2.2]Paracyclophanes in polymer chemistry and materials science

After a long period as model compounds in basic research [2.2]paracyclophanes are quickly gaining in practical importance. They can be incorporated into numerous polymeric systems in which they either lose (the so-called Parylenes) or retain their layered structure, and they can be used for the construction of unsaturated molecular scaffolds characterized not only by conventional (lateral) pi-electron overlap but also by cofacial pi-electron interactions. Surfaces generated from and with [2.2]paracyclophanes possess interesting biological, photophysical, and optoelectronic properties.     

Synthesis of perfluoro[2.2]paracyclophane

A synthesis of perfluoro[2.2]paracyclophane has been sought ever since the partially fluorinated octafluoro[2.2]paracyclophane (AF4) was prepared and its chemistry studied. This compound has now been prepared in 39% yield from the precursor, 1,4-bis(chlorodifluoromethyl)-2,3,5,6-tetrafluorobenzene by its reaction with Zn when heated in acetonitrile at 100 degrees C. Two preparations of the precursor, first from 1,4-dicyano-2,3,5,6-tetrachlorobenzene and an improved method beginning from 1,2,4,5-tetrachlorobenzene, are also described as are key comparisons to our related synthesis of AF4.     

Regioselective Functionalization of [2.2]Paracyclophanes: Recent Synthetic Progress and Perspectives

[2.2]Paracyclophane (PCP) is a prevalent scaffold that is widely utilized in asymmetric synthesis, π‐stacked polymers, energy materials, and functional parylene coatings that finds broad applications in bio‐ and materials science. In the last few years, [2.2]paracyclophane chemistry has progressed tremendously, enabling the fine‐tuning of its structural and functional properties. This Minireview highlights the most important recent synthetic developments in the selective functionalization of PCP that govern distinct features of planar chirality as well as chiroptical and optoelectronic properties. Special focus is given to the function‐inspired design of [2.2]paracyclophane‐based π‐stacked conjugated materials by transition‐metal‐catalyzed cross‐coupling reactions. Current synthetic challenges, limitations, as well as future research directions and new avenues for advancing cyclophane chemistry are also summarized.     

Surface‐Initiated Ring‐Opening Polymerization of ϵ‐Caprolactone from a Patterned Poly(hydroxymethyl‐ p‐xylylene)

A new strategy toward patterned polymer brushes combining the spatially controlled deposition of poly[(hydroxymethyl‐p‐xylylene)‐co‐(p‐xylylene)] ( 1 ) by chemical vapor deposition (CVD) polymerization of 4‐(hydroxymethyl)[2.2]paracyclophane and surface‐initiated ring‐opening polymerization was developed. Patterns of polymer brushes with thicknesses between 53 and 538 Å were created. The approach does not require photolithographic tools and has potential applicability to a wide range of different substrates, such as glasses, polymers, metals or composites.     

Diastereoselective Hartwig-Buchwald reaction of chiral amines with rac-[2.2]paracyclophane derivatives

A Hartwig-Buchwald addition of a variety of chiral amines to rac-4-bromo-[2.2]paracyclophane and rac-trifluoromethanesulfonic acid (4-[2.2]paracyclophane) ester was performed with high diastereoselectivities. Kinetic racemic resolution of the starting materials was achieved, providing a rapid access to enantiomerically enriched 4-bromo-[2.2]paracyclophane and the corresponding enantiomerically pure [2.2]paracyclophane amines. Additionally, the first reaction of a secondary amine with a [2.2]paracyclophane halide was achieved.     

o-Thioquinones on [2.2]paracyclophanes: an example of totally stereocontrolled hetero Diels-Alder reactions

The reaction of 4-hydroxy[2.2]paracyclophane with phthalimidesulfenyl chloride allowed the preparation of a suitable precursor for a paracyclophane-o-thioquinone. This species participates in an inverse electron demand hetero Diels-Alder reaction with different electron-rich alkenes to give the expected benzoxathiin cycloadducts with complete control of regio- and stereochemistry.     

