Nucleophilic substitution by addition-elimination

Reactions of powerful alkyllithiums with halo pyridines, quinolines, and diazines may lead to nucleophilic substitution (by addition-elimination or hetaryne mechanisms), ring opening, halogen-scrambling, and coupling reactions, which compete with the desired DoM process. 

These results rule out substitution by addition-elimination because that mechanism requires the nucleophile to attach itself to the carbon from which the leaving group departs... 

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

AU four of the elementary reactions in a cationic polymerization involve electrophilic or cationic intermediates. Thus, initiation, propagation, transfer, and termination may be classified as either nucleophilic substitution, electrophilic addition, elimination, rearrangement, or possibly as a pericyclic reaction. Initiation occurs in alkene polymerizations by either addition of acid to the alkene, or by ionization of a covalent initiator followed by addition of the resulting carbocationic intermediate to an olefin s double bond. Although initiation is an electrophilic addition (AdE) reaction in... 

In summary, aryl halides can undergo substitution by addition-elimination, SrnI, or elimination-addition mechanisms under basic conditions. The addition-elimination mechanism is most reasonable when the arene is electron-poor. When the arene is not electron-poor, the SrnI mechanism is most reasonable either when the nucleophile is a heavy atom or is delocalized, when light is required, or when a catalytic amount of a one-electron reducing agent is required. The elimination-addition mechanism is most reasonable when the arene is not electron-poor and when very strong base (pk b > 35) is used. 

SECTION 10.5. NUCLEOPHILIC AROMATIC SUBSTITUTION BY ADDITION-ELIMINATION... 

Nucleophilic Aromatic Substitution by Addition-Elimination (Section 22.3B)... 

In Summary Nucleophilic attack on the carbonyl group of carboxylic acid derivatives is a key step in substitution by addition-elimination. Either acid or base catalysis may be observed. For carboxylic acids, the process is complicated by the poor leaving group (hydroxide) and competitive deprotonation of the acid by the nucleophile, acting as a base. With less basic nucleophiles, addition can occur. 

Although nucleophilic aromatic substitution by the elimination-addition mecha nism IS most commonly seen with very strong amide bases it also occurs with bases such as hydroxide ion at high temperatures A labeling study revealed that hydroly SIS of chlorobenzene proceeds by way of a benzyne intermediate... 

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

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

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

Chapters 1 and 2 dealt with formation of new carbon-carbon bonds by reactions in which one carbon acts as the nucleophile and another as the electrophile. In this chapter we turn our attention to noncarbon nucleophiles. Nucleophilic substitution is used in a variety of interconversions of functional groups. We discuss substitution at both sp3 carbon and carbonyl groups. Substitution at saturated carbon usually involves the Sjv2 mechanism, whereas substitution at carbonyl groups usually occurs by addition-elimination. 

Nitroalkenes are generally prepared by the substitution reaction of [i-nitro sulfides and sulfoxides with a variety of carbon nucleophiles via an addition-elimination sequence. This method is particularly useful for the preparation of cyclic nitroalkenes (Eq. 4.100).126... 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

In contrast, oxime ethers and esters are usually stable in solution but the E/Z isomerization can be induced by acids " or by irradiation ". Recently, Narasaka and colleagues"" "" studied the equilibration-isomerization of (E)-O-acyl oximes 239 in the presence of an acid in a nucleophilic solvent (equation 71). Isomerization probably proceeds via protonation of the oxime nitrogen followed by addition-elimination of a nucleophilic solvent until the equilibrium of E and Z isomers is achieved. The isomerization of the more labile 0-acyloximes occurs either by an Sjv2 substitution at the oxime nitrogen with acids and/or by acyl exchange through the formation of a mixed anhydride and the free oxime. 

Unactivated aryl halides also undergo nucleophilic displacement via electron transfer in the initial step the so-called SRN1 mechanism. It is now clear that in the case of heteroaromatic compounds, nucleophilic substitution by the Srn process often competes with the addition-elimination pathway. The SRN reactions are radical chain processes, and are usually photochemically promoted. For example, ketone (895) is formed by the SRN1 pathway from 2-chloroquinoxaline (894) (82JOC1036). 

Intramolecular nucleophilic substitution by the anions of o-haloanilides is another viable oxindole synthesis. This is a special example of the category Ic process described in Section 3.06.2.3. The reaction is photo-stimulated and the mechanism is believed to be of the electron-transfer type SRN1 rather than a classical addition-elimination mechanism. The reaction is effective when R = H if 2 equivalents of the base are used to generate the dianion (equation 202) (80JA3646). 

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