Syntheses and Crystal Structures of Functionalized Tetramethyl Resorcinarenes

Tetramethyl resorcinarene, which was obtained by acidic condensation of resorcinol with paraacetoaldehyde, was chemically modified to the functionalized O-acyl, O-tosyl and O-acetate derivatives by corresponding acylation, p-toluenesulfonylation and alkylation reactions. The single crystal structures of these functionalized resorcinarenes and the complex of tetramethyl resorcinarene with 2,2'-bipyridine were determined by X-ray diffraction method. All these resorcinarenes adopt the all-cis configuration with four methyl groups stretching to the down rim and form 1D or 2D structures through H-bonds.     

Multivalent macrocyclic hosts: histone surface recognition, guest binding, and delivery by cyclophane-based resorcinarene oligomers

As a new class of host for both specific proteins and hydrophobic molecular guests, cyclophane-based resorcinarene oligomers were designed on the basis of a molecular design that allows the assembly of four or 12 anionic resorcinarenes on a cyclophane skeleton. We prepared a cyclophane-based resorcinarene tetramer (4), constructed with a tetraaza[6.1.6.1]-paracyclophane skeleton and four resorcinarenes bearing heptacarboxylic acid residues that connect to the macrocycle through amide linkages. In addition, we prepared an extended analogical dodecamer (12), which was constructed with a pentakis(cyclophane) skeleton and 12 resorcinarenes. The cyclophane-based resorcinarene oligomers exhibited potent recognition capabilities toward histone, a small basic protein of eukaryotic chromatins. The binding constants (K) of cyclophane-based resorcinarene tetramer 4 and dodecamer 12 with histone were determined to be 1.3x107 and 8.4x107 M-1, respectively, by means of surface plasmon resonance measurements. The K values of 4 and 12 with histone were 31- and 200-fold larger than that of an untethered reference resorcinarene, reflecting the multivalency effects in resorcinarenes. In addition to that, cyclophane-based resorcinarene tetramer 4 and dodecamer 12 captured hydrophobic guests such as 6-p-toluidinonaphthalene-2-sulfonate, with respective binding constants of 2.4x103 and 2.5x104 M-1 in an aqueous HEPES buffer as evaluated by fluorescence spectroscopy. Furthermore, the resorcinarene oligomers were also found to act as guest carriers from the bulk aqueous phase to histone surfaces, as confirmed by fluorescence spectroscopy.     

A sulfonated calix[4]resorcinarene with l-pipecolinic acid groups as a water-soluble chiral NMR solvating agent

A water-soluble calix[4]resorcinarene containing l-pipecolinic acid groups is investigated as a chiral NMR solvating agent for aromatic-containing substrates. The substrates form complexes by insertion of the aromatic ring into the cavity of calix[4]resorcinarene. Compounds with phenyl, naphthyl, indole, indoline and pyridyl rings were investigated. The substrates also have ammonium or carboxylate functional groups. The effectiveness of the calix[4]resorcinarene with l-pipecolinic acid groups is compared to similar reagents with proline, hydroxyproline, and α-methylproline moieties that have previously been reported. The derivative with l-pipecolinic acid usually produces better enantiomeric discrimination compared to previous calix[4]resorcinarene reagents.     

Resorcinarene-based cavitands with chiral amino acid substituents for chiral amine recognition

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (), alanine undecyl resorcinarene acid () and glycine undecyl resorcinarene acid (), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of , , and with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary l-tartaric acid and the monoacid phthalyl alanine (). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary l-tartaric acid only binds one amine guest strongly. The simple compound , which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.     

Regioselective acylation of aminoresorcinarenes

The acid catalyzed hydrolytic cleavage of the oxazine rings in the readily available tetraoxazine derivatives of resorcinarenes results in tetraaminoresorcinarenes. A similar process applied to C₂-symmetrical bisoxazine resorcinarene tetratosylates affords C_2v-symmetrical resorcinarenediamines. The mild acylation of these resorcinareneamines with BOC-anhydride or para-nitrophenyl ester proceeds selectively at the nitrogen atoms without affecting the hydroxyl groups. Most of the resulting resorcinareneamides are thus obtained in preparative yields and can be easily purified by simple crystallizations. In the crystalline state the compounds obtained are found to bind chloride anions through hydrogen bonds and electrostatic interactions and to display a chiral arrangement of hydrogen bonded functional groups at the wide rim of the macrocycle.     

