Diazotization of anilines

Dia2oaminoben2ene has also been prepared by the action of nitrous acid gas on aniline in alcohol by the action of silver nitrite on aniline hydrochloride and together with phenylurea by the action of nitrosophenylurea on aniline in methyl alcohol. Niementowski and Roszkowski have reported studies on the diazotization of aniline, aniline hydrochloride, and aniline sulfate with sodium nitrite and silver nitrite. The procedure described is adapted from that of Fischer. ... 

The preparation of an aryl fluoride—e.g. fluorobenzene 3—starting from an aryl amine—e.g. aniline 1—via an intermediate arenediazonium tetrafluoroborate 2, is called the Schiemann reaction (also called the Balz-Schiemann reaction) The diazotization of aniline 1 in the presence of tetrafluoroborate leads to formation of a benzenediazonium tetrafluoroborate 2 that can be converted into fluorobenzene 3 by thermolysis. 

Although Hammett convincingly explained the nitrosation of aliphatic amines and the diazotization of aniline under the conditions employed by Schmid and others, one unsatisfactory point remained namely the second-order kinetic equation obtained by Hantzsch and the workers who followed him for diazotization in a more weakly acidic medium. Comparison of experimental details shows that at concentrations of free mineral acid below 0.05 m the reaction is apparently second-order, but it becomes third-order at higher concentrations of acid. 

The rate-determining step in the diazotization of aniline in aqueous perchloric acid below concentrations of 0.05 m (pH >0.7) is the formation of N203. The following A-nitrosation step is faster (rate equation of Scheme 3-12). However, with aromatic amines that are weaker nucleophiles than aniline, e.g. 4-nitroaniline, nitrosation is slower than the formation of N203, and the rate is second-order with respect to nitrous acid and first-order in amine (Scheme 3-13, Larkworthy, 1959). 

On increasing the acidity still further (>0.1 m H2S04, i.e., H0< 1), the rate of diazotization of aniline passes through a minimum and then increases rapidly (region B in Fig. 3-1). The plot in Figure 3-1 is a somewhat schematic representation of the minimum, the position of which depends very much on the concentration of nitrous acid. Moreover, with other aromatic amines the plot is not exactly the same, but it can be explained by analogous arguments. 

Fig. 3-1. Variation in rate of diazotization of aniline with acidity (after Ridd, 1965). H0 = -log h0.

At acid concentrations of more than about 70 % HC104 (by weight), the rate of diazotization of aniline reaches a maximum and then rapidly decreases, corresponding to region C in Figure 3-1. The exact position of the maximum depends on the nature of the amine (Fig. 3-3). 

Fig. 3-3. Diazotization of aniline (O), 4-methyl-aniline ( ), and 4-chloroaniline ( ) in the region of maximum rate (after Ridd, 1965).

The deuterium isotope effect is thought to arise from the effect on the equilibrium position of this A-nitrosation. This is also the case for the diazotization of aniline, but the isotope effect is larger, because two deprotonations are involved in the kinetics. 

Table 3-1. Equilibrium constants Kxno (Scheme 3-28) and rate constants for diazotization of aniline (Ar2, Scheme 3-29) and of 1-naphthylamine (k2 and k-2/k Scheme 3-34) in water by nitrosyl chloride, nitrosyl bromide, nitrosyl thiocyanate, S-nitrosothiuronium ion [(NH2)2CSNO], and dinitrogen trioxide at 25 °C.

Abia et al. (1989) also measured and evaluated the rates of diazotization of aniline and of 2- and 4-chloroaniline in the presence of thiosulfate. These authors found that the rates with aniline decrease under comparable conditions in the order NOCl> NOBr > N203 > NOSCN > (H2N)2CSNO+ > S203NCr. 

For substituted anilines (Thompson and Williams, 1977) and for 1-naphthylamine and a series of derivatives thereof (Castro et al., 1986a), k2 and the ratio Ar 2/Ar3 have been determined for nucleophilic catalysis with Cl-, Br-, SCN-, and SC(NH2)2. The values of k2 correspond fairly well to those found for the diazotization of aniline, but those of Ar 2/Ar3 increase markedly in the above sequence (Table 3-1). As k3 is expected to be independent of the presence of Cl- or Br- and to show little dependence on that of SCN- or thiourea, the increase in k 2/k3 for this series must be due mainly to 2. Indeed, the value of log(Ar 2/Ar3) shows a linear correlation with Pearson s nucleophilicity parameter n (Pearson et al., 1968). This parameter is based on nucleophilic substitution of iodine (as I-) in methyl iodide by various nucleophiles. The three investigations on nucleophilic catalysis of diazotization demonstrate that Pearson s criteria for bimolecular nucleophilic substitution at sp3 carbon atoms are also applicable to substitution at nitrogen atoms. 

