SOLID-SUPPORTED PORPHYRINS FOR CATALYSIS AND SENSING

Abstract CHAPTER 1: GENERAL INTRODUCTION This PhD thesis is focused on the development of porphyrin-based strategies for the synthesis of useful fine chemicals by using convenient both homogeneous and heterogeneous approaches. Regarding the use of innovative heterogeneous systems, in recent years our group developed the possibility of grafting anionic porphyrins onto ColourCatcher® (CC) sheets, a laundry item used for capturing leaking dye during washes. CC is composed of a non-texture sheet made of cellulose and other natural fibres, and its surface is functionalised with organic ammonium groups positively charged. The employ of this innovative technique of supporting porphyrins onto the eco-friendly cheap day-life CC support allowed to create a little library of heterogenized porphyrins with different applications in sensor and catalysis fields. CHAPTER 2: AZOBENZENE SYNTHESIS PROMOTED BY CoTPP The first part of the thesis was devoted to the synthesis of azobenzenes, valuable compounds largely applied in textile, medical, and dye industries by a dehydrogenative coupling of anilines that occurs in the presence of CoII(TPP) (TPP=dianion of tetraphenyl porphyrin) catalyst and 4-nitrophenyl azide oxidant specie. Nine substituted compounds were obtained in yields up to 72% together with 4-nitrophenyl amine, which is the stoichiometric by-product of the process. The procedure displayed good sustainability due to the almost quantitative recovery of pure 4-nitrophenyl amine that can be converted into the azide oxidant reagent and re-used to pave the way for an efficient circular process. After the investigation of the reaction scope, a mechanistic study was performed and the achieved data supported the occurrence of a radical mechanism mediated by putative nitrene radical cobalt intermediate1. Unfortunately, the grafting step of cobalt porphyrin onto CC sheets was unsuccessful therefore the synthesis of azobenzene under heterogeneous conditions was not investigated. CHAPTER 3: CYCLOPROPANE SYNTHESIS VIA CARBENE-TRANSFER This chapter reports the investigation on the transfer of carbene moiety to unsaturated and saturated substrates promoted by hemin derivative and by hemin derivative grafted onto the ColourCatcher® sheets. The cyclopropanation of α-methyl styrene by ethyl diazoacetate (EDA) was employed in solvent-less condition as the model reaction to test the catalytic efficiency of CC-based heterogeneous catalysts. Before testing the heterogeneous catalyst, the catalytic activity of the hemin derivative (5) was investigated under homogeneous conditions, which was obtained by the esterification of the carboxyl groups of hemin and the replacement of the apical chlorine of hemin with a methoxy group to make the catalyst soluble in organic reaction medium. Thus, experimental conditions of the catalytic reaction were optimized, and the desired compound was obtained in 92% yield, and 92% selectivity with a trans/cis ratio of 74:26 at 166 °C in 1 hour. We attempted the heterogenization of the catalyst onto ColourCatcher® sheet by applying the already used grafting method2 to hematin sodium salt and the resulting supported porphyrin was refluxed in methanol to obtain 5@CC. 5@CC was applied in cyclopropanation reactions in the same condition employed for the homogeneous reactions; cyclopropanes were obtained in 78% yields with selectivity and trans/cis ratio identical to that observed in the presence of catalyst 5. Very interestingly, no catalyst leaching was observed. The reaction scope was investigated using various diazo compounds, revealing different yields and diastereoselectivities. Notably, the system was active by applying challenging acceptor-acceptor ethyl diazo malonate (EDM) yielding the corresponding cyclopropane in 46% yield. A preliminary study in flow chemistry was also performed, using 5@CC at 60 °C in solvent-free condition by pumping a α-methyl styrene solution of EDA through a column packed with the heterogenized catalyst. The solution was left in the packed column for a residence time of 30 minutes and recycled 5 consecutive times. The corresponding cyclopropane was obtained in 15% yield and 74:26 trans/cis selectivity. These results must be considered very preliminary and reaction conditions will be optimized in order to maximize yields and selectivity. Overall, these data contribute insights into the catalytic performance of hemin derivatives in cyclopropanation reactions emphasizing the potential of heterogeneous catalysts in solvent-free systems and under flow chemistry conditions. CHAPTER 4: PHOTOOXIDATIVE SYNTHESIS OF IMINES FROM AMINES AND CARBOXYLIC ACID FROM ALDEHYDES This chapter reports a method which exploits the feature of porphyrin to generate active oxygen species from molecular oxygen in the presence of white light in view of employing the very well-known activity of ROS species in the oxidation of various substrates. An A3B type zinc anionic fluorinated porphyrin (Zn10) was synthesized, fluorinated ones are a class of porphyrin showing a very good photo activity, to graft it onto the ColourCatcher® sheet (Zn10@CC) and use it to promote photooxidation reactions. The porphyrin Zn(10) was supported onto ColourCatcher® sheet by using a slightly modified procedure already used in our previous work2 by soaking the ColourCatcher® sheet into a tetrahydrofuran/water (1:2) solution of Zn(10) and the obtained Zn(10)@CC catalyst was washed and dried. The obtained material was employed to promote the photooxidative coupling of amines to obtain imines. Once reaction conditions were optimized, ten different substrates