Ortho Effect in Dissociation of Benzoic Acids with Electron-Accceptor Substituents Using the AISE Theory; Relation to para Substitution and Solvent

2002 ◽  
Vol 67 (5) ◽  
pp. 596-608 ◽  
Author(s):  
Oldřich Pytela ◽  
Jiří Kulhánek
Keyword(s):  
Electron Acceptor ◽  
Dissociation Constants ◽  
Electrostatic Force ◽  
Substituent Effects ◽  
Alternative Interpretation ◽  
Ring Closure ◽  
Reaction Centre ◽  
Benzoic Acids ◽  
Carboxylate Group ◽  
The Given

Potentiometric titration at 25 °C has been used to measure the dissociation constants of 2- and 4-substituted benzoic acids with electron-acceptor substituents in methanol, N,N-dimethylformamide, acetonitrile, and acetone. But for a few exceptions, no significant differences have been found between the dissociation constants measured and those given in literature. Using the measured pKa values, those of 3-substituted derivatives taken from literature (measured in the same solvents) and those of 3- and 4-substituted derivatives measured in water, the so far missing substituent constants σi of NO and CH3SO substituents have been determined by Alternative Interpretation of Substituent Effects (AISE). The previously published relationships and the σi constants have been used to calculate the σm and σp constants for the given substituents and compare them with literature. The agreement was the better, the more reliable the corresponding Hammett substituent constant was. Using a non-linear regression model, we have analysed the structure of matrix of pKa values of ten 2-X-benzoic acids (X is electron-acceptor substituent) measured in the given organic solvents and in water. It has been found that in non-aqueous solvents the conjugate base of benzoic acid is stabilised by intramolecular hydrogen bond if X is COOH and SO2NH2 or electrostatic force if X is CH3SO. On the other hand, in water the carboxylate group is out of the plane of the benzene ring due to interaction between the solvated reaction centre and substituent, this being the case with all the substituents except for X = CHO, CH3CO, NO, and CN. In all the solvents used, intramolecular ring closure takes place between the carboxylate group and substituent X = CH3CO, CHO, and NO, this phenomenon being the most important in water.

Chemometric Analysis of Substituent Effects. XI. Solvent Effects on Dissociation of 2,6-Disubstituted Benzoic Acids

1997 ◽  
Vol 62 (6) ◽  
pp. 913-924 ◽  
Author(s):  
Jiří Kulhánek ◽  
Oldřich Pytela
Keyword(s):  
Benzoic Acid ◽  
Solvent Effects ◽  
Dissociation Constants ◽  
Substituent Effects ◽  
Carbon Chain ◽  
Graphical Analysis ◽  
Point Of View ◽  
Reaction Centre ◽  
Benzoic Acids ◽  
Protic Solvents

Eleven symmetrically 2,6-disubstituted benzoic acids (with the following substituents: OCH3, OC2H5, OC3H7, OCH(CH3)2, OC4H9, CH3, F, Cl, Br, I, and NO2) have been synthesized and their dissociation constants measured potentiometrically in methanol, ethanol, propan-1-ol, propan-2-ol, butan-2-ol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, and 1,2-dichloroethane. The experimental data obtained have been analyzed from the point of view of solvent effects on acidity of the individual derivatives. Different behaviour found with benzoic acid and the disubstituted derivatives in protic solvents is due to changes in solvation. The different character of solvation of benzoic acid and the disubstituted derivatives depends on the type of substitution, being manifested only in 2,6-disubstituted benzoic acids. The graphical analysis has shown a distinct trend in the increase of magnitude of deviation of the point of benzoic acid in the series: propan-2-ol, butan-2-ol, propan-1-ol, ethanol, methanol. This order correlates with the steric demands of carbon chain of the alcohols used. The abnormal behaviour of benzoic acid in the dissociation in these alcohols as compared with that of its 2,6-disubstituted derivatives is due to the different extent of solvation of the reaction centre caused by steric hindrance. Against the expectation, benzoic acid appears to be a weaker acid in protic solvents, whereas its alkoxy derivatives are stronger acids. The solvation also minimizes the inductive effect of alkoxy groups in the symmetrically 2,6-disubstituted derivatives. In aprotic solvents the acidity of 2,6-dialkoxybenzoic acids is also increased, in this case as a result of sterically forced deviation of the reaction centre and/or the substituents out of the plane of benzene ring.

