Porphyrins in 1,3-Dipolar Cycloaddition Reactions

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Porphyrins in 1,3-Dipolar Cycloaddition Reactions: Synthesis of a Novel Pyrazoline-fused Chlorin and a Pyrazole-fused Porphyrin Porphyrinsin1,3-DipolarCycload itonReactioM. Ana ns G. Silva, Augusto C. Tomé, Maria G. P. M. S. Neves, José A. S. Cavaleiro*

Abstract: b-Nitro-meso-tetraphenylporphyrin reacts with diazomethane to give a pyrazoline-fused chlorin as the main product. This compound was converted into the corresponding pyrazolefused porphyrin, by treatment with DBU, and into a methanochlorin by refluxing in toluene. Key words: cycloadditions, diazo compounds, porphyrins, chlorins, pyrazolines

The synthesis and study of the properties of porphyrin macrocycles with extended p systems is a subject of increasing importance. Both carbo- and heterocyclic [b]fused porphyrins are being prepared and their use in medicine and in the production of new electronic materials is being evaluated.1–3 In recent years, we have developed new methods for the synthesis of novel porphyrinic derivatives by chemical modification of the macrocycle at the b-pyrrolic positions. Those methods involve Diels– Alder reactions,4–6 1,3-dipolar cycloadditions (with azomethine ylides7 and nitrones8) and 1,5-electrocyclizations.9 In this publication we report an extension of the 1,3-dipolar cycloaddition approach to the synthesis of the novel pyrazoline-fused chlorin 2 by the reaction of b-nitromeso-tetraphenylporphyrin 110 with diazomethane. This chlorin could be further converted into the pyrazole-fused porphyrin 3, by treatment with DBU, or into the methanochlorin 4, by refluxing in toluene. This compound 4 is a new chlorin derivative although other methanochlorins have previously been obtained by addition of carbenes to the zinc complex of meso-tetraphenylporphyrin11 or by the reaction of stabilized carbanions, derived from ‘active methylene’ compounds, with the zinc complex of b-nitromeso-tetraphenylporphyrin.12,13 The addition of diazomethane to b-nitro-meso-tetraphenylporphyrin 1 was performed at room temperature and afforded the pyrazoline-fused chlorin 2 (41% yield) as the main product.14 Two minor products were also obtained and were identified as the pyrazole-fused porphyrin 3 (lower Rf, 7% yield) and the methanochlorin 4 (higher Rf, 3% yield). Since only one pyrazoline was obtained, this reaction is site and regiospecific. All the spectroscopic data of the main product support the structure 2:15 the Synlett 2002, No. 7, 01 07 2002. Article Identifier: 1437-2096,E;2002,0,07,1155,1157,ftx,en;D09802ST.pdf. © Georg Thieme Verlag Stuttgart · New York ISSN 0936-5214

mass spectrum confirms that it is a monoadduct [parent peak at m/z 702 [M + H]+ and two fragment peaks at m/z 674 and 655 corresponding to the loss of N2 or HNO2, respectively] and the UV/Vis absorption spectrum indicates that it is a chlorin (lmax = 639 nm). In the aliphatic region the 1H NMR spectrum displays three double doublets at d = 4.75, 5.08 and 5.45 ppm corresponding to the resonances of H-23trans, H-23cis and H-3, respectively. The coupling constants JH23trans-H23cis = 19.0 Hz, JH23trans-H3 = 4.7 Hz and JH23cis-H3 = 9.2 Hz confirm the configuration shown in structure 2. Treatment of pyrazoline-fused chlorin 2 with DBU (15 min at r.t.) afforded pyrazole-fused porphyrin 3 (72%) via elimination of nitrous acid. The UV/Vis (lmax = 585 nm), mass (m/z 655 [M + H]+ and 654 [M+]) and 1H NMR spectra of compound 3 are compatible with an aromatic structure. In contrast with chlorin 2, the 1H NMR spectrum of porphyrin 3 does not show any signal in the aliphatic region of the spectrum. The H-23 proton of the pyrazole ring appears as a singlet at d = 7.04 ppm.16 Thermal extrusion of nitrogen from pyrazoline-fused chlorin 2 (one day in refluxing toluene) yielded the methanochlorin 4 (24% yield).17 In this reaction, together with unchanged starting pyrazoline 2 (27%), a significant amount of b-nitro-meso-tetraphenylporphyrin 1 (48%) was also obtained. The formation of this compound can be explained as a result of a retrocycloaddition process. The mass spectrum of compound 4 shows the parent ion peaks at m/z 674 [M + H]+ and 673 [M+] which confirms the loss of nitrogen. Its UV/Vis absorption spectrum indicates that it is a chlorin (lmax = 646 nm). Its 1H NMR spectrum shows, in the aliphatic region, three double doublets at d = 1.95, 3.36 and 4.59 ppm corresponding to the resonances of H-21trans, H-21cis and H-3, respectively. The coupling constants JH21trans-H21cis = 5.2 Hz, JH21trans-H3 = 5.4 Hz and JH21cis-H3 = 10.0 Hz support the configuration shown in structure 4 (Scheme). It is worthy of mention that both nitrochlorins 2 and 4 are stable at room temperature and can be stored during several months without decomposition. In conclusion, the 1,3-dipolar cycloaddition reaction of bnitro-meso-tetraphenylporphyrin with diazomethane is site and regiospecific, yielding, as the main product, the pyrazoline-fused chlorin 2 in a reasonable yield.

