Electrophilic heterocyclization of 6-alken(yn)ylsulfanyl-pyrazolo[3,4-d] pyrimidin-4(5H)-ones

Article abstract of DOI:10.1134/S1070428008090194

6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-pyrazolo[3,4-d]pyrimidin- 4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo- [3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl) pyrazolo[3,4-d]pyrimidin-4(5H)-ones with sulfuric acid.

Full text of DOI:10.1134/S1070428008090194

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 9, pp. 1362–1368. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © A.V. Bentya, R.I. Vas’kevich, A.V. Bol’but, M.V. Vovk, V.I. Staninets, A.V. Turov, E.B. Rusanov, 2008, published in Zhurnal
Organicheskoi Khimii, 2008, Vol. 44, No. 9, pp. 1377–1383.
Electrophilic Heterocyclization of 6-Alken(yn)ylsulfanyl-
pyrazolo[3,4-d]pyrimidin-4(5H)-ones
A. V. Bentyaa, R. I. Vas’kevicha, A. V. Bol’buta, M. V. Vovka, V. I. Staninetsa,
A. V. Turovb, and E. B. Rusanova
a Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
bentya@gmail.com
b Taras Shevchenko Kiev National University, Kiev, Ukraine
Received December 12, 2007
Abstract—6-Allylsulfanyl-1-arylpyrazolo[3,4-d]pyrimidin-4(5H)-ones react with iodine and sulfuric acid to
give angular pyrazolothiazolopyrimidine derivatives. The reaction of 6-(prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-
pyrazolo[3,4-d]pyrimidin-4(5H)-one with sulfuric acid gives angularly fused pyrazolo[4,3-e][1,3]thiazolo-
[3,2-a]pyrimidin-4-one, whereas in the reaction with sodium methoxide linearly fused pyrazolo[3,4-d][1,3]-
thiazolo[3,2-a]pyrimidin-4-one was formed. Linearly fused pyrazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazole
derivatives were also obtained by reaction of 1-aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)pyrazolo[3,4-d]pyrimi-
din-4(5H)-ones with sulfuric acid.
DOI: 10.1134/S1070428008090194
Pyrazolo[3,4-d]pyrimidines are structural isomers
molecular electrophilic cyclization. Insofar as these
of purine; they have attracted increased researchers’ centers are nonequivalent (the N7 atom seems to be
attention due to the fact that some pyrazolo[3,4-d]-
pyrimidine derivatives were found to act as adenosine
receptor antagonists [1, 2]. Biological activity of pyra-
zolo[3,4-d]pyrimidines is determined primarily by the
nature of substituents on N1, C4, and C6 [3–5]. There-
fore, we believed to be important to obtain previ-
ously unknown 6-alkenylsulfanyl- and 6-alkynylsul-
fanyl-substituted pyrazolo[3,4-d]pyrimidines and, with
account taken of relations revealed in [6–8], use them
in the synthesis of new derivatives of the tricyclic
pyrazolothiazolopyrimidine system. Despite limited
number of known representatives of this series,
effective calcium channel blockers [9] and compounds
possessing a strong antiphlogistic activity [10] were
found among these compounds.
preferred for ring closure [6–8]), we tried to equalize
their reactivities via introduction of a bulky aryl sub-
stituent into position 1 of the pyrazolo[3,4-d]pyrimi-
dine system (N1 atom in the pyrazole ring). As a result,
we anticipated ring closure with participation of N5.
Intramolecular electrophilic cyclization of 6-allyl-
sulfanyl derivatives IIa and IIb by the action of iodine
in chloroform gave the corresponding angular tricyclic
pentaiodides IIIa and IIIb. The reaction time was
14 days at room temperature (yield 65%), while the
cyclization of other pyrimidine systems is known to be
complete in 2 days (yield >90%) [6–8]. Salts IIIa and
IIIb were converted into 1-aryl-8-iodomethyl-7,8-di-
hydro-4H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimi-
din-4-ones IVa and IVb by treatment with sodium
sulfite. Compounds IVa and IVb did not undergo de-
hydroiodination on heating with morpholine at 70°C;
this fact differentiates them from analogous thiazolo-
pyrimidinone derivatives which readily lose hydrogen
iodide under similar conditions [6–8]. On the other
hand, treatment of IVb with sodium acetate in DMSO
at 70°C gave 8-methylidene derivative Vb. Increased
stability of iodomethyl derivatives IVa and IVb to
As starting compounds we selected 6-thioxopyra-
zolo[3,4-d]pyrimidin-4(5H)-ones Ia and Ib which
were prepared according to the procedure described in
[11]. By reaction of Ia and Ib with allyl bromide we
obtained 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-
4(5H)-ones IIa and IIb (Scheme 1). Molecules IIa and
IIb possess two nucleophilic centers (N5 and N7 atoms
in the pyrimidine ring) which can be involved in intra-
1362

ELECTROPHILIC HETEROCYCLIZATION OF 6-ALKEN(YN)YLSULFANYL-...
