卟啉及铁卟啉的合成方法研究

Synthesis of p -substituted tetraphenylporphyrins and corresponding ferric complexes with mixed-solvents methodZhicheng SUN 1,Yuanbin SHE (✉)1,Rugang ZHONG 21Institute of Green Chemistry and Fine Chemicals,Beijing University of Technology,Beijing 100124,China 2College of Life Science &Bioengineering,Beijing University of Technology,Beijing 100124,China©Higher Education Press and Springer-Verlag 2009Abstract By using mixed-solvents method,five kinds of p -substituted tetraphenylporphyrin compounds [T(p -R)PPH 2,R =NO 2,Cl,CH 3,OCH 3,OH]were synthesized by the condensation of p -substituted benzaldehyde with pyrrole in mixed solvents (propionic acid,acetic acid and nitrobenzene),and corresponding ferric complexes [T(p -R)PPFe III Cl]were synthesized in dimethylformamide.The above free base porphyrins were obtained in 30%–50%yields,metalation yields were up to 90%and total yields of ferric complexes were 27%–50%.Effects of reactive conditions,solvents and oxidants on yields of free base porphyrins were investigated and the relevant mechanism was discussed.Structures of the above porphyrin complexes were characterized by ultraviolet-visible (UV-Vis),infrared (IR)and far infrared (FIR)spectroscopy.Keywords porphyrin,metalloporphyrin,mixed-solvents,synthesis,characterization1IntroductionSubstituted tetraphenylporphyrin complexes with conju-gated macrocycles have been essential to the study of biomimetic chemistry in recent years [1–5].The porphyrin iron complexes are mostly used for the models of cytochrome P-450in which the dioxygen has been activated by metalloporphyrins under mild conditions [6,7].Based on that,the substituted metalloporphyrins present high catalytic activities and high selectivities in the catalytic oxidation of hydrocarbons without co-reducing reagents.So the catalytic effect of metalloporphyrins on the activity of inert C-H bonds has been given considerable attention [8].However,the yields of substituted tetraphenylporphyrin complexes are lower and the cost of synthesis is still expensive,which have exceedingly restricted their current applications.Herein,the study on ef ficient synthesis methods for improving the yields of metalloporphyrin complexes is obviously necessary.Chemists have developed a few synthetic methods to provide convenient access to synthesize substituent tetraphenylporphyrin complexes [9–11].The prevalent method of synthesis involves a mixed aldehyde condensa-tion with pyrrole via Adler method in re fluxing propionic acid [12].Nevertheless,several limitations remain on the scope of synthetic porphyrin chemistry.One of these is the synthesis of porphyrins with only one solvent, e.g.,propionic acid or dimethylformamide,which brings the problems of a higher boiling point and inconsistent polarity [13].Therefore,the porphyrin complexes are often with low yields and the synthetic method is not universal for porphyrin complexes with various substituents.In this paper,a series of para -substituted tetraphenyl-porphyrin compounds and the ferric complexes [T(p -R)PPFe III Cl]were synthesized by using mixed-solvents method (Scheme 1).Different reaction conditions were investigated and the yields of porphyrin complexes were improved remarkably.This approach proved to be effective for the synthesis of a varity of metalloporphyrins.2Experimental2.1Reagent and instrumentAll chemicals were obtained commercially and used as received unless otherwise noted.Pyrrole was redistilled before use.Dichloromethane was dehydrated.Neutral Al 2O 3was baked at 100°C for 5h.Ultraviolet-visible (UV-Vis)spectra were obtained on HITACHI U-3010.Infrared (IR)spectra were obtained onReceived September 18,2008;accepted November 10,2008E-mail:sheyb@Front.Chem.Eng.China 2009,3(4):457–461DOI 10.1007/s11705-009-0169-6Nicolet A V ATAR-360.Far Infrared (FIR)spectra were recorded on Brucker VERTEX 70.2.2Synthesis of porphyrin and metalloporphyrinSynthesis of T(p -R)PPH 2[e.g.T(p -NO 2)PPH 2].40mL of propionic acid,20mL of nitrobenzene and 20mL of acetic acid were added to a 250mL flask.The mixture was allowed to re flux and was stirred for 30min.To the solution,10mmol of substituted benzaldehyde in 20mL of propionic