Cyclofunctionalization of 6-alkenylsulfanylpyrazolo[3,4-d]-pyrimidin-4(5H)-ones with arenesulfenyl chlorides

Article abstract of DOI:10.1134/S1070428009120161

Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in acetic acid in the presence of LiClO₄ w

Full text of DOI:10.1134/S1070428009120161

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 12, pp. 1847–1852. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.I. Vas’kevich, A.V. Bentya, V.I. Staninets, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 12,
pp. 1848–1853.
Cyclofunctionalization of 6-Alkenylsulfanylpyrazolo[3,4-d]-
pyrimidin-4(5H)-ones with Arenesulfenyl Chlorides
A. I. Vas’kevich, A. V. Bentya, and V. I. Staninets
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine
e-mail: bentya@gmail.com
Received March 2, 2009
Abstract—Reactions of 6-allylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one with arenesulfenyl chlorides in
chloroform gave products of addition of the latter at the exocyclic double bond, while analogous reactions in
acetic acid in the presence of LiClO4 were accompanied by intramolecular electrophilic cyclization involving
the N7 atom. 6-Cinnamylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-one reacted with arenesulfenyl chlorides in
acetic acid in the absence of electrolyte to produce fused pyrazolo[4′,3′:5,6]pyrimido[2,1-b][1,3]thiazine
derivatives. Introduction of a bulky phenyl group into position 1 of the pyrazolo[3,4-d]pyrimidine system
reduces the yield of the corresponding intramolecular cyclization product at N7 as a result of concurrent
formation of acyclic addition product.
DOI: 10.1134/S1070428009120161
Intramolecular electrophilic cyclization of unsatu-
rated functionally substituted compounds by the action
of sulfenyl chlorides provides a convenient synthetic
route to heterocyclic systems [1, 2]. Sulfenyl chlorides
are known to react with olefins in weakly ionizing
medium to form weakly polar intermediates (sulfurane
or contact ion pair), and the final products were mainly
AdE adducts. Addition of salts, e.g., lithium perchlo-
rate, to the reaction mixture favors formation of more
polar intermediates, such as solvent-separated ion pairs
and solvated ions, which are responsible for non-
addition reaction pathways, including intramolecular
electrophilic cyclization [3]. Reactions of arenesul-
fenyl chlorides with alkenylsulfanyl-substituted quin-
azolinones and thieno[2,3-d]pyrimidinones afforded
mainly angular intramolecular electrophilic cyclization
products, whereas 2-alkenylsulfanylpyrimidin-4(3H)-
ones under analogous conditions gave rise to mixtures
of isomeric cyclization products at the N1 and N3
atoms of the pyrimidine ring [4, 5].
Scheme 1.
O
O
N
NH
N
ArSCl, AcOH
LiClO4
N
N
AcONa
ClO4
N
H
N
H
N
S
S
O
ArS
ArS
IIa–IIc
IIIa–IIIc
NH
N
CH2
N
N
S
H
O
O
I
SPh
NH
Cl
N
PhSCl, CHCl3
AcONa, DMSO
N
N
N
N
N
S
N
S
H
H
SPh
IV
V
Ar = 4-O2NC6H4 (a), Ph (b), 4-MeC6H4 (c).
1847

VAS’KEVICH et al.
1848
Scheme 2.
O
NH
Cl–
O
N
N
N
H
N
S
ArSCl, AcOH
NH
··
H
H
N
H
N
S
Ph
H
H
S
VI
Ar
A
O
N
O
NH
N
N
N
AcONa
Cl–
N
N
S
N
S
H
H
Ph
Ph
SAr
VIIa–VIIc
SAr
VIIIa–VIIIc
Ar = 4-O2NC6H4 (a), Ph (b), 4-MeC6H4 (c).
