Disubstituted Naphthalenes Research Articles

The effect of substituents and their positions on a series of disubstituted naphthalene bromide salts towards intermolecular interactions and crystal packing

Naphthalene derived dications bearing different N-heterocyclic substituents appended at different positions demonstrated conformational flexibility and interesting self-assembled packing motifs when crystallised in the solid state as bromide salts.

Balancing from FRET to SET and Further to Photochemistry

AbstractDyads of the hypsochromically absorbing energy donor benzoperylenetriscarboximide and the more bathochromically absorbing perylenebiscarboximide with various spacers were synthesized by means of the Sonogashira reaction where the transition moments of the donor and the acceptor are orthogonal causing zero for the geometry factor of κ for the simple p‐phenylene spacer. Exciton interactions were extinguished; however, the energy transfer by RET (resonance energy transfer) proceeded unaltered efficiently in contrast to the theory where vibronic effects were made responsible therefore. A lateral shift of donor and acceptor by means of a disubstituted naphthalene as the spacer was of no influence. The replacement of the naphthalene by the more electron rich pyrene caused a switch from RET to a photo‐induced single electron transfer (SET). RET as a very fast feeder allowed the suppression the formation of triplets of the donor and subsequent the generation of singlet oxygen and allowed to protect the dyad against photochemical degradation. Finally, the influence of the distance between donor and acceptor was studied.

Triphenylamine disubstituted naphthalene diimide: elucidation of excited states involved in TADF and application in near-infrared organic light emitting diodes

A new TADF emitter is presented showing near-infrared efficient emission.

Single molecules of terrylene in di-substituted naphthalenes crystallizing in the herringbone pattern

2,3-Dichloronaphthalene and 2,3-dibromonaphthalene were synthesized, their crystal structures determined, and vibronic spectra of single terrylene molecules in the crystals indicated lowering of the guest symmetry.

ChemInform Abstract: Thermal Cyclization of Phenylallenes that Contain ortho‐1,3‐Dioxolan‐2‐yl Groups: New Cascade Reactions Initiated by 1,5‐Hydride Shifts of Acetalic H Atoms.

A series of 2-(1,3-dioxolan-2-yl)phenylallenes that contained a range of substituents (alkyl, aryl, phosphinyl, alkoxycarbonyl, sulfonyl) at the cumulenic C3 position were prepared by using a diverse range of synthetic strategies and converted into their respective 1-(2-hydroxy)-ethoxy-2-substituted naphthalenes by smooth thermal activation in toluene solution. Electron-withdrawing groups at the C3 position accelerated these tandem processes, which consisted of 1) an initial hydride-like [1,5]-H shift of the acetalic H atom onto the central cumulene carbon atom; 2) a subsequent 6π-electrocyclic ring-closure of the resulting reactive ortho-xylylenes; and 3) a final aromatization step with concomitant ring-opening of the 1,3-dioxolane fragment. If the 1,3-dioxolane ring of the starting allenes was replaced by a dimethoxymethyl group, the reactions led to mixtures of two disubstituted naphthalenes, which were formed by the migration of either the acetalic H atom or the methoxy group, with the latter migration occurring to a lesser extent. Two of the final 1,2-disubstituted naphthalenes were converted into their corresponding naphtho-fused dioxaphosphepine or dioxepinone through an intramolecular transesterification reaction. A DFT computational study accounted for the beneficial influence of the 1,3-dioxolane fragment on the carbon atom from which the H-shift took place and also of the electron-withdrawing substituents on the allene terminus. Remarkably, in the processes that contained a sulfonyl substituent, the conrotatory 6π-electrocyclization step was of lower activation energy than the alternative disrotatory mode.

