Substituted quinolinones. Part 19. New and unexpected results from oxidation of 3-acetyl-1-alkyl- 4-hydroxyquinolin-2(1H)-ones using selenium dioxide

Article abstract of DOI:10.1080/10426507.2013.787999

Oxidation of 3-acetyl-1-alkyl-4-hydroxyquinolin-2(1H)-ones using selenium dioxide under Riley conditions was described. The oxidation reaction produced a mixture of 2 unexpected α-keto acid and its dehydrated dimer derivatives. The oxidation reaction was studied under different reaction conditions in order to maximize the yields and optimize reaction conditions. Also, 1-alkyl-4-hydroxy-3-(2-nitroacetyl)quinolin-2(1H)-one and/or 3-acetyl-1-alkyl-4-diflouro-boryloxyquinolin-2(1H)-one derivatives were subjected to the same oxidation reaction giving rise improved reaction yields and selectivity in case of the boron-complex. Alkaline degradation of the dehydrated dimers led to formation of the 4-hydroxy-2-oxoquinoline-3-carboxylic acids while under the same conditions the α-keto acids underwent deoxalylation.

Full text of DOI:10.1080/10426507.2013.787999

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Substituted Quinolinones. Part 19.
New and Unexpected Results from
Oxidation of 3-Acetyl-1-Alkyl- 4-
Hydroxyquinolin-2(1H)-Ones Using
Selenium Dioxide
Mohamed Abass a , Hassan A. Allimony a & Heba Hassan a
a Department of Chemistry, Faculty of Education , Ain Shams
University, Roxy, Heliopolis , Cairo , Egypt
Accepted author version posted online: 05 Apr 2013.Published
online: 03 Oct 2013.
To cite this article: Mohamed Abass , Hassan A. Allimony & Heba Hassan (2013) Substituted
Quinolinones. Part 19. New and Unexpected Results from Oxidation of 3-Acetyl-1-Alkyl- 4-
Hydroxyquinolin-2(1H)-Ones Using Selenium Dioxide, Phosphorus, Sulfur, and Silicon and the Related
Elements, 188:12, 1799-1810, DOI: 10.1080/10426507.2013.787999
To link to this article: http://dx.doi.org/10.1080/10426507.2013.787999
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Phosphorus, Sulfur, and Silicon, 188:1799–1810, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.787999
SUBSTITUTED QUINOLINONES. PART 19. NEW
AND UNEXPECTED RESULTS FROM OXIDATION OF
3-ACETYL-1-ALKYL- 4-HYDROXYQUINOLIN-2(1H)-ONES
USING SELENIUM DIOXIDE
Mohamed Abass, Hassan A. Allimony,
and Heba Hassan
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy,
Heliopolis, Cairo, Egypt
GRAPHICAL ABSTRACT
Abstract Oxidation of 3-acetyl-1-alkyl-4-hydroxyquinolin-2(1H)-ones using selenium dioxide
under Riley conditions was described. The oxidation reaction produced a mixture of 2 unex-
pected α-keto acid and its dehydrated dimer derivatives. The oxidation reaction was studied
under different reaction conditions in order to maximize the yields and optimize reaction con-
ditions. Also, 1-alkyl-4-hydroxy-3-(2-nitroacetyl)quinolin-2(1H)-one and/or 3-acetyl-1-alkyl-
4-diflouro-boryloxyquinolin-2(1H)-one derivatives were subjected to the same oxidation reac-
tion giving rise improved reaction yields and selectivity in case of the boron-complex. Alkaline
degradation of the dehydrated dimers led to formation of the 4-hydroxy-2-oxoquinoline-3-
carboxylic acids while under the same conditions the α-keto acids underwent deoxalylation.
[Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the following free supple-
mental files: Additional figures].
Keywords: Riley Oxidation reaction; selenium dioxide; quinolinone; α-keto acid; difluoro-
boron complex; alkaline degradation
INTRODUCTION
Extensive research work has been made on the efficient synthesis of α-dicarbonyl
compounds, as interesting building blocks, due to their biological importance and their
utility as synthons for various valuable synthetic organic compounds.1–3 A comprehensive
Received 9 December 2012; accepted 26 February 2013.
Address correspondence to Mohamed Abass, Department of Chemistry, Faculty of Education, Ain Shams
University, Roxy, Heliopolis, 11757 Cairo, Egypt. E-mail: m.abass@chemist.com
1799

