Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the reaction products

Article abstract of DOI:10.1016/j.tet.2017.02.007

The reaction of tertiary α-chloroketones with ethanolamine has not been hitherto described in the literature. Herein, we describe the reaction of tertiary 3-chloroquinoline-2,4-diones with ethanolamine to give novel 3-(2-hydroxyethylamino)quinoline-2,4-di

Full text of DOI:10.1016/j.tet.2017.02.007

Tetrahedron xxx (2017) 1e11
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Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and
rearrangement of the reaction products
a
,
*
a
b
a
ꢀ
ꢁ
ꢁ
ꢀ a
ꢁ
Antonín Klasek , Filip Kremen , Hana Kremenova , Antonín Lycka , Michal Rouchal
a Department of Chemistry, Faculty of Technology, Tomas Bata University in Zlín, CZ-762 72, Zlín, Czechia
Faculty of Science, University of Hradec Kralove, CZ-500 03, Hradec Kralove 3, Czechia
b
ꢀ
ꢀ
ꢀ
ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of tertiary
a
-chloroketones with ethanolamine has not been hitherto described in the
Received 3 October 2016
Received in revised form
23 January 2017
Accepted 3 February 2017
Available online xxx
literature. Herein, we describe the reaction of tertiary 3-chloroquinoline-2,4-diones with ethanolamine
to give novel 3-(2-hydroxyethylamino)quinoline-2,4-diones. These compounds provide 3-(2-
oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-diones and new compounds with dimeric character after re-
action with triphosgene. Molecular rearrangement proceeds during the reaction of 3-(2-
hydroxyethylamino)quinoline-2,4-diones with isocyanic acid. Three types of reaction products arise:
2-(2-hydroxyethyl)imidazo[1,5-c]quinazoline-3,5-diones, 3-(2-hydroxyethyl)-3,3a-dihydro-2H-imidazo
[4,5-]quinoline-4(5H)diones and primarily 5-hydroxy-1-(hydroxyethyl)-10H-spiro[imidazolidine-5,30-
indole]-2,20-diones. The reaction mechanism and product stereochemistry are discussed. The 1H, 13C and
15N NMR spectra of the prepared compounds were measured, and all resonances were assigned from
appropriate two-dimensional experiments.
Keywords:
Isocyanic acid
Rearrangement
Triphosgene
Spiro-compounds
1H, 13C and 15N NMR
© 2017 Elsevier Ltd. All rights reserved.
1. Introduction
2,4-diones 2 with easily accessible and inexpensive ethanolamine.
We presumed that the reaction would proceed through the for-
In our previous paper we studied the reaction of 3-
with ammonia and primary
mation of 3-(3-hydroxyethyl)amino derivatives 3, whose reactions
with isocyanic acid can lead, according to our experiences, to more
complex products of the molecular rearrangements than as with
simple 3-alkylaminoquinolinediones.
chloroquinoline-2,4-diones
2
amines.1 The reaction proceeded smoothly and 3-amino or 3-
alkylaminoquinoline-2,4-diones were prepared in good yields.
These compounds rearrange during reaction with urea,2,3 nitro-
urea,4,5 isocyanates,6 isothiocyanates,7e9 and isocyanic and iso-
thiocyanic acids10,11 to give a broad palette of new heterocyclic
2. Results and discussion
compounds:
imidazo[1,5-c]quinazoline-3,5-diones,
3-(3-
The reaction of 2 with ethanolamine (Scheme 1) proceeded
easily and in good yields (Table 1). In all cases, 3-(3- hydroxyethyl)
amino derivatives 3 were obtained, and their NMR spectra are given
a benzyl group, 3-
hydroxyderivatives 4b, e, h and minor compounds 5e, h were
also obtained.
The formation of compounds 4 was the result of the hydrolysis
of 3. The structure of the condensation products 5 was established
by the analysis of very complicated NMR spectra (Table 3), in which
the chemical shifts of eOH groups were absent. These compounds
acylureido)-2,3-dihydro-1H-indol-2-ones, 4-alkylidene-10H-spiro
[imidazolidine-5,30-indole]-2,20-diones and spiro-linked imidazo-
line-2-thiones. 3-Aminoquinoline-2,4-quinolinediones were also
reduced12 by NaBH4 and the reaction products were converted to 3-
alkyl/aryl-2,3-dihydro-1H-indol-2-ones. With regard to the inter-
esting results described above, we carried out some of the afore-
mentioned reactions using an amine containing yet another
functional group, potentially capable to participate during the
molecular rearrangement.
in Table 2. When substituent R2 was
In this paper, we describe the reactions of 3-chloroquinoline-
arose from the reaction of 3-chloroderivatives
2 with 4-
hydroxyquinolin-2-one 1, stemming from the reductive hydrolysis
of 2 in alkaline medium. The conversion of 2 to 1 in alkaline me-
dium is known.13 The structures of 5e and 5h were confirmed by
their synthesis from 1 and 2, though in very small yields. The main
* Corresponding author.
E-mail address: klasek@ft.utb.cz (A. Klasek).
ꢀ
http://dx.doi.org/10.1016/j.tet.2017.02.007
0040-4020/© 2017 Elsevier Ltd. All rights reserved.
ꢀ
Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
2
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
Scheme 1.
Table 1
reaction of 3 with triphosgene, identified as dimeric compounds 7,
Reaction of 3-chloroquinolinediones 2 with ethanolamine.
8, and 9 (Scheme 1, Tables 6 and 7). Compounds 7 were symmetric
dimers created from two molecules of compound 3 and tri-
phosgene and signals corresponding to one carbon possessed half
the intensity of the other signals in their 13C NMR spectra. More-
over, these signals showed the appropriate cross-peaks in the 2D
1He13C HMBC spectrum due to existence of 3J(13C, OCH2), providing
clear evidence for the existence of an OC(¼O)O fragment in com-
pounds 7. Proton signals from NH groups were not detected prob-
ably due to rapid exchange with water protons, but their presence
follows from MS data.
Starting compound
Product(s), (yield, %)
2a
2b
2c
2d
2e
2f
2g
2h
2i
3a (51)
3b (24), 2b (3), 4b (11)
3c (69)
3d (68)
3e (31), 4e (15), 5e (4)
3f (88)
3g (65)
3h (17), 4h (9), 5h (5)
3i (56)
The precursors of compounds 9 contained NH protons in posi-
tion 1; however, no acidic protons were detected in the 1H NMR
spectra of 9 (Table 6). Two types of C]O groups in a ratio of 2:1
were found in the NMR spectra of compounds 9. The correlation
between the protons in the OCH2 group and the carbonyl group of
relative intensity one and correlation of protons of NCH2 group and
the carbonyl group with a two-fold intensity through 3J(C]O, CH2)
in HMBC spectra help correct the structure of 9. The 2D 1He15N in
the HMBC spectra of compounds 9 were of key importance in the
correct determination of their constitution because the 15N chem-
ical shifts resonating at ca. ꢀ145 ppm clearly indicate the presence
of a so-called “pyridine” type of nitrogen in the molecule. The
alternative possibility corresponding to the existence of a NeC(¼O)
eN fragment instead of OeC(¼O)eN can thus be excluded. Com-
pounds 8 are unsymmetric and likely arise from the reaction of 7
with an additional molecule of triphosgene. The 1H and 13C NMR
spectra of compounds 8 (Table 7) are rather complicated, but the
typical chemical shifts observed in symmetrical compounds 7 and 9
were relatively easily detected in these spectra. Thus, compounds 8
contain - in one molecule - structural motifs from both compounds
7 and 9. Analogously, the 15N chemical shifts resonating at
ca. ꢀ144 ppm and (ꢀ285 5) ppm belong to a structural motif that
is similar to that from compound 7, and those observed at
ca. ꢀ241 ppm and (ꢀ341 3) ppm belong to a structural motif that
is similar to that from compound 9.
product was starting compound 1, arising from the reductive hy-
drolysis of 2.
After obtaining compounds 3, we studied their reaction with
triphosgene in order to install an additional ring on the molecule.
We obtained compounds 6 in all cases (Table 4), and their NMR
spectra are given in Table 5. The structure of compounds 6 were
also proposed according to the results obtained from ESI-MS ex-
periments. In the first-order mass spectra of compounds 6 the so-
dium adduct of the molecule [MþNa]þ represents the most
abundant ion (except for compound 6a). This signal was usually
accompanied by a singly charged signal that was twice as high,
which we assigned to the sodium adduct of the dimer [2$M þ Na]þ.
Furthermore, we studied the gas-phase behavior of compounds 6 in
detail using ESI-MS/MS experiments under collision-induced
dissociation (CID). In the ESI-MS/MS spectra of compounds 6a, 6d
and 6g, three independent neutral losses were observed. These
neutral losses were assigned as a water molecule (18 m/z), carbon
dioxide (44 m/z) and C4H8 from the butyl chain (56 m/z). Only one
neutral loss at m/z 87 was observed in the case of compounds 6b, 6e
and 6h. According to the structures of these compounds, we pro-
pose that the covalent bond between C(3) and the nitrogen atom
was cleaved and the neutral loss of oxazolidin-2-one (87 m/z)
occurred. In the case of compounds 6b, 6e and 6h, the [MþH]þ ion
was not successfully isolated, and tandem mass spectra were not
recorded.
The formation of compounds 7, 8, and 9 is rather surprising and
shows that, in the presence of catalytic N,N-dimethylaminopyr-
idine, triphosgene can react with not only the amino group, but also
In several cases, minor compounds were also obtained from the
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Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
3
Table 2
1H and 13C chemical shifts of compounds 3 in DMSO-d6.
