Hammett Substituent Constants Research Articles

10.1007/s11176-008-2014-x

The effective total charges on the nitro groups of m- and p-substituted nitrobenzenes were calculated ab initio by the RHF/3-21G method. The calculated charges were correlated with the Hammett constants of substituents in the aromatic ring. The correlation equations obtained can be used for predicting and evaluating the reactivity of aromatic nitro compounds.

Nonlinear Hammett plots in pyridinolysis of 2,4-dinitrophenyl X-substituted benzoates: change in RDS versus resonance contribution

Second-order rate constants (k(OH)-) have been measured for nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzoates (1a-j) with Z-substituted pyridines in 80 mol% H(2)O/20 mol% DMSO at 25.0 +/- 0.1 degrees C. The Hammett plots for the reactions of 1a-j with pyridines consist of two intersecting straight lines, i.e., a large rho value for the reactions of substrates (1a-c) possessing an electron-donating group (EDG) in the benzoyl moiety and a small one for substrates (1e-j) bearing an electron-withdrawing group (EWG). The nonlinear Hammett plots have been attributed to stabilization of the ground state of substrates 1a-c through resonance interactions between the electron-donating substituent and the carbonyl functionality, since the corresponding Yukawa-Tsuno plots exhibit excellent linear correlations with large r values. It has been shown that substrates are not unusually more reactive than would be expected from the Hammett substituent constants, but rather, substrates 1a-c exhibit lower reactivity than would be predicted. The Brønsted-type plots for pyridinolysis of 1a-j are linear with beta(nuc) = 0.74-0.98, indicating that the reaction proceeds through a stepwise mechanism in which the second step is the RDS. It has been concluded that the electronic nature of the substituent X in the benzoyl moiety does not influence the RDS, but the degree of bond formation (or the effective charge on the nucleophilic site) in the transition state becomes more significant as the substituent X changes from a strong EDG to a strong EWG.

Shannon entropy as a new measure of aromaticity, Shannon aromaticity

Based on the local Shannon entropy concept in information theory, a new measure of aromaticity is introduced. This index, which describes the probability of electronic charge distribution between atoms in a given ring, is called Shannon aromaticity (SA). Using B3LYP method and different basis sets (6-31G**, 6-31+G** and 6-311++G**), the SA values of some five-membered heterocycles, C(4)H(4)X, are calculated. Significant linear correlations are observed between the evaluated SAs and some other criteria of aromaticity such as ASE, Lambda and NICS indices. According to the obtained relationships, the range of 0.003 < SA < 0.005 is chosen as the boundary of aromaticity/antiaromaticity. Using B3LYP/6-31+G** level of theory, the Shannon aromaticities for a series of mono-substituted benzene derivatives are calculated and analyzed. It is found that the least standard deviation between the aromaticities and the best linear correlation with the Hammett substituent constants are observed for the new index in comparison with the other indices. Also the values of the new index are evaluated for some substituted penta- and heptafulvenes, which successfully predict the order of aromaticity in these compounds. Applying this index to some non-benzonoids, linear and angular polyacenes also give satisfactory results and prove to be quite suitable for determining the local aromaticity of different rings in polyaromatic hydrocarbons.

Designing Acid/Acid Co-Crystals through the Application of Hammett Substituent Constants

The designed creation of co-crystals between substituted benzoic acids was investigated by the co-crystallization of 32 acid/acid combinations. Systems with differing signs of their Hammett substituent constants were found to successfully form co-crystals in 90% of the cases, while those with the same sign were successful in only 25% of the cases. The systems where single-crystal structure determination was possible displayed both co-crystal and salt formation, with the co-crystal systems displaying a tendency towards salt-like character with increasing difference in Hammett constant of the component species. Thus the bonding preferences and structure within acid/acid co-crystal systems may be tailored by selection of the functional groups upon the acid components.

