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14Porphyrins Порфирины
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DOI: 10.6060/mhc170398o
[3+2]-Cycloaddition Reaction between Tetraphenylporphyrinylazide and Ferrocenyl Dipolarophiles
Elena Yu. Osipova,a@ Alexey N. Rodionov,ab Elena F. Kudryashova,ac Nadezhda V. Konovalova,c and Alexander A. Simenelad
aA.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow, Russian Federation
hEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russian Federation Moscow Technological University, Institute of Fine Chemical Technologies, 119571 Moscow, Russian Federation dNational University of Science and Technology "MISIS", 119049 Moscow, Russian Federation @Corresponding author E-mail: jdyotvet@yandex.ru
The regioselectivity of [3+2]-cycloaddition reaction of tetraphenylporphyrinylazide with ferrocenyl dipolarophiles in the absence of copper(I) salts was studied.
Keywords: [3+2]-Cycloaddition, tetraphenylporphyrin, ferrocene.
Реакция [3+2]-циклоприсоединения тетрафенилпорфиринилазида с ферроценсодержащими диполярофилами
Е. Ю. Осипова^@ А. Н. Родионов,^ Е. Ф. Кудряшова,^ Н. В. Коновалова^ А. А. Сименел^
Федеральное государственное бюджетное учреждение науки Институт элементоорганических соединений им. А.Н. Несмеянова Российской академии наук, 119991 Москва, Российская Федерация ьФедеральное государственное бюджетное учреждение науки Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук, 119991 Москва, Российская Федерация
сМосковский технологический университет, Институт тонких химических технологий, 119571 Москва, Российская Федерация
Национальный исследовательский технологический университет «МИСиС», 119049 Москва, Российская Федерация ®Е-тай: jdyotvet@yandex.ru
Исследована реакция [3+2]-циклоприсоединения тетрафенилпорфиринилазида с ферроценсодержащими диполярофилами в отсутствии солей меди. Показано, что реакция протекает региоселективно.
Ключевые слова: [3+2]-Циклоприсоединение, тетрафенилпорфирин, ферроцен.
For many years, porphyrins have been successfully used in PDT.[1] Ferrocenylheterocyclic compounds have been found to exhibit a wide range of biological activities (e.g. antitumor[23] and antimicrobial[4]). Ferrocene containing porphyrins have already been synthesized by various synthetic methods.[5-12] The difference of bounding ways in the ferrocenylporphyrin assemblies suggests the variety of applications. Their donor-acceptor properties have been
employed to study photoinduced electron transfer processes and to simulate photosynthesis active sites.[13-18] Thus, such structures have been used as molecular sensors[19,20] and for an increase of memory density that allowed multibit information storage.[21-23]
Previously, we have studied the reductive amination reaction of ferrocenylpyrazolecarboxaldehydes with 5-( p-aminophenyl)-10,15,20-triphenylporphyrin.[22 24 25]
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[3+2]-Cycloaddition Reaction between Tetraphenyl Porphyrinazide and Ferrocenyl Dipolarophiles
Therefore, we used these reactions to produce ferrocene-porphyrins in which the ferrocene is linked to porphyrin through the pyrazole. Moreover, the possibility of applying of synthesized compounds for sonodynamic therapy was studied.
In present work, we construct porphyrin - heterocycle -ferrocene triad by means of [3+2]-cycloaddition reaction with azidotetraphenylporphyrin. The possibility of using diketones as dipolarophiles stems from the fact that they exist mostly in the enol form due to the keto-enol tautomerism. The regioselectivity of dipolar addition to such substrates depends mainly on the relative stability of the resulting enol forms.
O O
EWG
Fe
OH O
EWG
O OH
EWG
Fe
Fe
Figure 1. Keto-enol tautomerism in ferrocene-containing P-diketones.
diisopropylethylamine (DIPEA) in toluene) led to the conclusion that the best yields of porphyrins 3a and 3b can be obtained using DIPEA in toluene.1 In this case, regioselectivity does not depend on the nature of the base.
Noteworthy, that the reaction proceeds at the absence of toxic copper salts. This is very important because we are planning to study the application of these compounds for sonodynamic therapy of cancer and inflammations. Moreover, in the absence of copper the target porphyrins 3a and 3b remain metal-free, which simplifies their purification. The structures of the compounds synthesized were established on a basis of 2D heteronuclear NMR correlations.
Hereby, ferrocenylheterocyclic porphyrins were synthesized by means of [3+2]-cycloaddition reaction between tetraphenylporphyrinylazide and ferrocenyl dipolarophiles. The effectiveness of the method was established using DIPEA as a base in toluene. Structures of the resulted substances were confirmed by UV, NMR-spectroscopy and ESI mass-spectrometry methods. At the next stage of work it is planned to study the electrochemical properties and biological activity of these compounds.
