November 2009
Facile Synthesis of 10-tert-Butyl[1]benzoxepino[3,4-b][1,3]-
dioxolo[4,5-g]quinolin-12(6H)-ones
1193
measured with a Varian Inova 400 NMR spectrometer at 400
MHz. The reported chemical shifts were against TMS. Ele-
mental analysis was performed using an Elementar Vario EL-
III element analyzer. HPLC/MS analysis was performed on a
HP 1100 system HPLC/MS spectrometer.
General Procedure for the Preparation of 6-[(tert-Butyl
phenoxy)methyl][1,3]dioxolo[4,5-g]quinoline-7-carboxylic
acids (3a–d). To 0.046 g metal sodium (2 mmol) dissolved in
8 mL CH3CH2OH tert-butyl phenol (2 mmol) and 0.676 g
ethyl 6-(bromomethyl)[1,3]dioxolo[4,5-g]quinoline-7-carboxy-
late (1) (2 mmol) were added. The mixture was refluxed for 2
hours. Then 60% (v/v) ethanolic potassium hydroxide solution
15 mL was added to the reaction mixture and continued to
reflux for 2 hours, cooled, and acidified with 1 M HCl solu-
tion. The resulting crude product was recrystalized from 95%
ethanol to afford compounds 3a–d.
The pure product 5 was obtained by recrystalization from
THF-H2O. Yield 37%, mp 196 to 197ꢀC. IR (KBr): 3019,
1641 (C¼O), 1598, 1559, 1505, 1457, 1400, 1365, 1297,1222,
1168, 1109, 929. 1H NMR (400 MHz, CDCl3): 5.41 (s, 2H,
Oxepan-H), 6.16 (s, 2H, OCH2O), 7.13 to 7.20 (m, 2H, ArH),
7.26 (s, 1H, ArH), 7.40 (s, 1H, ArH), 7.51 to 7.54 (m, 2H,
ArH), 8.29 to 8.31 (m, 1H, ArH), 8.60 (s, 1H, ArH). Anal.
Calcd. For C18H11NO4: C, 70.82; H, 3.63; N, 4.59 Found: C,
70.63; H, 3.78; N, 4.57%.
General Procedure for the Preparation of Title Com-
pounds (4a–d). 6-[(tert-Butylphenoxy)methyl][1,3]dioxolo[4,5-
g]quinolin-7-carboxylic acids (3a–d) (1 mmol) and Eaton’s re-
agent (8 mL) were added to round flask (25 mL) and stirred at
80ꢀC for 3 hours. Then, the reaction mixture was poured
slowly with stirring into an icy saturated sodium carbonate so-
lution. The crude products were obtained after filtration and
washed with water. The pure product 4a–d was obtained by
recrystalization from ethanol.
10-tert-Butyl[1]benzoxepino[3,4-b][1,3]dioxolo[4,5-g]qui-
nolin-12(6H)-one (4a). Yield 65%, mp 201 to 203ꢀC. IR
(KBr): 3033, 2925, 2779, 1647 (C¼O), 1604, 1586, 1457,
1400, 1249, 1029, 949 (OCH2O). 1H NMR (400 MHz,
CDCl3): d ¼ 1.34 (s, 9H, 3-t-butyl), 5.43 (s, 2H, Oxepan-H),
6.25 (s, 2H, OCH2O), 7.24 to 7.27 (m, 1H, ArH), 7.47 (s, 1H,
ArH), 7.61 (s, 1H, ArH), 7.83 (s, 1H, ArH), 8.12 to 8.14 (m,
1H, ArH), 8.74 (s, 1H, ArH). Anal. Calcd. For C22H19NO4: C,
73.12; H, 5.30; N, 3.88 Found: C, 73.37; H, 5.18; N, 3.92%.
10-tert-Butyl-8-fluoro[1]benzoxepino[3,4-b][1,3]dioxolo[4,
5-g]quinolin-12(6H)-one (4b). Yield 49%, mp 215 to 217ꢀC.
IR (KBr): 3031, 2927, 2791, 1637 (C¼O), 1616, 1471, 1242,
1073, 1028 (COC), 951 (OCH2O). 1H NMR (400 MHz,
CDCl3): d ¼ 1.39 (s, 9H, t-butyl), 5.58 (s, 2H, Oxepan-H),
6.27 (s, 2H, OCH2O), 7.29 to 7.31 (m, 1H, ArH), 7.52 (s, 1H,
ArH), 7.85 (s, 1H, ArH), 8.13 to 8.16 (m, 1H, ArH), 8.78 (s,
1H, ArH). Anal. Calcd. For C22H18FNO4: C, 69.65; H, 4.78;
N, 3.69 Found: C, 69.89; H, 4.61; N, 3.70%.
10-tert-Butyl-8-chloro[1]benzoxepino[3,4-b][1,3]dioxolo[4,
5-g]quinolin-12(6H)-one (4c). Yield 52%, mp 226 to 227ꢀC.
IR (KBr): 3011, 2920, 2815, 1647 (C¼O), 1591, 1461, 1400,
1245, 1038 (COC), 948 (OCH2O). 1H NMR (400 MHz,
CDCl3): d ¼ 1.32 (s, 9H, t-butyl), 5.57 (s, 2H, Oxepan-H),
6.26 (s, 2H, OCH2O), 7.19 to 7.23 (m, 1H, ArH), 7.47 (s, 1H,
ArH), 7.81 to 7.84 (m, 1H, ArH), 8.11 to 8.13 (m, 1H, ArH),
8.66 (s, 1H, ArH). Anal. Calcd. For C22H18ClNO4: C, 66.75;
H, 4.85; N, 3.54 Found: C, 66.46; H, 4.91; N, 3.60%.
