10.1002/chem.201904027
Chemistry - A European Journal
FULL PAPER
MgSO4. After filtration and concentration under reduced pressure, the
residue was purified by silica chromatography (EtOAc/Hexanes 1:5) to
afford 7AQ (691 mg, 83%) as brown solid. 1H-NMR (400 MHz, d6-DMSO,
ppm): δ = 8.55 (dd, J = 4.0, 1.6 Hz, 1H), 7.98 (dd, J = 8.0, 1.6 Hz, 1H),
7.57 (d, J = 8.4 Hz,1H), 7.04 (dd, J = 8.0, 4.4 Hz, 1H), 6.96 (dd, J = 8.4,
2.0 Hz, 1H), 6.90 (d, J = 2.0 Hz, 1H), 5.73 (2H, s). HRMS (EI, m/z): calcd
for (C9H9N2)+: 145.0760; Found: 145.0754.
Different from previously published N-H intramolecular H-
bonded molecules undergoing ESIPT,[1,2] 7AQs do not possess
intramolecular H-bond. Therefore, the previously established
correlation among H-bond strength, ESIPT kinetics and ESIPT
thermodynamics cannot be applied. Nevertheless, for 7AQs the
results show that the more acidic is the NR-H the more exergonic
is ESPT whereas the rate of ESPT increases as increasing the
quinoline –N- basicity. The latter may infer that the rate
determining step for methanol catalyzed ESPT lies in the proton
donation to the quinoline –N- site.
2,2,2-Trifluoro-N-(quinolin-7-yl)acetamide (TFA-7AQ). To a solution of
7AQ (162 mg, 1.12 mmol) in CH2Cl2 (5 mL) was added 2,2,2-
trifluoroacetic acid (190 uL, 1.35 mmol) and the mixture was stirred at
room temperature for 16 hrs. The result was neutralized carefully with
10% NaOH(aq) and then extracted with CH2Cl2 (3 x 10 mL). The combined
organic extracts were dried over anhydrous MgSO4 and the filtrate was
concentrated. The residue was purified by silica chromatography
(EtOAc/Hexanes 1:3) to afford TFA-7AQ (204 mg, 75% yield) as white
solid. 1H NMR (400 MHz, CDCl3, ppm) δ = 8.91 (dd, J = 4.4, 1.6 Hz, 1 H),
8.44 (brs, 1 H), 8.23 (d, J = 1.6 Hz, 1 H), 8.14 (dd, J = 8.4, 1.6 Hz, 1H),
7.88 (dd, J = 8.8, 2.0 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1 H), 7.40 (dd, J = 8.4,
4.4 Hz, 1 H). 13C NMR (100 MHz, d6-DMSO, ppm) δ = 155.2, 144.5, 142.0,
141.3, 130.6, 122.3, 121.7, 115.3, 115.0, 95.1 ppm. IR (KBr, cm-1) 3213,
2993, 1716, 1630, 1566, 1504, 1466, 1441, 1394, 1319, 1279, 1204,
1151, 841, 753. HRMS (EI, m/z): calcd for C11H8N2OF3 (M+H)+:
241.0589; Found: 241.0589.
Experimental Section
All reactions were carried out in oven- or flame-dried glassware under
a positive pressure of argon. All reagents and solvents were purchased
commercially and used without further purification. TLC was performed
on Merck 5735 DC-plastikfolien Kieselgel 60 F254 precoated plates.
Flash column chromatography was performed on silica gel (Merck 7736
Kieselgel 60H). 1H and 13C NMR spectra were recorded on Bruker AVIII
or Varian Unity-400 MHz spectrometers in CDCl3, or d6-DMSO. The
chemical shifts were reported in δ ppm relative to the internal standard.
HRMS data was obtained from a Waters LCT Premier XE (ESI-TOF/MS)
and FOEL JMS-HX110. HR-FAB mass spectra and HR-EI mass spectra
were conducted on a JMS-700 double focusing mass spectrometer
(JEOL, Tokyo, Japan) with a resolution of 8000(3000) (5% valley
definition). The FT-IR spectra were recorded on a Bomen-MB-100 FT-IR
spectrometer.
4-Methyl-N-(quinolin-7-yl)benzenesulfonamide (Ts-7AQ). To
a
solution of 7AQ (100 mg, 0.69 mmol) in pyridine (2 mL) was added p-
toluenesulfonyl chloride (158 mg, 0.83 mmol) and the mixture was stirred
at room temperature for 16 hrs. The solution was neutralized carefully
with 10% HCl(aq) and extracted with CH2Cl2 (3 x 10 mL). The combined
organic extracts were dried over anhydrous MgSO4. After filtration and
concentration under reduced pressure, the residue was purified by silica
chromatography (CH3OH/CH2Cl2 1:50) to afford Ts-7AQ (165 mg, 79%
yield) as yellow solid. 1H-NMR (400 MHz, d6-DMSO, ppm): δ = 10.73 (s,
1H), 8.75 (d, J = 4.0 Hz, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 8.8 Hz,
1H), 7.70 (d, J = 8.0 Hz, 2H), 7.61 (s, 1H), 7.37-7.29 (m, 4H), 2.26 (s, 3H).
