Addition, nucleophilic mechanism

A number of compounds of the general type H2NZ react with aldehydes and ketones m a manner analogous to that of primary amines The carbonyl group (C=0) IS converted to C=NZ and a molecule of water is formed Table 17 4 presents exam pies of some of these reactions The mechanism by which each proceeds is similar to the nucleophilic addition-elimination mechanism described for the reaction of primary amines with aldehydes and ketones... 

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

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

The generally accepted mechanism for nucleophilic aromatic substitution m nitro substituted aryl halides illustrated for the reaction of p fluoromtrobenzene with sodium methoxide is outlined m Figure 23 3 It is a two step addition-elimination mechanism, m which addition of the nucleophile to the aryl halide is followed by elimination of the halide leaving group Figure 23 4 shows the structure of the key intermediate The mech anism is consistent with the following experimental observations... 

Section 23 6 Nucleophilic aromatic substitutions of the type just shown follow an addition—elimination mechanism... 

Other aryl halides that give stabilized anions can undergo nucleophilic aromatic substitution by the addition-elimination mechanism Two exam pies are hexafluorobenzene and 2 chloropyridme... 

The product of this reaction as its sodium salt is called a Meisenheimer complex after the Ger man chemist Jacob Meisenheimer who reported on their formation and reactions in 1902 A Meisenheimer complex corresponds to the product of the nucleophilic addition stage in the addition-elimination mechanism for nucleophilic aromatic substitution... 

The reaction of benzenesulfomc acid with sodium hydroxide (first entry m Table 24 3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substi... 

Addition-elimination mechanism (Section 23 6) Two stage mechanism for nucleophilic aromatic substitution In the addition stage the nucleophile adds to the carbon that bears... 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

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 alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

SECTION 10.5. NUCLEOPHILIC AROMAHC SUBSTITUTION BY THE ADDITION-ELIMINATION MECHANISM... 

Nucleophilic Aromatic Substitution by the Addition-Elimination 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. 

The addition-elimination mechanism uses one of the vacant n orbitals for bonding interaction with the nucleophile. This permits addition of the nucleophile to the aromatic ring without displacement of any of the existing substituents. If attack occurs at a position occupied by a potential leaving group, net substitution can occur by a second step in which the leaving group is expelled. 

Kinetic studies have shown that the enolate and phosphorus nucleophiles all react at about the same rate. This suggests that the only step directly involving the nucleophile (step 2 of the propagation sequence) occurs at essentially the diffusion-controlled rate so that there is little selectivity among the individual nucleophiles. The synthetic potential of the reaction lies in the fact that other substituents which activate the halide to substitution are not required in this reaction, in contrast to aromatic nucleophilic substitution which proceeds by an addition-elimination mechanism (see Seetion 10.5). 

A fluormated enol ether formed by the reaction of sodium ethoxide with chlorotnfluoroethylene is much less reactive than the starting fluoroolefin To replace the second fluorine atom, it is necessary to reflux the reaction mixture. The nucleophilic substitution proceeds by the addition-elimination mechanism [30] (equation 26). 

The reaction of benzenesulfonic acid with sodium hydroxide (first entry in Table 24.3) proceeds by the addition-elimination mechanism of nucleophilic aromatic substitution (Section 23.6). Hydroxide replaces sulfite ion (S03 ) at the carbon atom that bear s the leaving group. Thus, p-toluenesulfonic acid is converted exclusively to p-cresol by an analogous reaction ... 

Cyclohexadienyl anion (Section 23.6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism. It is represented by the general structure shown, where Y is the nucleophile and X is the leaving group. 

Heterocyclic compounds may show a higher tendency than carbocycles to react with nucleophiles according to the addition-elimination mechanism than via arynes. 

Both in the laboratory and in living organisms, the reactions of carbonyl compounds take place by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, and carbonyl condensation. These... 

A slightly more complex example concerns hydrolysis in competition with nucleophilic addition. The mechanism in aqueous solutions is... 

Since chlorine is always in more than a hundred-fold excess compared to bromine the reaction is occurring by pseudo monomolecular kinetics. The reaction occurs via nucleophilic aromatic substitution by an addition-elimination mechanism, the so-called SjsfAr mechanism (ref. 24). 

The difference in reactivity is not as much as is generally observed in nucleophilic aromatic substitution in solution by an addition-elimination mechanism (ref. 25). Substituents with electron withdrawing capabilities enhance the rate of the reaction therefore decabromobiphenyl ether reacts nearly 2 times faster than 1,2,3,4-tetrabromodibenzodioxin. 

Nucleophilic substitution at a vinylic carbon is difficult (see p. 433), but many examples are known. The most common mechanisms are the tetrahedral mechanism and the closely related addition-elimination mechanism. Both of these mechanisms are impossible at a saturated substrate. The addition-elimination mechanism has... 

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