Nitroarene derivatives

B5mn E, Hong B, De Castro KA, Lim M, Rhee H (2007) One-pot reductive mono-A-alkylation of aniline and nitroarene derivatives using aldehydes. J Org Chem 72(25) 9815-9817. doi 10. 1021/jo701503q... 

Figure 31.13 Regioselective hydroaminomethylation of vinylarenes with aniline or nitroarene derivatives in an aqueous microemulsion catalyzed by a sol-gel-entrapped Rh complex.

IARC. 1984. Carbon blacks, mineral oils, (lubricant base oils and derived products) and some nitroarenes. IARC Monogr Eval Carcinog Risk Chem Hum 33 86-167. 

The foregoing examples show that the nucleophilic attack to nitroarenes at the o>T/ o-position followed by cyclization is a general method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion derived from ethyl isocyanoacetate as the reactive anion for the preparation of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyrimidines depending on the structure of nitroarenes (Eqs. 9.56 and 9.57).89 The synthesis of pyrroles is discussed in detail in Chapter 10. 

Catalysed oxidation of primary and secondary amines generally has little synthetic value. Primary amines yield either a mixture of nitriles and amides (ca. 30%) or, in the case of arylamines, the azo derivatives (42-99%) [39], Symmetrical and non-symmetrical azoarenes are also produced in good yields ( 60%) from the reaction of acetanilides with nitroarenes under basic solidtliquid conditions, although higher yields are obtained using TDA-1 [40],... 

TABLE 10.19 C. BIOLOGICAL PROPERTIES OF PAHs ANL) PACs. II MUTAGENICITY Mutagenic Activities of Several Nitroarenes ( — S9) and Benzolalpyrene Strains TA98 and TA100 and Several Derivative Strains"-0 481 ( + S9) Assayed with... 

Watanabe, M., M. Ishidate, Jr., and T. Nohmi, "A Sensitive Method for the Detection of Mutagenic Nitroarenes Construction of Nitroreductase-Overproducing Derivatives of Salmonella ty-phimurium Strains TA98 and TA100, Mutat. Res., 216, 211-220 (1989). 

The alkylation reaction is limited to nitro-substituted arenes and heteroarenes and is highly chemoselec-tive nucleophilic displacement of activated halogens, including fluorine, was not observed. The regio-selectivity is determined by the bulkiness of the silicon reagent. With unhindered silyl derivatives a strong preference for ortho addition was observed, as in the example of equation (6). With bulkier reagents attack took place exclusively at the para position (Scheme 1). The success of this reaction, which could not be reproduced with alkali enolates, was attributed at least in part to the essentially nonbasic reaction conditions under which side processes due to base-induced reactions of nitroarenes can be effectively eliminated.12... 

A convenient one-step conversion of moderately activated nitroarenes to phenols was achieved in DMSO via nucleophilic nitrite displacement by the anion of an aldoxime.153 TTie resulting O-arylaldox-ime is rapidly cleaved to the phenol derivative under the reaction conditions. The reaction is also applicable to activated fluorides and even to 2-chloropyridine which, at 110 °C, is converted to 2-pyridone in 72% yield.153 A somewhat related process concerns the synthesis, in 82-92% yield, of 4-alkoxybenzoni-triles (45 R = Me, CH2-oxirane, CHrfh, CHMeCTfcMe from O-alkyl-4-nitrobenzaldoximes (44) via hydride-induced elimination of the alkoxide followed by alkoxy denitration (Scheme 17).154... 

The resin-bound phenylene diamine intermediates 3 are then generated by nitro group reduction with tin(II) chloride in NMP and cyclization/ aromatization with a wide variety of aldehydes gave the resin-bound benzimidazole intermediates 4. The treatment of this intermediate with 50% TFA/DCM liberates the substituted 3-(benzoimidazol-l-yl)-propionic acid derivative 4a. Analysis of this intermediate by HPLC and LC-MS gave a measure of the purity of the resin-bound product and enabled the optimization of conditions for the incorporation of the Rl-nitroarenes and R2-aldehydes by an iterative process. 

Phenols may be prepared by diazotization of the corresponding aniline derivative. The problem simplifies itself, therefore, to the preparation of m-bromoaniline. Recognizing that arylamines are ultimately derived from nitroarenes, we derive the retrosynthetic sequence of intermediates ... 

Schemes 72 and 73 show that transformation of aH-adducts 248 and 254 into nitroso derivatives 250 and 255 needs a proton source. That is why the above cyclizations proceed easily in alcohol but are not feasible in aprotic solvents. However, to perform the cyclization of nitroarenes into benzoxazoles in aprotic solvents it is enough to add a Lewis acid. Thus, nitrobenzenes 257 with active methylene compounds bearing vicarious leaving groups Z in the presence of DBU and MgCl2 in DMF, pyridine or even benzene provide anthraniles 258 (Scheme 74) (98PJC2384). Yields of 258 vary from trace to 83% depending on solvent, base and nature of substituents in both reagents.

Substituted quinoline N-oxides have been prepared via the base-induced cyclization of alkylidene derivatives of O-nitroarylacetonitriles, which are readily available via the vicarious nucleophilic substitution cyanomethylation of nitroarenes followed by Knoevenagel condensation [9]. 

Scheme 16) <1963OS(43)40>. Numerous examples of similar reductive cyclizations of appropriate nitroarenes leading to derivatives of indole are discussed in CHEC-III . 

Reactions of 2-lithio-l,3-dithiane (161) with nitroarenes gave 1,4- and 1,6-addition products whereas 2-methyl and 2-phenyl-l,3-dithiane derivatives provide only 1,6-addition products. These conjugate-addition products are transformed into the respective nitroaromatic compounds by in situ oxidation with oxygen or DDQ. In the case of 4-chloronitrobenzene, the 1,4-addition product with respect to the nitro group was mainly obtained242. A SET mechanism was proposed242, as in the case of alkyl iodides243. 

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