Effect Of Ortho-substituents Research Articles

Rhodium-Catalyzed Atroposelective [2 + 2 + 2] Cycloaddition of Ortho-Substituted Phenyl Diynes with Nitriles: Effect of Ortho Substituents on Regio- and Enantioselectivity.

Axially chiral 3-(2-halophenyl)pyridines were successfully synthesized in high yields with excellent enantioselectivity by the cationic rhodium(I)/(S)-H8-BINAP complex-catalyzed atroposelective [2 + 2 + 2] cycloaddition of (o-halophenyl)diynes with nitriles. Interestingly, regio- and enantioselectivity highly depend on ortho substituents on the phenyl group of diynes. When the ortho substituents were methoxy and methoxycarbonyl groups, axially chiral 3-arylpyridines were obtained as a major product, while enantioselectivity was lowered significantly. On the other hand, when the ortho substituents were alkyl groups, regioselectivity was switched to give achiral 6-arylpyridines in high yields.

Divergent reaction pathways in gold-catalyzed cycloisomerization of 1,5-enynes containing a cyclopropane ring: dramatic ortho substituent and temperature effects.

A gold(i)-catalyzed cycloisomerization of easily available 1,5-enynes containing a cyclopropane ring has been developed, efficiently providing cyclobutane-fused 1,4-cyclohexadiene, tricyclic cyclobutene, biscyclopropane and 1,3-cyclohexadiene derivatives in moderate to excellent yields. When the phenyl group was not ortho substituted, 1,4-cyclohexadienes could be produced. With an ortho substituent, three different products could be selectively synthesized by control of the temperature and the used gold(i) catalyst. The 1,5-enyne substrate first undergoes a classical enyne cycloisomerization to form a tricyclic cyclobutene key intermediate, which undergoes subsequent transformation to produce the desired products. A plausible reaction mechanism was proposed according to deuterium labeling experiments and intermediate trapping experiments, as well as DFT calculations. In our current reaction, the ortho substituent on the phenyl group controls the reaction outcome and the ortho substituent effect was found to originate from steric and electronic factors.

Molecular engineering for efficient and selective iron porphyrin catalysts for electrochemical reduction of CO2 to CO.

Iron porphyrins Fe-pE, Fe-mE, and Fe-oE were synthesized and their electrochemical behavior for CO2 reduction to CO has been investigated. The controlled potential electrolysis of Fe-mE gave exclusive 65% Faradaic efficiency (FE) whereas Fe-oE achieved quasi-quantitative 98% FE (2% H2) for CO production.

Theoretical study on the influence of different para-substituents on 13C NMR of the single carbonyl curcumin analogues

The structure of eight kinds of different para-substituents curcumin analogues has been optimized at the level of B3LYP/6-31G(d,p), under which the stability has been verified by means of vibration analysis. Moreover, NMR spectra of curcumin analogues compounds have been studied at the level of B3LYP/6-311G(d,p) by GIAO method. The results show that the structure of eight compounds, a larger conjugated system, has good planarity. The effect of ortho-substituents on bond lengths and bond angles is greater than para and meta. Different substituents and different positions of substituents all have different influence on NMR of the single carbonyl curcumin analogues. In general, after the hydrogen atom on the benzene ring is substituted by other groups, the δ value of α-C changes significantly, the δ value of ortho-carbon atom may also have great change, but the δ value change of meta-carbon atoms is not too obvious. The effect of substituent electronegativity on α-C atoms presents obvious regularity, while the influence of conjugate effect on carbon atoms of benzene ring is more complex. Finally, the bigger substituted alkyl is, the more the δ value of α-C increases.

Unexpected Beneficial Effect of ortho-Substituents on the (S)-Proline-Catalyzed Asymmetric Aldol Reaction of Acetone with Aromatic Aldehydes

An intriguing effect of electronegative 2,6-substituents on the stereochemical outcome of (S) -proline-catalyzed aldol reactions between benzaldehyde derivatives and acetone is reported. Remarkably high enantioselectivities can be achieved with such substrates.

