ChemInform Abstract: Synthesis of 4(5)-Phenacyl-imidazoles from Isoxazole Side-Chain Rearrangements.

The reaction must be carried out under nitrogen atmosphere in deoxygenated solvent to prevent the oxidation of the imidazole products.

Effect of protonation and deprotonation on the gas phase reactivity of fluorinated 1,2,4-triazines

Positive and negative electrospray mass spectrometry (MS), in-time and in-space MS n experiments, high-resolution and accurate mass measurements obtained with an Orbitrap, together with density functional theory calculations have been used to study the gas-phase ion chemistry of a series of fluorinated 1,2,4-triazines. As a result of low-energy collision-induced dissociations, occurring in an ion trap and in a triple quadrupole, their protonated and deprotonated molecules show interesting features depending on the nature and structure of the precursor ions. The occurrence of elimination/hydration reactions produced by positive ions in the ion trap is noteworthy. Decompositions of deprotonat…

Mass spectrometry of surfactant aggregates.

In contrast with the enormous amount of literature produced during many decades in the field of surfactant aggregation in liquid, liquid crystalline and solid phases, only a few investigations concerning surfactant self-assembling in the gas phase as charged aggregates have been carried out until now. This lack of interest is disappointing in view of the remarkable theoretical and practical importance of the inherent knowledge. The absence of surfactant–solvent interactions makes it easier to study the role of surfactant–surfactant forces in determining their peculiar self-assembling features as well as the ability of these assemblies to incorporate selected solubilizate molecules. Thus, t…

Fluorinated Heterocyclic Compounds. An Effective Strategy for the Synthesis of Fluorinated Z-Oximes of 3-Perfluoroalkyl-6-phenyl-2H-1,2,4-triazin- 5-ones via a Ring-Enlargement Reaction of 3-Benzoyl-5-perfluoroalkyl-1,2,4-oxadiazoles and Hydrazine

The reaction of 3-benzoyl-5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine has been investigated, evidencing the possibility of competitive reaction paths. Nucleophilic addition of the hydrazine to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring opening and ring closure with enlargement, leads with high yield and in very mild experimental conditions to the formation of Z-oximes of 3-perfluoroalkyl-6-phenyl-2H-1,2,4-triazin-5-ones (11a-c) as major products of the reaction. In turn, the hydrazine can attack the electrophilic carbonyl carbon giving 4-perfluoroacylamino-5-phenyl-2H-1,2,3-triazoles (13a-c) through the well-known Boulton-Katritzky rearrangement of the inter…

Synthesis and chemical characterization of CuII, NiII and ZnII complexes of 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole ligands

Abstract The synthesis and structural characterization of Ni II , Cu II and Zn II complexes of two chelating 1,2,4-oxadiazole ligands, namely 3,5-bis(2′-pyridyl)-1,2,4-oxadiazole (bipyOXA) and 3-(2′-pyridyl)5-(phenyl)-1,2,4-oxadiazole (pyOXA), is here reported. The formed hexacoordinated metal complexes are [M(bipyOXA) 2 (H 2 O) 2 ](ClO 4 ) 2 and [M(pyOXA) 2 (ClO 4 ) 2 ], respectively (M = Ni, Cu, Zn). X-ray crystallography, 1 H and 13 C NMR spectroscopy and C, N, H elemental analysis data concord in attributing them an octahedral coordination geometry. The two coordinated pyOXA ligands assume a trans coplanar disposition, while the two bipyOXA ligands are not. The latter result is a possib…

Synthesis, characterization, cellular uptake and interaction with native DNA of a bis(pyridyl)-1,2,4-oxadiazole copper(II) complex

The copper(II) complex of 3,5-bis(2'-pyridyl)-1,2,4-oxadiazole was synthesized and characterized. X-Ray crystallography revealed that the complex consists of a discrete [Cu(3,5-bis(2'-pyridyl)-1,2,4-oxadiazole)(2)(H(2)O)(2)](2+) cation and two ClO(4)(-) anions. The Cu(II) coordination sphere has a distorted octahedral geometry and each ligand chelates the copper ion through the N(4) nitrogen of the oxadiazole ring and the nitrogen of one pyridine moiety. The coordinated water molecules are in cis position and each of them is H-bonded to the 5-pyridyl nitrogen of the oxadiazole ligand and to an oxygen of the perchlorate anion. Biological assays showed that, despite the free ligand not being …

Do electrospray mass spectra of surfactants mirror their aggregation state in solution?