Use of Correlation of1H and13C Chemical Shifts of N-Arylsuccinanilic Acids,N-Arylsuccinimides, N-Arylmaleanilic Acids, and N-Arylmaleimides with the Hammett Substituent Constants for the Studies of Electronic Effects

A series of N-arylsuccinanilic acids, N-arylsuccinimides, N-arylmaleanilic acids, and N-arylmaleimides was prepared and their NMR spectra were examined by correlating the <TEX>$^1H\;and\;^{13}C$</TEX> chemical shift values with the corresponding Hammett <TEX>$\sigma$</TEX> values. The carbonyl carbons of the amides show a normal correlation with <TEX>$\sigma$</TEX> but those of the imides show an inverse correlation.

Quantitative structure–activity relationships for estimating the aryl hydrocarbon receptor binding affinities of resveratrol derivatives and the antioxidant activities of hydroxystilbenes

Quantitative structure–activity relationships (QSARs) were developed for the aryl hydrocarbon receptor (AhR) binding affinity of non-fluorinated and fluorinated cis and trans 3,4′,5-substituted resveratrol derivatives. Lower quality QSAR fits were found when all compounds were modeled together, in contrast to strong correlations with Hammett substituent constants and atomic charges for separate non-fluorinated/fluorinated and cis/trans groupings. The collective findings suggest little promise in developing new resveratrol derivatives with significantly higher AhR binding affinity beyond the range already mapped by the available experimental data sets. The results also suggest that future QSAR searches for AhR binding affinity among resveratrol derivatives will likely need to proceed in a more constrained class-by-class fashion owing to the potentially different mechanistic implications from changes in the types/positions of aromatic substitution and the cis/trans geometrical isomerism. The antioxidant activity of hydroxystilbenes can be accurately modeled using high-quality empirical univariate relationships with various molecular descriptors. In comparison, correlations between theoretical bond dissociation enthalpies and ionization energies of the molecular and dissociated forms yielded lower quality QSAR fits with the antioxidant behavior.

Substituent effects of α,β-unsaturated aldehyde compounds in inverse electron demand Hetero-Diels–Alder reactions: A theoretical study

The present work describes the new theoretical study for behaviour estimation of some α,β-unsaturated aldehyde derivatives in inverse electron demand Hetero-Diels–Alder reactions. The theoretical scale has shown rationalization between electrophilic activation/deactivation effects and electron withdrawing (EW) and electron releasing (ER) substituents in these molecules. The electrophilicity values that evaluated with HF/6-31G∗ method shows a good linear relationship with the σ p Hammett substituent constants. These results are in excellent agreement with respect to experimental results.

Substituent effects in the tuning of excited-state intramolecular proton transfer and optical properties of the derivatives of 2-(2-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole

The intramolecular proton transfer process and optical properties of a series of derivatives of 2-(2-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole (HOXD) have been studied. The effects of electron-donating and -withdrawing substituents on the intramolecular proton transfer and optical properties in the S0 and S1 states have been investigated to find out the relationships between them and the Hammett substituent constants (δ p). The statistically valid linear correlations are observed between the δ p and the ionization potential (IP), electron affinity (EA), the relative energies (ΔE) and the direct energy barriers (ΔE d) of the intramolecular proton transfer reactions, and the optical properties of HOXD and its substituted derivatives. The λ abs, λ fl, and λ ph of the electron-withdrawing substituted derivatives have bathochromic shifts, while the corresponding values of the electron-donating substituted derivatives show hypsochromic shifts compared with the parent compound HOXD. A successful tuning in the emission color was achieved: the emission wavelength was substituent δ p dependent, providing a powerful strategy for predicting the optical properties of novel electroluminophores. The effects of substituents on the intramolecular proton transfer and optical properties for 2-(2-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole and its diverse derivatives have been theoretically investigated with the aim to get the relationships between the ESIPT reactions, optical properties, and the Hammett substituent constants (δ p).