In continuation of these studies, in the present work
we examined reactions of arenesulfenyl chlorides
(4-O2NC6H4SCl, PhSCl, and 4-MeC6H4SCl) with 6-al-
kenylsulfanylpyrazolo[3,4-d]pyrimidin-4(5H)-ones I,
VI, and IX. The goal of this work was to elucidate
how the structure of the initial compounds (specifi-
cally, the presence of a substituent in the pyrazole ring
and the nature of the exocyclic alkenyl group) is
related to chemo- and regioselectivity of their reactions
with arenesulfenyl chlorides.
sorption band at 1635–1630 cm–1 due to stretching
vibrations of the carbonyl group [6, 7].
Compound I reacted with benzenesulfenyl chloride
in chloroform to give acyclic addition product, pyra-
zolopyrimidinone IV. The regioselectivity of the addi-
tion of PhSCl at the allyl fragment of I was confirmed
by subsequent intramolecular cyclization of compound
IV by the action of sodium acetate in dimethyl sulfox-
ide, which afforded linearly fused pyrazolopyrimido-
thiazine V. In this case, the cyclization involved the
N5 atom of the pyrazolopyrimidine system, as clearly
followed from the presence of carbonyl absorption
band at 1715 cm–1 in the IR spectrum of V [6, 8].
The reactions of 6-allylsulfanylpyrazolo[3,4-d]-
pyrimidin-4(5H)-one (I) with arenesulfenyl chlorides
in acetic acid in the presence of LiClO4 gave the corre-
sponding cyclization products, 8-arylsylfanylmethyl-4-
oxo-4,5,7,8-tetrahydro-1H-pyrazolo[4,3-e][1,3]thia-
zolo[3,2-a]pyrimidin-9-ium perchlorates IIa–IIc, in
62–84% yield, depending on the substituent in the
para position of benzene ring in the initial arenesul-
fenyl chloride (Scheme 1). Perchlorates IIa–IIc were
converted into the corresponding bases IIIa–IIIc by
the action of sodium acetate. As followed from the
1H NMR and IR data, closure of dihydrothiazole ring
involves the N7 atom in the pyrazolopyrimidine sys-
Unlike allylsulfanyl derivative I, in the reactions of
6-cinnamylsulfanylpyrazolo[3,4-d]pyrimidinone VI
with arenesulfenyl chlorides in acetic acid intramolec-
ular cyclization products VIIa–VIIc were formed in
the absence of LiClO4 (Scheme 2). The presence of
a phenyl group at the terminal carbon atom of the
allylic fragment of VI stabilizes carbocation interme-
diate A, so that internal nucleophilic center of the sub-
strate (N7 atom) successfully competes with external
nucleophile (chloride ion) generated from arenesul-
fenyl chloride.
1
tem. The 8-H signal in the H NMR spectra of salts
IIa–IIc and bases IIIa–IIIc appeared as a multiplet in
the region δ 5.33–5.43 and 5.09–5.30 ppm, respec-
tively. The IR spectra of IIIa–IIIc contained an ab-
The structure of pyrazolopyrimidothiazines VIIa–
VIIc and VIIIa–VIIIc follows from their 1H NMR and
1
IR spectra. In the H NMR spectra of VIIa–VIIc,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

CYCLOFUNCTIONALIZATION OF 6-ALKENYLSULFANYLPYRAZOLO-...
1849
Scheme 3.
O
N
O
O
PhSCl, AcOH
LiClO4
NH
NH
NH
N
N
N
ClO4
+
CH2
N
N
N
S
N
S
Cl
N
S
H
Ph
Ph
SPh
PhS
IX
X
XI
O
N
O
N
AcONa, H2O
DMSO
SPh
N
N
AcONa, DMSO
N
N
X
XI
N
N
S
S
H
Ph
PhS
XII
XIII
methylene protons in the thiazine ring resonated in the
region δ 3.15–3.42 ppm, and the 8-H and 9-H signals
were located at δ 4.60–5.11 and 5.97–6.17 ppm; the
corresponding signals in the spectra of VIIIa–VIIIc
were observed at δ 3.05–3.30, 4.53–5.02, and 5.92–
6.09 ppm, respectively. Stretching vibrations of the
carbonyl group in salts VIIa–VIIc and bases VIIIa–
VIIIc give rise to IR absorption bands at 1730 and
1630 cm–1, respectively [6, 7].
of X and XIII, the carbonyl stretching vibration band
was observed at 1690 and 1650 cm–1, respectively.
