Benzene Nucleophilic aromatic substitution reactions

Bifunctional catalysis has also been observed by Pietra and Vitali35 for a more typical nucleophilic aromatic substitution reaction, that of 2,4-dinitrofluorobenzene and piperidine in benzene. For this reaction triethylamine does not have an... 

The reactions between 2,4-dinitrohalogenobenzenes and X-substituted anilines in benzene produce the usual diphenylamines 109 by nucleophilic aromatic substitution reaction 28. The inspection of reaction mixtures by UV/VIS spectroscopy at zero reaction... 

In Chapter 16, we will look at the reactions of substituted benzenes. First we will study reactions that change the nature of the substituent on the benzene ring and we will see how the nature of the substituent affects both the reactivity of the ring and the placement of any incoming substituent. Then we will look at three types of reactions that can be used to synthesize substituted benzenes other than those discussed in Chapter 15— reactions of arene diazonium salts, nucleophilic aromatic substitution reactions, and reactions that involve benzyne intermediates. You will then have the opportunity to design syntheses of compounds that contain benzene rings. 

A variety of substituents can be placed on a benzene ring by means of nucleophilic aromatic substitution reactions. The only requirement is that the incoming group be a stronger base than the group that is being replaced. 

Benzene rings with substituents other than halo, nitro, sulfonic acid, alkyl, and acyl can be prepared by first synthesizing one of these substituted benzenes and then chemically changing the substituent. The kinds of substituents that can be placed on benzene rings are greatly expanded by reactions of arene dia-zonium salts, nucleophilic aromatic substitution reactions, and reactions involving a benzyne intermediate. The relative positions of two substituents on a benzene ring are indicated either by numbers or by the prefixes ortho, meta, and para. 

Replacing one of benzene s carbons with a nitrogen forms pyridine, an aromatic compound that undergoes electrophilic aromatic substitution reactions at C-3 and nucleophilic aromatic substitution reactions at C-2 and C-4. Pyridine is less reactive than benzene toward electrophihc aromatic substitution and more reactive toward nucleophilic aromatic substitution. Quinohne and isoquinohne are aromatic compounds with both a benzene ring and a pyridine ring. 

Aniline reacts with nitrous acid to give benzenediazonium salts, which react with a variety of reagents via a substitution reaction. These reagents include cuprous salts, aqueous acid, iodide, hypophosphorous acid, and activated benzene derivatives. Nucleophilic substitution at the sp carbon of a halo-benzene derivative does not occur unless high heat and pressure are used. Electron-withdrawing substituents on the benzene ring significantly lower the temperature required for the reaction. Nucleophiles for this nucleophilic aromatic substitution reaction include water, hydroxide, alkoxide, and amines. 

Explain why the intermediate cydohexadienyl anion in the nucleophilic aromatic substitution reaction (see Discussion section) is not aromatic, even though it has the same number of tt electrons (6) as the starting benzene derivative. 6-194. Complete each of the following reactions and name the expected product of each ... 

Chapter 19 focuses on the reactions of benzene and substituted benzenes. Although benzene, alkenes, and dienes are all nncleophiles (becanse they all have carbon-carbon tt bonds), benzene s aromaticity causes it to react in a way that is qnite different from the way alkenes and dienes react You will see how a substituent can be placed on a benzene ring and some reactions that can change the substiment after it is on the ring. You will also learn how a substituent affects both the reactivity of a benzene ring and the placement of an incoming snbstituent Chapter 19 also describes two additional types of reactions that can be used to synthesize snbstituted benzenes the reactions of arene diazonium salts and nucleophilic aromatic substitution reactions. 

Since pyridine is less reactive than benzene in electrophilic aromatic substitution reactions, it should not be surprising that pyridine is more reactive than benzene in nucleophilic aromatic substitution reactions. The electron-withdrawing nitrogen atom that destabilizes the intermediate in electrophilic aromatic substitution stabilizes the intermediate in nucleophilic aromatic substitution. Notice that, in nucleophilic aromatic substitution reactions, the ring has a leaving group that can be replaced by a nucleophile. 

