Cyclohexane A values

Some basic nitrogen substituents at C-2 of oxane show a tendency to adopt the equatorial position on protonation which, on the basis of the cyclohexane A values, looked abnormally high. This was called the antianomeric effect. However, when the corrected A values are considered, the shift toward the equatorial position is a perfectly normal consequence of the extra bulk introduced by the hydrogen atom (Franck 1983). The experimental proofs for the antianomeric effect could not be confirmed using contemporary techniques (Fabian et al. 1994). 

Table 4 Cyclohexane A values and FP and TP anomeric energy (AAE) values, in kcal/mol...

Substitution of a methyl group at C(3) or C(4) of cyclohexene is opposed by one less 1,3-diaxial interaction than in cyclohexane. Accordingly, the preference for the equatorial orientation of a methyl group in cyclohexene is somewhat less than in cyclohexane. A value of 1 kcal/mol has been suggested for the conformational energy of the methyl group in 4-methylcyclohexene based on epoxidation rates. ... 

For most substituents the equatorial position is preferred, and the magnitude of this preference (AG°) is called the cyclohexane A value. A large number of cyclohexane A values have been determined (Table 2.14). The A value is one measure of the steric size of a substituent, in that larger groups tend to have larger A values (for another measure of steric size. 

Usually cyclohexane A values are reported as AG° values, but for some substituents, AH° and AS° values are also available. Such values are shown below for methyl and isopropyl (equatorial to axial interconversion). Consider the two chair con-formers of c/s-1 -methyl-4-isopropy Icyclohexane. Calculate the percentage of each form present at (a) 300 K, (b) 100 K, and (c) 75 K. 

How do you rationalize the fact that the cyclohexane A value for phenyl (2.8) is bigger than that for isopropyl (2.21) ... 

These parameters show that the rate of the hydrolysis reaction is faster with hydrogen than methyl, and slows as the R group incrementally increases in size to f-butyl (that is, Es becomes more negative). Phenyl, however, comes out surprisingly large in this analysis (Es = -2.55). In Chapter 2 we noted that efforts to characterize the steric size of a group will be strongly context dependent, and this is an example. In an alternative measure of the steric size of substituents—the cyclohexane A value (Table 2.14)—phenyl is much smaller than f-butyl. 

TABLE 4.3 Free-Enei Differences between Equatorial and Axial Substituents on j Cyclohexane Ring (A Values)... 

In 5-alkyl-substituted 1,3-dioxanes, the 5 substituent has a much smaller preference for the equatorial position than in cyclohexane derivatives the A values are much lower. This indicates that the lone pairs on the oxygens have a smaller steric requirement than the C—H bonds in the corresponding... 

The steric parameters for the estimation of reactant state effects were chosen to be the conformational free energy differences for cyclohexane axial-equatorial equilibria (A-values) (8). In order to establish the methyl group as the standard size group, modified A-values (A ) for the various groups were used, by simply subtracting the A value for the methyl group (1.70) from the A values of the various substituents ... 

Bourn (107) as 10.8 kcal mole-1 (AH4 temperature range 156—246 K solution of cyclohexane in carbon disulfide). By applying an interesting trapping technique Anet and coworkers (110) have recently measured a value of 5.3 kcal mole-1 for the barrier of the reverse twist/chair process (AH4 temperature range 72.5—74.0 K solid state). Our calculated (for the gas phase) activation enthalpies AH4 for the former process are at 73,... 

To evaluate the absolute kinetics of recombination from Eq. (7.27), it is necessary to obtain a reliable value of fes in addition to a measured from scavenging experiments. For electron scavenging in cyclohexane by biphenyl, Rzad et al. (1970) used fes = 3.0 x 10u M s-1 on the basis of the a value of scavenging... 

Studies on the quenching of photoexcited 9-phenan-thrylmethyl pivalate by MEK, a model forathe-PMMA-Phe/MEK system, provide a value of k 7.3 X 108 M s in cyclohexane (11). This value is nearly one order of magnitude lower than the diffusion-controlled rate. For reactions in which a diffusion step precedes a chemical step, the relationship between k and kd ff is given by ... 

Bonhoeffer and Farkas estimated k3/k2 100 and claimed that at 15 % decomposition the photolysis is completely self inhibited. More recent work by Ogg and Williams9,10 showed that for the photolysis with 2537 A radiation, k3/k2 is independent of HI pressure (50-150 torr), independent of temperature and has a value 3.5+0.3. The effect of cyclohexane as an inert diluent11 was to increase k3/k2 to 7.0+0.4 at 155°, which value remained constant at high cyclohexane hydrogen iodide ratios. This result was attributed to collisional thermalisation of the hot H atoms produced by 2537 A radiation and this limiting high-pressure value of k3/k2 = (k3/k2)aa was considered to be that for thermally equilibrated H atoms. 

If one methyl group is replaced by phenyl, the a-ICSs seem to tend to stronger shieldings in the cyclohexane conformer 143 a value of ca. — 7 can be estimated... 

Likewise, the N derivatives of carbazoles undergo PFR [116-118], Upon irradiation in cyclohexane A-acetyl-carbazole (157) gives the following products (quantum yields in parentheses) [119] 1-acetylcarbazole (158) (0.10), 3-acetyl-carbozole (159) (0.09), and carbazole (160) (0.06) (Scheme 43). The analogous A-acetyldiphenylamine gives the ortho- and para-acetylated products along with diphenylaniline with quantum yields of 0.20,0.096, and 0.048, respectively [119], Table 10 shows that these values decrease from cyclohexane to ethanol, but less markedly than in the case of acetanilide (see Table 8). 

Use of a hydrocarbon solvent such as cyclohexane can discriminate these compounds either as the only measured value or as a value to be subtracted from the octanol value (Alog P) [19-21]. Unfortunately, cyclohexane is a poor solvent for many compounds and does not have the utility of octanol. Groups which hydrogen bond and attenuate actual membrane crossing compared to their predicted ability based on octanol are listed in Figure 1.4. The presence of two or more amide, carboxyl functions in a molecule will significantly impact on membrane crossing ability and will need substantial intrinsic lipophilicity in other functions to provide sufficient hydrophobicity to penetrate the lipid core of the membrane. 

Taft steric values. A, values from the axial-equatorial conformational equilibrium in cyclohexane v, Charton steric parameters. ... 

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