Heterocyclic analogs of xanthiones: 5,6-fused 3-methyl-1-phenylpyrano[2,3- c]pyrazol-4(1H) thiones - Synthesis and NMR (1H, 13C, 15N) data

Article abstract of DOI:10.1002/mrc.2609

Various [5,6]pyrano[2,3-c]pyrazol-4(1H)-thiones were synthesized in high yields by treatment of the corresponding [5,6]pyrano[2,3-c]pyrazol-4(1H)-ones with Lawesson's reagent. Detailed NMR spectroscopic studies were undertaken of the title compounds. Comp

Full text of DOI:10.1002/mrc.2609

Research Article
Received: 10 February 2010
Revised: 17 March 2010
Accepted: 17 March 2010
Published online in Wiley Interscience: 22 April 2010
(www.interscience.com) DOI 10.1002/mrc.2609
Heterocyclic analogs of xanthiones: 5,6-fused
3-methyl-1-phenylpyrano[2,3-c]pyrazol-4(1H)
thiones – synthesis and NMR (1H, 13C, 15N) data
Valerie Huemer, Gernot A. Eller and Wolfgang Holzer∗
Various [5,6]pyrano[2,3-c]pyrazol-4(1H)-thiones were synthesized in high yields by treatment of the corresponding
[5,6]pyrano[2,3-c]pyrazol-4(1H)-oneswith Lawesson’sreagent. DetailedNMRspectroscopicstudieswereundertakenofthetitle
compounds. Complete and unambiguous assignment of chemical shifts (1H, 13C, 15N) and coupling constants (1H,1H; 13C,1H)
was achieved by the combined application of various one- and two-dimensional (1D and 2D) NMR spectroscopic techniques.
Unequivocal mapping of most 13C,1H spin coupling constants is accomplished by 2D (δ, J) long-range INEPT spectra with
c
selective excitation. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Keywords: 1H NMR; 13C NMR; 15N NMR; [5,6]pyrano[2,3-c]pyrazol-4(1H)-thiones; Lawesson’s reagent
Introduction
reagents.[11,15,16] Lawesson’s reagent (2,4-bis(4-methoxyphenyl)-
1,3,2,4-dithiadiphosphetane 2,4-disulfide) has been commonly
used for this purpose and usually permits efficient conversion of
ketones into thioketones.[17–19] Employing this method, namely
by treatment of compounds 4 with 0.5 equivalents of Lawesson’s
reagent in boiling toluene, we obtained the corresponding target
compounds 5 in high yields (Scheme 2). In the same manner,
thiones 7 and 9, required for comparison purposes, were synthe-
sized from oxo compounds 6 and 8, respectively (Scheme 2). The
latter were prepared according to known procedures (6,[2,20] 8[21]).
In the course of a program devoted to the synthesis of new
heterocyclic scaffolds for bioactive compounds,[1–10] we recently
presented the synthesis of various [5,6]pyrano[2,3-c]pyrazol-
4(1H)-ones of type 4 via reaction of 2-pyrazolin-5-ones 1 with
o-haloheteroarenecarbonyl chlorides 2 and the subsequent
ring closure of the resulting 4-heteroaroylpyrazol-5-ols
3
(Scheme 1). Following this approach, we have obtained type 4
compounds carrying – among others – a pyridine (all positional
isomers),[1] quinoline,[1] thiophene (all positional isomers),[2,3]
benzo[b]thiophene,[2] and thieno[2,3-b]thiophene system[3] as
the variable heteroaromatic moiety (‘Het’) condensed to the
central γ -pyranone ring.
NMR Spectroscopic Investigations
The1HNMRdataof compounds 4a–j, 6–9arecollectedinTable 1.
