First triazole-bridged unsymmetrical porphyrin dyad via click chemistry

Article abstract of DOI:10.1021/jo702018s

(Chemical Equation Presented) Click chemistry has been successfully applied in the synthesis of the first example of a triazole-bridged porphyrin dyad containing N₂S₂ porphyrin and N₄ or ZnN ₄ porphyrin subunits, and fluorescence study indicated a possibility of singlet-singlet energy transfer from the N₄ or ZnN₄ porphyrin subunit to the N₂S₂ porphyrin subunit.

Full text of DOI:10.1021/jo702018s

versatile Cu(I)-catalyzed 1,3-diploar cycloaddition protocol to
porphyrin chemistry are very scarce.5
First Triazole-Bridged Unsymmetrical Porphyrin
Dyad via Click Chemistry
Photoinduced electron and energy transfer are two important
processes involved in natural photosynthesis. Several covalently
linked porphyrin dyads have been prepared to study these
processes.6 Recently, we developed methods to synthesize the
functionalized heteroporphyrin building blocks and used them
for the synthesis of several covalently linked ethyne-, phenyl-
ethyne-, and diphenylethyne-bridged unsymmetrical porphyrin
dyads containing two dissimilar porphyrin subunits such as N4-
N3S, N4-N3O, N3O-N3S, N3S-N2S2, etc.7 The excited-state
properties of these porphyrin dyads were studied to identify the
suitable porphyrin dyad in which maximum unidirectional
singlet-singlet energy transfer occurs for molecular electronic
applications. In continuation of our efforts toward the synthesis
of heteroporphyrin-based porphyrin assemblies, we describe our
attempts toward the synthesis of the first triazole-bridged
porphyrin dyad containing N2S2 porphyrin and N4/ZnN4 por-
phyrin subunits using click chemistry. The preliminary photo-
physical study supported an efficient energy transfer from N4/
ZnN4 porphyrin subunit to N2S2 porphyrin subunit on selective
excitation of N4/ZnN4 porphyrin subunit.
Sokkalingam Punidha, Jasmine Sinha, Anil Kumar, and
Mangalampalli Ravikanth*
Department of Chemistry, Indian Institute of Technology,
Bombay, Powai, Mumbai 400 076, India
raVikanth@chem.iitb.ac.in
ReceiVed September 13, 2007
The N2S2 porphyrin containing alkyne functional group and
the N4 porphyrin building block containing azide functional
group were synthesized over a sequence of steps as shown in
Schemes 1 and 2, respectively. The required thiophene, 3,4-(2-
methyl-2-hydroxymethylpropane-1,3-diyldioxy)thiophene 1 was
synthesized in four steps starting from thiophene by slight
modifications of a reported procedure.8 The thiophene diol 2
was synthesized by treating 1 equiv of a 2,5-dilithiated derivative
of thiophene 1 with 2.5 equiv of p-tolualdehyde in n-hexane.
The TLC analysis showed the formation of the desired diol with
some amount of thiophene mono-ol. The required diol 2 was
separated by column chromatography and afforded pure diol 2
as a colorless solid in 62% yield. The diol 2 was characaterized
Click chemistry has been successfully applied in the synthesis
of the first example of a triazole-bridged porphyrin dyad
containing N2S2 porphyrin and N4 or ZnN4 porphyrin
subunits, and fluorescence study indicated a possibility of
singlet-singlet energy transfer from the N4 or ZnN4 por-
phyrin subunit to the N2S2 porphyrin subunit.
1
by H and 13C NMR, IR, mass, and elemental analysis.
(5) Devaraj, N. K.; Decreau, R. A.; Ebina, W.; Collman, J. P.; Chidsey,
C. E. D. J. Phys. Chem. B 2006, 110, 15955-15962.
“Click” chemistry represents a modular approach toward
synthesis that uses only the most practical transformations to
make connections with excellent fidelity.1 The Cu(I)-catalyzed
Huisgen 1,3-dipolar cycloaddition of alkynes and azides to give
1,4-disubstituted 1,2,3-triazoles has emerged as a powerful
linking reaction and found widespread applications ranging from
combinatorial drug research,2 material science,3 to bioconjugate
chemistry.4 Interestingly, the reports on application of this
(6) (a) Thamyongkit, P.; Muresan, A. Z.; Diers, J. R.; Holten, D.; Bocian,
D. F.; Lindsey, J. S. J. Org. Chem. 2007, 72, 5207-5217. (b) Wagner, R.
W.; Johnson, T. E.; Li, F.; Lindsey, J. S. J. Org. Chem. 1995, 60, 5266-
5273. (c) Sazanovich, I. V.; Balakumar, A.; Muthukumaran, K.; Hindin,
E.; Kirmaier, C.; Diers, J. R.; Lindsey, J. S.; Bocian, D. F.; Holten, D.
