(2,3-Dibromopropyl)sulfonylarenes in S,N-tandem heterocyclizations. A new synthesis of thiazolopyrimidines

Full text of DOI:10.1007/s11178-005-0300-1

Russian Journal of Organic Chemistry, Vol. 41, No. 7, 2005, pp. 1097–1099. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 7, 2005,
pp. 1117–1118.
Original Russian Text Copyright © 2005 by Shklyarenko, Chernitsa, Yakovlev.
SHORT
COMMUNICATIONS
(2,3-Dibromopropyl)sulfonylarenes in S,N-Tandem
Heterocyclizations. A New Synthesis of Thiazolopyrimidines
A. A. Shklyarenko, B. V. Chernitsa, and V. V. Yakovlev
Institute of High-Molecular Compounds, Russian Academy of Sciences, Bol’shoi pr. V.O. 31, St. Petersburg, 199004 Russia
e-mail: synthon@inbox.ru
Received February 4, 2005
Pyrimidine derivatives occupy an important place
in the chemistry of heterocyclic compounds, for they
exhibit a broad spectrum of biological activity [1].
Molecules of many biologically active natural com-
pounds include five-membered saturated rings fused to
a pyrimidine base; examples are batzelladines [2],
ptilomycalins [3], and saxitoxins [4].
from the [M – Me]+, [M – Me – CO]+, and [M – Me –
CH3CN]+ ions. The fragmentation patterns were pro-
posed in accordance with the data of [7, 8]. The
absence of isomeric products in the reaction mixtures
indicates high chemo- and regioselectivity of the
process and suggests concerted mechanism typical of
tandem reactions [9].
7-Amino-3-phenylsulfonylmethyl-2,3-dihydro-
While continuing our studies in the field of tandem
heterocyclizations [5, 6], we have synthesized dihydro-
thiazolo[3,2-a]pyrimidines via S,N-tandem alkylation
of 2-thiouracils with aryl 2,3-dibromopropyl sulfones.
All reactions were carried out in ethanol, the molar
ratio of aryl 2,3-dibromopropyl sulfone II, nucleophile
I, and potassium hydroxide was 1:2:4, and the reac-
tion mixture was stirred for 8 h at room temperature.
The yields of products IIIa–IIIh were 80–90%. The
structure of compounds IIIa–IIIh was proved by the
1H NMR and mass spectra. In addition, the structure of
IIIa in crystal was studied by X-ray analysis. The
structure of molecule IIIa is shown in figure.
The 1H NMR spectra of IIIa–IIIh contained signals
from the CH2CHCH2 group, which gave rise to
an AA'XMM' system with two chiral centers typical of
a thiazolidine ring. Compounds IIIa–IIId showed in
the mass spectra the following most characteristic frag-
ment ions: [M – CO]+, [M – SO2 – OH]+, [M – SO2 –
SH]+. The mass spectra of IIIe–IIIh contained peaks
5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (IIIa). Yield
1
95%, mp 263–264°C (from EtOH–DMF). H NMR
spectrum, δ, ppm: 3.75 d (1H, CH), 3.66 m (2H, CH2),
3.79 m (1H, CH), 4.73 s (1H, Harom), 5.11 m (1H, CH),
6.35 br.s (2H, NH2), 6.67 m (2H, Harom), 7.75 m (1H,
H
arom), 7.94 d (2H, Harom). Mass spectrum, m/z (Irel, %):
323 (31.8) [M]+, 259 (1.8), 226 (31.6), 154 (100).
7-Amino-3-(4-methylphenylsulfonylmethyl)-2,3-
dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIIb). Yield 89%, mp 134–135°C (from EtOH–DMF).
1H NMR spectrum, δ, ppm: 2.47 s (3H, CH3), 3.69 m
(1H, CH), 3.78 m (2H, CH2), 3.91 m (1H, CH), 4.75 s
(1H, Harom), 4.94 m (1H, CH), 6.37 br.s (2H, NH2),
7.42 d (2H, Harom), 7.82 d (2H, Harom). Mass spectrum,
m/z (Irel, %): 337 (27.7) [M]+, 273 (1.2), 258 (0.6), 240
(29.8), 168 (100).
7-Amino-3-(4-nitrophenylsulfonylmethyl)-2,3-
dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIIc). Yield 86%, mp 242–243°C (from EtOH–DMF).
O
O
CH2SO2Ar
R
R
NH
N
+
BrCH2CHBrCH2SO2Ar
S
R'
N
H
S
R'
N
Ia, Ib
IIa–IId
IIIa–IIIh
I, R = H, R' = NH2 (a); R = Et, R' = Me (b); II, Ar = Ph (a), 4-MeC6H4 (b), 4-O2NC6H4 (c), 2-naphthyl (d); III, R = H, R' = NH2,
Ar = Ph (a), 4-MeC6H4 (b), 4-O2NC6H4 (c), 2-naphthyl (d); R = Et, R' = Me, Ar = Ph (e), 4-MeC6H4 (f), 4-O2NC6H4 (g), 2-naphthyl (h).
1070-4280/05/4107-1097 © 2005 Pleiades Publishing, Inc.

