A convenient approach to heterocyclic building blocks: Synthesis of novel ring systems containing a [5,6]pyrano[2,3-c]pyrazol-4(1H)-one moiety

Article abstract of DOI:10.3390/12010060

Starting from commercially available educts, a straightforward synthetic route to new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-, tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are prepared from 3-methyl-1-phenyl-2- pyrazolin-5-one and the corresponding o-haloarenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane: pyrimidino[4′,5′:5,6]pyrano[2, 3-c]pyrazol-4(1H)-one, thieno[3′,2′:5,6]pyrano[2,3c]pyrazol-4-(1H)- one, thieno[3′,4′:5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3″,2″:4′,5′]thieno-[2′,3′:5,6] pyrano[2,3-c]pyrazol-4(1H)-one, [1,3]dioxolo[5′,6′][1] benzothieno[2′,3′:5,6]pyrano-[2,3-c]pyrazol-4(1H)-one, pyridazino[4′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-one, and pyrazolo[4″,3″:5′,6′]pyrido[3′,4′:5,6] pyrano[2,3-c]pyrazol-6(9H)-one. While the latter two ring systems are directly obtained due to a spontaneous intramolecular substitution reaction, in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF). Detailed NMR spectroscopic investigations (¹H-, ¹³C-, ¹⁵N-) with the obtained compounds were undertaken to unambiguously prove the new structures.

Full text of DOI:10.3390/12010060

Molecules 2007, 12, 60-73
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
A Convenient Approach to Heterocyclic Building Blocks:
Synthesis of Novel Ring Systems Containing a
[5,6]Pyrano[2,3-c]pyrazol-4(1H)-one Moiety
Gernot A. Eller * and Wolfgang Holzer †
Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna,
Althanstrasse 14, A-1090 Vienna, Austria; † E-mail: wolfgang.holzer@univie.ac.at
* Author to whom correspondence should be addressed. E-mail: gernot.eller@univie.ac.at
Received: 15 January 2007; in revised form: 24 January 2007 / Accepted: 24 January 2007 /
Published: 26 January 2007
Abstract: Starting from commercially available educts, a straightforward synthetic route to
new heterocyclic building blocks is exemplified with the one- or two-step synthesis of tri-,
tetra-, or pentacyclic ring systems. Representatives of the following novel ring systems are
prepared from 3-methyl-1-phenyl-2-pyrazolin-5-one and the corresponding o-halo-
arenecarbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane:
pyrimidino[4',5':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, thieno[3',2':5,6]pyrano[2,3c]pyrazol-
4-(1H)-one,
[2',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, [1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano-
[2,3-c]pyrazol-4(1H)-one, pyridazino[4',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one, and
thieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one,
thieno[3'',2'':4',5']thieno-
pyrazolo[4'',3'':5',6']pyrido[3',4':5,6]pyrano[2,3-c]pyrazol-6(9H)-one. While the latter two
ring systems are directly obtained due to a spontaneous intramolecular substitution reaction,
in the other reactions uncyclised 4-aroylpyrazol-5-ols are produced, which are cyclised into
the target heterocycles in a subsequent synthetic step (i.e. treatment with NaH in DMF).
Detailed NMR spectroscopic investigations (1H-, 13C-, 15N-) with the obtained compounds
were undertaken to unambiguously prove the new structures.
Keywords: Fused-ring systems, NMR spectroscopy, heterocyclic building blocks,
acylations, pyrazolones.

Molecules 2007, 12
61
Introduction
The search for biologically active compounds is the driving force in pharmaceutical synthesis.
Since the majority of new molecules entering clinical studies contains at least one heterocyclic moiety
– predominantly N-heterocyclic ones [1] – the modification of these ring systems plays an important
role during drug development [2, 3]. Thus, there is always a specific need for novel heterocyclic ring
systems, both for finding new hit structures and in optimisation of lead compounds. Although
theoretically unlimited, in practical terms and due to technical and economical reasons, only a very
limited number of heterocycles is available for medicinal chemistry today.
Figure 1.
O
O
O
O
HOOC
H2N
i-Pr
Me
N
N
O
N
O
NH2
xanthone
amlexanox
A
γ
(dibenzo- -pyrone)
(Aphthasol™)
Our own interest in new and easily accessible heterocyclic building blocks stems from our ongoing
research on xanthone (= dibenzo-γ-pyrone) derivatives, in which one of the benzene rings is replaced
with a pyrazole nucleus and the other with a different heterocyclic moiety [4–6]. These interesting
substructures occur in several bioactive compounds, such as in the anti-ulcer drug, amlexanox
(Aphthasol™) [7, 8] or in the A2-subtype selective adenosine receptor antagonist A [9] (Figure 1).
Consequently we investigated several synthetic strategies to facilitate alteration of this biologically
interesting scaffold. While our primary research was based on synthetic approaches for the convenient
variation of the substituents at the pyrazole core (in particular those of positions C-3, N-1 and N-2)
[10, 11], we turned our interest to the modification of the molecule's skeleton as well as the possibility
of introducing substituents at other positions. The combination of these approaches would obviously
allow access to specifically customised molecules. Nevertheless, only a few skeletons – mainly
tricyclic ones like the possible four pyridines [4] – have been reported as successfully attempted up to
the present.
Results and Discussion
The purpose of this study is to report the convenient one- or two-step synthesis of novel
heterocyclic ring systems (Table 1) containing a [5,6]pyrano[2,3-c]pyrazol-4(1H)-one moiety starting
from commercially available educts. Thus, 2-pyrazolin-5-one 1 (a tautomer of 5-hydroxypyrazole
[12]) was reacted with the corresponding o-haloarenecarbonyl chlorides 2b–8b (Figure 2) in the
presence of excess calcium hydroxide in boiling 1,4-dioxane (the 'Jensen' method [13]) to affect the
selective acylation at the pyrazole C-4. However, the target compounds 9 and 10 were directly

