Synthesis of fluorinated 2-phenyl-4-quinolones from pyrrole-2,3-diones

Article abstract of DOI:10.1039/b202128e

A series of substituted 2-phenyl-4-quinolones 8-11 have been synthesized in good yields via flash vacuum thermolysis (FVT) of 1-aryl-4-cyano-5-phenylpyrrole-2,3-diones 7a-e and 1-aryl-4-methoxycarbonyl-5-phenylpyrrole-2,3-diones 7f-j. The pyrrolediones 7

Full text of DOI:10.1039/b202128e

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Synthesis of fluorinated 2-phenyl-4-quinolones from pyrrole-2,3-
diones†
V. V. Ramana Rao and Curt Wentrup*
1
Department of Chemistry, The university of Queensland, Brisbane, Qld 4072, Australia.
E-mail: wentrup@mailbox.uq.edu.au
Received (in Cambridge, UK) 28th February 2002, Accepted 11th April 2002
First published as an Advance Article on the web 23rd April 2002
A series of substituted 2-phenyl-4-quinolones 8–11 have been synthesized in good yields via flash vacuum thermolysis
(FVT) of 1-aryl-4-cyano-5-phenylpyrrole-2,3-diones 7a–e and 1-aryl-4-methoxycarbonyl-5-phenylpyrrole-2,3-diones
7f–j. The pyrrolediones 7 were prepared from amines 3 and benzoylacetonitriles 5a–e or methyl 3-arylamino-3-
phenylprop-2-enoates 5f–j.
Introduction
Over the past two decades quinolone antibiotics of type 1 have
received considerable attention and resulted in an enormous
amount of research on new structural modifications to improve
the overall spectrum of antibacterial activity. Worldwide efforts
have delivered highly successful antibiotics such as cipro-
floxacin (1, R = cyclopropyl; X = piperazinyl) and norfloxacin
(1, R = ethyl; X = piperazinyl),1,2 related naphthyridone anti-
biotics such as enoxacin3 and trovafloxacin,4 and several other
drugs.5 Recent literature indicates that there is a number of
new fluoroquinolone drugs in very late clinical development.6 A
typical requirement for high antibiotic activity is a carboxylic
acid function in position 3 and a fluorine in position 6 of the
quinolone ring. A saturated heterocyclic amine group is usually
present in position 7. In the course of our research on the
rearrangements and cyclization of ketenes, we have found that
imidoylketenes 2 can be generated in several different ways,
viz. by rearrangement of oxoketenimines formed from tri-
azoles,7 from 5-aminomethylene-derivatives of Meldrum’s acid
derivatives,8 and by CO extrusion from pyrrole-1,2-diones.9
The imidoylketenes cyclize efficiently to 4-quinolones. Here
we report the synthesis of a series of (7,8-substituted) 2-phenyl-
6-fluoro-4-quinolones 8–11 by means of flash vacuum
thermolysis (FVT) of pyrrolediones 7. It has been shown in
another context that 2-phenylquinolones are efficient cytotoxic
agents against human lung carcinoma.10
Table
1
Yields and physical data for methyl 3-arylamino-3-
phenylprop-2-enoates 5f–j and nitriles 5a–e
Results and discussion
Compd.
Yield (%)
Mp/ЊC
Reaction of substituted anilines 3a–e with benzoylacetonitrile
4a and methyl benzoylacetate 4f in AcOH at 80 ЊC without
solvent afforded the corresponding cinnamic nitriles 5a–e
(enamino esters) and propionates 5f–j in yields of 52–87%
(Table 1). Treatment with oxalyl chloride afforded the
pyrrolediones 7. It has been reported that HCl evolved during
the reaction could cause partial decomposition of the
pyrrolediones to tetrahydrofurantrione derivatives 6 when
phenyl and aliphatic amines were used (Scheme 1).11 Indeed, in
some of our initial reactions with 5i,j we obtained only the
colourless triones (6i,j) in place of the usually brightly coloured
pyrrolediones. This problem was overcome by adding the
5a
5b
5c
5d
5e
5f
75
78
81
80
45
82
70
87
56
52
142–144
134–136
154–156
151–152
oil
91–93
46–48
96–98
oil
5g
5h
5i
5j
oil
oxalyl chloride at Ϫ50 ЊC, and the products 7a–j were obtained
in excellent yields (82–94%). Yields, analytical data and charac-
teristic IR frequencies are reported in Table 2.
