A Novel Route to Calix[4]arenes. 2. Solution- and Solid-State Structural Analyses and Molecular Modeling Studies (original) (raw)

Functionalization of calix[4]arenes by alkylation with 2-(chloromethyl)pyridine hydrochloride

The Journal of Organic Chemistry, 1992

The syntheses, structures, and conformations of nine of the 13 possible [ (2-pyridylmethyl)oxy]calix[4]arene conformers obtainable by direct substitution on calix[4]arenes la,b are described. The conformer distribution in the exhaustive 0-alkylation of la,b with 2-(chloromethyl)pyridine hydrochloride (PicC1-HC1) in N,N-dimethylformamide (DMF) is strongly affected by the base applied: NaH induces only cone conformers, while KzC03 or CszC03 lead preferentially to partial cone and/or 1,a-alternate conformers, depending on the para substituent of the starting calix[(]arene. Single-crystal X-ray analyses on tetra-0-alkylated cone lk,l and partial cone 2c have been conducted. Molecule lk has a distorted cone conformation with pendant OCH,Py groups; a methanol of solvation is hydrogen bonded to one pyridine N atom and is exo to the calix cavity. The crystal structure of 11 contains two independent distorted cone shaped molecules per asymmetric unit which differ principally in the relative orientations of the OCH,Py groups. In the partial cone conformer 20 the conformation adopted is such that the pendant OCHzPy group of the rotated aryl ring lies in, and effectively fills, the calix cavity produced by the remaining three aryl rings; as in lk a methanol of solvation is hydrogen bonded to a pyridine N atom exo to the calix cavity. Regioselective syn-proximal (l,Z-) or syn-distal(l,3-) difunctionalization at the lower rim of calix[4]arenes has been also achieved. Syn-1,2-disubstituted derivatives have proved to be useful intermediates for the stereoselective synthesis of tTi-O-alkylated cone conformers, &[4]arenea with mixed ligating groups in the sequence AABB at the lower rim, for inherently chiral calix[4]arenes, and for the transfer of proximal regioselectivity from the lower to the upper rim. On the basis of stepwise 0-alkylation of calix[4]arenes, and with the aid of MM2 calculations on the involved intermediates and their anions, a possible genesis of the various conformers is proposed.

Alkanediyl Bridged Calix[4]arenes: Synthesis, Conformational Analysis, and Rotational Barriers

Journal of The American Chemical Society, 1996

In calix [4]arenes when one methylene bridge carries an alkyl or aryl substituent, two diastereomeric cone conformations are possible in which this substituent assumes the equatorial or axial position. Two diastereomers with cis or trans arrangement of the substituents exist for the corresponding compounds with two substituted bridges, and diastereomeric cone conformations have to be considered additionally in most cases. Molecular mechanics calculations predict an energetical preference of the equatorial position of the substituents in both systems. This preference is markedly more pronounced for alkyl groups than for aryl groups. To test these predictions a series of calix[4]arenes in which one (4) or two opposite (5) methylene bridges are substituted by alkyl or aryl groups was synthesized by fragment condensation. For these calixarenes the solution conformations, the equatorial/axial conformational equilibria, and the energy barriers for the cone to cone ring inversion were determined by 1 H NMR spectroscopy. The experimental energy differences between the two cone conformations correlate well with the calculated ones. Free energies of activation ∆G q for the cone to cone ring inversion of the monoalkyl substituted compounds 4 increase in the order methyl < tert-butyl < ethyl < isopropyl. For the bisalkyl substituted compounds (5b-d) only the cis-isomer could be isolated while cis-and trans-isomers were obtained for 5a and for the bisaryl compounds 5e-g. Among the cis-isomers 5a-d exist exclusively as the equatorial conformers, while the conformational equilibrium is strongly solvent dependent for 5e-g. Single crystal X-ray structures were obtained for several calixarenes with one (4b) or two substituted bridges (5e-g). Here the substituents are found exclusively in the equatorial position, and the molecular conformation is similar to the calculated one.

