Subject nucleophilic aromatic

Nucleophilic aromatic substitution has been the subject of frequent and extensive reviews1-10. The data on reaction rates, reaction products, substituent effects, salt effects, etc. are all readily available and need not be reassembled here. In spite of this abundance of both data and discussion, some questions of mechanism remain incompletely resolved. 

Substituted 1,2,3-triazole 1-oxides 448 have been reported to undergo electrophilic and nucleophilic aromatic substitution and are subject to debromination, proton-metal exchange, and halogen-metal exchange followed by electrophilic addition. Transmetallation and cross-coupling have not been described. 3-Substituted 1,2,3-triazole 1-oxides 448 can be proton-ated or alkylated at the O-atom and they can be deoxygenated and deal-kylated. The individual reactions are described in Section 4.2.7.1-4.2.7.14. 

Aliphatic and aromatic nucleophilic substitution reactions are also subject to micellar effects, with results consistent with those in other reactions. In the reaction of alkyl halides with CN and S Oj in aqueous media, sodium dodecyl sulfate micelles decreased the second-order rate constants and dodecyltrimethylammonium bromide increased them (Winters, 1965 Bunton, 1968). The reactivity of methyl bromide in the cationic micellar phase was 30 to 50 times that in the bulk phase and was negligible in the anionic micellar phase a nonionic surfactant did not significantly affect the rate constant for n-pentyl bromide with S2O3-. Micellar effects on nucleophilic aromatic substitution reactions follow similar patterns. The reaction of 2, 4-dinitrochlorobenzene or 2, 4-dinitrofluorobenzene with hydroxide ion in aqueous media is catalyzed by cationic surfactants and retarded by sodium dodecyl sulfate (Bunton, 1968, 1969). Cetyltrimethylammonium bromide micelles increased the reactivity of dinitrofluorobenzene 59 times, whereas sodium dodecyl sulfate decreased it by a factor of 2.5 for dinitrochlorobenzene, the figures are 82 and 13 times, respectively. A POE nonionic surfactant had no effect. 

The anionic a complexes formed between polynitroaromatic compounds and bases (1, 2), commonly known as Meisenheimer complexes, are used as models of the reaction intermediates that are considered to be formed in activated nucleophilic aromatic substitution reactions (3-6), as well as being of intrinsic interest. Thus, numerous studies describe the formation and transformation of such a complexes (7-14). As a result, a variety of structural types of these species have been characterized and subjected to detailed investigation. A number of theoretical studies relating to these species have also been reported (15). 

If the aromatic moiety of a cinnamylamine derivative has an ort/io-halogen substituent, 1,2-dihydroquinoline would be obtained yia the subsequent S Ar reaction. In the presence of catalytic amounts of tosylamide, MBH adduct 603 was rearranged to the thermodynamically more stable tosylamide derivative, which then could be easily subjected to nucleophilic aromatic substitution reaction at the ortho position, giving 1,2-dihydroquinoline 605 in 81% yield. Furthermore, using DBU as a base, elimination of p-toluenesulfinic acid afforded quinoline 606 in 69% yield (Scheme 4.178). However, interestingly, Xn-substituted MBH adducts 607 were directly converted into quinolines 608 in a one-pot reaction in moderate yields. The discrepancy between 604 and 607... 

Astruc has also reported the use of arene complexes of iron and ruthenium in the design of star-shaped complexes. The cyclopentadienyliron moiety in 93 (Scheme 25) was utilized to activate the complexed arene toward bromobenzyla-tion to produce 95. Following photolytic demetallation, 96 was reacted with 97 to yield the /jexa-metallic complex 98. These complexed arenes were then subjected to nucleophilic aromatic substitution reactions with 99 allowing for the isolation of 100. 

In spite of the faet that the nucleophilic aromatic substitution in electron-deficient aromatic rings (SNAr) is one of the most venerable organic reactions, it is still a subject of debate. The generally accepted meehanism for this reaction is the classical addition-elimination sequence that involves the formation of a Meisenhei-mer-type intermediate 1 (Scheme 33.1). 

The first example of iron-activated nucleophilic aromatic substitution on solid phase has been presented by Ruhland et al. [141], who attached [(cyclopentadienyl)-benzene Fe(II)] PF6 to polymer-bound piperazine (Scheme 55). The complex 68 was subjected to a variety of nucleophiles using different protocols. The decomplexation was achieved by irradiation in the presence of phenanthroline, and in the final step the resin-bound products were cleaved with methyl chloroformate to give corresponding carbamates in good yields. 

The reaction of aryl (and alkenyl) halides with enolates and other acidic carbon nucleophiles is subject of intense investigations and has been reviewed several times. This reaction enables a smooth a-arylation of enolates that is complement to nucleophilic aromatic substitution reactions (Scheme 5-119). 

In most reviews of enamine chemistry the reactions of iminium salts are scattered throughout the review and are consequently not covered in a comprehensive manner. This chapter will be an attempt to look at reactions that, at one stage or another, proceed by nucleophilic addition to the iminium intermediate. The subject of enamines has been reviewed 1-4) and certain aspects of iminium salt chemistry such as reduction of aromatic quaternary salts have been treated in detail (5). Consequently, the reduction of aromatic quaternary salts with complex hydrides will be presented here only briefly. Although the literature (especially 1950-1967) has been checked with care, the author can make no claim to completeness. The... 

To derive the maximum amount of information about intranuclear and intemuclear activation for nucleophilic substitution of bicyclo-aromatics, the kinetic studies on quinolines and isoquinolines are related herein to those on halo-1- and -2-nitro-naphthalenes, and data on polyazanaphthalenes are compared with those on poly-nitronaphthalenes. The reactivity rules thereby deduced are based on such limited data, however, that they should be regarded as tentative and subject to confirmation or modification on the basis of further experimental study. In many cases, only a single reaction has been investigated. From the data in Tables IX to XVI, one can derive certain conclusions about the effects of the nucleophile, leaving group, other substituents, solvent, and comparison temperature, all of which are summarized at the end of this section. 

Mixed condensations of esters are subject to the same general restrictions as outlined for mixed aldol reactions (Section 2.1.2). One reactant must act preferentially as the acceptor and another as the nucleophile for good yields to be obtained. Combinations that work best involve one ester that cannot form an enolate but is relatively reactive as an electrophile. Esters of aromatic acids, formic acid, and oxalic acid are especially useful. Some examples of mixed ester condensations are shown in Section C of Scheme 2.14. Entries 9 and 10 show diethyl oxalate as the acceptor, and aromatic esters function as acceptors in Entries 11 and 12. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

Figure 1.11 Tyrosine residues are subject to nucleophilic and electrophilic reactions. The unprotonated phe-nolate ion may be alkylated or acylated using a variety of bioconjugate reagents. Its aromatic ring also may undergo electrophilic addition using diazonium chemistry or Mannich condensation, or be halogenated with radioactive isotopes such as 12iI.

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