58
F. Yaremenko et al. / Journal of Molecular Structure 874 (2008) 57–63
ketones were reported as potent antagonists of specific che-
mokine (CXCR2) receptors [6] and prospective anticancer
agents [7].
was kept in cold for 24 h. The precipitate of 5p was fil-
tered and washed with chloroform. The filtrate was
diluted with acetone and kept in cold for 24 h. The pre-
cipitated solid of 4p was filtered off, washed with acetone
and dried.
Even though 2-aminothiazoline (1) and its derivatives
have been investigating for many years, surprisingly limited
information is available on the heterocyclization of 1 with
a,b-unsaturated carbonyl compounds. We know paper [8]
and patent [9], but the synthetic information described in
them lack important structural details. Authors of [8]
inform about the possibility to oxidize the 7-hydroxy group
to keto group in the reaction of MnO2 with 5-R-7-hydroxy-
5H-2,3,6,7-tetrahydrothiazolo[2,3-a]pyrimidines which has
no second substituent in position 7. Surprisingly, nothing
is mentioned about both the formation of diastereomers
and the dehydratation. According to our experience, these
processes are very difficult to avoid.
Compound 5p. 1H NMR (DMSO-d6) d: 3.30 (m, 4H, C2-
H), 3.70 (m, 4H, C3-H), 3.86 (s, 6H, OCH3), 7.12–8.30 (m,
12H, CHarom.), 8.37–8.40 (m, 4H, CHarom.).
2.2. Instruments
1H and 13C NMR spectra were recorded on Bruker AM-
300 spectrometer using CDCl3 or DMSO-d6 as the solvent
at 25 °C and TMS as the internal standard. Mass spectra
were recorded on FINNIGAN MAT. INCOS 50 instru-
ment at 70 eV. Microanalyses were carried out on LECO
CHNS-900 elemental analyzer.
2. Experimental
2.3. X-ray diffraction study
2.1. Synthesis
Crystals of compounds 3i and 4p for X-ray diffraction
experiments were grown in acetone at 20 °C.
The general procedure for the preparation of 5-R-7-
hydroxy-7-R0-5H-2,3,6,7-tetrahydrothiazolo[2,3-a]pyrimidines
3a–j, 5,7-diaryl-5H-2,3-dihydrothiazolo[2,3-a]pyrimidines 4k,
m,o and 5,50-bis-5-(4-fluorophenyl)-7-phenyl-2,3-dihydro-
thiazolo[2,3-a]pyrimidine 5r. Amine 1 (0.80 g, 8.0 mmol)
was added to the acetone solution of a corresponding alde-
hyde or ketone 2. The mixture was stirred until complete
dissolution of 1 and kept at room temperature in dark
(time of the reaction is 1 day for 3c, 2 days for 3a,f, 4 days
for 3b,d, 5 days for 3g, 13 days for 3i, 17 days for 3e, 20
days for 3h, 30 days for 3j and 5r). The precipitate formed
was filtered off, washed with acetone and dried.
Crystals of 3i are triclinic. At 293 K a = 10.001(2),
˚
b = 11.247(2), c = 13.904(3) A, a = 90.42(2)°, b = 109.94
´
3
˚
(2(8)°, c = 104.39(2)°, V = 1426(2) A , Mr = 262.37, Z =
4, the space group is P1, dcalc = 1.218 g/cm3, l(MoKa) =
0.218 mmꢀ1, F(000) = 560. Intensity of 8003 reflections
(4774 independent, Rint = 0.047) were measured on the
ꢁXcalibur-3ꢂ diffractometer (graphite monochromated
MoKa radiation, CCD detector, x-scaning, 2Hmax = 50°).
The structure was solved by the direct method using SHEL-
XTL package [10]. Positions of hydrogen atoms were calcu-
lated geometrically and refined using the ‘‘riding’’ model
with Uiso = nUeq of a non-hydrogen atom bonded with
the given hydrogen atom (n = 1.5 for methyl and hydroxyl
groups and n = 1.2 for other hydrogen atoms). The full-
matrix least-squares refinement against F2 in the anisotropic
approximation using 4533 reflections was converged to
R1 = 0.056 (for 1686 reflections with F > 4r(F)),
wR2 = 0.088, S = 0.746. Atomic coordinates and crystallo-
graphic parameters have been deposited to the Cambridge
Crystallographic Data Centre (CCDC 636587).
Compound 5r. 1H NMR (DMSO-d6) d: 3.30 (m, 4H, C2-
H), 4.0 (m, 4H, C3-H), 7.10–7.70 (m, 10H, CHarom.), 7.97–
8.20 (m, 8H, CHarom.).
7-Hydroxy-7-methyl-5-phenyl-5H-2,3,6,7-tetrahydro-
thiazolo[2,3-a]pyrimidine (3d). The mixture of amine 1 (15
mmol, 1.50 g) and benzalacetone (2d) (15 mmol, 1.50 g) in
DMF (3 ml) was heated on water-bath for 4 h. Then the
reaction mixture cooled down and poured into the 100 ml
of ice water. Resulting precipitate was recrystallized from
acetone.
7-(4-Methoxyphenyl)-5-phenyl-5H-2,3-dihydrothiazol-
o[2,3-a]pyrimidine (4l). The mixture of amine 1 (15 mmol,
1.50 g) and chalcone 2l (10 mmol, 2.40 g) in DMF (5 ml)
was refluxed for 0.5 h. The resulting solution cooled down,
diluted with acetone (40 ml) and kept in cold for 24 h. The
precipitate formed was filtered off, washed with acetone
and dried.
Crystals of 4p are orthorhombic. At 293 K a = 8.637(2),
´
3
˚
˚
b = 10.878(2), c = 18.003(4) A, V = 1691.4(6) A , Mr =
367.42, Z = 4, the space group is P212121, dcalc = 1.443 g/
cm3, l(MoKa) = 0.217 mmꢀ1, F(000) = 768. Intensity of
1734 reflections were measured on an automatic four circles
Siemens P3/PC diffractometer (graphite monochromated
MoKa radiation, H/2H scaning, 2Hmax = 50°). The struc-
ture was solved by the direct method using SHELXTL
package [10]. Positions of hydrogen atoms were calculated
geometrically and refined using the ‘‘riding’’ model with
Uiso = nUeq of a non-hydrogen atom bonded with the given
hydrogen atom (n = 1.5 for methyl group and n = 1.2 for
other hydrogen atoms). The full-matrix least-squares refine-
ment against F2 in the anisotropic approximation using
1697 reflections was converged to R1 = 0.066 (for 1122
7-(4-Methoxyphenyl)-5-(4-nitrophenyl)-5H-2,3-dihydro-
thiazolo[2,3-a]pyrimidine 4p and 5,50-bis-5-(4-nitrophenyl)-
7-(4-methoxyphenyl)-2,3-
dihydrothiazolo[2,3-a]pyrimi-
dine 5p. The mixture of amine 1 (15 mmol, 1.50 g) and
chalcone 2p (10 mmol, 2.40 g) in chloroform (50 ml) was
refluxed for 18 h. Then the reaction mixture was evapo-
rated down to volume of 10 ml and the resulting solution