Assignment of signals due to N-phenyl system is easy considering
therelativeintensitiesandthecouplingpatterns(Ph-2,6resembles
a doublet, Ph-3,5 and Ph-4 a triplet). The mapping of signals of
protons attached to the variable heterocyclic system (‘Het’) at the
‘east end’ of the condensed systems (according to Scheme 2)
is mainly based on chemical shift considerations and on COSY,
NOE difference and one-dimensional (1D) TOCSY experiments.[22]
Moreover, information from the 1H-coupled 13C NMR spectra can
be employed to achieve unambiguous assignments. Thus, for
instance, in thiophene containing systems 5e, 5g, and 5j carbons
being in alpha position to the sulfur atom can be distinguished
from those in β positions on the basis of their 1J(13C,1H) coupling
constants (α-C: 1J ∼ 190 Hz; β-C: 1J ∼ 175 Hz)[23] (Table 3). Via
correlations in the HSQC spectra, then, also the corresponding
1H-signals can be easily assigned. Protons located in position 5 of
the anellated ring system receive a downfield shift as a result of the
Thioanalogsofflavones,isoflavones,xanthones,andrelatedsys-
tems have received considerable attention due to the importance
of such molecules in biology and photochemistry as well as their
usefulnessassyntheticbuildingblocks.[11] Consideringthesefacts,
in the present paper we report on the synthesis of the thio analogs
5 of the above-mentioned polycycles 4, in which the pyran-4-one
moiety is replaced by the corresponding pyran-4-thione. More-
over, we present the results of extensive NMR (1H, 13C, 15N) studies
undertaken with the title compounds and some related systems,
with full and unambiguous assignment of all chemical shifts and
most spin coupling constants. The obtained data of these rare
condensed heteroaromatic systems can be considered as valuable
and reliable reference material for databases used in NMR predic-
tion programs such as CSEARCH[12]/NMRPREDICT[12,13] and ACD/C
+ H predictor.[14] Such programs have become very popular in the
last few years, particularly for predicting 13C-NMR chemical shifts.
Results and Discussion
∗
Correspondenceto:Wolfgang Holzer,DepartmentofDrugandNaturalProduct
Synthesis,FacultyofLifeSciences,UniversityofVienna,Althanstrasse14,A-1090
Vienna, Austria. E-mail: wolfgang.holzer@univie.ac.at
Chemistry
The transformation of carbonyl compounds into their thio
analogs can be achieved by the application of many different
Department of Drug and Natural Product Synthesis, University of Vienna,
A-1090 Vienna, Austria
c
Magn. Reson. Chem. 2010, 48, 476–482
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Synthesis and NMR data on heterocyclic analogs of xanthiones
O
R3
N
R3
N
O
R3
O
Cl
Het
Het
Het
N
O
N
R1
N
N
X
O
X
OH
R1
R1
1
2
3
4
Scheme 1. Synthesis of [5,6]pyrano[2,3-c]pyrazol-4(1H)-ones 4.
S
O
Me
N
Me
Lawesson's reagent
toluene, reflux
Het
N
Het
N
N
O
O
Ph
Ph
4a-j, 6, 8
5a-j, 7, 9
S
S
S
S
Me
Me
3
Me
Me
5
N
4
4a
8a
3a
9a
6
N
N
2 N
1 N
N
N
N
9
7
N
N
N
O
O
O
N
O
8
Ph
Ph
Ph
Ph
5a
5b
5c
5d
S
S
S
Me
Me
3
Me
N
4
3a
4a
S 5
2 N
1 N
N
S
6
8
S
N
N
7a
5
O
O
8a
O
7
Ph
Ph
Ph
5e
5f
5g
S
S
S
Me
Me
Me
6
9
4
5
9
4
4
5
5a
4a
3a
3a
9b
4a
8b
4a
9b
3a
3
3
3
S
S
7
8
5a
5a
6
2
2
N
N
1 N
2 N
1 N
Ph
10
11
9
6
S
1 N
O
N
O
O
7
11a
10a
10a
9a
8a
9a
7
10
Ph
Ph
8
8
5h
5i
5j
O
S
S
O
Me
3
Me
N
Me
Me
N
4
5
8
4a
8a
3a
6
7
2
N
N
9
O
1 N
N
N
N
9a
O
S
S
Ph
Ph
Ph
Ph
6
7
8
9
Scheme 2. Synthesis and atom numbering of the investigated compounds.
magnetic anisotropy of the adjacent C S bond. Thus, chemical
shifts of H-5 in 5b and 5h (pyridine 2-H, quinoline 4-H) come close
to 10 ppm.
the N-phenyl system or only small impact on those of 3-Me, C-3,
and peripheral carbon atoms of the heteroaromatic system, the
chemical shifts of the carbon atoms belonging to the central
pyrane ring change drastically. Thus, in compounds 4 there is a
pronounced ‘push–pull situation’ leading to a strong polarization
of the pyrane C C bonds – reflected by large chemical shifts of
carbons attached to the pyrane O-atom and small ones of those
in β-position to the ring oxygen. In contrast, with compounds
5 this polarization effect is much less developed, resulting in
an upfield shift for carbons directly bonded to the pyrane
O-atoms, whereas those in β-position receive a marked downfield
shift compared to the corresponding signals in compounds 4.