Position
3a
3b
3c
3d
3e
3f
3g
3h
3i
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d
(C)
d(H)
d
(C)
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d(C)
d(H)
d
(C)
d
(H)
d(C)
2
3
e
172.6
72.6
e
172.1
73.1
e
171.7
76.1
e
172.4
73.1
e
171.7
73.9
e
171.2
76.7
e
172.5
73.5
e
171.8
73.8
e
171.3
76.9
e
e
e
e
e
e
e
e
e
4
4a
5
6
7
8
8a
NH
NHCH2
e
196.5
119.2
126.7
122.8
136.4
116.4
141.7
e
e
196.3
119.4
126.4
122.6
136.4
116.2
141.5
e
e
194.1
118.5
127.2
123.0
136.5
114.9
141.2
e
e
195.3
120.5
127.0
123.0
136.4
115.8
142.6
e
e
195.2
120.9
127.0
122.9
136.4
115.5
142.4
e
e
193.2
120.8
127.4
123.3
136.4
116.0
142.3
e
e
195.1
120.1
127.1
123.1
135.9
116.5
143.5
e
e
195.4
120.6
126.9
123.1
136.1
116.4
143.4
e
e
193.9
120.5
127.5
123.3
135.8
116.6
143.0
e
e
e
e
e
e
e
e
e
e
7.76
7.12
7.60
7.09
e
7.68
7.03
7.48
6.89
e
7.70
7.08
7.59
7.10
e
7.85
7.22
7.37
7.42
e
7.77
7.14
7.58
7.11
e
7.81
7.21
7.73
7.42
e
7.90
7.19
7.51
6.33
e
7.85
7.12
7.38
6.11
7.81
7.13
7.45
6.33
e
2.60
2.41
2.35
3.34
3.38
4.52
10.98
e
2.66
2.34
2.42
3.36
3.02
2.50
2.55
2.39
2.72
2.38
2.33
3.39
3.05
2.61
2.51
3.53
3.48
4.58
3.55
e
2.71
2.51
2.85
2.56
2.49
3.40
3.10
2.61
2.51
3.48
46.7
46.6
47.1
46.6
46.7
47.1
46.6
46.7
47.0
CH2O
60.8
60.8
3.47
60.8
3.39
60.9
60.8
61.0
3.42
60.9
60.8
60.9
OH
e
4.50
10.94
e
e
4.57
11.26
e
e
4.48
3.41
e
e
4.49
3.28
e
e
e
4.51
e
e
4.52
e
e
4.57
e
e
10(R1)
20(R1)
30(R1)
40(R1)
10(R2)
e
e
e
29.7
e
29.5
e
30.0
e
137.4
130.3
129.2
128.9
39.4
137.3
130.3
129.0
128.9
46.7
137.4
130.3
129.1
128.8
137.4
e
e
e
7.61
7.33
7.35
1.86
7.60
7.19
7.56
3.22,
3.15
e
7.63
7.37
7.34
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
1.69
39.3
3.10
3.06
e
45.5
e
137.8
1.72
1.69
1.10
1.02
1.10
0.73
39.6
3.06
3.02
e
47.0
e
137.9
20(R2)
1.12
25.1
134.0
7.36
126.6
25.1
133.6
7.32
126.8
1.20
25.2
133.6
7.48
126.9
30(R2)
40(R2)
50(R2)
1.12
0.74
22.3
13.8
6.96
7.10
7.10
130.0
127.8
126.9
7.33
7.30
128.8
128.6
22.2
13.7
6.85
7.06
7.06
129.7
127.6
126.7
7.32
7.32
128.9
128.7
1.20
0.77
22.2
13.8
7.00
7.16
7.16
130.2
127.9
127.2
7.35
7.35
129.1
129.1
Table 3
1H, 13C and 15N chemical shifts of compounds 5 in DMSO-d6.
Position
5e
5h
Position
5e
5h
d
(H)
d
(C)
d
(H)
d
(C)
d(H)
d
(C)
d
(H)
d(C)
1
2
3
4
4a
5
6
7
e
ꢀ248.5a
167.4
89.5
190.2
120.9
126.6
123.3
136.9
115.6
141.6
29.4
e
e
e
e
e
11
12
13
14
14a
15
16
17
18
18a
e
ꢀ241.9a
162.5
119.2
157.9
119.0
123.9
122.8
135.2
114.6
138.1
29.7
e
e
e
e
e
167.0
88.5
190.4
e
162.3
119.6
157.4
e
e
e
e
e
e
b
121.0
e
e
b
118.1
c
c
7.60
7.05
7.44
6.79
e
7.94
7.26
7.62
7.56
e
b
c
b
b
122.0
137.4
115.6
139.1
7.41
5.99
e
137.4
116.6
142.7
8
8a
6.55
e
10(R1)
20(R1)
30(R1)
40(R1)
10(R2)
3.02
e
e
b
139.1
10(R11
20(R11
30(R11
40(R11
10(R12
)
)
)
)
)
3.63
e
e
b
137.7
c
c
e
b
b
c
c
b
b
c
c
e
e
e
e
e
e
e
e
3.69
3.62
e
49.4
3.88
48.5
3.93
3.74
e
30.8
3.88
31.2
20(R2)
30(R2)
40(R2)
50(R2)
131.2
127.9
127.5
125.6
e
b
131.1
20(R12
30(R12
40(R12
50(R12
)
)
)
)
137.3
129.9
127.7
127.6
e
b
136.1
c
c
6.83
6.93
6.80
6.86
7.03
7.03
b
b
c
c
b
b
c
c
a
d(
15N).
b
c
1H chemical shits: 6.90e7.77, overlapped signals.
13C chemical shits: 127.3e130.7.
the hydroxyl group in the tautomeric form of the lactam.
group were used only in our earlier papers.10 Three different types
of products were isolated from the reactions of .3-(3-hydroxyethyl)
quinoline-2,4-diones. In consilience with the described results of
the analogous reaction of 3-butylaminoquinolinediones,10 imida-
zoquinazoline 10a arose from starting compound 3a, which was
unsubstituted at N(1) (Scheme 2). 1-Substituted compounds 3
changed to 11 through intermediate B and primarily to 12 through
intermediate C (Scheme 2). The NMR spectra of compounds 10 and
Interesting results were obtained from the reaction of com-
pounds 3 with isocyanic acid, which was generated from potassium
cyanate in a solution of acetic acid (Table 4). According to the
literature, the reaction of a-aminoketones with isocyanic acid was
frequently used for the preparation of imidazolin-2-ones. However,
only primary15,16 or secondary17e19 amino groups were present in
the starting compounds. Compounds bearing the tertiary amino
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Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
4
Table 4
Results of the reaction of 3-chloroquinolinediones 3 with triphosgene (TP) and KOCN.
Starting compound
Reagent
Product(s), (yield, %)
Starting compound
Reagent
Product(s), (yield, %)
3a
3b
3c
3d
3e
3f
3g
3h
3i
TP
TP
TP
TP
TP
TP
TP
TP
TP
6a (42), 8a (19), 9a (3)
6b (17), 8b (22), 3b (26)
6c (23), 8c (34), 9c (8)
6d (31), 3d (9)
6e (37), 3e (15)
6f (28)
6g (23), 7g (6), 3g (20)
6h (44), 3h (8)
6i (25), 7i (11), 3i (4)
3a
3b
3c
3d
3e
3f
3g
3h
3i
KOCN
KOCN
KOCN
KOCN
KOCN
KOCN
KOCN
KOCN
KOCN
10a (42)
12b (34)
12c (42)
11d (30)
11e (3), 12e (30)
12f (76)
12g (33)
12h (45)
12i (36)
Table 5
1H, 13C and 15N chemical shifts and 1J(15N, H) (Hz, 0.3 Hz) of compounds 6 in DMSO-d6.
Position
6a
6b
6c
6d
6e
6f
6g
6h
6i
d(H)
d(C)
d
(H)
d(C)
d(H)
d(C)
d(H)
d
(C)
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d(C)
d(H)
d(C)
d
(H)
d(H)
1
2
3
4
4a
5
6
7
8
8a
NCH2
NCH2
e
244.9a
171.2
69.1
e
e
e
e
e
e
e
e
e
251.5a
168.8
74.5
e
e
e
e
e
e
e
e
170.8
68.7
194.6
119.7
126.0
122.4
136.1
116.0
141.1
e
e
169.3
74.2
190.5
118.8
127.6
123.2
136.6
116.5
140.6
e
e
170.7
69.6
192.4
120.1
127.2
122.4
136.8
116.1
142.4
e
e
170.4
69.2
193.5
120.9
126.4
122.9
136.4
115.3
142.0
e
e
e
170.7
69.8
192.6
119.7
127.4
123.6
136.6
116.9
143.3
e
e
170.4
68.9
e
168.3
74.8
e
e
e
e
e
e
e
e
e
e
193.6
118.9
126.8
122.9
136.6
116.6
141.5
286.5a
44.0
e
e
e
e
e
189.4
120.0
127.8
123.7
136.8
116.2
141.6
287.4b
45.8
e
e
194.2
120.7
126.6
122.2
136.2
116.3
143.0
e
189.3
119.8
128.1
124.0
136.5
117.0
142.4
e
e
e
e
e
e
e
e
e
7.78
7.14
7.64
7.12
e
7.59
6.93
7.35
6.68
e
7.76
7.10
7.58
7.07
e
7.89
7.27
7.78
7.42
e
7.71
7.06
7.47
6.91
e
7.84
7.20
7.70
7.38
e
7.94
7.24
7.54
6.39
e
7.79
7.06
7.29
6.94
e
7.90
7.19
7.59
6.37
e
e
e
e
e
e
e
e
e
3.97
3.91
4.48
4.44
e
4.13
44.1
3.38
3.23
4.41
4.38
e
45.8
3.99
3.89
4.48
4.44
e
44.0
4.17
4.11
4.56
4.51
e
44.1
3.39
3.20
4.43
4.38
e
3.95
44.0
4.15
44.0
64.6
3.33
3.24
4.39
45.7
63.9
CH2O
64.1
4.52
64.3
63.8
64.1
64.4
63.8
4.48
64.2
4.54
C¼O
158.1
90.3b
e
e
157.8
e
158.2
e
158.2
29.8
e
157.8
29.4
e
158.2
30.3
e
e
158.4
137.0
129.1
128.8
130.6
130.4
129.2
35.8
e
158.1
136.9
129.1
128.4
130.6
130.2
129.1
43.5
e
158.3
136.9
129.1
128.7
130.7
130.5
129.4
130.4
10(R1)
20(R1)
11.15
e
10.96
e
11.44
e
3.41
e
3.19
e
3.53
e
e
e
e
e
e
7.42
7.12
7.64
7.61
7.59
2.11
7.03
6.98
7.63
7.56
7.52
3.49
3.45
e
7.50
7.18
7.60
30(R1)
e
e
e
e
e
e
e
e
e
e
e
e
40(R1)
10(R2)
e
e
e
e
e
e
e
e
e
e
7.50
e
1.95
35.8
3.40
3.33
e
43.4
130.7
1.95
1.12
36.0
25.2
3.38
3.31
e
43.9
130.9
20(R2)
1.20
1.10
1.20
0.76
e
25.0
131.0
7.42
129.6
131.0
7.44
129.7
1.29
25.3
131.0
7.50
130.0
30(R2)
40(R2)
50(R2)
22.0
13.5
e
6.94
7.03
7.03
130.0
127.7
127.6
7.45
7.45
e
128.4
130.2
e
1.20
0.74
e
21.9
13.5
e
6.80
6.99
6.99
129.6
127.5
127.6
7.32
7.44
e
128.2
130.9
e
1.29
0.76
e
22.0
13.6
e
7.03
7.14
7.14
130.3
128.0
127.9
7.41
7.41
e
128.3
130.5
e
a
d
(
15N).
1J(15N, H).
b
11 are given in Table 8. The formation of compounds analogous to
11 was previously observed in the reaction of 3-
alkylaminoquinoline-2,4-diones with nitrourea.5
Additional compounds unsubstituted at N(1) (3b, c) reacted
dissimilarly to 3a. From these compounds and 3e, f, h, i, novel
spiro-compounds 12 were obtained (Scheme 2). We determined
analogous structures, but otherwise substituted, for the products of
the reaction of compound 3 with isocyanates.14 These results show
that transformation of intermediate B to C is preferred over B to D
and also over deprotonation to 11.
for protons from NH groups (Table 9). Such an unwanted reaction
course must have been caused by the presence of the hydroxyethyl
group as a substituent at the nitrogen atom at position 3. A
hydrogen bond can be created between the two hydroxyl groups in
compounds 12 stabilizing these groups against deprotonation to 11.
