Steric hindrance of solvation

The correlations with data on gas phase reactions have served to establish that the parameters calculated by our methods are indeed useful for the prediction of chemical reactivity data. Their application is, however, not restricted to data obtained in the gas phase. This has been shown through a correlation of pK values (in H O) of alcohols with residual electronegativity and polarizability parameters, by including a parameter that is interpreted to reflect steric hindrance of solvation ( ),... 

When non-bonded compression does eventually appear, its effects on both AH and AS are unmistakeable. A sharp increase in AH, as is observed, for example, for the hydrolysis of ethyl trimethylacetate, is accompanied by a decrease in AS, as expected if steric hindrance of solvation is occurring. 

A final remark about effects of steric hindrance of solvation of polar groups shall complete the discussion of optical rotations at the wavelength of the sodium-D-line. It seems that the truncated TTOR approach (equations 2, 3 and 5) remains valid for 1,1-diphenylcyclopropanes, if the target group for solvation (such as COOH or CH2OH) is sterically not strongly hindered. This is seen from the calculated and observed rotations of 71-74. 

More interesting with regard to the effect of esterification on the rotation than with respect to the effect of deuteration are the recently synthesized optically active deuterated acid 110 and its ester 111 Generally, the rotations of acids and their corresponding esters (measured in the same solvent) differ by no more than 39 % (cf., for instance, 83 and 84,34 (Table 3) and 73). The data of 110 and 111 may be taken as a further demonstration of the role of the solvent on optical rotations of cyclopropanecarboxylic acids, in particular, steric hindrance of solvation of the COOH group. 

Furthermore, as most investigations are performed in solution, also steric hindrances of solvation or other solvent effects (e.g., hydrogen bonding effects), have to be taken into consideration, if real experimental situations are treated. 

The same conclusion was reached in a kinetic study of solvent effects in reactions of benzenediazonium tetrafluoroborate with substituted phenols. As expected due to the difference in solvation, the effects of para substituents are smaller in protic than in dipolar aprotic solvents. Alkyl substitution of phenol in the 2-position was found to increase the coupling rate, again as would be expected for electron-releasing substituents. However, this rate increase was larger in protic than in dipolar aprotic solvents, since in the former case the anion solvation is much stronger to begin with, and therefore steric hindrance to solvation will have a larger effect (Hashida et al., 1975 c). 

A comparison of the second-order rate coefficients for nitration of 2,4,6-tri-methylpyridine and 1,2,4,6-tetramethylpyridinium ion (both at the 3-position) shows similarity of profile in the common acidity region and a rapidly increasing rate with acidity for the trimethyl compound at acidities below 90 wt. % (where the usual maximum is obtained). These two pieces of evidence show reaction to occur on the conjugate acid as also indicated by the large negative entropy of activation. Surprisingly, the tetramethyl compound is less reactive than the trimethyl compound so maybe this is an example of steric hindrance to solvation. Calculation of the encounter rate also showed that reaction on the free base was unlikely. 

Contrary to the results obtained with carbon tetrachloride solvent and entirely in accord with the postulate that the effect arises from the steric hindrance to solvation, the rates of cleavage of ArSnR3 compounds in methanol decrease on increasing the size of the group R. This is shown by the rate coefficients in Table 265, though it is difficult to draw any conclusion from the Arrhenius parameters... 

The behavior of the different amines depends on at least four factors basicity, nucleophilicity, steric hindrance and solvation. In the literature (16), 126 aliphatic and aromatic amines have been classified by a statistical analysis of the data for the following parameters molar mass (mm), refractive index (nD), density (d), boiling point (bp), molar volume, and pKa. On such a premise, a Cartesian co-ordinate graph places the amines in four quadrants (16). In our preliminary tests, amines representative of each quadrant have been investigated, and chosen by consideration of their toxicity, commercial availability and price (Table 1). 

Steric effects on both the amide and the acyloxyl side chain are similar. Tert-butyl and adamantyl groups on the amide side chain in 29v, 29x, 29c, and 29e (Table 2 entries 53 and 54, 63 and 65) result in lower stretch frequencies that, on average, are only 40 cm-1 higher than their precurser hydroxamic esters. Streck and coworkers have suggested that such changes in dialkyl ketones can be ascribed to destabilisation of resonance form II through steric hindrance to solvation which, in the case of tert-butyl counteracts the inductive stabilisation.127... 