1363
Scheme 1.
O
O
O
N
NH
NH
NH
CH2=CHCH2Br
3I2, CHCl3
N
N
N
I5
CH2
N
N
N
N
H
S
N
S
S
R
R
R
ICH2
Ia, Ib
IIa, IIb
IIIa, IIIb
O
N
O
N
N
N
AcONa, Δ
Na2SO3
N
N
N
N
S
S
R
4-MeC6H4
ICH2
H2C
Vb
IVa, IVb
O
N
(1) H2SO4
(2) NaHCO3
N
N
N
IIa, IIb
S
R
Me
VIa, VIb
H2SO4
O
N
Vb
CH
NH
CH CCH2Br
≡
O
O
N
N
Ib
CH2
Me
N
S
MeONa
N
N
R
N
N
N
VIIb
N
S
S
N
R
R
A
VIIIb
R = Ph (a), 4-MeC6H4 (b).
dehydroiodination is likely to be related to steric
hindrances created by the aryl substituent on N1.
hybridizations of the C5 and C6 atoms, and the bond
angle distribution in the pyrimidin-4-one fragment is
somewhat unusual, although it remains fairly typical
[12–14] of structurally related heterocycles. Thus the
endocyclic bond angles at C4 and N4 are appreciably
reduced to 115.49(18) and 114.96(16)°, respectively,
whereas the endocyclic angle at C5 is increased to
127.69(19)° relative to the ideal value for conjugated
six-membered heterocycles (120°). No conjugate inter-
molecular contacts were detected in crystal.
The structure of compound IVb was unambigu-
ously determined by X-ray analysis. Crystals of pyra-
zolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one IVb
belong to centrosymmetric space group (Fig. 1). The
bicyclic pyrazolopyrimidine fragment is almost planar
due to conjugation: the mean-square deviation of
atoms from the plane is 0.017 Å; the S1, C6, and C7
atoms of the dihydrothiazole ring deviate from that
plane by 0.195, –0.100, and 0.302 Å, respectively, and
the C9–C14 benzene ring is turned through a dihedral
angle of 62.0° with respect to the pyrazolopyrimidine
fragment. The C5–S1 [1.735(2) Å] and C6–S1 bonds
[1.802(3) Å] are nonequivalent because of different
6-Allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-
ones IIa and IIb in the presence of concentrated sul-
furic acid underwent intramolecular cyclization to give
angular 7,8-dihydro-4H-pyrazolo[4,3-e][1,3]thiazolo-
[3,2-a]pyrimidin-4-one derivatives VIa and VIb.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

BENTYA et al.
1364
Scheme 2.
Cl
O
Ph
O
N
Ph
S
NH
N
Ia, Ib
N
N
N
N
N
S
R
R
IXa, IXb
Xa, Xb
R = Ph (a), 4-MeC6H4 (b).
6-(Prop-2-yn-1-ylsulfanyl)pyrazolopyrimidinone
VIIb was obtained by alkylation of compound Ib with
prop-2-yn-1-yl bromide. The reaction of VIIb with
concentrated sulfuric acid also afforded compound Vb,
and the exocyclic double bond in the latter failed to
migrate into the thiazole ring even on prolonged heat-
ing in concentrated sulfuric acid at 70°C. On the other
hand, the use of sodium methoxide as condensing
agent changes the direction of cyclization of com-
pound VIIb, and the product is linearly fused pyrazolo-
[3,4-d][1,3]thiazolo[3,2-a]pyrimidinone VIIIb. We be-
lieve that the primary cyclization product is 6-meth-
ylidene derivative A which undergoes double bond
migration to give compound VIIIb.
