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Oxidative aromatization of novel tetrahydrochromeno[4,3-b]quinolines using silica sulfuric acid/NaNO2
⁎Corresponding author. Tel./fax: +98 9366799944. shimi50@yahoo.com (Mohammad Reza Rezaei)
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Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Peer review under responsibility of King Saud University.
Abstract
A combination of silica sulfuric acid and sodium nitrite in the presence of wet SiO2 was used as an effective oxidizing agent for the oxidative aromatization of novel Tetrahydrochromeno[4,3-b]quinolines to their corresponding pyridine derivatives under reflux and heterogeneous conditions in high yields.
Keywords
Chromeno[4,3-b]quinoline
Oxidative aromatization
Silica sulfuric acid
1 Introduction
Tetrahydrochromeno–quinoline derivatives are found to exhibit a wide range of biological activities (Helmchen et al., 1986; Yamanaka et al., 2000), including psychotropic, anti-allergic, anti-inflammatory and estrogenic behavior (Munoz et al., 1982; Yamada et al., 1992; Lee et al., 2004). Among them, Tetrahydrochromeno[4,3-b]quinolines are an important class of 1,4-dihydropyridines (DHPs) and NADH models (Fig. 1).![Structure of Hantzsch 1,4-DHPs I and chromeno[4,3-b]quinolines II.](/content/184/2017/10/1_suppl/img/10.1016_j.arabjc.2012.07.037-fig1.png)
Structure of Hantzsch 1,4-DHPs I and chromeno[4,3-b]quinolines II.
In the human body, 1,4-dihydropyridine compounds are oxidized to pyridine derivatives by the action of cytochrome P-450 in the liver (Guengerich et al., 1991). The oxidation of 1,4-DHPs to the corresponding pyridine derivatives constitutes the principal metabolic route in biological systems as well as a facile access to the corresponding pyridine derivatives (Stout and Meyers, 1982), which show anti-hypoxic and anti-ischemic activities from the easily available DHPs (Khadikar and Borkat, 1998; Sabitha et al., 2003). Therefore, oxidative aromatization of tetrahydrochromenoquinolines has attracted continuing interests of organic and medicinal chemists and a plethora of protocols has been developed.
Initially a series of novel tetrahydrochromeno[4,3-b]quinoline derivatives(1a–n, Scheme 1) were prepared via the reaction of 4-aminocoumarin with 2-benzylidene-cyclohexane-1,3-dione derivatives in solvent free system at 200–210 °C, according to our recently reported work (Miri et al., 2011), and they were used to investigate their conversion to the corresponding pyridines.![Oxidative aromatization of Tetrahydrochromeno[4,3-b]quinolines.](/content/184/2017/10/1_suppl/img/10.1016_j.arabjc.2012.07.037-fig2.png)
Oxidative aromatization of Tetrahydrochromeno[4,3-b]quinolines.
Herein, we report a simple, efficient and heterogeneous procedure for the aromatization of tetrahydrochromeno[4,3-b]quinoline derivatives using SiO2–OSO3H/NaNO2/wet SiO2 at reflux in CHCl3.
Therefore, a variety of tetrahydrochromeno–quinoline derivatives were subjected to aromatization via a combination of SSA/NaNO2 in chloroform at the reflux temperature with high yields (Table 1).
GroupG
Substrate
Product
MP(°C)
Yield (%)⁎
o-CH3
1a
2a
210–212
71
m-CH3
1b
2b
172–174
64
p-CH3
1c
2c
241–243
68
o-OCH3
1d
2d
180–182
71
m-OCH3
1e
2e
155–157
66
p-OCH3
1f
2f
185–187
75
o-Cl
1g
2g
253–255
66
m-Cl
1h
2h
188–190
68
p-Cl
1i
2i
281–283
70
m-NO2
1j
2j
161–163
70
p-NO2
1k
2k
265–267
67
m-Br
1l
2l
184–186
64
p-Br
1m
2m
279–281
65
H
1n
2n
121–123
74
Aromatization of tetrahydrochromeno[4,3-b]quinolines to the corresponding pyridines was carried out under completely heterogeneous conditions at refluxing chloroform. The aromatization procedure is very simple and the products are easily isolated from the reaction media by simple filtration and evaporation of chloroform.