6-[(4-tert-Butylphenoxy)methyl][1,3]dioxolo[4,5-g]quin-
oline-7-carboxylic acid (3a). Yield 86%; mp 204 to 205ꢀC.
IR (KBr): 3393 (COOH), 3058, 2937, 2786, 1712 (C¼O),
1
1610, 1502, 1426, 1245, 1047 (COC), 947 (OCH2O). H NMR
(400 MHz, CDCl3): d ¼ 1.30 (s, 9H, t-butyl), 5.51 (s, 2H, O-
CH2-Ar), 6.10 (s, 2H, OCH2O), 6.76 to 6.82 (m, 2H, ArH),
6.91 (m, 2H, ArH), 7.38 to 7.41 (m, 2H, ArH), 8.44 (s, 1H,
ArH). Anal. Calcd. For C22H21NO5: C, 69.64; H, 5.58; N, 3.69
Found: C, 69.72; H, 5.63; N, 3.65%.
6-[(4-tert-Butyl-2-fluorophenoxy)methyl][1,3]dioxolo[4,5-g]
quinoline-7-carboxylic acid (3b). Yield 79%, mp 185 to
187ꢀC. IR (KBr): 3410 (COOH), 3064, 2930, 2853, 1698
(C¼O), 1599, 1497, 1410, 1237, 1041 (COC), 948 (OCH2O).
1H NMR (400 MHz, CDCl3): d ¼ 1.36 (s, 9H, t-butyl), 5.59
(s, 2H, O-CH2-Ar), 6.21 (s, 2H, OCH2O), 6.89 to 7.17 (m, 3H,
ArH), 7.31 (s, 1H, ArH), 7.48 (s, 1H, ArH), 8.65 (s, 1H, ArH).
Anal. Calcd. For C22H20FNO5: C, 66.49; H 5.07; N 3.52
Found: C 66.53; H 5.12; N 3.59%.
6-[(4-tert-Butyl-2-chlorophenoxy)methyl][1,3]dioxolo[4,5-g]
quinoline-7-carboxylic acid (3c). Yield 77%, mp 216 to
217ꢀC. IR (KBr): 3421 (COOH), 3048, 2936, 2855, 1701
(C¼O), 1579, 1514, 1428, 1240, 1035 (COC), 947 (OCH2O).
1H NMR (400 MHz, CDCl3): d ¼ 1.33 s (9H, t-butyl), 5.58 s
(2H, O-CH2-Ar), 6.20 s (2H, OCH2O), 7.12 to 7.18 m (2H,
ArH), 7.32 to 7.35 m (1H, ArH), 7.41 to 7.55 m (2H, ArH),
8.54 s (1H, ArH). Anal. Calcd. For C22H20ClNO5: C, 63.85;
H, 4.87; N, 3.38 Found: C, 63.92; H, 4.85; N, 3.48%.
6-[(2,4-Di-tert-Butylphenoxy)methyl][1,3]dioxolo[4,5-g]quin-
oline-7-carboxylic acid (3d). Yield 68%, mp 178 to 180ꢀC.
IR spectrum (KBr), v, cmꢁ1: 3432 (COOH), 3044, 2939, 2851,
1707 (C¼O), 1580, 1507, 1449, 1422, 1243, 1046 (COC), 950
(OCH2O). 1H NMR (400 MHz, CDCl3): d ¼ 1.31 (s, 9H,
t-butyl), 1.37 (s, 9H, t-butyl), 5.55 (s, 2H, O-CH2-Ar), 6.19
(s, 2H, OCH2O), 7.08 to 7.21 (m, 3H, ArH), 7.35 to 7.41
(m, 2H, ArH), 8.61 (s, 1H, ArH). Anal. Calcd. For
C26H29NO5: C, 71.70; H, 6.71; N, 3.22 Found: C, 71.82; H,
6.69; N, 3.28%.
8,10-Di-tert-Butyl[1]benzoxepino[3,4-b][1,3]dioxolo[4,5-g]
quinolin-12(6H)-one (4d). Yield 58%, mp 241 to 243ꢀC. IR
(KBr): 3015, 2923, 2810, 1636 (C¼O), 1596, 1462, 1400,
1237, 1036 (COC), 949 (OCH2O). 1H NMR (400 MHz,
CDCl3): d ¼ 1.35 (s, 9H, t-butyl), 1.34 (s, 9H, t-butyl), 5.40
(s, 2H, Oxepan-H), 6.23 (s, 2H, OCH2O), 7.07 to 7.10 (m,
1H, ArH), 7.43 (s, 1H, ArH), 8.01 to 8.03 (m, 1H, ArH), 8.12
(s, 1H, ArH), 8.67 (s, 1H, ArH). Anal. Calcd. For C26H27NO4:
C, 74.80; H, 6.52; N, 3.35 Found: C, 74.68; H, 6.59; N,
3.29%.
Synthesis of [1]benzoxepino[3,4-b][1,3]dioxolo[4,5-g]quino-
lin-12(6H)-one (5). The 6-[(4-tert-butylphenoxy)methyl][1,3]-
dioxolo[4,5-g]quinoline-7-carboxylic acid (3a) (0.38 g,
1
mmol) and polyphosphoric acid (12 g) were added to round
flask (25 mL) and stirred at 150ꢀC for 2.5 hours. Then, the
reaction mixture was poured into icy water and neutralized
with an icy saturated sodium carbonate solution. The crude
products were obtained after filtration and washed with water.
REFERENCES AND NOTES
[1] Larsen, R. D.; Corley, E. G.; King, A. O. J Org Chem
1996, 61, 3398.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet