Electrophilic aromatic substitutions chlorination

Phenol is the starting material for 2,4-dichlorophenoxyacetic acid via electrophilic aromatic substitution. Chlorination of phenol gives 2,4-dichlorophenol and the sodium salt of this compound is reacted with sodium chloroacetate and acidification gives 2,4-dichlorophenoxyacetic acid. 

This pattern is also followed for other electrophilic aromatic substitutions— chlorination, bromination, sulfonation, and so on. Toluene undergoes mainly ortho,para substitution, whereas nitrobenzene undergoes meta substitution. 

Reaction of benzamhde (C6H5NHCC6H5) with chlorine in acetic acid yields a mixture of two monochloro denvatives formed by electrophilic aromatic substitution Suggest reasonable structures for these two isomers... 

Electrophilic aromatic substitution (Section 22.14) Arylamines are very reactive toward electrophilic aromatic substitution. It is customary to protect arylamines as their A/-acyl derivatives before carrying out ring nitration, chlorination, bromination, sulfonation, or Friedel-Crafts reactions. 

Aryl chlorides and bromides are conveniently prepared by electrophilic aromatic substitution. The reaction is limited to chlorination and bromination. Fluorination is difficult to control iodi-nation is too slow to be useful. 

In general, if condensation polymers are prepared with methylated aryl repeat units, free radical halogenatlon can be used to introduce halomethyl active sites and the limitations of electrophilic aromatic substitution can be avoided. The halogenatlon technique recently described by Ford11, involving the use of a mixture of hypohalite and phase transfer catalyst to chlorinate poly(vinyl toluene) can be applied to suitably substituted condensation polymers. 

Because the initial electrophilic attack and carbocation formation results in loss of aromatic stabilization, the electrophiles necessary for electrophilic aromatic substitution must be more reactive than those that typically react with alkenes. Thus, chlorination or... 

A historically important method, first used about 1900, is sulfonation of benzene followed by desulfonation with caustic. This is classic aromatic chemistry. In 1924 a chlorination route was discovered. Both the sulfonation and chlorination reactions are good examples of electrophilic aromatic substitution on an aromatic ring. Know the mechanism of these reactions. These routes are no longer used commercially. 

PCBs are made by the chlorination of biphenyl by electrophilic aromatic substitution (know this mechanism ). A typical sample might contain some of the chloro derivatives shown here. 

Dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) dominated the herbicide market up to the late 1960s. These are sometimes called phenoxy herbicides. Phenol is the starting material for 2,4-D. Chlorination via electrophilic aromatic substitution (know the mechanism ) gives 2,4-dichlorophenol. The sodium salt of this compound can react with sodium chloroacetate (Sn2) and acidification gives 2,4-D. 

Two electrophilic aromatic substitution reactions need to be performed chlorination and Friedel-Crafts acylation. The order in which the reactions are carried out is important chlorine is an ortho, para director, and the acetyl group is a meta director. Since the groups are meta in the desired compound, introduce the acetyl group first. 

Aromatic compounds react mainly by electrophilic aromatic substitution, in which one or more ring hydrogens are replaced by various electrophiles. Typical reactions are chlorination, bromination, nitration, sulfonation, alkylation, and acylation (the last two are Friedel-Crafts reactions). The mechanism involves two steps addition of the electrophile to a ring carbon, to produce an intermediate benzenonium ion, followed by proton loss to again achieve the (now substituted) aromatic system. 

Furosemide can also be synthesized starting with 2,4-dichlorobenzoic acid (formed by chlorination and oxidation of toluene). Reaction with chlorosulfonic acid is an electrophilic aromatic substitution via the species -S02C1 attacking ortho and para to the chlorines and meta to the carboxy-late. Ammonolysis to the sulfonamide is followed by nucleophilic aromatic substitution of the less hindered chlorine by furfurylamine (obtained from furfural—a product obtained by the hydrolysis of carbohydrates). 

In the non-phenolic oxidative coupling reaction the electron-rich arene 19 undergoes electron transfer yielding the radical cation 20, which is preferably treated in chlorinated solvents or strongly acidic media. Attack of 20 on the electron-rich reaction partner 21 will proceed in the same way as an electrophilic aromatic substitution involving adduct 22 which extrudes a proton. The intermediate radical 23 is subsequently oxidized to the cationic species 24 which forms the biaryl 25 by rearomatization. In contrast with the mechanism outlined in Scheme 5, two different oxidation steps are required. 

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