Novel hexadeca substituted phthalocyanines containing naphthoxy or quinolinoxy groups

Phthalocyanines (Pc's) and porphyrins (P's), as the most common and important tetrapyrrole derivatives have been at the focus of multidisciplinary interests for more than one century. Porphyrins are either naturally occuring molecular systems or original synthetic products, whereas phthalocyanines derive exclusively from synthetic laboratory work. Phthalocyanines were discovered by accident at the beginning of the 20th century. The word "phthalocyanine" is derived from the combination of Greek words 'naphtha' (rock oil) and 'cyanine' (dark blue) and it was first used by Prof. Reginald P. Linstead of the Imperial College of Science and Technology in 1933 to describe a new series of organic compounds. Phthalocyanines are 18 -electron aromatic macrocycles comprising four isoindole units linked together through their 1,3-positions by aza bridges. Phthalocyanine and its derivatives are a class of organic functional materials that display interesting catalytic, optical, and electronic properties in addition to their widespread use as blue and green colorants. Apart from their traditional use as dyes and pigments, during the last few years, phthalocyanines have been intensively studied due to their applications in many scientific areas such as photoconducting agents in photocopying devices, chemical sensors, data storage systems, electrocatalyst, electrochromic materials, liquid crystals, non-linear optical devices and photodynamic therapy. Most of the applications of phthalocyanines derive from their characteristic -conjugation systems. Dyeing stuff properties result from intense colors even in very small amount due to high molar extinction coefficient and also to be used as a photodynamic therapy agent is based on that having 18-π electron system's activation-deactivation ability by laser light. The catalytic activity of phthalocyanines is used to convert and to remove unwanted sulfur effluents to less deleterious disulphides and sulphates in oil sweetening. These intensely colored Pc compounds exhibit a pronounced aromatic character according to the Hückel rule. The combination of aromaticity in an extended π-system including four fused benzenoid aromatics is essential not only for strong color in the visible range of λ ~650-750 nm but also especially in the solid state for an excellent thermal and chemical stability of mostly planar Pcs. The Pc can contain in the center two protons or about 70 metals and metalloids as cations in different oxidation states. When compared to tetra- or octa-substituted phthalocyanines, the hexadeca-substituted phthalocyanines, especially those having three different substituents on each benzo group are relatively scarce studied. Within the scope of this study, the preparation of novel hexadeca amphiphilic metallo and metal-free phthalocyanines carrying two or three different substituents on each benzo group has been achieved by using microwave irradiation. As the introduction of hexyloxy, naphtoxy and quinolinoxy substituents, phthalocyanines become soluble both polar and apolar solvents. The introduction of these groups not only enhances the solubility, but also prevents its molecular aggregation in solution for steric reasons, thus potentially providing exceptional photophysical characteristics for PDT applications. In addition to that quaternized quinolinoxy substituents render them water solubility and amphiphilicity. In the first part of this thesis, we report on the synthesis and characterisation of zinc and metal-free phthalocyanines which carry hexyloxy groups on the non-peripheral positions and chloro groups on the peripheral positions. For this purpose, first we prepared 4,5-dichloro-3,6-dihydroxyphthalonitrile by reduction reaction of 2,3-dichloro-5,6-dicyano-1,4- benzoquinone with Na2S2O5. After that, 4,5-dichloro-3,6-bis(hexyloxy)phthalonitrile (1) was obtained through displacement reaction of 4,5-dichloro-3,6-dihydroxyphthalonitrile with 1-iodohexane in presence of tetrabutylammonium bromide in KOH solution at 120 oC for 6 hours. This reaction has been effectively