Switching from compound 6 to 7 shows the same typical effects
(C-3a: 104.9 → 116.3 ppm; C-4a: 123.3 → 127.9 ppm; C-8a:
154.4 → 149.7 ppm; C-9a: 152.9 → 146.5 ppm). The chemical
shift of C-4 rises between 20 and 25 ppm in the transformation 4
→ 5 or 6 → 7. The order of magnitude regarding these changes is
The 13C NMR chemical shifts of the investigated compounds
are collected in Table 2. Assignments are based on HSCQ (HMQC),
HMBC,andlong-rangeINEPTexperimentswithselectiveexcitation
(INAPT).[22] In rare cases (for instance, distinction of C-6 vs C-8 in 9),
HMQC-COSY spectra were consulted. Within type 5 compounds,
the signals due to the N-phenyl ring show a high degree of
consistency; this is also the case for δ(3-Me), δ(C-3), and δ(C-3a).
The C S (C-4) resonance is located between 190 and 198 ppm
and is, of course, to some degree dependent on the nature
of the variable heteroaromatic system. Comparison of the 13C
chemical shift data of compounds 5 with those of corresponding
type 4 moieties[1–3] clearly shows the effects of replacing the
central pyran-4-one by a pyran-4-thione system. Whereas this
replacement has nearly no influence on the chemical shifts of
c
Magn. Reson. Chem. 2010, 48, 476–482
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

V. Huemer, G. A. Eller and W. Holzer
Table 1. 1H NMR chemical shifts of 5a–j, 6–9 (δ in ppm, CDCl3)
Compounds
Ph 2,6
Ph 3,5
Ph 4
3-Me
H-5
H-6
H-7
H-8
Other H
Instr.j
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
6
7.86
7.84
7.89
7.97
7.86
7.85
7.82
8.00
7.94
7.90
7.87
7.89
7.71
7.71
7.55
7.56
7.59
7.56
7.55
7.55
7.54
7.58
7.61
7.59
7.54
7.55
7.56
7.58
7.41
7.43
7.45
7.41
7.41
7.41
7.40
7.43
7.45
7.44
7.38
7.40
7.45
7.47
2.78
2.77
2.79
2.81
2.80
2.77
2.78
2.83
2.77
2.81
2.69
2.80
2.81
2.90
–
8.87a
–
8.66c
7.51d
7.77e
–
6.95g
8.15
7.81
–
7.64a
8.80b
–
8.69d
7.22e
7.18f
–
7.93a
7.39b
9.00c
–
–
a
a
a
a
a
b
a
a
a
b
a
b
b
b
9.83b
8.49c
9.15d
–
–
–
–
–
–
8.36f
7.66g
9.64h
–
–
–
–
–
7.65
7.55
7.48i
7.68
7.68
7.60
7.56
7.91
7.48
7.44i
7.51
7.49
7.54
7.49
8.11 (H-9)
8.02 (H-9)
–
–
–
–
–
–
8.33
8.76
8.64
9.17
7.43
7.42
7.53
7.49
7
8
9
a 3J(6, 7) = 8.4 Hz, 4J(6, 8) = 1.4 Hz, 3J(7, 8) = 4.3 Hz.
b 4J(5, 7) < 1 Hz, 5J(5, 8) < 1 Hz, 3J(7, 8) = 5.7 Hz.
c 3J(5, 6) = 5.3 Hz, 5J(5, 8) < 1 Hz, 4J(6, 8) < 1 Hz.
d 3J(5, 6) = 7.9 Hz, 4J(5, 7) = 2.0 Hz, 3J(6, 7) = 4.6 Hz.
e 3J(6, 7) = 5.6 Hz.
f 4J(5, 7) = 3.8 Hz.
g 3J(5, 6) = 6.0 Hz.
h Singlet.
i 3J(7, 8) = 5.4 Hz.
j a: recorded at 300 MHz; b: recorded at 500 MHz.
