Search

Oligothiophene derivatives play a central role in the formulation of materials used in devices in the field of organic electronics. In this work, we report the results of the study of UV-vis absorption and fluorescence spectra, in several solvents, of a series of oligothiophenes recently synthesized in our laboratory. The studied oligothiophenes present different structures due to several factors: the donor– acceptor (D–A) or acceptor–donor–acceptor (A–D–A) architecture, the number of thiophene rings in the backbone (ranging from three to eight), the number and position of solubilizing octyl chains in the backbone, and the type of acceptor moieties (from Knoevenagel condensation either with ethyl cyanoacetate or 3-ethylrhodanine). Since solvents with different polarities were adopted, we provide a detailed analysis on the observed positive and negative solvatochromism effects depending on the symmetry of the oligomers, the lengths of the backbones and the kind of acceptors adopted. Moreover, the electrochemical synthesis of a new donor–acceptor oligothiophene (which can be assumed as a model compound) by anodic dimerization is reported, along with the voltammetric analysis of the obtained product.

Thiophene derivatives, either “small molecules,” oligomers, or polymers, play a role of primary importance among organic semiconductors, therefore, they have numerous and different technological applications in the field of Organic Electronics. For this reason, thiophene-based materials are found in devices, such as Organic Light-Emitting Diodes (OLEDs), Organic Field-Effect Transistors (OFETs), organic solar cells (OSCs), organic photodetectors, etc. Oligothiophenes and polythiophenes have common excellent charge transport properties and synthetic procedures that are now well established. Furthermore, oligothiophenes do not possess the intrinsic disadvantages of polythiophenes, such as the lack of welldefined structures and the inevitable presence of impurities. Electrochemistry can give a significant contribution to the field of oligothiophenes not only by allowing the determination of the Highest-Occupied Molecular Orbital (HOMO) and the Lowest-Unoccupied Molecular Orbital (LUMO) energy levels by the means of Cyclic Voltammetry (CV), but also through rendering oligothiophenes syntheses more expeditiously in comparison with the classical organic ones. This review outlines the application of electrochemistry techniques in the synthesis of oligothiophene derivatives.

The anodic oxidation of 1-butyl-3-methylimidazolium tetrafluoroborate (BMIm-BF4) efficiently generates BF3 from BF4-. This Lewis acid, strongly bound to the ionic liquids, can be efficiently used in classical BF3-catalyzed reactions. We demonstrated the BF3/BMIm-BF4 reactivity in four reactions, namely, a domino Friedel-Crafts/lactonization of phenols, the Povarov reaction, the Friedel-Crafts benzylation of anisole, and the multicomponent synthesis of tetrahydro-11H-benzo[a]xanthen-11-ones. In comparison with literature data using BF3-Et2O in organic solvents, in all the presented cases, analogous or improved results were obtained. Moreover, the noteworthy advantages of the developed method are the in situ generation of BF3 (no storing necessity) in the required amount, using only the electron as redox reagent, and the recycling of BMIm-BF4 for multiple subsequent runs.

Organic electrochemistry is a technique that allows for the heterogeneous redox reactions avoiding both the use of stoichiometric amounts of redox reagents and the resulting formation of stoichiometric by-products. In fact, the redox reagent in these reactions is the electron, which is naturally eco-friendly and produces no side compounds. It is therefore quite obvious that electrochemistry can be classified as a “green” technology. The use of this methodology in the synthesis of β-lactams is not a novelty, but the growing interest in this class of biologically active compounds, due to the discovery of new fields of application (after a moment of decrease in interest due to antibiotic resistance) has been a stimulus for the search for more efficient electrochemical ways to synthesize and transform β-lactams. Thus, this review deals with the twenty-first-century applications of electroorganic technique to the chemistry of β-lactams, by analyzing first the syntheses classified by the type of reactions (cyclization, cycloaddition, etc.) and then by manipulating the β-lactam structure, using it as a synthon. Lastly, the importance of this technique is demonstrated by a study of a pilot plant scale reduction of a cephalosporanic acid derivative to a commercially important antibiotic.

