Thermal and photochemical approaches to the synthesis of v/c-tricarbonyl compounds from 4-hydroxyquinolin-2(1h)-ones

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Thermal and Photochemical
Approaches to the Synthesis of vic-
Tricarbonyl Compounds from 4-
Hydroxyquinolin-2(1H)-ones
Jia-Hai Ye a , Zhichun Qin a , Bin Zhou a , Wenchao Zhang a , Guirong
Tian a , Lei Yuan a & Jian-Hua Xu b
a Department of Applied Chemistry, Nanjing University of Science
and Technology, Nanjing, P. R. China
b Department of Chemistry, Nanjing University, Nanjing, P. R. China
Published online: 14 Apr 2009.
To cite this article: Jia-Hai Ye , Zhichun Qin , Bin Zhou , Wenchao Zhang , Guirong Tian , Lei Yuan
& Jian-Hua Xu (2009): Thermal and Photochemical Approaches to the Synthesis of vic-Tricarbonyl
Compounds from 4-Hydroxyquinolin-2(1H)-ones, Organic Preparations and Procedures International:
The New Journal for Organic Synthesis, 41:1, 83-87
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Organic Preparations and Procedures International, 41:83–87, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print
DOI: 10.1080/00304940802711085
OPPI BRIEFS
Thermal and Photochemical Approaches
to the Synthesis of vic-Tricarbonyl Compounds
from 4-Hydroxyquinolin-2(1H)-ones
Jia-Hai Ye,1 Zhichun Qin,1 Bin Zhou,1
Wenchao Zhang,1 Guirong Tian,1 Lei Yuan,1 and Jian-Hua Xu2
1Department of Applied Chemistry, Nanjing University of Science and
Technology, Nanjing, P. R. China
2Department of Chemistry, Nanjing University, Nanjing, P. R. China
vic-Tricarbonyl compounds are important both as interesting synthetic intermediates and as
biologically active compounds.1–6 As a result, the investigation of synthetic methodology
of vicinal triketones remains of current research interest. However, the preparation of vic-
tricarbonyl compounds from 1,3-dicarbonyl compounds usually requires their initial trans-
formation to an active precursor such as the keto-phosphorane or enamine, which is then
readily oxidized to the tricarbonyls either thermally (e.g. by ozone) or photochemically.7–12
Hypervalent iodine (V and III) compounds have also been used as alternative oxidants
but the explosive character is a drawback for hypervalent iodine (V) and the employ-
ment of the ozone as the co-oxidant restricts practical application of hypervalent iodine
(III).13–14 Two decades ago, Wasserman et al. described the dye-sensitized photooxidation
of cyclic enolic 1,3-dicarbonyl compound with singlet oxygen. However, for heterocyclic
1,3-dicarbonyl compounds, such as 4-hydroxycoumarin, none of the corresponding trione
was obtained under this dye-sensitized reaction condition.15 Shortly thereafter, Wamhoff
et al. reported the synthesis of quinolinetriones from the singlet oxygen photolysis of dihalo-
4-hydroxyquinolin-2(1H)-one.16 With the goal of expanding the scope of an efficient route
to vic-tricarbonyl compounds, we now report the convenient synthetic methods of vic-
heterocyclic tricarbonyl compounds directly from enolic dicarbonyl compounds through
photochemical and thermal approaches without the co-oxidant.
In the context of our research interest in the photochemistry of quinoline and
isoquinoine derivatives,17–18 the synthesis of vic-tricarbonyls was achieved from the
reaction of 4-hydroxyquinolin-2(1H)-ones with singlet oxygen using methylene blue
Submitted November 1, 2007.
Address correspondence to Jia-Hai Ye, Department of Applied Chemistry, Nanjing University
of Science and Technology, Nanjing 210094, P. R. China. E-mail: yejiahai@mail.njust.edu.cn
83

84
Ye et al.
(MB) or rose bengal (RB) as the sensitizers. Irradiation of a solution of 1a (0.05 mol L−1
)
and the sensitizer RB (5×10−4 mol L−1) in 20 ml methanol under oxygen atmosphere at
room temperature with light of wavelength > 500 nm resulted in smooth consumption
of the starting material and gave the quinolin-2,3,4-trione 2a (12%) and its hydrate 3a
(72%) as the products (Scheme 1). The RB sensitized photooxygenation of 1b under
Scheme 1
similar conditions gave the corresponding triketone 2b and its hydrate 3b in 98% total
yield. But only the corresponding triketone was obtained in the photooxygenation of 1c.