Table 2. 13C NMR chemical shifts of 5a–j, 6–9 (δ in ppm, CDCl3)
Compounds Ph 1 Ph 2,6 Ph 3,5 Ph 4 3-Me C-3 C-3a
136.5 121.4 129.5 127.8 15.9 151.0 118.4 197.3 141.7
C-4
C-4a
C-5
–
C-5a
C-6
C-7
C-8
Other C
5a
5b
5c
5d
5e
5f
–
–
–
–
–
–
–
148.5 127.2 127.2 C-8a: 146.9; C-9a: 145.6
136.4 121.6 129.6 128.0 15.8 150.9 117.2 196.6 123.0 152.3
136.5 121.5 129.6 128.0 15.8 150.9 117.6 195.9 131.9 120.8
136.6 121.4 129.6 127.8 15.7 150.8 116.5 197.3 122.8 139.8
–
153.0 112.2 C-8a: 155.1; C-9a: 145.7
141.8 C-8a: 145.0; C-9a: 146.0
146.2
–
122.7 152.2
134.8 117.4
–
–
–
–
C-8a: 154.4; C-9a: 147.1
C-7a: 147.7; C-8a: 148.1
C-7a: 146.5; C-8a: 148.3
C-7a: 156.8, C-8a: 147.8
136.7 121.4 129.5 127.7 15.3 149.2 114.5 190.9 135.8
–
136.7 121.6 129.4 127.7 15.9 150.9 114.8 195.1 135.3 127.4
136.6 121.3 129.5 127.7 15.6 149.9 115.8 193.5 133.2 124.0
–
105.6
–
5g
5h
116.8
136.6 121.8 129.6 127.9 15.9 151.2 115.8 197.9 121.7 141.9 127.3 129.9 127.1 133.2 C-9: 127.8; C-9a: 147.9;
C-10a: 152.5; C-11a:
147.5
5i
5j
136.9 121.1 129.6 127.7 15.3 149.0 115.6 191.1 135.0
136.8 121.4 129.6 127.8 15.4 149.0 114.3 190.4 138.8
–
–
140.8 123.7 128.8 125.5 C-9: 122.2; C-9a: 128.7;
C-9b: 141.8; C-10b:
147.7
145.0
–
130.1 118.5 C-8a: 134.9; C-8b: 140.3;
C-9a: 147.5
6
7
8
9
137.0 121.2 129.4 127.3 14.1 148.1 104.9 173.5 123.3 126.8
136.8 121.2 129.4 127.5 16.0 150.8 116.3 197.9 127.9 129.3
138.5 123.0 129.7 128.4 14.2 152.5 115.5 177.4 131.2 129.2
138.3 123.2 129.7 128.6 17.6 155.0 126.7 202.9 136.4 132.7
–
–
–
–
125.2 133.7 117.6 C-8a: 154.5; C-9a: 152.9
125.7 133.6 117.8 C-8a: 149.7; C-9a: 146.5
127.0 131.9 126.7 C-8a: 132.9; C-9a: 139.8
127.5 131.3 126.7 C-8a: 127.5; C-9a: 134.0
in good agreement with those found by Still and coworkers within
the changeover from xanthone (9H-xanthen-9-one) to xanthione
(9H-xanthene-9-thione), with C-8a/C-9a 121.5 → 128.7 ppm, C-
4a/C-10a 155.7 → 150.1 ppm, and C-9 176.6 → 204.4 ppm
(Fig. 1).[24]
Comparing the 13C chemical shifts of compounds 6, 7, 8, and
9 explicitly demonstrates the effect of replacing the ring oxygen
by sulfur (6 → 8, 7 → 9) and by changing C O to C S (6
→ 7, 8 → 9) on the example of the benzene-fused tricycle
(Fig. 2, see also Table 2). In Fig. 1, the corresponding changes
can be recognized for the transitions xanthone → thioxanthone,
xanthione → thioxanthione as well as for those of xanthone →
xanthione and thioxathone → thioxanthione.[24–26]
In Table 3, the 13C,1H coupling constants of the investigated
compounds are summarized. The data are mainly extracted from
the fully 1H-coupled 13C NMR spectra (gated decoupling). In
ambiguous cases, 2D (δ,J) long-range INEPT spectra with selective
excitation[27] were used for the definitive mapping of long-range
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 476–482

Synthesis and NMR data on heterocyclic analogs of xanthiones
upfield shift of N-8 (−102.3 ppm). In 5b (‘para’ position of O-8 and
N-6), this effect is less pronounced (δ N-6 −77.4 ppm), whereas
in 5a (δ N-5 −65.7 ppm) and 5c (δ N-7 −56.3 ppm) it has only
very little influence. Comparison of the 15N chemical shifts of
N-1 and N-2 in compounds 6-9 clearly indicates the effect of
substituting C O by C S (6 → 7, 8 → 9) as well as substitution
of the ring oxygen atom by sulfur (6 → 8, 7 → 9). Whereas
the former transformation leads to only small effects (∼3 ppm
upfield shift for N-1, ∼2.5 ppm downfield shift for N-2), the
changeover from pyrane to thiopyrane affects δ(N-1) (∼15 ppm
downfield shift) and δ(N-2) (∼20 ppm downfield shift) much more
distinctively. Again, the latter effect can be casually explained
by the less pronounced electron-releasing mesomeric effect of
sulfur compared to oxygen. Comparison of the 15N chemical shift
data of compounds 4[1–3] with those of 5, in principle, shows
similar effects as found with the transformation 6 → 7, namely
2–3 ppm upfield shift for pyrazole N-1 and 2–2.5 ppm downfield
shift for pyrazole N-2. The pyridine 15N atoms in 5a–d suffer
small downfield shifts in relation to the corresponding type 4
compounds.
