Nitro-activated SNAr

SNAr substitutions of activated aromatic halides, especially aromatic fluorides, provide useful means for the construction of aromatic diethers or amines. Primary and secondary amines react with l, 2-dihalo-4,5-dinitrobenzene to give nitro group substitution at room temperature. The halogen substituents on the ring remain unsubstituted and can be used in further transformation (Eq. 9.5).8... 

Carbanions of a-chloroalkyl phenyl sulfones react with nitrobenzenes to effect direct nucleophilic replacement of hydrogens located ortho and para to the nitro group (Eq. 9.24).38 A very important feature is that VNS of hydrogen usually proceeds faster than conventional SNAr of halogen located in equally activated positions (Eq. 9.25).38 The rule that VNS of... 

Solvent-free SNAr reactions under solid-liquid PTC conditions were realized by using methoxide or phenoxide as nucleophiles. The main results, and comparison with those from classical heating, are indicated in Tab. 5.24 for activated (e.g. 4-nitro-halobenzenes) or nonactivated (e.g. a-naphthyl halides) substrates [74]. 

Thus, PTC methodology can be effectively applied to a weak nucleophile SnAr reaction under a variety of PTC and reaction conditions. This may prove to be particularly useful for fluoroalkoxylation. That is, we have recently demonstrated (26h) that 2,2,2-trifluoroethoxide ion reacts under HMPA solvent conditions at or near room temperature with an extended range of substrates which contain a more active leaving group (nitro) than chloro. The former reaction occurs usefully even for substrates containing the weakly activating amido functionality. Similiar reactions may be possible for these substrates under PTC conditions. 

Jawdosiuk et al.220 have treated 4-chloro- and 4-nitropyridine N-oxides (145) with substituted phenylacetonitrile. This is in agreement with the well-known activating effect of N-oxides toward SNAr reactions the results show that nitro is a better leaving group than chloro. 

Activated nitro and halo substituents have been efficiently replaced by a variety of alkyl groups via SsAx reaction with carbanions. Examples include the displacement of the nitro group in compounds (10 X = 4-PhCO, 4-MeOCO, 4-CN, 4-N02, 4-PhS02, 3,5-(CF3>2) by the anion of 2-nitropropane in HMPA at room temperature (equation 2),83 and the reaction of p-dinitrobenzene with several ketones, esters and nitriles (RH equation 3) in Bu OK/liquid NH3 at -70 C.84 Interestingly, under the latter reaction conditions, p-chloronitrobenzene gave the product of alkylation rather than of SNAr displacement of chloride, as in equation (4).85 Further examples include the dehalogenation of p-halonitrobenzenes by 9-fluorenyl anions in DMSO at room temperature,34 and dehalogenation and denitration reactions by the carbanions of phenyl- and diphenyl-acetonitrile in DMSO or under PTC conditions.86... 

The isolation of the first halobenzene complex, (q6-chlorobenzene)tricarbonylchromium(0), allowed a test for a direct analog of classical SNAr reactivity.15 The activating effect of the Cr(CO>3 unit was found to be comparable to a single p-nitro substituent in reaction with methoxide in methanol and the substituted arene ligand was detached with mild oxidation (equation 2). 

A similar behavior in a different reaction (Table XVII) shows that when the coplanarity of a N02 group is prevented in an SNAr reaction, the activating power of the nitro group, due in part to its resonance accepting effect (less than that of a ring nitrogen (54JCS1190). 

The diol 493 cyclized by intramolecular SnAr of the sterically hindered benzimiazole-activated nitro group by the primary or the secondary alkoxide in the presence of NaH to give the 1,5-oxazocine 495 (8%) and the thermodynamically more favored 1,4-oxazepine 494 (70%) (Equation 19) <2003OL4795, 2005USP0239767>. 

Nitro derivatives of a variety of heteroaromatic compounds enter the VNS reactions with alkyl hydroperoxide anions to produce the expected hydroxylation products [41, 137-139]. For instance, the VNS hydroxylation of 2-chloro-5-nitropyridine with ferf-butylhydroperoxide was shown to give 2-chloro-5-nitro-6-hydroxypytidine that exists in its tautomeric form of pyridone [41] (Scheme 44). It should be stressed that the SNAr of chlorine located in the highly activated position 2 was not competing with the VNS. 

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