Reaction of 4-hydroxy-2-quinolones with thionyl chloride-preparation of new spiro-benzo[1,3]oxathioles and their transformations

Article abstract of DOI:10.1016/j.tet.2012.11.034

4-Hydroxy-2-quinolones (1) react with thionyl chloride to give new spiro-benzo[1,3]oxathioles (3) and bis(4-hydroxy-2-quinolone-3-yl)sulfides (2) and small quantities of 3-chloro-4-hydroxyquinolin-2-ones (4). Compounds 3 afford sulfides 2 by heating in di

Full text of DOI:10.1016/j.tet.2012.11.034

Tetrahedron 69 (2013) 492e499
Contents lists available at SciVerse ScienceDirect
Tetrahedron
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Reaction of 4-hydroxy-2-quinolones with thionyl
chloridedpreparation of new spiro-benzo[1,3]oxathioles and their
transformations
a
,
a
a
b
c
*
ꢀ
ꢁ
ꢁ
ꢁ ꢂꢁ ꢁ
Antonín Klasek , Ondrej Rudolf , Michal Rouchal , Antonín Lycka , Ales Ruzicka
a Department of Chemistry, Faculty of Technology, Tomas Bata University, CZ-762 72 Zlín, Czech Republic
b Research Institute for Organic Syntheses (VUOS), Rybitví 296, CZ-533 54 Pardubice 20, Czech Republic
c Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, 53210 Pardubice, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 August 2012
Received in revised form 15 October 2012
Accepted 7 November 2012
Available online 14 November 2012
4-Hydroxy-2-quinolones (1) react with thionyl chloride to give new spiro-benzo[1,3]oxathioles (3) and
bis(4-hydroxy-2-quinolone-3-yl)sulfides (2) and small quantities of 3-chloro-4-hydroxyquinolin-2-ones
(4). Compounds 3 afford sulfides 2 by heating in different solvents and [1,4]oxathiino[3,2-c:5,6-c0]di-
quinoline-6,8(5H,9H)-diones (6) by reaction with triphenylphosphine. The reconversion of compounds 2
to 3 was achieved using bromine. The reaction mechanisms are discussed for all transformations. All
compounds were characterized by IR, 1H, and 13C NMR (in some cases also 15N NMR) spectroscopy, and EI
and/or ESI mass spectrometry. The X-ray structure was determined for compound 3b.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Bis(4-hydroxyquinolin-2-one-3-yl)sulfides
b-Dicarbonyl compounds
1,4-Oxathiines
Pummerer rearrangement
Spiro-compounds
O
O
1. Introduction
O
SCN
S
H2SO4
In our preceding paper,1 we described the modified Riemsch-
neider reaction of 3-thiocyanatoquinoline-2,4-diones (A). When
a benzyl group was present at the 3 position of the starting com-
pounds, rapid C-debenzylation was observed, yielding [1,3]oxathiolo
[4,5-c]quinoline-2,4-diones (B) and mixtures of primarily mono- (C),
di- (D), and trisulfides (E) from 4-hydroxy-3-sulfanylquinolin-2-ones
(Scheme 1). The results of ESI-MS measurements provided evidence
that the dominant compound in these mixtures was disulfide D. Re-
peated fraction crystallization produced the pure compounds Ca
(R1¼H), Cc (R1¼Ph), Db (R1¼Me), and Dc (R1¼Ph), albeit in poor
yields.
CH2Ph
P2O5 or AlCl3
N
R1
O
N
R1
O
B
A
R1 = H (a), Me (b), Ph (c)
OH
OH
X
+
N
R1
O O
N
R1
C; X = S; D; X = S2; E; X = S3
Scheme 1.
In the literature, only seven symmetric sulfides derived from 4-
hydroxy-3-sulfanylquinoline-2-ones are described: Ca,2 Cb,3 Cc,1
and four derivatives of Ca substituted with chlorine in the ben-
zene nucleus.4 A more extensive group of sulfides based on 4-
hydroxy-3-sulfanylquinoline-2-one scaffold consists of un-
symmetrical sulfides, which arise from the reaction of 4-hydroxy-
2-quinolones with aromatic disulfides.5
Compound Cb was prepared in 87% yield by refluxing of ethyl 2-
cyano-2(10-methyl-20,40-dioxo-20,40-dihydro-1H0spiro[[1,3]dithi-
ethane-2,30-quinoline]-4-ylidene)acetate in DMSO.3 Ziegler and
Kappe2 reported the preparation of compound Ca by the reaction of
4-hydroxyquinoline-2-one with thionyl chloride in 60e68% yield
but failed to adequately describe the characterization of the prod-
uct: the only information given was Ca is a colorless compound of
mp 370 ꢀC (dec), insoluble in all common solvents. Therefore, we
decided to prepare Ca (hereafter 2a) using the published2 pro-
cedure and compare the reaction product with what we1 prepared
from 3-thiocyanatoquinoline-2,4-dione Aa.
To the best of our knowledge, the corresponding disulfides (D)
and trisulfides (E) have not yet been described in the literature.
* Corresponding author. Fax: þ420 57 72 10 722; e-mail address: klasek@ft.utb.cz
ꢀ
(A. Klasek).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.034

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
493
7
8
This manuscript reports that the reaction of 4-hydroxy-2-
6
5
quinolones 1 with thionyl chloride does not proceeds as un-
ambiguously as previously described.2,4 The main reaction products
3 arise from a Pummerer-like rearrangement of the reaction in-
termediates, and compounds 2 are products of their subsequent
transformation.
9
5a
OH
9a
N
R
9b
O
4´
1
O
SOCl2
4
6´
2
3a
3
S
O
3´
N
R
O
1
2´
3
7´
N 1´
R
O
8´
a
b
c
2. Results and discussion
R
H
Me Ph
OH
4
OH
OH
5
8
5´
We repeated the previously published reaction of 1a with thionyl
chloride, which was reported to produce compound 2a.2 The ratio of
reactants, reaction time, and treatment of the crude product were
identical tothose in the original study. In the original procedure,2 the
crude product was boiled in DMF after washing with water and
ethanol. Given that the reaction time was not reported, we used
15 min of boiling. However, we obtained a yellow compound of mp
>325 ꢀC exhibiting two characteristic IR absorption bands at 1722
and 1693 cmꢁ1 rather than a colorless compound. Similar results
were obtained starting from compounds 1b and 1c (Table 1).