Two stereogenic centers at C(4) and C(5) are present in com-
pounds 12. However, in contrast to the results in our preceding
paper,14 we never obtained two racemates. In all cases, only one
pure racemate arose. Therefore, the addition of water to interme-
diate C (Scheme 2) is probably stereoselective. However, this re-
action course could also be caused by the instability of one of the
incipient racemates. A previous paper14 described that (4R*,5R*)
racemates are unstable and converts to (4R*,5S*) racemates, even
while standing in a DMSO solution.
In the NMR spectra of compounds 12, signals corresponding to
two aliphatic quaternary carbons d 69.5e75.5 ((C(4)) and 83.7e85.1
((C(5)) ppm and two unambiguously distinguishable hydroxyl
groups were detected (Table 9). The hydroxyl group proton in the
hydroxyethyl fragment exists, as expected, as a triplet. Singlets
corresponding to two additional acidic protons were undoubtedly
differentiated using a 1D 1He15N HSQC doublets due to the exis-
tence of doublets due to the existence of 1J(15N, H) were observed
If we assume the presence of a hydrogen bond between the two
hydroxyl groups in 12, than a relative configuration of (4R*,5R*) is
feasible, as well as (4R*,5S*). According to the NMR spectra, the
signals corresponding to hydrogens at C(40) and C(50) lies in narrow
ꢀ
Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
5
Table 6
Characteristic 1H, 13C and 15N chemical shifts of compounds 7 and 9 in DMSO-d6.a
3. Conclusions
In conclusion, the 3-chloroquinoline-2,4-diones react with
ethanolamine to give their 3-(3-hydroxyethyl)amino derivatives 3
in good yields. The reaction of these compounds with triphosgene
provide 3(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-diones 6 and
minor compounds with dimeric character. The most remarkable
result of this paper is the rearrangement of compounds 3 into
imidazoquinazolines 10, imidazoquinolones 11 and spiro-
compounds 12. The formation of novel spiro-diols 12 is especially
interesting from a theoretical viewpoint and also, owing to the
simple reaction protocol, opens a path to further transformations of
these compounds. Due to the significant biological activity of a
number of indole derivatives, compounds 12 may also be inter-
esting structures for study in this research area.
Position
7g
7i
9a
9c
d
(H)
d
(C
d
(H)
d
(C)
d
(H
d
(C)
d
(H)
d(C)
1
2
3
4
4a
5
6
7
8
8a
N(C]O)
NCH2
e
e
e
e
e
231.5b
172.2
74.0
194.9
120.2
e
e
e
e
e
231.0b
171.0
77.1
192.8
120.7
e
145.7b
167.5
69.7
192.7
121.9
126.6
127.2
136.6
127.1
145.8
e
e
e
e
e
144.6b
165.9
71.4
191.5
123.2
e
e
e
e
7.88 127.1
7.17 123.1
7.49 135.8
6.31 116.4
7.77 127.5
7.08 123.3
7.38 135.7
6.28 116.6
7.77
7.37
7.74
7.39
e
7.79 126.5
7.33 127.4
7.64 136.6
7.29 127.1
e
143.5
e
e
143.5
e
e
145.1
c
e
e
e
152.5
e
152.1d
2.73 42.9
2.76 43.3
3.97, 40.3
3.73 40.7
3.47 282.7b
4.17 64.4
4.11
e
e
e
343.9b 2.70 339.5b 3.73
291.7b
65.2
CH2O
4.07 67.9
4.02
4.11 67.8
4.07
4.40
OC(¼O)O
10(R1)
e
154.5
137.5
e
154.5
137.5
e
e
e
154.2c
e
153.8d
e
4. Experimental section
e
e
20(R1)
7.34 130.2
7.54 130.5
7.65 130.2
e
e
4.1. General
30(R1)
40(R1)
10(R2)
7.59 129.2
7.54 128.9
1.84 39.1
129.1
128.8
135.7
e
e
e
e
e
e
e
e
e
e
e
e
Melting points were determined on a Kofler block. IR (KBr)
spectra were recorded on a Smart OMNI-Transmission Nicolet iS10
spectrophotometer. The 1H, 13C and 15N NMR spectra were recorded
on a Bruker Avance 500 spectrometer (500.13 MHz for 1H,
e
2.00
1.93
1.19
1.08
1.16
0.77
34.1
132.2
20(R2)
1.18 25.2
126.9
25.8
7.36 126.7
e
125.76 MHz for 13C and 50.68 MHz for 15N) in DMSO-d6. 1H and 13
C
30(R2)
40(R2)
1.18 22.1
0.76 13.8
129.1
129.0
21.4
13.6
7.43 130.2
7.43 130.8
e
e
chemical shifts are given on the d scale (ppm) and are referenced to
¼ 0.0). 15N Chemical shifts were referenced to an
a
internal TMS (
external neat nitromethane in a capillary (
d
The numbering of compounds 7 and 9 for NMR-purpose in Table 6 starts from
N(1) and continues to C(8a).
d
¼ 0.0). All 2D experi-
b
d(
15N).
ments (gradient-selected (gs)eCOSY, gs-NOESY, gs-HMQC, gs-
HMBC) were performed using manufacturer's software (TOPSPIN
3.2). The positive-ion EI mass spectra were measured on a Shi-
madzu QP-2010 instrument within the mass range m/z ¼ 50e600
using direct inlet probe (DI). Samples were dissolved in dichloro-
c
d
e
Intensity ratio of signals at 152.5 and 154.2 ppm was 2:1.
Intensity ratio of signals at 152.1 and 153.8 ppm was 2:1.
1H chemical shits: 7.30e7.60 ppm, overlapped signals.
methane (30 m mL of the solution was evaporated in
g mLꢀ1) and 10
interval of
with appearance of signals at
d
7.46e7.82 and 6.83e7.08 ppm. This is in conformity
7.71e7.82 for C(40) and 7.14e7.24 (C-
DI cuvette at 50 ꢁC. The ion source temperature was 200 ꢁC; the
energy of electrons was 70 eV. Only signals exceeding relative
abundance of 5% are listed. The electrospray mass spectra (ESI-MS)
were recorded using an amaZon X ion-trap mass spectrometer
(Bruker Daltonics, Bremen, Germany) equipped with an electro-
spray ion source. All experiments were conducted in both positive
d
50) in the NMR spectra of analogous compounds bearing sub-
stituents at N(1) and N(3) and having a relative configuration of
(4R*,5S*), confirmed by X-ray crystallography.14 On the other hand,
these signals for compounds possessing a relative configuration
(4R*,5R*) lies at d
5.63e5.67 and 6.46e6.57 ppm.14 This comparison
show that compounds 12 are (4R*,5S*) racemic diastereoisomers.
and negative polarity mode. Individual samples (with
a
Table 7
Characteristic 1H, 13C and 15N chemical shifts and 1J(15N, H) (Hz, 0.3 Hz) of compounds 8 in DMSO-d6.a
Position
8a
8b
8c
Position
8a
8b
8c
d
(H)
d
C)
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d
(C)
d
(H)
d(C)
1
2
3
4
4a
5
6
7
8
8a
NCH2
NCH2
e
ꢀ145.3b
167.6
69.7
e
ꢀ145.1b
166.6
71.1
e
ꢀ144.3b
166.9
71.4
10
e
ꢀ245.5b
172.5
73.0
e
ꢀ243.7b
171.7
73.5
e
ꢀ244.5b
171.4
76.3
e
e
e
20
e
e
e
e
e
e
30
40
4a'
50
6
700
80
8a'
NH
NCH2
e
e
e
e
192.7
121.9
126.7
127.0
136.6
127.2
141.6
ꢀ291.6b
40.0
e
192.0
121.9
126.7
127.1
136.8
127.4
141.4
ꢀ292.5b
40.4
e
191.5
123.2
126.5
127.2
136.5
127.3
141.1
ꢀ280.9b
43.3
e
196.0
119.1
126.6
122.7
136.3
116.3
145.8
ꢀ343.1b
42.9
e
195.8
119.4
126.3
122.6
136.3
116.2
145.9
ꢀ338.5b
42.8
e
193.7
119.3
127.0
122.9
136.4
116.4
145.1
ꢀ339.4b
40.8
e
e
e
e
e
e
7.76
7.39
7.74
7.39
e
7.86
7.42
7.79
7.47
e
7.78
7.38
7.63
7.39
e
7.73
7.10
7.59
7.08
e
7.66
7.04
7.49
6.90
e
7.69
7.06
7.56
7.08
e
e
e
e
n.o.
2.63
2.59
4.08
n.o.
2.68
2.58
4.08
n.o.
2.64
3.91
3.72
4.35
4.01
3.86
4.40
4.31
e
3.72
3.47
4.30
4.24
e
CH2O
65.0
65.2
64.3
CH2O
67.9
67.7
4.11
67.9
C¼O
e
e
152.5
e
151.8
e
152.1
e
C¼O
e
154.3
92.3c
e
154.3
91.3c
e
154.2
91.8c
10(R1)
e
e
10(R1)
10.96
10.96
11.26
a
The numbering of compounds 8 for NMR-purpose in Table 7 starts from N(1) and continues to C(8a).
b
c
d
(
15N).
1J(15N, H).
ꢀ
Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
6
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
Scheme 2.
of 6.0 dm3 minꢀ1, nebulizer pressure of 8.0 psi. Nitrogen was used
Tables 8
1H and 13C chemical shifts of compounds 10 and 11 in DMSO-d6.
as the nebulizing and drying gas for all experiments. Tandem mass
spectra were collected using collision-induced dissociation (CID)
with He as the collision gas after isolating the required ions. Col-
umn chromatography was carried out on silica gel (Merck, grade
60, 70e230 mesh) using successive mixtures of chloroform/ethanol
(in ratios from 99:1 to 8:2) (S1) or benzene/ethyl acetate (in ratios
from 99:1 to 8:2) (S2). Reactions as well as the course of separation
and also the purity of substances were monitored by TLC (elution
systems benzene/ethyl acetate (4:1) (S3), chloroform/ethanol (9:1
and 1:1) (S4 and S5), hexane/ethyl acetate (4:1) (S6), and chloro-
form/ethyl acetate (7:3) (S7) on Alugram® SIL G/UV254 foils
(Macherey-Nagel). Elemental analyses (C, H, N) were performed
with a EA Flash EA 1112 Elemental Analyzer (Thermo Fisher
Scientific).