1800
M. ABASS ET AL.
variety of methods are described in literature for the preparation of α-diketones, in particular
oxidation of active α-methyl or methylene ketones to the corresponding α-dicarbonyls.4,5
The typical 80 years old Riley oxidation reaction comprising oxidation using selenium
dioxide,6 was traditionally applied in oxidation of allylic, benzylic, carbonyl compounds,
and in general for α-activated methylene compounds. Selenium dioxide has been most
efficaciously employed for the oxidation of activated α-methyl or methylene compounds
to α-carbonyl compounds.7–9
In continuation with our current research program devoted to synthesis of new 3-
heterocyclic derivatives of 4-hydroxyquinolin-2(1H)-ones,10–13 we planned to prepare some
3-glyoxal derivatives as synthones of more 3-heterocyclic substituted quinoline-2(1H)-one
derivatives. To approach this target, we developed the known Riley oxidation method using
different reaction conditions in order to optimize the yields of oxidation of 3-acetyl-1-
alkyl-4-hydroxyquinolin-2(1H)-ones. This article describes optimization of the reaction
conditions and also some new results with this reaction.
RESULTS AND DISCUSSION
During our attempts to prepare α-keto aldehyde derivatives via the known Riley oxi-
dation of 3-acetyl-4-hydroxyquinolin-2(1H)-ones, using selenium dioxide, two unexpected
products have been obtained; none of them has the aldehyde or hemiacetal functions. Thus,
according to literature reports,7,14 oxidation of the 3-acetyl derivatives 1a, b (R = Me, Et)
might lead to the corresponding 2-(1-alkyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-
oxoacetaldehydes 2a, b or their cyclic hemiacetal forms 3a, b.15,16 Under the classic Riley
oxidation conditions, this reaction gave a mixture of two products. The major product
is soluble in aqueous sodium carbonate solution. This enabled us to separate the ma-
jor product which was characterized as the α-keto acid; 2-(1-alkyl-4-hydroxy-2-oxo-1,
2-dihydroquinolin-3-yl)-2-oxoacetic acids 5a, b (R = Me, Et). The minor product 6a, b (R
= Me, Et) is insoluble in aqueous sodium carbonate solution but soluble in boiling sodium
hydroxide solution and is crystallizable from hot acetic acid (Scheme 1). The structure of
both products 5 and 6 was established on the basis of their spectral data. IR spectra of the
major product 5a, b revealed the presence of two strong stretching absorption bands at v
1751–1755 cm−1 due to carboxylic C O group and v 1690–1695 cm−1 due to ketonic C O
1
group. H NMR spectra showed the absence of the aldehydic proton and disappearance
of the acetyl CH3 protons. Interestingly, it is noted that spectra of both compounds 5a,
b revealed a deuterium-exchangeable proton observed as a singlet signal at δ 5.75–5.86
due to C H at position 3 of the quinoline moiety, a signal which can be attributed to the
existence of usual enol–ketone tautomerism.
13C NMR spectra of α-keto acids 5a, b confirmed the presence of specific signals
attributable to two C O groups of α-oxocarboxylic acid function; revealing two down-field
shifts at δ 190–192 and ∼172. Anyhow, some recent literature reports depicted for related
findings where oxidation of aryl ketones using selenium dioxide gave the corresponding
α-hydroxy acids17 or α-keto acids.18,19 Formation of the α-keto acids 5a, b can be simply ex-
plained by fast oxidation of the possible hemiacetal intermediates 3a, b which can afford the
corresponding 5-alkylfuro[3,2-c]quinoline-2,3,4(5H)-triones 4a, b. These furoquinolinetri-
ones are easily hydrolyzed upon reaction work up with aqueous sodium carbonate or even
during the reaction course via the formed water or the ambient moisture. The structure of
the minor products 6a, b was concluded on basis of their spectral and analytical data. In the
same time, the chemical experiments indicated the absence of carboxylic acid function, and

SUBSTITUTED QUINOLINONES. PART 19
1801
Scheme 1
the IR spectra of these products showed the existence of strong stretching absorption bands
due to carbonyl functions appeared at ν 1716–1731 and ν 1684 cm−1. The first absorption
vibration may be attributed to the α-lactone C O, while the second one back to different
carbonyls. The chart is complicated in the region ν 1684–1640 cm−1 which discloses the
existence of more carbonyl functions including β,β-lactone C O of pyranetrione and α,γ -
lactam C O of quinolinedione. 1H NMR spectrum of the product 6b showed the presence
of two sets for two different ethyl groups, at δ 1.17 (NCH2CH3) and 4.00-4.20 (NCH2CH3),
indicating the inclusion of two moieties of N-ethylquinolin-2-one in this molecule. This
prediction was fortified by appearance of chemical shifts due to two benzo with relative
integration of eight aromatic protons. Similar results were observed with the other deriva-
tive 6a. 13C NMR spectra of these two products 6a, b revealed specific chemical shifts at δ
184–190 and 166–172 which gave a good support for the existence of different lactone and
lactam carbonyls. Even mass spectra of these two products did not show their molecular
ion peaks but fragmentation pattern of both clearly integrated and in good accordance with
the results obtained from elemental analyses of both. Building on the above data, it was
concluded that the minor products are 1ꢁ-alkyl-2-(1-alkyl-2,4-dioxo-1,2-dihydroquinolin-
3(4H)-ylidene)-1ꢁH-spiro[pyran-4,3ꢁ-quinoline]-2ꢁ,3,4ꢁ,5,6(2H)-pentaones 6a, b (R = Me,
Et) (Scheme 1). This structure is obtainable via cyclo-dimerization of the related α-keto
acids 5a, b, which can be resulted in during heating of the reaction mixture. Thus, we
have noted that prolonged heating of the reaction mixture increases the yield ratio of
the dimers 6a, b on cost of the α-keto acids 5a, b. Vostrov et al. reported a close ther-
mal cyclo-dimerization for some furan-2,3-diones.20 Even in the present case we did not
separate furoquinolinetriones 4a, b but as depicted in scheme 2 the α-keto acids 5a, b
can lead to the dimers 6a, b via cyclo-dimerization accompanied with loss of two water
molecules. We have examined different reaction condition aiming to obtain α-keto acids
as sole product of this reaction and to check how the formation of the minor product takes