S
4´
Cl
O
3´
2´
3
2
O
N
R
N
R
N
O
8´
4
2
R
O
2
12
13
1
3
11
10
13a
14b
Cl
Cl
O
4
14a
13b
6
O
1
4
2
9a
9N
c´
8
c
3
N5
5
6a
N
R
7a
R
S
R
6
7
5
6
O
O
Scheme 2.
Table 1
Results of the reaction of compounds 1 with thionyl chloride (Method A)
7.73
H
Entry
Starting compound
R
Products (yields,a %)
1
2
3
4
5
6
7
8
9
1a
H
3a (83)
3a (88), 4a (7)
3a (85), 4a (6)
3a (85), 4a (3)
7.88
H
12.17
-239.2
3.69/29.5
CH3
N
N
H
O
O
O
O
93.1
S
105.8
1b
1c
Me
Ph
3b (51), 6b (8)
184.4
O
O
S
2b (43), 3b (25), 4b (3), 5b (2), 6b (3)
2b (23), 3b (38), 4b (3), 6b (4)
2c (11), 3c (41)
3b
3a
-258.4
N
O
N
O
H
CH3
3.47/30.4
H
2c (32), 3c (25)
7.56
11.24
10
2c (39), 3c (20), 4c (6), 6c (2)
Fig. 1. Correlations of NeH and C(50)eH protons with C(2) and C(3a) in gs-HMBC
spectrum of 3a and peri and CH3 protons with nitrogen atoms in gs-He15NeHMBC
spectrum of 3b.
a
For NMR spectra of compounds 2, 4 and 5 see Table 4, for those of compounds 6
see Table 5.
nitrogen atoms was observed in the gs-1He15NeHMBC spectrum of
compound 3b (Fig. 1, right formula). The 2,6- and 3,5-carbons of the
phenyl ring(s) were non-equivalent due to a hindered rotation in
compound 3c. The NMR data are collected in Table 2.
Until recently, we were unable to prepare single crystals of
compounds 3aec. We have now obtained a single crystal of 3b
using the liquid diffusion method6 with dichloromethane and
benzene as the solvent-precipitant pair. The molecular structure of
compound 3b, confirmed by single-crystal X-ray diffraction, is il-
lustrated in Fig. 2.
In both cases, the main product was a yellow or orange com-
pound exhibiting the two above-mentioned characteristic IR ab-
sorption bands. Based on elemental analysis, the yellow compound
prepared from 1a has the composition C18H10N2O4S (350.35),
which differs from the composition of 2a, C18H12N2O4S (352.36).
The molecular weight of 350 was subsequently confirmed using
ESI-MS analysis. In the 13C NMR spectrum, the yellow product ob-
tained from 1a exhibits signals corresponding to two non-
equivalently substituted quinoline moieties as well as two NH
groups, eight eCH] atoms for the benzene nucleus, and ten qua-
ternary carbon atoms. The signal at 184.4 ppm suggests that one
keto group is present in the molecule. Based on these results, we
proposed the structure 3a (Scheme 2) for the product of the re-
action 1a with thionyl chloride. The analogous NMR results for the
compounds prepared from 1b and 1c were used to propose the
structures 3b and 3c as the base scaffold is undoubtedly identical
for each isolated compounds. The complete assignment of the
carbon atoms using NMR spectra was rather difficult because the
most important parts of the molecules 3, which involve atoms
other then carbon, do not contain the hydrogen atoms necessary to
obtain correlated HMBC spectra. Moreover, the proton resonances
of the 1,2-disubstituted benzene rings overlapped. Thus, gs-TOCSY
and gs-HMQCeRELAY experiments were performed in addition to
the classical (gs)-COSY, gs-HMQC, and gs-HMBC measurements.
The resonance of the carbonyl group at 184 ppm was key in dif-
ferentiating the 1,2-disubstituted benzene rings using gs-HMBC
correlations in all compounds 3. Moreover, NH protons were used
for correlation with C(2) and C(3a) in the gs-HMBC spectrum of
compound 3a (Fig.1, left formula). Independently, the correlation of
the peri protons and methyl group protons with the corresponding
Although 46 examples of oxathia spiro compounds structures
are available in the Cambridge Structural Data Base, there is no
structural match to the structure of 3. The structure of 3b is com-
posed of two nearly perpendicular planes defined by both aromatic
systems with an interplanar angle of 76.64 (5)ꢀ. The primary de-
viation from these planes occurs for carbon atom C10 (spiro one, for
ꢂ
numbering see Fig. 2), which lies 0.266 (3) A above the plane
ꢂ
containing the oxathia cycle and 0.488 (3) A above the second
plane. Three additional atoms or groups deviate from their parent
ꢂ
rings: two methyl groups (0.526 (3) and 0.601 (3) A) and the oxygen
atom O4 of one of the carbonyl groups. All the other interatomic
distances and angles are in line with previous findings in the lit-
erature.7 The molecular system does not contain any H-bonding.
The ESI-MS measurements of compounds 3 were performed in
both the positive- and the negative-ion polarity modes. In the
positive-ion first-order mass spectra, three signals at m/z corre-
sponding to the protonated molecular ion [MþH]þ and its sodium
[MþNa]þ and potassium [MþK]þ adducts were determined for
each structure. Moreover, these ions were accompanied by several
types of higher associates: the protonated dimer [2MþH]þ (3b) and

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
494
Table 2
z for 3c) led to the neutral loss of the second carbon monoxide
1H and 13C chemical shifts of compounds 3 in DMSO-d6
molecule and the formation of the corresponding protonated benzo
[b]azet-2(1H)-one and [1,3]oxathiolo[4,5-b]indol-2-ylium. Com-
pounds 3b and 3c were also analyzed using electron impact ioni-
zation mass spectrometry (EI-MS). Contrary to the ESI-MS
experiments, the direct loss of two carbon monoxide molecules
(56 m/z) is the typical fragmentation pathway observed in the EI-
MS spectra of compounds 3b and 3c.