acid was slowly added.Then 10mmol of freshly distilled pyrrole in 10mL of nitrobenzene was added simultaneously to the flask in 15min.The resulting mixture was heated at re flux for 2h.When the temperature of the flask dropped to 50°C –60°C,30mL of methanol was added to the solution.After that,the solution was filtrated under reduced pressure and afforded the blue-purple power.Puri fication by column chromatography (Al 2O 3,CH 2Cl 2as the eluent)afforded above 30%yield of T(p -R)PPH 2.Synthesis of T(p -R)PPFeCl [e.g.T(p -NO 2)PPFeCl].To the solution of 0.2mmol of T(p -R)PPH 2in 30mL dimethylformamide,2mmol of FeCl 2$4H 2O in three portions over 30min was added.The mixture was re fluxedand the reaction process was monitored by thin-layer chromatography (TLC)whenever possible.When TLC indicated no free base porphyrin the reaction was stopped.The resulting mixture was cooled to 50°C –60°C and 40mL 6mol/L of HCl was added to the solution.The solid in the solution was filtrated and washed with 3mol/L of HCl until the filtrate no longer appeared green.The resulting solid was vacuum-dried and afforded above 90%yield of T(p -R)PPFeCl.The structures of the above porphyrins were characterized by UV-Vis,IR and FIR.3Results and discussion3.1Structure characterization of porphyrins and metalloporphyrinsThe characterization results of T(p -R)PPH 2and T(p -R)PPFeCl are listed in Table 1.In Table 1,When free base porphyrins formed metalloporphyrin complexes through metal ions inserting into the porphyrin ring and bonding four N atoms,the numbers and intensity of the Q band decreased obviously and the soret band showed a slightly red shift from 418toScheme 1Synthesis of para -substituted tetraphenylporphyrin complexes458Front.Chem.Eng.China 2009,3(4):457–461420nm(for example T(p-Cl)PPH2and T(p-Cl)PPFeCl). The reason might be that the structural symmetry with the C4v point group of metalloporphyrin compounds was improved and the gap in the energy level decreased compared with that of free base porphyrins with the D2h point group.Therefore,the UV-Vis spectrum of metallo-porphyrin was different from that of free base porphyrin. IR spectrum clearly showed the different absorption frequencies for functional groups of metalloporphyrin pared with free base porphyrin com-plexes,as the N–H bond stretching frequency located at 3300cm–1of free base porphyrin complexes disappeared,the vibrations of the characteristic functional group Fe-porphyrin rings located at1000cm–1were seen,which indicated the formation of para-substituted tetraphenyl-porphyrin iron complexes.The absorptions located at about360cm–1were axial Fe–Cl bond vibrational frequencies of para-substituted porphyrin complexes[14]. The above results showed that the synthetic complexes were the products,as expected.3.2Effect of reactive conditions on yield of porphyrin and metalloporphyrinThe free base porphyrins were synthesized by using mixed-solvents method and the yields were higher than those from other general methods such as Adler method. The comparison of yields using the two synthetic methods is shown in Table2.From Table2,it can be seen that the synthetic method was improved by mixed-solvents method and the yields of substituted tetraphenylporphyrins were obviously higher (from30.2%to50.1%)than those of Adler method(from 6.1%to17.0%).In Adler method,the propionic acid played a role of catalyst besides being a solvent,but its polarity was unchangeable and the boiling point was higher,which resulted in the impurity of the product and the starting materials being dipyrrins[12].In addition,the oxidant had an important effect on the purity and yield of the product. The reaction intermediate was oxidized by the oxygen in air in Adler method and the oxidation was not absolute so that the yields of substituted tetraphenylporphyrins were lower.The conversion of para-substituted benzaldehyde and pyrrole to free base porphyrin was a multistep process,and slight variations in solvent,temperature and oxidant brought great impact on the yield and purity of the product.By mixing propionic acid,acetic acid and nitrobenzene in different proportions,the dipyrrins were prevented from formation