Friedlaender approach for the incorporation of 6-bromoquinoline into novel chelating ligands

Article abstract of DOI:10.1021/ol034559q

Nitration of 3-bromobenzaldehyde followed by sodium dithionite reduction provides 5-bromo-2-aminobenzaldehyde, which undergoes the Friedlaender condensation with a variety of enolizable ketones to afford bidentate and tridentate 6-bromoquinoline derivativ

Full text of DOI:10.1021/ol034559q

ORGANIC
LETTERS
2
003
Vol. 5, No. 13
251-2253
Friedl a1 nder Approach for the
Incorporation of 6-Bromoquinoline into
Novel Chelating Ligands
2
Yi-Zhen Hu, Gang Zhang, and Randolph P. Thummel*
Department of Chemistry, UniVersity of Houston, Houston, Texas 77204-5003
thummel@uh.edu
Received March 31, 2003
ABSTRACT
Nitration of 3-bromobenzaldehyde followed by sodium dithionite reduction provides 5-bromo-2-aminobenzaldehyde, which undergoes the
Friedl a1 nder condensation with a variety of enolizable ketones to afford bidentate and tridentate 6-bromoquinoline derivatives. These species
may be dimerized with Ni(0) to form biquinolines or treated under Sonogashira conditions to afford 6-alkynyl derivatives. Examination of
optical properties indicate an unusually high emission quantum yield for 6,6′-biquinolines.
In the burgeoning field of nanoscale chemistry, the organized
synthesis of polynuclear metal complexes holds considerable
promise for the construction of useful molecular devices.
pyridine rings are connected in a meta rather than a para
fashion. These ligands form helical rather than linear com-
plexes, and tertiary structural considerations are of consider-
1
4
Early work centered on bridging ligands in which two, most
often equivalent, metal binding centers were incorporated
able importance.
2
into a single molecule. Often these metal binding centers
were chelating groups, and the polypyridines have received
3
considerable attention in this regard. Molecules such as
quaterpyridine or sexipyridine (1, n ) 1, 2) have multiple
binding sites that involve critical spacial demands since the
(
1) (a) Leininger, S.; Olenyuk, B.; Stang, P. J. Chem. ReV. 2000, 100,
8
53. (b) Fabbrizzi, L., Poggi, A., Eds. Transition Metals in Supramolecular
Chemistry; Kluwer: Dordrecht, 1994. (c) Lehn, J.-M. Supramolecular
Chemistry: Concepts and ProspectiVes; VCH: Weinheim, 1995. (d) Baxter,
P. N. W.; Khoury, R. G.; Lehn, J.-M.; Baum, G.; Fenske, D. Chem. Eur.
J. 2000, 6, 4140.
(
2) (a) Balzani, V.; Juris, A.; Venturi, M.; Campagna, S.; Serroni, S.
Chem. ReV. 1996, 96, 759. (b) Steel, P. J. Coord. Chem. ReV. 1990, 106,
27. (c) Sauvage, J.-P.; Collin, J.-P.; Chambron, J.-C.; Guillerez, S.; Coudret,
C.; Balzani, V.; Barigelletti, F.; De Cola, L.; Flamigni, L. Chem. ReV. 1994,
4, 4, 993. (d) Kalyanasundaram, K.; Nazeeruddin, M. K. Inorg. Chim.
Acta 1994, 226, 213.
3) (a) Kaes, C.; Katz, A.; Hosseini, M.-W. Chem. ReV. 2000, 100, 3553.
b) Kalyanasundaram, K. Photochemistry of Polypyridine and Porphyrin
Complexes; Academic Press: San Diego, 1992.
To organize a polychelating ligand in a more linear
fashion, it is preferable to join the binding units in an axial
sense, as in polypyridine 2, where 3,3′-bipyridine is the
repeating unit. Such systems still present concerns associated
with the rotational mobility between adjacent pyridine rings.
2
9
5
(
(
These concerns are addressed in molecules such as 3 where
1
0.1021/ol034559q CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/06/2003