Synthesis of Resorcinarene Derivatives by the Catalyzed Mannich Reaction,Part 2: Resorcinarene Derivatives with Unsaturated Bonds

The conditions of a simple synthesis of alkenyloxymethyl and the alkynyloxymethyl derivatives of resorcinarene by the Mannich reaction catalyzed with iminodiacetic acid are described. The synthesis presented in this article is effective and uses readily available and inexpensive substrates.     

Cyclophane-based tetra(resorcinarene) as a host for both histone and hydrophobic molecular guests

A cyclophane-based resorcinarene tetramer, which is constructed with a tetraaza[6.1.6.1]paracyclophane and four resorcinarenes bearing hepta(carboxylic acid) residues that connect the macrocycle through amide linkages, was prepared. The binding constant of the cyclophane-based resorcinarene with immobilized histone was determined to be 1.3 × 10⁷ M⁻¹ by surface plasmon resonance measurements, which was 31-fold larger than that of the resorcinarene monomer bearing octacarboxylic acids. Moreover, the cyclophane-based tetra(resorcinarene) acted as a host toward hydrophobic molecular guests such as 6-p-toluidinonaphthalene-2-sulfonate.     

The Synergistic Extraction of Lanthanide Ions by a Mixture of Calix[4]resorcinarene or its Dimethylamino-, Piperidyl- or Trimethylammoniummethylated Derivatives and 1,10-Phenanthroline in n-Heptanol

The alkylaminomethylatedcalix[4]resorcinarene derivatives, modified bydimethylamino-, piperidyl- and trimethylammoniummoieties, have been synthesised to investigate theirextractability towards lanthanide ions and to comparewith the extractability of calix[4]resorcinarene. Both calix[4]resorcinarene and its derivatives have beenshown to synergistically affect lanthanide ionextraction from neutral aqueous solutions by1,10-phenanthroline through outer-sphere interactionof lanthanide bis-phenanthrolinate cations withdeprotonated forms of calix[4]resorcinarene. Thederivatives with dimethylamino- andpiperidylmethylated moieties are shown to be moreeffective extractants in comparison with theunsubstituted one.     

Reactions on a solid surface. A simple, economical, and efficient acylation of alcohols and amines over Al2O3

Al(2)O(3) brings about a rapid acylation of a range of alcohols and amines with acid chlorides and acid anhydrides, respectively. Amines are easily Boc- and Cbz-protected on reaction with Boc-anhydride and Cbz-Cl, respectively. The acylation of phenols is slow enough to allow chemoselective acylation of alcohols and amines in the presence of phenols.     

Synthesis of novel, boron-containing cavitands derived from calix[4]resorcinarenes and their molecular recognition of biologically important polyols in Langmuir films

An efficient synthetic route for the synthesis of cavitands derived from calix[4]resorcinarene and its tetrabromo derivative was elaborated. A large-scale preparation was achieved in excellent yield, by replacing the high-boiling solvents with acetone. The tetrabromocavitands were transformed into tetra-boronic acid cavitands via lithiation with butyllithium and reaction with triethylborate. Two lipophilic cavitands bearing four boronic acid residues were demonstrated to form stable Langmuir monolayers at the water-air interface. These cavitand receptors differ in bridging unit between oxygen atoms, i.e. one contains a one-carbon unit and the other a two-carbon unit. l-sorbose, d-galactose, d-glucose, and d-cellobiose were selected for molecular recognition studies using the Langmuir techniques. The unsubstituted tetra-n-undecyl calix[4]resorcinarene was used as a reference receptor compound. Differences in surface potential were diagnostic of the different types of binding forces, which can occur.     

Novel network polymers based on calixresorcinarenes

The novel network polymers 2a-2d based on calix[4]resorcinarene derivatives were obtained with yields 2a: 80%, 2b: 90%, 2c: 70%, 2d: 70%. Polymers 2a and 2b containing fragments of tetramethylcalix[4]resorcinarene or tetraphenylcalix[4]resorcinarene as a repeating units were synthesized by condensation cis-tetramethylcalix[4]resorcinarene or cis-tetraphenylcalix[4]resorcinarene with formaldehyde. Polymers 2c and 2d containing fragments of furylcalix[4]resorcinarene were obtained by condensation of formaldehyde with products of calix[4]resorcinarene and furfural interaction. The IR spectra and sorption properties of the polymers were researched. It is found out that 2a-2d can participate in the cation-exchange reaction.     

