Synthesis of meso-extended tetraarylporphyrins

Article abstract of DOI:10.1021/jo070191p

(Chemical Equation Presented) The synthesis of five new meso-tetraarylporphyrins having pyridine, pyrimidine, or nitrile groups extending tetragonally via alkynyl linkages from the para positions is described. The radial extension is nearly double that of

Full text of DOI:10.1021/jo070191p

Synthesis of meso-Extended Tetraarylporphyrins
Christopher Richardson and Christopher A. Reed*
Department of Chemistry, UniVersity of California, RiVerside, California 92521-0403
chris.reed@ucr.edu
ReceiVed January 30, 2007
The synthesis of five new meso-tetraarylporphyrins having pyridine, pyrimidine, or nitrile groups extending
tetragonally via alkynyl linkages from the para positions is described. The radial extension is nearly
double that of common porphyrins such as tetra-p-pyridylporphyrin. Practical quantities can be produced
by Pd-coupling protocols when traditional methods fail. Applications of these extended porphyrins in
the area of porous metal-organic frameworks are anticipated.
Introduction
available.14-18 The control of pore size and the maintenance of
structural integrity after solvent removal from the pores are two
of the critical issues that must be addressed before practical
applications can result.19-22 More robust structures can be
produced using bridging ligands with metalloporphyrins5 or
fullerenes as supramolecular pillars11 but typically at the expense
of pore size.
An active area of contemporary chemistry is the assembly
of new materials using porphyrin building blocks. Particularly
intriguing are the possibilities with porous metal-organic
frameworks (MOFs), sometimes called “artificial zeolites”. In
seminal work in the early 1990s, Robson combined the
tetragonal shape propagation properties of tetraarylporphyrins
with metal-directed coordinate bond formation to produce porous
framework solids whose voids were filled with exchangeable
solvent molecules.1 In the past decade or so, a variety of infinite
framework, lamellar, and ribbon structures have been discovered
using tetraarylporphyrins that contain peripheral groups capable
of forming metal-ligand coordinate bonds in a divergent
manner,1-13 and a number of reviews on this topic are now
(7) Sharma, C. V. K.; Broker, G. A.; Huddleston, J. G.; Baldwin, J. W.;
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10.1021/jo070191p CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/27/2007
4750
J. Org. Chem. 2007, 72, 4750-4755

Synthesis of meso-Extended Tetraarylporphyrins
SCHEME 1
For the most part, work in this area has been restricted to a
few easily synthesized or commercially available tetraarylpor-
phyrins, such as 5,10,15,20-tetrakis(4-cyanophenyl)porphyrin or
5,10,15,20-tetrakis(4-pyridyl)porphyrin:
SCHEME 2
With the possibility of metal-organic frameworks with larger
pore sizes in mind, we have synthesized analogues of these
popular porphyrins having radial extensions of N-donor groups
designed to bind metal ions.
poor solubility of intermediates in the acidified solvent.27 In
this paper, we explore these limitations with alkynyl-linked
benzaldehydes containing basic groups and then improve the
methodology by employing palladium cross-coupling reactions
on a preformed tetra(p-bromophenyl)porphyrin.
Palladium cross-coupling methodologies are playing an
increasingly important role in porphyrin synthesis.28-31 Excellent
protocols have been developed for Suzuki,32 Stille,33 Negishi,34
and Sonogashira conditions involving porphyrin coupling
partners. The simplicity of the experimental procedure, the wide
availability of acetylenes, advances in the catalyst formulation,35
and the efficiency of coupling all contribute to the popularity
of the Sonogashira reaction in porphyrin chemistry. It is these
factors that prompted us to explore its utility in the current study.
Results and Discussion
Preparation of Alkynyl Benzaldehydes. The benzaldehydes
6, 7,36 8,37 9, and 10 were each produced in good yield (78-
88%) by the Sonogashira reaction of 4-ethynylbenzaldehyde
with the appropriate bromide (Scheme 1). Compound 6 was
also produced from the reverse coupling partners in equally good
yield (80%) (Scheme 2).
Compounds 6-9 were isolated as colored solids which, when
necessary, could be purified by sublimation to colorless
compounds, albeit with some product loss due to decomposition.
Compound 10 could not be sublimed but could be recrystallized
to analytical purity, despite the retention of a golden color.