치환기를 가진 다섯 자리 질소-산소 (N2O3)계 리간드의 합성 및 전이금속(II) 이온과의 착물 안정도상수 결정

Hydrochloric acid salt of a new <TEX>$N_2O_3$</TEX> pentadentate ligand, N,N'-Bis(2-Hydroxybenzyl)-1,3-diamino-2-propanol(H-BHDP 2HCl) was synthesized. Br-BHDP 2HCl, CI-BHDP 2HCl, <TEX>$CH_3-BHDP$</TEX> 2HCl and <TEX>$CH_3O$</TEX>-BHDP 2HCl having Br, Cl, <TEX>$CH_3$</TEX> and <TEX>$CH_3O$</TEX> substituents at 5-position of the phenol group of H-BHDP 2HCl were also synthesized. The potentiometry study in aqueous solution revealed that the proton dissociations of the synthesized ligands occurred in four steps and their order of the calculated overall proton dissociation constants(<TEX>$log{\beta}_p$</TEX>) was Br-BHDP < Cl-BHDP < H-BHDP < <TEX>$CH_3O-BHDP$</TEX> < <TEX>$CH_3-BHDP$</TEX>. The order showed a similar trend to that of Hammett substituent constants(<TEX>${\delta}_p$</TEX>). The order of the stability constants(<TEX>$logK_{ML}$</TEX>) was Co(II) < Ni(II) < Cu(II) < Zn(II) < Cd(II) < Pb(II). The order in their stability constants (<TEX>$logK_{ML}$</TEX>) of each transition metal complex agreed with that of the overall proton dissociation constants (<TEX>$log{\beta}_p$</TEX>).

From diacetylferrocene to 1,1′-ferrocenyldiimines: Substituent effects on synthesis, molecular structure, electrochemical behavior and optical absorption property

A series of 1,1′-ferrocenyldiimines [Fe{( η 5-C 5H 4)–C(Me)N–R} 2], where R = n-hexyl 1a, cyclohexyl 1b, phenyl 1c, 4-methoxyphenyl 1d, 3-methoxyphenyl 1e, 4-nitrophenyl 1f, and 3-nitrophenyl 1g, have been synthesized by reactions of ca. 1:2 M ratio of 1,1′-diacetylferrocene and the corresponding amines. While ca. 1:1 M ratio of the starting materials was employed, acetylferrocenylimines [Fe{( η 5-C 5H 4)–C(CH 3) O}{( η 5-C 5H 4)–C(CH 3) N–R}], where R = 4-nitrophenyl 2f, and 3-nitrophenyl 2g, were obtained. Single crystal X-ray structural analysis revealed that the two cyclopentadienyl rings in 1d, 1e, 1g, 2f, and 2g were antiperiplanar staggered, anticlinal eclipsed, anticlinal eclipsed/synclinal eclipsed, synclinal eclipsed, and synclinal eclipsed to each other in solid state, respectively. All synthesized ferrocene derivatives exhibited a reversible one-electron redox process in their cyclic voltammograms, and the values of their redox potentials relied on the R groups. The correlation between the redox potential and the Hammett substituent constant, σ p was quite well, with a correlation coefficient of 0.98. The UV–vis spectra showed that their optical property was also substituent dependent.

Electron ionization mass spectra and tautomerism of substituted 2‐phenacylquinolines

Tautomerism has been studied conventionally in solutions or in the solid state. However, the importance of mass spectrometry in the gas phase was realized relatively late. 2-Phenacylquinolines are known to undergo ketimine-enaminone tautomerism. The ratio of tautomers is dependent on the nature of the phenyl ring substituent and the Hammett substituent constants sigma. Theoretical calculations indicate the presence of ketimine and enaminone tautomers in the gas phase. The electron ionization mass spectra of eight 2-phenacylquinolines (ketimine form) were recorded at 70 eV in order to determine the fragmentation routes and to screen for the presence of their enaminone tautomers, (Z)-2-benzoylmethylene-1,2-dihydroquinolines, in the gas phase. The relative abundances or total ion currents of some ions correlated with the Hammett substituent constants and Hammett-Brown constants. The product ions [M-CO](+.) and [M-HCO](+) were observed. A reaction mechanism is suggested for the formation of these ions, requiring skeletal rearrangements. The results furnish information relating to tautomerism in the gas phase.

