Pd-Catalyzed Amidation of 2-Chloro- and
,7-Dichloro-1,8-naphthyridines
SCHEME 1. UPy (1)-Napy (2) Heterocomplexation
2
G. B. W. L. Ligthart, Haruki Ohkawa,
Rint P. Sijbesma,* and E. W. Meijer*
Laboratory of Macromolecular and Organic Chemistry,
EindhoVen UniVersity of Technology, P.O. Box 513, 5600 MB
EindhoVen, The Netherlands
r.p.sijbesma@tue.nl; e.w.meijer@tue.nl
ReceiVed September 6, 2005
SCHEME 2. Traditional 2,7-Diamido-1,8-naphthyridine
Synthesisa
a
i: NH4OH, 180 °C, 24 h. ii: Acid chloride, Et3N, CHCl3.
7
workers reported the strong and selective complementary com-
plexation of the 6[1H] tautomeric form of a ureido-pyrimidinone
The catalytic amidation between 2-chloro- and 2,7-dichloro-
1
(UPy) with 2,7-diamido-1,8-naphthyridines 2 (Napy) via
1,8-naphthyridines and primary amides bearing functional
quadruple hydrogen bonds between acceptor-donor-donor-
acceptor (ADDA) and donor-acceptor-acceptor-donor (DAAD)
arrays (Scheme 1). Subsequently, we showed that this hetero-
complex formation exhibits a concentration-dependent selectiv-
groups is reported. When Pd(OAc) , xantphos, and K CO
2
2
3
are used, it is possible to obtain symmetric as well as non-
symmetric 2,7-diamido-1,8-naphthyridines in 50-90% yield
with good functional-group tolerance. Monoamidation of 2,7-
dichloro-1,8-naphthyridine using 0.9 equiv of the amide
proceeded with good selectivity compared to the formation
of the diamide, but as a result of the difficult isolation of
the product, isolated yields were poor to moderate (22-42%).
6
-1 8
ity with Ka(UPy-Napy) ) >10 M . The high selectivity and
strength render the UPy-Napy heterodimer very attractive for
constructing supramolecular architectures. The literature pro-
cedure to synthesize these diamidonaphthyridines 2 uses 2,7-
9
diamino-1,8-naphthyridine obtained by aminolysis of either the
9
nonsymmetric 7-acetamido-2-chloro-1,8-naphthyridine or the
1
0
symmetric 2,7-chloro-1,8-naphthyridine (Scheme 2).
The use of intermolecular interactions to organize two- or
three-dimensional structures from synthetic molecules through
The aminolysis reaction requires high pressures and temper-
atures, thus creating a potential safety hazard. Furthermore, the
isolated diamino product is often of low purity. A subsequent
reaction with an acid chloride yields the diamido derivatives in
1
a spontaneous and reversible process is termed self-assembly.
Among several noncovalent interactions, multiple hydrogen-
bond arrays have received much attention for their use in self-
7
c,9
2
low to moderate yields (Scheme 2).
Therefore, improving
assembly processes. Specifically, quadruple hydrogen-bonding
3
the synthetic route toward functionalized Napy derivatives is a
key issue in the development of complementary quadruple
hydrogen bonding for self-assembly.
units have been demonstrated to be very useful in supramo-
lecular polymer chemistry as a result of their strength and
4
directionality. Although self-complementary quadruple hydrogen-
bonding motifs have been available since 1997, developing
complementary quadruple hydrogen-bonding units has been
much more challenging. Zimmerman et al. were the first to
(
5) (a) Brammer, S.; L u¨ ning, U.; K u¨ hl, C. Eur. J. Org. Chem. 2002,
054. (b) S o¨ ntjens, S. H. M.; Meijer, J. T.; Kooijman, H.; Spek, A. L.; van
Genderen, M. P. H.; Sijbesma, R. P.; Meijer, E. W. Org. Lett. 2001, 3,
887.
(6) For a more recent example of the use of Napy in supramolecular
4
5
3
report a complementary quadruple hydrogen bond with a 2,7-
diamido-1,8-naphthyridine derivative.3c,6 Recently, Li and co-
systems, see: Park, T.; Zimmerman, S. C.; Nakashima, S. J. Am. Chem.
Soc. 2005, 127, 6520.
(
(
1) Lawrence, D. S.; Jinag, T.; Levett, M. Chem. ReV. 1995, 95, 2229.
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3
(
3) (a) Sijbesma, R. P.; Beijer, F. H.; Brunsveld, L.; Folmer, B. J. B.;
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1
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0.1021/jo051864b CCC: $33.50 © 2006 American Chemical Society
Published on Web 12/03/2005
J. Org. Chem. 2006, 71, 375-378
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