Steric Substituent Constants Research Articles

A multinuclear NMR spectroscopy study of alkoxysilanes

17O, 29Si, and 13C NMR spectra of more than 100 mono-, di-, tri- and tetra-alkoxysilanes R 4− n Si(OR′) n ; R = C n H 2 n+1 , Ph, CH 2Cl, CH 2Br; R′ = C n H 2 n+1 , CH 2Ph, CH 2CH 2Cl, CH 2CHCH 2, CH 2CCH, CH 2CF 3. (CH 2) 3Cl, (CH 2) 3CN have been studied. Linear relationships between the chemical shifts of 17O, 29Si, 13C in alkoxysilanes and the inductive and steric constants of substituents R and R′ were observed. Different transmission of electronic effects along the SiO bond in various directions was revealed by means of 13C, 29Si, 17O NMR spectroscopy and correlation analysis. The results are discussed in terms of ( pd) π-bonding between the oxygen and silicon atoms in compounds containing an SiO bond.

Quantitative structure-activity relationships of herbicidal N′-substituted phenyl- N-methoxy- N-methylureas

Relationships between three types of herbicidal activity of N′-substituted phenyl- N-methoxy- N-methylureas and substitution at the benzene ring were analyzed by the Hansch-Fujita method. First, the Hill inhibitory activity was correlated with electronic (σ) as well as hydrophobic (π) substituent constants. The existence of an optimum value of hydrophobicity for substituents was suggested to reach the target site of action. Second, bliaching activity observed for the 3-substituted but not for 4-substituted compounds was correlated with π, σ, and steric substituent constant, E s. Third, the postemergent herbicidal activity was shown to correlate linearly with the Hill inhibitory activity, pI 50, and hydrophobic parameter, π.

COMPLEXING, REDOX AND EXTRACTIVE PROPERTIES OF CYCLIC AND ACYCLIC DERIVATIVES OF PHOSPHORUS DITHIOACIDS

Abstract Various types of acyclic and cyclic derivatives of phosphorus dithioacids form stable chelate complexes with nickel(II), cobalt(II) and silver(I) ions. Stability constants of these complexes and redox potentials of the systems disulfide/dithioacid have been determined. It has been shown that for each individual type of complex with dithiophosphoric, dithiophosphonic or dithiophosphinic ligands stability depends on the steric nature of the substituents at phosphorus. Correlations between the logarithm of stability constants and the sum of steric constants of substituents exist in these series. It is true also with regard both to a variation of redox potentials and reduction rate constants for copper(II) complexes. Phosphorus dithioacids with cyclic substituents form less stable metalion complexes and can be used as selective extraction reagents.

QSAR for Cholinesterase Inhibition by Organophosphorus Esters and CNDO/2 Calculations for Organophosphorus Ester Hydrolysis

AbstractQuantitative structure‐activity relationships were derived for acetyl‐ and butyrylcholinesterase inhibition by various organophosphorus esters. Bimolecular inhibition rate constants correlate well with hydrophobic substituent constants, and with the presence or absence of cationic groups on the inhibitor, but not with steric substituent constants. CNDO/2 calculations were performed on a separate set of organophosphorus esters, RR′P(O)X, where R and R′ are alkyl and/or alkoxy groups and X is fluorine, chlorine or a phenoxy group. For each subset with the same X, the CNDO‐derived net atomic charge at the central phosphorus atom in the ester correlates well with the alkaline hydrolysis rate constant. For the whole set of esters with different X, two equations were derived that relate either charge and leaving group steric bulk, or orbital energy and bond order to the hydrolysis rate constant.

Nucleophilic reactions of fluoroolefins.IV. Regioselectivity in the reactions of 1-phenylpentafluoropropenes with alkyllithium reagents

Reactions of 1-phenylpentafluoropropenes 1a – c with a number of alkyllithium reagents were investigated in detail. In all cases mixtures of 1-alkly-1-phenyltetrafluoropropenes 2 and 2-alkyl-1-phenyltetrafluoropropenes 3 were obtained. The ratio of products 2 and 3 is strongly influenced by both the electronegativity of the benzene ring substituents and the bulk of the alkyl group of the alkyllithium reagents. The increase of both of these factors favours formation of 2-alkyl-substituted alkenes 3 with a reduced yield of 1-alkyl-substituted alkenes 2 . The influence of the benzene ring substituents in alkenes 1 obeys the Hammett type correlation, while the influence of the bulk of the alkyllithium reagents exhibits good relationships with the Fellous and Luft scale of steric substituent constants E x s ; no linear correlation with other scales of steric constants was found. Overall regioselectivity, in the reaction of 1-phenylpentafluoropropenes 1 with alkyllithium reagents, considering both the influence of the benzene ring substituents and steric factors, is expressed by the Pavelich-Taft type equation. Observed direction of the influence of the bulk of the alkyllithium reagents on the ratio of products 2 and 3 is interpreted in terms of steric strains influencing the geometry and free energy of the supposed intermediates involved in these reactions.

