Aromatic compounds SNAr

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Electrophilic aromatic substitution of hydrogen (for which the symbol SnAr is usually used, while H is omitted) is a well-developed synthetic procedure which is widely used for structural modification of aromatic compounds [1]. 

The SNAr reaction of polyhalo aromatic compounds has been discussed (30). For the displacement of fluorine para to substituent R, the relative stability of the transition state appears to foDow the order H I > Br >C1 > F, in contrast to the normal electron-attracting influence exerted by the halogen. The stability sequence is directly related to the chemical softness of the substituents. The fragment R-C may be regarded as a soft-soft combination [R C]. 

The most widely used approach to the preparation of PESs in both academic research and technical production is a polycondensation process involving a nucleophilic substitution of an aromatic chloro- or fluorosulfone by a phenoxide ion (Eq. (3)). Prior to the review of new PESs prepared by nucleophilic substitution publications should be mentioned which were concerned with the evaluation and comparison of the electrophilic reactivity of various mono- and difunctional fluoro-aromats [7-10]. The nucleophilic substitution of aromatic compounds may in general proceed via four different mechanism. Firstly, the Sni mechanism which is, for instance, characteristic for most diazonium salts. Secondly, the elimination-addition mechanism involving arines as intermediates which is typical for the treatment of haloaromats with strong bases at high temperature. Thirdly, the addition-elimination mechanism which is typical for fluorosulfones as illustrated in equations (3) and (4). Fourthly, the Snar mechanism which may occur when poorly electrophilic chloroaromats are used as reaction partners will be discussed below in connection with polycondensations of chlorobenzophenones. 

Smith, Jason A., 431 Sn2+ compounds, 233 Sn4+ compounds, 232 SNAr reaction. See also Nucleophilic aromatic substitution reaction poly(arylene ether sulfone) synthesis via, 336-340... 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

The Sundberg indole synthesis using aromatic azides as precursors of nitrenes has been used in synthesis of various indoles. Some kinds of aryl azides are readily prepared by SNAr reaction of aromatic nitro compounds with an azide ion. For example, 2,4,6-trinitrotoluene (TNT) can be converted into 2-aryl-4,6-dinitroindole, as shown in Eq. 10.60.83... 

We have recently reported ( ) several synthetic studies of weak nucleophile SnAr reactions. In the latter cases (26f-1), new synthetic methodology was reported for the direct introduction of fluoroalkoxy groups into a variety of aromatic systems. These reports represent synthetically useful procedures for obtaining some otherwise inaccessible fluoroalkoxy materials but, unfortunately, they require the use of a dipolar, aprotic solvent (usually hexamethylphosphoramide, HMPA) and, in some cases, elevated temperatures. However, because of their diverse and important applications ( ), the syntheses of these and other organofluoro compounds continue to be of interest. For example, two recent reports of useful fluoroalkoxy materials include the insecticide activity exhibited by fluoroalkoxy substituted 1,3,4-oxadiazoles... 

Thus, carbon 1 of 2,4-dinitrohalobenzene has the lowest electron density, and the halogen in position 1 is easily displaced by a nuclephile in a rate-determining step of an SNAr reaction with hydroxide, alkoxide, and primary or secondary amino compounds [94]. As the nucleophile becomes attached to the carbon, the compound is converted to an unstable nonaromatic species, the Meisenheimer complex [91]. Restoration of aromaticity facilitates elimination of the halogen in a fast step, in this particular case giving 2,4-dinitroanisole. 

The rate enhancements observed in these nucleophilic aromatic substitution reactions when using crown-complexed ions and tetraalkylam-monium ions are indeed not surprising. Many examples are known of increased reactivity in nucleophilic substitutions due to complexation with crown compounds (24), also in SNAr reactions (25, 26). In our system, however, this normal effect is accompanied by an inhibiting effect on the competing reduction path, which is discussed under Reduction Channel. 

There are two major variants of ONSH with nucleophiles sensitive to oxidation (a) addition is an irreversible process and (b) equilibrium of the reversible addition is shifted in favor of the adducts. Nucleophilic organometallic compounds, alkyllithium and alkyl-magnesium reagents, are active enough to add irreversibly to nitroarenes in positions occupied by hydrogen to form the adducts [72]. Due to irreversibility of the addition, the SNAr reaction on treatment of ortho- and para-halonitrobenzenes with these C-nucleophiles is not observed. Further oxidation of the formed adducts with a variety of oxidants, preferably KMn04, affords products of oxidative nucleophilic alkylation. This reaction appears to be an important method for direct incorporation of alkyl substituents into aromatic rings (Scheme 14) [72, 73]. 

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