Haloarenes nucleophilic attack

Where reactivity is low, as for example with non-activatcd haloarenes, soliddiquid conditions are to be preferred over liquid liquid conditions and better yields are frequently obtained when TDA-1 is used as the catalyst instead of a quaternary ammonium salt [28]. Although not activated to nucleophilic attack, 2-chlorophenol reacts with ethanol under solid liquid conditions with microwave irradiation in the presence of benzyltrimethylammonium chloride to produce the ether in 70% yield [44], It is possible that the procedure has potential for further exploitation. 

Haloarene chromium tricarbonyl complexes are activated to nucleophilic attack by thiolate anions [58, 59]. High yields of the thioethers are obtained under liquiddiquid two-phase conditions, but optimum yields are achieved under soliddiquid conditions. In many cases the thioether is produced directly but, where the reaction mixture contains thioether and its chromium complex, the thioether can be isolated by degradation of the complex with iodine or an excess of the thiol. Both 1,2- and 1,4-dichlorobenzenes yield only monothioethers, even when an excess of thiolate anion is used. In contrast, 1,3-dichlorobenzenes produce a mixture of the mono- and dithioethers [59]. Aryl allyl thioethers have been produced under catalysed Heck reaction conditions from S-allyl thiocarbamates and iodobenzene [60]. 

Finding ways to make nonactivated haloarenes susceptible to nucleophilic attack has always been a great challenge for chemists. Catalysis with transition metal complexes has proven to be efficient in activating inert aryl-halogen bonds and performing various nucleophilic displacement reactions (Eq. 25) [ 178]. The... 

Due to their availability, haloarenes are frequently used for synthetic reactions, and when nucleophilic attack is rate limiting, as is usually the case, the reactivity order is F C1, Br>I. Although reaction can occur in unactivated systems, this requires the use of high temperatures and/or pressures and may be aided by metal catalysts. Thus, reaction of chlorobenzene with aqueous sodium hydroxide or ammonia can yield phenol and aniline, respectively. In systems containing one or more EWGs, reaction with alkoxides or phenoxides can be used to form alkyl aryl ethers and... 

Complexes of haloarenes undergo nucleophilic substitution of the halogen by stabilized carbanions to generate the substituted arene complex. - This reaction occurs with nucleophiles that add reversibly to the arene ring because the kinetically preferred site of attack is ortho and meta to the halogen. As noted above, extrusion of the halogen and a productive substitution reaction occurs upon addition to the less-favored carbon located ipso to the halogen (Equation 11.53). 

We should examine why it is that electron-withdrawing groups only accelerate the reaction when they are positioned ortho or para to the halogen to be substituted. If we first consider the reaction of an unsubstituted haloarene with a nucleophile, then the charge in the Meisenheimer complex produced can only be located on the positions ortho and para to the position of the attack (Figure 13.16). 

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