Benzyne mechanism reactivity

Species such as 5 and 6 are called benzynes (sometimes dehydrobenzenes), or more generally, arynes, and the mechanism is known as the benzyne mechanism. Benzynes are very reactive. Neither benzyne nor any other aryne has yet been isolated under ordinary conditions, but benzyne has been isolated in an argon matrix at 8 where its IR spectrum could be observed. In addition, benzynes can be trapped for example, they undergo the Diels-Alder reaction (see 15-58). It should be noted that the extra pair of electrons does not affect the aromaticity. The... 

The photostimulated reaction of l-bromo-2,4,6-trimethylbenzene (a substrate with no o-hydrogen atoms in order to avoid the benzyne mechanism) with NH2 ions gave 1-amino-2,4,6-trimethylbenzene (70%) and the reduction product 1,3,5-trimethylbenzene (6%). This reaction did not occur in the dark221. By competition experiments of NH2 ions with Ph2P" ions toward 2,4,6-trimethylphenyl radicals, it was found that Ph2P ions are 6.4 times more reactive than NH2 ions221, whereas NH2 ions are twice more reactive than acetone enolate ions toward the same radical in liquid ammonia222. 

In summary, the benzyne mechanism operates when the halobenzene is unactivated toward nucleophilic aromatic substitution, and forcing conditions are used with a strong base. A two-step elimination forms a reactive benzyne intermediate. Nucleophilic attack, followed by protonation, gives the substituted product. 

Nucleophilic aromatic substitutions have been studied in detail. Either of two mechanisms may be involved, depending on the reactants. One mechanism is similar to the electrophilic aromatic substitution mechanism, except that nucleophiles and carban-ions are involved rather than electrophiles and carbocations. The other mechanism involves benzyne, an interesting and unusual reactive intermediate. 

Cyclopentadienone is an elusive compound that has been sought for many years but with little success. Molecular orbital calculations predict that it should be highly reactive, and so it is it exists only as the dimer. The tetraphenyl derivative of this compound is to be synthesized in this experiment. This derivative is stable, and reacts readily with dienophiles. It is used not only for the synthesis of highly aromatic, highly arylated compounds, but also for examination of the mechanism of the Diels-Alder reaction itself. Tetraphenylcyclopentadienone has been carefully studied by means of molecular orbital methods in attempts to understand its unusual reactivity, color, and dipole moment. In Chapter 48 this highly reactive molecule is used to trap the fleeting benzyne to form tetraphenylnaphthalene. Indeed, this reaction constitutes evidence that benzyne does exist. 

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. 

This phenol synthesis is different from the nucleophilic aromatic substitutions discussed in the previous section because it takes place by an elimination addition mechanism rather than an addition/elimination. Strong base first causes the elimination of HX from halobenzene in an E2 reaction, yielding a highly reactive benzyne intermediate, and a nucleophile then adds to benzyne in a second step to give the product. The two steps are similar to those in other nucleophilic aromatic substitutions, but their order is reversed elimination before addition for the benzyne reaction rather than addition before elimination for the usual reaction. 

Problem 3.13. In the Stiles reaction, the highly reactive compound benzyne is obtained by treatment of anthranilic acid (2-aminobenzoic acid) with NaNC>2 and HC1. Draw a mechanism for this reaction. 

Because the ring prevents linearity of the C—C=C—C unit and it bonding in that unit is weak, benzyne is strained and highly reactive. This enhanced reactivity is evident in the second stage of the elimination-addition mechanism as shown in steps 2... 

Phenyl aryl sulfides are prepared in excellent yield from benzyne and ethyl aryl sulfides by a similar mechanism (10 examples, 87-97% yields). Even o-bis(phenylthio)benzene could be obtained (90%) from the corresponding bis(ethylthio)benzene and excess benzyne. When Ar in these reactions was a 9-anthryl group similar reactions occurred except for 9- -butylthioanthracene 583, which gave Diels-Alder adducts 584 and 585 instead. Apparently, steric hindrance at the sulfur is sufficient to negate its effectiveness as a nucleophile, even toward the highly reactive and sterically unencumbered benzyne. 