IXb failed to react with iodine, but they readily under-
went intramolecular ring closure by the action of con-
centrated sulfuric acid with formation of linearly fused
7,8-dihydro-4H,6H-pyrazolo[3′,4′:4,5]pyrimido[2,1-b]-
[1,3]thiazin-4-ones Xa and Xb. Obviously, in this case
the cyclization involved the N5 atom of the pyrazolo-
pyrimidine system.
However, the formation of angular products like XI
in the cyclization of IXa and IXb cannot be ruled out.
Structures X and XI possess similar spin systems;
therefore, they cannot be distinguished on the basis of
1
the H and 13C NMR spectra. To solve this problem,
13
we recorded HMQC and HMBC heteronuclear C–1H
correlation (through one and 2–3 chemical bonds, re-
By alkylation of 6-thioxopyrazolopyrimidinones Ia
and Ib with cinnamyl chloride we obtained the corre-
sponding 6-(3-phenylprop-2-en-1-ylsulfanyl) deriva-
tives IXa and IXb (Scheme 2). Compounds IXa and
spectively) spectra of compound Xb (see table).
O
N
N
I1
N
N
R
Ph
C8
XIa, XIb
C15
C12
C13
C6
C5
S1
C7
In order to assign 13C signals using heteronuclear
correlation data, it was necessary to identify the
1H NMR signals first. It was fairly easy to do on the
basis of the signal multiplicities. Further confirmations
were made using two-dimensional COSY and NOESY
techniques. Correlations through one chemical bond in
the HMQC spectrum allowed us to reliably assign
signals from carbon atoms linked to hydrogen, and
quaternary carbon atoms were identified by analysis of
correlations through 2–3 chemical bonds in the HMBC
spectrum. Here, the most important was correlation be-
tween the 5-H proton in the thiazine ring (δ 6.28 ppm)
and C4 in the pyrimidine ring (δC 156.8 ppm). Such
correlation is possible only when compound Xb has
linear structure. Figure 2 shows the chemical shifts of
protons and carbon nuclei in molecule Xb, as well as
the principal correlations in the HMBC spectrum of
C14
N4
C9
C3
N3
O1
N1
C11
C10
C2
C4
N2
C1
Fig. 1. Structure of the molecule of 8-iodomethyl-1-(4-tolyl)-
1,4,7,8-tetrahydropyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrim-
idin-4-one (IVb) according to the X-ray diffraction data.
Principal bond lengths (Å) and bond angles (deg): N1–N2
1.378(3), C1–N2 1.308(3), C3–N1 1.342(3), C1–C2 1.396(3),
C2–C3 1.370(3), C2–C4 1.436(3), C3–N4 1.361(3), C4–O1
1.216(3), C4–N3 1.394(3), C5–N3 1.278(3), C5–N4 1.373(2),
C5–S1 1.735(2), C6–S1 1.802(3), C6–C7 1.517(3), C7–N4
1.470(2), C8–I1 2.126(2); C1N2N1 104.97(19), C3N1N2
110.06(18), N1C3N4 130.23(17), N1C3C2 108.56(18), N2C1C2
112.6(2), C3C2C1 103.8(2), N3C4C2 115.49(18), C3N4C5
114.96(16), N4C3C2 121.21(18), C3C2C4 120.8(2), N3C5N4
127.69(19), C5N3C4 119.71(18), C5S1C6 92.10(10).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

ELECTROPHILIC HETEROCYCLIZATION OF 6-ALKEN(YN)YLSULFANYL-...
1365
H7.34
8.23H
Xb. It was interesting that the HMBC spectrum re-
7.14
vealed no correlation between 3-H in the pyrazole ring
(δ 8.23 ppm) and carbonyl carbon atom in the pyrimi-
dine ring, which are separated by three chemical
bonds. A probable reason is that the corresponding
coupling constant is close to zero. Analogous pattern
was observed in the spectra of other structurally related
compounds.
H
136.9
O
N
126.5
129.5
7.28
6.28
N
7.87 H
H
H
104.6
156.8
160.1
128.1
N
122.0
139.1
7.34
H
150.4
136.6
53.2
28.6
130.7
137.0
2.76
N
H
H
2.30
S 24.1
2.35
2.60
H
H3C
21.3
In the IR spectra of angular tricyclic compounds
IVa, IVb, Vb, VIa, and VIb, absorption bands due to
stretching vibrations of the carbonyl group are located
in the region 1660–1665 cm–1, while linearly fused
derivatives VIIIb, Xa, and Xb displayed carbonyl
absorption bands at 1715 (VIIIb) and 1700 cm–1 (X).
