One-Pot Synthesis of Metallopyrazinoporphyrazines Using 2,3-Diaminomaleonitrile and 1,2-Dicarbonyl Compounds Accelerated by Microwave Irradiation
A one-pot microwave-assisted synthesis of metallopyrazinoporphyrazines as porphyrazine derivatives carrying six-membered pyrazine rings annulated at the periphery of the tetrapyrrolic macrocycle is described starting from 2,3-diaminomaleonitrile, 1,2-dicarbonyl compounds, metal salts, and urea.
Tetrapyrrolic macrocycles of porphyrins, phthalocyanines, and related compounds, modified by the attachment of peripheral substituents, have attracted significant attention for many years because of their industrial applications in diverse areas, especially in modern technologies [1–4], such as elaboration of Langmuir-Blodgett films [5–7], chemical sensors [8, 9], nonlinear optical materials [10–12] biomedical agents for diagnosis, and therapy  as well as sensitizers in solar cells [14–16].
Porphyrazines (Pzs), as an important class of phthalocyanine analogues or porphyrinoid macrocycles, carrying heterocyclic rings, such as diazepine, pyridine, and pyrazine rings, directly annulated to the pyrrole rings of the porphyrazine core, have been presented in recent years as optical agents with clear advantages over the porphyrins [17–25]. Porphyrins are either naturally occurring molecular systems or original synthetic products, whereas Pzs are derived exclusively from synthetic laboratory work. An area of further expansion of new Pzs macrocycles can be directed to the synthesis of new phthalocyanines-like macrocycles opening a route to new forms of investigation and promising potential practical applications .
Metal complexes of Pzs (MPzs) ligands have been at the focus of interest because of their high electronic delocalization, biological significance, and numerous potential technological applications such as electronic, magnetic, photophysical, and photosensitizing properties of Pzs [27–31]. It has been found that functional groups fused to the peripheral positions of MPzs are integrated to the macrocyclic core more effectively than that of phthalocyanines [32–34]. It implies that the modification of the structure influences the photosensitizing properties .
There are only a few reports for the synthesis of Pzs under mild and efficient conditions. On the other hand, attempts for direct synthesis of Pzs carrying unprotected vicinal NH2 groups from 2,3-diaminomaleodinitrile were unsuccessful [17–20]. Due to the importance of these macrocycles, introduction of new, efficient, and inexpensive protocol for this purpose is of prime importance.
Microwave-assisted organic reactions are well known as environmentally benign transformations that can improve a diverse area of chemical processes. In particular, the reaction time and energy input of these processes are assumed to be mostly reduced in comparison with reactions of a long duration at high temperatures under conventional heating conditions .
In continuation of our study to develop new procedures in various types of chemical transformations [37–41], herein, we wish to study the synthesis of MPPzs (5a–h) by a one-pot coupling reaction of 2,3-diaminomaleonitrile (1), various 1,2-dicarbonyl compounds (2), urea (3), and metal salts (4) under microwave irradiation conditions (Scheme 1).
2. Results and Discussion
In a typical experiment, the synthesis of MPPzs was carried out by mixing 2,3-diaminomaleonitrile 1 (1 mmol) with 1,2-dicarbonyl compounds 2 (1 mmol), urea 3 (4 mmol), and metal salts 4 (0.5 mmol) under microwave irradiation conditions. In this step, the reaction conditions were optimized with various molar ratios of raw materials. It was found that, the molar ratio of 1 : 1 : 4 : 0.5 from 1 : 2 : 3 : CuCl2·2H2O obtained the best results under microwave irradiation conditions. As the reaction proceeded after 5 min colorful solid gradually appeared at medium power level option of microwave oven. After completion of the reaction, the crude product was washed with water and filtered off and the solid residue purified further by washing with EtOH to give pure MPPz of 5a in 80% yield. It is important to note that in the absence of CuCl2·2H2O or urea the yield of reaction intensively decreased. In addition, excess amounts of them did not increase the yield of the reaction considerably.
To explore the scope and limitations of the reaction, the optimized protocol was applied to other substrates. The procedure was extended to various raw materials and different metal salts such as CoCl2, FeCl2·4H2O, and ZnCl2. As can be seen from Table 1, the different starting materials are converted to MPPzs in good yields after 5–10 min. In general, these results showed that the CuCl2·2H2O among metal salts and 1,2-bis(4-methoxyphenyl) ethane-1,2-dione within dicarbonyl compounds produce the best yields.
PPzs of metal salt are prepared efficiently from 1,2-bis(4-methoxyphenyl) ethane-1,2-dione. However, synthesis of these compounds from biacetyl was not so successful and yields of the reaction were lower than the other derivatives. As a result, the reaction gave excellent results in the cases of using aromatic 1,2-dione, independently of the metal salts.