† Electronic supplementary information (ESI) available: spectroscopic
data of compounds 5–11 (Tables S1–S3). See http://www.rsc.org/
suppdata/p1/b2/b202128e/
The IR spectra of pyrrolediones 7a–e displayed characteristic
absorption at 2219–2228 cmϪ1 due to the CN stretching
1232
J. Chem. Soc., Perkin Trans. 1, 2002, 1232–1235
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b202128e

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Table 2 Yields and physical data for the 1-aryl-4-cyano-5-phenylpyrrole-2,3-diones 7a–e and 1-aryl-4-methoxycarbonyl-5-phenylpyrrole-2,3-diones
7f–j
Calcd (%) (Found)
C
νmax/cmϪ1
IR
Compd.
Yield (%)
Mp/ЊC
Molecular formula
H
N
7a
7b
7c
7d
7e
7f
75
82
85
87
94
86
89
83
84
86
224–22614
207–209
187–189
171–173
151–153
221–223
218–220
172–174
179–181
147–149
C17H10N2O2
C17H9N2O2F
C17H9N2O2F
C17H8N2O2F2
C17H7N2O2F3
C18H13NO4
C17H12NO4F
C17H12NO4F
C17H11NO4F2
C17H10NO4F3
74.45 (74.31)
69.86 (69.95)
69.86 (69.84)
65.67 (65.80)
61.89 (62.20)
70.36 (70.14)
66.46 (66.56)
66.46 (66.30)
62.97 (63.09)
59.83 (59.79)
3.65 (3.62)
3.08 (3.08)
3.08 (3.07)
2.58 (2.58)
2.06 (2.13)
4.23 (4.46)
3.69 (3.74)
3.69 (3.74)
3.20 (3.24
2.77 (2.66)
10.22 (10.00)
9.59 (9.57)
9.59 (9.57)
8.96 (9.03)
8.48 (8.54)
4.56 (4.91)
4.30 (4.25)
4.30 (4.24)
4.08 (3.95)
3.88 (3.82)
2222, 1769, 1724
2228, 1773, 1719
2219, 1773, 1727
2223, 1783, 1735
2225, 1773, 1735
1769, 1727, 1714
1771, 1731, 1712
1773, 1727, 1719
1773, 1735, 1723
1778, 1741, 1724
7g
7h
7i
7j
Scheme 1
vibration, and at 1720–1780 cmϪ1 due to the five-membered
ring dione. Similar absorptions were observed for 7f–j at 1710–
1775 cmϪ1. The 13C NMR spectra of 7a–e displayed charac-
teristic peaks at δ 175–176, 155.5–156.3 and 87.5–88.5 due to
the two carbonyls and the CN group, respectively.12 The 9-
fluoro derivative 7c exhibits doublets due to carbon–fluorine
couplings in the 13C NMR spectrum. The doublet at δ 129.0
ppm was assigned to the C-7 (JCF = 9 Hz), a doublet at
δ 116.9 ppm to C-8 (JCF = 23 Hz), and a doublet at 162.4 ppm
to C-9 (JCF = 250 Hz), on the basis of chemical shifts,
coupling constants, and a DEPT experiment. Likewise, signals
were observed for 7f–j at δ 177–178.0, 156–157, 161–161.5
δ 12.7–13.1 due to N–H, and 7.25–8.40 (m) due to aromatic
protons. The 13C NMR spectra of compounds 8a–e displayed
signals at δ 172–175 (C᎐O), 116–117 (CN). The 13C NMR
᎐
spectrum of the 6-fluoro compound 8c displayed doublets due
to carbon–fluorine couplings. The doublet at δ 122.1 ppm was
assigned to the C-5 (JCF = 25.3 Hz), a doublet at 159.4 ppm to
C-6 (JCF = 243 Hz), a doublet at 109.3 to C-7 (JCF = 22.9 Hz),
and a doublet at 122.4 to C-8 (JCF = 8.6 Hz) on the basis of
chemical shifts, coupling constants, and a DEPT experiment.
The 13C NMR spectra of compounds 9a–e showed signals at
δ 176–179 (C᎐O) and 165–165.3 (COOH) (Table S2).
᎐
Alkylation of 8a–d with ethyl iodide in the presence of
potassium carbonate yielded the O-ethyl derivatives 10a,c,d
(16–30%) and only in one case the N-ethyl compound, 10b. The
methylation of 2-phenylquinolines with methyl iodide was
reported to yield a mixture of N and O-alkylated products,
but when ethyl or higher alkyl halides were used, only the O-
and 51.8 due to C-4, C-5, ester C᎐O, and CH , respectively
᎐
3
(Table S1).