Solvent hydrogen bonding and structural effects on nucleophilic aromatic substitution reactions. Part-2 : Reaction of benzenesulphonyl chloride with anilines in propan-2-ol/2-methylpropan-2-ol mixtures

Substitution reactions of fourteen para- and meta-substituted anilines with benzenesulphonyl chloride in different mole fractions of propan-2-ol in 2-methylpropan-2-ol have been investigated conductometrically. The second order rate constants correlates satisfactorily with pK a values of the anilines and also with the Hammett's substituent constant. The para-substituted anilines shows a satisfactory correlation with Charton's LDR equation. The results of these correlations indicate the formation of an electron deficient transition state. The rate data correlate satisfactorily with macroscopic solvent parameters such as relative permittivity, e r and polarity, E T N . Multiple correlation analysis of the rate data via Kamlet-Taft's solvatochromic parameters reveals that the solvent dipolarity/polarizability plays a dominant role in governing the reactivity.

Substituent Chemical Shifts of 2-Aryl Derivatives of Benzimidazole, Benzimidazolium Ion, and Benzimidazoline

NMR spectra of a series of 2-arylbenzimidazoles, 2-aryl-1,3-dimethylbenzimidazolium iodides, and 2-aryl1,3-dimethylbenzimidazolines were examined by correlating 1 H and 13 C chemical shift values with the Hammett substituent constants σ. The signals corresponding to C-2 of the imidazole ring show good correlation with the largest ρ values in each series. The ρ values for C-2 of the benzimidazoles and the benzimidazolium ions were very close, but that of the benzimidazoline was about a half of the former series.

Determination of the Electrophilicity Parameters of Diethyl Benzylidenemalonates in Dimethyl Sulfoxide: Reference Electrophiles for Characterizing Strong Nucleophiles

The second-order rate constants of the reactions of nine substituted diethyl benzylidenemalonates 1 a-i with the carbanions 2 a-e have been determined spectrophotometrically in dimethyl sulfoxide (DMSO). Product studies show that the nucleophiles attack regioselectively at the electrophilic C==C double bond of the Michael acceptors to form the carbanionic adducts 4. The correlation log k(20 degrees C)=s(N+E) allows the determination of the electrophilicity parameters E for the electrophiles 1 a-i from the rate constants determined in this work and the previously published N and s parameters for the nucleophiles 2 a-e. The electrophilicities E for compounds 1 a-i cover a range of six units (-17.7>E>-23.8) and correlate excellently with Hammett's substituent constants sigma(p). The title compounds are roughly ten orders of magnitude less reactive than analogously substituted benzylidene Meldrum's acids, their cyclic analogues. Due to their low reactivities, compounds 1 a-i are suitable reference electrophiles for determining the reactivities of highly reactive nucleophiles, such as carbanions with 16<N<30.

Structural Modulation of Oxidative Metabolism in Design of Improved Benzothiophene Selective Estrogen Receptor Modulators

Raloxifene and arzoxifene are benzothiophene selective estrogen receptor modulators (SERMs) of clinical use in postmenopausal osteoporosis and treatment of breast cancer and potentially in hormone replacement therapy. The benefits of arzoxifene are attributed to improved bioavailability over raloxifene, whereas the arzoxifene metabolite, desmethylarzoxifene (DMA) is a more potent antiestrogen. As polyaromatic phenolics, benzothiophene SERMs undergo oxidative metabolism to electrophilic quinoids. The long-term clinical use of SERMs demands increased understanding of correlations between structure and toxicity, with metabolism being a key component. A homologous series of 4'-substituted 4'-desmethoxyarzoxifene derivatives was developed, and metabolism was studied in liver and intestinal microsomes. Formation of glutathione conjugates was assayed in rat liver microsomes and novel adducts were characterized by liquid chromatography-tandem mass spectrometry. Formation of glucuronide conjugates was assayed in human intestine and liver microsomes, demonstrating formation of glucuronides ranging from 5 to 100% for the benzothiophene SERMs: this trend was inversely correlated with the loss of parent SERM in rat liver microsomal incubations. Molecular orbital calculations generated thermodynamic parameters for oxidation that correlated with Hammett substituent constants; however, metabolism in liver microsomes correlated with a combination of both Hammett and Hansch lipophilicity parameters. The results demonstrate a rich oxidative chemistry for the benzothiophene SERMs, the amplitude of which can be powerfully modulated, in a predictable manner, by structural tuning of the 4'-substituent. The predicted extensive metabolism of DMA was confirmed in vivo and compared with the relatively stable arzoxifene and F-DMA.