were tested by employing white LED as the light source. Desired imines were obtained in yields up to 100% with complete selectivity. The nature and the activity of the supported catalyst allowed it to work with the low catalytic loading of 0.3% and it was also possible to recover the catalyst by a simple filtration avoiding any other purification. In order to better expand the reaction scope, the catalytic efficiency of heterogeneous system Zn(3) was tested in the photooxidation of hexanal using acetonitrile as the reaction solvent, 1.0 atm. of oxygen and irradiating with a household lamp.3 The model reaction was also performed with homogeneous catalyst Zn(10), and acquired data revealed a higher activity of the supported complex with respect to that of the free porphyrin in promoting the photooxidation. The reaction conditions were optimized, and the reaction was run with five different aldehydes that were converted into corresponding acids in good yields and complete selectivity. CHAPTER 5: CARBON DIOXIDE CYCLOADDITION REACTION – HOMOGENEOUS CONDITIONS A large part of this PhD thesis was devoted to develop eco-compatible strategies for the valorisation of CO2 into useful fine chemicals. The fixation of CO2 by cyclization with tensioned heterocycles such as epoxide and aziridines has been extensively studied, therefore it has been compulsive to enhance the bio-compatibility of the procedure by using simple and low-cost catalysts and, when possible, move from homogeneous to heterogeneous systems. For this purpose, bis-protonated porphyrins was synthesised by treating commercially available TPPH2 with different acids. The so-obtained bifunctional catalysts present a protonated core that acts as Lewis acid and two counter-anions that are a source of nucleophiles. Complexes reported in Scheme 8 can promote the synthesis of N‐alkyl oxazolidinones by the CO2 cycloaddition to corresponding aziridines. They are able to activate CO2 thanks to their acidic behaviour while the presence of nucleophilic anions is responsible for the aziridine opening that becomes nucleophile enough to attack activated carbon dioxide. After that, a ring closing process is responsible for the formation of the desired. The catalytic system does not require the presence of any Lewis base or additive and shows appealing features in terms of cost‐effectiveness and eco‐compatibility. The metal‐free methodology is active by using the low catalytic loading of 1% mol and the chemical stability of the protonated porphyrin allowed its recycling for three consecutive times without any decrease in performance. In addition, a DFT study was performed to suggest how a simple protonated porphyrin can mediate the CO2 cycloaddition to aziridines yielding oxazolidinones4. In view to transfer the same catalytic system under heterogeneous conditions, another A3B type porphyrin was synthesized, it bore a suitable linker with an anionic moiety to graft the porphyrin onto the ColourCatcher® sheet. Then, the already used grafting method2 was employed to support the porphyrin 5 on CC and the heterogeneous material was treated with HCl vapour to protonate the porphyrin core. Unfortunately, the synthesized free-metal heterogeneous catalyst was not active in promoting the oxazolidinones synthesis. CHAPTER 6: CARBON DIOXIDE CYCLOADDITION REACTION – HETEROGENEOUS CONDITIONS This chapter reports the utilization of hemin derivatives to promote the CO2 cyclization reaction with tensioned heterocycles such as epoxide and aziridines to synthesize respectively cyclic carbonates and oxazolidinones. In order to enhance the catalytic activity without losing the eco-compatibility of the catalyst, hemin-derivatives were supported onto CC, which displays very good eco-friendly characteristics due to their biological nature. First, the organic-soluble 4 complex was synthesized and tested for promoting cycloaddition of CO2 to epoxides and aziridine under homogeneous conditions. Catalyst 4 was employed in the reaction of CO2 with styrene oxide and N-butyl-2-phenyl aziridine as model reactions, respectively. While the synthesis of oxazolidinone occurred at 125° C, 1.2 MPa of CO2 pressure, 16 hours of reaction time with 1% of catalyst loading and without any additive, the synthesis of cyclic carbonates required milder conditions (100 °C, 0.6 MPa of CO2 pressure and 4 hours of reaction time) with a lower catalyst loading (0.7 mol%). However, in this last case, the presence of tetra butyl ammonium chloride (1.4 mol%) as the co-catalyst was required. At this point, in order to move from a homogeneous system to a heterogeneous one, hemin was treated with a NaOH solution to obtain the hematin sodium salt 6 suitable to be grafted onto ColourCatcher® sheet by soaking it directly into the basic hematin solution.2 The so-obtained 5@CC catalyst was tested to promote the same model reactions previously studied under homogeneous conditions. While 5@CC did not promote the reaction between CO2 with styrene oxide, the desired oxazolidinone from aziridine was obtained in 70% yield with 95% selectivity of regioisomer B. The reaction scope of the oxazolidinones synthesis was also investigated by testing ten different aziridines. Corresponding oxazolidinones were obtained in yields up to 91% with 100% selectivity. Finally, the reaction mechanism was elucidated through DFT calculations. CHAPTER 7: POLYHYDROXYURETHANES SYNTHESIS PROMOTED BY DEEP EUTETIC SOLVENTS Chapter 7 reports the work done at the University Claude Bernard Lyon-1 where, under the supervision of Prof. B. Andrioletti, the use of cyclic carbonates to produce poly hydroxy urethanes (PHU), a greener substitute for