Photooxygenation of 1a-1c in methanol with Methylene Blue (MB) as the sensitizer gave
results similar to that with RB as a sensitizer but in slightly lower total yields (Table 1).
In addition to the dye-sensitized photooxidation of 1, we next focused our interest on the
thermal oxidation of 1. After many usual oxidants were tested, inexpensive commercially
available PhI(OAc)2 (iodobenzene diacetate, IBD), was found to be an effective reagent for
the oxidation of 4-hydroxyquinolin-2(1H)-ones. 4-Hydroquinolin-2-ones 1 was oxidized
by IBD (1.5 equiv.) in the presence of base, followed by the hydrolysis using 6N HCl
as the catalyst under reflux to afford the expected triketones 2 in moderate overall yield
(Scheme 2). It should be noted that when the substitutent on nitrogen was Ph, the fully
hydrated vicinal tricarbonyl compound (2c·3H2O) was obtained.
Scheme 2
In conclusion, the new efficient synthetic routes of vicinal heterocyclic tricarbonyl
compounds from 4-hydroxyquinolin-2(1H)-ones through thermal and photochemical ap-
proaches were conveniently achieved.

Synthesis of vic-Tricarbonyl Compounds
85
Table 1
Dye-sensitized photooxygenation of 1
Irradiation
time (h)
Products and
Yields (%)
Substrate
Sensitizer
1a
1b
1c
1a
1b
1c
RB
RB
RB
MB
MB
MB
26
21
42
42
38
35
2a (12), 3a (72)
2b (10), 3b (88)
2c (75)
2a (11), 3a (65)
2b (9), 3b (72)
2c (64)
Experimental Section
All commercial available reagents used were AR grade. MeOH and THF were distilled
according to the standard method prior to use. Mps were measured on a YANACO mi-
1
croscopic melting point apparatus and are uncorrected. H NMR spectra were recorded
on Bruker 300 spectrometer in CDCl3 with SiMe4 as an internal standard. J values are
given in Hz. IR spectra were taken on a Nicolet 5DXFT-IR spectrometer. Mass spectra
were recorded on a VG ZAB-HS spectrometer. Elemental analyses were obtained using a
Perkin-Elmer-240C analyzer.
General Procedure for the Preparation of 2 and 3.
(a) Photochemical Reaction. All the photolyses were carried out with light of wavelength
longer than 300 nm from a 500 W medium-pressure mercury lamp in a cooled glass
water-jacketed vessel. Solutions of 4-hydroquinolin-2-ones 1 (3 mmol) and RM or MB
(0.03 mmol) in 100 ml methanol were placed in several glass tubes (20 ml each) and
irradiated around the light source under constant dry oxygen bubbling. The course of
reaction was monitored by TLC. At the end of the reaction, the solvent was removed
and the residue was subjected to silica gel column chromatography with ethyl ac-
etate and petroleum (b.p. 60–90oC) as eluent for gradient elution to afford the products
2 and 3.
(b) Thermal Reaction. A mixture of IBD (3 mmol), KOH 6 mmol) and 4-
hydroquinolin-2-ones 1 (2 mmol) was stirred in MeOH (15 ml) at 0◦C, then for 12 h
at room temperature. After the reaction was stopped, the solvent was removed in vacuo
and water was added and the product was extracted with ethyl acetate (3×8 mL). The
combined organic layer was dried over anhydrous MgSO4 and evaporated to give the crude
compound. This crude compound was dissolved in 10 mL THF and 2 mL 6N HCl was
added. The mixture was heated at 80◦C for 2 h. Then the solvent was removed in vacuo
and water was added and the product was extracted with ethyl acetate (3×10mL). The
combined organic layer was dried over anhydrous MgSO4 and evaporated to give crude
product which was purified by column chromatography on silica gel with ethyl acetate and
petroleum (bp 60–90oC) as eluent for gradient elution to give the product 2.

86
Ye et al.