The structure of compound X was also confirmed
by its transformation into pyrazolopyrimidothiazine
XIІ by the action of sodium acetate in DMSO. Judging
by the position of the carbonyl absorption band in the
IR spectrum (1700 cm–1), compound XIІ is a linearly
fused heterocyclic system [6, 8].
Thus the chemoselectivity of reactions of 6-allyl-
sulfanylpyrazolo[3,4-d]pyrimidinone I with arenesul-
fenyl chlorides strongly depends on the conditions.
The reactions in chloroform give the corresponding
acyclic addition products, while intramolecular electro-
philic cyclization at the N7 atom occurs in acetic acid
in the presence of LiClO4. Closure of thiazine ring in
the reaction of cinnamylsulfanyl-substituted pyrazolo-
pyrimidinone VI in the reaction with ArSCl in acetic
acid does not require the presence of electrolyte.
Introduction of a bulky phenyl substituent into position
1 of the pyrazolopyrimidine system leads to reduced
yield of the corresponding intramolecular cyclization
product at N7 because of concurrent formation of the
acyclic addition product. Appreciable effect of LiClO4
on the reaction direction should also be noted.
We then examined the behavior of 6-allylsulfanyl-
1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (IX)
in analogous reactions with arenesulfenyl chlorides.
The presence of a bulky phenyl group on the N1 atom
of the pyrazolopyrimidine system should hinder intra-
molecular cyclization at the N7 atom. In fact, com-
pound IX reacted with benzenesulfenyl chloride in
acetic acid in the presence of lithium perchlorate to
give a mixture of two products at a ratio of 2 :1
1
(according to the H NMR data). The major product
was compound X resulting from addition of PhSCl at
the exocyclic double bond, and the minor one was
angular intramolecular cyclization product XI
(Scheme 3). We failed to isolate perchlorate XI as
individual substance, and it was converted into free
base XIII by the action of sodium acetate.
EXPERIMENTAL
The structure of compounds X and XIIІ was
1
determined on the basis of the H and IR data. Adduct
1
The IR spectra were recorded in KBr on a UR-20
X displayed in the H NMR spectrum signals in the
1
spectrometer. The H NMR spectra were measured
region δ 3.53–4.01 ppm from protons in the two
methylene groups and one CH proton (PhSCH). The
1H NMR spectrum of XІIІ contained signals at δ 2.92–
3.08 (2H, CH2), 3.27–3.31 (1H, CH), 3.80–3.86 (1H,
CH), and 4.76–4.83 ppm (1H, CH). In the IR spectra
from solutions in DMSO-d6 on Varian VXR-300 in-
strument (300 MHz) using TMS as internal reference.
Perchlorates ІІa–IIc (general procedure). A solu-
tion of 0.22 g (2 mmol) of lithium perchlorate in 10 ml
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

VAS’KEVICH et al.
1850
of acetic acid was added at 15–20°C under stirring to
a suspension of 0.42 g (2 mmol) of compound I in
10 ml of acetic acid, a solution of 2.1 mmol of arene-
sulfenyl chloride in 10 ml of acetic acid was added
dropwise, and the mixture was stirred for 5–6 h and
left to stand for 12 h. The precipitate was filtered off
and washed on a filter with petroleum ether.
8-(4-Nitrophenylsulfanylmethyl)-7,8-dihydro-
1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-
one (ІІІa). Yield 0.34 g (95%), mp 284–286°C. IR
spectrum, ν, cm–1: 1635 (C=O), 1585, 1555, 1510,
1
1435, 1380, 1340, 1260, 1230, 1165, 1095. H NMR
spectrum, δ, ppm: 3.52–3.56 m (1H, CH), 3.69–
3.81 (2H, CH2), 3.89–3.96 m (1H, CH), 5.22–5.30 m
(1H, CH), 7.67 d (2H, Harom, J = 9.0 Hz), 8.06 d (2H,
8-(4-Nitrophenylsulfanylmethyl-4-oxo-4,5,7,8-
tetrahydro-1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]-
pyrimidin-9-ium perchlorate (ІIa). Yield 0.57 g
(62%), mp 294–296°C. IR spectrum, ν, cm–1: 1735
(C=O), 1600, 1560, 1520, 1430, 1380, 1340, 1260,
Harom, J = 9.0 Hz), 8.38 s (1H, 3-H), 13.75 s (1H, NH).