O
S
129.5
126.3
128.7
121.5
123.5
134.4
124.4
134.5
176.6
204.4
O
O
150.1
155.7
117.7
129.8
118.0
131.6
xanthone
xanthione
O
S
137.5
129.2
180.0
126.2
132.2
125.9
133.3
211.6
S
S
131.9
137.2
125.9
126.9
thioxanthone
thioxanthione
Figure 1. 13
C
NMR chemical shifts of xanthone,[24] xanthione,[24]
thioxanthone,[25] and thioxanthione[26] (CDCl3).
14.1
O
16.0
Me
S
Me
In conclusion, we have presented an efficient synthesis of
various novel [5,6]pyrano[2,3-c]pyrazol-4(1H)-thiones (5a–j) and
given full and unambiguous assignments of 1H, 13C, and 15N NMR
chemical shifts. Moreover, an analysis of many spin coupling
constants (1H,1H: 13C,1H) with the investigated systems was
provided.
129.3
117.8
126.8
127.9
123.3
104.9
116.3
150.8
148.1
125.2
133.7
125.7
133.6
173.5
197.9
N
N
N 152.9
N 146.5
O 154.5
O 149.7
117.6
136.8
137.0
121.2
129.4
121.2
129.4
6
7
127.5
127.3
Experimental
14.2
17.6
O
S
Me
Me
132.7
126.7
129.2
126.7
131.2
136.4
115.5
126.7
All NMR experiments were performed using standard NMR spec-
troscopic techniques.[22] The 1H NMR and 13C NMR spectra were
recorded from CDCl3 solutions either on a Varian UnityPlus NMR
spectrometer (300 MHz for 1H, 75 MHz for 13C) or on a Bruker
Avance 500 instrument (500 MHz for 1H, 125 MHz for 13C) at 25 ◦C
using 5-mm direct detection broad-band probes and deuterium
lock. The center of the solvent signal was used as an internal
standard, which was related to tetramethylsilane with δ 7.26 ppm
(1H) and δ 77.0 ppm (13C). The re◦cording conditions were the
152.5
155.0
127.0
131.9
127.5
131.3
177.4
202.9
N
N
N 139.8
N 134.0
S 132.9
S 127.5
138.5
138.3
123.0
129.7
123.2
129.7
8
9
128.6
128.4
Figure 2. 13C NMR chemical shifts of 6–9 (CDCl3).
1
following: H NMR: pulse angle 30 , acquisition time 5 s, digital
1
13C,1H coupling constants. Thus, for instance, in the H-coupled
13C NMR spectrum of 5b, the signal due to C-8a (155.1 ppm) is split
by 9.7, 7.6, and 3.8 Hz coupling. In the 2D (δ,J) long-range INEPT
spectra with selective excitation of H-7, the signal of C-8a is split by
9.7 Hz - thus assigning 3J(C8a,H7) to be 9.7 Hz - whereas in a similar
experiment upon selective excitation of H-5, the C-8a signal is split
by 7.6 Hz. Hence, the correct assignments 3J(C8a,H7) = 9.7 Hz,
3J(C8a,H5) = 7.6 Hz, and 2J(C8a,H8) = 3.8 Hz (following indirectly)
canbeunequivocallygiven. Expectedly, 13C,1Hcoupling constants
at the pyrazole moiety of compounds 5 are hardly different from
the corresponding ones in 4.[1–3] In this regard, also the changes
of couplings within the variable heteroaromatic systems are not
significant.
