Conformation substituents, effects

Many studies have been made of substituent effects in saturated heterocyclic six-membered rings. For a detailed discussion the review of Eliel and Pietrusziewicz should be consulted [Pg.15]

The assignment of resonances in Table 14.2 results from summation of substituent effects as listed in Table 14.1. The data refer to conformer I for conformer II the C atoms pairs C-l/C-2, C-3/C-6, C-4/C-5 and C-7/C-8 change places. 

To obtain qualitative information about a molecule, such as its moleculip orbitals, atomic charges or vibrational normal modes. In some cast semi-empirical methods may also be successfully used to predict energy-trends arising from alternate conformations or substituent effects in qualitative or semi-quantitative way (but care must be taken in this area). 

Ring-flip (Section 4.6) A molecular motion that converts one chair conformation of cyclohexane into another chair conformation. The effect of a ring-flip is to convert an axial substituent into an equatorial substituent. 

A good correlation with ordinary Hammett a values was based on 16 well-behaved substituents, and p-SOMe conformed well to this. Various other substituents showed deviations which were attributed to enhanced + R effects. These included p-SPh and this was explained in terms of 7t(pd) bonding, which was thus taken to play no part in the effect of p-SOMe on the methyl hyperfine splitting. More recently several 4-substituted benzyl radicals of the type RSO C6H4CH2 (n — 0,1 or 2 R = Me, Ph, Tol, COMe or OMe) have been examined by ESR spectroscopy249. The ability to delocalize spin density onto the substituent decreases in general as n increases and the effect of R depends on the oxidation state of sulfur. These authors have devised a new scale of substituent effects (sigma dot... 

In conformity with our previous approach, we classify substituent effects on heterocyclopropane rings into four categories. They are substituted heterocyclopropyl sets, heterocyclopropylidene sets, heterocyclopropylene sets and hetero-cyclopropanes with heteroatom reaction sites. 

Thorough analysis of the coupling constants suggests that vicinal and cross-ring coupling can be valuable when used for stereochemical assignments in thietane oxides and dioxides, provided one takes into consideration the conformational changes and the substituent effects . 

Comparing the potentials across each row, we can test the idea of additivity of ortAo-substituent effects for 2-fluoro, 6-chloro, and then 2-fluoro-6-chloro substitution. The definition of a = 0 changes across each row to permit easy visual addition of the potentials in the physically appropriate manner to assess the degree of additivity of ort/io-chlorine and ort/io-fluorine substituent effects. For o-fluorotoluene and 2-fluoro-6-chlorotoluene, a = 0 denotes the (minimum-energy) pseudo-trans conformation for o-chlorotoluene, a=0 denotes the pseudo-cis conformation. The notion of additivity has considerable merit in all three electronic states. 

The rationalization of the conformational anomeric effect solely based on electrostatic interactions fails to account for these solvent effects. Another interpretation based on bond polarizability in 1,1-dialkoxyalkyl systems calls electronic transfer from a non bonding electron pair of one oxygen atom to the empty cr c 0 orbital from the other alkoxy substituent (Fig. 10).16... 

As conformational anomeric effects represent only a fraction (—1 to —3 kcal/mol) of the global enthalpic anomeric effect or gem-dioxy stabilizing effect (—6 to —17 kcal/mol), additional factors have to be taken into account. Depending on substitution, steric factors can affect the relative stability of acetal conformers. Dubois et al.2S have demonstrated that in furanose pyranose derivatives a bulky substituent at the furanose... 

On the basis of the above analysis, substituent effects on the energy difference between the and Cee conformation of R—X—R molecules can be readily under-... 

Much work has been done to determine sets of substituent effects in specific conformationally mobile or rigid frameworks, since a knowledge of such effects often furnishes valuable conformational information. For instance, it was concluded from yg- and 8-SCS values that substituents (X = OH, I) on the C(19) methyl group in some cholest-S-enes prefer an antiperiplanar orientation [X-C(19)H2-C(10)-C(1)] with respect to C(l) (81). In the following, SCS information for various classes of cyclic systems is discussed, with particular emphasis on configurational and conformational analysis. 

The foregoing examples of differential reactivities of rotamers may be summarized by saying that the reactivity is controlled by the steric factor. The difference in the reactivities of rotamers of 9-(2-bromomethyl-6-methyl-phenyl)fluorene (56) in SN2 type reactions falls in the same category (176). However, the substituent effect is not limited to a steric one there can be conformation-dependent electronic effects of substituents as well. A pertinent example is found in the reactivity of the bromomethyl compound (56) when the rotamers are heated in a trifluoroacetic acid solution (Scheme 10). The ap form gives rise to a cyclized product, whereas the sp form remains intact (176). The former must be reacting by participation of the it system of the fluorene ring. 

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