Chemometrical Analysis of Substituent Effects. V. ortho Effect

1994 ◽  
Vol 59 (9) ◽  
pp. 2005-2021 ◽  
Author(s):  
Oldřich Pytela ◽  
Josef Liška
Keyword(s):  
Dissociation Constants ◽  
Substituent Effects ◽  
Reaction Centre ◽  
Benzoic Acids ◽  
Electronic Effects ◽  
Substituent Constant ◽  
Zero Values ◽  
Substituent Constants ◽  
Substituted Benzoic Acids ◽  
Intramolecular Hydrogen

The dissociation constants of nineteen ortho substituted benzoic acids have been determined in eight organic solvents (methanol, ethanol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, 1,2-dichloroethane). The correlation between the σI, σR, and υ constants were unsuccessful due to neglecting the description of intramolecular hydrogen bond effect. The method of conjugated deviations has been applied to the results obtained and to those given in literature for ortho substituted benzoic acids (the dissociation constants, the reaction with diphenyldiazomethane, 33 sets), and values of three types of substituent constants have been determined for 29 substituents. The first of these substituent constants, σoi, describes the electronic effects and was adjusted with the application of the isoparameter relation (σoi as a function of σmi) suggested in previous communications. This constant (after excluding the substituents NHCOCH3 and OCOCH3) correlates very well (R = 0.993) with the σI and σR constants. The second substituent constant, σHGi, describes the interaction of the reaction centre (the oxygen atom of carboxylate anion) with the substituent, and it has non-zero values for the substituents OH, SH, NH2, NHCH3, NHCOCH3, COOH, CONH2, and SO2NH2. The third substituent constant, σSi, describes the steric effects and is not significantly related to any of the known quantities of this type. The set given was tested together with the triad of σI, σR, and υ on the definition set and on a set extended by other 28 sets of processes with ortho substituted compounds. On the whole, the set of substituent constants suggested explains 94.6% of variability of data, whereas only 66.0% are explained with the use of σI, σR, and u constants. Moreover, the tests have shown that the σoi constant is not suitable for interpretations of processes involving direct conjugation between the reaction centre and substituent.

Chemometric Analysis of Substituent Effects. XII. Application of Relationship Between 2- and 4-Substitution of Benzene Ring to Study ortho Effect in Selected Compounds with Different Reaction Centres

1999 ◽  
Vol 64 (10) ◽  
pp. 1617-1628 ◽  
Author(s):  
Oldřich Pytela ◽  
Ondřej Prusek
Keyword(s):  
Hydrogen Bond ◽  
Benzoic Acid ◽  
Electron Pair ◽  
Dissociation Constants ◽  
Substituent Effects ◽  
Reaction Centre ◽  
Benzoic Acids ◽  
Hydrogen Bond Formation ◽  
Latent Structures ◽  
Substituted Benzoic Acids

Three model compounds have been selected to study the relationship between ortho and para substitution: benzoic acid, phenol, and aniline. Sixteen substituents have been chosen involving also those capable of potential interaction between ortho substituent and the reaction centre. For the combinations given, literature presents 25 pairs of data obtained by measuring a particular process for both the ortho and para substituted derivatives. The missing dissociation constants of 16 ortho substituted benzoic acids in water and ethanol and 16 para substituted benzoic acids in dimethyl sulfoxide and pyridine have been measured by potentiometric titration. The data matrices were submitted to analysis by the methods of projection of latent structures (PLS) and principal component analysis (PCA). It has been found that the substituent effects from ortho and para positions have the same character unless the ortho substituents interact with the reaction centre. Such interactions can change the experimentally found value by as much as 20% of its magnitude. The most significant interaction is a hydrogen bond formation. Out of the three models studied the most extensive interactions are present in benzoic acid, whereas almost none were observed in aniline. The capability of donation of electron pair to a hydrogen bond decreases in the substituent series COCH3 > SO2CH3 > NO2. The capability of donation of proton to a hydrogen bond with electron-pair donor decreases in the substituent series OH > NHCOCH3 ≈ SH > NH2 > SO2NH2.

