Amines diazotizations, nitrosylsulfuric acid

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

For these reasons there are limits to the extent to which the acid concentration can be increased gradually as the basicity of the amines decreases. Nevertheless, diazotization can be carried out without difficulty in 90-96% sulfuric acid. It has already been mentioned that nitrous fumes are given off as soon as nitrite is added to sulfuric acid of lower concentration, but solid sodium nitrite can be dissolved in 90-96% sulfuric acid at 0-10°C smoothly and without evolution of gas. Nitrosylsulfuric acid, N0+HS04, is formed. Directions for the preparation of 2 m nitrosylsulfuric acid are given by Fierz-David and Blangey (1952, p. 244), but sodium hydrogen sulfate crystallizes after some time from acid of this strength so that it is best to prepare a stock solution of 1 m sodium nitrite in 96% sulfuric acid, which is quite stable at room temperature. 

The nitrosylsulfuric acid method is particularly suitable for the diazotization of di- and trinitroanilines and aminoanthraquinones. Such amines may be added directly to the nitrosylsulfuric acid, but it is preferable to run the appropriate amount of nitrosylsulfuric acid into a solution of the amine in 96% sulfuric acid. In general, these diazotizations can be carried out at room temperature. The end-point is determined in the usual manner with iodide paper, but only after first diluting a few drops with ice. On completion, the whole is diluted with ice. The test with iodide paper fails in the case of polynitrodiazonium salts. 

Diazotization is the reaction of a primary aromatic amine with a nitrosating agent, such as sodium nitrite or, to a lesser extent, with nitrosylsulfuric acid N0S04H, nitrous gases, or organic nitrites in an aqueous acidic solution at a temperature between 0 and 5°C, converting the amine to its diazonium salt ... 

Nitrosylsulfuric acid is employed for amines of very low basicity e.g., those with more than one electronegative function. Compounds such as di- and trinitroani-lines, halogenated nitroanilines, and tetrahalogenanilines will not react under more moderate conditions. If necessary, these amines can also be diazotized after dissolving them in a mixture of glacial acetic acid and concentrated hydrochloric acid. 

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. 

Amines which are considerably or entirely insoluble in water are dissolved in glacial acetic acid or in other organic media, possibly mixed with water e.g., alcohols or aprotic solvents. Addition of acid is followed by a typical diazotization reaction in an aqueous sodium nitrite solution. Other possible sources of the nitrosating species NO include nitrosylsulfuric acid, nitrosylchloride, alkylnitrite, and nitrous gases. 

Nitrosylsulfuric acid, prepared by dissolving sodium nitrite in concentrated sulfuric acid, is employed for amines of low basicity, whose diazonium salts will hydrolyze in dilute acid. In order to synthesize Pigment Orange 5, for instance, 2,4-dinitroaniline is dissolved in concentrated sulfuric acid and diazotized preferably with nitrosylsulfuric acid. Coupling is carried out with a (3-naphthol suspension, produced by acidifying a sodium naphtholate solution. 

The rates of diazotizations in nitrosylsulfuric acid can be increased favorably by the addition of acetic or propionic acid. A mixture of the two acids is frequently used as an additive in diazotizations of heteroaromatic amines, as it has a lower melting point than acetic acid (0 °C or lower), but little is mentioned about it in the scientific literature... 

Frequently, weakly basic amines, such as negatively substituted 4-nitroandines or aminoheterocycles, must be diazotized. These reactions require concentrated sulfuric acid, phosphoric acid (85 wt %), glacial acetic acid, propionic acid, or mixtures of thereof as the reaction medium, with nitrosylsulfuric acid as the reagent. On an industrial scale, this reaction is conducted preferably in enameled, stirred vessels. Whenever the stability of the amine or the diazonium salt permits, diazotization is carried out in concentrated sulfuric acid at slightly elevated temperature (10-40 °C). With regard to safety, factors such as temperature and concentration must be controlled carefully to avoid explosion [42],... 

The diazotization of the amines is carried out in the usual manner. The volume of water is kept at a minimum since the success of the reaction depends in part on the efficiency with which the unstable intermediate is extracted from the aqueous layer by the organic liquid. Either the previously prepared amine hydrochloride is employed or a paste of the hydrochloride is prepared by dissolving the amine in concentrated hydrochloric acid and then cooling rapidly with stirring. For diazotization a nearly saturated solution of sodium nitrite (1 g. in 2 cc. of water) is used. Little work has been done with very weakly basic amines in the diazo reaction.48 In one instance, the base, l-nitro-2-naphthylamine, was diazotized by means of nitrosylsulfuric acid in sulfuric acid benzene was added and then sodium hydroxide until the mixture was slightly alkaline.49 For the very weak bases, the nitrosoacetyl reaction is recommended, since it is carried out entirely under anhydrous conditions. 

The synthesis of diazonium salts of less basic amines does not proceed satisfactorily under the above conditions because of the reduced nucleophilic nature of the amino group and the reaction is usually carried out in concentrated sulfuric acid. The addition of sodium nitrite to concentrated sulfuric acid produces the stable nitrosylsulfuric acid, (NOHSO ). Diazotization of the most weakly basic amines is carried out using nitrosylsulfuric acid in a mixture of one part of propionic acid in five parts of acetic acid at 0-5 °C. The propionic acid prevents the mixture from freezing. 

The practical applicability and accuracy of the PSC method can be demonstrated by the examples of the thermal decomposition of aromatic diazonium salts in sulfuric acid, (important intermediates for the production of dyestuffs). The diazotation of both the amines was carried out by nitrosylsulfuric acid. 

The ease of diazotization depends markedly on the basicity of the amine. Extremely weakly basic amines are diazotizable only by special methods, usually with nitrosylsulfuric acid (NOHSO4). 

Picramide is diazotized by treating a solution of the amine in (glacial acetic acid with nitrosylsulfuric add (prepared by dissolving sodium nitrite in concentrated sulfuric add).61 Addition of ice-cold water to the diazonium solution results in immediate decomposition of the diazonium salt.61-62- /... 

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