Synthesis of the first azomethine derivatives of Pd II coproporphyrins i and II Текст научной статьи по специальности «Химические науки»

Порфирины

Porphyrins

Макрогэтэроцмклы

Статья

Paper

http://macroheterocycles.isuct.ru

DOI: 10.6060/mhc140274z

Synthesis of the First Azomethine Derivatives of Pd" Coproporphyrins I and II

Alexander N. Volov,a Ilya A. Zamilatskov,a@ Igor S. Mikhel,a Dina R. Erzina,a Gelii V. Ponomarev,b Oscar I. Koifman,c and Aslan Yu. Tsivadzea

Dedicated to the Corresponding member of Russian Academy of Sciences Prof. Oscar I. Koifman

on the occasion of his 70th Anniversary

aA.N. Frumkin Institute of Physical Chemistry and Electrochemistry of Russian Academy of Sciences, 119991 Moscow, Russia

bResearch Institute of Biomedical Chemistry RAMS, 119121 Moscow, Russia cIvanovo State University of Chemistry and Technology, 153000 Ivanovo, Russia @Corresponding author E-mail: joz@mail.ru

The effective synthesis of Pd(II) monofunctional azomethine derivatives of coproporphyrin isomers I andII is reported. The proposed method is based on the interaction of a "phosphorus complex", generated in situ by Vilsmeier-Haack reaction, with various amines. The reaction with palladium complex of coproporphyrin II gave Schiff bases as a mixture of two structural isomers in 4:1 ratio. The structure of the obtained compounds was determined using 1H, 13C, 1H-1H NOESY and UV-vis spectroscopy and mass spectrometry data.

Keywords: Porphyrin, palladium, coproporphyrin, azomethine, Vilsmeier-Haack reaction.

Синтез первых азометиновых производных Pdn копропорфиринов I и II

А. Н. Волов,a И. А. Замилацков,а@ И. С. Михель,1 Д. Р. Эрзина,1 Г. В. Пономарев,13 О. И. Койфман,с А. Ю. Цивадзе1

Посвящается Член-корреспонденту РАН Оскару Иосифовичу Койфману

по случаю его 70-летнего юбилея

аИнститут физической химии и электрохимии им. А.Н. Фрумкина РАН, 119071 Москва, Россия ьИнстиут биомедицинской химии им. В.Н. Ореховича РАМН, 119832 Москва, Россия сИвановский государственный химико-технологический университет, 153000 Иваново, Россия @ E-mail: joz@mail. ru

Предложен эффективный метод синтеза Pd(II) монофункциональных азометиновых производных копропорфиринов I и II. Предлагаемый метод основан на взаимодействии так называемого "фосфорного комплекса", получаемого in situ путем реакции Вильсмейра-Хаака, с различными аминами. Реакция с палладиевым комплексом копропорфирина II приводит к образованию оснований Шиффа в виде смеси двух структурных изомеров в отношении 4:1. Строение полученных соединений установлено с привлечением методов ЯМР H, 13С, H-HNOESY и УФ спектроскопии, а также данных масс-спектрометрии.

Ключевые слова: Порфирин, палладий, копропорфирин, азометин, реакция Вильсмейра-Хаака.

