Academic literature on the topic 'Five-membered heteroaromatic molecules'

Large amplitude motions (LAMs) form a fundamental phenomenon that demands the development of specific theoretical and Hamiltonian models. In recent years, along with the strong progress in instrumental techniques on high-resolution microwave spectroscopy and computational capacity in quantum chemistry, studies on LAMs have become very diverse. Larger and more complex molecular systems have been taken under investigation, ranging from series of heteroaromatic molecules from five- and six-membered rings to polycyclic-aromatic-hydrocarbon derivatives. Such systems are ideally suited to create families of molecules in which the positions and the number of LAMs can be varied, while the heteroatoms often provide a sufficient dipole moment to the systems to warrant the observation of their rotational spectra. This review will summarize three types of LAMs: internal rotation, inversion tunneling, and ring puckering, which are frequently observed in aromatic five-membered rings such as furan, thiophene, pyrrole, thiazole, and oxazole derivatives, in aromatic six-membered rings such as benzene, pyridine, and pyrimidine derivatives, and larger combined rings such as naphthalene, indole, and indan derivatives. For each molecular class, we will present the representatives and summarize the recent insights on the molecular structure and internal dynamics and how they help to advance the field of quantum mechanics.

Thiazole, a five-membered heteroaromatic ring, is an important scaffold of a large number of synthetic compounds. Its diverse pharmacological activity is reflected in many clinically approved thiazole-containing molecules, with an extensive range of biological activities, such as antibacterial, antifungal, antiviral, antihelmintic, antitumor, and anti-inflammatory effects. Due to its significance in the field of medicinal chemistry, numerous biologically active thiazole and bisthiazole derivatives have been reported in the scientific literature. The current review provides an overview of different methods for the synthesis of thiazole and bisthiazole derivatives and describes various compounds bearing a thiazole and bisthiazole moiety possessing antibacterial, antifungal, antiprotozoal, and antitumor activity, encouraging further research on the discovery of thiazole-containing drugs.

The geometry-based HOMA (Harmonic Oscillator Model of Aromaticity) descriptor, based on the reference compounds of different delocalizations of n- and π-electrons, can be applied to molecules possessing analogous bonds, e.g., only CC, only CN, only CO, etc. For compounds with different heteroatoms and a different number of CC, CX, XX, and XY bonds, its application leads to some discrepancies. For this reason, the structural descriptor was modified and the HOMED (Harmonic Oscillator Model of Electron Delocalization) index defined. In 2010, the HOMED index was parameterized for compounds with C, N and O atoms. For parametrization, the reference molecules of similar delocalizations of n- and π-electrons were employed. In this paper, the HOMED index was extended to compounds containing the CP, CS, NN, NP, PP, NO, NS, PO, and PS bonds. For geometrical optimization of all reference molecules and of all investigated heterocompounds, the same quantum–chemical method {B3LYP/6-311+G(d,p)} was used to eliminate errors of the HOMED estimation. For some tautomeric systems, the Gn methods were also employed to confirm tautomeric preferences. The extended HOMED index was applied to five-membered heterocycles, simple furan and thiophene, and their N and P derivatives as well as for tautomeric pyrrole and phosphole and their N and P derivatives. The effects of additional heteroatom(s) in the ring on the HOMED values for furan are parallel to those for thiophene. For pyrroles, aromaticity dictates the tautomeric preferences. An additional N atom in the ring only slightly affects the HOMED values for the favored and well delocalized NH tautomers. Significant changes take place for their rare CH forms. When intramolecular proton-transfer is considered for phosphole and its P derivatives, the PH tautomers seem to be favored only for 1,2,3-triphosphole/1,2,5-triphosphole and for 1,2,3,5-tetraphosphole. For other phospholes, the CH forms have smaller Gibbs energies than the PH isomers. For phosphazoles, the labile proton in the favored form is linked to the N atom. The PH forms have smaller HOMED indices than the NH tautomers but higher than the CH ones.

