Calix[6]arene Derivatives as Pivotal Components of Working Devices and Molecular Machine Prototypes

This Ph.D. thesis describes the synthesis, characterization and study of calix[6]arene derivatives as pivotal components for the construction of molecular machine prototypes. Initially, the ability of a calix[6]arene wheel to supramolecularly assist and increase the rate of a nucleophilic substitution reaction was exploited for the synthesis of two constitutionally isomeric oriented rotaxanes. Then, the synthesis and characterization of several hetero-functionalised calix[6]arene derivatives and the possibility to obtain molecular muscle prototypes was reported. The ability of calix[6]arenes to form oriented pseudorotaxane towards dialkyl viologen axles was then exploited for the synthesis of two calixarene-based [2]catenanes. As last part of this thesis, studies on the electrochemical response of the threading-dethreading process of calix[6]arene-based pseudorotaxanes and rotaxanes supported on glassy carbon electrodes are reported.

Cation complexation by chemically modified calixarenes. 11. Complexation and extraction of alkali cations by calix[5]- and -[6]arene ketones. Crystal and molecular structures of calix[5]arene ketones and Na+ and Rb+ complexes

A series of four calix[5]arenes and three calix[6]arenes (R-calixarene-OCH2COR1) (R = H or Bu-t) with alkyl ketone residues (R-1 = Me or Bu-t) on the lower rim have been synthesized, and their affinity for complexation of alkali cations has been assessed through phase-transfer experiments and stability constant measurements. The conformations of these ketones have been probed by H-1 NMR and X-ray diffraction analysis, and by molecular mechanics calculations. Pentamer 3 (R R-1 = Bu-t) possesses a symmetrical cone conformation in solution and a very distorted cone conformation in the solid state. Pentamer 5 (R = H, R-1 = Bu-t) exists in a distorted 1,2-alternate conformation in the solid state, but in solution two slowly interconverting conformations, one a cone and the other presumed to be 1,2-alternate, can be detected. X-ray structure analysis of the sodium and rubidium perchlorate complexes of 3 reveal the cations deeply encapsulated by the ethereal and carbonyl oxygen atoms in distorted cone conformations which can be accurately reproduced by molecular mechanics calculations. The phase-transfer and stability constant data reveal that the extent of complexation depends on calixarene size and the nature of the alkyl residues adjacent to the ketonic carbonyls with tert-butyl much more efficacious than methyl.

Assembly of supramolecular compounds with water-soluble calix[4]arenes

Three new copper compounds, Cu-2[C12H8N2](2)[C28H2OS4O16][H2O](11.9) (1), Cu-2[C12H8N2](3)[C28H20S4O16][H2O](5) (2), and Cu-2[C12H8N2](4)[C24H12S8O16][H2O](10.5) (3), were hydrothermally synthesized and structurally determined by X-ray diffraction and TG-DTA analyses. Interestingly, Compounds 1 and 2 were synthesized in a one-pot reaction. Complexes 1 and 3 contain capsule units, which are further assembled into three-dimensional (3-D) architectures with a-Po-related topology by pi-pi stacking and/or hydrogen-bonding interactions.

Selective Synthesis of Oxacalix[6]arenes and Mixed Oxacalix[4]arenes

Calixarenesare macrocycles composed of benzene rings meta linked to each other by one carbon atom. These exotic compounds can be used for a variety of purposes including metalleaching for environmental cleanup, surface technology, luminescent probes, nuclear waste treatment, among others. A variety of calixarenesexist, including azacalix[n]arenesthiocalix[n]arenes(where n = the number of benzene rings) and oxacalix[n]arenes; these macrocycles use nitrogen, sulfur and oxygen, respectively, as the atom whichlinks the benzene rings together. My research has focused on synthesizing oxacalix[6]arenes (“hexamer”) in high yield, which is a synthetic challenge because it is generally accepted that oxacalix[n>4]arenes will thermodynamically decompose to the oxacalix[4]arene (“tetramer”); i.e. heating the reaction mixture will yield the tetramer, not the hexamer. To generate the hexamer, “trimer”precursors have been synthesized, in the hopes of facilitating hexamer ring closure.

