The catalytic effect of catiohic amino micelles on the hydrolysis of substituted phenyl esters

The catalytic effects of two aminocationic micelles on the hydrolysis of substituted phenyldecanoate esters and a positively charched benzoate ester (CPNBA) were determined. The micellaric catalysts were of the general structure [CH₃(CH₂)₃N(CH₃)₂(CH₂)_nNH₂]Br where n=2 (micelle 1); n=3 (micelle 2). The kinetics followed the expression: k_obs =k_o+k_cat x K_a/(K_a+H⁺)+k^o_OH[OH^-]. From the comparison of the kc OH rates with specific base catalysis rates deduced from reactions in non catalytic micelles, it was concluded that the kc OH term, is compatible mainly with an aminolysis reaction catalyzed by hydorxide ion. The Hammett and Bronsted correlations (p=2.8; β=1.0), in addition to the very small deuterium isotope effect, suggested that kcat corresponded with a nucleophilic mechanism. The Bronsted plot of log k_cat vs pKa of the phenolate leaving groups in micelles 1 and 2 showed a biphasic behaviour. The break in the curve occured at pK_o=5.89 and pK_o=6.78 respectively. The partition ratio k^±/k_-a of the zwiterionic tetrahedral intermediate was derived from the experimental data and produced the following correlation: log k^±/k_-a=-0.92pK_o+0.43pK_N+2.466. The ester CPNBA exhibited a deuterium isotope effect of 2.1. From product analysis it was concluded that the reaction proceeds via a general base catalysis of aminolysis.     

Radical copolymerization of acrylic monomers. IV. Effect of substituents on the radical polymerization and copolymerization of phenyl acrylates

The kinetics of radical polymerization of phenyl, ortho-chlorophenyl, and para-chlorophenyl acrylates, as well as their copolymerization with methyl methacrylate, have been studied dilatometrically. The results obtained indicate that the overall rate of polymerization is affected by the flexibility of the growing radicals. However, the copolymerization of these monomers with methyl methacrylate gives overall rates rather similar for all three systems, being fundamentally regulated by the formation of reversible π complexes between the donor aromatic rings and the acceptor methacrylic double bonds. Dilatometric methods for the study of the copolymerization reactions have been tested and the corresponding binary bonding frequencies B_ij and conversion factors K_ij have been calculated for the copolymerization of ortho- and para-chlorophenyl acrylates with methyl methacrylate.     

Effect of substituents on the kinetic energy release in unimolecular decompositions of substituted anisoles

The kinetic energy relased on the loss of a CH₃ ? radical from para substituted anisoles appears to depend on the nature of the substituent. The application of the dual parameter equation of Yukawa and Tsuno yields a linear correlation with the T_0.5-values. The mesomeric effect predominates strongly over the inductive effect.     

Effect of meta electron-donating groups on the electronic structure of substituted phenyl nitrenium ions

Density functional theory (UB3LYP/6-31G(d,p)) was used to determine substituent effects on the singlet-triplet-state energy gap for 21 meta-substituted phenylnitrenium ions. It was found that strongly electron-donating substituents stabilize the triplet state relative to the singlet state. With sufficiently strong meta electron donors (e.g., m,m'-diaminophenylnitrenium ion) the triplet is predicted to be the ground state. Analysis of equilibrium geometries, Kohn-Sham orbital distributions, and Mulliken spin densities for the triplet states of this series of nitrenium ions leads to the conclusion that there are two spatially distinct types of low-energy triplet states. Simple arylnitrenium ions such as phenylnitrenium ions as well as those having electron-withdrawing or weakly donating meta substituents have lowest-energy triplet states that are n,pi in nature. That is, one singly occupied molecular orbital is orthogonal to the plane of the phenyl ring and one is coplanar. These n,pi triplets are generally characterized by large ArNH bond angles (ca. 130-132 degrees ) and an NH bond that is perpendicular to the plane of the phenyl ring. In contrast, meta donor arylnitrenium ions have a lowest-energy triplet state best described as pi,pi. That is, both singly occupied molecular orbitals are orthogonal to the aromatic ring. Such pi,pi states are characterized by NH bonds that are coplanar with the phenyl ring and have ArNH bond angles that are more acute (ca. 110-111 degrees ). These triplet nitrenium ions have electronic structures analogous to those of meta-benzoquinodimethane derivatives.     