Found, %: C 46.51; H 3.02; N 19.34; S 17.77.
C14H11N5O3S2. Calculated, %: C 46.53; H 3.07;
N 19.38; S 17.74.
8-(Phenylsulfanylmethyl)-7,8-dihydro-1H-pyra-
zolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-one
(ІІІb). Yield 0.28 g (90%), mp 245–247°C. IR spec-
trum, ν, cm–1: 1630 (C=O), 1590, 1555, 1435, 1385,
1170, 1100 (ClO4–). H NMR spectrum, δ, ppm: 3.69–
1
3.87 m (3H, CH2, CH), 4.01–4.08 m (1H, CH), 5.40 m
(1H, CH), 7.68 d (2H, Harom, J = 8.4 Hz), 8.07 d (2H,
Harom, J = 8.4 Hz), 8.62 s (1H, 3-H), 14.32 br.s (1H,
NH). Found, %: C 36.34; H 2.58; Cl 7.63; N 15.59;
S 13.91. C14H12ClN5O7S2. Calculated, %: C 36.41;
H 2.62; Cl 7.68; N 15.61; S 13.88.
1
1260, 1170, 1080. H NMR spectrum, δ, ppm: 3.51–
3.64 m (3H, CH2, CH), 3.87–3.93 m (1H, CH), 5.12–
5.23 m (1H, CH), 7.15–7.28 m (3H, Harom), 7.41 d (2H,
Harom, J = 7.5 Hz), 8.35 s (1H, 3-H), 13.69 s (1H, NH).
Found, %: C 53.11; H 3.80; N 17.65; S 20.29.
C14H12N4OS2. Calculated, %: C 53.15; H 3.82;
N 17.71; S 20.27.
4-Oxo-8-(phenylsulfanylmethyl)-4,5,7,8-tetra-
hydro-1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrim-
idin-9-ium perchlorate (ІІb). Yield 0.53 g (64%),
mp 123–125°C. IR spectrum, ν, cm–1: 1720 (C=O),
1610, 1560, 1440, 1385, 1340, 1265, 1120, 1090 (ClO4–).
1H NMR spectrum, δ, ppm: 3.56–3.61 m (1H, CH),
3.73–3.80 m (3H, CH2, CH), 5.33–5.43 m (1H, CH),
7.17–7.23 m (3H, Harom), 7.33–7.04 m (2H, Harom),
8.59 s (3-H), 14.18 br.s (1H, NH). Found, %: C 40.30;
H 3.11; Cl 8.44; N 13.42; S 15.36. C14H13ClN4O5S2.
Calculated, %: C 40.34; H 3.14; Cl 8.50; N 13.44;
S 15.38.
8-(4-Methylphenylsulfanylmethyl)-7,8-dihydro-
1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4-
one (ІІІc). Yield 0.25 g (75%), mp 288–290°C. IR
spectrum, ν, cm–1: 1630 (C=O), 1590, 1555, 1435,
1
1385, 1265, 1180. H NMR spectrum, δ, ppm: 2.25 s
(3H, CH3), 3.51–3.58 m (3H, CH, CH2), 3.85–3.92 m
(1H, CH), 5.09–5.18 m (1H, CH), 7.05 d (2H, Harom
,
J = 8.4 Hz), 7.29 d (2H, Harom, J = 8.1 Hz), 8.35 s (1H,
3-H), 13.67 s (1H, NH). Found, %: C 54.47; H 4.25;
N 16.91; S 19.44. C15H14N4OS2. Calculated, %:
C 54.52; H 4.27; N 16.96; S 19.41.
