Zong et al.
SO4, and concentrated under vacuum. The residue was purified by
chromatography on silica eluting with hexanes/ethyl acetate
(85:15) to afford an orange oil (880 mg, 60%): 1H NMR (CDCl3)
δ 7.73 (s, 2H), 5.73 (d, 2H, J ) 2.4 Hz), 4.43 (d, 2H, J ) 2.4 Hz),
3.94 (q, 4H, J ) 6.9 Hz), 1.39 (t, 6H, J ) 6.9 Hz).
washed with EtOH (5 mL). Recrystallization of the residue from
CHCl3/Et2O (1:1) afforded a beige solid (55 mg, 22%), mp > 300
°C: 1H NMR (CDCl3) δ 9.18 (dd, J ) 2.1, 4.2 Hz, 2H), 8.92 (dd,
J ) 0.9, 8.1 Hz, 2H), 8.91 (d, J ) 8.1 Hz, 2H), 8.37 (d, J ) 8.7
Hz, 2H), 8.27 (dd, J ) 1.8, 7.8 Hz, 2H), 7.96 (t, J ) 7.5 Hz, 2H),
7.78 (dd, J ) 0.9 Hz, 7.8 Hz, 2H), 7.54 (dd, J ) 4.2, 8.1 Hz, 2H);
MS (ESI) m/z 437 (M)+, 495 (M + 58)+. Anal. Calcd for C28H16N6‚
0.75 H2O: C, 74.74; H, 3.92; N, 18.68. Found: C, 74.75; H, 3.38;
N, 18.40.
3,6-Di-(6′-[1′′,8′′-naphthyrid-2′′-yl]-pyridin-2′-yl)pyridazine (6).
A suspension of 3,6-di-(6′-acetylpyrid-2′-yl)pyridazine (18, 55 mg,
0.17 mmol), 2-aminonicotinaldehyde (52 mg, 0.43 mmol), and
saturated ethanolic KOH (0.3 mL) in absolute ethanol (15 mL) was
refluxed for 24 h. The resulting mixture was concentrated to about
3 mL, water (3 mL) was added, and the precipitate was filtered
and washed with ethanol (2 mL) and ether (2 mL) to afford an
off-white solid (72 mg, 85%), mp > 300 °C: 1H NMR (CDCl3 +
CH3OD) δ 9.15 (dd, J ) 4.2, 2.4 Hz, 2H), 8.98-8.91 (m, 6H),
8.86 (d, J ) 8.1 Hz, 2H), 8.40 (dd, J ) 8.7 Hz, 2H), 8.30 (dd, J )
8.1, 1.5 Hz, 2H), 8.14 (t, J ) 8.1 Hz, 2H), 7.55 (dd, J ) 8.1, 4.2
Hz, 2H); MS (ESI) m/z 491 (M + 1)+. Anal. Calcd for C30H18N8‚
H2O: C, 70.86; H, 3.96; N, 22.03. Found: C, 70.49; H, 3.66; N,
21.86.
3,6-Diacetyl-pyridazine (13).12 In acetone (3 mL) was dissolved
3,6-bis-(1′-ethoxyvinyl)-pyridazine (620 mg, 2.82 mmol) and
hydrochloric acid (2 M, 1.8 mL). The solution was stirred overnight
at room temperature. The resulting precipitate was collected, washed
with water, and dried under vacuum at 50 °C. A light-yellow solid
(370 mg, 80%) was obtained, mp 151-152 °C (lit.12 mp 150.4-
150.8 °C): 1H NMR (CDCl3) δ 8.26 (s, 2H), 2.94 (s, 6H).
3,6-Di-(1′,8′-naphthyrid-2′-yl)pyridazine (1). A suspension of
3,6-diacetylpyridazine (13, 29 mg, 0.18 mmol), 2-aminonicotinal-
dehyde (19, 57 mg, 0.53 mmol), EtOH (2.5 mL), and pyrrolidine
(0.1 mL) was refluxed under Ar for 15 h. Additional 19 (19 mg,
0.18 mmol) was added and the solution was refluxed for 5 h. The
solvent was removed in vacuo, and the residue was purified by
chromatography on alumina eluting with MeOH/CH2Cl2 (1:20).
Further purification by recrystallization from CH2Cl2 yielded a
yellow solid (27 mg, 46%), mp > 270 °C: 1H NMR (CDCl3) δ
9.23 (s, 2H), 9.21 (dd, J ) 1.8, 3.9 Hz, 2H), 9.07 (d, J ) 8.4 Hz,
2H), 8.45 (d, J ) 8.1 Hz, 2H), 8.31 (dd, J ) 2.1, 8.4 Hz, 2H), 7.58
(dd, J ) 4.2, 8.1 Hz, 2H); 13C NMR (CDCl3) δ 172.8, 158.3, 156.5,
155.8, 138.4, 137.1, 126.7, 123.5, 122.8, 120.3; MS (ESI) m/z 337
(M + 1)+. Anal. Calcd for C20H12N6‚0.25H2O: C, 70.48; H, 3.67;
N, 24.67. Found: C, 70.69; H, 3.50; N, 24.48.