Stereoselective synthesis of homoallylic alcohols of the [2.2]paracyclophane series and their use as auxiliaries in asymmetric allylboration of aldehydes

Stereoselectivity of allylboration of 4-formyl[2.2]paracyclophane, 4-acetyl[2.2]paracyclophane, and 4-hydroxy-5-formyl[2.2]paracyclophane was studied and the relative configurations of the homoallylic alcohols obtained were established. Optically pure (Sp,Sc)-(+)-4-(4-hydroxy-1-methylbut-3-enyl)[2.2]paracyclophane and (Rc,Sc)-(+)-4-hydroxy-5-(4-hydroxybut-3-enyl)[2.2]paracyclophane were synthesized. The possibility of using (Sp,Sc)-(+)-4-(4-hydroxy-4-methylbut-3-enyl)[2.2]paracyclophane as a recoverable chiral auxiliary in asymmetric allylboration of aldehydes was demonstrated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 914–921, May, 2000.     

Suzuki aryl cross-coupling chemistry using derivatives of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane

An exploration into the scope of Suzuki aryl cross-coupling chemistry using derivatives of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane is reported. The coupling of 4-iodo-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane with various aryl boronic acids and boronic acid pinacol esters was successful, with the exception of very sterically demanding systems, such as mesityl. The synthesis of the previously unreported 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophanyl-4-boronic acid is described, together with various Suzuki aryl cross-coupling reactions of this new system. Using standard Suzuki methodology, it was possible to prepare dicyclophanes bearing two octafluoro[2.2]paracyclophane units separated by both one and two benzene rings.     

Backbone‐Degradable Polymers Prepared by Chemical Vapor Deposition

Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone‐degradable polymer directly synthesized via CVD. The CVD co‐polymerization of [2.2]para ‐cyclophanes with cyclic ketene acetals, specifically 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO), results in well‐defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals to [2.2]para ‐cyclophanes as well as the hydrophobicity of the films. These coatings address an unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.     

Novel ligands based on bromosubstituted hydroxycarbonyl [2.2]paracyclophane derivatives: synthesis and application in asymmetric catalysis

New planar-chiral hydroxycarbonyl [2.2]paracyclophane derivatives, 4-acetyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-АНРС, 63%) and 4-benzoyl-13-bromo-5-hydroxy[2.2]paracyclophane (Br-BHPC, 53%), were synthesized and reacted with the enantiomers of α-phenylethylamine to form corresponding Schiff bases, 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-ethyl]-[2.2]paracyclophane and 12-bromo-4-hydroxy-5[1-(1-phenyl-ethylimino)-(phenyl)methylen-[2.2]paracyclophane. The diastereomers of the imines were resolved and their absolute configurations and consequently the corresponding configurations of the enantiomers of Br-АНРС were determined by X-ray diffraction. Enantiomerically pure Schiff bases were applied as ligands to form catalysts for the enantioselective addition reaction of diethylzinc with benzaldehyde where 1-phenylpropanol was obtained with 77–91% ee.     

Transannular Hydrogen Bonding in Planar‐Chiral [2.2]Paracyclophane‐Bisamides

A series of [2.2]paracyclophane‐bisamide regioisomers and alkylated comparators were designed, synthesized, and characterized in order to better understand the transannular hydrogen bonding of [2.2]paracyclophane‐based molecular recognition units. X‐Ray crystallography shows that transannular hydrogen bonding is maintained in the solid‐state, but no stereospecific self‐recognition is observed. The assignment of both transannularly and intermolecularly hydrogen bonded N?H stretches could be made by infrared spectroscopy, and the effect of transannular hydrogen bonding on amide bond rotation dynamics is observed by ¹H‐NMR in nonpolar solvents. The consequences of transannular hydrogen bonding on the optical properties of [2.2]paracyclophane is observed by comparing alkylated and non‐alkylated pseudo‐ortho 4,12‐[2.2]paracyclophane‐bisamides. Finally, optical resolution of 4‐mono‐[2.2]paracyclophane and pseudo‐ortho 4,12‐[2.2]paracyclophane‐bisamides was achieved through the corresponding sulfinyl diastereoisomers for circular dichroism studies. Transannular hydrogen bonding in [2.2]paracyclophane‐amides allows preorganization for self‐complementary intermolecular assembly, but is weak enough to allow rapid rotation of the amides even in nonpolar solvents.     

