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V. Martınez-Barrasa et al. / Tetrahedron 56 (2000) 2481–2490
2487
1-[Benzyl(3, 5-dibromopyridin-2-yl)amino]pyridinium
bromide (7n). Reaction time, 48 h. White solid (3.55 g,
71%, methanol/ethyl acetate), mp 124–126ЊC; [Found: C,
40.80; H, 2.59; N, 8.71. C17H14Br3N3 requires C, 41.06; H,
2.84; N, 8.45%]; Rf (10% triethylamine/ethanol) 0.15; nmax
(KBr) 3020, 1668, 1612, 1421, 1365, 1046 cmϪ1; dH
(300 MHz. CD3OD) 9.24 (2H, d, J5.9 Hz, H2(6)), 8.62
(1H, t, J7.7 Hz, H4), 8.59 (1H, d, J1.8 Hz, H60), 8.48
(1H, d, J1.8 Hz, H40), 8.09 (2H, dd, J7.7, 5.9 Hz,
H3(5)), 7.47–7.44 (2H, m, H-Ph), 7.32–7.30 (3H, m,
H-Ph), 5.19 (2H, s, CH2-N).
(1H, d, J8.6 Hz, H30), 7.05 (1H, dd, J7.1, 5.5 Hz, H50),
4.95 (1H, t, J5.1 Hz, OH), 4.23 (2H, t, J5.1 Hz, CH2-N),
3.68 (2H, q, J5.1 Hz, CH2-OH).
1-[1-(2-Hydroxyethyl)-1H-pyridin-2-ylideneamino]pyri-
dinium bromide (23). White plates (0.27 g, 9%, ethanol),
mp 168–170ЊC; [Found: C, 48.42; H, 4.96; N, 14.20.
C12H14BrN3O requires C, 48.67; H, 4.76; N, 14.19%]; Rf
(10% triethylamine/ethanol) 0.17; nmax(KBr) 3323, 3293,
3059, 1639, 1550, 1071, 763 cmϪ1; dH (300 MHz. DMSO-
d6) 8.86 (2H, d, J5.9 Hz, H2(6)), 8.44 (1H, t, J7.7 Hz,
H4), 8.13 (2H, dd, J7.7, 5.9 Hz, H3(5)), 7.80 (1H, dd,
J6.5, 1.4 Hz, H60), 7.46 (1H, ddd, J9.1, 6.5, 1.4 Hz,
H40), 6.43 (1H, bt, J6.5 Hz, H50), 6.05 (1H, d,
J9.1 Hz, H30), 4.98 (1H, t, J5.5 Hz, OH), 4.20 (2H, t,
J5.5 Hz, CH2-N), 3.84 (2H, q, J5.5 Hz, CH2-OH).
1-[4-Bromobenzyl(pyridin-2-yl)amino]pyridinium bro-
mide (7p). Reaction time, 48 h. White solid (3.24 g, 77%,
ethanol), mp 188–190ЊC; [Found: C, 48.57; H, 3.60; N,
10.10. C17H15Br2N3 requires C, 48.49; H, 3.59; N, 9.98%];
Rf (10% triethylamine/ethanol) 0.17; nmax (KBr) 3429,
3033, 1582, 1269, 1172, 786 cmϪ1; dH (300 MHz. DMSO-
d6) 9.34 (2H, dd, J6.7, 1.2 Hz, H2(6)), 8.76 (1H, bt,
J7.8 Hz, H4), 8.29 (2H, dd, J7.8, 6.7 Hz, H3(5)), 8.19
(1H, dd, J5.0, 1.9 Hz, H60), 7.91 (1H, ddd, J8.4, 7.4,
1.9 Hz, H40), 7.55 (2H, d, J8.4 Hz, H-Ph), 7.39 (2H, d,
J8.4 Hz, H-Ph), 7.21 (1H, d, J8.4 Hz, H30), 7.16 (2H,
dd, J7.4, 5.0 Hz, H50), 5.40 (2H, s, CH2-N).