For more than a century, stoichiometric methods were presumed in the preparation of benzonitriles in laboratory and industry. These particularly include the Rosenmund-von Braun reaction of aryl halides, the diazotization of anilines and subsequent Sandmeyer reaction, and the ammoxidation. Because of (over)stoichiometric amounts of metal waste, lack of functional group tolerance, and harsh reaction conditions, these methods do not meet the criteria of modern sustainable synthesis. 

For a representative and relatively recent example of a comparative kinetic investigation of diazotization of aniline and 1-naphthylamine with various catalysts X-, reference is made to the work of Castro and coworkers98. These authors found that the (overall) rates decrease under comparable conditions in the order X = Cl- > Br- > N()2 >... 

On the other hand, 2,4-dichloro-5-fluorobenzoyl chloride (15) employed in Scheme 1 was prepared from a more readily available commercial source, 2,4-dichloro-5-methylphenylamine (22). Diazotization of aniline 22 and treatment with dimethylamine formed triazene 23. When triazene 23 was dissolved in excess anhydrous HF, the... 

The largest tonnage product, fluorobcnzcnc (3), is manufactured by the diazotization of aniline (1) in strong aqueous hydrogen fluoride. The intermediate diazonium fluoride 2 is decomposed in situ without isolation from solution. Despite the considerable safety and corrosion problems presented by the reaction mixtures, the technology was developed in the 1980s to provide a worldwide capacity of several thousand tons. Other fluoroaromatics such as fluorotoluenes are also manufactured by this route. 

Thus, the diazotization of anilines in tetrafiuoroboric acid with nitrogen oxides (N203, N204, and more generally NO,) or their crystalline complexes with boron trifluoride has been examined.176-178... 

In competitive studies (73IJS295, 74AHC(16)123) using aprotic diazotization of aniline to generate phenyl radicals, it has been shown that the relative rates of phenylation for furan and thiophene compared to benzene are 11.5 and 2.6, respectively. The partial rate factors... 

Cleavage of the S—S bond of (40) also occurs on reaction with phenyl radicals obtained by decomposition of A-nitrosoacetanilide or aprotic diazotization of aniline. The main... 

Fig. 13.72. Diazotization of aniline and its conversion to other types of intermediates.

Sianesi and co-workers39,40 utilized o-aminophenylacetonitrile (48) as starting material for a four-step synthesis of compounds related to 47. Thus, diazotization of aniline 48 and treatment of the diazonium salt with S02/Cu2Cl2 yielded the sulfonyl chloride 49 (Eq. 11). Treatment of 49 with primary amines produced the corresponding sulfonamides 50 which were cyclized by sulfuric acid to the 3-imino compounds 51. Finally, aqueous hydrolysis of the imine 51 produced the desired 1,2-benzothiazin-3 (2H)-one 1,1-dioxides (47) (R = H, Et, and Ph) (Eq. 11). 

Halogen exchange with a fluoride anion is one of the two main techniques to introduce a fluorine atom on an aromatic nucleus, which is a useful complement of diazotization of anilines in hydrogen fluoride or thermal decomposition of arenediazonium fluoroborates (Schiemann reaction). It is used on an industrial scale to produce, for example, 2,6-difluorobenzonitrile (the precursor of the insecticide Diflubenzuron) or 2,4-difluoroaniline (the precursor of Diflufenican or other herbicides). 

Phenyl diazonium chloride is obtained first hy the diazotization of aniline with nitrous acid as explained earlier, which on coupling with (l-naphthol in the presence of NaOH solution yields the desired coupled product phenyl-azo-P-naphthol. A mole of HCl is eliminated which instantly reacts with NaOH from the medium to produce NaCl and H2O. Importantly, hoth diazotization and coupling reactions are required to he carried out between 0-5°C. 

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