Inorg. Chem. 2003, 42, 6616-6628. (d) Winters, M. U.; Ka¨rnbratt, J.;
Blades, H. E.; Wilson, C. J.; Frampton, M. J.; Anderson, H. L.; Albinsson,
B. Chem. Eur. J. 2007, 13, 7385-7394. (e) Winters, M. U.; Ka¨rnbratt, J.;
Eng, M.; Wilson, C. J.; Anderson, H. L.; Albinsson, B. J. Phys. Chem. C
2007, 7192-7199. (f) Locos, O. B.; Arnold, D. P. Org. Biomol. Chem.
2006, 902-916. (g) Osuka, A.; Shimidzu, H. Angew. Chem., Int. Ed. Engl.
1997, 36, 135-137. (h) Aratani, N.; Osuka, A.; Kim, Y. H.; Jeong, D. H.;
Kim, D. Angew. Chem., Int. Ed. Engl. 2000, 39, 1458-1462.
(1) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int.
Ed. Engl. 2001, 40, 2004-2021. (b) Maria, V. G.; Mar´ıa, J. A.; OÄ scar, L.
Synthesis 2007, 1589-1620.
(2) (a) Lee, L. V.; Mitchell, M. L.; Huang, S.-J.; Fokin, V. V.; Sharpless,
K. B.; Wong, C.-H. J. Am. Chem. Soc. 2003, 125, 9588-9589. (b) Brik,
A.; Muldoon, J.; Lin, Y.-C.; Elder, J. H.; Goodsell, D. S.; Olson, A. J.;
Fokin, V. V.; Sharpless, K. B.; Wong, C.-H. ChemBioChem 2003, 4, 1246-
1248.
(3) (a) Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.; Scheel,
A.; Voit, B.; Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.; Fokin, V. V.
Angew. Chem. 2004, 43, 3928-3932. (b) Helms, B.; Mynar, J. L.; Hawker,
C. J.; Frechet, J. M. J. J. Am. Chem. Soc. 2004, 126, 15020-15021.
(4) (a) Wang, Q.; Chan, T. R.; Hilgraf, R.; Fokin, V. V.; Sharpless, K.
B.; Finn, M. G. J. Am. Chem. Soc. 2003, 125, 3192-3193. (b) Burley, G.
A.; Gierlich, J.; Mofid, M. R.; Nir, H.; Tal, S.; Eichen, Y.; Carell, T. J.
Am. Chem. Soc. 2006, 128, 1398-1399.
(7) (a) Kumaresan, D.; Agarwal, N.; Ravikanth, M. J. Chem. Soc., Perkin
Trans. 1 2001, 1644-1648. (b) Kumaresan, D.; Agarwal, N.; Gupta, I.;
Ravikanth, M. Tetrahedron 2002, 58, 5347-5356. (c) Gupta, I.; Agarwal,
N.; Ravikanth, M. Eur. J. Org. Chem. 2004, 1693-1697. (d) Kumaresan,
D.; Datta, A.; Ravikanth, M. Chem. Phys. Lett. 2004, 395, 87-91. (e) Gupta,
I.; Ravikanth, M. J. Org. Chem. 2004, 69, 6796-6811. (f) Punidha, S.;
Agarwal, N.; Ravikanth, M. Eur. J. Org. Chem. 2005, 2500-2517. (g)
Punidha, S.; Ravikanth, M. Synlett 2005, 14, 2199-2203. (h) Gupta, I.;
Frohlich, R.; Ravikanth, M. Chem. Commun. 2006, 3726-3728. (i) Punidha,
S.; Agarwal, N.; Gupta, I.; Ravikanth, M. Eur. J. Org. Chem. 2007, 1168-
1175. (j) Rai, S.; Ravikanth, M. Tetrahedron 2007, 63, 2455-2465. (k)
Gupta, I.; Ravikanth, M. Inorg. Chim. Acta 2007, 360, 1731-1742.
(8) Kros, A.; Nolte, R. J. M.; Sommerdijk, N. A. J. M. J. Polym. Sci.
