Naphthyl Substituents Research Articles

Hydrophobically Directed Selective Reduction of Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mutagenic N-Acyloxy-N-alkoxyamides: Probes for Drug - DNA Interactions

N-acyloxy-N-alkoxyamides are direct-acting mutagens in Salmonella typhimurium TA100 and react with DNA at N7 of guanine and N3 of adenine. From extensive mutagenicity data a quantitative structure–activity relationship (QSAR) has been derived that predicts activity to be dependent upon hydrophobicity (represented by log P) and stability to chemical reactions (through the pKA value of the leaving carboxylic acid group). Sterically bulky substituents (represented by Taft ES parameters) reduce activity. Deviations from this QSAR highlight structural features that can enhance or impede association of small molecules with DNA. Naphthyl, pyrenyl, and fluorenyl substituents raise activity significantly, possibly through an intercalative effect. The influence of a single sterically bulky tert-butyl group remote from the reactive nitrogen is adequately modelled by the QSAR. However, substrates with two or more such groups show radically reduced activity, most likely through a groove exclusion process. Branching close to the reactive centre strongly reduces activity in line with a steric inhibition of reaction with DNA.

Hydrophobically directed selective reduction of ketones.

Three hydrophobic borohydrides carrying phenyl, pentafluorophenyl, and beta-naphthyl groups were used to reduce ketones in water and in methanol. With ketones carrying phenyl, naphthyl, or biphenyl substituents, there was preferential reduction in methanol of competing acetyl groups, either intermolecular or intramolecular, but preferential reduction of the aryl ketones in water. In the most extreme case, there was a 40-fold selectivity reversal. Lithium borohydride showed no such change in selectivity and favored acetyl reduction in both solvents. Salt and cosolvent effects indicate that hydrophobic packing is involved in the reaction of hydrophobic reagents with the aryl ketones. Some special interaction of the pentafluorophenyl group with aryl rings was also detected.

Studies on some new meso-aryl substituted octabromo-porphyrins and their Zn(II) derivatives

A series of porphyrins with various tolyl (H 2TTHP) and naphthyl substituents (H 2TNHP) at the meso-positions, their octabromoderivatives (H 2TTBP and H 2TNBP) with Br substituents at β-pyrrole positions and also their Zn(II) derivatives have been synthesised and characterised by 1H NMR, electronic, fluorescence and electrochemical studies. These have the meso-carbons bonded to tolyl moieties at ortho-, meta- and para-positions of the tolyl groups and at the α- or β-position of the naphthyl group. For the octabromoporphyrins, pronounced deshielding of NH protons and a moderate shift of meso-aryl protons to a lower δ value are observed compared to their nonbrominated species. The electronic spectra of ZnTTHP and ZnTNHP have almost the same B and Q bands while the B band of their free-base analogues have H 2TNHP absorbing at a higher wavelength than H 2TTHP. All the octabromoderivatives exhibit a pronounced red shift for both B and Q bands (compared to their nonbrominated forms) and show meso-substituent dependent change in both free-base and metallated forms. The above observations are interpreted in terms of moderate conjugative interaction of the aryl substituent with the π framework and also in terms of energy level reordering which alters the HOMO–LUMO gap. Consistent with the absorption spectral data the emission bands of all the bromoporphyrins were also seen to be red shifted considerably. Significant decrement in quantum yield ( φf) was observed for the bromocompounds. While the φf of nonbrominated porphyrins is seen to be higher than their Zn(II) derivatives the reverse order is observed for the bromoderivatives. The ability of the Zn 2+ ion to make the bromoporphyrins resistant to distortion by bridging the central cavity can be attributed as the cause for this interesting observation. Cyclic voltammetric studies exhibit characteristic quasi-reversible/irreversible oxidation–reduction features for all the free-bases and Zn(II) derivatives. The bromoderivatives on the other hand manifest marginally harder oxidation and very easy reduction features. The data are interpreted in terms of electron withdrawing ability of Br atoms and to reordering of HOMO and LUMO levels due to distortion in the porphyrin ring.

1-(p-Biphenyl)-4′-(2-naphthyl)cubane

In the title compound, C30H22, the bi­phenyl and naphthyl substituents are each planar to within 0.03 Å. They extend from the cubane like the wings of a butterfly, with a slight dihedral angle of 9.4 (2)° between their planes. In the crystal structure, the naphthyl groups form close-packed stacks, with cubyls and bi­phenyls extending alternately to the right and the left.