Thermal Cyclization of Phenylallenes That Contain ortho‐1,3‐Dioxolan‐2‐yl Groups: New Cascade Reactions Initiated by 1,5‐Hydride Shifts of Acetalic H Atoms

A series of 2-(1,3-dioxolan-2-yl)phenylallenes that contained a range of substituents (alkyl, aryl, phosphinyl, alkoxycarbonyl, sulfonyl) at the cumulenic C3 position were prepared by using a diverse range of synthetic strategies and converted into their respective 1-(2-hydroxy)-ethoxy-2-substituted naphthalenes by smooth thermal activation in toluene solution. Electron-withdrawing groups at the C3 position accelerated these tandem processes, which consisted of 1) an initial hydride-like [1,5]-H shift of the acetalic H atom onto the central cumulene carbon atom; 2) a subsequent 6π-electrocyclic ring-closure of the resulting reactive ortho-xylylenes; and 3) a final aromatization step with concomitant ring-opening of the 1,3-dioxolane fragment. If the 1,3-dioxolane ring of the starting allenes was replaced by a dimethoxymethyl group, the reactions led to mixtures of two disubstituted naphthalenes, which were formed by the migration of either the acetalic H atom or the methoxy group, with the latter migration occurring to a lesser extent. Two of the final 1,2-disubstituted naphthalenes were converted into their corresponding naphtho-fused dioxaphosphepine or dioxepinone through an intramolecular transesterification reaction. A DFT computational study accounted for the beneficial influence of the 1,3-dioxolane fragment on the carbon atom from which the H-shift took place and also of the electron-withdrawing substituents on the allene terminus. Remarkably, in the processes that contained a sulfonyl substituent, the conrotatory 6π-electrocyclization step was of lower activation energy than the alternative disrotatory mode.

Inhibition of the hypoxia-inducible factor pathway by a G-quadruplex binding small molecule

The hypoxia-inducible transcription factor (HIF) co-ordinates the response of tumours to low oxygen by stimulating genes involved in metabolism and angiogenesis. HIF pathway activation is associated with decreased progression-free survival and increased mortality; compounds that target this pathway are potential agents for the treatment of a range of solid tumour malignancies. Renal cancers are likely to be particularly sensitive to inhibition of the HIF pathway since ~80% show constitutive activation of HIF. We have previously described the di-substituted naphthalene derivative, CL67, which binds to a G-quadruplex higher-order structure in the HIF promoter sequence in vitro. We show here that CL67 blocks HIF expression leading to inhibition of HIF-transactivation and down-regulation of downstream target genes and proteins in renal carcinoma cell lines and in a mouse xenograft model of renal cancer. This inhibition is independent of pathways that control HIF abundance through oxygen-dependant degradation and oxygen dependant HIF sub-unit expression.

A thermodynamic approach to the selectivity of liquid crystalline reentrant phases

The thermodynamic characteristics and selectivity of sorption of disubstituted benzene, pyridine, and naphthalene by the p-n-nonyloxybenzoyloxy-p′-cyanoazobenzene, p-n-hexyloxycinnamoyloxy-p′-cyanoazobenzene liquid crystalline phases and their mixture was studied by gas chromatography. The reentrant nematic phase of a mixture of mesogens was found to possess high selectivity to structural isomers. The results of manifestation of liquid crystalline phase selectivity are discussed on the basis of the enthalpy and entropy characteristics of solution of sorbates.

Medium Effect on the Geometric Isomerism of a Centrosymmetrically Disubstituted Naphthalene Derivative with Flexible Methoxytriethylene Glycol Chains

The geometric isomeric diversity of a centrosymmetrically disubstituted naphthalene derivative with flexible methoxytriethyleneglycol chains has been investigated both in the liquid and the solid state. Owing to the fact that the exocyclic C(Aryl)-O linking appears to be essentially a double bond, the material can exist in discrete geometric isomers. Variable temperature ultraviolet absorption and fluorescence spectroscopy combined with single crystal X-ray diffraction reveal the nature of the various stereoisomers present in the liquid and solid phase. Computational support is also given wherever possible. In solution, the material exists predominantly as a mixture of two rapidly interconverting stereoisomers; namely, the thermodynamically preferred cis, cis and the energetically closest lying cis, trans configuration. In the solid state, optical spectroscopic methods provide evidence for the presence of a small amount of the energetically highly unstable trans, trans stereoisomer, kinetically trapped in the lattice defined by the scaffold of the predominant cis, cis isomeric form. Unlocking of the seemingly frozen cis, cis right arrow over left arrow trans, trans equilibrium was observed in the molten state.