Preparations of Porphyrins under Adler-Longo Condi-
tions. Compounds 6-8 were reacted with pyrrole under Adler-
Longo conditions for 20 min (Scheme 3). From these reactions,
Alkynyl linkages from the para positions of the meso-aryl
groups maintain a rigid propagation of tetragonal shape. A
related meta-alkynyl derivative has recently been used to prepare
a bisporphyrin box.23
The most commonly employed method for making a sym-
metrical tetraarylporphyrin continues to be the Rothemund
synthesis from a benzaldehyde24 using Adler and Longo’s
modification.25 Many porphyrins are also amenable to Lindsey
conditions.26 However, there are significant problems when
benzaldehydes bearing heterocyclic moieties are used. Adler-
Longo conditions typically give low yields, and Lindsey
conditions can fail all together. This has been attributed to the
(27) Gryko, D.; Lindsey, J. S. J. Org. Chem. 2000, 65, 2249-2252.
(28) Sharman, W. M.; Van Lier, J. E. J. Porphyrin Phthalocyanines 2000,
4, 441-453.
(29) Setsune, J.-I. J. Porphyrin Phthalocyanines 2000, 8, 93-102.
(30) Wagner, R. W.; Ciringh, Y.; Clausen, C.; Lindsey, J. S. Chem.
Mater. 1999, 11, 2974-2983.
(19) Eddaoudi, M.; Moler, D. B.; Li, H. L.; Chen, B. L.; Reineke, T.
M.; O’Keeffe, M.; Yaghi, O. M. Acc. Chem. Res. 2001, 34, 319-330.
(20) Kitagawa, S.; Kitaura, R.; Noro, S. Angew. Chem., Int. Ed. 2004,
43, 2334-2375.
(31) Loewe, R. S.; Tomizaki, K.-y; Youngblood, W. J.; Bo, Z.; Lindsey,
J. S. J. Mater Chem. 2002, 12, 3438-3451.
(32) Shi, B.; Boyle, R. W. J. Chem. Soc., Perkin Trans. 1 2002, 1397-
1400.
(33) Shanmugathasan, S.; Johnson, C. K.; Edwards, C.; Matthews, E.
K.; Dolphin, D.; Boyle, R. W. J. Porphyrin Phthalocyanines 2000, 4, 228-
232.
(21) Kitagawa, S.; Noro, S. Nakamura, T. Chem. Commun. 2006, 701-
707.
(22) Mueller, U.; Schubert, M.; Teich, F.; Puetter, H.; Scheirle-Arndt,
K.; Pastre, J. J. Mater Chem. 2006, 16, 626-636.
(23) Ikeda, A.; Ayabe, M.; Shinkai, S.; Sakamoto, S.; Yamaguchi, K.
Org. Lett. 2000, 2, 3707-3710.
(24) Rothemund, P. J. Am. Chem. Soc. 1935, 57, 2010-2011.
(25) Adler, A. D.; Longo, F. R.; Finarelli, J. D. J. Org. Chem. 1967, 32,
476.
(34) DiMagno, S. G.; Lin, V. S.-Y.; Therien, M. J. J. Org. Chem. 1993,
58, 5983-5993.
(35) Wagner, R. W.; Johnson, T. E.; Li, F.; Lindsey, J. S. J. Org. Chem.
1995, 60, 5266-5273.
(36) Sorensen, U. S.; Pombo-Villar, E. Tetrahedron 2005, 61, 2697-
2703.
(26) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827-836.
(37) Gryko, D. T.; Piechota, K. E. J. Porphyrin Phthalocyanines 2002,
6, 81-97.
J. Org. Chem, Vol. 72, No. 13, 2007 4751

Richardson and Reed
SCHEME 3
SCHEME 5
Having identified the limits of porphyrin-forming reactions
using Adler-Longo and Lindsey conditions, we turned our
attention toward the use of cross-coupling protocols with a
preformed porphyrin. This takes advantage of a higher-yielding
porphyrin synthesis but demands high efficiency in the subse-
quent 4-fold coupling reaction. Successful 4-fold couplings have
been reported39 but not with N-heterocycles.
SCHEME 4
Preparation of the Alkynes. Following the excellent pro-
cedure detailed by Thorand and Krause,40 we coupled 4-bro-
mopyridine, 5-bromopyrimidine, and 4-bromobenzonitrile with
trimethylsilylacetylene in THF/triethylamine (Scheme 5). Stan-
dard methods were used for deprotection of the silylethers,41
and compounds 11,42 12, and 1343,44 were isolated as colorless
solids in good yields (75-81%).
Preparation of Porphyrins by Cross-Coupling with Alkynes.
Our strategy was to use the easily prepared 5,10,15,20-tetrakis-
(4-bromophenyl)porphyrin and couple it to the alkyne in the
final step. This makes best use of the alkyne and also reduces
the amount of Pd catalyst needed compared to the earlier
procedures (Scheme 1). To the best of our knowledge, there is
only one example of 4-fold coupling of an alkyne to 5,10,15,-
20-tetrakis(4-bromophenyl)porphyrin. Chan and co-workers39
used trimethylsilylacetylene and PdCl2(PPh3)2 in triethylamine
to produce the 4-fold coupled product in 78% yield. These
conditions, however, gave no coupled product with our alkynes.
