Stability order

One important experimental fact is that the rate of reaction of alcohols with hydro gen halides increases m the order methyl < primary < secondary < tertiary This reac tivity order parallels the carbocation stability order and is readily accommodated by the mechanism we have outlined... 

Dihydroazoles can exist in at least three forms (cf. Section 4.01.1.3), which in the absence of substituents are tautomeric with each other. The forms in which there is no hydrogen on at least one ring nitrogen normally predominate because imines are generally more stable than vinylamines in aliphatic chemistry. Thus for dihydropyrazoles the stability order is A" (hydrazone) (288) > A (azo) (289) >A (enehydrazine) (290). 

There is an excellent correlation between these data and the gas-phase data, in terms both of the stability order and the energy differences between carbocations. A plot of the gas-phase hydride affinity versus the ionization enthalpy gives a line of slope 1.63 with a correlation coefficient of 0.973. This result is in agreement with the expectation that the gas-phase stability would be somewhat more sensitive to structure than the solution-phase stability. The energy gap between tertiary and secondary ions is about 17kcal/mol in the gas phase and about 9.5 kcal/mole in the SO2CIF solution. 

AMI calculations give a different stability order (AAHf = -2.3 kcal/mol). It was remarked that because of the high dipole moment of 111 =... 

The stability order of 133 in the gas phase and in aqueous solution is given by... 

Fig. 7. Scheme of the intermolecular forces stabilizing ordered structures in polypeptides and proteins m... 

For example, ethylene has AF.f hvdr0g = —137 kj/mol (-32.8 kcal/mol), but when one alkyl substituent is attached to the double bond, as in l-butene( the alkene becomes approximately 10 kj/mol more stable (A/-Phydr0g = -126 kj/mol). Further increasing the degree of substitution leads to still further stability. As a general rule, alkenes follow the stability order ... 

The stability order of alkenes is due to a combination of two factors. One is a stabilizing interaction between the C=C tr bond and adjacent C-H a bonds on substituents. In valence-bond language, the interaction is called hyperconjugation. In a molecular orbital description, there is a bonding MO that extends over the four-atom C=C—< -H grouping, as shown in Figure 6.6. The more substituents that are present on the double bond, the more hyperconjugation there is and the more stable the alkene. 

The second point to explore involves carbocation stability. 2-Methyl-propene might react with H+ to form a carbocation having three alkyl substituents (a tertiary ion, 3°), or it might react to form a carbocation having one alkyl substituent (a primary ion, 1°). Since the tertiary alkyl chloride, 2-chloro-2-methylpropane, is the only product observed, formation of the tertiary cation is evidently favored over formation of the primary cation. Thermodynamic measurements show that, indeed, the stability of carbocations increases with increasing substitution so that the stability order is tertiary > secondary > primary > methyl. 

One way of determining carbocation stabilities is to measure the amount of energy required to form the carbocation by dissociation of the corresponding alkyl halide, R-X - R+ + X . As shown in Figure 6.10, tertiary alkyl halides dissociate to give carbocations more easily than secondary or primary ones. As a result, trisubstituted carbocations are more stable than disubstituted ones, which are more stable than monosubstituted ones. The data in Figure 6.10 are taken from measurements made in the gas phase, but a similar stability order is found for carbocations in solution. The dissociation enthalpies are much lower in solution because polar solvents can stabilize the ions, but the order of carbocation stability remains the same. 

U A more highly substituted carbocation is more stable than a less highly substituted one. That is, the stability order of carbocafions is tertiary > secondary > primary > methyl. 

Figure 10.2 Energy diagram for alkane chlorination. The relative rates of formation of tertiary, secondary, and primary radicals are the same as their stability order.

We can thus expand the stability ordering to include vinylic and allylic radicals. 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

We saw in Section 6.9 that the stability order of alkyl carbocations is 3° > 2° > 1° > —CH3. To this list we must also add the resonance-stabilized allvl and benzyl cations. Just as allylic radicals are unusually stable because the... 

Because of resonance stabilization, a primary allylic or benzylic carbocation is about as stable as a secondary alkyl carbocation and a secondary allylic or benzylic carbocation is about as stable as a tertiary alkyl carbocation. This stability order of carbocations is the same as the order of S l reactivity for alkyl halides and tosylates. 

