Inductive Substituents and Heteroatoms

The replacement of a C atom in a conjugated system by a heteroatom such as N may be considered the simplest example of a purely inductive substituent effect. The influence on the orbital energies may then be estimated by first-order perturbation theory using the relation 

While first-order effects of purely inductive substituents on excitation energies of alternant hydrocarbons vanish, higher-order perturbation theory gives nonzero contributions. Thus, Murrell (1963), using second-order perturbation theory, derived the relation 

It follows that the shift of the benzene Lb band can be written as 

Substitution Pattern Intensity Enhancement Substitution Pattern Intensity Enhancement  

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Several reports on theoretical calculations have appeared for six-membered aromatic heterocycles involving one group 14 heteroatom [41, 42, 241-246], Ottoson and coworkers calculated that 7t-electron-donor substituents in 2,4,6-positions could enhance the stability of these heterobenzenes [247], in addition to the steric bulk of the substituents, and inductive stabilization via ipso-silyl substitution by groups such as Tbt. 

The effect of introduction of an additional heteroatom (88ZOR1799), inductive substituents (90ZOR1793), mesomeric substituents (88ZOR1806), and effect of ben-zannulation (90ZOR1387) on the position of the tautomeric equilibrium of azines with various functional groups were investigated by PMO semiempirical calculations. It was shown that the transition from pyridine to analogous 2-pyrimidine or... 

Hiickel calculations of the electron affinities of these substituted compounds have been carried out. The heteroatom inductive and resonance parameters, ht and ku have been established for the previously mentioned substituents, and were determined by a procedure different from normal. The Hiickel calculations were made on the difference in electron affinity from the parent compound, and the parameters were adjusted to agree with the experimental change in electron affinity. In general, Hiickel calculations have severe limitations however, when the calculations are made only on the AEA, the inaccuracy of the Hiickel estimate of the aromatic framework is minimized. As a result good agreement was obtained between the Hiickel estimates and the experimental A EA. 

The effect of inductive substituents on the n energy of an adjacent conjugated system can be immediately deduced from Rule 1 (Section 4.6). Introduction of a + / substituent at position i in a conjugated system will make that carbon atom more electronegative and so will qualitatively mimic the effect of replacing that carbon atom by a heteroatom. Equally, a — / substituent will have a diametrically opposite effect. One can sum up these conclusions in the following rule ... 

If the reactions of the same substituents on heteroaromatic azoles and on benzene rings are compared, the differences in the reactivities are a measure of the heteroatoms influence. Such influence by the mesomeric effect is smaller when the substituent is /3 to a heteroatom than when it is a or y. The influence by the inductive effect is largest when the substituent is a to a heteroatom. 

A heteroatom (in ring A) will control the electron density at the position of ring closure by its inductive and resonance effects. If the substituent increases the electron density of the ring, then ring closure will be facilitated by the heteroatom. If the heteroatom decreases electron density, then the ring closure will be hindered. 

A DFT study of enolborane addition of o -heteroatom-substituted aldehydes has focused on the relevance of the Cornforth and polar Felkin-Anh (PKA) models for asymmetric induction.154 Using chiral substrates, MeCH(X)CHO, polar (X = F, Cl, (g) OMe) and less polar (X = SMe, NMe2, PMe2) substituents have been examined. The former favour Cornforth TS structures, the latter PKA. TS preferences have been correlated with the relative energy of the corresponding rotamer of the uncomplexed aldehyde. An in-depth study of addition of ( > and (Z)-enolborane nucleophiles to 2-methoxypropanal successfully predicts experimentally determined diastereofacial selectivities. 

The effects of substituents in the benzenoid ring on the rate of exchange at the 2-position of benzothiazole have also been measured (Table 8.15) (76JHC1021). These parallel those for benzimidazole (Table 8.14) and notable is the small difference between the effects at the 5- and the 6-positions. This may be attributed to the fact that only inductive effects are important in base-catalyzed exchange, and they may be transmitted through either heteroatom with comparable facility. 

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