Amine nitrite mixtures

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. 

It is further recommended that amine-nitrite mixtures be kept away from electrophilic carbonyl compounds and gem-di-halides capable of supporting immonium ion formation, for example in the preservation of amine-rich fish products with formaldehyde ( ) or in the use of methylene chloride as an aerosol propellant (13). It also seems advisable to avoid storing treflan and related herbicides in the presence of... 

Add 20 g. of /)-bromoaniline to 20 ml. of water in a 250 ml. beaker, and warm the mixture until the amine melts. Now add 23 ml. of concentrated hydrochloric acid and without delay stir the mixture mechanically in an ice-water bath, so that a paste of fine /> bromo-aniline hydrochloride crystals separates. Maintain the temperature of the stirred mixture at about 5° whilst slowly adding from a dropping-funnel a solution of 8 5 g. of sodium nitrite in 20 ml. of water con tinue the stirring for 20 minutes after the complete addition of the nitrite. 

Meihylamine hydrochloride method. Place 100 g. of 24 per cent, methyl-amine solution (6) in a tared 500 ml. flask and add concentrated hydrochloric acid (about 78 ml.) until the solution is acid to methyl red. Add water to bring the total weight to 250 g., then introduce lSO g. of urea, and boil the solution gently under reflux for two and three-quarter hours, and then vigorously for 15 minutes. Cool the solution to room temperature, dissolve 55 g. of 95 per cent, sodium nitrite in it, and cool to 0°. Prepare a mixture of 300 g. of crushed ice and 50 g. of concentrated sulphuric acid in a 1500 ml. beaker surrounded by a bath of ice and salt, and add the cold methylurea - nitrite solution slowly and with mechanical stirring and at such a rate (about 1 hour) that the temperature does not rise above 0°. It is recommended that the stem of the funnel containii the methylurea - nitrite solution dip below the surface of the acid solution. The nitrosomethylurea rises to the surface as a crystalline foamy precipitate. Filter at once at the pump, and drain well. Stir the crystals into a paste with about 50 ml. of cold water, suck as dry as possible, and dry in a vacuum desiccator to constant weight. The yield is 55 g. (5). 

This crude amine is added, with cooling, to a solution of 100 cc. of concentrated hydrochloric acid (sp. gr. 1.18) in 350 cc. of water. The solution of the hydrochloride is cooled in an ice bath, and stirred rapidly, while a solution of 41.5 g. (0.6 mole) of sodium nitrite in 150 cc. of water is added slowly. During this addition the temperature should not be allowed to rise above 120. After all the nitrite has been added, the mixture is allowed... 

Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits. For example, diazotization of n-butylamine gave 25% 1-butanol, 5.2% 1-Chlorobutane, 13.2% 2-butanol, 36.5% butenes (consisting of 71% 1-butene, 20% trans-2-butene, and 9% cw-2-butene), and traces of butyl nitrites. ... 

The monovalent Co chemistry of amines is sparse. No structurally characterized example of low-valent Co complexed exclusively to amines is known. At low potentials and in non-aqueous solutions, Co1 amines have been identified electrochemically, but usually in the presence of co-ligands that stabilize the reduced complex. At low potential, the putative monovalent [Co(cyclam)]+ (cyclam = 1,4,8,11-tetraazacyclotetradecane) in NaOH solution catalyzes the reduction of both nitrate and nitrite to give mixtures of hydroxylamine and ammonia.100 Mixed N-donor systems bearing 7r-acceptor imine ligands in addition to amines are well known, but these examples are discussed separately in Section 6.1.2.1.3. 

The LCM baths use a mixture of nitrate/nitrite eutectic salts. As it contains up to 40% sodium nitrite the salt system is toxic and can cause water pollution, and also cause nitrosation of volatile secondary amines. 

Very feebly basic amines cannot usually be diazotised in dilute acid media and in these instances the reaction has to be carried out in a concentrated acid, normally sulphuric acid. The usual technique is first to dissolve dry sodium nitrite in the concentrated acid, when reaction occurs in two stages (Scheme 4-8), resulting in the formation of nitrosylsulphuric acid (4.5). The nitrosyl ion - nitrous acid equilibrium has been evaluated spectroscopically. In 96% sulphuric acid the 15N-n.m.r. signal is characteristic of the free nitrosyl ion [4]. Reaction (2) of Scheme 4.8 is slow at room temperature and it is desirable to heat the mixture to 70 °C in order to attain equilibrium within a reasonable time. After cooling, the amine is added gradually and after a short time the reaction mixture is poured onto ice, giving an aqueous solution of the diazonium salt [20]. 