One important feature in the gas phase chemistry of surfactants is to ascertain whether their aggregates produced by electrospray ionization reflect those formed in the starting solution. With this aim, we have performed ESI-MS, ESI-MS/MS and ER-MS spectra of bis(2-ethylhexyl)sulfosuccinate (AOTNa) solutions in different solvents, i.e. water, water/methanol, methanol and n-hexane. The results clearly indicate that, notwithstanding the strongly different aggregation state in solution (direct micelles in water and in water/methanol, molecular dispersion in methanol and reverse micelles in n-hexane) and marked effects of the solvent polarity on the total ionic current, the surfactant aggregate…

Synthesis of fluorinated 1,2,4-oxadiazin-6-ones through ANRORC rearrangement of 1,2,4-oxadiazoles

Abstract The reaction of 3-ethoxycarbonyl-5-perfluoroalkyl-1,2,4-oxadiazoles with hydroxylamines has been investigated, evidencing the possibility of competitive reaction paths. Nucleophilic addition of hydroxylamine to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring-opening and ring-closure with enlargement, leads to high yield and in very mild experimental conditions to the formation of 5-hydroxyamino-3-perfluoroalkyl-6 H -1,2,4-oxadiazin-6-ones, one of these presenting water gelation ability. In turn, reactions with N -methylhydroxylamine lead the exclusive formation of 4-perfluoroacylamino-2-methyl-2 H -1,2,5-oxadiazol-3-ones through the well known Boulton–Katritzk…

Gas phase infrared multiple photon dissociation spectra of positively charged sodium bis(2-ethylhexyl)sulfosuccinate reverse micelle-like aggregates

The capability of infrared multiple photon dissociation (IRMPD) spectroscopy to gain structural information on surfactant-based supramolecular aggregates has been exploited to elucidate intermolecular interactions and local organization of positively charged sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) aggregates in the gas phase. A detailed analysis of the stretching modes of the AOTNa CO and SO(3)(-) head groups allows one to directly probe their interactions with sodium counterions and to gain insight in their organization within the aggregate. Similarities and differences of the IRMPD spectra as compared to the infrared absorption spectrum of micellized AOTNa in CCl(4) have been analy…

Supramolecular Aggregates in Vacuum: Positively Mono-Charged Sodium Alkanesulfonate Clusters

The formation and structural features of positively mono-charged aggregates of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and sodium methane—(MetS), butane—(ButS) and octane—(OctS) sulfonate molecules in the gas phase have been investigated by electrospray ionization mass spectrometry, energy-resolved mass spectrometry and density functional theory (DFT) calculations. The experimental results show that the center-of-mass collision energy required to dissociate 50% of these mono-charged aggregates scantly depends on the length of the alkyl chain as well as on the aggregation number. This, together with the large predominance of mono-charged species in the mass spectra, was rationalized i…

Design, Synthesis and Characterization of a Visible-Light-Sensitive Molecular Switch and Its PEGylation Towards a Self-Assembling Molecule.

HBDI-like chromophores represent a novel set of biomimetic switches mimicking the fluorophore of the green fluorescent protein that are currently studied with the hope to expand the molecular switch/motor toolbox. However, until now members capable of absorbing visible light in their neutral (i. e. non-anionic) form have not been reported. In this contribution we report the preparation of an HBDI-like chromophore based on a 3-phenylbenzofulvene scaffold capable of absorbing blue light and photoisomerizing on the picosecond timescale. More specifically, we show that double-bond photoisomerization occurs in both the E-to-Z and Z-to-E directions and that these can be controlled by irradiating …

Densely PEGylated polybenzofulvene brushes for potential applications in drug encapsulation

The technique of grafting side chains onto a linear polymeric backbone is commonly used to confer to the new polymeric material with desired properties, such as tunable solubility, ionic charge, biocompatibility, or specific interactions with biological systems. In this paper, two new polybenzofulvene backbones were assembled by spontaneous polymerization of the appropriate benzofulvene monomers (4,6-PO-BF3k and 4&rsquo

