1
94ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2008
-1
IR (KBr): νmax 2848, 1676, 1588 cm .ꢀNMRꢀ(CDCl ):ꢀdꢀ1.30–2.18ꢀ
3
(
2
1
m,ꢀ10H),ꢀ3.13ꢀ(m,ꢀ1H),ꢀ7.60ꢀ(d,ꢀJ = 9ꢀHz,ꢀ2H),ꢀ7.77ꢀ(d,ꢀJ = 9ꢀHz,ꢀ
1
3
H),ꢀ10.03ꢀ(s,ꢀ1H)ꢀ CꢀNMRꢀ(CDCl )ꢀd,25.9,ꢀ26.0,ꢀ33.0,ꢀ41.7,ꢀ109.5,ꢀ
3
23.1, 126.9, 132.1, 133.4, 145.7, 170.5 and 177.5; Anal calcd for
C H BrN OS: C, 52.31; H, 4.13; N, 10.77%. Found: C, 52.71; H,
1
7
16
3
4
.27; N, 11.20%.
Crystal structure determination ofꢀ3
The X-ray diffraction data were collected on a Bruker Smart CCD
Area Detector System using MoKa (0.71073Å) radiation for the
crystal. Intensity data were collected up to a maximum of 27.26°
for the compound in the w–ф scan mode. The data were processed
1
6
usingꢀ SAINTPLUS. A total of 12,499 reflections were collected,
resultingꢀinꢀ3360ꢀ(Rint = 0.023) independent reflections of which the
number of reflections satisfying I>2 σ(I) criteria were 2538. These
were treated as observed. The structure was solved by direct methods
1
7
and difference Fourier synthesis using SHELXS97. ꢀTheꢀpositionsꢀ
and anisotropic displacement parameters of all non–Hydrogen
atoms were included in the full matrix least-square refinement using
1
8
SHELXL97. Then the hydrogen atoms were fixed geometrically and
were refined isotropically. The R indices for all data were R ꢀ=ꢀ0.0597ꢀ
1
andꢀwR = 0.1173. The R factor for ‘observed’ data finally converged
2
toꢀ0.0427ꢀwithꢀwR ꢀ=ꢀ0.1078.ꢀTheꢀmaximumꢀandꢀminimumꢀvaluesꢀ
2
-3
of residual electron density were 0.711 and –0.661 eÅ . Molecular
diagramsꢀwereꢀgeneratedꢀusingꢀORTEP.
1
9
Fig. 2ꢀ Viewꢀdownꢀtheꢀaꢀaxis,ꢀshowingꢀtheꢀC–H…Oꢀinteractions.
Supplementary material
Centre.ꢀTheꢀdepositionꢀnumberꢀisꢀ671066.
conformation, since the bond angles in it are all nearly
ideallyꢀ tetrahedralꢀ showingꢀ thatꢀ ringꢀ strainꢀ isꢀ negligibleꢀ
owing to puckering. The molecules are linked in chains
through C–H∙∙∙O hydrogen bond interactions (Fig. 2).ꢀ Forꢀ
the intermolecular C(6)–H(6)∙∙∙O(1') bonding the following
geometry is found: C–H 0.93 Å, H∙∙∙O 2.39 Å, C∙∙∙O 3.27 Å;
C–H∙∙∙Oꢀangleꢀ159°.
Received 20 December 2007; accepted 26 March 2008
Paper 07/5007
doi: 10.3184/030823408X305969
Theꢀauthorsꢀhaveꢀearlierꢀworkedꢀwithꢀimidazo[2,1-b][1,3,4]ꢀ
References
11-13
thiadiazoles containing pharmacophoric substituents.
ꢀ
ꢀ 1ꢀ J.ꢀStanley,ꢀGer.Offen., 1977, 2 704 288; Chem. Abstr.,ꢀ1977,ꢀ87, 201 546c.
