C ), 121.4 (C ),
mL solution of 4-G (2.906 g, 2.72 mmol, 1.0 eq) in chloroform.
2
2
T
0
0
3
2
3
3
4
21.8 (d, J = 6.8 Hz, C ), 128.3 (C ), 129.7 (C ), 131.4 (C ),
CP 1 1 T 1
31.8 (C ), 133.7 (C ), 135.8 (C ), 139.7 (d, JCP = 13.4 Hz,
After one night the amount of solvent was reduced to a few
milliliters and then added dropwise to a large amount of pentane.
The product precipitated readily and the solvent was filtered off by
means of a canula. This process was repeated three times. Dendrimer
3
4
4
3
0
0
T
2
1
1
2
CH=NꢀNꢀP ), 151.5 (d, J = 7.0 Hz, C , C ), 155.0 (d, J = 7.0
1
CP
0
T
CP
1
Hz, C ), 172.8 (NCO), 190.7 (CHO).
1
5
-G was obtained as a white (pale yellow) solid with a yield of 4.68
1
3
1
1
Bifunctional dendrimer 7-G . Compound 4-G1 (1.00 g, 0.367
mmol, 1.0 eq), 0.95 g of malonic acid (9.17 mmol, 25 eq) and 45 µL
g (2.50 mmol, 92%). P{ H}ꢀNMR (121.5 MHz, CDCl , δ): 8.3 (m,
N P ), 62.4/62.6 (s, P ). HꢀNMR (300 MHz, CDCl , δ): 1.41 (m,
2
1
3
1
3
3
1
3
(
3)
(2)
(4)
(6)
of freshly distilled (on CaH ) piperidine (0.459 mmol, 1.25 eq) were
H, C H ), 1.63 (m, 4H, C H , C H ), 1.85 (m, 1H, C H ), 2.12
2
2
2
2
2
3
(1)
(6)
3
dissolved in 15 mL of freshly distilled pyridine (on CaH ) and left to
(t, J = 7.2 Hz, 2H, C H CO), 2.45 (m, 1H, C H ), 2.77 (t, J
2
HH
2
2
HH
(
7)
stir overnight at 95°C. The mixture was then refluxed for 15 minutes
=
3
7.2 Hz, 2H, CH Ar), 3.14 (m, 17H, C H S, P ꢀNꢀCH ), 3.45 (m,
2 2 1 3
H, C HꢀS, CH N), 5.64 (br s, 1H, NH), 6.91ꢀ7.06 (m, 12H, C H,
(
5)
2
more to remove the CO and let to cool down before precipitating it
2
2
T
2
3
3
on ice cooled HCl (37%). The precipitate was subsequently washed
with water (3 times) and ether (2 times) and dried under vacuum. In
order to obtain the sodium salt, the product was taken into water and
C H), 7.58ꢀ7.65 (m, 12H, C H, C H), 7.70 (s, 5H, CH=N).
0
T
0
13
1
(2/4)
(3)
C{ H}ꢀNMR (75.5 MHz, CDCl , δ): 25.4 (C H ), 28.9 (C H ),
3
2
2
2
(2/4)
3
3
2.0 (d, J = 13.2 Hz, P ꢀNꢀCH ), 34.6 (C H ), 35.2 (CH Ar),
CP 1 3 2 2
(
1)
(7)
(6)
1
2.25 mL of 0.1996 M NaOH (aq) (excess) was added dropwise
6.4 (C H ), 38.5 (C H S), 40.3 (C H ), 40.7 (CH NH), 56.5
2
2
2
2
(
5)
2
2
3
3
yielding a slightly turbid solution. The overall yield was 0.811 g of
(
(
(
C H), 121.1 (C ), 121.4 (C ), 128.6 (C ), 129.7 (C ), 131.3
C ), 135.9 (C ), 140.8 (br d, J = 20.1 Hz, CH=NꢀNꢀP ), 149.0
C ), 151.7 (C ), 173.0 (NCO).
T 0 0 T
4
4
3
the sodium salt 7-G (241 µmol, 66%). The NMR spectra were
1
0
T
CP
1
1
1
recorded before ion exchange (COOH terminated dendrimer).
T
0
3
1
1
1
P{ H}ꢀNMR (121.5 MHz, DMSOꢀd , δ): 8.4 (s, N P ), 62.0 (s, P ).
6
3
3
1
(3)
HꢀNMR (300 MHz, DMSOꢀd , δ): 1.22 (m, 2H, C H ), 1.42 (m,
H, C H , C H ), 1.75 (m, 1H, C H ), 1.96 (m, 2H, CH CO),
.29 (m, 1H, C H ), 2.58 (m, 2H, CH Ar), 3.04 (m, 2H, C H S),
.27ꢀ3.41 (m, 18H, C HꢀS, CH NH, P ꢀNꢀCH ), 5.35 (br s, 1H,
6
2
Bifunctional dendrimer 6-G . N,Nꢀdiethylethylenediamine (765
µL, 5.35 mmol, 10 eq) was added dropwise to a 150 mL THF
solution of 5-G (1.002 g, 5.36 mmol, 1.0 eq). The reaction was left
to stir at room temperature overnight. A white solid appeared during
the reaction. The precipitate was washed with dry THF and
diethylether and lyophilized. Dendrimer 6-G1 was obtained as a
white powder (1.226 g, 405 µmol, 76 %). P{ H}ꢀNMR (121.5
MHz, CD OD, δ): 8.5 (s, N P ), 70.4 (s, P ). HꢀNMR (300 MHz,
1
(
4)
(2)
(6)
4
2
3
2 2 2 2
(
6)
(7)
2
2
2
1
(
5)
2
1
3
3
NH), 6.43 (d, J = 15.9 Hz, 10H, CH=CHCO ), 6.80 (m, 2H,
HH
2
2
3
2
2
C H), 7.03 (m, 12H, C H, C H), 7.16 (m, 20H, C H), 7.19 (d,
T
T
0
1
3
3
3
3
1
1
JHH = 15.9 Hz, 10H, CH=CHCO ), 7.61 (m, 30H, C H, C H), 7.85
2 0 1
1
(s, 3H, CH=NꢀN), 7.91 (s, 2H, CH=NꢀN), 12.4 (s, 10H, COOH).