Hydration/elimination reactions of trapped protonated fluoroalkyl triazines

Physicochemical Properties of A New PEGylated Polybenzofulvene Brush for Drug Encapsulation

A new polymer brush was synthesized by spontaneous polymerization of benzofulvene macromonomer 6-MOEG-9-T-BF3k bearing a nona(ethylene glycol) side chain linked to the 3-phenylindene scaffold by means of a triazole heterocycle. The polymer structure was studied by SEC-MALS, NMR spectroscopy, and MALDI-TOF MS techniques, and the results supported the role of oligomeric initiatory species in the spontaneous polymerization of polybenzofulvene derivatives. The aggregation features of high molecular weight poly-6-MOEG-9-T-BF3k-FE were investigated by pyrene fluorescence analysis, dynamic light scattering studies, and transmission electron microscopy, which suggested a tendency towards the format…

Characterization of gas phase aggregates of bis(2-ethylhexyl)sulfosuccinate (AOT) and divalent metal ions. Elimination of radical species in the decomposition pathways of even-electron [AOTMIICl2]– anions

Structure and properties of even-electron anionic species formed by bis(2-ethylhexyl)sulfosuccinate (AOT) and divalent metal ions (MII) with stoichiometry [AOTMIICl2]– have been investigated by using electrospray ionization and different mass spectrometry techniques, such as high resolution, accurate mass measurements, collision-induced dissociation (CID) multiple-stage mass spectrometry. Owing to CID, eliminations of neutrals, mainly consisting in hydrochloric acid, 2-ethyl-1-hexene and 2-ethylhexanol, and an unexpected loss of an alkyl radical have been observed. The radical anions [C4HO6SMIICl]–• so produced have been characterized by MS3 experiments. Density functional theory calculatio…

Five-to-Six Membered Ring-rearrangements in the Reaction of 5-Perfluoroalkyl-1,2,4-oxadiazoles with Hydrazine and Methylhydrazine

The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-oxadiazoles with hydrazine or methylhydrazine as bidentate nucleophiles has been investigated. The reaction occurred through the addition of the bidentate nucleophile to the C(5)-N(4) double bond of the 1,2,4-oxadiazole followed by ring-opening and ring-closure (ANRORC) involving the second nucleophilic site of the reagent. This ring-closure step could involve either the original C(3) of the 1,2,4-oxadiazole (giving a five-to-five membered ring rearrangement) or an additional electrophilic center linked to it (exploiting a five-to-six membered ring rearrangement). An alternative initial nucleophilic attack may involve the additional elec…

Synthesis of 4(5)-phenacyl-imidazoles from isoxazole side-chain rearrangements

A novel base-induced rearrangement of isoxazoles into imidazole derivatives is reported. In the isoxazole series, this represents the first example of a three-atom side-chain rearrangement involving a CNC sequence. The reactions are carried out under nitrogen and produced 2-aryl-4(5)-phenacyl-5(4)-phenyl-imidazoles in high yields. In the presence of oxygen, a cascade rearrangement-oxidation reaction sequence was observed and imidazole derivatives bearing an oxidized side-chain were isolated.

Spatially ordered surfactant assemblies in the gas phase: negatively charged bis(2-ethylhexyl)sulfosuccinate-alkaline metal ion aggregates

The formation and structural features of negatively charged aggregates of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) surfactant molecules in the gas phase have been investigated by electrospray ionization mass spectrometry (ESI-MS) and density functional theory calculations. Mainly driven by the interactions of alkali metal ions both with the oxygen atoms of the sulfonate group and with the succinate moiety of the AOT− anion, spatially ordered supramolecular assemblies, characterized by an internal core composed of surfactant counterions and hydrophilic head groups surrounded by the surfactant alkyl chains pointing outwards, are formed. Calculations have shown that surfactant self-organ…

Gas phase charged aggregates of bis(2-ethylhexyl)sulfosuccinate (AOT) and divalent metal ions: first evidence of AOT solvated aggregates

Assembling and chelating properties of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) towards divalent metal ions have been investigated in the gas phase by electrospray ionization mass spectrometry. A variety of positively charged monometallated and mixed metal aggregates are formed. Interestingly, several ions contain solvent (MeOH, H2O) molecules and constitute the most abundant AOT cationic aggregates not containing sodium. These species are the first example of solvated AOT-metal ion aggregates in the gas phase. By increasing the surfactant aggregation number, the abundance of solvated species becomes lower than that of unsolvated ones. Decompositions of ionic species have been studied…

Electrospray ion mobility mass spectrometry of positively charged sodium bis[2-ethythexyl)sulfosuccinate aggregates.