In comparison with the previously reported multistep procedures [17, 18, 26, 42], this work has some advantages such as higher yields, atom economy, and mild reaction conditions. Furthermore, our protocol does not require any protection/deprotection of functional groups (Scheme 2) .
In summary, we have described an efficient microwave-assisted procedure for the synthesis of porphyrazine derivatives carrying six membered pyrazine rings annulated at the periphery of the tetrapyrrolic macrocycle starting from simple and readily available precursors including 2,3-diaminomaleonitrile, 1,2-dicarbonyl compounds, metal salts, and urea. This new multicomponent protocol for the preparation of synthetically, biologically, and technologically relevant MPPzs includes some important aspects like the fast and simple reaction, easy workup procedure, and high atom economy.
3.1. Materials and Equipment
All solvents, chemicals, and reagents were purchased from Merck, Fluka, and Sigma-Aldrich international chemical companies. Melting points were measured on an Electrothermal 9200 apparatus and are uncorrected. IR and UV-Vis spectra were recorded with a Shimadzu IR-470 spectrometer and UV-Vis Shimadzu 2100, respectively. The elemental analyses were performed with an Elementar Analysensysteme GmbH VarioEL. The microwave oven was a Samsung model GE-4020W (max. 900 W) with five power level options (option used for this experiment: medium 50% power).
3.2. General Procedure for the Preparation of MPPzs (5a–h)
2,3-Diaminomaleonitrile (1 mmol), 1,2-dicarbonyl compound (1 mmol), metal salt (0.5 mmol), and urea (4 mmol) were taken in a round bottomed flask. Then, the resulting mixture was irradiated in a domestic microwave oven at medium state for appropriate time. As the reaction proceeded, colorful solid gradually appeared. After completion of the reaction, the crude product was washed with water (4 × 10 mL) to give dark-green solid. Then, the precipitated solid was dried under vacuum and the solid residue was purified by washing three times in boiling EtOH (3 × 5 mL) until the filtrate was colorless. The solid was dissolved in DMF and filtered through a cartridge filter to remove any inorganic impurities that may have been present. Concentration of the filtrate afforded 5a–h as dark green to blue solids.
3.3. Characterization of the Products
5a: Dark blue solid; mp > 200°C. IR (KBr): υ, cm−1 1604 (m), 1500 (w), 1457 (m), 1415 (m), 1328 (w), 1282 (m), 1166 (s), 1085 (m), 1067 (m), 897 (m), 871 (m), 799 (s), 775 (m), 752 (w). UV-Vis (DMSO): , nm 638, 556, 445. Anal. Calcd for C32H24CuN16: C, 55.21; H, 3.47; N, 32.19. Found C, 55.34; H, 3.56; N, 32.10.
5b: Dark blue solid; mp > 200°C. IR (KBr): υ, cm−1 1602 (m), 1500 (w), 1457 (m), 1415 (s), 1328 (w), 1282 (m), 1166 (s), 1085 (m), 1067 (m), 897 (m), 871 (m), 799 (s), 775 (w), 752 (w). UV-Vis (DMSO): , nm 655, 564, 457. Anal. Calcd for C80H56CuN16O8: C, 67.05; H, 3.94; N, 15.64. Found C, 67.12; H, 4.08; N, 15.53.
5c: Dark greenish blue solid; mp > 200°C. IR (KBr): υ, cm−1 1604 (m), 1515 (w), 1485 (m), 1420 (s), 1326 (s), 1284 (m), 1153 (w), 1085 (s), 1024 (m), 948 (m), 910 (w), 871 (m), 778 (s), 756 (m). UV-Vis (DMSO): , nm 615, 597, 420. Anal. Calcd for C32H24CoN16: C, 55.58; H, 3.50; N, 32.41. Found C, 55.63; H, 3.46; N, 32.58.
5d: Dark green solid; mp > 200°C. IR (KBr): υ, cm−1 1604 (m), 1516 (w), 1484 (m), 1420 (s), 1326 (m), 1284 (s), 1153 (m), 1115 (s), 1085 (w), 1024 (m), 948 (w), 912 (m), 871 (w), 778 (s), 756 (m). UV-Vis (DMSO): , nm 625, 617, 426. Anal. Calcd for C80H56CoN16O8: C, 67.27; H, 3.95; N, 15.69. Found C, 67.36; H, 4.13; N, 15.52.
