Reaction of β-Vinyl-meso-tetraphenylporphyrin with o-Quinone Methides

Abstract

The hetero-Diels-Alder reaction of β-vinyl-meso-­tetraphenylporphyrinatozinc(II) with quinone methides generated in situ from Knoevenagel reaction of 2-hydroxy-1,4-naphthoqui­none, 4-hydroxycoumarin, and 4-hydroxy-6-methylcoumarin with paraformaldehyde and directly from o-hydroxybenzyl alcohol derivatives is reported.

Key words

porphyrin - o-quinone methide - naphthoquinone - coumarin - o-hydroxybenzyl alcohol - hetero-Diels-Alder

References and Notes

• 1 Handbook of Porphyrin Science   Vol. 4 and 12:  Kadish K. Smith KM. Guilard R. World Scientific Publishing Company; Singapore: 2010. 
• 2a Tomé AC. Neves MGPMS. Cavaleiro JAS. J. Porphyrins Phthalocyanines  2009,  13:  408 
• 2b Cavaleiro JAS. Tomé AC. Neves MGPMS. In Handbook of Porphyrin Science   Vol. 2:  Kadish K. Smith KM. Guilard R. World Scientific Publishing Company; Singapore: 2010.  p.193 
• 3a Ferreira VF. Ferreira SB. da Silva FC. Org. Biomol. Chem.  2010,  8:  4793 ; and references cited therein
• 3b Salas CO. Faúndez M. Morello A. Maya JD. Tapia RA. Curr. Med. Chem.  2011,  18:  144 
• 4a Kady MM. Brimer L. Furu P. Lemmich S. Nieslen HM. Thiilborg ST. Thastrup O. Christenesen SB. Planta Med.  1992,  58:  334 
• 4b Mahmoud AA. Ahmed AA. Linuma M. Tanaka T. Phytochemistry  1998,  47:  543 
• 5a Florence X. Sebille S. de Tullio P. Lebrun P. Pirotte B. Bioorg. Med. Chem.  2009,  17:  7723 
• 5b Rapposelli S. Breschi MC. Calderone V. Digiacomo M. Martelli A. Testai L. Vanni M. Balsamo A. Eur. J. Med. Chem.  2011,  46:  966 
• 6a Rokita SE. Quinone Methides   Wiley; Hoboken: 2009. 
• 6b Tietze LF. Rackelman N. In Multicomponent Reactions   Zhu J. Bienaymé H. Wiley-VCH; Weinheim: 2005.  p.121 
• 6c da Silva FC. Ferreira SB. Kaiser CR. Pinto AC. Ferreira VF. J. Braz. Chem. Soc.  2009,  20:  1478 
• 6d Ferreira SB. da Silva FC. Bezerra FAFM. Lourenco MCS. Kaiser CR. Pinto AC. Ferreira VF. Arch. Pharm. Chem. Life Sci.  2010,  343:  81 
• 6e Appendino G. Cravotto G. Toma L. Annunziata R. Palmisano G. J. Org. Chem.  1994,  59:  5556 
• 6f Khoshkholgh MJ. Lotfi M. Balalaie S. Rominger F. Tetrahedron  2009,  65:  4228 
• 6g Yadav JS. Reddy BVS. Narsimhaswamy D. Lakshmi PN. Narsimulu K. Srinivasulu G. Kunwar AC. Tetrahedron Lett.  2004,  45:  3493 
• 7 Tomé AC. Lacerda PSS. Neves MGPMS. Cavaleiro JAS. Chem. Commun.  1997,  1199 
• 8a Faustino MAF. Neves MGPMS. Tomé AC. Silva AMS. Cavaleiro JAS. ARKIVOC  2005,  (ix):  332 
• 8b Oliveira KT. Silva AMS. Tomé AC. Neves MGPMS. Neri CR. Garcia VS. Serra OA. Iamamoto Y. Cavaleiro JAS. Tetrahedron  2008,  64:  8709 
• 9 Callot HJ. Tetrahedron  1973,  29:  899 
• 11 Wang H. Wang Y. Han KL. Peng XJ. J. Org. Chem.  2005,  70:  4910 
• 14 Van de Waters RW. Pettus TRR. Tetrahedron  2002,  58:  5367 ; and references cited therein
• 18 Dorrestijn E. Kranenburg M. Ciriano MV. Mulder P. J. Org. Chem.  1999,  64:  3012 