Position
3a
3b
3c
dH
dC
dH
dC
dH
dC
2y30
3a
4
5
5a
6
7
8
d
93.1
105.8
157.3
d
d
93.2
d
93.6
d
d
105.6
156.6
d239.2a
139.4
115.9
131.7
122.9
122.5
110.7
156.0
ꢁ258.4a
165.9
184.0
118.6
128.1
123.9
136.9
116.6
142.1
29.5
d
105.9
156.6
d
d
d
d
d
d
d
d
138.7
116.1
131.3
122.8
122.0
110.1
157.3
d
d
d
140.6
116.4
131.4
123.1
122.3
110.7
156.6
d
Only a few compounds based on the 2,2-dicarbonyl-2H-[1,3]-
oxathiole structural motif are described in the literature, four of
which are spirocyclic compounds conformable to that of structure 3.
From dimedone, 40,40,6,6-tetramethyl-6,7-dihydro-20H,60H-spiro
[1,3-benz-oxathio-2,10-cyclohexane]-20,4,60(5H)-trione has been
prepared in several different ways.8e16 One approach was the re-
action of dimedone with thionyl chloride in benzene.9,10,15 The for-
mation of [1,3]oxathioles was also described in the reaction of
dibenzoylmethane with thionyl chloride.17,18 Compounds analogous
to 3 were also prepared by the reaction of 4-hydroxy-1-propyl-1,8-
naphtyridin-2(1H)-one and 4-hydroxy-1-propylquinolin-2(1H)-
one with thionyl chloride and the oxidation of primarily formed
sulfides with manganese dioxide.19 Unfortunately, the correspond-
ing sulfides are insufficiently described. Because the yellow coloring
of first such compound and its melting point are almost identical to
those of the final [1,3]oxathiole, it is unclear whether the primary
product was sulfide or [1,3]oxathiole, or perhaps even a mixture of
both compounds.
7.49
7.67
7.38
7.75
d
7.73
7.81
7.48
7.83
d
6.69
7.60
7.48
7.90
d
9
9a
9b
d
d
d
10
d
d
d
20
d
166.1
184.4
117.0
128.0
123.5
136.7
117.3
141.0
d
d
d
165.9
183.9
118.5
128.1
123.9
136.4
117.2
143.1
40
d
d
d
4a0
d
d
d
50
7.88
7.25
7.72
7.19
d
7.97
7.36
7.83
7.50
d
8.05
7.33
7.60
6.49
d
60
70
80
8a0
1 (N-5)
2 (N-5)
3 (N-5)
4 (N-5
1 (N-10)
2 (N-10)
3 (N-10)
4 (N-10)
12.17
d
3.69
d
d
b
136.8
c
d
d
b
b
c
c
d
d
d
d
d
d
d
d
11.24
d
d
3.47
d
30.4
d
d
b
136.8
c
d
b
b
c
c
d
d
d
d
These examples show a strong tendency of b-dicarbonyl com-
d
d
d
d
pounds to form a [1,3]oxathiole ring it their reactions with thionyl
chloride and suggest that the analogous reaction, giving products 3,
also proceeds with 4-hydroxyquinolin-2-ones 1. The mechanism of
the reaction of 1 with thionyl chloride can be explained by the initial
formation of intermediate F, which can be further transformed by
two ways (Scheme 3): the Pummerer-like rearrangement of F to G,
which reacts with compound 1 to give the intermediate H, cyclizing
to the final compound 3, and the reaction of the intermediate F with
the starting compound 1 to give the intermediate I, liable to
Pummerer-like rearrangement to the intermediate H. The formation
of the intermediate thiocarbonylylide J during the transformation of
the intermediate H to the final compound 3 is not possible under the
given reaction conditions. The formation of intermediate J analog
was described by Oka et al.,17 but the reaction was carried out in the
presence of triethylamine.
a
d(
15N).
b
c
Strongly overlapped and broadened signals at 7.59e7.76 and 7.41e7.52 ppm.
130.4, 130.1, 129.3, 129.2, 129.1, 128.9, 128.3, 128.1 (2,6- and 3,5-carbons of
phenyl ring(s) are non-equivalent due to a hindered rotation).
In addition to 40,40,6,6-tetramethyl-6,7-dihydro-20H,60H-spiro[1,3-
benzoxathio-2,10-cyclohexane]-20,4,60(5H)-trione, the only reaction
product in the presence of pyridine, 2-(4,4-dimethyl-2,6-dioxoc-
yclohexylthio)-5,5-dimethylcyclohexane-1,3-dione is also formed in
the reaction of dimedone with thionyl chloride in the absence of
pyridine.10,15 We found that, in addition to compounds 3b and 3c,
compounds 2b and 2c arise through the reaction of
4-hydroxyquinolin-2-ones 1b and 1c with thionyl chloride (Table 1,
Scheme 2). Unfortunately, we were unable to isolate compound 2a,
which is reportedly one of the mainproducts of the reaction of 1a with
thionyl chloride.2,4 From the reaction of compounds 1 with thionyl
chloride, four minority compounds (4a, 4b, 4c, 5b) were also isolated
(Table 1). According to the literature, compound 4a arises from the
reaction of 4-hydroxy-3-phenyliodonium-2-quinolone methanesul-
fonate with hydrogen chloride20,21 or the reduction of 3,3-
dichloroquinoline-2,4-dione with zinc.22e24 Its N-methyl derivative
4b arises from the reaction of 4-hydroxy-1-methyl-3-
phenyliodoniumquinolin-2-one methanesulfonate with hydrogen
chloride,20 the chlorination of 4-hydroxy-1-methylquinolin-2-one
with N-chloro-succinimide,25,26 the reaction of 4-hydroxy-1-methyl-
3-nitroquinolin-2-one with phosphorus oxychloride,27 and the re-
duction of 3,3-dichloro-1-methylquinoline-2,4-dione.28 Compound
5b was prepared by the reaction of 4-hydroxy-1-methyl-3-
nitroquinolin-2-one with thionyl chloride27 and the chlorination of
Fig. 2. Molecular structure (ORTEP 50% probability level) of 3b C6H6. Selected in-
ꢀ
ꢂ
teratomic distances [A] and angles [ ]: S1 C5 1.7543 (17), S1 C10 1.8665 (17), O2 C4
1.364 (2), O2 C10 1.4161 (19), O4 C14 1.212 (2), O3 C11 1.211 (2), N2 C11 1.372 (2), N2
C12 1.421 (2), N2 C20 1.465 (2), O1 C1 1.235 (2), C5 C4 1.344 (2), C5 C1 1.434 (2), N1 C1
1.391 (2), N1 C2 1.396 (2), N1 C19 1.465 (2), C5 S1 C10 86.09 (8), C4 O2 C10 109.06 (12),
C11 N2 C12 122.78 (14), C11 N2 C20 117.49 (14), C12 N2 C20 118.74 (13).