Molecules 2007, 12
62
obtained in the reaction of the acid chlorides 2b and 3b with pyrazolone 1, without isolation of the
expected 4-aroylpyrazol-5-ols (Scheme 1).
Figure 2. Structure of o-haloarenecarbonyl chlorides 2b–8b.
O
O
O
S
S
Y
N
Y
Cl
Me
Cl
Cl
N
N
Br
S
Cl
S
O
O
O
O
N
SMe
S
O
O
Y
Y
Y
Cl
Me
N
N
Br
Cl
N
Cl
Cl
2
3
4
5
6
7b
8b
–
2a 6a: Y = OH
SOCl2
2b
–6b: Y = Cl
Obviously, spontaneous intramolecular cyclisation did occur (only) in these two cases, leading to
formation of two new bonds (C–C and O–C, respectively) in a single reaction step in these molecules.
This fact could be correlated with the activity towards nucleophilc aromatic substitution of the leaving
halogen in the presumptive intermediates 21 and 22 (Figure 3). In electron-rich aromatic compounds
(which are known to be less reactive towards nucleophilic aromatic substitutions) such as thiophene
derivatives 17–20 or even in the pyrimidine example 16 (where the halogen atom is situated meta to
the activating N atom and hence the least active position in such pyridines), no cyclisation was
observed. However, ring closure occurred spontaneously in the reactions of the acid chlorides 2b and
3b, in which the halogen was situated ortho or para to the activating N atom. This behaviour is in full
agreement with the observations made in cyclisation reactions leading to different pyridino[5,6]-
pyrano[2,3-c]pyrazol4(1H)-ones [4].
Scheme 1. Synthesis of the title compounds.
O
O
O
Me
Me
Me
(a)
2b 3b
(a)
4b 8b
activ.
hetero-
cycl.
inact.
hetero-
cycl.
N
N
N
,
–
N
N
O
N
O
Ph
Ph
Ph
9
,
10
–
11 15
1
(a)
(b)
O
Me
4b 8b
–
inact.
hetero-
cycl.
N
N
O
H
Cl(Br)
Ph
–
16 20
(a) o-haloarenecarbonyl chloride (2b–8b), Ca(OH)2, 1,4-dioxane. (b) NaH, DMF.

Molecules 2007, 12
63
When the uncyclised intermediates were isolated, the transformation into the target ring systems
was achieved by treatment of 4-aroylpyrazol-5-ols 16–20 with sodium hydride in refluxing
dimethylformamide.
Figure 3. Intermediate 4-Aroylpyrazol-5-ols 16–22.
O
O
O
Me
Cl
Me
Me
N
SMe
4
5
2
N
N
N
N
Me
N
N
6
N
O
H
N
N
O
H
N
N
N
O
H
Cl
Cl
Cl
Ph
Ph
Ph
21*
22*
Me
O
16
O
O
O
4
Me
4 Me
Me
S
6a S
Me
S
2
5
3a O
8a O
3
2
3
4
2
5
4
6
7
4a
7a
2
S
5
3
3a
N
N
N
N
8
N
O
H
S
N
O
H
N
O
H
N
O
H
Br
Br
Cl
Cl
Ph
Ph
Ph
Ph
17
18
19
20
* not isolated.
NMR spectroscopy
Recently, assignment of NMR signals (mainly 13C-NMR lines) using prediction programs [14]
such as CSEARCH [15] or ACD/C+H NMR Predictor [16] has become increasingly popular.
However, the quality of such empirical predictions strongly depends on the availability in the
corresponding databases of reliable material data from related structures. Thus, in cases where
insufficient (or low quality) data is available for the description of a specific chemical environment,
the prediction results are poor. The latter seems to be the case for many condensed heterocyclic
systems containing few protons. This lack of high quality data provided the motivation for us to
perform detailed NMR spectroscopic investigations of all novel compounds prepared and also their
precursors. Full and unambiguous assignment for all proton (1H-), carbon (13C-), and nitrogen (15N-)
resonances could be achieved by the combined application of different NMR spectroscopic techniques
13
[17] such as NOESY [18], NOE-difference experiments (1H{1H} [18] as well as C{1H} [18–20]),
fully 1H-coupled 13C-NMR spectra, APT, HMQC, gs-HMSC, and gs-HMBC spectra. The assignments
were also be facilitated by experiments with selective excitation such as 1D-TOCSY [21], 1D-
HETCOR [22], and selective long-range INEPT experiments [23]. 13C,1H spin coupling constants were
also determined and unequivocally assigned by two-dimensional (δ, J) long-range INEPT spectra with
selective excitation [24]. The 15N-NMR spectra were mainly recorded using the gradient selected,
sensitivity enhanced HMBC sequence [25].
The assignment of the numerous lines due to quaternary carbon atoms has not been a trivial task.
For instance, in target compounds 9–15, the chemical shifts of the two carbon atoms directly attached
to the pyran oxygen atom often closely resemble each other. Despite this fact, an unequivocal
1
13
distinction was possible on basis of the H-coupled C-NMR spectra. The signal of the carbon atom
located between pyrazole N-1 and the pyran oxygen always appears as a singlet, whereas the signal of

Molecules 2007, 12
64
the opposite pyran O–C atom is split by couplings to protons belonging to the system condensed on the
‘right’ side of the pyran ring. In compound 14 this diagnostic coupling is small (3JC8b,H8=1.0 Hz) and
emerges only after pronounced resolution enhancement. Discrimination of C-5a vs. C-8a in 14, C-5a
vs. C-10a in 15, and C-5 vs. C-7 in 13 is based on the upfield shift of the latter signal in each pair due
to the influence of the pyran oxygen atom. In the fused pyrimidine derivative 11 the discrimination of
the lines due to C-4a and C-8a (144.4 ppm, 146.0 ppm) is not possible considering the 1H-coupled 13C-
NMR spectrum, since both signals show a 3 Hz splitting due to coupling with H-8. Here, unambiguous
assignment of C-8a was achieved via a heteronuclear 13C{1H} NOE-difference experiment. Irradiation
of the H-8 transition only enhanced the signal of the spatially close C-8a whereas the line of the more
distant C-4a remained unaffected (Figure 3).
Figure 3. Unambiguous 13C-NMR signal assignment of C-4a and C-8 in compound 11 in
CDCl3: 13C{1H}-NOE on C-8 and C-8a upon selective irradiation of H-8.
C-8
O
4
Me
4a N
SMe
3
3a
9a
6
8a
8
C-3
N
N
N
O
Ph
H
C-8a
C-4a
11
Ph C-1
C-9a
146.0
150.1
152
150
148
146
144
Chemical Shift (ppm)
142
140
138
136
A similar approach was used to support the discrimination of the signals due to C-3a and C-6a in 4-
acylpyrazolone 19 (enhancement of the C-3a signal after irradiation of H-4). In the latter compound,
the signal of H-4 (attached to the carbon atom in β-position to the thiophene S-atom 6) can be simply
distinguished from that of H-5 (attached to C-5, in α-position to S-6) considering the larger 1J coupling
constants in the thiophene α-C,H fragment (in 19: 1JC5,H5=189.3 Hz > 1JC4,H4=173.3 Hz). This criterion
was also employed to achieve correct assignments in compounds 7b, 12, 14, and 17.
In most cases, assignment of 15N-NMR signals was easily made on basis of chemical shift
considerations together with correlations emerging from the gs-HMBC spectra. As an illustrative
example, the 15N,1H HMBC spectrum of compound 10 is displayed in Figure 4.