Self-assembly of Tetraurea Calix[4]arenes

We have elaborated a multistep strategy to synthesize ABAB-type tetraureas. There are overall nine steps but they involve very simple chemistry. The sequence starts with a 1,3-dialkylation and this is the step in which a difference between distal phenolic units is introduced. The selective ipso-nitration in the next step is based on the difference in reactivity between free phenolic units and alkylated ones. The direct reaction of tetraamino calixarene with tolylisocyanate appears not to be an appropriate method to synthesize 1,3-ditolylurea calixarenes but can be used to get tetraureas of ABBB- and AABB-types in two steps with yields of about 60%. A complete regioselective dimerization was obtained with mono-loop derivatives in which two adjacent urea residues are covalently connected. As predicted/expected the loop prevents the formation of one regioisomer, and only the dimer in which the open-chain residue slips through the loop is formed. To synthesize mono-loop tetraureas 1,2-diBoc protected tetraamino calixarene was acylated with activated di-urethanes under high dilution conditions. Di-loop compounds were synthesized by two different ways. In the reaction of tetraamine and di-urethanes the yield is about 30-40%. The second method is based on the metathesis reaction within a suitable heterodimer. For this strategy, tetraurea derivatives with residues which have terminal double bonds were prepared. The exclusive formation of the heterodimer with tetratosylurea as template is the key point in this strategy. Metathesis followed by hydrogenation give exceptionally good yields (> 80%) of the loop compounds. All the NMR data for di-loop compounds confirm that the loops prevent the interaction of the urea residues which are connected and thus, as expected, the di-loop derivatives do not form homodimers. The heterodimer between di-loop compounds and tetratolylurea (open-chain tetraureas) was the only species observed for a 1:1 mixture in benzene or chloroform. The rational synthesis of bis-[2]catenanes was a consequence of the selective formation of one regioisomer of mono-loop derivatives and the exclusive formation of heterodimers by di-loop derivatives. The formation of interlocking-ring in the synthesis of bis-[2]catenanes is an additional evidence that one open-chain residue slips through the loop in mono- or di-loop derivatives. Exceptionally good yields in the synthesis of bis-[2]catenanes are due to the high preorganization in the dimer which undergoes the metathesis. This preorganization decreases the number of the wrong connections and favors the new connections to be formed. Although the procedure for working up the reaction mixture should be still improved, these results are promising. A C2-symmetrical bis-[2]catenane was successfully resolved by column chromatography using a chiral stationary phase. Thus it should be possible to separate a larger amount to obtain pure enantiomers for further studies.

Tetraurea derivatives of calix[4]arenes and oligocalix[4]arenes, synthesis and self-assembly = Tetraharnstoff-Derivate von Calix[4 ]arenen und Oligocalix[4]arenen, Synthese und Selbstorganisierung

Wide rim tetraurea calix[4]arenes form hydrogen bonded dimeric capsules in apolar solvents in the presence of a suitable guest, which must be included in the cavity. The monomeric and dimeric form are never observed simultaneously under usual conditions. In general the combination of two different alkyl or aryl tetraurea derivatives results in the mixture of two homodimers and a heterodimer, however, only the heterodimeric species is observed in the 1:1 mixture of aryl and tosyl ureas. The (hetero)dimerization of oligourea calix[4]arenes (units) was used to construct larger structures via self-assembly of multiple calixarenes (building blocks) containing two (or more) covalently connected units. Among these self-assembled structures linear or branched polymers, cyclic oligomers and well-organized dendrimers were envisaged. The synthesis of the building blocks requires the preparation of calix[4]arene units possessing one (or more) functional group at the narrow or wide rim. Finally the oligourea units were covalently connected either directly or via suitable spacers within appropriate building blocks using amide bonds. Self-assembly properties of such building blocks were investigated.

Self-assembled structures based on functionalized calix[4]arenes and calix[8]arenes = Selbstorganisierte Strukturen basierend auf funktionalisierten Calix[4]- und Calix[8]arenen

Calix[4]arenes with urea functions attached to the p-positions of the phenolic units usually form dimers in apolar solvents. Tetraureas functionalized by pyridyl and carboxyl groups form dimers only with bis- or tetraloop tetraureas. This heterodimerization was used for the synthesis of a bis-[3]catenane. Tetraureas functionalized with sulfide functions were synthesized for the preparation of monolayers from the dimeric capsules containing electrochemically active guests on gold. Bis-tetraureacalix[4]arenes singly-linked via their wide rim by rigid spacers were synthesized and their self-assembly to polymers in apolar solvents was proved by the 1H NMR spectroscopy and AFM studies. Dimerization of the first example of the tetraurea calix[4]arenes bridged in 1,3-positions at the narrow rim was proved by 1H NMR spectroscopy. Calix[8]arenes functionalized by urea, amido or naphthalimido groups at their p-positions self-assemble to columnar structures by hydrogen bonding or by π-π-stacking.