13C NMR (100 MHz, d6-DMSO, ppm) δ = 151.1, 148.1, 143.5, 138.9,
136.9, 135.6, 129.8, 126.7, 124.4, 120.3, 120.1, 115.6, 20.9 ppm. IR (KBr,
cm-1) 3062, 2873, 1626, 1579, 1510, 1450, 1362, 1323, 1158, 1091, 972,
836, 663. HRMS (FAB, m/z): calcd for C16H15N2O2S (M+H)+: 299.0854;
Found: 299.0854.
7-Nitro-1, 2, 3, 4-tetrahydroquinoline. 1, 2, 3, 4-tetrahydroquinoline
(5.305 g, 39.8 mmol) was added dropwise into conc. H2SO4 (15 mL) in
an ice bath. After stirring for 30 mins, it was added dropwise the mixture
of conc. HNO3 (3 mL) in conc. H2SO4 (8 mL) and stirred at 0℃ for another
3 hrs. The result was poured into ice water and neutralized to pH = 6 with
Na2CO3(aq). After filtration, the filtrate was extracted with EtOAc (3 x 20
mL). The organic layer was dried over anhydrous MgSO4, concentrated,
and purified by silica column chromatography (EtOAc/Hexanes 1:10) to
afford the title compound (3.920 g, 55% yield) as orange oil. 1H-NMR (400
MHz, d6-DMSO, ppm) δ = 7.26 (s, 1H), 7.21 (dd, J = 8.2, 2.4 Hz, 1H),
7.05 (d, J = 8.0 Hz, 1H), 6.40 (s, 1H), 3.22 (t, J = 6.4 Hz, 2H), 2.74 (t, J =
6.4 Hz, 2H), 1.79 (m, 2H). HRMS (EI, m/z): calcd for (C9H11N2O2)+:
179.0815; Found: 179.0809.
N-(Quinolin-7-yl)acetamide (Ac-7AQ). To a solution of 7AQ (165 mg,
1.14 mmol) in CH2Cl2 (5 mL) was added acetic anhydride (162 uL, 1.72
mmol) and the mixture was stirred at 70℃ for 10 hrs. The reaction solution
was neutralized carefully with 10% NaOH(aq) and extracted with CH2Cl2
(3 x 10 mL). The combined organic extracts were dried over anhydrous
MgSO4. After filtration and concentration under reduced pressure, the
residue was purified by silica chromatography (CH3OH/CH2Cl2 1:50) to
afford Ac-7AQ (181 mg, 85% yield) as white solid. 1H NMR (400 MHz,
d6-DMSO, ppm) δ = 10.28 (s, 1H), 8.80 (d, J = 4.4 Hz, 1 H), 8.38 (s, 1 H),
8.23 (d, J = 8.0 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1
H), 7.37 (dd, J =8.0, 4.0 Hz, 1 H), 2.10 (s, 3H). 13C NMR (100 MHz, d6-
DMSO, ppm) δ = 169.0, 150.7, 148.4, 139.5, 135.9, 128.5, 125.2, 120.8,
120.0, 116.7, 24.6 ppm. IR (KBr, cm-1) 3052, 3012, 2345, 1675, 1623,
1586, 1545, 1500, 1458, 1435, 1370, 1353, 835. HRMS (FAB, m/z): calcd
for C11H11N2O (M+H)+: 187.0871; Found: 187.0876.
7-Nitroquinoline. To a solution of 7-nitro-1, 2, 3, 4-tetrahydroquinoline
(500 mg, 1.94 mmol) in CH2Cl2 (60 mL) was added DDQ (879.5 mg, 3.88
mmol) and the mixture was stirred for 30 mins. The solid was removed
and the filtrate was extracted with CH2Cl2 (3 x 20mL) followed by washing
with brine. The combined organic extracts were dried over anhydrous
MgSO4. After filtration and concentration under reduced pressure, the
residue was purified by silica chromatography (EtOAc/Hexanes 1:5) to
afford 7-nitroquinoline (312 mg, 92%) as yellow oil. 1H-NMR (400 MHz,
d6-DMSO, ppm): δ = 9.10 (dd, J = 4.0, 1.2 Hz, 1H), 8.80 (s, 1H), 8.57 (d,
J = 8.4 Hz, 1H), 8.33 (dd, J = 5.4, 2.4 Hz, 1H), 8.26 (d, J = 8.8 Hz, 1H),
7.76 (dd, J = 8.4, 2.0 Hz, 1H). HRMS (EI, m/z): calcd for (C9H7N2O2)+:
175.0508; Found: 175.0513.
7-Aminoquinoline (7AQ). A suspension of SnCl2 (4.355 g, 22.97 mmol)
in conc. HCl (35 mL) was added to a solution of 7-nitro-quinoline (1 g,
5.74 mmol) in acetic acid (17.5 mL). The mixture was heated at 70℃ for
30 mins and then allowed to cool to room temperature. The mixture was
treated with 10% NaOH(aq) to pH = 12 and then extracted with CH2Cl2 (3
x 10 mL). The combined organic extracts were dried over anhydrous
tert-Butyl quinolin-7-ylcarbamate (Boc-7AQ). To a solution of 7AQ
(500 mg, 3.47 mmol) in anhydrous THF (10 mL) was added NaHMDS
(3.81 mL, 7.63 mmol, 2M in THF) at room temperature under nitrogen
atmosphere. The mixture was stirred for 15 mins and then di-tert-butyl
dicarbonate (794 mg, 3.64 mmol) in anhydrous THF (5 mL) was added
dropwise into the solution. The reaction mixture was stirred overnight
This article is protected by copyright. All rights reserved.