used in the preparation of variety of alkyl and alkoxy phthalonitrile derivatives. In order to make a comparison between the influences of the substituents on the fluorescence, it was decided to synthesize pc derivatives of compound 1. The zinc phthalocyanine (2) was synthesized by cyclotetramerisation of 1 in anhydrous 1-hexanol using anhydrous zinc salt (Zn(CH3COO)2) and an N-donor base DBU at 160 oC for 18 hours. Compound 2 was purified by column chromatography on silica gel with 1:5 ethylacetate/n-hexane as the eluent and obtained in 15.5% yield. Cyclotetramerisation of the phthalonitrile derivative was confirmed by the disappearance of the sharp CN vibration of the reactant. The UV-Vis absorption spectra of zinc phthalocyanine 2 in THF exhibited intense Q absorption at 728 nm. Conversion of the dinitrile 1 into the metal-free Pcs (3) was accomplished in a mixture of 1-hexanol in the presence of lithium. Li2Pc complexes are unstable towards water and acid, and can easily be converted to the metal-free Pcs. In the 1H NMR spectrum of 2 and 3, chemical shifts due to the alkyl protons were observed between 4.33 and 0.93 ppm as expected. The second part in the synthesis of the target hexadeca substituted phthalocyanines was to obtain 4-chloro-5-(2-naphthoxy)-3,6-bis-(hexyloxy)phthalonitrile (4). Compound 4 was prepared by displacement of the one chloro group of 4,5-dichloro-3,6-bis(hexyloxy)phthalonitrile with the -OH function of the 2-naphthol at 45 oC in dry DMF under N2 atmosphere for 48 hours. The product was purified by recrystallization from hot ethanol and obtained as light yellow needle in 48% yield. In case of high temperature, both chloro groups were substituted and 4,5-bis(2-naphthoxy)-3,6-bis-(hexyloxy)phthalonitrile (11) was obtained. This was accomplished by base-catalyzed nucleophilic aromatic displacement reaction between 4,5-dichloro-3,6-bis(hexyloxy)phthalonitrile and 2-naphthol in dry DMF using potassium carbonate as the base at 110 oC for 8 h under N2 atmosphere. The product was purified by column chromatography on silica gel by using dichloromethane/petroluemether mixture as the eluent and obtained as dark yellow solid in 51% yield. Cyclotetramerization of phthalonitrile 4 in the presence of 1,8-diazobicyclo[5,4,0]- 7-ene and anhydrous metal salts [Zn(CH3COO)2, CoCl2, Cu(CH3COO)2, MnCl2, InCl3] at 160 oC in 1-hexanol for 20 minutes or 30 minutes under microwave irradiation gave metallophthalocyanines (5-9) respectively. The cyclization of 4 was achieved by using lithium in 1-hexanol, and then acidification with HCl resulted with the formation of metal-free derivative (10). Characterization of the products was carried out a combination of methods including FT-IR, elemental analysis, mass spectroscopy, UV-Vis spectroscopy, 1H NMR and 13C NMR. The symmetrically hexadeca-substituted metallophthalocyanines (Zn(II), Co(II), Cu(II)) (12-14) were obtained from the phthalonitrile derivative 11 and corresponding anhydrous metal salts (Zn(CH3COO)2, CoCl2 and Cu(CH3COO)2) catalyzed by DBU in 1-hexanol using microwave irradiation. Metal-free derivative (15) was accomplished in a mixture of 1-hexanol in the presence of lithium and then acidification with HCl. The newly synthesized phthalocyanines were obtained purely after column and/or preparative chromatography on silica gel by using THF/n-hexane, CHCl3, and CHCl3/n-hexane mixture as the eluents. The dark green products are extremely soluble in polar and apolar solvents such as acetone, CHCl3, CH2Cl2, THF, DMF and DMSO. In the third part of this work, we describe the synthesis and characterization hexadeca-substituted phthalocyanine derivatives, which carry 6-quinolinoxy groups on the peripheral and hexyloxy substituents on the non-peripheral positions. The latter phthalonitriles were designed to make phthalocyanines soluble in water by quaternization of quinolinoxy groups. The first part in the synthesis of the target water soluble phthalocyanines was to obtain 4-chloro-5-(6-quinolinoxy)-3,6-bis-(hexyloxy)phthalonitrile (16). Compound 16 was prepared by displacement of the one chloro group of 4,5-dichloro-3,6-bis(hexyloxy)phthalonitrile