4-substituted Anilines Research Articles

Chemical modification of lysine residues in cytochrome P450LM2 (P450IIB4): Influence on heme liganding of arylamines

Treatment of cytochrome P450LM2 with fluorescein isothiocyanate to introduce up to two equivalents of fluorophore per polypeptide chain resulted in the selective derivatization of lysine residues. CD-spectral measurements revealed the overall conformation as well as the immediate heme environment of the hemoprotein to remain unaffected by attachment of the label. Modification caused decreased affinity of p-phenylenediamine and other 4-substituted anilines for the heme site, whereas there was a rise in the extent of substrate interaction. Experiments with pigment containing acetylated lysines gave analogous results, suggesting that the observed phenomenon was due to charge neutralization. There was linear correlation between the Hammett σ p values and both the optical dissociation constants for arylamine binding to intact enzyme and the dipole moments of the anilines, indicating that basicity along with electronic factors controlled heme liganding; lipophilicity appeared to be of minor importance. Introduction of fluorescein isothiocyanate into the oxygenase was found to influence the bond-making process through modulating basicity of the nitrogenous compounds, but perturbation of optimal spacial orientation of the amine nitrogen toward the heme iron also might have been operative. The lysines studied seem to represent metabolically inactive elements of the substrate channel located on the cytosolic surface of the aggregates, as evidenced by steady-state fluorescence measurements. A hydrophilic segment in the cytochrome P450LM2 molecule that would accommodate the critical residues is discussed.

Fluorine and Trifluoromethyl Substituted Anilines: Site Selective Metalation and Electrophilic Substitution

When treated with tert-butyllithium in tetrahydrofuran at -50 °C, N-BOC (tert-butoxycarbonyt) protected fluoroanilines and trifluoromethylanilines undergo metalation at the nitrogenadjacent position. If, however, the nitrogen carries two alkyl or trimethylsilyl groups as substituents and highly polar metalating reagents such as butyllithium activated by N,N,N′N″,N″-pentamethyldiethylenetriamine (PMDTA) or potassium tert-butoxide are employed, the fluoroaniline derivatives are preferentially deprotonated next to the halogen atom.

Alkylation of nucleic acids by DNA-targeted 4-anilinoquinolinium aniline mustards: Kinetic studies

The rate constants for hydrolysis of a series of 4-substituted aniline mustards Ar-X- pC 6H 4-N(CH 2CH 2Cl) 2, where Ar is 4-anilinoquinolinium and X = O, CH 2, CONH and CO, have been measured in water and 0.02 M imidazole buffer at 37°C and in 50% aqueous acetone at 66°C. The equilibrium binding constants of the compounds and their hydrolysis products to nucleic acids of differing base composition have been determined at varying ionic strengths, and the results are consistent with the compounds binding as expected in the DNA minor groove. The alkylating reactivity of the mustards towards these nucleic acids has been measured in water at 37°C and in 0.01 M HEPES buffer over a range of temperatures from 25°C to 60°C. Evaluation of the thermodynamic parameters for these kinetic and equilibrium studies suggests that the interaction with nucleic acids is via an internal S N2 mechanism involving an aziridinium ion.

Determination of the substituent constant σp- for the thioamide group -CSNH2 from the ionization of anilines and phenols

Thermodynamic ionization constants pKa 2.62 ± 0.01 for the primary aromatic amino group of 4-aminothiobenzamide and pKa 8.28 ± 0.01 for the phenolic hydroxy group of 4-hydroxythiobenzamide have been determined by ultra-violet spectrophotometry at 25°C. By using these pKa values and the Hammett equations (log Ka vs σ) for the ionization of fourteen 3- or 4-substituted phenols and thirteen 3- or 4-substituted anilines the substituent constant σp- = 0.68 (from the ionization of anilines) or σp- = 0.73 (from the ionization of phenols) of the thioamide group -CSNH2 was calculated.

Structural studies of halogen-substituted polyanilines by X-ray photoelectron spectroscopy

The intrinsic oxidation states, the imine/amine ratios in particular, of the halogen monosubstituted polyanilines prepared by the oxidative chemical polymerization in HCl and H 2SO 4 media were determined quantitatively by X-ray photoelectron spectroscopy (XPS). Neither the type of halogen substituent (Cl, Br and I), nor the position of substitution, nor the protonic acid media caused a significant variation in the intrinsic oxidation states of the resulting polymers. The N 1s core-level spectra revealed an imine/amine ratio of 0.5:1 or less in all of the polymer bases. The position of substitution caused a wide variation in the polymer yield, with 2-substituted aniline giving the highest yield. Protonation by H 2SO 4 gave rise to monovalent sulfate anions and nitrogenonium cations. However, ‘protonation’ by HCl resulted only in covalently bonded chlorine, with most of the imine nitrogens remaining unprotonated.