These data are consistent with those reported in [6–8]
for angular and linear thiazolo(thiazino)pyrimidinones.
Compound IIIb was characterized by a carbonyl ab-
sorption frequency of 1740 cm–1 in the IR spectrum.
H
3.07
Fig. 2. Correlations in the HMBC spectrum of 6-phenyl-1-
(4-tolyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3′,4′:4,5]pyrimido-
[2,1-b][1,3]thiazin-4-one (Xb).
Fourier difference series, and their positions were re-
fined in isotropic approximation; only hydrogen atom
in the methyl group (C15H3) were localized on the basis
of geometry considerations. The final divergence
factors were R1 = 0.0429 and wR2 = 0.0743, goodness
of fit 1.044 (for all independent reflections), and R1 =
0.0294, wR2 = 0.0696, GOF = 1.044 [for reflections
with I > 2σ(I)]. The residual electron density from the
Fourier difference series after the last iteration was
0.77 and –0.72 e/Å3. The complete set of crystallog-
raphic data for compound Xb was deposited to the
Cambridge Crystallographic Data Center (entry
no. CCDC 664997).
EXPERIMENTAL
The IR spectra were recorded in KBr on a UR-20
1
spectrometer. The H NMR spectra were measured
from solutions in DMSO-d6 on a Varian VXR-300
spectrometer (300 MHz) using tetramethylsilane as
internal reference; the 1H NMR spectrum of compound
Xb was also recorded in CDCl3 on a Varian Mercury-
400 instrument (400 MHz).
6-Allylsulfanyl-1-aryl-1H-pyrazolo[3,4-d]pyri-
midin-4(5H)-ones IIa and IIb (general procedure).
Compound Ia or Ib, 4 mmol, and allyl bromide,
The X-ray diffraction data for a single crystal of
compound IVb, 0.2×0.3×0.50 mm, were acquired at
room temperature on a Bruker Smart Apex II diffrac-
tometer (λMoKα irradiation, graphite monochromator,
Heteronuclear 13C–1H correlations in the NMR spectra of
6-phenyl-1-(4-tolyl)-4,6,7,8-tetrahydro-1H-pyrazolo-
[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4-one (Xb)
θ
max = 31.17°, spherical segment –13 ≤ h ≤ 13, –11 ≤
k ≤ 11, –31 ≤ l ≤ 32). Monoclinic crystals, space group
P21/n (no. 14); C15H13IN4OS; M 424.25; unit cell pa-
rameters: a = 8.900(2), b = 7.800(2), c = 22.213(6) Å;
δH, ppm HMQC, δC, ppm
HMBC, δC, ppm
150.4, 104.6
β = 95.432(4)°; V = 1535.1(7) Å3; Z = 4; dcalc
=
8.23
7.87
7.34
136.9
1.836 g/cm3; μ = 2.229 mm–1; F(000) = 832. Total of
11150 reflections were measured, 4560 of which were
independent (averaging factor R = 0.0183). The struc-
ture was solved by the direct method and was refined
by the full-matrix least-squares procedure in aniso-
tropic approximation using SHELXS97 and
SHELXL97 software packages [15, 16]. The refine-
ment procedure was performed using 3577 reflections
with I > 2σ(I) (240 refined parameters, 14.9 reflections
per parameter); the weight scheme ω = 1/[σ2(Fo2) +
(0.0329P)2 + 0.6135R] was applied, where R = (Fo2 +
2Fc2)/3; the ratio of the maximal (average) shift and
the error in the last iteration was 0.014 (0.000). All
hydrogen atoms were visualized objectively from
122.0
137.0, 130.3, 122.0
130.3, 129.5
139.1, 136.5, 130.3, 129.5,
126.1, 122.0, 21.3
7.28
7.14
6.28
128.1
126.1
052.2
129.5, 126.1
129.5, 128.1, 126.1, 53.2
160.1, 156.8, 139.1, 126.1,
24.1
3.07
2.75
2.60
2.35
2.30
024.1
028.6
024.1
028.6
021.3
53.2, 160.1
24.1
28.6
137.0, 130.3, 122.0
–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

BENTYA et al.
1366
0.41 ml (4.7 mmol), were added in succession to a so-
lution of 0.188 g (4.7 mmol) of sodium hydroxide in
30 ml of ethanol, and the mixture was stirred for 1 h on
heating under reflux. The mixture was cooled, and the
precipitate was filtered off and washed with water and
ethanol.
