Steric effects in aliphatics

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Taft steric Steric effects in aliphatic and ortho-substituted aromatic systems... 

J. M. Tedder, The importance of polarity, bond strength and steric effects in determining the site of attack and the rate of free radical substitution in aliphatic compounds, Tetrahedron, 1982, 38, 313-329. 

Steric effects in solvolysis has been the subject of a further report by Brown and Peters this year. The change in the alkyl group R in (116), (117), and (118) from Me to Bu increases the rates by factors of 39600, 140(KX), and 1120000. The differences are much greater than those found in the more flexible aliphatic or alicyclic systems, and the use of such models to estimate steric interactions in norbornyl derivatives can therefore lead to serious errors. Intramolecular steric interactions have also been monitored in a study of the kinetics of methanolysis of various tertiary chlorides and p-nitrobenzoates based on the norborn-2-yl system. 

The occurrence of steric as well as polar substituent effects in aliphatic systems and orf/io-substituted aromatic systems complicates the devising of correlation equations. A typical situation is shown in Figure 2. There is clearly no simple relationship between the rates of alkaline hydrolysis of the ethyl esters of the alkanoic acids and the strengths of the acids themselves. Little progress was made until the early 1950s, when Taft made an excellent start in developing linear free energy relationships in this area. This topic is sometimes referred to as the separation of polar, steric, and resonance effects and is the subject of Section 3. 

As mentioned in Section 1, the occurrence of steric as well as polar effects in aliphatic systems and orr/io-substituted aromatic systems complicates correlation analysis. Little progress in developing LFER in this area was made until R. W. Taft in 1952 devised a procedure for separating polar, steric, and resonance effects, based on an analysis of the rate coefficients of basic and acidic hydrolysis of esters. Considerable use has been made of this Taft analysis and of substituent parameters developed from it. 

The solubility of a compound is thus affected by many factors the state of the solute, the relative aromatic and aliphatic degree of the molecules, the size and shape of the molecules, the polarity of the molecule, steric effects, and the ability of some groups to participate in hydrogen bonding. In order to predict solubility accurately, all these factors correlated with solubility should be represented numerically by descriptors derived from the structure of the molecule or from experimental observations. 

A very interesting steric effect is shown by the data in Table 7-12 on the rate of acid-catalyzed esterification of aliphatic carboxylic acids. The dissociation constants of these acids are all of the order 1(T, the small variations presumably being caused by minor differences in polar effects. The variations in esterification rates for these acids are quite large, however, so that polar effects are not responsible. Steric effects are, therefore, implicated indeed, this argument and these data were used to obtain the Es steric constants. Newman has drawn attention to the conformational role of the acyl group in limiting access to the carboxyl carbon. He represents maximum steric hindrance to attack as arising from a coiled conformation, shown for M-butyric acid in 5. 

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