Synthesis, x-ray structure, and self-assembly of functionalized bis(2,2′:6′,2″-terpyridinyl)arenes

Article abstract of DOI:10.1021/ol0364529

meta-Bis(terpyridinyl)phenol has been synthesized from O-benzyl-3,5- di(formyl)phenol in three steps. Its alkylation afforded a series of bisterpyridinylarenes, which can be self-assembled to afford the corresponding hexametallomacrocycles possessing Fe(I

Full text of DOI:10.1021/ol0364529

ORGANIC
LETTERS
2004
Vol. 6, No. 8
1197-1200
Synthesis, X-ray Structure, and
Self-Assembly of Functionalized
Bis(2,2′:6′,2′′-terpyridinyl)arenes
Pingshan Wang, Charles N. Moorefield, and George R. Newkome*
Departments of Polymer Science and Chemistry, Goodyear Polymer Center,
The UniVersity of Akron, Akron, Ohio 44325-4717
newkome@uakron.edu; www.dendrimers.com
Received December 17, 2003
ABSTRACT
meta-Bis(terpyridinyl)phenol has been synthesized from O-benzyl-3,5-di(formyl)phenol in three steps. Its alkylation afforded a series of
bisterpyridinylarenes, which can be self-assembled to afford the corresponding hexametallomacrocycles possessing Fe(II), Zn(II), or Ru(II)
connectivity.
Terpyridines1 have found application in many fields such as
luminescent materials,2 molecular biology,3-5 medical diag-
Scheme 1. Synthesis of the Key 3,5-Di(terpyridinyl)Phenol 6
nostics and action sensors,4 self-assembly,5 preorganized
molecular devices,6 and photoactive molecular-scale wires.7
More recently, linear and dendritic bisterpyridine complexes
have played a fundamental role in supramolecular polymers,
nonlinear optical materials, and nanosciences.8,10-13 Thus,
the terpyridine ligand is ubiquitous in molecular construction.
from Dienone or Tetraketone Intermediatesa
Our synthetic strategy for hexamer self-assembly is based
on m-bis(terpyridinyl)arenes possessing the critical 120°
angle with respect to the two ligating moieties. Herein, we
describe a facile synthesis of the pivotal 3,5-di(terpyridinyl)-
phenol (6; Scheme 1), which can be readily functionalized
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a Route A: (a) 2.2 equiv of acetylpyridine/NaOH; (b) pyridinium
salt 4, NH4OAc/HOAc. Route B: (a) 4.4 equiv of acetylpyridine/
NaOH; (b) NH4OAc/HOAc.
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by alkylation. Previously, we reported 1-(methyl, bromo, and
hydroxymethyl)-3,5,-bis(terpyridinyl)arenes, which are useful
in the self- and directed-assembly14,15 of homonuclear
10.1021/ol0364529 CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/13/2004