Molecules 2007, 12
65
Figure 4. 15N,1H-HMBC spectrum of compound 10 in CDCl3.
O
6
5
Me
7
N4
N8
Me
N9
Ph
O
N3
N2
1
10
Me
F2 Chemical Shift (ppm)
6.5 6.0 5.5
9.5
9.0
8.5
8.0
7.5
7.0
5.0
4.5
4.0
3.5
3.0
2.5
2.0
H-5
Ph
3-Me
1-Me 7-Me
168
176
184
192
200
208
216
224
232
240
248
256
264
272
280
288
296
304
312
320
N-3
N-9
N-4
N-8
N-2
1
13
15
1
13
Table 1. H-, C-, and N-NMR chemical shifts as well as selected H,1H and C,1H
Spin-Coupling Constants of the Novel Ring Systems 9–15.
Entry Structure
NMR data
O
4
9
1H-NMR (500 MHz, CDCl3) δ: 2.66 (3H, s, Me), 7.43 (1H, m, Ph
H-4), 7.56 (2H, m, Ph H-3,5), 7.92 (2H, m, Ph H-2,6), 8.36 (1H, s,
H-5).
5
Me
Cl
3
3a
9a
4a
8a
6
N
N
N
O
N
13C-NMR (125 MHz, CDCl3) δ: 14.0 (Me, J=129.7 Hz), 105.1 (C-
1
Ph
3
3a, JC3,Me=2.8 Hz), 121.6 (Ph C-2,6), 122.7 (C-4a, 2JC4a,H5=1.3 Hz),
1
126.9 (C-5, J=179.0 Hz), 128.3 (Ph C-4), 129.7 (Ph C-3,5), 136.1
2
(Ph C-1), 148.7 (C-3, JC3,Me=7.2 Hz), 152.2 (C-9a), 155.5 (C-6,
3
2JC6,H5=0.9 Hz), 160.3 (C-8a, JC8a,H5=7.1 Hz), 169.7 (C-4,
3JC4,H5=4.3 Hz).
15N-NMR (50 MHz, CDCl3) δ: −189.5 (N-1), −89.6 (N-2), −8.6 (N-
8), 19.9 (N-7).

Molecules 2007, 12
66
Table 1. Cont.
NMR data
Entry Structure
O
6
10
1H-NMR (300 MHz, CDCl3) δ: 2.67 (3H, s, 7-Me), 2.74 (3H, s, 1-
Me), 4.11 (3H, s, NMe), 7.42 (1H, m, Ph H-4), 7.56 (2H, m, Ph H-
3,5), 7.87 (2H, m, Ph H-2,6), 9.30 (1H, s, H-5). 1H-NMR (300 MHz,
DMSO-d6) δ: 2.59 (3H, s, 7-Me), 2.68 (3H, s, 1-Me), 4.05 (3H, s,
NMe), 7.50 (1H, m, Ph H-4), 7.65 (2H, m, Ph H-3,5), 7.94 (2H, m,
Ph H-2,6), 9.17 (1H, s, H-5).
5
Me
7
6a
5a
N
3a
9a
10a
N
Me
10b
N
O
N
N
Ph
1
Me
1
13C-NMR (75 MHz, CDCl3) δ: 14.0 (7-Me, J=129.4 Hz), 14.3 (1-
Me, 1J=128.8 Hz), 34.1 (NMe, 1J=140.9 Hz), 103.3 (C-10b,
4
3
3JC10b,1Me=3.0 Hz, JC10b,H5=1.2 Hz), 105.8 (C-6a, JC6a,7Me=2.8 Hz),
2
111.8 (C-5a, JC5a,H5=7.9 Hz), 121.3 (Ph C-2,6), 127.9 (Ph C-4),
2
129.5 (Ph C-3,5), 136.6 (Ph C-1), 140.4 (C-1, JC1,1Me=7.2 Hz),
2
1
148.3 (C-7, JC7,7Me=7.2 Hz), 149.9 (C-5, J=186.2 Hz), 151.6 (C-
3
3
9a), 154.4 (C-3a, JC3a,NMe=2.1 Hz, JC3a,H5=15.5 Hz), 155.5 (C-10a,
3JC10a,H5=8.3 Hz), 172.6 (C-6, 3JC6,H5=2.2 Hz).
15N-NMR (50 MHz, CDCl3) δ: −202.4 (N-3), −191.6 (N-9), −119.8
(N-4), −94.8 (N-8), −66.8 (N-2).
O
4
11
1H-NMR (300 MHz, CDCl3) δ: 2.68 (3H, s, 3-Me), 2.68 (3H, s,
SMe), 7.42 (1H, m, Ph H-4), 7.55 (2H, m, Ph H-3,5), 7.82 (2H, m,
Ph H-2,6), 8.96 (1H, s, H-8).
Me
4a N
SMe
3
3a
9a
6
8a
8
N
N
N
O
13C-NMR (75 MHz, CDCl3) δ: 14.1 (3-Me, J=129.6 Hz), 14.8
1
Ph
1
3
(SMe, J=141.8 Hz), 107.8 (C-3a, JC3a,3Me=2.8 Hz), 121.5 (Ph C-
2,6), 128.0 (Ph C-4), 129.6 (Ph C-3,5), 136.4 (Ph C-1), 144.4 (C-4a,
2
3JC4a,H8=3.0 Hz), 146.0 (C-8a, JC8a,H8=3.0 Hz), 148.8 (C-3,
1
2JC3,3Me=7.2 Hz), 150.1 (C-8, J=187.4 Hz), 151.5 (C-9a), 170.2 (C-
6, 3JC6,SMe=4.7 Hz, 3JC6,H8=12.8 Hz), 170.7 (C-4, 4JC4,H8=2.0 Hz).
15N-NMR (50 MHz, CDCl3) δ: −191.9 (N-1), −108.9 (N-5), −91.1
(N-2), −80.2 (N-7).
O
4
12
1H-NMR (300 MHz, CDCl3) δ: 2.68 (3H, s, Me), 6.95 (1H, d,
Me
3
3JH6,H5=5.9 Hz, H-6), 7.39 (1H, m, Ph H-4), 7.42 (1H, d, JH5,H6=5.9
3
3a
8a
4a
5
6
7a
N
Hz, H-5), 7.42 (2H, m, Ph H-3,5), 7.81 (2H, m, Ph H-2,6).
N
O
S
1
13C-NMR (75 MHz, CDCl3) δ: 14.1 (Me, J=129.3 Hz), 106.5 (C-
Ph
3a, 3JC3a,Me=2.7 Hz), 116.2 (C-6, 1J=191.2 Hz, 2JC6,H5=6.5 Hz), 121.3
1
2
(Ph C-2,6), 121.4 (C-5, J=175.0 Hz, JC5,H6=3.5 Hz), 126.0 (C-4a,
3
2JC4a,H5=4.3 Hz, JC4a,H6=8.1 Hz), 127.6 (Ph C-4), 129.5 (Ph C-3,5),
136.8 (Ph C-1), 147.8 (C-3, 2JC3,Me=7.1 Hz), 153.8 (C-8a), 163.7 (C-
7a, 3JC7a,H6=8.7 Hz, 3JC7a,H5=11.4 Hz), 171.0 (C-4).
15N-NMR (50 MHz, CDCl3) δ: −193.4 (N-1), −94.8 (N-2).