Benzene and substituted benzenes are nucleophiles, so they react with electrophiles in electrophilic aromatic substitution reactions. If the electron density of the benzene ring is reduced by strongly electron-withdrawing groups, a halo-substituted benzene can undergo a nucleophilic aromatic substitution reaction. 

Pyridine is much less nucleophilic than benzene, so it undergoes electrophilic aromatic substitution reactions only under rigorous conditions. However, halo-substituted benzenes readily undergo nucleophilic aromatic substitution reactions. 

C-3 and nucleophilic aromatic substitution reactions at C-2 or C-A. Pyridine is less reactive than benzene toward electrophihc aromatic substitution and more reactive than benzene toward nucleophilic aromatic substitution. 

Four nucleophilic aromatic substitution reactions with amines have been studied for deuterium isotope effects. Hawthorne (81) found that the rates of reaction of o- and p- nitrochlorobenzene with piperidine in xylene are not altered by substitution of deuterium for hydrogen on the amino group of the nucleophile. Similarly, 2,4-dinitrochlorobenzene reacts at identical rates with -butylamine and with iV,iV-dideuterio-n-butylamine containing 0.75% ethanol (76). Under the conditions of the rate measurements the deuterated amine does not undergo exchange with either the chloroform or the ethanol present. Finally, the reaction of trichloro-s-triazene with aniline shows no isotope effect with AT,JV-dideuterioaniline in benzene as well as in benzene saturated with deuterium oxide (82). 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

A long series of studies of aromatic nucleophilic substitution included the kinetics of reactions of l-chloro-2,4-bis(trifluoromethylsulfonyl)benzene, 3-nitro-4-chlorophenyl trifluoromethyl sulfone and 2-chlorophenyl trifluoromethyl sulfone with sodium methox-ide or ammonia in methanol . The SO2CF3 group was found to have an enormous accelerating effect, in accord with the value of 1.65, based on the dissociation of anilinium ion. Further examples of the promotion of nucleophilic aromatic substitution by fluoro-substituted sulfonyl groups are given by Yagupol skii and coworkers . 

The usual kinetic law for S/v Ar reactions is the second-order kinetic law, as required for a bimolecular process. This is generally the case where anionic or neutral nucleophiles react in usual polar solvents (methanol, DMSO, formamide and so on). When nucleophilic aromatic substitutions between nitrohalogenobenzenes (mainly 2,4-dinitrohalogenobenzenes) and neutral nucleophiles (amines) are carried out in poorly polar solvents (benzene, hexane, carbon tetrachloride etc.) anomalous kinetic behaviour may be observed263. Under pseudo-monomolecular experimental conditions (in the presence of large excess of nucleophile with respect to the substrate) each run follows a first-order kinetic law, but the rate constants (kQbs in s 1 ruol 1 dm3) were not independent of the initial concentration value of the used amine. In apolar solvents the most usual kinetic feature is the increase of the kabs value on increasing the [amine]o values [amine]o indicates the initial concentration value of the amine. 

Pyridine, on the other hand, is more reactive than benzene towards nucleophilic aromatic substitution. This is effectively reaction towards the C=N imine function, as described above. Attack is... 

Polyetherimides (PEI) are polyimides containing sufficient ether as well as other flexibi-lizing structural units to impart melt processability by conventional techniques, such as injection molding and extrusion. The commercially available PEI (trade name Ultem) is the polymer synthesized by nucleophilic aromatic substitution between 1,3-bis(4-nitrophthalimido) benzene and the disodium salt of bisphenol A (Eq. 2-209) [Clagett, 1986]. This is the same reaction as that used to synthesize polyethersulfones and polyetherketones (Eq. 2-206) except that nitrite ion is displaced instead of halide. Polymerization is carried out at 80-130°C in a polar solvent (NMP, DMAC). It is also possible to synthesize the same polymer by using the diamine-dianhydride reaction. Everything being equal (cost and availability of pure reactants), the nucleophilic substitution reaction is probably the preferred route due to the more moderate reaction conditions. 

---