N. A. Mir et al. / Tetrahedron Letters 55 (2014) 1706–1710
1707
compounds with imidazo[2,1-b]thiazole and thiazolo[3,2-a]benz-
imidazole as core structure include antimicrobial agent,5,6 antitu-
mor agent,7–13 antiallergic agents,14 antihelminthic15,16 and
antibacterial agents.17,18
Keeping in view the broad spectrum of biological properties of
these compounds, the chemistry and synthesis of polycyclic com-
pounds possessing core scaffold imidazo[2,1-b]thiazole have at-
tracted enormous attention. Zhang et al. synthesized
benzo[d]imidazo[2,1-b]thiazoles based on aromatic nucleophilic
substitution reactions starting from binucleophile substrates.19
Mukherjee et al. reported microwave assisted synthesis of desired
products attached to a variety of quinoxalinone molecules.20 Re-
cently Khodaei et al. used electrochemically induced tandem het-
eroannulation method for the synthesis of tetracyclic
imidazo[2,1-b]thiazoles.21 Moreover, several ‘authors’ have used
microwave assisted Ugi-type multicomponent reaction of hetero-
cyclic amidines with aldehydes and isocyanides to generate the de-
sired products.22,23 George and co-workers have earlier reported
that the reaction of imidazole, pyrazole and aziridine derivatives
with dibenzoylacetylene (DBA) yields a mixture of E and Z
isomeric adducts.24–26 Interestingly, the reaction of dimethylacety-
lenedicarboxylate (DMAD) with 2-aminobenzothiazole and
2-aminobenzimidazole has been reported to give 2-oxopyrimi-
do[1,2-a]benzothiazole and 2-oxopyrimido[1,2-a]benzimidazole
respectively, as shown in Scheme 1.27 Herein, we report a highly
Ph
O
N
OH
Ph
S
N
(a)
(b)
Ph
O
efficient catalyst-free one pot synthesis of
a
series of imi-
OH
Ph
N
dazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles by
the reaction of DBA with 2-aminothiazole/imidazole and 2-merca-
ptoimidazole derivatives respectively.28
N
S
The reaction of an equimolar mixture of 2-aminothiazole 10
with dibenzoylacetylene 8 in the presence of toluene at room tem-
perature led to the formation of 2-(6-hydroxy-6-phenylimi-
dazo[2,1-b]thiazol-5(6H)-ylidene)-1-phenylethanone 20 in good
yields. The structure of the product was unambiguously confirmed
by single crystal analysis as shown in Figure 2 (CCDC 923809). The
reaction was then employed with a series of compounds like, thiaz-
olin, thiazole, benzothiazole, benzimidazole, thioimidaozole and
thiobenzimidazole derivatives (Scheme 2). To our delight these
compounds also led to the formation of imidazo[2,1-b]thiazoles
and benzo[d]thiazolo[3,2-a]imidazoles in moderate to good yields
as shown in Table 1. The results exhibited the feasibility to con-
struct biologically important imidazo[2,1-b]thiazole and
benzo[d]thiazolo[3,2-a]imidazole analogues.
(c)
(d)
Ph
The reaction pathway may be represented by the reaction se-
quence shown in Scheme 3 involving the attack of the thiazolyl
double bond on one of the acetylenic carbons of DBA followed by
proton transfer to form 29 which may inturn undergo cyclization
to give the desired product 20. It is pertinent to mention here that
the pyrimido derivative was not detected in any case as observed
in the reaction of amino derivatives of benzothiazole/benzimid-
azole with DMAD reported by Ogura et al.27 The reason for the dif-
ference in reactivity of DBA and DMAD with 2-amino derivatives of
thiazole/imidazole to give five and six membered ring system
respectively could be attributed on the basis of ease of leaving
group (–OCH3) in case of DMAD and due to steric factors that get
decreased in case of the final product whilst reacting with DBA.
The structure of the synthesized products (19–28) was well
characterized by IR, 1H NMR, 13C NMR and mass spectral analyses.
O
OH
N
Ph
NH
N
(e)
(f)
Figure 2. (a) Single crystal structure of 20 (CCDC 923809), (b) 2D view of 20. (c)
Single crystal structure of 22 (CCDC 923810), (d) 2D view of 22, (e) Single crystal
structure of 24 (CCDC 923808) and (f) 2D view of 24.
The IR spectrum of 20 showed strong absorption bands at
1623 cmÀ1 and 1552 cmÀ1 which were assigned respectively to
the carbonyl group and exocyclic C@C bond in conjugation with
the carbonyl group. The 1H NMR displayed a characteristic singlet
at d 3.34 ppm which was assigned to proton of the OH group. A
sharp singlet for olefinic proton resonating slightly down field at
d 6.57 ppm due to adjacent strong electron withdrawing carbonyl
group was also observed. A cluster of peaks ranging between d
7.22 and 7.98 ppm were assigned to aromatic protons. The 13C
NMR also showed distinctive peak at d 187.5 ppm corresponding
to carbonyl carbon. Further structural confirmation was provided
H3CO
O
H3COOC
X
N
N
X
NH2
+
O
-CH3OH
OCH3
N
O
X=S,O,NH
Scheme 1. Earlier work by Ogura et al.27
Mir, Niyaz A.
