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Scheme 1 Proposed reaction mechanism.
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´ ´
also reacted with formamides, which derived from aromatic
and aliphatic amines in good yields under the recommended
reaction conditions (3d–n). A similar phenomenon was also
observed in the reaction of benzoxazoles with formamides
(3l and 3m vs. 3j and 3k). The N-phenyl formamides derived
from aromatic amines reacted with benzoxazole (1b) smoothly
to generate the direct dehydrogenative cross-coupling products
(3d–h) in good yields under present reaction conditions. When
the para-positions of the phenyl rings in N-(substituted
phenyl)formamides were occupied by a methyl or a methoxy
group, the product yields were superior to that of N-phenyl
formamide (3g and 3h vs. 3d). Meanwhile, when the ortho- or
meta-positions of the phenyl rings in N-(substituted phenyl)-
formamides were attached with a methyl group, the product
yields were comparable to that of N-phenyl formamide
(3d vs. 3e and 3f). It is obvious that ortho-position effect was
not observed in the reaction of N-(2-methylphenyl)formamide
as one of the substrates (3e). More simple oxazole and thiazole
derivatives also reacted with formamides to afford the corres-
ponding products in good yields (3o–q).
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A plausible mechanism for this reaction was proposed in
Scheme 1. It may involve a free radical process. Firstly, radical
initiator TBPB underwent a homolytic cleavage to generate a
carboxyl radical and an alkoxyl radical. Subsequently, they
abstract hydrogens from benzothiazole and DMF, forming the
corresponding free radicals, which react with each other to
generate the corresponding cross-coupling product through termi-
nation of two radicals. The homo-coupling product (I) was also
obtained in 10% yield, and no (II) was observed in the reaction. It
should be noted that the reaction was suppressed by a radical
scavenger, such as TEMPO in a dose-dependent manner.14
In summary, we have developed a metal- and base-free
approach toward the direct C2 amidation of azoles with
formamides via C–H activation. Benzothiazole, thiazoles, as
well as benzoxazoles and oxazole reacted with diverse forma-
mides smoothly in the presence of commercially available
TBPB at 100 1C in toluene to generate the direct dehydro-
genative cross-coupling products in good yields. The findings
offer a new, simple and mild method for the synthesis of useful
azoles derivatives15 and the detailed mechanistic study is
currently underway.
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¨
This work was financially supported by the National
Science Foundation of China (Nos. 20972057 and 20102039).
14 W. Liu, H. Cao, H. Zhang, H. Zhang, K. H. Chung, C. He,
H. Wang, F. Y. Kwong and A. Lei, J. Am. Chem. Soc., 2010,
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Notes and references
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8948 Chem. Commun., 2011, 47, 8946–8948
This journal is The Royal Society of Chemistry 2011