Halonitrobenzene

Benzo-fusion onto halonitrobenzenes (Table VIII, p. 277) produces acceleration of aminations or alkoxylations (Tables XII and XIII) except for 3-halo-2-nitronaphthalenes which are analogous to 3-haloisoquinolines. 

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... 

A one-pot synthesis of benzothiazolones from 2-halonitrobenzenes has been reported (equation 23).197 The proposed mechanism involves the displacement of halide by some sulfide species (H2S or HS, n = integer) generated in situ, followed by nitro reduction and condensation with SCO. 

A 16,000-member library was synthesized using this procedure. Twenty-one halonitrobenzenes were combined with 20 halides and half were converted to the sulfone, resulting in 840 3-amino-l,5-benzothiazepine derivatives. These were then reacted with 19 carboxylic acids. Table V shows a representative example of the reagents used. A small random sample of 480 compounds from the library was analyzed by HPLC/MS. Figure 4 shows the purity distribution for the library. Most of the compounds were prepared in high purity. 

The exocyclic amino group of 5-aminotetrazole is reactive in nucleophilic substitution of halogen atoms in halonitrobenzenes. For example, the synthesis of 5-picrylaminotetrazole 406 is based on this process <1999THS(3)467>. Finally, 5-aminotetrazole and l-methyl-5-aminotetrazole 407 undergo a Mannich reaction with formaldehyde and trinitromethane with formation of products 408 (R = H, Me) . 

This reaction was suggested to occur by an S l and a cage collapse process181. On the other hand, other halonitrobenzenes, such as m- and /7-iodonitrobenzenes and o-chloro or 6>-bromo nitrobenzenes, did not react under the same conditions. 

The reaction of o- and /7-halonitrobenzenes (Cl, Br, F) with the sodium salt of ethyl cyanoacetate in DMSO gave almost quantitatively the substitution products183. These reactions were found to be markedly diminished by adding small amounts of/>-, m- and o-DNBs, but were not influenced by addition of radical scavengers1843. Based on these results and kinetic studies it was suggested that they proceed via a non-chain radical nucleophilic substitution184. 

The study of the structure, synthesis, and reactivity of aromatic compounds has been one of the cornerstones of the teaching of organic chemistry. An account of the historical and sometimes disputed dream of Kekule [1] is followed by the beautiful logic of electrophilic aromatic substitution rules [2], which allows students to predict syntheses of sparsely substituted aromatics. Aside from a brief diversion into reactions of halonitrobenzenes with nucleophiles [3], this topic constitutes a large chapter in our 1st year organic education but by the time we teach upper year organic majors and graduate students, aromatic chemistry... 

Reduction of halonitrobenzenes in liquid NH3 to form stable radical anions [136]... 

Perhaps the most striking example of such behavior is the reduction of halonitrobenzenes and haloben-zonitriles [i]. Even when the reduction of haloben-zenes occurs at more negative potentials than that of nitrobenzenes or benzonitriles, in halonitrobenzenes and halobenzonitriles the acceptance of the first electron yields a radical anion, sufficiently stable to eliminate the halide ion. The resulting radical of nitrobenzene or ben-zonitrile accepts the second electron and a proton. This is followed by the usual reduction of the NO2 or CN group. Thus formally, the C-X bond is reduced before the NO2 or CN group. 

Iridium,204,205 together with osmium, has been not widely used in catalytic hydrogenation. Recently, however, iridium or iridium-based catalysts have been shown to be effective in various hydrogenations, such as in selective hydrogenation of a,P-unsaturated aldehydes to allylic alcohols (Section 5.2), of aromatic nitro compounds to the corresponding hydroxylamines (Section 9.3.6), of halonitrobenzenes to haloanilines without loss of halogen (Section 9.3.2), and in the stereoselective hydrogenation of carbon to carbon double bonds (see, e.g., eqs. 3.25-3.27 and Table... 

Baumeister et al. studied the hydrogenation of various halonitrobenzenes using Raney Ni modified with amidine derivatives.115 Formamidine acetate (19b) has been found to be the most effective inhibitor for dehalogenation. It has been shown that the dehalogenation occurs as a consecutive reaction after the halogenated aniline has been formed. A typical example with use of this inhibitor is shown in eq. 9.51 for the hydrogenation of l-chloro-2,4-dinitrobenzene in comparison with dicyandiamide. It is noted that the reaction time could be shortened with 19b compared to that with 19a. 

Platinum catalysts have been shown to be highly selective for the hydrogenation of halonitrobenzenes to haloanilines. A number of effective platinum catalysts or catalyst systems have been described in the literature, mostly in patents.96 Dovell and Greenfield found that the sulfides of the platinum metals and cobalt were highly selective in the hydrogenation of halo-substituted nitrobenzenes.117-119 There was no detectable dechlorination with the sulfides of palladium, platinum, rhodium, ruthenium, and cobalt no detectable debromination occurred with platinum sulfide trace debromination occurred with rhodium sulfide and cobalt sulfide and appreciable debromination occurred with palladium sulfide. Typical hydrogenations with 5% platinum sulfide on carbon catalyst are given in eqs. 9.52 and 9.53 with 2,5-dichloronitrobenzene and p-bromobenzene, respectively.118... 

Some of other effective platinum catalysts are sulfided platinum on carbon120 or platinum catalysts with inhibitors such as bis(2-hydroxyethyl)sulfide,121 morpholine,122 polyamines,123 phosphorous acid,105 phosphoric acid,124 and dicyandiamide.96 Dicy-andiamide was originally used as an effective inhibitor for Raney Ni, as described above (see eq. 9.50).113 Hydrogenations of halonitrobenzenes with use of these platinum catalysts are summarized in Table 9.5. In one patent, it is claimed that ethano-lamine is a better inhibitor than morpholine for Pt-C. Thus, 3,4-dichloronitrobenzene was hydrogenated over Pt-C modified with iron oxide in the presence of 1.2 mol% ethanolamine to give 3,4-dichloroaniline containing only 235 ppm of 4-chloroaniline, compared to 548 ppm with morpholine as the inhibitor.125... 

TABLE 9.5 Hydrogenation of Halonitrobenzenes to Haloanilines over Platinum Catalysts... 

Dehalogenation tends to occur during the hydrogenation of halonitrobenzenes to haloaminobenzenes (Section 9.3.2). In the hydrogenation of / -chloronitrobenzene in ethanol at room temperature and atmospheric pressure, the degree of dechlorination increased in the order 5% Rh-C (2%) < 5% Pt-C (23%) < 5% Pd-C (53%) at the uptake of 3 equiv of hydrogen.236... 

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