Molecules 2007, 12
67
Table 1. Cont.
Entry Structure
NMR data
O
4
13
1H-NMR (500 MHz, CDCl3) δ: 2.70 (3H, s, Me), 7.15 (1H, d,
3JH7,H5=3.3 Hz, H-7), 7.40 (1H, m, Ph H-4), 7.54 (2H, m, Ph H-3,5),
7.85 (2H, m, Ph H-2,6), 8.12 (1H, d, 3JH5,H7=3.3 Hz, H-5).
Me
5
7
3
3a
4a
7a
S
8a
N
N
O
13C-NMR (125 MHz, CDCl3) δ: 14.2 (Me, J=129.3 Hz), 104.8 (C-
1
Ph
3a, 3JC3a,Me=2.5 Hz), 105.7 (C-7, 1J=190.0 Hz, 3JC7,H5=4.3 Hz), 121.6
1
3
(Ph C-2,6), 126.3 (C-5, J=192.2 Hz, JC5,H7=5.9 Hz), 127.5 (Ph C-
4), 129.4 (Ph C-3,5), 129.5 (C-4a), 137.0 (Ph C-1), 148.7 (C-3,
2JC3,Me=7.1 Hz), 151.4 (C-7a, 3JC7a,H5=11.2 Hz), 154.7 (C-8a), 171.2
(C-4, 3JC4,H5=2.1 Hz).
O
4
14
1H-NMR (300 MHz, CDCl3) δ: 2.68 (3H, s, Me), 7.40 (1H, d,
Me
4a S 5a S
3
3JH8,H7=5.4 Hz, H-8), 7.41 (1H, m, Ph H-4), 7.47 (1H, d, JH7,H8=5.4
3
3a
9a
7
8
8b
8a
N
Hz, H-7), 7.56 (2H, m, Ph H-3,5), 7.87 (2H, m, Ph H-2,6).
N
O
1
13C-NMR (75 MHz, CDCl3) δ: 14.0 (Me, J=129.3 Hz), 105.8 (C-
Ph
3a, 3JC3a,Me=2.8 Hz), 117.9 (C-8, 1J=173.9 Hz, 2JC8,H7=4.1 Hz), 121.2
(Ph C-2,6), 127.0 (C-4a, 5JC4a,H7=0.8 Hz), 127.5 (Ph C-4), 129.5 (Ph
1
2
C-3,5), 130.2 (C-7, J=188.4 Hz, JC7,H8=6.9 Hz), 134.9 (C-8a,
3
2JC8a,H8=5.5 Hz, JC8a,H7=10.5 Hz), 137.1 (Ph C-1), 142.6 (C-5a,
3JC5a,H7=7.7 Hz, JC5a,H8=9.6 Hz), 147.2 (C-3, JC3,Me=7.1 Hz), 147.5
(C-8b, 3JC8b,H8=1.0 Hz, 4JC8b,H7=0.8 Hz), 153.1 (C-9a), 170.2 (C-4).
15N-NMR (50 MHz, CDCl3) δ: −193.2 (N-1), −93.8 (N-2).
1H-NMR (500 MHz, CDCl3) δ: 2.71 (3H, s, Me), 6.13 (2H, s, H-8),
7.24 (1H, s, H-6), 7.34 (1H, s, H-10), 7.43 (1H, m, Ph H-4), 7.59
(2H, m, Ph H-3,5), 7.91 (2H, m, Ph H-2,6).
3
2
O
4
15
6
Me
4a S
6a O
9a O
3
3a
5a
8
11a
10b
10a
N
10
N
O
1
13C-NMR (125 MHz, CDCl3) δ: 14.1 (Me, J=129.3 Hz), 99.6 (C-
Ph
1
4
1
10, J=168.0 Hz, JC10,H6=1.3 Hz), 102.3 (C-8, J=174.9 Hz), 102.9
1
4
3
(C-6, J=168.7 Hz, JC6,H10=1.3 Hz), 106.2 (C-3a, JC3a,Me=2.7 Hz),
3
121.2 (Ph C-2,6), 122.4 (C-4a), 122.5 (C-10a, JC10a,H6=6.3 Hz),
2
127.5 (Ph C-4), 129.6 (Ph C-3,5), 134.7 (C-5a, JC5a,H6=1.5 Hz,
3JC5a,H10=7.7 Hz), 137.1 (Ph C-1), 147.3 (C-3, 2JC3,Me=7.1 Hz), 147.7
2
3
3
(C-9a, JC9a,H10=4.2 Hz, JC9a,H8=1.9 Hz, JC9a,H6=6.1 Hz), 149.6 (C-
3
4
2
10b, JC10b,H10=3.2 Hz, JC10b,H6=0.9 Hz), 150.3 (C-6a, JC6a,H6=4.0
Hz, 3JC6a,H8=1.9 Hz, 3JC6a,H10=6.9 Hz), 153.3 (C-11a), 170.5 (C-4).
15N-NMR (50 MHz, CDCl3) δ: −193.2 (N-1), −94.5 (N-2).
Experimental
Materials and Methods
Melting points were determined on a Reichert–Kofler hot-stage microscope and are uncorrected.
Mass spectra were obtained on a Shimadzu QP 1000 instrument (EI, 70 eV) and on a Finnigan MAT

