Leo C. Groenen

Syn-1,2-dialkylated calix[4]arenes: general intermediates in the NaH/DMF tetraalkylation of calix[4]arenes

In DMF or acetonitrile with NaH as a base at room temperature the tetraalkylation of calix[4]arenes 1a and 1b proceeds via the syn-1,2-disubstituted products to the tetraalkylated calix[4]arenes in the cone conformation. With KH as a base the tetraalkylated calix[4]arenes are predominantly formed in the partial cone conformation, and the reaction proceeds via both the syn-1,3-di and the syn-1,2-disubstituted products. Also the solvent influences the pathway via which tetraalkylation takes place. The syn-1,2-disubstituted calix[4]arenes 4-6 can be isolated in 15-55 % from the NaH/DMF or MeCN reactions when only 2.2 equiv of the electrophile are used.

Synthesis of Monoalkylated Calix(4)arenes via Direct Alkylation

A new one-step procedure for the synthesis of monoalkylated calix[4]arenes is presented. Reaction of calix[4]arene 1a or 1b with 1.2 equivalent of a weak base (K2CO3 in MeCN or CsF in DMF) and excess of alkylating agent affords the monoalkylated calix[4]arenes in moderate to good yields

The tertiary amino effect in heterocyclic synthesis : mechanistic and computational study of the formation of six-membered rings

The mechanism of the ring closure of [2-(1-pyrrolidinyl)phenylmethylene]-propanedinitrile (2a) to l,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-4,4-dicarbonitrile (3a) has been studied by kinetic measurements using 1H-NMR spectroscopy. It could be shown that the rate-determining step consists of an intramolecular 1,5 hydrogen transfer, which is accompanied by charge separation within the- molecule. The calculated (AM1) and experimental (X-ray) molecular structure of 2a are in fairly good agreement. In the ground state geometry a 1,5 hydrogen transfer will most likely take place suprafacially. Subsequent rotation of the former vinyl group and C-C-bond formation, leading to a six-membered ring, also take place in a stereochemically defined way.

Spectroscopic and crystallographic study of 27,28-diethoxy-p-tert-butylcalix[4]arenes

The molecular conformation of the anti form of the title compound, i.e. with the two neighbouring phenylethylether fragments in anti positions, is a partial cone. The conformation is stabilized by two intramolecular hydrogen bonds. These bonds involve both the phenolic OH groups as donors and a hydroxyl group and an ethoxygroup as acceptors. FT-IR solid state spectra reveal two OH bands at 3388 and 3175 cm?1 which is in accordance with the observed hydrogen-bond configuration. In CCl4 solution the partial cone is preserved for the anti form (3378 and 3187 cm?1) while the corresponding syn form mainly adopts a cone conformation characterized by O---H stretching vibrations at 3360 and 3168 cm?1.

Solvent effects on the conformations and hydrogen bond structure of partially methylated p-tert-butylcalix[4]arenes

The effect of the solvent on the conformations of unsubstituted p-tert-butylcalix[4]arene (1) and its methyl ethers 2–6 has been investigated by 1H NMR spectroscopy. The conformational distribution of the 1,2-dimethyl ether 4 and of the tetramethyl ether 6 is strongly influenced by the solvent used. The exact geometry of the cone conformation of the 1,3-dimethyl ether 3 and of the 1,2-dimethyl ether 4 changes from distinct C2 symmetry in CCl4 to close to C4 symmetry in CS2. It seems that inclusion of a small solvent molecule (e.g. CS2) in the cone conformation can take place. Spectra recorded at temperatures up to 125°C in CDCl2CDCl2 showed that the mono- and 1,3-di-methyl ethers are fixed in the cone conformation, whereas the unsubstituted calix[4]arene and the tetramethyl ether are flexible. These observations support a concerted mechanism for the cone-to-cone interconversion in 1, in which two or more phenol rings rotate simultaneously.The hydrogen bonding in partially methylated calix[4]arenes was investigated by IR spectroscopy. In all calix[4]arenes with neighbouring hydroxy groups, a strong cooperativity effect of 80% or more was observed. The exact geometry of the cone conformation affects the strength of the hydrogen bonds, because it influences the O–H ⋯ O angle in the calix[4]arene. The effect of the solvent on the geometry of the cone conformation is translated in differences of up to 79 cm–1 in the OH-stretch frequencies for spectra recorded in CCl4 and in CS2.

Selectively dehydroxylated calix[4]arenes and 1,3-dithiocalix[4]arenes; novel classes of calix[4]arenes

Selective modification of calix[4]arenes either by selective dehydroxylation via the reductive removal of phosphate(s), or via the Newman–Kwart rearrangement of 1,3-bis(dimethylthiocarbamoyl)calix[4]arenes yields calix[4]arenes 3 and 1,3-dithiocalix[4]arenes 6, respectively.

Calix[4]arenes, Molecular Platforms for Supramolecular Structures

A new strategy for the synthesis of receptor molecules comprises the combination of medium-sized molecules to which functional groups for intermolecular interactions can be attached. Most efforts concern the functionalization of calix[4]arenes, but other building blocks like cyclodextrins and octols are used as well. Selective mono-, 1,2-di, 1,3-di-, and tetraalkylation of calix[4]arenes can be achieved by variation of the alkylation conditions. The calix[4]arenes can be (selectively) functionalized at the “upper rim” by a variety of methods including ipso-nitration. Combination of the calix[4]arenes with crown ethers to calixcrowns gave receptors with a high K+/Na+-selectivity and with terphenyls calixspherands were obtained that form kinetically stable complexes with Na+, K+ and Rb+. Bridging of calix[4]arene with a salophene moiety gave a receptor for urea that can effectively transport urea through a supported liquid membrane. Calix[4]arenes can be combined covalently to double and triple calixarenes and with selectively functionalized octols. When substituted with hydrogen bond donors and acceptors like 2-pyridone, calixarenes undergo self-association to larger aggregrates.

A Conformational Study of the Calixspherand and Its Complexes with Alkali-Metal Cations

The calixpherand 2 forms kinetically very stable complexes with alkalimetal cations. This molecule is not completely preorganized for binding of a cation, as is evidenced from the results of NOESY spectroscopy and X-ray diffraction measurements. Both in CDCl3 solution and in the solid state the free ligand adopts a cone conformation, whereas the Na+ complex adopts a flattened partial cone conformation. Molecular-mechanics calculations with different programs give rather biased results. Calculations with QUANTA(the all atom CHARMM-force field) correctly predict the conformation of the free ligand but not of the complexes, whereas with MACROMODEL(the united atom AMBER-force field) the experimentally observed conformation had the lowest energy only for the Na+ complex. The calculated geometries of the experimentally found conformations of the free ligand and the Na+ complex agree well with the X-ray structures, especially for the structures that were obtained with QUANTA. A comparison of the calculated structures of the Na+, K+ and Rb+ complexes showed that larger cations force the terphenyl bridge to bend away, thereby opening up the cage of the ligand and making the cation more accessible to solvent molecules. This might explain the considerably lower kinetic and thermodynamic stability of the Rb+ complex compared with those of the Na+ and K+ complexes.