Fe(II) or Ru(II) metallomacrocycles (Figure 1) and their
heteronuclear counterparts.16
purification (i.e., 2 or 3), and changing the solvent media
from acetic acid to formamide.19,20 The rationale in the
simpler cases for the diminished conversions has been
presented;21,22 in these bisterpyridine formations, combina-
tions of the proposed intermediates lead to further decline
in yield.
Single crystals of dienone 2, suitable for X-ray analysis,
were grown from a mixed CH2Cl2 and EtOAc solvent (1:1
v/v); a triclinic structure was subsequently confirmed (Figure
2). Two molecules of the dienone were observed to be
Figure 1. Hexameric metallomacrocycles by self- and directed-
assembly from O-alkyl-3,5-bisterpyridinylphenol ligands.
Figure 2. X-ray structure of 3,5-di(pyridylpropenonyl)-O-benzyl
phenol 2.
To instill utilitarian functionality into these unique building
blocks, the creation of 3,5-di(terpyridinyl)phenol was effected
in three steps beginning with dialdehyde17,18 1; two different
routes (Scheme 1) were employed. In Route A, the addition
of 2.2 equiv of 2-acetylpyridine to dialdehyde 1 in EtOH
generated the pale yellow, crystalline dienone 2. Without
further purification, treatment of 2 with NH4OAc and
pyridinium salt 4 in AcOH afforded (12%) the desired
benzyl-protected, bisligand 5. Alternatively, the addition of
4.4 equiv of 2-acetylpyridine formed the tetraketone 3, which
was then reacted with excess NH4OAc to give 22% of the
same bisterpyridine 5 (see Supporting Information). These
two methods have traditionally been used for over two
decades in the synthesis of monoterpyridines; however, both
methods are usually more efficient (ca. 50%). For the
bisterpyridine derivatives, yields have approached 35% using
a combination of prolonged reaction times, intermediate
stacked 3.42 Å apart with respect to the distance between
the two pyridine-benzene-pyridine planes. The benzyl rings
are nearly perpendicular (88°) to the pyridine-benzene-
pyridine plane, and the benzyl ring face-to-face distance
averaged 3.53 Å.
The structure of O-benzyl-3,5-di(terpyridinyl)phenol 5,
obtained from crystals grown in the mixed solvent CHCl3
and EtOAc (2:1 v/v), was confirmed by X-ray analysis
(Figure 3), which revealed one terpyridine to be coplanar
with the phenol ring while the other terpyridine is twisted,
relative to that plane, by 25°. The pyridine rings of the
terpyridinyl moieties adapted an anti conformation typical
of all such structures, and the benzyl and phenol planes are
juxtaposed 41.8° relative to each other.
Deprotection of the phenol group in bisligand 5 (Scheme
1) was readily accomplished by hydrogenation23 (10% Pd/
C, 60 psi H2) affording (87%) the desired alcohol 6; notably,
(8) Funeriu, D. P.; Lehn, J.-M.; Fromm, K. M.; Fenske, D. Chem. Eur.
J. 2000, 6, 2103-2111.
(9) Harriman, A.; Ziessel, R. Chem. Commun. 1996, 1707-1716.
(10) Lohmeijer, B. G. G.; Schubert, U. S. Angew. Chem., Int. Ed. 2002,
41, 3825-3829.
1
it was insoluble in CHCl3. H NMR (DMSO-d6) spectra of
(11) Schubert, U. S.; Eschbaumer, C. Angew. Chem., Int. Ed. 2002, 41,
2893-2926.
alcohol 6 revealed the complete disappearance of the benzyl
group absorptions at 7.57-7.39 ppm (C6H5) and 5.27 ppm
(CH2) along with the appearance of a new peak at 10.16
ppm (ArOH), thus supporting its formation. As well, upfield
(12) Lohmeijer, B. G. G.; Schubert, U. S. J. Polym. Sci., Part A: Polym.
Chem. 2003, 41, 1413-1427.
(13) Lohmeijer, B. G. G.; Schubert, U. S. Macromol. Chem. Phys. 2003,
204, 1072-1078.
(14) Newkome, G. R.; Cho, T. J.; Moorefield, C. N.; Baker, G. R.;
Saunders: M. J.; Cush, R.; Russo, P. S. Angew. Chem., Int. Ed. 1999, 38,
3717-3721.
(19) Storrier, G. D.; Colbran, S. B.; Craig, D. C. J. Chem. Soc., Dalton
Trans. 1997, 3011-3028.
(15) Newkome, G. R.; Cho, T. J.; Moorefield, C. N.; Cush, R.; Russo,
P. S.; God´ınez, L. A.; Saunders, M. J. Chem. Eur. J. 2002, 8, 2946-2954.
(16) Newkome, G. R.; Cho, T. J.; Moorefield, C. N.; Mohapatra, P. P.;
God´ınez, L. A. Chem. Eur. J. 2004, in press.
(20) Sasaki, I.; Daran, J. C.; Balavoine, G. G. A. Synthesis 1999, 815-
820.
(21) Siemeling, U.; der Bru¨ggen, J. V.; Vorfeld, U.; Stammler, A.;
Stammler, H.-G. Naturforsch, B: Chem. Sci. 2003, 58b, 443-446.
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Scand. 1997, 51, 760-766.
(23) Heathcock, C. H.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93, 1746-
1757.
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Chem. 2003, 119, 141-149.
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2 1979, 672-675.
1198
Org. Lett., Vol. 6, No. 8, 2004