8-Iodomethyl-1-phenyl-1,4,7,8-tetrahydropyra-
zolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one (IVa).
Yield 0.34 g (83%), mp 230°C (decomp.; from etha-
nol–DMSO). IR spectrum, ν, cm–1: 1660 (C=O), 1590,
1560, 1475, 1410, 1240, 1195. 1H NMR spectrum, δ,
ppm: 2.91 d (1H, CH, J = 10.8 Hz), 3.18 t (1H, CH,
J = 10.5 Hz), 3.34 d (1H, CH, J = 11.7 Hz), 3.80–
3.86 m (1H, CH), 4.61–4.68 m (1H, CH), 7.62–7.69 m
(3H, Harom), 7.71–7.77 m (2H, Harom), 8.17 s (1H, CH).
Found, %: C 40.73; H 2.65; I 30.81; N 13.54; S 7.73.
C14H11IN4OS. Calculated, %: C 40.99; H 2.70; I 30.93;
N 13.66; S 7.82.
6-Allylsulfanyl-1-phenyl-1H-pyrazolo[3,4-d]pyri-
midin-4(5H)-one (IIa). Yield 0.87 g (77%), mp 237°C
1
(from ethanol–DMSO). H NMR spectrum, δ, ppm:
3.92 d (2H, CH2, J = 6.6 Hz), 5.17 d (1H, CH, J =
10.5 Hz), 5.34 d (1H, CH, J = 16.8 Hz), 5.93–6.07 m
(1H, CH), 7.41 t (1H, Harom, J = 7.5 Hz), 7.58 t (2H,
Harom, J = 7.5 Hz), 8.08 d (2H, Harom, J = 7.8 Hz),
8.26 s (1H, CH), 12.75 s (1H, NH). Found, %:
C 59.09; H 4.19; N 19.63; S 11.31. C14H12N4OS. Cal-
culated, %: C 59.14; H 4.25; N 19.70; S 11.28.
8-Iodomethyl-1-(4-tolyl)-1,4,7,8-tetrahydropyra-
zolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one
(IVb). Yield 0.37 g (87%), mp 242°C (decomp.,
ethanol–DMSO). IR spectrum, ν, cm–1: 1660 (C=O),
1
6-Allylsulfanyl-1-(4-tolyl)-1H-pyrazolo[3,4-d]-
pyrimidin-4(5H)-one (IIb). Yield 1.07 g (90%),
mp 254–255°C (from ethanol–DMSO). 1H NMR spec-
trum, δ, ppm: 2.38 s (3H, CH3), 3.89 d (2H, CH2, J =
6.3 Hz), 5.16 d (1H, CH, J = 10.2 Hz), 5.32 d (1H, CH,
J = 17.4 Hz), 5.91–6.05 m (1H, CH), 7.36 d (2H,
Harom, J = 7.8 Hz), 7.92 d (2H, Harom, J = 8.1 Hz),
8.22 s (1H, CH), 12.70 s (1H, NH). Found, %:
C 60.34; H 4.63; N 18.70; S 10.90. C15H14N4OS. Cal-
culated, %: C 60.38; H 4.73; N 18.78; S 10.75.
1590, 1560, 1480, 1435, 1410, 1240, 1200. H NMR
spectrum, δ, ppm: 2.44 s (3H, CH3), 2.91 d (1H, CH,
J = 9.6 Hz), 3.18 t (1H, CH, J = 10.8 Hz), 3.33 d (1H,
CH, J = 11.7 Hz), 3.80–3.86 m (1H, CH), 4.61–4.67 m
(1H, CH), 7.44 d (2H, Harom, J = 7.8 Hz), 7.62 d (2H,
Harom, J = 8.4 Hz), 8.14 s (1H, CH). Found, %:
C 42.34; H 3.14; I 29.82; N 13.13; S 7.58.
C15H13IN4OS. Calculated, %: C 42.46; H 3.09; I 29.91;
N 13.21; S 7.56.
8-Methylidene-1-(4-tolyl)-1,4,7,8-tetrahydro-
pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one
(Vb). a. Anhydrous sodium acetate, 0.05 g
(0.65 mmol), was added to a solution of 0.21 g
(0.5 mmol) of compound IVb in 5 ml of DMSO, and
the mixture was stirred for 3 h at 70°C. The mixture
was cooled and poured into water, and the precipitate
was filtered off and washed with water.