Hydroxylations of substituted naphthalenes by Escherichia coli expressing aromatic dihydroxylating dioxygenase genes from polycyclic aromatic hydrocarbon-utilizing marine bacteria

Bioconversion experiments of various mono- or di-substituted naphthalenes such as dimethylnaphthalenes were carried out using the cells of Escherichia coli that expressed aromatic dihydroxylating dioxygenase genes ( phnA1A2A3A4 and phdABCD) from polycyclic aromatic hydrocarbon-utilizing marine bacteria, Nocardioides sp. KP7 and Cycloclasticus sp. A5, respectively. We found that the former dioxygenase PhnA1A2A3A4 had broad substrate preference for these compounds and often was able to hydroxylate their methyl groups. Specifically, 1,4-dimethylnaphthalene was predominantly bioconverted into 1,4-dihydroxymethylnaphthalene.

Synthesis of hydroxy, epoxy, nitrato and methoxy derivatives of tetralins and naphthalenes

Stereoselective syntheses are described for cis,trans,cis-2,3,5-tribromo-1,4-dihydroxytetralin, trans,trans,cis-2,3,5-tribromo-1,4-dihydroxytetralin, trans,trans,trans-1,4-dihydroxy-2,3-dibromotetralin, trans,trans,trans-1-hydroxy-2,3,4-tribromotetralin, cis,cis,cis-1,2-epoxy-3,5-dibromo-4-hydroxytetralin, anti-1,2:3,4-diepoxytetralin, 1-hydroxy-4-bromonaphthalene, trans,trans,trans-1,4-dinitrato-2,3-dibromotetralin, 1-nitrato-2,3,4-tribromotetralin, 2,3-dibromonaphthalene and 1-methoxy-4-nitrato-2,3-dibromonaphthalene. These isomeric arene oxides and disubstituted naphthalenes provide excellent precursors for a number of 1,4- and 2,3-disubstituted naphthalene derivatives that are difficult to prepare using other routes. The structures of the naphthalene and tetralin derivatives were assigned by NMR and other techniques.

Fluorescence of Metal–Ligand Complexes of Mono- and Di-Substituted Naphthalene Derivatives

In this work, metal ion complexes for several naphthalene derivatives have been investigated. Different working pH values were chosen: 2.5 for complexes with Zr(IV), 4.0 for complexes with Fe(III), 5.0 for complexes with Al(III), and 7.5 for complexes with Cu(II). A stoichiometry of 1:1 for all complexes except two has been established by use of the Benesi-Hildebrand method and the stability constants have been calculated. All complexes between naphthalene derivatives and Cu(II) and Fe(III) show fluorescence quenching. In the case of Al(III), all complexes provided enhanced fluorescence. For Zr(IV), only the complex with 3-hydroxy-2-naphthoic acid provided enhanced fluorescence. The value of the stability constants as a function of the substituents of naphthalene derivatives has been analyzed. One can conclude that Cu(II) showed the largest binding affinity for the mono-substituted derivatives. However, Al(III) and Zr(IV) produced greater selectivity for the di-substituted derivatives. Iron(III) showed no specific binding with any of the naphthalene derivatives.

Symmetry of van der Waals molecular shape and melting points of organic compounds

Long-known empirical regularities in melting points (mp) among molecular crystals of organic compounds with a closely related stoichiometry are dictated by a short-range molecular van der Waals term in their crystal field. This term, which acts as a symmetry-breaking perturbation on the averaged intermolecular interactions, is determined by the “contact” potential in the vicinity of molecules, i.e. by the shape of their van der Waals surface. To reflect the topology of the crystal field, an approximate van der Waals group Ğ of the average local field acting on a molecule and asymmetryas of the molecular surface composed of atomic van der Waals spheres, as its total misfit to Ğ, were introduced. The scheme was applied to organic compounds whose molecules have a mirror symmetry plane; the shape of two-dimensional sections of their van der Waals surfaces by this plane was analysed. Calculated values of molecular asymmetry parallel as yet uninterpreted trends in melting point data such as oscillations between “even” and “odd” n-alkanes CnH2n+2, reduced melting temperatures of monosubstituted derivatives with highly-symmetric molecular cores (e.g. toluene), and non-trivial mp orders among the isomers of disubstituted ethylenes C2H2X2 (“gem-<cis-<trans-”), substituted benzenes C6H4X2 (“meta-<ortho-<para-”), C6H3X3 (“1,2,4-<1,2,3-<1,3,5-”), C6H2X4 (“1,2,3,5-<1,2,3,4-<1,2,4,5-”), and disubstituted naphthalenes. The observed mp trends do not display any notable correlation with molecular moments of mass and charge distribution, thus being dictated mostly by van der Waals forces.

