Synthesis of novel 3-acyloxy-1,3-dihydro-2H-indol-2-ones and isomeric 4- acyl-1,4-dihydro-3,1-benzoxazin-2-ones: Double rearrangement of 3- hydroxyquinoline-2,4(1H,3H)-diones

Article abstract of DOI:10.1016/S0040-4020(00)00057-0

Substituted 3-hydroxyquinoline-2,4(1H,3H)-diones 3 were transformed into 3-acyloxy-1,3-dihydro-2H-indol-2-ones 4 and isomeric 4-acyl-1,4-dihydro-3,1- benzoxazin-2-ones 5. The influence of the substituents and the reaction conditions on the course of the r

Full text of DOI:10.1016/S0040-4020(00)00057-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1551–1560
Synthesis of Novel 3-Acyloxy-1,3-dihydro-2H-indol-2-ones and
Isomeric 4-Acyl-1,4-dihydro-3,1-benzoxazin-2-ones: Double
Rearrangement of 3-Hydroxyquinoline-2,4(1H,3H)-diones
a,
a
a
b,
*
*
´
´
ˇ
ˇ´
ˇ
Antonın Klasek, Kamil Koristek, Jirı Polis and Janez Kosmrlj
a
´
Department of Chemistry and Environmental Technology, Faculty of Technology, Technical University of Brno, 762 72 Zlın,
Czech Republic
bFaculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia
Received 15 October 1999; revised 23 December 1999; accepted 13 January 2000
Abstract—Substituted 3-hydroxyquinoline-2,4(1H,3H )-diones 3 were transformed into 3-acyloxy-1,3-dihydro-2H-indol-2-ones 4 and
isomeric 4-acyl-1,4-dihydro-3,1-benzoxazin-2-ones 5. The influence of the substituents and the reaction conditions on the course of the
reaction was studied. In the proposed mechanism a double rearrangement takes place; a-ketol rearrangement of 3, leading to a-hydroxy-b-
diketone intermediate 8, is followed by a rearrangement to the isomeric a-ketol-esters 4 and 5. ᭧ 2000 Elsevier Science Ltd. All rights
reserved.
Introduction
few 3-acyloxy-1,3-dihydro-2H-indol-2-ones 4 are known.
3-Acetoxy-5-bromo-1,3-dihydro-2H-indol-2-one was found
to have strong antihypoxic effects in mice subjected to
hypobaric hypoxia, for example.5 To the best of our knowl-
edge, there is no example of a 4-acyl-1,4-dihydro-3,1-
benzoxazin-2-one 5 described in the literature and only a
few synthetic approaches to the parent 1,4-dihydro-3,1-
benzoxazin-2-ones are documented.6 However, there is a
growing interest in their derivatives, triggered by their
potent bio-activity such as the inhibition of HIV reverse
transcriptase.7
Recently, reactions of 3-hydroxyquinoline-2,4(1H,3H)-
diones 3, natural metabolites of some Pseudomonas
species,1 with ethyl (triphenylphosphoranylidene)acetate
(Wittig reagent) have been described.2 They proceed
with high stereoselectivity to give E-4-ethoxycarbonyl-
methylene-3,4-dihydro-2-quinolones and to a small extent
3a-substituted
furo[2,3-c]quinoline-2,4(3aH,5H)-diones.
An independent synthesis of the latter by an intramolecular
Wittig reaction has been described.3 On the other hand,
under the same reaction conditions, 5,8-disubstituted
3-benzyl-3-hydroxyquinoline-2,4(1H,3H)-diones
3 have
Results and Discussion
been shown to react in a completely different manner yield-
ing primarily products of indoline 4 and benzoxazine 5
structural type. Their formation was proposed to take
place via a base catalysed molecular rearrangement of 3,
mediated by the Wittig reagent.4
Starting materials (3a–t, Scheme 1, Table 1) were prepared
by condensation of the corresponding anilines8 1a–t with
substituted diethyl malonates, followed by the oxidation2,9
of 4-hydroxy-2(1H)-quinolones 2a–t with peroxyacetic
acid.
In our present study we have tried to obtain additional infor-
mation on the mechanism of this rearrangement. Substituted
3-hydroxyquinoline-2,4(1H,3H)-diones 3 were exposed to
various organic bases. Additionally, we tried to find a
combination of reaction conditions and/or substituents
which would lead to the selective formation of 4 or 5.
Rearrangement of 3a–t was studied in refluxing xylene (in
some cases cyclohexanol) solutions in the presence, as well
as in the absence, of an organic base (Table 1). A catalytic
amount, 0.2 molar equivalent, of 4-(dimethylamino)pyridine
(DMAP), triphenylphosphane (Ph3P), triphenylphosphane
oxide (Ph3PO) or N,N,N,N-tetramethylguanidine (TMG)
was used as a base. Products were separated by column
chromatography.
Despite possessing significant biological activity, only a
Keywords: rearrangements; mechanisms; benzoxazines; indolinones;
quinolinones.
* Corresponding authors. E-mail: klasek@ft.vutbr.cz;
e-mail: janez.kosmrlj @uni-lj.si
For the most direct comparison with previous results,4 we
first focused our attention on 3a. By heating its xylene
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00057-0

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1552
Scheme 1.
Table 1. Results of the rearrangement of compounds 3a–t
3
R1
R2
R3
R4
R5
R6
Catalyst
Solvent
Time (h)
Isolated compounds (%)
4
5
6
3a
9b
33
76c
10
60
60
5
6
–
38
7
7
64
84
81
70
73
75
82
83
85
88
91
98
96
94
89
94
89
92
48
46
34
51
83
69
80
66
84
a
b
H
H
CH2Ph
C4H9
Cl
Cl
H
H
H
H
CH3
CH3
DMAP
DMAP
None
DMAP
None
DMAP
DMAP
DMAP
Ph3PO
Ph3P
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
c-C6H11OH
Xylene
c-C6H11OH
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
c-C6H11OH
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
c-C6H11OH
Xylene
5
3
3
2
2
5
3
3
3
3
3
3
5
5
12
5
39
31
8
8
0.3
–
27
4
–
–
–
–
–
–
–
16
2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
5
2
1
3
4
2
2
3
1
–
–
–
3
2
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
2
1
–
1
1
3
–
–
–
c
H
Ph
Cl
H
H
CH3
21
15
18
75
76
81
54
76
80
7
2
–
8
9
–
–
9
–
–
–
–
–
–
–
–
1
d
e
H
H
CH2Ph
C4H9
CH3
CH3
H
H
H
H
CH3
CH3
Ph3P
None
f
H
Ph
CH3
H
H
CH3
DMAP
None
DMAP
DMAP
Ph3P
DMAP
DMAP
Ph3P
DMAP
DMAP
DMAP
Ph3P
DMAP
Ph3P
DMAP
Ph3P
DMAP
Ph3P
DMAP
DMAP
Ph3P
g
h
H
H
CH2Ph
C4H9
H
H
H
H
H
H
H
H
6
i
j
H
CH3
Ph
C4H9
H
H
H
H
H
H
H
H
12
10
9
4
4
6
6
6
6
6
9
5
7
8
7
7
7
k
l
CH3
H
Ph
C4H9
H
H
H
Cl
H
H
H
H
m
n
H
H
H
C4H9
H
H
H
CH3
H
H
H
C4H9
H
CH3
CH3
o
CH2Ph
H
Cl
–
p
r
H
H
CH2Ph
C4H9
CH3
CH3
H
H
CH3
CH3
H
H
14
19
51
38
–
–
1
1
–
None
DMAP
TMG
Ph3P
Ph3P
s
t
H
Ph
CH3
H
H
CH3
CH3
H
H
9
6
9
9
4
8
13
13
–
CH3
C4H9
CH3
Ph3P
12
a Recovered starting material.
b Compound 7 was also isolated in 9% yield.
c Compound 8b was isolated in 5% yield.
solution under reflux in the presence of DMAP four
products were formed: dioxindole 4a, benzoxazinone 5a,
isatin 6a, and ester 7 in 39, 8, 5, and 9% yield, respectively,
accompanied by a small amount (9%) of unreacted starting
material (Scheme 2, Table 1).
formed by the reaction of 3a in the presence of the Wittig
reagent.4 Moreover, it is known that the esterification of
highly hindered tertiary alcohols (such as 3a) with acids
hardly proceeds in the presence of DMAP alone.10 The
transformation of 3a to 7 could be explained by the involve-
ment of ester 4a in a transesterification reaction. The
structure of 7 was confirmed by an independent synthesis
from 3a and phenylacetyl chloride.
4-Chloro-7-methylisatin (6a) is formed by the hydrolysis
and subsequent oxidation of 4a with air moisture and
oxygen, which is proved by an independent reaction (reflux
of a xylene solution of 4a in the presence of DMAP). The
formation of ester 7 is rather unexpected since it was not
We found that the conversion of starting compound 3,
mainly to dioxindole 4, is significant when the substituent

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1553
Scheme 2.