1-Aryl-8-iodomethyl-7,8-dihydro-1H-pyrazolo-
[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-ones IVa and
IVb (general procedure). A solution of 0.76 g
(3 mmol) in 50 ml of chloroform was added under
stirring to a solution of 1 mmol of compound IIa or
IIb in 20 ml of chloroform. The mixture was stirred
for 14 days at room temperature, and the precipitate of
salt IIIa or IIIb was filtered off and washed with
chloroform. The product was dissolved in 10 ml of
DMSO, a 5% aqueous solution of sodium sulfite was
added until the mixture turned colorless, and the pale
yellow precipitate was filtered off, washed with water,
and recrystallized from ethanol–DMSO.
b. Compound VIIb, 0.30 g (1 mmol), was dissolved
in 5 ml of concentrated sulfuric acid, and the solution
was left to stand for 14 h. It was then poured onto ice
and neutralized with sodium hydroxide, and the precip-
itate was filtered off, washed with water, and recrystal-
lized from ethanol–DMSO. Yield 0.11 g (74%, a),
0.27 g (91%, b), mp 304–306°C (from ethanol–
DMSO). IR spectrum, ν, cm–1: 1660 (C=O), 1585,
8-Iodomethyl-4-oxo-1-(4-tolyl)-4,5,7,8-tetrahy-
dro-1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimi-
din-9-ium pentaiodide (IIIb). Yield 0.71 g (67%),
mp 275°C (decomp.). IR spectrum, ν, cm–1: 1740
(C=O), 1595, 1550, 1225, 1060. 1H NMR spectrum, δ,
ppm: 2.44 s (3H, CH3), 2.90 d (1H, CH, J = 11.1 Hz),
3.19 t (1H, CH, J = 10.8 Hz), 3.38 d (1H, CH, J =
12.0 Hz), 3.84–3.90 m (1H, CH), 4.64–4.71 m (1H,
1
1550, 1485, 1345, 1220, 1190. H NMR spectrum, δ,
ppm: 2.37 s (3H, CH3), 4.13 s (2H, CH2), 4.21–4.22 m
(1H, CH), 4.87–4.88 m (1H, CH), 7.32 d (2H, Harom
,
J = 8.7 Hz), 7.47 d (2H, Harom, J = 8.4 Hz), 8.27 s (1H,
CH). Found, %: C 60.82; H 3.99; N 18.96; S 10.75.
C15H12N4OS. Calculated, %: C 60.79; H 4.08; N 18.91;
S 10.82.
CH), 7.46 d (2H, Harom, J = 7.8 Hz), 7.62 d (2H, Harom
,
J = 7.5 Hz), 8.20 s (1H, CH). Found, %: C 16.84;
H 1.35; I 71.53; N 5.21; S 2.96. C15H14I6N4OS. Calcu-
lated, %: C 17.00; H 1.33; I 71.85; N 5.29; S 3.03.
1-Aryl-8-methyl-1,4,7,8-tetrahydropyrazolo-
[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-ones VIa and
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ELECTROPHILIC HETEROCYCLIZATION OF 6-ALKEN(YN)YLSULFANYL-...
1367
VIb were synthesized as described above for com-
pound Vb (method b).
8.1 Hz), 7.90 d (2H, Harom, J = 8.1 Hz), 8.29 s (1H,
CH). Found, %: C 60.94; H 4.07; N 18.83; S 10.87.
C15H12N4OS. Calculated, %: C 60.79; H 4.08; N 18.91;
S 10.82.
8-Methyl-1-phenyl-1,4,7,8-tetrahydropyrazolo-
[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one (VIa).
Yield 0.26 g (92%), mp 280°C (decomp., from etha-
nol–DMSO). IR spectrum, ν, cm–1: 1660 (C=O), 1590,
1-Aryl-6-(3-phenylprop-2-en-1-ylsulfanyl)-1H-
pyrazolo[3,4-d]pyrimidin-4(5H)-ones IXa and IXb
(general procedure). Compound Ia or Ib, 4 mmol, was
added to a solution of 0.19 g (4.8 mmol) of sodium
hydroxide in 25 ml of ethanol, 0.67 ml (4.8 mmol) of
cinnamyl chloride was then added, and the mixture
was stirred for 1 h on heating under reflux. The mix-
ture was cooled, and the precipitate was filtered off
and washed with water and ethanol.
