Steric hindrance to protonation

From the shapes of the rate versus acid strength graphs obtained for mesit-aldehyde and triisopropylbenzaldehyde it was concluded that although neither compound was specific acid-catalysed, the latter compound showed the nearer tendency to this catalysis at the higher acid concentrations again this may be a manifestation of the greater steric hindrance to protonation by H3 S04 than by H30+. 

The behavior of imidate 118 under acidic conditions can be readily explained by the presence of the two methyl groups on the phenyl ring which create an important steric hindrance to protonation of the nitrogen atom in the resulting tetrahedral intermediate. The salt 118 reacts with water to give first a tetrahedral intermediate in the neutral T° form. However, the conversion... 

The steroidal cyclopropenes 4-6 provide isomeric butadienes by initial protonation and proton loss from the corresponding allyl cation. A detailed study indicates that regioselective cr-bond fission takes place because of steric hindrance to protonation by the bulky steroid ring from one side. 

The 18-crown-6-cyclic polyether-KBr complex catalyses the homogeneous liquid phase molecular oxygen oxidation of ethylbenzene to the hydroperoxide. The macrobicyclic ligands (cryptands) are strong bases but the rates of proton transfer from ethyl nitroacetate to the free base cryptand and to the mono-protonated cryptand are ca, 10 and 100-fold smaller, respectively, than that of transfer to a normal base of similar basicity. This is attributed either to steric hindrance to proton transfer or to proton transfer occurring only to the thermodynamically unfavourable exo-nitrogen conformation. However, a large kinetic isotope effect = 3.9) is observed for the protonation of cryptand... 

Steric effects on proton transfers between normal acids and bases are not uncommon (3, 4a, 10) although they are usually less dramatic than the ones reported here (11). On the other hand, steric hindrance to protonation of a nitrogen base by the hydronium ion is virtually unheard of except for recent reports of relatively modest rate depressions with 2,6-di-t-butylpyridine (12) and dipicrylamide (13). In this light our... 

The expected rate-enhancing effects of gem-dimethyl substituents were not seen in the base-catalysed cyclizations of ethyl A-(4-nitrophenyl)hydantoate (106 R, = Me, R = 4-O2NC6H4) and of ethyl A-phenylhydantoate (106 R R = Me, R° = Ph). Solvent kinetic isotope effects and other data led to the conclusion that the loss of the gem-dimethyl effects was due to steric hindrance to proton transfer of... 

Addition to cis- and /n t-2-butene theiefoie yields different optical isomers (10,11). The failure of chlorine to attack isobutylene is attributed to the high degree of steric hindrance to approach by the anion. The reaction intermediate stabilizes itself by the loss of a proton, resulting in a very rapid reaction even at ambient temperature (12). 

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

Substituent effect on the stability of the transition state for deprotonation (D, Figure 6). The addition of two ortho-methyl groups to Me-[8+] to give Me-[10+] results in an increase in kp for proton transfer to solvent from 1.4 x 106 s 1 to 8.3 x 107 s 1 (Table 1). There should be relatively little steric hindrance to the reaction of solvent with the /1-hydrogens of Me-[10+] because these are relatively distant from the ortho-methyl groups. However, the twisting about the CAr-Ca bond that minimizes steric interactions between the methyl... 

It may have been the dramatic 1964 publication of E.S. Lewis and L. Funderburk that forced the question of hydrogen tunneling in complex solution reactions near room temperature into the consciousness of a larger scientific public, particularly in physical-organic chemistry. This article presented isotope effects for proton abstraction from 2-nitropropane by a series of substituted pyridines, and the values rose sharply as the degree of steric hindrance to the reaction increased (Fig. 1). AU the observed H/D isotope effects, from 9.6 to 24, were larger than expected from the simplest version of the so-called semiclassical theory of isotope effects (Fig. 2). 

Fig. 1 Lewis and Funderburk found that the H/D primary kinetic isotope effects (25 °C in aqueous t-butyl alcohol) for proton abstraction from 2-nitropropane by pyridine derivatives all exceed the maximum isotope effect that could have been derived from the isotopic difference in reactant-state zero-point energies alone (a value around 7). The magnitude of the isotope effect increases with the degree of steric hindrance to reaction presented by the pyridine derivative, the identical results for 2,6-lutidine and 2,4,6-collidine ruling out any role for electronic effects of the substituents. The temperature dependence shown for 2,4,6-collidine is exceedingly anomalous the pre-exponential factor Ahis expected to be near unity but is instead about 1/7, while the value of AH — AH = 3030 cal/mol would have generated an isotope effect at 25 °C of 165 if the pre-exponential factor had indeed been unity.

These tautomeric equilibria support the view that in enamino-aldehyde, -ketone and -ester systems generally the relative basicities of the C- and O-protonation sites are comparable, whereas N-protonation is encountered only when steric hindrance to meso-merism is present and, exceptionally, in some solid salts. 

Whereas the cationic polymerization of furfurylidene acetone 3a engenders crosslinked structures (25), the use of anionic initiators results in linear structures (26). However, the propagation is preceded by an isomerization of the active species which eliminates the steric hindrance to propagation arising from the 1,2-disubstitution in the monomer structure. A proton shift from the 4- to the 2-position places the negative charge at the extremity of the monomer unit and the incoming monomer can add onto this anion without major restrictions. The polymer structure thus obtained is ... 

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