R3 is present in the molecule (Table 1). The yields are also
affected by the substituent R6; in the case of R6ˆH they are
distinctly lower. In contrast, benzoxazinone derivatives 5
arise as the main or even the only products when R2 is a
phenyl group (3c, f, s). It appeared that neither the nature of
the catalyst nor the solvent significantly affected the course
of the reaction. Surprisingly, the rearrangement also takes
place in the absence of catalyst, though the yields are
usually lower. Isatins 6 are formed to only a small extent
and their structures are confirmed by comparison with
independently prepared samples.11
also in accord with the results obtained from the rearrange-
ment of furo[2,3-c]quinoline-2,4(3aH,5H)-diones.4
In order to establish this reaction pathway we decided to
trap the isocyanate intermediates. Compounds 3e, l, and s
were subjected to the rearrangement conditions in cyclo-
hexanol solution. We found that none of the expected cyclo-
hexyl carbamates were formed; moreover, by comparison
with results obtained in xylene solution, only marginal
changes in product distribution were observed. As the
abstraction of the NH proton is a key step in this mechanism,
we decided to carry out the reaction with N-substituted
derivatives 3. Thus, xylene solutions of compounds 3j, k,
and t were heated in the presence of DMAP or Ph3P. In the
case of 3t and 3k no reaction was observed while 3j
rearranged, albeit in small yield, to dioxindole ester 4j
(Table 1). The formation of 4j indicates that, at least in
this particular case, the isocyanate mechanism is certainly
not operating.
Differentiation between isomeric 4 and 5 is achieved by
comparison of their 13C NMR; the chemical shift assign-
ment is based on our previous4 work. Three characteristic
resonances are found in the 13C NMR spectra for both
isomeric compounds (Fig. 1). In isomer 4 carbons C-2,
C-3, and ester carbonyl resonate in the range of d 173–
175, 69–71, 165–173 ppm, respectively, while isomer 5
can be recognised by the carbamate carbonyl (C-2), carbon
C-4, and ketone group (d 150–151, 76–79, and 192–
200 ppm) resonances.
Based on the above experiments, it is obvious that the iso-
cyanate mechanism no longer accounts for our current
observations. Another mechanistic possibility, which cannot
be ruled out, is shown in Scheme 3. First, 1,2-shift of
carboxamide group in a-ketol type rearrangement12 to inter-
mediate 8 is proposed.13 Indeed, small amounts (5%) of 8b
were isolated when xylene solution of 3b was refluxed in the
absence of base. Although it is known that the a-ketol
rearrangement occurs by acid or base catalysis,14 at least
two examples of a thermally induced reaction have also
been reported.15 In our case, this can be explained by an
intramolecular proton transfer.
Infrared spectra of dioxindole esters 4 show characteristic
absorption bands at 3200 cmϪ1 (broad), 1720–1760 cmϪ1
and 1610–1640 cmϪ1 assigned to the amino, ester, and
lactam group, respectively. However, the differentiation
between isomeric 4 and 5 cannot be unequivocally achieved
by their IR spectra alone, since the characteristic absorption
bands of both isomeric heterocycles appear in nearly the
same region.
Previously we demonstrated that by treating 5,8-disubsti-
tuted 3-benzyl-3-hydroxyquinoline-2,4(1H,3H)-diones
3
For the base-catalysed a-ketol rearrangement it has been
deduced that the migratory group acquires partial carbanio-
nic character. So, electron-withdrawing groups R3 would
facilitate the reaction, while electron-donating groups
would retard it. But in the case of 3a–t it seems that just
any group (e.g. Cl or Me) facilitates the rearrangement
better than hydrogen. One could account for it by steric
effects; a driving force for the formation of 8 could be
ascribed to a release of the steric strain between neighbour-
ing group R3 and the carbonyl oxygen of the initial
compound 3. Still, the relatively small sizes of the methyl
group and chlorine atom makes it less probable. We believe
that this phenomenon can be best rationalised by the a-ketol
rearrangement of 3 via a transition state with a diradicaloid
character, which has been recently suggested by Sprecher.16
with the Wittig reagent, products of indoline and benzoxa-
zine structural type are formed through a rearrangement of
the quinoline framework. We proposed a mechanism in
which the base-catalysed abstraction of NH proton is
followed by ring-opening ring-closure via intermediately
formed isocyanates (isocyanate mechanism). This was
Except for the case of 3b, intermediate 8 is too unstable to
be isolated or even detected in the crude reaction mixture. It
is further transformed to 5 and/or 4 most probably via an
epoxide intermediate 10 and/or 9 (Scheme 3). Closely
Figure 1. 13C NMR data for compounds 4 and 5.

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1554
Scheme 3.
related examples of a-hydroxy-b-diketone to a-ketol-ester
rearrangement,17 and vice versa,18 recently described in the
literature, have been accomplished under base catalysis;
however, thermal reactions have been reported as well.19
7.20 (dd, Jˆ8.0, 0.5 Hz, 1H, H-6), 8.49 (br s, 1H), 8.89 (br s,
1H). dC (CDCl3): 14.03, 17.53, 22.92, 23.36, 30.23, 110.84,
115.61, 123.57, 123.80, 125.21, 130.77, 137.68, 157.20,
163.70. Anal. calcd (found) for C14H16ClNO2: C 63.28
(63.29); H 6.07 (6.15); N 5.27 (5.32).
The mechanism proposed in Scheme 3 also explains well an
increase in the ratio 5/4 in the case of 3-phenyl derivatives
of 3 (R2ˆPh), in which path a is suppressed due to lower
reactivity of aromatic keto-group in the intermediate 8. A
more detailed analysis of the mechanism is beyond the
scope of the present work and will be the subject of a
forthcoming investigation.
2c: Colourless crystals, yield 36%, mp 274–275ЊC
(ethanol), IR: 3285, 3205, 3100, 3058, 1623, 1586, 1500,
1482, 1458, 1399, 1355, 1316, 1287, 1150, 972, 818, 778,
708, 648 cmϪ1. dH (CDCl3): 2.42 (s, 3H, Ar-CH3), 7.15 (d,
Jˆ8.0 Hz, 1H, H-6), 7.27 (d, Jˆ8.0 Hz, 1H, H-7), 7.47–
7.54 (m, 5H, Ph), 8.67 (br s, 1H). dC (DMSO-d6): 17.44,
112.67, 114.24, 122.66, 124.31, 127.18, 127.67, 127.95,
131.18, 131.45, 132.63, 138.59, 158.09, 161.80. EIMS,
m/z (%): 287 (Mϩ, 40, 37Cl), 285 (Mϩ, 100, 35Cl), 170
(38, 35Cl), 168 (95, 37Cl), 140 (20), 118 (8), 104 (20), 89
(25), 77 (26), 69 (12), 63 (16), 57 (12). Anal. calcd (found)
for C16H12ClNO2: C 67.26 (67.63); H 4.23 (4.54); N 4.90
(5.29).
Experimental
Melting points were determined on a Kofler block or
Gallenkamp apparatus. IR (KBr) spectra were recorded on
a Perkin–Elmer 421 and Mattson 3000 spectrophotometers.
NMR spectra were recorded on a Bruker DPX-300 spectro-
meter. Chemical shifts are given on the d scale (ppm)
and are referenced to internal TMS. MS spectra were
obtained on a VG-Analytical AutospecQ instrument.
Column chromatography was carried out on silica gel
(Kavalier, Votice). Elemental analyses (C, H, N) were
performed with a Perkin–Elmer 2400 CHN Analyzer.
2e: Colourless crystals, yield 83%, mp 167–170ЊC
(toluene), IR: 3409, 3276, 3028, 2956, 2931, 2869, 1707,
1672, 1626, 1620, 1570, 1479, 1444, 1267, 1207, 1161,
1082, 956, 848, 810, 787, 762 cmϪ1. dH (CDCl3): 0.96
(t, Jˆ7.2 Hz, 3H, CH3 of butyl), 1.38–1.50 (m, 2H, H-3
of butyl), 1.50–1.63 (m, 2H, H-2 of butyl), 2.37 (s, 3H,
C(8)-CH3), 2.65 (t, Jˆ7.6 Hz, 2H, H-1 of butyl), 2.76 (s,
3H, C(5)-CH3), 5.85 (br s, 1H, OH), 6.88 (d, Jˆ7.5 Hz,
1H, H-5), 7.17 (d, Jˆ7.5 Hz, 1H, H-6), 8.45 (br s, 1H,
NH). dC (DMSO-d6): 13.98, 17.28, 22.14, 22.47, 24.21,
30.35, 111.11, 114.29, 120.71, 124.38, 130.17, 133.25,
136.69, 159.94, 162.93. Anal. calcd (found) for
C15H19NO2: C 73.44 (73.39); H 7.81 (7.87); N 5.71 (5.99).
4-Hydroxy-2(1H)-quinolones (2a–t) and 3-hydroxy-
quinoline-2,4(1H,3H)-diones (3a–t) were prepared
according to the general procedure described in Ref. 4.
For physical and spectroscopic data of compounds 2a, 2d,
3a, and 3d, see Ref. 4 and for 3g–k, see Ref. 2.
