Basics of Electrophilic Substitution Reactions

As noted in the earlier section Basics of Electrophilic Substitution Reactions, the loss of the hydrogen ion (H ) requires the presence of a strong base. The chloride ion (CL) is a base, but it isn t strong enough to accomplish this task. However, as shown in the mechanism, the tetrachloro-aluminate ion (A1C1 ) is a sufficiently strong base. This process also regenerates the catalyst so that it s available to continue the process. 

Once formed, the electrophile behaves like any other electrophile, so the mechanism of the attack is the same as that for the previous situation where a nucleophile attacked the electrophile (described in the earlier section Basics of Electrophilic Substitution Reactions ). The attack leads to the formation of the resonance-stabilized sigma complex, followed by the loss of a hydrogen ion to a base. 

There is another important factor in the low reactivity of pyridine derivatives toward electrophilic substitution. The —N=CH— unit is basic because the electron pair on nitrogen is not part of the aromatic n system. The nitrogen is protonated or complexed with a Lewis acid under many of the conditions typical of electrophilic substitution reactions. The formal positive charge present at nitrogen in such species further reduces the reactivity toward electrophiles. 

Only two basic types of reactions have been reported for the pyrrolo-11,2-6Ipyridazine ring system a variety of electrophilic substitution reactions and some rather straightforward functional group manipulations of substituted ring systems. 

The density functional approach has been used in an investigation of the protonation of ferrocene, ruthenocene, and osmocene in the gas phase, and the general conclusion is that the addition of a proton to the carbon atoms in the cyclopentadienyl ring is favored in ferrocene, whereas metal protonation is favored with ruthenocene and osmocene. The results obtained from these calculations were used in the interpretation of electrophilic substitution reactions of metallocenes. The basicity of the ligand group l,l -bis(diphenylphosphino)metallocene has also been examined. This is an important aspect for catalysis because it has proved difficult to obtain results which... 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

Although pyrrole appears to be both an amine and a conjugated diene, its chemical properties are not consistent with either of these structural features. Unlike most other amines, pyrrole is not basic—the pKa of the pyrrolin-ium ion is 0.4 unlike most other conjugated dienes, pyrrole undergoes electrophilic substitution reactions rather than additions. The reason for both these properties, as noted previously in Section 15.5, is that pyrrole has six 77 electrons and is aromatic. Each of the four carbons contributes one... 

If we are correct in our assumption that the electrophilic substitution of aromatic species involves such a complexes as intermediates—and it has proved possible actually to isolate them in the course of some such substitutions (p. 136)—then what we commonly refer to as aromatic substitution really involves initial addition followed by subsequent elimination. How this basic theory is borne out in the common electrophilic substitution reactions of benzene will now be considered. 

Evaluation of the only appropriate Fukui function is required for investigating an intramolecular reaction, as local softness is merely scaling of Fukui function (as shown in Equation 12.7), and does not alter the intramolecular reactivity trend. For this type, one needs to evaluate the proper Fukui functions (/+ or / ) for the different potential sites of the substrate. For example, the Fukui function values for the C and O atoms of H2CO, shown above, predicts that O atom should be the preferred site for an electrophilic attack, whereas C atom will be open to a nucleophilic attack. Atomic Fukui function for electrophilic attack (fc ) for the ring carbon atoms has been used to study the directing ability of substituents in electrophilic substitution reaction of monosubstituted benzene [23]. In some cases, it was shown that relative electrophilicity (f+/f ) or nucleophilicity (/ /f+) indices provide better intramolecular reactivity trend [23]. For example, basicity of substituted anilines could be explained successfully using relative nucleophilicity index ( / /f 1) [23]. Note however that these parameters are not able to differentiate the preferred site of protonation in benzene derivatives, determined from the absolute proton affinities [24],... 

The intermediate tricyclic ketones 495 and 496 have been transformed to the methoxy-substituted derivative 97284,285) latter ketone is subject to hydrogen-deuterium exchange only under basic conditions and appears to exist entirely in the keto form despite the ready formation of its anion and successful methylation on oxygen . In agreement with the aromatic nature of 490, the hydrocarbon undergoes electrophilic substitution reactions... 

An equally serious problem is that the nitrogen lone pair is basic and a reasonably good nucleophile—this is the basis for its role as a nucleophilic catalyst in acylations. The normal reagents for electrophilic substitution reactions, such as nitration, are acidic. Treatment of pyridine with the usual mixture of HN03 and H2SO4 merely protonates the nitrogen atom. Pyridine itself is not very reactive towards electrophiles the pyridinium ion is totally unreactive. 

The ability of azoles to electrophilic substitution reactions is determined by the activity of reagents, the basicity of substrates, and the acidity of media. This caused some uncertainty in the interpretation of results and complicated a comparison of the reactivity of various azoles. The situation has changed after Katritzky and Johnson [1] have reported the criteria allowing, with a sufficient degree of reliance, the establishment in what form (base or conjugative acid) the compound reacts. The information on the mechanism of nitration of azoles was basically borrowed from the extensive literature on the nitration of aromatic hydrocarbons [2-8] therefore, we have found expedient to discuss briefly some works in this field. 

An electrophilic substitution reaction has been used for the key ladderforming step in the synthesis of soluble ladder-type poly(phenylene)s [51-53]. These aromatic polymers have a ribbon-like rigid, planar structure. They are of interest because of their optical and electronic properties [51,54,55]. The preparation of these polymers was accomplished by two basic steps. The first step was the construction of a substituted poly(p-phenylene) backbone. The ladder structure was obtained by a subsequent intramolecular electrophilic ring closure reaction. For example, the syn-... 

---