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Syntheses of meso-Substituted Porphodimethenes and Porphyrins with Exocyclic Ring Systems


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SYNTHESES OF mesoSUBSTITUTED PORPHODIMETHENES AND PORPHYRINS WITH EXOCYCLIC RING SYSTEMS By PARUL ANGRISH A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE UNIVERSITY OF FLORIDA 2003

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Copyright 2003 by Parul Angrish

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Dedicated to my parents

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ACKNOWLEDGMENTS I take this opportunity to place on record my deep sense of gratitude to my advisor, Dr. Michael J. Scott, for introducing me to the exciting field of porphyrin chemistry I am deeply indebted for his guidance through my thesis and his valuable advice at all times. I am very much grateful to Hubert Gill and Ivana Boidarevi for their constant assistance and support in and outside the lab. I would like to acknowledge Dr. Michael Harmjanz, a former post doctoral fellow in the group, who started the whole project. I would like to thank Dr. Javier Santamaria in getting me started with the project. My thanks are due to the rest of the Scott group members for their constant love and encouragement. I am at a total loss of words in expressing the depth of my emotion for my parents and sisters for their constant support and inspiration. Last but not least, I am thankful to my friends, especially Shakti and Rishabh, for making me feel comfortable during the most difficult and trying moments of my life. iv

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TABLE OF CONTENTS page ACKNOWLEDGMENTS.................................................................................................iv LIST OF FIGURES..........................................................................................................vii ABSTRACT.......................................................................................................................ix CHAPTER 1 INTRODUCTION TO TETRAPYRROLIC MACROCYCLES.................................1 Types of meso-Substituted Porphyrins.........................................................................2 Syntheses of meso-Substituted Porphyrins...................................................................3 Rothemund Method...............................................................................................3 Adler Method.........................................................................................................4 Two-Step One-Flask Room-Temperature Synthesis of Porphyrin (Lindsey Method)..............................................................................................................5 MacDonald [2+2] Condensation Reaction............................................................7 Electronic Spectra of Porphyrins..................................................................................9 2 PORPHODIMETHENE MACROCYCLES AND THEIR PROPERTIES...............10 3 PORPHYRINS BEARING EXOCYCLIC RING SYSTEMS...................................12 4 EXPERIMENTAL PROCEDURES...........................................................................13 Syntheses....................................................................................................................13 Synthesis of 4, 7-Di-tert-butylacenaphthene, (1)................................................13 Synthesis of 4,7-Di-tert-butyl-acenaphthenylester, (2).......................................14 Synthesis of 4,7-Di-tert-butylacenaphthenol, (3)................................................15 Synthesis of 4,7-Di-tert-butylacenaphthylene-1,2-dione, (4)..............................15 Synthesis of anti, (5) and syn, (6) Substituted porphodimethene........................15 Synthesis of Nickel (II)-Substituted porphodimethene, (7)................................16 Syntheses of Nickel trans and cis bis-Substituted cycloheptanone porphyrins, (8 and 9)...........................................................................................................17 Synthesis of Nickel cisbis-Substituted azulenone porphyrin, (10)...................18 Synthesis of Nickel transSubstituted monoazulenone porphyrin, (11)............19 X-ray crystallography.................................................................................................20 v

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5 RESULTS AND DISCUSSIONS...............................................................................22 Syntheses of Porphodimethenes.................................................................................22 Metallation of Porphodimethene................................................................................25 Syntheses of bis-Cycloheptanone porphyrins.............................................................26 Metallation of anti-Substituted porphodimethene with Ni (II)...................................31 Synthesis of Nickel-bis-Substituted cycloheptanone porphyrins...............................33 Synthesis of Nickel-bis-Substituted azulenone Porphyrins........................................34 LIST OF REFERENCES...................................................................................................37 BIOGRAPHICAL SKETCH.............................................................................................39 vi

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LIST OF FIGURES Figure page 1-1 Examples of tetrapyrrolic macrocycles in nature.....................................................1 1-2 Examples of tetrapyrrolic macrocycles namely porphyrin, porphyrinogen porphodimethene and chlorin respectively..............................................................2 1-3 Types of porphyrins.................................................................................................2 1-4 Rothemund method for the synthesis of meso-substituted porphyrins....................3 1-5 Conversion of meso-substituted chlorin to the corresponding porphyrin................4 1-6 Adler method for preparing meso-substituted porphyrin.........................................4 1-7 Formation of octamethyltetraphenylporphyrinogen via Adler method...................5 1-8 Two-step one-flask room-temperature syntheses of meso-substituted porphyrins................................................................................................................7 1-9 Types of meso-substituted porphyrins.....................................................................7 1-10 MacDonald [2+2] condensation affording a trans-meso-substituted porphyrin......8 2-1 The two synthetic pathways to obtain porphodimethene skeleton........................10 2-2 Difference between the electronic spectra of porphyrin vs porphodimethene......11 5-1 Reductive alkylation of zinc octaethylporphyrin...................................................22 5-2 Reaction of ketones, exemplified acetone, with aryl dipyrromethanes.................23 5-3 Dealkylation of porphyrinogen..............................................................................23 5-4 Condensation reaction between acenaphthenequinone and 2 equivalents of 2-(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole.........................................................23 5-5 Lindseys methodology of MacDonald [2+2] condensation for trans-substituted porphyrins..............................................................................................................24 vii

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5-6 MacDonald [2+2] condensation reaction between 5-substituted, -unsubstituted dipyrromethanes with acenaphthenequinone.........................................................24 5-7 Metallation of Porphodimethene............................................................................25 5-8 Time course UV-Visible spectra of palladium anti-porphodimethene..................26 5-9 Syntheses of bis-Cycloheptanone porphyrins........................................................27 5-10 Oxidative dehydrogenation of bis-cycloheptanone porphyrins.............................29 5-11 Synthesis of 4, 7Di-t-butylacenaphthenedione involving (1) Friedel-Crafts alkylation, (2) Esterification, (3) Hydrolysis, (4) Oxidation reaction respectively............................................................................................................29 5-12 MacDonald [2+2] condensation reaction between 5-mesityl dipyrromethane and 4,7-Di-tert-butylacenaphthaquinone......................................................................31 5-13 Metallation of anti-Substituted porphodimethene with Nickel (II).......................32 5-14 Syntheses of Nickel-bis-Substituted cycloheptanone porphyrins..........................33 5-15 Synthesis of Nickel-cis-bis-Substituted-azulenone porphyrin...............................34 5-16 Synthesis of Nickel-trans-Substituted monoazulenone porphyrin........................35 5-17 ORTEP diagram of the solid-state structure of Nickel cis-bis-Substituted azulenone porphyrin (10).......................................................................................36 viii

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Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Master of Science SYNTHESES OF meso-SUBSTITUTED PORPHODIMETHENES AND PORPHYRINS WITH EXOCYCLIC RING SYSEMS By Parul Angrish December, 2003 Chair: Michael. J. Scott Major Department: Chemistry Porphodimethenes have been synthesized utilizing MacDonald [2+2] condensation between 5-substituted dipyrromethane and substituted aromatic vicinal diketones. These macrocycles can be easily metallated utilizing various metal salts in refluxing chloroform-methanol mixture. Metalloporphodimethene exhibits divergent properties as compared to metalloporphyrins. Metalloporphodimethenes undergo oxidative rearrangement in presence of light and DDQ, generating highly substituted nonplanar porphyrins, cycloheptanoneporphyrins. Cycloheptanoneporphyrins are further oxidatively dehydrogenated using DDQ and anhydrous FeCl 3 resulting in perfectly flat porphyrins with exocyclic ring systems. These porphyrins exhibit various interesting features in the UV-visible spectra including intense Q-bands in the low energy region, which are desirable in various materials and medicinal applications. ix

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CHAPTER 1 INTRODUCTION TO TETRAPYRROLIC MACROCYCLES Tetrapyrrolic macrocycles such as porphyrins, corroles, chlorins and bactereochlorins are widely available in nature, performing diverse functions like catalysis, light harvesting, dioxygen transport, and electron transfer. 1 Figure 1-1 illustrates examples of a naturally occurring porphyrin and chlorin used for dioxygen transport and light harvesting respectively. NNNNFeCOOHHOOCiron protoporphyrin IXNNNNMgCH=CH2C2H5C20H39O2COMeOOHChlorophylls Figure 1-1. Examples of tetrapyrrolic macrocycles in nature. Because of the diverse biological roles performed by these tetrapyrrolic macrocycle, extensive studies are performed on artificial systems in order to understand the chemistry of the various biological systems. Herein, different types of tetrapyrrolic macrocycles are described in figure 1-2 namely porphyrin, porphyrinogen porphodimethene and chlorin respectively. One of the most important tetrapyrrolic macrocycles in nature, porphyrin, is a conjugated, planar ligand that is ubiquitous in living systems. Variety of substituents 1

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2 attached to the porphyrin periphery enable porphyrins to act as potential structural tools in diverse fields. NHNNHNNHHNNHNHNHNNHNNHNNHN Figure 1-2. Examples of tetrapyrrolic macrocycles namely porphyrin, porphyrinogen porphodimethene and chlorin respectively. Types of meso-Substituted Porphyrins Porphyrins can be classified into two main categories based on the pattern of substituents attached to the macrocycle namely: meso-substituted porphyrins and substituted porphyrins (Figure 1-3). NHNNHNNHNNHNRRRRRRRRRRRR(1)(2) Figure 1-3. Types of porphyrins: (1) meso-substituted porphyrin, and (2) substituted porphyrin. The substituted porphyrins closely resemble naturally occurring porphyrins like Protoporphyrin IX 1 The meso-substituted porphyrins are not found in nature but have wide applications as biomimetic models and as useful components in material chemistry, photodynamic therapy, molecular recognition, catalysis, electron transfer etc. 1 Since these can be prepared by simple synthetic methodology, the substituents at the meso

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3 positions can be readily adjusted utilizing alkyl, aryl, heterocyclic or organometallic groups as well as other porphyrins. Syntheses of meso-Substituted Porphyrins Rothemund Method The chemistry of mesosubstituted porphyrins has its foundation in the work of Rothemund in 1935. 2 Rothemund performed the synthesis of meso-tetramethylporphyrin by utilizing the condensation reaction between acetalaldehyde and pyrrole in methanol at various temperatures (Figure 1-4). Sealed vessels were employed to avoid the loss of volatile acetaldehyde. The reaction was carried out in the absence of an oxidant. Various aldehydes like propionaldehyde, benzaldehyde, n-butyraldehyde, -furaldehyde were utilized using this methodology. 3 CHONH+NHNNHNPhPhPhPhMeOH Figure 1-4. Rothemund method for the synthesis of meso-substituted porphyrins, exemplified for meso-substituted tetraphenylporphyrin. However, careful analysis of the products showed the presence of second porphyrinic substance (10-25%). 3 The contaminant was isolated using column chromatography and was shown to consist of chlorins. 4-6 Fortunately, chlorins can be easily oxidized to the corresponding porphyrins (Figure 1-5). Rothemund employed various synthetic modifications in order to optimize the reaction conditions and finally settling on high concentration of the starting materials. However, low yields of the desired porphyrins were still obtained, thereby limiting the

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4 scope of application. Further improvements involving high temperature syntheses were also devised, thereby avoiding the solvent altogether. 7 [O]-2e-, -2H+NHNNHNPhPhPhPhNHNNHNPhPhPhPh Figure 1-5. Conversion of meso-substituted chlorin to the corresponding porphyrin. Adler Method In the mid 1960s, Adler and coworkers modified the syntheses of meso substituted porphyrins by performing the condensation reaction between benzaldeyde and pyrrole (0.02M) in a wide range of acidic solvents under refluxing conditions in open an atmosphere. The main solvents employed were acetic acid, acetic acid in the presence of a metal salt, or benzene containing chloroacetic acid or triflouroacetic acid. 8 The highest yield was reported using refluxing benzene containing chloroacetic acid and the lowest yields were reported for solvents containing metal salt. NHNNHNPhPhPhPhRCO2HReflux, 30 min.NH+CHO Figure 1-6. Adler method for preparing meso-substituted porphyrin, exemplified for meso-substituted tetraphenylporphyrin. Various kinetic studies were performed by Adler and coworkers in order to improve the syntheses of porphyrins and these suggested the yield of porphyrins were

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5 dependent on the choice of solvent, acidity of solvent, temperature and initial concentration of reactants. 9 The methodology was further improved by employing propionic acid (bp: 141C) in place of acetic acid (bp: 118C) as the solvent. After a short reflux of the higher concentrations of aldehydes and pyrrole, porphyrin crystals could be isolated upon cooling of the solution, filtration and washing. This modified synthesis proved to be an important improvement over Rothemunds methodology and is known as the Adler or AdlerLongo method (Figure 1-6). 10 The final porphyrin product was also found to be contaminated with chlorins and were removed using oxidizing agents like, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, commonly known as DDQ. 11,12 Further investigations on the course of reaction products under anaerobic conditions were studied. 13 The experiments performed strongly suggested that porphyrinogen, meso-tetrahydro-tetraalkyl(aryl)-porphyrin, is the key intermediate formed upon aldehyde and pyrrole condensation in the reaction leading to porphyrin (Figure 1-7). NHHNNHHNPhPhPhPhPh-CHO +NHCH3CO2H Figure 1-7. Formation of octamethyltetraphenylporphyrinogen via Adler method. Two-Step One-Flask Room-Temperature Synthesis of Porphyrin (Lindsey Method) The Adler or AlderLongo method provided syntheses of a variety of meso-substituted porphyrins, particularly tetra-arylporphyrins with diverse aryl substituents. In order to broaden the scope of substituents on available model systems, various new

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6 methodologies were developed. In 1980s, a new approach for the syntheses of meso-substituted porphyrins under gentle conditions was developed namely, two-step oneflask room temperature syntheses of porphyrins or the Lindsey method. 14,15 Various facts were considered while designing the above mentioned synthetic methodology. First, Rothemund and Adler-Longo methodology employed harsh reaction conditions leading to the formation of porphyrins in low yields. In addition, syntheses of porphyrins bearing sensitive functional groups could not be achieved. As a result of these drawbacks, the need to accomplish the condensation reaction under gentle conditions became an obvious choice. Secondly, mild conditions were also desirable in order to avoid all the side reactions leading to undesired oligomers and side products. The synthetic methodology developed by Lindsey involved a condensation reaction between an aldehyde and pyrrole to form porphyrinogen, followed by the oxidation step sequentially. The synthesis involved is as follows (Figure 1-8). A solution of pyrrole (10mM) and benzaldehyde (10mM) was added to dry CH 2 Cl 2, followed by the addition of triflouroacetic acid or BF 3 -etherate as catalyst. Subsequent addition of DDQ, induce the conversion of porphyrinogen to the porphyrin at room temperature. The compound was further purified using column chromatography allowing the isolation of porphyrin in 35-40 % yield. 16 Lindseys method has been applied to syntheses of wide variety of meso-substituted porphyrins. Yield up to 50% can be achieved depending on the choice of aldehyde and acid.