Calix[4]arenes in the 1,3-alternate conformation

Calix[4]arenes fixed in the 1,3-alternate conformation offer an interesting platform for the attachment of further functionalities which has been less frequently used than the cone conformer. Several synthetic strategies were developed to attach four amino functions to the narrow rim, to the wide rim and to both rims of the calix[4]arene fixed in the 1,3-alternate conformation. Using different precursor groups (nitrile/phthalimide or nitro/phthalimide) which can be independently converted into amino functions opens the possibility to attach further groups selectively to the amino functions. Here the groups which is newly attached will determine the reaction sequence.

Synthesis and assembly of self-complementary calix[4]arenes.

A calix[4]arene was designed to reversibly dimerize and form an egg-shaped enclosure. Adhesive interactions in the assembly were provided by four self-associating ureas, which form a cyclic array containing 16 hydrogen bonds. The synthesis was completed in four steps from the previously described O,O',O",O"'-tetrabenzylcalix[4]arene. Evidence for dimerization of the calixarene tetraurea was provided by H NMR, mass spectrometry, and the observation of encapsulated molecules. The resulting cavity was of sufficient size to capture guests such as ethyl benzene and p-xylene.

A diffuse reflectance comparative study of benzil inclusion within p-tert-butylcalix[n]arenes (n=4, 6, and 8) and silicalite

Diffuse reflectance and laser-induced techniques were used to access photochemical and photophysical processes of benzil in solid supports, namely p-tert-butylcalix[n]arenes with n = 4, 6, and 8. A comparative study was performed using these results and those obtained with another electronically inert support, silicalite, which is a hydrophobic zeolite. In the latter substrate, ground-state benzil has the two carbonyl groups in an s-trans planar conformation while in the calixarenes a distribution of conformers exists, largely dominated by skew conformations where the carbonyl groups are twisted one to the other. In all substrates, room-temperature phosphorescence was obtained in air-equilibrated samples. The decay times vary greatly and the largest lifetime was obtained for benzil/p-tert-butylcalix[6]arene, showing that this host cavity well accommodates benzil, enhancing its room-temperature phosphorescence. p-tert-Butylcalix[6] and [8]arene molecules provide larger hydrophobic cavities than silicalite, and inclusion complexes are formed with these hosts and benzil as guest; p-tert-butylcalix[4]arene does not include benzil. This probe is deposited outside the calix[41 cavity, in the form of microcrystals. Triplet-triplet absorption of benzil was detected in all cases and is predominant in the silicalite channel inclusion case. Benzil ketyl radical formation occurs with inclusion in calix[6]arene and calix[8]arene. In the three cases, benzoyl radical was detected at long times (in the millisecond time scale). Product analysis and identification clearly show that the main detected degradation photoproducts in all substrates are benzoyl radical derivatives. Calix[6] and [8]arenes are able to supply hydrogen atoms that allow also another reaction, the reduction to benzoin through benzil ketyl radical formation.

Self-assembly of guest-induced calix[4]arene nanocapsules into three-dimensional molecular architecture

In the presence of NH3-Ag+-NH3, the calix[4]arenes can be induced into dimeric nanocapsules, which can be used as building units constructing a 3D molecular architecture with the appropriate secondary ligands and metal ions.

Novos receptores moleculares baseados em calix[4]arenos: aplicação à química sensorial

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Química

Halo-derivatised calix[4]tubes

Halo functionalisation of calix[4] tubes has been investigated through both derivatisation of individual calix[4]arenes and calix[4] tubes, using classical synthetic methods, to allow preparation of a series of novel derivatives. The solution and solid state properties are in accordance with the constituent calix[4] arenes adopting flattened cone arrangements which on complexation with potassium simplify to a regular cone. Electrospray and H-1 NMR studies, combined with molecular modelling have been used to ascertain the metal binding of this new series of cryptand like ionophores, demonstrating their retained selectivity for binding potassium over other Group 1 metals and the dependence on counter anion in the weak binding of silver.