Towards Multipotent Coatings: Chemical Vapor Deposition and Biofunctionalization of Carbonyl‐Substituted Copolymers

Future advances in designing bioactive materials, such as antithrombotic coatings for cardiovascular stents, will require widely applicable and robust methods of surface modification. In this paper, we report on the development of multifunctional polymer coatings made by chemical vapor deposition (CVD) copolymerization. Polymer coatings of various [2.2]paracyclophane derivatives were co‐deposited in controlled ratios and their chemical composition verified by FT‐IR and X‐ray photoelectron spectroscopy. Furthermore, preliminary biocompatibility of these coatings was assessed using human umbilical vein endothelial cells and 3T3 murine fibroblasts. The parallel immobilization of two different antithrombotic biomolecules onto a CVD‐based copolymer is also demonstrated by orthogonal immobilization strategies.

     

The first three aromatic tribromides of the [2.2]paracyclophane series

From the reaction mixtures in the uncatalyzed polybromination of [2.2]paracyclophane by the action of excess Br₂ in CCl₄, there have been found along with the known products — 4,15- and 4,16-dibromo[2.2]paracyclophanes — two new aromatic tribromides of this series, which have been isolated in pure form: 4,12,15- and 4,15,16-tribromo[2.2]paracyclophanes. Special experiments demonstrated that the mixtures of these tribromides are formed as a result of competitive monobromination of 4,15-dibromo[2.2]paracyclophane; the 4,15,16-tribromo[2.2]paracyclophane, together with still another newly isolated isomer of this series — 4,8,12-tribromo[2.2]paracyclophane — is formed as a result of competitive monobromination of 4,16-dibromo[2.2]paracyclophane. As an explanation of the features of the orienting effect of substituents in these competing reactions, a rule was proposed: On the conventional orientation (from the electronic point of view) of entry of the bromine atom into the substituted ring (para > ortho > meta), a steric limitation is imposed on its attack in the pseudo-gem-position, owing to the bulky bromine atom that is transannularly positioned above it in the neighboring aromatic ring. The structures of all of the tribromides were established on the basis of elemental analyses, mass spectrometry, and¹H NMR spectrometry (including PMR using the homonuclear Overhauser effect). The data obtained in this work indicate that the 4,12,15-tribromo[2.2]paracyclophane and 4,15,16-tribromo[2.2]paracyclophane are predecessors of the two tetrabromides previously obtained by Cram — 4,7,12,15- and 4,5,15,16-tetrabromo[2.2]paracyclophanes; and the 4,8,12-tribromo[2.2]paracyclophane is a possible predecessor of 4,8,12,16-tetrabromo[2.2]paracyclophane, which is unknown up to the present time.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1837–1843, August, 1992.     

Studies on the Syntheses of Multilayered [2. 2] Paracyclophanes

It is well-known that a number of double-layered compounds such as [2. 2]paracyclophane show anomalous physical and chemical properties due to the transannular π-electronic interaction between the stacked aromatic rings.²) Moreover, the interaction significantly increases with an increase of the layers as observed in a series of multilayered [2. 2]paracyclophanes³) and thereby it is of great interest to search a possibility of an organic semiconductor or its suitable model in them or their derivatives. However, such a study has been severely limited by great difficulty on the syntheses of the layered cyclophanes. While a number of synthetic methods have been developed for cyclophanes,²) only 1,6-Hofmann elimination method has so far been adopted to the preparation of multilayered [2.2]paracyclophanes.³) In practice, however, the yield is very low and becomes markedly poor with the increasing layers. Now we have studied some practical improvements on the preparation of multilayered [2.2]paracyclophanes.     