Molecules 2007, 12
68
8230 instrument (EI, 70 eV, HRMS). IR spectra were recorded on a Perkin-Elmer FTIR Spectrum
1000 spectrometer. Elemental analyses were performed at the Microanalytical Laboratory, University
of Vienna. 1H- and 13C-NMR spectra were recorded on a Varian UnityPlus 300 spectrometer at 28 °C
1
13
(299.95 MHz for H, 75.43 MHz for C) or on a Bruker Avance 500 spectrometer at 293 K (500.13
1
13
MHz for H, 125.77 MHz for C). The centre of the solvent signal was used as an internal standard
which was related to TMS with δ = 7.26 ppm (1H in CDCl3), δ = 2.49 ppm (1H in DMSO-d6), δ = 77.0
ppm (13C in CDCl3), and δ = 39.5 ppm (13C in DMSO-d6). The digital resolutions were 0.2 Hz/data
point in the H and 0.4 Hz/data point in the H-coupled 13C-NMR spectra (gated decoupling). 15N-
NMR spectra were obtained on a Bruker Avance 500 instrument with a ‘directly’ detecting broadband
observe probe and were referenced against external nitromethane (coaxial capillary). Systematic
names were generated with ACD/Name [26] according to the IUPAC recommendations and were also
checked manually to ensure correct use of nomenclature within this publication [27]. All starting
materials are commercially available and were purchased from Aldrich (1, 2a, 4a, 5a), Fluorochem
(8b), Frontier Scientific (6a), or Maybridge (3a, 7b), respectively. Product yields were not optimised.
1
1
o-Haloarenecarbonyl Chlorides 2b–6b: General Procedure.
A suspension of the commercially available o-haloarenecarboxylic acid 2a, 3a, 4a, 5a, or 6a
(3 mmol) in toluene (10 mL), DMF (1 drop), and excess SOCl2 (2 mL) were refluxed for 3 h. The
solvent and excess SOCl2 were removed under reduced pressure. Additional toluene (5 mL) was added
and the solvent was removed under reduced pressure. The remaining acid chlorides of type b were
used immediately, without further purification, in the next step. Commercially available acid chlorides
7b and 8b were used as purchased. Hitherto unpublished spectroscopic data of commercially available
starting materials are presented below.
1
3,6-Dichloropyridazine-4-carboxylic acid (2a). H-NMR (300 MHz, DMSO-d6) δ: 8.28 (1H, s, H-5),
9.72 (1H, s, OH); 13C-NMR (75 MHz, DMSO-d6) δ: 130.1 (C-5, 1J=181.3 Hz), 134.0 (C-4, 2JC4,H5=1.0
3
2
3
Hz), 152.0 (C-3, JC3,H5=7.5 Hz), 156.2 (C-6, JC6,H5=1.3 Hz), 163.0 (CO, JCO,H5=4.8 Hz); MS m/z
(%): 196 (M+, 8), 194 (M+, 54), 192 (M+, 71), 85 (57), 84 (100), 73 (47), 51 (49), 45 (59).
4-Chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (3a). 1H-NMR (300 MHz,
DMSO-d6) δ: 2.36 (3H, s, 3-Me), 3.32* (1H, br s, OH), 3.96 (3H, s, NMe), 8.85 (1H, s, H-6) * together
1
1
with trace H2O; 13C-NMR (75 MHz, DMSO-d6) δ: 14.5 (3-Me, J=128.9 Hz), 33.6 (NMe, J=140.9
2
3
2
Hz), 112.6 (C-3a), 118.5 (C-5, JC5,H6=8.2 Hz), 138.7 (C-4, JC4,H6=9.1 Hz), 141.3 (C-3, JC3,3Me=7.1
1
3
3
Hz), 151.2 (C-6, J=186.2 Hz), 151.5 (C-7a, JC7a,NMe=2.3 Hz, JC7a,H6=14.9 Hz), 165.2 (CO,
3JCO,H6=2.3 Hz); MS m/z (%): 227 (M+, 33), 226 (M+ − 1, 29), 225 (M+, 100), 224 (M+ − 1, 65).
1
5-Chloro-2-(methylthio)pyrimidine-4-carboxylic acid (4a). H-NMR (300 MHz, DMSO-d6) δ: 2.51
13
(3H, s, SMe), 7.40–10.20 (1H, br s, OH), 8.84 (1H, s, H-6); C-NMR (75 MHz, DMSO-d6) δ: 14.0
1
2
1
(SMe, J=141.9 Hz), 121.5 (C-5, JC5,H6=3.8 Hz), 157.0 (C-4), 158.2 (C-6, J=191.7 Hz), 164.5 (CO,
4JCO,H6=1.6 Hz), 169.9 (C-2, JC2,SMe=4.7 Hz, JC2,H6=12.4 Hz); 15N-NMR (50 MHz, DMSO-d6) δ:
3
3
−102.5 (N-3), −89.5 (N-1).