10

General Procedure for Preparing Compounds 8, 9, and 10a,b
In a round-bottom flask, equipped with a magnetic stirring bar, a solution of 2-hydroxy-1,4-naphthoquinone (1, 6.2 mg, 35.5 µmol) [or 4-hydroxycoumarins (2a, 5.7 mg; 2b, 6.2 mg; 35.5 µmol)], 1,4-dioxane (5 mL), paraformaldehyde (8.5 mg, 284 µmol), and porphyrin 4 (25 mg, 35.5 µmol) was heated at reflux until consumption of the starting porphyrin 4 (1-48 h). Quinone methide precursors were added at regular intervals. Dioxane was then removed under reduced pressure, CHCl₃ (50 mL) was added to the residue, and the mixture was washed with sat. aq NaHCO₃ (2 × 20 mL). The organic phase was concentrated under vacuum, and the residual crude product was purified by column chromatog-raphy on silica gel and subsequently by preparative TLC using CHCl₃ as the eluent.

12

Unequivocal proton and carbon assignments for all compounds were based on two-dimensional COSY, HSQC, and HMBC experiments.
Data for {2-(5,10-Dioxo-3,4,5,10-tetrahydro-2 H -benzo[ g ]chromen-2-yl)-5,10,15,20-tetraphenylporphyrinato}zinc(II) (8)
^¹H NMR (300 MHz, CDCl₃): δ = 2.12-2.32 (m, 2 H, H-3′ and H-4′), 2.54-2.79 (m, 2 H, H-3′ and H-4′), 4.95 (d, J = 8.3 Hz, 1 H, H-2′), 7.49-7.54 (m, 1 H, Hp-Ph), 7.65-7.76 (m, 13 H, Hm,p-Ph, H-7′ and H-8′), 8.07-8.11 (m, 2 H, H-6′ and H-9′), 8.14-8.23 (m, 8 H, Ho-Ph), 8.73 (d, J = 4.8 Hz, 1 H, H-β), 8.89 (d, J = 4.8 Hz, 1 H, H-β), 8.92 (d, J = 4.8 Hz, 1 H, H-β), 8.93 (s, 2 H, H-12 and H-13), 8.95 (d, J = 4.8 Hz, 1 H, H-β), 9.12 (s, 1 H, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.2 (C-4′), 29.4 (C-3′), 75.8 (C-2′), 120.4, 121.1, 121.2, 121.5, 121.7 (C-4′a and 2 C-quat), 126.0, 126.2, 126.3, 126.4, 126.6, 126.65, 126.7, 127.5, 128.3 (Co-Ph, Cm,p-Ph, C-6′, C-9′), 131.1; 131.6, 132.0, 132.2, 132.2, 132.5 (C-β), 132.9 (Co-Ph, C-3), 133.0, 133.3, 133.8, 134.4, 134.42, 134.7 (C-7′, C-8′, Co-Ph, Cm,p-Ph), 142.5, 142.6, 142.7,143.3 (C-1), 145.8, 147.9, 150.3, 150.4, 150.5, 150.6, 150.9, 156.2 (C-10a′), 179.5 (C-5′), 184.5 (C-10′); UV/vis (CHCl₃): λ_max (log ε) = 424 (4.94), 554 (4.57), 597 (3.96) nm. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₅₇H₃₇N₄O₃Zn: 889.2152; found: 889.2143.
Data for {2-(5,6-Dioxo-3,4,5,6-tetrahydro-2 H -benzo[ h ]chromen-2-yl)-5,10,15,20-tetraphenylporphyrinato}zinc(II) (9)
^¹H NMR (500 MHz, CDCl₃): δ = 2.16-2.24 (m, 2 H, H-3′ and H-4′), 2.58-2.61 (m, 1 H, H-3′), 2.71-2.75 (m, 1 H, H-4′), 5.08 (d, J = 10.2 Hz, 1 H, H-2′), 7.47-7.51 (m, 2 H, H-8′, 1 Hp-Ph), 7.55 (dt, J = 7.6, 1.6 Hz, 1 H, H-9′), 7.71-7.81 (m, 12 H, Hm,p-Ph, H-10′), 8.09 (dd, J = 7.6, 1.3 Hz, 1 H, H-7′), 8.16-8.24 (m, 8 H, Ho-Ph), 8.76 (d, J = 4.6 Hz, 1 H, H-β), 8.91 (d, J = 4.6 Hz, 1 H, H-β), 8.95 (s, 2 H, H-12 and H-13), 8.96 (d, J = 4.6 Hz, 1 H, H-β), 8.97 (d, J = 4.6 Hz, 1 H, H-β), 9.14 (d, J = 0.7 Hz, 1 H, H-3). ^¹³C NMR (125 MHz, CDCl₃): δ = 19.8 (C-4′), 29.8 (C-3′), 76.9 (C-2′), 114.2 (C-4′a), 120.4, 121.1, 121.4, 121.7, 124.2 (C-10′), 126.4, 126.5, 126.6, 126.7, 127.6, 127.7 (Cm,p-Ph), 128.6, 128.7 (Cm,p-Ph, C-7′), 129.9 (C-6′a), 130.6 (C-8′), 131.8, 132.27, 132.30, 132.33, 132.4, 132.43 (C-β), 132.6 (C-3, C-10′a), 133.4, 133.5, 134.36, 134.4, 134.42; 134.5 (C-o), 134.75 (C-9′), 142.3, 142.5, 142.7, 143.2 (C-1), 145.5, 147.7, 150.21, 150.4, 150.57, 150.6, 150.7, 150.8, 163.6 (C-10b′), 178.7 (C-5′), 179.7 (C-6′); UV/vis (CHCl₃): λ_max (log ε): 424 (4.85), 552 (4.52), 596 (3.96) nm. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₅₇H₃₇N₄O₃Zn: 889.2152; found: 889.2122.