Imidazolium-based dicationic ionic liquids (DILs) are gaining considerable space in the field of organocatalysis mainly due to the opportunities in offering new possible applicable structural variations. In addition to the well-known variables which made the ionic liquids (ILs) famous as the type of cation and anion used, the nature of the molecular spacer moiety turns out a further possibility to improve some physicochemical properties, for example, solubility, acidity, electrochemical behavior, and so on. For this reason, this class of ionic liquids has been considered as possible competitors to their corresponding monocationic salts in replacing common catalysts in organic synthesis, particularly in cases in which their bidentate nature could positively affect the catalytic activity. This mini-review is intended to highlight the progress carried out in the last six years in the field of organocatalysis, including DILs as such and as hybrids with polymers, nanomaterials, and composites.

The growing number of applications of ionic liquids (ILs) in industry have brought attention to the green credentials of synthesis, as well as their cytotoxicities and ecotoxicities both for their use and accidental leakage into the environment. With the abovementioned properties in mind, we designed a class of ILs with either cations bearing a gluconamide motif and aliphatic side chains or the anion incorporating a gluconic acid (derived from food waste) moiety. An IL with an imidazolium cation with an appended gluconic amide (bearing five hydroxyl groups) moiety was also synthesized for a useful comparison. Different structural features were considered, placing emphasis on the nature and length of the alkyl chain and the nature of the anion. For comparison, two ILs, one with a hydroxyl group and another without any hydroxyl groups, were prepared. Apart from the typical characterization of ILs, such as differential scanning calorimetry, thermogravimetric analysis, conductivity, and viscosity measurements, the main focus was placed on the evaluation of their cytotoxicities and ecotoxicities, performing tests with three cancer cell lines (HeLa, HTC-116, and MCF-7) and fish embryos (zebrafish). Data obtained have shed light on the relationship working between the physicochemical properties and the structural features of the ILs. Interestingly, these ILs are able to inhibit cell growth only at very high concentrations (IC50 ≈ 10–3 M) and they do not affect the vitality of fish embryos, allowing them to be classified as harmless solvents. To our surprise, the data collected show that derivatization with the “sweet” residue on the imidazolium cation completely removes the well-known toxicity effects of imidazolium ILs.

This review deals with the notable results obtained by the synergy between ionic liquids (ILs) and WO3 in the field of pollutant gas sensing and sulfur removal pretreatment of fuels. Starting from the known characteristics of tungsten trioxide as catalytic material, many authors have proposed the use of ionic liquids in order to both direct WO3 production towards controllable nanostructures (nanorods, nanospheres, etc.) and to modify the metal oxide structure (incorporating ILs) in order to increase the gas adsorption ability and, thus, the catalytic efficiency. Moreover, ionic liquids are able to highly disperse WO3 in composites, thus enhancing the contact surface and the catalytic ability of WO3 in both hydrodesulfurization (HDS) and oxidative desulfurization (ODS) of liquid fuels. In particular, the use of ILs in composite synthesis can direct the hydrogenation process (HDS) towards sulfur compounds rather than towards olefins, thus preserving the octane number of the fuel while highly reducing the sulfur content and, thus, the possibility of air pollution with sulfur oxides. A similar performance enhancement was obtained in ODS, where the high dispersion of WO3 (due to the use of ILs during the synthesis) allows for noteworthy results at very low temperatures (50 °C).

The benzoin condensation starting from benzaldehyde and the subsequent benzoin amidation to benzamide can be efficiently carried out under very mild conditions in an electrolysis cell. Among the advantages of using electrochemistry to generate our active reagents, the use of the easily dosed and non pollutant electron, instead of stoichiometric amounts of redox reagents or bases, usually renders the electrochemical methodology “greener” than classical organic reactions. Benzoin is obtained in good yield (85 %) carrying out the reaction in the room temperature ionic liquid BMIm-BF4. In this electrochemical reaction this liquid salt assumes the double role of solvent-supporting electrolyte system and precatalyst, yielding the corresponding N-heterocyclic carbene. The subsequent benzoin amidation is carried out by electrochemically generated superoxide anion, in the presence of an aliphatic primary or secondary amine. In this case the system superoxide/molecular oxygen acts as base and oxidant, yielding very good yields of benzamides (up to 89 %).