Part A: Polym. Chem. 2002, 40, 738-747.
10.1021/jo702018s CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/11/2007
J. Org. Chem. 2008, 73, 323-326
323

SCHEME 1. Synthesis of N2S2 Porphyrin Containing
Ethynyl Functional Group 5
SCHEME 2. Synthesis of N4 Porphyrin Containing Azide
Functional Group 8
SCHEME 3. Synthesis of Triazole-Bridged Porphyrin Dyad
9 under “Click” Reaction Conditions
The diol 2 was condensed with known 16-thiatripyrrane9 3
in dichloromethane in the presence of a catalytic amount of
BF3-etherate followed by oxidation with DDQ. TLC analysis
of the reaction mixture indicated the formation of porphyrin 4
as the sole porphyrin product. Column chromatography on silica
gave the desired porphyrin 4 as a purple solid in 8% yield. The
molecular ion peak at 821 in the ES-MS spectrum confirmed
1
porphyrin 4. In the H NMR spectrum, the two â-thiophene
protons appeared as a singlet at 9.64 ppm and the four â-pyrrole
protons appeared as two sets of doublets corresponding to two
protons each at 8.46 and 8.59 ppm. The absorption spectrum
of 4 showed four Q-bands and one Soret band which were red-
shifted as compared to 5,10,15,20-tetraphenyl-21,23-thiapor-
phyrin10 (S2TPP) due to the presence of the propylene dioxy
methanol substituent at the â-thiophene ring of porphyrin 4.
The N2S2 porphyrin containing alkyne functional group 5 was
prepared by reacting 4 with propargyl tosylate in the presence
of NaH/DABCO in THF at room temperature overnight. The
crude porphyrin was purified by silica gel column chromatog-
raphy, using petroleum ether/dichloromethane (50:50), and
afforded the pure porphyrin 5 in 52% yield. The molecular ion
peak at 859 in the ES-MS spectrum and the ethyne CH proton
signal as a singlet at 4.18 ppm in the 1H NMR spectrum
confirmed the porphyrin 5. The absorption spectrum of 5 showed
four Q-bands and one Soret band with peak positions matching
those of porphyrin 4.
at 80 °C overnight followed by column chromatographic
purification. Compound 8 was confirmed by spectroscopic
techniques.
The triazole-bridged porphyrin dyad 9 was prepared under
click reaction conditions by reacting 5 and 8 in the presence of
sodium ascorbate and CuSO4 in a water-acetone mixture at
room temperature for 4 days (Scheme 3).1 After standard
workup, the crude compound was subjected to silica gel column
chromatographic purification and pure pophyrin dyad 9 was
obtained as a purple solid in 46% yield. The dyad 9 was
confirmed by molecular ion peak at 1615 in the ES-MS spectrum
1
and the H NMR spectrum in which the signals correspond to
both porphyrinic subunits and bridging methylene and triazole
groups were present (Supporting Information). The Zn(II)
derivative of 9 (Zn9) was prepared by treating 9 in dichlo-
romethane with methanolic Zn(OAc)2 at refluxing temperature
for 1 h and purified by silica gel column chromatography. The
Zn(II) ion forms a complex only with the N4 porphyrin subunit
of dyad 9.
The absorption spectrum of dyads 9 and Zn9 is essentially a
linear combination of absorption spectra of both the porphyrin
subunits indicating no ground state interaction between the two
porphyrin subunits. The redox potentials of dyads 9 and Zn9
and monomers were measured (Supporting Information) by
cyclic voltammetry, and differential pulse voltammetric mea-
surements at a glassy carbon electrode in dichloromethane
containing 0.1 M TBAP showed that the redox potentials are
in the same range as those of their corresponding monomeric
analogues indicating the absence of electronic interaction
between two porphyrin subunits in dyads 9 and Zn9. However,
the steady-state fluorescence spectrum of dyad 9 and Zn9
The other required porphyrin building block, N4 porphyrin
azide 8 was synthesized from hydroxyl porphyrin 6 as shown
in Scheme 2. The porphyrin 6 was converted to bromo porphyrin
7 by treating 6 with 20 equiv of 1,3-dibromopropane in DMF
in the presence of K2CO3 overnight at room temperature
followed by column chromatographic purification. The molec-
1
ular ion peak at 795 in the ES-MS spectrum and a clean H
NMR spectrum confirmed porphyrin 7 (Supporting Information).