Reactivity of p-Substituted Benzaldoximes in the Cleavage of p-Nitrophenyl Acetate: Kinetics and Mechanism

2004 ◽  
Vol 69 (2) ◽  
pp. 397-413 ◽  
Author(s):  
Jan Pícha ◽  
Radek Cibulka ◽  
František Hampl ◽  
František Liška ◽  
Patrik Pařík ◽  
...  
Keyword(s):  
Dissociation Constants ◽  
Substituent Effects ◽  
Statistical Modelling ◽  
Reaction Centre ◽  
Deprotonated Form ◽  
Rate Limiting Step ◽  
Reaction Constant ◽  
Reaction Constants ◽  
Intramolecular Hydrogen ◽  
The Given

Eleven p-substituted benzaldoximes (p-XC6H4CH=NOH, where X = H, CH3, CF3, F, Cl, Br, OCH3, N(CH3)2, COOCH3, CN, NO2) have been synthesized and their dissociation constants determined in 10% (v/v) aqueous dioxane at 35 °C. Under the same conditions, the pseudo-first order rate constants kobs of their reactions with p-nitrophenyl acetate (PNPA) were measured at pH values from 7.8 to 10.8 and at concentrations coxime ranging from 0 to 4.00 × 10-3 mol l-1. The kinetic model and mechanism of the said reaction was proposed by means of mathematical statistical modelling of the dependences of kobs on pH and coxime. The mechanism involves a pre-equilibrium (k-1/k1) in which PNPA forms a tetrahedral intermediate (THI) with the deprotonated form of oxime. In the given medium, THI is in equilibrium with the non-reactive conjugated acid THIH (dissociation constant Ka,THIH) which is stabilized by intramolecular hydrogen bond. Depending on pH, the rate-limiting step consists either in formation of THI from educts (pH < pKa,oxime) or in its spontaneous (k2) and oxime-catalyzed (k3, general acid catalysis) decomposition to products (pH > pKa,oxime). Evaluation of substituent effects on dissociation constants (Ka,oxime) of the oximes showed that there is no direct conjugation between the substituent and the reaction centre (the found reaction constant ρ(Ka,oxime) = 0.91). The transmission coefficient of the transfer of these effects through C=N-O grouping corresponds approximately to one bond. The reaction constants in the Hammett equation obtained from the regression model are: ρ(k-1Ka,THIH/k1) = 1.29, ρ(k2Ka,THIH) = 0.20 and ρ(k3Ka,THIH) = 0.67. These reaction constants have been discussed with the regard to the reaction mechanism suggested.

Chemometric Analysis of Substituent Effects. VIII. Alternative Interpretation of Substituent Effects (AISE)

1995 ◽  
Vol 60 (9) ◽  
pp. 1502-1528 ◽  
Author(s):  
Oldřich Pytela
Keyword(s):  
Multiple Bond ◽  
Substituent Effects ◽  
Alternative Interpretation ◽  
Class I ◽  
Reaction Centre ◽  
Correlation Equations ◽  
Class Iii ◽  
Substituent Constant ◽  
Chemical Models ◽  
The Individual

