Nucleophilic substitution substituted benzenes

In contrast, substituents in 1,2,4-triazoles are usually rather similar in reactivity to those in benzene although nucleophilic substitution of halogen is somewhat easier, forcing conditions are required. 

Pyridine, on the other hand, is more reactive than benzene towards nucleophilic aromatic substitution. This is effectively reaction towards the C=N imine function, as described above. Attack is... 

Nucleophilic aromatic substitutions Pyridine is more reactive than benzene towards nucleophilic aromatic substitutions because of the presence of electron-withdrawing nitrogen in the ring. Nucleophilic aromatic substitutions of pyridine occur at C-2 (or C-6) and C-4 positions. 

Now, because we have a pyridine and not a benzene ring, nucleophilic aromatic substitution can... 

These authors studied the action of several electrophilic and nucleophilic reagents on unsubstituted 1,2-benzoisoselenazole and found that while electrophiles attack the benzene ring, nucleophiles either substitute the 3-position of the heterocycle or cleave the ring. Thus nitration and bromina-tion led to the formation of monosubstituted derivatives at the 5 and 7 position. Potassium amide, however, gave the 3-amino derivative (5) [Eq. (5)]. 

Pyridine is less reactive than benzene toward electrophilic aromatic substitution and more reactive than benzene toward nucleophilic aromatic substitution. 

Chloro(trifluoromethyl)benzene undergoes nucleophilic substitution by the alkoxide anion to give compound A. 

Aniline reacts with nitrous acid to give benzenediazonium salts, which react with a variety of reagents via a substitution reaction. These reagents include cuprous salts, aqueous acid, iodide, hypophosphorous acid, and activated benzene derivatives. Nucleophilic substitution at the sp carbon of a halo-benzene derivative does not occur unless high heat and pressure are used. Electron-withdrawing substituents on the benzene ring significantly lower the temperature required for the reaction. Nucleophiles for this nucleophilic aromatic substitution reaction include water, hydroxide, alkoxide, and amines. 

Now let s look at why this substitution reaction occurs. The cloud of tt electrons above and below the plane of its ring makes benzene a nucleophile, so it reacts with an electrophile (Y" ). When an electrophile attaches itself to a benzene ring, a carbocation intermediate is formed. 

As a result, substituents that donate electrons to the benzene ring increase benzene s nucleophilicity and stabilize the partially positively charged transition state, thereby increasing the rate of electrophilic aromatic substitution these are called activating substituents. In contrast, substituents that withdraw electrons from the benzene ring deaease benzene s nucleophilicity and destabilize the transition state, thereby decreasing the rate of electrophilic aromatic substitution these are called deactivating substituents. 

Since pyridine is less reactive than benzene in electrophilic aromatic substitution reactions, it should not be surprising that pyridine is more reactive than benzene in nucleophilic aromatic substitution reactions. The electron-withdrawing nitrogen atom that destabilizes the intermediate in electrophilic aromatic substitution stabilizes the intermediate in nucleophilic aromatic substitution. Notice that, in nucleophilic aromatic substitution reactions, the ring has a leaving group that can be replaced by a nucleophile. 

Benzene and substituted benzenes are nucleophiles, so they react with electrophiles in electrophilic aromatic substitution reactions. If the electron density of the benzene ring is reduced by strongly electron-withdrawing groups, a halo-substituted benzene can undergo a nucleophilic aromatic substitution reaction. 

Consequently, it should be relatively acidic, even more acidic than an amide (plfa 22, Section 20-7). It is therefore likely that A is doubly deprotonated before attacking the benzene nucleus. Nucleophilic aromatic substitution is then readily formulated to assemble the first new ring. In the scheme below, only one—the dominating—resonance form of the anion resulting from nucleophilic attack on the arene is shown, that in which the negative charge is delocalized onto the carbonyl oxygen. 

Salmoria et al. (1998) carried out microwave-assisted aromatic nucleophilic substitutions reaction between disubstituted-benzenes and nucleophile piperidine or potassium t-butoxide in homogeneous medium such as dimethyl sulfoxide or di-methylformamide at atmospheric pressure to give substituted product. The rate was 2.7-12 time faster under MW condition, than under conventional condition. 

Nucleophilic substitution of benzene itself is not possible but the halogeno derivatives undergo nucleophilic displacement or elimination reactions (see arynes). Substituents located in the 1,2 positions are called ortho- 1,3 meta- and 1,4 para-. 

Piperazinothiazoies (2) were obtained by such a replacement reaction, Cu powder being used as catalyst (25. 26). 2-Piperidinothiazoles are obtained in a similar way (Scheme 2) (27). This catalytic reaction has been postulated in the case of benzene derivatives as a nucleophilic substitution on the copper-complexed halide in which the halogen possesses a positive character by coordination (29). For heterocyclic compounds the coordination probably occurs on the ring nitrogen. 

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