Introduction

Porphyrins and metalloporphyrins are widespread in nature; due to the aromatic bond system, porphyrins are very promising for use in various fields of science and technology. For instance, many achievements in supramolecular chemistry, including development of new materials, are related to porphyrin molecules linked by the intermolecular noncovalent bonds.[1-4] Due to the unique photophysical and photochemical properties, porphyrins and metalloporphyrins are used as sensors in bioassay,[5-7] active drug substances in cancer diagnostics and therapy.[8,9] Many fundamental studies in search of new sensors are presently carried out, which are aimed to find new multiparametric sensors, particularly covering such analytes as O2, CO2, etc.[10] The potential use of derivatives of mono-meso-substituted porphyrins and metalloporphyrins as multiparametric sensors for oxygen and H+ is one of the main factors driving ever-growing interest in the synthesis of new porphyrin derivatives.[11] The porphyrins have attracted even more attention from researchers in various fields due to their phototherapeutic properties in past two decades.[12-14] Porphyrin derivatives and related systems have been used as photosensitizers in cancer phototherapy. Hematoporphyrin Derivative, such as Photofrin®, Photosan® and Photogem® have regulatory approval; however, they are complex mixtures of oligomers with the weak absorption at ca. 620 nm. At the same time, the high degree of skin photosensitivity is a major drawback in the use of such compounds.[15-17] For the effective application in photodynamic therapy (PDT) the porphyrin samples should be water-soluble and hydrophilic, possess high values of photophysical parameters, such as phosphorescence lifetime and quantum yield of phosphorescence and emit in the infrared region of the spectrum with a Stokes shift at ca. 100 nm.[18] Recently, the most part of synthetic studies in this field was focused mainly on the meso-tetraaryl porphyrins,[19-20] but these compounds have bulky benzene rings, which make them inherently hydrophobic and limits their further use in the biological systems. To overcome such limitation, it is necessary to use hydrophilic porphyrins with good solubility in organic solvents and water such as isomeric coproporphyrins having four carboxyl groups. [21-22] In this paper we have developed the effective method of producing mono-substituted azomethine derivatives of coproporphyria I, II and their palladium(II) complexes that can be considered as phosphorescent labels and potential PDT candidates.

Experimental

Methylamine (38% aqueous solution), allylamine, propargyl-amine, POCl3 were purchased from Sigma-Aldrich, Fluka, Merck and used without further purification. Solvents were purified by standard procedures: CH2Cl2 and 1,2-dichloroethane were distilled over CaH2. Methanol (Merck, 99%) and N,N-dimethylformamide (Labscan, 99%) were used as received. Coproporphyrines I[21] and II[22] were prepared according to the described procedures. Palladium(II) complexes of coproporphyrins I (1) and II (4) were synthesized following the known procedures.[23]

UV-Vis electronic absorption spectra were registered using U-2900 (Hitachi) spectrophotometer and quartz rectangular

cells of 1-10 mm path length. 1H (600 MHz) NMR spectra were recorded at T = 298 K with a Bruker Avance III 600 spectrometer in CDCl3. Chemical shifts 5 are quoted in parts per million (ppm) downfield of tetramethylsilane. Coupling constants are given in Hz. 13C (150 or 75 MHz) NMR spectra were recorded on a Bruker Avance III 600 or Bruker AVANCE I 300 in CDCl3, respectively. The MALDI-TOF mass-spectra were obtained on a Ultraflex-II mass spectrometer (Bruker Daltonics) in a positive ion mode using reflection mode (20 mV target voltage) without matrix. Highresolution mass spectra were recorded on a Bruker ESI microTOF II mass spectrometer using electrospray ionization.

A typical procedure for synthesis of Pd(II) azomethine derivatives of coproporphyrin I and II. To a solution of Pd(II) coproporphyrin I tetraisopropyl ester (1) (47 mg, 0.05 mmol) in 25 mL of dry 1,2-dichloroethane the Vilsmeier reagent, in situ formed[24] from POCl3 (0.25 ml, 2.75 mmol) and N,N-dimethylformamide (0.25 ml, 3.25 mmol), was added at 75 oC. The resulting mixture was stirred for 5 hours at the same temperature and the reaction was monitored by TLC (CH2Cl2/MeOH, 99:1 by volume). Then the solution was evaporated and the residue obtained was dissolved in CH2Cl2 (25 ml) and washed with H2O (25 ml). The aqueous phase was extracted once with CH2Cl2 (25 mL). The combined organic phases were dried over Na2SO4, the salt was removed by filtration, and the solution was evaporated. Then the solid obtained was dissolved in a minimum amount of CH2Cl2 (5-10 ml) and an amine (0.25 mmol) was added. The reaction mixture was evaporated to afford the crude compound, which was purified by chromatography (silica gel). The traces of unreacted porphyrin were eluted first (CH2Cl2/MeOH, 99:1 by volume). Then the orange fraction of the azomethine derivative was collected (CH2Cl2/MeOH, 96:4).