FVT of compounds 7 at 500 ЊC yielded quinolones 8 in yields
of 60–88% (Table 3). Alkaline hydrolysis of 8a–e resulted in
1
4-oxoquinoline-3-carboxylic acids 9a–e. The H NMR spectra
1
of the quinolones 8 and 9 showed characteristic signals at
alkylated derivative was obtained.10 The H NMR spectra of
J. Chem. Soc., Perkin Trans. 1, 2002, 1232–1235
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Table 3 Yields and physical data for the 2-phenyl-4-quinolones 8–10
Calcd (%) (Found)
C
Comd.
Yield (%)
Mp/ЊC
Molecular formula
H
N
Mϩ
a
a
a
a
a
a
a
a
a
a
8a
8b
87
81
77
80
77
70
88
60
65
86
30
17
27
16
C16H10N2O
78.02 (77.82)
72.72 (72.95)
72.72 (72.73)
68.08 (68.06)
64.00 (64.09)
72.45
67.84
67.84 (67.97
63.78
4.10 (4.08)
3.41 (3.38)
3.41 (3.41)
2.83 (2.80)
2.33 (2.19)
4.15
3.53
3.53 (3.31)
3.00
11.38 (11.35)
10.60 (10.58)
10.60 (10.39)
9.93 (9.76)
9.33 (9.27)
5.28
4.95
4.95 (4.78)
4.65
246.0793
264.0697
264.0697
282.0611
300.0515
265.0730
283.0661
283.0651
301.0552
319.0437
274.1105
292.104
C16H9N2OF
C16H9N2OF
C16H8N2OF2
C16H7N2OF3
C16H11NO3
C16H10NO3F
C16H10NO3F
C16H9NO3F2
C16H8NO3F3
C18H14N2O
8c
8d
8e
9a
9b
9c
9d
9e
60.19
2.50
4.39
10a
10b
10c
10d
124–126
125–127
151–153
137–139
78.83 (78.87)
73.97(73.96)
73.97(74.29
69.67 (69.89)
5.11 (5.00)
4.45 (4.32)
4.45 (4.45
3.87 (3.85)
10.22 (10.00)
9.59 (9.48)
9.59 (9.48)
9.03 (8.80)
C18H13N2OF
C18H13N2OF
C18H12N2OF2
292.1013
310.0918
a > 300 ЊC.
the ethylated products 10a–d displayed signals at δ 1.3–1.6 (t,
3H) and δ 4.1–4.8 (q, 4H) which are readily assignable to the
ethyl group (Table S2). The 13C NMR spectra of compounds
10a,c and 10d displayed signals at δ 167–168 (C–O), 116.6–
117.7 (CN), 71 (CH2) and 15.7 (CH3), revealing that they are
O-alkylated products. In contrast, compound 10b displayed
General procedure for the preparation of 3-aryl-3-phenylamino-
propenenitriles 5a–e
A solution of substituted arylamines 3a–e (10 mmol), benzoyl-
acetonitrile 4a (50 mmol), and AcOH (50 mmol) was warmed at
80 ЊC for 3 h. The progress of the reaction was monitored by
GCMS to check for the absence of starting material 4a. The
reaction mixture was then cooled to room temperature. Solids
precipitated at room temperature in the cases where 3a,c,d were
used. In the other cases the mixture was diluted with benzene
(20 cm3), stirred, filtered, and the solid was washed with
benzene and dried. The filtrate, or the reaction mixture where
no solid precipitated, was diluted with water (50 cm3) and
extracted with CH2Cl2. The organic layer was washed with
10% HCl, and then with saturated NaCl solution, dried
over Na2SO4, and the solvent was evaporated. The residue was
purified by column chromatography on silica gel using benzene
as eluent. Yields and data are reported in Table 1.
signals at δ 173.5 (C᎐O), 105.1 (CN), 44.9 (CH ) and 14.1
᎐
2
(CH3), corresponding to an N-alkylated product. The IR
spectrum of 10b clearly shows the presence of a C᎐O absorp-
᎐
tion at 1622 cmϪ1. We could not isolate even small amounts of
alkylated products from 8e and 9a–e.