Position 10a
(H)
Position 11d
11e
(H)
11g
(H)
d
d
(C)
d(H)) dC
)
d
d
(C)
d
d(C)
1
e
119.8
254.6a
148.2
1
2
3
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
2
e
166.3
e
165.5
e
166.5
e
3
e
4
e
232.0a 3a
74.6
168.2
e
75.4
167.5
e
75.0
168.5
e
5
e
145.0
ꢀ64.6a
145.0
116.0
127.3
123.1
121.8
113.7
111.5
43.0
4
5
5a
6
6
e
6a
7
8
e
141.4
141.4
142.6
6.97
7.17
7.07
7.50
e
7.43 116.6 7.40 116.7 6.39 117.2
7.76 135.5 7.75 135.4 7.55 135.1
7.37 124.0 7.36 124.1 7.29 124.0
7.92 126.0 7.87 126.0 7.92 126.2
7
8
9
9
10
10a
10b
NCH2
9a
9b
NCH2
e
116.2
184.6
e
116.8
183.8
e
115.9
184.8
e
e
e
e
3.68
3.61 43.6
3.44
3.66 44.0
3.55
3.75 58.9
4.81
3.34 29.8
e
e
e
3.62 43.7
3.42
3.68 58.7
4.79
e
4.2. General procedure for the reaction of 3-chloroquinolin-2-ones
2 with ethanolamine
CH2O
OH
3.58
4.95
58.9
e
CH2O
OH
3.70 58.7
4.48
3.31 29.7
e
e
e
e
e
e
10(R1)
20(R1)
10.58 92.3b
10(R1)
20(R1)
136.9
To the solution of compound 1 (2 mmol) in DMF (10 mL), pul-
verized potassium carbonate (552 mg, 4 mmol) and ethanolamine
(0.13 mL, 2.1 mmol) were added and the mixture was stirred at
room temperature. The course of the reaction was monitored with
TLC. On completion, the reaction mixture was diluted with water
(20 mL). The product was filtered with suction, dried and crystal-
lized from an appropriate solvent. In cases where the crude product
was oily or waxy, the solution was extracted with chloroform
(3 ꢂ 20 mL). The collected extracts were dried with anhydrous
sodium sulfate, evaporated to dryness and the residue was sepa-
rated by column chromatography on silica gel.
e
e
e
e
e
e
e
e
7.48 129.5
7.27 129.0
7.55 130.3
130.0
7.63 129.1
3.62 35.3
3.42
30(R1)
e
e
30(R1)
40(R1)
10(R2)
e
e
40(R1)
10(R2)
2.83
23.1
2.35 35.3
2.10
1.18 24.2
0.86 21.2
0.75
3.47 41.7
3.14
20(R2)
30(R2)
1.52
1.44
29.1
21.9
20(R2)
30(R2)
e
131.9 1.97 24.4
6.78 129.7 0.86 21.3
0.75
7.18 128.0 0.75 13.7
40(R2)
50(R2)
0.93
13.8
40(R2)
50(R2)
0.75 13.6
e
e
7.56 127.7
e
e
a
d (
15N), b 1J(15N, H).
4.2.1. Major products
4.2.1.1. 3-(Hydroxyethylamino)-3-butylquinolin-2,4(1H,3H)-dione
(3a). Compound was prepared from 2a in 51% yield (282 mg;
elution system S2). Colorless solid, mp 62e68 ꢁC (ethyl acetate/
hexane). IR: 3425, 3235, 2958, 2927, 2860, 1702, 1667, 1612, 1597,
1485, 1361, 1313, 1251, 1063, 757, 665, 527 cmꢀ1. ESI-MS (pos.) m/z
(%): 277.1 [MþH]þ (100). ESI-MS (neg.) m/z (%): 573.1 [2M-
concentration of 500 ng mLꢀ1) were infused into the ESI source as
methanol:water (1:1, v:v) solutions via a syringe pump with a
constant flow rate of 3 m
L minꢀ1. The other instrumental conditions
were as follows: electrospray voltage of 4.2 kV, capillary exit
voltage of 140 V, drying gas temperature of 220 ꢁC, drying gas flow
ꢀ
Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007

ꢀ
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
7
Table 9
1H, 13C and 15N chemical shifts and 1J(15N, H) (Hz, 0.3 Hz) of compounds 12 in DMSO-d6.
Position
12b
(H)
12c
(H)
12e
(H)
12f
12h
(H)
12i
d
d
(C)
d
d
(C)
d
d
(C)
d
(H)
d
(C)
d
d
(C)
d(H)
d(C)
a
a
a
1
2
3
e
ꢀ287.3a
e
ꢀ288.7a
e
ꢀ286.6
159.2
e
ꢀ286.6a
161.1
ꢀ268.1 a
92.1b
75.1
84.1
e
ꢀ250.8 a
170.0
123.6
127.3
123.1
130.0
115.1
136.8
46.5
e
e
ꢀ286.5
e
ꢀ287.3a
e
159.0
e
161.0
e
e
e
159.0
e
161.1
a
a
a
7.45
e
ꢀ266.5
91.2b
69.5
83.7
e
7.67
e
ꢀ268.0
92.1b
74.8
85.1
e
7.67
e
ꢀ266.6
7.70
e
7.67
e
ꢀ265.8a
92.2b
70.0
7.89
e
ꢀ268.2
b
b
92.3
91.2
4
5
e
e
e
69.6
82.7
e
e
e
e
75.5
84.5
e
e
e
e
e
e
83.1
e
e
OH
6.85
e
6.46
e
7.00
e
6.57
e
7.00
e
6.74
e
a
a
a
a
10
ꢀ244.2
170.5
123.4
125.6
122.0
128.7
114.2
134.1
43.8
e
ꢀ243.7
170.5
122.5
127.4
122.7
129.8
115.3
134.9
46.5
e
ꢀ251.4
170.2
124.5
125.8
122.5
128.9
113.6
135.8
44.0
e
ꢀ231.0b
170.0
124.5
126.1
122.8
128.8
115.2
137.7
43.9
ꢀ229.2
170.2
123.4
127.7
123.3
129.8
116.3
137.8
46.4
e
20
e
e
e
e
e
e
3a'
e
e
e
e
e
e
40
7.52
6.83
6.87
6.34
e
7.46
6.97
7.28
6.99
e
7.63
6.95
7.04
6.50
e
7.56
7.08
7.41
7.28
e
7.74
6.98
6.89
5.57
e
7.62
7.07
7.22
6.31
e
50
60
70
7a'
NCH2
3.67
3.45
3.60
3.45
4.69
10.17
e
3.39
3.13
3.75
3.71
4.71
10.95
e
3.75
3.51
3.62
3.51
4.72
3.11
3.06
3.73
3.70
4.71
3.69
3.43
3.59
3.52
4.67
e
3.34
3.04
3.72
e
e
CH2O
60.2
e
59.4
e
60.2
e
59.4
e
60.2
e
59.3
e
OH
e
e
e
e
e
4.71
e
e
10(R1)
20(R1)
30(R1)
40(R1)
10(R2)
90.1b
e
90.0b
e
28.9
e
29.8
e
137.0
130.5
130.0
128.5
36.5
137.8
130.8
127.2
128.8
132.9
e
e
e
6.80
7.48
7.43
3.42
3.13
e
6.80
7.48
7.43
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
3.26
3.04
e
36.3
e
e
133.0
e
3.25
3.04
e
36.5
e
e
132.9
e
e
e
e
e
20(R2)
30(R2)
40(R2)
50(R2)
133.0
130.5
126.8
126.5
6.99
7.30
7.30
e
128.1
128.2
128.3
e
132.9
130.0
126.8
126.5
7.21
7.29
7.29
e
128.4
128.0
128.3
e
133.0
130.8
127.2
126.9
7.08
6.98
6.98
e
130.8
130.0
128.3
e
7.04
6.85
6.85
6.87
6.83
6.80
7.08
6.98
6.98
a
d
(
15N).
1J(15N, H).
b
2H þ Na]e (6), 274.9 [M-H]e (100). For C15H20N2O3 (276.33) calcd. C
4.2.1.5. 3-(Hydroxyethylamino)-1-methyl-3-benzylquinolin-
2,4(1H,3H)-dione (3e). Compound was prepared from 2e in 31%
yield besides 4e and 5e (201 mg, elution system S2). Colorless solid,
mp 154e156 ꢁC (ethyl acetate). IR: 3426, 3026, 2909, 1694, 1634,
1598, 1476, 1417, 1375, 1317, 1250, 1212, 1176, 1126, 1099, 1071, 1021,
65.20, H 7.30, N 10.14; found: C 65.28, H 7.38, N 9.99.
4.2.1.2. 3-(Hydroxyethylamino)-3-benzylquinolin-2,4(1H,3H)-dione
(3b). Compound was prepared from 2b in 24% yield (149 mg,
elution system S2). Colorless solid, mp 164e170 ꢁC (ethyl acetate/
hexane). IR: 3327, 3187, 3062, 2928, 2851, 1703, 1683, 1665 1612,
1595, 1486, 1457, 1436, 1373, 1297, 1235, 1158, 1047, 945, 912, 879,
851, 765, 726, 697, 666, 588, 504 cmꢀ1. ESI-MS (pos.) m/z (%): 311.1
[MþH]þ (100). ESI-MS (neg.) m/z (%): 308.9 [M-H]e (100). For
1003, 952, 914, 873, 843, 818, 769, 737, 705, 661, 643, 583, 518 cmꢀ1
.
ESI-MS (pos.) m/z (%): 325.1 [MþH]þ (100). For C19H20N2O3 (324.37)
calcd. C 70.35, H 6.21, N 8.64; found C 70.19, H 6.20, N 8.63.
4.2.1.6. 3-(Hydroxyethylamino)-1-methyl-3-phenylquinolin-
2,4(1H,3H)-dione (3f). Compound was prepared from 2f in 88%
yield (546 mg). Colorless solid, mp 130e133 ꢁC (hexane). IR: 3299,
3057, 2934, 2857, 1705, 1671, 1603, 1491, 1471, 1443, 1417, 1349,
1305, 1256, 1195, 1183, 1109, 1076, 1054, 1039, 899, 853, 800, 764,
724, 708, 656, 597, 525, 512 cmꢀ1. ESI-MS (pos.) m/z (%): 311.1
[MþH]þ (100). For C18H18N2O3 (310.35) calcd. C 69.66, H 5.85, N
9.03; found C 69.63, H 5.93, N 8.96.
C
18H18N2O3 (310.35) calcd. C 69.66, H 5.85, N 9.03, found C 69.62, H
5.96, N 8.93.
4.2.1.3. 3-(Hydroxyethylamino)-3-phenylquinolin-2,4(1H,3H)-dione
(3c). Compound was prepared from 2c in 69% yield (409 mg).
Colorless solid, mp 148e150 ꢁC (hexane). IR: 3061, 2982, 2921,1704,
1672, 1615, 1596, 1485, 1449, 1437, 1355,1321, 1254, 1232, 1199,1165,
1124, 1107, 1066, 1043, 1028, 944, 906, 833, 763, 749, 698, 668, 604,
544 cmꢀ1. ESI-MS (pos.) m/z (%): 297.1 [MþH]þ (100). ESI-MS (neg.)
m/z (%): 613.1 [2M-2H þ Na]e (6), 294.9 [M-H]e (100). For C17
H16N2O3 (296.32) calcd. C 68.91, H 5.44, N 9.45, found: C 68.95, H
5.68, N 9.48.