Biological activity of some schiff bases and their metal complexes

Schiff bases derived from salicylaldehyde and 2-substituted aniline and their metal chelates with Cu(II), Ni(II), and Co(II) ions were synthesized and screened for the antiinflammatory and antiulcer activity. The compound salicylidene-anthranilic acid (SAA) was found to possess the antiinflammatory and antiulcer activity. The copper complexes showed an increased antiulcer activity. The SAA is perhaps acting by influencing prostaglandin biosynthesis.

Relationships between structure, toxicity and genetic effects in Salmonella typhimurium and Saccharomyces cerevisiae for substituted aniline mustards

A series of 4-substituted aniline mustards of widely varying reactivities have been evaluated for their mutagenic effects in Salmonella typhimurium strains of varying uvrB gene and plasmid status, and for their ability to cause mitotic crossing-over in Saccharomyces cerevisiae. The 4-methyl aniline mustard N, N-bis(2-chloroethyl)-4-methylaniline and its corresponding half-mustard N-(2-chloroethyl)-4-methylaniline showed widely different effects in the various bacterial strains, with the half-mustard being much less toxic than the full mustard in the uvrB − strain TA100. However, in the uvrB − strain TA1978 +, possessing an intact excision repair system, both compounds were equally toxic and the full mustard was the more mutagenic. Both compounds were equally effective in promoting mitotic crossing-over in yeast. For a series of 4-substituted full mustards, the toxicity in S-typhimurium strain TA100 correlated with substituent electronic parameters in the same way as does mammalian cell toxicity, supporting the view that the primary mode of toxicity is via DNA cross-linking, even for unreactive analogues. However, there were no obvious correlations between substituent physicochemical properties and mutagenic potential in bacteria, suggesting that mutagenic events are subject to a variety of influences other than the reactivity of the mustard group. In contrast, the most chemically reactive compounds were the most toxic and most recombinogenic in yeast.

Synthesis and isomeric conversions of several 2-substituted 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid derivatives

Ethyl ester derivatives of 6- and 8-substituted 2-methyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been synthesized by treatment of the diethyl ester of acetylmalonic acid with 2- or 4-substituted anilines. Condensation of these newly synthesized quinolinecarboxylic acid derivatives with 4-nitrobenzaldehyde resulted in the formation of 6- and 8-substituted 2-[2-(4-nitrophenyl)-vinyl]-1, 4-dihydro-4-oxo-3-quinolinecarboxylic acids and ethyl esters of 6- and 8-substituted 2-[2-(4-nitrophenyl)vinyl]-4-acetoxy-3-quinolinecarboxylic acids. The tautomeric and conformational transformations of these newly synthesized compounds have also been investigated, using IR, NMR, and UV spectroscopy.

Anisotropy of magnetic susceptibility and molar Cotton-Mouton constants of six anilines and 1,3,5-trimethylhexahydro-1,3,5-triazine

The semiaxes of the magnetic susceptibility ellipsoid were determined for the Ph-N fragment in 4-substituted anilines and N,N-dimethylaniline. Deviations from additivity due to the additional paramagnetic contribution in a direction perpendicular to the plane of the aromatic ring were found.

Adsorption of Para Substituted Anilines from Cyclohexane Solution on Sepiolite

The adsorption processes of different para-substituted anilines from cyclohexane solution on natural sepiolite have been studied. The adsorption isotherms may be classified as type L-2 of the Giles classification in the p-bromoaniline and p-toluidine cases, and as type H-2 in the p-acetylaniline case. The experimental data points have been fitted to the Langmuir equation and the adsorption capacities, surface areas available to the amine molecules and apparent equilibrium constants have been calculated. The apparent thermodynamic magnitudes corresponding to the adsorption processes have also been determined.

Resonance and solvent effects on absorption spectra. Part 5. Substituent and solvent effects on infrared spectra of 2- and 4-substituted aniline derivatives

I.r. spectra of 2- and 4-substituted N-methyl- and N-acetylaniline derivatives in various solvents have been employed to examine intramolecular hydrogen bonding of amine hydrogen atoms with 2-substituents, or intermolecular hydrogen bonding with hydrogen-bond-acceptor (HBA) solvents. The N–H stretching frequencies, νNH′ in solvents having doubly bonded oxygen HBA base centres are well correlated according to the linear solvation energy relationship (LSER), XYZ = XYZ0+sπ*+bβ, where π* and β are the solvatochromic parameters that measure solvent dipolarity-polarizability and HBA basicity. The order of susceptibilites, b, to solvent basicities of νNH for the compounds studied is: CO2Me < COCH3∼ CN < NO2′ in contrast to susceptibilities of the corresponding u.v.-visible spectra, where the order is COCH3∼ CN < NO2 < CO2Me.

