Steric effects, and acidity

Hydrogen-bonding, steric effects, and acid-base properties of phenols are involved in their retention on silica gel and alumina with benzene and isopropylether as eluents. 

The factor 2.48 corresponds to the average of the available p values of alkaline hydrolysis from the Hammett equation and attempts to place a on the same scale as the and 0p electronic constants. Since base-catalyzed hydrolysis involves both inductive and steric effects and acid-catalyzed hydrolysis involves only the steric effect, removing the steric effect leaves only the inductive effect, assuming that in both reactions the steric effects are the same. 

It is generally accepted that hydrogen bonding, steric effects and acid/base proton transfer equilibria are the prime interactions involved in the formation of stable pre-polymerisation complexes. In addition, it is reasonable to assume that the other types of non-covalent interaction may contribute, although their role is more difficult to quantify (Figure 6.16) [15,17]. 

Hydrolysis reactions involving tetrahedral intermediates are subject to steric and electronic effects. Electron-withdrawing substituents faciUtate, but electron-donating and bulky substituents retard basic hydrolysis. Steric effects in acid-cataly2ed hydrolysis are similar to those in base-cataly2ed hydrolysis, but electronic effects are much less important in acid-cataly2ed reactions. Higher temperatures also accelerate the reaction. 

Various factors, including steric effects and the relative acidity of the P hydrogens, have been suggested as being most important in such eliminations. ... 

Taft was also able to isolate steric effects. For the acid-catalyzed hydrolysis of esters in aqueous acetone, long (kJh was shown to be insensitive to polar effects. In cases where resonance interaction was absent, this value was proportional only to steric effects (and any others that are not field or resonance). The equation is... 

Steric effects and FMO control have been combined in an elegant way to achieve regiospecific synthesis of pyrazole inhibitors of dihydroorotate dehydrogenase <2006SL901>. When the size of the propargylic acid ester 86 is increased from ethyl to diphenylmethyl, pyrazole 87 is formed from compound 85 regiospecifically (Scheme 3 Table 4) <2006H(68)1007>. 

A combination of steric and electrostatic factors is presumably decisive with regard to the form of the acid most stable in sulfuric acid solution. The simple protonated form XX of benzoic acid is stabilized by resonance structures sterically prohibited in mesitoic acids. The ortho methyl groups of mesitoic acid would interfere with a coplanar dihydroxymethylene group. On the other hand, the inductive and resonance effects of the methyl groups help stabilize the acylium ion form of mesitoic acid as in the formulae XXI. In the case of 2,4,6-tribromobenzoic acid the steric effect and its abetting electronic effects are not sufficient, and this acid behaves like benzoic acid.17 >177... 

A kinetic model was developed to describe the pH-dependent uncoupling activity of substituted phenols in bacterial photosynthetic membranes [2]. In this model, the overall uncoupling activity is quantitatively separated into the contribution of membrane concentration, which can be estimated by the Kmw, and of intrinsic activity. The intrinsic activity of an uncoupler is influenced not only by the hydrophobicity and acidity, but also by steric effects and by the charge distribution within the molecule [2]. 

According to Heathcock and his associates the configurational dependence on the ratio of Lewis acid to aldehyde must be related to steric effects, and they conclude that the aldols 103 and 102 result from the open transition states A and B, respectively (Scheme 9.33). If the Lewis acid is small, transition state A is preferred because it minimises gauche interactions about the forming bond, but if the Lewis... 

Development of a predictive model for the reactivity of annelated benzenes is facilitated by the partitioning of substituent effects into their steric and electronic parameters. In order for this to be accomplished, reference reactions are needed which depend uniquely on one type of parameter. Typically conformational equilibria serve as good references of steric effects, whereas acid-base equilibria serve as good references of electronic effects. 

Examples of the application of correlation analysis to oxime and hydroxamic acid pK data sets are considered below. In the best of all possible worlds all data sets have a sufficient number of substituents and cover a wide enough range of substituent electronic demand, steric effect and intermolecular forces to provide a clear reliable description of the kind and magnitude of structural effects on the property of interest. In the real world this is often not the case. We will therefore try to show how the maximum amount of information can be extracted from small data sets. 

In the previous chapter we described a systematic study of the interactions of small model peptides with a rather specific enzyme. In our attempt to systematize the effects of fluorinated amino acids on peptide and protein interactions we have established a model system that lays the foundation for a more general approach. How do the steric effects and the degree of fluorination as well as the polarity of fluoroalkyl amino acid side chains affect the folding of proteins and the strength of peptide-protein interactions In order to answer this central question we choose a very common folding motive, the a-helical coiled coil. 

The hypothesis put forth concerning steric effects in acid hydrolysis would have as its corollary the proposal that the role of the Ci component in cellulase enzyme system complexes is to disrupt the engagement of the C6 oxygen in the bifurcated intramolecular hydrogen bond and thus permit rotation of the C6 group into positions more favorable to hydrolytic attack. 

Carboxylic mixed anhydrides are very important for the rapid synthesis of peptides by the stepwise procedure,however the use of carboxylic mixed anhydrides,e.g.those derived from pivalic acid and a protected amino acid (1),suffers from two disadvantages. Firstly,regiospecificity of attack at the desired carboxyl function is largely determined by steric effects and will not be 100% for all coupling reactions.Secondly,such mixed anhydrides have a propensity towards disproportionation to symmetric anhydrides which is highly undesirable in terms of reaction efficiency.This latter process can be depressed by operation of the reaction at -15 °C, but with the concurrent decrease in reaction rate and,on large scale manufacture,increased costs. 

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