The structure of corrole can be derived from that of the corrin ring related to vitamin B12.1 It is a tetrapyrrolic macrocycle having one methine carbon less than a porphyrin ring through a direct pyrrole-pyrrole linkage. Corrole is also an 18π system and possesses aromaticity like that of most other porphyrinoids. The spectroscopic properties such as electronic absorption, redox chemistry, and photo chemical behavior are comparable to that of porphyrins. Despite the spectroscopic similarities of corroles with porphyrins, the synthesis of corroles is provenly difficult. The first synthesis of corroles was reported by Johnson and co-workers2 by a ring-closure method involving a metallo-dibromo-bi(dipyrryl methane) and formaldehyde in the presence of hydrochloric acid. The same group later reported the synthesis of heteroatom-containing corroles such as mesooxa3 and thiacorroles4 with the respective heteroatom-containing precursors. A [2 + 2] method for the synthesis of various corroles was developed by Broadhurst and co-workers.5 Another [2 + 2] condensation method was reported by Vogel and co-workers for the synthesis of tetraoxa
corroles.6 These methodologies mostly tailored for β-alkylsubstituted pyrroles lead to β-alkyl-substituted corroles. In 1993, the first report of corroles having meso substituents came from Paolesse and co-workers.7a The same group later reported a direct synthesis using a pyrrolic precursor by a self-condensation method. In this, the porphyrinogen thus obtained was made to react with a CoII salt and triphenyl phosphine to obtain the metalated corrole by a ring-contraction step.7b Only in 1999, three reports were published on the synthesis of metalfree meso phenyl corroles. Gross and co-workers8 reported the synthesis of corroles by a direct reaction between aryl aldehydes with pyrrole in acid-free conditions provided the aldehydes possess electron-withdrawing substituents. Paolesse and co-workers’9 method involves modified Rothemund conditions to get corroles in reasonable yields in excess pyrrole conditions. Even in the presence of excess pyrrole, the formation of TPP is observed along with N-confused porphyrin, sapphyrin, and of course corrole. At the same time, there was a report from this laboratory for the synthesis of triphenyl mono-oxa corrole as a byproduct from a [3 + 2] acid-catalyzed coupling of modified tripyrrane and a dipyrromethane.10 This corrole is distinct in the sense that it can form dianion just like porphyrins, thus facilitating the utility of the macrocycle as a ligand for divalent metal ions unlike all-aza corroles. Further, exploitation of such properties and the development of the chemistry of corroles require good synthetic methodology to enable their preparation in gram quantities. In continuation of our earlier communication,11 in the present paper we wish to report on three methods for the synthesis of mono-oxa corrole bearing one free meso carbon. The methodology is based on the simultaneous acid-catalyzed oxidative coupling and condensation to get the required corrole, i.e., the condensation and coupling occur in a one-pot, one-step reaction, and the addition of p-chloranil aromatizes the intermediate formed. It is shown that the methodology works for both normal and sterically hindered aldehydes under different conditions, unlike the previous methods described where electron-withdrawing substituents on the aldehydes are required. All reactions have been optimized for appropriate concentration of the reactants, the acid catalyst, and the solvent. Syntheses. Corrole synthesis generally consists of condensing aldehyde and pyrrole in the presence or absence of an acid, depending on the substituents on the
* To whom correspondence should be addressed. Present address: Director, Regional Research Laboratory, Trivandrum, Kerala 695 019. Phone: +91-471-2493599/2490324/2515220. Fax: +91-471-2491712. Email:
[email protected]. † Indian Institute of Technology Kanpur. ‡ National University of Singapore. (1) (a) Licoccia, S.; Paolesse, R. Struct. Bonding (Berlin) 1995, 84, 71-134. (b) Sessler, J. L.; Weghorn S. J. In Expanded, Contracted and Isomeric Porphyrins, Tetrahedron Organic Chemistry Series, Vol.15; Pergamom, New York, 1997; pp 11-125. (2) Johnson, A. W.; Kay, I. T. J. Chem. Soc. 1965, 1620-1629. (3) Johnson, A. W.; Kay, I. T. Proc. Chem. Soc. 1961, 168-169. (4) Johnson, A. W.; Kay, I. T.; Rodrigo, R. J. Chem. Soc. 1963, 23362342. (5) (a) Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc., Perkin Trans. 1 1972, 1124-1135. (b) Broadhurst, M. J.; Grigg, R.; Johnson, A. W. J. Chem. Soc., Chem. Commun. 1969, 23-24.