In summary, in this paper we have introduced another ability of SiO2–OSO3H/NaNO2 as an efficient oxidizing agent for the oxidation of tetrahydrochromeno[4,3-b]quinolines under heterogeneous conditions. Also the cheapness and availability of the reagent, easy and clean work-up and high yields make this method attractive for chemists.
2 Result and discussion
The prepared 7-aryl-9,10,11,12-tetrahydro-6H-chromeno[4,3-b]quinoline-6,8-dione 1 were aromatized in the presence of silica sulfuric acid (Salehi et al., 2006), NaNO2 and wet SiO2 in boiling chloroform (Miri et al., 2011). The presence of wet SiO2 provides an effective heterogeneous surface area for the in situ generation of nitrosonium ion (Scheme 2). This oxidizing reagent was used for converting thiols to their corresponding thionitrils (Zolfigol, 2001). Application of the most common oxidants for oxidation of dihydropyridines such as CrO3 (Grinsteins et al., 1967), MnO2 (Vanden Eynde and Mayence, 2003) ferric nitrate (Khadikar and Borkat, 1998; Sadeghi et al., 2001) nicotinum dichromate (Sadeghi et al., 2000) and Multi-wall Carbon Nanotubes modified with manganese complex (MWNTs) was unsuccessful (Siswana et al., 2008). The aromatization of DHPs afforded 7-Aryl-10,11-dihydro-6H-chromeno[4,3-b]quinoline-6,8-dione 2 in 64–75% yields (Table 1). The structure according to NMR (1H and 13C, COSY, HMBC, HMQC) and EI-MS spectra was proved to be aromatized 1,4-DHP cyclic with the formation of pyridine cycle. The 1H NMR spectra showed the high deshielding character of aliphatic protons from 1.8–2.9 in 1 to 2.18–3.41 in 2 which is attributed to the formation of pyridine. The protons belonging to CH and NH in compounds 1 disappeared in compounds 2. Mass spectrum and elemental analysis clearly support the proposed structure.
The tentative mechanism for the oxidative aromatization of tetrahydrochromenoquinolines.
3 Experimental
3.1 Materials and apparatus
Chemicals and all solvents used in this study were purchased from Merck AG and Aldrich Chemical. Melting points were determined on a Kofler hot stage apparatus and are uncorrected. The IR spectra were obtained on a Shimatdzu 470 spectrophotometer (potassium bromide disks). 1HNMR spectra were measured using a Bruker FT-500 spectrometer, and chemical shifts are expressed as δ (ppm) with tetramethylsilane as internal standard. The mass spectra were run on a Finnigan TSQ-70 spectrometer at 70 eV. Merck silica gel 60 F254 plates were used for analytical TLC; column chromatography was performed on Merck silica gel (70–230 mesh). Yields are of purified products and were not optimized.
3.2 General procedure for the oxidative aromatization of 7-aryl-9,10,11,12-tetrahydro-6H-chromeno[4,3-b]quinoline-6,8-dione derivatives
Compounds 1a–n (5.4 mmol), sodium nitrite (l6 mmol, 1.1 g), silica sulfuric acid (1.6 g) and silica gel (1.07 g) were refluxed in chloroform (100 ml) for 8 h. The mixture was cooled to room temperature and filtered. The filtrate was evaporated to dryness under reduced pressure, and the crude product was purified by short column chromatography (20–80% ethyl acetate/petroleum ether) to give 2a–n.
3.3 Spectral and physical data for selected compounds
3.3.1 7-(2-Methylphenyl)-10,11-dihydro-6H-chromeno[4,3-b]quinoline-6,8-dione (2a)
Yield = 71%, Mp = 210–212 °C.
IR (KBr)ν: 2922, 2848, 1754, 1691, 757 cm−1.