Acknowledgements. This work was supported by the Russian Foundation for Basic Research (RFBR No 16-3360163).
I
II
O O
EWG
Fe +
la,b
EWG = (a) COOEt, (b) CF3
DIPEA toluene
Fe
O EWG
N-
-NH N-
N
3a,b
Scheme 1. [3+2]-Cycloaddition between tetraphenylporphyrinazide and ferrocenyldiketones.
The preferential formation of ketoenol II is possible only in the presence of a strong electron-withdrawing group; in the other case, the formation of both enol forms is equally probable. Thus, in our work we used ferrocenoyl pyruvic ether (EWG=COOEt) as ferrocene-containing dipolarophiles and ferrocenoyl trifluoroacetone (EWG=CF3). Compounds 1a,b were obtained via Claisen condensation between acetylferrocene and diethyloxalate or ethyltrifluoroacetate respectively.[26] Indeed, it was shown by means of NMR spectroscopy that there was only one enol form II in solution at room temperature.
The reaction of tetraphenylporphyrinylazide[27] with ferrocenyl-containing dicarbonyl compounds leads to the formation of the desired 1,2,3-triazoles. It should be noted that the nature of the base plays a significant role. The use of various bases (potassium carbonate, sodium methoxide, triethylamine in toluene, pure triethylamine,
References and Notes
t General procedure. 5-(p-Azidophenyl)-10,15,20-triphenyl-porphyrin (2) (0.01 mmol) and appropriate ferrocenyl-diketone (1a,b) (0.01 mmol) were dissolved in toluene (5 mL). iV,iV-Diisopropylethylamine (0.01 mmol) was added and reaction mixture was refluxed for 3 h, cooled to room temperature and washed with water (3x15 mL), dried over Na2SO4. Solvent was removed in vacuo and the residue was chromatographed on silica (eluent: petroleum ether-ethyl acetate = 4:1).
1-(5-(p-(4-Ferrocenoyl-5-carboxyethyl-1,2,3-triazolyl)-phenyl)-10,15,20-triphenylporphyrin) (3a). Yield 60 %. Violet powder. MS (ESI) m/z (%): 967 (100) [M+H]+. UV-Vis (CH2Cl2) Xmax nm (e): 418 (202,000), 514 (10,000), 550 (5,000), 5892 (3,600), 648 (3,000). 1H NMR (CDCl3, 30 oC) 8H ppm: -2.76 (s, 2H, 2NH), 1.47 (t, 3H, J=8 Hz, CH3), 4.36 (s, 5H, Cp), 4.58-4.63 (m, 2H, CH2), 4.76 (s, 2H, Cp), 5.50 (s, 2H, Cp), 7.74-7.83 (m, 9H, Ph), 8.05-8.07 (d, 2H, J=8 Hz, Ph),
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8.23-8.25 (d, 6H, J=8 Hz, Ph), 8.43-8.45 (d, 2H, J=8 Hz, Ph), 8.85-8.93 (m, 8Haß, Py). 13C NMR (CDCl3, 30 oC) 8C ppm: 14.02; 63.45; 70.52; 71.48; 73.54; 117.46; 120.52; 122.45; 126.74; 127.84; 134.57; 135.33; 142.01; 144.57; 159.98.
1-(5-(p-(4-Ferrocenoyl-5-trifluormethyl-1,2,3-triazolyl) phenyl)-10,15,20-triphenylporphyrin) (3b). Yield 43 %. Violet powder. MS (ESI) m/z: 962.28 [M+H]+. UV-Vis (CH2Cl2) 1max nm (e): 418 (153,000), 514 (7,640), 551 (3,900), 589 (2,860) 645 (2,240). 1H NMR (CDCl3, 30 oC) 8H ppm: -2.76 (s, 2H, 2NH), 1.47 (t, 3H, J=8 Hz, CH3), 4.36 (s, 5H, Cp), 4.58-4.63 (m, 2H, CH2), 4.76 (s, 2H, Cp), 5.50 (s, 2H, Cp), 7.74-7.83 (m, 9H, Ph), 8.05-8.07 (d, 2H, J=8 Hz, Ph), 8.23-8.25 (d, 6H, J=8 Hz, Ph), 8.43-8.45 (d, 2H, J=8 Hz, Ph), 8.85-8.93 (m, 8Haß, Py). 13C NMR (CDCl3, 30 oC) 8C ppm: 63.45; 70.50; 71.45; 73.55; 117.46; 120.52; 124.50; 126.69; 127.84; 134.55; 136.26; 142.01; 147.74; 184.10.
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Received 15.03.2017 Accepted 24.04.2017
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