(6) (a) Behrens, F. Ph.D. Dissertation, University of Cologne, Germany, 1996. (b) Deorr, J. Ph.D. Dissertation, University of Cologne, Germany, 1996. (7) (a) Paolesse, R.; Licoccia, S.; Fanciullo, M.; Morganto, E.; Boschi, T. Inorg. Chim. Acta. 1993, 203, 107-114. (b) Paolesse, R.; Licoccia, S.; Bandoli, G.; Dolmella, A.; Boschi, T. Inorg. Chem. 1994, 33, 11711176. (8) (a) Gross, Z.; Galili, N.; Saltsman, I. Angew. Chem., Int. Ed. 1999, 38, 1427-1429. (b) Gross, Z.; Galili, N.; Simkhovich, L.; Saltsman, I.; Botoshansky, M.; Blaser, D.; Boese, R.; Goldberg, I. Org. Lett. 1999, 1, 599-602. (9) Paolesse, R.; Jaquinod, L.; Nurco, D. J.; Mini, S.; Sagoni, F.; Boschi, T.; Smith, K. M. Chem. Commun. 1999, 1307-1308. (10) Narayanan, S. J.; Sridevi, B.; Chandrashekar, T. K.; Englich, U.; Ruhlandt-Senge, K. Org. Lett. 1999, 1, 587-590. (11) Sankar, J.; Anand, V. G.; Venkatraman, S.; Rath, H.; Chandrashekar, T. K. Org. Lett. 2002, 4, 4233-4235.
Syntheses of Core-Modified Corroles by Three Different [3 + 1] Methodologies Jeyaraman Sankar,† Harapriya Rath,† Viswanathan PrabhuRaja,† Tavarekere K. Chandrashekar,*,† and Jagadese J. Vittal‡ Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India, and Department of Chemistry, National University of Singapore, 3 Science Drive, 117543 Singapore
[email protected] Received February 13, 2004
Abstract: Three new methods for syntheses of modified oxa corroles bearing one meso free carbon in reasonably good yields are reported. The formation of the meso carbon bridge and the direct pyrrole-pyrrole linkage occur in a single step by a simple condensation and coupling with TFA as a catalyst with appropriate precursors. The reactions are optimized with different conditions by varying the meso substituents, acid catalyst concentration, and the nature of the solvent to afford corroles in good yields.
10.1021/jo0497398 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/19/2004
J. Org. Chem. 2004, 69, 5135-5138
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SCHEME 1. Synthesis of Mono Meso Free Mono-Oxa Corrole from Pyrrole-2-carboxaldehyde
aldehyde,8 but it can also be prepared by the conventional Rothemund condensation reaction between pyrrole and benzaldehyde in acetic acid.12 In this method, the pyrrole is treated in excess to reduce the amount of formation of TPP. There are a few other methods also known in the literature: (a) condensing bipyrrole derivatives with dipyrromethane or (b) self-coupling of tetrapyrrane.13 The multistep synthesis of bipyrrole precursors and their stability under normal laboratory conditions decrease the yield of the expected corrole macrocycle. In the following sections, we discuss three different methodologies for the synthesis of core-modified corroles from easily available and air-stable precursors. The structure was verified with single-crystal X-ray diffraction of 4 (see Supporting Information). Method A. Previously the synthesis of mono-oxa corrole was made by the reaction of oxa tripyrrane with aryl dipyrromethane in the presence of TFA in dichloromethane followed by oxidation with p-chloranil.10 In this reaction, corrole is obtained as a byproduct, the main product being oxa smaragdyrin. In one of our earlier communications11 we have discussed the synthesis of mono-oxa corrole as the major product by arresting the formation of expanded corrole and other porphyrinoids by considering the reactivity of pyrrole-2-carboxaldehyde while keeping the other precursor, i.e., oxa tripyrrane, unaltered. This was also achieved under the catalysis of TFA (1 equiv) in dichloromethane solution followed by oxidation with p-chloranil (Scheme 1). The tripyrrane used, in fact, is stable to 1 equiv of TFA under normal laboratory conditions. By varying the meso substituents and the catalysts (both protic and Lewis acids) involved in this reaction, the yield of corrole was monitored. The versatility of the method was checked with various substitutions on the meso phenyl ring. The reaction works with even sterically bulkier groups such as mesityl group, and our observation shows the yield to be the least. The yield is comparatively more in the case of 4-tertiary butyl phenyl substitution. So, only the modified tripyrrane with this substituent is taken for further optimization trials. The next optimization lies with the variation of either the nature or the concentration of the acid catalyst. This causes a huge difference in the yield of the corrole formed. First it was tried by varying the TFA concentration from (12) Paolesse, R.; Nardis, S.; Sagone, F.; Khoury, R. G. J. Org. Chem. 2001, 66, 550-556. (13) Gryko, D. T. Eur. J. Org. Chem. 2002, 1735-1743 and references therein.