The absorption spectrum showed four Q-bands and one Soret
band and the peak positions matched those of 5,10,15,20-
tetraphenylporphyrin (H2TPP). The azido porphyrin 8 was
prepared by reacting bromoporphyrin 7 with NaN3 in acetone
(9) Heo, P.-Y.; Lee, C.-H. Bull. Korean Chem. Soc. 1996, 17, 515-
520.
(10) Gupta, I.; Ravikanth, M. Coord. Chem. ReV. 2006, 250, 468-518.
324 J. Org. Chem., Vol. 73, No. 1, 2008

FIGURE 2. Comparison of steady-state emission spectra of dyad
triazole bridged N4-N2S2 porphyrin dyad 9 (s) and diphenyl ethyne
bridged N4-N2S2 porphyrin dyad 10 (‚‚‚) in toluene, using λex ) 420
nm.
FIGURE 1. (a) Comparison of steady-state emission spectra of dyad
9 (s) and a 1:1 mixture of 5 and 8 (‚‚‚). The excitation wavelength
used was 420 nm. (b) Steady-state emission spectrum of dyad Zn9
recorded in toluene at the excitation wavelength 550 nm.
Zn9. More studies are required for the complete understanding
of the excited-state dynamics of dyads reported here.
In summary, we synthesized the appropriate ethyne and azide
porphyrin building blocks and used them for the synthesis of
the first triazole-bridged porphyrin dyad containing two different
porphyrin subunits under click reaction conditions. Collectively,
1H NMR, UV-vis, and redox potential data indicate that there
is no specific interaction between the two porphyrin subunits
in triazole-bridged dyads. However, the preliminary fluorescence
studies indicated a possibility of energy transfer from N4 or the
ZnN4 porphyrin subunit to the N2S2 porphyrin subunit in these
porphyrin dyads. The synthetic strategy reported here can be
extended to synthesize various other triazole-bridged porphyrin
dyads and other novel constructs to study their excited-state
dynamics, and such synthetic efforts are underway in our
laboratory.
recorded in toluene at room temperature (Figure 1) indicated a
possibility of energy transfer from the N4/ZnN4 porphyrin
subunit to the N2S2 porphyrin subunit in dyad 9.
When dyad 9 was excited at 420 nm where the N4 porphyrin
subunit absorbs strongly, the emission of the N4 porphyrin was
quenched by 97% and a strong emission from the N2S2
porphyrin subunit was observed (Figure 1a). Furthermore, when
a 1:1 mixture of porphyrin 5 and 8 was excited at 420 nm, the
emission was noted mainly from the N4 porphyrin subunit
(Figure 1a). These observations support the energy transfer from
the N4 porphyrin subunit to the N2S2 porphyrin subunit in the
triazole-bridged porphyrin dyad 9. We compared the photo-
physical properties observed for the triazole-bridged N4-N2S2
porphyrin dyad 9 with those of our previously reported6f
diphenylethyne-bridged N4-N2S2 porphyrin dyad 10, and the
comparison of steady-state emission spectra of 9 and 10 recorded
at 420 nm where the N4 porphyrin subunit absorbs strongly is
shown in Figure 2. In 10, on excitation at 420 nm where the N4
porphyrin subunit absorbs strongly, the emission was noted from
both N4 and N2S2 porphyrin subunits unlike in 9 in which the
major emission was noted from the N2S2 porphyrin subunit
(Figure 1a). Thus, it is clear from the study that on changing
the rigid diphenylethyne bridged porphyrin dyad 10 to a flexible
triazole-bridged porphyrin dyad 9, the energy transfer efficiency
from the N4 porphyrin subunit to the N2S2 porphyrin subunit is
