[1₄]Heterophane prototypes containing azolium and/or azole anion-binding motifs.

Revisiting a '3 + 1' convergent stepwise strategy permitted the synthesis of [1₄]imidazoliophane 2·2Br in excellent yield for a macrocyclization. The new [1₄]triazoliophane 3 and bis(1,2,3-triazolium) counterpart 4·2Cl were less synthetically accessible and the hybrid derivative 5·Cl proved troublesome to prepare. Triazolophane 3 was devoid of anion-binding affinities, while charged [1₄]heterophane prototypes showed a particular preference for acetate.

A simple halide-to-anion exchange method for heteroaromatic salts and ionic liquids.

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A(-) form) in non-aqueous media. The anion loading of the AER (OH(-) form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A(-) form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities.

Synthetic approaches to multifunctional indenes.

The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid.

A general halide-to-anion switch for imidazolium-based ionic liquids and oligocationic systems using anion exchange resins (A- form).

Further studies on the application of an AER (A(-) form) method broadened the anion exchange scope of representative ionic liquids and bis(imidazolium) systems. Depending on the hydrophobicity nature of the targeted imidazolium species and counteranions, different organic solvents were used to swap halides for assorted anions, proceeding in excellent to quantitative yields.

Indene-based frameworks targeting the 5-HT6 serotonin receptor: ring constraint in indenylsulfonamides using cyclic amines and structurally abbreviated counterparts.

Further studies in quest of 5-HT(6) serotonin receptor ligands led to the design and synthesis of a few selected examples of N-(inden-5-yl)sulfonamides with a ring-constrained aminoethyl side chain at the indene 3-position, some of which exhibited a high binding affinity, such as the pyrrolidine analogue 28 (K(i)=3nM). Moreover, the structurally abbreviated N-(inden-5-yl)sulfonamides showed K(i) values > or = 43 nM, which indicates that neither the N,N-aminoethyl nor the conformationally restricted aminoethyl side arm at the indene 3-position are required for binding. Selected compounds were then tested in a functional cAMP stimulation assay and found to act as 5-HT(6) antagonists, although with moderate potency at the micromolar level.

Identification of novel indanylsulfonamide guanylhydrazones as potent 5-HT6 serotonin receptor antagonists.

Changing the N,N-(dimethylamino)ethyl side chain in the N-[3-(aminoethyl)inden-5-yl]sulfonamide 5-HT(6) serotonin receptor agonists 1 by a conformationally rigid guanylhydrazone moiety at the indene 3-position led to the identification of the title indanylguanylhydrazones 6, which exhibited excellent binding affinities and an antagonistic response at the 5-HT(6) receptor, with K(i) and IC(50) values in the nanomolar range (K(i) >or= 1.2 nM, IC(50) >or= 47 nM, and I(max) View Article and Find Full Text PDF

Indene-based scaffolds. 2. An indole-indene switch: discovery of novel indenylsulfonamides as 5-HT6 serotonin receptor agonists.

Scaffold selection involving an indole-to-indene core change led to the discovery of a series of indenylsulfonamides that act as 5-HT6 serotonin receptor agonists. The variety of the targeted ligands and their synthetic complexity required multistep synthetic approaches. The novel indenylsulfonamides exhibited variable binding affinities for the 5-HT6 receptor, and the in vitro primary binding profiles of the preferred compounds revealed them to be 5-HT6 receptor agonists with Ki values > or =4.

Bis(imidazolium)-calix[4]arene receptors for anion binding.

Efficient access to the bis(imidazolyl)calixarene 2 and dicationic bis(imidazolium) salts 1a,b x 2X directly bonded to the upper rim of calixarene structure has been reported. Anion binding properties of the new receptors were studied by 1H NMR spectroscopic methods. Bis(N-butylimidazolium) dication 1a exhibited the best recognition properties toward carboxylate anions with a 1:1 receptor-anion binding stoichiometry, whereas the presence of a bulky group such as isopropyl (1b) increased the difficulty of both imidazolium moieties to be able to support the association with the same single anion.

