Quinoline-annulated porphyrins

Article abstract of DOI:10.1021/ol1031848

Porphyrin-2,3-dione mono- and dioximes were used as starting materials for the efficient syntheses of mono- and bis-quinoline-annulated porphyrins and their corresponding N-oxides. Owing to an extended π-system, these novel porphyrinoid chromophores show

Full text of DOI:10.1021/ol1031848

ORGANIC
LETTERS
2011
Vol. 13, No. 6
1322–1325
Quinoline-Annulated Porphyrins
†
Joshua Akhigbe, Matthias Zeller, and Christian Bruckner*
‡
,†
€
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060,
United States, and Department of Chemistry, Youngstown State University,
One University Plaza, Youngstown, Ohio 44555-3663, United States
c.bruckner@uconn.edu
Received December 31, 2010
ABSTRACT
Porphyrin-2,3-dione mono- and dioximes were used as starting materials for the efficient syntheses of mono- and bis-quinoline-annulated
porphyrins and their corresponding N-oxides. Owing to an extended π-system, these novel porphyrinoid chromophores show significantly red-
shifted UV-vis spectra compared to the parent porphyrins. A crystal structure exemplifies the nonplanar conformation of the macrocycle.
The maximum wavelength of absorbance (λmax) for the
prototypical and most readily synthesized porphyrin meso-
tetraphenylporphyrin is 648 nm. This is outside the ‘optical
window’ of tissue.1 Therefore, unmodified porphyrins can
find only limited use as spectroscopic labels, photosensiti-
zers, or imaging agents in tissue. Porphyrin reduction or ring
expansion may generate red-shifted chromophores.2 The
establishment of a covalent linkage between the β-position
and a flanking phenyl group, such as in 1, has also shown to
be a viable route toward bathochromically shifted meso-
tetraarylporphyrin-based chromophores, as long as the
linkage forces the phenyl group into (idealized) coplanarity
with the porphyrinic chromophore, thus extending the
π-conjugation pathway.3,4
† University of Connecticut.
‡ Youngstown State University.
(1) Generally speaking, the wavelength between 600 and 1300 nm.
Anderson, R. R.; Parrish, J. A. J. Invest. Dermatol. 1981, 77, 13–19. For
instance, the wavelengths of maximum penetration of breast tissue are
∼725 nm.Cerussi, A. E.; Berger, A. J.; Bevilacqua, F.; Shah, N.;
Jakubowski, D.; Butler, J.; Holcombe, R. F.; Tromberg, B. J. Acad.
Radiol. 2001, 8, 211–218.
In general, the strategy to expand the porphyrinic
π-conjugated electronic system by direct fusion of a
coplanar aromatic segment onto the periphery of the
(2) (a) Sessler, J. L.; Weghorn, S. Expanded, Contracted & Isomeric
Porphyrins; Pergamon Press: New York, NY, 1997. (b) The Porphyrin
Handbook, Vol. 2 - Heteroporphyrins, Expanded Porphyrins and Related
Macrocycles; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: San Diego, 2000; Vol. 2. (c) Flitsch, W. Adv. Heterocycl. Chem.
1988, 43, 73–126.
(3) (a) Fox, S.; Boyle, R. W. Tetrahedron 2006, 62, 10039–10054. (b)
Daniell, H. W.; Bruckner, C. Angew. Chem., Int. Ed. 2004, 43, 1688–
1691.
€
(4) McCarthy, J. R.; Hyland, M. A.; Bruckner, C. Org. Biomol.
Chem. 2004, 2, 1484–1491.
€
r
10.1021/ol1031848
Published on Web 02/15/2011
2011 American Chemical Society

Scheme 1. Synthesis and Acid-Induced Reactions of Porphyrin-2,3-dione Mono- and Dioximes
porphyrin has been shown to be quite versatile, whereby
the largest spectral shifts are achieved by annulation of
(multiple) polycyclic aromatic moieties (including other
porphyrins).5,6 Recent examples, such as the azulene- and
anthracene-fused porphyrins 2 and 3, introduced by
Osuka, Kim, and Anderson, respectively, are representa-
tive examples for such annulated porphyrins.6
Porphyrin-2,3-dione 4, introduced by the group of
Crossley,7 was shown to be a versatile molecule for the
generation of a structurally diverse family of β,β-annu-
lated systems by reaction of 4 with diamines.8 We report
here the formation and reactivity of the mono- and
dioximes of 4 (Scheme 1) and their conversion to mono-
and bis-quinoline-annulated chromophores that are also
characterized by bathochromically shifted optical spectra
when compared to the parent meso-tetraphenylporphyrin
or dione 4. We also report the formation and X-ray cry-
stal structure of a bis-quinoline-fused porphyrin quinoline-
N-oxide 12.
