Strong Transannular Interaction Research Articles

Computational Evaluation of N-Based Transannular Interactions in Some Model Fused Medium-Sized Heterocyclic Systems and Implications for Drug Design.

As part of a project on fused medium-sized ring systems as potential drugs, we have previously demonstrated the usefulness of Density Functional Theory (DFT) to evaluate amine nitrogen-based transannular interactions across the central 10-membered ring in the bioactive dibenzazecine alkaloid, protopine. A range of related hypothetical systems have been investigated, together with transannular interactions involving ring-embedded imino or azo group nitrogens and atoms or groups (Y) across the ring. Electrostatic potential energies mapped onto electron density surfaces in the different ring conformations were evaluated in order to characterise these conformations. Unexpectedly, the presence of sp2 hybridised nitrogen atoms in the medium-sized rings did not influence the conformations appreciably. The strength and type of the N…Y interactions are determined primarily by the nature of Y. This is also the case when the substituent on the interacting nitrogen is varied from CH3 (protopine) to H or OH. With Y = BOH, very strong interactions were observed in protopine analogues, as well as in rings incorporating imino or azo groups. Strong to moderate interactions were observed with Y = CS, CO and SO in all ring systems. Weaker interactions were observed with Y = S, O and weaker ones again with an sp3 hybridised carbon (Y = CH2). The transannular interactions can influence conformational preferencing and shape and change electron distributions at key sites, which theoretically could modify properties of the molecules while providing new or enhanced sites for biological target interactions, such as the H or OH substituent. The prediction of new strong transannular interaction types such as with Y = BOH and CS should be helpful in informing priorities for synthesis and other experimental studies.

Influence of transannular interaction over absorption and fluorescent properties of [2.2] paracyclophane and its phenyl derivatives

A significant bathochromic shift of the fluorescent and long-wavelength absorption bands of [2.2] paracyclophane comparing to corresponding bands of alkyl-benzenes is due to a strong transannular interaction, resulting in formation of a principally new excited state of lower energy. It is concluded that the fluorescent levels for alkylbenzene excimers and for the macrocycle are of the same nature. Analysis of [2.2] paracyclophane mono- and diphenylderivatives spectra shows that their intensive absorption bands (230–310 nm) are originated from electron transitions of biphenyl groups and weak long wavelength absorption (310–340 nm) and fluorescent bands are governed by the same electron transitions between ground and excimer-like excited states as in the case of non-substituted macrocycle.

Absorption and Luminescence Properties of [2.2]Paracyclophane due to Strong Transannular Interaction

The significant bathochromic shift of luminescence and long-wavelength absorption bands of [2.2]paracyclophane compared with the corresponding bands for molecules containing non-conjugated benzene chromophores was examined. The effect was due to strong interaction between π-orbitals of closely spaced benzene rings of the molecule that resulted in formation of an excited state of lower energy that was new in principle. It was concluded that the fluorescent state of the macrocycle and excimers formed by alkylbenzenes were of the same nature. The lowest electronic excited state of [2.2]paracyclophane appeared not only in emission but also in absorption. This explained the lack of an anomalous Stokes shift for it. The stronger shift of the macrocycle fluorescence band compared with the excimer band of alkylbenzenes was due to the fact that the highest occupied π-orbital of [2.2]paracyclophane was perturbed and located higher on the energy scale than for the chromophores of alkylbenzenes and polystyrene.

Quadratic susceptibility and first hyperpolarizability of the complex of Cr(CO)3 with [2.2]paracyclophane

The peculiarities of chemical bonding and nonlinear optical properties of the complex of Cr(CO)3 with [2.2]paracyclophane (Cr–pCp) have been studied by a combined experimental–theoretical approach. The Cr–pCp complex exhibits second harmonic generation, the efficiency of which was measured by the powder technique at 1064.2nm fundamental wavelength and estimated theoretically. The comparison of electronic structure of the Cr–pCp with benzene tricarbonyl chromium analogue has revealed an important role of intraligand charge transfer state in pCp moiety conditioned by a strong transannular interaction between aromatic rings which is responsible for the enhanced molecular hyperpolarizability of Cr–pCp.

1,2-dithiin annelated with bicyclo[2.2.2]octene frameworks. One-electron and two-electron oxidations and formation of a novel 2,3,5,6-tetrathiabicyclo[2.2.2]oct-7-ene radical cation with remarkable stability owing to a strong transannular interaction.

