Diazotization Sodium nitrite

A common route to nitropyrazoles involves the diazotization of the corresponding amino derivatives in the presence of excess sodium nitrite." Diazotization in the presence of sodium azide allows the introduction of the azido explosophore ."... 

Fluoroaromatics are produced on an industrial scale by diazotization of substituted anilines with sodium nitrite or other nitrosating agents in anhydrous hydrogen fluoride, followed by in situ decomposition (fluorodediazoniation) of the aryldiazonium fluoride (21). The decomposition temperature depends on the stabiHty of the diazonium fluoride (22,23). A significant development was the addition of pyridine (24), tertiary amines (25), and ammonium fluoride (or bifluoride) (26,27) to permit higher decomposition temperatures (>50° C) under atmospheric pressure with minimum hydrogen fluoride loss. 

Barium nitrite [13465-94-6] Ba(N02)2, crystallines from aqueous solution as barium nitrite monohydrate [7787-38-4], Ba(N02)2 H2O, which has yellowish hexagonal crystals, sp gr 3.173, solubihty 54.8 g Ba(NO2)2/100 g H2O at 0°C, 319 g at 100°C. The monohydrate loses its water of crystallization at 116°C. Anhydrous barium nitrite, sp gr 3.234, melts at 267°C and decomposes at 270 °C into BaO, NO, and N2. Barium nitrite may be prepared by crystallization from a solution of equivalent quantities of barium chloride and sodium nitrite, by thermal decomposition of barium nitrate in an atmosphere of NO, or by treating barium hydroxide or barium carbonate with the gaseous oxidiation products of ammonia. It has been used in diazotization reactions. 

Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

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. 

To a cold mixture of 800 cc. of 95 per cent ethyl alcohol and 200 cc. of concentrated sulfuric acid (Note i) in a 5-I. round-bottom flask, provided with an efficient mechanical stirrer, is added 250 g. (1.33 moles) of crude 3-bromo-4-aminotoluene (p. 8). The solution is stirred and cooled to 10° and a solution of 148 g. (2.05 moles) of d.s.p. sodium nitrite in 260 cc. of water is added from a separatory funnel. During this addition, the temperature of the mixture must not be allowed to rise above 10°. After all of the nitrite solution has been added, the mixture is stirred twenty minutes longer to complete the diazotization. 

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. ... 

In a 600-ml. beaker fitted with a thermometer and mechanical stirrer are placed 150 ml. of concentrated hydrochloric acid and 55 g. (0.32 mole) of o-bromoaniline. After brief stirring, 100 g. of ice is added and the beaker is surrounded by an ice-salt bath. The solution is then diazotized by the dropwise addition with stirring of a solution of 24.3 g. (0.35 mole) of sodium nitrite in 100 ml. of water, the temperature being kept at 0-5°. 

Hydrogenation reduces the nitro group to amino which is then diazotized using sodium nitrite and tetrafluoroboric acid. The diazotized crown was not isolated but the aq. solution was treated directly with sodium acetate and bis(dibenzylideneacetone)-pal-ladium(O) in acetonitrile solution. Ethylene was then introduced to the autoclave and the solution was allowed to stir for 2 days. 4 -Vinylbenzo-15-crown-5 was isolated (30% from 4 -nitrobenzo-15-crown-5) as a colorless solid (mp 43.5—44.2°) °. The synthesis is illustrated in Eq. (3.16). 

Note Note that the diazotization of primary aromatic amines can also be achieved by placing the chromatogram for 3 — 5 min in a twin-trough chamber containing nitrous fumes (fume cupboard ). The fumes are produced in the empty trough of the chamber by addition of 25% hydrochloric acid to a 20% sodium nitrite solution [2, 4], iV-(l-Naphthyl)ethylenediamine can be replaced in the reagent by a- or -naphthol [10, 14], but this reduces the sensitivity of detection [2]. Spray solutions Ila and lib can also be used as dipping solutions. 

New diazotization techniques for the Balz-Schiemann reaction feature alter native mtrosating agents in place of aqueous sodium nitrite or substitution of other salts such as arenediazonium hexafluorophosphates for arenediazoniuin fluoroborates... 

Nitrosyl chloride [55], nitrosyl fluoride-hydrogen fluoride liquid complexes (NOF3HF, NOF 6HF) [56], nitrous acid-hydrogen fluoride solutions [57, 5 ] nitrogen trioxide (prepared in situ from nitric oxide and oxygen) [59] and rert-butyl nitrite-hydrogen fluoride-pyndine [60] have been substituted for sodium nitrite in the diazotization step... 

Heavily fluonnated aminobenzenes, pyridines, and pyrimidines are diazotized in strong-acid media Solid sodium nitrite added directly to the fluonnated amine dissolved in 80% hydrofluonc acid, anhydrous hydrogen fluoride, or (1 1 wt/wt) 98% sulfuric acid in (86 14 wt/wt) acetic and propionic acids affords the electrophilic fluoroarenediazonium ion Addition of an electron rich aromatic to the resultant diazonium solution gives the fluoroareneazo compound [10 II] (equa tions 9 and 10)... 