As the use of lithium batteries became more and more wide-spread, the importance of the research on novel salts for batteries' electrolytes grew more and more important. The focus has been put on designing novel lithium and sodium salts which dissociate well in aprotic solvents and are electrochemically and thermally stable. Salts with heteroaromatic anions such as 2-trifluoromethane-4,5-dicyanoimidazolate (LiTDI) [1,2] are a promising alternative for the salts commonly used as charge carriers in lithium and sodium batteries. The class of new 4,5-dicyanoimidazolates ligands is based on N-heterocyclic five-membered ring substituted with nitrile group. Such a type of anions possesses four nitrogen donor centers able to coordinate cation, and is characterized by charge delocalization, both on imidazole ring and cyano substituents resulting in extended π electron system. In solid as well as liquid electrolytes one should expect the co-existence of a variety of ionic species, such as iosolated anions and cations solvated by solvent molecules, ionic pairs, for which the coordination sphere of cations is completed with solvent molecules, as well as dimers and aggregates with varied stoichiometry. The observed degree of aggregation depends mostly on the coordination properties of anions, their ability to form hydrogen bonds and their compatibility with the acidic properties of cations. The increase of the salt concentration should result in association process and the emergence of higher aggregates, up to polymeric systems, possessing structure of chains, ribbons, layers or networks. In order to define the coordination ability of the class of new ligands, we examined their organization modes in the alkali metal salts and have found a wide variety of mentioned motifs. Discovering and understanding the phenomena related to the organization of such systems in the solid state is crucial for the elaboration of novel electrolytes and should give information about cation and anion coordination in electrolytes. Our single-crystal diffraction studies have shown that new salts comprising 4,5-dicyano-2-(trifluoromethyl)imidazolato anion are interesting from the point of view of their crystalline structure, offering variety of possible coordination modes and are, therefore, worthy of examination.

Aromatic stabilization energies (ASE) for a set of 29 five-membered heteroaromatic compounds are calculated using molecular descriptors such as magnetic susceptibility exaltation (Λ), nucleus-independent chemical shifts (NICS), and electrotopological indices (EI) via linear, quadratic and cubic fitting polynomials. Theoretical estimations compare fairly well with experimental data when three variables multilinear regression equations are employed.

AbstractSelective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)‒NH2 can be converted into C(sp2)‒Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents.

Thiazole, a five-membered heteroaromatic ring, is an important framework of a large number of synthetic compounds. Its diverse pharmacological activity is mirrored in many clinically approved thiazole-containing molecules with, wide range of biological activities, such as antibacterial, antifungal, antiviral, anthelmintic, antitumor, and anti-inflammatory effects. The current review provides an overview of the biological activities of thiazole during the past years.