1
1555, 1470, 1405, 1240, 1200. H NMR spectrum, δ,
ppm: 0.96 d (3H, CH3, J = 6.0 Hz), 3.13 d (1H, CH,
J = 11.4 Hz), 3.74–3.80 m (1H, CH), 4.55–4.64 m (1H,
CH), 7.59–7.77 m (5H, Harom), 8.17 s (1H, CH).
Found, %: C 59.25; H 4.19; N 19.77; S 11.19.
C14H12N4OS. Calculated, %: C 59.14; H 4.25; N 19.70;
S 11.28.
1-Phenyl-6-(3-phenylprop-2-en-1-ylsulfanyl)-1H-
pyrazolo[3,4-d]pyrimidin-4(5H)-one (IXa). Yield
1.22 g (85%), mp 242°C (from ethanol). H NMR
spectrum, δ, ppm: 4.08 d (2H, CH2, J = 6.9 Hz), 6.35–
6.47 m (1H, CH), 6.65 d (1H, CH, J = 15.6 Hz), 7.2–
7.33 m (5H, Harom), 7.38–7.45 m (1H, Harom), 7.55–
7.6 m (2H, Harom), 8.09 d (2H, Harom, J = 8.7 Hz), 8.22 s
(1H, CH), 12.69 s (1H, NH). Found, %: C 66.54;
H 4.37; N 15.59; S 8.86. C20H16N4OS. Calculated, %:
C 66.65; H 4.47; N 15.54; S 8.90.
8-Methyl-1-(4-tolyl)-1,4,7,8-tetrahydropyrazolo-
[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one (VIb).
Yield 0.29 g (97%), mp >300°C (from ethanol–
DMSO). IR spectrum, ν, cm–1: 1665 (C=O), 1605,
1
1
1575, 1485, 1420, 1250, 1220. H NMR spectrum, δ,
ppm: 0.97 d (3H, CH3, J = 6.6 Hz), 2.43 s (3H, CH3),
3.12 d (1H, CH, J = 11.4 Hz), 3.72–3.78 m (1H, CH),
4.55–4.64 m (1H, CH), 7.42 d (2H, Harom, J = 7.8 Hz),
7.61 d (2H, Harom, J = 8.1 Hz), 8.14 s (1H, CH). Found,
%: C 60.51; H 4.81; N 18.67; S 10.69. C15H14N4OS.
Calculated, %: C 60.38; H 4.73; N 18.78; S 10.75.
6-(3-Phenylprop-2-en-1-ylsulfanyl)-1-(4-tolyl)-
1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (IXb).
Yield 1.06 g (71%), mp 216°C (from ethanol).
1H NMR spectrum, δ, ppm: 2.38 s (3H, CH3), 4.06 d
(2H, CH2, J = 6.9 Hz), 6.36–6.46 m (1H, CH), 6.64 d
(1H, CH, J = 15.0 Hz), 7.2–7.29 m (5H, Harom), 7.65 d
(2H, Harom, J = 8.4 Hz), 7.94 d (2H, Harom, J = 8.4 Hz),
8.22 s (1H, CH), 12.68 s (1H, NH). Found, %:
C 67.48; H 4.87; N 14.91; S 8.51. C21H18N4OS. Calcu-
lated, %: C 67.36; H 4.85; N 14.96; S 8.56.
6-(Prop-2-yn-1-ylsulfanyl)-1-(4-tolyl)-1H-pyra-
zolo[3,4-d]pyrimidin-4(5H)-one (VIIb). Compound
Ib, 0.98 g (4 mmol), was added to a solution of 0.19 g
(4.8 mmol) of sodium hydroxide in 30 ml of ethanol,
0.36 ml (4 mmol) of a 80% solution of prop-2-yn-1-yl
bromide in toluene was then added, and the mixture
was stirred for 1 h on heating under reflux. The mix-
ture was cooled, and the precipitate was filtered off
and washed with water and ethanol. Yield 1.04 g
1
(88%), mp 261–262°C. H NMR spectrum, δ, ppm:
1-Aryl-6-phenyl-4,6,7,8-tetrahydro-1H-pyrazolo-
[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4-ones Xa and
Xb were synthesized as described above for compound
Vb (method b) from pyrazolopyrimidines IXa and
IXb, respectively.