We conducted a survey of conditions using three commonly
employed solvents and two common catalysts (see Supporting
Information for details) and found success when using conditions
similar to those reported for the synthesis of tetravinylated
porphyrins via the Heck reaction,45 namely, a Pd(0) reagent in
DMF solvent at elevated temperature. Our procedure bears
similarity to the recently reported Heck (Cu-free Sonogashira)
alkynylation reaction of porphyrins46 and to a 4-fold coupling
reaction using a meso-tetrakis(ethynyl)porphyrin.47
the corresponding porphyrins 1-3 were isolated in better than
expected yields of ca. 11% after chromatographic purification.
We found it beneficial to use aldehydes purified by sublimation
in these reactions because then the porphyrin purification process
was facilitated.
The reactions of 9 and 10 resulted in the precipitation of much
solid during the porphyrin-forming reactions, presumably from
decomposition. Porphyrins could be isolated after chromatog-
raphy of each reaction mixture, but they always contained a
stubborn impurity, resistant to separation by chromatography
or recrystallization. Due to the low yield of these reactions (ca.
2%) and the problem of purification, this method was abandoned
for 4 and 5.
Preparation of Porphyrins Using Lindsey Conditions.
Reactions of benzaldehydes 9 and 10 were attempted using
Lindsey conditions. Upon addition of BF3‚OEt2 to the reaction
mixture of 9 and pyrrole in chloroform, an immediate precipitate
developed and no porphyrin was formed. We attribute this to
complexation of BF3 with the heterocyclic base, like that
encountered with other unprotected pyrimidines.38 In a separate
reaction with a Brønsted acid in place of the Lewis acid, the
addition of trifluoroacetic acid to the reaction mixture did not
lead to the formation of any porphyrin at room temperature,
even after 6 h. In contrast, the addition of BF3‚OEt2 to a mixture
of 10 and pyrrole in chloroform led smoothly to the formation
of porphyrin 5 after DDQ oxidation (Scheme 4). A pure product
was isolated in 23% yield after chromatography and crystal-
lization, providing a quite satisfactory preparation of this new,
extended porphyrin.
Each of the alkynes 11-13 was reacted with 5,10,15,20-
tetrakis(4-bromophenyl)porphyrin under the conditions outlined
(39) Chan, C.-S.; Tse, A. K.-S.; Chan, K. S. J. Org. Chem. 1994, 59,
6084-6089.
(40) Thorand, S.; Krause, N. J. Org. Chem. 1998, 63, 8551-8553.
(41) Austin, W. B.; Bilow, N.; Kelleghan, W. J.; Lau, K. S. Y. J. Org.
Chem. 1981, 46, 2280-2286.
(42) Holmes, B. T.; Pennington, W. T.; Hanks, T. W. Synth. Commun.
2003, 33, 2447-2461.
(43) Flatt, A. K.; Yao, Y.; Maya, F.; Tour, J. M. J Org. Chem. 2004,
69, 1752-1755.
(44) McIlroy, S. P.; Clo, E.; Nikolajsen, L.; Frederiksen, P. K.; Nielsen,
C. B.; Mikkelsen, K. V.; Gothelf, K. V.; Ogilby, P. R. J. Org. Chem. 2005,
70, 1134-1146.
(45) Pereira, M. M.; Muller, G.; Ordinas, J. I.; Azenha, M. E.; Arnaut,
L. G. J. Chem. Soc., Perkin Trans. 2 2002, 1583-1588.
(46) Ljungdahl, T.; Pettersson, K.; Albinsson, B.; Maartensson, J. J. Org.
Chem. 2006, 71, 1677-1687.
(38) Motmans, F.; Ceulemans, E.; Smeets, S.; Dehaen, W. Tetrahedron
Lett. 1999, 40, 7545-7548.
(47) Yen, W.-N.; Lo, S.-S.; Kuo, M.-C.; Mai, C.-L.; Lee, G.-H.; Peng,
S.-M.; Yeh, C.-Y. Org. Lett. 2006, 8, 4239-4242.
4752 J. Org. Chem., Vol. 72, No. 13, 2007

Synthesis of meso-Extended Tetraarylporphyrins
SCHEME 6
4-(4-Pyridinyl)benzaldehyde (6). The general procedure with
4-ethynylbenzaldehyde (3.40 g, 26.1 mmol), 4-bromopyridine
hydrochloride (5.26 g, 27.1 mmol), PdCl2(PPh3)2 (0.38 g,
2 mol %), Et3N (100 mL), and CuI (0.20 g, 4 mol %) was followed.
Silica gel treatment and sublimation gave pure 6 (4.34 g, 80%).