Alternative interpretation of substituent effects (AISE) starts from the presumption that a substituent only possesses a single property described by a single substituent constant. This property is transmitted to the reaction centre by three different ways depending on the interaction type in the triad reaction centre - basic skeleton - substituent. For interpretation it is substantial whether or not the substituent has p electrons at the atom adjacent to the basic skeleton. If it has none, the substituent belongs to class I and operates only by its basic effect described by the mentioned single substituent constant. Substituents of class II possess a free electron pair at the atom adjacent to the basic skeleton, and those of class III have a multiple bond between the first and the second atoms which is polarized in the direction from the basic skeleton. Substituent effects in class I are described by a substituent constant identical with σI constant. Substituents in classes II and III show additional effects proportional to the same constant. Hence, a separate treatment of substituent effects in the individual classes provides three straight lines intersecting in a common point. Mathematically, the description of substituent effects in this approach is expressed by a family of lines with a single explaining variable. The point of intersection, which is referred to as the iso-effect point, is not identical with the classic standard substituent - hydrogen - but is near to CN substituent. The approach given has the advantage of adopting a single substituent constant whose scale can be adjusted relatively precisely. Its drawback (like in the case of the correlation equations derived from the principle of separation of substituent effects) lies in a more extensive set of substituents needed for a correlation. The AISE principle has been applied to 318 series of experimental data describing effects of 32 substituents in a large variety of chemical models (aliphatic, alicyclic, aromatic, heteroaromatic, with or without direct conjugation between reaction centre and substituent) in both chemical reactions and equilibria. A comparison with two other correlation relations with two and three substituent constants for interpretation of substituent effects based on the principle of separation of the individual substituent effects showed that the closeness of AISE based correlations is comparable with that of the correlation equations currently used. It was somewhat less successful in the models with direct conjugation between reaction centre and substituent but the AISE principle can be used even in these cases.

Chemometrical Analysis of Substituent Effects. IV. Additivity of Substituent Effects in Dissociation of 3,5-Disubstituted Benzoic Acids in Organic Solvents

1994 ◽  
Vol 59 (7) ◽  
pp. 1637-1644 ◽  
Author(s):  
Oldřich Pytela ◽  
Jiří Kulhánek ◽  
Miroslav Ludwig
Keyword(s):  
Organic Solvents ◽  
Dissociation Constants ◽  
Quantitative Description ◽  
Substituent Effects ◽  
Benzoic Acids ◽  
Hammett Equation ◽  
Specific Solvation ◽  
Reaction Constant ◽  
Substituent Constants ◽  
The Individual

Ten 3,5-disubstituted benzoic acids have been synthesized containing all possible combinations of the following substituents: CH3O, CH3, Cl/Br, NO2. The dissociation constants of these acids have been measured in seven organic solvents (methanol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, 1,2-dichloroethane). It has been found that the effect of disubstitution is smaller than that due to interaction of substituents or their solvation and represents only about 0.2% of the effect caused by the individual substituents. The additivity in 3,5-disubstitution is about 2 - 3 times as good as that in 3,4-disubstitution. The quantitative description of substituent effects at the 3 and 5 positions is additive within the range of validity of the Hammett equation irrespective of the type of the substituent constants adopted, the addition of the multiplicative term being statistically insignificant. The solvent effect on 3,4- and 3,5-disubstituted derivatives is somewhat different at the same value of the reaction constant, due predominantly to the specific solvation of the 4-CH3O and 4-NO2 groups.

Chemometric Analysis of Substituent Effects. VI. A Study of ortho Effect in Dissociation of 2,6-Disubstituted Benzoic Acids

1995 ◽  
Vol 60 (5) ◽  
pp. 829-840 ◽  
Author(s):  
Jiří Kulhánek ◽  
Oldřich Pytela
Keyword(s):  
Latent Variables ◽  
Dissociation Constants ◽  
Additive Model ◽  
Substituent Effects ◽  
Point Of View ◽  
Steric Effects ◽  
Benzoic Acids ◽  
Hammett Equation ◽  
Substituent Constants ◽  
Substituted Benzoic Acids

Ten 2,6-disubstituted benzoic acids have been synthesized containing all possible combinations of the following substituents: CH3, OCH3, Cl, and NO2. The dissociation constants of these acids have been measured by potentiometric titration in methanol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, and 1,2-dichloroethane. The experimental data obtained together with the pK values of 2-substituted benzoic acids in the same solvents have been analyzed from the point of view of ortho effect and additivity of disubstitution. The mutual interaction between substituents was found to represent only 0.12% of the variability due to substitution and to contribute to the overall variability of data less than the interaction between the substituent and solvent by a factor of about 13. The analysis of data by the method of multiple linear regression revealed a contribution of steric effects beside the effects transmitted through the aromatic skeleton. The 2- and 6-substituents effects are additive within the validity of the Hammett equation, and an addition of a multiplicative term describing interactions between the substituents is statistically insignificant. Nonlinear regression has been adopted in the additive model with multiplicative term to find the inner substituent constants including all the effects of substituents from ortho position: the term describing the interaction between 2- and 6-substituents is statistically insignificant in this model. An application of the method of conjugated deviations revealed two statistically significant latent variables. The first one explains 91.5% of the variability of data and is connected with the substituent effects transmitted through the aromatic skeleton. The second one explains 7.5% of variability of data and predominantly reflects the steric effects of substituents.