3,6-Di-(1′,10′-phenanthrolin-2′-yl)pyridazine (7).8 To a stirred
solution of 13 (308 mg, 1.88 mmol) and 8-amino-7-quinoline-
carbaldehyde (800 mg, 4.64 mmol) in ethanol (10 mL) was added
pyrrolidine (0.4 mL). The reaction was heated at reflux for 30 h
under Ar. The resulting precipitate was filtered, washed with
ethanol, and dried to give a light-orange solid (634 mg, 77%), mp
>260 °C: 1H NMR (CDCl3) δ 9.36 (s, 2H), 9.31 (dd, 2H, J ) 1.5
Hz, 4.5 Hz), 9.12 (d, 2H, J ) 8.4 Hz), 8.51 (d, 2H, J ) 8.4 Hz)
8.33 (dd, 2H, J ) 8.4, 1.5 Hz), 7.91 (AB pattern, 4H, J ) 9.0 Hz),
7.72 (dd, 2H, J ) 8.4 Hz, 4.5 Hz), identical to material prepared
previously.8
2,7-Di-(1′,10′-phenanthrolin-2′-yl)-1,8-naphthyridine (8). A
mixture of 2,7-diacetyl-1,8-naphthyridine (36 mg, 0.168 mmol),
8-amino-7-quinolinecarbaldehyde (58 mg, 0.337 mmol), and pyr-
rolidine (0.3 mL) in ethanol (20 mL) was refluxed for 18 h. The
solvents were evaporated, and the residue was purified by chro-
matography on alumina eluting with CH2Cl2 followed by CH2Cl2-
EtOAc (95:5) to afford 8 (62 mg, 75%), mp > 270 °C: 1H NMR
(CDCl3) δ 9.42 (d, J ) 8.7 Hz, 1H), 9.35 (d, J ) 8.1 Hz, 1H),
9.32 (dd, J ) 4.5, 1.8 Hz, 1H), 8.53 (d, J ) 8.4 Hz, 1H), 8.52 (d,
J ) 8.1 Hz, 1H), 8.35 (dd, J ) 7.8, 1.8 Hz, 1H), 7.91 (AB, 2H),
7.72 (dd, J ) 7.5, 4.2 Hz, 1H); MS (ESI) m/z 487 (M + 1)+. Anal.
Calcd for C32H18N6-1.5 H2O: C, 74.85; H, 4.09; N, 16.37. Found:
C, 74.30; H, 3.83; N, 16.22.
6,6′-Di-(1′′,10′′-phenathrolin-2′′-yl)-2,2′-bipyridine (9). A mix-
ture of 6,6′-diacetyl-2,2′-bipyridine (92 mg, 0.38 mmol) and
8-amino-7-quinolinecarbaldehyde (134 mg, 0.78 mmol) in absolute
ethanol (15 mL) and pyrrolidine (0.3 mL) was heated at 80 °C for
15 h to produce a precipitate. The solid was collected, washed with
ethanol (5 mL) and ether (5 mL), and dried to afford a beige powder
(118 mg, 60%), mp > 310 °C: 1H NMR (800 MHz, DMSO-d6) δ
9.24 (broad, 2H), 9.10 (broad, 2H), 9.00 (broad, 2H), 8.91 (broad,
2H), 8.76 (broad, 2H), 8.58 (broad, 2H), 8.38 (broad, 2H), 8.13
(broad, 2H), 8.10 (broad, 2H), 7.87 (broad, 2H); MS (ESI) m/z
377 (M - 135)+, 513 (M + 1)+. Anal. Calcd for C34H20N6‚0.5
H2O: C, 78.31; H, 4.03; N, 16.12. Found: C, 77.73; H, 3.91; N,
15.67.
2,2′:7′,2′′-Ter[1,8]naphthyridine (2). A solution of 2,7-diacetyl-
1,8-naphthyridine (14, 37 mg, 0.17 mmol), 2-aminonicotinaldehyde
(45 mg, 0.37 mmol) in ethanol (10 mL), and a saturated solution
of KOH in ethanol (0.3 mL) was refluxed overnight. The precipitate
was collected and washed with ethanol and ether to give a beige
solid (54 mg, 81%), mp > 280 °C: 1H NMR (CDCl3 + CH3OD)
δ 9.20 (dd, J ) 2.1, 4.2 Hz, 2H), 9.18 (d, J ) 8.4 Hz, 2H), 9.12
(d, J ) 8.1 Hz, 2H), 8.53-8.49 (m, 4H), 8.43 (dd, J ) 1.5, 7.8
Hz, 2H), 7.66 (dd, J ) 4.5, 7.8 Hz, 2H); MS (ESI) m/z 387 (M +
1)+. Anal. Calcd for C24H14N6‚1.5H2O: C, 69.73; H, 4.11; N, 20.33.
