5902
R. Castillo et al. / Tetrahedron Letters 48 (2007) 5899–5903
17. (a) Zoller, T.; Ducep, J. B.; Hibert, M. Tetrahedron Lett.
1,3-Bis[3,5-bis(pyridin-1-ium-quinolin-2-ylaminomethyl)phen-
oxymethyl]benzene tetrabromide (6b): Brown solid,
(259 mg, 84%), mp > 190 °C (dec); IR (KBr): mmax
(cmꢀ1) 3004, 2932, 1617, 1598, 1504, 1471, 1430, 1324,
1214, 1163, 1046, 813, 676; 1H NMR (500 MHz, CD3OD):
d (ppm) 9.18 (8H, dd, J = 6.9 and 1.3 Hz; H2(6)), 8.72
(4H, tt, J = 7.7 and 1.3 Hz, H4), 8.34 (4H, d, J = 8.9 Hz,
H40), 8.21 (8H, dd, J = 7.7 and 6.9 Hz, H3(5)), 7.89 (4H,
br d, J = 8.2 Hz, H50), 7.67 (4H, ddd, J = 8.5, 6.9 and
1.4 Hz, H70), 7.57 (4H, br d, J = 8.5 Hz, H80), 7.51 (4H,
`
2000, 41, 9985–9988; (b) Hawker, C. J.; Frechet, J. M. J.
J. Am. Chem. Soc. 1990, 112, 7638–7647; (c) Leduc, M. R.;
`
Hawker, C. J.; Dao, J.; Frechet, J. M. J. J. Am. Chem. Soc.
1996, 118, 11111–11118.
18. Synthesis
of
1,3-bis[3,5-bis(bromomethyl)phenoxy-
methyl]benzene (3b): Alcohol 3a13 (410 mg, 1 mmol) and
PPh3 (4.4 mmol) were dissolved in dichloromethane
(150 mL) in a round-bottom flask and the mixture was
cooled to 0 °C. Under vigorous stirring NBS (4.4 mmol)
was added portionwise to the reaction mixture. After the
addition, the flask was placed in an ultrasonic bath for
90 min. As soon as the starting material had been
consumed (detected by TLC) the solvent was removed in
vacuo and the residue was purified by chromatography
(silica gel/CH2Cl2). Compound 3b was isolated as a white
solid (476 mg, 72%), mp: 146–147 °C; IR (KBr): mmax
(cmꢀ1) 2938, 2882, 1593, 1443, 1335, 1296, 1212, 1179,
1040, 853, 697, 553; 1H NMR (300 MHz, CDCl3): d (ppm)
7.49 (1H, br s, H2Xyl), 7.40 (3H, m, H4Xyl(6Xyl) and 5Xyl),
7.01 (2H, t, J = 1.5 Hz, H40), 6.93 (4H, d, J = 1.5 Hz,
H20(60)), 5.07 (4H, s, CH2O), 4.41 (4H, s, CH2Br); 13C
NMR (75 MHz, CDCl3): d (ppm) 159.1 (C1Ar), 139.7
(C3Ar(5Ar)), 136.9 (C1Xyl(3Xyl)), 129.0 (C2Xyl), 127.3
(C4Xyl(6Xyl)), 126.6 (C5Xyl), 122.2 (C4Ar), 115.5
(C2Ar(6Ar)), 70.0 (CH2O), 32.8 (CH2Br). Anal. Calcd for
C24H22Br4O2: C, 43.54; H, 3.35. Found C, 43.21; H,
3.22.