The electrochemical reduction of caffeine, never carried out previously, yielded in DMF–Et4NBF4 N-formyl-N,1-dimethyl-4-(methylamino)-1H-imidazole-5-carboxamide, a highly functionalized imidazole product derived from the opening of the uracil ring. This reactivity is different from that of the methylated salt of caffeine, the cathodic reduction of which leads to the opening of the imidazole ring. Moreover, the product obtained by cathodic reduction, formylated at the exocyclic amide nitrogen, is different from that formed by treatment in an aqueous solution of sodium hydroxide followed by formylation. The latter is formylated at the exocyclic amine nitrogen.

In the last twenty years, N-heterocyclic carbenes (NHCs) have been extensively studied for their application as organocatalysts in stereoselective synthesis as well as ligands for transition metals-promoted synthetic methodologies. Derived mainly from azolium salts, NHCs have demonstrated exceptional versatility in their generation usually performed by deprotonation or reduction (chemical or electrochemical). In particular, the generation of NHC under electrochemical conditions, starting from azolium-based ionic liquids, has proven to be a successful green approach and demonstrated wide applicability in organic synthesis. In this Personal Account, the application of electrogenerated NHCs in organic synthesis will be discussed, with a particular attention to the different reactivity in ionic liquids compared to classical organic solvents.

Candida albicans, in specific conditions, is responsible of severe invasive systemic candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic cells and biofilm. Some of the studied compounds (2b and 3b) were able to chelate Fe(III) and Cu(II), and showed an interesting activity on planktonic cells (MIC50 of 32 μg/mL and 16 μg/mL respectively) and on biofilm formation (BMIC50 of 32 μg/mL and 16 μg/mL respectively) in cultured ATCC 10,231C. albicans; this activity was reduced, in a concentration dependent way, by the addition of Fe(III) and Cu(II) to the culture media. Furthermore, the most active compound 3b showed a low toxicity on Galleria mellonella larvae.

The functionalization of the skeletal systems of heterocycles represents a significant goal for the development of new compounds. The heterocyclic molecule xanthine (3,7-dihydro-1Hpurine- 2,6-dione) is a purine base with a bicyclic ring skeleton and four different nitrogen atoms, three of them are -NH groups. The principal derivatives are the well known natural methylxanthines (e.g., caffeine, theophylline and theobromine) that have prominent physiological effects at a very low dose. The natural methylated xanthines, theophylline, theobromine and caffeine, are present in different plants such as the tea, cocoa and coffee species. For this reason natural xanthines can be considered as bio-based and renewable starting materials; their use in organic synthesis is strongly recommended in order to carry out sustainable chemistry. Essentially, the xanthine scaffold led to the preparation of numerous compounds very attractive in the pharmaceutical field, and these drugs are commercialized for a wide range of biological activities. The scope of this mini-review is to consider the use of natural xanthines as starting material in chemical transformations carried out in organic solvents, without the intent to be exhaustive of all the synthetically chemical applications. More information on the chemical and electrochemical reactivity of this structural core in an organic solvent can be useful for the scientific community. The effectiveness of natural xanthines can be improved by modifying the structures of these already biologically active compounds.

The cathodic reduction of dicationic imidazolium bromides, whose spacer is either an aliphatic chain or a xylyl group, leads to the formation of the corresponding N-heterocyclic carbenes (NHCs), which were isolated as the corresponding thiones, after reaction with elemental sulfur. The behaviour of the dications was compared with the corresponding monocations. The behaviour of dicarbenes depends on the nature of the spacer. This study evidenced that dicarbenes deriving from xylyl dications are less stable than the corresponding aliphatic ones (giving lower yields in thiones), due to a debenzylation reaction. On the other hand, the yields in thiones starting from aliphatic dications are higher than the corresponding monocations, suggesting a cooperative reduction at the electrode of the two imidazolium moieties. The cathodic process was confirmed using the co-electrogenerated hydrogen to reduce 2,2,2- trifluoroacetophenone to the corresponding alcohol.