A stable derivative of 1,2-dithiin annelated with bicyclo[2.2.2]octene frameworks 4 was synthesized as red crystals by the reaction of a dilithiated dimer of bicyclo[2.2.2]octene with elemental sulfur in 59% yield. The cyclic voltammetry of 4 in CH(2)Cl(2) at -78 degrees C showed two reversible oxidation waves at E(1/2) +0.18 V and +0.72 V versus Fc/Fc(+), indicating that the radical cation and dication of 4 are stable under these conditions. Upon chemical one-electron oxidation of 4 in a rather low concentration (4.0 x 10(-4) M) with a 1.5 equiv of SbCl(5) in CH(2)Cl(2), a radical cation 4.+ was formed, whose spin distribution was determined by ESR spectroscopy and by the results of theoretical calculations (UB3LYP/6-31G). The electronic absorption spectrum of 4.+ in CH(2)Cl(2) exhibited a maximum absorption at 428 nm (epsilon = 2.3 x 10(3)), which was hypsochromically shifted from that of neutral 4 (469 nm). When the radical cation 4.+ was produced in higher concentration (0.06 M) in CH(2)Cl(2), a disproportionation was found to take place to give a SbCl(6)(-) salt of remarkably stable radical cation 5.+ having a novel 2,3,5,6-tetrathiabicyclo[2.2.2]oct-7-ene structure. In the X-ray structure of 5.+SbCl(6)(-), the transannular distance (2.794(3) A) between the sulfur atoms was found to be less than the sum of the van der Waals radii of a sulfur atom (3.70 A), suggesting the existence of a bonding interaction between the two disulfide linkages. The theoretical calculations (UB3LYP/6-31G) suggested that this transannular interaction could be described as the resonance between the limiting structures, each of them having a two-center three-electron bond between two sulfur atoms belonging to two different disulfide linkages: thus, both the spin and positive charge are equally delocalized to the four sulfur atoms, causing a great stabilization of 5.+. On the other hand, the 1,2-dithiin radical cation 4.+ was found to readily react with triplet oxygen with subsequent rearrangement to give the 1,2-dithiolium derivative 6+ having a carboxyl group. Finally, the reaction of 4 with an excess amount of SbF(5) gave the corresponding dication 4(2+), which was found to be a 6pi aromatic system on the basis of the results of NMR measurement and theoretical calculations.

Synthesis and Properties of 4,4,9,9‐Tetramethyl‐1‐oxa‐cycloundecane‐5,6,7,8‐tetrone and 5,5,10,10‐Tetramethyl‐1‐oxa‐cyclotridecane‐6,7,8,9‐tetrone

AbstractThe synthesis of 4,4,9,9‐tetramethyl‐1‐oxa‐cycloundecane‐5,6,7,8‐tetrone (9) and 5,5,10,10‐tetramethyl‐1‐oxa‐cyclotridecane‐6,7,8,9‐tetrone (10) has been achieved in a multistep procedure. The key steps in this synthesis were the ring closure of 23 and 24 to 25 and 26, respectively, and the oxidation of the triple bond with RuO2/NaIO4 to the dihydroxydiketones 31 and 32. Compound 9 is the first cyclic tetraketone for which an intramolecular donor‐acceptor stabilization has been found. A strong transannular interaction between the ether oxygen and the C4O4 unit in 9 was detected by X‐ray studies on single crystals of 9. The transannular distance is 2.7–2.8 Å. Further evidence for a strong transannular interaction was obtained from the comparison of the reduction potential and the first band in the UV/Vis spectrum with the corresponding values from other openchain tetraketones. These findings were substantiated by PE investigations on 9. The crystal structures of the dihydroxy‐diketones 31 a and 32 a showed that, in the case of the eleven‐membered ring (31 a), there are also short transannular distances between the ether oxygen and the C2O2 moiety (2.5 Å and 2.9 Å). In the case of the thirteen‐membered ring (32 a), no transannular interactions were found in the solid state.

Simple preparation of sterically congested 1,9‐disubstituted dibenzothiophenes and formation of their dithia dications via transannular S‐S interaction

Abstract4,6‐Disubstituted thianthrene‐5‐oxides reacted with n‐butyllithium to afford sterically crowded 1,9‐disubstituted dibenzothiophenes (3) in moderate yields. The structures of the phenylthio derivative 3a and its monooxide 6a were determined by X‐ray crystallographic analysis, which revealed that the distances between the two outer sulfur atoms are 3.012 Å (3a) and 3.016 Å (6a). 1,9‐Disubstituted dibenzothiophenes 3 and their monooxides 6 afforded the corresponding dithia dications on dissolution in conc. sulfuric acid. The lower oxidation potentials of compounds 3 compared with other dibenzothiophene derivatives reveal evidence for strong transannular interaction between the two outer sulfur atoms.