Stereoselective Preparation of 10α‐ and 10β‐Aryl Derivatives of Dihydroartemisinin.

Lewis acid-catalysed arylation of the 10β-benzoate and, less effectively, the 10α-benzoate of dihydroartemisinin [DHA] with activated aromatic compounds, including naphthalenes, stereoselectively, provides 10α-aryl derivatives including disubstituted naphthalene derivatives. 2-Methoxynaphthalene provides the 1-, rather than the 3-substituted derivative. In contrast, 10β-aryl derivatives are obtained stereoselectively from the 10β-bromide, generated in situ from trimethylsilyl bromide and the TMS ether of 10α-DHA, and the corresponding aryl Grignard reagents. The 10α-aryl compounds are shown by NMR spectroscopy and X-ray crystallographic analysis to possess a chair pyranose ring with equatorial aryl group, whereas the 10β-aryl derivatives have a twist-boat pyranose ring with equatorial aryl group. The stereochemistry of the Lewis acid-catalysed arylations, which is common to that observed for the Lewis acid-catalysed arylation of pyranosyl glycosides with axial anomeric leaving groups in general, may be rationalized in terms of axial attack from the α or si face of the half-chair oxonium ion intermediate. On the other hand, the Grignard reagents activate the axial bromide to elimination through complexation, and thereby the aryl nucleophile attacks the incipient oxonium ion from the β or re face. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Stereoselective Preparation of 10α‐ and 10β‐Aryl Derivatives of Dihydroartemisinin

AbstractLewis acid‐catalysed arylation of the 10β‐benzoate and, less effectively, the 10α‐benzoate of dihydroartemisinin [DHA] with activated aromatic compounds, including naphthalenes, stereoselectively, provides 10α‐aryl derivatives including disubstituted naphthalene derivatives. 2‐Methoxynaphthalene provides the 1‐, rather than the 3‐substituted derivative. In contrast, 10β‐aryl derivatives are obtained stereoselectively from the 10β‐bromide, generated in situ from trimethylsilyl bromide and the TMS ether of 10α‐DHA, and the corresponding aryl Grignard reagents. The 10α‐aryl compounds are shown by NMR spectroscopy and X‐ray crystallographic analysis to possess a chair pyranose ring with equatorial aryl group, whereas the 10β‐aryl derivatives have a twist‐boat pyranose ring with equatorial aryl group. The stereochemistry of the Lewis acid‐catalysed arylations, which is common to that observed for the Lewis acid‐catalysed arylation of pyranosyl glycosides with axial anomeric leaving groups in general, may be rationalized in terms of axial attack from the α or si face of the half‐chair oxonium ion intermediate. On the other hand, the Grignard reagents activate the axial bromide to elimination through complexation, and thereby the aryl nucleophile attacks the incipient oxonium ion from the β or re face. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)

Photoinduced electron transfer between fullerenes (C 60/C 70) and disubstituted naphthalenes using laser flash photolysis

Photoinduced electron-transfer processes between fullerenes C 60/C 70 and disubstituted-naphthalenes have been studied by laser flash photolysis. Quantum yields ( Φ et T) and rate constants ( k et) of electron transfer from naphthalenes to the excited triplet states of C 60 ( 3 C 60 ∗ ) and C 70 ( 3 C 70 ∗ ) have been determined by observing the transient absorption bands in the wide wavelength VIS/NIR regions. The observed Φ et T and k et values depend significantly on the nature and position of the substituents. The k et values are seen to correlate well with the free energy changes (Δ G et) for the electron transfer reactions on the basis of Rehm–Weller relation. Addition of pyridine (Py) enhanced significantly the rates and efficiencies of photoinduced electron transfer process of dihydroxy-naphthalenes (DHN). However, the effect of Py in the dimethoxy-naphthalenes (DMN) is far less than that of DHN. In the presence of octylviologen (OV 2+), electron-mediation occurs from C 60 − to OV 2+ to generate OV +.