SHKLYARENKO et al.
1098
N3
3.69 m (3H, CH3), 3.91 m (1H, CH), 4.91 m (1H, CH),
7.42 d (2H, Harom), 7.82 d (2H, Harom). Mass spectrum,
m/z (Irel, %): 364 (60.1) [M]+, 349 (50.8), 321 (0.9),
308 (1.7), 195 (100).
C12
C11
O3
C4
C13
N2
6-Ethyl-7-methyl-3-(4-nitrophenylsulfonyl-
methyl)-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimi-
din-5-one (IIIg). Yield 80%, mp 193–194°C (from
C5
N1
C10
C3
C6
C1
1
C8
EtOH). H NMR spectrum, δ, ppm: 0.93 t (3H, CH3),
S2
C2
2.03 s (3H, CH3), 2.18 s (2H, CH2), 3.65 m (1H, CH),
3.82 m (1H, CH), 3.99 m (1H, CH), 4.13 m (1H, CH),
5.05 m (1H, CH), 8.28 d (2H, Harom), 8.45 d (2H,
C9
C7
S1
arom). Mass spectrum, m/z (Irel, %): 395 (61.8) [M]+,
O2
H
380 (48.6), 352 (1.1), 339 (2.6), 226 (100).
O1
6-Ethyl-7-methyl-3-(2-naphthylsulfonylmethyl)-
2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIIh). Yield 88%, mp 160–161°C (from EtOH).
1H NMR spectrum, δ, ppm: 0.90 t (3H, CH3), 2.04 s
(3H, CH3), 2.21 m (2H, CH2), 3.65 d (1H, CH), 3.82 m
(3H, CH3), 5.23 m (1H, CH), 7.68 m (2H, Harom),
7.89 d (1H, Harom), 8.02 d (1H, Harom), 8.14 m (2H,
Structure of the molecule of 7-amino-3-phenylsulfonyl-
methyl-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIIa) according to the X-ray diffraction data (hydrogen
atoms are not shown).
1H NMR spectrum, δ, ppm: 3.61 d (1H, CH), 3.74 m
(2H, CH2), 3.89 m (1H, CH), 4.69 s (1H, Harom),
5.06 m (1H, CH), 6.33 br.s (2H, NH2), 8.23 d (2H,
H
arom), 8.54 s (1H, Harom). Mass spectrum, m/z (Irel, %):
400 (63.5) [M]+, 385 (48.8), 357 (1.1), 344 (2.5),
H
arom), 8.44 d (2H, Harom). Mass spectrum, m/z (Irel, %):
368 (28.8) [M]+, 304 (2.1), 289 (0.9), 271 (33.1),
231 (100).
199 (100).
The mass spectra were obtained on a Micromass
ZDM-2000 GC–MS system (electrospray ionization,
positive ion detection) and on an MKh-1321 mass
spectrometer (electron impact, 70 eV, direct sample
7-Amino-3-(2-naphthylsulfonylmethyl)-2,3-di-
hydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIId). Yield 82%, mp 177–178°C (from EtOH–DMF).
1H NMR spectrum, δ, ppm: 3.61 m (1H, CH), 3.72 m
(2H, CH2), 3.78 m (1H, CH), 4.75 s (1H, Harom),
5.31 m (1H, CH), 6.36 br.s (2H, NH2), 7.68 m (2H,
1
admission into the ion source). The H NMR spectra
were recorded from solutions in DMSO-d6 on a Bruker
AM-500 spectrometer (500.13 MHz) using residual
proton signal of the solvent as reference. X-Ray anal-
ysis of a single crystal (0.32×0.30×0.26 mm) of com-
pound IIIa was performed at 293 K using an Enraf–
Nonius CAD-4 diffractometer. The structure was
solved by the direct method using SHELX-97 software
package [10].
H
arom), 7.89 d (1H, Harom), 8.02 d (1H, Harom), 8.13 m
(2H, Harom), 8.58 s (1H, Harom). Mass spectrum, m/z
(Irel, %): 373 (29.2) [M]+, 309 (2.1), 294 (1.1), 276
(30.8), 204 (100).
6-Ethyl-7-methyl-3-phenylsulfonylmethyl-2,3-
dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one
(IIIe). Yield 85%, mp 168–169°C (from EtOH).
1H NMR spectrum, δ, ppm: 0.92 t (3H, CH3), 2.05 s
(3H, CH3), 2.21 m (2H, CH2), 3.64 m (1H, CH), 3.82 m
(2H, CH2), 3.96 m (1H, CH), 4.97 m (1H, CH), 7.63 m
(2H, Harom), 7.72 m (1H, Harom), 7.96 d (2H, Harom).
Mass spectrum, m/z (Irel, %): 350 (62.2) [M]+, 335
(49.6), 307 (0.8), 294 (2.2), 181 (100).
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(2,3-DIBROMOPROPYL)SULFONYLARENES IN S,N-TANDEM HETEROCYCLIZATIONS.
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