Prediction of ortho substituent effect in alkaline hydrolysis of phenyl esters of substituted benzoic acids in aqueous acetonitrile

Abstract The second-order rate constants k for the alkaline hydrolysis of phenyl esters of meta-, para- and ortho-substituted benzoic acids, X-C6H4CO2C6H5, in aqueous 50.9% acetonitrile have been measured spectrophotometrically at 25°C. The log k values for meta and para derivatives correlated well with the Hammett σm,p substituent constants. The log k values for ortho-substituted phenyl benzoates showed good correlations with the Charton equation, containing the inductive, σI, resonance, σ○ R, and steric, E s B, and Charton υ substituent constants. For ortho derivatives the predicted (log k X)calc values were calculated with equation (log k ortho)calc = (log k H AN)exp + 0.059 + 2.19σI + 0.304σ○ R + 2.79E s B − 0.0164ΔEσI — 0.0854ΔEσ○ R, where DE is the solvent electrophilicity, ΔE = E AN — E H20 = −5.84 for aqueous 50.9% acetonitrile. The predicted (log k X)calc values for phenyl ortho-, meta- and para-substituted benzoates in aqueous 50.9% acetonitrile at 25°C precisely coincided with the experimental log k values determined in the present work. The substituent effects from the benzoyl moiety and aryl moiety were compared by correlating the log k values for the alkaline hydrolysis of phenyl esters of substituted benzoic acids, X-C6H4CO2C6H5, in various media with the corresponding log k values for substituted phenyl benzoates, C6H5CO2C6H4-X.

Ortho-substituent effect promoted rapid cleavage of amide C–N bond under mild conditions

This article reports the ortho-substituent effect on the cleavage of the amide C–N bond. In the structure of Nα-Phth-N-pyridinyl-amide, when the hydrogen atom in the 3-position of pyridine ring was replaced by alkoxy group, the amide C–N cleavage can take place in the 2-position of the pyridine ring. This transformation can proceed rapidly in methylamine ethanol solution under mild conditions to afford 2-amino-3-alkoxy pyridines.

Prediction of ortho substituent effect in alkaline hydrolysis of substituted phenyl benzoates in aqueous acetonitrile

The second-order rate constants k (dm3mol−1s−1) for alkaline hydrolysis of meta-, para- and ortho-substituted phenyl esters of benzoic acid, C6H5CO2C6H4-X, in aqueous 50.9% (v/v) acetonitrile have been measured spectrophotometrically at 25 °C. In substituted phenyl benzoates, C6H5CO2C6H4-X, the substituent effects log kX − log kH in aqueous 50.9% acetonitrile at 25 °C for para, meta and ortho derivatives showed good correlations with the Taft and Charton equations, respectively. Using the log k values for various media at 25 °C, the variation of the ortho substituent effect with solvent was found to be precisely described with the following equation: Δlog kortho = log kortho − log kH = 1.57σI + 0.93σ°R + 1.08EsB − 0.030ΔEσI − 0.069ΔEσ°R, where ΔE is the solvent electrophilicity, ΔE = ES − EH20, characterizing the hydrogen-bond donating power of the solvent. We found that the experimental log k values for ortho-, para- and meta-substituted phenyl benzoates in aqueous 50.9% acetonitrile at 25 °C, determined in the present work, precisely coincided with the log k values predicted with the equation (log kX)calc = (log kHAN)exp + (Δlog kX)calc where the substituent effect (Δlog kX)calc was calculated from equation describing the variation of the substituent effect with the solvent electrophilicity parameter, using for aqueous 50.9% CH3CN the solvent electrophilicity parameter, ΔE = −5.84. In going from water to aqueous 50.9% CH3CN, the ortho inductive term grows twice less as compared with the para polar effect. Copyright © 2013 John Wiley & Sons, Ltd.