Collision cross-sections (CCS) of positively singly and multiply charged aggregates of the surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) in the gas phase have been measured by quadrupole ion mobility time-of-flight mass spectrometry. Calibration of the observed drift times to the CCS of the AOTNa non-covalent aggregates was achieved by collecting, under the same experimental conditions, the drift times of a range of singly and multiply charged polyalanine peptides whose CCS had been obtained by conventional ion mobility spectrometry. Together with an obvious increase of the aggregate cross-section with the aggregation number, it was found that the aggregate cross-section increa…

Effects of the net charge on abundance and stability of supramolecular surfactant aggregates in gas phase

Self-assembling of amphiphilic molecules under electrospray ionization (ESI) conditions is characterized by quite unexpected phenomenology. The noticeable differences with respect to the condensed phase are attributable to the absence of the surfactant-solvent interactions, the presence of net charge in the aggregates, and the strong deviation from equilibrium conditions. Aiming to investigate the effects of the net charge on abundance and stability of supramolecular surfactant aggregates, positively and negatively charged aggregates of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and sodium methane sulfonate (MetS), butane sulfonate (ButS) and octane sulfonate (OctS) have been studied by E…

Surfactant self-assembling in the gas phase: bis(2-ethylhexyl)-sulfosuccinate divalent metal ion anionic aggregates

RATIONALE Investigation of fundamental aspects driving surfactant self-assembling and of the capability of including guest molecules or ions in their micellar aggregates is an exciting research field for theoretical and technological reasons. In this light, assembling and chelating properties of sodium bis(2-ethylhexyl)sulfosuccinate (AOTNa) towards divalent metal ion chlorides have been investigated in the gas phase by electrospray ionization mass spectrometry in negative ion mode, tandem mass spectrometry and energy-resolved mass spectrometry. METHODS Water/methanol solutions of AOTNa and chloride salts of nickel, magnesium, calcium and manganese, with different AOTNa/metal salt ratios, w…

Gas phase behavior of radical cations of perfluoroalkyl-1,2,4-triazines: an experimental and theoretical study

Electron ionization mass spectrometry and low-energy collision-induced decomposition reactions occurring in a tridimensional ion trap, together with density functional theory (DFT) calculations on neutrals, even- and odd-electron cations, have been used to study the gas-phase ion chemistry of a series of perfluoroalkyl-1,2,4-triazines. Loss of oxygen, due to thermal degradation occurring before ionization, likely involving the hydroxylamino group, has been observed. Compounds having a carbonyl group at position 6 of the triazine ring fragment in the source by elimination of NO followed by HF or CO. The decomposition pathways occurring due to CID experiments have shown interesting features d…

On the photoreaction of some 1,2,4-oxadiazoles in the presence of2,3-dimethyl-2-butene. Synthesis of N-imidoyl-aziridines

Fhe photochemistry of some 3,5-disubstituted 1,2,4-oxadiazoles in the presence of 2,3-dimethyl-2-butene has been investigated. The irradiation in acetonitrile yielded differently substituted N-imidoyl-aziridines through an aziridination reaction involving an acyliminonitrene intermediate. Pyrolysis of N-imidoyl-aziridines produced the corresponding N-allylamidines through a ring opening process.

CCDC 2071148: Experimental Crystal Structure Determination

Related Article: Marco Paolino, Mario Saletti, Annalisa Reale, Mariano Licciardi, Paola Varvarà, Arnaud Marquette, Jérémie Léonard, Claudia Bonechi, Alessandro Donati, Gianluca Giorgi, Germano Giuliani, Benedetta Carlotti, Fausto Ortica, Loredana Latterini, Mariangela Gentile, Eugenio Paccagnini, Massimo Olivucci, Andrea Cappelli|2022|Chem.-Eur.J.|28|e202201477|doi:10.1002/chem.202201477