Ortho substituent effect

Taft also defined the Es parameter for aromatic ortho substituents in a fashion similar to Eq. 3 4). Charton advanced evidence that the original value is linked rather with the polar substituent effect despite the original definition51. We have shown that the set of Es parameters defined by Eq. 3 and 4 can also be used to rationalize the steric effect of aromatic ortho substituents 7). In general, the ortho substituent effect in biological activity is analyzable as linear combination of substituent parameters 8) (Eq. 5),... 

Sotomatsu, T., Nakagawa, N., Fujita, T. (1987) Quantitative structure-activity studies of benzoylphenylurea larvicides. IV. Benzoyl ortho substituent effects and molecular conformation. Pestic. Biochem. Physiol. 27, 156-164. 

Despite their associated problems, attempts have been made to incorporate results from ortho substituents in free energy correlations. It might be necessary, for example, to predict physico-chemical properties of a compound with an ortho substituent which acts as a drug or is a putative intermediate in a proposed mechanism. Quantitation of the ortho substituent effect requires that both steric and polar effects be considered. The ortho effect can be fitted to a modified version of the Pavelich-Taft equation (Chapter 2, Equation 15) where the values... 

Dash, S.C. and Behera, G.B. (1980) A new steric parameter to explain ortho-substituent effect. Indian J. Chem., 19, 541-543. 

Cul-catalyzed coupling of amidine hydrochloride salts 172 with 2-halobenzoic acid and subsequent condensative cychzation worked well to provide 2-substituted quinazolinones 173 at room temperature (Scheme 60) [102, 103]. The ortho-substituent effect directed by the carboxylic acid group should be the reason of... 

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