N-Methylquinoline-2,3,4-trione (2a), mp. 125–127◦C; IR: 3050, 2830, 1720, 1605,
1
1462, 1360, 1312, 1105, 1085, 760 cm−1; H NMR (300 MHz, CDCl3): δ 3.30 (3H,
s, CH3), 7.00–7.94 (4H, m, ArH); Mass Spec. m/z(EI): 161 (M-C = O, 33), 146 (19),
133(23), 104(100), 90(23), 77(33).
Anal. Calcd for C10H7NO3: C, 63.49; H, 3.73; N, 7.40
Found: C, 63.63; H, 4.01; N, 7.41
N-Methyl-3,3-dihydroxyquinoline-2,3,4-trione (3a), mp. 82–84◦C (decomposed);
IR: 3340, 3100, 1708, 1640, 1600, 1472, 1385, 1295, 1100, 1025, 998, 770 cm−1; 1H NMR
(300 MHz, CDCl3): δ 3.35 (2H, br, 2OH), 3.48 (3H, s CH3),7.25–8.33 (4H, m, ArH); Mass
Spec. m/z(EI): 175 (M-H2O, 14), 147 (14), 131 (48), 119 (100), 104 (89), 90 (72), 77 (83).
Anal. Calcd for C10H9NO4: C, 57.97; H, 4.38; N, 6.76
Found: C, 57.99; H, 4.65; N, 6.47
N-Ethylquinoline-2,3,4-trione (2b), mp. 90–92◦C; IR: 3065, 2988, 2938, 1736, 1609,
1469, 1356, 1286, 1216, 1195, 1089, 759 cm−1; 1H NMR (300 MHz, CDCl3): δ 1.40 (3H,
t, J = 11.5, CH3), 3.81 (2H, q, J = 11.5, CH2), 7.10–7.54 (2H, m, ArH), 7.70–8.00 (2H,
m, ArH); Mass Spec. m/z(EI): 195 (M-C = O, 100), 167 (54), 139 (17), 115 (6), 90 (9), 77
(16).
Anal. Calcd for C11H9NO3: C, 65.02; H, 4.46; N, 6.89
Found: C, 65.25; H, 4.63; N, 6.80
N-Ethyl-3,3-dihydroxyquinoline-2,3,4-trione (3b), mp. 126–128◦C; IR: 3330, 3100,
3060, 2900, 2800, 1708, 1618, 1595, 1460, 1395, 1270, 1180, 1000, 922, 765 cm−1; 1H
NMR (300 MHz, CDCl3): δ 1.22 (3H, t, J = 9.5, CH3), 4.02 (2H, q, J = 9.5, CH2), 3.16
(2H, br, 2OH), 7.050–7.86 (4H, m, ArH); Mass Spec. m/z(EI): 189 (M- H2O, 6), 161 (14),
133 (31), 104 (100), 90 (26), 77 (39).
Anal. Calcd for C11H11NO4: C, 59.73, H: 5.01; N, 6.33
Found: C, 60.02, H: 5.26; N, 6.08
N-Phenylquinoline-2,3,4-trione (2c), mp. 136–138◦C; IR: 3030, 2800, 1715, 1603,
1460, 1355, 1295, 1175, 750 cm−1; 1H NMR (300 MHz, CDCl3): δ 7.00–7.81 (9H, m,
ArH); Mass Spec. m/z(EI): 206 (M-C = O, 6), 175 (19), 145 (23), 132 (57), 119 (100), 90
(69), 77 (73).
Anal. Calcd for C15H9NO3: C, 71.71; H, 3.61; N, 5.58
Found: C, 71.85; H, 3.45; N, 5.46
N-Phenylquinoline-2,3,4-trione trihydrates (2c), mp. 255–257◦C; IR: 3432, 3050,
1
1722, 1693, 1597, 1490, 1460, 1336, 1297, 1246, 1069, 846, 754 cm−1; H NMR
(300 MHz, CDCl3): δ 6.53 (9H, d, J = 8.4), 7.28–7.25 (13H, m, ArH+hydrates), 8.16
(1H, d, J = 7.2); Mass Spec. m/z(EI): 305 (10), 270 (100, M-H2O-OH), 242 (15), 195 (21),
167 (8).
Anal. Calcd for C15H15NO6: C, 59.01; H, 4.95; N, 4.59
Found: C, 58.85; H, 5.15; N, 5.60
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