Syntheses and conformations of persubstituted inverse calixarenes

Abstract

A series of ten inverse calix[n]arenes (2-11) bearing four to thirteen benzene units were prepared by starting from 3,4,5-trimethoxybenzaldehyde followed by LC separation on silica gel. In 2-11 the substitution pattern is interchanged compared with the usual calixarenes. The conformational analysis was undertaken by variable temperature 'H-NMR spectroscopy and by MM2 calculations. Calix[4]arene 2 is a rigid molecule and shows the 1,3-alternate conformation which in addition was proven by X-ray analysis. At low temperatures the calix[5]arene 3 adopts the uudod conformation, where a methyl group of one benzene unit residues in the cavity of the macrocycle. At low temperature calix[6]arene 4 forms a n 1 :2 equilibrium between the 1,3,5-alternate (ududud; 4E) and the uududu (4B) conformation. Conformation 4B can be regarded as a n intramolecular combination of a cone and an alternate arrangement of the benzene units. The calix[8]-arene shows the highest AG* value of the series and adopts an uuududdd conformation at low temperature. The inverse calixarenes 5 and 7-11 bearing seven and nine to thirteen aromatic units, respectively, are conformationally highly flexible systems even at low temperatures.The name calixarenes (Greek: calix = vase), originally introduced by Gutsche ['], describes polycyclic metacyclophanes, where alkyl phenols are connected by methylene bridges (A). In these structures the free OH groups are oriented in the same direction representing the ground of the vase while the alkyl residues from the rim. Compounds, in which these substituents are interchanged, are called inverse calixarenes (B) by us. The alteration of the substituents should change the general properties such as the chemical reactivity, complex formation and conformational behavior, because the most important property, i.e. the hydrogen bonding is less pronounced or not possible. The basic compound B has not yet been synthesized but, surprisingly, we were able to synthesize persubstituted derivatives of B starting from 3,4,5-trimethoxytoluene 1. Synthesis of 3-11Compound 1 available by catalytic hydrogenation of 3,4,5-trimethoxybenzaldehyde, reacts with paraformaldehyde in strong acidic solution. The composition and concentration of the reaction products strongly depends on the reaction conditions, in particular on the acid concentration. In the solvent combination THF/H2S04 10: 1.7 a tough oil is produced, which does not show aromatic proton signals in the NMR spectrum. From this oil the compounds 3-11 were isolated by chromatographic separation on silica gel followed by a recycling MPLC. 3-11 are colorless crystalline compounds with m.p. >29OoC. The compounds with aromatic rings >6 if crystallized are quite insoluble in common organic solvents. Therefore, all NMR investigations of these compounds were performed with a material not yet recrystallized. In fact, such adducts are observed in the laser desorption mass spectra of the high-molecular weight compounds 7-11.

Structure, Conformational Equilibrium, and Proton Affinity of Calix[4]arene by Density Functional Theory

“…Although the reduction to a small number of conformers simplifies considerably the task of modelling calix[4]arene by theoretical calculations, the size of the system makes a full first-principles approach difficult. Consequently, a significant number of works on these systems has been based on force field − or semiempirical molecular orbital approaches. ,,,

1 Calix[4]arene conformers. (a) cone, (b) partial-cone, (c) 1,2-alternate, (d) 1,3-alternate.

2 Hydrogen bonding in the calix[4]arene cone conformer.

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“…Although the reduction to a small number of conformers simplifies considerably the task of modelling calix [4]arene by theoretical calculations, the size of the system makes a full first-principles approach difficult. Consequently, a significant number of works on these systems has been based on force field [8][9][10][11][12][13][14][15][16][17] or semiempirical molecular orbital approaches. 8,11,18,19 In the present work we report density functional results for the structure, conformational equilibrium, and electronic properties of calix [4]arene.…”

Partial OH → Me Replacement in the Calixarene Scaffold: Preparation, Conformation, and Stereodynamics of Tetra-tert-butyl-25,27-dihydroxy-26,28-dimethylcalix[4]arene and Its Dimethyl Ether Derivative

“…One of the OH groups is nearly coplanar with the corresponding phenol ring, the torsional angle C(20)−C(15)−O(2)−H being 12°. 1,3-Alt conformations have been found in the crystal structures of 2c 9 and 2d 2 Crystal structure of tetra- tert -butyl-25,27-dihydroxy-26,28-dimethylcalix[4]arene ( 6 ).…”

“…Several [1 4 ] metacyclophane systems which incorporate intra annular methyl groups (e.g., 2a − d ) have been described in the literature. − These compounds were prepared by tetramerization of suitable precursors, and for the mesityl calixarene 2c , it has been concluded that the compound is conformationally rigid . Recent MM3 calculations have predicted that calixarene 2e possessing intra annular methyl groups should only be moderately more rigid than the corresponding OH-substituted systems .…”

Υπερμοριακή Χημεία

“…), σε πολύ μικρές αποδόσεις (<1 %) 83. Σε μία αντίδραση παρόμοια με τις προηγούμενες, το 3,4,5-τριμεθοξυ-τολουόλιο 192 αντιδρά με παραφορμαλδεΰδη σε όξινες συνθήκες και αποδίδει ένα μίγμα των ολιγομερών 19384 με n= 4-13 (Σχήμα 44). Τα καλιξ[4]αρένια που φέρουν υποκαταστάτες στην μεθυλενοσυνδετική ομάδα 195 παρασκευάζονται με όξινη καταλυόμενη αντίδραση τριφαινυλομεθανίων 194 με παραφορμαλδεΰδη 85 , με απόδοση 18-30 %.…”