Chloronitrobenzenes, nucleophilic

A hydrogen-bonded cyclic transition state can be postulated for a nucleophile like ethanolamine or ethylene glycol anion whose hydrogen bonding to an azine-nitrogen in aprotic solvents can facilitate reaction via a cyclic transition state such as 78, cf. Section II, F. Ethanolamine is uniquely reactive with 2-chloronitrobenzene by virtue of a cyclic solvate (17) of the leaving group, a postulate in line with kinetic evidence. 

Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing substituent in a position ortho or para to the leaving group. The more such substituents there are, the faster the reaction. As shown in Figure 16.18, only ortho and para electron-withdrawing substituents stabilize the anion intermediate through resonance a meta substituent offers no such resonance stabilization. Thus, p-ch oronitrobenzene and o-chloronitrobenzene react with hydroxide ion at 130 °C to yield substitution products, but m-chloronitrobenzene is inert to OH-. 

Vicarious nucleophilic substitution of nitroarenesThe carbanion (2, NaOCH,) of 1 reacts with p-chloronitrobenzene to give, after acidic workup, 5-chloro-2-nitrobenzyl p-tolylsulfone (3). The reagent 2 is typical of a number of carbanions which can undergo nucleophilic substitution ortho or para to nitro-... 

As seen from Table 4.2, activation energies of chlorine substitution in nitrochlorobenzenes under the action of diverse nucleophilic reagents are in agreement with a, of anion-radicals. Constants and of 4-chloronitrobenzene anion-radical are close to the and constants of nitrobenzene... 

We use the reaction of 3-chloronitrobenzene with the hydroxide ion to illustrate in Figure 8-1 the mechanism for a nucleophilic substitution reaction. 

Trudell and co-workers reported the N-arylation with 2-chloro-3-nitropyridine of [l,2,3]triazolines fused onto [4,5-dpyridazine (Scheme 5) and [4,5-,yjpyrimidine (Scheme 6) <2000JHC1597>. Substitution at the 2-position of the pyridine ring was confirmed by X-ray crystallographic analysis of products 8 and 9. Similarly, [l,2,3]triazolo[4,5-,yjpyrimidine gave 10 in low yield, after nucleophilic substitution of the chloro substituent activated by the nitro group in 2-chloronitrobenzene (Scheme 6). 

The methods of synthesis of diaryl and aryl alkyl selenides have been recently reviewed.215 4-Nitro-phenyl methyl selenide was obtained in 93% yield from the reaction of 4-chloronitrobenzene in DMF with a suspension of MeSeLi in THF, prepared from powdered Se and MeLi.216 Other mixed RSeAr selenides were synthesized via alkylation with RI of ArSe resulting from the nucleophilic substitution of unactivated haloarenes ArCl with MeSeLi in DMF at 120 C, followed by MeSe -induced demethyl-ation.217... 

Direct nucleophilic displacement of the halogen in an aryl halide is difficult and hydrolysis to phenols requires high temperatures and pressures the method is therefore only suitable on the large scale. The presence of a nitro group in the ortho or para position, however, makes the halogen more labile since electron withdrawal by the nitro group in these positions stabilises the intermediate anion by electron delocalisation. p-Chloronitrobenzene, for example, is hydrolysed to p-nitrophenol when heated with 15 per cent sodium hydroxide solution at about 150 °C. 

As can be seen from Table 4-2, the relative rates of chlorine substitution in nitrochlorobenzenes under the action of different nucleophilic reagents are in agreement with af of the anion radicals. The constants af and af of the 4-chloronitrobenzene anion radical are close to the af and af constants of the nitrobenzene anion radical. The pair of anion radicals of 2-chloronitrobenzene and nitrobenzene show the same agreement between af and af. In the anion radical of nitrobenzene, af is larger than af. The substitution of ethoxyl for chlorine in 4-chloronitrobenzene proceeds much more easily and requires a lower activation energy than the same substitution in 2-chloronitrobenzene. The spin density in position 4 of the anion radical of 1,3-dinitrobenzene is greater than that in position 2 (af > af). Therefore, l,3-dinitro-4-chlorobenzene is more active in nucleophilic substitution than l,3-dinitro-2-chlorobenzene. 

Hawthorne [31a] arrived at a similar conclusion when investigating the rate of reaction of o- and p- chloronitrobenzene with piperidine. The displacement of the chlorine atom from the ortho compound by piperidine at 116°C proceeds 80 times more rapidly than the similar reaction of the para compound. He also observed that substitution of D for H in the amino group in the nucleophile (piperidine) did not alter these rates of reaction. 

In the reaction of chloronitrobenzene and nitraniline with alkali the halogen atom or the amino group is only mobile in the 0 andp isomers and is replaceable by OH (also by CN, CNS etc.) much more readily than in chlorobenzene or aniline. This is a reaction of the nucleophilic OH- ion. 0-Nitrophenol and some -nitrophenol, but no meta, can indeed be produced from nitrobenzene with alkali also, though with difficulty. 

Use has been made of such considerations Epiotis has accounted for the differential reactivity of chloronitrobenzenes toward nucleophiles in terms of the spin distribution in nitrobenzene anion-radicals he has also correlated the reactivity of anisole and benzoate esters toward nucleophilic radicals... 

That pyridine species with decreased electron densities at positions adjacent to the nitrogen atom make significant contributions to the resonance hybrid even in the ground state has been shown by dipole measurements (12, 14). Interaction with a nucleophilic agent is consequently expected to follow a mechanism analogous to that involving o-chloronitrobenzene (Equation 4). 

An example of using sonication and PTC to improve an aromatic nucleophilic substitution reaction has been provided by Wu et al. [56]. Nine diphenyl ether compounds were synthesized from chloronitrobenzene and alkyl-substituted phenols with higher yields and shorter reaction period (Equation 7). 

Finally, the nucleophilic substitution reactions of mono-, di- and tri-chloronitrobenzenes 128 with N-methyl substituted cyclic tertiary amines 129... 

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