Palladium(II) azomethine derivative of coproporphyrin I with methylamine (3a). Yield 78%. 1H NMR: 10.55 (1H, s, CHN), 9.99 (1H, s, meso-H), 9.96 (1H, s, meso-H), 9.95 (1H, s, meso-H), 5.23 (1H, septet, J = 6.6, CH(CH3)2), 5.12 (1H, septet, J = 6.6, CH(CH3)2), 5.11 (1H, septet, J = 6.6, CH(CH3)2), 5.10 (1H, septet, J = 6.6, CH(CH3)2), 4.33 (2H, t, J = 7.2, CH2CH2C02), 4.31 (2H, t, J = 6.6, CH2CH2C02), 4.24 (2H, t, J = 7.8, CH2CH2C02), 4.00 (3H, s, NCH3), 3.96-3.93 (2H, m, CH2CH2C02), 3.59 (3H, s, P-CH3), 3.58 (3H, s, P-CH3), 3.55 (3H, s, P-QH3), 3.21 (4H, t, J = 7.8, CH2CH2C02), 3.11 (3H, s, P-CH3), 3.10 (2H, t, J = 7.2, CH2CH2C02), 2.90-2.87 (2H, m, CH2CH2C02), 1.37 (6H, d, J = 6.6, CH (CH3)2), 1.20 (6H, d, J = 6.6, CH(CH2)2), 1.17 (6H, d, J = 6.6, CH(CH3)2), 1.15 (6H, d, J = 6.6, CH(CH3)2). MS (MALDI-TOF) m/z: 968.5. Calcd. for [M]+ 968.5. UV-Vis (CHCl3) Xmax nm (log s-10"3, M-1cm-1): 397 (252), 516 (11.2), 549 (46.5). miX

Palladium(II) azomethine derivative of coproporphyrin I with allylamine (3b). Yield 81%. 1H NMR: 10.77 (1H, s, CHN), 10.03 (1H, s, meso -H), 10.00 (1H, s, meso -H), 9.99 (1H, s, meso -H), 6.39 (1H, ddt, , J = 16.8, J = 10.2, J ~ 6.6, NCH2CH), 5.55 (1H, dq, J = 16.8, J ~ 1.8, NCH2CHCH2), 5.38 (1H, dq, J = 10.2, J ~ 1.8, NCH2CHCH2), 5.20 (1H, septet, J = 6.6, CH(CH3)2), 5.14 (1H, septet, J = 6.6, CH(CH3)2), 5.11 (1H, septet, J = 6.6, CH(CH3)2), 5.10 (1H, septet, J = 6.6, CH(CH3)2), 4.85 (2H, dd, J = 6.0, J ~ 1.2, NCH2), 4.34 (2H, t, J = 7.2, CH2CH2C02), 4.32 (2H, t, J = 7.2, CH2CH2C02), 4.28 (2H, t, J = 7.8, CH^CH^), 4.03-4.00 (2H, m, CH2CH2C02), 3.60 (6H, s, P-CH3), 3.58 (3H, s, P-CH3), 3.22 (4H, t, J = 7.8, CH2CH2C02), 3.19 (3H, s, P-CH3), 3.12 (2H, t, J = 7.8, CH2CH2C02), 2.94-2.92 (2H, m, CH2CH2C02), 1.34 (6H, d, J = 6.6, CH(CH3)2), 1.21 (6H, d, J = 6.6, CH(CH3)2), 1.16 (6H, d, J = 6.6, CH(CH3\), 1.15 (6H, d, J = 6.6, CH(CH3)2). MS (MALDI-TOF) m/z: 9943.4. Calcd. for [M]+ 994.5. HRMS (ESI): calcd. for C52H66N5O8Pd 994.3959; found 994.3944 [M+H]+. HRMS (ESI): calcd. for C52H65N5NaO8Pd 1016.3778; found 1016.3763 [M+Na]+. UV-Vis (CHCl3) Xmax nm (log s-10"3, M4cm-1): 398 (251), 516 (11.4), 549 (46).

