Addition-elimination mechanism

The elimination-addition mechanism involves a highly unstable intermediate, which is referred to as dehydrobenzene or benzyne  

A characteristic feature of this mechanism is the substitution pattern in the product. The entering nucleophile need not always enter the ring at the carbon to which the leaving group was bound  

Benzyne has been observed spectroscopically jn an inert solid matrix at very low temperatures. For these studies, the molecule was generated photolytically  

Hoffmann, Dehydrobenzene and Cycloalkynes, Academic Press, New York (1967). 

There have been several structural representations of benzyne. The one most generally used represents benzyne as similar to benzene, but with a weak tt bond in the plane of the ring formed using two sp orbitals. Molecular-orbital calculations indicate that there is additional bonding between the dehydro carbons, 

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This reactivity pattern underlies a group of important synthetic methods in which an a-substituent is displaced by a nucleophile by an elimination-addition mechanism. Even substituents which are normally poor leaving groups, such as alkoxy and dialkylamino, are readily displaced in the indole series. 

The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution Benzyne... 

THE ELIMINATION-ADDITION MECHANISM OF NUCLEOPHILIC AROMATIC SUBSTITUTION BENZYNE... 

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... 

On the other hand labeling studies have shown that the base promoted hydro lysis of chlorobenzene (second entry m Table 24 3) proceeds by the elimination-addition mechanism and involves benzyne as an intermediate... 

Nucleophilic aromatic substitution (Chapter 23) A reaction m which a nucleophile replaces a leaving group as a sub stituent on an aromatic nng Substitution may proceed by an addition-elimination mechanism or an elimination-addition mechanism... 

There are several mechanisms by which net nucleophilic aromatic substitution can occur. In this section we will discuss the addition-elimination mechanism and the elimination-addition mechanism. Substitutions via organometallic intermediates and via aryl diazo-nium ions will be considered in Chapter 11 of Part B. 

SECTION 10.6. NUCLEOPHILIC AROMATIC SUBSTITUTION BY THE ELIMINATION-ADDITION MECHANISM... 

Nucleophilic Aromatic Substitution by the Elimination-Addition Mechanism... 

FIGURE 23.5 The elimination-addition mechanism of nucleophilic aromatic substitution. 

Although nucleophilic aromatic substitution by the elimination-addition mechanism is most commonly seen with very strong amide bases, it also occurs with bases such as hydroxide ion at high temperatures. A " C-labeling study revealed that hydrolysis of chlorobenzene proceeds by way of a benzyne intennediate. 

Nucleophilic aromatic substitution by the elimination-addition mechanism can lead to substitution on the same carbon that bore the leaving group or on an adjacent carbon. 

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. 

Aryl halides undergo substitution, although not through an Sn2 mechanism, but rather via a two-step addition-elimination mechanism. (An elimination-addition mechanism is also possible see Chapter 13, Problem 12.)... 

Finally, the elimination-addition mechanism has been proposed to explain the course of the weU-known Tschitschibabin reaction, but this extension of hetaryne chemistry has been rightly objected to by several authors. 

Primary and secondary aliphatic amines, morpholine and 2-methylaziridine and aniline and even the sterically hindered 2.2,6,6-tetramethylpiperidine readily react with 6-bromo-trithiadiazepine 7, in certain cases in the presence of /V./V-diisopropylethylamine, at room temperature by substitution of the bromine atom ammonia, for example, yields trithiadiazepin-6-amine 22 (R1 = R2 = H). There is compelling evidence that these reactions proceed by an elimination-addition mechanism via the heteroaryne, trithiadiazepyne 21.391... 

The chloro groups of 4,7-dichloro-l,2-diazocines (vide supra) can be sequentially substituted by O-, S- or W-nucleophiles.25 27 The reaction most likely proceeds via an elimination-addition mechanism utilizing the valence tautomeric diazabicyclo[4.2.0]octatriene forms. 

On the other hand, in the case of a-halogenoethyl sulphoxides 503 an SN2-type displacement occurs with mercaptide anions and leads to a-alkylthioethyl sulphoxides 504, while the elimination-addition mechanism is operative with alkoxide anions, affording jS-alkoxyethyl sulphoxides577,596 505 (equation 306). Finally, the reaction of 1-halogeno-l-methylethyl derivatives with both nucleophiles mentioned above occurs via the elimination-addition mechanism596 (equation 307). The substitution reaction can also take place intramolecularly (equation 308) and it proceeds very easily (cf. Section IV.A.2.C)484,600. 

Zwanenburg and Wagenaar148 have reported the rather unusual rearrangement of sulfone 81 to 82, after standing overnight at 0°, and suggested an elimination-addition mechanism, via initial isomerization of A3 to the A2-thiazoline-oxide with subsequent elimination and readdition of sulfmic acid, followed by spontaneous loss of water in a Pummerer-type aromatization reaction. 

The steps are the same as in the addition-elimination mechanism, but in reverse order. Evidence for this sequence is as follows (1) The reaction does not proceed without ethoxide ion, and the rate is dependent on the concentration of this ion and not on that of ArS. (2) Under the same reaction conditions, chloroacetylene gave 83 and 80. (3) Compound 83, treated with ArS, gave no reaction but, when EtO was added, 80 was obtained. It is interesting that the elimination-addition mechanism has even been shown to occur in five- and six-membered cyclic systems, where triple bonds are greatly strained. Note that both the addition-elimination and elimination-addition sequences, as shown above, lead to overall retention of configuration, since in each case both addition and elimination are anti. 

Mannich bases (see 16-15) of the type RCOCH2CH2NR2 similarly undergo nucleophilic substitution by the elimination-addition mechanism.The nucleophile replaces the NR2 group. 

This mechanism does not apply to unsubstituted or N,N-disubstituted aryl carbamates, which hydrolyze by the normal mechanisms. Carboxylic esters substituted in the a position by an electron-withdrawing group (e.g., CN or COOEt) can also hydrolyze by a similar mechanism involving a ketene intermediate. These elimination-addition mechanisms usually are referred to as ElcB mechanisms, because that is the name given to the elimination portion of the mechanism (p. 1308). 

For a review of elimination-addition mechanisms at a carbonyl carbon, see Williams, A. Douglas. K.T. Chem. Rev., 19l5, 75, 627. 

The elimination-addition mechanism involves a highly unstable intermediate called dehydrobenzene or benzyne.123 (See Section 10.6 of Part A for a discussion of the structure of benzyne.)... 

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