DEVELOPMENT OF A GRID SEARCH MOLECULAR MECHANICS MODELING STRATEGY TO STUDY ELUTION BEHAVIOR IN CYCLODEXTRIN MODIFIED CAPILLARY ELECTROPHORESIS

Novel methods to use molecular mechanics (MM) in modeling solute-receptor interactions are developed that are pertinent to computational studies of dynamic separation or sensing processes. Specifically, a grid search MM modeling approach is used to study separation behavior in cyclodextrin (CD)-modified capillary electrophoresis (CE). Laboratory CE separations of di-substituted naphthalene compounds are accomplished employing an anionic, single isomer carboxymethyl-CD as a running buffer additive. Computational work involved the docking of these solutes into the cavity of this CD using a systematic grid search to probe the interaction space. It was discovered that the size of incremental changes in position and dimensional freedom in defining the grid are significant parameters. At each grid position the configuration of the atoms in the complex is altered in a process to minimize energy. It was discovered that comprehensive minimization involving many iterations of the process is extremely important in locating true low energy conformers. Interaction energy contours, involving translation and rotation of the solute into the CD cavity, are produced that graphically reveals the strength of the CD-solute interaction. Increasing the number of minimization iterations from 100s to1000s resulted in remarkable changes in those contours, and improved the correlation between computationally determined and experimental distribution coefficients. The correct ordering of distribution coefficients was achieved with a few approaches, but with the comprehensive minimization approach experimental and computational coefficients were generally within a factor of 4 of each other. Moreover, the comprehensive minimization approach resulted in many points in the grid search, micro-positional states, that minimized to a single conformer. Consideration of the degeneracy of these states is also shown to be significant.

Separation of aromatic isomers on cyclophane-bonded stationary phases

A cyclophane (CP66)-bonded silica gel stationary phase (CP66-SP) was prepared and the retention of water-insoluble hydrophobic compounds on it was investigated in comparison with that on the CP44-bonded stationary phase (CP44-SP) reported previously. Like CP44-SP, it retained aromatic compounds more strongly than the corresponding alicyclic compounds, as was expected by the cavity size of the cyclophane. The CP66-SP also showed isomer-selectivity for monosubstituted and disubstituted naphthalenes, but its selectivity was perfectly reversed to that of the CP44-SP. On the CP66-SP, isomers having methyl and ethyl groups at β-position were eluted prior to those having groups at α-position, whereas on the CP44-SP β-substituted naphthalenes were retained more strongly than α-substituted ones. Isomers of three- and four-ring aromatic compounds were also separated on these cyclophane-bonded stationary phases. The retention order on the CP66-SP was almost opposite to that on the CP44-SP; on the CP66-SP, the retention order was phenanthrene>anthracene, and chrysene>1,2-benzanthracene >2,3-benzanthracene, whereas on the CP44-SP, anthracene>phenanthrene, and 2,3-benzanthracene>chrysene>1,2-benzanthracene. The retention mechanism of aromatic compounds is discussed on the basis of the structure of the cyclophane-involved complex.

ADDITIVITY OF PROTON AFFINITIES IN DISUBSTITUTED NAPHTHALENES

It is shown, by the MP2(fc)/6–31G**//HF/6–31G*+ZPE(HF/6–31G*) theoretical model and subsequent use of homodesmic reactions, that the absolute proton affinities in disubstituted naphthalenes involving F and CN substituents satisfy the simple additivity rule, which was previously found to hold in polysubstituted benzenes, the average absolute error being close to 1 kcal mol−1. The origin of the remarkable additivity of substituent effects in determining proton affinities in substituted aromatics and the variations in the values are briefly discussed. 415–419. © 1997 John Wiley & Sons, Ltd.

ADDITIVITY OF PROTON AFFINITIES IN DISUBSTITUTED NAPHTHALENES

It is shown, by the MP2(fc)/6–31G**//HF/6–31G*+ZPE(HF/6–31G*) theoretical model and subsequent use of homodesmic reactions, that the absolute proton affinities in disubstituted naphthalenes involving F and CN substituents satisfy the simple additivity rule, which was previously found to hold in polysubstituted benzenes, the average absolute error being close to 1 kcal mol−1. The origin of the remarkable additivity of substituent effects in determining proton affinities in substituted aromatics and the variations in the values are briefly discussed. 415–419. © 1997 John Wiley & Sons, Ltd.