(5) For recent select examples of aromatic systems fused to porphy-
rins, see: (a) Lash, T. D.; Werner, T. M.; Thompson, M. L.; Manley,
J. M. J. Org. Chem. 2001, 66, 3152–3159. (b) Gill, H. S.; Harmjanz, M.;
ꢀ
SantamarIa, J.; Finger, I.; Scott, M. J. Angew. Chem., Int. Ed. 2004, 43,
485–490. (c) Nakamura, N.; Aratani, N.; Shinokubo, H.; Takagi, A.;
Kawai, T.; Matsumoto, T.; Yoon, Z. S.; Kim, D. Y.; Ahn, T. K.; Kim,
D.; Muranaka, A.; Kobayashi, N.; Osuka, A. J. Am. Chem. Soc. 2006,
128, 4119–4127. (d) Hayashi, S.; Tanaka, M.; Hayashi, H.; Eu, S.;
Umeyama, T.; Matano, Y.; Araki, Y.; Imahori, H. J. Phys. Chem. C
2008, 112, 15576–15585. (e) Sooambar, C.; Troiani, V.; Bruno, C.;
Marcaccio, M.; Paolucci, F.; Listorti, A.; Belbakra, A.; Armaroli, N.;
Magistrato, A.; De Zorzi, R.; Geremia, S.; Bonifazi, D. Org. Biomol.
Chem. 2009, 7, 2402–2413. (f) Jiao, C. J.; Huang, K. W.; Guan, Z. P.; Xu,
Q. H.; Wu, J. S. Org. Lett. 2010, 12, 4046–4049. (g) Diev, V. V.; Hanson,
K.; Zimmerman, J. D.; Forrest, S. R.; Thompson, M. E. Angew. Chem.,
Int. Ed. 2010, 49, 5523–5526 and references therein.
(6) (a) Kurotobi, K.; Kim, K. S.; Noh, S. B.; Kim, D.; Osuka, A.
Angew. Chem., Int. Ed. 2006, 45, 3944–3947. (b) Davis, N. K. S.;
Pawlicki, M.; Anderson, H. L. Org. Lett. 2008, 10, 3945–3947. (c) Davis,
N. K. S.; Thompson, A. L.; Anderson, H. L. J. Am. Chem. Soc. 2011,
133, 30–31. (d) Davis, N. K. S.; Thompson, A. L.; Anderson, H. L. Org.
Lett. 2010, 12, 2124–2127.
Reaction of dione 4 with an ∼100-fold excess of
NH2OH HCl in pyridine at ambient temperature over
3
24 h forms one major product and a minor product (91%
and 5% isolated yields, respectively) that are identified as
the corresponding monooxime 5 (HR-MS ESIþ, 100%
CH3CN, suggests a composition of C44H30N5O2 for
MHþ) and bisoxime 6, respectively. A diagnostic signal
1
in the H NMR spectrum (CDCl3, 400 MHz) for 5 is a
(7) First report: (a) Crossley, M. J.; Burn, P. L. J. Chem. Soc., Chem.
Commun. 1987, 39–40. Alternative syntheses: (b) Crossley, M. J.;
Harding, M. M.; Sternhell, S. J. Org. Chem. 1988, 53, 1132–1137. (c)
Daniell, H. W.; Williams, S. C.; Jenkins, H. A.; Bruckner, C. Tetra-
hedron Lett. 2003, 44, 4045–4049. (d) Starnes, S. D.; Rudkevich, D. M.;
Rebek, J., Jr. J. Am. Chem. Soc. 2001, 123, 4659–4669.
(8) For recent examples, see: (a) Khoury, T.; Crossley, M. J. Chem.
Commun. 2007, 4851–4853. (b) Khoury, T.; Crossley, M. J. New J.