Palladium(II) azomethine derivative of coproporphyrin I with propargylamine (3c). Yield 80%. 1H NMR: 10.82 (1H, s,

CHN), 10.03 (1H, s, meso-Н), 9.98 (1H, s, meso-Н), 9.95 (1H, s, meso-Н), 5.35-5.33 (2H, m, CH2CCH), 5.21 (1H, septet, J = 6.6, CH(CH3)2), 5.16 (3H, septet, J = 6.6, CH(CH3)2), 4.33-4.31 (4H, m, CHfHf О2),), 4.28 (2H, t, J = 7.8, СН2СН2СО2),), 4.05 (2H, t, J = 7.8, СН2СН2СО2), 3.58 (6Н, s, ß-СНД 3.56 (3Н, s, ß-CH3), 3.49 (1Н, s, CH2CCH), 3.25 (4Н, t, J = 7.8, СН2СН2СО2), 3.20 (3Н, s, ß-CH3), 3.15 (2Н, t, J = 7.8, СН2СН2СО2), 2.94 (2Н, t, J = 7.8, СН2СН2СО2), 1.30 (6Н, d, J = 6.6, CH(CH3)2), 1.27 (6Н, d, J = 6.6, CH(CH3)2), 1.20 (6Н, d, J = 6.6, CH(CH3)2), 1.16 (6Н, d, J = 6.6, CH(CH3)2). MS (MALDI-TOF) m/z: 992.5. Calcd. for [M]+ 992.5. UV-Vis (CHCl3) Xmax nm (log sT0"3, M'W1): 397(253), 514(11.3), 549(46.5). maX

Palladium(II) azomethine derivative of coproporphyrin II with methylamine (major isomer) (7a). Yield 70%. 1Н NMR: 10.47 (1Н, s, CHN), 9.90 (2H, s, C5H and C15H), 9.87 (1Н, s, C20H), 4.28 (4Н, t, J = 7.8, C3CH2 and C17CH2), 4.24 (4H, t, J = 78, C7CH2 and C13CH2), 4.18 (4Н, q, J = 7.2, CH2CH3), 4.15 (4Н, q, J = 7.2, CH2CH3), 42.06 (3H, s, NCH3), 3.54 (6H s, C2CH3 and C18CH3), 3.22 (4H, t, J = 7.8, C3CH2CH2 and C17CH2CH2), 3.14 (4H, t, J = 7.8, C7CH2CH2 and C13CH2CH2), 3.14 (6H, s, C8CH3 and C12CH3), 1.18 (6Н, t, J =2 7.2, CH2CH3), 1.14 (6H, t, J = 7.2, CH2CH3). 13C{H} NMR (150.9 MHz): 173.12 and 173.10 (CO2Et), 166.1 (CHN), 140.2 (C arom.), 139.0 (C arom.), 138.6 (C arom) 138.5 (C arom.), 138.2 (C arom.), 137.9 (C arom.), 136.5 (C arom.), 136.2 (C arom.), 99.0 (C5 and C15), 98.8 (C20), 60.54 and 60.50 (CH2CH3), 49.2 (NCH3), 37.08 and 37.07 (CH2CO2Et), 21.8 and 21.7 (CH2CH2CO2), 18.4 and 18.3 (C2CH3 and C18CH3), 14.15 and 14.11 (CH2CH3), 11.7 (C8CH3 and C12CH3). MS (MALDI-TOF) m/z: 91(.(. Calcd. for [M]+ 912.4. HRMS (ESI): calcd. for C46H56N5O8Pd 912.3175; found 912.3170 [M+H]+. UV-Vis (CHCl3) >4inax nm (log s-10"3, M'W1): 397(248), 514(10.8), 549(45.5). ™X