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7 NHNHHNNHHN3 DDQ3 DDQH24 R-CHO + 4ClClOHCNCNOHOOCNCNClClTFA or BF3 etherateCH2Cl2, 25C+ 4 H2ORHHRHRRHNHHNNHHNRHHRHRRHNHNNHNRRRR Figure 1-8. Two-step one-flask room-temperature syntheses of meso-substituted porphyrins. MacDonald [2+2] Condensation Reaction Utilizing Lindseys methodology, symmetrical porphyrins, A 4 type (Figure 1-9), are isolated. In order to synthesize the less symmetrical, trans-substituted porphyrins, A 2 B 2 type (Figure 1-9), synthetic pathway based on the MacDonald [2+2] condensation of a dipyrromethane and an aldehyde was designed, as shown in figure 1-10. 17, 18 NHNNHNNHNNHN A AAAABAB(1)(2) Figure 1-9. Types of meso-substituted porphyrins: (1) A 4 Type Porphyrin and (2) A 2 B 2 Type Porphyrin.

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8 However, the synthesis may yield in a mixture of porphyrins namely; cis-A 2 B 2 and trans-A 2 B 2 which are difficult to separate. The condensation reaction leading to the formation of porphyrinogen proceeds reversibly and the rearrangement of substituents is referred as scrambling. 19, 20 The success of MacDonald [2+2] condensation requires minimum scrambling of the acid catalyzed condensation of dipyrromethane and an aldehyde. Various studies were performed in order to understand the origin of scrambling and the means to control it. 20 In general, sterically unhindered aldehydes favors scrambling. The implementation of MacDonald [2+2] condensation also requires the synthesis of the dipyrromethane. 21 The synthesis of trans-meso-substituted porphyrins is important as these porphyrins can act as potential components for various model systems in material and medicinal applications. NHHNNHHN3 DDQ3 DDQH2NHNNHNArArRR2 Ar-CHO + 2ClClOHCNCNOHOOCNCNClClTFA or BF3 etherateCH2Cl2, 25C+ 2 H2OHRRHHArArHNHHNNHHNHRRHHArArHRNHHN Figure 1-10. MacDonald [2+2] condensation affording a trans-meso-substituted porphyrin.

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9 Electronic Spectra of Porphyrins The word porphyrin is derived from the Greek work porphura meaning purple which is appropriate since all porphyrins are intensely colored. 22 The electronic absorption spectra of porphyrin consists of a strong absorption band around 400 nm (Soret or B band) and a weak absorption band around 550 nm (Q-band). 23 These observed electronic transitions results from transitions and they can be explained using Gouterman four orbital model involving two nearly degenerate orbitals, (a 1u and a 2u ) and two degenerate lowest unoccupied orbitals, (e gx e gy ). Thus, in principle, two transitions should be observed at almost same energy resulting from excitation from the two highest occupied molecular orbitals to the degenerate lowest unoccupied molecular energy, and should finally result in a coincident transition. However, two transitions are observed due to configurational interactions resulting from electronic rearrangement of the excited state configuration. The configurations can mix with other configurations in the molecule having same symmetry. As a result of this mixing, the two lowest unoccupied molecular orbitals are no longer degenerate thus, giving rise to two transitions of different intensities and wavelengths.

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CHAPTER 2 PORPHODIMETHENE MACROCYCLES AND THEIR PROPERTIES Porphodimethenes can be obtained as intermediates in the oxidation of porphyrinogen to porphyrins and metalloporphyrins. In addition, they can also be obtained via reductive alkylation / protonation of porphyrin or oxidative dealkylation / deprotonation of the porphyrinogen (Figure 2-1). 24 NHNNHNNHNNNHNHNHNHNH-2H2+H2HHHHHHHHHHHHHHHHHH Figure 2-1. The two synthetic pathways to obtain porphodimethene skeleton. In porphodimethenes, the two non-adjacent meso-carbons are saturated, thereby introducing sp 3 hybridization into the ring. Although the two halves of the molecule are still planar and conjugated, there is disruption of electronic communication between the two dipyrromethene units of the macrocycle. Thus, macrocycle adopts a roof like folded structure. The lack of electronic communication between the two halves of the macrocycle severely alters the electronic absorption properties of the macrocycle. The Soret band, as observed in porphyrins, is replaced by a characteristic methane band at lower energy (420-470 nm) with smaller extinction coefficient and the porphyrin Qbands at lower energy disappear (Figure 2-2). 10

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11 300400500600700 AbsWavelength (nm) 300400500600700 Wavelength (nm)Abs NHNNHNNHNNNHMeMeMeMeMesMesPhPhPhPh(1)(2)(3)(4) Figure 2-2. Difference between the electronic spectra of porphyrin vs porphodimethene, exemplified using meso-tetraphenyl porphyrin, (1) and meso-tetramethylmesityl porphodimethene, (2). 1 UV-visible spectrum, (3) and (4) corresponding to (1) and (2) respectively. 2 1Krl, V.; Sessler, J. L.; Zimmermann, R. S.; Seidel, D.; Lynch, V.; Andrioletti, B. Angew. Chem. Int. Ed. 2000, 39, 1055. 2 The UV-Visible spectra were generated by H.Gill.

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CHAPTER 3 PORPHYRINS BEARING EXOCYCLIC RING SYSTEMS In recent years, porphyrins have been utilized in diverse fields. Consequently, porphyrins are now designed with wide variety of substituents at the porphyrin periphery, exhibiting different electronic, steric and solubility properties. These include expanded porphyrins where one or more macrocyclic atoms are replaced by heteroatoms and non planar porphyrins incorporating sterically demanding substituents at the porphyrin backbone. Herein, utilizing the MacDonald [2+2] condensation, the synthesis of porphodimethenes is presented, followed by the metallation of porphodimethene. Metalloporphodimethenes undergo oxidative rearrangement in presence of light and DDQ, resulting in the formation of highly substituted nonplanar porphyrins which are further oxidatively dehydrogenated, generating a perfectly flat porphyrins with exocyclic ring systems. These porphyrins exhibit various interesting features in the UV-visible spectra including intense Q-bands in the low energy region, which are desirable in various materials and medicinal applications. 12

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CHAPTER 4 EXPERIMENTAL PROCEDURES General procedures. NMR spectra were recorded on either a Gemini 300 MHz, a VXR 300 MHz and or a Varian Inova 500 spectrometers. UV-visible absorption spectra were recorded on a Varian Cary 50 (UV-Vis) or a Varian Cary 500 (UV-Vis-NIR) spectrometers. High and low resolution mass spectral analyses were performed by The University of Florida Mass Spectroscopy Services using FAB and DIOS as the ionization methods. The solvents were either ACS or HPLC grade and were used as received or were dried and degassed by standard procedures wherever needed. The reactions under anhydrous conditions were performed using standard Schlenk techniques. 5Mesityldipyrromethane was prepared by a in the literature procedure. 20 The syntheses of compound (1),(2) and (3) were adapted by Dr. Javier Santamaria from previous work. 32,33 The syntheses of compound (4),(5) and (6) were designed by Dr. Javier Santamaria. Chromatography. Absorption column chromatography was preformed using chromatographic silica gel (Fisher, 200 mesh) or neutral alumina (Aldrich, Brokman I approx. 158 mesh, 58. Syntheses Synthesis of 4, 7-Di-tert-butylacenaphthene (1) A portion of anhydrous AlCl 3 (5.22 g 0.04 mol) was added in small amounts to a well-stirred mixture of acenaphthene (30.0 g, 0.20 mol) and t-butyl chloride (36.0 g, 0.39 mol) in 300 mL of CS 2 over the period of 1 hour. The reaction mixture was refluxed for 3 hours and the solvent was then removed via distillation. The residue obtained was 13

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14 dissolved in methylene chloride (200 mL), followed by quenching of AlCl 3 using cold dilute hydrochloric acid (0.3N). The organic layer was washed with water (2 x), dried over sodium sulfate and the solvent was removed in vacuo. The residue was filtered over silica (methylene chloride), the solvent was removed yielding a colorless solid which upon recrystallization from EtOH afforded the title compound (1) as thin, colorless needles. Yield: 26.0g (50 %). 1 H NMR (300 MHz, CDCl 3 ): = 7.51 (s, 2H), 7.33 (s, 2H), 3.37 (s, 4H), 1.40 (s, 18H). 13 C NMR (75 MHz, CDCl 3 ): = 151.46, 145.24, 136.46, 130.91, 117.65, 117.57, 35.54, 31.91, 30.77. Synthesis of 4,7-Di-tert-butyl-acenaphthenylester (2) A portion of (1) (5.0 g, 0.06 mol) was dissolved in 450 mL of glacial acetic acid followed by the addition of lead oxide (45g, 0.07 mol) in portions over the course of 1h, thereby maintaining the temperature around 85-90C. Red lead was subsequently added provided the color due to the previous addition was discharged. The reaction mixture was stirred for an additional 30 min at 85-90C, cooled to rt, diluted with 200 mL of water, and extracted with methylene chloride (2 x). The organic layer was washed with saturated sodium bicarbonate solution (3 x) and water (2 x), dried over Na 2 SO 4 and the solvent was removed under pressure affording the desired compound (2) as yellow viscous oil having fruity smell. Yield: 15.0 g (82%). 1 H NMR (300 MHz, CDCl 3 ): = 7.72 (d, 1H, J = 1.2 Hz), 7.60 (s, 1H), 7.58 (s, 1H), 7.37 (s, 1H), 6.62 (dd, 1H, J 1 = 7.2 Hz, J 2 = 1.9 Hz), 3.83 (dd, 1H, J 1 = 17.9, J 2 = 7.4 Hz), 3.30 (d, 1H, J = 18.0 Hz), 2.11 (s, 3H), 1.42 (s, 9H), 1.41 (s, 9H). 13 C NMR (75 MHz, CDCl 3 ): = 171.63, 152.17, 152.13, 141.64, 140.69, 135.42, 130.88, 121.22, 120.27, 118.32, 118.50, 76.73, 39.66, 35.99, 35.93, 32.21, 32.05, 21.80.

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15 Synthesis of 4,7-Di-tert-butylacenaphthenol (3) A portion of (2) (15.0 g, 0.05 mol) was dissolved in MeOH (25 mL) followed by the addition of sodium hydroxide (3.60g, 0.09 mol) dissolved in water (36 mL). The reaction mixture was refluxed for 3 hours. The solution was cooled to 0C. The white solid obtained was filtered, dried to afford alcohol (3), as a white amorphous solid. Yield: 10.0g (77%). 1 H NMR (300 MHz, CDCl 3 ): 7.68 (s,1H), 7.60 (d, 1H, J = 1.2 Hz), 7.57 (s, 1H), 7.35 (d, 1H, J = 1.2 Hz), 5.70 (bs, 1H), 3.78 (dd, 1H, J 1 = 17.5 Hz, J 2 = 7.0 Hz), 3.21 (d, 1H, J = 17.0 Hz), 1.99 (bs, 1H), 1.40 (s, 9H), 1.39 (s, 9H). 13 C-NMR (75 MHz, CDCl 3 ): = 151.64, 151.56, 144.85, 140.60, 134.15, 130.39, 120.13, 118.30, 117.93, 117.76, 74.66, 42.08, 35.43, 35.36, 31.66, 31.58. Synthesis of 4,7-Di-tert-butylacenaphthylene-1,2-dione (4) A mixture of (3) (13.5 g, 0.05 mol) and 54 g (0.49 mol) of SeO 2 was refluxed in 350 mL of 1, 4Dioxane for 12 h. The solvent was removed by distillation, and the residue was dissolved in 200 mL CH 2 Cl 2 followed by filtration over a silica plug (10 x 5 cm) and eluted with CH 2 Cl 2 The solvent was removed and the residue was crystallized from hexanes, affording dione, (4), as yellow needles. Yield: 9.0 g (64%). 1 H NMR (300 MHz, CDCl 3 ): 8.20 (d, 2H, J = 1.5 Hz), 8.17 (d, 2H, J = 1.2 Hz), 1.46 (s, 18H). 13 C NMR (75 MHz, CDCl 3 ): = 188.79, 152.35, 143.43, 130.90, 128.00, 127.87, 119.97, 35.91, 31.43. Synthesis of anti (5) and syn (6) Substituted porphodimethene A portion of (4) (2.35 g, 8 mmol) and 2.10 g (8 mmol) of 5-mesityldipyrromethane were dissolved in 1L of CH 2 Cl 2 and 1.1 mL (1.7 equivalents) of TFA was added. The reaction mixture was allowed to stir at room temperature for 1 h followed by the addition

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16 of 1.82 g (8 mmol) of DDQ to the greenish-blue solution. The color of the solution changed from greenish-blue to deep-red. The mixture was stirred for an additional hour. The volume was reduced to 50%, and the mixture was loaded on a neutral alumina column and using CH 2 Cl 2 as the eluting solvent. The orange solution was collected and the solvent was removed. The residue obtained was washed with CH 2 Cl 2 filtered, the solid obtained was collected in a fritted funnel and dried under vacuum, yielding 600 mg (14%) of the anti isomer, (5). The solvent was removed from the filtrate, containing the syn isomer and the remaining soluble anti isomer. The remaining residue containing syn and anti isomers were separated by column chromatography (silica, toluene) yielding an additional 45 mg (1%) of (5). Elution with CH 2 Cl 2 afforded the syn isomer, (6). Yield: Anti isomer: 15% (645 mg). UV-Vis [CH 2 Cl 2 max(log )]: 437(4.9) nm. 1 H NMR (300 MHz, CDCl 3 ): = 13.69 (s, 2H), 8.43 (s, 2H), 8.14 (s, 4H), 7.83 (s, 2H), 6.80 (s, 4H), 6.16 (d, 4H, J = 4.0 Hz), 5.96 (d, 4H, J = 4.0 Hz), 2.23 (s, 6H), 2.02(s, 12H), 1.54 (s, 18H), 1.47 (s, 18H). Yield: Syn isomer: 10% (430 mg). UV-Vis [CH 2 Cl 2 max(log )]: 441(5.0) nm. 1 H NMR (300 MHz, CDCl 3 ): = 14.06 (s, 2H), 8.21 (d, 2H, J = 1.5 Hz), 8.10 (d, 2H, J = 1.2 Hz), 8.01 (d, 2H, J = 1.2 Hz), 7.88 (d, 2H, J = 1.2 Hz), 6.84 (s, 2H), 6.77 (s, 2H), 6.15 (d, 4H, J = 4.1 Hz), 5.92 (d, 4H, J = 4.1 Hz), 2.26 (s, 6H), 2.19 (s, 6H), 1.92 (s, 6H), 1.48 (s, 18H), 1.43 (s, 18H). Synthesis of Nickel (II)-Substituted porphodimethene (7) A saturated methanolic solution of NiCl 2 .6H 2 O (5mL) was added to a solution of (5) (100 mg, 0.093mmol) in CHCl 3 (70 mL) and the reaction mixture was heated to reflux. The reaction progress was monitored with TLC (silica, methylene chloride/hexanes, 1:1) and UV-visible spectroscopy. The reaction mixture was refluxed