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Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal Fax +351(234)370084; E-mail: [email protected] Received 3 May 2002

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A. M. G. Silva et al. Ph

NH

NO2

N Ph

Ph N

HN

1

Ph

N N CH2 Et2O, rt, 30 d H

H

N

Ph

NH

Ph + N

N

NH Ph + Ph

N

2

21 2

N

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Ph

Ph 23

Hcis

3

Htrans Hcis

O2N

N N

Ph

23 2

NH

Htrans

- HNO2

Ph

HN

Ph

3

H Ph

N

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3

4

- N2

Scheme

Acknowledgement Thanks are due to the Fundação para a Ciência e a Tecnologia (FCT, Portugal) for funding the Organic Chemistry Research Unit and Project POCTI/1999/QUI/32851. One of us (A. M. G. Silva) also thanks FCT for a PhD grant.

References (1) Lash, T. D. J. Porphyrins Phthalocyanines 2001, 5, 267. (2) Kobayashi, N.; Konami, H. J. Porphyrins Phthalocyanines 2001, 5, 233. (3) Lash, T. D. In The Porphyrin Handbook, Vol. 2; Kadish, K. M.; Smith, K. M.; Guilard, R., Eds.; Academic Press: San Diego, 2000, Chap. 10, 125. (4) Tomé, A. C.; Lacerda, P. S. S.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. Chem. Commun. 1997, 1199. (5) Silva, A. M. G.; Tomé, A. C.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. Tetrahedron Lett. 2000, 41, 3065. (6) Alonso, C. M. A.; Neves, M. G. P. M. S.; Tomé, A. C.; Silva, A. M. S.; Cavaleiro, J. A. S. Tetrahedron Lett. 2001, 42, 8307. (7) Silva, A. M. G.; Tomé, A. C.; Neves, M. G. P. M. S.; Silva, A. M. S.; Cavaleiro, J. A. S. Chem. Commun. 1999, 1767. (8) Silva, A. M. G.; Tomé, A. C.; Neves, M. G. P. M. S.; Silva, A. M. S.; Cavaleiro, J. A. S.; Perrone, D.; Dondoni, A. Tetrahedron Lett. 2002, 43, 603. (9) Silva, A. M. G.; Faustino, M. A. F.; Tomé, A. C.; Neves, M. G. P. M. S.; Silva, A. M. S.; Cavaleiro, J. A. S. J. Chem. Soc., Perkin Trans. 1 2001, 2752. (10) b-Nitro-meso-tetraphenylporphyrin was obtained in 86% yield by nitration of TPP with Cu(NO3)2 in acetic anhydride, followed by acid treatment, according to the procedure described by: Giraudeau, A.; Callot, H. J.; Jordan, J.; Ezhar, I.; Gross, M. J. Am. Chem. Soc. 1979, 101, 3857. (11) Callot, H. J. Tetrahedron Lett. 1972, 1011.

