Conjugates discussion

The decrease in effective conjugation discussed above is much more important than any possible participation of phosphorus Sd z orbitals. Such weak d-orbital conjugation is not expected to lower the energy of the 7T2 MO to any significant degree. Fig. 15 roughly summarizes the orbital schemes of the two heterosystems. 

Alteration of the physico-chemical properties of the molecules seems to be a laborious, but promising, approach [114]. Comparable to the various kinds of conjugates discussed above, they require the synthesis of a new chemical entity (NCE), whilst changes in chemical stability, solubility, li-pophilicity configuration and enzyme liability can also be achieved that facilitate non-invasive administration [115]. 

A familiar feature of the electronic theory is the classification of substituents, in terms of the inductive and conjugative or resonance effects, which it provides. Examples from substituents discussed in this book are given in table 7.2. The effects upon orientation and reactivity indicated are only the dominant ones, and one of our tasks is to examine in closer detail how descriptions of substituent effects of this kind meet the facts of nitration. In general, such descriptions find wide acceptance, the more so since they are now known to correspond to parallel descriptions in terms of molecular orbital theory ( 7.2.2, 7.2.3). Only in respect of the interpretation to be placed upon the inductive effect is there still serious disagreement. It will be seen that recent results of nitration studies have produced evidence on this point ( 9.1.1). 

Substituents containing boron are of interest because of the possibility which the boron atom offers of conjugation of a vacant orbital with the 77-electrons of the benzene ring (—717). The case of phenylboronic acid has been discussed ( 5.3.4). 

We will not discuss the preparation of cumulated dienes They are prepared less readily than isolated or conjugated dienes and require special methods... 

As we discussed in Section 1 14 it is more useful to describe the basicity of amines m terms of the pA a s of their conjugate acids than as basicity constants Always bear m mind that... 

Cyclopentadiene contains conjugated double bonds and an active methylene group and can thus undergo a Diels-Alder diene addition reaction with almost any unsaturated compound, eg, olefins, acetylene, maleic anhydride, etc. The number of its derivatives is extensive only the reactions and derivatives considered most important are discussed. 

Aromatic pyrazoles and indazoles, in the broad sense defined in Sections 4.04.1.1.1 and 4.04.1.1.2, will be discussed here. Tautomerism has already been discussed (Section 4.04.1.5) and acid-base equilibria will be considered in Section 4.04.2.1.3. These two topics are closely related (Scheme 10) as a common anion (156a) or a common cation (156b) is generally involved in the mechanism of proton transfer (e.g. 78T2259). For aromatic pyrazoles with exocyclic conjugation there is also a common anion (157) for the three tautomeric forms... 

Exocyclic conjugation causes a small upheld shift of the ring hydrogen resonances, as can be seen in Table 6. The increase in tr-bond hxation also results in an increase in the 4,5 coupling constant to about 6.0 Hz. The use of coupling constants for the investigation of tautomerism is discussed in Section 4.17.5. 

Molecular orbital calculations predict that oxirane forms the cyclic conjugate acid (39), which is 30 kJ moF stabler than the open carbocation (40) and must surmount a barrier of 105kJmoF to isomerize to (40) (78MI50500). The proton affinity of oxirane was calculated (78JA1398) to be 807 kJ mol (cf. the experimental values of 773 kJ moF for oxirane and 777-823 kJ moF for dimethyl ether (80MI50503)). The basicity of cyclic ethers is discussed in (B-67MI50504). 

Procedures to compute acidities are essentially similar to those for the basicities discussed in the previous section. The acidities in the gas phase and in solution can be calculated as the free energy changes AG and AG" upon proton release of the isolated and solvated molecules, respectively. To discuss the relative strengths of acidity in the gas and aqueous solution phases, we only need the magnitude of —AG and — AG" for haloacetic acids relative to those for acetic acids. Thus the free energy calculations for acetic acid, haloacetic acids, and each conjugate base are carried out in the gas phase and in aqueous solution. 

Although the Hiickel method has now been supplanted by more complete treatments for theoretical analysis of organic reactions, the pictures of the n orbitals of both linear and cyclic conjugated polyene systems that it provides are correct as to symmetry and the relative energy of the orbitals. In many reactions where the n system is the primary site of reactivity, these orbitals correctly describe the behavior of the systems. For that reason, the reader should develop a familiarity with the qualitative description of the n orbitals of typical linear polyenes and conjugated cyclic hydrocarbons. These orbitals will be the basis for further discussion in Chapters 9 and 11. 

The examples that have been presented in this section illustrate the approach that is used to describe structure and reactivity effects within the framework of MO description of structure. In the chapters that follow, both valence bond theory and MO theory will be used in the discussion of structure and reactivity. Qualitative valence bond terminology is normally most straightforward for saturated systems. MO theory provides useful insights into conjugated systems and into effects that depend upon the symmetry of the molecules under discussion. 

---