1802
M. ABASS ET AL.
Scheme 2
place. Interestingly, heating of the α-keto acids 5a, b, in dioxane for long time (∼24 h),
effected cyclo-dimerization to afford the dimers 6a, b, in nearly quantitative yields. Hence,
this result enlighten the source of the dimers 6a, b and let us postulate dehydration as
the pathway for their formation. Although, dimerization process leading to the dimers 6a,
b comprising thermal ring-opening-ring closure of the furoquinolinetriones 4a, b cannot
be completely excluded since it is known that α-keto acids 5a, b are capable to undergo
thermal cyclization to the corresponding furoquinolinetriones 4a, b.
Furthermore, the oxidation reaction of these two acetyl derivatives 1a, b, in dioxane,
was carried out under different molar ratios of the reagent, selenium dioxide. It is observed
that duplicate amount of selenium dioxide is the best suitable molar ratio which gives the
highest yield of α-keto acids 5a, b (cf. Table 1). It is notable that duplicate molar ratio
of selenium dioxide nearly triplicates the yield of the desired α-keto acids 5a, b. In the
same time, further increase in amount of the reagent (molar ratios 1:3 and 1:4) abnormally
diminishes this yield. Even these last observations are in contrast with the known Le
Chatelier’s principle, we can suggest an explanation depending on the fact that solid SeO2
forms infinite chains with oxygen bridges (O-Se(O)-O-O-Se(O)-O-Se(O)-n).21 We expect

SUBSTITUTED QUINOLINONES. PART 19
1803
Table 1 Effect of concentration of selenium dioxide in oxidation reaction of acetyl derivatives 1a, b, in boiling
dioxane for 4 h, on the reaction yields
Products yield %
Acetyl derivatives 1a,b/SeO2 molar ratio (mol/mol)
5a
5b
6a
6b
1:1
1:2
1:3
1:4
24.0
90.0
34.0
35.0
20.0
60.0
30.0
32.5
7.6
4.4
9.8
5.8
3.0
8.0
2.0
3.0
that in higher concentrations more chains of this type are present and in the same time
diffusion of the selenium dioxide molecules may occur inside or between these chains,
leading to a considerable decrease in the concentration of the active oxidizing species; free
molecular monomers of selenium dioxide.
Studying of the reaction solvent was carried out to check the proper medium for
obtaining the highest yields of the α-keto acids 5a, b. Many literature reports showed
that the oxidation of active methyl and/or methylene compounds using selenium dioxide
can be carried out in different solvents likes dioxane, glacial acetic acid, ethanol, and
pyridine. However, dioxane as polar aprotic solvent is mostly used in such reactions and
we found that dioxane can be the solvent of choice in our case in which we get the highest
reaction yields in boiling dioxane. Other solvents, such as absolute ethanol, glacial acetic
acid, anhydrous pyridine, and pyridine-water (20:1), were examined in which glacial acetic
acid furnished good yields (50%) while others give moderate to low yields. In particular,
anhydrous pyridine and/or pyridine-water proved that basic organic solvents are not proper
in our case as they gave the lowest yields (1.7–7.8%) (Table 2).
The examination of the reaction time for oxidation of the acetyl derivative 1b (taken
as an example), using selenium dioxide at the molar ratio 1:2 (Cacetyl : CSeO2) in boiling
dioxane, revealed that there is a proportional increase in reaction yield with increase of
reaction time up to 4 h. Afterward, the yield of the product 5b reached a plateau stage with
constant maximum value (60%) (Table 3). These results clearly lead to conclude that 4 h
are enough time to get the highest yields in such oxidation. Similar results were obtained in
case of oxidation of another derivative 1a which gave (90%) yields of the product 5a after
4 h.
For further improvement of the yields of α-keto acids 5a, b, many runs of the oxidation
reaction with various additives were carried out under the previous optimized conditions
Table 2 Effect of solvent in oxidation reaction of acetyl derivatives 1a, b, using selenium dioxide (molar ratio
1:2), via boiling for 4 h, on the reaction yields
Products yield %
Solvent
5a
5b
6a
6b
Acetic acid
Dioxane
Ethanol
pyridine (anhydrous)
Pyridine (95%)
50.0
90.0
32.0
07.8
01.7
50.0
60.0
29.0
08.0
01.7
5.5
4.4
3.6
3.3
5.5
5.1
8.0
3.3
2.8
5.1