8-(4-Methylphenylsulfanylmethyl)-4-oxo-4,5,7,8-
tetrahydro-1H-pyrazolo[4,3-e][1,3]thiazolo[3,2-a]-
pyrimidin-9-ium perchlorate (ІIc). Yield 0.72 g
(84%), mp 183–185°C. IR spectrum, ν, cm–1: 1720
(C=O), 1600, 1560, 1440, 1380, 1260, 1110 (ClO4–).
1H NMR spectrum, δ, ppm: 2.23 s (3H, CH3), 3.48–
3.54 m (1H, CH), 3.75–3.82 m (2H, CH2), 4.03–
4.10 m (1H, CH), 5.35–5.40 m (1H, CH), 6.97 d (2H,
Harom, J = 8.1 Hz), 7.23 d (2H, Harom, J = 8.1 Hz),
8.62 s (1H, 3-H), 14.22 br.s (1H, NH). Found, %:
C 41.78; H 3.50; Cl 8.21; N 12.96; S 14.90.
C15H15ClN4O5S2. Calculated, %: C 41.81; H 3.51;
Cl 8.23; N 13.00; S 14.88.
6-[3-Chloro-2-(phenylsulfanyl)propylsulfanyl]-
1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (ІV). A so-
lution of 2.1 mmol of benzenesulfanyl chloride in
10 ml of chloroform was added drpwise under stirring
at 15–20°C to a suspension of 0.42 g (2 mmol) of
compound I in 10 ml of chloroform. The mixture was
stirred for 5–6 h and left to stand for 12 h. The
precipitate was filtered off and washed on a filter with
chloroform and petroleum ether. Yield 0.66 g (93%),
mp 149–151°C. IR spectrum, ν, cm–1: 1710 (C=O),
1
1590, 1400, 1245, 1160. H NMR spectrum, δ, ppm:
3.54–3.70 m (2H, CH2), 3.88–4.02 m (3H, CH, CH2),
7.32–7.48 m (3H, Harom), 7.54–7.62 m (2H, Harom),
8.14 s (1H, 3-H), 12.39 s (1H, NH). Found, %:
C 47.62; H 3.67; Cl 10.07; N 15.85; S 18.18.
C14H13ClN4OS2. Calculated, %: C 47.65; H 3.71;
Cl 10.05; N 15.88; S 18.17.
Compounds ІІІa–IIIc (general procedure). Per-
chlorate ІІa–IIc, 1 mmol, was dissolved in 10 ml of
DMSO, 5 ml of 20% aqueous sodium acetate was
added, and the precipitate was filtered off and washed
with water.
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CYCLOFUNCTIONALIZATION OF 6-ALKENYLSULFANYLPYRAZOLO-...
1851
7-Phenylsulfanyl-7,8-dihydro-6H-pyrazolo-
[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4(1H)-one
(V). A mixture of 0.35 g (1 mmol) of compound ІV
and 1.1 mmol of anhydrous sodium acetate in 10 ml of
DMSO was heated for 1 h at 60°C. Water was then
added dropwise until a colorless solid separated. The
precipitate was filtered off and washed with water.
Yield 0.21 g (68%), mp 105–107°C. IR spectrum, ν,
cm–1: 1715 (C=O), 1595, 1575, 1490, 1230, 1140,
0.83 g (94%), mp 258–260°C. IR spectrum, ν, cm–1:
1730 (C=O), 1630, 1600, 1540, 1390, 1250, 1180.
1H NMR spectrum, δ, ppm: 2.32 s (3H, CH3), 3.23 d
(2H, CH2, J = 2.4 Hz), 4.60–4.63 m (1H, CH), 5.97 d
(1H, CH, J = 2.1 Hz), 7.20–7.49 m (9H, Harom), 8.60 s
(1H, 3-H), 14.07 br.s (1H, NH). Found, %: C 56.91;
H 4.27; Cl 7.96; N 12.62; S 14.51. C21H19ClN4OS2.