with the -OH function of the 6-hydroxyquinoline at 45 oC in dry DMF under N2 atmosphere for 24 hours. Compound 16 was purified by column chromatography on silica gel with 1:1 THF/n-hexane as the eluent and obtained in 49% yield. In case of high temperature, both chloro groups were substituted and 4,5-bis(6-quinolinoxy)-3,6-bis-(hexyloxy)phthalonitrile (22) was obtained. This was accomplished by base-catalyzed nucleophilic aromatic displacement reaction between 4,5-dichloro-3,6-bis(hexyloxy)phthalonitrile and 6-hydroxyquinoline in dry DMF using potassium carbonate as the base at 110 oC for 6 h under N2 atmosphere. Then, the hexadeca-substituted metallophthalocyanines (Zn(II), Mn(III), In(III)) (17, 19, 20) were prepared from the phthalonitrile derivative 16 and corresponding anhydrous metal salts catalyzed by DBU in 1-hexanol under microwave irradiation. The formation of metal-free phthalocyanine (21) was carried out by using lithium in 1-hexanol, and then acidification with HCl. Metal and metal-free phthalocyanines (17, 19-21) were obtained as a statistical mixture of four regioisomers owing to the various possible positions of the 6-quinolinoxy and chloro side-chains relative to one another. This new complexes show good solubility in organic solvents such as diethylether, CHCl3, THF, CH2Cl2. Intense stretching bands of NH groups appeared at 3297 cm-1 in the FT-IR spectrum of 21. MALDI-TOF mass spectra of the phthalocyanines the presence of the characteristic peaks at m/z = 2089.62 [M]+ (17), 2228.55 [M-Cl+DHB]+ (19), 2292.70 [M-Cl+DHB] + (20) and 2026.38 [M]+ (21) confirmed the proposed structure. The symmetrically hexadeca-substituted metallophthalocyanines (Zn(II), Mn(III)Cl) (23, 25) were obtained from the phthalonitrile derivative 22 and corresponding anhydrous metal salts (Zn(CH3COO)2, MnCl2) catalyzed by DBU in 1-hexanol under microwave irradiation. The cyclization of 22 by using lithium in 1-hexanol, and then acidificatian with HCl resulted with the formation of metal-free phthalocyanine (26). These phthalocyanines are soluble to a certain extent in polar and apolar solvents such as acetone, THF, diethylether, CHCl3, CH2Cl2, DMSO, and DMF. The structure of the synthesized compounds was characterized by FT-IR, 1H NMR, 13C NMR, UV-Vis and MALDI-TOF mass spectroscopic methods The IR spectrums of phthalocyanines 23, 25, 26 confirmed the structures of target compounds by exhibiting the disappearence of C≡N band at 2233 cm-1 and the presence of aromatic CH stretching bands at 3059 cm-1. Intense stretching bands of NH groups appeared at 3293 cm-1 in the FT-IR spectrum of 26. The absorption peaks belong to Q-band of 23, 25 and 26 observed around 732, 800 and 728 nm. Quaternarization of zinc phthalocyanines (17, 23) was achieved by reaction with excess methyl iodide as methylating agent in chloroform at room temperature in the dark for 5 days. The hygroscopic phthalocyanine products (18, 24) with four and eight quaternary ammonium groups were obtained in high yields (~ 50 %). Quaternized products were soluble in water, methanol and DMSO, but insoluble in chloroform. In conclusion, four novel phthalonitrile derivatives and twenty one new phthalocyanines were synthesized in this study. The influences of the substituents on the hexadeca-substituted phthalocyanine framework and metal ion on the spectroscopic and photophysical properties were investigated. The energy transfer to zinc (2, 5) and metal-free (3, 10) phthalocyanine core and radiative decays of the naphthol emission and phthalocyanine core were examined. In addition to redox active and inactive metal ion, electrochemical and spectroelectrochemical studies on 6-9 metallophthalocyanines were reported in this work. The fluorescence emission and excitation spectra of zinc phthalocyanine 23 and it's water soluble derivative 24 was also examined. The quenching effect of quaternized zinc phthalocyanine (24) on the fluorescence intensity and the interaction between 24 and DNA/BSA (bovine serum albumin) were investigated. The results indicated that this water soluble zinc phthalocyanine can be used for biological and medicinal applications.