1804
M. ABASS ET AL.
Table 3 Effect of reaction time in oxidation reaction of acetyl derivative 1b, using
selenium dioxide (molar ratio 1:2), via boiling in dioxane, on the reaction yields
Products yield %
Reaction Time (h)
5b
6b
1
2
3
4
5
6
24
15.0
30.0
55.0
60.0
60.0
60.0
0
2.0
3.0
7.0
8.0
8.0
8.0
25.0
(molar ratio of acetyl 1a, b/SeO2 (1:2), in boiling dioxane, reaction time 4 h) (cf. Table 4).
Interesting results were obtained in which it was found that addition of dilute nitric acid
leads to a considerable increase in yield of the α-keto acids 5b. Under this condition, in
presence of dilute nitric acid, we did not separate the dimer 6b and also, no indication for
the formation of the black selenium due to presence of nitric acid which oxidized selenium
into selenium dioxide again. Addition of dilute hydrochloric acid leads to lower yields
of α-keto acids 5a, b, without any notable change in amount of the dimers 6a, b. Both
of tangestophosphoric acid (H3PW12O40) and potassium selenite afforded similar yields
of α-keto acids 5b (50%). Again as observed in case of use of the organic basic solvent,
pyridine, the experiments showed that addition of aqueous potassium hydroxide, as an
alkaline solution, to the dioxane solution, reduces the yields of α-keto acids 5a, b to nearly
one third of their value without any additives (20–39%) (Table 4). Anyhow as depicted in
Scheme (1) the mechanism of formation of the α-keto acids 5a, b revealed removal of water
via protonation of the selenius intermediate and this explained disfavor of basic additives
in such reaction and on the other hand advantage of addition of acid catalysts. The majority
of yield of products was completely inversed when sodium salt of the acetyl derivative 1b
was utilized in which we obtained only 1.1% of α-keto acids 5b and 18.5% of the dimer
6b (cf. Experimental Method (c)).
The 1-alkyl-4-hydroxy-3-(2-nitroacetyl)-quinoline-2-(1H)-ones 8a (R = Me)22 and
8b (R = Et)23 were prepared as depicted in Scheme 3. Due to the known activation by
Table 4 Effect of various additives in oxidation reaction of acetyl derivatives 1a,
b, using selenium dioxide (molar ratio 1:2), via boiling for 4 h in dioxane, on the
reaction yields
Products yield %
Additives
5a
5b
6a
6b
Without additives
H2O
90.0
—
—
40.0
—
39.0
—
60.0
35.0
89.0
40.0
50.0
20.0
50.0
4.4
—
—
4.4
—
4.4
—
8.0
9.0
0
8.0
2.0
8.5
9.5
Dilute HNO3 (25%)
Dilute HCl (25%)
H2O/H3PW12O40 (1%)
H2O/KOH (50%)
K2SeO3

SUBSTITUTED QUINOLINONES. PART 19
1805
Scheme 3
withdrawal inductive effect of nitro group on its neighboring methylene, it is thought that
nitroacetyl derivatives 8a, b can be straightforwardly oxidized using selenium dioxide,
under the above optimized conditions. This reaction hypothetically can lead to either
1-(1-alkyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-nitroethane-1,2-diones 10a, b or
furoquinoline-triones 4a,b (Scheme 2). However, characterization of the reaction products
showed that a mixture of the α-keto acids 5a, b and the corresponding dimers 6a, b were
obtained as same as previously described in case of oxidation of acetyl derivatives 1a, b.
Since it is known that complex formation of acetyl derivatives with boron compounds
substantially increases the reactivity of the methyl group of the acetyl moiety,24,25 it was
expected that boron complexes obtainable from the acetyl derivatives 1a, b are capable to
undergo facile oxidation with selenium dioxide. In the same time, utilizing acetyl-boron
chelate complexes may remove or avoid any effect of the hydroxyl group at position-4;
like H–bonding or enhancement of enol-ketone tautomerism. Hence, 3-acetyl-1-alkyl-4-
(difluoroboryloxy)-quinolin-2(1H)-ones 11a, b were readily obtained via the reaction of
boron trifluoride etherate with the acetyl derivatives 1a, b, in boiling benzene.24 1H NMR
spectrum of the complex 11b showed a signal of the methyl protons of acetyl group, at δ
∼2.7, more shifted down-field relative to its normal chemical shift as seen by the acetyl
derivatives 1a, b (δ ∼2.1).22 Out of the ordinary, the oxidation reaction of these complexes
11a, b, using selenium dioxide under the previously optimized conditions led to the α-keto
acids 5a, b, in yields 80–90% without any ratio for the formation of the dimers 6a, b
(Scheme 4). This may be explained by structural stereo-restriction and also absence of