Design and synthesis of novel rhodamine-based chemodosimeters derived from [2.2]paracyclophane and their application in detection of Hg2+ion

For a better insight into the spectroscopic properties of [2.2]paracyclophane in fluorescent probes, a novel rhodamine-based chemodosimeter bearing [2.2]paracyclophane 4a has been designed and synthesized. The probe 4a exhibits a highly selective and sensitive response to Hg²⁺ over other transition metal ions in aqueous solution. Its detection limit is determined to be 77 nM. The significant changes in the fluorescence color could be used for the naked-eye detection. Furthermore, the probe 4a shows good membrane permeability and can be applied to detect intracellular Hg²⁺ in human lung adenocarcinoma cells (A549 cells). The crystal structure and spectral properties of its congener 4b that contains one 12-bromo [2.2]paracyclophane group and rhodamine moiety are also investigated for a comparison.     

Synthesis, characterization, and spectroscopy of 4,7,12,15-[2.2]paracyclophane containing donor and acceptor groups: impact of substitution patterns on through-space charge transfer

This paper reports the synthesis of 4,7,12,15-tetra(4'-dihexylaminostyryl)[2.2]paracyclophane (1), 4-(4'-dihexylaminostyryl)-7,12,15-tri(4' '-nitrostyryl)[2.2]paracyclophane (2), 4,7-bis(4'-dihexylaminostyryl)-12,15-bis(4' '-nitrostyryl)-[2.2]paracyclophane (3), 4,7,12-tris(4'-dihexylaminostyryl)-15-(4' '-nitrostyryl)[2.2]paracyclophane (4), 4,15-bis(4'-dihexylaminostyryl)-7,12-bis(4' '-nitrostyryl)[2.2]paracyclophane (5), and 4,12-bis(4'-dihexylaminostyryl)-7,15-bis(4' '-nitrostyryl)[2.2]paracyclophane (6). These molecules represent different combinations of bringing together distyrylbenzene chromophores containing donor and acceptor groups across a [2.2]paracyclophane (pCp) bridge. X-ray diffraction studies show that the lattice arrangements of 1 and 3 are considerably different from those of the parent chromophores 1,4-bis(4'dihexylaminostyryl)benzene (DD) and 1,4-di(4'-nitrostyryl)benzene (AA). Differences are brought about by the constraint by the pCp bridge and by virtue of chirality in the "paired" species. The absorption and emission spectra of 1-6 are also presented. Clear evidence of delocalization across the pCp structure is observed. Further, in the case of 2, 3, and 4, emission from the second excited state takes place.     

Photochemical synthesis of [2.2](3,8)-pyridazinophane and quinolinophane-2(1H)-one as well as synthesis of [2](5,8)-quinolinophanes and fused spiro-pyranoindanoparacyclophanes

Syntheses of various classes of unreported heterophanes derived from [2.2]paracyclophane are herein reported. The key to their successful synthesis depends on the photochemical synthesis of pyridazinophane and quinolinophane-2(1H)-one from freshly prepared 4-([2.2]paracyclophanyl)-azo-4′-[2.2]paracyclophane and 4-([2.2]paracyclophanyl)cinnnamanilide, respectively. Reactions of 4-amino-[2.2]paracyclophane with either acetyl- or benzoylacetone afforded condensed products. Then ring closure using polyphosphoric acid (PPA) at 120°C gave, in near quantitative yields, quinolinophanes. Reactions of [2](4,7)-indano-[2]paracyclophane-1-ylidene-propanedinitrile with active methylene compounds afforded fused spiro-pyranoindanoparacyclophane derivatives.     