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17 for 12 hrs, cooled to rt and washed with water (2 x). The organic phase was dried over Na 2 SO 4 and the solvent was removed. The desired compound was purified by column chromatography (silica, hexanes/CH 2 Cl 2 /CHCl 3 1:1:1). The solvent was removed and crystallized from hexanes affording the desired compound as microcrystalline red solid. Yield: 70% (74 mg). UV-Vis [CH 2 Cl 2 max (log )]: 442(4.6) nm. 1 H NMR (300 MHz, CDCl 3, 25C): = 8.25 (d, 2H, J = 1.5 Hz), 8.16 (s, 2H), 7.87 (d, 2H, J = 1.2 Hz), 6.80 (s, 4H), 6.25 (s, 4H), 5.83 (s, 4H), 2.26 (s, 6H), 1.50 (s, 18H). 1 H NMR (300 MHz, CDCl 3, 52C): = 8.25 (d, 2H, J = 1.5 Hz), 8.16 (d, 2H, J = 1.2 Hz), 7.87 (d, 2H, J = 1.2 Hz), 6.80 (s, 4H), 6.25 (d, 4H, J = 4.4 Hz), 5.84 (d, 4H, J = 4.4 Hz), 2.26 (s, 6H), 2.05 (bs, 12H), 1.64 (s, 18 H), 1.50 (s, 18H). 1 H NMR (300 MHz, C 6 D 6, 75C): = 8.33 (d, 2H, J = 1.5Hz), 8.03 (d, 2H, J = 1.5 Hz), 7.80 (d, 2H, J = 1.5 Hz), 6.64 (s, 4H), 6.37 (d, 4H, J = 4.4 Hz), 6.10 (d, 4H, J = 4.1 Hz), 2.09 (s, 6H), 1.98 (bs, 12H), 1.59 (s, 18H), 1.36 (s, 18H). 1 H NMR (300 MHz, C 7 D 8, -80C): = 11.26 (s, 1H), 8.60 (s, 1H), 8.34 (s, 1H), 8.10 (s, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.73 (s, 1H), 7.57 (s, 1H), 6.57 (s, 2H), 6.40 (s, 4H), 6.36 (s, 4H), 6.00 (s, 2H), 2.41 (s, 6H), 2.09 (s, 12H), 1.36 (s, 18H), 1.33 (s, 18H). LRMS (DIOS) calcd for [M+H] + (C 76 H 75 N 4 0 2 Ni): 1133.5. Found 1133.1. Isotope Distribution Confirmed. Syntheses of Nickel trans and cis bis-Substituted cycloheptanone porphyrins (8 and 9) A portion of (7) (90 mg, 0.088 mmol) and 32 mg (0.141mmol) of DDQ were dissolved in 150 mL of dry, degassed CH 2 Cl 2 under an inert atmosphere and the reaction mixture was irradiated with a light source. The reaction progress was monitored using TLC (silica, CH 2 Cl 2 /hexanes, 2:1) indicating the formation of two new compounds within first five minutes. The reaction mixture was stirred for another 25 minutes and

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18 TLC (silica, CH 2 Cl 2 /hexanes, 2:1) indicated the complete disappearance of the starting material along with the formation of two compounds. The reaction mixture was washed with water (2 x), dried over Na 2 SO 4 and the solvent was removed. Column chromatography (silica, CH 2 Cl 2 /hexanes, 2:1) yielded the trans isomer (8), as the first compound to elute followed by the cis isomer (9). The solvents were removed from fractions, trans and cis isomers, and were crystallized from hexanes to produce microcrystalline green solid and very fine needles respectively, and dried under vacuum. Yield: (8): 22 % (20 mg). UV-Vis [CH 2 Cl 2 (log )]: 476(5.2), 692(4.7), 884(4.0) nm. 1 H NMR (300 MHz, CDCl 3 ): = 9.43 (d, 2H, J = 2.4 Hz), 9.38 (s, 2H), 8.35 (s, 6H), 7.94 (d, 2H, J = 1.5 Hz), 7.30 (s, 2H), 7.0 (s, 2H), 6.60 (d, 2H, J = 2.1 Hz), 2.52 (s, 6H), 2.50 (s, 6H), 1.61 (s, 18H), 1.27 (s, 6H), 1.23 (s, 18H). HRMS (FAB) calcd for [M+H] + (C 76 H 73 N 4 O 2 Ni): 1131.5087. Found 1131.5090. Yield: (9): 44% (40 mg). UV-Vis [CH 2 Cl 2 (log )]: 494(5.1), 672(4.4) nm. 1 H NMR (300 MHz, CDCl 3 ): = 9.45 (s, 2H), 9.41 (d, 2H, J = 2.4 Hz), 8.36 (d, 2H, J = 2.3 Hz), 8.32 (s, 4H), 8.0 (d, 2H, J = 2.1 Hz), 7.37 (s, 1H), 7.29 (s, 1H), 7.08 (s, 1H), 6.96 (s, 1H), 6.76 (d, 2H, J = 2.1 Hz), 2.71 (s, 3H), 2.57 (s, 3H), 2.51 (s, 3H), 2.32 (s, 3H), 1.62 (s, 18H), 1.40 (s, 3H), 1.33 (s, 18H), 1.18 (s, 3H). HRMS (FAB) calcd for [M+H] + (C 76 H 73 N 4 O 2 Ni): 1131.5087. Found 1131.5028. Synthesis of Nickel cisbis-Substituted azulenone porphyrin (10) A portion of DDQ (10 mg, 0.044 mmol) and FeCl 3 .6H 2 O (48 mg, 0.179 mmol) were added to 20 mg (0.018 mmol) of (9) dissolved in dry degassed CH 2 Cl 2 (25 mL), under an inert atmosphere. The reaction mixture was heated to reflux with stirring and progress was monitored using TLC (silica, CH 2 Cl 2 /hexanes, 1:1). After 15 minutes TLC

PAGE 28

19 indicated the formation of the desired compound. An additional fraction of 10 mg (0.044 mmol) of DDQ was then added to the flask. After 10 minutes, TLC indicated the complete disappearance of the starting material. The reaction mixture was washed with water (2 x), dried over Na 2 SO 4 and the solvent was removed. The desired compound was purified by column chromatography (silica, CH 2 Cl 2 /hexanes, 1:1) and slow removal of the solvents afforded the desired compound as a purple-black microcrystalline solid. Single crystals suitable for X-ray diffraction were grown by diffusion of pentanes into a saturated methylene chloride solution. Yield: 75% (15 mg). UV-Vis [CHCl 3 (log )]: 454(4.8), 513(4.8), 558(4.8), 846(4.2) nm. 1 H NMR (300 MHz, CDCl 3 ): = 8.71 (d, 2H, J = 2.3Hz), 8.46 (s, 2H), 7.60 (d, 2H, J = 2.4 Hz), 7.30 (s, 2H), 7.08 (s, 4H), 6.73 (s, 2H), 2.50 (s, 3H), 2.49 (s, 3H), 2.15 (s, 6H), 1.85 (s, 6H), 1.44 (s, 18H), 1.40 (s, 18H). HRMS (FAB) calcd for [M+H] + (C 76 H 69 N 4 O 2 Ni): 1127.4774. Found 1127.4786. Synthesis of Nickel transSubstituted monoazulenone porphyrin (11) A portion of DDQ (30 mg, 0.133 mmol) and FeCl 3 .6H 2 O (80 mg, 0.298 mmol) were added to 20 mg (0.018 mmol) of (8) dissolved in dry degassed CH 2 Cl 2 (25 mL) under an inert atmosphere. The reaction mixture was heated to reflux with stirring and progress was monitored using TLC (silica, CH 2 Cl 2 /hexanes, 1:1). After 3 h, additional amounts of DDQ (15 mg, 0.066 mmol) and FeCl 3 .6H 2 O (80 mg, 0.298 mmol) were added. Refluxing was continued for another 1 h. The reaction mixture was allowed to cool down to room temperature and washed with 25 mL of a freshly prepared aqueous solution containing 50 mg of NaBH 4 The resulting mixture was diluted with CH 2 Cl 2 (20 mL). The organic phase was washed with water (3 x), dried over Na 2 SO 4 and the solvent was removed. The compound was purified by column chromatography (silica,

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20 CH 2 Cl 2 /hexanes, 1:1). The solvents were removed, and the compound was crystallized from hexanes yielding reddish brown colored microcrystalline solid. Yield: 50% (10 mg). UV-Vis [CHCl 3 (log )]: 467(5.1), 579(4.7), 650(4.2), 832(4.3), 884(4.3) nm. 1 H NMR (300 MHz, CDCl 3 ): = 9.28 (d, 1H, J = 2.4 Hz), 8.77 (d, 1H, J = 2.6 Hz), 8.75 (d, 2H, J = 1.0 Hz), 8.31 (d, 1H, J = 2.4 Hz), 8.02 (d, 1H, J = 2.1 Hz), 7.84 (d, 1H, J = 5.0 Hz), 7.66 (d, 1H, J = 5.0 Hz), 7.60 (d, 1H, J = 2.1 Hz), 7.26 (s, 2H), 7.16 (s, IH), 7.12 (s, 1H), 7.10 (s, 1H), 7.03 (s, 1H), 6.90 (d, 1H, J = 2.1 Hz), 2.53 (s, 3H), 2.51 (s, 3H), 2.31 (s, 3H), 2.17 (s, 3H), 1.89 (s, 3H), 1.58 (s, 9H), 1.57 (s, 3H), 1.51 (s, 9H), 1.44 (s, 9H), 1.34 (s, 9H). HRMS (FAB) calcd for [M+H] + (C 76 H 71 N 4 O 2 Ni): 1129.4931. Found 1129.4830. X-ray crystallography Unit cell dimensions (Table 5-1) and intensity data were obtained by Prof. Michael. J. Scott on a Siemens CCD Smart diffractometer at 0C, with monochromatic Mo-K X-rays ( = 0.71073). The data collections nominally covered over a hemisphere of reciprocal space, by a combination of three sets of exposures; each set had a different angle for the crystal and each exposure covered 0.3 in The crystal to detector distance was 5.0 cm. The data sets were corrected empirically for absorption using SADABS. 35 The structure was solved using the Bruker SHELXTL software package for the PC, using the direct method option of SHELXS. The space group was determined from an examination of the systematic absences in the data, and the successful solution and refinement of the structure confirmed these assignments. All the hydrogen atoms were assigned idealized locations and were given thermal parameter equivalent to 1.2 to 1.5 times the thermal parameter of the carbon atom to which it was attached. Relevant crystallographic data are listed in Table 4-1.

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21 Table 4-1. X-ray data for crystal structure of compound (10).2CH 2 Cl 2 .1/2 Et 2 O Chemical Formula C 80 H 77 Cl 4 N 4 Ni O 2.50 Formula Weight 1334.97 Crystal System Monoclinic Space Group C2/c Z 8 Temp, K 173(2) D calc /gcm -3 1.206 a 29.4311(14) b 12.3021(6) c 41.325(2) deg 100.622(10) V A 14705.9(12) mm -1 0.457 Uniq. Data coll./obs. 17219/8058 R1 0.0560 wR2 0.1141

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CHAPTER 5 RESULTS AND DISCUSSIONS Syntheses of Porphodimethenes Buchler et al. extensively studied the chemistry of porphodimethenes but were only able to achieve the synthesis of porphodimethene via reductive alkylation of porphyrins (Figure 5-1). 25 This method yielded various isomeric products which were difficult to separate, thus lowering the yield of the preferred compound. In addition, the methodology is ill-suited for the synthesis of porphodimethene having aryl-substituents at all the four meso positions, thereby, limiting the ability to modify the macrocycle to investigate the electronic, steric and solubility properties of the resulting products. NNNN1. 2e-2. R-XNNNNRHRH(R = alkyl, X = Br, I)ZnZn Figure 5-1. Reductive alkylation of zinc octaethylporphyrin. 25 In recent years, several new synthetic routes for the synthesis of porphodimethenes have been reported. These include: condensation of pyrrole with sterically encumbered aldehydes, the reaction of ketones with aryl dipyrromethanes (Figure 5-2) 26 and dealkylation of porphyrinogen (Figure 5-3), 27 but these procedures are applicable only for the synthesis of meso-alkyl substituted porphodimethenes rather than meso-aryl substituted. 22

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23 ArNHHNNHNNNH A r A r + 1. acid2. DCQO 40 fold excess2 Figure 5-2. Reaction of ketones, exemplified acetone, with aryl dipyrromethanes. 26 NNNNSnRRRRRRRRNNNNSnRRRRRRSnCl4(THF)2ClClTHFTHF(R=alkyl) Figure 5-3. Dealkylation of porphyrinogen. 27 In 1986, Chang and co-workers demonstrated the condensation reaction between acenaphthenequinone and 2 equivalents of 2-(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole to yield the corresponding dipyrromethane (Figure 5-4). 28 In this paper, Chang reported that acenaphthenequinone displays the ability to act as an aldehyde. According to the MacDonald [2+2] condensation under Lindseys condition between 5-substituted dipyrromethane and aromatic vicinal diketones, should result in porphodimethenes rather than porphyrins (Figure 5-5). 17 NHNHOOOHNOOMeCOOMeCOOMe+ 2acid Figure 5-4. Condensation reaction between acenaphthenequinone and 2 equivalents of 2-(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole. 28

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24 Ar1NHHNOHR'NHNNHNA r 1Ar2Ar2Ar12+ 2(Ar2) 1. acid2. DDQ Figure 5-5. Lindseys methodology of MacDonald [2+2] condensation for trans-substituted porphyrins. 17 Inspired by these observations, Dr. Michael Harmjanz devised a synthetic strategy using the MacDonald [2+2] condensation, wherein 5-substituted, -unsubstituted dipyrromethanes can react with acenaphthenequinone in the presence of catalytic amounts of either BF 3 OEt 2 or TFA under Lindseys conditions, followed by oxidation with DDQ to produce porphodimethenes rather than porphyrins. 29 ArNHHNOONHNNHNArArOONHNNHN A rArOO1. TFA, CH2Cl222. DDQ2++HAntiSyn Figure 5-6. MacDonald [2+2] condensation reaction between 5-substituted, -unsubstituted dipyrromethanes with acenaphthenequinone, adapted from Harmjanz, M; Gill, H.S; Scott, M. J. J. Org. Chem. 2001, 66, 5374. Various porphodimethenes were then synthesized utilizing this simple methodology, exhibiting different stereoelectronic properties. 29, 30 The condensation

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25 yields two isomers syn and anti as described in the figure 5-6. The two isomers can be easily distinguished by 1 H NMR spectroscopy and UV-visible spectroscopy. Metallation of Porphodimethene Porphodimethenes are generally metallated under refluxing conditions in chloroform, using saturated methanolic solution of the desired metal salt (Figure 5-7). The progress of a reaction could be easily monitored with the help of thin-layer chromatography and UV-visible spectroscopy. The inclusion of metal into the macrocyclic cavity, cause a bathochromic shift of the main absorption band. HNNNNHArArOOM salt / MeOH ,CHCl3NNNNArArOOMAr =M = Me t al Figure 5-7. Metallation of Porphodimethene. The significance of metallating porphodimethene prior to porphyrin synthesis could be revealing with the purpose of exploring these macrocyclic systems. Since the presence of two sp 3 centers at the trans-positions in meso-substituted porphodimethenes severely alters the electronic and steric properties of porphodimethenes as compared to the porphyrins, metalloporphodimethenes should exhibit divergent electronic and steric properties as compared to metalloporphyrins. 27 Secondly, the metallation of porphodimethenes could also prove valuable for the synthesis of those metalloporphyrins

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26 which may not be accessible due to steric or electronic properties associated with the porphyrin peripheries under consideration. Syntheses of bis-Cycloheptanone porphyrins While measuring the quantitative UV-visible absorption and extinction coefficient of the palladium anti-porphodimethene, a color change from red to green was observed. 250350450550650750Wavelength (nm) NNNNArArOOPdanti-porphodimetheneAr = MesitylLightforms two products Figure 5-8. Time course UV-Visible spectra of palladium anti-porphodimethene In order to identify the species formed from this reaction, a time course UV-visible experiment was performed and each scan was recorded after one minute (Figure 5-8). During the reaction, the UV-visible spectra revealed numerous features. Two isosbestic points were observed suggesting the clean transformation of the metallated porphodimethene to new species. The characteristic absorption maxima experienced

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27 decrease in absorbance along with the formation of two new characteristic Soret bands, and Q-bands in the low energy region were also observed. From these observations it appears that porphodimethene, which is 2ereduced form of porphyrin, may be undergoing an oxidation reaction to yield the corresponding two porphyrin products. In light of above rationale, porphodimethenes were treated with excess DDQ in presence of light by H.Gill (Figure 5-9). The reaction was carried out under anhydrous conditions and may be undergoing a Norish Type1 process, characteristic of aromatic ketones. 31 Upon photolysis, aromatic ketones undergo -cleavage, leading to the formation of radicals. The radicals can then undergo secondary processes like decarbonylation, elimination and ring expansion leading to the formation of new products. Decarbonylation and elimination processes are generally observed in case of strained rings systems (3/4 membered ring) leaving ring expansion as the obvious Ar =NNNN A r ArPdOONNNNArArPdOONNNNArArOONNNNArArOOORANDsyn porphodimetheneanti porphodimethenetrans porphyrincis porphyrinPdPd1. LIGHT, 1.2 eq. DDQ2. 1.2 eq. DDQDry CH2Cl2 Figure 5-9. Syntheses of bis-Cycloheptanone porphyrins.

