Methods of Diazotization

The following methods are currently used to produce azo pigments on an industrial scale. The choice depends on the basicity and on the solubility of the individual product. 

An aqueous sodium nitrite solution is added to a cold solution or suspension of the primary aromatic amine in an excess of hydrochloric or sulfuric acid. A temperature of 0 to 5°C is maintained by adding ice directly to the reaction mixture. 

This method is particularly useful for aromatic aminocarboxylic and aminosulfonic acids, which are often only sparingly soluble in dilute acid. The amino compound is dissolved in water or in weak alkali and combined with a stoichiometric amount of sodium nitrite, upon which the resulting solution is poured into a mixture of acid and ice. Alternatively, the process may be reversed by pouring the acid into the amine-nitrite mixture. 

Amines of very low basicity undergo diazotization after being dissolved in concentrated sulfuric acid. The nitrosating agent is provided by nitrosylsulfuric acid, which is either purchased commercially or easily prepared by dissolving solid sodium nitrite in concentrated sulfuric acid. 

Sulfuric acid as a reaction medium may be replaced by glacial acetic acid or by a mixture of glacial acetic acid/nitrosylsulfuric acid. In the former case, half-concentrated hydrochloric acid is added, and diazotization proceeds in an aqueous sodium nitrite solution. The combination of glacial acetic acid/nitrosylsulfuric acid is a particularly useful medium for the bisdiazotization of 1,2-, 1,3-, or 1,4-di-aminobenzenes (phenylenediamines). 

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An increased hydrogen ion concentration, that is a considerably greater amount of acid than the theoretical two equivalents of Scheme 2-1, is necessary in the diazotization of weakly basic amines. The classic example of this is the preparation of 4-nitrobenzenediazonium ions 4-nitroaniline is dissolved in hot 5-10 m HC1 to convert it into the anilinium ion and the solution is either cooled quickly or poured onto ice. In this way the anilinium chloride is precipitated before hydrolysis to the base can occur. On immediate addition of nitrite, smooth diazotization can be obtained. The diazonium salt solution formed should be practically clear and should not become cloudy on standing in the dark. Some practice is necessary, and details can be found in the books emphasizing preparative aspects (Fierz-David and Blangey, 1952 Saunders and Allen, 1985 in Houben-Weyl, Vol. E 16a, Part II, the chapter written by Engel, 1990). These books give a series of detailed prescriptions for specific examples and a useful review of the principal variations of the methods of diazotization. Such reviews have also been written by Putter (1965) and Schank (1975). 

Monoaminoarenesulfonic acids exist in acid solution as zwitterions (2.3 in the case of sulfanilic acid), which are relatively insoluble in contrast to the corresponding bases (such as 2.4). For this reason the indirect method of diazotization is often employed in such cases. The aminoarenesulfonic acid is dissolved as the anion (2.4) by introducing the required amount of sodium carbonate or hydroxide, and nitrite is added to the approximately neutral solution, which is then run into mineral acid. Indirect diazotization is particularly recommended for the aminosulfonic acids of greater molecular mass but, contrary to some statements in the literature, the three anilinesulfonic acids themselves can be diazotized directly in suspension, the reaction proceeding quite smoothly after some practice. 

As the amines become more weakly basic, the normal method of diazotization becomes progressively more difficult. The equilibrium between amine and ammonium salt increasingly favors the former which, usually because of its poor solubility in water, is prevented from taking part in the reaction. Research into the mechanism of diazotization has demonstrated that the important step is the addition of the nitrosating agent to the base of the amine. Thus, the acidity for each diazotization should be so chosen that the equilibrium concentration of base corresponds to that of its saturated solution. This rule leads to the use of higer concentrations of aqueous mineral acid for weakly basic amines. 

The diazotization of heteroaromatic amines is a ticklish procedure. In spite of the great increase in interest for disperse dyes based on heterocyclic diazo components, little systematic knowledge is available. In a review of such diazo components13 practically nothing is mentioned on suitable methods of diazotization and on yields (which are in part low). The somewhat older review of Butler14 is, in this respect, more informative. So too is the section on synthesis in the general review on diazoazoles by Cirrincione and coworkers15. 

Furthermore, Weiss and coworkers66 developed also a method of diazotizing aminocyclopropenium salts with nitrosyl salts in the presence of two equivalents of trimethylchlorosilane to trap the water produced. In a modification of this method the authors showed that the use of the terf-butylated amine was an advantage, as the risk of oxidation of the alkylated amino group by the nitrosyl ion is less than in the case of the primary amine. This method would also appear to be suitable for the diazotization of other sensitive amines. 

In the classical methods of diazotization an equimolar amount of water is formed as by-product. In certain cases this is not desirable. One method for obtaining diazonium salts without formation of water is the rearrangement of N-nitroso-N-arylacetamides. Bamberger discovered in 1897 that A -nitrosoacetanilide decomposes easily in benzene to give biphenyl, acetic acid and dinitrogen (equation 10). Huisgen and Horeld showed that the key step of Bamberger s reaction is the isomerization of N-nitrosoacetanilide to the diazo acetate (27) and Suschitzky found that 27 dissociates into the diazonium-acetate ion pair 28 (equation 11). 