Compound 6 was also produced in the same manner from
4-ethynylpyridine (1.51 g, 14.6 mmol), 4-bromobenzaldehyde (2.47
g, 13.4 mmol), PdCl2(PPh3)2 (88 mg, 1 mol %), and CuI (69 mg,
2.5 mol %) in Et3N (50 mL). Yield 2.22 g, 80%: 1H NMR (300
MHz, CDCl3) δ 7.38 (d, 2H, JHH ) 4.6 Hz), 7.69 (d, 2H, JHH
)
8.2 Hz) 7.88 (d, 2H, JHH ) 6.7 Hz), 8.62 (d, 2H, JHH ) 4.6 Hz),
10.02 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 90.75, 93.20, 126.16,
128.82, 130.25, 131.24, 133.05, 136.73, 150.56, 191.88; m/z calcd
for C14H9N1O1 207.06933, found 207.06841. Anal. Calcd for
C14H9N1O1: C, 81.14; H, 4.38; N, 6.76. Found: C, 81.38; H, 4.65;
N, 6.61.
4-(3-Pyridinyl)benzaldehyde (7). The general procedure from
4-ethynylbenzaldehyde (1.14 g, 8.8 mmol), 3-bromopyridine (1.45
g, 9.2 mmol), PdCl2(PPh3)2 (120 mg, 2 mol %), and CuI (70 mg,
4 mol %) in Et3N (35 mL) was followed. EtOH (ca. 1 mL) was
added to the solid and the mixture sonicated/triturated before
filtering off a yellow-orange powder (1.42 g, 78%). Purification
in Scheme 6, and the 4-fold alkynylated compounds 1, 4, and
5 were isolated in ca. 70% yields.
Stoichiometry was important because excess alkyne led to
lower yields, and MALDI mass spectrometry indicated higher
than 4-fold levels of alkyne incorporation. Excess alkyne
incorporation has been seen in the Sonogashira reaction of other
porphyrin substrates.48 Reaction time was also important
because, given enough time, the alkynyl linkages become
hydrogenated to vinyl linkages.
1
by sublimation gives a colorless solid: H NMR (300 MHz, CDCl3)
δ 7.29 (t, 1H, JHH ) 4.1 Hz), 7.67 (d, 2H, JHH ) 8.2 Hz), 7.81 (d,
1H, JHH ) 8.2 Hz), 7.86 (d, 2H, JHH ) 8.2 Hz), 8.57 (d, 1H, JHH
) 5.1 Hz), 8.77 (s, 1H), 10.00 (s, 1H); 13C NMR (75 MHz, CDCl3)
δ 89.68, 91.52, 119.65, 123.07, 128.61, 129.55, 132.15, 135.75,
138.53, 149.12, 152.29, 191.24; m/z calcd for C14H9N1O1 207.06841,
found 207.06795. Anal. Calcd for C14H9N1O1: C, 81.14; H, 4.38;
N, 6.76. Found: C, 81.16; H, 4.48; N, 6.51.
Conclusions
4-(2-Pyridinyl)benzaldehyde (8). The general procedure from
4-ethynylbenzaldehyde (1.16 g, 8.9 mmol), 2-bromopyridine (1.43
g, 9.1 mmol), PdCl2(PPh3)2 (120 mg, 2 mol %), and CuI (70 mg,
4 mol %) in Et3N (35 mL) was followed. EtOH (ca. 1 mL) was
added to the solid and the mixture sonicated/triturated before
filtering off a tan powder (1.58 g, 85%). Purification by sublimation
gives a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.29 (t,
We have shown that acceptable yields of extended pyridine-
containing porphyrins 1-3 can be obtained under Adler-Longo
conditions. Lindsey conditions with BF3 catalysis are incompat-
ible with N-heterocyclic groups, but less basic cyano substituents
are tolerated, allowing a good synthesis of porphyrin 5 to
proceed. This finding is useful because subsequent derivatization
chemistry of the cyano groups is possible.
More flexible, however, is the palladium-catalyzed route to
extended porphyrins. This method did not display the functional
group incompatibility problems of Adler-Longo or Lindsey
conditions, allowing extended porphyrins to be synthesized on
a gram scale with operational simplicity. The yield on the last
step is particularly good, making efficient use of the materials
and the palladium catalyst.
1H, JHH ) 5.1 Hz), 7.56 (d, 1H, JHH ) 8.2 Hz), 7.71 (t, 1H, JHH
)
7.7 Hz), 7.74 (d, 2H, JHH ) 8.2 Hz), 7.87 (d, 2H, JHH ) 6.2 Hz),
8.64 (d, 1H, JHH ) 4.6 Hz), 10.02 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 87.93, 91.98, 123.32, 127.42, 128.38, 129.51, 132.51,
135.89, 136.32, 142.67, 150.17, 191.31; m/z calcd for C14H9N1O1
207.06841, found 207.06879. Anal. Calcd for C14H9N1O1: C, 81.14;
H, 4.38; N, 6.76. Found: C, 81.10; H, 4.47; N, 6.77.