2b: Colourless crystals, yield 41%, mp 164–167ЊC
(ethanol), IR: 3490, 3185, 2975, 2945, 2880, 1630, 1586,
1478, 1402, 1378, 1340, 1228, 1212, 968, 853, 833, 676,
650 cmϪ1. dH (CDCl3): 0.95 (t, Jˆ7.2 Hz, 3H, CH3 of
butyl), 1.37–1.50 (m, 2H, H-3 of butyl), 1.50–1.62 (m,
2H, H-2 of butyl), 2.43 (s, 3H, Ar-CH3), 2.69 (t,
Jˆ7.5 Hz, 2H, H-1 of butyl), 7.08 (d, Jˆ8.0 Hz, 1H, H-5),
2f: Colourless crystals, yield 73%, mp 284–285ЊC
(ethanol), IR: 3276, 3209, 3120, 2927, 2870, 1622, 1587,
1548, 1473, 1456, 1437, 1398, 1350, 1294, 1251, 1240,
1154, 1144, 812, 800, 771, 698 cmϪ1. dH (CDCl3): 2.40
(s, 3H, C(8)-CH3), 2.73 (s, 3H, C(5)-CH3), 6.24 (br s, 1H,
OH), 6.91 (d, Jˆ7.6 Hz, 1H, H-5), 7.23 (d, Jˆ7.6 Hz, 1H,

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1555
H-6), 7.45–7.59 (m, 5H, Ph), 8.48 (br s, 1H, NH). dC
(DMSO-d6ϩCDCl3): 17.42, 24.21, 112.33, 114.53,
120.73, 124.57, 127.11, 128.14, 130.92, 131.40, 133.01,
134.42, 137.57, 160.92, 162.25. EIMS, m/z (%): 265 (Mϩ,
100), 236 (6), 208 (6), 165 (5), 148 (72), 119 (28), 104 (13),
91 (18), 77 (20), 57 (14). Anal. calcd (found) for
C17H15NO2: C 76.96 (77.34); H 5.70 (5.71); N 5.28 (5.44).
877, 854, 750, 698 cmϪ1. dH (DMSO-d6): 2.28 (s, 3H, CH3),
2.69 (s, 3H, CH3), 3.95 (s, 2H, CH2Ph), 6.74 (br s, 1H, ArH),
6.92 (br s, 1H, ArH), 7.09–7.25 (m, 5H, Ph), 9.90 (br s, 1H),
11.20 (br s, 1H). dC (DMSO-d6): 20.79, 23.81, 27.90,
109.28, 111.99, 113.14, 125.37, 126.20, 127.85, 128.03,
135.61, 138.91, 139.07, 140.61, 160.46, 162.91. Anal.
calcd (found) for C18H17NO2: C 77.40 (77.75); H 6.13
(6.20); N 5.01 (4.82).
2l: Colourless crystals, yield 61%, mp 193–194ЊC (ethyl
acetate), IR: 3130, 2978, 2940, 1635, 1591, 1499, 1457,
1424, 1372, 1268, 1250, 1200, 1159, 1088, 901, 852, 822,
725, 701 cmϪ1. dH (CDCl3ϩDMSO-d6): 0.93 (t, Jˆ7.1 Hz,
3H, CH3 of butyl), 1.34–1.58 (m, 4H, H-3 and H-2 of butyl),
2.68 (t, Jˆ7.5 Hz, 2H, H-1 of butyl), 7.22 (d, Jˆ8.7 Hz, 1H,
H-8), 7.31 (dd, Jˆ8.7, 2.3 Hz, 1H, H-7), 7.94 (d, Jˆ2.3 Hz,
1H, H-5), 9.28 (br s, 1H, OH), 10.96 (br s, 1H, NH). dC
(DMSO-d6): 13.90, 22.18, 22.79, 30.21, 113.01, 116.63,
121.61, 124.95, 129.42, 135.94, 155.69, 163.23. Anal.
calcd (found) for C13H14ClNO2: C 62.03 (62.07); H 5.61
(5.63); N 5.56 (5.68).
2r: Colourless crystals, yield 48%, mp 200–206ЊC
(ethanol), IR: 3267, 3139, 3066, 2962, 2863, 1630, 1593,
1548, 1493, 1477, 1386, 1375, 1357, 1281, 1250, 1221,
1186, 1169, 1090, 1062, 1034, 927, 889, 875, 841, 748,
723, 694, 665 cmϪ1. dH (DMSO-d6): 0.89 (t, Jˆ6.8 Hz,
3H, CH3 of butyl), 1.30–1.40 (m, 4H, H-2 and H-3 of
butyl), 2.27 (s, 3H, Ar-CH3), 2.50–2.60 (m, 2H, H-1 of
butyl), 2.69 (s, 3H, Ar-CH3), 6.70 (s, 1H, ArH), 6.90 (s,
1H, ArH), 9.53 (br s, 1H), 11.09 (br s, 1H). dC (DMSO-
d6): 13.97, 20.78, 22.20, 22.46, 23.83, 30.45, 110.47,
112.03, 113.05, 126.03, 135.31, 138.42, 138.75, 159.59,
162.91. Anal. calcd (found) for C15H19NO2: C 73.44
(73.70); H 7.81 (8.04); N 5.71 (6.10).
2m: Colourless crystals, yield 78%, mp 192–194ЊC
(ethanol), IR: 3132, 3051, 2964, 2873, 1643, 1618, 1591,
1558, 1448, 1431, 1381, 1288, 1275, 1267, 1223, 1195,
1165, 1064, 954, 858, 812, 723 cmϪ1. dH (DMSO-d6):
0.90 (t, Jˆ7.0 Hz, 3H, CH3 of butyl), 1.28–1.48 (m, 4H,
H-2 and H-3 of butyl), 2.35 (s, 3H, Ar-CH3), 2.50–2.60 (m,
2H, H-1 of butyl), 7.15 (d, Jˆ8.3 Hz, 1H, ArH), 7.25 (dd,
Jˆ8.3, 1.5 Hz, 1H, ArH), 7.68 (br s, 1H, ArH), 9.87 (br s,
1H), 11.18 (br s, 1H). dC (DMSO-d6): 13.95, 20.59, 22.21,
22.77, 30.39, 111.71, 114.63, 115.23, 121.97, 129.61,
130.65, 135.26, 156.60, 163.34. Anal. calcd (found) for
C14H17NO2: C 72.70 (72.44); H 7.41 (7.37); N 6.06 (5.83).
2s: Colourless crystals, yield 40%, mp 334–336ЊC (acetic
acid), IR: 3280, 3074, 2948, 1639, 1587, 1558, 1442, 1386,
1350, 1292, 1236, 1199, 1126, 1089, 887, 868, 833, 762,
692 cmϪ1. dH (DMSO-d6): 2.25 (s, 3H, Ar-CH3), 2.66 (s,
3H, Ar-CH3), 6.75 (br s, 1H, ArH), 6.93 (br s, 1H, ArH),
7.28–7.34 (m, 3H, Ph), 7.36–7.43 (m, 2H, Ph), 9.43 (br s,
1H), 11.24 (br s, 1H). Anal. calcd (found) for C17H15NO2: C
76.96 (76.48); H 5.70 (5.55); N 5.28 (4.93).
2t: Colourless crystals, yield 81%, mp 188–189ЊC
(ethanol), IR: 3172, 2950, 1620, 1602, 1581, 1562, 1494,
1465, 1447, 1380, 1357, 1324, 1298, 1271, 1197, 1151,
1042, 929, 832, 754, 133, 668 cmϪ1. dH (DMSO-d6): 0.89
(m, 3H, CH3), 1.35 (m, 4H, CH2CH2), 2.37 (s, 3H, CH3),
2.58 (m, 2H, CH2), 2.73 (s, 3H, CH3), 3.55 (s, 3H, CH3),
6.83 (s, 1H, ArH), 7.11 (s, 1H, ArH), 9.54 (br s, 1H, OH). dC
(DMSO-d6): 13.95, 21.13, 22.18, 23.31, 24.50, 29.66, 30.37,
110.06, 112.65, 112.86, 126.53, 135.89, 138.90, 139.69,
158.43, 162.20. Anal. calcd (found) for C16H21NO2: C
74.10 (73.78); H 8.16 (7.88); N 5.40 (5.17).
2n: Colourless crystals, yield 82%, mp 203–204ЊC
(ethanol), IR: 3301, 2953, 2929, 2870, 1636, 1597, 1488,
1467, 1454, 1408, 1384, 1359, 1264, 1192, 1159, 1085,
1070, 904, 829, 801, 777, 746, 734, 709, 696 cmϪ1. dH
(DMSO-d6): 0.91 (t, Jˆ7.1 Hz, 3H, CH3 of butyl), 1.28–
1.50 (m, 4H, H-2 and H-3 of butyl), 2.42 (s, 3H, Ar-CH3),
2.55–2.65 (m, 2H, H-1 of butyl), 7.06 (dd, J1ˆJ2ˆ7.6 Hz,
1H, ArH), 7.29 (d, Jˆ7.6 Hz, 1H, ArH), 7.77 (d, Jˆ7.6 Hz,
1H, ArH), 9.95 (br s, 1H), 10.45 (br s, 1H). dC (DMSO-d6):
13.96, 17.23, 22.18, 22.73, 30.36, 111.39, 115.45, 120.42,
120.57, 122.83, 130.82, 135.61, 157.16, 163.76. Anal. calcd
(found) for C14H17NO2: C 72.70 (72.78); H 7.41 (7.66); N
6.06 (6.47).