Steric effects on the formation of alkyl radicals and alkyl carbenium ions

In order to determine the variation of the steric effect with branching on the formation of alkyl radicals and alkyl carbenium ions, logarithms of rate constants for formation were correlated with the branching equation. Significant correlations were obtained for all the sets studied. The results of the correlations are (1) the composition of the alkyl steric effect as a function of branching is highly variable both for alkyl radical and for alkyl carbenium ion formation. No single steric substituent constant could possibly account for all the data. (2) The relative importance of branching at C2 to that at C1 is a linear function of the amount of branching in the leaving group. This is true for both alkyl radical and alkyl carbenium ion formation. (3) Whereas branching at C1 and C2 causes steric acceleration in the formation of both alkyl radicals and alkyl carbenium ions, branching at C3 results in steric deceleration. The results demonstrate the utility of the branching equation in the study of the steric effects of alkyl groups. It is capable of representing the complete range of alkyl steric effects, and can detect a change from steric acceleration to steric deceleration due to branching at different carbon atoms of the same alkyl group. The expanded branching equation has been shown to be useful in the determination of the variation of alkyl steric effect with the order of branching at a given carbon atom. Radical formation is much more sensitive to a second branch at C1 than is carbenium ion formation.

Lead optimization: quantitative structure-activity relations

The optimization of bioactivity in a series is one of the aims in the design of crop protection chemicals. The approach of Hansch is the most developed model in this area. Here electronic, hydrophobic, and steric substituent constants are used for a quantitative analysis of the possible ways in which substitution may modulate bio- activity in a congeneric series (quantitative structure-activity relations; q.s.a.r.). An essential prerequisite of this approach is the availability of reliable substituent constants. The present state of the art is reviewed, with emphasis on steric parameters where several new approaches have been developed recently, and based upon recent q.s.a.r. studies from the literature as well as from our own laboratories. Q.s.a.r. may lead to significant regression equations, which can be used in different ways: the correlation between pesticidal activity and substituent properties provides the possibility of predicting the most favourable member of the class concerned. The resulting equations can also be given a physical interpretation in terms of the mode of action of the series studied. The scope and limitations of these applications are discussed.

Cautions regarding the physical interpretation of statistically based separation of the ortho substituent effect into inductive, mesomeric, and steric components—II : Acid catalysed esterification of benzoic acids by methanol and cyclohexanol

In order to attain a better insight into the composition of Taft E s o, constants the rate data of hydrion catalysed esterification of both m,p-substituted and o-substiluted benzoic acids by cyclohexanol and methanol were submitted to a statistical analysis using inductive mesomeric and steric substituent constants and various dummy variables differently structured. Furthermore a principal component analysis with subsequent identification of the first principal component via multiple regression analysis was applied. It has been demonstrated that in the reactions of m,p substituted compounds some substituents capable of exerting strong mesomeric effects show peculiar characteristics deviating from the general trend. Since the same result was obtained in the correlations of ortho substituted benzoic acids this effect was taken into account using an appropriate dummy variable which in all cases improved the multiple coefficient of determination. It is concluded that the esterification rates of the ortho substituted compounds depend essentially upon inductive and steric effects (taken away OMe OEt and NO 2) as proposed by Taft. While generally the E s o values may be regarded as some measure of a steric effect, this is not true for the methoxy and ethoxy groups.

Reactivities of, N-Alkylcitraconimides in the Radical Copolymerizations with Styrene or Methyl Methacrylate

The radical copolymerizations of N-alkylcitraconimide (RCI: R=C2H5, n-C3H7, i-C3H7, n-C4H9, i-C4H9, t-C4H9, n-C6H13, C6H5CH2) (M1) with styrene (ST) (M2) or methyl methacrylate (MMA) (M2) were carried out at 60°C, using azobisisobutyronitrile as the initiator in tetrahydrofuran in order to clarify the substituent effect on the copolymerizations. From the results obtained, the monomer reactivity ratios and the Q1 and e1 values were determined. It was found that the relative reactivities (1/r2) of RCI toward attack of a polystyryl radical could be correlated only by the polar-substituent constant (σ*) of the alkyl group in RCI, not by the steric-substituent constant (Es) in Taft’s equation: log (1/r2)=ρ*σ*+δEs. According to the above equation, the ρ* and δ values were obtained as 0.34 and 0, respectively, in the RCI–ST system. On the other hand, in the RCI–MMA system, both the ρ* and δ values were 0; that is, neither the polar nor the steric character of alkyl group in RCI contributed to the relative reactivities (1/r2) of the RCI toward attack of a poly(MMA) radical. It was also observed that both the Q1 and e1 values for RCI were independent of Taft’s σ* -substituent constant.