Computational and experimental studies of di- and tetrasubstituted calix[4]arenes

Chirality, 2002

Calixarenes are molecular bowls or baskets that have been demonstrated to serve as hosts for cations, anions, and neutral molecules. The central cavity and scaffolding of various functionalities on the upper and lower rims establishes this class of compounds as extremely important in supramolecular chemistry studies. In earlier studies, calixsugars (molecules that have sugar molecules appended to the upper rim of the calix) were prepared. Among the potential advantages of these molecules are increased water solubility and enhanced possibilities that these chiral attachments can promote enantiomeric selection. Computational studies, however, have indicated that the chosen calixsugars had significantly encumbered upper rims, suggesting that hostÀguest associations would be limited. In an attempt to understand those factors responsible for the favored conformations of calixsugars, a number of 5,17-disubstituted and tetrasubstituted calix[4]arenes were prepared and studied experimentally as well as by molecular mechanics conformational searching techniques. Chirality 14:173À179, 2002. Published 2002 Wiley-Liss, Inc.*

Synthetic and NMR Studies on Calix[ n ]Arene ( n = 4,6,8) Triflates, Mesylates, and Tosylates

Supramolecular Chemistry, 1998

The synthesis and full characterization of eight new calix[n]arene sulfonate esters including their conformational analysis were carried out. While ptBucalix[6]arene and ptBu-calixl81arene esters are conformationally labile in the temperature interval of 25 --lOO"C, p-tBu-calix[4]arene mono-and diesters were isolated as stable conformers at ambient temperature. Two l,%functionalised compounds of these derivatives, p-tert-butylcalixI4larene ditriflate (5) and dimesylate (6) were shown unexpectedly high conformational stability up to 100°C by dynamic N M R measurements. The N M R measurements confirm the pinched-cone conformation for both derivatives. For the dealkylated calix[rllarene derivatives the partial cone conformer of the hiesters have been obtained as major products in all cases.

An easy access to tetra-o-alkylated calix[4]arenes of cone conformation

Tetrahedron, 1995

Fully 0-alkylated calix[4larenes have been synthesbed by the alkylation of p-tertbutylcalix(4)arene and Its IJdialkylated derivatives in liquid-liquid phase-transfer catalytic process. 1Hd and lH2R2 could effeciently be deprotonated by aqueous NaOH (50% w/w)-toluene system and alkylated with alkyl (aralkyl, allyl) halogens in good yields affording cahx[4]arene tetraethers of cone conformation.

Conformational control in the synthesis of mixed tetraethers of calix[4]arene. Part 2

Tetrahedron, 1997

A/t~racl:. A series of mixed telraethers of culix[4]at~ne and p-tert-butylcalix[4]arene in which two distal substitueats a~re methyl and the other two 1-al~nyl groups with 3, 4 and 5 carbon atom chains have been by two metes which differ in the order in which the groups (methyl or alkanyl) were introduced. The ethers of p-tert-butylculix[4]arene were isolated as a mixture of cone (minor) and paRial cone (major) coufonmulens in dynamic equilibrium. For the ethers of calix[4]arene the couformationul outcome depended ou the method of synthesis. Up to thrne conformations could be detected: a cone, a peninl cone with m ani~l unit inverted, and a partial cone with an alkenyl-bearing ring inverted. IH NMR analysis of the complexes formed between these ethers and alkali metal iodides showed that both cone and cone mmplexe8 of the p-tert-butylculix[4]m-ene telraethers could be detected with lithium iodide, but only c.emplexes with the calix[4]arcoe deaivatives. Sodium iodide complexes were also formed with both sets of compounds but in all cases only the cone complex was detected.

X-ray crystal and molecular structure of upper rim monoformylated calix[4]arene system

Journal of Chemical Crystallography, 2000

Selective formylation under controlled conditions leads to the formation of a monoformylated compound 11-formyl-25,27-bis(ethoxycarbonylmethoxy)-calix[4]arene (1). The spectroscopic results indicated that the calix[4]arene is present in a cone conformation. The crystal and molecular structure of (1) has been determined by X-ray diffraction methods. The crystal data are monoclinic, space group P2 1 /c, M = 624.66, a = 10.341(1), b = 15.176(1), c = 20.121(1)Å, β = 91.90 • (1), V = 3156.0(4)Å 3 , Z = 4, D c = 1.315 g cm −3. The structure confirms the cone conformation for the molecule in the solid state as well.