1806
M. ABASS ET AL.
ketone–enol tautomerism from the intermediate complex 12a, b. This does not allow the
formed acid to dimerize as previously discussed in case of oxidation of the acetyl derivatives
1a, b (Scheme 2).
Finally, when the dimers 6a, b were subjected to boiling in aqueous sodium hydroxide
solution (15%), 1-alkyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids 15a, b
(R = Me, Et) were obtained.26 Formation of the acids 15a, b can be attributed to alkaline
hydrolysis (saponification) at the α-pyrone followed by another hydrolysis leading to the
α-keto acid disodium salts 13a, b. Consequently, decarbonylation took place affording
the corresponding acids 15a, b (Scheme 5). It was found that α-keto acids 5a, b tend to
undergo decarbonylation especially when treated with acidic or alkaline media or thermally.
Even though, in some times, it was noted that deoxalylation took place giving rise to 3-
unsubstituted 1-alkyl-4-hydroxyquinolin-2(1H)-ones 16a, b27(Scheme 5).
CONCLUSIONS
In conclusion, the Riley oxidation reaction of 3-acetyl-1-alkyl-4-hydroxyquinolin-
2(1H)-ones or their 3-nitroacetyl derivatives, using selenium dioxide under different reac-
tion conditions (molar ratio, solvent, and time), was designated to obtain the corresponding
α-keto aldehydes. The reaction leads to α-keto acids as the major products along with
didehydrated dimers as the minor product. Optimized conditions gave 60–90% yields of
the α-keto acids when duplicate molar ratio of selenium dioxide was reacted with the acetyl
derivatives, in boiling dioxane for 4 h. The reaction was carried out in presence of various
additives or solvents such as water, pyridine, acetic acid, nitric acid, hydrochloric acid,
tangestophosphoric acid, potassium hydroxide, and potassium selenite. This study showed
that basic media diminish the total all yields of the α-keto acid. Under the same conditions
of the difluoroboron complexes selectively give rise to the α-keto acid. Alkaline hydrolysis
of the dimers leads to degradation to give the corresponding carboxylic acids while similar
treatment of the α-keto acids yields the parent 4-hydroxyquinolinones.
EXPERIMENTAL SECTION
Melting points are uncorrected and were determined in open capillary tubes on
a digital Stuart-SMP3 melting point apparatus. IR spectra were recorded on a Perkin-
1
Elmer FT-IR 1650 spectrophotometer, using samples in KBr disks. H NMR (300 MHz)
and 13C NMR (75 MHz) spectra were recorded on Mercury–300BB or Gemini–300BB
spectrometers (δ), using DMSO-d6 or CDCl3 as solvents and TMS as an internal reference.
Mass spectra (70 eV) were obtained using a Shimadzu GC-2010 Gas–Chromatography
instrument mass spectrometer. Elemental microanalyses were performed on a Perkin-Elmer
CHN-2400 analyzer. The acetyl derivatives 1a, b22 and the nitroacetyl derivatives 9a, b22,23
were prepared according to the reported literature methods.
Formation of the α-Keto Acids 5a, b and the Dimers 6a, b
Method (a): From oxidation of the acetylquinolinones 1a, b, using Riley
reaction. To a solution of 10 mmol of the acetylquinolinone 1a (2.17 g) or 1b (2.31 g),
in dioxane (50 mL), selenium dioxide (2.22 g, 20 mmol) was added. The mixture was
heated under reflux for 4 h. The organic solution was filtered to remove the black selenium