On an industrial scale, diazotization reactions are carried out by dissolving the aromatic amine in hydrochloric or sulfuric acid. Despite the fact that 2 equivalents of acid per equivalent of amino group should theoretically suffice, as much as 2.5 to 3 equivalents per amino function are actually required to ensure complete diazonium salt formation. One equivalent of an aqueous sodium nitrite solution is added to the resulting mixture at 0 to 5°C. The exothermic nature of the reaction, combined with the heat sensitivity of most diazonium salts, makes it necessary to provide cooling, usually by direct addition of ice. 

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. 

Principally the same, but chemically simpler, sequence was used to prepare arylnitro anion-radicals from arylamines, in high yields. For instance, aqueous sodium nitrite solution was added to a mixture of ascorbic acid and sodium 3,5-dibromo-4-aminobenzenesulfonate in water. After addition of aqueous sodium hydroxide solution, the cation-radical of sodium 3,5-dibromo-4-nitro-benzenesulfonate was formed in the solution. The latter was completely characterized by its ESR spectrum. Double functions of the nitrite and ascorbic acid in the reaction should be underlined. Nitrite takes part in diazotization of the starting amine and trapping of the phenyl a-radical formed after one-electron reduction of the intermediary diazo compound. Ascorbic acid produces acidity to the reaction solution (needed for diazotization) and plays the role of a reductant when the medium becomes alkaline. The method described was proposed for ESR analytical determination of nitrite ions in water solutions (Lagercrantz 1998). 

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. 

For weakly basic amines, i.e. anilines with poly nitro groups, e.g. 2, 4,-dintro-6-bromoaniline, and also most heterocyclic amines, an alternative method must be adopted using nitrosylsulfuric acid. This diazotising medium can be made by dissolving sodium nitrite in concentrated sulfuric acid, but is also available preformed from chemical suppliers. The weakly basic amine is added gradually to the nitrosyl-sulfuric acid with cooling, and after reaction is complete the mixture is poured into ice and water to give a solution of the diazonium salt. 

Indeed, there were those who described the azide coupling method as racemization-free. [15l However, this viewpoint proved to be overly optimistic. In 1970, Sieber reported that during a synthesis of calcitonin M by the azide method, significant epimerization occurred during two of the segment condensation steps in one of these reactions 40% of the epimerized product was observed. 16 There is a crucial detail in the experimental procedure here. The workers used tert-butyl nitrite to convert a peptide hydrazide into a peptide azide, but did not isolate the azide as was typical for research at that time. Instead, they neutralized the active intermediate in situ with DIPEA and added the amino segment for acylation. This demonstrates another important theme in the control of epimerization, the presence of a tertiary amine in the reaction mixture, even if only as a neutralization equivalent, can result in the formation of epimerized products. Indeed, most observations of racemization during... 

St CA 45, 6l56(1951)(Reverse Redox method) 9) M. Halse, MeddNotskFarm-Selskap 16, 166-9(1954) CA 49, 13024(1955) (Determination of NG in mixtures with PETN) (Saponification to nitrite at 20°, then reaction with sulfanilic acid and a-naphthyl amine for a colorimetric measurment against nitrite standards) 10) P. Lhoste, MP 37, 149-52(1955)... 

To a mixture of 1 mole of the aromatic amine and 3-4 moles of hydrochloric acid (diluted 1 1 with water) is added, at 0°C, the requisite amount of sodium nitrite dissolved in a minimum amount of water. While maintaining the diazonium salt solution at ice temperatures, 200 ml of a cold saturated solution of zinc chloride is added with occasional stirring. After allowing the mixture to stand for some time in an ice bath, the product is filtered off, washed several times with small portions of ice-cold ethanol followed by anhydrous ether. The salt is then air-dried and finally dried in a vacuum desiccator. In most cases the yield is in the range 90-98 %. 

The amine (0.1 mole) is dissolved in a buffered (pH 4-5) solution of 500 ml of 60 % aqueous acetic acid and 68 gm of sodium acetate. The reaction mixture is warmed to 90°C. Then 69 gm (1.0 mole) of sodium nitrite dissolved in 100 ml of water is added dropwise over a 45 min period while heating at 90°C is continued. After the addition, the reaction mixture is heated for 2 hr, cooled, poured into 200 ml of cold water, and extracted three times with 200 ml portions of ether. The ether was washed with 10 % potassium carbonate solution until basic, then with saturated sodium chloride solution, dried, stripped, and distilled to obtain the products shown in the table. 

Since acetic acid and acetic anhydride mixtures are excellent solvents for amides derived from primary carbinamines and cyclohexylamines, A-nitroso derivatives can be prepared in this solvent medium with sodium nitrite. The method appears to be somewhat more rapid than that carried in an aqueous medium, but fails when amides derived from secondary carbinamines are to be nitrosated. As the reaction medium is one which will also acetylate primary amines, appropriate amines may be dissolved in the reaction medium and, in turn, acetylated and nitrosated without the isolation of the intermediate amide. 

---