4-(5-Pyrimidinyl)benzaldehyde (9). The general procedure from
4-ethynylbenzaldehyde (3.14 g, 24.1 mmol), 5-bromopyrimidine
(3.92 g, 24.7 mmol), PdCl2(PPh3)2 (0.20 g, 1.2 mol %), and CuI
(0.12 g, 2.6 mol %) in Et3N (100 mL) was followed. Silica gel
treatment and sublimation gave pure 9 (4.40 g, 88%): 1H NMR
(300 MHz, CDCl3) δ 7.71 (d, 2H, JHH ) 6.7 Hz), 7.90 (d, 2H, JHH
) 8.2 Hz), 8.88 (s, 2H), 9.18 (s, 1H), 10.04 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 86.50, 95.70, 119.89, 128.44, 130.30, 132.98,
136.87, 157.86, 159.42, 191.85; m/z calcd for C13H8N2O1 207.05584,
found 207.05579. Anal. Calcd for C13H8N2O1: C, 74.94; H, 3.87;
N, 13.45. Found: C, 75.26; H, 3.70; N, 13.15.
4-(4-Cyanophenyl)benzaldehyde (10). The general procedure
from 4-ethynylbenzaldehyde (2.76 g, 21.2 mmol), 4-bromoben-
zonitrile (3.86 g, 21.2 mmol), PdCl2(PPh3)2 (0.30 g, 2 mol %), PPh3
(0.11 g, 2 mol %), and CuI (0.16 g, 4 mol %) in Et3N (85 mL) was
followed. EtOH (ca. 1-2 mL) was added and the mixture sonicated/
triturated before filtering off a solid that was crystallized by layering
hexane (4-5 volumes) onto a solution of the title compound
dissolved in the minimum of hot CHCl3 (4.05 g, 83%): 1H NMR
(300 MHz, CDCl3) δ 7.65 (m, 4H), 7.69 (d, 2H, JHH ) 8.2 Hz),
7.90 (d, 2H, JHH ) 8.7 Hz), 10.04 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 91.15, 92.39, 112.17, 118.25, 127.32, 128.29, 129.57,
132.08, 132.21, 132.28, 135.96, 191.20; m/z calcd for C16H9N1O1
231.06841, found 231.06878. Anal. Calcd for C16H9N1O1: C, 83.10;
H, 3.92; N, 6.06. Found: C, 83.05; H, 3.67; N, 5.95.
The potential of tetraarylporphyrins with extended meso-
substituents can now be explored in studies of metal-organic
frameworks.
Experimental Section
General Procedure for Aldehyde Synthesis by Pd-Catalyzed
Coupling. A flask was charged with 4-ethynylbenzaldehyde
(1 equiv), the requisite arylbromide (1 equiv), PdCl2(PPh3)2 (1-2
mol %), and dry Et3N. The mixture was stirred magnetically
for 10 min with Ar bubbled through the solution before CuI (2-4
mol %) was added and a reflux condenser attached and the mixture
heated to reflux with stirring under Ar for 2 h. Following removal
of Et3N by rotary evaporation, CHCl3 was added and the solution
was filtered, washed with 15% aq K2CO3, H2O, and brine, dried
(MgSO4 or Na2SO4), and the CHCl3 removed. Compounds were
treated by passing through a plug of silica gel or by the addition of
EtOH and sonication/trituration before sublimation (<0.2 mm, heat
gun), whereupon colorless solids were obtained.
(48) Chen, Y.-J.; Lee, G.-H.; Peng, S.-M.; Yeh, C.-Y. Tetrahedron Lett.
2005, 46, 1541-1544.
J. Org. Chem, Vol. 72, No. 13, 2007 4753

Richardson and Reed
General Procedure for Porphyrins by Rothemund Synthesis.
Aldehydes 1-3 (1 equiv) and pyrrole (1 equiv) were placed in a
flask, and propionic acid was added and the mixture refluxed for
20 min. In the case of easily identified crystalline products, filtration
was used. Alternatively, the solvent was removed under reduced
pressure and the residue taken up in CHCl3 and loaded onto an
Al2O3 column and eluted with CHCl3. In all cases, chromatography
on silica gel eluting with CHCl3-alcohol mixtures was used, and
crystalline products were obtained by layering MeOH onto con-
centrated CHCl3 solutions.
