John Anthony MacPhee

Steric effects—I: A critical examination of the taft steric parameter—Es. Definition of a revised, broader and homogeneous scale. Extension to highly congested alkyl groups

Abstract The basic assumptions used in obtaining the Taft Es scale of steric parameters have been examined critically. Certain inconsistencies in the existing scale are pointed out which motivate a rigorous recalculation of the scale based on a single defining reaction: the acid catalysed esterification of carboxylic acids in MeOH at 40°. This revised Taft scale is termed Es. The scale includes 44 of the original groups cited by Taft with 50 additional values obtained from literature data and has been extended to extremely hindered alkyl groups (13 in number) by measurement based on competitive reactivity. The complete scale from its least hindered group (H, Es = 1.12) to its most hindered (t-BuPriMeC-, Es = −7.56) spans more than eight powers of ten. A definite levelling effect has been observed in the region of Es ~−6 and an inversion effect in two cases (i-Pr3C- and t-BuPriEtC-). Some currently used quantitative approaches to steric effects are discussed and compared in the light of the Es scale. The corrected steric parameters, Esc and Eso, have been shown not to be of general applicability and the use of the van der Waals radius relative to hydrogen subject to limitation.

Steric effects-II: Relationship between topology and the steric parameter. E's—topology as a tool for the correlation and prediction of steric effects

The steric effect of alkyl groups as characterized by the revised Taft Es parameter is analysed using an approach based on the DARC topological system and its PELCO correlation method. This approach involves an analysis of the systemativ variation of Es in a topological dequencing of alkyl groups and shows the existence of three regions of distinct behaviour: R I, a “normal” behaviour region (ca 6 Es units) in which the contribution of the introduction of successive Me groups to the overall steric effect increases monotonically (groups with 1 to 7 carbons); R II, a region, in which a “levelling” effect is observed, i.e. the contribution diminishes and becomes nil (groups with 8 and 9 carbons); and R III, where this contribution changes sign, “inversion” effect (groups with 10 carbons). Using a series of successive approximations, topological models are developed and tested. The conditions under which the topology may be used to represent the topography (i.e. the real 3-dimensional structure) are considered. The correlation of existing Es values and the reliable prediction of experimentally unavailable steric effects are direct consequences of this treatment.

Grignard reagent–acid chloride condensation in the presence of copper(I) chloride. A study of structural effects by direct and competition methods

The copper(I) chloride catalysed reaction between a Grignard reagent and an acid chloride in ether has been studied by using a competition method in which a pair of acid chlorides reacts with a single Grignard reagent, and by direct kinetic experiments in one case. The variation of relative rates produced by structural changes in the alkyl group of the acid chloride has been shown to correlate with the Taft polar parameter σ* but to be independent of the steric parameter ES(ρ*= 2·96 for EtMgBr; 6·01 for ButCH2MgCI; 12·7 for ButMgCl); this is in contrast with uncatalysed reactions of this type which have a marked sensitivity to steric effects. These results are consistent with a cyclic transition state in which chloride is displaced from acid chloride without addition to the carbonyl group, by either a mixed cuprate(I) intermediate [RCuX]–MgX+ or a loose RCu ⋯ MgX2 complex.

Concept of a sterically active environment in alicyclic structures

Abstract By seeking analogies in behavior between aliphatic and alicyclic carboxylic acids, it is possible to determine the sterically active sites of the latter.

Factors controlling the dissociation of aliphatic carboxylic acids in 80 % methylcellosolve - 20 % water. A case for the importance of polar effects

Abstract The dissociation constants of a wide range of aliphatic carboxylic acids in 80 % methylcellosolve- 20 % water have been investigated. The pK variation between the limits defined by the acids MeCO 2 H and i-Pr 3 CCO 2 H is controlled principally by polar effects as defined by σ * .

Steric limits to ester alkylation; synthesis of highly hindered esters via hexamethylphosphoramide-favoured enolization

The steric limits to the alkylation of carboxylic esters by alkyl iodides with lithium di-isopropylamide as base in the presence of hexamethylphosphoramide have been investigated by using, with modifications, a method originally proposed by Schlessinger et al. The influence of hexamethylphosphoramide in promoting ester enolization, as opposed to its influence on the alkylation step, as previously reported, has been examined. The formation of αα-disubstituted from α-monosubstituted esters takes place in high yields and appears to be only slightly influenced by the nature of the alkylating agent (Mel, Etl, or Pril). In contrast, the formation of ααα-trisubstituted for αα-disubstituted esters appears to be sensitive to the steric nature of the ester to be alkylated. Thus in the synthesis of tri-from mono-substituted esters the order of introduction of alkyl groups is critical. The failure of certain esters to react is interpreted as due to an inability to undergo enolization.