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28 choice. The ring expansion occurs via combination of 1,4 biradical leading to the formation of 7-membered ring system. The reaction progress was monitored by UV-visible spectroscopy and thin-layer chromatography and two products, cis and trans isomers, were obtained. The isomers were easily separated by column chromatography (silica, methylene chloride/hexanes, 2:1). The trans isomer elutes first. Both isomers are green solids and exhibit characteristic absorption maxima with a red shifted Soret band and the appearance of Q-bands in the low energy region. The isomers can be easily distinguished by 1 H NMR spectroscopy. In order to further investigate the chemistry behind these highly substituted porphyrins, the oxidative dehydrogenation of the above mentioned bis-cycloheptanone porphyrins were carried out in the presence of a Lewis acid and an oxidant (Figure 5-10). The resulting product suffered from poor solubility. In order to isolate and characterize these oxidative dehydrogenation products, the syntheses of porphodimethenes with sterically encumbered peripheries was carried out. The incorporation of the bulky tert-butyl groups on the acenaphthaquinone moiety was preferred to improve the solubility issues. The desired dione required for the MacDonald [2+2] condensation is not commercially available, so synthetic strategy was designed to isolate the desired 4,7-Di-t-butylacenaphthene-1,2-dione from the commercially available acenaphthene. The synthetic pathway involves four steps as shown in figure 5-11, where the first three steps namely, Friedel-Crafts alkylation leading to the formation of 4,7 Di-tbutylacenaphthene (1) followed by esterification of (1) yielding (2). The hydrolysis of (2) thereby generating an alcohol (3), were modified from published procedures. 32, 33 The

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29 NNNN A r ArPdOOORsparingly soluble purpleproductsNNNNArArPdOOFeCl3.6H20DDQAr = Figure 5-10. Oxidative dehydrogenation of bis-cycloheptanone porphyrins t-But-Bu, MeCOOHt-But-BuOOt-But-BuOHt-But-BuOONaOH/H2OtBuClAlCl3Pb3O4MeOHSeO21,4 DioxaneCS2 Figure 5-11. Synthesis of 4, 7Di-t-butylacenaphthenedione involving (1) Friedel-Crafts alkylation, (2) Esterification, (3) Hydrolysis, (4) Oxidation reaction respectively

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30 alcohol (3) was subjected to oxidation to the desired 1, 2-dione using selenium dioxide in refluxing 1,4-Dioxane. The fine yellow needles of the desired 1,2-dione (4) were obtained. The entire synthetic route was performed without the use of column chromatography. The products obtained in each step were characterized using 1 H and 13 C NMR spectroscopy. Utilizing MacDonald [2+2] condensation reaction under Lindseys condition, 4,7-Di-tert-butylacenaphthaquinone was condensed with 5-Mesityldipyrromethane in presence of TFA followed by subsequent oxidation with stoichiometric amounts of DDQ at room temperature (Figure 5-12). The reaction mixture was then filtered through a column of neutral alumina thereby yielding the desired mixture of anti (5) and syn (6) porphodimethene. Since (5) is only slightly soluble in methylene chloride, it can be immediately isolated from the reaction mixture in 14% yield. Column chromatography of the residue with toluene followed by methylene chloride yielded an additional 1% of the (5) followed by the isolation of the 10% of the (6). Both the isomers, (5) and (6) were obtained as bright orange solids and exhibits characteristic absorption maxima in UV-visible spectra at 437 and 441 nm respectively. The two isomers can be easily distinguished by 1 H NMR spectroscopy. Both the isomers exhibit two sets of doublets for the pyrrolic C-H protons between 5.95 and 6.18 ppm. The corresponding signal for porphyrins are observed around 8-9 ppm highlighting the lack of electronic communication between the two halves of the porphodimethene macrocycle leading to shielding for the pyrrolic protons. The resonance for the N-H proton for both the isomers appear downfield shifted (13.69 ppm: 5 and 14.06 ppm: 6) in the 1 H NMR spectra. Since

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31 (5) can be isolated in higher yields than (6), it was used exclusively for all the following reactions though both isomers react in the same manner. ArNHHNOONHNNHNArArOONHNNHNArArOO1. TFA22. DDQ2++HAntiSynRRRRRRRRRR15%10%CH2Cl2Ar =R = t-Butyl Figure 5-12. MacDonald [2+2] condensation reaction between 5-mesityl dipyrromethane and 4,7-Di-tert-butylacenaphthaquinone Metallation of anti-Substituted porphodimethene with Ni (II) Metallation of (5) with nickel was the next objective. The compound (5) was refluxed for 15 hours in chloroform and methanolic solution of Dichloronickel(II) hexahydrate (Figure 5-13). The reaction progress was monitored with the help of UV-visible spectroscopy and thin-layer chromatography. With the introduction of Ni (II) into the macrocyclic cavity, the main absorption band of (5) experienced a bathochromic shift. The reaction mixture was cooled, subjected to aqueous work-up followed by column chromatography (silica, methylene chloride/chloroform /hexanes, 1:1:1) afforded the desired product (7).

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32 NHNNHNArArOORRRRNiCl2.6H2O / MeOHCHCl3 / Reflux, 15 HrsAr =R = t ButylNNNNArArOORRRRNi Figure 5-13. Metallation of anti-Substituted porphodimethene with Nickel (II) In the 1 H NMR spectrum of (7), several resonances associated with aromatic and aliphatic protons could not be identified. This observation may be attributed to the fast flexing of the macrocycle on the NMR time scale, resulting in broadening of signals for the above mentioned protons. In order to identify all the resonances, variable temperature NMR studies were carried out at 52C (CDCl 3 ) and 75C (C 6 D 6 ), and the missing resonances could be resolved. At these temperatures, the rate of interconversion is fast on the NMR time scale, thereby generating a spectrum which is weighted average of the separate conformations. However, resonances corresponding to two naphthyl protons were still not observed and low temperature NMR (-80C, d-Toluene) measurements reveal all the protons. At -80C, the rate of interconversion is slow on the NMR time scale. As a result of which, the situation approximates to that of the rigid molecule and consequently, the observed spectrum can be interpreted in terms of a single rigid confirmation. A considerable downfield shift was also observed for one of the eight naphthyl protons and the resonance could be possibly assigned to the proton to the carbonyl group, close to the macrocycle. The shift may be attributed to the close proximity of the electron withdrawing carbonyl group and in addition to the low electron density experienced by the proton due to the induced magnetic field.

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33 Synthesis of Nickel-bis-Substituted cycloheptanone porphyrins The compound (7) was subjected to oxidation using light and excess DDQ, under anhydrous conditions (Figure 5-14). The progress of the reaction was monitored with the help of UV-visible spectroscopy and thin layer chromatography. The column chromatography (silica, methylene chloride/hexanes, 2:1) resulted in the separation of both the isomers namely, trans (8) and cis (9)-substituted cycloheptanone porphyrins. The compound (8) elutes first followed by (9) in comparatively higher yields than the former. Both the isomers are shiny green colored solids. The cis and trans isomers exhibit red shifted Soret band at 493 and 476 nm, and intense broad Q-bands in the low energy region at 672 and 692 nm respectively as compared to ZnTPP. The two isomers are distinguished by 1 H NMR spectroscopy. The compound (9) exhibits six resonances for the six mesityl methyl protons whereas three single sets of resonances are obtained for (8) NNNNA r ArNiOOANDNNNNArA r NiOORRRRRRRRNNNNArArOONiRRRRDDQ / LIGHTDry CH2Cl2Ar =R = t Butyl Figure 5-14. Syntheses of Nickel-bis-Substituted cycloheptanone porphyrins indicating lack of symmetry between the two halves of the macrocycle. In addition, both the isomers exhibit para methyl protons resonances are observed in the region between

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34 1.05-1.3 ppm as compared to the orthomethyl resonances (2.4-2.8 ppm) suggesting high electron density experienced by the former leading to significant shielding. Synthesis of Nickel-bis-Substituted azulenone Porphyrins The compound (9) was subjected to oxidative dehydrogenation reaction utilizing DDQ and FeCl 3 .6H 2 O under anhydrous conditions (Figure 5-15). The progress of the reaction was monitored with the help of UV-visible spectroscopy and thin layer chromatography. Column chromatography (silica, methylene chloride/hexanes in 1:1) afforded a perfectly flat porphyrin (10) bearing exocyclic ring systems. The compound (10) was characterized using 1 H NMR spectroscopy, revealing six sets of resonances for the aromatic protons and three single sets of resonances for the methyl protons. The compound displays significant bathochromic shift of the Soret band and intense (log = 4.8) Q-bands in the low energy region (850 nm). Single crystals were obtained via vapor diffusion of pentanes to the saturated methylene chloride solution (Figure 5-17). The solid state structure shows a relatively flat porphyrin. The space group of the compound NNNNA r ArNiOOFeCl3.6H20DDQ /Dry CH2Cl2RRRRArR== tbutylNNNNArArNiOORRRR Figure 5-15. Synthesis of Nickel-cis-bis-Substituted-azulenone porphyrin was C2/c. The porphyrin core, defined by the four nitrogens and metal exhibit a slight deviation from 90 and 180, and slightly longer metal-nitrogen bond lengths for N1 and

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35 N4 compared to N2 and N3. This observation may be attributed to the presence of electron withdrawing carbonyl groups close to Ni-N bond lengths. However, utilizing the same synthetic strategy for compound (8), the 1 H NMR spectrum indicated six single sets of resonances for mesityl methyl protons and four single sets were obtained for the t-butyl groups, indicating only one naphthyl hydrogen and pyrrole hydrogen of (8) underwent oxidative dehydrogenation leading to the formation of compound (11) (Figure 5-16). In comparison to compound (9), the oxidative dehydrogenation reaction proceeded at a slower rate. The trans-cycloheptanone having the same naphthyl substituents and palladium as a metal underwent complete transformation to trans-bis-azulenone product. 34 These observed facts suggest that the reaction may involve longer time leading to the formation of trans-bis-azulenone porphyrin, but, at the same time allowed the isolation of (11). The reaction progress was monitored with the help of UV-visible spectroscopy and thin layer chromatography. Column chromatography (silica, methylene chloride/hexanes, 1:1) afforded (11) and reveals a significant bathochromic shift of the Soret band along with an increase in intensity of and shifting of frequency of the Q-bands in the low energy region (884 nm). NNNN A rArNiOOFeCl3.6H20NNNNArArNiOODDQ /Dry CH2Cl2RRRRRRRRArR== tbutyl Figure 5-16. Synthesis of Nickel-trans-Substituted monoazulenone porphyrin.

PAGE 45

36 Figure 5-17. ORTEP diagram of the solid-state structure of Nickel cis-bis-Substituted azulenone porphyrin, (10). Hydrogen atoms are omitted for clarity.

PAGE 46

LIST OF REFERENCES 1. Kadish, K. M.; Smith, K. M.; Guilard, R. The Porphyrin Handbook, Academic Press, Burlington, MA, 1999. 2. Rothemund, P. J. Am. Chem. Soc. 1935, 57, 2010. 3. Rothemund, P. J. Am. Chem. Soc. 1939, 61, 2912. 4. Aronoff, S.; Calvin, M. J. Org. Chem. 1943, 8, 205. 5. Calvin, M.; Ball, R. H.; Aronoff, S. J. Am. Chem. Soc. 1943, 65, 2259. 6. Ball, R. H.; Dorough, G. D.; Calvin, M. J. Am. Chem. Soc. 1946, 68, 2259. 7. Rothemund, P.; Menotti, A.R. J. Am. Chem. Soc. 1941, 63, 267. 8. Adler, A. D.; Longo, F. R.; Shergalis, W. J. Am. Chem. Soc. 1964, 86, 3145. 9. Adler, A. D.; Sklar, L.; Longo, F. R.; Finarelli, J. D.; Finarelli, M. G. J. Heterocyclic Chem. 1968, 5, 669. 10. Adler, A. D.; Longo, F. R.; Finarelli, J. D.; Goldmacher, J.; Assour, J.; Korsakoff, L. J. Org. Chem. 1967, 32, 476. 11. Barnett, G. H.; Hudson, M. F.; Smith, K. M. Tetrahedron Lett. 1973, 2887. 12. Rousseau, K; Dolphin, D. Tetrahedron Lett. 1974, 4251. 13. Dolphin, D. J. Heterocyclic Chem. 1970, 7, 275. 14. Lindsey, J. S.; Hsu, H. C.; Schreiman, I. C. Tetrahedron Lett. 1986, 27, 4969. 15. Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.; Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827. 16. Geier, R. G. III.; Lindsey, J. S. J. Chem. Soc., Perkin Trans. 2 2001, 687. 17. Littler, B. J.; Miller, M. A.; Hung, C. H.; Wagner, R. W.; OShea, D. F.; Boyle, P. D.; Lindsey, J. S. J. Org. Chem. 1999, 64, 1391. 18. Arsenault, G. P.; Bullock, E.; MacDonald, S. F. J. Am. Chem. Soc. 1960, 82, 4384. 37

PAGE 47

38 19. Littler, B. J.; Ciringh, Y.; Lindsey, J. S. J. Org. Chem. 1999, 64, 2864. 20. Geier, R. G. III.; Littler, B. J.; Lindsey, J. S. J. Chem. Soc., Perkin Trans. 2 2001, 701. 21. Lee, C. H.; Lindsey, J. S. Tetrahedron 1994, 50, 1147. 22. (a) Milgrom, L.R. The Colors of Life: An Introduction to the Chemistry of Porphyrins and Related Compounds, OUP, Oxford, 1997. (b) Dolphin, D. The Porphyrins, Academic Press, New York, 1978. 23. Anderson, H. L. Chem. Commun. 1999, 23, 2323. 24. Re, N.; Bonomo, L.; DaSilva, C.; Solari, E.; Scopelliti, R.; Floriani, C. Chem. Eur. J. 2001, 7, 2536. 25. Buchler, J. A.; Puppe, L. Liebigs Ann. Chem. 1974, 1046. 26. Krl, V.; Sessler, J. L.; Zimmermann, R. S.; Seidel, D.; Lynch, V.; Andrioletti, B. Angew. Chem. Int. Ed. 2000, 39, 1055. 27. Bonomo, L.;Solari, E.; Rosario, S.; Floriani, C.; Re, N. J. Am. Chem. Soc. 2000, 122, 5312. 28. Chang, C. K; Kondylis, M. P. Chem. Commun. 1986, 316. 29. Harmjanz, M; Gill, H.S; Scott, M. J. J. Org. Chem. 2001, 66, 5374. 30. Harmjanz, M; Bozidarevic, I.; Scott, M. J. Org.Lett. 2001, 3, 2281. 31. O. L. Chapman, D. S. Weiss, Organic Photochemistry, Vol. 3, Dekker, New York, 1973, 197. 32. Illingworth, E.; Peters, A. T. J. Chem. Soc. 1952, 1602. 33. Fieser, L. F.; Cason, J. J. Am. Chem. Soc. 1940, 62, 432. 34. Gill, H. S.; Harmjanz, H.; Santamaria, H.; Finger, I.; Scott, M.J. in press. 35. Blessing, R. H. Acta. Cryst. Sect. A, 1995, 51, 33.