Molecules 2007, 12
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1
3-Chlorothieno[2,3-b]thiophene-2-carbonyl chloride (7b). H-NMR (300 MHz, CDCl3) δ: 7.31 (1H,
d, 3JH4,H5=5.4 Hz, H-4), 7.51 (1H, d, 3JH5,H4=5.4 Hz, H-5); 13C-NMR (75 MHz, CDCl3) δ: 119.9 (C-4,
2
3
4
1
1J=175.5 Hz, JC4,H5=4.1 Hz), 127.5 (C-3, JC3,H4=1.0 Hz, JC3,H5=0.8 Hz), 131.0 (C-5, J=189.0 Hz,
2JC5,H4=7.0 Hz), 131.5 (C-2, JC2,H5=1.0 Hz), 144.5 (C-6a, JC6a,H5=7.8 Hz, JC6a,H4=9.2 Hz), 146.3 (C-
3a, JC3a,H4=4.9 Hz, JC3a,H5=10.8 Hz), 156.8 (CO); MS m/z (%): 240 (M+, 3), 238 (M+, 14), 236 (M+,
5
3
3
2
3
18), 203 (42), 201 (100), 173 (18), 93 (15), 69 (18).
1
7-Chlorothieno[2,3-f][1,3]benzodioxole-6-carbonyl chloride (8b). H-NMR (300 MHz, CDCl3) δ:
5
5
13
6.13 (2H, s, H-2), 7.16 (1H, d, JH4,H8=0.5 Hz, H-4), 7.30 (1H, d, JH8,H4=0.5 Hz, H-8); C-NMR (75
MHz, CDCl3) δ: 101.2 (C-4, 1J=169.7 Hz), 102.1 (C-8, 1J=169.7 Hz), 102.5 (C-2, 1J=175.0 Hz), 127.4
3
3
3
(C-6), 130.0 (C-7, JC7,H8=3.8 Hz), 132.5 (C-7a, JC7a,H4=6.3 Hz), 136.9 (C-4a, JC4a,H8=7.4 Hz), 148.6
(C-8a, 2JC8a,H8=4.2 Hz, 3JC8a,H2=1.8 Hz, 3JC8a,H4=6.7 Hz), 151.5 (C-3a, 2JC3a,H4=3.8 Hz, 3JC3a,H2=1.7 Hz,
3JC3a,H8=7.2 Hz), 157.5 (CO); MS m/z (%): 278 (M+, 3), 276 (M+, 15), 274 (M+, 17), 241 (36), 239
(100), 211 (29), 201 (48), 69 (37).
Compounds 9, 10, 16–20: General Procedure.
Under anhydrous conditions, a solution/suspension of the corresponding o-haloarenecarbonyl
chloride 2b–8b (3 mmol) in anhydrous 1,4-dioxane (3–5 mL) was added to a suspension of pyrazolone
1 (523 mg, 3 mmol) and Ca(OH)2 (445 mg, 6 mmol) in anhydrous 1,4-dioxane (3–5 mL). The reaction
mixture was heated at reflux under stirring for 3 h. After cooling to room temperature, the mixture was
acidified with 2 M HCl (5–7 ml), stirred for 15 min, and poured into H2O (10–15 ml). After 30 min,
solid products were filtered off, washed with H2O, and recrystallised. NMR data of compounds 9 and
10 are presented in Table 1.
6-Chloro-3-methyl-1-phenylpyrazolo[4',3':5,6]pyrano[2,3-c]pyridazin-4(1H)-one
(9).
Off-white
needles (yield 66%); Mp 209–212.5 °C (aqueous ethanol); IR (KBr) cm−1: 1678; MS m/z (%): 315 (M+
+ 1, 6), 314 (M+, 36), 313 (M+ − 1, 27), 312 (M+, 100), 311 (M+ − 1, 45), 77 (37); Anal. Calcd. for
C15H9ClN4O2 (312.7106): C, 57.61; H, 2.90; N, 17.92. Found: C, 57.83; H, 3.12; N, 17.93.
1,3,7-Trimethyl-9-phenyl-3H-pyrazolo[3,4-b]pyrazolo[4',3':5,6]pyrano[2,3-d]pyridin-6(9H)-one (10).
Colourless needles (yield 63%); Mp 248.5–251 °C (aqueous ethanol); IR (KBr) cm−1: 1667; MS m/z
(%): 346 (M+ + 1, 19%), 345 (M+, 100), 344 (M+ − 1, 46); Anal. Calcd. for C19H15N5O2 (345.3547): C,
66.08; H, 4.38; N, 20.28. Found: C, 65.83; H, 4.44; N, 20.35.
[5-Chloro-2-(methylthio)pyrimidin-4-yl](5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methanone
1
(16). Colourless needles (yield 59%); Mp 212–217 °C (aqueous ethanol); H-NMR (500 MHz,
DMSO-d6) δ: 2.49 (3H, s, pyrazole 3-Me), 2.51 (3H, s, SMe), 7.00–10.00 (1H, br s, OH), 7.28 (1H, m,
Ph H-4), 7.46 (2H, m, Ph H-3,5), 7.60 (2H, m, Ph H-2,6), 8.82 (1H, s, pyrimidine H-6); 13C-NMR (125
MHz, DMSO-d6) δ: 13.7 (pyrazole 3-Me, 1J=130.3 Hz), 14.0 (SMe, 1J=141.8 Hz), 102.6 (pyrazole C-
3
2
4, JC4,3-Me=2.5 Hz), 120.7 (Ph C-2,6), 121.6 (pyrimidine C-5, JC5,H6=3.6 Hz), 126.1 (Ph C-4), 129.0