Palladium(II) azomethine derivative of coproporphyrin II with allylamine (major isomer) (7b). Yield 69%. 1Н NMR: 10.49 (1Н, s, CHN), 9.92 (2H, s, C^H and C15H), 9.88 (1Н, s, C20H), 6.39 (1Н, ddt, J = 16.8, J = 10.2, J ~ 6.6, NCH2CH), 5.55 (1Н, dq, J = 16.8, J ~ 1.8, NCH2CHCH2), 5.39 (1Н, dq (broad), J = 10.2, J ~ 1.8, NCH2CHCH2), 4.85 (2Н, dd, J = 6.2, J ~ 1.2, NCH2), 4.30 (4Н, t, J = 7.8, C3CH2 and C17CH2), 4.25 (4H, t, J = 7.8, C7CH2 and C13CH2), 4.18 (4Н, q, J= 7.2, CH2CH3), 4.15 (4Н, q, J = 7.2, CH2CH3), 3.55 (6H, s, C2CH3 and C18CH3), 3.23 (4H, t, J = 7.8, C3CH2CH2 and C17CH2CH2), 3.14 (4H, t, J = "7.8, C7CH2CH2 and C13CH2CH2), 3.12 (6H, s, C8CH3 and C12CH3), 1.18 (6H, t, J = 7.2, CH2CЯ3(, 1.13 (6H, t, J = 7.2, CH2CH3). 23C{H} NMR (150.9 MHz): 173.14 and 173.13 (CO2Et), 165.9 (CHN), 140.0 (C arom.), 138.8 (C arom.), 138.4 (C arom.), 138.3 (C arom.), 137.9 (C arom.), 136.4 (C arom.), 136.0 (C arom.), 134.6 (NCH2CH), 117.5 (NCH2CHCH2), 98.8 (C5 and C15), 98.7 (C20), 65.3 (NCH2), 60.55 and 60.51 (CH2CH3), 37.0 (CH2CO2Et), 21.7 and 21.6 (CRCECO), 18.3 (C,CH, and C,CH), 1^4.14 and

v 2 2 2/J ■ 2 3 18 3''

14.10 (CH2CH3), 11.7 (C8CH3 and C12CH3). MS (MALDI-TOF) m/z: 938.3. Calcd. for [M]+ 938.4. HRMS (ESI): calcd. for C48H58N5O8Pd 938.333(; found 938.33(4 [M+H]+. UV-Vis (CHCl3) Xmax nm (log s^10 -3, M-1cm-1): 397(249), 515 (10.5), 549(45.4).

Palladium(II) azomethine derivative of coproporphyrin II with propargylamine (major isomer) (7c). Yield 63%. 1H NMR: 11.24 (1H, s, CHN), 9.92 (2H, s, C^H and C15H), 9.86 (1H, s, C20H), 5.09 (2H, t, J = 2.4, CH2CCH), 4.38 (4H t, J = 7.8, C3CH2 and C17CH2), 4.36 (4H, t, J = 7.8, C7CH2 and C13CH2), 4.18 (4H, q, J = 7.2, CH2CH3), 4.15 (4H, q, J = 7.2, CH2CH3), 3.62 (6H, s, C2CH3 and C18CH3), 3.31 (6H, s, C8CH3 and C12CH3), 3.28 (4H, t, J = 7.8, C3CH2CH2 and C17CH2CH2), 3.21 (4H, t, J = 7.8, C7CH2CH2 and C^CH^H^, 2.94 (1H, t, J = 2.4, CH2CCH), 1.18 (6H, t, J =2 7.2, CH2CH3), 1.13 (6H, t, J = 7.2, CH2CH3). 13C{H} NMR (75.5 MHz): 173.1 (CO2Et), 167.3 (CHN), 140.0 (C arom.), 139.9 (C arom.), 138.7 (C arom.), 138.3 (C arom.), 138.27 (C arom.), 137.7 (C arom.),136.3 (C arom.), 135.9 (C arom.), 98.8 (C5 and C15), 98.6 (C20), 77.6 (NCH2C), 77.2 (NCH2CCH), 60.54 and 60.51(CH2CH3), 48.0 (NCH2), 37.0 (CH2CO2Et), 21.7 and 21.63 (CH2CH2CO2), 18.1 (C2CH3 and C18CH3), 14.14 and 14.11(CH2CH3), 11.7 (C8CH3 and

C12CH3). MS (MALDI-TOF) m/z: 937.6. Calcd. for [M+H]+ 937.4. HRMS (ESI): calcd. for C48H56N5O8Pd 936.3175; found 936.3162 [M+H]+. UV-Vis (CHCl3) Xmax nm (log s-10-3, M-1cm-1): 397(253), 514 (11.3), 549(46.5). ^