its sodium adduct [2MþNa]þ (3a and 3c) and doubly charged cal-
cium adduct [2MþCa]2þ observed in the ESI mass spectra of all of
the analyzed compounds. Unsurprisingly, only compound 3a also
provided signals in the negative-ion polarity mode: the deproto-
nated molecular ion [MꢁH]ꢁ and a signal with twice the intensity
of [MꢁH]ꢁ (i.e., [2Mꢁ2HþNa]ꢁ). More detailed structural in-
formation for compounds 3 was obtained from the tandem mass
spectra of the [MþH]þ ion. In the ESI-MS/MS spectra of compounds
3, two fragmentation pathways were observed: the cleavage of the
[1,3]oxathiole core and the neutral loss of carbon monoxide (28 m/
z) from the [MþH]þ ion. The further fragmentation (MS3) of the
[MþHꢁCO]þ product ion (323 m/z for 3a, 351 m/z for 3b and 475 m/

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
495
OH
O
O
O
S
OH
OH
Cl
S
Cl
SCl
O
Cl
SOCl2
1
SOCl2
- HCl
- HCl
O
O
N
R
N
R
N
R
N
R
O
N
R
O
G
F
H
1
1
- HCl
SOCl2
- HCl
O
O
O
S
N
R
OH
OH
O
S
O
O
S
O
N
R
N
R
O
O
N
R
N
R
O
N
R
O
3
J
I
Scheme 3.
4-hydroxy-1-methylquinolin-2-one with sulfuryl chloride29,30 or na-
scent chlorine.29 Thus, the literature indicates that the formation of
compounds 4a, 4b, 4c, and 5b during the reaction of 1a or 1b with
thionyl chloride is not surprising and can be readily explained.
However, it is much more difficult to explain the formation of
compounds 2. We found that these compounds not only arise
during the reaction of compounds 1 with thionyl chloride, but also
via the long-term boiling of compounds 3 in different solvents
(Table 3). The question is whether compounds 2 arise directly from
the reaction of 1 with thionyl chloride or after the further trans-
formation of compounds 3, the primary products. We believe that
the second possibility is more likely because we were unsuccessful
in isolation of compounds 2 from the reaction mixture after the
reaction of 1 with thionyl chloride in several cases (Table 1). The
subsequent transformation of the primarily generated 3 to sulfide 2
can also explain the finding that the yellow crude reaction product
of 1a discolors after heating in dimethylformamide to give sulfide
2a.2,4 However, the main issue is that the conversion of 3 to 2 is
a reduction process. Despite significant effort, we were unable to
find an analogous reaction in the literature. We performed several
experiments to convert compounds 3 to 2, using dimethylforma-
mide, acetic acid, or alcohols (Table 3). The conversion occurs very
quickly in benzyl alcohol and even more so in dimethylformamide,
but slowly in acetic acid and ethanol. The long-term boiling of 3c in
p-xylene (Table 3, entry 8) only results in the isolation of starting
material, insofar that the conversion of 3 to 2 is not thermal pro-
cess. Because there was no reducing agent in the reaction mixture
during conversion of 3 to 2 and the reaction must proceed through
C(2)eO bond fission, we suggest the nucleophilic attack of com-
pound 3 by water (from non-dried solvents) under the formation of
the thioketal K (Scheme 4). This compound could reduce to
compound 2 by a second nucleophilic attack by water, yielding
compound 2 and hydrogen peroxide, which is decomposed ther-
mally or by the reaction with the solvent. The possibility of the
nucleophilic attack of 3 or K with the solvent bearing the ex-
changeable hydrogen atom cannot be also excluded. Based on our
experience, the ‘positively charged’ heteroatoms in position 3 of the
quinoline-2,4-diones are very easily attacked by nucleophiles.31
An alternative but similar reaction mechanism for the reaction
of 3b and 3c with triphenylphosphine, providing 1,4-oxathiines
6a,b, is as follows. Because the sulfur atom in 3 remains part of
the product 6, the fission of the C(2)eO bond must be the first re-
action step. The nucleophilic attack of triphenylphosphine affords
the intermediate L, which cyclizes to betaine M (Scheme 4, path a).
The final oxathiines 6 arise from the elimination of triphenylpho-
spine oxide in a way typified by the final step of the Mitsunobu
reaction.32
In addition to 6b and 6c, sulfides 2b and 2c were also isolated
from the reaction of 3b and 3c with triphenylphosphine. These
compounds most likely arise from the addition of water to the
carbonyl group at C(4) of intermediate L (Scheme 4, path b) and
following the elimination of triphenylphosphine oxide from the
produced intermediate N. In the case of 3a, which is barely soluble
in the reaction medium, only sulfide 2a was isolated (Table 3).
Although the conversion of oxathioles based on a dimedone
scaffold to the corresponding thiiranes by reaction with triphe-
nylphosphine has been described,10 no reaction mechanism has
been proposed.
In agreement with the results described in Ref. 10 for dimedone-
derived analogs of 2, we found that compounds 2 can easily be
converted to compounds 3 by their reaction with bromine (Table 3).
The fruitfulness of the reaction depends on the solvent used. In
benzene, in which compound 2c is poorly soluble, the yield was low
and a large quantity of the starting compound 2c was isolated. In
dichloromethane, the yields of 3b and 3c were very good (Table 3,
entries 10 and 11). The attempt to prepare 3a from 2a failed due to
the negligible solubility of 2a in all common solvents.
Table 3
Results of the transformations of compounds 2 and 3
Entry
Starting
compound
R
Method
Time
(h)
Solvent
Products
(yields, %)
1
2
3
4
5
6
7
8
3a
H
B
B
B
B
B
B
B
B
C
C
C
C
D
D
D
3
0.25
5
DMF
2a (55), 3a (21)
2a (67)
2b (24), 3b (68)
2b (50)
2b (27), 3b (54)
2c (38), 3c (42)
2c (47)
3c (67)
2a (94)
3b (75)
3c (72)
BnOH
AcOH
DMF
EtOH
EtOH
3. Conclusions
3b
Me
5
In conclusion, the described reaction of 4-hydroxyquinolin-2-
ones 1 with thionyl chloride allows the preparation, in very good
yields, of spiro-compounds 3, which have not been previously de-
scribed in the literature. The results of our experiments also bear
evidence that compounds 3 and not2,4,19 sulfides 2 are the primary
products of this reaction.
