Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• chemistry can produce any substitution pattern there are few unsymmetrical [2.2]metaparacyclophanes (3) and only one X-ray crystallographic structure found in the CCDC database, and this is a triple-layered cyclophane [44]. We have been interested in the formation of substituted [2.2]paracyclophanes for a

• number of years [45][46][47][48][49][50][51][52], and have recently focused on 4-amino[2.2]paracyclophanes [14][53][54][55]. For the most part, we have avoided nitration. The literature is full of many different procedures, and the results can be unpredictable [55][56][57][58][59][60]. Yet nitration

• obviously presents one of the most direct routes to 4-amino[2.2]paracyclophanes so we returned to this venerable reaction. In this paper, we disclose a simple synthesis of 4-hydroxy-5-nitro[2.2]metaparacyclophane (5), a side-product from our nitration reactions. This chemistry offers a rapid route to non

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• -catalyzed acylation with isobutyric anhydride. This protocol allows for a reasonable synthetically useful s-factor of 20 and provides a novel entry to obtain this interesting planar chiral motive in an enantioenriched manner. Keywords: acylation; kinetic resolution; nucleophilic catalysis; paracyclophanes

• ; planar chirality; Introduction Substituted [2.2]paracyclophanes are fascinating planar chiral molecules [1][2][3][4][5][6][7][8][9][10][11][12] which have been systematically investigated since Brown and Farthing discovered the formation of the unsubstituted and achiral parent [2.2]paracyclophane (1

• utilized as building blocks for more demanding ligands and catalysts became a task of high importance. Thus, several strategies to access enantioenriched [2.2]paracyclophanes have been reported, either relying on classical resolution approaches or, more recently, making use of asymmetric catalysis to carry

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• sodium hydroxide solution instead of silver oxide for anion exchange, results in a significant improvement in product yield. Furthermore, four substituted [2.2]paracyclophanes were also prepared in this convenient way. Keywords: bromination; dimerization; H2O2–HBr system; paracyclophane; polymerization

• substituted [2.2]paracyclophanes were synthesized from substituted (4-methylbenzyl)trimethylammonium bromides in aqueous sodium hydroxide solution in the presence of a polymerization inhibitor (Table 4). It was found that the yields of dimer products were improved dramatically compared to the results obtained

• presence. For the dimerization of 12, the [2.2]paracyclophane (17) was obtained in 33% yield, and its structure was confirmed by NMR spectroscopy and elemental analysis. Similarly, dimerization of 13, 14, and 15 resulted in regiospecific 4,16-disubstituted [2.2]paracyclophanes 18, 19, and 20, respectively

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties

• Laura G. Sarbu,
• Lucian G. Bahrin,
• Peter G. Jones,
• Lucian M. Birsa and
• Henning Hopf

Beilstein J. Org. Chem. 2015, 11, 1917–1921, doi:10.3762/bjoc.11.207

• tetrathiafulvalene that incorporates two [2.2]paracyclophane units. Results and Discussion The synthesis of [2.2]paracyclophanes containing a tetrathiafulvalene moiety, follows a general route that involves the synthesis of the corresponding [2.2]paracyclophane-substituted 1,3-dithiol-2-ylium salts. These compounds

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• Sambasivarao Kotha Mukesh E. Shirbhate Gopalkrushna T. Waghule Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400 076, India 10.3762/bjoc.11.142 Abstract In this review we cover various approaches to meta- and paracyclophanes involving popular reactions. Generally

• bridges have been reported in the literature [53]. The representative [2,2]ortho-, meta-, and paracyclophanes (4–6) are shown in Figure 1. In general, cyclophanes with one aromatic ring and two alkyl bridges are called [n,n]metapara or [n,n]paraparacyclophanes (7, 8) based on the position of the

• attachment of the alkyl chain to the aromatic system. In this review we are not discussing orthocyclophanes but rather focus on meta- and paracyclophanes only. The aromatic ring present in the cyclophane system can be either heterocyclic or carbocylic in nature. If there is a heteroatom present in the