SUBSTITUTED QUINOLINONES. PART 19
1807
precipitate that formed during the course of reaction. The filtrate was collected and evap-
orated to give a solid residue which was dissolved in aqueous sodium carbonate solution
(100 mL, 2 M). The alkaline solution was filtered to remove insoluble materials. The clear
alkaline solution was collected and acidified using dilute hydrochloric acid (2 M) until
complete precipitation (ca. 200 mL). The precipitate was filtered, washed with water, dried
and crystallized to give the α-keto acids 5a, b. The above alkaline- insoluble materials were
collected, washed with cold water (2 × 20 mL), dried, and crystallized to give the dimers
6a, b.
2-(4-Hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)-2-oxoacetic acid (5a).
Crystallized from ethanol, yield: 2.2 g (90%), m. p. 203—205◦C (decomp.). IR (KBr,
cm−1), ν: 3447–2800 (H-bonded O–H), 3030 (C Harom), 2986 (C Haliph), 1751
(C Ocarboxylic), 1690 (C Oα-keto), and 1632 (C Oquinolone). 1H NMR (300 MHz, DMSO-
d6), δ: 3.50 (s, 3H, N–CH3), 5.75 (s, 1H, tautomeric 4-OH↔3-CH, disappeared on addition
of D2O), 7.35 (t, J = 7.8 Hz, 1H, 6-CH), 7.55 (d, J = 8.4 Hz, 1H, 8-CH), 7.83 (t, J =
7.8 Hz, 1H, 7-CH), and 8.08 (d, J = 8.1 Hz, 1H, 5-CH). 13C NMR (75 MHz, DMSO-d6),
δ: 192.5, 171.6, 165.0, 159.7, 141.9, 136.0, 125.0, 122.6, 115.4, 113.6, 102.4, and 28.6.
MS, m/z (Ir%): 248 (2.01) (M+1), 247 (12.58) (M+.), 230 (0.54), 219 (4.72), 203 (22.89),
175 (100), 161 (0.65), 133 (11), and 115 (1.64). Anal. Calcd. for C12H9NO5 (247.21): C,
58.30; H, 3.67; and N, 5.67%. Found C, 58.00; H, 3.50; and N, 5.40%.
2-(1-Ethyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-oxoacetic acid (5b).
Crystallized from ethanol, yield: 1.6 g (60%), m. p. 202—203◦C (decomp.). IR (KBr, cm−1),
ν: 3150–2800 (H-bonded O–H), 3080 (C Harom), 2964 (C Haliph),1755(C Ocarboxylic),
1695 (C Oα-keto), and 1632 (C O quinolone). 1H NMR (300 MHz, DMSO-d6), δ: 1.15 (t, J
= 7.2 Hz, 3H, N-CH2CH3), 4.15 (q, J = 6.9 Hz, 2H, N-CH2CH3), 5.86 (s, 1H, tautomeric
4-OH↔3-CH, disappeared on addition of D2O), 7.21 (t, J = 7.8 Hz, 1H, 6-CH), 7.47 (d,
J = 8.7 Hz, 1H, 8-CH), 7.67 (t, J = 6.9 Hz, 1H, 7-CH), and 8.06 (d, J = 6.6 Hz, 1H,
5-CH). 13C NMR (75 MHz, DMSO-d6), δ: 190.4, 173.0, 166.6, 161.0, 140.6, 134.2, 125.7,
121.4, 117.0, 103.3, 35.7, and 12.7. MS, m/z (Ir%): 262 (5.71) (M+1), 261 (26.3) (M+.),
233 (3.31), 217 (28.5), 216 (68.9), 189 (100), 174 (12.17), 161 (27.42), 132 (21.89), 120
(27.58), and 77 (44.75). Anal. Calcd. for C13H11NO5 (261.24) C, 59.77; H, 4.24; and N,
5.36%. Found C, 59.50; H, 4.10; and N, 5.30%.
1ꢁ-methyl-2-(1-methyl-2,4-dioxo-1,2-dihydroquinolin-3(4H)-ylidene)-1ꢁH-
spiro[pyran-4,3ꢁ-quinoline]-2ꢁ,3,4ꢁ,5,6(2H)-pentanone (6a). Crystallized from glacial
acetic acid, yield: 0.1 g (4.4%), m. p. 262—264◦C. IR (KBr, cm−1), ν: 3080 (C Harom),
2964 (C Haliph), 1716 (C Opyrone), 1683 (C Oketo), and 1631 (C Oquinolone). 1H NMR
(300 MHz, DMSO-d6), δ: 3.38 (s, 3H, N–CH3), 3.65 (s, 3H, N–CH3), 7.30 (t, J = 7.8 Hz,
1H, 6-CH), 7.43 (t, J = 7.5 Hz, 1H, 6ꢁ-CH), 7.68 (d, J = 9.0 Hz, 2H, 2 8-CH), 7.77 (t, J
= 8.0 Hz, 2H, 2 7-CH), 7.82 (d, J = 7.8 Hz, 1H, 5-CH), and 7.92 (d, J = 7.2 Hz, 1H,
5ꢁ-CH). 13C NMR (75 MHz, DMSO-d6), δ: 184.5, 166.9, 157.8, 156.7, 141.7, 139.6, 136.4,
131.6, 127.8, 123.5, 123.0, 122.7, 118.5, 116.3, 115.7, 111.3, 103.9, 89.3, 30.23, and
29.5. MS, m/z (Ir%): 458 (not detected) (M+.), 428 (11.56), 426 (40.96), 424 (23.95), 370
(7.49), 346 (10.28), 290 (11.10), 237 (11.37), 213 (11.41), 173 (31.24), 146 (43.57), 132
(36.69), 129 (32.51), 118 (12.47), 117 (C7H3NO+.) (100), 104 (45.15), and 91 (C6H5N+.).
Anal. Calcd. for C24H14N2O8 (458.39) C, 62.89; H, 3.08; and N, 6.11%. Found C, 62.70;
H, 3.00; and N, 6.10%.
1ꢁ-Ethyl-2-(1-ethyl-2,4-dioxo-1,2-dihydroquinolin-3(4H)-ylidene)-1ꢁH-
spiro[pyran-4,3ꢁ-quinoline]-2ꢁ,3,4ꢁ,5,6(2H)-pentanone (6b). Crystallized from glacial
acetic acid, yield: 0.19 g (8%), m. p. 250–252◦C. IR (KBr, cm−1), ν: 3080 (C Harom),