Molecules 2007, 12
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2
1
(Ph C-3,5), 135.8 (Ph C-1), 150.9 (pyrazole C-3, JC3,3-Me=6.7 Hz), 156.8 (pyrimidine C-6, J=190.5
Hz), 160.0 (pyrazole C-5), 163.0 (pyrimidine C-4, 3JC4,H6=3.7 Hz), 169.5 (pyrimidine C-2, 3JC2,SMe=4.7
Hz, 3JC2,H6=12.1 Hz), 182.8 (CO, 4JCO,H6=1.6 Hz); 15N-NMR (50 MHz, DMSO-d6) δ: −201.9 (pyrazole
N-1), −102.0 (pyrimidine N-3), −93.2 (pyrimidine N-1); the pyrazole N-2 was not found; IR (KBr)
cm−1: 1630; MS m/z (%): 362 (M+, 15), 360 (M+, 39), 326 (20), 325 (100), 201 (32), 159 (41), 91 (22),
77 (45); Anal. Calcd. for C16H13ClN4O2S (360.8180): C, 53.26; H, 3.63; N, 15.53. Found: C, 53.38; H,
3.78; N, 15.40.
(2-Bromo-3-thienyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methanone (17). Almost colourless
1
crystals (yield 73%); Mp 131–133 °C (aqueous ethanol); H-NMR (300 MHz, CDCl3) δ: 2.05 (3H, s,
3
3
Me), 7.04 (1H, d, JH4,H5=5.7 Hz, thiophene H-4), 7.31 (1H, m, Ph H-4), 7.38 (1H, d, JH5,H4=5.7 Hz,
thiophene H-5), 7.47 (2H, m, Ph H-3,5), 7.86 (2H, m, Ph H-2,6), 8.81 (1H, s, OH); 13C-NMR (75
MHz, CDCl3) δ: 14.2 (Me, 1J=128.9 Hz), 104.7 (pyrazole C-4, 3JC4,Me=2.6 Hz), 113.0 (thiophene C-2,
3JC2,H5=7.6 Hz, 3JC2,H4=12.4 Hz), 120.9 (Ph C-2,6), 126.9 (Ph C-4), 127.1 (thiophene C-4, 1J=172.2 Hz,
2JC4,H5=4.2 Hz), 127.5 (thiophene C-5, 1J=189.0 Hz, 2JC5,H4=6.8 Hz), 129.1 (Ph C-3,5), 137.1 (Ph C-1),
2
3
2
139.2 (thiophene C-3, JC3,H4=5.4 Hz, JC3,H5=8.7 Hz), 148.3 (pyrazole C-3, JC3,Me=7.0 Hz), 160.3
(pyrazole C-5), 186.8 (CO); 15N-NMR (50 MHz, CDCl3) δ: −190.3 (N-1), −100.6 (N-2); IR (KBr)
cm−1: 1619; MS m/z (%): 364 (M+, 7), 362 (M+, 7), 284 (18), 283 (100), 200 (13), 191 (16), 189 (13),
91 (17), 77 (26), 67 (24); Anal. Calcd. for C15H11BrN2O2S (363.2290): C, 49.60; H, 3.05; N, 7.71.
Found: C, 49.63; H, 3.20; N, 7.69.
(4-Bromo-3-thienyl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methanone (18). Almost colourless
1
crystals (yield 65%); Mp 120–121 °C (aqueous ethanol); H-NMR (300 MHz, CDCl3) δ: 2.03 (3H, s,
Me), 7.32 (1H, m, Ph H-4), 7.40 (1H, d, 3JH5,H2=3.3 Hz, thiophene H-5), 7.47 (2H, m, Ph H-3,5), 7.56
(1H, d, 3JH2,H5=3.3 Hz, thiophene H-2), 7.86 (2H, m, Ph H-2,6), 9.25 (1H, s, OH); 13C-NMR (75 MHz,
1
3
CDCl3) δ: 14.5 (Me, J=128.9 Hz), 104.8 (pyrazole C-4, JC4,Me=2.6 Hz), 108.7 (thiophene C-4,
2JC4,H5=1.0 Hz, JC4,H2=11.9 Hz), 120.9 (Ph C-2,6), 125.0 (thiophene C-5, J=192.8 Hz, JC5,H2=4.3
Hz), 126.9 (Ph C-4), 127.7 (thiophene C-2, 1J=189.3 Hz, 3JC2,H5=5.7 Hz), 129.1 (Ph C-3,5), 137.0 (Ph
3
1
3
2
3
2
C-1), 139.3 (thiophene C-3, JC3,H2=4.2 Hz, JC3,H5=8.0 Hz), 148.3 (pyrazole C-3, JC3,Me=6.9 Hz),
160.2 (pyrazole C-5), 186.6 (CO, JCO,H2=2.6 Hz); 15N-NMR (50 MHz, CDCl3) δ: −190.2 (N-1),
3
−100.7 (N-2); IR (KBr) cm−1: 1602; MS m/z (%): 364 (M+, 42), 362 (M+, 41), 283 (100), 200 (74), 191
(39), 189 (33), 91 (40), 77 (36), 69 (36), 67 (35); Anal. Calcd. for C15H11BrN2O2S (363.2290): C,
49.60; H, 3.05; N, 7.71; S, 8.83. Found: C, 49.79; H, 2.88; N, 7.51; S, 8.66.
(3-Chlorothieno[2,3-b]thien-2-yl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)methanone (19).
Yellowish crystals (yield 54%); Mp 193–197 °C (aqueous ethanol); 1H-NMR (300 MHz, DMSO-d6) δ:
2.29 (3H, s, Me), 4.32 (1H, s, OH), 7.30 (1H, m, Ph H-4), 7.32 (1H, d, 3JH4,H5=5.4 Hz, thienoth. H-4),
7.47 (2H, m, Ph H-3,5), 7.68 (2H, m, Ph H-2,6), 7.78 (1H, d, 3JH5,H4=5.4 Hz, thienoth. H-5); 13C-NMR
(75 MHz, DMSO-d6) δ: 13.4 (Me, 1J=129.2), 105.2 (pyrazole C-4, 3JC4,Me=2.7 Hz), 118.0 (thienoth. C-
3
4
1
2
3, JC3,H4=1.0 Hz, JC3,H5=0.9 Hz), 118.9 (thienoth. C-4, J=173.3 Hz, JC4,H5=4.8 Hz), 121.2 (Ph C-
1
2
2,6), 126.1 (Ph C-4), 129.0 (Ph C-3,5), 131.9 (thienoth. C-5, J=189.3 Hz, JC5,H4=7.4 Hz), 136.9 (Ph
3
3
5
C-1), 138.9 (thienoth. C-6a, JC6a,H5=8.0 Hz, JC6a,H4=9.1 Hz), 139.2 (thienoth. C-2, JC2,H5=0.8 Hz),