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• previously observed only in bismuth wires and carbon nanotubes [13]. Another interesting research area is the redox modulation of the chiroptical properties described in derivatives such as TTF-allenes [14], TTF-helicenes [15], or TTF-paracyclophanes [16]. Thus, to address the different opportunities offered

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• substituted and highly functionalized [2.2]paracyclophanes, which are displayed in general form in formula 1 in Figure 1. In this general structure we distinguish between bridge substituents [Sb]m, where the number of substituents m can lie between 1 and 8, and substituents that are anchored in the benzene

• ]paracyclophanes the octamethyl compound 5 is the most highly substituted derivative presently known [13][14]. Finally, various ethynylated derivatives 6 have been described by us recently [15], compounds that, inter alia, are of interest in materials science [16][17][18]. Among the oligo- or polysubstituted

• paracyclophanes with preparative potential, we think that those bearing nitrogen-containing functional groups, although known for many years [19], deserve more attention. A case in point is the (achiral) pseudo-geminal diamine 7 (Figure 2) [20], which has been used as a reusable spacer for “topochemical reaction

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• Analytical Chemistry, Technical University of Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany 10.3762/bjoc.10.266 Abstract An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo-exo-diene

• systems and their ability to form charge-transfer complexes [4][5][6][7]. Much attention is also being paid to the development of new functionalized [2.2]paracyclophanes that can be used in asymmetric synthesis [8], while the formation of new bridges, particularly functionalized ones, has been somewhat

• neglected so far. Functional groups in pseudo-geminally substituted [2.2]paracyclophanes often undergo highly specific reactions. This is due to the rigid framework and the short distance between the two aromatic rings within the [2.2]paracyclophane unit. Thus, unsaturated cyclophane bis(esters) undergo

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• , Postfach 3329, D-38106 Braunschweig, Germany Organisch-Chemisches Institut der Universität Heidelberg Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany, Fax: (+49) 6221-544205 10.3762/bjoc.10.209 Abstract Ethynyl[2.2]paracyclophanes are shown to be useful substrates for the preparation of complex

• ago we described the preparation of various ethynyl[2.2]paracyclophanes and suggested that these compounds could be developed into useful building blocks for the construction of larger, stereochemically complex carbon frameworks (scaffolds) [2]. This prediction is clearly becoming reality, as shown by

• (Scheme 2) [8]. In the present contribution we have extended these studies, employing 2 and 4 as building blocks. The chemistry of [m.n]paracyclophanes with (completely or partially) unsaturated molecular bridges has been poorly investigated, leaving much scope for further studies. Results and Discussion

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• generates a p-xylylene intermediate 174 (a p-quinodimethane) first, which subsequently stabilizes itself by dimerization; the tetrasubstituted [2.2]paracyclophanes 175 are produced in acceptable yields (max. 50%). This route constitutes the preparatively most satisfactory way to obtain highly functionalized

• [2.2]paracyclophanes. Unactivated triple bonds do not undergo cycloaddition (no reaction with tolane, 2-butyne, cyclooctyne, etc.). Switching to asymmetric triple-bond dienophiles, such as propiolic aldehyde (176), leads to a monosubstituted p-xylylene intermediate 177, which has four different options

• to dimerize. These provide the isomeric bisformyl [2.2]paracyclophanes 178 to 181 in about equal ratio and in a total yield of up to 45% [127]. The apparently disadvantageous production of a mixture of isomers is not a real handicap of this route since these adducts differ in their physical

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• tricyclic moiety (57) can just slightly be modified towards higher affinity to acetyl cation (381, 382). Inclusion of too many methyl groups as in 379 leads to disfavorable interactions and therefore to a decrease of the ACA value. The 2,2’-paracyclophanes (368, 371, 372, 380) are derived from DMAP (54) and

Use of mixed Li/K metal TMP amide (LiNK chemistry) for the synthesis of [2.2]metacyclophanes