3b: Pale yellow crystals, yield 46%, mp 151–152ЊC
(benzene–c-C6H12), IR: 3461, 3297, 2957, 2928, 2871,
1719, 1686, 1585, 1489, 1462, 1363, 1252, 1226, 1180,
1089, 1053, 956, 851, 806, 723 cmϪ1. dH (CDCl3): 0.84
(t, Jˆ7.1 Hz, 3H, CH3 of butyl), 1.19–1.32 (m, 4H, H-3
and H-2 of butyl), 1.80–2.02 (m, 2H, H-1 of butyl), 2.31
(s, 3H, Ar-CH3), 3.94 (s, 1H, OH), 7.12 (d, Jˆ8.2 Hz, 1H,
H-6), 7.29 (dd, Jˆ8.2, 0.6 Hz, 1H, H-7), 7.63 (s, 1H, NH).
dC (CDCl3): 13.74, 17.02, 22.45, 25.22, 39.76, 83.16,
117.11, 122.91, 126.04, 132.40, 136.62, 139.39, 171.68,
194.51. EIMS, m/z (%): 283 (Mϩ, 12, 37Cl), 281 (Mϩ, 36,
35Cl), 240 (11, 37Cl), 238 (33, 35Cl), 199 (45, 37Cl), 197 (100,
35Cl), 182 (3, 37Cl), 180 (10, 35Cl), 170 (3, 37Cl), 168 (10,
35Cl), 141 (7), 111 (7), 97 (15), 85 (26), 69 (35), 57 (54).
Anal. calcd (found) for C14H16ClNO3: C 59.68 (60.02); H
5.72 (5.92); N 4.97 (4.76).
2o: Colourless crystals, yield 32%, mp 270–271ЊC (acetic
acid), IR: 3247, 3174, 3060, 2962, 2933, 1627, 1593, 1562,
1479, 1454, 1388, 1319, 1211, 1190, 1159, 1109, 1070, 995,
916, 820, 773, 735, 700, 648 cmϪ1. dH (DMSO-d6): 2.47 (s,
3H, CH3), 3.96 (s, 2H, CH2Ph), 7.09–7.16 (m, 1H, ArH),
7.19–7.29 (m, 5H, ArH), 7.80 (d, Jˆ8.7 Hz, 1H, ArH),
10.50 (br s, 1H), 10.66 (br s, 1H). dC (DMSOϪd6): 13.77,
28.34, 110.40, 114.37, 120.68, 121.61, 121.67, 125.48,
127.91, 128.09, 134.84, 136.95, 140.46, 157.56, 163.81.
Anal. calcd (found) for C17H14ClNO2: C 68.12 (68.51); H
4.71 (4.67); N 4.67 (4.60).
2p: Colourless crystals, yield 82%, mp 196–199ЊC (acetic
acid), IR: 3278, 3155, 3084, 3026, 2971, 2862, 1631, 1595,
1558, 1493, 1452, 1386, 1376, 1230, 1197, 1189, 1082, 885,
3c: Pale yellow crystals, yield 67%, mp 182–185ЊC
(methanol), IR: 3668, 3456, 3249, 3095, 2970, 2922,

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A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1556
2842, 1724, 1680, 1487, 1450, 1359, 1282, 1259, 1180,
1155, 1049, 1030, 981, 954, 845, 812, 783, 750,
700 cmϪ1. dH (CDCl3): 2.28 (s, 3H, Ar-CH3), 4.45 (s, 1H,
OH), 7.06 (d, Jˆ8.2 Hz, 1H, H-6), 7.22 (d, Jˆ8.2 Hz, H-7),
7.31–7.39 (m, 5H, Ph), 7.83 (br s, 1H, NH). dC (DMSO-
d6ϩCDCl3): 17.35, 84.22, 118.50, 124.08, 124.80, 126.08,
128.72, 128.87, 130.17, 136.07, 137.48, 139.64, 170.41,
192.49. Anal. calcd (found) for C16H12ClNO3: C 63.69
(63.97); H 4.01 (3.98); N 4.64 (4.80).
139.15, 173.02, 196.23. Anal. calcd (found) for
C14H17NO3: C 68.00 (67.78); H 6.93 (6.59); N 5.66 (6.03).
3n: Pale yellow crystals, yield 64%, mp 121–123ЊC
(benzene–c-C6H12), IR: 1483, 3261, 3193, 3109, 2956,
2935, 2871, 1701, 1664, 1602, 1498, 1466, 1388, 1369,
1329, 1257, 1238, 1188, 1116, 1095, 1045, 899, 839, 793,
769, 754, 742, 719, 677 cmϪ1. dH (DMSO-d6): 0.76 (t,
Jˆ7.0 Hz, 3H, CH3 of butyl), 1.10–1.40 (m, 4H, H-3 and
H-2 of butyl), 1.60–1.80 (m, 2H, H-1 of butyl), 2.31 (s, 3H,
Ar-CH3), 5.63 (s, 1H, OH), 7.02 (dd, J1ˆJ2ˆ7.5 Hz, 1H,
H-6), 7.42 (d, Jˆ7.5 Hz, 1H, ArH), 7.58 (d, Jˆ7.5 Hz,
1H, ArH), 9.90 (br s, 1H, NH). dC (DMSO-d6): 13.65,
17.17, 21.87, 24.67, 39.26, 81.76, 119.48, 122.31, 124.44,
124.59, 137.02, 139.28, 173.15, 196.19. Anal. calcd (found)
for C14H17NO3: C 68.00 (68.27); H 6.93 (6.75); N 5.66
(5.62).
3e: Colourless crystals, yield 86%, mp 156–158ЊC
(ethanol), IR: 3462, 3270, 2942, 2920, 2845, 1695, 1664,
1602, 1577, 1500, 1365, 1252, 1178, 1161, 1078, 1032, 963,
861, 810, 753, 718, 654 cmϪ1. dH (CDCl3): 0.83 (t,
Jˆ7.2 Hz, 3H, CH3 of butyl), 1.19–1.31 (m, 4H, H-3 and
H-2 of butyl), 1.75–1.98 (m, 2H, H-1 of butyl), 2.27 (s, 3H,
C(8)-CH3), 2.56 (s, 3H, C(5)-CH3), 3.91 (s, 1H, OH), 6.90 (d,
Jˆ7.7 Hz, 1H, H-6), 7.26 (d, Jˆ7.7 Hz, 1H, H-7), 7.45 (br s,
1H, NH). dC (CDCl3): 13.78, 16.87, 20.88, 22.48, 25.28,
40.33, 82.90, 117.77, 121.39, 126.52, 136.25, 138.62,
139.61, 171.94, 197.43. EIMS, m/z (%): 261 (Mϩ, 45),
218 (55), 205 (6), 177 (100), 176 (96), 148 (16), 137 (7),
119 (16), 104 (15), 91 (21), 77 (22), 69 (35), 57 (48). Anal.
calcd (found) for C15H19NO3: C 68.94 (70.09); H 7.33
(7.20); N 5.36 (4.99).
3o: Colourless crystals, yield 92%, mp 187–188ЊC
(ethanol), IR: 3456, 3251, 3192, 3066, 2968, 2925, 2887,
1712, 1662, 1595, 1585, 1493, 1454, 1402, 1379, 1350,
1242, 1217, 1136, 1080, 1047, 1007, 914, 885, 829, 804,
785, 723, 712, 698, 681 cmϪ1. dH (DMSO-d6): 2.31 (s, 3H,
CH3), 3.32 (s, 2H, CH2Ph), 5.90 (s, 1H, OH), 6.94–7.02 (m,
2H, Ph), 7.10–7.18 (m, 3H, Ph), 7.20 (d, Jˆ8.4 Hz, 1H,
ArH), 7.51 (d, Jˆ8.4 Hz, 1H, ArH), 10.15 (br s, 1H, NH).
dC (DMSO-d6): 13.99, 45.87, 82.16, 118.79, 122.52, 123.20,
125.20, 126.70, 127.40, 130.05, 133.70, 140.36, 140.61,
172.44, 194.51. Anal. calcd (found) for C17H14ClNO3: C
64.67 (65.05); H 4.47 (4.39); N 4.44 (4.73).
3f: Colourless crystals, yield 65%, mp 190–194ЊC
(methanol), IR: 3562, 3525, 3487, 3448, 3238, 3085,
1712, 1670, 1614, 1579, 1502, 1450, 1388, 1367, 1284,
1180, 1157, 1142, 1080, 1028, 974, 850, 810, 787, 754,
700, 665 cmϪ1. dH (CDCl3): 2.28 (s, 3H, C(8)-CH3), 2.52
(s, 3H, C(5)-CH3), 4.49 (s, 1H, OH), 6.85 (d, Jˆ7.7 Hz,
1H, H-6), 7.21 (d, Jˆ7.7 Hz, 1H, H-7), 7.27–7.42 (m, 5H,
Ph), 7.77 (br s, 1H, NH). dC (CDCl3): 16.87, 20.96, 83.32,
118.49, 121.62, 125.73, 126.74, 129.10, 129.27, 136.47,
137.53, 138.19, 139.78, 170.35, 194.80. Anal. calcd
(found) for C17H15NO3: C 72.58 (72.43); H 5.37 (5.28); N
4.98 (5.15).