Since many biologically active compounds contain a sulfur
atom33,34 and two spiro-compounds analogous to 3 exhibit cysteine
protease inhibition activity,19 compounds 3 could also be in-
teresting structures for further study.
20
20
15
3.5
0.5
0.5
0.5
0.25
1
3c
Ph
DMF
p-xylene
CH2Cl2
CH2Cl2
CH2Cl2
PhH
PhMe
PhMe
PhMe
9
2a
2b
2c
H
Me
Ph
10
11
12
13
14
15
2c (31), 3c (26)
2a (53)
2b (27), 6b (61)
2c (18), 6c (37)
3a
3b
3c
H
Me
Ph
1
1

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A. Klasek et al. / Tetrahedron 69 (2013) 492e499
496
a
H2O
OH2
N
R
OH
N
O
O
O
O
OH
b
O
S
S
O
H2O
PPh3
S
PPh3
O
O
K
O
O
L
N
R
N
R
N
R
N
R
O
3
R
- H2O2
a
b
2
OH - Ph3PO
OH
O
O
S
O
O
S
- Ph3PO
PPh3
N
N
N
N
O
O
N
R
N
R
R
S
6
R
R
R
N
PPh3
M
O
O
O
O
Scheme 4.
4. Experimental
4.1. General
X-ray analysis. The X-ray data for colorless crystals of 3b C6H6,
(prepared by liquid diffusion method6 using dichloromethane and
benzene as solvent-precipitant pair) were obtained at 150 K using
Oxford Cryostream low-temperature device on a Nonius KappaCCD
ꢂ
Melting points were determined on a Kofler block or Gallen-
camp apparatus. IR (KBr) spectra were recorded on a Mattson 3000
spectrophotometer. The 1H, 13C, and 15N NMR spectra were recor-
ded on a Bruker Avance 500 spectrometer (500.13 MHz for 1H,
diffractometer with MoK
monochromator, and the
a
radiation (
l
¼0.71073 A), a graphite
f
and
c
scan mode. Data reductions were
performed with DENZO-SMN.35 The absorption was corrected by
integration methods.36 Structures were solved by direct methods
(Sir92)37 and refined by full matrix least-square based on F2
(SHELXL97).38 Hydrogen atoms were mostly localized on a differ-
ence Fourier map, however to ensure uniformity of the treatment of
the crystal, all hydrogen atoms were recalculated into idealized
positions (riding model) and assigned temperature factors Hiso
(H)¼1.2 Ueq (pivot atom) or of 1.5 Ueq for the methyl moiety with
125.76 MHz for 13C, and 50.68 MHz for 15N) in DMSO-d6. 1H and 13
C
chemical shifts are given on the
referenced to internal TMS (
ferred to external neat CH3NO2 in a co-axial capillary (
d scale (parts per million) and are
d
¼0.0). 15N chemical shifts were re-
d
¼0.0). All 2D
experiments (gradient-selected (gs)-COSY, gs-TOCSY, gs-HMQC, gs-
HMQC-RELAY, gs-HMBC) were performed using manufacturer’s
software. The positive-ion EI mass spectra were measured on
a Shimadzu QP-2010 instrument within the mass range m/
z¼50e600 using direct inlet probe (DI). Samples were dissolved in
2
ꢂ
CeH¼0.96 and 0.93 A for methyl and hydrogen atoms on sp car-
bon atoms, respectively.
There is disordered solvent (benzene) in the structure of 3b.
Attempts were made to model this disorder or split it into two
positions, but were unsuccessful. PLATON/SQUEZZE39 was used to
correct the data for the presence of disordered solvent. A potential
solvent volume of 258 A was found, 89 electrons per unit cell
worth of scattering were located in the void. The calculated stoi-
chiometry of solvent was calculated to be two molecules of ben-
zene per unit cell resulting in 84 electrons.
dichloromethane (30
m mL of the solution was
g mLꢁ1) and 10
evaporated in 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 spec-
trometer (Bruker Daltonics, Bremen, Germany) equipped with an
electrospray ion source. All experiments were conducted in the
positive as well as negative-ion polarity mode. Individual samples
(with a concentration of 500 ng mLꢁ1) were infused into the ESI
source as methanol or methanol/water (1:1, v:v) solutions via
3
ꢂ
Crystallographic data for 3b C6H6: C26H20N2O4S, M¼456.50, tri-
clinic, Pꢁ1, a¼9.2091 (5), b¼9.9390 (3), c¼12.2420 (4), ¼101.774
3
ꢂ
a
(4),
b
¼105.928 (3),
g
¼94.182 (3), Z¼2, V¼1044.86 (7) A ,
a syringe pump with a constant flow rate of 4
m
L minꢁ1. The other
Dcalcd¼1.451 g cmꢁ3
,
m
¼0.194 mmꢁ1; 21,453 reflections measured
instrumental conditions were as follows: electrospray voltage of
ꢂ4.2 kV, capillary exit voltage of ꢂ140 V, drying gas temperature of
220 ꢀC, drying gas flow of 6.0 dm3 minꢁ1, nebulizer pressure of
8.0 psi. Nitrogen was used as the nebulizing and drying gases for all
experiments. Tandem mass spectra were collected using collision-
induced dissociation (CID) with He as the collision gas after iso-
lating of the required ions. Column chromatography was carried
out on silica gel (Merck, grade 60, 70e230 mesh) using chloroform/
ethanol (in ratios from 99:1 to 8:2) (S1), successive mixtures of
benzene/ethyl acetate (in ratios from 99:1 to 8:2) (S2) and iso-
propylalcohol/acetic acid (9:1) (S3). 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) (S4), chloroform/
ethanol (9:1 and 1:1) (S5 and S6), chloroform/ethyl acetate (7:3)
(S7), and tetrahydrofuran/acetic acid (4:1) (S8) on AlugramÒ SIL G/
UV254 foils (MachereyeNagel). Elemental analyses (C, H, N) were
performed with a EA Flash EA 1112 Elemental Analyzer (Thermo
Fisher Scientific).
