Pyridinium ions, electrophilic substitution

On co-adsorbing phenol and methanol, the protonation of methanol occurs on the active acid sites as the labile protons released from the phenol reacted with methanol. Thus protonated methanol became electrophilic methyl species, which undergo electrophilic substitution. The ortho position of phenol, which is close to the catalyst surface, has eventually become the substitution reaction center to form the ortho methylated products (Figure 3). This mechanism was also supported by the competitive adsorption of reactants with acidity probe pyridine [79]. A sequential adsorption of phenol and pyridine has shown the formation of phenolate anion and pyridinium ion that indicated the protonation of pyridine. 

For example, 3-bromopyridine is formed when pyridine is reacted with bromine in the presence of oleum (sulfur trioxide in cone, sulfuric acid) at 130 °C (Scheme 2.4). Direct electrophilic substitution is not involved, however, aszwitterionic (dipolar) pyridinium-A-sulfonate is the substrate for an addition of bromide ion. Subsequently, the dihydropyridine that is formed reacts, possibly as a dienamine, with bromine to generate a dibromide, which then eliminates bromide ion from C-2. It is notable that no bromination occurs under similar conditions when oleum is replaced by cone, sulfuric acid alone instead, pyridinium hydrogensul-fate is produced. 

Electrophilic substitution of pyridine is further hindered by the tendency of the nitrogen atom to attack electrophiles and take on a positive charge. The positively charged pyridinium ion is even more resistant than pyridine to electrophilic substitution. 

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. 

Pyridinium, quinolinium, and isoquinolinium cations are the major species undergoing electrophile substitution reactions under acidic conditions [90AHC(47)1]. As expected from Table XXIII, the electrophilic reaction of pyridinium ion occurs at the 3-position, and an electrophile attacks at the 5- and 8-positions of quinolinium and isoquinolinium cations. Electrophile reactivity of 1 is rather low because of its electron accepting character. Molecular orbital calculations of its orientation did not give a consistent conclusion. Electron density and superdelocalizability (electrophile) predict that position 1 will be the most reactive towards an electrophile, while inspection of the localization energy (electrophile) predicts that electrophilic reaction takes place at position 4. 

Reactions of the quinolizinium ion have analogies with the pyridinium ion (see p 277/280). The quinolizinium ion as a deactivated heteroarene is resistant to electrophilic reactions. Bromination is one of the few exceptions. Firstly, it leads to the perbromide 5, then only under drastic SgAr conditions to the substitution product 6 ... 

Heteroarenes show specific side-chain reactivity at heterobenzylic C-H-bonds in position 2 or 4 to the ring hetero atom. This is responsible for a large number of base-catalyzed electrophilic C-C forming processes like aldol, Claisen and Mannich reactions with appropriately substituted pyrylium and pyridinium ions, pyridines, benzazines and benzodiazines. 

Common electrophilic substitutions such as nitration in sulphuric acid (p. 171) and sulphonation (p. 176), which lead to 3-substitution, involve the pyridinium ion. Evidence from tritiation studies (p. 164) shows that the... 

The diene-Br2 complex is again in equilibrium with the reagents, and nucleophilic attack at carbon can be carried out either by the bromide of the ammonium bromide ion pair, formed at the moment of the electrophilic attack, or by the less nucleophilic pyridine added in excess in the reaction medium. It is noteworthy that this mechanism is characterized by a rate- and product-limiting nucleophilic step which should be quite insensitive to steric hindrance around the double bond. In agreement with a weak influence of the steric effects, pyridinium perbromide reacts in chloroform and tetrahydrofuran with substituted conjugated and non-conjugated dienes to give selectively (>95%) bromine addition to the more alkylated double bond (equation 44). 

Practically all the reactions of quinolizinium ions are similar to those of pyridinium salts, thus they are resistant to electrophilic attack, but readily undergo nucleophilic addition, the initial adducts undergoing spontaneous electrocyclic ring opening to afford, finally, 2-substituted pyridines however the susceptibility of the cations to nucleophiles is not extreme - Uke simpler pyridinium salts they are stable to boiling water. 

The attack of the acid (154) on the readily polarizable 1,2-dithiafulvene (155) corresponds to the extremely ready addition of electrophilic reagents to the simple and vinylogous heptafulvene derivatives, which are iso-n-electronic with 155. The opening of the dithiole rings in 156 and 158 under the pressure of the carbanionoid electron pair liberated by the proton abstraction and of the free electron pair on the sulfur, as well as the elimination of elementary sulfur and the intramolecular electrophilic attack of the mercaptide ion (157) on the 5-position to form 158, are simply the typical reactions of 1,2-dithioles that have already been discussed (Section II, B, 3). The reactivity of the 3-methyl group in 154 finds many parallels in the ease of condensation of the methyl-substituted pyridinium, pyrylium, thiopyrylium, and tropylium salts, and particularly... 

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