Katz4b–d and others4e–h,j,n reported the preparation of sym-
metrically substituted oxacalix[4]aromatics using a one-pot
reaction method. Because of the different electronic nature
of heteroatoms from carbon, the heteroatombridged calix-
(hetero)aromatics exhibit interesting structural and molecular
recognition properties. It has been shown that, due to the
intrinsic nature of nitrogen that can adopt sp2 and/or sp3
electronic configurations to form or not to form conjugation
with its adjacent aromatic rings, azacalix[4]pyridine is able
to preorganize into different conformational and cavity
structures to interact with metal ions,5f anions,5e and both
aromatic and aliphatic diols and monools.5l It has also been
demonstrated that the cavity of 1,3-alternate aza- and/or
oxacalix[2]arene[2]triazines can be regulated by using dif-
ferent combinations of heteroatoms4a or varied substituents4k
on the bridging nitrogen atoms.
While the study of the preparation of smaller macrocyclic
heteroatom-bridged calix[n]aromatics (n ) 4) has been
fruitful,3–6 the synthesis of larger macrocycle homologues
has remained largely unexplored.14 The oligomerizations
between 1,3-phenylenediamine derivatives and 1,3-dibro-
mobenzene derivatives5h and oligomerization of N-methyl(3-
bromo)aniline,5b for example, have been reported to give a
mixture of azacalix[n]arene compounds in very low yields.
Azacalix[n]pyridine (n > 6) derivatives were obtained in
extremely low yield from condensation between 2,6-bis(p-
tolyamino)pyridine and 2,6-dibromopyridine or oligomer-
ization of 2-bromo-6-(p-tolylamino)pyridine.5j When we5e,m
studied the synthesis of azacalix[4]- and -[5]pyridines using
3 + 1 and 3 + 2 fragment coupling approaches, azacalix[8]-
and -[10]pyridines were obtained, respectively, in addition
to the target molecules. Following the same stepwise 3 + 1
strategy, Tsue reported the synthesis of azacalix[8]arene
derivative in good yield.5k Our continuing interest in the
synthesis of heteroatom-bridged calixaromatics led us to
undertake the current study. We report herein the fragment
coupling synthesis of azacalix[n]pyridines of various mac-
rocyclic ring sizes (n ) 6-9) and their complexation with
fullerenes C60 and C70.
Retrosynthetically, the disconnection of large macrocyclic
azacalixpyridines (n ) 6-9) can lead to two pieces of
fragments either of similar sizes or of very different sizes.
To achieve synthetic efficiency, a convergent fragment
coupling approach using two fragments of similar sizes was
pursued. Illustrated in Scheme 1 are the preparation of
different types of diamine and dibromide fragments. Starting
with 2,6-dibromopyridine 1 and methylamine 2, reiterative
aromatic nucleophilic substitution reactions afforded R,ω-
dibrominated and R,ω-diaminated linear oligomers. It is
worth noting that, except for the elevated reaction temper-
atures, the preparations were very practical. They were
carried out in a large scale and in high yield. Besides, they
required no expensive reagents or catalysts.
We started our investigation with the synthesis of
methylazacalix[7]pyridine by macrocyclic cross coupling
reaction between R,ω-dibrominated linear tetramer 6 and
R,ω-diaminated linear trimer 10. The reaction was systemati-
cally examined in terms of palladium catalyst, phosphine
ligand, solvent, and reaction temperature. As summarized
in Table 1, Pd2(dba)3 appeared as a better catalyst than PdCl2
and Pd(OAC)2 (entries 1-3), while dppp was superior than
other ligands such as dppe, P(c-Hex)3, and DPEphos (entries
3-6). The reaction was also sensitive toward the solvent
and temperature used. This has been exemplified by a higher
chemical yield of the product obtained in refluxing toluene
than in other solvents including 1,4-xylene, 1,4-dioxane, and
THF (entries 3 and 7-9) or in toluene but at lower
temperature (entries 3, 10, and 11). It is interesting to note
that while the catalyst loading did not seem critical in
determining the chemical yield of the product (see the
Supporting Information), the concentration of the substrate
affected the formation of the product (entries 3 and 12-15).
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