(
qmax¼27.5ꢀ), 4721 independent (Rint¼0.0339), 3851 with I>2
s(I),
244 parameters, S¼1.038, R1 (obs. data)¼0.0453, wR2 (all data)¼
ꢂꢁ3
0.1100; max, min electron density¼0.290, ꢁ0.244 e A
.
CCDC 890932 for 3b contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif.
4.2. General method for the reaction of compounds 1 with
thionyl chloride (Method A)
The solution of 4-hydroxyquinolin-2-one (1) (6 mmol) in di-
oxane (3.5 mL) and thionyl chloride (10 mL) was refluxed for
90 min. The mixture was evaporated to dryness in vacuo and the
residue was treated with water (30 mL). The precipitate was filtered
with suction and washed with water to the neutral reaction. Then
the precipitate was rinsed with hot ethanol (20 mL). The insoluble
and soluble portions were worked up separately by repeated

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
497
Table 4
crystallization or column chromatography. The results are given in
Table 1.
1H and 13C chemical shifts of compounds 2,a 4 and 5 in DMSO-d6
Position 2b
4a
4b
4c
5b
dH
dC
dH
dC
dH
dC
dH
dC
dH
dC
4.3. General method for transformation of spiro-compounds
2
3
4
4a
5
6
7
8
8a
OH
d
d
d
d
164.8
104.0
165.8
115.3
d
d
d
d
159.1
105.1
157.4
115.4
d
d
d
d
158.7
105.0
156.3
115.5
d
d
d
d
158.6
104.9
157.0
115.5
d
d
d
d
162.9
80.2
180.9
118.4
3 to sulfides 2 (Method B)
A yellow colored mixture of compound 3 (0.25 mmol) and ap-
propriate solvent (6 mL) was heated to reflux and the reaction was
monitored by TLC. After time stated in Table 3, the mixture was
evaporated to dryness and the residue was crystallized. In the case
of 3a (Table 3, entry 2), the reaction mixture was cooled and de-
posited 2a was obtained by filtration.
8.09 124.2 7.93
7.43 123.0 7.26
7.80 133.2 7.58
7.69 115.8 7.36
122.9 8.03 123.4 8.08 123.4 8.03 128.7
121.8 7.35 122.1 7.33 122.3 7.36 123.9
131.1 7.70 131.5 7.49 131.1 7.85 137.0
114.8 7.58 114.9 6.55 115.4 7.51 116.5
136.9
d
d
139.4
d
d
d
137.9
d
d
138.9
d
d
d
d
d
d
d
141.5
d
11.99
11.40
11.45
3.68 30.1
d
d
d
11.63
d
10 (N-1) 3.75 30.8 11.86b
d
137.7
d
20 (N-1)
30 (N-1)
40 (N-1)
d
d
d
d
d
d
d
d
d
d
d
d
d
7.38 129.3
7.66 130.1
7.58 128.9
d
4.4. General method for transformation of sulfides 2 to spiro-
compounds 3 (Method C)
d
d
d
d
a
For NMR data of compounds 2a and 2c see Ref. 1.
1J(15N)¼90.6 Hz.
b
To the solution of compound 2 (0.5 mmol) in the mixture of
dichloromethane (10 mL) and triethylamine (0.30 mL, 2.18 mmol),
a 0.195 M solution of bromine in dichloromethane (2.56 mL) was
added in one portion. The solution was stirred at room temperature
and the course of the reaction was monitored by TLC. After 30 min,
the spot corresponding to 2 disappeared and only that corre-
sponding to compound 3 was observed. The solution was evapo-
rated to dryness in vacuo, the residue was triturated with water and
filtered with suction. The filter cake was recrystallized from ethyl
acetate or benzene. The yields are given in Table 3. In the case of 2a,
only starting compound was isolated. In one case (Table 3, entry 11)
the reaction was performed in benzene.
339e340 ꢀC (benzene). For 2c, mp 325e326 ꢀC was reported.1 For
NMR and ESI-MS spectra see Ref. 1.
4.6.4. 20H-Spiro[1,3-oxathiolo[4,5-c]quinoline-2,30-quinoline]-
20,4,40(10H,5H)trione (3a). Compound was prepared from 1a by
Method A in respective yields 83%, 88%, and 85% (Table 1). Yellow
crystals, mp >325 ꢀC. IR: 3203, 3134, 3072, 2908, 2862, 1722, 1693,
1646,1604,1540,1500,1479,1429,1369,1149,1122, 947, 914, 785, 769,
750, 671, 611, 538 cmꢁ1. For NMR spectra see Table 2. ESI-MS (pos.)
m/z (%): 723.1 [2MþNa]þ (7), 389.1 [MþK]þ (24), 373.1 [MþNa]þ
(100), 370.1 [2MþCa]þ (40), 351.1 [MþH]þ (45). ESI-MS(neg.) m/z (%):
721.1 [2Mꢁ2HþNa]ꢁ (5), 349.1 [MꢁH]ꢁ (100). Anal. Calcd (found) for
4.5. General method for the reaction of spiro-compounds 3
with triphenylphosphine (Method D)
C18H10N2O4S: C 61.71 (61.89); H 2.88 (3.15); N 8.00 (7.92), S 9.15 (9.28).
4.6.5. 10,5-Dimethyl-20H-spiro[1,3-oxathiolo[4,5-c]quinoline-2,30-quin-
oline]-20,4,40(10H,5H)trione (3b). Compound was prepared from 1b
by Method A in respective yields 51%, 25%, and 38% (Table 1) and from
2b by Method C in 75% yield (Table 3). Yellow crystals, mp
278e281 ꢀC (ethyl acetate). IR: 3078, 2945, 2891, 1724, 1685, 1643,
1593, 1502, 1471, 1419, 1383, 1358, 1329, 1298, 1205, 1109, 1068, 999,
947, 773, 762, 748, 731, 642, 534 cmꢁ1. For NMR spectra see Table 2.
EI-MS m/z (%): 380 (16), 379 (23), 378 (Mþ, 100), 363 (22), 322 (6),
321 (9), 189 (11), 175 (13), 146 (31), 132 (14), 117 (48), 105 (11), 104
(20), 102 (11), 91 (12), 90 (15), 78 (12), 77 (21), 76 (9). ESI-MS (pos.)
m/z (%): 757.0 [2MþH]þ (7), 417.0 [MþK]þ (20), 401.0 [MþNa]þ (42),
398.0 [2MþCa]2þ (8), 379.1 [MþH]þ (100). Anal. Calcd (found) for
A suspension of compound 3 (0.3 mmol) and triphenylphos-
phine (0.091 g, 0.346 mmol) in toluene (6.6 mL) was heated to
reflux. The suspension comes to solution and after ca. 5 min the
new deposition of crystals started. After 1 h, the reaction mixture
was cooled and filtered with suction to give yellow compound 6. In
the case of 3a, only 2a was isolated (Table 3).