Found: C, 69.76; H, 3.89; N, 19.68.
6,6′-Di-(1′′,8′′-naphthyrid-2′′-yl)-2,2′-bipyridine (3). A suspen-
sion of 6,6′-diacetyl-2,2′-bipyridine (15, 50 mg, 0.21 mmol),
2-aminonicotinaldehyde (19, 62 mg, 0.57 mmol), EtOH (2.5 mL),
and pyrrolidine (0.1 mL) was refluxed under Ar for 23 h. The
suspension was filtered, and the residue was washed with EtOH
(10 mL). Recrystallization of the residue from CHCl3/Et2O (1:1)
afforded a yellow solid (48 mg, 56%), mp > 300 °C: 1H NMR
(CDCl3) δ 9.22 (dd, J ) 1.5, 3.6 Hz, 2H), 9.06 (d, J ) 8.7 Hz,
2H), 8.97 (dd, J ) 0.9, 7.8 Hz, 2H), 8.80 (d, J ) 7.8 Hz, 2H), 8.44
(d, J ) 8.4 Hz, 2H), 8.36 (dd, J ) 0.9, 8.1 Hz, 2H), 8.12 (t, J )
7.8 Hz, 2H), 7.60 (dd, J ) 3.9, 7.8 Hz, 2H); MS (ESI) m/z 413
(M)+.
2,9-Di-(1′,8′-naphthyrid-2′-yl)-1,10-phenanthroline (4). To a
suspension of 2,9-diacetyl-1,10-phenanthroline (16, 166 mg, 0.63
mmol) and 2-aminonicotinaldehyde (156 mg, 1.28 mmol) in
absolute ethanol (15 mL) at 80 °C was added KOH (100 mg) in
ethanol (2 mL). The mixture immediately turned red and the
resulting solution was refluxed overnight. After cooling to room
temperature, the precipitate was collected and washed with ethanol
(95%), absolute ethanol, and ether to afford a gray solid (211 mg,
77%), mp > 280 °C: 1H NMR (CDCl3 + CH3OD) δ 9.39 (d, J )
8.7 Hz, 2H), 9.22 (d, J ) 8.7 Hz, 2H), 9.13 (dd, J ) 4.2, 1.8 Hz,
2H), 8.53 (d, J ) 9.3 Hz, 2H), 8.50 (d, J ) 8.1 Hz, 2H), 8.34 (dd,
J ) 8.7, 1.8 Hz, 2H), 7.93 (s, 2H), 7.57 (dd, J ) 8.7, 4.2 Hz, 2H);
MS (ESI) m/z 437 (M +1)+. Anal. Calcd for C28H16N6‚H2O: C,
76.02; H, 3.77; N, 19.00. Found: C, 76.05; H, 3.53; N, 18.85.
1,2-Di[6′-(1′′,8′′-naphthyrid-2′′-yl)pyrid-2′-yl]ethyne (5). A
suspension of 1,2-di(6′-acetylpyrid-2′-yl)ethyne (17, 152 mg, 0.57
mmol), 2-aminonicotinaldehyde (19, 159 mg, 1.49 mmol), EtOH
(9 mL), CH2Cl2 (3 mL), and pyrrolidine (0.3 mL) was stirred at 25
°C for 3 days. The suspension was filtered, and the residue was
2,2′:9′,2′′-Ter[1,10]phenanthroline (10).17 A mixture of 2,9-
diacetyl-1,10-phenanthroline (31.5 mg, 0.12 mmol), 8-amino-7-
quinolinecarbaldehyde (45 mg, 0.26 mmol), and pyrrolidine (0.30
mL) in absolute ethanol (10 mL) was refluxed under Ar for 40 h.
The precipitate was collected, washed with ethanol, and dried under
vacuum to afford a beige solid (53 mg, 83%), mp > 300 °C: 1H
NMR (DMSO-d6): δ 9.48 (d, J ) 8.1 Hz, 2H), 9.32 (d, J ) 8.1
Hz, 2H), 9.24 (dd, J ) 4.5, 1.5 Hz, 2H), 8.88 (d, J ) 8.4 Hz, 2H),
8.84 (d, J ) 8.4 Hz, 2H), 8.58 (dd, J ) 8.1, 1.5 Hz, 2H), 8.20 (s,
172 J. Org. Chem., Vol. 71, No. 1, 2006