Torsional angles in N-substituted benzamides and related compounds by carbon-13 N.M.R. chemical shifts

The torsional angles in 30 N-substituted benzamides and related compounds have been estimated by the use of the 13C substituent chemical shifts of the meta and para carbon atoms. Steric interaction between the N-substituted groups and the ortho hydrogen atoms of the benzene ring is the major determinant of non-planarity in these systems. A linear relationship between steric substituent constants of the N-substituted groups of some benzamides and the torsional angles is proposed. Dynamic processes involving rotation about the C-N bond, nitrogen inversion and ring inversion contribute a dynamic steric effect to the overall steric interaction. The preferred conformations of some N-substituted groups is also discussed.

Steric effect of o-organosilyl substituents in dimerization of silicon-containing phenoxyl radicals

1. The stability of silicon-containing phenoxyl radicals depends on the degree of steric shielding of the reaction center, responsible for the dimerization, by the trialkylsilyl groups. 2. A linear relationship exists between the logarithms of the relative destruction rate constants of silicon-containing phenoxyl radicals and the sum of the steric constants of the alkyl substituents on the silicon atom. 3. The conversion of silicon-containing phenoxyl radicals to tetrasubstituted disiloxybiphenyls proceeds via the dimerization of the radicals to theα-ketomethyl form at the carbon atoms to which the trialkylsilyl groups, which migrate to the oxygen, are attached.

First thermodynamic dissociation constants of 5,5-disubstituted barbituric acids in water at 25 °C. Part 2. Structure–reactivity relationships (SRR). Linear free energy relationships which correlate C(5)-substituent effects with acid strength

First thermodynamic dissociation constants have been examined for the effect of C(5)-substituents on acid strength in a series of 14 5,5-disubstituted barbituric acids (Ia; R1= Me, R2= Me, Et, Pri or Ph; R1= Et, R2= Et, Pri, Ph, 3-NO2C6H4 or 4-NO2C6H4; R1= allyl, R2= Pri; R1= R2= allyl, Ph, Br, or Cl). Taft polar substituent constants, σ*, have been calculated for a number of groups. Steric factors have been investigated as an additional effect on reactivity in these derivatives: Taft steric substituent constants,Es, and the Newman six-number measure of steric effects have been used. A linear free-energy relationship (LFER) is established by multiple correlation, with the independent variables polar and steric substituent constants, and its significance for the reaction series is discussed.

Studies on 13C magnetic resonance spectroscopy. XVI. On the introduction of the entropy term .DELTA.S.DEG. for the elucidation of Ipso- and .ALPHA.-13C substituent-induced chemical shifts by an empirical approach.

^ C Substituent-induced chemical shifts (SCS) at the ipso and α positions of monosubstituted benzenes or methanes can be expressed by a linear combination of three kinds of empirical parameters, σi, σπ, and ΔS°. ΔS° represents the difference of the entropy (due to the substituent) between the standard entropy S°of the substituted compound and that of the parent one. The following results were obtained. SCSipso=63.9·σi-3.9·σπ+0.6ΔS°+-0.4·ΔS°-+3.8 (r=0.927, SD=4.9 ppm, n=13) SCSα=162.1·σi-10.1·σπ+1.2·ΔS°+-0.3·ΔS°-+2.3 (r=0.976, SD=4.9ppm, n=13) where + and - subscripts of ΔS° indicate electron-donating and -attracting groups, respectively. This treatment is also applicable for elucidation of the 13C SCS of analogous positions of many substituted aromatics and heteroaromatics, including ortho-disubstituted benzenes, and provides a reasonable and explicit chemical basis for the origin of the 13C SCSipso and SCSα. The same treatment also provides an explicit chemical basis for Mulliken's electronegativity scale and the steric substituent constant, Es.

Possible connection between lipophilicity and steric substituent constants

AbstractThe steric constants Es and ν have the greatest chance of being independent of lipophilic substituent constants. There is a high probability among hydrocarbon substituents that the steric constants correlate with the lipophilic ones, while in the case of polar substituents the probability is low.