1808
M. ABASS ET AL.
2986 (C Haliph), 1713 (C Opyrone), 1684 (C Oketo), 1636 (C Oquinolone), 1H NMR
(300 MHz, DMSO-d6), δ: 1.15 and 1.18 (m, 6H, 2 N-CH2CH3), 4.00 (q, J = 9.18 Hz, 2H,
N-CH2CH3), 4.20 (q, J = 8.28 Hz, 2H, N-CH2CH3), 7.25 (t, J = 9.0 Hz, 1H, 6-CH), 7.38
(t, J = 9.6 Hz, 1H, 6-CH), 7.43 (d, J = 9.6 Hz, 2H, 8-CH), 7.72 (t, J = 10.2 Hz, 2H,
7-CH), 7.8 (d, J = 10.2 Hz, 1H, 5-CH), and 7.9 (d, J = 8.4 Hz, 1H, 5-CH). 13C NMR
(75 MHz, DMSOd6), δ: 184.7, 166.6, 157.4, 156.8, 140.4, 138.5, 136.5, 131.7, 128.1,
123.4, 123.2, 122.5, 118.8, 116.0, 115.4, 111.5, 103.8, 89.3, 37.5, 37.1, 12.8, and 11.6.
MS, m/z (Ir%): 486 (not detected) (M+.), 458 (M-CO+.) (0.69), 456 (18.83), 454 (83.49),
452 (44.77), 426 (18.27), 425 (60.40), 423 (31.42), 422 (12.95), 261 (0.43), 217 (0.43),
208 (3.47), 188 (3.16), 187 (7.10), 172 (9.21), 146 (C9H8NO+) (100), 132 (10.41), 130
(16.83), 118 (15.52), 104 (12.33), 90 (36.47), 77 (28.81), and 76 (C6H4+.) (10.50). Anal.
Calcd. for C26H18N2O8 (486.44) C, 64.20; H, 3.73; and N, 5.76%. Found C, 64.15; H,
3.70; and N, 5. 70%.
Method (b): From Oxidation of the Acetylquinolinones 1a, b, Using
Different Additives
To a solution of 10 mmol of the 3-acetylquinolinones 1a (2.17 g) and/or 1b (2.31 g), in
dioxane (50 mL), selenium dioxide (2.22 g, 20 mmol), and a certain only one additive from
the following reagents: water (5 mL), dilute nitric acid (4 mL, 25%), dilute hydrochloric
acid (4 mL, 25%), aqueous tangestophosphoric acid solution (1%), aqueous potassium
hydroxide solution (2 mL, 50%), and/or potassium selenite (0.5 g), were added. The
mixture was heated under reflux for 4 h. The black selenium precipitate that formed during
the course of reaction was filtered and the dioxane solution filtrate was collected and
evaporated. The solid product was treated as in Method (a). Exceptionally, in case of using
nitric acid as additive, it was observed that no black selenium was formed and the clear
reaction solution was poured onto water to give a solid precipitate which was filtered and
worked up as in Method (a). The mentioned treatments yielded the α-keto acids 5a, b
and/or the dimers 6a, b, as cited in Table 4.
Method (c): From Oxidation of the Sodium Salt of the acetylquinol-
inone 1b
To a solution of sodium 3-acetyl-1-ethyl-2-oxo-1,2-dihydroquinolin-4-olate (Na-1b)
(2.53 g, 10 mmol), in dioxane (40 mL) and water (10 mL), selenium dioxide (2.22 g,
20 mmol) was heated under refluxing for 4 h. Afterward, the reaction mixture was left to
cool at room temperature and filtered off black selenium precipitates. The aqueous dioxane
solution was poured onto ice-cold water. The precipitate that formed was filtered, washed
with water, dried, and crystallized from glacial acetic acid to give the dimer 6b, yield: 0.45 g
(18.5%). The filtrate aqueous solution and washing water were collected and neutralized
using dilute hydrochloric acid. A solid precipitate was obtained and crystallized to give the
α-keto acid 5b, yield: 0.03 g (1.15%).
Method (d): From Oxidation of the Nitroacetyl Derivatives 9a, b
A mixture of 10 mmol of the 3-nitroacetylquinolinone 9a (2.62 g) or 9b (2.76 g) and
selenium dioxide (2.22 g, 20 mmol), in dioxane (50 mL), was heated under reflux for 4 h.
The organic solution was filtered off the black selenium precipitate, which formed during