Chemometrical Analysis of Substituent Effects. III. Additivity of Substituent Effects in Dissociation of 3,4-Disubstituted Benzoic Acids in Organic Solvents

1994 ◽  
Vol 59 (3) ◽  
pp. 627-638 ◽  
Author(s):  
Oldřich Pytela ◽  
Jiří Kulhánek ◽  
Miroslav Ludwig ◽  
Václav Říha
Keyword(s):  
Dimethyl Sulfoxide ◽  
Organic Solvents ◽  
Dissociation Constants ◽  
Substituent Effects ◽  
Proton Donor ◽  
Benzoic Acids ◽  
Correlation Equations ◽  
Hammett Equation ◽  
Validity Range ◽  
Reaction Constants

Sixteen 3,4-disubstituted benzoic acids (with all combinations of CH3O, CH3, Cl/Br, and NO2 substituents) have been synthesized and their dissociation constants measured in seven organic solvents (methanol, acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile, pyridine, 1,2-dichloroethane). The effect of disubstitution and the validity of additive correlation relationships based on the Hammett equation have been analyzed by means of the analysis of variance, comparison of overall residual standard deviations of correlation equations of additive and additive multiplicative type, and application of the Hammett equation with internal (latent, defined in various ways) parameters and external (taken from literature) parameters describing the substituent effects. The effect of disubstitution has been found to be additive and describable within the validity range of the substituent constants adopted - by applying the additivity principle without any additional correction for interactions between the two substituents. The same conclusion has been drawn from the comparison of overall residual deviations in correlation equations for mono- and disubstituted derivatives. The analysis of differences between the reaction constants of the Hammett equation applied to mono- and disubstituted benzoic acids has shown that in organic solvents the solvation of substituents makes various contributions. The substituent influence is stronger in polar aprotic solvents (acetone, dimethyl sulfoxide, dimethylformamide, acetonitrile) than that in the protic, basic, and less polar ones in which the stabilization by hydrogen bond becomes important, the role of proton donor being played either by the solvent itself (methanol) or by its conjugated acid (pyridine) or by a molecule of the dissociating acid as a consequence of homoconjugation (1,2-dichloroethane).

Substituent Effects on the Base-Catalysed Hydrolysis of Phenyl Esters of ortho-Substituted Benzoic Acids

2001 ◽  
Vol 66 (5) ◽  
pp. 770-784 ◽  
Author(s):  
Ingrid Bauerová ◽  
Miroslav Ludwig
Keyword(s):  
Substituent Effects ◽  
Uv Spectrophotometry ◽  
Reaction Centre ◽  
Benzoic Acids ◽  
Model Compounds ◽  
Pseudo First Order Reaction ◽  
Reaction Conditions ◽  
Substituted Benzoic Acids ◽  
Kinetics Of ◽  
Hydrolysis Of

Fourteen model phenyl esters of 2-substituted benzoic acids were synthesised. Structures and purity of model compounds were confirmed by 1H and 13C NMR spectroscopy, as well as by HPLC and elemental analysis. Kinetics of base-catalysed hydrolysis of model phenyl esters occurring by the BAc2 mechanism were measured by UV spectrophotometry in 50% (v/v) aqueous dimethyl sulfoxide solutions at 25 °C under pseudo-first-order reaction conditions (c(NaOH) = 0.001-1.0 mol l-1). Linear relation between J-E and log kobs with the slope close to unity was found for all model compounds. Neither one-parameter nor multiparameter Hammett-type description of variability of experimental data obtained for phenyl esters of 2-substituted benzoic acids was found. Two groups (conjugating and non-conjugating) were created by division of ortho-substituents in ortho-position using the AISE theory, based on their interaction with the reaction centre.

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