Indene-based scaffolds. Design and synthesis of novel serotonin 5-HT6 receptor ligands.

A series of novel indene derivatives designed by a scaffold selection gave access to several examples of (Z)-arylmethylideneindenes and indenylsulfonamides that acted as serotonin 5-HT(6) receptor ligands. Different synthetic multistep routes could be applied to these target compounds, each with their own complexity and limitations. A reasonable route involved the (3-indenyl)acetic acids as the key intermediates, and two alternatives were also examined.

1,2-Diaryl(3-pyridyl)ethanone oximes. Intermolecular hydrogen bonding networks revealed by X-ray diffraction.

The synthesis of a set of 1-aryl-2-aryl(3-pyridyl)ethanones 1-5 and the corresponding ketoximes 6-9 is reported. Structural studies of oximes 6, 7 and 9 were performed in solution using (1)H-NMR and in the solid state by X-ray crystallography, providing evidence of H-bonding networks. The crystal packing was controlled by homomeric intermolecular oxime.

Coordination features of bis(N-heterocyclic carbenes) and bis(oxazolines) with 1,3-alkylidene-2,4,6-trimethylbenzene spacers. Synthesis of the ligands and silver and palladium complexes.

The synthesis of simple imidazolium-based ligand precursors containing a 1,3-alkylidene-2,4,6-trimethylbenzene spacer was examined and different synthetic protocols were applied depending on the nature of the alkylidene arm. For a methylene arm, simple dications 5a,b.2CI were obtained directly.

Novel bis-betaines and betaines within [1(4)]meta-heterophane frameworks.

After prior selection of betaine building blocks for the construction of quadrupolar heterophane frameworks, a convergent "3+1" synthetic strategy is reported for the synthesis of the title macrocycles composed of heterocyclic betaine subunit(s). These typify the first example of simple cyclophanes constructed out of both highly pi-excessive and highly pi-deficient heteroaromatic moieties linked in a 1,3-alternating fashion. The chemical reactivity of the quadrupolar heterophanes 1a and 1c toward electrophiles under neutral conditions corroborated their bis-betaine structure.

Polynucleating open-chain systems with imidazole and proton-ionizable 1,2,4-triazole structural motifs.

A multistep route for obtaining the polynucleating open-chain systems 3-5 is reported. These advanced intermediates required elaborate processes that proceeded for the pentanuclear protophanes 3 in seven steps, whereas the trinuclear compounds 4 and 5 were obtained in six steps

Novel[1n]-meta-heterophane frameworks with a bis-betaine nature.

A convergent "5 + 1" and "5 + 3" synthetic strategy allowed the synthesis of the first examples of bis-betaines 2 and 3, a prototype of phanes that incorporate heterocyclic betaines. The structure of the quadrupolar macrocyclic systems 2 and 3 together with the dicationic [1(6)]- and [1(8)] meta-heterophane precursors 5*2X and 6*2X were examined by spectroscopy using 1H and 13C NMR techniques together with 1H-DNMR studies and electrospray ionization mass spectrometry.

Imidazolium molecular motifs located on dicationic frameworks. Electrospray mass spectrometric observation of carbenes: imidazolylidenes.

Electrospray ionization mass spectral analysis of simple dicationic imidazolium prototypes (M.2X) is reported and direct observation was obtained for proton-mediated ion-molecule reactions in the gas phase. The comparative ESI-MS study with heterophanes 1a.

Novel charged [1(4)]ăzolophanes: associative behaviour revealed by electrospray ionization.

Electrospray ionization mass spectrometry has been used to investigate simple multicharged [1(4)]heterophanes containing heterocyclic betaine subunits as building blocks. The formation of stable noncovalent polymolecular self-assembled structures in the gas phase is reported.