ꢀ 2ꢀ F.ꢀSuzuki,ꢀI.ꢀKawakami,ꢀS.ꢀYamamatoꢀandꢀY.ꢀKosai,ꢀJapan Kokai,ꢀ1977,ꢀ
The structural features, namely the angular orientation of
imidazothiadiazole ring system with respect to other rings in
the molecule as well as the C–H∙∙∙O hydrogen bond aided self
assembly are found to be common in all of them. Structural
comparisons of all these compounds seem to point towards a
unique binding mode to proteins in biological systems, which
necessitate the virtual screening of these entities via docking
studies.
7
776 432; Chem. Abstr.,ꢀ1978,ꢀ88,ꢀ100ꢀ351a.
3ꢀ D.C.H.ꢀBigg.ꢀA.W.ꢀFaullꢀandꢀS.R.ꢀPurvis,ꢀJ. Heterocyclic Chem.,ꢀ1977ꢀ
4, 603.
4ꢀ K.K.ꢀBargava,ꢀM.H.ꢀLee,ꢀY.ꢀJaung,ꢀL.S.ꢀCunningham,ꢀK.C.ꢀAgrawalꢀandꢀ
A.C.ꢀSartorelli, J. Med. Chem.,ꢀ1977,ꢀ20,ꢀ563.
5ꢀ K.ꢀMiyamoto,ꢀR.ꢀKoshiura,ꢀM.ꢀMori,ꢀH.ꢀYokoi,ꢀC.ꢀMori,ꢀT.ꢀHusegawaꢀandꢀ
K.ꢀTakatori,ꢀChem. Pharm. Bull.,ꢀ1985,ꢀ33,ꢀ5216
6ꢀ M.A.ꢀEldawy,ꢀS.A.ꢀShamsꢀEl-DineꢀandꢀK.M.ꢀEl-Brembaly,ꢀPharmazie,ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1
1
979ꢀ34,ꢀ144.
7ꢀ V.P.ꢀ Arya,ꢀ F.ꢀ Fernandesꢀ andꢀ V.ꢀ Sudarsanum, Indian J. Chem.,ꢀ 1972,ꢀ
0B,ꢀ598.
1
Experimental
8
G. Mazzone, F. Bonina, A.M. Panico, G. Puglisi, G. Morchetta,ꢀ
A.M.ꢀRoxas,ꢀA.ꢀCarlusoꢀandꢀG.ꢀBlandino,ꢀFarmaco, Ed. Sci.,ꢀ1984, 39, 585;
Chem. Abstr.,ꢀ1984,ꢀ101, 122ꢀ570k.
Melting points were determined in open capillaries. The IR spectra of
samples as KBr pellets were recorded on a Nicolet FT IR Spectrometer
(
3
model 410, USA). NMR spectra in CDCl were recorded on a Bruker
9
F. Palagiano, L. Arenare, E. Laraschi, P. de Caprariis, E. Abignente,ꢀ
M. D’Amico, W. Filippelli and F. Rossi, Eur. J. Med, Chem.,ꢀ1995,ꢀ30,ꢀ901.
3
ꢀ
00 MHz Spectrometer (Model RX-300, Switzerland) using TMS
as an internal standard. C, H and N analyses were carried out on a
Thermoquest CHN analyser (Carlo Erba, Italy).
ꢀ10ꢀ I.M.ꢀKhazi,ꢀR.S.ꢀKoti,ꢀA.K.ꢀGadad.ꢀC.S.ꢀMahajanashetti,ꢀY.B.ꢀShivakumarꢀ
andꢀM.V.ꢀAkki,ꢀIndian J. Chem.,ꢀ2004,ꢀ43B,ꢀ393.
ꢀ11ꢀ Noorꢀ Shahinaꢀ Begum,ꢀ D.E.ꢀ Vasundhara,ꢀ C.R.ꢀ Girija,ꢀ G.D.ꢀ Kolavi,ꢀ
V.S.ꢀHegdeꢀandꢀI.M.ꢀKhazi,ꢀJ. Chem. Res.,ꢀ2006,ꢀ286.