1-[Benzyl(pyrimidin-2-yl)amino]pyridinium bromide (8a).
This compound appeared as a mixture with the regioisomer
19a and was used in the next step without further purifica-
tion. Reaction time, 24 h. (2.74 g, 75% total yield, 55% for
8a), Rf (10% triethylamine/ethanol) 0.15, dH (300 MHz.
DMSO-d6) 9.31 (2H, dd, J6.9, 1.5 Hz, H2(6)), 8.75 (1H,
t, J7.7 Hz, H4); 8.64 (2H, d, J4.8 Hz, H40 (60)); 8.26
(2H, dd, J7.7, 6.9 Hz, H3(5)); 7.40–7.28 (5H, m, H-Ph);
7.22 (1H, t, J4.8 Hz, H50); 5.52 (2H, s, CH2-N). Regio-
isomer 19a (25%), Rf (10% triethylamine/ethanol) 0.15, dH
(300 MHz. DMSO-d6) 8.87 (2H, dd, J7.0, 1.6 Hz, H2(6)),
8.55 (1H, d, J5.5 Hz, H40); 8.45 (1H, d, J6.1 Hz, H60);
8.41 (1H, t, J7.7 Hz, H4); 8.05 (2H, dd, J7.7, 7.0 Hz,
H3(5)); 7.51–7.40 (5H, m, H-Ph); 6.72 (1H, dd, J6.1,
5.5 Hz, H50); 3.39 (2H, s, CH2-N).
1-[4-Methylbenzyl(pyridin-2-yl)amino]pyridinium bro-
mide (7q). Reaction time, 96 h. White solid (3.20 g, 90%,
ethanol), mp 192–194ЊC; [Found: C, 60.58; H, 4,79; N,
11.56. C18H18BrN3 requires C, 60.83; H, 5.09; N,
11.83%]; Rf (10% triethylamine/ethanol) 0.18; nmax(KBr)
3383, 3012, 2985, 1582, 1226, 780 cmϪ1; dH (300 MHz.
DMSO-d6) 9.29 (2H, dd, J6.8, 1.3 Hz, H2(6)), 8.70 (1H,
tt, J7.9, 1.3 Hz, H4), 8.22 (2H, dd, J7.9, 6.8 Hz, H3(5)),
8.16 (1H, dd, J5.1, 1.8 Hz, H60), 7.89 (1H, ddd, J8.4,
7.2, 1.8 Hz, H40), 7.27–7.21 (3H, m, H30, H-Ph), 7.13 (1H,
dd, J7.2, 5.1 Hz, H50), 7.11 (2H, d, J7.7 Hz, H-Ph), 5.34
(2H, s, CH2-N), 2.23 (3H, s, Me).
1-[4-Bromobenzyl(pyrimidin-2-yl)amino]pyridinium
bromide (8b). This compound appeared as a mixture with
the regioisomer 19b and was used in the next step without
further purification. Reaction time, 36 h. (3.04 g, 72% total
yield, 48% for 8b), Rf (10% triethylamine/ethanol) 0.15, dH
(300 MHz. DMSO-d6) 9.31 (2H, d, J5.5 Hz, H2(6)), 8.75
(1H, t, J7.0 Hz, H4); 8.62 (2H, d, J4.8 Hz, H40 (60));
8.30 (2H, bt, J7.3 Hz, H3(5)); 7.52 (2H, d, J8.4 Hz,
H-Ph); 7.35 (2H, d, J8.4 Hz, H-Ph), 7.21 (1H, t, J
4.8 Hz, H50); 5.48 (2H, s, CH2-N). Regioisomer 19b
(24%), Rf (10% triethylamine/ethanol) 0.15, dH
(300 MHz. DMSO-d6) 8.80 (2H, d, J6.5 Hz, H2(6)),
8.56 (1H, d, J5.4 Hz, H40); 8.40 (1H, d, J5.6 Hz, H60);
8.33 (1H, t, J7.5 Hz, H4); 8.05 (2H, dd, J7.5, 6.5 Hz,
H3(5)); 7.60 (2H, d, J8.4 Hz, H-Ph); 7.45 (2H, d,
J8.4 Hz, H-Ph); 6.70 (1H, dd, J5.6, 5.4 Hz, H50); 5.29
(2H, s, CH2-N).