Branched iV-chlorohydroxamic esters exhibit much lower carbonyl frequencies in their IR spectra. Series of Ai-(phenylethyloxy)amides (Table 2, entries 1-7) and Af-butoxy-amides (Table 2, entries 12-16) show a clear movement to lower carbonyl stretch frequencies with branching alpha to the carbonyl, in accord with greater inductive stabilization of the polar resonance form III of the carbonyl (Figure la). Neopentyl (entry 17) is a special case. While the group should contribute much more inductive stabilization than ethyl, its carbonyl stretch frequency is higher. Similar changes have been noted in the IR spectra of branched ketones and have been ascribed to a degree of steric hindrance to solvation and therefore destabilization of the polar resonance form Dl". ... 

A thermodynamic analysis (86UP1) of the effect of annelation on the acid-base properties of the couples imidazole/benzimidazole and pyra-zole/indazole in aqueous solution has shown that this effect is essentially determined by the enhanced electronic delocalization in the case of the anions of the benzazoles. The differential steric hindrance to solvation, on the other hand, does not seem to play a significant role. 

The cumyl cation (4) has been the subject of an X-ray crystallographic study, as its hexafluoroantimonate salt at —124 °C.31 It is nearly planar (8 ° twist), with a short bond between the C+ and the ring (1.41 A), consistent with benzylic delocalization. The Me—C+ bonds are also shortened, indicative of hyperconjugative interaction.31 However, calculations are taken to show that hyperconjugation is not important in isolated benzyl cations e.g. structures such as (6) are not important contributors to the overall structure of (5).32 The stabilization provided by alkyl groups would thus be because of their polarizability, and the Baker-Nathan effect would be due to steric hindrance to solvation.32 The heats of formation of some a-mcthylbcnzyl cations indicate that the primary stabilization in these species comes from the a-substitucnts, and that the stabilization provided by the aromatic ring is secondary.33... 

The authors explain this anomaly by pointing out that in benzo-phenanthrene itself the benzene rings are non-coplanar (Herbstein and Schmidt, 1954), and as a result the carboxyl group at position 1 could be approximately coplanar with the ring to which it is attached. This in turn would imply that the acid-weakening resonance effect becomes effective. This, together with the acid-weakening effect of steric hindrance to solvation, could account for the relative weakness of 1-benzophenanthroic acid. 

To improve the aqueous solubility of 5 we also synthesized a cyclopeptide 6 containing hydroxyproline subunits [24]. Although this compound is very water-soluble, and in solution adopts a similar conformation to 5, it only forms 1 1 complexes with anions. A reason for the inability of 7 to form 2 1 complexes could be that the hydroxyproline subunits in 6 are better solvated than prolines in aqueous solution, and the desolvation required for aggregation of two cyclopeptide molecules thus occurs less readily. Steric hindrance of hydroxyl groups from different cydopeptide moieties in the a dimeric complex of 6 could, moreover, also make aggregation difficult. Although peptide 6 cannot form sandwich-type complexes, it proved to be valuable for a quantitative determination of the anion affinity of 5, the results of which are summarized in Table 2.2.3 [24],... 

In agreement with this hypothesis, the steric hindrance to solvation, estimated from the difference in measured and additive pKa values (A) is greater for 2-t-butyl-4,6-diphenyl than for 2,4,6-triphenylpyridine, indicating an expected larger steric effect in the former (83JCS(P2)45). The best result is obtained with benzothiazol-2-yl, which tends to have a big steric effect in the plane of the pyridinium (entry 8) (Scheme 119). 

The solvolysis reaction has certain disadvantages. First, the 2-aryl-2-chloropropanes are often too reactive to be prepared in the pure state (because of easy thermal elimination of hydrogen chloride or self-condensation) and so have to be generated in situ from the corresponding alcohol and hydrogen chloride. Second, the reaction is carried out in a strongly solvating medium, and differential steric hindrance to solvation at various... 

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