1 -Chloro-2,4-dinitrobenzene, nucleophilic substitution

The hydroxy-nitro dye Naphthol Yellow S (6.233 Cl Acid Yellow 1) was discovered in 1879 by Caro and is still manufactured. It is produced by sulphonation of 1-naphthol to give l-naphthol-2,4,7-trisulphonic acid, followed by replacement of the 2- and 4-sulpho groups in nitric acid medium. Nucleophilic substitution of l-chloro-2,4-dinitrobenzene with 4-aminodiphenylamine-2-sulphonic acid gives Cl Acid Orange 3 (6.234). 

Nucleophilic displacement of 2-chloro-3-phenylquinoxaline with methylamine at 100°-150° and with sodium phenoxide in excess of phenol of 100° gives the expected 2-methylamino- and 2-phenoxy-3-phenylquinoxalines.155 2-Chloroquinoxaline and its 3-phenyl derivative undergo ring closure with aminoacetaldehyde dimethylacetal to an imidazo[l,2-a]quinoxaline.136 Nucleophilic substitution of 2-chloro-quinoxaline with hydroxide ion in water is accelerated by cationic micelles and retarded by anionic micelles. These results were correlated with reactions of l-chloro-2,4-dinitrobenzene, and the characteristics of their transition states were discussed.137... 

The simplest example of an aromatic nucleophilic substitution is the SnAt reaction between l-chloro-2,4-dinitrobenzene and piperidine, the two-step mechanism of which, given in Eq. (5-26), is now fully established [501-503], It involves formation of a Meisenheimer-type zwitterionic intermediate via a dipolar activated complex, followed... 

However, nucleophilic substitution is helped by the presence of electron-withdrawing groups in the molecule. Consequently, l-chloro-4-nitrobenzene is hydrolysed to 4-nitrophenol at 200 °C and 4-nitroaniline can be produced using ammonia in ethanol at 150 °C. The presence of two nitro groups further activates the halogen and l-chloro-2,4-dinitrobenzene reacts easily with a variety of nucleophiles. 

As in other nucleophilic substitutions, electron-withdrawing groups (NO2, CN, CO2H, SO3H) in ortho and para positions increase the reactivity of the aryl hahde to hydrolysis. For instance, chlorobenzene is best hydrolysed above 300 °C, whereas l-chloro-2,4-dinitrobenzene gives a 95% yield of 2,4-dinitrophenol at 100 °C . 

Martinez RD, Mancini PME, Vottero LR, Nudelman NS (1986) Solvent effects on aromatic nucleophilic substitutions. Part 4. Kinetics of the reaction of l-chloro-2,4-dinitrobenzene with piperidine in protic solvents. J Chem Soc Perkin Trans 2 1133-1138... 

However, a few specially substituted benzenes do undergo nucleophilic substitution in base. Electron-withdrawing groups on the ring are necessary for this reaction. For example, l-chloro-2,4-dinitrobenzene is converted into 2,4-dinitrophenol by treatment with sodium hydroxide in water (Fig. 14.95). 

Dinitration of p-chloro(trifluoromethyl)benzene will take place at the ring positions ortho to the chlorine. Compound A is 2-chloro-5-(trifluoromethyl)-l,3-dinitrobenzene. Trifluralin is formed by nucleophilic aromatic substitution of chlorine by dipropylamine. Trifluralin is N, A-dipropyl-4-(trifluoromethyl)-2,6-dinitroaniline. 

The range of nucleophiles that can participate in nucleophilic aromatic substitution is similar to the range of those that participate in, 1 reactions and includes alkoxides, " phenoxides, sulfides, fluoride ion, and amines. For reaction with aromatic amines with l-chloro-2,4-dinitrobenzene, the value of p is —4.0, indicting a substantial buildup of positive charge at nitrogen in the TS. Substitution by carbanions is somewhat less common. This may be because there are frequently... 

Aromatic halides are normally quite inert to the types of nucleophiles that readily displace halide ions from allgrl halides. However, when an aromatic compound contains strong electron-withdrawing nitro groups ortho or para (or both) to the halogen, nucleophilic aromatic substitution occurs quite readily. For example, when 1 -chloro-2,4-dinitrobenzene is heated at reflux in aqueous sodium carbonate followed by treatment with aqueous acid, it is converted in nearly quantitative yield to 2,4-dinitrophenol. 

A summary of ring activation would not be complete without mention of steric effects. Since nucleophilic attack occurs in a plane perpendicular to that of the aromatic ring, substitutions are not usually very sensitive to the bulk of orf/io-substituents. However, steric hindrance by an ortho-methyl substituent may be observed as the steric requirements of the nucleophile increase. Thus, the introduction of a 6-methyl group in l-chloro-2,4-dinitrobenzene causes rate decreases by factors of 14, 22, and 276 in reactions with methoxide, aniline, and piperidine, respectively. The first two figures are attributable to the electronic effect of the methyl substituent, but with piperidine, an additional steric effect is apparent [50]. 

There is some dependence on the basicity of the nucleophile, measured by the pK value of its corresponding acid particularly in series of structurally related nucleophiles. Examples are in the reactions of m- and p-substituted anilines with l-chloro-2,4-dinitrobenzene [1] and of substituted phenoxide ions with halogenonitrobenzenes [9]. Similarly, the reactivities of m- and p-substituted thiophenoxide ions with l-chloro-2,4-dinitrobenzene closely parallel their basicities [56]. 

Reactions involving amine nucleophiles have played an important part in the study of aromatic substitutions, partly because the observation of base catalysis in these reactions provides evidence for the two-step nature of the mechanism. Early work [1 ] on the reactions of aliphatic amines with l-chloro-2,4-dinitrobenzene in ethanol, where nucleophilic attack is rate limiting, showed the importance of steric effects so that, for example, wo-propylamine is roughly 10 times less reactive than n-propylamine. The general pathway for these reactions is shown in Scheme 6.10. Here, the base B may be excess of the nucleophile or added bases such as DABCO or hydroxide ions. The... 

FIGURE 14.95 Some substituted benzenes are reactive toward nucleophiles. l-Chloro-2,4-dinitrobenzene can be swiftly transformed into the corresponding phenol by hydroxide ion in water. 

PROBLEM 15.90 Select the reaction Nucleophilic aromatic substitution. Predict the H NMR spectra of the starting material (l-chloro-2,4-dinitrobenzene) and the product (AAmethyl-2,4-dinitroaniline). How would the IR data differ for the starting material and the product ... 

There has been a review commentary of substitutions in non-polar media addressing the question, are weak interactions responsible for kinetic catalytic behaviour in 5 NAr reactions A kinetic study of the reactions of picryl fluoride with alcohols in carbon tetrachloride shows that the order in alcohol is greater than unity. This is interpreted as evidence for specific interaction between the substrate and alcohol prior to rate-limiting reaction with a further alcohol molecule. Self-association of amine molecules to form dimers which act as the effective nucleophile is an alternative explanation for the high kinetic orders observed in non-polar solvents. Results for the reaction of l-chloro-2,4-dinitrobenzene with aromatic amines in toluene - " and in benzene-hexane mixtures have been interpreted on this basis. Rate constants have been measured for reactions of l-halo-2,4-dinitrobenzenes with primary and secondary amines in a variety of aprotic binary solvent systems and correlations have been attempted with solvatochromic data, including t(30) values. ... 

Treatment of l-chloro-2,4-dinitrobenzene with hydroxide replaces the halogen with the nucleophile, furnishing the corresponding substituted phenol. Other nucleophiles, such... 

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