3,5-Di(octenyloxy)benzyl chloride was synthesized in two
steps from 3,5-dihydroxybenzyl alcohol via alkylation using
8-bromo-1-octene. Subsequent treatment with SOCl2 afforded
the corresponding benzyl chloride, which, when reacted with
6, afforded (82%) the white microcrystalline bisterpyridine
1
7b. The H NMR spectrum exhibited alkene absorptions at
5.88-5.78 and 5.04-4.94 ppm, as well as a triplet at 4.01
ppm (OCH2) and singlet at δ 5.22 ppm (OCH2Ar); ESI-MS
data also confirmed the structure with mass peaks at m/z
899.6 (M+ + H) and m/z 921.6 amu (M+ + Na, 100%).
Attachment of the known, more lipophilic trisdodecyloxy-
benzyl group under similar conditions afforded 7c, whose
1H NMR spectrum exhibited similar absortion patterns, and
ESI-mass data [m/z 1200.9 amu (M+ + H, 100%)] confirmed
the structure.
Treatment of phenol 6 with 3-bromopropyl phthalimide
gave rise to the protected amine 7d, which was subsequently
deprotected by treatment with hydrazine to give the free
amine 7e. Conformation of the structure was supported (1H
NMR) by the disappearance of signals assigned to the
phthalimide moiety and ESI mass data of the precursor 7d,
which showed a signature peak at 766.4 amu (M+ + Na,
100%). Bisterpyridine 7f possessing a triester dendron
connected by urea functionality was generated (75%) by
treatment of amine 7e with the commercially available
isocyanate24,25 of Behera’s amine. Characterization (13C
NMR) included the observation of two new signals at 173.1
and 157.5 ppm, corresponding to the ester and urea carbonyl
moieties, respectively. The structure was further confirmed
by the appearance in ESI-MS spectrum of a peak at m/z
1077.7 amu (M+ + Na, 100%).
Figure 3. X-ray structure of O-benzyl-3,5-bis(terpyridinyl)-phenol
5.
shifts of singlets from 7.59 to 7.44 ppm (2,6-ArH) and from
7.95 to 7.77 ppm (4-ArH) were indicative of the transforma-
tion. Mass peaks (ESI-MS) at m/z 647.4 (M+ + H, 100%)
and m/z 579.2 amu (M+ + Na, 100%) for 5 and 6,
respectively, further support the assignments.
The 3,5-di(terpyridinyl)phenol 6, as a useful starting
monomer, can be easily alkylated (Scheme 2) using a series
The second method to produce the desired O-alkyl-3,5-
di(terpyridinyl)phenols was accomplished beginning with the
phenolic diester 8 in five-steps.
Scheme 2. Synthesis of O-Alkyl-di(terpyridinyl)phenol
Derivatives
Scheme 3. Synthesis of O-Alkyl-di(terpyridinyl)phenol
Derivatives Directly from 3,5-Di(methoxycarbonyl)phenol 8
of halogen-based reagents in the presence of K2CO3 using
DMF as a solvent; in some cases, KI was added as a catalyst
to afford (75-83%) the di(terpyridinyl)phenyl derivatives.
Hence, an n-hexyloxy moiety was introduced to afford the
white, crystalline 7a, which greatly enhanced the solubility
of both the ligand and corresponding hexametallomacro-
cycles whose properties and synthesis will be described
elsewhere. Formation of ether 7a was verified (1H NMR)
by a triplet at 4.17 ppm (OCH2) and a mass peak (ESI-MS)
appearing at m/z 641.5 amu (M+ + H, 100%).
Alkylation of 8 with either the C6 or C18 alkyl halide gave
the corresponding ethers, which were next reduced (LiAlH4)
Org. Lett., Vol. 6, No. 8, 2004
1199