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0.1 equiv to 1 equiv. The acid concentration is not increased above 1 equiv as the tripyrrane may not be stable and may undergo cleavage leading to unfavorable byproducts. The yield of the corrole increases from 9% to 15% by correspondingly increasing the acid concentration from 0.1 to 1 equiv. When the acid catalyst was changed from TFA to other protic acids, there was an interesting trend in the yields that made productive investigation of other possibilities by which maximum yields could be achieved. From this category, the most often used acid catalysts in porphyrin synthesis, such as p-TsOH (p-toluene sulfonic acid), chlorosulfonic acid, and methanesulfonic acid, were tried, and indeed all of these acids give corrole in the abovediscussed reaction. The good yield in this category is obtained with 0.1 equiv of chlorosulfonic acid, but an increase in the acid concentration results in no corrole formation. This is in accord with the observation that higher acid concentrations do not favor the formation of corrole in this method, as discussed earlier. Methane sulfonic acid and p-TsOH work better with 0.1 and 0.5 equiv, respectively (see Supporting Information Table 1). It is evident from the above discussion that corrole formation increases with the increase in acid concentration, though this triggers the cleavage of the tripyrrane moiety in higher acid concentrations. This could be overcome by using an acid that will not cleave the tripyrrane in higher concentrations to maximize the yield of the corroles. For that reason, Lewis acids could be viable alternatives. So the well-known Lewis acids in porphyrin syntheses such as BF3‚Et2O, SnCl4, and FeCl3 have been tried. However, in these cases not even a negligble amount of formation of corrole was noted, suggesting that the methodology is not suited to Lewis acids. This has been verified by using different acid concentrations. The next variable investigated was the solvent used for the reaction. In all of the above cases dichloromethane was taken as the only solvent. When the reaction was performed with THF as the solvent, no condensation occurred, except self-coupling of tripyrrane resulting in the formation of dioxarubyrin, a member of the expanded porphyrin family. This was verified with the previously reported results.14 When the pyrrole carboxaldehyde was taken in molar ratios double to that of tripyrrane, not much change was noted in the yield of the corrole, but an increase in the reaction time from 90 to 180 min before the addition of p-chloranil resulted in 1% increase in the yield. Lengthening of the reaction time above 180 min resulted in the formation of rubyrins along with corrole in lesser amounts. Method B. The main objective of the work is to facilitate the modified corrole synthesis and thereby ensure corrole in quantitative amounts for further studies. To this end, the precursors used are expected to be readily available and easy to obtain. In porphyrin synthesis, the meso carbon is usually introduced between two pyrrolic groups by MacDonald condensation of aldehydes with the pyrrolic precursors.15 On this basis, when the same oxa tripyrrane was treated with pyrrole and (14) Narayanan, S. J. P.; Srinivasan, A.; Sridevi, B.; Chandrashekar, T. K.; Senge, M. O.; Sugiura, K.; Sakata, Y. Eur. J. Org. Chem. 2000, 2357-2360.
SCHEME 2. Syntheses of Mono Meso Free Mono-Oxa Corrole by Two Different Methods
paraformaldehyde in the presence of TFA instead of pyrrole-2-carboxaldehyde, to obtain a meso position with no substituents, the target corrole was formed in decent yields. It worked when paraformaldehyde was condensed with the tripyrrane and pyrrole in the presence of a slightly higher concentration of the acid (Scheme 2). The main problem in this method is the solubility of paraformaldehyde in dichloromethane. The tripyrrane is soluble in dichloromethane, and the reaction conditions are suited with that solvent only well. So the possibility was in doubt, but after obtaining the corrole in trace amounts with 0.1 equiv of TFA resulted in the investigation of this reaction under different acid concentrations. When the acid concentration was increased gradually from 0.1 to 1 equiv, the yield too increased correspondingly, suggesting that paraformaldehyde is getting activated only under moderate acid concentrations. When the aldehyde was taken in a warm methanol solution to favor its solubility, there was no quantitative change in the yield of the corrole. Therefore, the aldehyde was taken in its other form, i.e., formalin. This resulted in a quantitative increase in the yield. The yield of the corrole in this reaction with 0.5 equiv of TFA went up to 13%, confirming the fact that the success of the reaction lies with the miscibility of the aldehyde with the solution, thereby facilitating the activation by the acid added. When the acid concentration was increased further to 1 equiv, the yield was nearly 15%. This method allows greater freedom to functionalize any of the precursors and to obtain the functionalized corrole in reasonably good yields. In any case, the time taken for the reaction was not allowed to exceed 180 min, thus minimizing the decomposition of the modified tripyrrane. Method C. Even though Paolesse and co-workers7b reported the synthesis of meso aryl-substituted corroles (15) Smith. K. M. In The Porphyrin Handbook 1; Kadish, K., Smith K. M., Guilard, R., Eds.; Academic Press: Boston, 1999; pp 13-14. (16) Sridevi, B.; Narayanan, S. J.; Srinivasan, A.; Reddy, M. V.; Chandrashekar, T. K. J. Porphyrins Phthalocyanines 1998, 63, 90769088.