Excited states of methano-bridged [10]-, [14]-, and [18]annulenes. Evidence for strong transannular interaction, and relation to homoaromaticity

Measurements of the absorption, polarized fluorescence, and MCD of 1,6-methano[10]annulene, 1,6:8,13-bismethano[14]annulene, and 1,6:8,17:10,15-trismethano[18]annulene along with the semiempirical p-electron and AVE calcns. on these and related annulenes are reported. The transannular interaction in the methano-bridged annulenes is strong, and these homoarom. mols. can be viewed as examples of arrested transition states along electrocyclic reaction paths. In addn. to the anticipated Lb, La, Bb, and Ba transitions originating in the conjugated (4N + 2)-electron annulene perimeter, at least one further low-energy transition is present, but its nature is not well understood. The MCD of the bridged annulenes agrees with the expectation based on the general theory for cyclic (4N + 2)-electron systems and the abs. signs agree with the relative size of orbital energy differences obtained from CNDO/S calcns.

ChemInform Abstract: THE HELIUM (HE I) PHOTOELECTRON SPECTRUM OF 1,2,6,7‐CYCLODECATETRAENE. EVIDENCE FOR A STRONG TRANSANNULAR INTERACTION

Chemischer InformationsdienstVolume 10, Issue 1 Physical Organic Chemistry ChemInform Abstract: THE HELIUM (HE I) PHOTOELECTRON SPECTRUM OF 1,2,6,7-CYCLODECATETRAENE. EVIDENCE FOR A STRONG TRANSANNULAR INTERACTION M. C. BOEHM, M. C. BOEHMSearch for more papers by this authorR. GLEITER, R. GLEITERSearch for more papers by this author M. C. BOEHM, M. C. BOEHMSearch for more papers by this authorR. GLEITER, R. GLEITERSearch for more papers by this author First published: January 2, 1979 https://doi.org/10.1002/chin.197901051AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume10, Issue1January 2, 1979 RelatedInformation

ChemInform Abstract: 5,8‐DIHYDROXY‐9,10‐DIHYDRO‐9,10‐(1,2)BENZENOANTHRACENE‐1,4‐DIONE. AN INTRAMOLECULAR TRIPTYCENE QUINHYDRONE

AbstractDas Dimethoxy‐anthracen (I) liefert mit p‐Benzochinon in siedendem Acetonitril in 86%iger Ausbeute ein 9,10‐Addukt, das dugch Isomerisierung mit Kaliumhydroxid und anschließende Oxidation zum Dimethoxychinon (III) führt.

Das He(I)‐Photoelektronenspektrum von 1,2,6,7‐Cyclodecatetraen. Hinweis auf eine starke transannulare Wechselwirkung

The He(I) Photoelectron Spectrum of 1,2,6,7-Cyclodecatetraene. Evidence for a Strong Transannular Interaction The photoelectron spectrum (He(I)) of 1,2,6,7-cyclodecatetraene (3) is discussed. The first four bands in the PE spectrum of 3 are assigned by comparison with calculated orbital energies according to MINDO/3. The interaction between both allenic units can be described by the interaction parameters β = −0.58 eV and β′ = −0.07 eV.

5,8-Dihydroxy-9,10-dihydro-9,10-[1,2]benzenoanthracene-1,4-dione. An intramolecular triptycene quinhydrone

The title compound (1) has been obtained either by the partial oxidation of the bishydroquinone (4) with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone or by the reaction between (4) and the bisquinone (5); it has a strong transannular interaction in spite of the apparently disadvantageous framework.

ESR studies of the triplet state of [n.n] paracyclophanes

ESR experiments were performed on the triplet state of randomly oriented paracyclophanes in a variety of rigid glasses at temperatures ranging from 103 to 15°K. Spectra were recorded for [2.2]; [3.3]; (4,7,12,15)-tetramethyl [2.2]-paracyclophane and stagger-ring paracyclophane. For all the samples except stagger ring, a four-ringed paracyclophane, only the Hmin feature was observed from which D*, the root-mean-square zero-field splitting, was calculated. For stagger ring the triplet spectrum has two features in the Δ ms= 1 region in addition to the Hmin feature. From these, the zero-field splittings, D and E, were calculated. The triplet spectra for the paracyclophanes show that there is strong transannular interaction with electron delocalization over all benzene rings. There is evidence for strongly coupled intramolecular exciton effects. The effect of increasing the inter-ring separation from [2.2] paracyclophane to [3.3] paracyclophane is to decrease the transannular interaction. The effect of methyl substitution is to increase transannular effects relative to the parent compound. Transannular interactions in stagger ring are greater than in [2.2] paracyclophane despite the increased electron delocalization possible through the introduction of more than two rings. The large value of E for stagger ring represents a significant deviation from axial symmetry for the zero-field-splitting tensor and indicates that the methylene bridges, the methyl substituents, or the ring distortion, may make important contributions to the electronic distribution of the triplet state.