Chem. 2009, 33, 1076–1086. (c) Crossley, M. J.; Sintic, P. J.; Walton, R.;
Reimers, J. R. Org. Biomol. Chem. 2003, 1, 2777–2782.
€
Org. Lett., Vol. 13, No. 6, 2011
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Figure 1. UV-vis spectra (CH2Cl2) of dione 4 (black trace),
monooxime 5 (tangerine trace), monoquinoline-fused 7 (green
trace), and quinoline N-oxide 11 (blue trace).
Figure 2. UV-vis spectra (CH2Cl2) of monoquinoline-fused 7
(green trace), monoquinoline-oxime 8 (red trace), bis-quinoline-
fused 9 (violet trace), and bis-quinoline-fused N-oxide 12
(turquoise trace).
broadened peak at 15.7 ppm that is exchangeable with
D2O, assigned to the oxime hydrogen that is H-bonded to
the neighboring carbonyl group. Of note is that reac-
tion of 5 over extended periods of time with excess
analogous to oxime 5, the signal for the strongly
H-bonded oxime hydrogen (at 15.9 ppm). The ketone-
to-oxime conversion of 7 to 8 perturbs the UV-vis
spectrum much more than the corresponding conversion
of dione 3 to oxime 5 (cf. Figures 1 and 2). Oxime 8 lends
itself to the formation of the bisquinoline-fused system 9.
The conversion generates a molecule with 2-fold symme-
try in its NMR spectra and only one imine stretching
frequency in its IR spectrum.9 Owing to the presence of
the two annulated quinoline systems forming a pyrrolo-
[3,2-b:4,5-b0]diquinoline moiety, a dramatically batho-
chromic UV-vis spectrum (λmax = 775 nm) is observed
(Figure 2), complementing the results obtained for other
annulated systems, such as 2 and 3.6
Bisoxime 6 can also be directly converted to bisquino-
line 9, albeit at significantly lower yield (12%) compared
to the stepwise approach (5f7f8f9, overall yield
∼40%).10 Upon treatment of bisoxime 6 with acid, the
majority of the starting material ring-fuses only once and
hydrolyzes to monofused ketone 7. The next common
product is the dehydration product 1,2,5-oxadiazole-
fused porphyrin 10. The latter is a novel porphyrin-fused
system, but since its UV-vis spectrum is very regular
porphyrin-like, compound 10 will not be discussed any
further.
NH2OH HCl in pyridine yields only small (<20% yield)
quantities of bisoxime 6.
3
The UV-vis spectrum of the monooxime 5 and the
starting material 4 are similar in that both have a much
broadened Q-band region (Figure 1). The bisoxime 6
possesses a much sharpened UV-vis spectrum (see Sup-
porting Information).
Treatment of olive-colored monooxime 5 with a strong
acid (p-TSA) under enforcing conditions (toluene, reflux)
converts it into a light brown product with a mass indica-
ting the loss of H2O (HR-MS ESIþ, 100% CH3CN,
suggests a composition of C44H28N5O for MHþ). The
1H NMR spectrum of this product shows the hallmarks
of the presence of an o-fused phenyl group (also con-
firmed by 2D NMR spectroscopy, see ESI).4 The 13C
NMR and IR (neat) spectra indicate the preservation of
the one β-imine and one β-ketone (at 151 and 196 ppm,
respectively). Taken together, the spectroscopic evidence
suggests quinoline-fused structure 7. This structure could
be indirectly confirmed by the X-ray crystal analysis of a
downstream product (see below).
The quinoline moiety fused to an oxochlorin frame-
work represents a novel motif in annulated porphyrins.
The steric requirements of this all-sp2-atom fusion imply,
first, an idealized coplanarity of the porphyrinoid chro-
mophore with the quinoline and, second, a steric clash
between the o0-hydrogen of the fused phenyl group with
the neighboring β-hydrogen. The latter may be alleviated
by a distortion of the chromophore from planarity. The
UV-vis spectrum of 7 is much different from that of the
starting material and shows an overall broadened Soret
band and an intensified, broadened, and red-shifted
Q-band region (Figure 1).
Serendipitously we found that oxidation of mono-
oxime 5 with DDQ also establishes a quinoline-fused
porphyrin, albeit as the quinoline-N-oxide 11 (Scheme 2).