4.2.1.7. 3-(Hydroxyethylamino)-3-butyl-1-phenylquinolin-
2,4(1H,3H)-dione (3g). Compound was prepared from 2g in 65%
yield (458 mg, elution system S2). Yellowish solid, mp 75e78 ꢁC
(hexane). IR: 3307, 2958, 1679, 1606, 1496, 1462, 1340, 1301, 1249,
1209, 1156, 1124, 1084, 1047, 941, 833, 764, 750, 703, 652 cmꢀ1. ESI-
MS (pos.) m/z (%): 727.3 [2M þ Na]þ (11), 705.2 [2M þ H]þ (8), 375.1
[MþNa]þ (9), 353.1 [MþH]þ (100). For C21H24N2O3 (352.43) calcd. C
71.57, H 6.86, N 7.95, found C 71.31, H 6.99, N 7.78.
4.2.1.4. 3-(Hydroxyethylamino)-1-methyl-3-butylquinolin-
2,4(1H,3H)-dione (3d). Compound was prepared from 2d in 68%
yield (395 mg). Colourless solid, mp 113e118 ꢁC (ethyl acetate). IR:
3304, 2965, 2876, 2855, 1663, 1608, 1506, 1473, 1421, 1378, 1356,
1304, 1270, 1249, 1206, 1118, 1100, 1084, 1042, 1030, 978, 943, 823,
881, 847, 827, 771, 752, 666, 643, 610, 587, 531 cmꢀ1. ESI-MS (pos.)
m/z (%): 291.1 [MþH]þ (100). For C16H22N2O3 (290.36) calcd. C
66.18, H 7.64, N 9.65, found: C 66.12, H 7.71, N 9.45.
4.2.1.8. 3-Benzyl-3-(hydroxyethylamino)-1-phenylquinolin-
2,4(1H,3H)-dione (3h). Compound was prepared from 2h in 17%
yield (131 mg, elution system S2) besides 4h and 5h. Colourless
solid, mp 115e118 ꢁC (hexane). IR: 3440, 3306, 3062, 2980, 2887,
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ꢀ
A. Klasek et al. / Tetrahedron xxx (2017) 1e11
8
1687, 1602, 1495, 1462, 1351, 1335, 1304, 1262, 1248, 1207, 1179,
1164, 1138, 1113, 1074, 1039, 1018, 988, 965, 953, 812, 756, 729, 701,
682, 650, 596, 577, 513 cmꢀ1. ESI-MS (pos.) m/z (%): 795.2
[2M þ Na]þ (12), 599.2 [3M þ Ca]2þ (5), 425.1 [MþK]þ (6), 409.1
[MþNa]þ (78), 406.1 [2M þ Ca]2þ (16), 387.1 [MþH]þ (100). ESI-MS
(neg.) m/z (%): 385.0 [M-H]e (100). For C24H22N2O3 (386.44) calcd. C
74.59, H 5.74, N 7.25, found C 74.44, H 5.98, N 6.98.
603.1 [2M-H]e (14), 300.9 [M-H]e (100). EI-MS: 302 (Mþ, 2), 260
(9), 259 (57), 218 (7), 217 (50), 215 (8), 218 (7), 217 (50), 215 (8), 200
(18), 188 (15), 187 (6), 186 (7), 176 (11), 175 (100), 174 (15), 172 (6),
161 (7), 146 (37), 130 (11), 128 (7), 120 (9), 119 (10), 92 (13), 90 (8),
77 (8), 68 (33), 65 (6), 55 (9), 54 (6), 42 (9), 41 (22). For C16H18N2O4
(302.33) calcd. C 63.56, H 6.00, N 9.27, found C 63.54, H 5.81, N 8.99.
4.3.2. 3-Benzyl-3(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-
dione (6b)
4.2.1.9. 3-(Hydroxyethylamino)-1,3-diphenylquinolin-2,4(1H,3H)-
dione (3i). Compound was prepared from 2i in 56% yield (81 mg,
elution system S2). Yellowish solid, mp 153e156 ꢁC (benzene). IR:
3464, 3326, 3061, 2920, 2851, 1702, 1665, 1598, 1493, 1460, 1338,
1299, 1246, 1190, 1163, 1148,1074, 926, 870, 766, 705, 575 cmꢀ1. ESI-
MS (pos.) m/z (%): 373.1 [MþH]þ (100). For C23H20N2O3 (372.42)
calcd. C 74.18, H 5.41, N 7.52, found C 73.99, H 5.51, N 7.35.
Compound was prepared from 3b in 17% yield (114 mg, elution
system S2) besides 3b and 8b. Colorless solid, mp 272e277 ꢁC
(benzene). IR: 3228, 3194, 3087, 2996, 2927, 1745, 1703, 1673, 1614,
1597, 1486, 1417, 1387, 1303, 1259, 1230, 1158, 1129, 1089, 1066,
1040, 979, 877, 766, 703, 686, 667, 604, 542, 525 cmꢀ1. ESI-MS (pos.)
m/z (%): 695.2 [2M þ Na]þ (13), 359.0 [MþNa]þ (100), 356.1
[2M þ Ca]2þ (16). ESI-MS (neg.) m/z (%): 334.9 [M-H]e (100). EI-MS:
m/z (%): 336 (Mþ, 3), 252 (4), 251 (24), 250 (36), 249 (100), 248 (77),
245 (10), 220 (5), 201 (12), 183 (7), 146 (12), 128 (5), 120 (5), 119 (7),
117 (8), 116 (7), 103 (6), 92 (17), 91 (93), 90 (13), 89 (6), 77 (10), 65
(11). For C19H16N2O4 (336.34) calcd. C 67.85, H 4.79, N 8.33, found: C
67.72, H 4.83, N 8.18.
4.2.2. Minor products
4.2.2.1. 3-Benzyl-3-(13-benzyl-12-oxo-11-methyl-11,12-
dihydroquinolin-14-yl)oxy)-1-methylquinoline-2,4(1H,3H)-dione
(5e). Compound was prepared from 2e in 4% yield (21 mg, elution
system S2). besides 3e and 4e. Colorless solid, mp 183e189 (ben-
zene/cyclohexane). IR: 3084, 3055, 3027, 3001, 2936, 1698, 1667,
1633, 1596, 1494, 1472, 1415, 1362, 1325, 1307, 1228, 1152, 1109,
1074, 1041, 1014, 992, 932, 762, 752, 725, 699, 665, 545, 528,
504 cmꢀ1. ESI-MS (pos.) m/z (%): 551.2 [MþNa]þ (13), 529.2 [MþH]þ
(100). For C34H28N2O4 (528.60) calcd. C 77.25, H 5.34, N 5.30, found
C 77.27, H 5.29, N 5.25. The structure was confirmed by the syn-
thesis from 1e and 2e.
4.3.3. 3-Phenyl-3-(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-
dione (6c)
Compound was prepared from 3c in 23% yield (148 mg, elution
system S2) besides 8c and 9c. Colorless solid, mp 158e164 C
(benzene/hexane). IR: 3255, 3062, 2989, 2905, 1747, 1706 besides
1684, 1613, 1596, 1486, 1449, 1419, 1354, 1322, 1254, 1225, 1160,
1121,1035, 993, 969, 961, 878, 852, 782, 768, 747, 732, 689, 666, 592,
540, 526 cmꢀ1. ESI-MS (pos.) m/z (%): 683.1 [2M þ K]þ (6), 667.1
[2M þ Na]þ (36), 645.2 [2M þ H]þ (15), 361.0 [MþK]þ (17), 345.1
[MþNa]þ (100), 323.1 [MþH]þ (31). ESI-MS (neg.) m/z (%): 665.0
[2M-2H þ Na]e (26), 643.0 [2M-H]e (23), 320.9 [M-H]e (100). EI-
MS: m/z (%): 323 (4), 322 (21), 238 (16), 237 (100), 236 (40), 229
(11), 221 (10),146 (11),132 (7),131 (9),130 (8),120 (11),119 (26),117
(13), 105 (7), 104 (27), 103 (30), 92 (14), 91 (6), 90 (9), 77 (17), 76 (9),
64 (6), 63 (5). For C18H14N2O4 (322.31) calcd. C 67.07, H 4.38, N 8.69,
found C 66.94, H 4.49, N 8.56.
4.2.2.2. 3-Benzyl-3-(13-benzyl-12-oxo-11-phenyl-11,12-
dihydroquinolin-14-yl)oxy)-1-phenylquinoline-2,4(1H,3H)-dione
(5h). Compound was prepared from 2h in 5% yield (33 mg, elution
system S2) besides 3h and 4h. Colorless solid, mp 111e119 ꢁC
(benzene). IR: 3062, 3030, 2925, 2850, 1742, 1704, 1673, 1648, 1599,
1493, 1464, 1351, 1299, 1270, 1220, 1155, 1098, 933, 877, 761, 700,
660, 595, 555 cmꢀ1. ESI-MS (pos.) m/z (%): 1327.5 [2M þ Na]þ (8),
691.2 [MþK]þ (18), 675.3 [MþNa]þ (100), 672.2 [2M þ Ca]2þ (19),
653.3 [MþH]þ (19). EA: For C44H32N2O4 (652.74) calcd. C 80.96, H
4.94, N 4.29, found C 80.89, H 5.04, N 4.15. The structure was
confirmed by the synthesis from 1h and 2h.
4.3.4. 3-Butyl-1-methyl-3(2-oxooxazolidin-3-yl)quinoline-
2,4(1H,3H)-dione (6d)
4.3. General procedure for the reaction of 3 with triphosgene
Compound was prepared from 3d in 31% yield (196 mg, elution
system S2). Yellowish oil. IR: 2959, 2929, 2872, 1748, 1707, 1669,
1602, 1474, 1414, 1362, 1301, 1258, 1231, 1154, 1143, 1118, 1038, 979,
931, 863, 828, 758, 730, 709, 663, 565, 532 cmꢀ1. ESI-MS (pos.) m/z
(%): 655.2 [2M þ Na]þ (20), 355.0 [MþK]þ (11), 339.1 [MþNa]þ
(100), 317.1 [MþH]þ (4). EI-MS: m/z (%): 317 (1), 316 (Mþ, 5), 273
(6), 232 (6), 231 (38), 215 (6), 214 (10), 202 (18), 201 (8), 200 (11),
190 (13), 189 (100), 188 (12), 187 (6), 186 (24), 175 (7), 160 (13), 146
(6), 134 (9), 133 (5), 132 (8), 105 (9), 104 (11), 91 (5), 85 (6), 84 (6), 83
(6), 78 (7), 77 (13), 71 (7), 68 (6), 57 (13), 55 (11), 43 (11), 41 (16). EA:
For C17H20N2O4 (316.35) calcd. C 64.54, H 6.37, N 8.86, found: C
64.23, H 6.53, N 8.59.
The solution of 3 (2 mmol) in benzene (50 mL) was cooled to
0
ꢁC, triethylamine (0.6 mL, 4.2 mmol) and 4-
dimethylaminopyridine (0.11 g, 0.9 mmol) were added and then
triphosgene (0.215 g, 0.75 mmol) was added in small portions
during 10 min. The suspension was stirred at room temperature for
5 h and evaporated to dryness. To the residue, water (20 mL) and
chloroform (15 mL) were added. The mixture was shaken, then
separated and the water portion was extracted with chloroform
(3 ꢂ 15 mL). The combined chloroform extracts were washed with
hydrochloric acid (2.5%, 15 mL), dried, and evaporated in vacuo. The
residue was chromatographed on silica gel.
