Ring–ring interconversion: the rearrangement of 6-(4-chlorophenyl)-3-
methyl-5-nitrosoimidazo[2,1-b][1,3]thiazole into 8-(4-chlorophenyl)-8-
hydroxy-5-methyl-8H-[1,4]thiazino[3,4-c][1,2,4]oxadiazol-3-one.
Elucidation of the reaction product through spectroscopic and
X-ray crystal structure analysis
a
b
b
c
Aldo Andreani, Roberta Billi, Barbara Cosimelli, Angelo Mugnoli,
a
,b
Mirella Rambaldi and Domenico Spinelli*
a
Dipartimento di Scienze Farmaceutiche, via Belmeloro 6, I-40126 Bologna, Italy
Dipartimento di Chimica Organica ‘A. Mangini’, via S. Donato 15, I-40127 Bologna, Italy
Dipartimento di Chimica e Chimica Industriale, via Dodecaneso 31, I-16146 Genova, Italy
b
c
The reactivity of 6-(4-chlorophenyl)-3-methyl-5-nitrosoimidazo[2,1-b][1,3]thiazole (a member of a class
of mutagenic compounds) with hydrochloric acid in ethanol has been investigated and the nature of the
reaction product unambiguously established on the basis of infrared, NMR and mass spectra and a crystal
structure determination.
In the course of our studies on nitrogen compounds (nitroso
c = 11.293(2) Å, α = 85.43(2), β = 72.84(2), γ = 82.26(3)Њ V =
622.6(3) Å (by least-squares refinement on diffractometer
1
3
and nitro derivatives) with mutagenic activity and on ring–ring
2
3
interconversions we have recently examined the reactivity of
-(4-chlorophenyl)-3-methyl-5-nitrosoimidazo[2,1-b][1,3]thia-
angles for 25 automatically centred reflections, λ = 0.7107 Å),
Ϫ3
¯
6
space group P1 (No. 2), Z = 2, D = 1.583 g cm , F(000) = 304.
c
zole 1 with hydrochloric acid. The study of the reactivity of
Crystal dimensions 0.38 × 0.42 × 0.29 mm, µ(Mo-Kα) = 4.79
cm .
Ϫ1
compounds showing biological activity is useful in providing
4
information concerning their biological transformations.
Several nitrosoimidazo[2,1-b][1,3]thiazoles have been shown to
Data collection and processing
be mutagenic on both base-pair and frame shift substitution
strains of Salmonella typhimurium and on yeast.
CAD-4 diffractometer, ω scan mode with scan width = 1.5Њ,
scan speed 0.9–20Њ min , graphite-monochromated Mo-Kα
5
Ϫ1
In order to gain more insight into the above mentioned reac-
tion of 1 and in view of its applicability to other 5-nitroso-
imidazo[2,1-b][1,3]thiazoles, we carried out a complete IR,
NMR ( H and C) and mass spectroscopic study. The proposed
product structure is in complete agreement with that obtained
from X-ray diffraction.
radiation; 3605 unique reflections measured (2.5 р θ р 30Њ),
3184 with F > 4σ(F). Absorption correction (max., min.
transmission factors = 1.00, 0.92). No crystal decay was
observed.
6
1
13
Structure determination and refinement
7
Direct methods, NRCVAX. The structure was solved with no
reference to a structural model; the identity of the peaks which
appeared on the E-map was assessed during the refinement, by
monitoring of bond distances and thermal factors. All hydro-
gen atoms were obtained from difference syntheses. Full-matrix
Experimental
H and C NMR spectra were determined in [ H ]DMSO
dimethyl sulfoxide) with a Varian Gemini 300 Instrument in
the Fourier transform mode at 21 ± 0.5 ЊC. Chemical shifts (δ)
are reported in ppm high frequency from tetramethylsilane as
the secondary reference. The mass spectra were recorded with a
VG70 70E apparatus. The IR spectra were obtained on a
Perkin-Elmer 1600 FTIR instrument. X-Ray diffraction data
were measured on an Enraf-Nonius CAD-4 diffractometer.
1
13
2
6
(
8
2
least-squares analysis (SHELXL93) on F , with all heavier
atoms refined as anisotropic and all hydrogens as isotropic. In
the last cycles, zero weight was given to three reflections affected
by extinction or experimental error. The weighting scheme
2
2
2
2
2
w = 1/[σ (F ) ϩ (0.0519P) ϩ 0.20P] with P = (Fo ϩ 2F )/3
o
c
2
and σ(F ) from counting statistics gave good agreement analy-
o
ses. Convergence was reached with a maximum shift-to-e.s.d.
Materials
ratio 0.001. Final R1 = 0.0359 (on F, 3184 reflections),
wR2 = 0.1009 (on F , 3602 reflections), with a goodness of fit
1b
2
Compound 1 was prepared according to a literature method.
-(4-Chlorophenyl)-8-hydroxy-5-methyl-8H-[1,4]thiazino-
3,4-c][1,2,4]oxadiazol-3-one 2. Compound 1 (1 g, 3.6 mmol)
8
S = 1.029. Scattering factors taken from SHELXL93. All
9
[
geometry calculations were done using PARST93. Standard
3
was suspended in ethanol (30 cm ) and treated at 80 ЊC under
deviations for bond lengths and bond angles not involving
hydrogen atoms are in the ranges 0.0014–0.0023 Å and 0.07–
0.16Њ, respectively. Atomic coordinates, thermal parameters,
bond distances, bond angles and torsion angles have been
deposited at the Cambridge Crystallographic Data Centre. For
details of the deposition scheme, see ‘Instructions for Authors’,
J. Chem. Soc., Perkin Trans. 2, 1997, Issue 1. Any request to the
CCDC for this material should quote the full literature citation
and the reference number 188/86. Tables of observed and calcu-
lated structure factors are available from the author (A. M.) on
request.
Ϫ3
3
stirring with hydrochloric acid (2 mol dm , 3 cm ) until com-
plete disappearance of the green colour (ca. 2.5 h). Removal of
the solvent left a light pink solid (0.90 g, 90% yield) which was
purified by recrystallization from ethanol (colourless crystals),
mp 190 ЊC (decomp.) (Found: C, 48.6; H, 3.1; N, 9.3; S, 10.9.
Calc. for C H ClN O S: C, 48.6; H, 3.1; N, 9.4; S, 10.8%;
1
2
9
2
3
Found m/z 296.001 91, C H ClN O S requires 296.002 24).
12
9
2
3
Crystal data
C H ClN O S, M = 296.7. Triclinic, a = 7.501(2), b = 7.770(2),
12
9
2
3
J. Chem. Soc., Perkin Trans. 2, 1997
2407