Thus, the condensation of 1-amino-2-benzylthioimidazoles with carbonyl compounds does not stop upon
formation of the imine due to further intramolecular cyclization leading to 3,4-dihydro-2H-imidazo-
[2,1-b][1,3,4]thiadiazines. A similar intramolecular cyclization occurs in the alkylation of the mercapto group in
imidazolylimines by phenacyl halides. This reaction is a convenient method for the fusion of a dihydrothiadiazine
ring and preparation of previously unreported 3,4-dihydro-2H-imidazo-[2,1-b][1,3,4]thiadiazines. A special feature of
this reaction is the formation of a C–C bond in the final heterocyclization step. The conditions for this reaction are a
basic medium and enhanced acidity of the methylene protons of the thioethers group.
EXPERIMENTAL
1
The H NMR spectra were taken on a Varian Unity-300 spectrometer at 300 MHz and on a Bruker
DPX-250 spectrometer at 250 MHz at 25°C with TMS as the internal standard.
X-ray Diffraction Structural Analysis of 11a. The study of 11a was carried out at 183(2) K on a
Syntex P21 automatic four-circle diffractometer using MoKα radiation, graphite monochromator, and
θ/2θ-scanning, 2θ < 60°. The unit cell parameters of the monoclinic crystal at -90°C grown from acetonitrile:
a = 13.154(3), b = 8.8690(18), c = 16.163(3) Å, β = 111.90(3)°, V = 1749.4(7) Å3, space group P21/n, Z = 4
(Z' = 1), M = 379.39, dcalc = 1.441 g/cm3, µ = 2.16 cm-1, F(000) = 748. A total of 5289 reflections were measured
(Rint = 0.0225) and 5101 independent reflections were used in the subsequent calculations and refinements.
The structure of 11a was solved by the direct method and refined by the method of least squares in the
anisotropic full-matrix approximation. The hydrogen atoms were localized from the electron density Fourier
difference map and their positions were refined isotropically. The final R = 0.0455 using 4258 reflections with
I ≥ 2σ(I), wR2 = 0.1032, GOOF = 1.072. All the calculations were carried out using the SHELXTL PLUS 5
program package [2].
The complete crystallographic data have been deposited at the Cambridge Crystallographic Data Center,
CCDC No. 633535.
Samples of starting hydrochloride salt of 1-amino-2-mercaptoimidazole 3a and 1-amino-2-mercapto-
6-phenylimidazole 3b were obtained according to reported procedures [3, 4].
1-Benzyl-3-(2-mercapto-1-imidazolylimino)-2,3-dihydro-2-indolone (4). Triethylamine (2 ml) was
added to a mixture of 0.3 g (2 mmol) hydrochloride salt of aminomercaptoimidazole 3a and N-benzylisatin
(0.47 g, 2 mmol) in glacial acetic acid (3 ml). The mixture was heated at reflux for 2 h. After cooling, water
(20 ml) was added to the reaction mixture. The precipitate formed was filtered off, washed with water, and dried.
The crude product was recrystallized from benzene.
1-[(4-Bromophenyl)methylideneamino]-1H-imidazole-2-thiol (5). Triethylamine (0.6 ml) was added
to a mixture of hydrochloride salt of aminomercaptoimidazole 3a (0.5 g, 3.3 mmol) and p-bromobenzaldehyde
(0.611 g, 3.3 mmol) in glacial acetic acid (10 ml) and the mixture was heated at reflux for 3.5 h. The precipitate
formed was filtered off and recrystallized from ethanol.
1'-Benzyl-2-(4-bromobenzoyl)spiro[imidazo[2,1-b][1,3,4]thiadiazine-3,3'-indol]-2'(1H)-one
(6).
Imidazolylisatinimine 4 (0.33 g, 1 mmol) was added to a solution of NaOH (0.04 g, 1 mmol) in ethanol (3 ml).
After dissolution, p-bromophenacyl bromide (0.28 g, 1 mmol) was added and the solution was heated at reflux
for 5 min. After cooling, water (20 ml) was added and the precipitate was filtered off. The crude product was
recrystallized from acetonitrile.
2-Benzoyl-3-(4-bromophenyl)-3,4-dihydro-2H-imidazo[2,1-b][1,3,4]thiadiazine (7a). Methylidene-
amino-1H-imidazole-2-thiol 5 (0.28 g, 1 mmol) was added to a solution of NaOH (0.04 g, 1 mmol) in ethanol
(3 ml). After the complete dissolution of 5, phenacyl bromide (0.2 g, 1 mmol) was added. The mixture was
stirred for 5 min and, then, water (20 ml) was added. The precipitate formed was filtered off and recrystallized
from acetonitrile.
1208
Kolodina