ChemInform Abstract: Synthesis and Antitumor Activity of cis‐Platinum Complexes of Aromatic Amines.

cis-Platinum complexes of aromatic amines were synthesized in water or at the interfacial layer between water and an organic solvent. The position of substitution of aniline derivatives had a marked effect on the synthesis of the complexes. The coordination of 2-substituted anilines needed a long time and the yields were low. That of 3- or 4-substituted anilines was fast, and the yields were high. Disubstituted or N-substituted anilines needed fairly long reaction times and the yields were lower than those of monosubstituted anilines; sometimes unidentified complexes were obtained or no reaction product was formed.Six synthesized cis-dichloro platinum(II) complexes which coordinate bis(4-aminophenol), bis(3-toluidine), bis(2-aminobiphenyl), bis(4-sulfamidoaniline), bis(1-naphthylamine) and bis(4-phenylazo-1-naphthylamine) had high antitumor activities against Sarcoma 180 ascites in female ICR/JCL mice. The dose of platinum of these effective complexes given to the mice was in the range of 7.37-105.76 mg/kg (26.44%-39.96%). This result suggests that the toxicity of the platinum complexes might depend on their carrier ligands.

Synthesis and antitumor activity of cis-platinum complexes of aromatic amines.

cis-Platinum complexes of aromatic amines were synthesized in water or at the interfacial layer between water and an organic solvent. The position of substitution of aniline derivatives had a marked effect on the synthesis of the complexes. The coordination of 2-substituted anilines needed a long time and the yields were low. That of 3- or 4-substituted anilines was fast, and the yields were high. Disubstituted or N-substituted anilines needed fairly long reaction times and the yields were lower than those of monosubstituted anilines; sometimes unidentified complexes were obtained or no reaction product was formed.Six synthesized cis-dichloro platinum(II) complexes which coordinate bis(4-aminophenol), bis(3-toluidine), bis(2-aminobiphenyl), bis(4-sulfamidoaniline), bis(1-naphthylamine) and bis(4-phenylazo-1-naphthylamine) had high antitumor activities against Sarcoma 180 ascites in female ICR/JCL mice. The dose of platinum of these effective complexes given to the mice was in the range of 7.37-105.76 mg/kg (26.44%-39.96%). This result suggests that the toxicity of the platinum complexes might depend on their carrier ligands.

Stability Constants for Complex Formation Between α-Cyclodextrin and Some Amines

□ Complex formation of α-cyclodextrin with 15 amines (including seven 4-substituted anilines) was studied by the potentiometric method, supplemented by direct UV spectrophotometry and a competitive indicator spectrophotometric method. The data were analyzed in terms of 1:1 and 1:2 complexes (amine–cyclodextrin ratios) and the stability constants K11a, K12a, K11b, and K12b, were evaluated; the subscripts indicate the stoichiometry and conjugate acid-base form. For all amines K11b was greater than K11a and K12a was 0. On the basis of the relationship of complex stability to amine structure, it was concluded that the primary binding site in anilines is the 4-substituent.

Reactions of Dichlorobis (Cyclopentadienyl) Titanium (IV) with Bident Ate Schiff Bases Derived from Salicylaldehyde and 4-Substituted Anilines

Abstract Dichlorobis (cyclopentadienyl) titanium(IV), Cp2TiCl2, reacts with bidentate Schiff bases such as salicylidene-4-anisidine, salicylidene-4-phenetidine, salicylidene-4-bromoaniline, salicylidene-4-iodoaniline and salicylidene-4-nitroaniline in a 1:1 molar ratio in refluxing tetrahydrofuran in the presence of trimethylamine, to yield Cp2Ti (SB)Cl, where (SB)− is the anion of the corresponding Schiff base, SBH. The derivatives have been characterised on the basis of their elemental analyses, molecular weights, conductance and spectral (IR, 1H NMR and electronic) characteristics.

Bis(indenyl)zirconium(IV) complexes of monofunctional bidentate salicylidimines

A series of (C9H7)2Zr(SB)Cl complexes whereSB − is the anion of bidentateSchiff base derived from salicylaldehyde and 4-substituted anilines, viz. salicylidene-4-ansidine, salicylidene-4-phenetidine, salicylidene-4-chloroaniline, salicylidene-4-bromoaniline, salicylidene-4-iodoaniline and salicylidene-4-nitroaniline, have been synthesized by the reaction of bis(indenyl)zirconium(IV) dichloride andSchiff base (SBH) in 1:1 molar ratio in refluxingTHF in the presence of triethylamine. The new derivatives have been characterized on the basis of their elemental analyses, conductance measurements and spectral (IR,1H-NMR, UV-VIS) studies.