Molecules 2007, 12
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2
3
144.3 (thienoth. C-3a, JC3a,H4=5.1 Hz, JC3a,H5=10.6 Hz), 149.6* (pyrazole C-3), 156.4* (pyrazole C-
5), 179.7 (CO). * broad signal; MS m/z (%): 376 (M+, 2), 374 (M+, 7), 339 (38), 218 (21), 201 (36),
200 (100), 91 (33); Anal. Calcd. for C17H11ClN2O2S2 (374.8644): C, 54.47; H, 2.96; N, 7.47. Found: C,
54.24; H, 3.04; N, 7.45.
(7-Chlorothieno[2,3-f][1,3]benzodioxol-6-yl)(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-
methanone (20). Dark red powder (yield 93%); Mp 143–147.5 °C; 1H-NMR (300 MHz, DMSO-d6) δ:
2.28 (3H, s, Me), 5.32 (1H, s, OH), 6.17 (2H, s, tricycle H-2), 7.29 (1H, m, Ph H-4), 7.29 (1H, s,
tricycle H-8), 7.47 (2H, m, Ph H-3,5), 7.62 (1H, s, tricycle H-4), 7.67 (2H, m, Ph H-2,6); 13C-NMR (75
1
1
MHz, DMSO-d6) δ: 13.5 (Me, J=129.3 Hz), 100.7 (tricycle C-8, J=168.1 Hz), 102.1 (tricycle C-4,
1
3
1J=170.6), 102.2 (tricycle C-2, J=176.3), 105.4 (pyrazole C-4, JC4,Me=2.5 Hz), 120.1 (tricycle C-7,
3JC7,H8=3.7 Hz), 121.2 (Ph C-2,6), 126.2 (Ph C-4), 129.0 (Ph C-3,5), 130.9 (tricycle C-7a, 3JC7a,H4=6.3),
2
3
132.3 (tricycle C-4a, JC4a,H4=1.6 Hz, JC4a,H8=7.7 Hz), 134.7 (tricycle C-6), 136.7 (Ph C-1), 147.8
(tricycle C-8a, 2JC8a,H8=3.8 Hz, 3JC8a,H4=6.9 Hz), 148.9 (tricycle C-3a, 2JC3a,H4=3.5 Hz, 3JC3a,H8=7.0 Hz),
149.7 (pyrazole C-3, 2JC3,Me=7.1 Hz), 156.7 (pyrazole C-5), 180.1 (CO); MS m/z (%): 414 (M+, 3), 412
(M+, 7), 378 (22), 377 (100), 256 (28), 212 (53), 211 (26), 200 (67), 91 (31); Anal. Calcd. for
C20H13ClN2O4S (412.8462) · 0.1 H2O: C, 57.68; H, 3.24; N, 6.73. Found: C, 57.61; H, 3.38; N, 6.53.
Cyclisation of 4-Aroylpyrazol-5-ols 16–20 into Compounds 11–15; General Procedure.
Under anhydrous conditions, the corresponding 4-aroylpyrazol-5-ol 16–20 (1 mmol) was
dissolved/suspended in anhydrous DMF (5 mL) and added to a suspension of NaH (60% in mineral
oil; 1 mmol) in anhydrous DMF (5 mL). The reaction mixture was heated at reflux overnight and the
solvent was then removed under reduced pressure. H2O (5 mL) was added to the residue and stirring
was continued for 1 h further. The precipitate formed was filtered off, washed with H2O and petroleum
ether and recrystallised. NMR data of compounds 11–15 are presented in Table 1.
3-Methyl-6-(methylthio)-1-phenylpyrazolo[4',3':5,6]pyrano[3,2-d]pyrimidin-4(1H)-one (11). Colour-
less needles (yield 67%); Mp 242.5–244.5 °C (aqueous ethanol); IR (KBr) cm−1: 1672; MS m/z (%):
325 (M+ + 1, 18), 324 (M+, 100), 77 (22); Anal. Calcd. for C16H12N4O2S (324.3571): C, 59.25; H, 3.73;
N, 17.27. Found: C, 59.29; H, 3.86; N, 17.06.
3-Methyl-1-phenylthieno[3',2':5,6]pyrano[2,3-c]pyrazol-4(1H)-one (12). Colourless needles (yield
92%); Mp 176–179 °C (aqueous ethanol); IR (KBr) cm−1: 1642; MS m/z (%): 283 (M+ + 1, 22), 282
(M+, 100), 281 (M+ − 1, 58), 77 (28); Anal. Calcd. for C15H10N2O2S (282.3171): C, 63.81; H, 3.57; N,
9.92. Found: C, 63.65; H, 3.79; N, 9.74.
3-Methyl-1-phenylthieno[3',4':5,6]pyrano[2,3-c]pyrazol-4(1H)-one (13). Beige powder (yield ≤ 5%);
Mp 138–145 °C; MS m/z (%): 283 (M+ + 1, 24), 282 (M+, 100), 281 (M+ − 1, 79), 77 (27); HRMS m/z:
282.0456 (Calcd for C15H10N2O2S: 282.0463).

Molecules 2007, 12
72
3-Methyl-1-phenylthieno[3'',2'':4',5']thieno[2',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one (14). Slightly
yellowish needles (yield 90%); Mp 239–243 °C; IR (KBr) cm−1: 1646; MS m/z (%): 339 (M+ + 1, 21),
338 (M+, 100), 337 (M+ − 1, 45), 77 (18); Anal. Calcd. for C17H10N2O2S2 (338.4035): C, 60.34; H,
2.98; N, 8.28. Found: C, 60.15; H, 3.27; N, 8.28.
3-Methyl-1-phenyl[1,3]dioxolo[5',6'][1]benzothieno[2',3':5,6]pyrano[2,3-c]pyrazol-4(1H)-one (15).
Almost colourless needles (yield 80%); Mp 324–327 °C (toluene); IR (KBr) cm−1: 1653; MS m/z (%):
377 (M+ + 1, 35), 376 (M+, 100), 375 (M+ − 1, 38), 91 (22), 77 (27); Anal. Calcd. for C20H12N2O4S
(376.3853): C, 63.82; H, 3.21; N, 7.44. Found: C, 63.59; H, 3.42; N, 7.33.
Acknowledgements
We are grateful to Dr. Csaba Szántay Jr. for providing a pulse sequence for the 13C{1H} NOE-
difference experiments and to Dr. L. Jirovetz for recording the mass spectra.
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