Calculated, %: C 56.94; H 4.32; Cl 8.00; N 12.65;
S 14.48.
1
1100. H NMR spectrum, δ, ppm: 3.25–3.44 m (1H,
Compounds VІІІa–VIIIc (general procedure).
Compound VIIa–VIIc, 1 mmol, was dissolved in
10 ml of DMSO, 5 ml of 20% aqueous sodium acetate
was added, and the precipitate was filtered off and
washed with water.
CH), 3.58–3.63 m (1H, CH), 4.04–4.37 m (3H, CH,
CH2), 7.33–7.51 m (5H. Harom), 8.03 s (1H, 3-Harom),
13.51 s (1H, NH). Found, %: C 53.11; H 3.80;
N 17.69; S 20.29. C14H12N4OS2. Calculated, %:
C 53.15; H 3.82; N 17.71; S 20.27.
8-(4-Nitrophenylsulfanyl)-9-phenyl-8,9-dihydro-
7H-pyrazolo[4′,3′:5,6]pyrimido[2,1-b][1,3]thiazin-
4(1H)-one (VІІІa). Yield 0.34 g (78%), mp 310–
312°C. IR spectrum, ν, cm–1: 1630 (C=O), 1600, 1540,
Chlorides VІІa–VIIc (general procedure). A solu-
tion of 2.1 mmol of the corresponding arenesulfenyl
chloride in 10 ml of acetic acid was added dropwise
under stirring at 15–20°C to a suspension of 0.57 g
(2 mmol) of compound VI in 20 ml of acetic acid. The
mixture was stirred for 5–6 h and was left to stand for
12 h, and the precipitate was filtered off and washed
on a filter with petroleum ether.
1
1430, 1390, 1340, 1255, 1185, 1100. H NMR spec-
trum, δ, ppm: 3.21–3.30 m (2H, CH2), 5.02 m (1H,
CH), 6.09 m (1H, CH), 7.31–7.49 m (5H, Harom),
7.82 d (2H, Harom, J = 8.7 Hz), 8.23 d (2H, Harom, J =
9.0 Hz), 8.40 s (1H, 3-H), 13.64 s (1H, NH). Found,
%: C 54.86; H 3.42; N 16.00; S 14.64. C20H15N5O3S2.
Calculated, %: C 54.91; H 3.46; N 16.01; S 14.66.
8-(4-Nitrophenylsulfanyl)-4-oxo-9-phenyl-
1,4,5,7,8,9-hexahydropyrazolo[4′,3′:5,6]pyrimido-
[2,1-b][1,3]thiazin-10-ium chloride (VІІa). Yield
0.75 g (79%), mp 290–292°C. IR spectrum, ν, cm–1:
9-Phenyl-8-phenylsulfanyl-8,9-dihydro-7H-pyra-
zolo[4′,3′:5,6]pyrimido[2,1-b][1,3]thiazin-4(1H)-one
(VІІІb). Yield 0.30 g (76%), mp 317–318°C. IR spec-
trum, ν, cm–1: 1650 (C=O), 1625, 1595, 1555, 1430,
1
1740 (C=O), 1590, 1520, 1340, 1250, 1180. H NMR
spectrum, δ, ppm: 3.29–3.42 m (2H, CH2), 5.09–
5.11 m (1H, CH), 6.17 m (1H, CH), 7.40–7.46 m (5H,
1
1395, 1260, 1180. H NMR spectrum, δ, ppm: 3.07–
H
H
arom), 7.83 d (2H, Harom, J = 8.7 Hz), 8.23 d (2H,
arom, J = 9.0 Hz), 8.61 s (1H, 3-H), 14.12 br.s (1H,
3.25 m (2H, CH2), 4.59–4.66 m (1H, CH); 5.94 m (1H,
CH), 7.17 d (2H. Harom, J = 7.2 Hz), 7.31–7.47 m (6H,
NH). Found, %: C 50.67; H 3.37; Cl 7.44; N 14.75;
S 13.55. C20H16ClN5O3S2. Calculated, %: C 50.68;
H 3.40; Cl 7.48; N 14.78; S 13.53.