Resonance and solvent effects on absorption spectra of some 2- and 4-( - M)-substituted aniline derivatives

The N-H protons of N-methyl-2-X-aniline derivatives remain intramolecularly hydrogen bonded in HBA (hydrogen bond acceptor) solvents where X = COOMe and NO2, but form intermolecular hydrogen bonds to the HBA solvents where X = CN. The order of response of vmax to solvent HBA basicity for the Cl → C2 bands of N-unsubstituted-2-(-M)-substituted aniline derivatives and the Cl → C4 bands of 4-(-M)-substituted aniline derivatives follows the orders of the hydrogen bond donor acidities of the amine protons, which are determined primarily by the mesomeric effects of the 2- and 4-substituents. The spectral data indicate that intramolecularly hydrogen bonded 2-(-M)-substituted aniline derivatives are near sp2 hybridized in non-HBA solvents and, unlike several 4-substitute anilines, do not undergo significant rehybridization in HBA solvents. Bath ochromic shifts resulting from hydrogen bonds by corresponding 2- and 4-substituted aniline derivatives to HBA solvents are of similar magnitudes.

ChemInform Abstract: CARBON‐13 CONTACT SHIFTS AND SPIN DELOCALIZATION MECHANISM FOR SUBSTITUTED ANILINES COMPLEXED WITH GADOLINIUM(III) CHELATES

Chemischer InformationsdienstVolume 13, Issue 27 Physical Organic Chemistry ChemInform Abstract: CARBON-13 CONTACT SHIFTS AND SPIN DELOCALIZATION MECHANISM FOR SUBSTITUTED ANILINES COMPLEXED WITH GADOLINIUM(III) CHELATES M. HIRAYAMA, M. HIRAYAMASearch for more papers by this author M. HIRAYAMA, M. HIRAYAMASearch for more papers by this author First published: July 6, 1982 https://doi.org/10.1002/chin.198227044AboutPDF 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. Volume13, Issue27July 6, 1982 RelatedInformation

ChemInform Abstract: APPLICATION OF PENNING IONIZATION ELECTRON SPECTROSCOPY TO STEREOCHEMISTRY. STERIC SHIELDING EFFECT OF METHYL GROUPS ON PENNING IONIZATION IN SUBSTITUTED ANILINES

Chemischer InformationsdienstVolume 13, Issue 23 Physical Organic Chemistry ChemInform Abstract: APPLICATION OF PENNING IONIZATION ELECTRON SPECTROSCOPY TO STEREOCHEMISTRY. STERIC SHIELDING EFFECT OF METHYL GROUPS ON PENNING IONIZATION IN SUBSTITUTED ANILINES K. OHNO, K. OHNOSearch for more papers by this authorS. FUJISAWA, S. FUJISAWASearch for more papers by this authorH. MUTOH, H. MUTOHSearch for more papers by this authorY. HARADA, Y. HARADASearch for more papers by this author K. OHNO, K. OHNOSearch for more papers by this authorS. FUJISAWA, S. FUJISAWASearch for more papers by this authorH. MUTOH, H. MUTOHSearch for more papers by this authorY. HARADA, Y. HARADASearch for more papers by this author First published: June 8, 1982 https://doi.org/10.1002/chin.198223044AboutPDF 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 onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume13, Issue23June 8, 1982 RelatedInformation

ChemInform Abstract: INFLUENCE OF SOLVENTS ON RATES OF REACTIONS OF 2,4‐DINITRO SUBSTITUTED HALOBENZENES WITH SUBSTITUTED ANILINES. III

Chemischer InformationsdienstVolume 10, Issue 15 Preparative Organic Chemistry ChemInform Abstract: INFLUENCE OF SOLVENTS ON RATES OF REACTIONS OF 2,4-DINITRO SUBSTITUTED HALOBENZENES WITH SUBSTITUTED ANILINES. III H. W. LEE, H. W. LEESearch for more papers by this authorI. LEE, I. LEESearch for more papers by this author H. W. LEE, H. W. LEESearch for more papers by this authorI. LEE, I. LEESearch for more papers by this author First published: April 10, 1979 https://doi.org/10.1002/chin.197915104Read the full textAboutPDF 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, Issue15April 10, 1979 RelatedInformation