Thiophene oligomers and polymers can be found in a huge number of materials with applications in the field of Organic Electronics. Chemical and electrochemical syntheses along with electrochemical studies and complete characterization of a series of new conjugated oligothiophene derivatives are reported. Two different molecular architectures, D-A (donor-acceptor) and A-D-A (acceptor-donor-acceptor), were taken into account. The results from voltammetric experiments and optical studies confirm the close relationship between the structure of these compounds and their electrochemical behaviour. This series of oligothiophenes shows low bandgaps, a mandatory requirement for their use in Organic Electronics, and, clearly, they are promising candidates for future synthetic studies in order to modify their optical and electrochemical properties to achieve better performances as organic semiconductors.

The story of mass spectrometry applied to the nanoparticles world is very young but actually it is expected to evolve as one of the most powerful tool for the characterization of the smaller-size nanoparticles in terms of composition, size, shape, surface chemistry, because of its versatility, sensitivity, reliability and the possibility to be coupled with high performance chromatographic separation techniques. A short overview on different fields where liquid chromatography coupled with mass spectrometry, nanomaterials and nanotechnology come together is herein given.

Controlled potential electrolyses of caffeine (CAF) were carried out at a Pt electrode in undried acetonitrile (ACN) and ACN-H2O and the products of the anodic oxidation were analyzed by HPLC-PDA-ESI-MS/MS. A higher current efficiency occurred in ACN-H2O, but an analogous chromatographic outline was found in both media, evidencing a reactive pathway of the electrogenerated radical cation CAF&bull, + with water, added or in trace, as nucleophile. No dimeric forms were evidenced, excluding any coupling reactions. Neither was 1,3,7-trimethyluric acid found, reported in the literature as the main oxidative route for CAF in water. Four main chromatographic peaks were evidenced, assigned to four proposed structures on the base of chromatographic and spectral data: a 4,5-diol derivative and an oxazolidin-2-one derivative were assigned as principal oxidation products, supporting a mechanism proposed in a previous work for the primary anodic oxidation of the methylxanthines olefinic C4 = C5 bond. Two highly polar degradation products were also tentatively assigned, that seemed generating along two different pathways, one opening the imidazolic moiety and another one opening the purinic one.

A protocol for the carboxylation of diamines employing quaternary ammonium hydrogen carbonates as C1 source is presented. The approach is used to obtain industrially relevant bis-O-alkyl carbamates with diverse structural features in very high yield, even on gram scale. The quaternary ammonium salts, formally acting as “transporters” of the carboxylating agent, can be recovered after the reaction, and recycled with high efficiency. Regeneration of the hydrogen carbonates on ion-exchange resin grants excellent atom economy in the process.

9-Methylcaffeinium iodide, a bio-based salt obtained by reaction of caffeine with methyl iodide, is an imidazolium salt. The electrochemical behaviour of 9-methylcaffeinium iodide was studied by means of cyclic voltammetry, differential pulse voltammetry and electrolysis. Its behaviour revealed to be very similar to that of common imidazolium salts. In fact, its cathodic reduction yielded the corresponding N-heterocyclic carbene, which was evidenced by its reaction products with dioxygen and with sulfur, although in low amounts. In fact, this electrogenerated carbene was very unstable and prone to add water, yielding a ring opening product (hymeniacidin) in high yield. Hymeniacidin is a natural product from the marine sponge Hymeniacidon sp. The voltammetric behaviour of isolated hymeniacidin confirmed the in situ formation of this ring opening product, by comparison of the voltammetric peak potentials of starting caffeinium salt and hymeniacidin. This study allowed to determine that hymeniacidin derives from NHC, and not by hydrolysis of the caffeinium salt.

The anodic oxidation of tetrafluoroborate anion yields the Lewis acid BF3. If this reaction is carried out in an imidazolium ionic liquid, a quite stable system containing BF3 is obtained, whose reactivity is similar to the one of BF3·Et2O, but less harmful. The two reagents’ stabilities were compared by computational analysis, strongly suggesting a higher stability for BF3/BMIm-BF4 system. The effect of substituents on the imidazolium ring and of the electrochemical configuration on BF3 reactivity were studied in a model reaction, styrene oxide isomerization. The experimental conditions were defined for the selective formation of phenylacetaldehyde or of 2-benzyl-4-phenyl-1,3-dioxolane. Moreover, the formation of N-heterocyclic carbene-BF3 adduct was confirmed when carrying out the electrolysis in an undivided cell. Electrogenerated BF3/BMIm-BF4 system demonstrated to be a valid alternative to commercial BF3·Et2O.

