Substituted substituents

Displacements such as this show all the usual characteristics of electrophilic aromatic substitution (substituent effects, etc., see below), but they are normally of much less preparative significance than the examples we have already considered. In face of all the foregoing discussion of polar intermediates it is pertinent to point out that homolytic aromatic substitution reactions, i.e. by radicals, are also known (p. 331) as too is attack by nucleophiles (p. 167). 

We have stated earlier that because of proximity effects, no generally applicable aj values may be derived for ortho substitution. Nevertheless, one can determine a set of apparent 0)ortho values for a specific type of reaction, as for example, for the dissociation of substituted phenols. Table 8.7 gives such apparent O)ortho constants for estimating pKa values of substituted phenols and anilines. Of course, in cases of multiple substitution, substituents may interact with one another, thereby resulting in larger deviations of experimental from predicted pKa values. Some example calculations using the Hammett equation are given in Illustrative Example 8.2. 

Scientists soon realized that if Kekule s structure were correct, substituting substituent groups for hydrogens on the 1,2 positions would lead to a different compound than substitution on the 1,6 positions. 

Parentheses are placed around prefixes defining substituted substituents and after the numerical multiplicative prefixes... 

Electrophilic substitution. Substituents on the benzene rings exert their usual influence on the orientation and ease of electrophilic substitution reactions. For example, further nitration (HN03H2S04S03) of nitroquinolines occurs meta to the nitro group as shown in 632 and 633. FriedelCrafts acylation of 8-methoxyquinoline succeeds (cf. 634) although this reaction fails with quinoline itself. 

Four major categories of LFERs have been developed over the past 60 years or so (Table 2). These relationships apply to a wide variety of classes of organic and inorganic compounds and a wide range of reactions—coordinative reactions (dissociation-association) of acids and metal complexes, hydrolysis, hydration, substitution, substituent group oxidations, electron exchange between metal ions, and so on. This section describes the basis for these categories of correlative relationships and the types of reactions to which they apply. 

Pyrimidine ring substitution Substituent effects on the pyrimidine ring were examined while retaining the 7,8-dimethoxy substitution pattern in the carbocyclic ring (Figure 9). A methyl group in the 3-position (L) decreased intravenous activity by more than 100-fold. Similarly, introduction of carbethoxyalkyl substituents in position 3 (LI and Lll) resulted in compounds which are inactive or considerably less active than the N-unsubstituted analog (XXXV). 

In both electrophilic and nucleophilic substitutions, substituents already present in the pyridine ring have the effects which would be expected of them, on electronic grounds, upon both orientation and activation. One feature of orientation commonly observed is the tendency of a substituent at C(3> to direct substitution more to C(2) than to C(6). Interaction between the substituent and the substituting reagent, in which the nitrogen lone pair may play a part, has been held ss to be responsible for this effect (p. 173). Substituent-reagent interactions account for similar features of benzene substitutions234. 

Determine the parent structure and define as (possibly further substituted) substituents all other constitutional or nomenclatorial elements present (Chapter 1). 

It is important to note that multiplying prefixes have no influence on the alphabetical order of prefixes. The names of substituted substituents are alphabetized as a whole otherwise such substituent groups are subject to the same rules as are applied to parent structures, with two exceptions a) even high-ranked characteristic groups are expressed as suffixes here and b) the linking position (free valence) has the lowest possible locant within the limitations put forth in Section 6.4. For chain substituents this is traditionally always locant 1. 

---