Structural Effects on Acidity

Now that a method is in hand to compare acid strengths quantitatively and predict the position of acid-base equilibria, a look at Table 3.1 reveals that organic 

How die structure of an acid induences its pKa provides a quantitative way to compare die structure of a compound with its reactivity (in this case acidity). Such structure-reactivity correlations are crucial for our understanding of how reactions take place and for being able to predict how a structural change will affect the outcome of a reaction. The ability to predict how a reaction will respond to changes in structure (or odier variables) takes us out of the realm of trial and error and into the realm of rational approaches to chemical transformations. Let us examine briedy some of die structural features which are major induences on acidity. 

This analysis suggests diat structural features which stabilize the conjugate base (often an anion) will therefore increase die acidity of an acid. While there are exceptions to diis general approach (e.g., comparison of die acidities of acids in die second and diird rows of die periodic table), it provides a sound basis for predicting what structural factors can increase or decrease the acidity of organic acids. 

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Sodium a-sulfonated fatty acid esters of long-chain alcohols have a structural effect on the Krafft point different from that of amphiphiles with short alkyl chains [60]. In a series of homologs with the same total carbon number the Krafft points are highest when the hydrophilic alkyl chain lengths in the a-sulfonated fatty acid and the alcohol are fairly long and equal. In this case the packing of the molecules becomes close and tight. 

As has been mentioned previously, one is most likely to find analogies to catalytic reactions on solids with acidic and/or basic sites in noncatalytic homogeneous reactions, and therefore the application of established LFERs is safest in this field. Also the interpretation of slopes is without great difficulty and more fruitful than with other types of catalysts. The structure effects on rate have been measured most frequently on elimination reactions, that is, on dehydration of alcohols, dehydrohalogenation of alkyl halides, deamination of amines, cracking of the C—C bond, etc. Less attention has been paid to substitution, addition, and other reactions. 

The structure effects on rate in the catalytic dehydration of alcohols on acidic catalysts also have been elucidated by quantum-chemical modeling of the adsorption complex in a series of alcohols R CH(OH)-CH3, using a proton as a simple model of the catalyst 69). It has been found that the protonation of the hydroxyl group causes an increasing weakening of the C—O bond in the order R = CHj, C2H5, /-C3H7, This corresponds... 

The zero slope found for transesterification (series 45) can be explained in accordance with the general view on acid-catalyzed reactions of organic acids and esters. The first step is the protonation of the acid or ester, which is followed by interaction with the alcohol (or water in ester hydrolysis). The absence of any observable influence of the alcohol structure on rate indicates that the rate-determining step must be the protonation of the ester. This is in contrast to the homogeneous reaction, in which this step is usually very rapid. The parallel dehydration of the alcohols exhibited a large structure effect on rate (Case 7 from Table II), confirming the independence of the two reaction routes. 

Structural effects on reactivity and properties of oximes and hydroxamic acids... 

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. 

Structural Effects on Carbanion Basicity-Carbon Acidity... 

It took some time to adopt a similar view of other heterogeneous elimination and substitution reactions. Most efficient experimental tools have been found in stereochemical studies, correlation of structure effects on rates and measurement of deuterium kinetic isotope effects. The usual kinetic studies were not of much help due to the complex nature of catalytic reactions and relatively large experimental error. The progress has been made possible also by the studies of surface acid—base properties of the solids and their meaning for catalysis (for a detailed treatment see ref. 5). 

In acetic acid it is possible to measure separately the equilibrium constant of proton transfer to form an ion pair and the constant for dissociation of ion pairs to form free ions. [I. M. Kolthoff and S. Bruckenstein, J. Amer. Chem. Soc., 78, I (1956) S. Bruckenstein and I. M. Kolthoff, J. Amer. Chem. Soc., 78, 10 (1956)]. G. W. Geska and E. Grunwald, J. Amer. Chem. Soc., 89, 1371, 1377 (1967) applied this technique to a number of substituted anilines and concluded that the equilibrium constant of the ionization step, rather than the overall acid dissociation constant, is the quantity that should be considered in discussions of effects of structural changes on acidity. 

Acidities of amines in solution are less well known than those of alcohols. Streit-wieser and co-workers report that cyclohexylamine is somewhat less acidic than triphenylmethane,88 but there is little information available about the effects of structural variation on acidity. In the gas phase, Brauman and Blair found the order (most acidic to least acidic) (C2H5)2NH > (CH3)3CCH2NH2 (CH3)3... 

A kinetic study of structural effects on the A-nitrosation of amino acids by nitrite in aqueous solution has established that the dominant term in the rate equation corresponds to nitrosation by dinitrogen trioxide.189 Nitrosation by intramolecular migration of the nitroso group from an initially nitrosated carboxylate group can compete when the transition state has a five- or six-membered ring structure. Nitrosation of A-methyl-4-tolylsulfonylguanidine involves rapid nitrosation of the N-... 

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