by the self-condensation of 2-(hydroxy phenyl methyl)pyrrole(8) followed by oxidation with CoII and triphenyl phosphine, they could not go beyond metalated derivatives. However, in the present case of mono-oxa corrole, the same precursor without the phenyl substituent should be capable of condensing and coupling simultaneously. Therefore 8 was condensed with the modified tripyrrane to get the mono-oxa corrole under the same conditions as described for Methods A and B. This too resulted in the formation of corrole in good yields (∼10%) (Scheme 2). When Lewis acids were used as catalysts, the yields were far from encouraging. With 2 equiv of BF3‚Et2O, only trace amounts of corrole were obtained, but with 1 equiv of TFA itself the yield was 9%. This reaction was also studied with other variables but was successful with only 0.5 equivalents of TFA. In all of the above methods, the corrole was obtained in significant yields, making these methods versatile for the synthesis of core-modified corroles. These methods, in common, depend on the dilution of the reactants taken in the reaction medium. For 1 mmol of the reactants, nearly 200 mL of the solvent is needed. The advantage of Method B with respect to Method A lies in the fact that we were able to get the desired corrole by taking precursors available on the shelf (e.g., pyrrole and formalin) instead of making pyrrole-2-carboxaldehyde. In Method C, we simply wanted to show that the method works for 2-(hydroxy phenyl methyl)-pyrrole also. Synthesis of core-modified mono meso free mono-oxa corrole has been achieved by three different [3 + 1] acidcatalyzed condensation and coupling methodologies. All three methodologies reported here are optimized well to get the corrole in reasonably good yields. The structural evidence for the macrocycle (4) comes from the solid-state structural characterization (see Supporting Information). Experimental Section Data for 7: FAB MS m/z (%) 563 (100%) [M+]; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 9.6 (s, 1H), 9.1 (d, J ) 5.2 Hz, 1H), 9.0 (br, 1H), 8.99 (s, 2H), 8.9 (d, J ) 4 Hz, 1H), 8.8 (d, J ) 5.2 Hz, 1H), 8.5 (br, 1H), 8.3 (d, J ) 4.8 Hz, 1H), 8.1 (d, J ) 8.4 Hz, 2H), 8.0 (d, J ) 8.4 Hz, 2H), 7.75 (d, J ) 8 Hz, 2H), 7.7 (d, J ) 8 Hz, 2H), 1.53 (s, 9H), 1.5 (s, 9H), -2.5 (s, 1H); UV-vis (CH2Cl2) λmax ( × 10-4 M-1 cm-1) 403 (9.20), 495 (0.51), 525 (0.94), 575 (0.32), 622 (0.65); (CH2Cl2/TFA) λmax ( × 10-4 M-1 cm-1) 400 (6.7), 419 (5.2), 528 (0.4), 566 (0.5), 614 (0.91). Anal. Calcd for C39H37N3O: C 83.09, H 6.62, N 7.45. Found: C 83.65, H 6.56, N 7.22. Data for 3: FAB MS m/z (%) 535 (100%) [M+]; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 9.6 (s, 1H), 9.0 (m, 3H), 8.9 (d, J ) 4 Hz,1H), 8.6 (d, J ) 4.8 Hz, 1H), 8.5 (d, J ) 4.8 Hz, 1H), 8.3 (br, 1H), 8.2 (d, J ) 4.8 Hz, 1H), 7.2 (s, 2H), 7.1 (s, 