Electronically, aldehydes are more reactive than ketones because of the greater polarization of aldehyde carbonyl groups. To see this polarity difference, recall the stability order of carbocations (Section 6.9). A primary carbocation is higher in energy and thus more reactive than a secondary carbocation because... 

Neither methyl nor ethyl fluoride gave the corresponding cations when treated with SbFs. At low temperatures, methyl fluoride gave chiefly the methylated sulfur dioxide salt, (CH3OSO) ShF while ethyl fluoride rapidly formed the rert-butyl and ferf-hexyl cations by addition of the initially formed ethyl cation to ethylene molecules also formed ° At room temperature, methyl fluoride also gave the tert-butyl cation. In accord with the stability order, hydride ion is abstracted from alkanes by super acid most readily from tertiary and least readily from primary positions. 

The stability order can be explained by hyperconjugation and by the field effect. In the hyperconjugation explanation, we compare a primary carbocation with a tertiary. It is seen that many more canonical forms are possible for the latter ... 

However, experiments in the gas phase gave different results. In reactions of OH with alkyltrimethylsilanes, it is possible for either R or Me to cleave. Since the R or Me comes off as a carbanion or incipient carbanion, the product ratio RH/MeH can be used to establish the relative stabilities of various R groups. From these experiments, a stability order of neopentyl > cyclopropyl > rcrt-butyl > n-pro-pyl > methyl > isopropyl > ethyl was found. On the other hand, in a different kind of gas-phase experiment, Graul and Squires were able to observe CHi ions, but not the ethyl, isopropyl, or (ert-butyl ions. 

As with carbocations, the stability order of free radicals is tertiary > secondary > primary, explainable by hyperconjugation, analogous to that in carbocations... 

For the SnI mechanism, a branching increases the rate, as shown in Table 10.4. We can explain this by the stability order of alkyl cations (tertiary > secondary > primary). Of course, the rates are not actually dependent on the stability of the ions, but on the difference in free energy between the starting compounds and the transition states. We use the Hammond postulate (p. 284) to make the assumption that the transition states resemble the cations and that anything (such as a branching) that lowers the free energy... 

Thus the observed orientation in both kinds of HBr addition (Markovnikov electrophilic and anti-Markovnikov free radical) is caused by formation of the secondary intermediate. In the electrophilic case, it forms because it is more stable than the primary in the free-radical case because it is sterically preferred. The stability order of the free-radical intermediates is also usually in the same direction 3°>2°>1° (p. 241), but this factor is apparently less important than the steric factor. Internal alkenes with no groups present to stabilize the radical usually give an approximately 1 1 mixture. 

The rate of leaving of a group is also dependent upon the other groups present and in particular the group trans to it (12). Table 6 gives some data. Whereas the thermodynamic data establish a stability order for binding of ligands... 

The enrichments and depletions displayed in Figure 1 are concordant with what would be expected if disorder were encoded by the sequence (Williams et al., 2001). Disordered regions are depleted in the hydrophobic amino acids, which tend to be buried, and enriched in the hydrophilic amino acids, which tend to be exposed. Such sequences would be expected to lack the ability to form the hydrophobic cores that stabilize ordered protein structure. Thus, these data strongly support the conjecture that intrinsic disorder is encoded by local amino acid sequence information, and not by a more complex code involving, for example, lack of suitable tertiary interactions. 

The stability order of carbocations is exactly the order of SN1 reactivity for alkyl halides and tosylates. 

A mechanistic study of acid and metal ion (Ni2+, Cu2+, Zn2+) promoted hydrolysis of [N-(2-carboxyphenyl)iminodiacetate](picolinato)chromate (III) indicated parallel H+- or M2+-dependent and -independent pathways. Solvent isotope effects indicate that the H+-dependent path involves rapid pre-equilibrium protonation followed by rate-limiting ring opening. Similarly, the M2+-dependent path involves rate-determining Cr-0 bond breaking in a rapidly formed binuclear intermediate. The relative catalytic efficiencies of the three metal ions reflect the Irving-Williams stability order (88). 

Equilibrium constants have been reported for the stepwise conversion of MeRe(NAr)2(PR3)2 to the mixed-phosphine and then the (PR3)2 derivative. Both steric and electronic factors come into play, typical of phosphines. The stability ordering is PMe3 > dmpe>PMe2Ph > P(OMe)2Ph > PEt3 > P(OEt)3 > PMePh2 > P(OEt)Ph2 > PPh3 (58). 

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