3p: Colourless crystals, yield 96%, mp 198–199ЊC
(benzene), IR: 3479, 3201, 3157, 3041, 2974, 2947, 2918,
2846, 1703, 1668, 1616, 1577, 1523, 1496, 1458, 1427,
1402, 1386, 1286, 1240, 1205, 1161, 1126, 1037, 924,
848, 756, 746, 712, 675 cmϪ1. dH (CDCl3): 2.37 (s, 3H,
Ar-CH3), 2.44 (s, 3H, Ar-CH3), 3.17 (d, Jˆ13.5 Hz, 1H,
CH2Ph), 3.28 (d, Jˆ13.5 Hz, 1H, CH2Ph), 4.07 (s, 1H,
OH), 6.74 (br s, 1H, ArH), 6.81 (br s, 1H, ArH), 7.01–
7.10 (m, 2H, Ph), 7.18–7.25 (m, 3H, Ph), 9.88 (br s, 1H,
NH). dC (CDCl3): 20.86, 21.76, 47.32, 82.81, 115.40,
127.63, 128.20, 128.27, 130.14, 133.20, 140.82, 141.88,
146.81, 172.77, 195.37. Anal. calcd (found) for
C18H17NO3: C 73.20 (73.55); H 5.80 (5.80); N 4.74 (4.61).
3l: Colourless crystals, yield 95%, mp 208–209ЊC (ethanol),
IR: 3467, 3259, 2956, 2873, 1705, 1682, 1610, 1481, 1410,
1359, 1244, 1171, 1130, 1086, 1035, 902, 843, 723,
661 cmϪ1. dH (CDCl3): 0.84 (t, Jˆ7.2 Hz, 3H, CH3 of
butyl), 1.19–1.48 (m, 4H, H-3 and H-2 of butyl), 1.77–
2.00 (m, 2H, H-1 of butyl), 3.79 (br s, 1H, OH), 7.00 (d,
Jˆ8.4 Hz, 1H, H-8), 7.53 (dd, Jˆ8.4, 2.4 Hz, 1H, H-7), 7.88
(d, Jˆ2.4 Hz, 1H, H-5), 8.93 (br s, 1H, NH). dC (DMSO-d6):
13.63, 21.90, 24.54, 81.67, 118.26, 120.17, 125.65, 126.36,
135.37, 140.21, 172.61, 194.96. Anal. calcd (found) for
C13H14ClNO3: C 58.32 (58.19); H 5.27 (5.26); N 5.23
(5.42).
3r: Colourless crystals, yield 79%, mp 158–162ЊC
(benzene), IR: 3473, 3344, 3222, 3165, 3016, 2952, 2927,
2871, 1701, 1664, 1616, 1577, 1520, 1464, 1427, 1402,
1386, 1288, 1226, 1211, 1180, 1155, 1120, 1099, 1026,
966, 900, 845, 808, 744, 679 cmϪ1. dH (CDCl3): 0.82 (t,
Jˆ7.1 Hz, 3H, CH3 of butyl), 1.15–1.30 (m, 3H), 1.35–
1.54 (m, 1H), 1.75–2.02 (m, 2H, H-1 of butyl), 2.35 (s,
3H, Ar-CH3), 2.57 (s, 3H, Ar-CH3), 4.06 (s, 1H, OH),
6.77 (br s, 1H, ArH), 6.79 (br s, 1H, ArH), 9.72 (br s, 1H,
NH). dC (CDCl3): 13.79, 21.00, 21.73, 22.49, 25.21, 40.75,
82.54, 115.14, 115.19, 128.12, 140.98, 141.94, 146.65,
173.45, 196.71. Anal. calcd (found) for C15H19NO3: C
68.94 (69.30); H 7.33 (7.13); N 5.36 (5.73).
3m: Colourless crystals, yield 74%, mp 174–177ЊC (ethyl
acetate), IR: 3473, 3188, 3120, 3068, 2954, 2868, 1701,
1662, 1620, 1508, 1421, 1379, 1329, 1271, 1244, 1192,
1157, 1118, 1092, 1037, 960, 910, 839, 821, 706, 669
cmϪ1. dH (DMSO-d6ϩCDCl3): 0.81 (t, Jˆ7.0 Hz, 3H,
CH3 of butyl), 1.10–1.40 (m, 4H, H-3 and H-2 of butyl),
1.65–1.85 (m, 2H, H-1 of butyl), 2.32 (s, 3H, Ar-CH3), 5.31
(br s, 1H, OH), 6.99 (d, Jˆ8.2 Hz, 1H, H-8), 7.32 (d,
Jˆ8.2 Hz, 1H, H-7), 7.55 (s, 1H, H-5), 10.58 (br s, 1H,
NH). dC (DMSO-d6ϩCDCl3): 13.74, 20.29, 22.25, 24.70,
39.90, 82.04, 116.27, 119.01, 126.57, 131.76, 136.43,
3s: Colourless crystals, yield 79%, mp 224–231ЊC (ethyl
acetate), IR: 3456, 3147, 3012, 2922, 1712, 1660, 1614,
1575, 1523, 1429, 1381, 1284, 1226, 1182, 1159, 1030,
881, 848, 745, 706, 696 cmϪ1. dH (DMSO-d6ϩCDCl3):

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A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1557
2.26 (s, 3H, Ar-CH3), 2.41 (s, 3H, Ar-CH3), 6.07 (s, 1H,
OH), 6.66 (br s, 1H, ArH), 6.75 (br s, 1H, ArH), 7.22–
7.31 (m, 3H, Ph), 7.32–7.40 (m, 2H, Ph), 10.87 (br s, 1H,
NH). dC (DMSO-d6ϩCDCl3): 20.99, 21.41, 83.05, 114.74,
115.95, 125.55, 126.86, 128.40, 128.46, 138.66, 140.72,
141.62, 145.20, 170.88, 194.59. Anal. calcd (found) for
C17H15NO3: C 72.58 (72.93); H 5.37 (5.51); N 4.98 (4.85).
4e: Pale yellow crystals, mp 107–110ЊC (c-C6H12), IR:
3165, 3093, 3039, 2954, 2933, 2871, 1749, 1724, 1633,
1604, 1508, 1454, 1425, 1348, 1284, 1242, 1163, 1089,
1053, 1039, 906, 806 cmϪ1
. dH (CDCl3): 0.97 (t,
Jˆ7.3 Hz, 3H, CH3 of butyl), 1.32–1.45 (m, 2H, H-3 of
butyl), 1.61–1.72 (m, 2H, H-2 of butyl), 2.20 (s, 6H,
2×Ar-CH3), 2.45 (t, Jˆ7.4 Hz, 2H, H-1 of butyl), 6.08 (s,
1H, H-3), 6.76 (d, Jˆ7.9 Hz, 1H, H-5), 7.00 (d, Jˆ7.9 Hz,
1H, H-6), 7.88 (br s, 1H, NH). dC (CDCl3): 13.67, 15.87,
17.63, 22.17, 27.00, 33.59, 70.10, 117.10, 122.31, 124.40,
131.47, 133.10, 140.42, 172.47, 174.91. EIMS, m/z (%): 261
(Mϩ, 12), 177 (100), 160 (29), 85 (15), 77 (16), 57 (45).
Anal. calcd (found) for C15H19NO3: C 68.94 (69.23); H 7.33
(7.61); N 5.36 (5.30).
3t: Colourless crystals, yield 85%, mp 70–74ЊC (benzene–
c-C6H12), IR: 3485, 3429, 2956, 1703, 1660, 1607, 1570,
1494, 1461, 1342, 1297, 1153, 1075, 1029, 847 cmϪ1. dH
(DMSO-d6): 0.74 (t, Jˆ7.1 Hz, 3H, CH3 of butyl), 0.95–
1.36 (m, 4H, H-3 and H-2 of butyl), 1.64 (m, 2H, H-1 of
butyl), 2.36 (s, 3H, Ar-CH3), 2.45 (s, 3H, Ar-CH3), 3.35 (s,
3H, N-CH3), 5.50 (s, 1H, CH), 6.88 (s, 1H, ArH), 7.04 (s,
1H, ArH). dC (DMSO-d6): 13.61, 20.71, 21.42, 21.84,
25.08, 30.13, 39.36, 82.51, 114.17, 117.20, 127.00,
139.67, 142.98, 144.60, 171.51, 196.61. Anal. calcd
(found) for C16H21NO3: C 69.79 (70.16); H 7.69 (8.00); N
5.09 (4.98).
