Electrophilic substitution reaction limitations

The range of preparatively useful electrophilic substitution reactions is often limited by the acid sensitivity of the substrates. Whereas thiophene can be successfully sulfonated in 95% sulfuric acid at room temperature, such strongly acidic conditions cannot be used for the sulfonation of furan or pyrrole. Attempts to nitrate thiophene, furan or pyrrole under conditions used to nitrate benzene and its derivatives invariably result in failure. In the... 

Other typical electrophilic aromatic substitution reactions—nitration (second entr-y), sul-fonation (fourth entry), and Friedel-Crafts alkylation and acylation (fifth and sixth entries)—take place readily and are synthetically useful. Phenols also undergo electrophilic substitution reactions that are limited to only the most active aromatic compounds these include nitrosation (third entry) and coupling with diazonium salts (seventh entry). 

Equation (7-85) is a selectivity-reactivity relationship, with lower values of Sf denoting lower selectivity. Lower values ofpt correspond to greater reactivity, with the limit being a partial rate factor of unity for an infinitely reactive electrophile. This selectivity-reactivity relationship is followed for the electrophilic substitution reactions of many substituted benzenes, although toluene is the best studied of these. 

Toluene (methylbenzene) is similar to benzene as a mononuclear aromatic, but it is more active due to presence of tbe electron-donating metbyl group. However, toluene is much less useful than benzene because it produces more polysubstituted products. Most of tbe toluene extracted for cbemical use is converted to benzene via dealkylation or disproportionation. Tbe rest is used to produce a limited number of petro-cbemicals. Tbe main reactions related to tbe cbemical use of toluene (other than conversion to benzene) are the oxidation of the methyl substituent and the hydrogenation of the phenyl group. Electrophilic substitution is limited to the nitration of toluene for producing mono-nitrotoluene and dinitrotoluenes. These compounds are important synthetic intermediates. 

As mentioned above, ferrocene is amenable to electrophilic substitution reactions and acts like a typical activated electron-rich aromatic system such as anisole, with the limitation that the electrophile must not be a strong oxidizing agent, which would lead to the formation of ferrocenium cations instead. Formation of the CT-complex intermediate 2 usually occurs by exo-attack of the electrophile (from the direction remote to the Fe center. Fig. 3) [14], but in certain cases can also proceed by precoordination of the electrophile to the Fe center (endo attack) [15]. 

What we shall be doing in the discussion that follows is comparing the effect that a particular Y would be expected to have on the rate of attack on positions o-/p- and m-, respectively, to the substituent Y. This assumes that the proportions of isomers formed are determined entirely by their relative rates of formation, i.e. that the control is wholly kinetic (cf. p. 163). Strictly we should seek to compare the effect of Y on the different transition states for o-, m- and p-attack, but this is not usually possible. Instead we shall use Wheland intermediates as models for the transition states that immediately precede them in the rate-limiting step, just as we have done already in discussing the individual electrophilic substitution reactions (cf. p. 136). It will be convenient to discuss several different types of Y in turn. 

In (—)-sparteine-mediated deprotonation and electrophilic substitution reactions, the minor enantiomer is close to the limits of exact determination. Therefore, the influence of the alkyl residue on selectivity was investigated for less efficient (/ ,/ )- ,2-bis(dimethyl-amino)cyclohexane/i-BuLi (equation 11)°. On the base of the isolated corresponding... 

As an example of a solvent-dependent electrophilic substitution reaction, the azo coupling (SsAr) reaction of 4-nitrobenzenediazonium tetrafluoroborate with N,N-dimethylaniline is given in Eq. (5-27) [504]. According to the two-step arenium ion mechanism, the activation process of the rate-limiting first step is connected with the dispersion of the positive charge. This should lead to a decrease in rate with increasing solvent polarity. 

Limitations on electrophilic substitution reactions with substituted benzenes... 

Limitations on Electrophilic Substitution Reactions with Substituted Benzenes... 

The limitations of the first method is that quite often the blocking group, being labile, is knocked-off during the electrophilic substitution reaction. With the second, the problem could be the ready availability of the starting compounds and removal of the blocking group. 

Electrophilic substitution reactions (Scheme 4) in many cases convert one derivative of a tervalent phosphorus acid into another and numerous examples have been given in Section II. Therefore, the following discussion will be limited to electrophilic reactions which are not treated in Section II because they give products that are not tervalent phosphorus acid derivatives, or because the reactions are of limited preparative value. 

Initially, it was decided that the donor substituent should contain the aromatic diamine functionality necessary for polymerization (27). However, the target monomer M-5 proved impossible to prepare by classical electrophilic substitution reactions. All attempts to couple triaiylamines substituted with peripheral electron donor groups with diazonium salts failed and resulted instead in deaiylation 18). The desired monomer M-5 was finally prepared by the Mills reaction of tris-p-aminophenylamine with p-nitronitrosobenzene 12 as shown in Scheme 2. This is an exceptionally versatile synthetic procedure limited only by the ability to prepare substituted nitrosobenzene partners. 

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