Substituent effects on the mass spectra of substituted phenyl acetates

The mass spectra of a series of meta- and para-substituted phenyl acetates have been examined. Substituent effects have been correlated with Δ (AP-IP) values and by using the Harrison and Chin approach. The bond-cleavage and rearrangement reactions of phenyl accetates are compared with the corresponding reactions of acetanilides and the differences attributed to the degree of transmission of polar effects in the two systems.     

The stoichiometric hydrogenation of substituted phenyl alkenes by hydridocobalt tetracarbonyl

The relative rates of hydrogenation of a series of styrenes, phenylpropenes, 1,1-diphenylethylenes, and 1,1-diphenylpropenes were measured. Compared to 1,1-diphenylethylene (k₂ = 2.42 X 10^-2 I mol^-1 sec^-1), 1,1-diphenylpropene and styrene have relative rates of 0.0045 and 0.011 respectively. The effect of 4-chloro and 4-methoxy substituents on both styrene and diphenylethylene is slightly rate enhancing. An unusual kinetic dependence occurs with mixtures of alkenes.     

The effect of phenyl substituents on the release rates of esterase-sensitive coumarin-based prodrugs

A coumarin-based prodrug system has been recently developed in our laboratory for the preparation of esterase-sensitive prodrugs of amines, peptides, and peptidomimetics. The drug release rates from this prodrug system were found to be dependent on the structural features of the drug moiety. In certain cases, the release can be undesirably slow for drugs that are secondary amines with relatively high pKa's. Aimed at finding ways to manipulate the release rates to suit the need of different drugs, we have examined the effect of the phenyl ring substitutions on the release kinetics of such prodrugs and found that appropriately positioned alkyl substituents on the phenyl ring could help to facilitate the release by as much as 16-fold. Therefore, introduction of alkyl substituents on the phenyl ring should allow us to manipulate the release rates and, therefore, time profiles for different drugs.     

Selectivity variation in hydrolysis of phenyl acetates by simple modifications of β-cyclodextrin.

By reaction of β-cyclodextrin 6-monotosylate with alkyl mercaptans, 6-deoxy-6-alkylthio-β-cyclodextrins, $\text{2}$, $\text{3}$, and $\text{4}$, were prepared. Studies of the hydrolyses of $\text{m}$- and $\text{p}$-substituted phenyl acetates showed that the well-known meta-selectivity effect occurred with $\text{2}$, while none was observed with $\text{4}$. This variation in selectivity was due to a change in the catalytic rate constant caused by the substituent on β-cyclodextrin.     

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

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 σ_m,p substituent constants. The log k values for ortho-substituted phenyl benzoates showed good correlations with the Charton equation, containing the inductive, σ_I, 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 + 2.19σ_I + 0.304σ^○ _R + 2.79E _s ^B ? 0.0164ΔEσ_I — 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.     

Evidence of substituent-induced electronic interplay. Effect of the remote aromatic ring substituent of phenyl benzoates on the sensitivity of the carbonyl unit to electronic effects of phenyl or benzoyl ring substituents

Carbonyl carbon (13)C NMR chemical shifts delta(C)(C[double bond]O) measured in this work for a wide set of substituted phenyl benzoates p-Y-C(6)H(4)CO(2)C(6)H(4)-p-X (X = NO(2), CN, Cl, Br, H, Me, or MeO; Y = NO(2), Cl, H, Me, MeO, or NMe(2) ) have been used as a tool to study substituent effects on the carbonyl unit. The goal of the work was to study the cross-interaction between X and Y in that respect. Both the phenyl substituents X and the benzoyl substituents Y have a reverse effect on delta(C)(C[double bond]O). Electron-withdrawing substituents cause shielding while electron-donating ones have an opposite influence, with both inductive and resonance effects being significant. The presence of cross-interaction between X and Y could be clearly verified. Electronic effects of the remote aromatic ring substituents systematically modify the sensitivity of the C[double bond]O group to the electronic effects of the phenyl or benzoyl ring substituents. Electron-withdrawing substituents in one ring decrease the sensitivity of delta(C)(C[double bond]O) to the substitution of another ring, while electron-donating substituents inversely affect the sensitivity. It is suggested that the results can be explained by substituent-sensitive balance of the contributions of different resonance structures (electron delocalization, Scheme 1).     

