New Straightforward Quinoline Synthesis
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Reichert apparatus and are uncorrected. Mass spectra were obtained on a MS
50 spectrometer. Chromatography was performed using Merck silica gel or
Aldrich activated neutral aluminum oxide (Brockmann I). Analytical TLC
was performed using 0.25 mm Merck Kieselgel 60 P254 precoated silica gel
plates. All solvents are reagent grade. Aldehydes 1a,[20] 2a[21] and hydrazones
2a,[18] 2b,[19] 2c[20] were prepared according reported procedures.
Preparation of Mannich adducts 4a–d. To a solution of starting
hydrazones 2a–c (2 mmol) in 1 mL of toluene at room temperature were
added aldehyde 1a–b (2.2 mmol), and N-benzylpiperazine (2.2 mmol). The
resulting mixture was heated at 808C for 8 hours. Solvents were evaporated,
and the crude purified by flash chromatography on silica gel with Et2O/
petroleum ether (PE) The following compounds were obtained.
N-f2-[1-(4-Benzyl-piperazin-1-yl)-3-oxo-2-(phenyl-hydrazono)-butyl]-
phenylg-acetamide (4a). Yield 93%. Brown oil. Rf : 0.60 (Et2O/PE, 50 : 50).
1H NMR (CDCl3, 400 MHz) d 13.11 (s, 1H, NH-Ph), 9.51 (s, 1H, NH-Ac),
7.84 (dd, J ¼ 8.1, 0.8 Hz, 1H), 7.56 (dd, J ¼ 8.0, 1.0 Hz, 1H), 7.42
(t, J ¼ 7.9 Hz, 2H), 7.35–7.25 (m, 8H, Har), 7.10 (t, J ¼ 7.4 Hz, 2H), 5.02
(s, 1H), 3.58 (d, J ¼ 13.0 Hz, 1H), 3.54 (d, J ¼ 13.0 Hz, 1H), 2.90–2.73
(m, 4H), 2.46 (s, 3H, Me–C55O), 2.37 (td, J ¼ 11.4, 2.0 Hz, 1H), 2.34 (s, 3H,
NH–CO-Me), 2.20 (td, J ¼ 11.4, 2.0 Hz, 2H), 1.94 (td, J ¼ 11.4, 2.0 Hz,
1H).13C NMR (CDCl3, 100.6 MHz) d 200.2, 169.3 (Cq, HN–C55O), 143.2,
138.5, 137.8, 136.4, 130.0, 129.7, 129.5, 128.9, 128.7, 127.6, 127.3, 126.1,
125.9, 123.3, 114.5, 63.2, 63.1, 53.8, 53.6, 52.8, 51.4, 25.0 (CH3, NHAc), 24.6
(CH3, Me–C55O). IR (CCl4, CaF2) n (cm21): 3317, 2810, 1698, 1650, 1602,
1554, 1453, 1367, 1296, 1264, 1231, 1003. Mass (ID ICP NH3) m/z 484
(MHþ), 307, 249, 178. Exact Mass (CI, CH4) m/z calculated: 484.2713;
found: 484.2705 (MHþ).
N-f2-[1-(4-Benzyl-piperazin-1-yl)-3-oxo-3-phenyl-2-(phenylhydrazono)-
propyl]-phenylg-acetamide (4b). Yield 93%. Brown solid M.p. 95–978C.
Rf : 0.60 (Et2O/PE, 50 : 50). 1H NMR (CDCl3, 400 MHz) d 13.44 (s, 1H, NH-
Ph), 9.64 (s, 1H, NH-Ac), 7.86 (d, J ¼ 10.9 Hz, 2H), 7.84 (d, J ¼ 7.4 Hz, 2H),
7.66–7.64 (m, 1H), 7.56–7.52 (m, 1H), 7.44 (t, J ¼ 7.4 Hz, 2H), 7.39 (t,
J ¼ 7.8 Hz, 2H), 7.35–7.27 (m, 6H), 7.16–7.11 (m, 3H), 7.09 (t, J ¼ 7.3 Hz,
1H), 5.23 (s, 1H), 3.60 (d, J ¼ 13.0 Hz, 1H), 3.54 (d, J ¼ 13.0 Hz, 1H), 3.00–
2.93 (m, 2H), 2.89–2.86 (m, 1H), 2.82–2.80 (m, 1H), 2.53–2.48 (m, 1H),
2.39 (s, 3H, O55C–Me), 2.30–2.22 (m, 2H), 2.07–2.02 (m, 1H). 13C NMR
(CDCl3, 100.6 MHz) d 194.3, 169.4, 143.3, 138.5, 138.0, 137.8, 136.6, 132.0,
131.1, 130.1, 129.5, 129.0, 128.7, 127.9, 127.8, 127.4, 126.4, 126.2, 123.4,
114.7, 64.4, 63.1, 53.9, 53.6, 53.1, 51.4, 24.8 (O55C–CH3). IR (CCl4, CaF2) n
(cm21): 3325, 3064, 3030, 2940, 2810, 1698, 1548, 1452, 1296, 1238. Mass
(ID ICP NH3) m/z 545 (Mþ.), 369, 310, 178. Micro analysis: found: C 74.91,
H 6.63, calculated: C 74.84, H 6.47.