Solvent effects on some newmeso-aryl substituted octabromoporphyrins

A series of porphyrins with tolyl and naphthyl substituents at themeso positions, their octabromoderivatives (OBP) with Br substituents at β-pyrrole positions are synthesised and characterised by chemical analysis,1H NMR and electronic spectral studies. It is seen that all the OBPs exhibit pronounced red shifts in both the Soret andQ bands of their electronic spectra compared to their non-brominated form in various polar and nonpolar solvents, the energy difference Δv being in the range 2300–2700 cm−1. The high energyB band of naphthyl porphyrins (both brominated and nonbrominated) are found to be more red-shifted than that of tolyl porphyrins, owing to the noticeable mesomeric effect of the naphthyl groups. Detailed spectral studies reveal that while none of the nonbrominated porphyrin show solvent-dependent change in theirB andQ bands, all the OBPs manifest significant shifts depending on the nature of solvents. Solvent-solute interaction can be considered to be of strong dipole-dipole nature for OBPs with polar solvents and of π-π type with aromatic non-polar solvents. In the brominated form we find two categories of porphyrins exhibiting distinctly different absorption phenomena in aromatic solvents. The OBPs havingmeso-groups not shielding the porphyrin π-framework exhibit additional absorption peaks (split Soret peaks and broadened Q bands) in some aromatic solvents. This could be explained in terms of π-π type donor-acceptor (DA) complex formation between such bromoporphyrins (acceptor) and the aromatic solvent molecules (donor) that is not possible for OBPs that have bulkymeso groups that block the approach of aromatic solvent molecules close to the porphyrin framework

Studies on iron(III) and manganese(III) derivatives of new meso-aryl substituted and brominated porphyrins

A series of FeIII and MnIII porphyrins with various tolyl and naphthyl substituents at the meso positions, and their perbromoderivatives with Br substituents at the β-pyrrole positions, have been synthesised and investigated. As seen in the case of the free-base porphyrins, both FeIII and MnIII derivatives of the Br-substituted porphyrins also exhibit pronounced red-shifts in both B and Q bands compared to their nonbrominated analogues. This is attributed to the electron-withdrawing ability of eight Br substituents at β-pyrrole positions and is also due to distortion brought about in the π-framework by the bulky substituents including those at the meso positions. The naphthyl groups seem to be making mesomeric contributions for both nonbrominated and brominated porphyrins of these metal ions as is evident from the higher wavelength absorption of the B band as compared to the tolyl derivatives. While the meso-substituent do not exhibit any isomer dependent change on the electronic properties of FeIII porphyrins, they show a noticeable effect in the MnIII derivatives. During the metallation of meso-tetratolylporphyrins by FeIII ions μ-oxo dimeric compounds are formed, while the naphthyl porphyrins and the bromoderivatives do not form such dimeric species. The presence of bulky groups at the meso positions and heavy bromines on the β-pyrrole positions can be considered to prevent the formation of catalytically inert μ-oxo dimers.

Trans-2-(2-Naphthyl)-3-(phenylselenyl)tetrahydropyran

The crystal structure of the title compound, C21H20OSe, has established the absolute configuration and shows that the tetrahydrofuran ring adopts a chair conformation, with both the phenyl­selenyl and naphthyl substituents occupying equatorial positions.

Rhodium complexes of 3,4-di(β-naphthyl)-2,5-diarylcyclopentadienone: indirect detection of slowed naphthyl rotation

In the solid state, [(acetylacetonate)-3,4-di(β-naphthyl)-2,5-diarylcyclopentadienone]rhodium(I) ( 4a, aryl=phenyl, 4b, aryl= m-xylyl) exist as head-to-tail dimers in which each rhodium is bonded to the γ-carbon of the acetylacetonate ligand in the other half of the molecule. These dimers are also favoured in solution at low temperature, and restricted naphthyl rotation results in the formation of numerous conformers whereby the naphthyls can adopt either proximal or distal orientations. These rotamers can be detected by observation of the 1H- and 13C-NMR methyl resonances in the acetylacetonate moiety. Triphenylphosphine cleaves the dimers ( 4a and 4b) to give the corresponding monomers, (C 4Ar 2(naphthyl) 2CO)Rh(acac)PPh 3 ( 5a and 5b), and the crystal structure of 5a exhibits a proximal/distal disorder of one naphthyl substituent. The rotamers of 5a and 5b are also present in solution, and the variable-temperature 31P-NMR spectra yield activation enthalpies of 8.2±0.5 kcal mol −1 for naphthyl rotation in each compound.

Conformational studies by dynamic NMR. 90. Structure and stereodynamics of the rotamers of di- and tri-alpha-naphthylphenyl derivatives.