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(12) Jaquinod, L.; Gros, C.; Olmstead, M. M.; Antolovich, M.; Smith, K. M. Chem. Commun. 1996, 1475. (13) Jaquinod, L.; Gros, C.; Khoury, R. G.; Smith, K. M. Chem. Commun. 1996, 2581. (14) Reaction of b-nitro-meso-tetraphenylporphyrin with diazomethane: a solution of 1 (50.6 mg, 0.08 mmol) in diethyl ether (200 mL) was saturated twice with diazomethane and allowed to stand at r.t. during 15 d. The reaction was monitored by TLC and UV/Vis spectra. Since after this period a significant quantity of porphyrin 1 remained, the reaction mixture was saturated again with diazomethane and left at r.t. for another period of 15 d. The solvent was then evaporated to dryness and the residue was purified by column chromatography in silica gel using a mixture of petroleum ether–dichloromethane (1:1) as eluent. The first fraction corresponded to a small amount of the methanochlorin 4 (1.7 mg, 3%) and the second one to the unchanged starting porphyrin 1 (23.0 mg, 45%). The third fraction was the pyrazoline-fused chlorin 2 (22.2 mg, 41%), which was followed by a small amount of the pyrazole-fused porphyrin 3 (3.3 mg, 7%). (15) Spectroscopic data for chlorin 2: 1H NMR (300 MHz, CDCl3, J in Hz): d = –2.15 and –2.12 (2 s, 2 H, NH); 4.75 (dd, 1 H, J = 19.0 and J = 4.7, H-23trans); 5.08 (dd, 1 H, J = 19.0 and J = 9.2, H-23cis); 5.45 (dd, 1 H, J = 9.2 and J = 4.7, H-3); 7.56–7.62, 7.70–7.78, 7.87–7.90 and 7.99–8.24 (4 m, 20 H, H-Ph); 8.29 and 8.38 (2 dd, 2 H, J = 4.9 and J = 1.8, H-b); 8.51 and 8.54 (2 d, 2 H, J = 4.9, H-12,13); 8.67 and 8.72 (2 dd, 2 H, J = 4.9 and J = 1.8, H-b). MS (LSIMS): 702 [M + H]+, 674 [(M – N2) + H]+, 655 [(M – HNO2) + H]+, 627 {[(M – HNO2) – N2] + H}+. UV/Vis (CH2Cl2): lmax/nm (log e): 639 (4.47), 588 (3.98), 546 (4.29), 516 (4.24), 410 (5.39). Anal. Calcd for C45H31N7O2.H2O: C, 75.09; H, 4.62; N, 13.62. Found: C, 74.86; H, 4.19; N, 14.10. (16) Spectroscopic data for porphyrin 3: 1H NMR (300 MHz, CDCl3, J in Hz): d = –2.86 (s, 2 H, NH); 7.04 (s, 1 H, H-23); 7.73–7.91 (m, 12 H, Hmeta+para-Ph); 8.17–8.22 (m, 8 H, Hortho-Ph); 8.75 (s, 2 H, H-12,13); 8.84–8.96 (m, 4 H, H-b).

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Porphyrins in 1,3-Dipolar Cycloaddition Reactions

7.78 (m, 12 H, Hmeta+para-Ph); 7.98–8.23 (m, 8 H, Hortho-Ph); 8.46 (dd, 1 H, J = 4.9 and J = 1.5, H-b), 8.52 (s, 2 H, H12,13); 8.56 (dd, 1 H, J = 4.9 and J = 1.5, H-b), 8.70–8.73 (m, 2 H, H-b); UV/Vis (CH2Cl2): lmax/nm (rel. int.): 646 (12%), 592 (7%), 548 (10%), 519 (11%), 415 (100%). MS (LSIMS): 674 [M + H]+, 673 [M+]. MS-HRFAB exact mass m/z for C45H31N5O2 [M + H]+: calcd 674.2556, found 674.2542.

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UV/Vis (CH2Cl2): lmax/nm (log e): 639 (3.18), 585 (3.90), 546 (3.88), 513 (4.34), 417 (5.67). MS (LSIMS): 655 [M + H]+, 654 [M+]. MS-HRFAB exact mass m/z for C45H30N6 [M + H]+: calcd 655.2610, found 655.2628. (17) Spectroscopic data for methanochlorin 4: 1H NMR (300 MHz, CDCl3, J in Hz): d = –2.08 (s, 2 H, NH), 1.95 (dd, 1 H, J = 5.4 and J = 5.2, H-21trans); 3.36 (dd, 1 H, J = 10.0 and J = 5.2, H-21cis); 4.59 (dd, 1 H, J = 10.0 and J = 5.4, H-3); 7.61–

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© Thieme Stuttgart · New York