4f: Pale violet crystals, mp 231–234ЊC (acetic acid), IR:
3182, 3099, 2935, 2852, 1743, 1718, 1635, 1604, 1508,
1450, 1421, 1334, 1315, 1288, 1248, 1111, 1070, 1043,
1026, 860, 806, 758, 731, 710, 667 cmϪ1. dH (CDCl3):
2.21 (s, 3H, Ar-CH3), 2.22 (s, 3H, Ar-CH3), 6.30 (s, 1H,
H-3), 6.76 (d, Jˆ7.9 Hz, 1H, H-5), 7.02 (d, Jˆ7.9 Hz, 1H,
H-6), 7.45 (m, 2H, m-Ph), 7.59 (m, 1H, p-Ph), 7.97 (br s, 1H,
NH), 8.09 (m, 2H, o-Ph). dC (DMSO-d6ϩCDCl3): 15.98,
17.26, 70.80, 116.77, 122.20, 123.31, 128.64, 128.69,
129.42, 131.16, 132.22, 133.61, 141.45, 164.53, 173.68.
EIMS, m/z (%): 281 (Mϩ, 35), 176 (82), 160 (24), 117
(7), 105 (100), 97 (8), 83 (7), 77 (24), 69 (6), 57 (7).
Anal. calcd (found) for C17H15NO3: C 72.58 (72.81); H
5.37 (4.99); N 4.98 (4.51).
General procedure for the rearrangement of 3-hydroxy-
quinoline-2,4(1H,3H)-diones (3a–t)
A mixture of 3 (5 mmol) and the catalyst (1 mmol, Table 1)
in xylene or cyclohexanol (15 mL) was refluxed for 2–12 h
(Table 1). After cooling, the precipitated unreacted
starting material 3 was filtered off with suction. Filtrate
was evaporated and products 4–8 (Table 1) were separated
by column chromatography, using benzene and then suc-
cessive mixtures of benzene–ethyl acetate (in ratios from
99:1 to 8:2) as eluents. For yields see Table 1. For physical
and spectroscopic data of compounds 4a and 4d, see Ref. 4.
4h: Colourless crystals, mp 72–74ЊC (c-C6H12), IR: 3220,
2960, 2933, 2873, 1737, 1695, 1620, 1599, 1469, 1388,
1361, 1346, 1327, 1292, 1261, 1230, 1197, 1165, 1153,
1105, 1036, 941, 906, 887, 841, 767, 744, 658 cmϪ1. dH
(CDCl3): 0.92(t, Jˆ7.3 Hz, 3H, CH3 of butyl), 1.32–1.45
(m, 2H, H-3 of butyl), 1.62–1.73 (m, 2H, H-2 of butyl), 2.47
(dt, Jˆ7.5, 0.8 Hz, 2H, H-1 of butyl), 5.95 (s, 1H, H-3), 6.86
(d, Jˆ7.7 Hz, 1H, H-8), 7.04 (dd, Jˆ7.7, 7.6 Hz, 1H, H-6),
7.31 (d, Jˆ7.5 Hz, 1H, H-5), 7.71 (br s, 1H, NH). dC
(CDCl3): 13.67, 22.16, 26.93, 33.65, 70.12, 110.48,
123.08, 125.06, 125.71, 130.26, 141.71, 173.14, 174.81.
EIMS, m/z (%): 233 (Mϩ, 22), 149 (100), 132 (42), 119
(24), 104 (20), 93 (25), 85 (30), 77 (26), 57 (53). Anal.
calcd (found) for C13H15NO3: C 66.94 (67.16); H 6.48
(6.55); N 6.00 (6.24).
4-Chloro-7-methyl-2-oxo-1,3-dihydro-2H-indol-3-yl
pentanoate (4b): Pale yellow crystals, mp 108–113ЊC
(c-C6H12), IR: 3165, 3100, 3043, 2982, 2960, 2885, 1756,
1731, 1628, 1605, 1488, 1434, 1290, 1248, 1219, 1119,
1098, 1026, 968, 812 cmϪ1
. dH (CDCl3): 0.92 (t,
Jˆ7.3 Hz, 3H, CH3 of butyl), 1.31–1.45 (m, 2H, H-3 of
butyl), 1.62–1.73 (m, 2H, H-2 of butyl), 2.22 (s, 3H,
Ar-CH3), 2.47 (t, Jˆ7.5 Hz, 2H, H-1 of butyl), 6.05 (s,
1H, H-3), 6.92 (d, Jˆ8.4 Hz, 1H, H-5), 7.05 (d, Jˆ8.4 Hz,
1H, H-6), 8.19 (br s, 1H, NH). dC (CDCl3): 13.67, 15.86,
22.15, 26.95, 33.44, 69.70, 118.54, 121.67, 123.26, 128.62,
132.72, 141.83, 172.31, 174.50. Anal. calcd (found) for
C14H16ClNO3: C 59.68 (59.83); H 5.72 (5.87); N 4.97 (5.25).
4j: Pale yellow oil, IR: 3714, 2953, 2931, 2873, 1739, 1615,
1494, 1470, 1375, 1353, 1260, 1159, 1091, 1022, 753 cmϪ1
.
dH (CDCl3): 0.92 (t, Jˆ7.3 Hz, 3H, CH3 of butyl), 1.38 (m,
2H, H-3 of butyl), 1.67 (m, 2H, H-2 of butyl), 2.45 (m, 2H,
H-1 of butyl), 3.22 (s, 3H, CH3), 5.96 (s, 1H, H-3), 6.83 (d,
Jˆ7.5 Hz, 1H), 7.06 (dd, J1ˆJ2ˆ7.5 Hz, 1H), 7.30–7.40
(m, 2H). dC (CDCl3): 13.68, 22.17, 26.38, 26.93, 33.68,
69.74, 108.48, 123.07, 124.63, 125.51, 130.27, 144.55,
172.36, 173.16. EIMS, m/z (%): 247 (Mϩ, 12), 163 (100),
146 (28), 111 (12), 97 (18), 91 (20), 85 (22), 77 (12), 71
(25), 57 (47). HR EIMS calcd for C14H17NO3: 247.1208,
found: 247.1201.
4c: Pale yellow crystals, mp 221–222ЊC (ethyl acetate), IR:
3195, 3099, 2933, 1745, 1722, 1626, 1601, 1485, 1452,
1423, 1332, 1315, 1282, 1248, 1203, 1138, 1111, 1072,
802, 792, 762, 706 cmϪ1. dH (CDCl3): 2.24 (s, 3H,
Ar-CH3), 6.26 (s, 1H, H-3), 6.92 (d, Jˆ8.3 Hz, 1H, H-5),
7.07 (d, Jˆ8.3 Hz, 1H, H-6), 7.45 (m, 2H, m-Ph), 7.59 (m,
1H, p-Ph), 8.10 (m, 2H, o-Ph), 8.16 (br s, 1H, NH). dC
(DMSO-d6ϩCDCl3): 16.10, 70.13, 118.75, 121.43,
122.34, 128.27, 128.43, 128.91, 129.89, 132.78, 133.45,
143.13, 165.02, 173.50. EIMS, m/z (%): 303 (Mϩ, 5,
37Cl), 301 (Mϩ, 17, 35Cl), 198 (5, 37Cl), 196 (16, 35Cl),
182 (5, 37Cl), 180 (15, 35Cl), 139 (5, 37Cl), 137 (16, 35Cl),
123 (14), 111 (18), 105 (100), 97 (34), 83 (38), 69 (62), 57
(52), 55 (45). Anal. calcd (found) for C16H12ClNO3: C 63.69
(63.90); H 4.01 (3.96); N 4.64 (4.84).
4o: Colourless crystals, mp 190–193ЊC (benzene), IR: 3487,
3402, 3180, 3145, 3064, 3031, 2923, 1761, 1724, 1622,
1601, 1495, 1454, 1336, 1282, 1234, 1219, 1185, 1074,
1069, 1022, 985, 879, 814, 798, 760, 733, 710, 692 cmϪ1
.

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1558
dH (CDCl3): 2.26 (s, 3H, Ar-CH3), 3.76 (m, 2H, Ph-CH2),
5.89 (s, 1H, H-3), 6.95–7.05 (m, 2H), 7.24–7.38 (m, 5H),
8.39 (br s, 1H, NH). dC (CDCl3): 13.85, 40.75, 70.78,
118.30, 122.66, 123.63, 123.72, 127.40, 128.70, 129.26,
133.09, 136.40, 141.43, 170.81, 174.17. EIMS, m/z (%):
317 (Mϩ, 4, 37Cl), 315 (Mϩ, 11, 35Cl), 199 (53, 37Cl), 197
(100, 35Cl), 182 (18, 37Cl), 180 (40, 35Cl), 152 (10), 91 (53).
HR EIMS calcd for C17H1435ClNO3: 315.0662, found:
315.0671.
200.02 (CH2CvO). EIMS, m/z (%): 315 (Mϩ, 5), 196
(100), 168 (16), 140 (10), 119 (6), 91 (16). Anal. calcd
(found) for C17H14ClNO3: C 64.67 (64.51); H 4.47 (4.49);
N 4.44 (4.32).
