Mechanism, aromatization aryne

Nucleophilic aromatic substitution can also occur by an elimination-addition mechanism This pathway is followed when the nucleophile is an exceptionally strong base such as amide ion m the form of sodium amide (NaNH2) or potassium amide (KNH2) Benzyne and related arynes are intermediates m nucleophilic aromatic substitutions that pro ceed by the elimination-addition mechanism... 

Elimination-addition mechanism (Section 23.8) Two-stage mechanism for nucleophilic aromatic substitution. In the first stage, an aryl halide undergoes elimination to form an aryne intermediate. In the second stage, nucleophilic addition to the aryne yields the product of the reaction. 

Arynes are intermediates in certain reactions of aromatic compounds, especially in some nucleophilic substitution reactions. They are generated by abstraction of atoms or atomic groups from adjacent positions in the nucleus and react as strong electrophiles and as dienophiles in fast addition reactions. An example of a reaction occurring via an aryne is the amination of o-chlorotoluene (1) with potassium amide in liquid ammonia. According to the mechanism given, the intermediate 3-methylbenzyne (2) is first formed and subsequent addition of ammonia to the triple bond yields o-amino-toluene (3) and m-aminotoluene (4). It was found that partial rearrangement of the ortho to the meta isomer actually occurs. 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

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... 

This is clearly an elimination/addition mechanism [in contrast to the addition/elimination of SN2 (aromatic)] and formally parallels, in its genesis, the elimination reactions of simple alkyl halides that we shall consider subsequently (p. 246). Direct evidence in support of the aryne pathway is provided by the fact that the halides (98), (99) and (100),... 

Aromatic substitution, a quantitative treatment of directive effects in, 1, 35 Aromatic substitution reactions, hydrogen isotope effects in, 2, 163 Aromatic systems, planar and non-planar, 1, 203 Aryl halides and related compounds, photochemistry of, 20, 191 Arynes, mechanisms of formation and reactions at high temperatures, 6, I A-Se2 reactions, developments in the study of, 6,63... 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

C Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution. Arynes... 

Alkanamines have acid strengths corresponding to Ka values of about 10 33, which means that their conjugate bases are powerfully basic reagents. Therefore they are very effective in causing elimination reactions by the E2 mechanism (Section 8-8) and aromatic substitution by the aryne mechanism (Section 14-6C). The following example illustrates this property in a useful synthesis of a benzenamine from bromobenzene ... 

Nucleophilic aromatic substitutions are more difficult in principle. Here, three types of mechanisms are discussed (Scheme 6.3) addition-elimination mechanism (SNAr), elimination-addition mechanism (SN1) and aryne mechanism. In addition, radical-type mechanisms are also possible. 

A variation on the aryne mechanism for nucleophilic aromatic substitution (discussed above, Scheme 2.8) is the SrnI mechanism (see also Chapter 10). Product analysis, with or without radical initiation or radical inhibition, played a crucial role in establishing a radical anion mechanism [21]. The four isomeric bromo- and chloro-trimethylbenzenes (23-X and 25-X, Scheme 2.9) reacted with potassium amide in liquid ammonia, as expected for the benzyne mechanism, giving the same product ratio of 25-NH2/23-NH2 = 1.46. As the benzyne intermediate (24) is unsymmetrical, a 1 1 product ratio is not observed. 

Efficient ortho-difunctionalization of aromatics (87) can be achieved by insertion of arynes into the C-C a -bonds of /3-dicarbonyls (88), using a simple aryne source (89) under mild conditions.338 The /1-dicarbonyl reactant can be a dione (aromatic or aliphatic), or a diester (including dilactones). A mechanism involving the formation of a benzocyclobutane is proposed. 

The classification within this section is based on the structural (rather than the mechanistic) relationship between the starting materials and products. Mechanistically, all of the reactions considered in this section involve nucleophilic substitution as the first step, except for aromatic substitution via the aryne mechanism, which involves elimination followed by nucleophilic addition. 

In reactions that proceed by the elimination-addition mechanism (often called the aryne mechanism), the bases used commonly are stronger than those used in reactions proceeding by the addition-elimination mechanism. Also, in this reaction, the aromatic ring does not need to be activated by electron-withdrawing substituents, although a reasonable leaving group (usually a halide) must be present. 

The aryne intermediate is usually written with a triple bond and a delocalized aromatic system, as shown in 3-44. The anion in the side chain reacts as a nucleophile with the electrophilic aryne. The resulting anion, 3-45, can remove a proton from ammonia to give 3-46. Because the product has been reached, we usually stop writing the reaction mechanism at this point. However, in the reaction mixture, amide will remove a proton from the carbon a to the cyano group of 3-46. Only during workup will the anion be protonated to give back 3-46. 

The reaction conditions, sodamide in ammonia, as well as the lack of electron-withdrawing groups directly attached to the aromatic ring, suggest the aryne mechanism (mechanism 2) rather than the nucleophilic aromatic substitution (mechanism 1). There are several additional problems with mechanism 1. 

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