For the palladium-catalyzed cyclotrimerization of arynes, a mechanism similar to the accepted mechanism for [2+2+2] cycloaddition of alkynes may be proposed (Scheme 15). Though it has not been studied in depth, some experimental results support it. Firstly, aryne-forming conditions are necessary for the reaction to proceed (see Table 1, entry 8) no reaction of trifiate 55 takes place at room temperature in the presence of the catalyst if fluoride is absent, which rules out a mechanism initiated by the oxidative addition of the aryl trifiate to palladium. Data obtained in the closely related cocycloadditions of benzyne with alkynes, discussed below, hkewise point to benzyne as the reactive species. Secondly, the benzyne-palladium complex 67 is a plausible initial intermediate because the ability of group 10 metals to coordinate benzyne is well known (see Sect. 1.2.2), and although benzyne complexes of palladium have eluded isolation (apparently because of their instability) [7,26], they may well be able to exist as transient intermediates in a catalytic cycle such as that shown in Scheme 15. Thirdly, it is known that benzyne complex 34 can form metallacy-cles similar to 68, albeit with dcpe as hgand instead of PPhj [26]. 

Scheme 25 shows plausible mechanisms for both the Pd(PPh3)4-catalyzed and the Pd2(dba)3-catalyzed cocycloadditions of benzyne and DMAD. Although further investigation is needed to determine these mechanisms in detail, a pathway similar to the one generally accepted for alkyne cyclotrimer-ization is consistent with reports on the reactivity of aryne complexes of group 10 elements [66]. 

The preceding sections have demonstrated the enhanced reactivity of the C-F bonds of fluoroalkyl groups when coordinated to a metal. The same principle can apply to the ortho-C-F bonds of M-CeFs complexes. Hughes et a/. have shown that [M(77 -C5Me5)(H)(C6F5)(PMe3)] (M = Rh, Ir) reacts with butyllithium to form ry -tetrafluorobenzyne complexes (Scheme 53), the first examples of fluorinated benzyne complexes to be isolated. The mechanism of this reaction is unknown.They are readily converted into tetrafluorophenyl derivatives by protonation. 

A general consideration of reactive intermediates in 1956 by Leffler suggested that assignments of reaction mechanisms very often assume intermediates that have not been isolable for direct study and the physical reahty of such intermediates depends on their relation to similar substances that do happen to be stable enough to study directly. Study of reactive intermediates focuses not only on ions, free radicals, and carbenes but also on other reactive species such as benzynes and ketenes, which were recognized around 1900. With advances in experimental methods of generation and detection of such species, as well as improvements in... 

We can illustrate this mechanism with the reaction of bromobenzene and amide ion. In the first step (see the following mechanism), the amide ion initiates an elimination by abstracting one of the ortho protons because they are the most acidic. The negative charge that develops on the ortho carbon is stabilized by the inductive effect of the bromine. The anion then loses a bromide ion. This elimination produces the highly unstable, and thus highly reactive, benzyne. Benzyne then reacts with any available nucleophile (in this case, an amide ion) by a two-step addition reaction to produce aniline. 

Important reactive metal-containing intermediates (e.g., metal-benzyne complexes, MtC02" ) and processes (e.g., decarbonylation, oxidation, reductive addition) of practical interest have been characterized using various mass spectral methods, and provide insight as to the mechanisms of organometallic reactions. 

What reactions of halides do you know besides displacement The El and E2 reactions compete with displacement reactions (Chapter 7). If HCl were lost from chlorobenzene, a cyclic alkyne, called benzyne (or dehydrobenzene), would be formed. This symmetrical bent alkyne might be reactive enough to undergo an addition reaction with the amide ion. If this were the case, the labeled material must produce two differently labeled products of addition (Fig. 14.113), because the NH2 can attack either carbon of the alkyne. This mechanism is the elimination-addition version of the SnAt reaction. 

Because of the overlap of the sp orbitals in the second 7t bond of benzyne, the bond is very reactive toward nucleophiles. Attack of a nucleophile such as amide ion can occur at either carbon atom of the triple bond. Subsequent protonation of both of the two possible anions yields the product mixture. These two steps constitute the addition portion of the mechanism. 

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