SUBSTITUTED QUINOLINONES. PART 19
1809
the course of reaction. The filtrate was collected and treated as in above Method (a) to give
the α-keto acids 5a, yield: 1.98 g (80%) and 5b, yield: 1.41 g (54%), along with the dimers
6a, yield: 0.12 g (5%) and 6b, and yield: 0.22 g (9%).
Method (e): From oxidation of the Boron Difluoride Complexes 11a, b
To a solution of 10 mmol of the boron difluoride complex 11a (2.65 g) or 11b
(2.79 g), in dioxane (50 mL), selenium dioxide (2.22 g, 20 mmol) was added. The reaction
mixture was heated under reflux for 4 h. The black selenium precipitate that formed,
during the course of reaction, was filtered. The dioxane solution filtrate was evaporated to
give a pale yellow solid material. The solid residue was completely dissolved in aqueous
sodium carbonate solution (100 mL, 2 M) and filtered off to give a clear alkaline solution.
Acidification of the alkaline solution using dilute hydrochloric acid (100 mL, 2 M) gave a
quantitative precipitate. The precipitate was filtered, dried, and crystallized from ethanol to
give the α-keto acids 5a, yield: 2.22 g (90%) and 5b, yield: 2.09 g (80%).
3-acetyl-4-(difluoroboryloxy)-1-methylquinolin-2(1H)-one (11a). This compound
was prepared as described in literature; yield 86%, m. p. 226–228◦C (Lit.24 m. p.
226–227◦C).
3-Acetyl-4-(difluoroboryloxy)-1-ethylquinolin-2(1H)-one (11b)
In a 3-neck flask, fitted with a stirrer and a dropping funnel, a solution of the
acetylquinolinone 1b (2.31 g, 10 mmol), in dry benzene (50 mL), was heated under reflux.
Then a solution of boron trifluoride etherate (1.56 g, 11 mmol), in benzene (5 mL), was
added drop-wise and the reaction mixture was refluxed for 4 h. The excess benzene was
evaporated and the yellow precipitate was collected, dried, and crystallized from benzene.
Yield: 2.23 g (80%), m. p. 216–218◦C. IR (KBr, cm−1), ν: 3080 (C Harom), 2946, 2917
(C Haliph), 1658 (C Oketo), 1616 (C Oquinolone), 1374, 1204 (O–BF2), and 1057 (B–F). 1H
NMR (300 MHz, DMSO-d6), δ: 1.20 (t, J = 6.9 Hz, 3H, N-CH2CH3), 2.74 (s, 3H, COCH3),
4.24 (q, J = 6.9 Hz, 2H, N-CH2CH3), 7.33 (t, J = 8.1 Hz, 1H, 6-CH), 7.59 (d, J = 9.3 Hz,
1H, 8-CH), 7.79 (t, J = 7.2 Hz, 1H, 7-CH), and 8.12 (d, J = 7.8 Hz, 1H, 5-CH). MS, m/z
(Ir%): 280 (15.19) (M + 1), 279 (100) (M+.), 278 (77.90), 264 (48.92), 251 (72.54), 236
(88.55), 222 (25.57), 208 (12.95), 192 (13.72), 188 (4.89), and 161 (1.79). Anal. Calcd. for
C13H12BF2NO3 (279.05) C, 55.96; H, 4.33; and N, 5.02%. Found C, 56.10; H, 4.20; and
N, 4.80%.
1-Alkyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids 15a, b
To an aqueous sodium hydroxide solution (20 mL, 15%) 2 mmol of the dimer 6a
(0.92 g) and/or 6b (0.97 g) was added. The reaction suspension was heated under reflux.
After 2 h, it was observed that the reaction mixture turned to a clear brownish solution
which was boiled for additional 4 h. The clear alkaline solution was left to cool, diluted
with water (30 mL), and filtered off. Acidification using dilute hydrochloric acid led to a
solid precipitate which was filtered, washed thoroughly with cold water (50 mL), dried, and
crystallized from ethanol to give the acids 15a, yield: 0.68 g (78%), m. p. 265–266◦C (Lit.26
m. p. 268–269◦C) and 15b, yield: 0.71 g (76%), m. p. 262–264◦C (Lit.26 m. p. 266–267◦C).

1810
M. ABASS ET AL.
1-Alkyl-4-hydroxyquinolin-2(1H)-ones 16a, b
A solution of 10 mmol of the α-keto acids 5a (2.47 g) and/or 5b (2.61 g), in aqueous
sodium hydroxide (20 mL, 15%), was heated under reflux for 6 h. Then the alkaline solution
was filtered off and the clear filtrate was acidified using dilute hydrochloric acid (10%) till
complete precipitation. The precipitate, so formed, was filtered, washed with water several
times, dried, and crystallized from methanol, to give the quinolinones 16a, yield: 1.19 g
(68%), m. p. 261–262◦C (Lit.27 m. p. 268◦C) and 16b, yield: 1.49 g (79%), m. p. 258–259◦C
(Lit.27 m. p. 264◦C).
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