5b: Colourless crystals, mp 173–188ЊC (c-C6H12), IR: 3280,
2980, 2960, 2890, 1760, 1730, 1500, 1480, 1415, 1385,
1290, 1260, 1210, 1150, 1055, 1020, 965, 825, 800, 770,
750, 690, 660 cmϪ1. dH (CDCl3): 0.86 (t, Jˆ7.3 Hz, 3H,
CH3 of butyl), 1.28 (m, 2H, H-3 of butyl), 1.55 (m, 2H,
H-2 of butyl), 2.23 (s, 3H, CH3), 2.61 (m, 2H, H-1 of
butyl), 6.03 (s, 1H, CH), 7.04 (d, Jˆ8.3 Hz, 1H, H-6),
7.10 (d, Jˆ8.3 Hz, 1H, H-7), 7.48 (br s, 1H, NH). dC
(CDCl3): 13.70, 15.97, 22.10, 25.40, 38.01, 80.14, 114.40,
121.50, 123.91, 129.05, 132.32, 135.22, 151.11, 201.73.
EIMS, m/z (%): 283 (Mϩ, 2, 37Cl), 281 (Mϩ, 6, 35Cl), 198
(38, 37Cl), 196 (77, 35Cl), 177 (17), 168 (11), 149 (6), 140
(7), 97 (11), 85 (84), 77 (20), 69 (43), 57 (100). HR EIMS
calcd for C14H1635ClNO3: 281.0819, found: 281.0825.
4p: Pale yellow crystals, mp 135–136ЊC (benzene–c-
C6H12), IR: 3489, 3419, 3159, 3118, 3086, 3028, 2910,
2854, 1753, 1728, 1629, 1607, 1498, 1456, 1413, 1379,
1348, 1281, 1213, 1142, 1074, 1039, 1028, 953, 902, 841,
789, 760, 704, 621 cmϪ1. dH (DMSO-d6): 1.93 (s, 3H,
Ar-CH3), 2.22 (s, 3H, Ar-CH3), 3.78 (s, 2H, CH2Ph), 5.96
(s, 1H, H-3), 6.47 (s, 1H, ArH), 6.54 (s, 1H, ArH), 7.02–
7.04 (m, 5H, Ph), 10.46 (br s, 1H, NH). dC (DMSO-d6):
17.13, 21.11, 39.82, 70.11, 108.09, 119.69, 123.76,
126.90, 128.31, 129.22, 133.79, 134.80, 139.48, 142.95,
169.82, 173.29. EIMS, m/z (%): 295 (Mϩ, 15), 177 (100),
160 (54), 149 (11), 111 (15), 105 (26), 97 (24), 91 (51), 83
(27), 71 (34), 69 (35), 57 (49). HR EIMS calcd for
C18H17NO3: 295.1208, found: 295.1200.
5c: Colourless crystals, mp 188–189ЊC (ethyl acetate), IR:
3371, 3253, 3207, 3145, 3064, 2989, 2864, 1753, 1687,
1589, 1489, 1464, 1446, 1367, 1278, 1242, 1225, 1190,
1089, 1074, 1062, 991, 962, 951, 883, 862, 806, 756, 737,
725, 694 cmϪ1. dH (CDCl3): 2.23 (s, 3H, Ar-CH3), 6.83 (s,
1H, H-4), 6.98 (d, Jˆ8.2 Hz, 1H, H-6), 7.11 (d, Jˆ8.2 Hz,
1H, H-7), 7.36 (br s, 1H, NH), 7.53 (m, 2H, m-Ph), 7.65 (m,
1H, p-Ph), 8.11 (m, 2H, o-Ph). dC (CDCl3): 16.20, 76.87,
114.58, 121.65, 123.54, 128.84, 128.97, 129.62, 132.31,
134.07, 134.26, 135.25, 150.49, 192.34. EIMS, m/z (%):
303 (Mϩ, 8, 37Cl), 301 (Mϩ, 25, 35Cl), 277 (4, 37Cl), 275
(12, 35Cl), 273 (10), 264 (10), 198 (5, 37Cl), 196 (16, 35Cl),
137 (7), 105 (100), 95 (11), 77 (35), 69 (48), 57 (25). Anal.
calcd (found) for C16H12ClNO3: C 63.69 (63.91); H 4.01
(4.03); N 4.64 (4.34).
4r: Colourless crystals, mp 96–102ЊC (c-C6H12), IR: 3193,
3130, 2931, 2869, 1736, 1693, 1628, 1606, 1464, 1373,
1342, 1271, 1140, 1165, 1140, 1109, 1076, 1035, 1005,
958, 895, 839, 733, 694, 615 cmϪ1. dH (DMSO-d6): 0.87
(t, Jˆ7.3 Hz, 3H, CH3 of butyl), 1.32 (m, 2H, H-3 of
butyl), 1.54 (m, 2H, H-2 of butyl), 2.10 (s, 3H, Ar-CH3),
2.24 (s, 3H, Ar-CH3), 2.40 (t, Jˆ7.3 Hz, 2H, H-1 of butyl),
5.96 (s, 1H, H-3), 6.48 (s, 1H, ArH), 6.58 (s, 1H, ArH),
10.45 (br s, 1H, NH). dC (DMSO-d6): 13.45, 17.32, 21.14,
21.39, 26.54, 32.69, 69.61, 108.13, 119.92, 123.77, 134.68,
139.43, 142.98, 171.67, 173.48. EIMS, m/z (%): 261 (Mϩ,
16), 177 (100), 160 (35), 149 (20), 121 (15), 85 (21), 77
(16), 69 (21), 57 (40). Anal. calcd (found) for C15H19NO3: C
68.94 (69.29); H 7.33 (7.56); N 5.36 (5.60).
5f: Colourless crystals, mp 182–187ЊC (ethanol), IR: 3392,
3261, 3132, 2960, 2925, 2864, 1747, 1734, 1685, 1622,
1587, 1508, 1467, 1446, 1377, 1325, 1282, 1244, 1203,
1088, 1057, 968, 891, 868, 808, 758, 702, 654 cmϪ1. dH
(CDCl3): 2.11 (s, 3H, Ar-CH3), 2.21 (s, 3H, Ar-CH3), 6.60
(s, 1H, H-4), 6.80 (d, Jˆ7.8 Hz, 1H, Ar-H), 7.04 (br s, 1H,
NH), 7.06 (d, Jˆ7.8 Hz, 1H, Ar-H), 7.52 (m, 2H, m-Ph),
7.63 (m, 1H, p-Ph), 8.03 (m, 2H, o-Ph). dC (CDCl3): 16.08,
18.49, 77.59, 115.02, 120.22, 124.93, 128.88, 129.31,
131.25, 132.57, 133.66, 133.96, 134.72, 150.77, 193.95.
EIMS, m/z (%): 281 (Mϩ, 9), 176 (100), 148 (11), 105
(68), 77 (36), 57 (16). Anal. calcd (found) for C17H15NO3:
C 72.58 (72.80); H 5.37 (5.37); N 4.98 (5.22).
4s: Pale yellow crystals, mp 189–193ЊC (acetic acid), IR:
3172, 3120, 2936, 1745, 1720, 1631, 1608, 1449, 1247,
1144, 1097, 1067, 840, 707 cmϪ1. dH (CDCl3): 2.20 (s,
3H, Ar-CH3), 2.30 (s, 3H, Ar-CH3), 6.27 (s, 1H), 6.58 (s,
1H), 6.66 (s, 1H), 7.44 (m, 2H, m-Ph), 7.58 (m, 1H, p-Ph),
8.09 (m, 3H, o-Ph, NH). dC (CDCl3): 17.94, 21.68, 70.15,
108.80, 119.75, 125.31, 128.49, 128.97, 130.13, 133.53,
136.09, 140.74, 141.81, 165.38, 174.32. EIMS, m/z (%):
281 (Mϩ, 39), 176 (88), 160 (34), 147 (8), 117 (10), 105
(100), 91 (10), 77 (49), 57 (11). HR EIMS calcd for
C17H15NO3: 281.1052, found: 281.1059.
5s: Colourless crystals, mp 219–222ЊC (benzene–c-C6H12),
IR: 3243, 3196, 3136, 2919, 1704, 1625, 1595, 1448, 1391,
1322, 1307, 1282, 1219, 1089, 975, 913, 844, 814, 753, 698,
637 cmϪ1. dH (DMSO-d6): 2.01 (s, 3H, Ar-CH3), 2.20 (s,
3H, Ar-CH3), 6.55 (br s, 1H, ArH), 6.62 (br s, 1H, ArH),
7.07 (s, 1H, H-4), 7.57 (m, 2H, m-Ph), 7.70 (m, 1H, p-Ph),
8.01 (m, 2H, o-Ph), 10.15 (br s, 1H, NH). dC (DMSO-d6):
18.17, 20.68, 76.42, 112.22, 112.38, 125.07, 128.74,
128.97, 133.79, 134.62, 134.67, 136.34, 138.89, 150.05,
195.36. EIMS, m/z (%): 281 (Mϩ, 4), 176 (100), 149 (10),
120 (6), 105 (40), 77 (27), 57 (13). Anal. calcd (found)
for C17H15NO3: C 72.58 (72.92); H 5.37 (5.14); N 4.98
(4.53).