2.38 s (3H, CH3), 3.29 t (1H, CH, J = 3.0 Hz), 4.06 d
(2H, CH2, J = 2.4 Hz), 7.35 d (2H, Harom, J = 8.4 Hz),
8.05 d (2H, Harom, J = 8.4 Hz), 8.24 s (1H, CH), 12.79 s
(1H, NH). Found, %: C 60.72; H 4.03; N 18.98;
S 10.73. C15H12N4OS. Calculated, %: C 60.79; H 4.08;
N 18.91; S 10.82.
1,6-Diphenyl-4,6,7,8-tetrahydro-1H-pyrazolo-
[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4-one (Xa).
Yield 0.20 g (56%), mp 192°C (from ethanol). IR
spectrum, ν, cm–1: 1705 (C=O), 1530, 1440, 1400,
6-Methyl-1-(4-tolyl)-1H-pyrazolo[3,4-d][1,3]thia-
zolo[3,2-a]pyrimidin-4-one (VIIIb). A mixture of
0.15 g (0.5 mmol) of compound VIIb and 0.017 g
(0.75 mmol) of sodium in 15 ml of methanol was
stirred for 5 days at room temperature. The precipitate
was filtered off and washed with water and methanol.
Yield 0.05 g (34%), mp 226–227°C. IR spectrum, ν,
cm–1: 1715 (C=O), 1530, 1395, 1190, 1155, 1095.
1H NMR spectrum, δ, ppm: 2.37 s (3H, CH3), 2.71 s
(3H, CH3), 6.92 s (1H, CH), 7.34 d (2H, Harom, J =
1
1190, 1130, 1080. H NMR spectrum, δ, ppm: 2.27–
2.40 m (1H, CH), 2.58–2.69 m (1H, CH), 2.75–2.84 m
(1H, CH), 3.07–3.15 m (1H, CH), 6.31 s (1H, CH),
7.17 d (2H, Harom, J = 6.9 Hz), 7.27–7.44 m (4H,
Harom), 7.56–7.61 m (2H, Harom), 8.04 d (2H, Harom, J =
8.1 Hz), 8.29 s (1H, CH). Found, %: C 66.73; H 4.49;
N 15.43; S 8.82. C20H16N4OS. Calculated, %: C 66.65;
H 4.47; N 15.54; S 8.90.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 9 2008

BENTYA et al.
1368
7. Vas’kevich, R.I., Khripak, S.M., Staninets, V.I., Zborov-
6-Phenyl-1-(4-tolyl)-4,6,7,8-tetrahydro-1H-pyra-
skii, Yu.L., Nesterenko, A.M., and Pirozhenko, V.V.,
Ukr. Khim. Zh., 2000, no. 11, p. 47.
8. Orysyk, V.V., Dobosh, A.A., Zborovskii, Yu.L., Stani-
nets, V.I., and Khripak, S.M., Ukr. Khim. Zh., 2001,
no. 9, p. 46.
zolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4-one
(Xb). Yield 0.18 g (48%), mp 181–182°C (from etha-
nol). IR spectrum, ν, cm–1: 1705 (C=O), 1535, 1450,
1
1400, 1200, 1130. H NMR spectrum, δ, ppm: 2.28–
2.42 m (4H, CH3, CH), 2.58–2.68 m (1H, CH), 2.76–
2.84 m (1H, CH), 3.07–3.15 m (1H, CH), 6.3 s (1H,
CH), 7.16 d (2H, Harom, J = 7.2 Hz), 7.28–7.42 m
(5H, Harom), 7.90 d (2H, Harom, J = 8.1 Hz), 8.26 s
(1H, CH). Found, %: C 67.21; H 4.71; N 15.01;
S 8.50. C21H18N4OS. Calculated, %: C 67.36; H 4.85;
N 14.96; S 8.56.
9. Guccione, S., Modica, M., Longmore, J., Show, D., Bar-
retta, G.U., Santagati, A., Santagati, M., and Russo, F.,
Bioorg. Med. Chem. Lett., 1996, vol. 6, p. 59.
10. Russo, F., Guccione, S., Romeo, G., Baretta, G.U.,
Pueci, S., Caruso, A., Amico-Roxas, V., and Cutuli, V.,
Eur. J. Med. Chem., 1993, vol. 28, p. 363.
11. Schmidt, P., Eichenberger, K., Wilhelm, M., and
Druey, J., Helv. Chim. Acta, 1959, vol. 42, p. 349.
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