四烷基间苯二酚杯芳烃八[N-(2-吡啶甲基)乙酰胺]的合成和分子结构

为深入开展杯芳烃为骨架的超分子拓扑结构的组装和性能,开展了间苯二酚杯芳烃八取代吡啶酰胺的合成和分子结构的研究。 以四丙基、四己基和四庚基间苯二酚杯芳烃为原料,使用α-氯乙酸甲酯实现O-烃基化,后者在无溶剂条件下与2-氨甲基吡啶反应实现酰胺化,制备了烷基间苯二酚杯芳烃八[N-(2-吡啶甲基)乙酰胺]衍生物。 用X衍射方法测定了四丙基间苯二酚杯芳烃八乙酸甲酯、四丙基以及四己基间苯二酚杯芳烃八[N-(2-吡啶甲基)乙酰胺]的单晶分子结构。 在晶体中,间苯二酚杯芳烃都以全顺式构型存在,在成环的四个间苯二酚单元中,1,3-位的两个间苯二酚单元处于近直立构象,2,4-位的另两个间苯二酚单元处于近平伏构象,而4个烷基皆处于分子的下缘,8个乙酰胺支链伸向分子的外围。     

Effects of acyl donor type, catalyst type, and reaction conditions on the activity and selectivity of Friedel-Crafts acylation

Acylation of anisole and 3-methylanisole was performed with several acylating reagents (acetylation by AcCl and Ac₂O and bromoacetylation by BrAcCl and (BrAc)₂O) over different solid acid catalysts. The reaction conditions were optimized with respect to the acylation reagent, overall yield, solid acid catalyst, and the products selectivities. While acylation of anisole with acetyl chloride or acetic anhydride resulted in its full conversion to para-substituted acetophenone, the use of bromoacetyl bromide or bromoacetic anhydride yielded also the ortho-substituted product. Acylation of 3-methylanisole also yielded both para- and ortho-substitutions, and the products distribution was affected by the reaction conditions and catalyst type. It was found that while more acidic catalysts (caesium salt of heteropolyacid and zeolites) were the most active towards anisole acylation, the most active catalysts for the acylation of 3-methylanisole were ion-exchange catalysts. Employing HY-740 zeolite resulted in the highest ortho-selectivity in the acylation of anisole with bromoacetyl bromide and bromoacetic anhydride and in the acylation of 3-methylanisole with acetic anhydride.     

A sulfonated calix[4]resorcinarene with α-methyl-l-prolinylmethyl groups as a water-soluble chiral NMR solvating agent

A water-soluble calix[4]resorcinarene containing α-methyl-l-prolinylmethyl groups was investigated as a chiral NMR solvating agent. Substrates form complexes by insertion of the aromatic ring into the cavity of the calix[4]resorcinarene. Amino acid derivatives with phenyl or indole rings, ammonium substrates with pyridyl, indane or dihydroindole rings, and phenyl-containing substrates with carboxylic acid and/or hydroxyl groups were studied. The effectiveness of the α-methyl-l-prolinylmethyl calix[4]resorcinarene is compared to similar reagents with proline and hydroxyproline moieties that have previously been reported. The α-methyl-l-prolinylmethyl derivative causes larger enantiomeric discrimination of one or more ¹H resonances than the previous systems for most of the substrates.     

Functional modification,self-assembly and application of calix[4]resorcinarenes

As a special subset of calix[4]arene, calix[4]resorcinarene is an excellent molecular platform which could be modified by introducing functional groups to multiple sites at the upper and lower rims. There are mainly three ways to build functionalized calix[4]resorcinarene derivatives: (1) modification on the C-2 sites of calix[4]resorcinarenes; (2) modification on the phenolic hydroxyl groups of calix[4]resorcinarenes; (3) modification on the bridging methylenes at lower rim of calix[4]resorcinarenes. Functionalized calix[4]resorcinarene derivatives play an important role in the development of self-assembly chemistry, among which hydrogen bonding and metal coordination are the two most common interactions to obtain multicomponent structures. Moreover, due to the excellent topological structures and various active substituents of functionalized calix[4]resorcinarene derivatives, their applications in various fields, such as nanoparticles, catalysts, fluorescent materials, and sensors, have been briefly presented in this paper.