PAGE 48

BIOGRAPHICAL SKETCH Parul Angrish was born in India, on August 11, 1977. She received a Bachelor of Science from St. Stephens College, University of Delhi, India and Master of Science from the Indian Institute of Technology, Kanpur, India. After completing her masters she joined the Department of Chemistry, University of Florida, in 2001.Her research interests are synthetic organic and inorganic chemistry. 39


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SYNTHESES OF meso-SUBSTITUTED PORPHODIMETHENES AND
PORPHYRINS WITH EXOCYCLIC RING SYSTEMS


















By

PARUL ANGRISH


A THESIS PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE

UNIVERSITY OF FLORIDA


2003

































Copyright 2003

by

Parul Angrish

































Dedicated to my parents















ACKNOWLEDGMENTS

I take this opportunity to place on record my deep sense of gratitude to my advisor,

Dr. Michael J. Scott, for introducing me to the exciting field ofporphyrin chemistry I am

deeply indebted for his guidance through my thesis and his valuable advice at all times.

I am very much grateful to Hubert Gill and Ivana Bozidarevic for their constant

assistance and support in and outside the lab. I would like to acknowledge Dr. Michael

Harmjanz, a former post doctoral fellow in the group, who started the whole project. I

would like to thank Dr. Javier Santamaria in getting me started with the project. My

thanks are due to the rest of the Scott group members for their constant love and

encouragement.

I am at a total loss of words in expressing the depth of my emotion for my parents

and sisters for their constant support and inspiration. Last but not least, I am thankful to

my friends, especially Shakti and Rishabh, for making me feel comfortable during the

most difficult and trying moments of my life.
















TABLE OF CONTENTS

page

A C K N O W L E D G M E N T S ................................................................................................. iv

L IST O F FIG U R E S .... ...... ...................... ........................ .. ....... .............. vii

ABSTRACT .............. .................. .......... .............. ix

CHAPTER

1 INTRODUCTION TO TETRAPYRROLIC MACROCYCLES ................................ 1

Types of m eso-Substituted Porphyrins .............. .... ............... .....................2
Syntheses of meso-Substituted Porphyrins ............................ ................................3
R them und M ethod .......... ...... .................... ................ ................ .. .. 3
A dler M ethod............... .. ................ ... .............. ........ ................4
Two-Step One-Flask Room-Temperature Synthesis of Porphyrin (Lindsey
M eth o d ) ........... ........... ...... ........... ...... ....... ............... ..... ... ...... 5
MacDonald [2+2] Condensation Reaction........... .............................7
Electronic Spectra of Porphyrins ........... ......... .......................... ........ ........... 9

2 PORPHODIMETHENE MACROCYCLES AND THEIR PROPERTIES ..............10

3 PORPHYRINS BEARING EXOCYCLIC RING SYSTEMS.............. .................12

4 EXPERIMENTAL PROCEDURES .....................................................13

Syntheses ............................................................... .. .. ............. 13
Synthesis of 4, 7-Di-tert-butylacenaphthene, (1) .............................................13
Synthesis of 4,7-Di-tert-butyl-acenaphthenylester, (2)......................................14
Synthesis of 4,7-Di-tert-butylacenaphthenol, (3)............................................. 15
Synthesis of 4,7-Di-tert-butylacenaphthylene- 1,2-dione, (4)..............................15
Synthesis of anti, (5) and syn, (6) Substituted porphodimethene.....................15
Synthesis of Nickel (II)-Substituted porphodimethene, (7) .............................16
Syntheses of Nickel trans and cis -bis-Substituted cycloheptanone porphyrins,
(8 an d 9 ) ....................................................................................... ......... 17
Synthesis of Nickel cis- bis-Substituted azulenone porphyrin, (10) ...................18
Synthesis of Nickel trans- Substituted monoazulenone porphyrin, (11) ............19
X -ray crystallography ............................. ...... .................... .. ...... .... ..... ...... 20









5 RESULTS AND DISCU SSION S........................................ ........................... 22

Syntheses of Porphodim ethenes ......................................................................22
Metallation of Porphodimethene .....................................................25
Syntheses of bis-Cycloheptanone porphyrins.......................... ... ............. 26
Metallation of anti-Substituted porphodimethene with Ni (II)................................31
Synthesis ofNickel-bis-Substituted cycloheptanone porphyrins ...............................33
Synthesis ofNickel-bis-Substituted azulenone Porphyrins.................... ........ 34

LIST OF REFEREN CE S ........................................ ........................... ............... 37

BIO GRAPH ICAL SK ETCH .................................................. ............................... 39
















LIST OF FIGURES


Figure p

1-1 Examples of tetrapyrrolic macrocycles in nature............... ................ ..............1

1-2 Examples of tetrapyrrolic macrocycles namely porphyrin, porphyrinogen
porphodim ethene and chlorin respectively. ........................................ ..................2

1-3 Types of porphyrins. ............................... .................................... .. ............ .... ... .2

1-4 Rothemund method for the synthesis of meso-substituted porphyrins .................3

1-5 Conversion of meso-substituted chlorin to the corresponding porphyrin ............4

1-6 Adler method for preparing meso-substituted porphyrin............... ...................4

1-7 Formation of octamethyltetraphenylporphyrinogen via Adler method ...............5

1-8 Two-step one-flask room-temperature syntheses of meso-substituted
porphyrins. .......................................... ............................. .. 7

1-9 Types of meso-substituted porphyrins. ............................................................7

1-10 MacDonald [2+2] condensation affording a trans-meso-substituted porphyrin......8

2-1 The two synthetic pathways to obtain porphodimethene skeleton ......................10

2-2 Difference between the electronic spectra of porphyrin vs porphodimethene. ..... 11

5-1 Reductive alkylation of zinc octaethylporphyrin...........................................22

5-2 Reaction of ketones, exemplified acetone, with aryl dipyrromethanes. ................23

5-3 D ealkylation of porphyrinogen. ............................ ......... ...................... ........ 23

5-4 Condensation reaction between acenaphthenequinone and 2 equivalents of 2-
(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole..................... ........ ......................... 23

5-5 Lindsey's methodology of MacDonald [2+2] condensation for trans-substituted
porphyrins. ........................................................................... 24









5-6 MacDonald [2+2] condensation reaction between 5-substituted, P-unsubstituted
dipyrromethanes with acenaphthenequinone...................................... ............ 24

5-7 Metallation of Porphodimethene.............................................................25

5-8 Time course UV-Visible spectra of palladium anti-porphodimethene..................26

5-9 Syntheses of bis-Cycloheptanone porphyrins............. .... .................27

5-10 Oxidative dehydrogenation of bis-cycloheptanone porphyrins ...........................29

5-11 Synthesis of 4, 7- Di-t-butylacenaphthenedione involving (1) Friedel-Crafts
alkylation, (2) Esterification, (3) Hydrolysis, (4) Oxidation reaction
resp ectiv ely .........................................................................2 9

5-12 MacDonald [2+2] condensation reaction between 5-mesityl dipyrromethane and
4,7-Di-tert-butylacenaphthaquinone ................. .... ........ ...............31

5-13 Metallation of anti-Substituted porphodimethene with Nickel (II).....................32

5-14 Syntheses of Nickel-bis-Substituted cycloheptanone porphyrins..........................33

5-15 Synthesis of Nickel-cis-bis-Substituted-azulenone porphyrin.............................34

5-16 Synthesis of Nickel-trans-Substituted monoazulenone porphyrin ...................35

5-17 ORTEP diagram of the solid-state structure of Nickel cis-bis-Substituted
azulenone porphyrin (10) ............................................... ............. ............... 36















Abstract of Thesis Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Master of Science

SYNTHESES OF meso-SUBSTITUTED PORPHODIMETHENES AND
PORPHYRINS WITH EXOCYCLIC RING SYSTEMS

By

Parul Angrish

December, 2003

Chair: Michael. J. Scott
Major Department: Chemistry

Porphodimethenes have been synthesized utilizing MacDonald [2+2] condensation

between 5-substituted dipyrromethane and substituted aromatic vicinal diketones. These

macrocycles can be easily metallated utilizing various metal salts in refluxing

chloroform-methanol mixture. Metalloporphodimethene exhibits divergent properties as

compared to metalloporphyrins. Metalloporphodimethenes undergo oxidative

rearrangement in presence of light and DDQ, generating highly substituted nonplanar

porphyrins, cycloheptanoneporphyrins. Cycloheptanoneporphyrins are further oxidatively

dehydrogenated using DDQ and anhydrous FeC13, resulting in perfectly flat porphyrins

with exocyclic ring systems. These porphyrins exhibit various interesting features in the

UV-visible spectra including intense Q-bands in the low energy region, which are

desirable in various materials and medicinal applications.














CHAPTER 1
INTRODUCTION TO TETRAPYRROLIC MACROCYCLES

Tetrapyrrolic macrocycles such as porphyrins, corroles, chlorins and

bactereochlorins are widely available in nature, performing diverse functions like

catalysis, light harvesting, dioxygen transport, and electron transfer.1 Figure 1-1

illustrates examples of a naturally occurring porphyrin and chlorin used for dioxygen

transport and light harvesting respectively.

CH=CH2

C2H5


NN N
SFe / N N
H



C20H3902C o 0
COOH HOOC I
Me
iron protoporphyrin IX Chlorophylls

Figure 1-1. Examples of tetrapyrrolic macrocycles in nature.

Because of the diverse biological roles performed by these tetrapyrrolic

macrocycle, extensive studies are performed on artificial systems in order to understand

the chemistry of the various biological systems. Herein, different types of tetrapyrrolic

macrocycles are described in figure 1-2 namely porphyrin, porphyrinogen

porphodimethene and chlorin respectively.

One of the most important tetrapyrrolic macrocycles in nature, porphyrin, is a

conjugated, planar ligand that is ubiquitous in living systems. Variety of substituents









attached to the porphyrin periphery enable porphyrins to act as potential structural tools

in diverse fields.



N H NH N N

HN H HN HN HN



Figure 1-2. Examples of tetrapyrrolic macrocycles namely porphyrin, porphyrinogen
porphodimethene and chlorin respectively.

Types of meso-Substituted Porphyrins

Porphyrins can be classified into two main categories based on the pattern of

substituents attached to the macrocycle namely: meso-substituted porphyrins and f-

substituted porphyrins (Figure 1-3).


R
R R R




R HN HN



(1) (2)

Figure 1-3. Types of porphyrins: (1) meso-substituted porphyrin, and (2) f-substituted
porphyrin.

The f-substituted porphyrins closely resemble naturally occurring porphyrins like

Protoporphyrin IX1. The meso-substituted porphyrins are not found in nature but have

wide applications as biomimetic models and as useful components in material chemistry,

photodynamic therapy, molecular recognition, catalysis, electron transfer etc.1 Since

these can be prepared by simple synthetic methodology, the substituents at the meso-









positions can be readily adjusted utilizing alkyl, aryl, heterocyclic or organometallic

groups as well as other porphyrins.

Syntheses of meso-Substituted Porphyrins

Rothemund Method

The chemistry of meso-substituted porphyrins has its foundation in the work of

Rothemund in 1935.2 Rothemund performed the synthesis of meso-tetramethylporphyrin

by utilizing the condensation reaction between acetalaldehyde and pyrrole in methanol at

various temperatures (Figure 1-4). Sealed vessels were employed to avoid the loss of

volatile acetaldehyde. The reaction was carried out in the absence of an oxidant. Various

aldehydes like propionaldehyde, benzaldehyde, n-butyraldehyde, a-furaldehyde were

utilized using this methodology.3

Ph

CHO

S+ Ph H Ph
MeOH h
H N HN

Ph

Figure 1-4. Rothemund method for the synthesis of meso-substituted porphyrins,
exemplified for meso-substituted tetraphenylporphyrin.

However, careful analysis of the products showed the presence of second

porphyrinic substance (10-25%).3 The contaminant was isolated using column

chromatography and was shown to consist of chlorins.46 Fortunately, chlorins can be

easily oxidized to the corresponding porphyrins (Figure 1-5).

Rothemund employed various synthetic modifications in order to optimize the

reaction conditions and finally settling on high concentration of the starting materials.

However, low yields of the desired porphyrins were still obtained, thereby limiting the









scope of application. Further improvements involving high temperature syntheses were

also devised, thereby avoiding the solvent altogether.

Ph Ph


N N
[0]
Phh H
h HN -2e-, -2H HN h


h h

Figure 1-5. Conversion of meso-substituted chlorin to the corresponding porphyrin.

Adler Method

In the mid 1960's, Adler and coworkers modified the syntheses of meso-

substituted porphyrins by performing the condensation reaction between benzaldeyde and

pyrrole (0.02M) in a wide range of acidic solvents under refluxing conditions in open an

atmosphere. The main solvents employed were acetic acid, acetic acid in the presence of

a metal salt, or benzene containing chloroacetic acid or triflouroacetic acid.8 The highest

yield was reported using refluxing benzene containing chloroacetic acid and the lowest

yields were reported for solvents containing metal salt.

Ph

CHO
A\N
+rH + n- RCO2H Ph
N Reflux, 30 min. HN
H

h

Figure 1-6. Adler method for preparing meso-substituted porphyrin, exemplified for
meso-substituted tetraphenylporphyrin.

Various kinetic studies were performed by Adler and coworkers in order to

improve the syntheses of porphyrins and these suggested the yield of porphyrins were









dependent on the choice of solvent, acidity of solvent, temperature and initial

concentration of reactants.9 The methodology was further improved by employing

propionic acid (bp: 1410C) in place of acetic acid (bp: 1180C) as the solvent. After a

short reflux of the higher concentrations of aldehydes and pyrrole, porphyrin crystals

could be isolated upon cooling of the solution, filtration and washing. This modified

synthesis proved to be an important improvement over Rothemund's methodology and is

known as the Adler or Adler-Longo method (Figure 1-6).10 The final porphyrin product

was also found to be contaminated with chlorins and were removed using oxidizing

agents like, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, commonly known as DDQ.11,12

Further investigations on the course of reaction products under anaerobic

conditions were studied.13 The experiments performed strongly suggested that

porphyrinogen, meso-tetrahydro-tetraalkyl(aryl)-porphyrin, is the key intermediate

formed upon aldehyde and pyrrole condensation in the reaction leading to porphyrin

(Figure 1-7).