5e: Light olive gray solid; mp > 200°C. IR (KBr): υ, cm−1 1601 (m), 1478 (w), 1448 (m), 1404 (s), 1327 (m), 1278 (s), 1152 (m), 1112 (w), 1087 (w), 884 (m), 775 (s), 748 (m). UV-Vis (DMSO): , nm 654, 645, 569. Anal. Calcd for C32H24FeN16: C, 55.82; H, 3.51; N, 32.55. Found C, 55.93; H, 3.42; N, 32.67.
5f: Light olive gray solid; mp > 200°C. IR (KBr): υ, cm−1 1601 (m), 1478 (w), 1448 (m), 1404 (s), 1327 (s), 1278 (m), 1150 (w), 1088 (m), 884 (w), 775 (s), 749 (m). UV-Vis (DMSO): , nm 668, 662, 575. Anal. Calcd for C80H56FeN16O8: C, 67.42; H, 3.96; N, 15.72. Found C, 67.56; H, 4.15; N, 15.67.
5g: Light greenish blue solid; mp > 200°C. IR (KBr): υ, cm−1 1600 (m), 1462 (s), 1416 (s), 1325 (m), 1282 (w), 1158 (m), 1112 (m), 1065 (w), 948 (m), 864 (w), 775 (s), 752 (m). UV-Vis (DMSO): , nm 642, 563, 414. Anal. Calcd for C32H24N16Zn: C, 55.06; H, 3.47; N, 32.10. Found C, 54.98; H, 3.52; N, 32.27.
5h: Dark greenish blue solid; mp > 200°C. IR (KBr): υ, cm−1 1600 (m), 1462 (s), 1415 (m), 1325 (s), 1282 (m), 1158 (w), 1112 (m), 1065 (m), 948 (w), 864 (m), 775 (s), 752 (w). UV-Vis (DMSO): , nm 658, 602, 498, 388. Anal. Calcd for C80H56N16O8Zn: C, 66.97; H, 3.93; N, 15.62. Found C, 67.06; H, 4.10; N, 15.53.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors would like to thank partial support from the Research Council of the Iran University of Science and Technology.
“Phthalocyanines: properties and materials,” in The Porphyrin Handbook, K. M. Kadish, K. M. Smith, and R. Guilard, Eds., vol. 17, Academic Press, San Diego, Calif, USA, 2003.View at: Google Scholar
H. J. Berthold, J. Thiem, A. Zaliani, and T. Schotten, “Spiro-annelated Zn-phthalocyanine: a novel building block for molecular architecture?” Synthesis, vol. 20, pp. 3569–3575, 2010.View at: Google Scholar
R. M. Banavali and K. S. Ho, “Pyrazinoporphyrazines as markers for liquid hydrocarbons,” US Patent 7157611, 2007.View at: Google Scholar
K. S. Suslick, N. A. Rakow, M. E. Kosal, and J.-H. Chou, “The materials chemistry of porphyrins and metalloporphyrins,” Journal of Porphyrins and Phthalocyanines, vol. 4, pp. 407–413, 2000.View at: Google Scholar
Y. J. Li, Y. Fan, X. G. Ren et al., “Synthesis of a substituted phthalocyaninato-polysiloxane and its Langmuir-Blodgett films,” Journal of Porphyrins and Phthalocyanines, vol. 2, no. 6, pp. 527–530, 1998.View at: Google Scholar