The crystal structure of 1,3,5-tris(4-methylnaphth-1-yl)benzene, 1, shows one naphthyl substituent in an anti relationship to the other two. On the other hand, low temperature (-70 degrees C) (1)H NMR spectra in solution show the presence of a second rotational conformer (rotamer) having all the three naphthyl substituents in a syn relationship. The interconversion barrier between the anti (77%) and syn (23%) rotamers of 1 was determined by line shape simulation of the temperature-dependent NMR spectra (Delta G(++) = 12.1 kcal mol(-1)). In the analogous disubstituted meta and paraderivatives, that is, 1,3- and 1,4-bis(4-methylnaphth-1-yl)benzene (2 and 3, respectively), the presence of both the anti and syn rotamers was also detected by low-temperature NMR spectroscopy. In the latter compounds, the proportions of the anti and syn forms are nearly equal, and the corresponding anti to syn interconversion barriers were found to be lower (11.4 and 11.1(5) kcal mol(-1), respectively) than those of the trisubstituted derivative 1.

Synthesis and Electronic Spectra of (N-1-Naphthyl-ethylenediamine)- dichloroplatinum(II). Fluorescence of the Appended Naphthyl Substituent

Abstract Pt(naph-en)Cl2 with naph-en =N-(1-naphthyl)- ethylenediamine was synthesized and spectroscopically characterized. The complex shows a fluorescence at λmax = 405 nm, which originates from the appended naphthyl substituent present as an electronically isolated chromophore.

Novel five‐membered ring formation by oxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts

AbstractOxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts (6) gave five‐ or six‐mem‐bered rings depending on the aryl substituent. The olefins 6a and 6b with a phenyl or naphthyl substituent resulted in a normal six‐membered ring formation to afford 6a‐azoniapicene and 6a‐azoniabenzo[b]picene salts (7 and 8), respectively. In contrast, the photo‐reaction of pyridyl substituted derivative 6c resulted in novel five‐membered ring formation to yield 3b‐azonia‐5‐(2‐pyridyl)acephenanthrylene salt (10).

ChemInform Abstract: Almond Oxynitrilase‐Catalyzed Transformation of Aldehydes is Strongly Influenced by Naphthyl and Alkoxy Substituents.

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Almond oxynitrilase-catalyzed transformation of aldehydes is strongly influenced by naphthyl and alkoxy substituents

Different α- and β-substituted aldehydes have been submitted to the catalytic action of almond oxynitrilase (PaHNL), in order to explore the influence of a stereocenter already present in the substrate on the selectivity of this enzyme. [1]The results indicate that naphthyl and alkoxy substituents in the α- and also in the β-position to the aldehyde group significantly influence the stereochemical outcome of the PaHNL-catalyzed transformation.

PH-Functional Phosphines with 1,1'-Biphenyl-2,2'-bis(methylene) and 1,1'-Binaphthyl-2,2'-bis(methylene) Backbones.

The first PH-functional phosphines (1, 3, and 5) containing the 1,1'-binaphthyl-2,2'-bis(methylene) or 1,1'-biphenyl-2,2'-bis(methylene) backbone have been obtained by two-phase phosphination of 2,2'-bis(halomethyl)-1,1'-binaphthyls with PH(3) or in a protected-group synthesis using P(SiMe(3))(3) as the starting material. The 4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]phosphepine (1) is configurationally stable, as indicated by the inequivalence of the two CH(2) and naphthyl substituents in the (13)C{(1)H} NMR spectra. The X-ray crystal structure of 1.0.5C(6)H(5)CH(3) shows an intracyclic C-P-C angle of 99.5(2) degrees, the interplanar angle of the phosphepine ring system being 67.6(5) degrees. The borane adduct 7 of the secondary phosphine 1 has been employed for the syntheses of atropisomeric mono- and bidentate ligands (8-14) with the bulky 1,1'-binaphthyl moieties. Results of force field calculations on the conformations of 1, 3, and 14 are presented. The ability of these phosphines to form mononuclear and polynuclear complexes with transition-metal centers is discussed. Compound 14 exhibits a large variety of low-energy conformations, and some of them seem to be capable of forming mononuclear transition-metal complexes.