Harom), 7.58 d (2H, Harom, J = 6 Hz), 8.38 s (1H, 3-H),
13.61 s (1H, NH). Found, %: C 54.86; H 3.42;
N 16.00; S 14.64. Calculated, %: C 54.91; H 3.46;
N 16.01; S 14.66.
4-Oxo-9-phenyl-8-phenylsulfanyl-1,4,5,7,8,9-
hexahydropyrazolo[4′,3′:5,6]pyrimido[2,1-b][1,3]-
thiazin-10-ium chloride (VІІb). Yield 0.82 g (96%),
mp 271–274°C. IR spectrum, ν, cm–1: 1730 (C=O),
1630, 1590, 1540, 1420, 1390, 1300, 1250, 1180,
8-(4-Methylphenylsulfanyl)-9-phenyl-8,9-dihy-
dro-7H-pyrazolo[4′,3′:5,6]pyrimido[2,1-b][1,3]thia-
zin-4(1H)-one (VІІІc). Yield 0.30 g (74%), mp 306–
308°C. IR spectrum, ν, cm–1: 1630 (C=O), 1610, 1540,
1
1070. H NMR spectrum, δ, ppm: 3.15–3.28 m (2H,
1
1425, 1390, 1255, 1185. H NMR spectrum, δ, ppm:
CH2), 4.65–4.71 m (1H, CH), 5.97–6.01 d (1H, CH),
7.21–7.28 m (2H, Harom), 7.30–7.52 m (6H, Harom),
7.55–7.63 m (2H, Harom), 8.47 s (1H, 3-H), 13.83 s
(1H, NH). Found, %: C 55.97; H 3.94; Cl 8.22;
N 13.01; S 14.98. C20H17ClN4OS2. Calculated, %:
C 56.00; H 3.99; Cl 8.26; N 13.06; S 14.95.
2.33 s (3H, CH3), 3.05–3.23 m (2H, CH2), 4.53–4.55 m
(1H, CH), 5.92 d (1H, CH), 7.15–7.24 m (4H, Harom),
7.32–7.49 m (5H, Harom), 8.40 s (1H, 3-H), 13.58 br.s
(1H, NH). Found, %: C 62.01; H 4.42; N 13.73;
S 15.75. C21H18N4OS2. Calculated, %: C 62.05;
H 4.46; N 13.78; S 15.77.
8-(4-Methylphenylsulfanyl)-4-oxo-9-phenyl-
1,4,5,7,8,9-hexahydropyrazolo[4′,3′:5,6]pyrimido-
[2,1-b][1,3]thiazin-10-ium chloride (VІІc). Yield
Compounds X and XІІI. A solution of 0.22 g
(2 mmol) of lithium perchlorate in 10 ml of acetic acid
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

VAS’KEVICH et al.
1852
was added under stirring at 15–20°C to a suspension of
0.57 g (2 mmol) of compound IX in 10 ml of acetic
acid, a solution of 2.1 mmol of benzenesulfenyl chlo-
ride in 10 ml of acetic acid was then added dropwise,
and the mixture was stirred for 5–6 h and left to stand
for 12 h. The precipitate of compound X was filtered
off and washed on a filter with acetic acid and petro-
leum ether. The filtrate was evaporated, and the residue
was washed with water and ground in acetone. The
crystalline product (compound XI with an impurity
of X) was filtered off and dissolved in 5 ml of DMSO,
3 ml of 20% aqueous sodium acetate was added, and
the precipitate (compound XIII) was filtered off and
washed with water.
(XII). Compound X, 0.43 g (1 mmol), was dissolved
in 5 ml of DMSO, 1.1 mmol of dry sodium acetate was
added, and the mixture was heated for 1 h at 60°C. The
mixture was diluted with 10 ml of water, and the
precipitate was filtered off, washed with water and
alcohol, and recrystallized from ethanol. Yield 0.33 g
(85%), mp 173–174°C (from ethanol). IR spectrum, ν,
cm–1: 1700 (C=O), 1595, 1560–1540, 1510, 1470,
1440, 1400, 1380, 1310, 1210, 1190, 1110, 1090.
