Sodium nitrite with acid

The nitrosations are usually carried out with conventional reagents. The most common procedures involve (a) sodium nitrite with acids in an aqueous system, (b) sodium nitrite in acetic anhydride, (c) nitrogen trioxide, (d) nitrosyl chloride in the presence of a base, and (e) dinitrogen tetroxide in the presence of a base. 

Nitrous acid is unstable and must be prepared in the reaction solution by mixing sodium nitrite with acid. 

The kinetics of these reactions markedly favor sodium nitrite production. If some sodium nitrate is formed, it can be easily separated by differential crystallization. Otherwise, sodium nitrate can be formed by treating sodium nitrite with nitric acid ... 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

The nitrosation of primary aromatic amines 1 with nitrous acid 2 and a subsequent dehydration step lead to the formation of diazonium ions 3. The unstable nitrous acid can for example be prepared by reaction of sodium nitrite with aqueous hydrochloric acid. 

The cymidiu sulphouic acid is then diazotised in the usual manner by treating with sodium nitrite in acid solution and the diazo body reduced with alkaline tin chloride solution, or with formic acid and powdered copper, or with other relatively gentle reducing agents. The 3 or 5 cymidin sulphonic acid gives by the above process one and the same cymene sulphonic acid, viz., l-methyl-3-sulphonic-4-isopropyl benzene. 

Primary aromatic amines are first diazotized by the action of sodium nitrite in acid solution and then coupled, for instance, with 1-naphthol to form azo dyes (cC Bratton-Marshall reagent, Vol. 1 a). ... 

When o-Nitroaniline is treated by sodium nitrite in acid medium and then by an inorganic sulphide, it forms an explosive diazonium sulphide. Note that even though the presence of a nitrated group does not help, it certainly is not a factor that is vital to cause the explosion, since this is a property that is common to all these diazonium salts whatever the nature of the substitution on the ring. The situation is exactly the same with p-nitroaniline. 

Sodium nitrite with sulphuric acid (this carries a danger of fibre degradation)... 

The reaction sequence is the usual one. The hydrochloride of the aromatic amine is diazotized with sodium nitrite/hydrochloric acid and subsequently coupled onto a Naphthol AS derivative. 

Benzenedlazonlum chloride is prepared by the reaction of anUme with nitrous acid at 273-278K. Nitrous acid is produced In the reaction mixture by the reaction of sodium nitrite with hydrochloric acid. The conversion of prlmaiy aromatic amines into diazonium salts is known as diazotisation. Due to its Instability, the diazonium salt Is not generally stored and is used immediately after its preparation. 

Phenylhydrazine. 10 g of freshly distilled aniline are added to a solution of 30 g coned hydrochloric acid in 75 cc of water and diazotized with 30 cc of water containing 8 g sodium nitrite, with external cooling below 5°. 30 g sodium chloride are added with very fast stirring and cooling of -5°. A solution of 60 g of stannous chloride in 25 g coned hydrochloric acid are then added and allowed to stand. Phenylhydrazine hydrochloride separates after 4-12 hours and is filtered off, washed with a saturated NaCl solution, treated with an excess caustic soda solution, and extracted with ether. The ethereal solution is dried with caustic potash, the ether is removed by evaporation, and the phenylhydrazine is purified by freezing or distilling in vacuo. Tield 10 g 90% theoretical. 

Methoxy-l-Nitroso-2-Naphthol. A fine suspension of 8 g of the above naphthol in dilute acetic acid (this can be accomplished by adding 75 g of ice to 38 cc of acetic acid) is treated rapidly with 3.17 g of solid sodium nitrite, with vigorous stirring. The mixture is stirred at -5° for 20 min and an additional. 35 g of sodium nitrite is added. Continue stirring for 20 min and the resulting yellow, brown solid is collected, washed well with water, then with methanol and dried. Yield 8.4 g. 

A benzofuran ring replaces one of the benzene rings of the biphenyl moiety present in many of the sartans in the rather more complex drug saprisartan (80-10). It is of note, further, that the acidic proton is provided in this case by a trifluorosulfo-namide instead of the more common tetrazole ring. Construction of the imidazole fragment begins by nitrosation of the (3-ketoester (79-1) by means of sodium nitrite in acid to afford the oxime (79-2). Reaction with acetyl chloride leads to the ester (79-3). Reaction of this last intermediate with the iminoether from propionitrile then affords the imidazole (79-4). 

Typical nitrosating agents are sodium nitrite with mineral acids or pentyl nitrite with mineral acids. A relatively new reagent, nitrosylsulfuric acid, has been used to nitrosate primary aromatic amines. 

Other cyclobutanecarboxylic acid derivatives have also been converted to nitrogen-substituted cyclobutanes.37 43 47,339 For example, ran.s-2-(cyanomethyl)cyclobutanecarbohydrazide reacted with sodium nitrite/hydrochloric acid in methanol to give methyl traw-2-(cyanomethyl)-cyclobutylcarbamate (3).43... 

A mixture of sodium nitrite with ammonium chloride may decompose with time to form unstable ammonium nitrite. The presence of moisture and of acids favours the decomposition of a mixture of sodium nitrite with ammonium chloride. On the other hand, alkaline reaction and absence of moisture stabilize the system. Experiments have shown that for all practical purposes the mixture is best stabilized by the addition of 2% sodium carbonate. Ammonium carbonate or magnesium oxide may also be used. 

Diazonium compounds are usually prepared in mineral acid solution, and the nitrous acid generated from sodium nitrite. Sufficient acid must be used to generate nitrous acid and to form the salt of the base, and still leave the solution acid. In practice 2J—2f mols. of hydrochloric acid are generally employed. In most cases it is essential that the reaction be carried out at about 0°, as many diazonium solutions decompose above this temperature. The reaction goes very readily in some cases but in others, and especially where an acid group is present, e.g., naphthylamine sul-phonic acids, the reaction is only carried out with difficulty. It is possible to diazotise a solid in suspension, but the reaction is usually very slow. If the solid is dissolved and reprecipitated in a fine state of division the action goes much more quickly. 

According to E. Divers, normal mercuric hyponitrite, HgNa02, is obtained by precipitation from sodium hyponitrite and mercuric nitrate. The mixed soln. of sodium hydroxide and hyponitrite obtained by reducing sodium nitrite with sodium amalgam is diluted and almost neutralized by dil. nitric acid keeping the soln. ice-cold all the time. It is then poured into a soln. of mercuric nitrate which must not be in excess, and should contain as little free acid as possible. The slightly turbid mother-liquor is decanted from the precipitate, and, after being neutralized... 

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