3
3
3
1
13
1
(2/4)
3
C{ H}ꢀNMR (75.5 MHz, DMSOꢀd , δ): 25.5 (C H ), 28.8
6
2
CD OD, δ): 1.26 (t, J = 7.2 Hz, about 10H, NCH CH ), 1.33 (t,
3
HH
2
3
(
3)
2
(2/4)
3
+
(3)
(C H ), 33.4 (2d, J = 11.9 Hz, P ꢀNꢀCH ), 34.6 (C H ), 34.9
2 CP 1 3 2
(CH Ar), 35.7 (C H ), 38.5 (C H S), 56.5 (C HꢀS), 119.9 (Arꢀ
CH=CH), 120.7 (C ), 121.4 (C ), 121.8 (d, J = 4.1 Hz, C ),
T 0 CP 1
128.7 (C ), 129.0 (C ), 130.2 (C ), 132.2 (C ), 132.4 (C ), 137.2
(C ), 141.1 (CH=NꢀN), 143.1 (ArꢀCH=CH), 148.4 (C ), 151.0
T T
(C ), 151.7 (C ), 167.9 (COOH), 172.3 (NCO). (C H and
JHH = 7.2 Hz, about 50H, N CH CH ), 1.40 (m, 2H, C H ), 1.66
2
3
2
(
1)
(7)
(5)
(
2)
(4)
(6)
3
2 2 2
(m, 4H, C H , C H ), 1.85 (m, 1H, C H ), 2.16 (t, J = 7.2 Hz,
2 2 2 HH
2
2
3
2
(
1)
(6)
3
2
H, C H CO), 2.43 (m, 1H, C H ), 2.78 (t, J = 7.2 Hz, 2H,
2 2 HH
3
3
3
4
4
3
0 T 1 1 0
CH Ar), 2.97 (q, J = 7.2 Hz, about 6H, NCH CH ), 3.12 (m, 2H,
C H S), 3.15ꢀ3.50 (m, 91H, C HꢀS, CH N, P ꢀNꢀCH ,
N CH CH ), 6.82 (m, 2H, C H), 7.00ꢀ7.11 (m, 12H, C H, C H),
7
2
HH
2
3
4
1
(
7)
(5)
2
2
1
3
1
1
(6)
+
2
3
2
0
1
2
2
3
T
T
0
3
13
1
CH NH hidden by DMSO).
2
.70ꢀ7.81 (m, 15H, C H, CH=NꢀNꢀP ). C{ H}ꢀNMR (75.5 MHz,
0
1
+
(2/4)
CD OD, δ): 7.8 (N CH CH ), 9.0 (NCH CH ), 25.4 (C H ), 28.5
3
2
3
2
3
2
(
3)
2
(2/4)
Bifunctional dendrimer 5-G . To an ice cooled 70 mL CHCl
2 3
(C H ), 31.4 (2d, J = 10.6 Hz, P ꢀNꢀCH ), 34.4 (C H ), 35.5
2 CP 1 3 2
(
1)
(7)
(6)
solution of 3.97 g of compound 4-G (1.46 mmol, 1.0 eq) were
1
(CH Ar), 36.2 (C H CO, CH ꢀNꢀP ), 38.0 (C H S), 40.0 (C H ),
2 2 2 1 2 2
3
added 64 mL (0.24 M, 15.3 mmol, 10.5 eq) of H NNMeP(S)Cl in
2
2
4
0.4 (CH NHCO), 49.0 (NꢀCH CH ), 52.2 (d, J = 6.9 Hz, P ꢀNꢀ
2 2 3 CP 1
(
5)
2
2
3
CHCl . The reaction mixture was stirred at room temperature for two
3
CH CH ), 56.5 (C HꢀS), 120.5 (C ), 120.9 (C ), 128.0 (C ),
1
2
2
T
0
0
3
4
4
hours and checked with NMR for completion. The volume of CHCl3
was reduced and the mixture was precipitated from pentane several
times until the excess of H NNMeP(S)Cl was completely removed.
29.7 (C ), 133.2 (C ), 136.4 (C ), 137.7 (m, CH=NꢀNꢀP ), 150.8
T 0 T 1
1
1
(m, C , C ), 174.5 (NCO).
0 T
2
2
Dendrimer 5-G was obtained as a pale yellow solid in 94% yield
2
Bifunctional dendrimer 4-G . In a Schlenk tube under argon
31
1
1
(
5.97 g, 1.37 mmol). P{ H}ꢀNMR (121.5 MHz, CDCl , δ): 8.3 (s,
3
atmosphere were mixed 4.68 g of 5-G (2.50 mmol, 1.0 eq), 7.00 g
1
1
N P ), 61.9 (s, P ), 62.8 (s, P ). HꢀNMR (300 MHz, CDCl , δ): 1.35
3
3
1
2
3
of pꢀhydroxybenzaldehyde (57.4 mmol, 23 eq, excess to accelerate
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012