Palladium(II) azomethine derivative of coproporphyrin II with methylamine (minor isomer) (8a). Yield 15%. 1Н NMR: 10.95 (1Н, s, СЯ N), 10.08 (3H, s, meso-Н ), 4.37 (4Н, t, J = 7.8, СН2СН2СО2), 4.32 (4Н, q, J = 7.2, C#2CH3), 4.18 (4Н, q, J = 7.2, CHCH3), 4.08-4.05 (4H, m, СН2СН2СО2), 4.00 (3H, s (broad), NCH3), 3.62 (6H, s, ß-CH3), 3.59 (6H, s, ß-CH3), 3.28 (4H, t, J = 7.8, CH2CH2C02), 2.99-2.96 (4Н, m, СН2СН2СО2), 1.30 (6H, t, J = 7.2, CH2CH3), 1.15 (6H, t, J = 7.2, CH2CH3). MS (MALDI-TOF) m/z: 912.2. Calcd. for [M]+ 912.4. HRMS (ESI): calcd. for C46H56N5O8Pd 912.3175; found 912.3167 [M+H]+. UV-Vis (CHCl3) Xmax nm (log s-10"3, M-1cm-1): 397(248), 515 (10.8), 549(45.5).

Palladium(II) azomethine derivative of coproporphyrin II with allylamine (minor isomer) (8b). Yield 14%. 1Н NMR: 10.89 (1Н, s, CHN ), 9.98 (2H, s, meso-Н ), 9.97 (1Н, s, meso-Н ), 6.36 (1Н, ddt, J = 16.8, J = 10.2, J ~ 6.6, NCH2CH), 5.54 (1Н, d (broad), J = 16.8, NCH2CHCH2), 5.35 (1Н, d (broad), J = 10.2, NCH2CHCH2), 4.82 (2Н, dd, J = 6.6, J ~ 1.2, NCH2), 4.32-4.29 (4H, m, С^2СН2СО2), 4.27 (4Н, q, J = 7.2, CH2CH3), 4.17 (4Н, q, J = 7.2, CH2CH3), 4.03-4.00 (4H, m, СН^Н^О^, 3.57 (6H, s, ß-CH3), 3.54 (6H, s, ß-CH3), 3.25 (4H, t, J = 7.8, СН^СО^, 2.97-2.94 (4Н, m, СН2СН2СО2), 1.32 (6Н, t, J = 7.2, CH2CH3), 1.15 (6H, t, J = 7.2, CH2CH3). MS (MALDI-TOF) m/z: 938.1. Calcd. for [M]+ 938.4. UV-Vis (CHCl3) Xmax nm (log s-10-3, M-1cm-1): 398(249), 516 (10.5), 551(45.4).

Palladium(II) azomethine derivative of coproporphyrin II with propargylamine (minor isomer) (8c). Yield 11%. 1Н NMR: 11.44 (1Н, s, CHN), 10.10 (2H, s, meso-Н), 10.09 (1Н, s, meso-Н), 5.10 (2Н, t (broad), J ~ 2.4, СН2ССН), 4.38 (4Н, t, J = 7.8, СН^Н^О^, 4.29 (4Н, q, J = 7.2, CH2CH3), 4.17 (4Н, q, J = 7.2, C^CH^, 4.11-4.08 (4H, m, СН^Н^ОД 3.62 (6H, s, ß-CH3), 3.61 (6H, s, ß-CH3), 3.29 (4H, t, J = 7.8, СН3CН3СО3), 3.00-2.97 (4Н, m, СН^СО^, 2.90 (1Н, t, J ~ 2.4, Œ^CCH), 1.34 (6H, t, J = 7.2, CH^), L15 (6Н, t, J = 7.2, CH^H,). MS (MALDI-TOF) m/z: 9371. Calcd. for [M+H]+ 937.4. UV-Vis (CHCl3) Xmax nm (log s^10-3, M-1cm-1): 397(249), 515 (10.5), 549.5(45.4). ™X

Results and Discussion

The corresponding palladium(II) complexes 1 and 4[23] were selected as starting compounds for synthesis of azomethine derivatives of coproporphyria (Schemes 1 and 2). For the synthesis of azomethine derivatives of coproporphyrin isomers I and II we have used method based on the reaction of imine salt, the so-called "phosphorus complex" generated in situ via the Vilsmeier-Haack reaction, with different amines. This method was successfully applied in the chemistry of porphyrins earlier.[25]

The Vilsmeier-Haack reaction of palladium complex of coproporphyrin II (4) gave the corresponding Schiff bases as two structural isomers in 4:1 ratio. We assume that the direction and the yield of this reaction strongly depends on substituents in adjacent pyrrole rings. Thus the formation of minor isomers 8a-c with low yields could be explained by the sterically hindered propionic residues at adjacent p-positions that complicates the reaction at this center. The minor isomer was separated using 1% MeOH solution in dichloromethane, and then the major product was isolated using the CH2Cl2/ MeOH (96:4) system. The new compounds were purified by column chromatography and characterized by a combination of mass spectrometry (MALDI-TOF and HR ESI) and 'H,

Scheme 1. The synthesis of compounds 3a-c.