The literature reveals that the most successful antibacterial
quinolones are substituted with piperazinyl, or pyrrolidinyl
groups at position 7.5 The condensation of compounds 8d and
9d with piperazine and cis-2,6-dimethylpiperazine in pyridine
gave the substituted quinolones 11 in 20–30% yields. The IR
spectra of 11a and 11b displayed characteristic absorptions at
ca. 3440–3480, 2220, and 1637 cmϪ1 due to NH, CN, and CO
groups, respectively. The presence of the piperazine moiety in
11a was confirmed by its 1H NMR spectrum showing an eight
proton signal at δ 3.0. Similarly, the cis-3,5-dimethylpiperazinyl
moiety in 11b gave rise to a doublet at δ 0.47 due to 2 × CH3,
followed by a triplet at 1.85 (2 × CH) and a doublet at 2.82
(2 × CH2). The 13C NMR spectrum displayed prominent signals
at δ 41.7 and 41.8 due to the piperazine methylene groups and
at 105.1 and 173.6 due to CN and CO groups, respectively.
Readily assignable doublets due to C–F coupling were observed
for 11b at δ 110.2 ppm (JCF = 23.2 Hz), 151.6 (JCF = 244.6 Hz),
144.8 (JCF = 10.5 Hz), and 116.1 (JCF = 7 Hz) and assigned to
C-5, C-6, C-7, and C-8, respectively. Similar data were obtained
for compounds 11a and 11c,d (Table S3).
General procedure for the preparation of methyl 3-aryl-3-aryl-
aminoprop-2-enoates 5f–j
A solution of substituted arylamines 3a–e (10 mmol), methyl
benzoylacetate 4f (50 mmol), and AcOH (50 mmol) was stirred
at 80 ЊC for 3 h, diluted with water (50 cm3), and extracted with
CH2Cl2 (3 × 25 cm3). The combined organic phase was washed
with 10% HCl, brine, dried over Na2SO4, and the solvent
was evaporated. The residue was purified by column chroma-
tography on silica gel using CHCl3 as eluent. Yields and melting
points are reported in Table 1.
General procedure for the preparation of 1-aryl-4-cyano-
5-phenylpyrrole-2,3-diones 7a–e
In conclusion, FVT of pyrrole-2,3-diones 7 allows the
preparation of fluorinated 2-phenyl-4-quinolones which are, in
turn, precursors of variously substituted 2-phenylquinolones.
To a solution of 5a (1.5 g, 6.8 mmol) in dry ether (30 cm3) was
added oxalyl chloride (0.95 g, 7.48 mmol) at 5 ЊC. The reaction
mixture was brought to room temperature and stirred for 1 h.
The precipitated solid was filtered and washed with dry ether
(10 cm3) to give 7a. For each compound 5b–e the method was
similar to that described for 5a, except that after addition of
oxalyl chloride, the mixture was brought to reflux slowly and
stirred for 1 h. Yields, melting points, analytical data and IR
frequencies of the CN and CO groups are given in Table 2.
Experimental
Melting points are uncorrected. IR spectra were recorded on a
Perkin–Elmer 1700 or 2000 FTIR spectrometer, NMR spectra
on a Bruker AC2000 (200 Hz), and mass spectra (70 eV) on a
Kratos MS25RFA instrument. Column chromatography was
performed on silica gel (200–400 mesh). GCMS was carried
out using a capillary column BP5 (0.25 mm × 30 m × 0.25 µm)
with a pressure of 20 psi and He as the carrier gas. The
FVT apparatus was as previously reported for preparative
scale work (77 K isolation).13 The substituted anilines, benzoyl-
acetonitrile and methyl benzoylacetate are commercially
available.
General procedure for the preparation of 1-aryl-4-methoxy-
carbonyl-5-phenylpyrrole-2,3-diones 7f–j
To a solution of 5f (2 g, 7.9 mmol) in dry ether (40 cm3)
was added oxalyl chloride (1.1 g, 8.7 mmol) slowly at Ϫ50 ЊC.
The reaction mixture was stirred at Ϫ40 ЊC for 1 h. The usual
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workup as above gave 2.1 g (86%) of 7f. For the compounds
5g–j, the method was similar to that described for 5f, except
that after the addition of oxalyl chloride, the reaction mixture
was brought to Ϫ10 ЊC in the course of 1 h and stirred for an
additional 1 h. In the case of compound 5j, the reaction mixture
was brought to room temperature in the course of 1 h and then
stirred for an additional 1 h. Yields, melting points, analytical
data and IR frequencies of the CO groups are given in Table 2,
and spectroscopic data in Table S1.