Quantitative Structure-Activity Relationships and Carminative Activity II: Steric Considerations

The unexplained variation in the relationships between carminative activities and octanol-water distribution coefficients of various classes of compounds was explained. The steric substituent constant (Es) value, van der Waals volume, and molecular connectivity were introduced into a previously derived correlation. Each parameter brought about an improvement, and molecular connectivity was the most successful. Correlations containing molecular connectivity terms explained the excess variation. The results were in agreement with a mechanism in which carminative activity depended on the availability of the oxygen atom in the functional group of the molecule and was reduced when the substituent attached to the oxygen hindered the interaction between the oxygen atom and the receptor.

Correlation of activation energies of radical–molecule metathesis reactions with enthalpic, polar, and steric parameters

AbstractIt is shown that the activation energies E oF chlorine atom abstraction by cyclohexyl radicals and hydrogen atom abstraction by Cl atoms from polychloroalkanes can be correlated with the bond dissociation energies D and the Taft polar and steric substituent constants σ* and Es by the expression: where ΔE and ΔD represent the differences between the E and D values of a given substrate and those of a reference compound (CH3 substituted substrate) and α, ρ, and δ are the corresponding correlation coefficients. The use of this expression allows quantitative evaluation of the relative contribution of the various factors affecting the activation energies of these reactions and estimation of related thermochemical data.

Structure and reactivities of alkyl vinyl ketones in their radical copolymerizations with styrene

AbstractTo clarify the effect of the alkyl substituents in alkyl vinyl ketones (RVK) on their radical copolymerizations, the copolymerizations of six such alkyl vinyl ketones with styrene were investigated. From the results obtained, the relative reactivities of RVK toward the polystyryl radical were correlated with the Taft equation: log (1/r1) = ρ*σ* + δEs, in which σ* and Es are polar and steric substituent constants, respectively, and ρ* and δ are reaction constants. The values of ρ* and δ obtained were 0.40 ± 0.05 and 0, respectively. It was observed that the Q and e values obtained for RVK increased with increasing of σ* values, and that both relative reactivities and Q,e values of methyl vinyl ketone also increased with increasing of the ET values of the solvents used. From the spectral determination of the RVK monomers, it was also found that their n–π interactions were related to the copolymerization reactivities. Furthermore, the radical polymerization of tert‐butyl vinyl ketone (t‐BVK) with azobisisobutyronitrile (AIBN) was investigated, and its rate Rp was found to be expressed by the following rate equation: Rp = k [AIBN]0.5[t‐BVK]1.0.

Solvent effects on radical polymerization of cyclododecyl acrylate, 1. Homopolymerization

AbstractThe radical homopolymerization of cyclododecyl acrylate at 60°C in benzene, tetrahydrofuran, or dioxane was studied and compared with that of cyclohexyl acrylate. The difference in the polymerization rates of the acrylates could not be interpreted in terms of the polar and steric substituent constants of ester groups in Taft's equation. Remarkable solvent effects on the polymerization rates for both acrylates were also found in the same manner and ascribed to the polar nature of the used solvents.

Kinetic comparison of the relative susceptibility to steric hindrance of an intra- and an inter-molecular cleavage of the ester bond in a series of 2- and 4-carbamoylphenyl esters of 2,4,6-trialkylated benzoic acids

The rates of intramolecular nucelophilic attack by the amide group and of intermolecular nucleophilic attack by hydroxide ion on the ester carbonyl group of a series of carbamoylphenyl esters of 2,4,6-trialkylated benzoic acids have been determined. Both the intra- and inter-molecular processes showed a closely similar response to progressive increase of steric hindrance about the ester carbonyl group. An excellent correlation of rates along both reaction series with the steric substituent constant (Es) derived by Taft from hydrolyses of esters of aliphatic acids indicated that progressive decoupling of the aromatic ring and the ester group with increasing 2,6-substitution was negligible (except when the substituent is hydrogen).

Salt‐catalyzed addition reaction of monoepoxides with philosamia cynthia ricini and bombyx mori silk fibroins

AbstractThe heterogeneous addition reaction of various monoepoxides with silk fibroins of Philosamia cynthia ricini and Bombyx mori was investigated at 45–75°C by use of aqueous solutions of various salts as padding catalysts. The effects of salt on the epoxide–silk fibroin reactions were attributed mainly to the nucleophilicity of the anions and also to the acidity or the electronegativity of the cations. The effect of the substituent of the epoxide on the add‐ons was elucidated by the modified Taft equation, (log W − log W0)/σ* = ρp + ρsEs/σ*, where W0 and W are the add‐ons for the reaction of a given compound and of its substituted derivatives, σ* and Es are the polar and the steric substituent constants, ρp and ρs are the polar and the steric reaction constants, respectively. Histidine, lysine, arginine, tyrosine, serine, and acidic amino acids were found to react. The reactivity difference between Philosamia cynthia ricini and Bombyx mori fibroins towards the epoxide was discussed in the light of the observed phenomena.