치환된 Styryl 4-Methyl-1-naphthyl Ketones에서의 합성과 스펙트럼 linearity

A series of substituted styryl 4-methyl-1-naphthyl ketones [(2E)-1-(4-methyl-1-naphthyl)-3-phenyl-2-propen-1-ones] were synthesized eco-friendly under solvent free conditions using a green catalyst SiO 2 -H 2 SO 4 in an oven. The catalyst silica is reusable and the yields of chalcones are more than 90%. They are characterized by their physical constants, micro analysis, infrared (KBr, 4000-400 cm -1 ) and NMR both 1 H and 13 C and Mass spectral data. From infrared spectra, the s-cis and s-trans vibrations of carbonyl group and deformation modes CH in-plane and out of plane, -CH=CH- out of plane and >C=C< out of plane of vinyl parts, from NMR spectra the ethylenic proton, carbons and carbonyl carbon chemical shifts (ppm) are assigned. These spectral data are correlated with various Hammett substituent constants. From the results of statistical analysis the effect of substituents on CO, a and β proton, carbons and deformation modes are explained.

Solvent hydrogen bonding and structural effects on nucleophilic substitution reactions: Part 4 — Reaction of 2-chloro-5-nitropyridine with para-substituted anilines in acetonitrile/dimethylformamide mixtures

Substitution reactions of some para-substituted anilines with 2-chloro-5-nitropyridine were carried out conductometrically in acetonitrile/dimethylformamide mixtures. The various thermodynamic parameters for the reactions have been reported and discussed along with the validity of the isokinetic relationship. The correlation of second-order rate constants with Hammett's substituent constants yields a fairly linear straight line with negative slope. The rate data correlate satisfactorily (100 r 2 ~ 93%) with Reichardt's macroscopic solvent parameter, E T(30) . While correlation with Kamlet–Taft's solvatochromic parameters is excellent (100 R 2 ~ 99%) and the computed percentage contribution of these parameters ( P α = 29%, P β = 13%, P π ⁎ = 58%) suggests that both specific and non-specific solute–solvent–solvent interactions influence the reactivity. The solvation model proposed is well supported by the solvatochromism exhibited by aniline in the solvent mixture under investigation. The molar extinction coefficient ( ε max) of aniline varies appreciably up to ~ 25% with the change in mole fraction of the mixture. The multivariate correlation analysis of ɛ max (with α, β, π⁎) suggests that the solvation around NH 2 moiety of aniline through hydrogen bond donor (HBD) property is found to be dominant in the solvation process and consequently in altering the rate. The observation is that the dominance of HBD property in solvation is further confirmed by the cyclic voltammetric oxidation of aniline in the solvent mixture.

Alkyloxy- and aryloxy-titanocenes: Synthesis, solid-state structure and cyclic voltammetric studies

Alkyloxy- and aryloxy-functionalized titanocenes of type [Ti](Cl)(OR) (R = Me ( 2), CH 2PPh 2 ( 3), CH 2Fc ( 4), C 6H 5 ( 5), C 6H 4-4-C N ( 6), C 6H 4-4-NO 2 ( 7), C 6H 4-4-Me ( 8), C 6H 4-4-OMe ( 9), C 6H 4-4-C(O)Me ( 10), C 6H 4-4-CO 2Me ( 11), C 6H 4-3-NO 2 ( 12); [Ti] = (η 5-C 5H 4SiMe 3) 2Ti; Fc = (η 5-C 5H 4)(η 5-C 5H 5)Fe) were synthesized by the reaction of [Ti]Cl 2 ( 1) with ROH in a 1:1 molar ratio and in presence of Et 2NH. Diaryloxy-titanocenes ( e.g., [Ti](OC 6H 4-4-NO 2) 2 ( 13)) are accessible, when the ratio of 1 and ROH is changed to 1:2. This synthesis methodology also allowed the preparation of dinuclear complexes of composition ([Ti](Cl)) 2(μ-OC 6H 4O) ( 14) and ([Ti](Cl)(μ-OC 6H 4-4)) 2 ( 15) by the reaction of 1 with hydroquinone or 1,1′-dihydroxybiphenyl in a 2:1 stoichiometry. Cyclic voltammetric studies show the characteristic [Ti(IV)/Ti(III)] reductions. It was found that the potentials of the alkyloxy titanocenes 2– 4 do not differ, while for the aryloxy-titanocenes 5– 15 the reduction potentials correlate linearly with the σ p/m Hammett substituent constants showing a strong influence of the substituents on the electron density at titanium. The structures of titanocenes 4, 5, 9, and 11– 13 in the solid state are reported. Typical for these organometallic sandwich compounds is a distorted tetrahedral coordination geometry around titanium with D1–Ti–D2 angles (D1, D2 = centroids of the cyclopentadienyl ligands) of ca. 130 °. In comparison to FcCH 2O-functionalized 4, for the aryloxy-titanocenes 5, 9, and 11– 13 a significant larger Ti–O–C angle was found confirming electronic interactions between the titanium atom and the appropriate aryl group.