5,10,15,20-Tetrakis(4-(4-pyridinylethynyl)phenyl)porphyrin
(1). The general procedure from 6 (1.00 g, 4.8 mmol), pyrrole
(0.32 g, 4.8 mmol), and propionic acid (20 mL) was followed. The
crystallized solid was collected on a frit, washed with hot water (3
× 10 mL) and then ethanol (3 × 5 mL), chromatographed on silica
gel (2 × 20 cm, CHCl3-MeOH, 95:5) for purification, and
recrystallized giving beautiful, shiny purple needles (120 mg,
10%): 1H NMR (300 MHz, CDCl3) δ -2.78 (br s, 2NH), 7.54 (d,
8H, JHH ) 6.1 Hz), 7.98 (d, 8H, JHH ) 8.6 Hz), 8.25 (d, 8H, JHH
) 8.0 Hz), 8.70 (d, 8H, JHH ) 5.5 Hz), 8.89 (s, 8H); UV-vis λnm
(log ꢀ) 424 (5.43), 519 (4.09), 555 (3.91), 592 (3.59), 649 (3.53);
MALDI mass spectrum m/z calcd for C72H43N8 1019.3605, found
1019.3602. Anal. Calcd for C72H42N8: C, 84.85; H, 4.15; N, 11.00.
Found: C, 84.64; H, 4.13; N, 10.99.
5,10,15,20-Tetrakis(4-(3-pyridinylethynyl)phenyl)porphyrin
(2). The general procedure from 7 (1.00 g, 4.8 mmol), pyrrole
(0.32 g, 4.8 mmol), and propionic acid (20 mL) was followed. After
the Al2O3 (8 × 10 cm, CHCl3) and silica gel chromatography (4 ×
30 cm, CHCl3-EtOH, 97.5:2.5), crystallization gave shiny purple
needles (131 mg, 11%): 1H NMR (300 MHz, CDCl3) δ -2.76 (br
s, 2NH), 7.37 (m, 4H, JHH ) 8.2 Hz), 7.96 (m, 12H), 8.26 (d, 8H,
JHH ) 6.2 Hz), 8.64 (d, 4H, JHH ) 4.9 Hz), 8.90 (s, 8H), 8.94 (s,
4H); UV-vis λnm (log ꢀ) 425 (5.76), 519 (4.36), 555 (4.19), 592
(3.87), 649 (3.83); MALDI mass spectrum m/z calcd for C72H43N8
1019.3605, found 1019.3627. Anal. Calcd for C72H42N8: C, 84.85;
H, 4.15; N, 11.00. Found: C, 85.32; H, 4.33; N, 10.33.
5,10,15,20-Tetrakis(4-(2-pyridinylethynyl)phenyl)porphyrin
(3). The general procedure from 7 (1.00 g, 4.8 mmol), pyrrole
(0.32 g, 4.8 mmol), and propionic acid (20 mL) was followed. After
the Al2O3 (8 × 10 cm, CHCl3) and silica gel chromatography (4 ×
30 cm, CHCl3-EtOH, 97:3), crystallization gave shiny purple
needles (126 mg, 10.5%): 1H NMR (300 MHz, CDCl3) δ -2.79
(br s, 2NH), 7.33 (t, 4H, JHH ) 6.0 Hz), 7.69 (d, 4H, JHH ) 7.7
Hz), 7.78 (t, 4H, JHH ) 7.5 Hz), 8.02 (d, 8H, JHH ) 7.9 Hz), 8.24
(d, 8H, JHH ) 7.9 Hz), 8.72 (d, 4H, JHH ) 4.6 Hz), 8.90 (s, 8H);
UV-vis λnm (log ꢀ) 424 (5.79), 518 (4.37), 554 (4.21), 593 (3.87),
648 (3.84); MALDI mass spectrum m/z calcd for C72H43N8
1019.3605, found 1019.3578. Anal. Calcd for C72H42N8: C, 84.85;
H, 4.15; N, 11.00. Found: C, 82.07; H, 3.68; N, 9.00.
5,10,15,20-Tetrakis(4-(4-cyanophenylethynyl)phenyl)porph-
yrin (5). To a two-necked flask charged with 10 (0.50 g, 2.16 mmol)
and a stir bar was attached a reflux condenser fitted with an Ar
gas supply and a suba-seal. After three evacuation-refill cycles,
dry, oxygen-free CHCl3 (200 mL) and pyrrole (0.15 mL, 2.16
mmol) were admitted through the seal. After stirring a few minutes,
BF3‚OEt2 (0.27 mL, 2.16 mmol) was added via syringe and the
mixture stirred for 1 h at rt. DDQ (0.45 g 1.98 mmol) and Et3N
(1.5 mL) were then added, and the mixture was refluxed 1 h. After
removing ca. 3/4 of the solvent by rotary evaporation, the reaction
mixture was loaded directly onto an Al2O3 column (8 × 15 cm,
CHCl3) and a single fraction collected. The volume was reduced
by rotary evaporation until near saturation, and the solution was
loaded onto silica gel (4 × 30 cm, CHCl3) and the fraction following
a small head band was collected and crystallized by layering
methanol onto a concentrated CHCl3 solution to gave a purple solid
(140 mg, 23%): 1H NMR (300 MHz, CDCl3) δ -2.78 (br s, 2NH),
7.74 (m, 16H), 7.96 (d, 8H, JHH ) 7.9 Hz), 7.25 (d, 8H, JHH ) 7.9
Hz), 8.88 (s, 8H); UV-vis λnm (log ꢀ) 425 (5.62), 519 (4.23), 555
(4.07), 592 (3.74), 648 (3.68); MALDI mass spectrum m/z calcd
for C80H43N8 1115.3605, found 1115.3527. Anal. Calcd for
C80H42N8: C, 86.15; H, 3.80; N, 10.05. Found: C, 86.18; H, 3.91;
N, 10.32.
