Nitroarenes, ring hydrogenation

Selective ring hydrogenation of nitroarenes l,5-Dinitro-3-azabicyclo[3.3.1]non-6-enes from 1,3-dmitrobenzenes via 3,5-bis- c/-nitrocyclohexenes... 

Selective ring hydrogenation of nitroarenes Partial ring hydrogenation s. 18, 80 Hydrogenation of cyclimmonium salts selective and preferential s. 16, 53 ... 

The carbanion of 2,3-dimethylthiazolidine-4-one reacted with nitroarenes to give either a ting opened product (50) via a VNS (vicarious nucleophilic substitution) reaction or a product resulting from oxidative nucleophilic substitution of hydrogen (51). Ring opening VNS reactions with 5-membered 5-heterocycles are limited to those heterocycles which show some conformational flexibility <96TL983>. 

Direct cyclisation of ortfto-alkynyl-anilines can be effected simply by treatment with tetra-n-bntylam-monium fluoride, potassium f-butoxide or potassium hydride, or simply with gold(III) chloride. Treatment of l-(2-arylethynyl)-2-nitroarenes with indium and aqneons hydrogen iodide prodnces 2-aryl-indoles, the reagent combination both reduces the nitro to amine and then the acid activates the alkyne for the ring closure. Copper(II) salts or diethylzinc in refluxing toluene can be ntihsed with IV-sulfonyl-ort/fo-alkynyl-anilines. 

In a so-called vicarious nucleophilic substitution of hydrogen,75 2,3-diphenylpyrido[2,3-6]-pyrazine is alkylated in the 8-position by [(chloromethyl)sulfonyl]benzene. This reaction proceeds by addition of the carbanion to the electron-deficient ring position of a nitroarene or electrophilic heteroaromatic system, followed by base-induced -elimination of the corresponding hydrogen halide.76,77 As with quinoxalines and naphthyridines, the reaction with pyrido[2,3-6]pyrazines also affords products bisannulated at the pyrazine or the pyridine moiety, depending on the kind of 2/3-substitution (cf. Section 7.2.3.1.2.2.2.). 

In a so-called vicarious nucleophilic substitution of hydrogen, the carbanion of an arene halomethyl sulfone adds to the electron-deficient ring position of nitroarenes or azaaromatic systems such as quinoxalines and naphthyridines, followed by base-induced /(-elimination of the corresponding hydrogen halide.73... 

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]. 

Since the quinoline ring system is often encountered in pharmaceuticals, plant protection agents, photoactive compounds, etc., a search for new synthetic pathways to quinoline derivatives continues to be of a substantial interest. There are numerous examples of synthesis of quinolines and their condensed analogues via nucleophilic substitution of hydrogen in nitroarenes. One can classify those into two broad categories ... 

The 2,1 -benzisoxazole (anthranil) ring system is of interest as a key intermediate for the synthesis of other heterocycles. 2,1-Benzisoxazoles can be derived from the direct multistep domino reaction of some carbanions with nitroarenes or by conversion of the products of nucleophilic substitution of hydrogen in nitroarenes. As early as in 1960, Davis and Pizzini reported that the reaction of 4-chloronitrobenzene with phenylacetonitrile in the presence of potassium hydroxide in protic media affords 3-phenyl-5-chloro-2,l-benzisoxazole in high yield [80] (Scheme 17). 

---