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Data for {2-(5-Oxo-2,3,4,5-tetrahydro-2 H -pyrano[3,2- c ]chromen-2-yl)-5,10,15,20-tetraphenylporphyrinato}zinc(II) (10a)
^¹H NMR (500 MHz, CDCl₃): δ = 2.25-2.29 (m, 2 H, H-3′ and H-4′), 2.61-2.67 (m, 2 H, H-3′ and H-4′), 5.04 (d, J = 8.5 Hz, 1 H, H-2′), 7.19 (ddd, J = 8.1, 7.2, 1.0 Hz, 1 H, H-9′), 7.34 (dd, J = 8.5, 1.0 Hz, 1 H, H-7′), 7.40-7.45 (m, 1 H, Hp-Ph), 7.49 (ddd, J = 8.5, 7.2, 1.4 Hz, 1 H, H-8′), 7.71-7.81 (m, 12 H, Hm,p-Ph, H-10′), 8.16-8.23 (m, 8 H, Ho-Ph), 8.75 (d, J = 4.6 Hz, 1 H, H-β), 8.90 (d, J = 4.6 Hz, 1 H, H-β), 8.94 (s, 2 H, H-12 and H-13), 8.95 (d, J = 4.6 Hz, 1 H, H-β), 8.97 (d, J = 4.6 Hz, 1 H, H-β), 9.15 (d, J = 0.5 Hz, 1 H, H-3). ^¹³C NMR (125 MHz, CDCl₃): δ = 20.9 (C-3′), 30.0 (C-4′), 75.9 (C-2′), 101.2 (C-4′a), 115.9 (C-10′a), 116.5 (C-7′), 120.5, 121.1, 121.3, 121.6, 122.5 (C-10′), 123.7 (C-9′), 126.4, 126.5, 126.6, 126.7, 127.6, 127.7, 128.5 (Cm,p-Ph), 131.2 (C-8′), 131.7, 132.3, 132.35, 132.6 (C-β), 133.4, 133.5, 134.37, 134.4, 134.42, 134.47, 134.5 (Co-Ph), 142.3, 142.4, 142.5, 142.7, 143.5 (C-1), 145.6, 147.8, 150.2, 150.4, 150.5, 150.6, 150.9, 152.4 (C-6′a), 160.7 (C-10′b), 163.4 (C-5′). UV/vis (CHCl₃): λ_max (log ε): 425 (4.94), 555 (4.54), 596 (4.00) nm. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₅₆H₃₇N₄O₃Zn: 877.2152; found: 877.2116.

15

General Procedure for Preparing 11a-c
A mixture of porphyrin 4 (10 mg, 14.2 µmol) and appropriate benzyl alcohol (3a, 1.7 mg; 3b, 2.2 mg; 14.2 µmol) was refluxed in o-dichlorobenzene (3 mL) in a sealed tube until consumption of starting porphyrin 4 (monitored by TLC) with addition of quinone methide precursors at regular intervals. After completion of reaction (6-26 h) the mixture was loaded on a silica column or preparative TLC plate and eluted with PE. Further elution with CHCl₃ gave the corresponding adducts.