N-Heterocyclic olefin (NHO) can be generated by simple cathodic reduction of BDMImBF4-DMF solution or neat BDMImBF4 (BDMImBF4=1-butyl-2,3-dimethyl-1H-imidazolium tetrafluoroborate; DMF=dimethylformamide). In the latter case, the use of any organic solvent and chemical base is avoided. To prove the presence of NHO, its adduct with benzaldehyde was isolated. The electrochemical behavior of NHO is very similar to that of the corresponding N-heterocyclic carbene (NHC, from 1- butyl-3-methyl-1H-imidazolium tetrafluoroborate), showing that it is electroactive at the anode, and this peculiarity can be exploited to verify its presence in a solution. The main difference between NHO and NHC is in the nucleophilic site (exocyclic for NHO, endocyclic for NHC). Electrogenerated NHO stability (evaluated by cyclic voltammetry) and its catalytic ability (evaluated in the transesterification reaction) were compared with those of electrogenerated NHC.

We studied how changing the anion affects the self-assembly of three diimidazolium salts bearing a perylene bisimide spacer. In particular we used [BF 4 − ] and [NTf 2 − ] based salts together with a mixed salt bearing both [I − ] and [BF 4 − ] anions. Thermal as well as concentration and temperature dependent spectroscopic investigations revealed that changing the anion impacts on solid state and solution aggregation, leading to articulate thermotropic behaviors and contrasting solvent effects, respectively. We also studied the electrochemical behavior of the salts to verify if changing the anion alters the redox properties of the salts. Finally, different anions also lead to very different aggregate morphologies, as evidenced by SEM and TEM measurements.

Carboxylation of aliphatic and benzyl diamines with electrochemically activated CO2 led to the synthesis of bis-O-alkyl carbamates in high yields. Reaction conditions, including the geometry of the electrochemical cell, were discussed and optimized. This resulted in a significant reduction of unwanted material associated with the reaction, overcoming the economic and environmental restrictions to its application on large scale.

The cathodic reduction of acetonitrile solutions containing a tetraalkylammonium salt leads to the formation of the cyanomethyl anion (-CH2CN, cyanomethanide). This electrolysis can be carried out under very simple experimental conditions (constant-current electrolyses), using various cathodic materials, controlling the amount of base by simply controlling the amount of charge. Despite the fact that the mechanism for this electrochemical reaction is still debated (and it depends on the cathodic material), the outcome of the electrolysis is the formation of a strong base, -CH2CN (pKa 31.3 for acetonitrile in DMSO). The chemical behavior of this electrogenerated base (EGB) strongly depends on its counterion, which in this case is a tetraalkylammonium cation, with a low charge density and thus not coordinated. The very weak interaction between R4N+ and -CH2CN renders the cyanomethyl anion a "naked" ion, and thus highly reactive. In particular, the cyanomethyl anion can react as a base and as a nucleophile. In the first case, it behaves as a strong base and, after deprotonation of a weak acidic substrate, transforms itself into a solvent molecule, acetonitrile, thus generating no byproducts. In the second case, the reactivity as a nucleophile of the cyanomethyl anion obviously depends on the reaction partner. When an electrophile is present in the reaction mixture, a cyanomethylation is obtained (e.g., with aromatic aldehydes, possessing no acidic hydrogen atoms, which undergo nucleophilic attack on the carbonyl carbon atom by -CH2CN); on the contrary, when no reagent is present other than acetonitrile and tetraalkylammonium salt, an attack on the parent molecule leads to the acetonitrile dimer, 3-aminocrotononitrile, which in turn can behave as a base and/or as a nucleophile. In this regard, some authors report that it is preferable to carry out the electrogeneration of the cyanomethyl anion under different experimental conditions, i.e., using an undivided cell and a sacrificial magnesium anode. In this way, a Grignard-type reagent is formed (Mg(CH2CN)2) which highly stabilizes the cyanomethyl anion, preventing its dimerization. It should be noted that in our laboratory the electrogenerated tetraalkylammonium cyanomethanide was extensively used in various reactions (both acid-base and nucleophile-electrophile, vide infra), and in almost no case, the amount of acetonitrile dimer formed exceeded 5%, confirming the validity of this electrochemical methodology to generate a very efficient base. Moreover, when in the reaction mixture both a weak acid and an electrophile are present, the prevalent reactivity of the cyanomethyl anion is as a base, leaving the possibility of a cyanomethylation reaction to those cases in which no acidic substrate is present. We have successfully used the electrogenerated cyanomethyl anion in many base-induced reactions, as the synthesis of the β-lactam ring (chiral or not), the insertion of carbon dioxide into amines and amino alcohols, the activation of elemental sulfur and insertion into carbonyl compounds, the selective alkylation of difunctional compounds, etc.