and the reaction time was decreased.Moreover,the reaction produced an intermedi-ate(porphyrinogen)and a byproduct(dihydroporphyrin, TPC)which were usually difficult to oxidize.The structures of porphyrinogen and TPC are shown in Fig.1. The condensation of para-substituted benzaldehyde and pyrrole required an excellent oxidant because the oxidation of porphyrinogen and TPC determined the formation of porphyrins.The efficient synthesis of p-substituted tetraphenylpor-phyrin compounds with mixed-solvents method was not only of universal value for the preparation of symmetrical porphyrin compounds but also for theoretical reasons for the higher yields of porphyrins.By changing the ratio of mixed solvents(propionic acid,acetic acid and nitroben-zene),the acidity(p K a=3.2)of the reaction system was adjusted and the protonation of the reactant was moder-ated.Further,the polarity of mixed solvents could be adjusted to accelerate the formation of porphyrin and was fit for the extract of the product after stilling for severalTable1Data of UV-Vis,IR and FIR of T(p-R)PPH2and T(p-R)PPFeClentry compound l max/(CH2Cl2,nm)IR/cm–1FIR/(νFe–Cl,cm–1) 1T(p-NO2)PPH2424,516,551,594,6042924,1595,1347,966,800–2T(p-Cl)PPH2418,514,549,589,6453315,1559,1348,965,796–3T(p-CH3)PPH2419,516,551,592,6473328,1560,1350,967,798–4T(p-OCH3)PPH2421,518,555,593,6503320,1606,1350,967,805–5T(p-OH)PPH2417,513,551,592,6463427,1606,1350,967,804–6T(p-NO2)PPFeCl422,514,5832925,1595,1346,999,8023687T(p-Cl)PPFeCl420,509,5733133,1593,1335,998,8013598T(p-CH3)PPFeCl418,452,5113022,1494,1338,999,7993609T(p-OCH3)PPFeCl421,509,5712923,1604,1337,997,81035910T(p-OH)PPFeCl418,5033424,1603,1336,998,809336Table2Comparison of synthetic yields between two methodsentry compound ratio of mixedsolvent(V/V)a)yield/(mixedsolvents method,%)yield/(Adlermethod,%)1T(p-NO2)PPH260∶20∶3030.2 6.12T(p-Cl)PPH260∶20∶3050.116.83T(p-CH3)PPH240∶10∶2037.017.04T(p-OCH3)PPH240∶20∶2044.513.75T(p-OH)PPH240∶20∶2035.713.2a)Ratio of mixed solvents represents the mixture ratio of propionic acid,glacialacetic acid and nitrobenzeneZhicheng SUN et al.p-Substituted tetraphenylporphyrins and corresponding ferric complexes459hours.The mixed solvents might increase the solubility of the by-product so as to separate the porphyrin easily.Next,the boiling point of the reaction system might be controlled by mixing different solvents and altering the ratio of solvents.In summary,the yields of porphyrins were improved obviously by using two kinds of organic carboxylic acids as catalyst and nitrobenzene as oxidant.Based on the synthesis of free base porphyrins by mixed-solvents method,the yields of para -substituted metalloporphyrins are shown in Table 3.By using free base porphyrin to synthesize metalloporphyrin,the metal ion was almost absolutely inserted in the porphyrin ring and the yields of products were higher.4ConclusionsFive kinds of para -substituted tetraphenylporphyrin com-pounds and corresponding porphyrin iron complexes were obtained by mixed-solvents method.The experiment results showed that the para -substituted tetraphenylpor-phyrin compounds in mixed solvents formed crystals easily and the yields were higher.By using nitrobenzene as oxidant,the yields of porphyrins were doubled compared with those of the reaction system without nitrobenzene.Therefore,the optimum method for synthesizing metallo-porphyrins involved a two-step process of the synthesis of free base porphyrins and the metalation approach.Acknowledgements This work was supported by the Project of the National Natural Science Foundation of China (Grant Nos.20776003,20576005)and the Key Project of Natural Science Foundation of Beijing (No.2061001).References1.Haber J,Matachowski L,Pamin K,Poltowicz J.The effect of peripheral substituents in metalloporphyrins on their catalytic activity in Lyons system.J Mol Catal A Chem,2003,198(1–2):215–2212.Tagliatesta P,Pastorini A.Remarkable selectivity in the cyclopro-panation reactions catalysed by an halogenated iron meso -tetraphenylporphyrin.J Mol Catal A Chem,2003,198(1–2):57–613.Zakharieva O,Trautwein A X,Veeger C.Porphyrin-Fe(III)-hydroperoxide and 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