approach, orthoesters can also be used as annelating agents
(scheme 1). As reported in the literature, benzimidazoles7
were prepared from orthoesters in the presence of hexa-
fluoroisopropyl alcohol, aminosulfonic acid, or zirconium
oxychloride as catalysts. For the benzothiazoles,8 silica-
supported fluoroboric acid or Bi(OTf)3 can be used in the
condensation reaction with orthoesters. Polyphosphoric acid
(PPA) and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH)
are also interesting agents for the preparation of benzoxaz-
oles.9 The main shortcoming of this methodology resides in
the limited diversity of the orthoesters employed. Indeed,
only three or four commercially available orthoesters are rou-
tinely screened.
functionalities suitable for the preparation of libraries in
medicinal chemistry oriented synthesis.12 At the onset of
our study, the chlorine-containing orthoesters 10 and 11
and their unsaturated analogues 14 and 15 were prepared
Table 1. Condensation of Anilines and Chlorinated Orthoesters
Scheme 1. Preparation of Heteroaromatic Bicycles
The pharmacological potential of these heterocycles,
combined with the limited access to high structural
complexity, due to the paucity of orthoesters available
(typically R1 = H, Me, Et, Ph), and the harsh conditions
used in previously reported condensation reactions,
incited us to revisit this ring-forming process.
Overtheyears, ourlaboratoryhasprepareda widerange
of functionalized orthoesters using the modified Pinner
sequence described in Scheme 2.10 In this method, an
imidate salt11 formed from a nitrile such as 7 is subse-
quently converted into the corresponding orthoester 8.
Scheme 2. Modified Pinner Sequence
These orthoesters are particulary interesting since
their substituents can be converted into a wide variety of
(8) (a) Patil, A. V.; Lee, S. H.; Bandgar, B. P. Bull. Korean Chem. Soc.
2010, 31, 1719. (b) Mohammadpoor-Baltork, I.; Khosropour, A. R.;
Hojati, S. F. Monatsh. Chem. 2007, 138, 663. (c) Mohammadpoor-
Baltork, I.; Khosropour, A. R.; Hojati, S. F. Catal. Commun. 2007, 8,
1865.
(9) (a) Jared, F. M.; Andrew, J. M.; El-Malika, J. Org. Lett. 2008, 10,
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142, 87. (c) Mylari, B. L.; Scott, P. J.; Zembrowski, W. J. Synth.
Commun. 1989, 19, 2921. (d) Mohammadpoor-Baltork, I.; Moghadam,
M.; Tangestaninejad, S.; Mirkhani, V.; Zolfigol, M. A.; Hojati, S. F.
J. Iran Chem. Soc. 2008, 5, S65.
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a Isolated yields after column chromatography on silica gel or
recrystallization.
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(f) Maulide, N.; Marko, I. E. Org. Lett. 2007, 19, 3757. (g) De Bo, G.;
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