ddd, J = 8.2, 6.9 and 1.3 Hz, H60), 7.35 (4H, m, H2Xyl
,
H4Xyl(6Xyl) and H5Xyl), 7.29 (4H, d, J = 8.9 Hz, H30), 7.28
(2H, ap t, J = 1.4 Hz, H4Ar), 7.15 (8H, d, J = 1.4 Hz,
H2Ar(6Ar)), 5.53 (8H, s, CH2N), 5.12 (4H, s, CH2O); 13C
NMR (75 MHz, CD3OD): d (ppm) 161.0 (C1Ar), 156.5
(C20), 149.8 (C2(6)), 149.3 (C4), 147.3 (C80a), 141.3 (C40),
138.7 (C1Xyl(3Xyl)), 138.2 (C3Ar(5Ar)), 131.9 (C70), 130.6
(C3(5)), 129.9 (C5Xyl), 128.9 (C50), 128.6 (C80), 128.3
(C4Xyl(6Xyl)), 127.9 (C2Xyl), 127.0 (C40a), 126.9 (C60),
122.8 (C4Ar), 117.1 (C2Ar(6Ar)), 111.0 (C30), 70.9 (CH2O),
58.6 (CH2N).
21. For compounds 5b and 6c, due to the low solubility of
aminides 4b and 4e in AcOEt, washing was done with
acetone.
22. (a) Reyes, M. J.; Burgos, C.; Izquierdo, M. L.; Alvarez-
Builla, J. Tetrahedron 2004, 60, 1093–1097; (b) Reyes, M.
J.; Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron Lett.
2004, 45, 8713–8715.
´
´
´
´
19. (a) Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.;
23. Burgos, C.; Delgado, F.; Garcıa-Navıo, J. L.; Izquierdo,
M. L.; Alvarez-Builla, J. Tetrahedron 1995, 31, 8649–
8654.
Alvarez-Builla, J. Tetrahedron Lett. 1993, 34, 2019–2020;
´
´
(b) Carceller, R.; Garcıa-Navıo, J. L.; Izquierdo, M. L.;
´
Alvarez-Builla, J.; Fajardo, M.; Gomez-Sal, P.; Gago, F.
24. Synthesis of N-[5-(4-hydroxymethylphenyl)pyridin-2-yl]-
pyridinium aminide (4e): Pd(PPh3)4 (57 mg, 5 mmol %), 4-
hydroxymethylphenylboronic acid (1.5 mmol) and pyrid-
inium N-(5-bromo-pyridin-2-yl) aminide23 (1 mmol) were
dissolved in a toluene:ethanol mixture (4:1, 15 mL).
K2CO3 (10 mmol) was added and the mixture was stirred
under argon and heated under reflux for 8 h. The system
was allowed to reach room temperature, the catalyst and
inorganic salts were filtered off through Celite and washed
with acetonitrile until no color was observed in the filtrate.
The combined filtrates were evaporated to dryness. The
crude residue was purified by flash chromatography on a
silica gel column with ethanol as the eluent. Compound 4e
was obtained as a red solid (255 mg, 92%, toluene), mp
168–169 °C; IR (KBr): mmax (cmꢀ1) 3233, 2850, 1599, 1465,
1374, 1328, 1146, 1042, 1008, 808, 761, 518; 1H NMR
(300 MHz, CD3OD): d (ppm) 8.80 (2H, dd, J = 7.0 and
1.2 Hz, H2(6)); 8.05 (1H, tt, J = 7.7 and 1.2 Hz, H4); 7.98
(1H, dd, J = 2.5 and 0.7 Hz, H60); 7.83 (2H, dd, J = 7.7
and 7.0 Hz, H3(5)); 7.72 (1H, dd, J = 8.8 and 2.5 Hz,
H40); 7.50 (2H, ap d, J = 8.4 Hz, H200(600)); 7.39 (2H, ap d,
J = 8.4 Hz, H300(500)); 6.62 (1H, dd, J = 8.8 and 0.7 Hz,
H30); 4.63 (2H, s, CH2); 13C NMR (75 MHz, CD3OD): d
164.9 (C20), 144.8 (C2(6)), 144.6 (C60), 140.7 (C400), 139.0
(C100), 137.8 (C4), 137.0 (C40), 128.7 (C300(500)), 128.5
(C3(5)), 126.4 (C200(600)), 125.3 (C50), 112.3 (C30), 70.0
(CH2). MS (CI, m/z): 278 (100, M + 1), 277 (47), 260 (25),
201 (65). HRMS (ESI-TOF, CH3OH): [M+H]+ calcd for
C17H16N3O, 278.12879; found, 278.13210.