2009/2010
Due to its prominent directionality and strength, H-bonds are ones of the most widely used non-covalent interactions in supramolecular chemistry. Despite its relative high strength (energy of an H-bond in the gas phase typically ranges between 0−5 Kcal mol−1) in comparison with other non-covalent interactions, association of two molecules by means of a single H-bond leads to complexes displaying low thermodynamical stabilities, thus limiting their exploitation in the non-covalent synthesis of functional materials for real-world applications. Thereby, when stronger interactions are required, the general engineering approach focuses on the covalent synthesis of rigid planar molecular scaffolding in which several H-bonding donating (D) and accepting (A) moieties are arranged into a so-called ‘H-bonding array’. Due to the selective recognition processes and to the tunability of their association strength, multiple H-bonding arrays have become an indispensable molecular module in the tool-box of supramolecular chemists, allowing, through selective self-assembly and/or self-organization processes, the bottom-up preparation of functional materials such as liquid crystals, patterned surfaces and supramolecular polymers. In principle, the stability of H-bonded supramolecular complexes could be modulated in an indefinite number of ways. For example, when stronger interactions (e.g., higher association constant values) are required, the increase of the number of the H-bonding sites represents one of the efficient strategy to reinforce the stability of the ultimate assembly. Nevertheless, a strong Ka value is not always requested. In fact, whilst highly stable complexes are required in the field of supramolecular polymers, whose properties at the molecular level (such as degree of polymerization, Dp, and viscosity) result linearly correlated to the Ka values, these may instead be detrimental for the construction of more sophisticated hierarchized nano-architectures, arising from a delicate interplay between internal (e.g. ii stacking, solvophobic/solvophilic interactions) and external (e.g. time, temperature, concentration, etc.) factors. The aim of this thesis is to design and synthesize novel triple H-bonding arrays (DAD, ADD and DDD) based on five-membered heteroaromatic rings. The proposed use of thiolyl, oxolyl, azolyl, and triazolyl scaffoldings for recognition systems, it is intended as a mean to better achieve the control on the binding properties and selectivity of triple H-bondind recognition arrays, allowing an easy tunability of the binding motifs. With the variation of the substituents and the heteroatom onto the hetero-aromatic rings, it has been intended to create a selection of versatile, structurally similar, host-guest pairs complexes that display different association constants (Ka) in order to better match the requirements of different supramolecular applications. Focusing on the most relevant factors that influence the association constants of hydrogen bonded complexes, in the first part of Chapter 1 the reader is introduced on how specific H-bonding arrays, featuring wide ranges of Ka values (spanning among eight orders of magnitude) can be designed. Subsequently, the second part is focused on the physical and chemical properties of a large variety of H-bonding assembled molecular modules that upon self-assembly and self-organization processes opened new ways towards novel fascinating applications. Figure 1 Designed H-bonding arrays based on 5-membered heterocycles. Chapter 2 deals with the description of the synthetic efforts undertaken towards the preparation of the DAD and DDD H-bonding arrays. The first two subsections (2.1-2) describe the rethrosynthetic approaches and the results of the unsuccessful methodological routes (through Buchwald-Hartwig amidation cross-coupling reactions, reduction of azido-derivatives and nucleophilic addition of organo-metallic reagents to isocyanate derivatives as produced through Curtius rearrangement) tackled to introduce amidic and/or ureidic functions at the 2-position of five-membered heteroaromatic rings. Several DAD H-bonding arrays based on thiolyl scaffolding were successfully synthesized (sections 2.3). Figure 2 Synthesized thiolyl DAD H-bonding arrays. In section 2.4 are presented the synthetic step undertaken in the attempt to generate DAD arrays based on oxalyl derivatives. Unfortunately the introduction of electron-donating groups such as amidic or carbamic functions to the ring led to very unstable intermediates, and thus the amido-oxolyl derivatives capable of recognition mediated by triple H bonding were never isolated. Figure 3 Synthesized oxolyl-protected DAD H-bond array. The synthetic strategies towards the synthesis of DDD arrays based on of azolyl scaffolding are described in section 2.5. Protected azolyl module 182 (see Figure 4) was synthesized in thirteen steps starting from the pyrrole module. Unfortunately, due to the complications encountered in the cleavage of the N-azolyl protecting group, the synthesis of the azolyl DDD H-bonding arrays based could not be finally accomplished. Figure 4 Synthesized azolyl-protected DDD H-bond array. Section 2.6 presents the synthesis of newly designed self-adapting ADD/DDD H-bonding array based on ureido-triazolyl scaffoldings. Exploiting the prototropic equilibrium of the triazole nucleus the modules synthesized are expected to show an ADD or a DDD arrangement of the binding sites depending on the H-bonding functionalities of the complementary guest used for the complexation. Figure 5 Synthesized triazolyl-based ureido H-bonding arrays. Prototropic self-adapting properties: from a DDD to a ADD H-bonding array. Due to solubility limitations in common organic solvents (e.g., CDCl3 and CD2Cl2), the molecular recognition ability in solution could not be studied and further modifications of the molecular structural properties are required.