An exploration of Suzuki aryl cross coupling chemistry involving [2.2]paracyclophane derivatives

Suzuki aryl cross coupling reactions using derivatives of [2.2]paracyclophane were examined. A variety of aryl boronic acids and pinacolate esters were successfully cross coupled with 4-bromo[2.2]paracyclophane under standard Suzuki conditions. Whilst an excellent tolerance for electron donating and withdrawing groups was observed, cross coupling reactions with highly sterically demanding borates (e.g. mesityl) were unsuccessful. The preparation and stability of the previously unreported [2.2]paracyclophanyl-4-boronic acid, -pinacolate ester and -dimethyl ester are described, along with the utility of these systems in Suzuki aryl cross coupling reactions. Application of this methodology led to a dicyclophane containing two [2.2]paracyclophane units separated by a 4-4' connected biphenyl spacer group.     

Rigid cyclophanes that illustrate stereochemical principles

All of the point groups common to organic chemistry except two are illustrated by known compounds that are rigid [2.2]paracyclophane derivatives. Examples are given of transannular directing effects by acetyl, nitro, and acetoxyl substituents attached to [2.2]paracyclophane. In bromination or chloromethylation, proton loss of a sigma complex is rate-determining, and the oxygens already in the molecule remove the proton being substituted. The synthesis of [2.2.2](1,2,4)cyclophane and [3.2.2](1,2,5)cyclophane, and their unusual chemical properties are described. Transannular hydride shifts out of methyl groups due to proximity effects are reported. Torsional racemizations and epimerizations of [2.2]paracyclophane derivatives are reviewed. The diradical intermediates formed have been intercepted by either H· donors, or by addition to substituted olefins. To account for the stereochemical course of addition and substitution reactions in the side-chains of [2.2]- and [4,2]paracyclophanes, new types of bridged carbonium ions are suggested. Conformational equilibria in the four-carbon side-chain of [4.2]paracyclophane derivatives are discussed.     

Binuclear rhenium(I) complexes with bridging [2.2]paracyclophane-diimine ligands: probing electronic coupling through pi-pi interactions

Two pseudo-para substituted bis-diimino[2.2]paracyclophane ligands (4,16-bis(picolinaldimine)-[2.2]paracyclophane (BPPc) and 4,16-bis(methyl-picolinaldimine)-[2.2]paracyclophane (BmPPc)) were prepared by the condensation reaction of the appropriate picolinaldimine with 4,16-diamino-[2.2]paracyclophane (2). An improved synthesis of 2 from [2.2]paracyclophane also is reported. BPPc (3a): monoclinic, P2(1)/c, a = 8.2238(11) A, b = 15.336(2) A, c = 8.4532(11) A, beta = 98.578(3) degrees, V = 1054.2(2) A(3), Z = 2. To investigate the binding properties of the bis-diimino[2.2]paracyclophane ligands, binuclear rhenium(I) tricarbonyl chloride complexes [Re(CO)(3)Cl](2)(micro-BPPc) (5a) and [Re(CO)(3)Cl](2)(micro-BmPPc) (5b) were prepared and fully characterized by infrared spectroscopy, (1)H NMR spectroscopy, elemental analysis, UV-visible absorption spectroscopy, and cyclic voltammetry. Two model complexes, Re(tolyl-pyCa)(CO)(3)Cl (4) (tolyl-pyCa = N-(p-tolyl)-2-pyridinecarboxaldimine) and [Re(CO)(3)Cl](2)(micro-PBP) (6) (PBP = p-phenylenebis(picolinaldimine)), also are reported. The dimeric compounds 5 and 6 each undergo two one-electron, predominantly diimine-centered reduction processes. Spectroscopic data and comproportionation constants (5a, 23 +/- 9; 5b, 23 +/- 9; 6, 2750 +/- 540) are consistent with relatively weak interactions between the diimine groups mediated by the paracyclophane bridging group, and these results are consistent with steric and electronic factors.