卟啉及铁卟啉的合成方法研究

1、 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 &Bioen

2、gineering, Beijing University of Technology, Beijing 100124, China©Higher Education Press and Springer-Verlag 2009Abstract By using mixed-solvents method, ve kinds of p -substituted tetraphenylporphyrin compounds T(p -RPPH 2, R =NO 2, Cl, CH 3, OCH 3, OHwere synthesized by the condensation of p

3、 -substituted benzaldehyde with pyrrole in mixed solvents (propionicacid, acetic acid and nitrobenzene, and corresponding ferric complexes T(p -RPPFe III Clwere synthesized in dimethylformamide. The above free base porphyrins were obtained in 30% 50%yields, metalation yields were up to 90%and total

4、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 (IRand f

5、ar infrared (FIRspectroscopy.Keywords porphyrin, metalloporphyrin, mixed-solvents, synthesis, characterizationSubstituted 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 u

6、sed 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 reage

7、nts. 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 appli

8、cations. Herein, the study on ef cient 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 sy

9、nthesis involves a mixed aldehyde condensa-tion with pyrrole via Adler method in re uxing 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 dimethylforma

10、mide, 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-por

11、phyrin compounds and the ferric complexes T(p -R PPFe III Clwere synthesized by using mixed-solvents method (Scheme1. 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

12、metalloporphyrins.2.1Reagent 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°Cfor 5h.Ultraviolet-visible (UV-Visspectra were obtained on HITACH

13、I U-3010. Infrared (IRspectra were obtained onReceived September 18, 2008; accepted November 10, 2008E-mail:sheybFront. Chem. Eng. China 2009, 3(4:457 461DOI 10.1007/s11705-009-0169-6Nicolet A V ATAR-360. Far Infrared (FIRspectra were recorded on Brucker VERTEX 70.2.2Synthesis of porphyrin and metal

14、loporphyrin Synthesis of T(p -RPPH 2e.g.T(p -NO 2PPH 2.40mL of propionic acid, 20mL of nitrobenzene and 20mL of acetic acid were added to a 250mL ask. The mixture was allowed to re ux and was stirred for 30min. To the solution, 10mmol of substituted benzaldehyde in 20mL of propionic acid was slowly

15、added. Then 10mmol of freshly distilled pyrrole in 10mL of nitrobenzene was added simultaneously to the ask in 15min. The resulting mixture was heated at re ux for 2h. When the temperature of the ask dropped to 50°C 60°C,30mL of methanol was added to the solution. After that, the solution

16、was ltrated under reduced pressure and afforded the blue-purple power. Puri cation by column chromatography(Al2O 3, CH 2Cl 2as the eluent afforded above 30%yield of T(p -RPPH 2.Synthesis of T(p -RPPFeCl e.g.T(p -NO 2PPFeCl.To the solution of 0.2mmol of T(p -RPPH 2in 30mL dimethylformamide, 2mmol of

17、FeCl 2$4H 2O in three portions over 30min was added. The mixture was re uxed and the reaction process was monitored by thin-layer chromatography (TLCwhenever possible. When TLC indicated no free base porphyrin the reaction was stopped. The resulting mixture was cooled to 50°C 60°Cand 40mL

18、6mol/Lof HCl was added to the solution. The solid in the solution was ltrated and washed with 3mol/Lof HCl until the ltrate no longer appeared green. The resulting solid was vacuum-dried and afforded above 90% yield of T(p -RPPFeCl. The structures of the above porphyrins were characterized by UV-Vis

19、, IR and FIR. 3.1Structure characterization of porphyrins and metalloporphyrinsThe characterization results of T(p -RPPH 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 f

20、our N atoms, the numbers and intensity of the Q band decreased obviously and the soret band showed a slightly red shift from 418 to420nm (forexample T(p -ClPPH 2and T(p -ClPPFeCl. The reason might be that the structural symmetry with the C 4v point group of metalloporphyrin compounds was improved an

21、d the gap in the energy level decreased compared with that of free base porphyrins with the D 2h 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 m

22、etalloporphyrin complexes. Compared 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 at 1000cm 1were seen, which indicated the for

23、mation of para -substituted tetraphenyl-porphyrin iron complexes. The absorptions located at about 360cm 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 react