2H), 2.53 (s, 3H), 2.52 (s, 3H), 1.8 (s, 6H), 1.7 (s, 6H), -2.3 (s, 1H); UV-vis (CH2Cl2) λmax ( × 10-4 M-1 cm-1) 405 (8.0), 494 (0.3), 522 (0.6), 571 (0.2), 619 (0.6); (CH2Cl2/TFA) λmax ( × 10-4 M-1 cm-1) 396 (5.0), 415 (5.0), 451 (0.2), 565 (0.4), 607 (0.9). Anal. Calcd for C37H33N3O: C 82.96, H 6.21, N 7.84. Found: C 83.1, H 6.07, N 7.52. Data for 4: EI mass m/z (%) 480 (95%) [M+]; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 9.6 (s, 1H), 9.1 (d, J ) 5.6 Hz, 1H), 9.05 (br, 1H), 9.0 (s, 2H), 8.9 (d, J ) 4.4 Hz, 1H), 8.7 (d, J ) 4.8, 1H), 8.5 (br, 1H), 8.4 (d, J ) 4.0 Hz, 1H), 8.1 (d, J ) 8.0 Hz, 2H), 7.9 (d, J ) 7.2 Hz, 2H), 7.5, (d, J ) 8.0 Hz, 2H), 7.4 (d, J ) 7.2 Hz, 2H), 2.6 (s, 3H), 2.5 (s, 3H), -2.5 (s, 1H); UV-vis (CH2Cl2) λmax ( × 10-4 M-1 cm-1) 404 (9.0), 495 (0.5), 524 (0.9), 574 (0.3), 622 (0.6); (CH2Cl2/TFA) λmax ( × 10-4 M-1 cm-1) 399 (6.0),
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418 (5.0), 528 (0.4), 565 (0.5), 613 (0.9). Anal. Calcd for C33H25N3O: C 82.66, H 5.25, N 8.76. Found: C 82.71, H 5.12, N 8.57. Data for 5: FAB MS m/z (%) 511 (100%) [M+]; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 9.6 (s, 1H), 9.1 (d, J ) 5.6 Hz, 1H), 9.0 (m, 1H), 8.98 (s, 2H), 8.9 (d, J ) 4.4 Hz, 1H), 8.8 (d, J ) 5.6 Hz, 1H), 8.5 (m, 1H), 8.4 (d, J ) 4.4 Hz, 1H), 8.1 (d, J ) 8.4 Hz, 2H), 8.0 (d, J ) 8.4 Hz, 2H), 7.2 (d, J ) 8.4 Hz, 2H), 7.1 (d, J ) 7.2 Hz, 2H), 4.0 (s, 3H), 3.9 (s, 3H), -2.4 (s, 1H); UV-vis (CH2Cl2) λmax ( × 10-4 M-1cm-1) 404 (19), 496 (1.0), 525 (2.0), 576 (0.5), 623 (1.0); (CH2Cl2/TFA) λmax ( × 10-4 M-1cm-1) 408 (9.0), 419 (10.3), 528 (9.0), 567 (0.9), 617 (2.0). Anal. Calcd for C33H25N3O3: C 77.48, H 4.93, N 8.21. Found: C 78.20, H 4.71, N 8.13. Data for 6: FAB MS m/z (%) 451 (100%) [M+]; 1H NMR (400 MHz, CDCl3, 25 °C, TMS) δ 9.6 (s, 1H), 9.1 (d, J ) 5.12 Hz, 1H), 9.0 (m, 1H), 8.99 (s, 2H), 8.9 (d, J ) 4.4 Hz, 1H), 8.7 (d, J ) 5.16 Hz, 1H), 8.5 (m, 1H), 8.3 (d, J ) 4.4 Hz, 1H), 8.2 (d, J ) 7.32 Hz, 2H), 8.0 (m, 2H), 7.6 (m, 6H), -2.5 (s, 1H); UV-vis (CH2-
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Cl2) λmax ( × 10-4 M-1 cm-1) 408 (9.4), 495 (0.7), 525 (1.0), 576 (0.4), 623 (0.7); (CH2Cl2/TFA) λmax ( × 10-4 M-1 cm-1) 406 (4.7), 419 (5.0), 528 (0.4), 567 (0.5), 617 (1.0). Anal. Calcd for C31H21N3O: C 82.46, H 4.69, N 9.31. Found: C 82.62, H 4.65, N 9.15.
Acknowledgment. This work was supported by grants from the Department of Science and Technology (DST) and Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi. J.S, H.R., and V.P.R thank CSIR for their fellowship. Supporting Information Available: Characterization data including FAB MS, UV-vis data, 1H NMR data, X-ray crystal data in CIF format, and general experimental procedures of selected compounds. This material is available free of charge via the Internet at http://pubs.acs.org. JO0497398