Finally, Table 4 gives the 15N NMR data of 5a–j and 6–9. Within
thecompound5series,the15Nchemicalshiftsofpyrazolenitrogen
atoms N-1 (−196.5 to −194.3 ppm) and N-2 (−93.1 to −90.7 ppm)
are very consistent, indicating the marginal influence of the
variable heterocyclic system on these resonances. In contrast,
the 15N chemical shift of the pyridine N-atom in compounds
5a-d is strongly influenced by the distinct electron donating
resonance (+M) effect of the oxygen atom O-9: in 5d, O-9 and
N-8 are located in the ‘ortho’ position leading to a considerable
resolution 0.2 Hz/data point, spectral width 16 ppm, 16 transients,
relaxationdelay5 s;broad-banddecoupled13CNMRspectra:pulse
angle 30◦, acquisition time 2 s, digital resolution 0.5 Hz/data point,
spectral width 220 ppm, 128–1024 transients, relaxation delay
2 s, exponential multiplication with 1.0 Hz line broadening factor
before FT; gated decoupled 13C NMR spectra: as above but ac-
quisition time 2.5 s, digital resolution 0.4 Hz/data point, 512–8192
transients,relaxationdelay2.5 s,resolutionenhancementbyGaus-
sian weighting (Varian: lb = −0.15, gf = 0.7; Bruker: lb = −0.6,
gb = 0.2) before FT. Full and unambiguous assignments were
achieved by consequent application of fully 1H-coupled 13C NMR
spectra (gated decoupling), gs-HSQC[28] (1024 × 256 data matrix,
10 ppm for 1H, 160 ppm for 13C, 4 transients accumulated per t1
increment; optimized for J = 160 Hz, qsine multiplication in both
dimensions), and gs-HMBC[29] (1024×256 data matrix, 10 ppm for
1H, 180 ppm for 13C, 8 transients accumulated per t1 increment;
optimized for J = 8 Hz, sine multiplication in both dimensions)
techniques to all compounds. The unequivocal mapping of 13C,1H
coupling constants was performed via 2D long-range INEPT (δ,J)
spectra with selective excitation (DANTE)[27] of unequivocally as-
signed proton resonances (12–24 Hz excitation width, optimized
for J = 8 Hz, 32 increments for 20 Hz width in F1, 128 transients
c
Magn. Reson. Chem. 2010, 48, 476–482
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

V. Huemer, G. A. Eller and W. Holzer
Table 3. Selected 13C,1H spin coupling constants of 5a–j, 6–9 (Hz, CDCl3)
Compounds 1J(3-Me) 2J(3,3-Me) 3J(3a,3-Me) 3J(4,5)
Other couplings
5a
5b
5c
5d
129.7
129.7
129.7
129.6
7.2
7.2
7.3
7.2
2.4
2.4
2.6
2.7
–
3J(4a,6) = 12.3, 3J(4a,8) = 3.8, 4J(4a,7) = 1.2; 1J(6) = 183.7, 2J(6, 7) = 3.0, 3J(6, 8) = 7.8;
1J(7) = 166.8, 2J(7, 6) = 9.8; 1J(8) = 166.9, 2J(8, 7) = 1.1, 3J(8, 6) = 6.5; 2J(8a,8) =
3.7, 3J(8a,7) = 9.7, 4J(8a,6) = 1.7
–
2J(4a,5) = 6.4, 3J(4a,8) = 3.8, 4J(4a,7) = 1.4; 1J(5) = 187.0, 3J(5, 7) = 12.0; 1J(7) = 182.8,
2J(7, 8) = 1.4, 3J(7, 5) = 13.8; 1J(8) = 168.2, 2J(8, 7) = 8.9, 4J(8, 5) = 1.6; 2J(8a,8) =
3.8, 3J(8a,5) = 7.6, 3J(8a,7) = 9.7
5.0
4.9
2J(4a,5) = 1.1, 3J(4a,6) = 7.4, 3J(4a,8) = 4.0; 1J(5) = 169.0, 2J(5, 6) = 9.5, 4J(5, 8) = 1.6;
1J(6) = 183.1, 2J(6, 5) = 2.4, 3J(6, 8) = 11.9; 1J(8) = 185.0, 2J(8, 6) = 11.5,
4J(8, 5) = 1.0; 2J(8a,8) = 3.3, 3J(8a,5) = 7.6, 4J(8a,6) = 1.8
2J(4a,5) = 0, 3J(4a,6) = 7.4, 4J(4a,7) = 1.5; 1J(5) = 168.2, 2J(5, 6) = 1.9, 3J(5, 7) = 6.5;