5-Chloro-8-methyl-4-phenylacetyl-1,4-dihydro-2H-3,1-
benzoxazin-2-one (5a): Colourless crystals, mp 198–203ЊC
(ethanol), IR: 3260, 3210, 3145, 1752, 1598, 1501, 1468,
1390, 1301, 1262, 1211, 1050, 971, 811, 766, 749,
718 cmϪ1. dH (DMSO-d6): 2.17 (s, 3H, Ar-CH3), 3.85 and
4.01 (two d, Jˆ16.8 Hz, 2H, CH2Ph), 6.35 (s, 1H, H-4),
7.00–7.30 (m, 7H, Ph, Ar-H), 9.90 (s, 1H, NH). dC
(DMSO-d6): 16.26 (C(8)-CH3), 43.58 (Ar-CH2), 79.03
(C-4), 114.39 (C-4a), 122.76 (C-8), 123.16 (C-6), 126.68
(C-40), 127.75 (C-5), 128.13 (C-30 and C-50), 129.33 (C-20
and C-60), 132.61 (C-7), 133.12, 136.07, 150.45 (C-2),

´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1559
4-Chloro-7-methyl-1H-indole-2,3-dione (6a): Orange
crystals, mp 281–286ЊC (acetic acid), Lit.11 273ЊC, IR:
3429, 3207, 3101, 3082, 3022, 1736, 1624, 1587, 1487,
1454, 1388, 1317, 1265, 1246, 1221, 1192, 1043, 983,
929, 879, 810, 706 cmϪ1. dH (DMSO-d6): 2.16 (s, 3H,
Ar-CH3), 6.97 (d, Jˆ8.2 Hz, 1H, H-6), 7.39 (dd, Jˆ8.2,
0.5 Hz, 1H, H-5), 11.22 (s, 1H, NH). dC (DMSO-d6):
15.07, 114.29, 120.37, 123.25, 128.28, 139.90, 150.47,
159.13, 181.54. Anal. calcd (found) for C9H6ClNO2: C
55.26 (55.27); H 3.09 (3.08); N 7.16 (7.21).
CO). EIMS, m/z (%): 283 (Mϩ, 1, 37Cl), 281 (Mϩ, 4, 35Cl),
199 (30, 37Cl), 197 (76, 35Cl), 104 (8), 84 (86), 78 (36), 69
(37), 56 (100). Anal. calcd (found) for C14H16ClNO3: C
59.68 (59.54); H 5.72 (5.66); N 4.97 (4.68).
Independent synthesis of 3-benzyl-5-chloro-8-methyl-3-
phenylacetoxyquinoline-2,4(1H,3H)-dione (7)
To the solution of phenylacetic acid (136 mg, 1 mmol) in
benzene (3 mL), 0.1 mL (98 mg, 1.23 mmol) of pyridine
and 0.4 mL (655 mg, 5.5 mmol) of thionyl chloride were
added. After 0.5 h standing at ambient temperature the solu-
tion was refluxed for 0.5 h and evaporated to dryness in
vacuo. The residue was extracted with benzene (3 mL)
and filtered. To the filtrate, the solution of 3a (158 mg,
0.5 mmol) in benzene (5 mL) and pyridine (0.5 mL) was
added. After 0.5 h standing, the reaction mixture was
refluxed for 0.5 h, cooled and filtrated. The filtrate was
washed with HCl (10%, 5 mL), water and sodium hydro-
gencarbonate (5%, 5 mL). After evaporation of organic
layer the residue was column chromatographed using the
solvent system as described above. Crude 7 (120 mg,
55%) was crystallised from ethanol to give 85 mg of
product identical to compound which was isolated from
rearrangement of 3a.
6d: Orange crystals, mp 274–276ЊC (benzene), Lit.11
267ЊC, IR: 3425, 3205, 3100, 1722, 1632, 1590, 1509,
1379, 1321, 1276, 1254, 1167, 962, 812, 715 cmϪ1. dH
(DMSO-d6ϩCDCl3): 2.19 (s, 3H, Ar-CH3), 2.48 (s, 3H,
Ar-CH3), 6.72 (d, Jˆ7.8 Hz, 1H, Ar-H), 7.18 (d,
Jˆ7.8 Hz, 1H, Ar-H), 10.76 (s, 1H, NH). dC (DMSO-
d6ϩCDCl3): 15.31, 17.52, 115.77, 118.88, 124.92, 137.73,
139.21, 149.22, 160.08, 185.48. Anal. calcd (found)
for C10H9NO2: C 68.56 (68.75); H 5.18 (5.38); N 8.00
(7.98).
6p: Orange crystals, mp 246–249ЊC (ethanol), Lit.20 241–
243ЊC, IR: 3430, 3204, 2922, 2871, 2360, 2332, 1755, 1727,
1715, 1627, 1603, 1459, 1376, 1331, 1272, 1146, 1073,
1036, 923, 853, 753, 683 cmϪ1. dH (DMSO-d6): 2.29 (s,
3H, Ar-CH3), 2.39 (s, 3H, Ar-CH3), 6.52, (s, 1H, ArH),
6.67 (s, 1H, ArH), 10.92 (br s, 1H, NH). dC (DMSO-d6):
17.27, 21.97, 110.03, 113.66, 125.31, 139.50, 149.46,
151.07, 159.62, 183.93. Anal. calcd (found) for
C10H9NO2: C 68.56 (68.87); H 5.18 (5.32); N 8.00 (7.79).
Acknowledgements
This study was supported by the Grant Agency of the Czech
Republic (Grant No. 203/97/0033) and The Ministry of
Science and Technology of Slovenia. We would like to
ˇ
3-Benzyl-5-chloro-8-methyl-3-phenylacetoxyquinoline-
2,4(1H,3H)-dione (7): Colourless crystals, yield 9%, mp
169–171ЊC (ethyl acetate), IR: 3230, 3182, 3090, 3015,
2912, 1756, 1728, 1692, 1589, 1492, 1465, 1366, 1157,
1131, 1041, 989, 836, 743, 718 cmϪ1. dH (CDCl3): 2.07
(s, 3H, Ar-CH3), 3.32 (s, 2H, PhCH2), 3.85 (s, 2H,
PhCH2), 6.97 (d, Jˆ8.1 Hz, 1H, H-6), 6.98–7.35 (m, 11
H, H-7, 2×Ph), 7.88 (br s, 1H, NH). dC (CDCl3): 16.66,
29.70, 40.12, 42.91, 84.37, 117.43, 122.06, 125.92,
127.19, 127.80, 127.92, 128.54, 129.58, 130.20, 131.06,
132.92, 132.94, 136.24, 139.43, 167.91, 170.66, 188.30.
EIMS, m/z (%): 435 (Mϩ, 15, 37Cl), 433 (Mϩ, 45, 35Cl),
317 (4, 37Cl), 315 (12, 35Cl), 297 (56), 199 (6, 37Cl), 197
(18, 35Cl), 168 (7), 139 (10), 118 (12), 103 (9), 91 (100), 77
(12), 65 (24), 57 (7). Anal. calcd (found) for C25H20ClNO4:
C 69.20 (69.53); H 4.65 (4.92); N 3.23 (3.12).
ˇ
thank Dr Bogdan Kralj and Dr Dusan Zigon (Mass
ˇ
Spectrometry Centre, Jozef Stefan Institute, Ljubljana,
Slovenia) for mass spectral measurements. The authors
ˇ
´
are also indebted to Mrs H. Gerzova for technical help.
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4-Chloro-3-hydroxy-7-methyl-3-valeryl-1,3-dihydro-
2H-indol-2-one (8b): Pale yellow crystals, yield 5%, mp
119–121ЊC (benzene), IR: 3427, 3166, 3098, 3037, 2958,
2945, 2875, 1747, 1729, 1713, 1624, 1601, 1481, 1424,
1406, 1371, 1288, 1218, 1167, 1122, 1066, 999, 862, 790,
747, 730, 604 cmϪ1. dH (CDCl3): 0.81 (t, Jˆ7.3 Hz, 3H,
CH3 of butyl), 1.22 (m, 2H, H-3 of butyl), 1.58 (m, 2H,
H-2 of butyl), 2.20–2.40 (m, 5H, Ar-CH3, H-1 of butyl),
5.11 (s, 1H, OH), 6.94 (d, Jˆ8.3 Hz, 1H, H-5), 7.11 (dd,
Jˆ8.3, 0.5 Hz, 1H, H-6), 9.39 (br s, 1H, NH). dC (CDCl3):
13.62 (C-4 of butyl), 16.07 (C(7)-CH3), 21.91 (C-3 of butyl),
25.42 (C-2 of butyl), 35.78 (C-1 of butyl), 83.97 (C-3),
119.15 (C-7), 123.86 (C-3a), 124.14 (C-5), 128.71 (C-4),
133.46 (C-6), 142.26 (C-7a), 174.80 (C-2), 201.64 (Butyl-
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´
A. Klasek et al. / Tetrahedron 56 (2000) 1551–1560
1560
M.; Seitz, S. P. US Pat. 5874430; Chem. Abstr. 1999, 130, 196659.
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