Aromatic nitro compounds intramolecular

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

The reduction of aromatic nitro compounds to the corresponding amines was catalyzed by [Ru3(CO)i2] in combination with aliphatic amine cocatalysts (95). A mixture of diglyme and water was used as a solvent, turnover frequencies were about 5000 h-1, and a CO partial pressure of 20-50 atm was necessary. The reaction is highly selective for aromatic amines. It was speculated that the reaction proceeds via an intramolecular hydrogen transfer in a hydrido-metal-nitrene intermediate without prior formation of H2 in the water gas shift reaction. 

Reduction of T [l-(2-nitrophenyl)-l//-pyrrol-2-yl]sulfonyl -acetone or -1-phenylethan-l-one with sodium borohy-dride and 5% palladium on carbon, a reagent known to convert aromatic nitro compounds to hydroxylamines, triggers intramolecular interaction and gives pyrrolo[l,2- ][3,l,6]benzothiadiazocine derivatives 90 (Equation 11 <2001MI1405, 2004T8807>). This method was further successfully applied to the reductive cyclization of 2- [l-(2-nitrophenyl)-17/-pyrrol-2-yl]sulfanyl acetonitrile. 

Also aromatic nitro compounds with the vacant ort/to-position relative to the nitro group can be regarded as a good structural basis for the synthesis of condensed nitrogen heterocycles through cyclizations with this nitro group or by means of intramolecular displacement of the latter (for numerous examples of these transformations, [214], authored by professors Svyatoslav Shevelev and Alexey Starosotnikov). 

Schi-f-f bases are probably intermediately -formed during the deoxigenation reactions o-f aromatic nitro compounds with carbon monoxide <150 atm), at 165-170"C, in the presence o-f ortho-phtalaldehyde and with Rh final products are N-aryl-isoindolin-l-ones hydrogen atom o-f the -free carbonyl -function ... 

Nucleophilic aromatic substitutions involving loss of hydrogen are known. The reaction usually occurs with oxidation of the intermediate either intramolecularly or by an added oxidizing agent such as air or iodine. A noteworthy example is the formation of 6-methoxy-2-nitrobenzonitrile from reaction of 1,3-dinitrobenzene with a methanol solution of potassium cyanide. In this reaction it appears that the nitro compound itself functions as the oxidizing agent (10). 

Nitro compounds, in particular aromatic and heterocyclic derivatives, absorb strongly in the near UV. They have properties similar to ketones in their excited state. These compounds are characterized by an unpaired electron in the n0 orbital and thus by a radical character. A typical example of this radical character is the easy intramolecular hydrogen abstraction in nifedipine and related vasodilators (Sch. 7) (18). Another manifestation of the radical character of the nitro group is the rearrangement often observed with nitrated five-membered heterocycles, as in the case of metronidazole (Sch. 8) (19). 

The rest of the synthesis is more straightforward the nitro group can be reduced to an amine, which immediately forms an enamine by intramolecular attack on the more reactive carbonyl group (the ketone) to give the aromatic indole. Since the nitro compound is made by nitration of a benzene ring, the preferred symmetry is very different from that needed for the Fischer synthesis. Nitration of para-xylene (1,4-dimethylbenzene) is a good example. 

The selective nucleophilic displacement of one ortho nitro group from 2,4,6-trinitrotoluene by esters of mercap-toacetic acid followed by oxidation leads to 2-(alkoxycarbonyl)methylsulfonyl compounds. These sulfones react with aromatic aldehydes under Knoevenagel conditions to produce thiochroman 1,1-dioxides 477, probably via a stilbene and a subsequent intramolecular Michael addition. Activating groups other than nitro are compatible with the route (Scheme 167) <2003RJ0397>. 

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