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Molbank 2006, M521 |
The First Example of Oxidative
Nucleophilic Substitution of Hydrogen
in meso-Aryl Ring of the 5,10,15,20-Tetraphenylporphyrin Derivatives
Agnieszka Mikus, Edyta Kisielińska, and
Stanisław Ostrowski*
Institute
of Chemistry, University of Podlasie, ul. 3 Maja 54, 08-110
E-mail: [email protected]
* Author
to whom correspondence should be addressed
Received:
Keywords: Porphyrins, Carbanions, Oxidative Nucleophilic
Substitution of Hydrogen, Zinc
Abstract:
A synthesis
of [2-nitro-5-(10,15,20-triphenylporphyrin-5-yl)-phenyl]phenyl-acetonitrile
zinc complex by the reaction of the respective nitroporphyrin with the anion of
benzyl cyanide, followed by addition of DDQ, is described. This is the first
example of this type of process in the nitrophenyl side ring of meso-tetraarylporphyrin derivatives.
The
synthesis of unsymmetrical, double functionalized in meso-aryl ring, porphyrins is of significant importance due to
their potential application as sensitizers in photodynamic cancer therapy
(PDT).1
Amongst
other methods, a very attractive one seems to be oxidative nucleophilic
substitution of hydrogen (ONSH2) in nitrophenyl moiety of the
respective starting porphyrin. Herein, we present the first example of this
type of functionalization in the reaction of
5-(4-nitrophenyl)-10,15,20-triphenylporphyrin zinc complex3 with
phenylacetonitrile carbanion (in DMF, at room temperature) followed by addition
of DDQ. This leads to the substitution of hydrogen product, in the position ortho- to the NO2 group, in
35% yield.
Scheme 1
To a
stirred solution of t-BuOK (71 mg,
0.63 mmol) in anhydrous DMF (5 mL, under argon), a solution of
5-(4-nitrophenyl)-10,15,20-triphenylporphyrin zinc(II)3 (1; 50 mg, 0.069 mmol) and benzyl
cyanide (19 mg, 0.16 mmol) in DMF (3 mL) was added dropwise via syringe at room temperature during ca 2 min. After an additional 2 min of
stirring, DDQ (23 mg, 0.10 mmol) was added in a one portion and the mixture was
stirred for 3 min. Then, the mixture was poured into 3% HCl containing ice (80
mL). The precipitate was filtered, washed with water (3 × 15 mL), and then
dissolved in CHCl3 (40 mL). After drying with anhydrous MgSO4
and evaporation of the solvent, the residue was chromatographed (silica gel
230-400 mesh; eluent: CHCl3 / n-hexane,
2: 1) to give: starting porphyrin 1
– 15.4 mg (31%), and product 3 –
13.9 mg (24%; 35% for recovered substrate).
Melting point: > 300 °C
IR (CH2Cl2,
cm-1): 2246 (CN), 1598, 1583, 1525 (asym. NO2), 1487,
1441, 1340 (sym. NO2).
1H NMR (CDCl3, 200 MHz):
9.04 (d, J = 4.8 Hz, 1 H, Hβ-pyrrole),
8.99-8.94 (m, 5 H, Hβ-pyrrole), 8.89 (d, J = 4.8 Hz, 1 H, Hβ-pyrrole), 8.69 (d, J = 4.8 Hz, 1 H, Hβ-pyrrole),
8.65 (d, J = 1.6 Hz, 1 H, H-2 of
H-Ar(NO2)), 8.49 (part of AB system, J = 8.3 Hz, 1 H, H-5 of H-Ar(NO2)), 8.40 (part of AB system
coupled with another proton, J = 8.3
Hz, 1.6 Hz, 1 H, H-6 of H-Ar(NO2)), 8.28-8.16 (m, 6 H, H-Ph),
7.86-7.68 (m, 9 H, H-Ph), 7.58-7.31 (m, 5 H, CH(CN)Ph), 6.54 (s, 1 H, CH(CN)).
UV-VIS
(CHCl3): λmax (log ε
): 589.5 (3.79), 548.0 (4.47), 510.5 (3.70), 418.5 (5.55, Soret band), 348.0
nm (4.20).
MS (EI), m/z (% rel. int.): 836 (1.0, M+ ˙), 810 (0.9, M-CN), 733 (0.5), 678 (2), 677 (4), 676 (3), 675 (4), 674 (1.1), 77 (41), 44 (100, CO2+).
MS (ESI), m/z (% rel. int.): 842 (11), 841 (16),
840 (46), 839 (50), 838 (80), 837 (57), 836 (100) [isotopic M+]. The molecular formula
was confirmed by comparing the theoretical and experimental isotope patterns
for the M+ ion (C52H32N6O2Zn)
– found to be identical within the experimental error limits.
References
1. (a) Hsi, R. A.; Rosenthal, D. I.; Glatstein, E. Drugs 1999, 57, 725-734. (b) Nyman, E. S.; Hynninen, P. H. J. Photochem. Photobiol. B 2004, 73, 1-28.
2. (a) Mąkosza, M.; Staliński, K. Tetrahedron 1998, 54, 8797-8810. (b) Mąkosza, M.; Staliński, K. Polish J. Chem. 1999, 73, 151-161.
3. Ostrowski, S.; Mikus, A.; Shim, Y. K.; Lee, J.-Ch.; Seo, E.-Y.; Lee, K.-I.; Olejnik, M. Heterocycles 2002, 57, 1615-1626.
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