C. C. Leznoff and A. B. P. Lever, Phthalocyanines: Properties and Applications, vol. 3, VCH, New York, NY, USA, 1993.
C. M. Drain, J. T. Hupp, K. S. Suslick, M. R. Wasielewski, and X. Chen, “A perspective on four new porphyrin-based functional materials and devices,” Journal of Porphyrins and Phthalocyanines, vol. 6, no. 4, pp. 243–258, 2002.View at: Google Scholar
S. Venugopal Rao and D. Narayana Rao, “Excited state dynamics in phthalocyanines studied using degenerate four wave mixing with incoherent light,” Journal of Porphyrins and Phthalocyanines, vol. 6, no. 3, pp. 233–237, 2002.View at: Google Scholar
S. V. Rao, N. K. M. N. Srinivas, D. N. Rao et al., “Studies of third-order optical nonlinearity and nonlinear absorption in tetra tolyl porphyrins using degenerate four wave mixing and Z-scan,” Optics Communications, vol. 182, no. 1–3, pp. 255–264, 2000.View at: Google Scholar
M. K. Nazeeruddin, R. Humphry-Baker, D. L. Officer, W. M. Campbell, A. K. Burrell, and M. Grätzel, “Application of metalloporphyrins in nanocrystalline dye-sensitized solar cells for conversion of sunlight into electricity,” Langmuir, vol. 20, no. 15, pp. 6514–6517, 2004.View at: Publisher Site | Google Scholar
M. K. Nazeeruddin, R. Humphry-Baker, M. Grätzel, and B. A. Murrer, “efficient near IR sensitization of nanocrystalline TIO2 films by ruthenium phthalocyanines,” Chemical Communications, vol. 6, pp. 719–720, 1998.View at: Google Scholar
P. A. Stuzhin and C. Ercolani, “Porphyrazines with annulated heterocycles,” in The Porphyrin Handbook, K. M. Kadish, K. M. Smith, and R. Guilard, Eds., vol. 15, p. 263, Academic Press, New York, NY, USA, 2003.View at: Google Scholar
S. L. J. Michel, S. Baum, A. G. M. Barrett, and B. M. Hoffman, “Peripherally functionalized porphyrazines: novel metallomacrocycles with broad, untapped potential,” Progress in Inorganic Chemistry, vol. 50, pp. 473–590, 2001.View at: Google Scholar
J. C. Maziere, R. Santus, P. Morliere et al., “Cellular uptake and photosensitizing properties of anticancer porphyrins in cell membranes and low and high density lipoproteins,” Journal of Photochemistry and Photobiology B, vol. 6, no. 1-2, pp. 61–68, 1990.View at: Google Scholar
J. Osterloh and M. G. H. Vicente, “Mechanisms of porphyrinoid localization in tumors,” Journal of Porphyrins and Phthalocyanines, vol. 6, no. 5, pp. 305–324, 2002.View at: Google Scholar
M. P. Donzello, C. Ercolani, and P. A. Stuzhin, “Novel families of phthalocyanine-like macrocycles-porphyrazines with annulated strongly electron-withdrawing 1,2,5-thia/selenodiazole rings,” Coordination Chemistry Reviews, vol. 250, no. 11-12, pp. 1530–1561, 2006.View at: Publisher Site | Google Scholar
C. S. Velazquez, W. E. Broderick, M. Sabat, A. G. M. Barrett, and B. M. Hoffman, “Metal-encapsulated porphyrazines: synthesis, x-ray crystal structure and spectroscopy of a tetratin-star-nickel(porphyrazine)S8 complex,” Journal of the American Chemical Society, vol. 112, pp. 7408–7410, 1990.View at: Publisher Site | Google Scholar
E. G. Sakellariou, A. G. Montalban, H. G. Meunier et al., “Synthesis and photophysical properties of peripherally metallated bis(dimethylamino)porphyrazines,” Journal of Photochemistry and Photobiology A, vol. 136, no. 3, pp. 185–187, 2000.View at: Google Scholar
J. Fitzgerald, W. Taylor, and H. Owen, “Facile synthesis of substituted fumaronitriles and maleonitriles: precursors to soluble tetraazaporphyrins,” Synthesis, no. 9, pp. 686–688, 1991.View at: Google Scholar
J. P. Fitzgerald, B. S. Haggerty, A. L. Rheingold, L. May, and G. A. Brewer, “Iron octaethyltetraazaporphyrins: synthesis, characterization, coordination chemistry, and comparisons to related iron porphyrins and phthalocyanines,” Inorganic Chemistry, vol. 31, no. 11, pp. 2006–2013, 1992.View at: Google Scholar
M. Polat and A. Gül, “Synthesis of new porphyrazines with tertiary or quaternized aminoethyl substituents,” Dyes and Pigments, vol. 45, no. 3, pp. 195–199, 2000.View at: Google Scholar
R. Z. U. Kobak, E. S. Öztürk, A. Koca, and A. Gül, “The synthesis and cyclotetramerisation reactions of aryloxy-,arylalkyloxy-substituted pyrazine-2,3-dicarbonitriles and spectroelectrochemical properties of octakis(hexyloxy)-pyrazinoporphyrazine,” Dyes and Pigments, vol. 86, pp. 115–122, 2010.View at: Publisher Site | Google Scholar
A. Loupy, Microwave in Organic Synthesis, Wiley-VCH, Weinheim, Gemany, 2002.
E. M. Bauer, C. Ercolani, P. Galli, I. A. Popkova, and P. A. Stuzhin, “Tetrakis(selenodiazole)porphyrazines—1: tetrakis(selenodiazole)porphyrazine and its Mg(II) and Cu(II) Derivatives. Evidence for their Conversion to Tetrakis(pyrazino)porphyrazines through Octaaminoporphyrazines,” Journal of Porphyrins and Phthalocyanines, vol. 3, no. 5, pp. 371–379, 1999.View at: Google Scholar