Stability alkyl substitution

One of the most important and general trends in organic chemistry is the increase in carbocation stability with additional alkyl substitution. This stability relationship is fundamental to imderstanding many aspects of reactivity, especially of nucleophilic... 

For alkyl-substituted alkynes, there is a difference in stereochemistry between mono-and disubstituted derivatives. The former give syn addition whereas the latter react by anti addition. The disubstituted (internal) compounds are considerably ( 100 times) more reactive than the monosubstituted (terminal) ones. This result suggests that the transition state of the rate-determining step is stabilized by both of the alkyl substituents and points to a bridged intermediate. This would be consistent with the overall stereochemistry of the reaction for internal alkynes. 

The stereochemistry of addition is usually anti for alkyl-substituted alkynes, whereas die addition to aryl-substituted compounds is not stereospecific. This suggests a termo-iecular mechanism in the alkyl case, as opposed to an aryl-stabilized vinyl cation mtermediate in the aryl case. Aryl-substituted alkynes can be shifted toward anti addition by including bromide salts in the reaction medium. Under these conditions, a species preceding the vinyl cation must be intercepted by bromide ion. This species can be presented as a complex of molecular bromine with the alkyne. An overall mechanistic summary is shown in the following scheme. 

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

A number of alkyl-substituted cyclobutadienes have been prepared by related methods Increasing alkyl substitution enhances the stability of the compounds. The tetra-/-butyl derivative is stable up to at least 150°C but is very reactive toward oxygen. This reactivity reflects the high energy of the HOMO. The chemical behavior of the cyclobutadienes as a group is in excellent accord with that expected from the theoretical picture of the structure of these compounds. 

The groups at the termini of the 1,4-pentadiene system also affect the efficiency and direction of the the di-7c-methane reaction. The general trend is that cyclization oceurs at the diene terminus that best stabilizes radical character. Thus, a terminus substituted with aryl groups will cyclize in preference to an unsubstituted or alkyl-substituted terminus ... 

The rates of hydration of alkenes increase dramatically with increasing alkyl substitution (see table at left). This is usually attributed to the relative stabilities of carbocations formed as intermediates in the initial (and rate-hmiting) step of the reaction, e.g., for hydration of propene. 

Disubstituted and trisubstituted isoxazoles are generally stable to alcoholic and aqueous alkali. Such stability of the ring is characteristic both of alkyl-substituted compounds and of the esters, nitriles, etc., of isoxazole carboxylic acids,for example (127 ->128). 

Azonine anions 1 (X = N M + ), the parent compound 1 (X = NH) and, to a lesser extent, alkyl-substituted derivatives (X = NR), however, can be classified as aromatic, as they are flat, display high thermal stability and exhibit diatropic properties. 

Since it is clear that the presence of an unshared pair of electrons on the sulfur of the sulfoxide group leads to no special instability in the case of the known thiirene oxides (i.e., 18a, 28a,b and the first alkyl-substituted thiirene oxide 30 recently synthesized60), the reduced antiaromatic properties of the thiirene oxides relative to that of thiirenes have been manifested experimentally. As far as the possibility of electron-attracting conjugative stabilization involving the sulfur atom in thiirene oxides is concerned, the experimental evidence accumulated so far is not decisive. Thus, the chemical shift of the vinylic carbon of... 

There is no ready explanation for the relative instability of the alkyl-substituted cyclopentadienylthallium(I) compounds. The change in the hydrocarbon substrate, which results from introduction of an alkyl group, is likely to be small and insufficient to account for the dramatic stability differences [in the case of 9-R-substituted fluorenes, for example, where R = H, CHj, C2H5, or terf-butyl, the maximum difference in p. units between any two compounds is only 1.6 (9)]. The change in orbital overlap caused by introduction of an alkyl group is also likely to be small the l,T-dialkylferrocenes, for example, are stable compounds 137). At present, the only plausible explanation appears to be that the relative stabilities of the crystal lattices vary markedly 169). 

Since amine-phosphorus(III) halide condensation reactions are well-established low-energy routes to phosphorus-nitrogen bonds, they provide a logical starting point for examination of skeletally stabilized molecule synthesis. For our initial studies, reactants that are phenyl substituted as opposed to alkyl substituted... 

Addition is initiated by the positively polarised end (the less electronegative halogen atom) of the unsymmetrical molecule, and a cyclic halonium ion intermediate probably results. Addition of I—Cl is particularly stereoselective (ANTI) because of the ease of formation (and relative stability compared with carbocations) of cyclic iodonium ions. With an unsymmetrical alkene, e.g. 2-methylpropene (32), the more heavily alkyl-substituted carbon will be the more carbocationic (i.e. the less bonded to Br in 33), and will therefore be attacked preferentially by the residual nucleophile, Cle. The overall orientation of addition will thus be Markownikov to yield (34) ... 

Finally, the major structural features in the substrate promoting E2 elimination are those that serve to stabilise the resultant alkene or, more particularly, the T.S. that precedes it. Such features include increasing alkyl substitution at both a- and //-carbon atoms (leading to alkenes of increasing thermodynamic stability), or introduction of a phenyl group that can become conjugated with the developing double bond. 

The reaction of cyclohexaamylose with a series of p-carboxyphenyl esters is an example of a decelerating effect which may be clearly attributed to nonproductive binding. Rate effects imposed by cyclohexaamylose on the hydrolyses of three such esters are summarized in Table IX. As the hydrophobicity of the ester function is increased by alkyl substitution, the hydrolysis is inhibited the stability of the inclusion complex, on the other... 

Crowe proposed that benzylidene 6 would be stabilised, relative to alkylidene 8, by conjugation of the a-aryl substituent with the electron-rich metal-carbon bond. Formation of metallacyclobutane 10, rather than 9, should then be favoured by the smaller size and greater nucleophilicity of an incoming alkyl-substituted alkene. Electron-deficient alkyl-substituents would stabilise the competing alkylidene 8, leading to increased production of the self-metathesis product. The high trans selectivity observed was attributed to the greater stability of a fra s- ,p-disubstituted metallacyclobutane intermediate. 

Stabilization of the vinyl cations 8-10 by aryl substituents is important but even substituents without strong resonance effects provide adequate stabilization to allow the synthesis of persistent vinyl cations at ambient temperature. This is demonstrated by the synthesis and isolation of the salts of alkyl-substituted vinyl cations 19 and 20, and their characteristic NMR parameters are summarized in Table 1. 

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