The o-aminophenylpropiolic acid 4 (20 g) in water (60 mL) and aqueous ammonia (9 mL, d = 0.88) was added with shaking during 15 minutes to a mixture prepared from ferrous sulfate (220 g), water (440 mL), and aqueous ammonia (110 mL, d = 0.88). After 45 minutes, with occasional shaking but no external cooling, the suspension was filtered. The residue was washed with water, and the combined filtrates were treated with ammonium acetate (60 g) and made weakly acidic with acetic acid. The solution was then cooled to 0°C by addition of crushed ice, and then made acidic to Congo-red with concentrated hydrochloric acid (70-80 mL). Additional hydrochloric acid (20 mL, 2 N) was immediately added, and the turbid solution which resulted was diazotized with 20% aqueous sodium nitrite, after which the mixture was kept at 70°C. The cinnoline acid 6 was separated over 45 minutes as a dark brown, granular solid (12.5 g), m.p. 260-265°C. ... 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

Forty-three grams (0.25 mole) of />-bromoaniline (Note 1) and 20 cc. of water are warmed in a 400-cc. beaker until the bromoaniline melts, and then 50 cc. of concentrated hydrochloric acid (sp. gr. 1.19) is added with mechanical stirring. The mixture is heated and stirred until solution is practically complete (Note 2). The beaker is then set in a dish of ice water and the solution is stirred as it cools in order to precipitate the />-bromoaniline hydrochloride in fine crystals. A few small pieces of ice are added and the cold (about 0-5 °) suspension is diazotized with a solution of 18 g. of sodium nitrite in 36 cc. of water to an end point with starch-iodide paper. 

Bromo-6,7,8,9-tetrahydro-l//-3-benzazepin-2-amine(6) with thiocyanate ion undergoes substitution of bromide to give the thiocyanatotetrahydro-l//-3-benzazepine 7.105 Attempts to replace bromide by azide ion failed, as did diazotization of the amine group with sodium nitrite in 6 M sulfuric acid. Oddly, treatment of the aminobromo compound with sodium borohydride in methanol results not in reduction, but in methoxy-debromination to give the 2-methoxy derivative which, on the basis of HNMR spectral data, is best represented as the 2-imino tautomer 8. 

To 375 cc. (4.3 moles) of hydrochloric acid (sp. gr. 1.18) and 200 g. of ice is added 139.6 g. (1.5 moles) of aniline. The resulting solution is diazotized with a solution of 103.5 S (x-5 moles) of c. p. sodium nitrite, ice being added to the reaction mixture, as necessary, in order to keep the temperature below 50. The final volume of the diazotized solution is about 1 1. This solution is added in a slow stream from a dropping funnel to the potassium selenide solution, which is being vigorously stirred with a mechanical stirrer. When all the diazotized solution has been added, the red aqueous solution is decanted from the dark oil which forms and is heated to boiling (Note 4). It is then poured back on the oil, the mixture is well stirred (Note 5), 200 cc. of chloroform is added, and the selenium collected on a filter and washed with a little more chloroform (Note 6). After the chloroform layer is separated, the aqueous layer is again... 

Sodium hypochlorite, 16, 4 Sodium metabisulfite, 13, 29 Sodium methylate, 17, 34 Sodium nitrite, see Diazotization, Nitro-sation... 

Usually, diazotization can be carried out by allowing sodium nitrite to act on a solution of the amine in mineral acid at about 0 °C. The overall equation for this process is shown in Scheme 2-1. 

In contrast to the acid, sodium nitrite should not in general be added in excess. Firstly, as far as the ratio of amine to nitrite is concerned, diazotization is practically a quantitative reaction. In consequence, it provides the most important method for determining aromatic amines by titration. Secondly, an excess of nitrous acid exerts a very unfavorable influence on the stability of diazo solutions, as was shown by Gies and Pfeil (1952). Mechanistically the reactions between aromatic diazonium and nitrite ions were investigated more recently by Opgenorth and Rtichardt (1974). They showed that the primary and major reaction is the formation of aryl radicals from the intermediate arenediazonitrite (Ar —N2 —NO2). Details will be discussed in the context of homolytic dediazoniations (Secs. 8.6 and 10.6). 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

In certain cases where the heteroaromatic amine is insufficiently soluble in aqueous acid, it can be dissolved in the minimum volume of an organic solvent miscible with water. Dilute mineral acid and a solution of sodium nitrite are then added. An example is the diazotization of 2-phenyl-3-amino-4-acetyl-5-methyl-pyrrole (Dattolo et al., 1983). 

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. 

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 specific detection of aromatic nitro compounds is a second example. These can be converted by reduction to primary amines, which are then diazotized and coupled to yield azo dyes (cf. reagent sequence Titanium(III) chloride — Bratton-Marshall reagent ). Sodium nitrite —naphthol reagent, diazotized sulfanilic acid and other reagents specific for amino groups (e.g. ninhydrin, fluorescamine, DOOB, NBD chloride [9]) can also be used in the second stage of the reaction (Fig. 21). 

The diazotization reaction can also be initiated via the vapor phase, e. g. with ethyl nitrite that can be generated in one trough of a twin-trough chamber by adding a few drops of cone, hydrochloric acid to a mixture of ethanol and saturated aqueous sodium nitrite solution (1 + 1) [3] the less volatile amyl nitrite can be used as an alternative [3]. 

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). ... 

Sodium nitrite ers in this case the chromatograms are merely sprayed with sulfanilic acid solution (2% fTTlO mol hydrochloric acid) [5], Diazotized 4-nitroaniline can also be used in place of ... 

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