Ph


HN-
Ph-CHO + hCH3C02H p h
N H HN
H

h

Figure 1-7. Formation of octamethyltetraphenylporphyrinogen via Adler method.

Two-Step One-Flask Room-Temperature Synthesis of Porphyrin (Lindsey Method)

The Adler or Alder-Longo method provided syntheses of a variety of meso-

substituted porphyrins, particularly tetra-arylporphyrins with diverse aryl substituents. In

order to broaden the scope of substituents on available model systems, various new









methodologies were developed. In 1980's, a new approach for the syntheses of meso-

substituted porphyrins under gentle conditions was developed namely, two-step one-

flask room temperature syntheses of porphyrins or the Lindsey method.14'15 Various facts

were considered while designing the above mentioned synthetic methodology. First,

Rothemund and Adler-Longo methodology employed harsh reaction conditions leading

to the formation of porphyrins in low yields. In addition, syntheses of porphyrins bearing

sensitive functional groups could not be achieved. As a result of these drawbacks, the

need to accomplish the condensation reaction under gentle conditions became an obvious

choice. Secondly, mild conditions were also desirable in order to avoid all the side

reactions leading to undesired oligomers and side products.

The synthetic methodology developed by Lindsey involved a condensation reaction

between an aldehyde and pyrrole to form porphyrinogen, followed by the oxidation step

sequentially. The synthesis involved is as follows (Figure 1-8). A solution of pyrrole

(10mM) and benzaldehyde (10mM) was added to dry CH2C12, followed by the addition of

triflouroacetic acid or BF3-etherate as catalyst. Subsequent addition of DDQ, induce the

conversion of porphyrinogen to the porphyrin at room temperature. The compound was

further purified using column chromatography allowing the isolation of porphyrin in 35-

40 % yield.16 Lindsey's method has been applied to syntheses of wide variety of meso-

substituted porphyrins. Yield up to 50% can be achieved depending on the choice of

aldehyde and acid.











4R-CHO +4 /\ TFA or BF3 etherate KN -lN HN H
4 R-CHO + 4 + 4 H20
N CH2C12,25C H NHHN R
H /
RH


H R R

R NH HN H NH N-
H NHHN R R N HN R
3 DDQ 3 DDQH2
R H O OH R

CI CN CI- CN
H

Figure 1-8. Two-step one-flask room-temperature syntheses of meso-substituted
porphyrins.

MacDonald [2+2] Condensation Reaction

Utilizing Lindsey's methodology, symmetrical porphyrins, A4 type (Figure 1-9), are

isolated. In order to synthesize the less symmetrical, trans-substituted porphyrins, A2B2

type (Figure 1-9), synthetic pathway based on the MacDonald [2+2] condensation of a

dipyrromethane and an aldehyde was designed, as shown in figure 1-10.17'18






H H /



(1) (2)

Figure 1-9. Types of meso-substituted porphyrins: (1) A4 Type Porphyrin and (2) A2B2
Type Porphyrin.









However, the synthesis may yield in a mixture of porphyrins namely; cis-A2B2 and

trans-A2B12, which are difficult to separate. The condensation reaction leading to the

formation of porphyrinogen proceeds reversibly and the rearrangement of substituents is

referred as "scrambling."19' 20 The success of MacDonald [2+2] condensation requires

minimum scrambling of the acid catalyzed condensation of dipyrromethane and an

aldehyde. Various studies were performed in order to understand the origin of scrambling

and the means to control it.20 In general, sterically unhindered aldehydes favors

scrambling. The implementation of MacDonald [2+2] condensation also requires the

synthesis of the dipyrromethane.21 The synthesis of trans-meso-substituted porphyrins is

important as these porphyrins can act as potential components for various model systems

in material and medicinal applications.

RH

TFA or BF3 etherate Ar NH HN H + 2 H20
2Ar-CHO +2 HHN CH2C12,25C H HNH Ar

RH
R H R

Ar NH HN H N HN
HHN Ar Ar Ar

R H 3 DDQ 3 DDQH2 R
O OH
CI- CN CI OCN
CI0 CN CI0 CN
O OH

Figure 1-10. MacDonald [2+2] condensation affording a trans-meso-substituted
porphyrin.









Electronic Spectra of Porphyrins

The word porphyrin is derived from the Greek work porphura meaning purple

which is appropriate since all porphyrins are intensely colored.22 The electronic

absorption spectra of porphyrin consists of a strong absorption band around 400 nm

(Soret or B band) and a weak absorption band around 550 nm (Q-band).23 These

observed electronic transitions results from H I* transitions and they can be explained

using "Gouterman four orbital model" involving two nearly degenerate H orbitals, (alu

and a2u) and two degenerate lowest unoccupied H* orbitals, (egx, egy). Thus, in principle,

two transitions should be observed at almost same energy resulting from excitation from

the two highest occupied molecular orbitals to the degenerate lowest unoccupied

molecular energy, and should finally result in a coincident transition. However, two

transitions are observed due to configurational interactions resulting from electronic

rearrangement of the excited state configuration. The configurations can mix with other

configurations in the molecule having same symmetry. As a result of this mixing, the two

lowest unoccupied molecular orbitals are no longer degenerate thus, giving rise to two

transitions of different intensities and wavelengths.














CHAPTER 2
PORPHODIMETHENE MACROCYCLES AND THEIR PROPERTIES

Porphodimethenes can be obtained as intermediates in the oxidation of

porphyrinogen to porphyrins and metalloporphyrins. In addition, they can also be

obtained via reductive alkylation / protonation of porphyrin or oxidative dealkylation /

deprotonation of the porphyrinogen (Figure 2-1).24

HH H H


H N H _2H2 H N H +H2 H

H NH H NH HN

H

Figure 2-1. The two synthetic pathways to obtain porphodimethene skeleton.

In porphodimethenes, the two non-adjacent meso-carbons are saturated, thereby

introducing sp3 hybridization into the ring. Although the two halves of the molecule are

still planar and conjugated, there is disruption of electronic communication between the

two dipyrromethene units of the macrocycle. Thus, macrocycle adopts a roof like folded

structure. The lack of electronic communication between the two halves of the

macrocycle severely alters the electronic absorption properties of the macrocycle. The

Soret band, as observed in porphyrins, is replaced by a characteristic "methane" band at

lower energy (420-470 nm) with smaller extinction coefficient and the porphyrin Q-

bands at lower energy disappear (Figure 2-2).













(1) (2)


S 400 500 600 700
Wavelength (nm)
(3)


500
Wavelength (nm)
(4)


Figure 2-2. Difference between the electronic spectra of porphyrin vs porphodimethene,
exemplified using meso-tetraphenyl porphyrin, (1) and meso-
tetramethylmesityl porphodimethene, (2).1 UV-visible spectrum, (3) and (4)
corresponding to (1) and (2) respectively.2













1Krhl, V.; Sessler, J. L.; Zimmermann, R. S.; Seidel, D.; Lynch, V.; Andrioletti, B. Angew. Chem. Int. Ed.
2000,39, 1055.


2 The UV-Visible spectra were generated by H.Gill.


j "














CHAPTER 3
PORPHYRINS BEARING EXOCYCLIC RING SYSTEMS

In recent years, porphyrins have been utilized in diverse fields. Consequently,

porphyrins are now designed with wide variety of substituents at the porphyrin periphery,

exhibiting different electronic, steric and solubility properties. These include expanded

porphyrins where one or more macrocyclic atoms are replaced by heteroatoms and non

planar porphyrins incorporating sterically demanding substituents at the porphyrin

backbone. Herein, utilizing the MacDonald [2+2] condensation, the synthesis of

porphodimethenes is presented, followed by the metallation of porphodimethene.

Metalloporphodimethenes undergo oxidative rearrangement in presence of light and

DDQ, resulting in the formation of highly substituted nonplanar porphyrins which are

further oxidatively dehydrogenated, generating a perfectly flat porphyrins with exocyclic

ring systems. These porphyrins exhibit various interesting features in the UV-visible

spectra including intense Q-bands in the low energy region, which are desirable in

various materials and medicinal applications.














CHAPTER 4
EXPERIMENTAL PROCEDURES

General procedures. NMR spectra were recorded on either a Gemini 300 MHz, a

VXR 300 MHz and or a Varian Inova 500 spectrometers. UV-visible absorption spectra

were recorded on a Varian Cary 50 (UV-Vis) or a Varian Cary 500 (UV-Vis-NIR)

spectrometers. High and low resolution mass spectral analyses were performed by The

University of Florida Mass Spectroscopy Services using FAB and DIOS as the ionization

methods. The solvents were either ACS or HPLC grade and were used as received or

were dried and degassed by standard procedures wherever needed. The reactions under

anhydrous conditions were performed using standard Schlenk techniques. 5-

Mesityldipyrromethane was prepared by a in the literature procedure.20 The syntheses of

compound (1),(2) and (3) were adapted by Dr. Javier Santamaria from previous work.32'33

The syntheses of compound (4),(5) and (6) were designed by Dr. Javier Santamaria.

Chromatography. Absorption column chromatography was preformed using

chromatographic silica gel (Fisher, 200-425 mesh) or neutral alumina (Aldrich, Brokman

I approx. 158 mesh, 58A.

Syntheses

Synthesis of 4, 7-Di-tert-butylacenaphthene (1)

A portion of anhydrous AlC13 (5.22 g, 0.04 mol) was added in small amounts to a

well-stirred mixture of acenaphthene (30.0 g, 0.20 mol) and t-butyl chloride (36.0 g, 0.39

mol) in 300 mL of CS2, over the period of 1 hour. The reaction mixture was refluxed for

3 hours and the solvent was then removed via distillation. The residue obtained was









dissolved in methylene chloride (200 mL), followed by quenching of AlC13 using cold

dilute hydrochloric acid (0.3N). The organic layer was washed with water (2 x), dried

over sodium sulfate and the solvent was removed in vacuo. The residue was filtered over

silica (methylene chloride), the solvent was removed yielding a colorless solid which

upon recrystallization from EtOH afforded the title compound (1) as thin, colorless

needles. Yield: 26.0g (50 %). 1HNMR (300 MHz, CDC13): 6 = 7.51 (s, 2H), 7.33 (s, 2H),

3.37 (s, 4H), 1.40 (s, 18H). 13C NMR (75 MHz, CDC13): 6 = 151.46, 145.24, 136.46,

130.91, 117.65, 117.57, 35.54, 31.91, 30.77.

Synthesis of 4,7-Di-tert-butyl-acenaphthenylester (2)

A portion of(1) (5.0 g, 0.06 mol) was dissolved in 450 mL of glacial acetic acid

followed by the addition of lead oxide (45g, 0.07 mol) in portions over the course of lh,

thereby maintaining the temperature around 85-900C. Red lead was subsequently added

provided the color due to the previous addition was discharged. The reaction mixture was

stirred for an additional 30 min at 85-900C, cooled to rt, diluted with 200 mL of water,

and extracted with methylene chloride (2 x). The organic layer was washed with saturated

sodium bicarbonate solution (3 x) and water (2 x), dried over Na2SO4 and the solvent was

removed under pressure affording the desired compound (2) as yellow viscous oil having

fruity smell. Yield: 15.0 g (82%). 1HNMR (300 MHz, CDC13): 6 = 7.72 (d, 1H, J= 1.2

Hz), 7.60 (s, 1H), 7.58 (s, 1H), 7.37 (s, 1H), 6.62 (dd, 1H, J1 = 7.2 Hz, J = 1.9 Hz), 3.83

(dd, 1H, J1 = 17.9, J = 7.4 Hz), 3.30 (d, 1H, J= 18.0 Hz), 2.11 (s, 3H), 1.42 (s, 9H), 1.41

(s, 9H). 13C NMR (75 MHz, CDCl3): 6 = 171.63, 152.17, 152.13, 141.64, 140.69, 135.42,

130.88, 121.22, 120.27, 118.32, 118.50, 76.73, 39.66, 35.99, 35.93, 32.21, 32.05, 21.80.









Synthesis of 4,7-Di-tert-butylacenaphthenol (3)

A portion of (2) (15.0 g, 0.05 mol) was dissolved in MeOH (25 mL) followed by

the addition of sodium hydroxide (3.60g, 0.09 mol) dissolved in water (36 mL). The

reaction mixture was refluxed for 3 hours. The solution was cooled to 0C. The white

solid obtained was filtered, dried to afford alcohol (3), as a white amorphous solid. Yield:

10.0g (77%). H NMR (300 MHz, CDC13): 6 7.68 (s, H), 7.60 (d, 1H, J= 1.2 Hz), 7.57

(s, 1H), 7.35 (d, 1H, J= 1.2 Hz), 5.70 (bs, 1H), 3.78 (dd, 1H, J1 = 17.5 Hz, J2 = 7.0 Hz),

3.21 (d, 1H, J= 17.0 Hz), 1.99 (bs, 1H), 1.40 (s, 9H), 1.39 (s, 9H). 13C-NMR (75 MHz,

CDC13): 6 = 151.64, 151.56, 144.85, 140.60, 134.15, 130.39, 120.13, 118.30, 117.93,

117.76, 74.66, 42.08, 35.43, 35.36, 31.66, 31.58.

Synthesis of 4,7-Di-tert-butylacenaphthylene-1,2-dione (4)

A mixture of (3) (13.5 g, 0.05 mol) and 54 g (0.49 mol) of SeO2 was refluxed in

350 mL of 1, 4- Dioxane for 12 h. The solvent was removed by distillation, and the

residue was dissolved in 200 mL CH2C2 followed by filtration over a silica plug (10 x 5

cm) and eluted with CH2C12. The solvent was removed and the residue was crystallized

from hexanes, affording dione, (4), as yellow needles. Yield: 9.0 g (64%). 1H NMR (300

MHz, CDCl3): 6 8.20 (d, 2H, J= 1.5 Hz), 8.17 (d, 2H, J= 1.2 Hz), 1.46 (s, 18H). 13C

NMR (75 MHz, CDC13): 6 = 188.79, 152.35, 143.43, 130.90, 128.00, 127.87, 119.97,

35.91, 31.43.

Synthesis of anti (5) and syn (6) Substituted porphodimethene

A portion of (4) (2.35 g, 8 mmol) and 2.10 g (8 mmol) of 5-mesityldipyrromethane

were dissolved in 1L of CH2C2 and 1.1 mL (1.7 equivalents) of TFA was added. The

reaction mixture was allowed to stir at room temperature for 1 h followed by the addition









of 1.82 g (8 mmol) of DDQ to the greenish-blue solution. The color of the solution

changed from greenish-blue to deep-red. The mixture was stirred for an additional hour.