4.3.1. 3-Butyl-3(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-dione
(6a)
4.3.5. 3-Benzyl-1-methyl-3(2-oxooxazolidin-3-yl)quinoline-
2,4(1H,3H)-dione (6e)
Compound was prepared from 3a in 42% yield (254 mg, elution
system S2) besides 8a and 9a. Colorless solid, mp 103e108 C
(benzene/hexane). IR: 3188, 3087, 2960, 2929, 2870, 1738, 1707,
1671, 1612, 1485, 1413, 1386, 1364, 1302, 1255, 1229, 1158, 1127,
1039, 976, 846, 769, 735, 682, 667, 603, 567, 526 cmꢀ1. ESI-MS (pos.)
m/z (%): 627.2 [2M þ Na]þ (14), 605.2 [2M þ H]þ (16), 473.1
[3M þ Ca]2þ (7), 341.0 [MþK]þ (16), 325.1 [MþNa]þ (58), 303.1
[MþH]þ (100). ESI-MS (neg.) m/z (%): 625.1 [2M-2H þ Na]e (7),
Compound was prepared from 3e in 37% yield (259 mg, elution
system S1). Colorless solid, mp 200e207 ꢁC (benzene/hexane). IR:
3029, 2979, 2922, 1743, 1700, 1665, 1602, 1474, 1455, 1441, 1414,
1369, 1318, 1302, 1264, 1240, 1170, 1142, 1036, 977, 922, 911, 867,
760, 737, 704, 663, 584, 546, 508 cmꢀ1. ESI-MS (pos.) m/z (%): 723.2
[2M þ Na]þ (7), 389.0 [MþK]þ (19), 373.0 [MþNa]þ (100), 370.0
[2M þ Ca]2þ (9), 351.0 [MþH]þ (4). For C20H18N2O4 (350.37) calcd. C
68.56, H 5.18, N 8.00; found C 68.51, H 5.26, N 7.82.
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A. Klasek et al. / Tetrahedron xxx (2017) 1e11
9
4.3.6. 1-Methyl-3-phenyl-3(2-oxooxazolidin-3-yl)quinoline-
6.54, N 7.45.
2,4(1H,3H)-dione (6f)
Compound was prepared from 3f in 28% yield (188 mg, elution
system S2). Colorless solid, mp 199e204 ꢁC (benzene/hexane). IR:
3086, 2957, 2907, 1740, 1708, 1669, 1601, 1496, 1473, 1447, 1407,
1359, 1299, 1240, 1227, 1207, 1144, 1095, 1065, 1036, 1002, 976, 916,
871, 831, 769, 758, 713, 699, 665, 618, 571, 524 cmꢀ1. ESI-MS (pos.)
m/z (%): 695.2 [2M þ Na]þ (18), 375.1 [MþK]þ (47), 359.1 [MþNa]þ
(100), 356.1 [2M þ Ca]2þ (12), 337.1 [MþH]þ (95). EI-MS: m/z (%):
336 (Mþ, 4), 252 (17), 251 (100), 250 (56), 133 (7), 132 (6), 130 (7),
105 (17), 104 (21), 103 (16), 78 (6), 77 (12), 57 (6). For C19H16N2O4
(336.34) calcd. C 67.85, H 4.79, N 8.33, found:C 67.95, H 4.91, N 8.17.
4.3.11. Bis(2-((2,4-dioxo-1,3-diphenyl-1,2,3,4-tetrahydroquinolin-
3-yl)amino)ethyl carbonate (7i)
Compound was prepared from 3i in 11% yield (85 mg, elution
system S2) besides 6i. Colorless solid, mp 131e135 ꢁC (benzene). IR:
3462, 3064, 3035, 2957, 2857, 1747, 1710, 1676, 1601, 1492, 1462,
1402, 1337, 1256,1161, 1072,1024, 1003, 917, 868, 761, 699, 656, 606,
571, 515 cmꢀ1. ESI-MS (pos.) m/z (%): 809.2 [MþK]þ (6), 793.2
[MþNa]þ (100), 771.3 [MþH]þ (53). For C47H38N4O7 (770.83) calcd.
C 73.23, H 4.97, N 7.27, found C 72.99, H 5.16, N 7.12.
4.3.12. 2-((3-Butyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)
amino)ethyl (2-(9a-butyl-2,9-dioxo-9,9a-dihydrooxazolo[5,4-b]
quinolin-1(2H)-yl)ethyl) carbonate (8a)
4.3.7. 3-Butyl-1-phenyl-3(2-oxooxazolidin-3-yl)quinoline-
2,4(1H,3H)-dione (6g)
Compound was prepared from 3g in 23% yield (174 mg, elution
system S1) besides 7g. Colorless solid, mp 165e175 ꢁC (benzene/
cyclohexane). IR: 3063, 2961, 2929, 2873, 1739, 1704, 1672, 1601,
1492, 1465, 1415, 1349, 1303, 1258, 1236, 1186, 1168, 1027, 1073,
Compound was prepared from 3a in 19% yield (115 mg, elution
system S1) besides 6a and 9a. Colorless solid, mp 68e84 ꢁC
(cyclohexane). IR: 3070, 2959, 2928, 2853, 1815, 1750, 1691, 1672,
1600, 1485, 1463, 1371, 1260, 1190, 1158, 1035, 999, 953, 884, 786,
765, 676, 651, 626, 564, 535 cmꢀ1. ESI-MS (pos.) m/z (%): 643.2
[MþK]þ (10), 627.2 [MþNa]þ (100), 624.2 [2M þ Ca]2þ (7), 605.3
[MþH]þ (67). ESI-MS (neg.) m/z (%): 603.1 [M-H]e (100). EI-MS: m/z
(%): 604 (Mþ, 3), 548 (4), 547 (12), 390 (13), 389 (6), 388 (23), 303
(17), 302 (19), 285 (14), 260 (10), 259 (56), 258 (32), 257 (6), 245
(37), 244 (5), 243 (35), 231 (6), 230 (5), 229 (30), 227 (8), 217 (26),
216 (20), 215 (70), 214 (8), 203 (17), 202 (38), 201 (100), 200 (13),
198 (8), 189 (20), 188 (18), 187 (17), 186 (19), 185 (6), 176 (7), 175
(57),174 (22),173 (18),172 (8),161 (14),160 (6),148 (7),147 (10),146
(64), 145 (7), 144 (8), 132 (18), 131 (6), 130 (38), 128 (19), 120 (28),
119 (27), 118 (10), 117 (8), 116 (8), 104 (7), 103 (7), 102 (15), 93 (7), 92
(22), 91 (10), 90 (27), 89 (17), 84 (68), 82 (8), 77 (16), 76 (10), 68 (18),
65 (9), 64 (8), 63 (7), 55 (7), 54 (16), 51 (6), 45 (21), 44 (64), 42 (51),
1039, 978, 915, 852, 821, 756, 731, 711, 695, 662, 612, 576, 517 cmꢀ1
.
ESI-MS (pos.) m/z (%): 779.3 [2M þ Na]þ (30), 417.1 [MþK]þ (14),
401.1 [MþNa]þ (100), 379.1 [MþH]þ (3). For C22H22N2O4 (378.42)
calcd. C 69.83, H 5.86, N 7.40, found C 69.85, H 6.06, N 7.22.
4.3.8. 3-Benzyl-1-phenyl-3(2-oxooxazolidin-3-yl)quinoline-
2,4(1H,3H)-dione (6h)
Compound was prepared from 3h in 44% yield (363 mg, elution
system S2). Colorless solid, mp 226e231 ꢁC (benzene/hexane). IR:
3075, 3029, 2970, 2914, 1752, 1695, 1663, 1603, 1489, 1463, 1410,
1365, 1301, 1257, 1238, 1223, 1180, 1162, 1120, 1091, 1071, 1043, 969,
902, 865, 817, 767, 738, 706, 691, 661, 613, 550, 507 cmꢀ1. ESI-MS
(pos.) m/z (%): 847.2 [2M þ Na]þ (6), 451.0 [MþK]þ (16), 435.1
[MþNa]þ (100), 432.0 [2M þ Ca]2þ (14), 413.1 [MþH]þ (4). For
41 (35). d(
13C): 196.0, 192.7, 172.5, 167.6, 154.3, 152.5, 145.6, 141.6,
C
25H20N2O4 (412.44) calcd. C 72.80, H 4.89, N 6.79, found C 73.01, H
136.6, 136.3, 127.2, 127.0, 126.7, 126.6122.7, 121.9, 119.1, 116.3, 73.0,
69.7, 37.9, 64.9, 42.9, 40.4, 34.2, 25.8, 25.0, 22.1, 21.4. For C32H36N4O8
(604.65) calcd. C 63.56, H 6.00, N 9.27, found C 63.77, H 6.25, N 8.91.
4.89, N 6.56.
4.3.9. 1,3-diphenyl-3(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-
dione (6i)
4.3.13. 2-((3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)
amino)ethyl (2-(9a-benzyl-2,9-dioxo-9,9a-dihydrooxazolo[5,4-b]
quinolin-1(2H)-yl)ethyl) carbonate (8b)
Compound was prepared from 3i in 25% yield (199 mg, elution
system S2) besides 7i. Colorless solid, mp 261e265 ꢁC (benzene).
IR: 3504, 3065, 2971, 2917, 1761, 1716, 1685, 1601, 1491, 1462, 1452,
1409, 1341, 1302, 1285, 1237, 1167, 1119, 1041, 1002, 969, 916, 864,
762, 716, 665, 607, 517 cmꢀ1. ESI-MS (pos.) m/z (%): 819.2
[2M þ Na]þ (18), 437.0 [MþK]þ (8), 421.0 [MþNa]þ (100), 418.0
[2M þ Ca]2þ (7), 399.0 [MþH]þ (3). For C24H18N2O4 (398.41) calcd. C
72.35, H 4.55, N 7.03, found:C 72.51, H 4.75, N 6.98.
Compound was prepared from 3b in 22% yield (148 mg, elution
system S2) besides 6b. Colorless solid, mp106-114 ꢁC (cyclohexane).