General Procedure for Synthesis of Terminal Alkynes by
Sonogashira Reaction. A modified Schlenk flask was charged with
requisite arylbromide (1 equiv), PPh3 (2.5 mol %), PdCl2(PPh3)2
(3-5 mol %), and a stir bar and evacuated-refilled three times
with Ar. THF (to give ca. 0.5 M solution), Et3N (1.5 equiv [2.25
equiv in the case of 11]), and trimethylsilylacetylene (1.5 equiv)
were added by syringe, and the mixture was stirred for 15 min
under Ar before CuI (2-2.5 mol %) was added and the Teflon
screw valve closed and the reaction stirred at rt. After reaction,
THF was removed under reduced pressure, hexane added, and the
mixture filtered over Celite. The filtrate was washed with H2O and
the hexane removed. The residual solid was dissolved in MeOH
(to give ca. 0.5 M solution), K2CO3 (0.1 g/10 mmol) added, and
the mixture stirred at rt for 1.5 h. The reactions were worked up
by removal of some MeOH by rotary evaporation, dilution with
H2O, extraction with Et2O (4×), drying (MgSO4 or Na2SO4), and
removal of solvent. The residues were purified by chromatography
on silica gel or sublimation (<0.5 mm, heat gun) to give a colorless
solids.
4-Ethynylpyridine (11). Following the general procedure from
4-bromopyridine hydrochloride (1.80 g, 9.25 mmol), PPh3 (40 mg,
2.5 mol %), PdCl2(PPh3)2 (250 mg, 3 mol %), Et3N (3.0 mL,
21.5 mmol), trimethylsilylacetylene (1.10 g, 11.2 mmol), and CuI
(37 mg, 1.7 mol %) in THF (20 mL) for 8 h gave a dark solid after
work up. MeOH/K2CO3 treatment and subsequent workup gave a
dark residue that was purified by passing through a plug of silica
gel (CH2Cl2) and then sublimation (0.72 g, 75%). NMR data were
consistent with those reported.40
5-Ethynylpyrimidine (12). Following the general procedure
from 5-bromopyrimidine (5.10 g, 32.1 mmol), Ph3P (0.21 g,
0.80 mmol), PdCl2(PPh3)2 (1.10 g, 5 mol %), Et3N (4.86 g, 48.1
mmol), trimethylsilylacetylene (4.72 g, 48.1 mmol), and CuI (0.12
g, 2 mol %) in THF (60 mL) for 16 h gave a golden solid following
workup. The residue after MeOH/K2CO3 treatment and workup was
1
purified by sublimation (2.70 g, 81%): H NMR (300 MHz, CDCl3)
δ 3.40 (s, 1H), 8.80 (s, 2H), 9.15 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 84.40, 119.89, 157.23, 159.29; m/z calcd for C6H4N2
104.03694, found 104.03745. Anal. Calcd for C6H4N2: C, 69.22;
H, 3.87; N, 26.91. Found: C, 68.89; H, 3.63; N, 27.00.
4-Ethynylbenzonitrile (13). Following the general procedure
from 4-bromobenzonitrile (4.97 g, 27.3 mmol), PPh3 (0.17 g,
2.5 mol %), PdCl2(PPh3)2 (0.96 g, 5 mol %), Et3N (4.23 g, 41.8
mmol), trimethylsilylacetylene (4.05 g, 41.2 mmol), and CuI
(0.17 g, 2.5 mol %) in THF (60 mL) for 16 h at rt gave a yellow
solid after workup. The residue after MeOH/K2CO3 treatment and
workup was purified by column chromatography on silica gel
eluting with CH2Cl2-hexanes (1:3, Rf 0.2) to give 13 as a colorless
solid (2.67 g, 77%): 1H NMR (300 MHz, CDCl3) δ 3.30 (s, 1H),
7.61 (d, 2H), 7.56 (d, 2H); 13C NMR (75 MHz, CDCl3) δ 81.49,
81.84, 112.36, 118.19, 126.99, 131.99, 132.65; m/z calcd for C9H5N1
127.04220, found 127.04172. Anal. Calcd for C9H5N1: C, 85.02;
H, 3.96; N, 11.02. Found: C, 85.01; H, 3.89; N, 11.09.
