Elimination addition reactions nucleophilic aromatic substitution with

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 ... 

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... 

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. 

Some of the reactions in this chapter operate by still other mechanisms, among them an addition-elimination mechanism (see 13-15). A new mechanism has been reported in aromatic chemistry, a reductively activated polar nucleophilic aromatic substitution. The reaction of phenoxide with p-dinitrobenzene in DMF shows radical features that cannot be attributed to a radical anion, and it is not Srn2. The new designation was proposed to account for these results. 

The most broadly useful intermediates for nucleophilic aromatic substitution are the aryl diazonium salts. Aryl diazonium ions are usually prepared by reaction of an aniline with nitrous acid, which is generated in situ from a nitrite salt.75 Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and a carbocation (see Section 10.1), aryl diazonium are stable enough to exist in solution at room temperature and below. They can also be isolated as salts with nonnucleophilic anions, such as tetrafluoroborate or trifluoroacetate.76 The steps in forming a dizonium ion are addition of the nitrosonium ion, +NO, to the amino group, followed by elimination of water. 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

The reason this reaction is suitable is that it involves nucleophilic aromatic substitution by the addition-elimination mechanism on a p-nitro-substituted aryl halide. Indeed, this reaction has been carried out and gives an 80-82% yield. A reasonable synthesis would therefore begin with the preparation of p -ch I oron itrobenzene. 

In one method the polypeptide is reacted with Sanger s reagent, 2,4-dinitrofluo-robenzene (DNFB). The nucleophilic nitrogen of the N-terminal amino acid displaces the fluorine in a nucleophilic aromatic substitution reaction. (This reaction follows an addition—elimination mechanism see Section 17.11.) The polypeptide is then hydrolyzed to its individual amino acid components. Because the bond between the nitro-... 

Nucleophilic aromatic substitution reactions of nitro-substituted thiophenes have been utilized to prepare biologically active thiophenes including reverse transcriptase <02H(57)97> and nitric oxide synthase <02JHC857> inhibitors. The addition-elimination reaction of 2-chloro-3-nitrothiophene (56) with metallated indole 57 afforded 58 which was transformed into the corresponding thiophene-fused azepino[5,4,3-cd]indoles 59 <02H(57)1831>. 

The reaction of aromatic halides with tertiary phosphines requires special reaction conditions, as they are not susceptible to the simple nucleophilic substitution reaction. Strong heating, generally in a closed pressure tube, with the tertiary phosphine in the presence of a nickel(II) halide salt allows substitution of the halogen by phosphorus, probably by way of an addition-elimination reaction. 

Dioxanes have been synthesized from l-O-allyl-l,2-diols by radical addition of per-fluoroalkyl iodides and subsequent nucleophilic cyclization.561 With sodium hydride, elimination occurs from iodides such as 1.3 other bases also give unsatisfactory results, whereas N-bromosuccinimide seems to be the reagent of choice for the cyclization to 1,4-dioxane 14. Similar results arc obtained with dibromodimethylhydantoin.561 Dihydrobenzofurans are synthesized by cyclodehydration utilizing the Vilsmeier reagent (chloromethylene)dimethylam-monium chloride is most practical.562 Nucleophilic aromatic substitution reactions with catechol derivatives also give the six-membered heterocycles.563 564 1.4-Dioxan-2-ones arc pre-... 

As exemplified by equation (2), the Perkin condensation of o-hydroxybenzaldehydes is an important method for the synthesis of substituted coumarins. An interesting variation on this procedure has been reported recently. Heating a mixture of o-fluorobenzaldehyde, 2-thiopheneacetic acid, acetic anhydride and triethylamine affords directly the coumarin (20 equation 13) instead of the expected cinnamic acid (21). The reaction proceeds similarly with several arylacetic acids. The reaction presumably proceeds through the cinnamic acids (21). The observed product can conceivably arise by direct nucleophilic displacement involving the carboxylate or by an elimination/addition (benzyne) mechanism. The authors note that when 2-fluorobenzaldehyde is replaced by its 2-bromo analog in this reaction, the substituted cinnamic acid (22) is the major product and the corresponding coumarin (20) is obtained only in low yield. It is suggested that since it is known that fluoride is displaced more rapidly in nucleophilic aromatic substitution reactions, while bromo aromatic compounds form benzynes more rapidly, this result is consistent with a nucleophilic displacement mechanism. 

Nucleophilic aromatic substitution reactions follow the well-established two-step addition-elimination mechanism via a Meisenheimer intermediate (Fig. 8.3). Indeed, reaction of fluoride ion with trifluoro- -triazine, gives the corresponding perfluorocarbanion system that has been directly observed by NMR spectroscopy, supporting this mechanistic rationale. This reactivity has been termed mirror-image chemistry, which contrasts the very well-known chemistry of... 

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