Grazie alla marcata direzionalità e forza presentate, i legami idrogeno rappresentano uno delle interazioni non covalenti più usate in chimica supramolecolare. Nonostante la forza di legame sia maggiore in confronto ad altre interazioni non covalenti (l’energia di un legame idrogeno in fase gassosa varia in genere tra 0-5 Kcal mol-1), l’associazione di due molecole per mezzo di un singolo legame idrogeno porta alla formazione di complessi con scarsa stabilità termodinamica, limitandone lo sfruttamento nella sintesi non covalente di materiali funzionali. L’approccio per ottenere interazioni non covalenti più forti è basato sulla sintesi di moduli molecolari planari in cui siano presenti diverse funzioni donatrici (D) e accettrici (A) di legame idrogeno disposti a formare i così detti ‘H-bonding arrays’. Gli H-bonding arrays sono diventati moduli indispensabili per la fabbricazione di materiali funzionali quali cristalli liquidi, superfici organizzate e polimeri supramolecolari, tramite l’approccio ‘’bottom-up” a causa della loro selettivita’ nei processi di riconoscimento e alla possibilita’ di modulare la loro forza di legame La stabilita’ termodinamica dei complessi supramolecolari formati tramite legami idrogeno puo’ essere variata in diversi modi. Ad esempio, quando sono richieste interazioni piu’ forti (es. costanti di associazione più elevate) e’ possibile aumentare il numero di funzioni accettrici e/o donatrici all’interno dell’ array. Complessi particolarmente stabili sono richiesti nel campo della polimerizzazione supramolecolare, dove le proprieta’ macroscopiche (es. grado di polimerizzazione, Dp, e viscosità) sono lineramente correlate al valore della Ka. Alti valori della costante di associazione possono essere dannosi, invece, nella costruzione di nano-architetture gerarchizzate, dove ordine a livello nano e microscopico e’ raggiunto, non solo tramite legami a idrogeno, ma tramite l’effetto concertato di fattori interni (es. π- π stacking, interazioni solvofobiche/solvofiliche) ed esterni (es. tempo, temperatura, concentrazione, etc.). L’obiettivo di questa tesi è progettare e sintetizzare nuovi array di tripli legami idrogeno (DAD, ADD e DDD) basati sulle molecole di tiofene, furano, pirrolo e triazolo. Utilizzando anelli a 5 termini e’ infatti possibile ottenere una famiglia di coppie host-guest, che presentano una simile struttura chimica ma differenti costanti di associazione. La modulazione della Ka in questi sistemi puo’ avvenire tramite la variazione dell’etroatomo sull’anello o tramite l’introduzione di sostituenti nelle posizioni β, permettendo cosi’ la costruzione di una libreria di moduli molecolari versatili in grado di rispondere al meglio ai requisiti dalle diverse applicazioni supramolecolari. Concentrandosi sui fattori che influenzano le costanti di associazione dei complessi formati tramite legami idrogeno, nella prima parte del Capitolo 1 viene descritto come modificazioni strutturali degli array portano alla formazione di complessi i cui valori di Ka variano in un intervallo di 8 ordini di grandezza. La seconda parte e’ invece focalizzata sulle proprieta’ chimico-fisiche di nuovi materiali funzionali formati tramite processi di auto-assemblaggio e auto-organizzazione degli array precedentemente descritti. Figura 1 Progettazione di array di legami idrogeno basati su etero cicli a 5 termini. Nel Capitolo 2 vengono mostrati i tentativi di sintesi intrapresi per la preparazione degli array di legami idrogeno di tipo DAD e DDD . I primi 2 paragrafi (2.1-2) descrivono l’analisi retro-sintetica e gli studi metodologici effettuati al fine di sviluppare una via sintetica per l’introduzione di funzioni ammidiche e/o ureidiche in posizione 2 degli anelli etero-aromatici. Le metodologie descritte sono: la reazione di ammidazione per accoppiamento ossidativo di Buchwald-Hartwig, la riduzione di azido-derivati e l’addizione nucleofila di reagenti organo-metallici a isocianati prodotti tramite il riarrangiamento di Curtius. Diversi DAD array di legami idrogeno basati sulla molecola di tiofene sono stati sintetizzati con successo (paragrafo2.3). Figura 2 DAD array di legami idrogeno basati sulla molecola di tiofene sintetizzati. Nel paragrafo 2.4 sono presentati gli step sintetici affrontati nel tentativo di generare DAD array basati su derivati ossolici. Sfortunatamente l’introduzione di gruppi elettron-donatori (ammidi o carbammati) sull’anello conduce alla formazione d’intermedi particolarmente instabili. Per questo motivo sistemi DAD di legami a idrogeno basati su derivati ammidici della molecola di furano non sono mai stati isolati. Figura 3 DAD array di legame idrogeno basato su scheletro furanico sintetizzato con la funzione ammidica protetta. Nel paragrafo 2.5 sono descritte le strategie sintetiche affrontate nel tentativo di sintetizzare DAD array basati sulla molecola di pirrolo. L’intermedio azolico protetto 182 (vedi Figura 4) è stato sintetizzato in tredici passaggi sintetici partendo dalla molecola di pirrolo. Sfortunatamente, a causa delle complicazioni incontrate durante la rimozione del gruppo protettore dell’azoto pirrolico, la sintesi di moduli DDD basati su derivati azolici non è stata portata a termine. Figure 4 DDD array di legame idrogeno basato sulla molecola di pirrolo sintetizzato con l’azoto dell’eterociclo protetto. Il paragrafo 2.6 presenta la sintesi di moduli auto adattabili ADD/DDD basati su derivati ureido-triazolici. Sfruttando l’equilibrio prototropico del nucleo triazolico il modulo sintetizzato dovrebbe mostrare una disposizione ADD o DDD dei siti di legame che dipende dal modulo complementare usato nel processo di complessazione. Figure 5 Array di legami idrogeno basati su derivati ureidotriazolici sintetizzati. Proprieta’ di auto-adattamento: da DDD a ADD array. Le capacita’ di riconoscimento molecolare di questi sistemi in soluzione non sono state studiate a causa della loro limitata solubilita’. Ulteriori modifiche strutturali sono pertanto necessarie.
XXII Ciclo
1981

In the past decades, there have been extensive research efforts in developing new highly efficient organic materials with large second order susceptibilities because of their potential applications in optical signal processing and frequency conversion. Molecules possessing a large firstorder molecular hyperpolarizability ß are an essential prerequisite for achieving large macroscopic susceptibilities χ(2). The molecular nonlinearity of the classical, nonlinear optically active molecule, which usually contains an electron donor and an electron acceptor connected by a π-conjugated core, can be enhanced by increasing the electron donor or electron acceptor strength, elongating the length of the conjugated core, and reducing the ground state aromatic character.