General Procedure for Porphyrin Synthesis by Pd-Catalyzed
Coupling. A modified Schlenk tube was charged with 5,10,15,-
20-tetrakis(4-bromophenyl)porphyrin (ca. 100 mg, 0.11 mmol), the
desired alkyne (4.5-5 equiv), Pd(PPh3)4 (10 mol %), dry Et3N
(1 mL), dry DMF (20 mL), and a magnetic stir bar. The mixture
was degassed by three freeze-pump-thaw cycles before being
back-filled with Ar and closing the Teflon screw valve. The contents
of the tube were stirred and heated at 140 °C for 48 h. After cooling,
the solvents were removed under reduced pressure to dryness, and
the purple solid was taken up in CHCl3 (ca. 30 mL) and sonicated
before filtering through Celite. After removal of solvent, the residue
was redissolved in the minimum of hot CHCl3, and methanol was
then layered onto the solution; the crystals that formed were
collected by filtration and washed with methanol and hexane.
4754 J. Org. Chem., Vol. 72, No. 13, 2007

Synthesis of meso-Extended Tetraarylporphyrins
5,10,15,20-Tetrakis(4-(4-pyridinylethynyl)phenyl)porphyrin
(1). 5,10,15,20-Tetrakis(4-bromophenyl)porphyrin (108.3 mg, 0.116
mmol), 4-ethynylpyridine (60.7 mg, 0.589 mmol), Pd(PPh3)4
(11.3 mg, 10 mol %). Yield 80.2 mg, 68%.
5,10,15,20-Tetrakis(4-(5-pyrimidinylethynyl)phenyl)porphy-
rin (4). 5,10,15,20-Tetrakis(4-bromophenyl)porphyrin (108.7 mg,
0.117 mmol), 5-ethynylpyrimidine (56.8 mg, 0.546 mmol), Pd-
(PPh3)4 (13.5 mg, 10 mol %). Yield 85.6 mg, 72%: 1H NMR (300
MHz, CDCl3) δ -2.78 (br s, 2NH), 7.98 (d, 8H, JHH ) 7.9 Hz),
8.27 (d, 8H, JHH ) 7.9 Hz), 8.89 (s, 8H), 9.02 (s, 8H), 9.24 (s,
4H); UV-vis λnm (log ꢀ) 425 (5.62), 519 (4.23), 555 (4.07), 592
(3.74), 648 (3.68). Anal. Calcd for C68H38N12‚0.5H2O: C, 79.13;
H, 3.81; N, 16.28. Found: C, 79.01; H, 4.11; N, 15.93.
triethylamine (20 mL). Ar was bubbled through the magnetically
stirred solution with a fritted bubbler for 1 h before 5,10,15,20-
tetrakis(4-bromophenyl)porphyrin (1.03 g, 1.11 mmol), 5-ethy-
nylpyrimidine (0.53 g, 5.10 mmol), and Pd(PPh3)4 (121 mg, 10
mol %) were added under a flow of Ar and a reflux condenser
attached. The contents were heated at 130 °C with stirring for 60
h under Ar. The same general procedure as above was followed
for the isolation and purification (0.77 g, 59%).
Acknowledgment. We thank Professor Peter D. W. Boyd
for his valued input to this work. It was supported by NIH Grant
GM 23851.
5,10,15,20-Tetrakis(4-(4-cyanophenylethynyl)phenyl)porph-
yrin (5). 5,10,15,20-Tetrakis(4-bromophenyl)porphyrin (101.7 mg,
0.109 mmol), 4-ethynylbenzonitrile (64.2 mg, 0.505 mmol), Pd-
(PPh3)4 (12.9 mg, 10 mol %). Yield 84.1 mg, 70%.
Procedure for Large-Scale Porphyrin Synthesis by Pd-
Catalyzed Coupling. 5,10,15,20-Tetrakis(4-(5-pyrimidinylethy-
nyl)phenyl)porphyrin (5). To a single-necked round-bottomed
flask were placed reagent grade DMF (200 mL) and reagent grade
Supporting Information Available: Further experimental
procedures, 1H NMR spectra for compounds 1-13, 13C NMR
spectra for compounds 6-10, 12, 13, mass spectra for compounds
1-9, 11-13, UV-visible spectra for compounds 1-5. This
material is available free of charge via the Internet at http://pubs.acs
.org.
JO070191P
J. Org. Chem, Vol. 72, No. 13, 2007 4755