> 300 ЊC; IR (KBr) ν 3483, 2220, 1638, 1576, 1491, 1259, 1170,
1126, 1037, 1009, 794, 690 cmϪ1; δH(200 MHz; DMSO-d6) 2.49–
3.46 (m, 8H), 7.0–7.04 (d, 1H), 7.59–7.77 (m, 6H), 12.3 (br s);
13C NMR: See Table S3; Found Mϩ, 348.1388. C20H17N4OF
requires Mϩ, 348.1386.
Compounds 11b–d were analogously prepared using
piperazine and cis-2,6-dimethylpiperazine. Data are reported
below.
3-Cyano-6-fluoro-2-phenyl-7-(cis-3,5-dimethylpiperazin-1-yl)-
4-quinolone 11b. Light brown solid (20 mg, 30%) mp > 300 ЊC,
IR (KBr) ν 3443, 2221, 1637, 1571, 1491, 1384, 1273, 1101, 794,
General procedure for the preparation of 6,7,8-substituted-
3-cyano-2-phenyl-4-quinolones 8a–e
768, 699 cmϪ1 1H NMR (DMSO-d6) δ 0.47 (d, 6H), 1.85
;
Compounds 7a–e (0.3–1 mmol) were vaporized at 110–120 ЊC
(depending on volatility) into the pyrolysis tube at 500 ЊC in
the course of 4 h. The pyrolysates were condensed on a liq.
N2 cold finger at 77 K. Upon completion of the pyrolysis, the
system pressure was equalised with N2. The products collected
from the cold finger were stirred with acetone, the insoluble
solids were filtered and recrystallized from CHCl3–MeOH
(3 : 1). Yields, melting points and analytical data are reported
in Table 3, and spectroscopic data in Table S2.
(t, 2H), 2.82 (d, 4H), 6.52–6.56 (m, 1H), 6.87–6.89 (m, 2H),
6.97–7.04 (s, 1H), 7.08–7.11 (m, 3H); 13C NMR: See Table S3;
Found: Mϩ, 376.1736. C22H21N4OF requires, 376.1699.
6-Fluoro-1,4-dihydro-4-oxo-2-phenyl-7-(piperazin-1-yl)quino-
line-3-carboxylic acid 11c. Pale brown solid, (26 mg, 25%); mp
> 300 ЊC IR(KBr) ν 3456, 1636, 1597, 1488, 1383, 1291, 1260,
890, 771, 698 cmϪ1; 1H NMR (DMSO-d6) δ 2.49–3.19 (m, 8H),
7.27–7.99 (m, 7H); 13C NMR: See Table S3; Found: [Mϩ
CO2] 323.1426. C19H18N3OF requires [Mϩ Ϫ CO2] 323.1423.
Ϫ
General procedure for the preparation of 6,7,8-substituted-1,4-
dihydro-4-oxo-2-phenylquinoline-3-carboxylic acids 9a–e
6-Fluoro-1,4-dihydro-4-oxo-2-phenyl-7-(cis-2,6-dimethyl-
piperazin-1-yl)quinoline-3-carboxylic acid 11d. Cream solid
(25 mg, 19%); mp > 300 ЊC IR(KBr) ν 3452, 1639, 1573, 1513,
1478, 1384, 1272, 1178, 1100, 1048 cmϪ1; 1H NMR (DMSO-d6)
δ 0.58 (d, 6H), 1.85 (t, 2H), 2.05 (s, 4H), 7.3–7.9 (m, 7H), 11.6
(br s); 13C NMR: See Table S3; Found: [Mϩ Ϫ CO2] 351.1687.
C21H22N3OF requires [Mϩ Ϫ CO2] 351.1754.
The crude solids obtained by a procedure similar to that
described above for the cyanoquinolones using compounds 7f–j
were stirred with 20% KOH (5 cm3) at 80 ЊC for 3 h. After the
reaction, the insoluble solids were filtered and the filtrate was
acidified with 10% HCl. The precipitated solid was filtered,
washed with water, and dried to give the compounds 9a–e.
Yields and analytical data are reported in Table 3, and spectro-
scopic data in Table S2.
Acknowledgements
This work was supported by the Australian Research Council.