1HNMR (CDCl3, 500 MHz), δ (ppm): 2.02 (s, 3H, CH3), 2.24 (q, 2H, J = 6.6 Hz, H10), 2.66 (t, 2H, J = 6.6 Hz, H9), 3.38 (t, 2H, J = 6.6 Hz, H11), 6.81 (d, 1H, J = 7.0 Hz, H15), 7.23 (t, 1H, J = 7.0 Hz H17), 7.28–7.35 (m, 3H, H16, H18, H4), 7.40 (t, 1H, J = 8.0 Hz, H2), 7.61 (t, 1H, J = 8.0 Hz, H3), 8.68 (d, 1H, J = 8.0 Hz, H1).
13C NMR(CDCl3-d), δ: 20.01, 20.98, 34.61, 40.13, 115.13, 116.90, 118.83, 124.61, 124.89, 125.58, 126.09, 127.44, 127.69, 129.26, 133.33, 134.24, 137.84, 153.43, 154.13, 156.39, 157.92, 169.58, 196.14.
MS: m/z (%), 355 (M+, 44), 340 (44), 327 (37), 299(100), 271(37), 151(50), 126 (50), 114 (63), 100(44), 87(25).
3.3.2 7-(3-Cholorophenyl)-10,11-dihydro-6H-chromeno[4,3-b]quinoline-6,8-dione (2h)
Yield = 68%, Mp = 188–190 °C.
IR (KBr)ν: 3018, 2853, 1744, 1691, 757 cm−1.
1H NMR (CDCl3, 500 MHz), δ (ppm): 2.23–2.28 (q, 2H, J = 6.5 Hz, H10), 2.67–2.70 (t, 2H, J = 6.5 Hz, H9), 3.39–3.40 (t, 2H, J = 6.5 Hz, H11), 7.02 (d, 1H, J = 7.0 Hz, H16), 7.10 (s, 1H, H14), 7.30 (d, 1H, J = 8.0 Hz, H4), 7.37–7.42 (m, 3H, H2, H17, H18), 7.62 (t, 1H, J = 8.0 Hz, H3), 8.68 (d, 1H, J = 8.0 Hz, H1).
13C NMR (CDCl3-d) δ: 20.85, 34.57, 40.24, 114.86, 116.88, 118.64, 124.59, 124.72, 126.15, 126.27, 127.26, 127.62, 129.16, 133.49, 133.90, 139.79, 153.38, 154.04, 154.48, 158.07, 169.64, 196.08.
MS: m/z (%), 377 (M++2, 10), 375 (M+, 30), 340 (30), 319(27), 289(14), 227(44), 127 (44), 120 (100), 100(64), 87(32), 74(36).
3.3.3 7-(4-Bromophenyl)-10,11-dihydro-6H-chromeno[4,3-b]quinoline-6,8-dione (2m)
Yield = 65%, Mp = 279–281 °C.
IR (KBr)ν: 3042, 2922, 1745, 1693, 771 cm−1.
1H NMR (CDCl3, 500 MHz), δ (ppm): 2.24 (q, 2H, J = 6.5 Hz, H10), 2.67 (t, 2H, J = 6.5 Hz, H9), 3.38 (t, 2H, J = 6.4 Hz, H11), 6.98 (d, 1H, J = 8.3 Hz, H14,H18), 7.32 (d, 1H, J = 7.0 Hz, H4), 7.40(t, 1H, J = 7.0 Hz, H2), 7.58 (d, 1H, J = 8.3 Hz, H15, H17),7.62(t, 1H, J = 70 Hz, H3), 8.67 (d, 1H, J = 7.0 Hz, H1).
13C NMR (CDCl3-d), δ: 20.87, 34.56, 40.28, 114.92, 116.91, 118.68, 124.71, 126.16, 126.26, 127.40, 127.91, 131.19, 133.48, 136.99, 153.39, 154.08, 155.10, 158.23, 169.57, 196.34.
MS: m/z (%), 421 (M++2, 11), 419 (M+, 11), 330(13), 289(100), 216(22), 149(20), 83(31), 57(76).
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Further reading
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