IR: 3300, 3064, 3032, 2925, 2853, 1815, 1747, 1391, 1668, 1599, 1785,
1758,1369,1261,1158,1084,1034,1002, 947, 769, 749, 703, 680, 651,
576, 527, 498 cmꢀ1. ESI-MS (pos.) m/z (%): 711.2 [MþK]þ (13), 695.2
[MþNa]þ (100), 692.2 [2M þ Ca]2þ (9), 673.2 [MþH]þ (47). ESI-MS
(neg.) m/z (%): 671.1 [M-H]e (100). EI-MS m/z (%): 336 (2), 293 (6),
292 (20), 248 (4), 202 (5), 201 (13), 161 (5), 146 (5), 130 (6), 92 (12),
4.3.10. Bis(2-((2,4-dioxo-3-butyl-1-phenyl-1,2,3,4-
tetrahydroquinolin-3-yl)amino)ethyl carbonate (7g)
91 (100), 90 (7), 65 (11), 44 (12). d(
13C): 195.8, 192.0, 171.7, 166.6,
Compound was prepared from 3g in 6% yield (44 mg, elution
system S2) besides 6g. Oil, with hexane colorless solid, mp
77e93 ꢁC (hexane). IR: 3347, 3067, 3040, 2957, 2930, 2871, 1748,
1808, 1673, 1600, 1492, 1463, 1403, 1346, 1300, 1259, 1160, 1072,
1024, 962, 759, 702, 664, 587, 515 cmꢀ1. ESI-MS (pos.) m/z (%): 769.3
[MþK]þ (6), 753.4 [MþNa]þ (100), 731.4 [MþH]þ (47). EI-MS: m/z
(%): 730 (Mþ, 0.01), 429 (2), 378 (3), 334 (6), 322 (6), 321 (22), 318
(5), 294 (8), 293 (23), 292 (9), 291 (22), 278 (16), 277 (20), 276 (12),
265 (13), 264 (25), 263 (9), 262 (14), 252 (21), 251 (100), 250 (37),
249 (6), 248 (11), 238 (5), 237 (12), 236 (5), 223 (7), 222 (13), 221
(6), 210 (7), 209 (6), 208 (9), 296 (29), 295 (28), 294 (5),180 (11),168
(15),167 (29),166 (12),140 (15),139 (9),128 (25),113 (6),112 (9),111
(6), 110 (8), 99 (6), 98 (12), 97 (9), 92 (10), 91 (7), 85 (31), 84 (38), 83
(12), 82 (6), 77 (31), 71 (11), 70 (6), 69 (13), 68 (7), 57 (28), 56 (9), 55
(26), 54 (11), 51 (16), 45 (12), 44 (49), 43 (25), 42 (22), 41 (30). For
154.3, 151.8, 145.9, 141.4, 136.7, 136.3, 133.7, 132.4, 130.0, 129.9,
128.6, 128.2, 127.8, 127.4, 127.1, 127.0, 126.7, 126.5, 122.6, 121.9, 119.4,
116.2, 73.5, 71.1, 67.7, 65.2, 45.6, 42.8, 38.9. For C38H32N4O8 (672.68)
calcd. C 67.85, H 4.79, N 8.33, found C 67.69, H 5.01, N 8.16.
4.3.14. 2-((3-phenyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)
amino)ethyl (2-(9a-phenyl-2,9-dioxo-9,9a-dihydrooxazolo[5,4-b]
quinolin-1(2H)-yl)ethyl) carbonate (8c)
Compound was prepared from 3c in 34% yield (219 mg, elution
system S2) besides 6c and 9c. Yellowish solid, mp 110e128 ꢁC
(hexane). IR: 3063, 2961, 2924, 2859, 1815, 1747, 1693, 1600, 1486,
1449, 1357, 1263, 1192, 1158, 1115, 1033, 991, 943, 887, 764, 749, 698,
668, 628, 590 cmꢀ1. ESI-MS (pos.) m/z (%): 645.2 [MþH]þ (100). ESI-
MS (neg.) m/z (%): 1287.1 [2M-H]e (23), 643.0 [M-H]e (100). EI-MS:
m/z (%): 644 (Mþ, 0.46), 323 (9), 322 (43), 279 (6), 278 (30), 277 (8),
265 (10), 263 (21), 261 (8), 250 (7), 249 (15), 238 (10), 237 (61), 236
C
43H46N4O7 (730.85) calcd. C 70.67, H 6.34, N 7.67, found: C 70.39, H
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A. Klasek et al. / Tetrahedron xxx (2017) 1e11
10
(47), 235 (10), 222 (5), 221 (24), 220 (9), 219 (7), 218 (6), 207 (9), 180
(8), 179 (6), 175 (10), 152 (6), 148 (8), 147 (10), 146 (46), 132 (15), 131
(8),130 (22),120 (32),119 (44),118 (13),117 (19),105 (20),104 (100),
103 (29), 102 (7), 92 (25), 91 (13), 90 (29), 89 (14), 77 (49), 76 (24),
[MþH]þ (100). ESI-MS (neg.) m/z (%): 623.1 [2M-2H þ Na]e (14),
601.0 [2M-H]e (7), 300.0 [M-H]e (100). EI-MS: m/z (%): 301 (Mþ,
87), 259 (15), 258 (100), 228 (9), 215 (23), 214 (15), 186 (5), 173 (6),
172 (6), 171 (10), 129 (5), 118 (5), 45 (7), 44 (6). For C16H19N3O3
(301.34) calcd. C 63.77, H 6.36, N 13.97, found C 63.51, H 6.51, N
14.06.
64 (10), 63 (12), 51 (18), 50 (12), 45 (11), 44 (71), 42 (33). d(
13C):
193.7, 191.5, 171.4, 165.9, 154.2, 152.1, 145.1, 141.1, 137.3, 136.5, 136.4,
132.3, 130.7, 130.2, 129.6, 128.9, 128.7, 127.3, 127.2, 126.7, 126.5123.2,
122.9, 119.3, 116.4, 76.3, 71.4, 64.3, 43.3, 40.8. ForC36H28N4O8
(644.63) calcd. C 67.07, H 4.38, N 8.69, found: C 66.95, H 4.54, N
8.43.
4.4.2. 3a-butyl-3-(2-hydroxyethyl)-5-methyl-3,3a-dihydro-2H-
imidazo[4,5-c]quinoline-2,4(5H)dione (11d)
Compound was prepared from 3d in 30% yield (189 mg, elution
system S2). Yellowish solid, mp 161e163 ꢁC (benzene). IR: 3384,
2950, 2872,1711,1696,1612,1472,1432,1367,1351,1284,1190,1162,
1112, 1075, 1051, 1014, 989, 970, 846, 777, 766, 726, 681, 649, 569,
535 cmꢀ1. ESI-MS (pos.) m/z (%): 653.3 [2M þ Na]þ (17), 354.0
[MþK]þ (9), 338.1 [MþNa]þ (100), 335.1 [2M þ Ca]2þ (14), 316.1
[MþH]þ (5). EI-MS: m/z (%): 315 (Mþ, 23), 297 (26), 285 (11), 272
(25), 257 (5), 241 (14), 229 (13), 228 (31), 215 (11), 214 (17), 201
(25), 200 (15), 188 (8), 185 (9), 173 (11), 132 (5), 130 (6), 129 (14), 128
(100), 98 (11), 84 (63), 57 (15), 55 (10), 45 (15), 43 (9), 41 (17). For C
17H21N3O3 (315.37) calcd. C 64.74, H 6.71, N 13.32, found: C 64.68, H
6.70, N 13.29.
4.3.15. Bis[(2-(2,9-dioxo-9a-butyl-9,9a-dihydrooxazolo][5,4-b]
quinolin-1(2H)-yl)ethyl) carbonate (9a)
Compound was prepared from 3a in 3% yield (19 mg, elution
system S2) besides 6a. Colorless solid, mp 85e98 ꢁC (hexane). IR:
3068, 2961, 2934, 2873, 1813, 1752, 1712, 1690, 1600, 1570, 1462,
1376, 1339, 1259, 1195, 1157, 1128, 1098, 1035, 999, 955, 883, 861,
783, 768, 752, 674, 651, 625, 564, 536, 501 cmꢀ1. ESI-MS (pos.) m/z
(%): 669.2 [MþK]þ (17), 653.2 [MþNa]þ (100), 650.2 [2M þ Ca]2þ
(10), 631.2 [MþH]þ (2). EI-MS: m/z (%): 631 (13), 630 (Mþ, 34), 587
(9), 558 (15), 557 (44), 302 (9), 286 (8), 285 (48), 284 (6), 259 (19),
244 (16), 243 (100), 242 (10), 241 (37), 240 (8), 231 (5), 230 (9), 229
(64), 228 (9), 227 (27), 217 (7), 215 (17), 214 (55), 213 (16), 212 (9),
211 (15), 202 (6), 201 (25), 200 (7), 199 (10), 198 (24), 197 (8), 187
(8),186 (10),185 (18),184 (12),183 (8),175 (12),174 (6),158 (12),157
(6), 146 (61), 144 (10), 142 (9), 132 (13), 131 (8), 130 (75), 129 (8), 128
(8), 121 (29), 120 (8), 116 (6), 110 (8), 104 (6), 103 (6), 102 (18), 90
(17), 89 (23), 84 (8), 77 (8), 76 (7), 68 (13), 54 (14), 45 (9), 44 (25), 42
(14), 41 (24). For C33H34N4O9 (630.64) calcd. C 62.85, H 5.43, N 8.88,
found: C 62.81, H 5.69, N 8.69.
4.4.3. 3a-benzyl-3-(2-hydroxyethyl)-5-methyl-3,3a-dihydro-2H-
imidazo[4,5-c]quinoline-2,4(5H)dione (11e)
Compound was prepared from 3e in 3% yield (21 mg, elution
system S2) besides 12e. Colorless solid, mp 215e220 ꢁC (benzene).
IR: 3453, 1730, 1693, 1670, 1608, 1471, 1418, 1366, 1347, 1292, 1134,
1080, 1017, 776, 754, 705, 649, 592 cmꢀ1. ESI-MS (pos.) m/z (%):
721.2 [2M þ Na]þ (15), 388.0 [MþK]þ (7), 372.1 [MþNa]þ (100),
369.1 [2M þ Ca]2þ (13), 350.1 [MþH]þ (12). ESI-MS (neg.) m/z (%):
348.0 [M-H]e (100). For C20H19N3O3 (349.38) calcd. C 68.75, H 5.48,
N 12.03, found: C 68.62, H 5.52, N 11.93.
4.3.16. Bis[(2-(2,9-dioxo-9a-phenyl-9,9a-dihydrooxazolo][5,4-b]
quinolin-1(2H)-yl)ethyl) carbonate (9c)
Compound was prepared from 3c in 8% yield (54 mg, elution
system S2) besides 6c and 8c. Colorless solid, mp 227e236 ꢁC
(benzene/hexane). IR: 3254, 1746, 1706, 1613, 1596, 1486, 1449,
1419, 1354, 1254, 1225, 1121, 1035, 782, 768, 732, 689, 666,
592 cmꢀ1. ESI-MS (pos.) m/z (%): 709.1 [MþK]þ (26), 693.2 [MþNa]þ
(100), 671.2 [MþH]þ (93). EI-MS: m/z (%): 672 (10), 671 (40), 670
(Mþ, 94), 322 (24), 306 (15), 305 (78), 304 (62), 278 (6), 277 (12),
275 (7), 263 (41), 262 (14), 261 (50), 250 (14), 249 (8), 248 (14), 247
(61), 237 (32), 236 (32), 235 (10), 234 (12), 233 (11), 231 (7), 221
(11), 220 (37), 219 (29), 218 (11), 208 (9), 191 (10), 190 (8), 179 (7),
153 (15), 146 (100), 132 (11), 131 (11), 130 (63), 120 (9), 119 (9), 118
(11),117 (29),105 (16),104 (44), 103 (28), 102 (11), 91 (8), 90 (31), 89
(43), 77 (28), 76 (19), 63 (6), 51 (9), 50 (7), 44 (25. For C37H26N4O9
(670.62) calcd. C 66.27, H 3.91, N 8.35, found: C 65.99, H 4.07, N 8.07.