´
Tetrahedron 1994, 50, 4995–5012; (c) Garcıa de Viedma,
A.; Martinez-Barrasa, V.; Burgos, C.; Izquierdo, M. L.;
Alvarez-Builla, J. J. Org. Chem. 1999, 64, 1007–1010; (d)
Martınez-Barrasa, V.; Delgado, F.; Burgos, C.; Garcıa-
´
´
´
Navıo, J. L.; Izquierdo, M. L.; Alvarez-Builla, J. Tetra-
hedron 2000, 56, 2481–2490; (e) Reyes, M. J.; Delgado, F.;
Izquierdo, M. L.; Alvarez-Builla, J. Tetrahedron 2002, 58,
8573–8579.
20. General procedure for the alkylation of pyridinium N-
aminides 4 with tetrabromo derivatives 2b or 3b: In a flame-
dried round-bottom flask under an inert atmosphere, the
corresponding tetrabromo derivative 2b or 3b (0.2 mmol)
and aminide 4 (1 mmol) were suspended in DMF (5 mL).
The reaction was stirred at room temperature for 72 h
until the halogenated derivative had been consumed
(detected by TLC). The solvent was removed under
vacuum, the crude product was redissolved in the mini-
mum volume of DMF (ꢁ1 mL) and the solution was
added to vigorously stirred AcOEt (50 mL). The solid
precipitate was filtered off and recrystallized from EtOH
and a few drops of MeOH to give the corresponding pure
tetra-salts 5 and 6 as brownish solids.
1,6-Bis[3,5-bis(pyridin-1-ium-pyridin-2-ylaminomethyl)phen-
oxy]hexane tetrabromide (5a): brownish solid (225 mg,
85%), mp > 162 °C (dec); IR (KBr): mmax (cmꢀ1): 3010,
2935, 1595, 1470, 1432, 1298, 1160, 776, 746, 685; 1H
NMR (500 MHz, CD3OD): d (ppm) 9.23 (8H, dd, J = 6.4
and 1.4 Hz, H2(6)), 8.74 (4H, tt, J = 7.8 and 1.4 Hz, H4),
8.22 (12H, m, H3(5) and 60), 7.90 (4H, ddd, J = 8.7, 7.5
and 1.7 Hz, H40), 7.19 (10H, m, H30, H50 and H4Ar), 7.00
(4H, d, J = 1.0 Hz, H2Ar (H6Ar)), 5.58 (8H, s, CH2N), 3.98
(4H, t, J = 6.4 Hz, CH2O), 1.76 (4H, m, CH2b), 1.52 (4H,
m, CH2c); 13C NMR (125 MHz, CD3OD): d (ppm) 161.6
(C1Ar), 158.3 (C20), 149.7 (C2(6)), 149.2 (C60), 149.2 (C4),
140.6 (C40), 137.8 (C3Ar(5Ar)), 130.6 (C3(5)), 122.4 (C4Ar),
120.8 (C30), 116.5 (C2Ar(6Ar)), 111.0 (C50), 69.4 (CH2O),
58.6 (CH2N), 30.2 (CH2b), 26.9 (CH2c).
´
´
25. Sanchez, A.; Nunez, A.; Burgos, C.; Alvarez-Builla, J.
˜
Tetrahedron Lett. 2006, 47, 8343–8346.
26. General procedure for the reduction of pyridinium tetrakis
salts 5 and 6: In a round-bottom flask the corresponding
tetra-salt 5 or 6 (0.1 mmol) was dissolved in AcOH/MeOH
(2:1, 30 mL). Zn dust (40 mmol) was added and the
mixture was stirred at room temperature for 12 h. During
this time a color change was observed. The crude mixture
was evaporated to dryness and treated with a mixture of