1-[4-Nitrobenzyl(pyridin-2-yl)amino]pyridinium bro-
mide (7r). Reaction time, 48 h. White solid (2.09 g, 54%,
ethanol), mp 185–187ЊC; [Found: C, 52.53; H, 4.03; N,
14.20. C17H15BrN4O2 requires C, 52.73; H, 3.90; N,
14.47%]; Rf (10% triethylamine/ethanol) 0.19; nmax (KBr)
3355, 3026, 2951, 1595, 1425, 786 cmϪ1; dH (300 MHz.
DMSO-d6) 9.42 (2H, dd, J6.8, 1.4 Hz, H2(6)), 8.80 (1H,
tt, J7.8, 1.4 Hz, H4), 8.32 (2H, dd, J7.8, 6.8 Hz, H3(5)),
8.22–8.19 (3H, m, H60, H-Ph), 7.89 (1H, ddd, J8.5, 7.3,
1.7 Hz, H40), 7.78 (2H, d, J8.4 Hz, H-Ph), 7.17 (1H, dd,
J7.3, 5.0 Hz, H50), 7.09 (1H, d, J8.5 Hz, H30), 5.59 (2H,
s, CH2-N).
1-[2-Hydroxyethyl(pyridyn-2-yl)amino]pyridinium bro-
mide (7s). This compound appeared as a mixture with the
regioisomer 23. Separation by fractional crystallization
(ethanol) provides the pure compound. Reaction time,
216 h. White solid (0.80 g, 27%, ethanol), mp 100–102ЊC;
[Found: C, 48.40; H, 4.96; N, 14.27. C12H14BrN3O requires
C, 48.67; H, 4.76; N, 14.19%]; Rf (10% triethylamine/
ethanol) 0.17; nmax(KBr) 3345, 3323, 3049, 2953, 1583,
1047, 885 cmϪ1; dH (300 MHz. DMSO-d6) 9.36 (2H, dd,
J6.6, 1.5 Hz, H2(6)), 8.81 (1H, tt, J7.9, 1.5 Hz, H4),
8.33 (2H, dd, J7.9, 6.6 Hz, H3(5)), 8.09 (1H, dd, J5.5,
1.8 Hz, H60), 7.83 (1H, ddd, J8.6, 7.1, 1.8 Hz, H40), 7.09
1-[4-Methylbenzyl(pyrimidin-2-yl)amino]pyridinium
bromide (8c). This compound appeared as a mixture with
the regioisomer 19c and was used in the next step without
further purification. Reaction time, 36 h. (2.61 g, 73% total
yield, 49% for 8c), Rf (10% triethylamine/ethanol) 0.15, dH
(300 MHz. DMSO-d6) 9.28 (2H, dd, J7.0, 1.4 Hz, H2(6)),
8.75 (1H, tt, J7.7, 1.4 Hz, H4); 8.63 (2H, d, J5.1 Hz, H40
(60)); 8.26 (2H, dd, J7.7, 7.0 Hz, H3(5)); 7.24–7.20 (3H,
m, H50, H-Ph); 7.10 (2H, d, J7.7 Hz, H-Ph), 5.47 (2H, s,
CH2-N), 2.23 (3H, s, Me). Regioisomer 19c (24%), Rf (10%
triethylamine/ethanol) 0.15, dH (300 MHz. DMSO-d6) 8.80
(2H, d, J6.5 Hz, H2(6)), 8.56 (1H, d, J5.4 Hz, H40); 8.41