NaBH4 reduction of 11 regenerates 7, though a DDQ
oxidation of 7 does not lead to 11. Quinoline-fused system
7 and its N-oxide analogue 11 show very similar NMR
spectroscopic properties, and the presence of the oxygen
is only clearly demonstrated by MS. The presence of
the N-oxide has, however, an influence on the UV-vis
(9) Solubility problems prevented the recording of 13C NMR of 9,
but its Ni(II) complex is soluble and characterized, including 13C NMR
spectrum; see Supporting Information.
(10) Also considering the inefficient synthesis of bisoxime 6, the
direct synthesis of bisquinoline 9 is not at all advantageous.
The β-keto functionality of 7 is susceptible to conver-
sion to the corresponding oxime 8. Diagnostic peaks
for resulting oxime 8 in the 1H NMR spectrum are,
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Org. Lett., Vol. 13, No. 6, 2011

Scheme 2. Oxidation-Induced Reactions of Oximes 5 and 8
spectrum of the chromophore, highlighting the direct
conjugation of the quinoline with the porphyrinic chro-
mophore (Figure 1).
Figure 3. Single crystal X-ray structure of bis-quinoline-fused
N-oxide system 12. (A) Top view. (B) View along axis indicated
in A by arrow. Disorder or hydrogens attached to sp2-carbons
not shown for clarity. Steric interaction between the β-hydro-
gens and the neighboring quinoline hydrogens is indicated. For
full crystallographic information, see Supporting Information.
Reaction of β-keto N-oxide 11 with hydroxylamine
converts it to quinoline oxime 8; i.e., the N-oxide moiety
is lost in the process (Scheme 2). Oxidation of this oxime
establishes once again a fused quinoline N-oxide moiety,
thus forming the mono-N-oxide of the bis-quinoline-
fused compound 9, N-oxide 12. Again, the N-oxidation
of 9 has a surprisingly strong effect on the UV-vis
spectrum of 12.
Crystals of 12 suitable for investigation by single crystal
X-ray diffractometry could be grown by diffusion of
MeOH into a solution of 12 in CHCl3 (Figure 3). The
structure confirms the deduced connectivity of 12 and, by
inference, confirms also the structure of the mono- and
bis-quinoline fused systems 7-9 and 11. Most noticeable,
the pentacyclic pyrrole-fused bis-quinoline moiety is
nearly planar, while the porphyrinic macrocycle is sig-
nificantly nonplanar. Most likely, the steric interactions
between the β-hydrogens on the pyrrole and the hydro-
gens on the neighboring quinoline force the macrocycle
into the observed conformation.
quinoline-annulated porphyrin chromophores with sig-
nificantly bathochromic spectra compared to regular
porphyrins. The red shift is rationalized by the presence
of an extended porphyrinic π-system. Thus, we have
merged Crossley’s β,β0-annulation strategies with meso-
β-fusions to generate a novel meso-β,β0-meso-annulated
system. We have also shown a further modulation of the
chromophore by N-oxidation of the annulated heterocycle.
Studies investigating the metal complexes, particularly
those of group 10 metal ions, and a detailed photophysi-
cal characterization of the novel chromophores are
ongoing.
Acknowledgment. This work was supported by the
U.S. National Science Foundation under Grant Number
CHEM-0517782 (to C.B.). The diffractometer was funded
by NSF Grant 0087210, by Ohio Board of Regents Grant
CAP-491, and by YSU.
The quinoline-annulated porphyrins possess low
(0.1 to 10-3 %) fluorescence and singlet oxygen quantum
yields, an effect likely due to the interaction of the
porphyrinic π-system with the imine/ketone functional-
ities. A detailed study of the ground and excited state
photophysical parameters of these chromophores is cur-
renly ongoing.
Supporting Information Available. Experimental pro-
cedures and characterization data of new compounds,
including representative reproductions of 1H, 13C NMR
and IR spectra. X-ray crystallographic data of compound
13 in CIF format. This material is available free of charge
via the Internet at http://pubs.acs.org.
In conclusion, we have shown that porphyrin-2,3-dione
mono- and bisoximes can be utilized in the generation of
Org. Lett., Vol. 13, No. 6, 2011
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