6
811 provides the 3,3′-dimethylene-6-bromobiq (11) in 88%
yield. A similar 2:1 condensation of 6 with 1,2-cyclohex-
anedione (9) provides a 68% yield of the dimethylene-
bridged 6,6′-dibromobiq derivative 12.
1
,10-phenanthroline (phen) is the repeating unit. The syn
orientation of the two chelating pyridine moieties is enforced
by fusion of the central benzo-ring.
1
2
Another serious problem in polychelating ligands is
electronic communication between each subunit. Such com-
munication is strongly affected by the dihedral angle between
two adjacent aromatic units. These units normally prefer a
more orthogonal conformation, which is unfavorable to the
π-overlap required for effective communication. One solution
is the incorporation of alkynyl linker groups that allow more
efficient electronic communication.7
The ligand 2,2′-biquinoline (biq) is a benzalogue of 2,2′-
bipyridine that presents some electronic advantages over its
simpler counterpart. The extended π-system provides a more
delocalized molecule whose π*-state provides a lower energy
metal-to-ligand charge transfer (MLCT) for transition metal
complexes. This MLCT results in a lower energy absorption
that extends considerably further into the visible region of
the spectrum. To incorporate quinoline into ligand systems,
we have developed a simple synthesis of 6-bromoquinolines
and report on the utility of this approach.
These bromoquinolines may be coupled with Ni(0) gener-
2
ated from the treatment of NiCl with zinc and triphen-
1
3
ylphosphine. The 2,2′-di(2′′-pyridyl)-6,6′-biquinoline (13)
is obtained in 27% yield, while the dimer of 11 is obtained
by a similar reaction in 77% yield. An important part of this
coupling process involves sonication of the crude product
with KCN to scavenge any Ni(II) byproduct that may have
The nitration of 3-bromobenzaldehyde with nitric and
sulfuric acids provides 5-bromo-2-nitrobenzaldehyde (5),
14
complexed with the desired ligand.
8
which may be reduced to 6 in modest yield with sodium
dithionite. This reduction method is preferred over the more
traditional method involving iron and HCl since it provides
pure product directly without the need for chromatographic
9
separation. The aminoaldehyde 6 then undergoes Friedl a¨ nder
10
condensation with 2-acetylpyridine (7) to provide 6-bromo-
-(2′pyridyl)-quinoline (10) in 65% yield. In an analogous
fashion, the condensation of 6 with the tetrahydroacridone
2
(4) (a) Potts, K. T.; Raiford, K. A. G.; Keshavarz-K., M. J. Am. Chem.
Soc. 1993, 115, 2793. (b) Chotalia, R.; Constable, E. C.; Neuburger, M.;
Smith, D. R.; Zehner, M. J. Chem. Soc., Dalton Trans. 1996, 22, 4207. (c)
Constable, E. C.; Chotalia, R. J. Chem. Soc., Chem. Commun. 1992, 1, 64.
The alkynyl-linked analogue 16 may be prepared by two
sequential Sonogashira reactions. The first coupling between
1 and 2-methyl-3-butyn-2-ol, followed by base-promoted
(
1
d) Constabel, E. C.; Ward, M. D.; Tocher, D. A. J. Am. Chem. Soc. 1990,
12, 1256.
1
removal of the acetone protecting group, provides the
(
5) (a) Schwab, P. F. H.; Noll, B. C.; Michl, J. J. Org. Chem. 2002, 67,
7
a
5
476. (b) Schwab, P. F. H.; Fleischer, F.; Michl, J. J. Org. Chem. 2002,
6-ethynyl derivative 15 in 92% overall yield. This species
is then coupled with another equivalent of 11 to afford the
bis-biq alkyne 16 in 71% yield. When the same coupling
approach is applied to the dibromo derivative 12, the bis-
ethynyl species 17 may be prepared in 94% overall yield.
Coupling this species with 2 equiv of the 6-bromobiq 11
affords a low yield of what appears by mass spectroscopy
6
7, 443. (c) Khatyr, A.; Ziessel, R. Org. Lett. 2001, 3, 1857.
(6) (a) Hu, Y.-Z.; Xiang, Q.; Thummel, R. P. Inorg. Chem. 2002, 41,
3
423. (b) Toyota, S.; Woods, C. R.; Benaglia, M.; Haldimann, R.;
W a¨ rnmark, K.; Hardcastle, K.; Siegel, J. S. Angew. Chem., Int. Ed. 2001,
0, 751. (c) Liu, S.-X.; Michel, C.; Schmittel, M. Org. Lett. 2000, 2, 3959.
d) Heuft, M. A.; Fallis, A. G. Angew. Chem., Int. Ed. 2002, 41, 4520. (e)
Dietrich-Buchecker, C.; Jim e´ nez, M. C.; Sauvage, J.-P. Tetrahedron Lett.
999, 40, 3395. (f) Joshi, H. S.; Jamshidi, R.; Tor, Y. Angew. Chem., Int.
Ed. 1999, 38, 2722. (g) Hurley, D. J.; Tor, Y. Tetrahedron Lett. 2001, 42,
217.
7) (a) Khatyr, A.; Ziessel, R. J. Org. Chem. 2000, 65, 7814. (b) Khatyr,
4
(
1
7
(
(10) (a) Riesgo, E. C.; Jin, X.; Thummel, R. P. J. Org. Chem. 1996, 61,
1, 3017. (b) Thummel, R. P. Synlett 1992, 1. (c) Cheng, C.-C.; Yan, S.-J.
Org. React. 1982, 28, 37.
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(12) Thummel, R. P.; Lefoulon, F. J. Org. Chem. 1985, 50, 666.
(13) Janiak, C.; Deblon, S.; Uehlin, L. Synthesis 1999, 959.
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Soc., Dalton Trans. 1990, 1669.
A.; Ziessel, R. J. Org. Chem. 2000, 65, 3126. (c) Ley, K. D.; Li, Y.; Johnson,
J. V.; Powell, D. H.; Schanze, K. S. Chem. Commun. 1999, 1749. (d)
Walters, K. A.; Ley, K. D.; Cavalaheiro, C. S. P.; Miller, S. E.; Gosztola,
D.; Wasielewski, M. R.; Bussandri, A. P.; van Willigen, H.; Schanze, K.
S. J. Am. Chem. Soc. 2001, 123, 8329.
(
8) Behr, L. C. J. Am. Chem. Soc. 1954, 76, 3674.
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2252
Org. Lett., Vol. 5, No. 13, 2003