1J(6) = 167.7, 2J(6, 5) = 0.9, 2J(6, 7) = 8.1; 1J(7) = 182.8, 2J(7, 6) = 4.3,
3J(7, 5) = 8.9; 3J(8a,5) = 8.5, 3J(8a,7) = 13.5, 4J(8a,6) = 1.4
5e
5f
129.5
129.5
129.6
7.2
7.2
7.2
2.6
2.4
2.5
–
2.8
0
3J(4a,6) = 5.2, 3J(4a,7) = 5.8; 1J(6) = 188.0, 2J(6, 7) = 4.5; 1J(7) = 175.2, 2J(7, 6) = 4.1;
2J(7a,7) 0.9, 3J(7a,6) = 12.8
2J(4a,5) = 2.4, 3J(4a,7) = 6.3; 1J(5) = 193.2, 3J(5, 7) = 5.2; 1J(7) = 190.2, 3J(7, 5) = 4.5;
2J(7a,7) = 0, 3J(7a,5) = 10.8
5g
2J(4a,5) = 3.7, 3J(4a,6) = 8.5; 1J(5) = 176.1, 2J(5, 6) = 3.5; 1J(6) = 191.7, 2J(6, 5) = 6.8;
3J(7a,5) = 11.0, 3J(7a,6) = 8.6
5h
5i
129.5
129.5
129.5
7.1
7.2
7.2
2.6
2.7
2.8
5.5
–
1J(5) = 166.4, 3J(5, 6) = 4.7; 3J(10a,5) = 9.8
3J(9b,9) = 3.4
5j
–
3J(5a,7) = 7.8, 3J(5a,8) = 9.5; 1J(7) = 188.5, 2J(7, 8) = 6.8; 1J(8) = 174.2, 2J(8, 7) = 4.1;
2J(8a,8) = 5.7, 3J(8a,7) = 10.5
6
7
129.2
129.6
7.2
7.2
2.7
2.5
4.1
5.2
–
2J(4a,5) = 0, 3J(4a,6) = 8.2, 3J(4a,8) = 4.4, 4J(4a,7) = 1.4; 1J(5) = 165.4, 3J(5, 7) = 8.1;
1J(6) = 163.3, 3J(6, 8) = 8.2; 1J(7) = 161.7, 3J(7, 5) = 9.5; 1J(8) = 163.6,
3J(8, 6) = 7.9; 2J(8a,8) = 3.7, 3J(8a,5) = 8.8, 3J(8a,7) = 11.1, 4J(8a,6) = 1.6
8
9
129.4
129.7
7.1
7.1
2.5
2.2
4.0
5.4
–
3J(4a,6) = 6.9, 3J(4a,8) = 6.9
Table 4. 15N NMR chemical shifts of 5a–j, 6–9 (δ in ppm, CDCl3)
Compounds
N-1
N-2
Other N
Compounds
N-1
N-2
Other N
5a
5b
5c
5d
5e
5f
−196.1
−194.6
−195.3
−194.7
−195.7
−196.5
−196.0
−91.1
−91.8
−90.7
−91.8
−91.8
−93.1
−92.9
N-5: −65.7
5h
5i
5j
6
−194.3
−195.2
−195.3
−193.2
−196.2
−178.3
−181.6
−92.3
−91.6
−91.4
−96.2
−93.5
−75.8
−73.5
N-10: −116.4
N-6: −77.4
–
–
–
–
–
–
N-7: −56.3
N-8: −102.3
–
–
–
7
8
5g
9
accumulated per t1 increment; zero-filling to 128 data points in
the F1 dimension, shifted sine multiplication in F1). The 15N NMR
spectra (CDCl3) were obtained on a Bruker Avance 500 instru-
ment (50.69 MHz) equipped with a 5-mm broad-band observe
probe (BBFO) at 25 ◦C and were referenced against external, neat
nitromethane: 1H,15N gs-HMBC experiments (Bruker standard pro-
gram ‘inv4gplplrndqf’,[29] 2048 × 256 data matrix, 10 ppm for 1H,
200 ppm for 15N, 32 transients accumulated per t1 increment;
65 ms delay for the evolution of the 15N,1H long-range coupling,
optimized for J = 8 Hz, zero-filling to 1K data points in the F1 di-
mension,sinemultiplicationinbothdimensions)wereundertaken.
Melting points were determined on a Reichert–Kofler hot-
stage microscope and are uncorrected. The mass spectra were
obtained on a Shimadzu QP 1000 instrument (EI, 70 eV). The
elemental analyses (C, H, N) were performed at the Microanalytical
Laboratory, University of Vienna.
General procedure for the synthesis of 5a–j, 7, and 9
To a solution of the appropriate oxo compound (4a–j,[1–3] 6,[2]
8[21]) (1 mmol) in toluene (15 ml) was added Lawesson’s reagent
(202 mg, 0.5 mmol)andthemixturewasheatedtorefluxovernight
(∼14 h). Then, the solvent was removed under reduced pressure
and the residue was subjected to column chromatography (silica
gel, eluent: CH2Cl2 or CH2Cl2 –MeOH, 100 : 3) to afford the colored
thiones 5a–j, 7, and 9. For analytical purposes, the products were
recrystallized from an appropriate solvent given below.
