Chemoselective nitro group

There is no problem of chemoselectivity here it is not possible to reduce the aliphatic NO group in (10) without reducing the aromatic NO group too. This is easily solved by introducing the aromatic nitro group after the reduction. 

The. selective hydrogenation of a nitro group in the presence of other reactive functionalities is a frequently encountered problem in fine chemicals manufacture. Ciba-Geigy (Novartis). scientists developed, in collaboration with a catalyst manufacturer, a new Pt/Pb on CaCO. catalyst that allows the chemoselective hydrogenation of an aromatic nitro group in the presence of C=C, C=0, C=N as well as Cl or Br substituents in selectivities > 95% (even C C groups react very slowly) (Bader et al., 1996). Eqn. (3) shows an example (Bader eJ a/., 1996). 

These reaction conditions also permit the chemoselective quantitative reduction of benzaldehyde to benzyl alcohol without any concomitant reduction of either acetophenone or 3,3-dimethylbutan-2-one present in the same reaction mixture.83 Additionally, this useful method permits the reduction of aldehyde functions in polyfunctional compounds without affecting amide, anhydride, eth-ylenic, bromo, chloro, or nitro groups.79,80,319... 

Silylation of AN is chemoselective (path (a)) that is, in no case does the silicon atom form the Si-C bond (path (b)). Moreover, if the initial AN contains a functional group at the a-C atom, the trialkylsilyl fragment in the resulting SENA is bonded, as a rule, to the oxygen atom of the nitro group. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Amidine derivatives are effective dehalogenation inhibitors for the chemoselective hydrogenation of aromatic halonitro compounds with Raney nickel catalysts. The best modifiers are unsubstituted or N-alkyl substituted formamidine acetates and dicyandiamide which are able to prevent dehalogenation even of very sensitive substrates. Our results indicate that the dehalogenation occurs after the nitro group has been completely reduced i.e. as a consecutive reaction from the halogenated aniline. A possible explanation for these observations is the competitive adsorption between haloaniline, nitro compound, reaction intermediates and/or modifier. The measurement of the catalyst potential can be used to determine the endpoint of the desired nitro reduction very accurately. 

Reaction of 4-nitro-2,l,3-benzoselenadiazole 143 with ethyl isocyanoacetate in the presence of 1,8-diazabicy-clo[5.4.0]undec-7-ene (DBU) in tetrahydrofuran (THF) at room temperature gave the pyrrole-fused product 146 in 56% yield as the sole product (Scheme 9) <1996J(P1)1403>. Reaction of 5-nitro-2,l,3-benzoselenadiazole 147 with ethyl isocyanoacetate under similar reaction conditions gave the pyridimine iV-oxide-fused product 150 in 28% yield as the sole product. Proposed mechanism for the formation of pyrrole and pyrimidine rings involves initial attack of the ethyl isocyanoacetate anion at the /3-position to the nitro groups forming the anionic intermediates 145 and 148 and the resonance structure intermediate 149. The reactivity and chemoselectivity were explained by the steric effect in the intermediates. 

The high chemoselectivity of BHCl2 SMe2 was demonstrated in the selective reduction of azide group in the presence of an ester, halide, nitrile, and nitro group (Equation (257)).1073 The reduction of azides with BHCl2-SMe2 was faster than the hydroboration of alkenes. 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

Figure 2.51 Chemoselective hydrogenation of nitro groups with modified Pt catalysts developed by Solvias. Functional groups not converted are in blue. The boxed reaction is an example of chemoselective hydrogenation of a nitro group in the presence of an allyl ester. Source adapted from Blaser et al. [298, 299].

As is apparent from Table 2, the chemoselective reduction of nitro groups often requires a modified catalyst system. This approach has a long history which is documented in the reference books cited and is also well described in reviews... 

Sulfide reduction has an even broader selectivity profile than catalytic hydrogenation or the Bechamp reduction and enables the chemoselective reduction of nitro compounds in presence of C=C, azo, or other nitro groups. The method is insensitive to by-products and high levels of impurities. Depending on pH, different reduction agents with the following stoichiometries are applicable ... 

Carboxylic acids, esters, amides, nitriles, nitro groups and most aromatic nuclei are not reduced under ionic hydrogenation conditions (133). An organosiloxane, polymethylhydrosiloxane [9004-73-3] (PMHS), is most economically favored for large-scale reductions. Polymethylhydrosiloxane is a versatile low cost hydride transfer reagent having a hydride equivalent weight of 60. Reactions are catalyzed by Pd or dibutyltinoxide. The choice of reaction conditions leads to chemoselective reduction, eg, allyl reductions in the presence of ketones and aldehydes (134—136). Esters are reduced to... 

The key intermediate benzothiazine 25 was accessed via displacement of fluoride in the dinitrobenzene 23 with the lithium salt of methyl thioglycolate to provide thioether 24, which after tin(II)-mediated reduction of the nitro groups and cyclization furnished benzothiazine 25 in modest yield (Scheme 6). It was noted by the authors that other methods of reduction such as hetero- or homogenous hydrogenation did not improve the yields for this step. It is also noteworthy that subsequent chemoselective reduction of the ester group to give the requisite alcohol proved problematic due to the ease of reduction of the benzothiazinone amide functionality. 

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