With the aim to obtain organic salts with potential applications in high performance molecular electronics, we combined properties of π-conjugated spacers, like 1,4-diethynylbenzene and 1,6-diethynylpyrene, with the ones of both imidazole and imidazolium units. Physico-chemical properties of obtained fluorescent organic salts were investigated performing thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC) and cyclic voltammetry measurements (CV). Photophysical behavior of the salts was analyzed in conventional solvents and ionic liquids, by UV–vis and fluorescence investigation. Solution phase aggregation study revealed that these salts self-assemble in conventional solvents and ionic liquids, leading to aggregation induced emission processes. Notably, emission was maintained also in the solid state, with higher or lower intensity compared with the solution, depending on which spacer is present. This latter, also impacts on the morphology of the aggregates, allowing fine tuning the properties of the supramolecular materials formed.

In order to obtain multi-functional molecules for Alzheimer’s disease, a series of deferiprone derivatives has been synthesized and evaluated in vitro with the hypothesis that they can restore the cholinergic tone and attenuate the dyshomeostasis of the metals mainly involved in the pathology. These compounds were designed as dual binding site AChE inhibitors: they possess an arylalkylamine moiety connected via an alkyl chain to a 3-hydroxy-4-pyridone fragment, to allow the simultaneous interaction with catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme. Deferiprone moiety and 2-aminopyridine, 2-aminopyrimidine or 2,4-diaminopyrimidine groups have been incorporated into these compounds, in order to obtain molecules potentially able to chelate bio-metals colocalized in Aβ plaques and involved in the generation of radical species. Synthesized compounds were tested by enzymatic inhibition studies towards EeAChE and eqBChE using Ellman’s method. The most potent EeAChE inhibitor is compound 5a, with a Ki of 788 ± 51 nM, while the most potent eqBChE inhibitors are compounds 12 and 19, with Ki values of 182 ± 18 nM and 258 ± 25 nM respectively. Selected compounds, among the most potent cholinesterases inhibitors, were able to form complex with iron and in some cases with copper and zinc. Moreover, these compounds were characterized by low toxicity on U-87 MG Cell Line from human brain (glioblastoma astrocytoma).

The contamination with water of the cathodic ACN-Et4NBF4 solution gave us the opportunity to investigate alkyl isocyanate reactivity toward electrogenerated anions. The cathodic reduction of a ACN-Et4NBF4 solution led to the formation of both hydroxide and cyanomethyl anions. The reaction of the catholyte with cyclohexylisocyanate led to the exclusive formation of acetamidated product, with no traces of cyanomethylated one. On the contrary, when reacting with benzaldehyde only the cyanomethylated was isolated. Considering that the acetamidated product of benzaldehyde is reported to be unstable (thus its formation cannot be excluded), various experiments were carried out in order to understand the anomalous reactivity of cyclohexylisocyanate. Moreover, computational analysis allowed to state the higher stability of acetamidated product with respect to the cyanomethylated one. The possibility of a concerted reaction, instead of acetamide anion formation prior to the reaction, is still an open question.