The volume was reduced to 50%, and the mixture was loaded on a neutral alumina

column and using CH2C12 as the eluting solvent. The orange solution was collected and

the solvent was removed. The residue obtained was washed with CH2C12, filtered, the

solid obtained was collected in a fritted funnel and dried under vacuum, yielding 600 mg

(14%) of the anti isomer, (5). The solvent was removed from the filtrate, containing the

syn isomer and the remaining soluble anti isomer. The remaining residue containing syn

and anti isomers were separated by column chromatography (silica, toluene) yielding an

additional 45 mg (1%) of (5). Elution with CH2C12 afforded the syn isomer, (6). Yield:

Anti isomer: 15% (645 mg). UV-Vis [CH2C12, Xmax(log s)]: 437(4.9) nm. 1H NMR (300

MHz, CDC13): 6 = 13.69 (s, 2H), 8.43 (s, 2H), 8.14 (s, 4H), 7.83 (s, 2H), 6.80 (s, 4H),

6.16 (d, 4H, J= 4.0 Hz), 5.96 (d, 4H, J= 4.0 Hz), 2.23 (s, 6H), 2.02(s, 12H), 1.54 (s,

18H), 1.47 (s, 18H). Yield: Syn isomer: 10% (430 mg). UV-Vis [CH2C12, Xmax(log s)]:

441(5.0) nm. 1HNMR (300 MHz, CDC13): 6 = 14.06 (s, 2H), 8.21 (d, 2H, J= 1.5 Hz),

8.10 (d, 2H, J= 1.2 Hz), 8.01 (d, 2H, J= 1.2 Hz), 7.88 (d, 2H, J= 1.2 Hz), 6.84 (s, 2H),

6.77 (s, 2H), 6.15 (d, 4H, J= 4.1 Hz), 5.92 (d, 4H, J= 4.1 Hz), 2.26 (s, 6H), 2.19 (s, 6H),

1.92 (s, 6H), 1.48 (s, 18H), 1.43 (s, 18H).

Synthesis of Nickel (II)-Substituted porphodimethene (7)

A saturated methanolic solution ofNiCl2.6H20 (5mL) was added to a solution of

(5) (100 mg, 0.093mmol) in CHC13 (70 mL) and the reaction mixture was heated to

reflux. The reaction progress was monitored with TLC (silica, methylene

chloride/hexanes, 1:1) and UV-visible spectroscopy. The reaction mixture was refluxed









for 12 hrs, cooled to rt and washed with water (2 x). The organic phase was dried over

Na2SO4 and the solvent was removed. The desired compound was purified by column

chromatography (silica, hexanes/CH2Cl2/CHC13, 1:1:1). The solvent was removed and

crystallized from hexanes affording the desired compound as microcrystalline red solid.

Yield: 70% (74 mg). UV-Vis [CH2C12, ax(log s)]: 442(4.6) nm. 1H NMR (300 MHz,

CDCl3,25C): 6 = 8.25 (d, 2H, J= 1.5 Hz), 8.16 (s, 2H), 7.87 (d, 2H, J= 1.2 Hz), 6.80 (s,

4H), 6.25 (s, 4H), 5.83 (s, 4H), 2.26 (s, 6H), 1.50 (s, 18H). 1HNMR (300 MHz, CDC13,

520C): 6 = 8.25 (d, 2H, J= 1.5 Hz), 8.16 (d, 2H, J= 1.2 Hz), 7.87 (d, 2H, J= 1.2 Hz),

6.80 (s, 4H), 6.25 (d, 4H, J= 4.4 Hz), 5.84 (d, 4H, J= 4.4 Hz), 2.26 (s, 6H), 2.05 (bs,

12H), 1.64 (s, 18 H), 1.50 (s, 18H). H NMR (300 MHz, C6D6,750C): 6 = 8.33 (d, 2H, J

= 1.5Hz), 8.03 (d, 2H, J= 1.5 Hz), 7.80 (d, 2H, J= 1.5 Hz), 6.64 (s, 4H), 6.37 (d, 4H, J=

4.4 Hz), 6.10 (d, 4H, J= 4.1 Hz), 2.09 (s, 6H), 1.98 (bs, 12H), 1.59 (s, 18H), 1.36 (s,

18H). 1H NMR (300 MHz, C7D8,-800C): 6 = 11.26 (s, 1H), 8.60 (s, 1H), 8.34 (s, 1H),

8.10 (s, 1H), 7.93 (s, 1H), 7.85 (s, 1H), 7.73 (s, 1H), 7.57 (s, 1H), 6.57 (s, 2H), 6.40 (s,

4H), 6.36 (s, 4H), 6.00 (s, 2H), 2.41 (s, 6H), 2.09 (s, 12H), 1.36 (s, 18H), 1.33 (s, 18H).

LRMS (DIOS) calcd for [M+H] (C76H75N402Ni): 1133.5. Found 1133.1. Isotope

Distribution Confirmed.

Syntheses of Nickel trans and cis -bis-Substituted cycloheptanone porphyrins (8 and
9)

A portion of (7) (90 mg, 0.088 mmol) and 32 mg (0.141mmol) of DDQ were

dissolved in 150 mL of dry, degassed CH2C12 under an inert atmosphere and the reaction

mixture was irradiated with a light source. The reaction progress was monitored using

TLC (silica, CH2C2/hexanes, 2:1) indicating the formation of two new compounds

within first five minutes. The reaction mixture was stirred for another 25 minutes and









TLC (silica, CH2Cl2/hexanes, 2:1) indicated the complete disappearance of the starting

material along with the formation of two compounds. The reaction mixture was washed

with water (2 x), dried over Na2SO4, and the solvent was removed. Column

chromatography (silica, CH2Cl2/hexanes, 2:1) yielded the trans isomer (8), as the first

compound to elute followed by the cis isomer (9). The solvents were removed from

fractions, trans and cis isomers, and were crystallized from hexanes to produce

microcrystalline green solid and very fine needles respectively, and dried under vacuum.

Yield: (8): 22 % (20 mg). UV-Vis [CH2C12, X(log s)]: 476(5.2), 692(4.7), 884(4.0) nm.

1HNMR (300 MHz, CDC13): 6 = 9.43 (d, 2H, J= 2.4 Hz), 9.38 (s, 2H), 8.35 (s, 6H), 7.94

(d, 2H, J= 1.5 Hz), 7.30 (s, 2H), 7.0 (s, 2H), 6.60 (d, 2H, J= 2.1 Hz), 2.52 (s, 6H), 2.50

(s, 6H), 1.61 (s, 18H), 1.27 (s, 6H), 1.23 (s, 18H). HRMS (FAB) calcd for [M+H]

(C76H73N402Ni): 1131.5087. Found 1131.5090. Yield: (9): 44% (40 mg). UV-Vis

[CH2C12, X(log s)]: 494(5.1), 672(4.4) nm. 1H NMR (300 MHz, CDC13): 6 = 9.45 (s, 2H),

9.41 (d, 2H, J= 2.4 Hz), 8.36 (d, 2H, J= 2.3 Hz), 8.32 (s, 4H), 8.0 (d, 2H, J= 2.1 Hz),

7.37 (s, 1H), 7.29 (s, 1H), 7.08 (s, 1H), 6.96 (s, 1H), 6.76 (d, 2H, J= 2.1 Hz), 2.71 (s,

3H), 2.57 (s, 3H), 2.51 (s, 3H), 2.32 (s, 3H), 1.62 (s, 18H), 1.40 (s, 3H), 1.33 (s, 18H),

1.18 (s, 3H). HRMS (FAB) calcd for [M+H]+ (C76H73N402Ni): 1131.5087. Found

1131.5028.

Synthesis of Nickel cis- bis-Substituted azulenone porphyrin (10)

A portion of DDQ (10 mg, 0.044 mmol) and FeCl3.6H20 (48 mg, 0.179 mmol)

were added to 20 mg (0.018 mmol) of (9) dissolved in dry degassed CH2C12 (25 mL),

under an inert atmosphere. The reaction mixture was heated to reflux with stirring and

progress was monitored using TLC (silica, CH2Cl2/hexanes, 1:1). After 15 minutes TLC









indicated the formation of the desired compound. An additional fraction of 10 mg (0.044

mmol) of DDQ was then added to the flask. After 10 minutes, TLC indicated the

complete disappearance of the starting material. The reaction mixture was washed with

water (2 x), dried over Na2SO4, and the solvent was removed. The desired compound was

purified by column chromatography (silica, CH2C2/hexanes, 1:1) and slow removal of

the solvents afforded the desired compound as a purple-black microcrystalline solid.

Single crystals suitable for X-ray diffraction were grown by diffusion of pentanes into a

saturated methylene chloride solution. Yield: 75% (15 mg). UV-Vis [CHC13, k(log s)]:

454(4.8), 513(4.8), 558(4.8), 846(4.2) nm. 1HNMR (300 MHz, CDC13): 6 = 8.71 (d, 2H,

J= 2.3Hz), 8.46 (s, 2H), 7.60 (d, 2H, J= 2.4 Hz), 7.30 (s, 2H), 7.08 (s, 4H), 6.73 (s, 2H),

2.50 (s, 3H), 2.49 (s, 3H), 2.15 (s, 6H), 1.85 (s, 6H), 1.44 (s, 18H), 1.40 (s, 18H). HRMS

(FAB) calcd for [M+H]+ (C76H69N402Ni): 1127.4774. Found 1127.4786.

Synthesis of Nickel trans- Substituted monoazulenone porphyrin (11)

A portion of DDQ (30 mg, 0.133 mmol) and FeCl3.6H20 (80 mg, 0.298 mmol)

were added to 20 mg (0.018 mmol) of (8) dissolved in dry degassed CH2C12 (25 mL)

under an inert atmosphere. The reaction mixture was heated to reflux with stirring and

progress was monitored using TLC (silica, CH2Cl2/hexanes, 1:1). After 3 h, additional

amounts of DDQ (15 mg, 0.066 mmol) and FeCl3.6H20 (80 mg, 0.298 mmol) were

added. Refluxing was continued for another 1 h. The reaction mixture was allowed to

cool down to room temperature and washed with 25 mL of a freshly prepared aqueous

solution containing 50 mg of NaBH4. The resulting mixture was diluted with CH2C2 (20

mL). The organic phase was washed with water (3 x), dried over Na2SO4, and the solvent

was removed. The compound was purified by column chromatography (silica,









CH2Cl2/hexanes, 1:1). The solvents were removed, and the compound was crystallized

from hexanes yielding reddish brown colored microcrystalline solid. Yield: 50% (10 mg).

UV-Vis [CHC13, X(log s)]: 467(5.1), 579(4.7), 650(4.2), 832(4.3), 884(4.3) nm. 1H NMR

(300 MHz, CDC13): 6 = 9.28 (d, 1H, J= 2.4 Hz), 8.77 (d, 1H, J= 2.6 Hz), 8.75 (d, 2H, J

= 1.0 Hz), 8.31 (d, 1H, J= 2.4 Hz), 8.02 (d, 1H, J= 2.1 Hz), 7.84 (d, 1H, J= 5.0 Hz),

7.66 (d, 1H, J= 5.0 Hz), 7.60 (d, 1H, J= 2.1 Hz), 7.26 (s, 2H), 7.16 (s, IH), 7.12 (s, 1H),

7.10 (s, 1H), 7.03 (s, 1H), 6.90 (d, 1H, J= 2.1 Hz), 2.53 (s, 3H), 2.51 (s, 3H), 2.31 (s,

3H), 2.17 (s, 3H), 1.89 (s, 3H), 1.58 (s, 9H), 1.57 (s, 3H), 1.51 (s, 9H), 1.44 (s, 9H), 1.34

(s, 9H). HRMS (FAB) calcd for [M+H] (C76H71N402Ni): 1129.4931. Found 1129.4830.

X-ray crystallography

Unit cell dimensions (Table 5-1) and intensity data were obtained by Prof Michael.

J. Scott on a Siemens CCD Smart diffractometer at -800C, with monochromatic Mo-Ka

X-rays (k = 0.71073A). The data collections nominally covered over a hemisphere of

reciprocal space, by a combination of three sets of exposures; each set had a different D

angle for the crystal and each exposure covered 0.30 in co. The crystal to detector distance

was 5.0 cm. The data sets were corrected empirically for absorption using SADABS.35

The structure was solved using the Bruker SHELXTL software package for the PC, using

the direct method option of SHELXS. The space group was determined from an

examination of the systematic absences in the data, and the successful solution and

refinement of the structure confirmed these assignments. All the hydrogen atoms were

assigned idealized locations and were given thermal parameter equivalent to 1.2 to 1.5

times the thermal parameter of the carbon atom to which it was attached. Relevant

crystallographic data are listed in Table 4-1.









Table 4-1. X-ray data for crystal structure of compound (10).2CH2C12.1/2 Et20
Chemical Formula Cso H77 C14 N4 Ni 02.50
Formula Weight 1334.97
Crystal System Monoclinic
Space Group C2/c
Z 8
Temp, K 173(2)
Dcaic/gcm3 1.206
a A29.4311(14)
bA 12.3021(6)
cA 41.325(2)
, deg 100.622(10)
VA 14705.9(12)
i, mm 0.457
Uniq. Data coll./obs. 17219/8058
R1 0.0560
wR2 0.1141














CHAPTER 5
RESULTS AND DISCUSSIONS

Syntheses of Porphodimethenes

Buchler et al. extensively studied the chemistry of porphodimethenes but were only

able to achieve the synthesis of porphodimethene via reductive alkylation of porphyrins

(Figure 5-1).25 This method yielded various isomeric products which were difficult to

separate, thus lowering the yield of the preferred compound. In addition, the

methodology is ill-suited for the synthesis of porphodimethene having aryl-substituents at

all the four meso positions, thereby, limiting the ability to modify the macrocycle to

investigate the electronic, steric and solubility properties of the resulting products.


RH

N N 1 2e- 1 N
Zn Z Zn /
N N 2. R-X N N

(R = alkyl, X = Br, I)
IR H

Figure 5-1. Reductive alkylation of zinc octaethylporphyrin. 25

In recent years, several new synthetic routes for the synthesis of porphodimethenes

have been reported. These include: condensation of pyrrole with sterically encumbered

aldehydes, the reaction of ketones with aryl dipyrromethanes (Figure 5-2)26 and

dealkylation of porphyrinogen (Figure 5-3),27 but these procedures are applicable only for

the synthesis of meso-alkyl substituted porphodimethenes rather than meso-aryl

substituted.










Ar
0 -N NH--
1. acid N \

2 NH H N / 2. DCQ NH N
40 fold excess

Ar

Figure 5-2. Reaction of ketones, exemplified acetone, with aryl dipyrromethanes. 26
R R R

THF
N\
R R SnCl4(THF)2 \/
n R n
R \N R
S THF \ (R=alkyl)

R RR

Figure 5-3. Dealkylation of porphyrinogen. 27

In 1986, Chang and co-workers demonstrated the condensation reaction between

acenaphthenequinone and 2 equivalents of 2-(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole

to yield the corresponding dipyrromethane (Figure 5-4).28 In this paper, Chang reported

that 'acenaphthenequinone' displays the ability to act as an aldehyde. According to the

MacDonald [2+2] condensation under Lindsey's condition between 5-substituted

dipyrromethane and aromatic vicinal diketones, should result in porphodimethenes rather

than porphyrins (Figure 5-5).17

o\ O H 0
+ 2 OMe acid HCOOMe
+2 \ 0 / \ NH
0-NH
COOMe

Figure 5-4. Condensation reaction between acenaphthenequinone and 2 equivalents of 2-
(ethyloxycarbonyl)-3-ethyl-4-methylpyrrole. 28














2 +2
NH HN H N
R'
(Ar2


1. acid
2. DDQ
2. DDQ


v Arl

Figure 5-5. Lindsey's methodology of MacDonald [2+2] condensation for trans-
substituted porphyrins. 17

Inspired by these observations, Dr. Michael Harmjanz devised a synthetic strategy

using the MacDonald [2+2] condensation, wherein 5-substituted, P-unsubstituted

dipyrromethanes can react with acenaphthenequinone in the presence of catalytic

amounts of either BF3-OEt2 or TFA under Lindsey's conditions, followed by oxidation

with DDQ to produce porphodimethenes rather than porphyrins.29


Ar H

2 ---
NH HNO





2 O


NH Ar N
Anti
1. TFA, CH2C2 Ar
2. DDQO



S


Figure 5-6. MacDonald [2+2] condensation reaction between 5-substituted, P-
unsubstituted dipyrromethanes with acenaphthenequinone, adapted from
Harmjanz, M; Gill, H.S; Scott, M. J. J. Org. Chem. 2001, 66, 5374.

