Nitro compounds aromatic, nucleophilic substitution

Arylations of nitro compounds can be achieved by aromatic nucleophilic substitution using aromatic nitro compounds, as discussed in Chapter 9.100 Komblum and coworkers reported displacement of the nitro group of nitrobenzenes by the anion of nitroalkanes. The reactions are usually carried out in dipolar aprotic solvents such as DMSO or HMPA, and nitroaromatic rings are substituted by a variety of electron-withdrawing groups (see Eq. 5.63).101... 

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. 

In certain cases, light promotes substitution reactions in aromatic compounds.34 One of the fascinating features of these reactions is an almost complete change in regioselectivity from that observed in the ground-state reactions. When the nitrocatechol ether 8.1 is irradiated in alkali or in methylamine, the nucleophilic substitution takes place meta to the nitro group. The nucleophilic substitution of p-nitroanisole 8.2, however, takes place para to the X-substituent. 

There has been a major review of substitution by the radical-chain 5rn1 mechanism. It has been shown that reaction by the SrnI pathway of the enolate anions of 2- and 3-acetyl-l-methylpyrrole may yield a-substituted acetylpyrroles. The dichotomy of reactions of halonitrobenzenes with nucleophiles has been nicely summarized major pathways include reduction via radical pathways and. SnAt substitution of halogen. EPR spectroscopy has been used to detect radical species produced in the reactions of some aromatic nitro compounds with nucleophiles however, whether these species are on the substitution pathway is questionable. The reaction of some 4-substimted N,N-dimethylanilines with secondary anilines occurs on activation by thallium triacetate to yield diphenylamine derivatives radical cation intermediates are proposed. ... 

Nucleophilic aromatic substitutions involving loss of hydrogen are known. The reaction usually occurs with oxidation of the intermediate either intramoleculady 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). 

A mechanism of this type permits substitution of certain aromatic and ahphatic nitro compounds by a variety of nucleophiles. These reactions were discovered as the result of efforts to explain the mechanistic basis for high-yield carbon alkylation of the 2-nitropropane anion by p-nitrobenzyl chloride. p-Nitrobenzyl bromide and iodide and benzyl halides that do not contain a nitro substituent give mainly the unstable oxygen alkylation product with this ambident anion ... 

When aromatic nitro compounds are treated with cyanide ion, the nitro group is displaced and a carboxyl group enters with cine substitution (p. 854), always ortho to the displaced group, never meta or para. The scope of this reaction, called the von Richter rearrangement, is variable. As with other nucleophilic aromatic substitutions, the reaction gives best results when electron-withdrawing groups are in ortho and para positions, but yields are low, usually < 20% and never > 50%. 

The 2-alkylene-substituted aromatic nitro compound 1011, which is readily accessible via vicarious nucleophilic substitution (VNS) [88-90] of 4-fluoronitroben-... 

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

There are many cine substitution reactions of aromatic nitro compounds using various nucleophiles.100 In this chapter, the cine-substitution reactions using the anion of nitroalkanes... 

Amination of aromatic nitro compounds is a very important process in both industry and laboratory. A simple synthesis of 4-aminodiphenyl amine (4-ADPA) has been achieved by utilizing a nucleophilic aromatic substitution. 4-ADPA is a key intermediate in the rubber chemical family of antioxidants. By means of a nucleophibc attack of the anilide anion on a nitrobenzene, a o-complex is formed first, which is then converted into 4-nitrosodiphenylamine and 4-nitrodiphenylamine by intra- and intermolecular oxidation. Catalytic hydrogenation finally affords 4-ADPA. Azobenzene, which is formed as a by-product, can be hydrogenated to aniline and thus recycled into the process. Switching this new atom-economy route allows for a dramatic reduction of chemical waste (Scheme 9.9).73 The United States Environmental Protection Agency gave the Green Chemistry Award for this process in 1998.74... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Nucleophilic substitution is the widely accepted reaction route for the photosubstitution of aromatic nitro compounds. There are three possible mechanisms11,12, namely (i) direct displacement (S/v2Ar ) (equation 9), (ii) electron transfer from the nucleophile to the excited aromatic substrate (SR wlAr ) (equation 10) and (iii) electron transfer from the excited aromatic compound to an appropriate electron acceptor, followed by attack of the nucleophile on the resultant aromatic radical cation (SRi w 1 Ar ) (equation 11). Substituent effects are important criteria for probing the reaction mechanisms. While the SR wlAr mechanism, which requires no substituent activation, is insensitive to substituent effects, both the S/v2Ar and the Sr+n lAr mechanisms show strong and opposite substituent effects. 

Besides the well-estabhshed nucleophilic photosubstitutions of various groups in aromatic nitro compounds, a small number of other substitutions at excited aromatic nitro compounds have become apparent. 

There are not many successful examples of arylation of carbanions by nucleophilic aromatic substitution. A major limitation is the fact that aromatic nitro compounds often react with carbanions by electron-transfer processes.111 However, such substitution can be carried out under the conditions of the SRN1 reaction (see Section 11.4). 

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

The facile nucleophilic displacement of a 4-methoxy group from pyrylium salts provides syntheses of 4-substituted pyrans. In the presence of triethylamine, 4-methoxypyrylium salts react with aromatic nitro compounds to give 4-benzylidene-4//-pyrans (73JOC2834). 

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