4.6. Isolated compounds
4.6.1. 3-(1,2-Dihydro-4-hydroxy-2-oxoquinolin-3-ylthio)-4-hydroxy-
quinolin-2(1H)-one (2a). Compound was prepared from 3a in re-
spective yields 67 and 55% by Method B and from 3a in 53% yield by
Method D (Table 3). Colorless crystals, mp >330 ꢀC, For IR, NMR and
ESI-MS spectra see Ref. 1.
C
20H14N2O4S: C 63.48 (63.37); H 3.73 (3.74); N 7.40 (7.33), S 8.47
(8.31). For crystallographic data of 3b see paragraph 4.1.
4.6.6. 10,5-Diphenyl-20H-spiro[1,3-oxathiolo[4,5-c]quinoline-2,30-
quinoline]-20,4,40(10H,5H)trione (3c). Compound was prepared from
1c in respective yields 41%, 20%, and 25% (Table 1, Method A) and from
2c in respective yields 72% and 26% (Table 3, Method C). Orange
crystals, mp 288e292 ꢀC (ethyl acetate). IR: 3066, 3033, 3014, 1720,
1693, 1655, 1597, 1493, 1460, 1383, 1338, 1248, 1149, 1107, 1043, 970,
764, 754, 694, 623 cmꢁ1. For NMR spectra see Table 2. EI-MS m/z (%):
504 (15), 503 (34), 502 (Mþ,100), 446 (5), 445 (14), 413 (10), 251 (10),
195 (11), 179 (10), 167 (13), 166 (11), 77 (18). ESI-MS (pos.) m/z (%):
1027.2 [2MþNa]þ (5), 541.2 [MþK]þ (29), 525.2 [MþNa]þ (92), 522.2
[2MþCa]2þ (21), 503.2 [MþH]þ (100). Anal. Calcd (found) for
4.6.2. 3-(1,2-Dihydro-4-hydroxy-1-methyl-2-oxoquinolin-3-ylthio)-
4-hydroxy-1-methylquinolin-2(1H)-one (2b). Compound was pre-
pared from 1b in respective yields 43% and 23% (Table 1, Method A)
and from 3b in respective yields 24%, 50% and 27% (Table 3, Method
B), and 27% (Table 3, Method D). Colorless crystals, mp 302e310 ꢀC
(ethanol). For 2b, mp >300 ꢀC was reported.3 IR: 3089, 2945, 1635,
1577, 1502, 1468, 1329, 1294, 1174, 1163, 1113, 1074, 1043, 752, 673,
451 cmꢁ1. For NMR spectra see Table 4. ESI-MS (pos.) m/z (%): 419.1
[MþK]þ (13), 403.2 [MþNa]þ (80), 381.2 [MþH]þ (100). Anal. Calcd
(found) for C20H16N2O4S: C 63.14 (63.07); H 4.24 (4.05); N 7.36
(7.33), S 8.43 (8.31).
C30H18N2O4S: C 71.70 (71.65); H 3.61 (3.85); N 5.57 (5.49), S 6.38 (6.17).
4.6.3. 3-(1,2-Dihydro-4-hydroxy-1-phenyl-2-oxoquinolin-3-ylthio)-
4-hydroxy-1-phenylquinolin-2(1H)-one (2c). Compound was pre-
pared from 1c in respective yields 11%, 32%, and 39% (Table 1,
Method A) and from 3c in respective yields 38% and 47% (Table 3,
Method B), and 18% (Table 3, Method D). Colorless crystals, mp
4.6.7. 3-Chloro-4-hydroxyquinolin-2-one (4a). Compound was
prepared from 1a besides 3a in respective yields 7%, 6%, and 3%
(Table 1, Method A). Colorless crystals, mp 269e274 ꢀC. For 4a, mp
276 ꢀC was reported.22 IR: 3137, 3005, 2900, 1643, 1606, 1549, 1460,
1361, 1280, 1265, 1236, 1159, 1086, 860, 748, 673, 532, 469 cmꢁ1. For

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
498
NMR spectra see Table 4. EI-MS m/z (%): 197 (17), 196 (6), 195
(Mþ(35Cl), 52),132 (11),121 (9),120 (100),102 (11),100 (16), 92 (27),
77 (15), 76 (13), 75 (10), 65 (15), 51 (14), 45 (12), 44 (34), 43 (16).
ESI-MS (pos.) m/z (%): 413.1 [2M(35Cl)þNa]þ (59), 312.6 [3M(35Cl)þ
Ca]2þ (77), 234.1 [M(35Cl)þK]þ (30), 218.1 [M(35Cl)þNa]þ (75),196.1
[M(35Cl)þH]þ (100). ESI-MS (neg.) m/z (%): 411.0 [2M(35Cl)ꢁ
2HþNa]ꢁ (7), 194.1 [M(35Cl)ꢁH]ꢁ (100). Anal. Calcd (found) for
C9H6ClNO2: C 55.26, H 3.09, N 7.16; C 55.22, H 3.04, N 7.14.
(24), 362 (Mþ, 100), 333 (9), 301 (8), 181 (9), 128 (12), 102 (10), 77
(12). ESI-MS (pos.) m/z (%): 747.2 [2MþNa]þ (5), 401.1 [MþK]þ (5),
385.2 [MþNa]þ (44), 363.2 [MþH]þ (100). Anal. Calcd (found) for
C
20H14N2O3S (362.40): C 66.28 (65.97); H 3.89 (3.87); N 7.73 (7.57),
S 8.85 (8.64).