Asymmetric Dearomatizing Spirolactonization of Naphthols Catalyzed by Spirobiindane-Based Chiral Hypervalent Iodine Species

This report details the development of a spirobiindane-based chiral hypervalent iodine reagent, especially focusing on its structural elucidation for effective asymmetric induction of the chiral spiro center during the oxidative dearomatizing spirolactonization of naphthols. In this study we synthesized a new series of ortho-functionalized spirobiindane catalysts and demonstrated that the enantioselectivity can be dramatically improved by the presence of the substituents ortho to the iodine atom. The structural elucidation of a spirobiindane-based hypervalent iodine catalyst has led to further improvement in the stereoselective construction of the spiro center during the oxidative dearomatizing spirolactonization of naphthols. Thus, catalytic oxidation with the highest reported level of enantioselectivity in hypervalent iodine chemistry has been achieved with also an excellent level of asymmetric induction (92% ee for substrate 3a). As a result, this study, dealing with a series of modified iodine catalysts, can provide important clues about the transition state and reaction intermediate to help scientists understand the origin of the stereoselectivity. A plausible transition-state model and intermediate in the reaction for the stereoselective formation of spirolactone products are postulated by considering the ortho-substituent effect and the results of X-ray analysis. In this reaction model, the high enantiomeric excess obtained by using the spirobiindane catalysts could be well explained by the occupation of the equatorial site and extension of the surroundings around the hypervalent iodine bonds by the introduced ortho-substituent. Thus, this study would contribute to estimation of the chiral hypervalent iodine compounds in asymmetric reactions.

Ortho Substituent effects on the anticonvulsant properties of 4-hydroxy-trifluoroethyl phenols

2,6-Dialkylphenols with isopropyl and sec-butyl substituent are well known anesthetic compounds. The 4-substitution with 1-hydroxy-2,2,2-trifluoroethyl (4-HTFE) group in these compounds led to the discovery of compounds with anticonvulsant activity in the 6Hz (32mA) model of partial epilepsy. In the present study a series of 2-alkyl-4-HTFE phenols with the 6-position being replaced with either hydrogen and bromine were designed, synthesized and tested to evaluate the effect of ortho-substitution on the anticonvulsant property. The studies show that 2-substituted branched alkyl chain (iso-propyl and sec-butyl) is necessary for the anti-seizure effect. Phenols with 2-substituted linear alkyl groups (methyl, ethyl and n-propyl) having no substitution at 6-position were found to be devoid of antiseizure effects. The 6-substitution with bromine moderately reduces the anticonvulsant effect in the compounds with branched alkyl chains, but led to enhanced anticonvulsant effect in the compound with a linear alkyl chain. This study shows that 4-HTFE phenols having isopropyl or sec-butyl ortho groups produce good antiseizure protection in the 6Hz therapy-resistant mouse model.

Unequivocal Experimental Evidence for a Unified Lithium Salt-Free Wittig Reaction Mechanism for All Phosphonium Ylide Types: Reactions with β-Heteroatom-Substituted Aldehydes Are Consistently Selective for cis-Oxaphosphetane-Derived Products

The true course of the lithium salt-free Wittig reaction has long been a contentious issue in organic chemistry. Herein we report an experimental effect that is common to the Wittig reactions of all of the three major phosphonium ylide classes (non-stabilized, semi-stabilized, and stabilized): there is consistently increased selectivity for cis-oxaphosphetane and its derived products (Z-alkene and erythro-β-hydroxyphosphonium salt) in reactions involving aldehydes bearing heteroatom substituents in the β-position. The effect operates with both benzaldehydes and aliphatic aldehydes and is shown not to operate in the absence of the heteroatom substituent on the aldehyde. The discovery of an effect that is common to reactions of all ylide types strongly argues for the operation of a common mechanism in all Li salt-free Wittig reactions. In addition, the results are shown to be most easily explained by the [2+2] cycloaddition mechanism proposed by Vedejs and co-workers as supplemented by Aggarwal, Harvey, and co-workers, thus providing strong confirmatory evidence in support of that mechanism. Notably, a cooperative effect of ortho-substituents in the case of semi-stabilized ylides is confirmed and is accommodated by the cycloaddition mechanism. The effect is also shown to operate in reactions of triphenylphosphine-derived ylides and has previously been observed for reactions under aqueous conditions, thus for the first time providing evidence that kinetic control is in operation in both of these cases.

The N-Aryl Aminocarbonyl ortho-Substituent Effect in Cu-Catalyzed Aryl Amination and Its Application in the Synthesis of 5-Substituted 11-Oxo-dibenzodiazepines

Double amination of ortho-substituted aryl bromides proceeded under mild conditions to afford 5-substituted 11-oxo-dibenzodiazepines, which revealed that there is a strong ortho-substituent effect caused by N-aryl aminocarbonyl groups during copper-catalyzed aryl amination.

