Chloronitrobenzenes, nucleophilic substitution

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-... 

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... 

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. 

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... 

One group of aryl halides that do undergo nucleophilic substitution readily consists of those that bear a nitro group ortho or para to the halogen. p-Chloronitrobenzene reacts with sodium methoxide at 85°C to give p-nitroanisole. The position of the nitro group on the ring is important. 

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). 

The diamines were synthesized through the aromatic nucleophilic substitution of corresponding diols with / -chloronitrobenzene or /7-fluoronitrobenzene in the presence of potassium carbonate, followed by catalytic reduction with hydrazine monohydrate and Pd/C (such as synthesis of DBAPB and DBTFAPB in Scheme 2.6). As illustrated in Scheme 2.7, bis(ether anhydride)s were prepared by a three-stage synthetic procedure starting from the nucleophilic nitrodisplacement reaction of 4-nitrophthalonitrile with diols (15A 15F, Scheme 2.7) in dry DMF in the presence of potassium carbonate at room temperature. Use of high temperature (in excess of 100 °C) was avoided as it led to dark colored products in the case of 16A 16F. The nitrodisplacement reactions led to a series of new bis(ether nitrile)s (16A 16F, Scheme 2.7). The bis(ether dinitrile)s were then hydrolyzed in an alkaline solution in the presence of hydrogen peroxide to obtain the corre-... 

Nitrophenols are less important as intermediates than chlorophenols. Nitrophenols can be obtained by nitration of phenol or, preferably, by nucleophilic substitution of the corresponding chloronitrobenzenes (see Chapter 5.8.1) with alkali solution. Nitration of phenol yields an o-/p-mixture consisting of around 55% o-nitrophenol and 45% p-nitrophenol separation of the isomers is possible by steam distillation. 

Angrish et al. (2005) reported a rapid and efficient method for aromatic nucleophilic substitution reaction of chloronitrobenzene with number of substituted amines in presence of l-butyl-3-methylimidazolium tetrafluoroborate ionic liquid (green reaction media) to give N-substituted nitrobenzene under microwave irradiation. 

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-. 

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... 

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. 

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