     

The Structural Diversity of Benzofuran Resorcinarene Leads to Enhanced Fluorescence

An unexpected and previously unknown resorcinarene mono‐crown with a fused benzofuran moiety in its macrocyclic core was obtained as a byproduct from a bridging reaction of tetramethoxy resorcinarene with tetraethylene glycol ditosylate. The formation of the fused benzofuran moiety in the resorcinarene macrocycle resulted in a unique rigid and puckered boat conformation, as shown by XRD studies in the solid state. Modification of the macrocycle was also observed to affect the photophysical properties in solution by enhancing the fluorescence brightness compared with a conventional resorcinarene macrocycle. The fluorescent properties enabled unique detection of structural features, that is, the rigid boat conformation with the conjugated benzofuran system and the more flexible crown bridge part, in solution.     

Microwave‐Assisted Synthesis of Calix[4]resorcinarene Hydroxamic Acids

New calix[4]resorcinarenes bearing hydroxamic acid groups, calix[4]resorcinarene hydroxamic acids (CRAHAs), have been synthesized.     

Separation of cis- and trans-isomers of thioxanthene and dibenz[b,e]oxepin derivatives on calixarene- and resorcinarene-bonded high-performance liquid chromatography stationary phases

The chromatographic behavior of six calix[n]arene phases (n=4, 6, 8) and one calix[4]resorcinarene phase is described for the separation of cis- and trans-isomers of three thioxanthene (flupentixol, clopenthixol, chlorprothixene) and one benz[b,e]oxepin derivative (doxepin). The influences of two different organic modifiers (MeOH, MeCN) for the separation of the isomers on every column are described. Different selectivities of the stationary phases exist as a function of the ring size of the calixarenes and their substitution at the "upper rim" with p-tert.-butyl groups. Furthermore, the influence of free phenol groups on the resorcinarene phase is discussed. Relations between structural elements of the analytes and the retention behavior on the stationary phases are found. The selectivity of the calixarene and resorcinarene stationary phases is compared with a RP-C18 phase containing the same base silica. Advantages of the resorcinarene as well as of the calixarene columns exist for the separation of cis- and trans-isomers of three compounds dependent from the substitution in position 2 of the thioxanthenes, respectively the kind of the basic side chain of all substances.     

Functionalization of the periphery of calix[4]resorcinarenes with P(III)-containing substituents via hydroxy,trimethylsiloxy, and ethoxy-tethered trimethylsiloxy intermediates

Unlike C-undecylcalix[4]resorcinarene, C-methylcalix[4]resorcinarene 1 reacted with chlorodifluorophosphine in the absence of an auxiliary base to give the unstable octakis(difluorophosphite)-substituted derivative 2. The existence of two conformational isomers of 2 in solution was observed by ¹⁹F and ³¹P NMR spectroscopy. Attempts to react the octakis(trimethylsilyl)calix[4]resorcinarene 3 and its tetrabromo derivative 4 with phosphorus trichloride and chlorodifluorophosphine were unsuccessful. The ethoxy-tethered C-methyl-octakis(trimeth-ylsilyl)calix[4]resorcinarene 5 was allowed to react with 2-chloro-1,3,5-trimethyl-1,3,5-triaza-2σ³λ³-phosphorin-4,6-dione and chlorodifluorophosphine. By substitution of all trimethylsilyl groups, the octakis(phosphorus(III))-substituted compounds 6 and 7 were formed. As for 2, dynamic behavior in solution was observed for 6 and 7, arising from the equilibrium between different conformational isomers. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:553–558, 1998     

Formation of ionic associates from oppositely charged calix[4]resorcinarene host molecules in the presence of guest molecules

The conditions for the formation and existence of capsular dimeric associates in a solution were studied. The associates are formed by the oppositely charged resorcinarene derivatives (tetrakis(dimethylaminomethyl)calix[4]resorcinarene hydrochloride and tetrakis(sulfonato- methyl)calix[4]resorcinarene). Possibilities of formation of a capsule in the presence of the molecules giving inclusion complexes with one of the macrocycles were considered. Switching between two states “capsular associate—mixture of original macrocycless” is achieved by controlling the ionic strength of the solution. The interaction of the host—guest complexes with complementary resorcinarene leads to capsular associate closure with the synchronous displacement of the guest molecules into the aqueous solution bulk.