Toward electrophilic reagents nitration

The 5-position of selenazoles is very reactive towards electrophilic reagents. Nitration of 2-alkylselenazoles affords 5-nitro derivatives under relatively mild conditions. 2-... 

Compared with the parent benzothiazinotropones, these oxides exhibit a greater reactivity toward electrophilic reagents. This is explained by the greater electron density on the rings due to the easier deprotonation of NH. Bromination takes place at C-9 and C-7, and nitration at C-9. 

Aromatic amines are usually very reactive towards electrophilic reagents yielding derivatives substituted at carbon atoms. Reactions such as nitration and bromination can be applied to the amine as such, or to the amine previously protected at the nitrogen site. Although the derivatives from these reactions are useful for identification and possibly quantitative purposes, the site and stoichiometry of the substitution are specific for every system, and no generalisation can be made. Aryldiazonium salts undergo coupling reactions with aromatic amines to yield azo dyes, which can be used for detection and determination. In Table 12 some of the aryldiazonium salts used in analysis are listed. 

When unsubstituted, C-5 reacts with electrophilic reagents. Thus phosphorus pentachloride chlorinates the ring (36, 235). A hydroxy group in the 2-position activates the ring towards this reaction. 4-Methylthiazole does not react with bromine in chloroform (201, 236), whereas under the same conditions the 2-hydroxy analog reacts (55. 237-239. 557). Activation of C-5 works also for sulfonation (201. 236), nitration (201. 236. 237), Friede 1-Crafts reactions (201, 236, 237, 240-242), and acylation (243). However, iodination fails (201. 236). and the Gatterman or Reimer-Tieman reactions yield only small amounts of 4-methyl-5-carboxy-A-4-thiazoline-2-one. Recent kinetic investigations show that 2-thiazolones are nitrated via a free base mechanism. A 2-oxo substituent increases the rate of nitration at the 5-position by a factor of 9 log... 

Indole is very reactive towards electrophiles, and it is usually necessary to employ reagents of low reactivity. Nitration with HNO3-H2SO4 is... 

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. 

Notice that the regioselectivity is the same as it was with pyrrole—the 2-position is more reactive than the 3-position in both cases. The product ketones are less reactive towards electrophiles than the starting heterocycles and deactivated furans can even be nitrated with the usual reagents used for benzene derivatives. Notice that reaction has occurred at the 5-position in spite of the presence of the ketone. The preference for 2- and 5-substitution is quite marked. 

Reactions with electrophilic reagents take place with substitution at C-3 or by addition at the pyridine nitrogen. All the aza-indoles are much more stable to acid than indole (cf. 20.1.1.9), no doubt due to the diversion of protonation onto the pyridine nitrogen, but the reactivity towards other electrophiles at C-3 is only slightly lower than that of indoles. Bromination and nitration occur cleanly in all four parent systems and are more controllable than in the case of indole. Maniuch and Vilsmeier reactions can be carried out in some cases, but when the latter fails, 3-aldehydes can be prepared by reaction with hexamine, possibly via the anion of the azaindole. Alkylation under neutral conditions results in quatemisation on the pyridine nitrogen and reaction with sodium salts allows A-1-alkylation. Acylation under mild conditions also occurs at N-1. The scheme below summarises these reactions for the most widely studied system - 7-azaindole. Acylation at C-3 in all four systems can be carried out at room temperature in the presence of excess aluminium chloride. ... 

It is interesting to note that the pyridine ring in thienol 2,3-6 pyridine-A-oxide (53) is more reactive toward electrophiles than is the thiophene ring81 moreover, the orientation in nitration of this molecule depends on the reagent. 

The addition reactions discussed in Sections 4.1.1 and 4.1.2 are initiated by the interaction of a proton with the alkene. Electron density is drawn toward the proton and this causes nucleophilic attack on the double bond. The role of the electrophile can also be played by metal cations, and the mercuric ion is the electrophile in several synthetically valuable procedures.13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethanesulfonate, or nitrate salts are more reactive and preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 The cation may be predominantly bridged or open, depending on the structure of the particular alkene. The addition is completed by attack of a nucleophile at the more-substituted carbon. The nucleophilic capture is usually the rate- and product-controlling step.13,16... 

Electrophilic substitution reactions of 5-hydroxybenzo[6]thiophene have been investigated in some detail. The 4-position is the most reactive toward nitration,152 nitrosation,497 bromination,422 and formylation (Duff procedure).338 Dibromination in the presence of acetate ion affords 4,6-dibromo-5-hydroxybenzo[6]thiophene,421,422, 497 and not the 3,4-dibromo derivative, as previously believed.542 Dichlorination similarly affords the 4,6-dichloro derivative,421 and not 4,4-dich loro-4,5-dihydrobenzo[6]thiophen-5-one, as reported earlier by Fries d al.542 An interesting comparison can be made between the behavior of 5-hydroxy benzo[6]thiophene and 2-naphthol in electrophilic substitution reactions. It is clear that both positions ortho to the hydroxyl group in 5-hydroxybenzo[6]thiophene are attacked, in contrast to 2-naphthol, where only the 1-position is attacked even in the presence of an excess of the reagent. Disubstitu-... 

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