Hydrodechlorination of para-substituted chlorobenzenes over a ruthenium/carbon catalyst

The hydrodechlorination (HDC) of chlorobenzene (abbreviated as CLB) and seven types of para-substituted chlorobenzenes (para-amino, -methoxy, -methyl, -chloro, -trifluoromethyl, -acetyl and -cyano: abbreviated as CLAN, CLAS, CLTN, DCLB, CLTF, CLAP and CLBN, respectively) were performed over 5%-ruthenium/carbon (Ru/C) under a hydrogen pressure of 0.5–1.5MPa at 523K.In the HDC of these model compounds, except for CLAP and CLBN, reductive cleavage between the carbon and chlorine atoms took place and dechlorinated compounds were produced preferentially. In the reaction of CLAP and CLBN, on the other hand, hydrogenation and/or hydrogenolysis of the substituent coincided with the HDC and a wide variety of products was observed accompanying the HDC product.For the chlorobenzenes of the simple HDC, the HDC reaction rate constants decreased in the orders of CLAN≫CLB≈CLTN≈CLAS and CLB>DCLB≫CLTF, respectively.In the reaction of the chlorobenzenes of the electron-donating substituent, the reaction constant (lnk/k0) has no relevance to the Hammett substituent constant (σp0). In the case of the chlorobenzenes possessing the electron-withdrawing substituent, on the other hand, it was indicated that the electron-withdrawing substituent suppressed the HDC reactivity of chlorobenzenes, although no proportional relationship was observed between the reaction rate constant and the Hammett substituent constant.To explore the factors affecting the HDC reactivity, quantum calculation according to the DFT method (B3LYP/LANL2DZ) was applied to the “chlorobenzenes-Ru10” complex. As a result of the calculation, chlorobenzenes were adsorbed through a chlorine atom on the edge atom of the Ru10 cluster. The magnitude of the adsorption energy, moreover, decreased in the order of CLAN>CLAS≈CLB≈CLTN and CLB>DCLB>CLTF, respectively. These orders of adsorption energy are similar to that of the HDC reaction rate constant. It was concluded that adsorption energy is a useful parameter for the reactivity index of the HDC.

Accurate calculation of N1s and C1s core electron binding energies of substituted pyridines. Correlation with basicity and with Hammett substituent constants

Substituent shifts of the energetics of four related ionization processes of pyridines and benzoic acids (Fig. 1) were investigated. The first process is core-electron ionization of gas-phase pyridines (Fig. 1A), while the second concerns gas-phase acid-base reaction between a substituted pyridine and a conjugated acid (Fig. 1B), and the third and fourth processes are the acid dissociation of substituted benzoic acids in aqueous solution (Fig. 1C) and in vacuum (Fig. 1D), respectively. Core-electron binding energies for the first process were calculated using density-functional theory with the scheme Δ E KS (PW86x-PW91c/TZP+ C rel)//HF/6-31G∗. Average absolute deviation of calculated core electron binding energy shifts at N atom in substituted pyridines from experiment was 0.08 eV. The shift at N coincides highly with that at a ring carbon atom. The four shifts corresponding to the four processes shown in Figs. 1A–D correlate strongly with one another, with numerical values fairly close to each other when expressed in unit of electron volts.