16

Data for [2-(Chroman-2-yl)-5,10,15,20-tetraphenylporphyrinato]zinc(II) (11a)
^¹H NMR (300 MHz, CDCl₃): δ = 2.14-2.26 (m, 1 H, H-3′), 2.43-2.55 (m, 1 H, H-3′), 2.56-2.74 (m, 2 H, H-4′), 4.95 (d, J = 9.6 Hz, 1 H, H-2′), 6.85-6.94 (m,2 H, H-6′ and H-8′), 7.07-7.21 (m, 2 H, H-5′ and H-7′), 7.53-7.59 (m, 1 H, Hp-Ph), 7.68-7.80 (m, 11 H, Hm,p-Ph), 8.15-8.23 (m, 8 H, Ho-Ph), 8.73 (d, J = 4.7 Hz, 1 H, H-β), 8.89 (d, J = 4.7 Hz, 1 H, H-β), 8.91 (d, J = 4.7 Hz, 1 H, H-β), 8.92 (s, 2 H, H-12 and H-13), 8.95 (d, J = 4.7 Hz, 1 H, H-β), 9.16 (s, 1 H, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 26.2 (C-4′), 31.7 (C-3′), 74.2 (C-2′), 117.1 (C-8′), 120.0 (C-6′), 120.6, 120.9, 121.1, 121.5, 122.1 (C-4′a), 126.1, 126.5, 126.55, 127.0, 127.5, 128.1 (C-7′, Cm,p-Ph), 129.5 (C-5′), 131.5, 131.9, 132.0, 132.1, 132.4, 132.5 (C-β), 133.3, 133.7, 134.3, 134.4, 134.42, 134.6 (Co-Ph), 142.6, 142.7, 142.8, 145.9, 146.5 (C-1), 148.4, 150.0, 150.2, 150.3, 150.5, 150.9, 155.6 (C-8′a). UV/vis (CHCl₃): λ_max (log ε): 420 (4.98), 548 (4.59) nm. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₅₃H₃₇N₄Ozn: 809.2253; found: 809.2273.

17

Data for {2-[8-(2-Hydroxybenzyl)chroman-2-yl)]-5,10,15,20-tetraphenylporphyrinato}zinc(II) (11c)
^¹H NMR (300 MHz, CDCl₃): δ = 2.17-2.75 (m, 4 H, H-3′and H-4′), 3.79 (d, J = 14.4 Hz, 1 H, CH₂), 3.92 (d, J = 14.4 Hz, 1 H, CH₂), 4.97 (dd, J = 10.4, 1.1 Hz, 1 H, H-2′), 6.47 (dd, J = 8.0, 1.1 Hz, 1 H, H-3′′), 6.75 (dt, J = 7.5, 1.1 Hz, 1 H, H-5′′), 6.84 (t, J = 7.4 Hz, 1 H, H-6′), 6.87 (s, 1 H, OH), 6.93-6.97 (m, 2 H, H-5′ and H-4′′), 7.12 (dd, J = 7.4, 1.4 Hz, 1 H, H-7′), 7.20 (dd, J = 7.5, 1.6 Hz, 1 H, H-6′′), 7.52-7.55 (m, 1 H, Hp-Ph), 7.66-7.76 (m, 11 H, Hm,p-Ph), 8.17-8.33 (m, 8 H, Ho-Ph), 8.77 (d, J = 4.7 Hz, 1 H, H-β), 8.89 (d, J = 4.7 Hz, 1 H, H-β), 8.93 (s, 2 H, H-β), 8.95 (s, 2 H, H-β), 9.26 (s, 1 H, H-3). ^¹³C NMR (75 MHz, CDCl₃): δ = 26.3 (C-4′), 30.5 (CH₂), 31.2 (C-3′), 75.3 (C-2′), 116.4 (C-3′′), 120.3 (C-5′′), 120.6, 120.8 (C-6′), 121.07, 121.13, 121.4, 122.2 (C-4′a), 126.2, 126.4, 126.5 (Cm,p-Ph), 127.0 (Cm,p-Ph, C-1′′), 127.5, 127.6, 127.8 (C-8′), 128.1 (C-4′′,
C-7′, C-5′, Cm,p-Ph), 128.2, 130.4 (C-6′′), 130.5; 131.5, 132.06, 132.1, 132.2, 132.4 (C-β), 132.8 (C-3), 133.4, 133.6, 134.4, 134.5, 134.9 (Co-Ph), 142.8, 142.9, 144.9, 145.8, 148.1, 150.2, 150.2, 150.4, 150.4, 150.5, 150.8, 151.6 (C-8′a), 154.0 (C-2′′). UV/vis (CHCl₃): λ_max (log ε): 420 (5.72), 547 (4.59) nm. HRMS (ESI⁺): m/z [M]⁺ calcd for C₆₀H₄₂N₄O₂Zn: 914.2594; found: 914.2583.