Iodocyclization of N-Aryl-3-phenylpropiolamides by I2/CAN: A Convenient Route for the Selective Synthesis of Quinolin-2-ones

A general method has been developed for the selective synthesisof 3-iodoquinolin-2-ones and spiro[4.5]trienesvia intramolecular iodocyclization of N-( ORTHO-substituted aryl)-3-phenylpropiolamidesusing iodine/cerium(IV) ammonium nitrate reagent undermild reaction conditions. The electronic effect of ORTHO-substituents(electron-rich and electron-deficient group) triggers the two differentreaction pathways resulting to iodocyclized quinolin-2-one and IPSO-iodocyclized spiro-type compounds.

Kinetics of Proton Transfer between Ortho Substituted Benzoic Acids and the Carbinol Base of Crystal Violet in Toluene. Ortho Effect on the Reactivity of Benzoic Acids in Apolar Aprotic Solvents

Apolar aprotic solvents are particularly advantageous for investigating the intrinsic ortho effect free from complications of specific solvent effects. A kinetic study for toluene-phase proton transfers between ortho F, Cl, Br, I, OMe, OEt, OPh, OAc, Me, NO(2), COMe, COPh, OH, NH(2), and H benzoic acids and crystal violet carbinol base has shown the forward rate constant (log k(+1)) is the most appropriate reactivity parameter in toluene. log k(+1) (toluene) as compared to other reported reactivity parameters in benzene, toluene, or chlorobenzene has been found more sensitive to the ortho substituent effect. The regression results of the correlation of log k(+1) (toluene) of the acids (except OH and NH(2) substituted ones) according to seven ortho effect models are all very significant, and the best result is given by Fujita-Nishioka's model. The overall analysis reveals that a substituent's ortho effect pattern is a 58:24:18 ratio of its ordinary electrical, proximity electrical, and steric effects and that the proximity electrical effect is the major component to account for the peculiarity of the substituent's ortho effect. The results further favor the transmission of this effect mainly through the molecular cavity. The effect may, however, be outweighed by the steric component for bulky enough substituents, e.g., Me. The enhanced strength exhibited by salicylic acid in toluene has been quantitatively described using Pytela-Liška's σ(HB)(i) parameter. The abnormally high log k(+1) observed for anthranilic acid in toluene has been ascribed to a very extensive homoconjugation in its acid-acid anion complex induced by the acid's three hydrogen bond donors.

An ab initio molecular orbital study of intramolecular hydrogen bonding in ortho-substituted arylamides: Implications for the parameterization of molecular mechanics force fields

The aromatic oligoamide (arylamide) foldamer class, characterized by the repetitive aromatic-amide pattern, is one of the most intensively studied foldamer families. In this article, the potential energy profiles with regard to torsional motions around the two types of aromatic-amide bonds (C(a)-C(p) and C(a)-N) are obtained at the B3LYP/6-311G(d,p) level of theory. The effect of ortho substituents with different hydrogen bonding abilities (OCH(3) vs. SCH(3) ) on the torsional potential profiles is analyzed in detail. There are several findings that have implications in foldamer design. The ortho-SCH(3) substituent on the benzene ring produces a much more flexible arylamide backbone with respect to the OCH(3) substituent, as it restricts the C(a)-C(p) torsion to a lesser extent. Interestingly, the rigidifying effect of the ortho-SCH(3) substituent on the C(a)-N torsion is very similar to that of the OCH(3) substituent on the same linkage type. In addition, the SCH(3) substituent prefers a perpendicular orientation with respect to the benzene ring to the in-plane one. It is also found that reparameterization of the corresponding torsional parameters, sometimes specific to the ortho substituent type, in the general amber force field is necessary for an accurate description of the backbone torsions in arylamides. Six sets of partial charge/torsional parameters for each linkage (C(a)-C(p) or C(a)-N)/substituent (OCH(3) or SCH(3) ) combination are obtained based on the ab initio torsional profiles. Initial assessments of these parameters show good agreement with the ab initio results.