1H NMR spectrum, δ, ppm: 3.29–3.36 m (1H, CH),
3.62–3.67 m (1H, CH), 4.00–4.15 m (1H, CH), 4.19–
4.29 m (1H, CH), 4.35–4.40 m (1H, CH), 7.33–7.61 m
(8H, Harom), 8.00–8.02 m (2H, Harom), 8.30 s (1H, 3-H).
Found, %: C 61.18; H 4.07; N 14.26; S 16.32.
C20H16N4OS2. Calculated, %: C 61.20; H 4.11;
N 14.27; S 16.34.
6-[3-Chloro-2-(phenylsulfanyl)propylsulfanyl]-1-
phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one (X).
Yield 0.36 g (42%), mp 180–182°C. IR spectrum, ν,
cm–1: 1690 (C=O), 1570, 1400, 1220, 990, 960.
1H NMR spectrum, δ, ppm: 3.53–4.01 m (5H, 2CH2,
CH), 7.30–7.53 m (8H, Harom), 8.06 d (2H, Harom, J =
8.4 Hz), 8.26 s (1H, 3-H), 12. 80 s (1H, NH). Found,
%: C 55.98; H 3.95; Cl 8.24; N 13.03; S 14.96.
C20H17ClN4OS2. Calculated, %: C 56.00; H 3.99;
Cl 8.26; N 13.06; S 14.95.
REFERENCES
1. Nicolaou, K.C., Seitz, S.P., Sipio, W.J., and Blount, J.F.,
J. Am. Chem. Soc., 1979, vol. 101, p. 3884.
2. Abd El-Samii, Z.K., Monatsh. Chem., 1995, vol. 126,
p. 609.
3. Smit, W.A., Zefirov, N.S., Bodrikov, I.V., and Kri-
mer, M.Z., Acc. Chem. Res., 1979, vol. 12, p. 282.
1-Phenyl-8-(phenylsulfanylmethyl)-7,8-dihydro-
pyrazolo[4,3-e][1,3]thiazolo[3,2-a]pyrimidin-4(1H)-
one (XIII). Yield 0.15 g (19%), mp 225–227°C. IR
spectrum, ν, cm–1: 1650 (C=O), 1580, 1560, 1470,
4. Vas’kevich, A.I. and Staninets, V.I., Ukr. Khim. Zh., 2006,
no. 11, p. 37.
5. Vas’kevich, A.I. and Staninets, V.I., Ukr. Khim. Zh., 2006,
no. 3, p. 44.
1
1410, 1240. H NMR spectrum, δ, ppm: 2.92–3.08 m
6. Vas’kevich, R.I., Khripak, S.M., Staninets, V.I., Zborov-
skii, Yu.L., and Chernega, A.N., Russ. J. Org. Chem.,
2000, vol. 36, p. 1061.
(2H, CH2), 3.27–3.31 m (1H, CH), 3.80–3.86 m (1H,
CH), 4.76–4.83 m (1H, CH), 7.07–7.24 m (5H, Harom),
7.52–7.73 m (5H, Harom), 8.05 s (1H, 3-H). Found, %:
C 61.17; H 4.09; N 14.25; S 16.33. C20H16N4OS2. Cal-
culated, %: C 61.20; H 4.11; N 14.27; S 16.34.
7. Bentya, A.V., Vas’kevich, R.I., and Staninets, V.I., Ukr.
Khim. Zh., 2008, vol. 12, p. 94.
8. Bentya, A.V., Vas’kevich, R.I., Bol’but, A.V., Vovk, M.V.,
Staninets, V.I., Turov, A.V., and Rusanov, E.B., Russ. J.
Org. Chem., 2008, vol. 44, p. 1362.
1-Phenyl-7-phenylsulfanyl-7,8-dihydro-6H-pyra-
zolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-4(1H)-one
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009