3,4-Dibromotetrahydro-λ6-thiophene 1,1-dioxide in S,N-tandem heterocyclizations. Synthesis of tetrahydrothienothiazolopyrimidines

Full text of DOI:10.1134/S1070428007040318

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 4, pp. 639–640. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © A.A. Shklyarenko, V.V. Yakovlev, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 4, p. 640.
SHORT
COMMUNICATIONS
3,4-Dibromotetrahydro-λ6-thiophene 1,1-Dioxide in S,N-Tandem
Heterocyclizations. Synthesis of Tetrahydrothieno-
thiazolopyrimidines
A. A. Shklyarenko and V. V. Yakovlev
“Applied Chemistry” Russian Research Center, pr. Dobrolyubova 14, St. Petersburg, 197198 Russia
e-mail: synthon@inbox.ru
Received November 17, 2006
DOI: 10.1134/S1070428007040318
1H NMR and mass spectra. The 1H NMR spectra of IIa
Pyrimidine derivatives possess important pharma-
cological properties [1]. Among these, the most promi-
nent are such naturally occurring alkaloids as batzella-
dines [2], ptilomycalins [3], saxitoxins [4], and luoto-
nins [5]; their molecules include five-membered satu-
rated rings fused to a pyrimidine base. We previously
showed [6] that 2,3-dibromopropyl sulfones readily
undergo heterocyclization with 2-thiouracils. While
continuing studies on tandem heterocyclizations, we
have synthesized tetrahydrothienothiazolopyrimidine
derivatives via S,N-tandem alkylation of 2-thiouracils
Ia and Ib with 3,4-dibromotetrahydro-λ6-thiophene
1,1-dioxide. The reactions were carried out in ethanol
at room temperature, the reactant ratio dibromosulfo-
lane–2-thiouracil I–potassium hydroxide being 1:2:4;
the reactions were complete in 8 h, and the yields of
products IIa and IIb were 78–80%.
and IIb contained signals from the CH2CHCHCH2
fragment as an ABMM'NN' spin system having four
chiral centers. In the mass spectra of IIa and IIb, the
most characteristic were peaks from the following frag-
ment ions: [M – SO2H]+, [M – SO2]+, [M – SO2 – SH]+,
[M – SO2 – SH – C2H2]+. The fragmentation pattern
was proposed on the basis of published data [7, 8]. The
absence of isomeric compounds among the products
indicates that the reaction is chemo- and regioselective
and that the process follows a concerted mechanism
typical of tandem reactions [9].
2-Amino-5a,6,8,8a-tetrahydro-4H-7λ6-thieno-
[3',4':4,5][1,3]thiazolo[3,2-a]pyrimidin-4-one 7,7-di-
oxide (IIa). Yield 78%, mp 276–277°C (from EtOH–
1
DMF). H NMR spectrum, δ, ppm: 3.38 m (2H, CH),
3.65 m (2H, CH), 4.56 m (1H, CH), 4.85 s (1H, Harom),
5.33 m (1H, CH), 6.38 br.s (2H, NH2). Mass spectrum,
m/z (Irel, %): 259 (100) [M]+, 194 (30.5), 195 (51.1),
162 (62.2), 136 (58.8).
O
Br
Br
NH
+
S
N
2-Methoxy-5a,6,8,8a-tetrahydro-4H-7λ6-thieno-
[3',4':4,5][1,3]thiazolo[3,2-a]pyrimidin-4-one 7,7-di-
oxide (IIb). Yield 80%, mp 263–264°C (from EtOH–
R
N
H
S
O
O
Ia, Ib
1
O
DMF). H NMR spectrum, δ, ppm: 3.56 m (2H, CH),
O
N
O
S
3.68 m (2H, CH), 3.77 s (3H, CH3), 4.79 m (1H, CH),
5.33 s (1H, Harom), 5.43 m (1H, CH). Mass spectrum,
m/z (Irel, %): 274 (100) [M]+, 209 (36.6), 210 (52.4),
177 (64.9), 151 (48.6).
S
R
IIa, IIb
1
The H NMR spectra were recorded from solutions
R = NH2 (a), MeO (b).
in DMSO-d6 on a Bruker AM-500 spectrometer
(500.13 MHz) using the residual proton signal of
the solvent as reference. The mass spectra (electron
Products IIa and IIb were isolated as individual
substances, and their structure was confirmed by the
639

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640
3. Heys, L., Moore, C.G., and Murphy, P.J., Chem. Soc.
Rev., 2000, vol. 29, p. 57.
4. Kishi, Y., Heterocycles, 1980, vol. 14, p. 1477.
5. Santosh, B.M. and Narshinha, P.A., Syhthesis, 2002,
p. 323.
6. Shklyarenko, A.A., Chernitsa, B.V., and Yakovlev, V.V.,
Russ. J. Org. Chem., 2005, vol. 41, p. 1097.
7. Ponomarev, D.A. and Takhistov, V.V., Recent Advances in
Analytical Techniques, Attaur-Rahman, M., Ed., Reading:
Hardwood Academic, 2002, p. 369.
impact, 70 eV) were obtained on an MKh-1321 mass
spectrometer with direct sample admission into the ion
source. LC–MS analysis was performed on a Micro-
mass ZDM-2000 instrument (electrospray ionization,
positive ion registration).
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 4 2007