Vinylidene complexes of osmium(0) derived from 1-naphthyl- or 2-naphthyl-carbyne complexes by hydride addition to the naphthyl substituents. The crystal structure of Os(CC 10H 8)(CO) 2(PPh 3) 2

When treated with lithium triethylborohydride, the cationic carbyne complexes [Os(–CR)(CO) 2(PPh 3) 2] +(R=1-naphthyl, 1; R=2-naphthyl, 2) form 3 and 4, respectively, which both have the formula Os(C 11H 8)(CO) 2(PPh 3) 2. NMR studies of these two isomeric vinylidene complexes show that the product derived from the 1-naphthyl carbyne cation involves attack at the naphthyl ring in the position para to the carbyne carbon to give 3, while that derived from the 2-naphthyl carbyne cation involves attack at the naphthyl ring in the position ortho to the carbyne carbon to give 4. The structure of 4 has been confirmed by an X-ray crystal structure determination. Addition of HCl to the vinylidene complexes 3 or 4 results in the formation of the corresponding naphthylmethyl complexes, Os(CH 2R)Cl(CO) 2(PPh 3) 2 (R=1-naphthyl, 5; R=2-naphthyl, 6).

Effect of N9-methylation and bridge atom variation on the activity of 5-substituted 2,4-diaminopyrrolo[2,3-d]pyrimidines against dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.

The effect of N9-methylation and bridge atom variation on inhibitory potency and selectivity of 2,4-diaminopyrrolo[2,3-d]pyrimidines against dihydrofolate reductases (DHFR) was studied. Specifically three nonclassical 2,4-diamino-5-((N-methylanilino)methyl)pyrrolo[2,3-d]pyrimidines with 2',5'-dimethoxyphenyl (2), 3',4'-dichlorophenyl (3), 1'-naphthyl (4), one classical analogue with a 4'-L-glutamate substituent (10), and four nonclassical 2,4-diamino-5-((phenylthio)methyl)pyrrolo[2,3-d]pyrimidines with 3',4'-dimethoxyphenyl (5), 3',4'-dichlorophenyl (6), 1'-naphthyl (7), and 2'-naphthyl (8) substituents were synthesized. The classical and nonclassical analogues were obtained by displacement of the intermediate 2,4-diamino-5-bromomethylpyrrolo[2,3-d]pyrimidine, 14, with appropriately substituted N-methylaniline, thiophenols, or 4-(N-methylamino)benzoyl-L-glutamate. Compounds 2-8 and 10 were evaluated against Pneumocystis carinii (pc), Toxoplasma gondii (tg), and rat liver (rl) DHFRs. The N-methyl and thiomethyl analogues were more inhibitory than their corresponding anilinomethyl analogues (previously reported) against all three DHFRs. The inhibitory potency of these analogues was greater against rlDHFR than against tgDHFR which resulted in a loss of selectivity for tgDHFR compared to the N9-H analogues. The classical N9-methyl analogue 10 was more potent and about 2-fold more selective against tgDHFR than its corresponding desmethyl analogue. All of the analogues, 2-8 and 10, were more selective than trimetrexate (TMQ) against pcDHFR (except 4) and significantly more selective than TMQ against tgDHFR.

The synthesis of (S)-(+)-gossypol via an asymmetric Ullmann coupling

The first asymmetric total synthesis of (S)-(+)-gossypol is described using chiral oxazolines as the naphthyl substituent in a highly diastereoselective aryl–aryl coupling.

Synthesis of N- and B-Substituted Derivatives of closo-Amino-undecahydro-dodecaborate(1-) Anion

The synthesis of nitrogen and boron substituted derivatives of the 1-amino-closo-dodecaborate anion(1-) 1 is reported. Reasonable yields of the [R2NH-B12H11]- derivatives (R = C6H5CH2, 2-C10H7CH2, n-C16H33, n-C12H25) were obtained via conventional alkylation of 1 in aqueous propan-2-ol, starting from bulky primary alkylhalides. These [R2NH-B12H11]- derivatives were subsequently methylated by dimethyl sulfate under similar conditions. Reaction of 1 with palmitoyl chloride gave under anhydrous conditions the corresponding N-acyl derivative. Reaction of 1 with hydroxymethyl-18-crown-6 tosylate in THF in the presence of NaH led to the novel [(18-crown-6-CH2)2NH-B12H11]- anion, the Cs+ salt of which exhibits unusual solubility properties. A direct cyclization reaction of pentaethylene glycol ditosylate with 1 gave under similar conditions [(15-azacrown)-5-B12H11]-, the first known closo-borate anion with an attached aza-crown ring. These species exhibit potentially interesting complexation efficiency and solubility properties. Selective substitution of the boron cage by a bulky naphthyl substituent was achieved by palladium-mediated cross-coupling reaction between 1 and 1-BrMgC10H7. All derivatives were characterized by high-field 11B, 1H NMR and negative FAB mass spectrometry methods.

Structure-activity relationships of selective estrogen receptor modulators: modifications to the 2-arylbenzothiophene core of raloxifene.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.