• Marco Blangetti,
• Patricia Fleming and
• Donal F. O'Shea

Beilstein J. Org. Chem. 2011, 7, 1249–1254, doi:10.3762/bjoc.7.145

• [2.2]cyclophane structures and have extensively studied their unusual physical and chemical properties induced by the close spatial proximity of their aryl rings [8]. Undoubtedly the most studied of the series (ortho, meta and para) are the [2.2]paracyclophanes, which have seen a recent resurgence of

Intraannular photoreactions in pseudo-geminally substituted [2.2]paracyclophanes

• Henning Hopf,
• Vitaly Raev and
• Peter G. Jones

Beilstein J. Org. Chem. 2011, 7, 658–667, doi:10.3762/bjoc.7.78

• : paracyclophanes; photoadditions; photoisomerizations; proximity effects; topochemical reaction control; vinylcyclopropanes; X-ray structural analysis; Introduction Photodimerizations of crystalline aromatic or olefinic compounds are among the oldest known organic photoreactions. In this type of reaction the

• paracyclophanes not be observed, this would not necessarily constitute a proof against diradical(oid) intermediates in these reactions. However, if derivatives such as 21 were among the photoproducts the involvement of radicals in the photoisomerizations would be indicated. We therefore reacted the bis-aldehyde 9

• photoisomerization of the tetraene 11 to the cyclooctadiene-bridged cyclophanes 13 and 15 and the iosmerization of 22 to 23 and 24 remain to be established, these processes allow the introduction of a completely new type of additional bridge into [2.2]paracyclophanes. For several of these new polycyclic molecules

Preparation and NMR spectra of four isomeric diformyl[2.2]paracyclophanes (cyclophanes 66)

• Ina Dix,
• Henning Hopf,
• Thota B. N. Satyanarayana and
• Ludger Ernst

Beilstein J. Org. Chem. 2010, 6, 932–937, doi:10.3762/bjoc.6.104

• , and were characterized by their spectroscopic data. The individual isomers can now be easily identified from their 1H NMR spectra even if only one of them is present. Keywords: cyclophanes; diformyl[2.2]paracyclophanes; layered compounds; NMR spectroscopy; structure assignment; Introduction

• beginning to attract the attention of other research groups [6][7][10][11][12][13]. Results and Discussion Separation of the diformyl[2.2]paracyclophanes 4 We have separated the isomer mixture 4 by different methods. The easiest way is by middle pressure liquid chromatography (MPLC), which readily affords

• of all isomers and may hence be easily separated. NMR spectra of the diformyl[2.2]paracyclophanes 4 As the 1H and 13C NMR spectra of [2.2]paracyclophane-4-carbaldehyde have previously been fully assigned and, hence, the influence of the substituent upon the 1H and 13C NMR chemical shifts of all

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Enantiospecific synthesis of [2.2]paracyclophane- 4-thiol and derivatives

• Gareth J. Rowlands and
• Richard J. Seacome

Beilstein J. Org. Chem. 2009, 5, No. 9, doi:10.3762/bjoc.5.9

• developing a ‘tool-box’ for the synthesis of enantiomerically enriched [2.2]paracyclophane derivatives based on the chemistry of [2.2]paracyclophane sulfoxides [15][31][32][33]. This methodology has allowed us to develop routes to enantiomerically pure 4-monosubstituted [2.2]paracyclophanes [31] along with a

Microwave assisted synthesis of triazoloquinazolinones and benzimidazoquinazolinones

• Aboul-Fetouh E. Mourad,
• Ashraf A. Aly,
• Hassan H. Farag and
• Eman A. Beshr

Beilstein J. Org. Chem. 2007, 3, No. 11, doi:10.1186/1860-5397-3-11

• cycloadditions of alkenyl [2.2]paracyclophanes. [25] Previously, we also prepared various heterocycles such as triazoloes, [26] acridinones, [27] and pyrazolidines [28]. In this publication our goal is to synthesize known and/or new of fused quinalzolines, namely triazoloquinazolinones and