3-Methyl-1-phenylpyrazolo[4ꢁ,3ꢁ: 5,6]pyrano[3,2-b]pyridine-4(1H)-
thione (5a)
Yield: 88%; mp: 242–244 ◦C (toluene); MS: m/z (%) = 294 (M+ + 1,
20), 293 (M+, 100), 292 (M+ − 1, 41), 260 (22), 157 (34), 146 (22), 77
(42), 51 (27). Anal. calcd. for C16H11N3OS (293.34): C, 65.51; H, 3.78;
N, 14.32. Found: C, 65.34; H, 3.58; N, 14.25.
c
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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 476–482

Synthesis and NMR data on heterocyclic analogs of xanthiones
3-Methyl-1-phenylpyrazolo[4ꢁ,3ꢁ: 5,6]pyrano[3,2-c]pyridine-4(1H)-
3-Methyl-1-phenylthieno[3ꢁꢁ,2ꢁꢁ: 4ꢁ,5ꢁ]thieno[2ꢁ,3ꢁ: 5,6]pyrano[2,3-
thione (5b)
c]pyrazole-4(1H)-thione (5j)
Yield: 93%; mp: 205–207 ◦C; MS: m/z (%) = 294 (M+ + 1, 22),
293 (M+, 100), 292 (M+ − 1, 33), 77 (28), 51 (17). Anal. calcd. for
C16H11N3OS (293.34): C, 65.51; H, 3.78; N, 14.32. Found: C, 65.49; H,
3.75; N, 13.94.
Yield: 83%; mp: 245–246 ◦C (toluene); MS: m/z (%) = 355 (M+ + 1,
20), 354 (M+, 100), 177 (12), 77 (22), 51 (15). Anal. calcd. for
C17H10N2OS3 (354.47): C, 67.60; H, 2.84; N, 7.90. Found: C, 57.47; H,
2.65; N, 7.80.
3-Methyl-1-phenylpyrazolo[4ꢁ,3ꢁ: 5,6]pyrano[2,3-c]pyridine-4(1H)-
thione (5c)
3-Methyl-1-phenylchromeno[2,3-c]pyrazole-4(1H)-thione(7)
Yield: 98%; mp: 185–187 ◦C (literature[20] mp: 189–190 ◦C); MS:
m/z (%) = 293 (M+ + 1, 21), 292 (M+, 100), 291 (M+ − 1, 33), 146
(11), 91 (18), 77 (23), 51 (15). C17H12N2OS (292.35).
Yield: 94%; mp: 177–179 ◦C (toluene); MS: m/z (%) = 294 (M+ + 1,
20), 293 (M+, 100), 292 (M+ − 1, 31), 91 (19), 77 (33), 51 (20). Anal.
calcd. for C16H11N3OS· 0.1 H2O (293.34/295.15): C, 65.11; H, 3.82;
N, 14.24. Found: C, 65.38; H, 3.80; N, 13.83.
3-Methyl-1-phenylthiochromeno[2,3-c]pyrazole-4(1H)-thione(9)
Yield: 86%; mp: 183–185 ◦C (literature[21] mp: 208–210 ◦C); MS:
m/z (%) = 309 (M+ + 1, 23), 308 (M+, 100), 307 (M+ − 1, 48), 263
(26), 172 (19), 146 (11), 138 (12), 120 (11), 83 (10), 77 (51), 69 (27),
57 (22), 55 (17), 51 (44). C17H12N2S2 (308.42).
3-Methyl-1-phenylpyrazolo[4ꢁ,3ꢁ: 5,6]pyrano[2,3-b]pyridine-4(1H)-
thione (5d)
Yield: 90%; mp: 224–225 ◦C (toluene); MS: m/z (%) = 294 (M+ + 1,
19), 293 (M+, 100), 292 (M+ − 1, 27), 91 (21), 77 (36), 51 (22). Anal.
calcd. for C16H11N3OS (293.34): C, 65.51; H, 3.78; N, 14.32. Found:
C, 65.19; H, 3.61; N, 14.10.
Acknowledgement
˙
˙
The authors cordially thank Mrs Egle Arbacˇiauskiene for experi-
mental assistance.
3-Methyl-1-phenylthieno[2ꢁ,3ꢁ: 5,6]pyrano[2,3-c]pyrazole-4(1H)-
thione (5e)
Yield: 95%; mp: 177–178 ◦C (toluene); MS: m/z (%) = 299 (M+ + 1,
16), 298 (M+, 100), 91 (11), 77 (19), 51 (13). Anal. calcd. for
C15H10N2OS2 (298.38): C, 60.38; H, 3.38; N, 9.39. Found: C, 60.37; H,
3.24; N, 9.05.
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c
Magn. Reson. Chem. 2010, 48, 476–482
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

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Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 476–482