to be the trimeric ligand, but further characterization was
prevented by poor solubility.
Table 1. Photophysical Data for Quinoline Derivativesa
emissionb
absorption
compound
λmax, nm (ꢀ, M- cm-1
227 (40 500), 261 (64 700),
43 (20 800), 358 (24 200)
254 (37 900), 324 (14 600),
39 (11 900)
228 (39 000), 265 (58 500),
46 (20 900), 362 (27 900)
230 (45 200), 268 (61 000),
49 (24 900), 364 (35 700)
227 (33 500), 264 (55 500),
50 (49 100)
228 (51 700), 277 (69 300),
78 (65 600)
232 (34 800), 267 (54 500),
50 (22 000), 367 (29 000)
229 (54 700), 273 (57 800),
77 (72 500), 395 (67 700)
234 (39 700), 274 (56 800),
57 (26 800), 375 (39 400)
256 (90 600), 325 (40 200),
41 (34 600)
254 (77 600), 306 (14 300),
20 (sh, 12 900)
1
)
λΕΜ, nm
10 φΕΜ
3
d
biq-2c
422
4.33
3
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
9
0
none
3
377, 389
379, 393
386, 396
405, 426
403
1.66
4.10
658
310
6.14
350
13.5
2.94
100
3
3
3
3
3
408, 430
389, 405
365
3
A tridentate system incorporating two 6-bromoquinoline
moieties can be prepared in a similar fashion by the con-
densation of the aminoaldehyde 6 with 2,6-diacetylpyridine.
Once again, solubility problems thwarted the complete char-
acterization of the parent ligand 19a, but the 4-t-butyl ana-
logue was formed in 57% yield from the corresponding
3
3
356, 372
3
4
-tert-butyl-2,6-diacetylpyridine (18b).15
a
Solvent: CH2 Cl2-MeOH (99:1), 25 °C. b Excited at the long-wave-
length absorption maximum. c 3,3′-Dimethylene-2,2′-biquinoline. Error:
d
(10%.
moiety found in 14. The very strong emission (φ ) 0.658)
observed for 13 seems to bear out this premise. As a further
test, we prepared the parent 6,6′-biquinoline (20) by the
16
dimerization of 6-bromoquinoline and found that it emitted
at 352 and 372 nm with φ ) 0.100. Future work will report
the coordination properties of these systems.
The bromo- and alkynyl-quinolines, as well as the coupled
derivatives, were characterized by their NMR spectra, mass
spectra, and elemental analyses (see Supporting Information).
Since the prepared molecules were to be used as ligands for
the preparation of potentially photoactive transition metal
complexes, it was of interest to measure their absorption and
emission properties. These properties were recorded in
Acknowledgment. We thank the Robert A. Welch
Foundation (E-621) and the Texas Higher Education Coor-
dinating Board for financial support of this work.
CH
2
Cl
2 3
-CH OH (99:1), and the data are collected in Table
1. The 2,2′-biquinoline derivatives show long-wavelength
absorptions in the range of 358-375 nm, while the dimeric
species 14 and 16 show absorptions that are about twice as
intense at somewhat lower energies (378 and 395 nm). All
the monomeric species except 10 emit when excited into their
long-wavelength band with quantum yields in the range of
Supporting Information Available: Full experimental
details for the preparation of compounds 5, 6, 10-17, 19,
and 20. This material is available free of charge via the
Internet at http://pubs.acs.org.
-3
OL034559Q
1.66-13.5 × 10 . The dimeric species, however, show more
intense emissions with quantum yields that are about 2 orders
of magnitude greater. We suspected that the stronger
emission might be due to the presence of the 6,6′-biquinoline
(
15) N u¨ ckel, S.; Burger, P. Organometallics 2001, 20, 4345.
(16) Benito, Y.; Canoira, L.; Rodriguez, J. G. Appl. Organomet. Chem.
1987, 1, 535.
Org. Lett., Vol. 5, No. 13, 2003
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