Various porphodimethenes were then synthesized utilizing this simple

methodology, exhibiting different stereoelectronic properties.29'30 The condensation









yields two isomers syn and anti as described in the figure 5-6. The two isomers can be

easily distinguished by 1H NMR spectroscopy and UV-visible spectroscopy.

Metallation of Porphodimethene

Porphodimethenes are generally metallated under refluxing conditions in

chloroform, using saturated methanolic solution of the desired metal salt (Figure 5-7).

The progress of a reaction could be easily monitored with the help of thin-layer

chromatography and UV-visible spectroscopy. The inclusion of metal into the

macrocyclic cavity, cause a bathochromic shift of the main absorption band.





NH Nf Msalt/MeOH N
N Ar HN A,CHCl3 0r N




Ar=


M =Metal

Figure 5-7. Metallation of Porphodimethene.

The significance of metallating porphodimethene prior to porphyrin synthesis could

be revealing with the purpose of exploring these macrocyclic systems. Since the presence

of two sp3 centers at the trans-positions in meso-substituted porphodimethenes severely

alters the electronic and steric properties of porphodimethenes as compared to the

porphyrins, metalloporphodimethenes should exhibit divergent electronic and steric

properties as compared to metalloporphyrins.27 Secondly, the metallation of

porphodimethenes could also prove valuable for the synthesis of those metalloporphyrins









which may not be accessible due to steric or electronic properties associated with the

porphyrin peripheries under consideration.

Syntheses of bis-Cycloheptanone porphyrins

While measuring the quantitative UV-visible absorption and extinction coefficient

of the palladium anti-porphodimethene, a color change from red to green was observed.





Light
\ N Li forms two products
N ... N
-Pd -7 O


Ar
anti-porphodimethene
Ar = Mesityl











250 350 450 550 650 750
Wavelength (nm)


Figure 5-8. Time course UV-Visible spectra of palladium anti-porphodimethene

In order to identify the species formed from this reaction, a time course UV-visible

experiment was performed and each scan was recorded after one minute (Figure 5-8).

During the reaction, the UV-visible spectra revealed numerous features. Two isosbestic

points were observed suggesting the clean transformation of the metallated

porphodimethene to new species. The characteristic absorption maxima experienced










decrease in absorbance along with the formation of two new characteristic Soret bands,

and Q-bands in the low energy region were also observed.

From these observations it appears that porphodimethene, which is 2e- reduced

form of porphyrin, may be undergoing an oxidation reaction to yield the corresponding

two porphyrin products. In light of above rationale, porphodimethenes were treated with

excess DDQ in presence of light by H.Gill (Figure 5-9). The reaction was carried out

under anhydrous conditions and may be undergoing a Norish Typel process,

characteristic of aromatic ketones.31 Upon photolysis, aromatic ketones undergo a-

cleavage, leading to the formation of radicals. The radicals can then undergo secondary

processes like decarbonylation, elimination and ring expansion leading to the formation

of new products. Decarbonylation and elimination processes are generally observed in

case of strained rings systems (3/4 membered ring) leaving ring expansion as the obvious


Pd


Ar
anti porphodimethene


Ar
O





Ar
1. LIGHT, 1.2 eq. DDQ trans porphyrin
2.1.2 eq. DDQ AND
Dry CH2CI2


d
Ar
--M N--=

Ar
syn porphodimethene


Ar=

Figure 5-9. Syntheses of bis-Cycloheptanone porphyrins.


cis porphyrin









choice. The ring expansion occurs via combination of 1,4 biradical leading to the

formation of 7-membered ring system.

The reaction progress was monitored by UV-visible spectroscopy and thin-layer

chromatography and two products, cis and trans isomers, were obtained. The isomers

were easily separated by column chromatography (silica, methylene chloride/hexanes,

2:1). The trans isomer elutes first. Both isomers are green solids and exhibit

characteristic absorption maxima with a red shifted Soret band and the appearance of Q-

bands in the low energy region. The isomers can be easily distinguished by 1H NMR

spectroscopy.

In order to further investigate the chemistry behind these highly substituted

porphyrins, the oxidative dehydrogenation of the above mentioned bis-cycloheptanone

porphyrins were carried out in the presence of a Lewis acid and an oxidant (Figure 5-10).

The resulting product suffered from poor solubility. In order to isolate and

characterize these oxidative dehydrogenation products, the syntheses of

porphodimethenes with sterically encumbered peripheries was carried out. The

incorporation of the bulky tert-butyl groups on the acenaphthaquinone moiety was

preferred to improve the solubility issues. The desired dione required for the MacDonald

[2+2] condensation is not commercially available, so synthetic strategy was designed to

isolate the desired 4,7-Di-t-butylacenaphthene-1,2-dione from the commercially available

acenaphthene. The synthetic pathway involves four steps as shown in figure 5-11, where

the first three steps namely, Friedel-Crafts alkylation leading to the formation of 4,7 Di-t-

butylacenaphthene (1) followed by esterification of (1) yielding (2). The hydrolysis of (2)

thereby generating an alcohol (3), were modified from published procedures.32' 33 The



















FeCI3.6H20
DDQ


sparingly soluble purple
products


Ar=


Figure 5-10. Oxidative dehydrogenation of bis-cycloheptanone porphyrins


t- BuCI
AIC13


- -


Pb304
A, MeCOOH


0 0

SeO2
1,4 Dioxane
t-Bu t-Bu t-E


MeOH
NaOH/H20


Figure 5-11. Synthesis of 4, 7- Di-t-butylacenaphthenedione involving (1) Friedel-Crafts
alkylation, (2) Esterification, (3) Hydrolysis, (4) Oxidation reaction
respectively


0 Ar






Ar 0









alcohol (3) was subjected to oxidation to the desired 1, 2-dione using selenium dioxide in

refluxing 1,4-Dioxane. The fine yellow needles of the desired 1,2-dione (4) were

obtained. The entire synthetic route was performed without the use of column

chromatography. The products obtained in each step were characterized using 1H and 13C

NMR spectroscopy.

Utilizing MacDonald [2+2] condensation reaction under Lindsey's condition, 4,7-

Di-tert-butylacenaphthaquinone was condensed with 5-Mesityldipyrromethane in

presence of TFA followed by subsequent oxidation with stoichiometric amounts of DDQ

at room temperature (Figure 5-12). The reaction mixture was then filtered through a

column of neutral alumina thereby yielding the desired mixture of anti (5) and syn (6)

porphodimethene. Since (5) is only slightly soluble in methylene chloride, it can be

immediately isolated from the reaction mixture in 14% yield. Column chromatography of

the residue with toluene followed by methylene chloride yielded an additional 1% of the

(5) followed by the isolation of the 10% of the (6). Both the isomers, (5) and (6) were

obtained as bright orange solids and exhibits characteristic absorption maxima in UV-

visible spectra at 437 and 441 nm respectively. The two isomers can be easily

distinguished by H NMR spectroscopy. Both the isomers exhibit two sets of doublets for

the pyrrolic C-H protons between 5.95 and 6.18 ppm. The corresponding signal for

porphyrins are observed around 8-9 ppm highlighting the lack of electronic

communication between the two halves of the porphodimethene macrocycle leading to

shielding for the pyrrolic protons. The resonance for the N-H proton for both the isomers

appear downfield shifted (13.69 ppm: 5 and 14.06 ppm: 6) in the 1H NMR spectra. Since









(5) can be isolated in higher yields than (6), it was used exclusively for all the following

reactions though both isomers react in the same manner.





NHHN 1. TFA HN
2. DDQ RNH Ar
+ Anti
0 O CH2C12 Ar 15%
R + R
2

R R 0
R R N HN

R / Sy R
Syn
Ar Ar 10%


R = t-Butyl

Figure 5-12. MacDonald [2+2] condensation reaction between 5-mesityl dipyrromethane
and 4,7-Di-tert-butylacenaphthaquinone

Metallation of anti-Substituted porphodimethene with Ni (II)

Metallation of (5) with nickel was the next objective. The compound (5) was

refluxed for 15 hours in chloroform and methanolic solution of Dichloronickel(II)

hexahydrate (Figure 5-13). The reaction progress was monitored with the help of UV-

visible spectroscopy and thin-layer chromatography. With the introduction ofNi (II) into

the macrocyclic cavity, the main absorption band of (5) experienced a bathochromic shift.

The reaction mixture was cooled, subjected to aqueous work-up followed by column

chromatography (silica, methylene chloride/chloroform /hexanes, 1:1:1) afforded the

desired product (7).









R R

NiC2.6H20 / MeOH \
/ \ HN CHCl3 / Reflux, 15 Hrs

RNAr N
Ar
SAr
Ar = '


R = t Butyl

Figure 5-13. Metallation of anti-Substituted porphodimethene with Nickel (II)

In the 1H NMR spectrum of (7), several resonances associated with aromatic and

aliphatic protons could not be identified. This observation may be attributed to the fast

flexing of the macrocycle on the NMR time scale, resulting in broadening of signals for

the above mentioned protons. In order to identify all the resonances, variable temperature

NMR studies were carried out at 520C (CDC13) and 75C (C6D6), and the missing

resonances could be resolved. At these temperatures, the rate of interconversion is fast on

the NMR time scale, thereby generating a spectrum which is weighted average of the

separate conformations. However, resonances corresponding to two naphthyl protons

were still not observed and low temperature NMR (-800C, d-Toluene) measurements

reveal all the protons. At -800C, the rate of interconversion is slow on the NMR time

scale. As a result of which, the situation approximates to that of the rigid molecule and

consequently, the observed spectrum can be interpreted in terms of a single rigid

confirmation. A considerable downfield shift was also observed for one of the eight

naphthyl protons and the resonance could be possibly assigned to the proton a to the

carbonyl group, close to the macrocycle. The shift may be attributed to the close

proximity of the electron withdrawing carbonyl group and in addition to the low electron

density experienced by the proton due to the induced magnetic field.










Synthesis of Nickel-bis-Substituted cycloheptanone porphyrins

The compound (7) was subjected to oxidation using light and excess DDQ, under

anhydrous conditions (Figure 5-14). The progress of the reaction was monitored with the

help of UV-visible spectroscopy and thin layer chromatography. The column

chromatography (silica, methylene chloride/hexanes, 2:1) resulted in the separation of

both the isomers namely, trans (8) and cis (9)-substituted cycloheptanone porphyrins.

The compound (8) elutes first followed by (9) in comparatively higher yields than the

former. Both the isomers are shiny green colored solids. The cis and trans isomers exhibit

red shifted Soret band at 493 and 476 nm, and intense broad Q-bands in the low energy

region at 672 and 692 nm respectively as compared to ZnTPP. The two isomers are

distinguished by H NMR spectroscopy. The compound (9) exhibits six resonances for

the six mesityl methyl protons whereas three single sets of resonances are obtained for (8)

Ar




R 0
R


/ /N



N N DDQ / LIGHT
0 Ni / Dry CH2C12 AND
N Ar Ar



Ar = Ni

R / R
R = t Butyl
Ar

Figure 5-14. Syntheses of Nickel-bis-Substituted cycloheptanone porphyrins

indicating lack of symmetry between the two halves of the macrocycle. In addition, both

the isomers exhibitpara methyl protons resonances are observed in the region between









1.05-1.3 ppm as compared to the ortho- methyl resonances (2.4-2.8 ppm) suggesting high

electron density experienced by the former leading to significant shielding.

Synthesis of Nickel-bis-Substituted azulenone Porphyrins

The compound (9) was subjected to oxidative dehydrogenation reaction utilizing

DDQ and FeCl3.6H20 under anhydrous conditions (Figure 5-15). The progress of the

reaction was monitored with the help of UV-visible spectroscopy and thin layer

chromatography. Column chromatography (silica, methylene chloride/hexanes in 1:1)

afforded a perfectly flat porphyrin (10) bearing exocyclic ring systems. The compound

(10) was characterized using 1H NMR spectroscopy, revealing six sets of resonances for

the aromatic protons and three single sets of resonances for the methyl protons. The

compound displays significant bathochromic shift of the Soret band and intense (logs =

4.8) Q-bands in the low energy region (850 nm). Single crystals were obtained via vapor

diffusion of pentanes to the saturated methylene chloride solution (Figure 5-17). The

solid state structure shows a relatively flat porphyrin. The space group of the compound

Ar Ar


SN N DDQ/FeC3 6H20 N N
N N / Dr ryCH2C2 N N
R RR R
Ar Ar

Ar =

R = t- butyl

Figure 5-15. Synthesis of Nickel-cis-bis-Substituted-azulenone porphyrin

was C2/c. The porphyrin core, defined by the four nitrogens and metal exhibit a slight

deviation from 900 and 1800, and slightly longer metal-nitrogen bond lengths for N1 and









N4 compared to N2 and N3. This observation may be attributed to the presence of

electron withdrawing carbonyl groups close to Ni-N bond lengths.

However, utilizing the same synthetic strategy for compound (8), the 1H NMR

spectrum indicated six single sets of resonances for mesityl methyl protons and four

single sets were obtained for the t-butyl groups, indicating only one naphthyl hydrogen

and /? pyrrole hydrogen of (8) underwent oxidative dehydrogenation leading to the

formation of compound (11) (Figure 5-16). In comparison to compound (9), the oxidative

dehydrogenation reaction proceeded at a slower rate. The trans-cycloheptanone having

the same naphthyl substituents and palladium as a metal underwent complete

transformation to trans-bis-azulenone product.34 These observed facts suggest that the

reaction may involve longer time leading to the formation of trans-bis-azulenone

porphyrin, but, at the same time allowed the isolation of (11). The reaction progress was

monitored with the help of UV-visible spectroscopy and thin layer chromatography.

Column chromatography (silica, methylene chloride/hexanes, 1:1) afforded (11) and

reveals a significant bathochromic shift of the Soret band along with an increase in

intensity of and shifting of frequency of the Q-bands in the low energy region (884 nm).

Ar Ar

N N R N N R
/ \N/ ~~ DDQ / FeCI3 6H20 \N
N N Dry CH2C12 N

S Ar O Ar O


K--v
Ar

R = t-butyl

Figure 5-16. Synthesis of Nickel-trans-Substituted monoazulenone porphyrin.


































Figure 5-17. ORTEP diagram of the solid-state structure of Nickel cis-bis-Substituted
azulenone porphyrin, (10). Hydrogen atoms are omitted for clarity.
















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BIOGRAPHICAL SKETCH

Parul Angrish was born in India, on August 11, 1977. She received a Bachelor of

Science from St. Stephen's College, University of Delhi, India and Master of Science

from the Indian Institute of Technology, Kanpur, India. After completing her master's

she joined the Department of Chemistry, University of Florida, in 2001.Her research

interests are synthetic organic and inorganic chemistry.