1
4
Compoundsꢀ 1, m.p.ꢀ 246–248°Cꢀ (lit. ꢀ m.p.ꢀ 243–245°C)ꢀ andꢀ 2,
15
m.p. 107–110°Cꢀ(lit. ꢀm.p.108–109°C)ꢀwereꢀpreparedꢀbyꢀliteratureꢀ
ꢀ12ꢀ Noorꢀ Shahinaꢀ Begum,ꢀ D.E.ꢀ Vasundhara,ꢀ C.R.ꢀ Girija,ꢀ G.D.ꢀ Kolavi,ꢀ
procedures.
V.S.ꢀHegdeꢀandꢀI.M.ꢀKhazi,ꢀJ. Chem. Cryst.,ꢀ2007,ꢀ3,ꢀ193.
2
-Cyclohexyl-5-formyl-6-(4-bromophenyl)imidazo[2,1-b][1,3,4]
ꢀ13ꢀ Noorꢀ Shahinaꢀ Begum,ꢀ D.E.ꢀ Vasundhara,ꢀ G.D.ꢀ Kolaviꢀ andꢀ I.M.ꢀ Khazi,ꢀ
thiadiazoleꢀ (3): Vilsmeier Haack reagent was prepared by adding
POCl3 (3 ml) to cold DMF (20 ml). Then 2-cyclohexyl-6-(4-
bromophenyl)imidazo[2,1-b][1,3,4]thiadiazoleꢀ (3.2ꢀ g,ꢀ 8.84ꢀ mmol)ꢀ
Acta Cryst.,ꢀ2007,ꢀE63,ꢀo1955.
1
4
A. Foroumadi, T.M. Danesh and A. Shafiee, Arzneim.-Forsch., Drug Res.,ꢀ
999,ꢀ49, 1035.
1
wasꢀ addedꢀ toꢀ theꢀ reagentꢀ andꢀ theꢀ resultingꢀ solutionꢀ wasꢀ stirredꢀ atꢀ
1
1
5
6
W.L. Judefind and E.M. Reid, J. Am. Chem. Soc., 1991,ꢀ63,ꢀ2490.
Bruker, SAINT PLUS 1998, Program for data reduction, Bruker Axs Inc.,
Madison, Wisconsin, USA.
o
0
C for 30 min. Stirring was continued for 2 h at room temperature,
followed by further stirring for 2 h at 60°C. The reaction mixture was
poured into cold 10% aqueous Na CO ꢀandꢀstirredꢀatꢀ90°Cꢀforꢀ2ꢀh.ꢀ
2
3
17 G.M. Sheldrick, SHELXS97 1997, Program for the solution of crystal
structures, University of Göttingen, Germany.
18 G.M. Sheldrick, SHELXL97 1997, Program for crystal structure
refinement, University of Göttingen, Germany.
After cooling, the solution was extracted with chloroform, washed
withꢀwater,ꢀandꢀdriedꢀoverꢀanhydrousꢀsodiumꢀsulfate.ꢀTheꢀsolventꢀwasꢀ
removed under reduced pressure to provide the product 3ꢀ(2.43ꢀg,ꢀ
7
1
0%). The crystals for X-ray were obtained as colourless cubes, m.p.
44–146°Cꢀ byꢀ slowꢀ evaporationꢀ ofꢀ aꢀ solutionꢀ ofꢀ 3 in chloroform.
ꢀ19ꢀ L.J.ꢀFarrugia,ꢀORTEP-3ꢀforꢀWINDOWS-AꢀVersionꢀofꢀORTEP-111ꢀwithꢀaꢀ
Graphical User Interface (GUI). J. Appl. Cryst.,ꢀ1997,ꢀ30,ꢀ565.
PAPER:ꢀ07/5007