High-Performance Liquid Chromatographic Enantioseparation of Atropisomeric Biphenyls on Seven Chiral Stationary Phases

The HPLC enantioseparation of eight racemic atropisomeric biphenyls on commercially available polymeric Chiralcel OD-H, Lux Cellulose-1, Lux Cellulose-2, Chiralcel OJ, Lux Amylose-2 and Chiralpak OT(+) and on the brush-type Whelk-O1 columns, both in normal-phase mode and in polar organic solvent mode, has been investigated. The attempts to enantioseparate the selected biphenyls on Whelk-O1 were unsuccessful. All compounds were well resolved on almost one of the polymeric columns. Lux Cellulose-2 showed to be suitable for enantioseparation of all biphenyls. The effect of mobile phase, temperature, type of chiral selector and analyte structure on enantioseparation are examined and discussed. 2-Propanol and ethanol were employed as mobile phase modifiers and their influence on the retention and enantioseparation was investigated. Also a ternary mobile phase (n-hexane/2-propanol/methanol 91:6:3) was employed to test the separation of the eight biphenyls. In same cases, the elution with pure ethanol provided good enantioseparation in shorter elution times. The experimental data evidenced the complemental chiral recognition capabilities of polysaccharide-based CSPs. Noteworthy, Lux Cellulose-1 and Chiralcel OD-H contain the same chiral selector, but the first one exhibited higher retention factors. The evaluation of chromatographic data provided information about the chiral recognition mechanisms. In this regard, we report on the effect of ortho and meta biphenyl substituents on the retention and enantioseparation. In addition, computational evaluation of electrostatic potentials of analytes furnished a very interesting piece of information about the enantioseparability as well as the chiral recognition mechanisms on the evaluated chiral selectors. Keywords: Atropisomeric biphenyls, Enantiomeric separation, High-performance liquid chromatography, Molecular recognition, Polymetacrylate stationary phases, Polysaccharide stationary phases, catalysts, asymmetric synthesis, enantiomers, Melanoma Cell, analogues, chiral biphenyls, nuclear magnetic resonance, Chromatographic Screening, buffer

17O NMR study of ortho and alkyl substituent effects in substituted phenyl and alkyl esters of benzoic acids

17O NMR spectra for 44ortho-,meta- andpara-substituted phenyl and alkyl benzoates (C6H5CO2C6H4-X, C6H5CO2R) at natural abundance in acetonitrile were recorded. Substituent effects on the17O NMR chemical shifts, δ(17O), of the carbonyl oxygen and the single-bonded phenoxy (OPh) and alkoxy (OR) oxygens have been studied. The δ(17O) values of the carbonyl oxygen forparaderivatives showed a good correlation with the σ° constants. The δ(17O) values of carbonyl oxygen fororthoderivatives were found to be described well with the Charton equation containing the inductive, σI, resonance, σ°R, and steric,EsB, substituent constants in case the data treatment was performed separately for electron-donating +Rand electron-attracting –Rsubstituents. The electron-donating +Rorthoandparasubstituents in substituted benzoates caused shielding and the electron-withdrawing –Rsubstituents produced deshielding of the O signal. The steric interaction oforthosubstituents with the ester group decreased the electron density at the carbonyl oxygen. In alkyl benzoates the δ(17O) values were found to be described well with the inductive, σI, and the steric,EsB, substituent constants.

Effect of ortho-substituents on the stereochemistry of 2-( o-substituted phenyl)-1 H-imidazoline–palladium complexes