4.6.12. 5,9-Diphenyl-[1,4]oxathiino[3,2-c:5,6-c0]diquinoline-6,8(5H,
9H)-dione (6c). Compound was prepared from 1c (Table 1, Method
A) in 2% yield and from 3c (Table 3, Method D) in 37% yield. Yellow
crystals, mp >335 ꢀC. IR: 3037, 1651, 1602, 1491, 1448, 1321, 1209,
1109, 766, 702, 623, 511 cmꢁ1. For NMR spectra see Table 5. EI-MS
m/z (%) 488 (11), 487 (33), 486 (Mþ, 100), 243 (13), 242 (20), 77
(15), 44 (19). ESI-MS (pos.) m/z (%): 995.2 [2MþNa]þ (3), 525.2
[MþK]þ (16), 509.2 [MþNa]þ (40), 506.2 [2MþCa]2þ (6), 487.2
[MþH]þ (100). Anal. Calcd (found) for C30H18N2O3S: C 74.06
(73.91); H 3.73 (3.95); N 5.76 (5.72), S 6.59 (6.34).
4.6.8. 3-Chloro-4-hydroxy-1-methylquinolin-2-one (4b). Compound
was prepared from 1b in 3% yield (Table 1, Method A). Yellowish
crystals, mp 226e231 ꢀC (chloroform/hexane). For 4b, mp
229e231 ꢀC was published.40 IR: 3050, 1628, 1608, 1587, 1566, 1271,
1221, 1161, 1078, 866, 741, 646, 582 cmꢁ1. For NMR spectra see Table
4. ESI-MS (pos.) m/z (%): 441.1 [2M(35Cl)þNa]þ (27), 333.6
[3M(35Cl)þCa]2þ (27), 248.1 [M(35Cl)þK]þ (15), 232.1 [M(35Cl)þNa]þ
(63), 210.2 [M(35Cl)þH]þ (100). ESI-MS (neg.) m/z (%): 208.1
[M(35Cl)eH]ꢁ (100). Anal. Calcd (found) for C10H8ClNO2: C 57.30
(57.05); H 3.85 (3.74); N 6.68 (6.51).
Acknowledgements
This study was supported by the internal grant of TBU in Zlín
(No. IGA/FT/2012/015), funded from the resources of specific uni-
4.6.9. 3-Chloro-4-hydroxy-1-phenylquinolin-2-one (4c). Compound
was prepared from 1c in 6% yield (Table 1, Method A). Colorless
crystals, mp 263e272 ꢀC (ethanol). For 4c, mp 264 ꢀC was reported.23
IR: 3062,1631,1591,1550,1496,1334,1294,1184,1155,1080, 858, 752,
698, 658, 625, 467 cmꢁ1. For NMR spectra see Table 4. EI-MS m/z (%):
273 (22), 272 (44), 271 (Mþ(35Cl), 71), 270 (100),196(11),195(10),167
(25), 166 (11), 77 (34), 76 (16), 75 (11), 51 (27). ESI-MS (pos.) m/z (%):
565.1 [2M(35Cl)þNa]þ (26), 426.6 [3M(35Cl)þCa]2þ (11), 310.1
[M(35Cl)þK]þ (18), 294.1 [M(35Cl)þNa]þ (100), 272.1 [M(35Cl)þH]þ
(56). ESI-MS (neg.) m/z (%): 270.1 [M(35Cl)ꢁH]ꢁ (100). Anal. Calcd
(found) for C15H10ClNO2: C 66.31 (66.61); H 3.71 (3.74); N 5.16 (5.18).
ꢁ
ꢀ
versity research. The authors thank Mrs. H. Gerzova (Faculty of
Technology, Tomas Bata University in Zlín) for technical help.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.11.034.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
4.6.10. 3,3-Dichloro-1-methylquinoline-2,4(1H,3H)-dione (5b). Com-
pound was prepared from 1b in 2% yield (Table 1, Method A). Yellow
crystals, mp 144e148 ꢀC (cyclohexane). For 5b, mp 147 ꢀC was re-
ported.29 IR: 3118, 3093,1705,1678,1601,1469,1360,1296,1145, 845,
781, 746, 646, 573, 528 cmꢁ1. For NMR spectra see Table 4. ESI-MS
(pos.) m/z (%): 509.0 [2M(35Cl2)þNa]þ (8), 384.5 [3M(35Cl2)þCa]2þ
(12), 266.1 [M(35Cl2)þNa]þ (64), 244.1 [M(35Cl2)þH]þ (45), 180.1
[M(35Cl2)þHꢁHCOCl]þ (100). Anal. Calcd (found) for C10H7Cl2NO2: C
49.21, H 2.89, N 5.74; found C 49.32, H 2.86, N 5.66.
References and notes
ꢁ
ꢁ
ꢀ
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95, 1352e1372.
2. Ziegler, E.; Kappe, T. Monatsh. Chem. 1965, 96, 77e81.
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6,8(5H,9H)-dione (6b). Compound was prepared from 1b in re-
spective yields 8%, 3%, and 4% (Table 1, Method A), and from 3b in
61% yield (Table 3, Method D). Yellow crystals, mp >335 ꢀC. IR: 3077,
1655, 1624, 1597, 1460, 1417, 1336, 1305, 1151, 1113, 1045, 748, 667,
629, 503 cmꢁ1. For NMR spectra see Table 5. EI-MS m/z (%): 363
Table 5
1H and 13C chemical shifts of compounds 6
6ba
6cb
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Position
dH
dC
dH
dC
1, 13
2, 12
3, 11
4, 10
4a, 9a
6, 8
6a, 7a
13a, 14b
13b, 14a
10 (N-5, 9)
20 (N-5, 9)
30 (N-5, 9)
40 (N-5, 9)
8.24
7.62
7.86
7.67
d
123.8
127.2
134.9
117.4
139.5
162.8
107.8
116.5
154.1
32.8
d
8.26
7.47
7.59
6.87
d
121.8
123.3
131.5
115.9
138.7
158.2
106.1
113.0
149.5
136.8
129.1
130.3
129.4
d
d
d
d
28. Wittmann, H. Monatsh. Chem. 1965, 96, 523e526.
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d
d
d
d
ꢀ
ꢁ
ꢁ
31. Klasek, A.; Polis, J.; Mrkvicka, V.; Kosmrlj, J. J. Heterocycl. Chem. 2002, 39,
1315e1320.
3.93
d
d
7.45
7.70
7.65
32. Swamy, K. C. K.; Kumar, N. N. B.; Balaraman, E.; Kumar, V. P. P. Chem. Rev. 2009,
109, 2551e2651.
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d
d
d
d
a
Measured in CF3COOD.
Measured in DMSO-d6.
b

ꢀ
A. Klasek et al. / Tetrahedron 69 (2013) 492e499
499
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