polyurethanes (PU) was investigated. The production of this polymer leads to a great health and environmental problem because PUs are synthesized employing isocyanates, toxic and hazardous building blocks5. PHU can be obtained by aminolysis of bis-cyclic carbonates and diamines but the synthesis of polymer with a long chain is still a challenging issue. This problem is due to the lower reactivity of cyclic carbonates with respect to their corresponding isocyanates and also to the high association grade of the oligomers that are formed during the polymerization, which strongly affects their solubilization and mass transfer6. B. Andrioletti and G. Shen recently devised a pioneering methodology for synthesizing PHUs by using furan-2,5-dicarboxylate bis-cyclic carbonate and some diamines in the presence of deep eutectic solvents (DES). These molecules are environmentally friendly solvents composed of two or more substances, usually one H-bond donor and one H-bond acceptor, that are in charge of both activatimg carbonyl groups and disrupting hydrogen-bond interactions among the oligomers. This dual action enhances the overall reaction yield and improves the outcome of the synthetic process.7 Starting from this previous work, this project aims to investigate i) the method's dependence on reaction conditions and ii) its robustness, applying it in the reaction of various bis-cyclic carbonates and diamines. Through this approach, the dependence of the outcome of the process on the reaction conditions applied was investigated. The advantages of employing the DES in the PHU synthesis was analyzed by studying the model reaction between bis-glycerol bis-cyclic carbonate (BGBC) 89 and isophorone diamine (IPDA) a. Three distinct solvent systems were compared for the PHU synthesis: an organic DES, a metal-based DES, and a conventional solvent that was previously utilized in the literature. On the basis of previous data already acquired by B. Andrioletti and G. Shen7, the organic-based DES composed of urea/choline chloride (1:2) (reline) was selected as the organic deep eutectic solvent. On the other hand, the metal-based DES, consisting of ZnCl2/urea (1:3.5),8 was chosen due to the Lewis acid properties of zinc chloride, which can activate the cyclic carbonate carbonyl group via nucleophilic attack and finally, acetonitrile was chosen as traditional organic solvent due to its sustainability and effectiveness.9 Achieved results revealed the superiority of reline with respect to the other two solvents in terms both of conversion and the resulting polymer's molecular weight. Considering positive results in employing reline, the dependence of the reaction efficiency on the experimental conditions such as concentration, temperature and time was studied. Concentration doesn’t play a fundamental role, whereas when the polymerization was run at a temperature below 60 °C a complete conversion couldn’t be reached even with increasing reaction time. Then, best performances were observed by running the reaction with a concentration of 1.0 M, for 16 hours at 60 °C, 89a was obtained in a 100% yield with a satisfying polymer’s molecular weight. The robustness of the method was then demonstrated by synthesizing six different PHUs in quantitative yields with good polymer chain length by applying three bis-cyclic carbonates and two aliphatic primary diamines. Moreover, the synthesis was successfully scaled up on a multigram scale, demonstrating the effectiveness of the method. Even if the methodology did not work by using a less reactive aromatic bis-amine5 as the reactant, acquired data highlighted the advantages of reline in PHU synthesis, offering insights into optimal conditions and expanding the method's applicability to diverse monomers with excellent results. CHAPTER 8: DEVELOPMENT OF A SUSTAINABLE SENSOR FOR MERCURY IN DRINKABLE WATER Moving from catalysis to the sensor field, this chapter describes the investigation done to develope a cheap and sustainable chemical sensor for mercury ion detection in drinking water. To do that, the ability of porphyrins to reversibly coordinate mercury ions with a consequent change of color was exploited, making it possible using UV-vis spectroscopy to appreciate the interaction between the mercury ion and the porphyrin. Following Lindsey’s strategy10, a tetra(4-carboxyphenyl)porphyrin (TCPPH2) was synthesized, a meso-substituted porphyrin with four carboxylic groups pointing outside the ring, those make it water-soluble. And its behaviour to coordinate reversibly Hg2+ in water and its consequent change of colour by UV/vis. spectroscopy were investigated. After having assessed the feasibility of detecting mercury ions in water, a grafting method to support our porphyrin onto the ColourCatcher® was developed: TCPPH2 was treated with NaOH(aq), it became a tetra-anionic porphyrin that can interact with the cationic functionalizations of the ColourCatcher® forming ionic bond, obtaining the desired supported porphyrin (TCPPH2@CC). After the porphyrin was supported, tests to study the reversibility of the coordination of the mercury ions and to optimize the proper porphyrin loading onto the sheet to maximize the efficiency of the sensor were performed. The applicability of this porphyrin sensor was tested by Prof. Paolesse’s group in Rome by using a homemade instrument prepared at Tor Vergata University. The instrumental setup showed remarkable sensitivity, capable of detecting mercury even in traces in aqueous samples (down to 1 × 10-8 M) to detect even mercury in a concentration lower than the permissible limit in drinking water. 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