Palladium complexes composed of [Pd(Ln) 2Cl 2] ( n = 1, 2, 3, 4, 6), [ L5a] 2[PdCl 4] and [Pd( L5b) 2], where L1 = 4,5-dihydro-2-phenyl-1 H-imidazole (=2-phenyl-1 H-imidazoline), L2 = 2-( o-fluorophenyl)-1 H-imidazoline, L3 = 2-( o-methylphenyl)-1 H-imidazoline, L4 = 2-( o- tert-butylphenyl)-1 H-imidazoline, L5a = 2-( o-hydroxyphenyl)-1 H-imidazolinium, L5b = 2-(1 H-imidazolin-2-yl)phenolate, and L6 = 2-( o-methylphenyl)-1 H-imidazole, were synthesized. Molecular structures of the isolated palladium complexes were characterized by single crystal X-ray diffraction analysis. The effect of ortho-substituents on the phenyl ring on trans-chlorine geometry was noted for complexes [Pd( L1) 2Cl 2] 1a and 1b, [Pd( L2) 2Cl 2] 2 and [Pd( L6) 2Cl 2] 6, whereas cis-chlorine geometry was observed for [Pd( L3) 2Cl 2] 3 and [Pd( L4) 2Cl 2] 4. PdCl 2 reacts with 2-( o-hydroxyphenyl)-1 H-imidazoline in DMF to give [ L5a] + and [ L5b] – so that [ L5a] 2[PdCl 4] 5a and [Pd( L5b) 2] 5b were obtained. In complex 5b, as an N,O-bidentate ligand, two ligands L5b coordinated with the central Pd(II) ion in the trans-form. The coordination of PdCl 2 with 2-( o-hydroxyphenyl)-1 H-imidazolines in solution was investigated by NMR spectroscopy.

An Unsymmetrical Iron(II) Bis(imino)pyridyl Catalyst for Ethylene Polymerization: Effect of a Bulky Ortho Substituent on the Thermostability and Molecular Weight of Polyethylene

Three new iron(II) 2,6-bis(imino)pyridyl complexes bearing bulky and unsymmetrical substituted aniline groups, [2-(CH(CH3)(C6H5))-4-R1-6-R2-C6H2N═C(CH3)]2C5H3NFeCl2 (1, R1 = H, R2 = methyl; 2, R1 = methyl, R2 = methyl; 3, R1 = H, R2 = methoxy), were synthesized. The unsymmetrical bis(imino)pyridyl ligand L2 contains three isomers that can be detected by 1H NMR and 13C NMR spectroscopy. However, the corresponding complex 2 exhibits only one isomer in solution. X-ray diffraction of 2 confirms that the iron complex adopts a Cs configuration. These complexes activated by methylaluminoxane (MAO) have high catalytic activities for ethylene polymerization and produce linear polyethylenes with bimodal or broad molecular weight distribution. The steric and electronic effects of the ortho substituents on the aniline moiety distinctly affect the molecular weight of the obtained polyethylene. In comparison with 1 and 3, having a single ortho substituent on the aryl rings, and the typical complex 4, containing o-diiso...

Influence of solvent on the ortho substituent effect in the alkaline hydrolysis of phenyl esters of substituted benzoic acids

AbstractThe second‐order rate constants k (dm3 mol−1 s−1) for the alkaline hydrolysis of phenyl esters of meta‐, para‐ and ortho‐substituted benzoic acids in aqueous 5.3 M NaClO4 and 1.0 M Bu4NBr were measured by UV/Vis spectrophotometry at 25 °C. The variations in the ortho inductive, ortho resonance, as well as meta and para polar effects with solvent parameters were studied using data for the alkaline hydrolysis of phenyl esters of substituted benzoic acids in various media. The dependence of the ortho substituent effect on solvent can be precisely described with the following equation: Δlog kortho = log kortho − log kH = 0.059 + 2.19σI + 0.304σ°R + 2.79E − 0.016ΔEσI − 0.085ΔEσ°R, where ΔE is the solvent electrophilicity, ΔE = ES − EH2O, characterizing the hydrogen‐bond donating power of the solvent. The increase in the meta and para polar substituent effects with decrease in the solvent hydrogen‐bond donor capacity (electrophilicity) was approximately to the same extent (−0.068ΔEσ°m,p) as the resonance term for the ortho substituents. The steric term of ortho substituents was independent of the solvent parameters. The variations in the ortho inductive, ortho resonance, as well as meta and para polar substituent effects with the solvent electrophilicity were to the same extent as in phenyl benzoates containing the substituents in the phenyl part. The substituent effects in the alkaline hydrolysis of ethyl benzoates appeared to vary with the solvent electrophilicity nearly to the same extent as in the alkaline hydrolysis of substituted phenyl esters of benzoic acids. Copyright © 2009 John Wiley & Sons, Ltd.