Probably first obtained by Hantzsch and Arapides (105) by condensation of a,/3-dichlorether with barium thiocyanate, and identified by its pyridine-like odor, thiazole was first prepared in 1889 by G. Popp (104) with a yield of 10% by the reduction in boiling ethanol of thiazol-2-yldiazonium sulfate resulting from the diazotization of 2-aminothiazole. prepared the year before by Traumann (103). The unique cyclization reaction affording directly the thiazole molecule was described in 1914 by Gabriel and Bachstez (106). They applied the method of cyclization, developed by Gabriel (107, 108), to the diethylacetal of 2-formylamino-ethanal and obtained thiazole with a yield of 62% - Thiazole was also formed in the course of a study on the ease of decarboxylation of the three possible monocarboxylic acids derived from it (109). On the other... 

Synthesis. Methods of synthesis have changed Htde since the synthesis of Basic Red 2. One method starts with o-toluidine [95-53-4] C H N, which is diazotized and coupled to form amino azotoluene [97-56-3] Amino azotoluene is reduced to one mole each of o-toluidine and... 

This method is suitable only for the preparation of 4-substituted and/or 3,4-disubstituted derivatives, the substituents being only alkyl, aryl or heteroaryl groups. The presence of electron-withdrawing groups in the unsaturated side chain prevents the cyclization step. This is understandable if the influence of such groups on the stability of the intermediate carbonium ion is considered. Of more limited application is the analogous cyclization of diazotized o-aminophenylpropiolic acids, the reaction being referred to as the Richter synthesis (Scheme 70). A related synthesis (also referred to as the Neber-Bossel synthesis)... 

The most suitable method of fast and simple control of the presence of dangerous substances is analytical detection by means of simplified methods - the so-called express-tests which allow quickly and reliably revealing and estimating the content of chemical substances in various objects. Express-tests are based on sensitive reactions which fix analytical effect visually or by means of portable instalments. Among types of indicator reactions were studied reactions of complex formation, oxidation-reduction, diazotization, azocoupling and oxidative condensation of organic substances, which are accompanied with the formation of colored products or with their discoloration. 

The procedure described for the preparation of 3-hydroxycin-choninic acid is adapted from that reported. This synthesis is successful when bromopyruvic acid or its ethyl ester is substituted for chloropyruvic acid. The reaction of isatin with chloropyruvic acid to produce 3-hydroxycinchoninic acid has been reported however, no details or physical properties were given. This method offers a decided advantage over the method involving diazotization of the difficultly accessible 3-aminocinchoninic acid. ... 

There are several methods for generation of benzyne in addition to base-catalyzed elimination of hydrogen halide from a halobenzene, and some of these are more generally applicable for preparative work. Probably the most convenient method is diazotization of o-aminobenzoic acid. Concerted loss of nitrogen and carbon dioxide follows diazotization and generates benzyne. Benzyne can be formed in this manner in the presence of a variety of compounds with which it reacts rapidly. 

Among examples of the use of this method of internuclear cycliza-tion in heterocyclic chemistry is the conversion of diazotized amino-laudanosine (14) to 2,3,5,6-tetramethoxyaporphine (15), Eq, (23). ... 

Many different nucleophiles—halide, hydride, cyanide, and hydroxide among others—react with arenediazonium salts, yielding many different kinds of substituted benzenes. The overall sequence of (1) nitration, (2) reduction, (3) diazotization, and (4) nucleophilic substitution is perhaps the single most versatile method of aromatic substitution. 

Another redox reaction leading to arenediazonium salts was described by Morkov-nik et al. (1988). They showed that the perchlorates of the cation-radicals of 4-A,A-dimethylamino- and 4-morpholinoaniline (2.63) react with gaseous nitric oxide in acetone in a closed vessel. The characteristic red coloration of these cation-radical salts (Michaelis and Granick, 1943) disappears within 20 min., and after addition of ether the diazonium perchlorate is obtained in 84% and 92% yields, respectively. This reaction (Scheme 2-39) is important in the context of the mechanism of diazotization by the classical method (see Sec. 3.1). 

A widely significant and crucial investigation of the mechanism of diazotization was made in 1899 by Hantzsch and Schumann widely significant because it was one of the first mechanistic investigations using appropriate methods of organic chemistry - extremely crucial because it influenced all subsequent investigations in the field of diazotization mechanisms until 1958. 

Summarizing the discussion in this section, it is obvious that the various forms of diazotization methods became understandable only after the long historical development leading to the breakthrough by Hughes, Ingold, and Ridd in 1950 to 1958. 

In the context of the stability of the nitrosoamine intermediate in the diazotization of heteroaromatic amines relative to that in the case of aromatic amines, the reversibility of diazotization has to be considered. To the best of our knowledge the reverse reaction of a diazotization of an aromatic amine has never been observed in acidic solutions. This fact is the basis of the well-known method for the quantitative analysis of aromatic amines by titration with a calibrated solution of sodium nitrite (see Sec. 3.3). With heteroaromatic amines, however, it has been reported several times that, when using amine and sodium nitrite in the stoichiometric ratio 1 1, after completion of the reaction nitrous acid can still be detected with Kl-starch paper,... 

The Pschorr reaction is a method of synthesis of phenanthrenes from diazotized Z-2-aminostilbenes. A traditional procedure involves heating with a copper catalyst. Improved yields are often observed, however, if the diazonium ion is treated with iodide ion. Suggest a mechanism for the iodide-catalyzed reaction. 

The overall process can be related to two operations diazotization and coupling. Out of the vast number of patents concerning continuous methods of azo pigment formation, the following examples have been chosen. 

Pathway I is the method that first comes to mind but presents somewhat of a problem. It is not possible to synthesize the product in a straightforward two-step sequence by simply coupling two equivalents of diazotized amine with the bifunctional coupling component. This reaction does not afford a definitive product, since the monoazo compound is frequently insoluble enough to precipitate and is thus eliminated from further reaction. 

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