Benzyne mechanism halides

Unactivated aryl halides can be converted to amines by the use of NaNH2, NaNHR, or NaNR2. With these reagents, the benzyne mechanism generally operates, so cine substitution is often found. Ring closure has been effected by this type of reaction,for example. 

Direct high-temperature microwave-assisted aminations of a variety of aryl halides [257] or aryl triflates [258] under transition metal-free conditions have also been reported, probably involving a benzyne mechanism. 

With very strong bases, such as amide ion, NHj, unactivated aryl halides undergo substitution by an elimination-addition (benzyne) mechanism. 

Unactivated aryl iodides undergo the conversion Arl — ArCHj when treated with tris(diethylamino)sulfonium difluorotrimethylsilicate and a palladium catalyst.131 A number of methods, all catalyzed by palladium complexes, have been used to prepare unsymmetrical biaryls (see also 3-16). In these methods, aryl bromides or iodides are coupled with aryl Grignard reagents,152 with arylboronic acids ArB(OH)2,153 with aryltin compounds Ar-SnR3,154 and with arylmercury compounds.155 Unsymmetrical binaphthyls were synthesized by photochemically stimulated reaction of naphthyl iodides with naphthoxide ions in an SrnI reaction.156 Grignard reagents also couple with aryl halides without a palladium catalyst, by the benzyne mechanism.157 OS VI, 916 65, 108 66, 67. 

When electron-withdrawing groups were attached to the aryl halide as in /7-chloro, p-bromo and /7-iodobenzonitriles and 4-bromobenzophenone, most of the reaction with 143 follows the benzyne mechanism, yielding anilines. When the aryl halides were added to a... 

Aryl halides are converted to phenols if activating groups are present or if exceedingly strenuous conditions are employed. When the reaction is carried out at high temperatures, cine substitution is observed, indicating a benzyne mechanism. The reaction has been done using NaOH on Montmorillonite KIO and AgNOa with microwave irradiation. ... 

NaNHR, or NaNR2. Lithium dialkylamides also react with aryl halides to give the A-arylamine. With these reagents, the benzyne mechanism generally operates, so cine substitution is often found. The reaction of an amine, an aryl halide, and potassium tert-butoxide generates the A -aryl amine. A -Arylation was accomplished with butyllithium and a secondary amine using Ni/C-diphenylpho-sphinoferrocene (dppf). Ring closure has been effected by this type of reaction, as in the conversion of 16 to the tetrahydroquinoline. 

To determine the regiochemistry of halide replacement by amide ion, Roberts and co-workers studied the reaction of chlorobenzene-1- C and iodobenzene-l- C with KNH2 in liquid NH3, as shown in Figure 8.60. The observation of nearly equal yields of the two products is most consistent with the benzyne mechanism (Figure 8.59). ... 

Halobenzenes undergo nucleophilic aromatic substitution through either of two mechanisms. If the halobenzene has a strongly electron-withdrawing substituent in the ortho or para position, substitution occurs by addition of a nucleophile to the ring, followed by elimination of halide from the intermediate anion. If the halobenzene is not activated by an electron-withdrawing substituent, substitution can occur by elimination of HX to give a benzyne, followed by addition of a nucleophile. 

The scope of this reaction appeared to be limited to dialkylamides and electron-neutral aryl halides. For example, nitro-, acyl-, methoxy-, and dimethylamino-substituted aryl halides gave poor yields upon palladium-catalyzed reaction with tributyltin diethylamide. Further, aryl bromides were the only aryl halides to give any reaction product. Vinyl bromides gave modest yields of enamines in some cases. Only unhindered dialkyl tin amides gave substantial amounts of amination product. The mechanism did not appear to involve radicals or benzyne intermediates. 

Reacts with aryl halides to yield anilines by a benzyne aromatic substitution mechanism (Section 16.8). 

We take up the aryl halides in a separate chapter because they differ so much from the alkyl halides in their preparation and properties. Aryl halides as a class are comparatively unreactive toward the nucleophilic substitution reactions so characteristic of the alkyl halides. The presence of certain other groups on the aromatic ring, however, greatly increases the reactivity of aryl halides in the absence of such groups, reaction can still be brought about by very basic reagents or high temperatures. We shall find that nucleophilic aromatic substitution can follow two very different paths the bimolecular displacement mechanism for activated aryl halides and the elimination-addition mechanismy which involves the remarkable intermediate called benzyne. 

We have seen that electron-withdrawing groups activate aryl halides toward nucleophilic substitution. In the absence of such activation, substitution can be made to take place, by use of very strong bases, for example. But when this is done, substitution does not take place by the mechanism we have just discussed (the so-called bimolecular mechanism), but by an entirely different mechanism the benzyne (or elimination-addition) mechanism. Let us f rst see what this mechanism is, and then examine some of the evidence for it. 

All the elimination reactions listed in Review Table 2 occur by the same E2 mechanism. Though they appear different, the elimination of an alkyl halide to yield an alkene (reaction 1), the elimination of a vinylic halide to yield an alkyne (reaction 2), and the elimination of an aryl halide to yield a benzyne (reaction 3) are ail E2 reactions,... 

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