increased. Similarly, the fluorescence spectrum of Zn9 was
recorded at 550 nm where the ZnN4 porphyrin subunit absorbs
strongly, the ZnN4 porphyrin emission was quenched to 98%,
and a strong emission from the N2S2 porphyrin subunit was
observed (Figure 1b) supporting an energy transfer from the
ZnN4 porphyrin subunit to the N2S2 porphyrin subunit in dyad
Experimental Section
Triazole-Bridged N4-N2S2 Porphyrin Dyad 9. Compound 5
(30 mg, 3.49 mmol) dissolved in acetone (3 mL) was placed in a
100-mL round-bottom flask fitted with a reflux condenser. Com-
pound 8 (26 mg, 3.49 mmol) dissolved in acetone (2 mL) was added
to the solution followed by the addition of sodium ascorbate (13.8
mg, 0.70 mmol) and CuSO4 (8.7 mg, 0.35 mmol) dissolved in water
(1 mL), then the mixture was stirred until a clear solution was
obtained. The reaction mixture was stirred at 80 °C for 96 h. After
standard workup with dichloromethane, the crude reaction mixture
was purified by silica gel column chromatography, using dichlo-
romethane as eluent, and the desired porphyrin dyad 9 was collected
as a purple solid in 46% yield (4.2 mg). Mp >300 °C. IR (KBr
1
film): ν 3068, 2927, 2850, 1577, 1042, 980, 790, 580 cm-1. H
NMR (400 MHz, CDCl3, 25 °C): δ -2.79 (s, 2 H), 1.28 (s, 3 H),
2.50 (t, J ) 12.0 Hz, 6.1 Hz, 2 H), 2.75 (s, 21 H), 3.76-3.85 (m,
J. Org. Chem, Vol. 73, No. 1, 2008 325

4 H), 4.01 (d, J ) 12.2 Hz, 2 H), 4.11 (d, J ) 12.0 Hz, 2 H),
4.38-4.44 (m, 4 H), 7.30 (s, 1 H), 7.46-7.64 (m, 12 H), 7.91 (d,
J ) 7.8 Hz, 2 H), 8.00 (d, J ) 7.8 Hz, 2 H), 8.08-8.18 (m, 16 H),
8.44 (d, J ) 4.0 Hz, 2 H), 8.60 (d, J ) 4.0 Hz, 2 H), 8.84-8.86
(m, 8 H), 9.62 (s, 2 H) ppm. ES-MS: C106H87N9O4S2, calcd av
mass 1614.9, obsd m/z 1615.0 (M+,100%). Anal. Calcd: C, 78.83;
H, 5.43; N, 7.81; S, 3.97. Foumd: C, 78.79; H, 5.47; N, 7.85; S,
4.01. UV-vis (in toluene, λmax/nm, ꢀ/mol-1 dm3 cm-1): 417
(403 158), 439 (188 651), 521 (21 034), 536 (28 272), 578 (sh),
646 (3363), 704 (6810).
(m, 4 H), 4.02 (d, ) 12.2 Hz, 2 H), 4.11 (d, J ) 12.0 Hz, 2 H),
4.38-4.45 (m, 4 H), 7.31 (s, 1 H), 7.46-7.65 (m, 12 H), 7.92 (d,
J ) 7.8 Hz, 2 H), 8.02 (d, J ) 7.8 Hz, 2 H), 8.09-8.19 (m, 16 H),
8.45 (d, J ) 4.0 Hz, 2 H), 8.60 (d, J ) 4.0 Hz, 2 H), 8.84-8.86
(m, 8 H), 9.62 (s, 2 H) ppm. ES-MS: C106H85N9O4S2Zn , calcd av
mass 1678.3, obsd m/z 1679.1 (M+ + H, 35%). Anal. Calcd: C,
75.85; H, 5.10; N, 7.51; S, 3.82. Found: C, 75.81; H, 5.12; N,
7.55; S, 3.78. UV-vis (in toluene, λmax/nm, ꢀ/mol-1 dm3 cm-1):
422 (345 690), 440 (263 401), 521 (20 781), 546 (13 692), 582 (sh),
636 (2045), 704 (6731).
Triazole-Bridged ZnN4-N2S2 Porphyrin Dyad Zn9. A solu-
tion of 9 (3.1 mg, 0.18 mmol) and Zn(OAc)2 (10 mg, 9.29 mmol)
in dichloromethane/methanol (3:1, 20 mL) was stirred at room
temperature for 2 h. The crude compound was purified by silica
gel column chromatography, using dichloromethane as eluent, and
the desired porphyrin Zn9 was collected as a violet solid in 76%
Acknowledgment. We thank DST and BRNS for financial
support. S.P. and J.S. thank CSIR, New Delhi for a fellowship.
Supporting Information Available: Experimental procedures
and full spectroscopic data for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
yield (1.9 mg). H NMR (400 MHz, CDCl3, 25 °C): δ 1.28 (s, 3
H), 2.52 (t, J ) 12.0 Hz, 6.1 Hz, 2 H), 2.76 (s, 21 H), 3.77-3.85
JO702018S
326 J. Org. Chem., Vol. 73, No. 1, 2008