OEt CK OEt

0;s/>Et CK OEt

POCI3, DMF

C2H4CI2, 75°C, 5h

OEt O. OEt

OEt

OEt

O^ OEt

CH2CI2,10 min

Me

VMe

V

y

Pd

M N-R

//—Me

O OEt ЕЮ 7 a-c

OEt O. OEt

R = Me, allyl, propargyl

Scheme 2. The synthesis of compounds 7a-c and 8a-c.

13C and Щ-Щ NOESY NMR and UV-Vis spectroscopy (see Experimental Section for the data and Scheme 3).

First of all, to characterize the structure of the prepared azomethine derivatives, 1H NMR spectroscopical investigations were carried out. For example, compound 7a has resonances at 10.47, 9.90 (double intensity) and 9.87 ppm which correspond to the protons of CH=N-Me fragment and three free weso-positions.

The connectivity between the azomethine residue and the porphyrin core in complexes 7a-c was determined from 1H-1H NOESY spectra. For instance, there is a correlation between a proton of the imine fragment (10.49 ppm) and the

protons of P-Me group (3.12 ppm) in the NOESY spectrum of 7b (Figure 1).

The imine CH=N- and the allyl CH2 protons (4.85 ppm) have a correlation as well. Altogether, it means that the imine fragment is placed between the methyl groups of respective pyrroles and excludes any alternative structure of complex 7b. It is also important to note, that the presence of cross peaks between protons of the azomethine fragment and the allyl, proves the (E)-configuration of the double C=N bond. These correlations confirmed the structure of the azomethine fragment, as well as a connectivity between the imine part and the porphyrin core.

OH O. QEt

Table 1. Absorption characteristics of azomethine derivatives in

CHCl3.

Scheme 3. The numbering scheme for complexes 7a-c.

Compound Soret X (nm) max v ' Qx Qy

1 392 512 546

3a 397 516 549

3b 398 516 549

3c 397 514 549

4 393 511 546

7a 397 514 549

7b 397 515 549

7c 397 514 549

8a 397 515 549

8b 398 516 551

8c 397 515 549

Figure 1. Щ-Щ NOESY spectrum of compound 7b in CDCl3 at 298 K.

The electronic absorption spectral data of obtained complexes 3a-c, 7a-c and 8a-c in comparison with the data for starting compounds 1 and 4 are given in Table 1. The pronounced bathochromic shifts (3-5 nm) of the Soret band and the Q-bands were observed in all cases.

The 13C NMR spectroscopic data are also in good agreement with structures of complexes 7a-c (see Experimental Part).

MALDI-TOF mass spectrometric examination of all synthesized compounds proved the mononuclear nature of the palladium complexes with the detection of molecular ions. HR ESI mass spectrometry additionally confirmed

the elemental composition of compounds 3b, 7a-c and 8a. Unfortunately, numerous attempts to grow single crystals of the new complexes suitable for an X-ray diffraction study have failed.

Conclusion

In summary, a new route for the preparation of Pd(II) coproporphyrin azomethine derivatives was suggested. This approach gives an access to the straightforward synthesis of unsymmetrical coproporphyrins bearing

different substituents at the nitrogen atom. Some detailed 1H-1H NOESY NMR studies of obtained complexes were performed as well. This information should be useful for the design and synthesis of new coproporphyrin azomethine derivatives. Further investigations concerned to the synthesis of related Pd(II) coproporphyrin complexes and their use in photochemical investigations are currently in progress.

Acknowledgements. This work was supported by Russian Foundation for Basic Research (Grant No. 12-03-00927-a) and Presidential Grant for young scientists (MK-361.2014.3).

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Received 11.03.2014 Accepted 05.08.2014