General procedure for the preparation of 6,7-substituted
3-cyano-1-ethyl-2-phenyl-4-quinolone 10b or 6,7-substituted
3-cyano-4-ethoxy-2-phenyl-4-quinolones 10a,c,d
References
(a) A mixture containing 150 mg (0.61 mmol) of 8a, 165 mg
(1.22 mmol) of K2CO3, and 5 cm3 of DMF was heated at
100 ЊC for 30 minutes with stirring. To this mixture was added
285 mg (1.83 mmol) of ethyl iodide. The resulting mixture was
allowed to stir at the same temperature for 3 h and filtered
to remove insoluble materials. The filtrate was concentrated to
dryness in a vacuum. The residue was taken up in water
(10 cm3) and the solid which separated was filtered and washed
with water, dried, and chromatographed on silica gel with
benzene–chloroform (1 : 1) to give 10a. Yields and analytical
data for 10a–d are reported in Table 3, and spectroscopic data
in Table S2.
(b) To a solution of 8a (60 mg, 0.23 mmol) in dry THF
(5 cm3) was added butyllithium (0.23 mmol) at Ϫ50 ЊC. The
turbid mixture was clear when brought to room temperature.
Ethyl iodide (18 mg, 0.23 mmol) was added at room tempera-
ture and the mixture was stirred for 10 h at reflux temperature.
The yield of 10a was 10%.
1 D. Niccolai, L. Tarsi and R. J. Thomas, Chem. Commun., 1997,
2333–2342.
2 K. Grohe, Chem. Brit., 1992, 34.
3 J. Matsumoto, T. Miyamoto, A. Minamida, Y. Nishimura, H. Egawa
and H. Nishimura, J. Med. Chem., 1984, 27, 292.
4 E. Vilsmaier and T. Goertz, Synthesis, 1998, 739 and references
therein.
5 Y. Kimura, S. Atarashi, K. Kowakami, K. Sato and I. Hayakawa,
J. Med. Chem., 1994, 37, 3344 and references therein.
6 S. J. Brickner, Chem. Ind. (London), 1997, 131.
7 B. E. Fulloon and C. Wentrup, J. Org. Chem., 1996, 61, 1363;
V. V. Ramana Rao and C. Wentrup, J. Chem. Soc., Perkin Trans. 1,
1998, 2583.
8 C. Wentrup, V. V. Ramana Rao, W. Frank, B. E. Fulloon,
D. W. J. Moloney and T. Mosandl, J. Org. Chem., 1999, 64, 3608.
9 B. Fulloon, H. A. A. El-Nabi, G. Kollenz and C. Wentrup,
Tetrahedron Lett., 1995, 36, 6547; H. Briehl, A. Lukosch and
C. Wentrup, J. Org. Chem., 1984, 49, 2772.
10 S.-C. Kuo, H.-Z. Lee, J.-P. Juang, Y.-T. Lin, T.-S. Wu, J.-J. Chang,
D. Lednicer, K. D. Paull, C. M. Lin, E. Hamel and K.-H. Lee,
J. Med. Chem., 1993, 36, 1146.
11 T. Sano, Y. Horiguchi, J. Toda, K. Imafuku and Y. Tsuda, Chem.
Pharm. Bull., 1984, 121, 497.
General procedure for the preparation of 7-substituted-3-cyano-
6-fluoro-1,4-dihydro-2-phenyl-4-quinolones or 7-substituted-1,4-
dihydro-6-fluoro-4-oxoquinoline-3-carboxylic acids 11
12 For the 13C NMR spectra of pyrrolediones see G. Kollenz, G. Penn,
W. Ott, K. Peters, E.-M. Peters and H. G. von Schnering, Chem.
Ber., 1984, 117, 1310; K. P. Netsch, PhD Thesis, Universität
Marburg, Germany, 1985.
A mixture of 8d (200 mg, 0.71 mmol), piperazine (305 mg,
3.5 mmol), and pyridine (5 cm3) was heated 115 ЊC with stirring.
After 12 h, the mixture was evaporated to dryness. The solid
residue was quenched with water (5 cm3) and neutralized with
AcOH to give a cream solid (40 mg, 16%) identified as 11a, mp
13 A. Kuhn, C. Plüg and C. Wentrup, J. Am. Chem. Soc., 2000, 122,
1945; C. Wentrup, R. Blanch, H. Briehl and G. J. Gross, J. Am.
Chem. Soc., 1988, 110, 1874.
14 W. Zankowska-Jasinska, J. Golus, Z. Kamela and A. Kolasa,
Pol. J. Chem., 1987, 61, 141.
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1235