Constant steric substituent

Figure 5. Logarithm of the relative activity of 3-alkyl-pyrocatechols (line 1) and 3,5-dialkylpyrocatechols (lines 2, 3) vs. the substituent steric constants Es...

A regular decrease in the half-wave potentials for the hydroquinone series is caused by the substituents in position 2 its shift bears a linear relationship to the substituent steric constants (20). It is apparent from the relationship of the logarithm of relative activity to the half-wave potentials E0 (Figures 2 and 3) that the relationship in the entire series of the derivatives is not linear. The activity declines with the half-wave potentials in comparison with hydroquinone and derivatives substituted by methyl, ethyl, and isopropyl groups with derivatives substituted by tertiary alkyl groups, however, a reverse relationship was found, as was... 

This parameter is often used as a substituent steric constant in - Hansch analysis. In order to put the molar refractivities of the substituents on approximately the same scale as the - hydrophobic substituent constants Jt, the substituent MR values are often scaled down by the factor 0.1. 

It is obvious, fipom some of the series of substituents in Table 7-11, that the steric constant reflects intuitive notions of group size, and Taft " pointed out close parallels with van der Waals radii. For asymmetrical groups a single van der Waals radius cannot be defined, and the situation is complicated by conformational flexibility. Nevertheless, empirical relationships can be established, and Kutter and Hansch gave Eq. (7-55),... 

Hansch, C., Leo, A. (1979) Substituent Constants for Correlation Analysis in Chemistry and Biology. Wiley-Interscience, New York. Hansch. C., Leo, A. J., Hoekman, D. (1995) Exploring QSAR, Hydrophobic, Electronic, and Steric Constants. ACS Professional Reference Book, American Chemical Society, Washington, D.C. 

The works of Maurel and Tellier 82), Rhzicka and Cerveny 83, 84), Litvin, Freidlin, and Tilyaev (55) and Brown and Ahuja 86), who have used extensive series of alkenes, confirmed the Lebedev s rule. With 1-alkenes C -Cn) on palladium, platinum, and rhodium catalysts, the initial reaction rate decreased with the length of the chain, and with Pd and Pt a hnear dependence on the number of carbon atoms was obtained 83) (series 53). An example of the influence of the number of substituents on the carbon atoms of the double bond is shown in Fig. 4. It is evident that the mere presence of the substituent is more important than its nature. However, this secondary factor has been accounted for by using the sums of the Taft polar (7 or steric constants for all substituents on C=C. Cerveny and Rfizicka 84) have found excellent linear relationships between the initial hydrogenation rate of 15 alkenes on 3 different Pt catalysts and 2 (series 54), and... 

Nieuwstad, Klapwijk, and van Bekkum (105) have added to the knowledge of aromatic hydrogenation by their study of the influence of alkyl substituents in the 1 and 2 positions of naphthalene on the rate. Tetrahydro-naphthalenes were the products of hydrogenation over palladium at 80°C. The selectivity of the reaction was also followed and expressed as the ratio of the rate constants for the saturation of the unsubstituted and substituted rings, respectively. Steric effects play an important role, and, beside steric hindrance by the bulky substituents, steric acceleration also has been observed, the latter being caused by a release of the strain between the 1-alkyl group and hydrogen in position 8. 

For characterization of the steric and electronic contributions of the substituents, the constant c was introduced and defined as the intercept difference for the basic tetrahydrooxazine system 389 and the compound in question. A positive c value indicates stabilization a negative c value means a destabilizing effect of the substituents (Table VIII). 

Regression analysis is currently the most widely used correlative method in drug design. This is because it simplifies problems within a set of compounds by using a limited number of descriptors, notably the Hansch hydrophobic constant n, Hammet constants, or other electronic characteristics of substituents, and the Taft steric constant Eg. 

An example for such a parameter is the steric constant Sb which can be used as an alternative to E, or o. This constant has been derived on the assumption that the steric effect of a substituent is mainly due to branching24 . By regression... 

These Es parameters estimated by Eq. 4 for hetero atom substituents can be combined with those originally developed for various alkyl groups as a set of steric constants for QSAR studies of aromatic systems 6). Thus, apart from the original definition for the intramolecular steric effect, the combined set of Es parameters is able to represent intermolecular steric effects as well. The original Taft E, values for unsymmetrical alkyl groups seem to represent effective steric dimension of the groups which is scaled on the same standard as those for symmetric monoatomic substituents where the effective dimension coincides with the van der Waals radius. 

For the characterization of the electronic and steric effects of substituents on the catalytic properties of tertiary aliphatic amines, Bogatkov et al. 71,72) proposed a correlation between the steric hindrance of R1R2R3N amines by means of the En(En) constants which are identical with steric constants ES(E9) according to Taft for isosteric hydrocarbon substrates R1 R2R3C. On this basis, they proposed the following linear correlation for the nucleophilic activity of amines ... 

If steric effects of substituents do not affect the formation of the complex and A (e.g. TCNE) is constant, coefficients a and b in equation 19 depend on D only130. In approximation 18, hvcr and Ip depend on the inductive and resonance effects of the X substituents for constant D128,129. As the donor properties of X become stronger, the HOMO energy increases and the hvcr and Ip values decrease. 

Bowden-Wooldridge steric constant -> steric descriptors (O number of atoms in substituent specific positions)... 

Both the b and k values were estimated by regression analysis from the Taft steric constant Es and the Charton steric constant in an iterative procedure using 96 substituents. The k values are equal to 1.0 for the second period elements, except for the fluorine atom (k = 0.8) k = 1.2,1.3, and 1.7 for the third, fourth, and fifth period elements, respectively. 

Steric substituent constants (or steric substituent parameters) are descriptors of substituent groups that measure the substituent steric effects on the reactivity centres of a molecule, based on differences in the rate and equilibrium constants of selected chemical reactions. 

The Taft steric constant Es was proposed as a measure of steric effects that a substituent X exerts on the acid-catalyzed hydrolytic rate of esters of substituted acetic acids XCH2COOR [Taft, 1952], The basic assumption is that the effect of X on acid hydrolysis is purely steric, as the reaction constant q for acid hydrolysis of substituted esters is close to zero. 

The Fujita steric constant Ef [Fujita et al, 1973 Fujita and Iwamura, 1983] was defined to evaluate the global steric effect for branched alkyl substituents of the type CR1R2R3 by the following correlation equation ... 

Values of the Taft steric constants are collected in Table S-2 for some substituents. A Model of the Frontier Steric Effect is a theoretical approach recently proposed to estimate the Taft steric constant of substituents on the basis of the fundamental characteristics of the constituent atoms [Cherkasov and Jonsson, 1998b] ... 

Directly obtained from the van der Waals radii is also the Bowden-Young steric constant R [Bowden and Young, 1970]. This measures the steric hindrance of the substituent, calculated as the distance (in A) from the aromatic carbon atom to which the substituent is bonded to the periphery of the van der Waals radius of the substituent, using known distances and van der Waals radii, and referred to that of the unsubstituted compound, i.e. Ru = 0. 

The Idoux steric constant A6 is defined as the change in the six-position number, i.e. the difference between the six-position number of the X substituent of the ester XCOOX and the six-position number of the same substituent X in the part X of the ester [Idoux et al, 1973 Idoux et al, 1977],... 

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