Effect of substituents on chemical shift of protons of the amino group in PMR spectra of substituted aminopyridines

The effect of substituents on the chemical shift of the protons of the amino group in six series of m- and p-substituted 2-, 3-, and 4-aminopyridines (in DMSO) was studied by correlation analysis using the inductive and resonance constants. The peculiarities of the pyridine ring in the transmission of the electronic effects of substituents are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 54–59, January, 1990.     

Enantioseparation of 2‐(substituted phenyl)propanoic acids by high‐speed countercurrent chromatography and investigation of the influence of substituents in enantiorecognition

This paper concentrates on the enantioseparation of racemic 2‐(substituted phenyl)propanoic acids by high‐speed countercurrent chromatography with substituted β‐cyclodextrin as the chiral selector, and an investigation of the influence of the substituent on the benzene ring in enantiorecognition between the chiral selector and enantiomer of each racemate is presented. This is an extension research of our previous work on the enantioseparation of 2‐phenyl propanoic acid derivatives, to investigate the relationship between the value of enantioseparation factor and the different substituent on the benzene ring. In total, ten racemic 2‐(substituted phenyl)propanoic acids were investigated, of which four including 2‐(4‐nitrophenyl)propanoic acid, 2‐(4‐methylphenyl)propanoic acid, 2‐(4‐hydroxyphenyl)propanoic acid, and 2‐(4‐chlorophenyl)propanoic acid, were studied by countercurrent chromatography for the first time, and two racemates were successfully enantioseparated. The distribution ratio and enantioseparation factor for all the ten racemates were determined by enantioselective liquid–liquid extraction. The results showed that an electron‐donating group on the benzene ring presents a higher enantiorecognition induced by chiral selector than that of racemates with an electron‐withdrawing group on the benzene ring.     

Structure-reactivity correlation in the pyridinolysis of substituted phenyl acetates

The pyridinolysis of substituted phenyl acetates in acetonitrile was investigated with an electric conductivity method. The rates of these reactions were increased with electron-donating group in pyridine and electron-withdrawing group in phenyl acetate, ϱ_x (X;substituents in phenyl ring) values increase gradually according to the electron-donating ability in pyridine substituents, but the |ϱ_y|(Y;substituents in pyridine ring) values decrease with that of substituents. The β values increase with increasing electron-withdrawing ability of the substituents in the phenyl ring, it can be inferred that N---C bond formation increases progressively p-methyl to p-nitrophenyl acetates. This is in agreement with prediction of substituent effects for a simple S_N2 displacement reaction. The sensitivity parameters, β and ϱ, are inter-related and are themselves sensitive to the reactivity of the system. All above results are interpreted in terms of a dissociative S_N2 mechanism involving a metastable tetrahedral intermediate.     

Geometry and energy of substituted phenyl cations

The geometry and the energy of a number of substituted phenyl cations have been calculated for both spin states at the UB3LYP/6-31G(d) level (o-, m-, p-Me, OMe, NH(2), CN, NO(2)) or at the UB3LYP/6-311++G(2d,p) level (o-, m-, p-SiMe(3), SMe). The geometric differences were assessed by means of a self-organizing neural network. The triplets maintain a regular hexagonal structure that is minimally affected by substituents, while in the singlets C1 puckers inward and, when an electron-donating group is present, shifts out of the plane. The triplets have the character of aromatic radical ions and are strongly stabilized by electron-donating substituents, independently of the position of the latter. In the case of singlets, the effect of substituents on the energy is weaker and depends on the position (the largest effect is exerted when the group is in meta). A two-parameter correlation of all of the triplet energies shows the predominant mesomeric effect of the substituents. In the case of singlets, linear correlations are obtained only when each position is treated separately and when the predominant effect is inductive for the ortho and, less markedly, the para position, whereas at the meta position, mesomeric and inductive effects are comparable. The ground state is determined to be the singlet for the parent cation and for electron-withdrawing substituted ions. With electron-donating substituents, the triplet is the ground state for ortho and para derivatives, while the two spin states are roughly isoenergetic when the donating group is in the meta position. These data allow predicting the reactivity of each cation.