to the bishydroxymethyl derivatives (10a and b) in the
anticipated high overall yields. Conversion to bisaldehydes
11a and b was then accomplished (61-68%) by oxidization
(pyridinium chlorochromate, PCC).
acetone, DMSO, and CHCl3, in contrast to that of nonalky-
lated metallohexamers. The analogous Fe(II) hexamer [Figure
1, R ) n-C6H13, M ) Fe(II)] was also prepared (91%) by a
one-pot self-assembly method via reaction of the bisligand
7a with FeCl2.
In the final two steps, aldehydes 11a and b were each
transformed to oily terpyridine intermediates via reaction with
2-acetylpyridine and, without the purification of intermedi-
ates, were treated with a large excess (20X) of NH4OAc/
HOAc and refluxed 4-8 h, to afford black solutions; workup
and column chromatography (Al2O3) afforded (15-22%)
pale yellow solids 7a and 7g. Both alkoxy derivatives were
confirmed by NMR and ESI MS [m/z 641.5 amu (M+ + H,
100%) and m/z 809.7 amu (M+ + H, 100%) for 7a and 7g,
respectively].
In conclusion, 3,5-di(terpyridinyl)phenol has been syn-
thesized and transformed to utilitarian derivatives for self-
assembly to metallohexamacrocycles using Fe(II) and Ru(II).
An alternative route, using 3,5-di(methoxy-carbonyl)phenol,
has generated a five-step route to O-alkyl-3,5-di(terpyridi-
nyl)phenols. The structures of these monomers were char-
1
acterized by means of H and 13C NMR, as well as mass
spectrometry. Experiments in further self-assembly are
currently ongoing.
In a preliminary experiment, reaction of ligand 7a with 1
equiv of RuCl3‚nH2O under reducing conditions (N-ethyl-
morpholine) afforded, via self-assembly, the desired hex-
americ, metallomacrocycle [Figure 1; R ) n-C6CH13, M )
Ru(II); 41% after column chromatography (SiO2) eluting with
H2O/MeCN/KNO3 (ratio of 1:7:1)]. Following exchange of
Acknowledgment. We gratefully acknowledge financial
support from the Air Force Office of Scientific Research
(F49620-02-1-0428), the National Science Foundation (DMR-
0196231 and CHE-0116041), and the Ohio Board of
Reagents. We also gratefully thank Ms. Kathleen M. Wol-
lyung (University of Akron) for efforts to obtain mass spectra
and Dr. Frank Fronczek (Louisiana State University) and Mr.
Matthew Panzner (University of Akron) for solving the
crystal structures reported herein.
-
the counterions to PF6 , the structure was confirmed by its
1H NMR spectrum, which possessed a characteristic triplet
absorption at 4.50 ppm (OCH2) and a singlet at 9.28 ppm
indicative of the 3′,5′-PyH. MALDI-TOF mass spectrometry
-
showed peaks at m/z 7055.59 [M+ - 1PF6 ], 6911.03 [MH+
-
-
- 2PF6 ], and 6766.43 amu [MH+ - 3 PF6 ]. Notably, this
12+ charged hexamer possesses significantly enhanced
solubilities in common organic solvents such as MeCN,
Supporting Information Available: Synthetic proce-
dures, spectral data, and crystallographic information. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(24) Newkome, G. R.; Weis, C. D. Org. Prep. Proced. Int. 1996, 28,
485-488.
(25) Newkome, G. R.; Weis, C. D.; Moorefield, C. N.; Fronczek, F. R.
Tetrahedron Lett. 1997, 38, 7053-7056. Available from Molecular
Constructs, Ltd.
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