24、ive 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 Table 2.From T

25、able 2, 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%to 50.1% than those of Adler method (from 6.1%to 17.0%.In Adler method, the propionic acid played a role of catalyst besides bein

26、g 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

27、 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 o

28、xidant 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 (porphyrinogenand a b

29、yproduct (dihydroporphyrin, TPC which were usually dif cult 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

30、 porphyrins.The ef cient 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

31、solvents (propionicacid, acetic acid and nitroben-zene, the acidity (pK 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 t for the extract of the p

32、roduct after stilling for severalTable 1Data of UV-Vis, IR and FIR of T(p -RPPH 2and T(p -RPPFeClentry compound l max /(CH2Cl 2, nm IR/cmFIR/(Fe Cl , cm 1T(p -NO 2PPH 2424, 516, 551, 594, 6042924, 1595, 1347, 966, 8002T(p -ClPPH 2418, 514, 549, 589, 6453315, 1559, 1348, 965, 796 3T(p -CH 3PPH 2419,

33、516, 551, 592, 6473328, 1560, 1350, 967, 798 4T(p -OCH 3PPH 2421, 518, 555, 593, 6503320, 1606, 1350, 967, 805 5T(p -OHPPH 2417, 513, 551, 592, 6463427, 1606, 1350, 967, 804 6T(p -NO 2PPFeCl 422, 514, 5832925, 1595, 1346, 999, 802368 7T(p -ClPPFeCl 420, 509, 5733133, 1593, 1335, 998, 801359 8T(p -CH

34、 3PPFeCl 418, 452, 5113022, 1494, 1338, 999, 799360 9T(p -OCH 3PPFeCl 421, 509, 5712923, 1604, 1337, 997, 810359 10T(p -OHPPFeCl 418, 5033424, 1603, 1336, 998, 809336Table 2Comparison of synthetic yields between two methodsentry compound ratio of mixed solvent (V/Vayield/(mixedsolvents method, %yiel

35、d/(Adler method, %1T(p -NO 2PPH 260 20 3030.26.1 2T(p -ClPPH 260 20 3050.116.8 3T(p -CH 3PPH 240 10 2037.017.0 4T(p -OCH 3PPH 240 20 2044.513.7 5T(p -OHPPH 240 20 2035.713.2 a Ratio of mixed solvents represents the mixture ratio of propionic acid, glacial acetic acid and nitrobenzeneZhicheng SUN et

36、al. p -Substituted tetraphenylporphyrins and corresponding ferric complexes 459hours. 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 alterin

37、g 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

38、 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.Five kinds of para -substituted tetraphenylporphyrin com-pounds and corresponding porphyrin iron complexes were ob

39、tained 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 s

40、ystem 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 (G

41、rantNos. 20776003, 20576005 and the Key Project of Natural Science Foundation of Beijing (No.2061001.1. 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. Ta

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43、ytic intermediates in cytochrome P450-catalyzed hydroxylation reac-tions:a molecular orbital study. Biophysical Chemistry, 2000, 88(1 3:11 344. Davydov R, Makris T M, Kofman V, Werst D E, Sligar S G, Hoffman B M. Hydroxylation of camphor by-reduced oxy-cytochrome P450cam:Mechanistic implications of

44、EPR and ENDOR studies of catalytic intermediates in native and mutant enzymes. J Am Chem Soc, 2001, 123(7:1403 14155. Guo C C, Liu Q, Wang X T, Hu H Y. Selective liquid phase oxidation of toluene with air. Applied Catalysis A-General, 2005, 282(1 2:55 596. Yuan Y, Ji H B, Chen Y X, Han Y, Song X F,

45、She Y B, Zhong R G. Oxidation of cyclohexane to adipic acid using Fe-porphyrin as a biomimetic catalyst. Org Process Res Dev, 2004, 8(3:418 4207. Wang L Z, She Y B, Zhong R G, Ji H B, Zhang Y H, Song X F. A green process for oxidation of p -nitrotoluene Catalyzed by metalloporphyrins under mild conditions. Org Process Res Dev,Table 3Metalation yield and total yield of para -substituted metallo-porphyrinentry compound metalation yield/%total yield /(two-step,%1T(p -NO 2PPFeCl 92.027.82T(p -ClPPFeCl 99.549.83T(p -CH 3PPFeCl 90.433