4.4.4. 3a-butyl-3-(2-hydroxyethyl)-5-phenyl-3,3a-dihydro-2H-
imidazo[4,5-c]quinoline-2,4(5H)dione (11g)
Compound was prepared from 3g in 33% yield (249 mg).
Colorless solid, mp 107e113 ꢁC (benzene/hexane). IR: 3473, 3089,
2960, 2931, 2874, 1718, 1697, 1606, 1493, 1465, 1431, 1358, 1339,
1281, 1248, 1163, 1123, 1053, 775, 756, 699, 684, 653, 601, 578,
513 cmꢀ1. ESI-MS (pos.) m/z (%): 777.3 [2M þ Na]þ (9), 416.1 [MþK]þ
(7), 400.1 [MþNa]þ (100), 397.1 [2M þ Ca]2þ (17), 378.1 [MþH]þ (5).
EI-MS: m/z (%): 377 (Mþ, 49), 359 (15), 346 (17), 334 (31), 291 (9),
290 (14), 276 (11), 263 (20), 250 (17), 194 (9), 128 (100), 84 (53), 77
(19), 57 (6), 51 (5), 45 (5), 44 (9), 41 (9). For C22H23N3O3 (377.43)
calcd. C 70.01, H 6.14, N 11.13, found C 70.19, H 6.27, N 11.01.
4.4.5. (4R*,5S*)-5-benzyl-5-hydroxy-1-(hydroxyethyl)-10H-spiro
[imidazolidine-5,30-indole]-2,20-dione (12b)
4.4. General procedure for the reaction of 3 with potassium cyanate
Compound was prepared from 3b in 34% yield (240 mg, elution
system S1). Colorless solid, mp 202e211 ꢁC (THF/cyclohexane). IR:
3382, 3065, 2992, 2931, 1712, 1678, 1603, 1496, 1452, 1409, 1314,
1295, 1238, 1185, 1160, 1136, 1096, 1072, 1036, 1015, 972, 870, 839,
802, 760, 728, 701, 685, 657, 625, 575, 550 cmꢀ1. ESI-MS (pos.) m/z
(%): 729.2 [2M þ Na]þ (33), 392.0 [MþK]þ (11), 376.1 [MþNa]þ
(100). ESI-MS (neg.) m/z (%): 705.1 [2M-H]e (8), 351.9 [M-H]e (100).
For C19H19N3O4 (353.37) calcd. C 64.58, H 5.42, N 11.89, found: C
64.43, H 5.57, N 11.61.
To the stirring solution of 3 (2 mmol) in acetic acid (6 mL), solid
KNCO (0.2535 g, 3125 mmol) was gradually added during 5 min at
room temperature. After 18 h, crushed ice was added and the
mixture was extracted with chloroform (3 ꢂ 10 mL). The collected
extracts were dried and evaporated to dryness. The residue was
crystallized from appropriate solvent or column chromatographed.
4.4.1. 1-butyl-2-(2-hydroxyethyl)imidazo[1,5-c]quinazoline-
3,5(2H,6H)-dione (10a)
4.4.6. (4R*,5S*)-5-hydroxy-1-(hydroxyethyl)-5-phenyl-10H-spiro
[imidazolidine-5,30-indole]-2,20-dione (12c)
Compound was prepared from 3c in 42% yield (285 mg).
Colorless solid, mp 262e268 ꢁC (ethanol). IR: 3196, 3063, 2974,
2922, 2880, 1686, 1600, 1493, 1461, 1410, 1372, 1336, 1298, 1249,
1205, 1130, 1091, 1070, 1046, 1021, 982, 949, 900, 820, 753, 703, 659,
601, 575 cmꢀ1. ESI-MS (pos.) m/z (%): 701.2 [2M þ Na]þ (28), 528.1
Compound was prepared from 3a in 42% yield (263 mg).
Colorless solid, mp 271e274 ꢁC (ethanol). IR: 3423, 3207, 3097,
2959, 2926, 2875, 1754, 1672, 1631, 1609, 1586, 1488, 1468, 1435,
1380, 1340, 1311, 1288, 1259, 1058, 948, 897, 866, 802, 750, 696, 630,
586, 546 cmꢀ1. ESI-MS (pos.) m/z (%): 625.2 [2M þ Na]þ (41), 471.2
[3M þ Ca]2þ (21), 340.1 [MþK]þ (22), 324.1 [MþNa]þ (82), 302.1
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[3M þ Ca]2þ (20), 378.0 [MþK]þ (6), 362.0 [MþNa]þ (100), 359.0
[2M þ Ca]2þ (20). ESI-MS (neg.) m/z (%): 699.1 [2M-2H þ Na]e (6),
677.0 [2M-H]e (13), 337.9 [M-H]e (100). EI-MS: m/z (%): 339 (Mþ, 8),
322 (21), 321 (100), 290 (37), 278 (11), 277 (46), 265 (11), 248 (6),
247 (16), 237 (12), 236 (20), 234 (13), 219 (10), 206 (8), 205 (8), 203
(8), 148 (8), 146 (35), 130 (6), 120 (60), 118 (28), 117 (14), 104 (36),
103 (8), 65 (8), 51 (8), 45 (8), 44 (7). For C18H17N3O4 (339.35) calcd. C
63.71, H 5.05, N 12.38, found: C 63.62, H 4.95, N 12.27.
366 (14), 354 (6), 338 (8), 337 (11), 310 (9), 263 (22), 250 (14), 235
(9), 222 (8), 213 (7), 195 (19), 194 (14), 167 (6), 148 (100), 130 (13),
117 (14), 105 (19), 104 (95), 91 (12), 77 (40), 51 (11), 45 (16). For
C24H21N3O3 (415.44) calcd. C 69.39, H 5.10, N 10.11, found: C 69.22,
H 5.21, N 9.91.
5. Preparation of compounds 5
To the solution of compound 2 (0.5 mmol) and 1 (0.5 mmol) in
DMF (4 mL), pulverized potassium carbonate (164 mg, 1 mmol) was
added and the mixture was stirred at r.t. The course of the reaction
was monitored with TLC. After fade away of the spot corresponding
to compound 2, the reaction mixture was diluted with water (8 ml).
The deposited product was filtered with suction. The filtrate was
extracted with chloroform (3 ꢂ 10 mL). The collected extracts were
evaporated to dryness and separated by column chromatography
on silica gel. From the reaction of 1e with 2e, compound 5e (2%),
identical to compound isolated from the reaction of 2e with etha-
nolamine, was obtained. From the reaction of 1h with 2h, com-
pound 5h (3%), identical to compound isolated from the reaction of
2h with ethanolamine, was obtained.
4.4.7. (4R*,5S*)-5-benzyl-5-hydroxy-1-(hydroxyethyl)-10-methyl-
10H-spiro[imidazolidine-5,30-indole]-2,20-dione (12e)
Compound was prepared from 3e in 30% yield (220 mg, elution
system S2) besides 11e. Colorless solid, mp 115e130 ꢁC (benzene).
IR: 3296, 2939, 1702, 1668, 1476, 1414, 1370, 1307, 1232, 1139, 1120,
1097, 1074, 1009, 970, 756, 701, 681, 654, 606, 564, 539 cmꢀ1. ESI-
MS (pos.) m/z (%): 757.3 [2M þ Na]þ (14), 406.0 [MþK]þ (17),
390.1 [MþNa]þ (100), 387.1 [2M þ Ca]2þ (19). ESI-MS (neg.) m/z (%):
733.1 [2M-H]e (5), 365.9 [M-H]e (100). For C20H21N3O4 (367.40)
calcd. C 65.38, H 5.76, N 11.44, found: C 65.41, H 5.76, N 11.24.
4.4.8. (4R*,5S*)-5-hydroxy-1-(hydroxyethyl)-10-methyl-5-phenyl-
10H-spiro[imidazolidine-5,30-indole]-2,20-dione (12f)
Compound was prepared from 3f in 76% yield (537 mg). Color-
less solid, mp 232e239 ꢁC (benzene). IR: 3208, 1689, 1664, 1606,
1472, 1410, 1367, 1304, 1274, 1130, 1094, 1052, 1027, 968, 948, 853,
810, 758, 703, 655, 627, 507 cmꢀ1. ESI-MS (pos.) m/z (%): 729.2
[2M þ Na]þ (13), 392.0 [MþK]þ (13), 376.1 [MþNa]þ (100), 373.1
[2M þ Ca]2þ (13). ESI-MS (neg.) m/z (%): 705.1 [2M-H]e (10), 351.9
[M-H]e (100). EI-MS: m/z (%): 335 (40), 317 (12), 305 (11), 304 (33),
292 (9), 291 (6), 279 (8), 277 (7), 276 (17), 275 (16), 261 (11), 251
(10), 250 (16), 248 (14), 222 (8), 201 (33), 188 (8), 173 (14), 160 (11),
148 (100), 131 (14), 130 (19), 118 (14), 117 (22), 105 (20), 104 (100),
77 (36), 76 (6), 51 (8), 45 (14). For C19H19N3O4 (353.37) calcd. C
64.58, H 5.42, N 11.89, found: C 64.30, H 5.43, N 11.68.
Acknowledgements
A. K., F. K., H. K., and M. R. thank for the financial support from
the internal grant of TBU in Zlin No. IGA/FT/2016/004), funded from
the resources of specific university research. The authors thank
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Mrs. H. Gerzova (Faculty of Technology, Tomas Bata University in
Zlín) for technical help.
References
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4.4.9. (4R*,5S*)-5-benzyl-5-hydroxy-1-(hydroxyethyl)-10-phenyl-
10H-spiro[imidazolidine-5,30-indole]-2,20-dione (12h)
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Compound was prepared from 3h in 45% yield (387 mg, elution
system S2). Colorless solid, mp 233e238 (ethyl acetate). IR: 3406,
3320, 2937, 1718, 1682, 1606, 1497, 1446, 1411, 1352, 1306, 1236,
1133, 1073, 1053, 1021, 977, 765, 701, 655, 630, 562 cmꢀ1. ESI-MS
(pos.) m/z (%): 881.3 [2M þ Na]þ (16), 663.2 [3M þ Ca]2þ (8),
468.1 [MþK]þ (24), 452.1 [MþNa]þ (100), 449.1 [2M þ Ca]2þ (28).
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calcd. C 69.92, H 5.40, N 9.78, found: C 69.77, H 5.36, N 9.52.
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spiro[imidazolidine-5,30-indole]-2,20-dione (12i)
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Compound was prepared from 3i in 36% yield (299 mg). Color-
less solid, mp 214e218 ꢁC (ethyl acetate). IR: 3461, 3284, 2923,
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853.3 [2M þ Na]þ (39), 642.2 [3M þ Ca]2þ (6), 454.1 [MþK]þ (15),
438.1 [MþNa]þ (100), 435.1 [2M þ Ca]2þ (17). ESI-MS (neg.) m/z (%):
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Please cite this article in press as: Klasek A, et al., Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the
reaction products, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.02.007