Diazotates, formation

Diazotate formation ArN2O0CI + eOH = Ar—N=N—OH + Cle diazoic acid Diazotate salts are formed reversibly from diazonium salts in basic solution. 

When an aqueous solution of a diazonium salt is added to an alkaline solution of a phenol, coupling occurs with formation of an azo-compound (p. 188). If ho vc cr the ntiueous solution of the diazonium salt, t. . ., />-bromohenzene diazonium chloride, is mixed with an excess of an aromatic hydrocarbon, and aqueous sodium hydroxide then added to the vigorously stirred mixture, the diazotate which is formed, e.g., BrC,H N OH, dissolves in the hydrocarbon and there undergoes decomposition with the formation of nitrogen and two free radicals. The aryl free radical then reacts with the hydrocarbon to give a... 

Methyl-5-aminothia2ole-4-carboxylic acid is diazotized with isoamyl nitrite in the presence of furan in 1.2-dichloroethane to give a mixture of products 163 (53%), 164 (33%). 165 (11%), and 166 (3%) (Scheme 104) (334). This reactivity experiment was carried out to examine the possibility of the occurrence of 4,5-dehydrothiazole (hetaryne). Hetaryne intermediates seem not to be involved as an intermediate in the reaction. The formation of 163 through 166 can be rationalized in terms of the intermediacy of 166a. 

The product of this series of steps is an alkyl diazonium ion, and the amine is said to have been diazotized Alkyl diazonium ions are not very stable decomposing rapidly under the conditions of their formation Molecular nitrogen is a leaving group par excel lence and the reaction products arise by solvolysis of the diazonium ion Usually a car bocation intermediate is involved... 

This type of cyclization is important only for the formation of cinnolines. In all cases, the starting compounds have an ortho amino group, which upon diazotization undergoes ring closure with the other functionality, most frequently with a multiple bond. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

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. 

Among the reagents that are classified as weak electrophiles, the best studied are the aromatic diazonium ions, which reagents react only with aromatic substrates having strong electron-donor substituents. The products are azo compounds. The aryl diazonium ions are usually generated by diazotization of aromatic amines. The mechanism of diazonium ion formation is discussed more completely in Section 11.2.1 of Part B. 

Aromatic nitro compounds are often strongly colored. They frequently produce characteristic, colored, quinoid derivatives on reaction with alkali or compounds with reactive methylene groups. Reduction to primary aryl amines followed by diazotization and coupling with phenols yields azo dyestuffs. Aryl amines can also react with aldehydes with formation of Schiff s bases to yield azomethines. 

When the 4,4 -dinitroazoxyfurazan 240 reacted with ammonia in anhydrous CHCI3, a mixture of live compounds was formed (Scheme 162) (000HAC48). Compound 241 (59%) was the predominant product. However, the most interesting result of this reaction is the isolation of 3-azido-4-nitrofurazan (3%) and triazene 242 (13%). The formation of these compounds could be explained by reacting the intermediate diazotate generated from the leaving nitrofurazanazoxy moiety with ammonia and with 3-amino-4-nitrofurazan, respectively. 

The preparation of an aryl fluoride—e.g. fluorobenzene 3—starting from an aryl amine—e.g. aniline 1—via an intermediate arenediazonium tetrafluoroborate 2, is called the Schiemann reaction (also called the Balz-Schiemann reaction) The diazotization of aniline 1 in the presence of tetrafluoroborate leads to formation of a benzenediazonium tetrafluoroborate 2 that can be converted into fluorobenzene 3 by thermolysis. 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

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 some cases the use of nitrosylsulfuric acid may be avoided if 1-naphthalenesul-fonic acid is added to moderately concentrated sulfuric acid (20-60%). This greatly reduces the evolution of nitrous fumes compared with a solution of pure sulfuric acid of the same hydrogen ion concentration. It has not yet been investigated whether the phenomenon is due to the formation of an ion pair, [C10H7 —SO NO+], or whether it is simply a solubility effect. In any case, the total acidity range of 4-12 m has thereby become available for diazotization technically crude sulfonation mixtures are used after dilution with water, for example, a solution of total acidity 4 m, of which 2.7 m is due to sulfuric acid. A further advantage of the method lies in the stabilizing effect of the naphthalenesulfonic acid on the diazonium compounds formed (see Sec. 2.3). 

In all the diazotization reactions discussed in Sections 2.1-2.4 an equimolar amount of water is formed as byproduct. There are two general pathways for obtaining diazonium salts without formation of water. One is based on the rearrangement of 7V-nitroso-7V-arylacetamides, the other on the nitrosation of a monoarylated sp2-hybridized nitrogen compound by nitrosating reagents XNO in which X is a weak nucleophile. 

Research into the mechanism of diazotization was based on Bamberger s supposition (1894 b) that the reaction corresponds to the formation of A-nitroso-A-alkyl-arylamines. The TV-nitrosation of secondary amines finishes at the nitrosoamine stage (because protolysis is not possible), but primary nitrosoamines are quickly transformed into diazo compounds in a moderately to strongly acidic medium. The process probably takes place by a prototropic rearrangement to the diazohydroxide, which is then attacked by a hydroxonium ion to yield the diazonium salt (Scheme 3-1 see also Sec. 3.4). 

It has already been pointed out that nitrosation is probably the first step in diazotization. Ingold (1952) describes the reaction as N-nitrosation and classifies it as an electrophilic substitution, together with related processes such as the formation of 4-nitrosophenol, an example of a C-nitrosation. It was probably Adamson and Kenner (1934) who first applied these ideas to diazotization and realized that in aniline itself the electron density at the nitrogen atom is greater than in the anilinium ion, so that the base is more reactive. On the other hand, the nitrosoacidium ion (3.1), the addition product of nitrous acid and a proton, is a more powerful electrophilic reagent than the HN02 molecule. They therefore represented the first step of diazotization as in Scheme 3-5. 

Schmid s observation of the dependence of the reaction rate on the square of the concentration of nitrous acid was interpreted by Hammett (1940, p. 294) as due to the rate-limiting formation of dinitrogen trioxide, N203. The consequent attack of the amine by N203 was postulated to be faster therefore the concentration of the amine has no influence on the overall rate (zero order with respect to amine). Similarly, Hammett regards the second factor of Schmid s equation for diazotization in the presence of hydrochloric or hydrobromic acid as the result of the formation of nitrosyl halide. 

The rate-determining step in the diazotization of aniline in aqueous perchloric acid below concentrations of 0.05 m (pH >0.7) is the formation of N203. The following A-nitrosation step is faster (rate equation of Scheme 3-12). However, with aromatic amines that are weaker nucleophiles than aniline, e.g. 4-nitroaniline, nitrosation is slower than the formation of N203, and the rate is second-order with respect to nitrous acid and first-order in amine (Scheme 3-13, Larkworthy, 1959). 

As in the case of diazotization by N203 (Sec. 3.1), either the formation of XNO or the nitrosation of the amine (or of the aminium ion) may be rate-limiting. Under most experimental conditions the second alternative applies. If a steady-state concentration of XNO exists (which is however, not always the case) the reaction system of Schemes 3-26 and 3-27 yields the rate equation shown in Scheme 3-29 if it is the amine base (ArNH2) that is nitrosated. Xa is the acidity constant of the conjugate acid (ArNH3). 

The rate-limiting step in diazotizations with nitrosyl halides can in some cases be the formation of the nitrosyl halide (Scheme 3-26) this occurs with very reactive aniline derivatives (Hughes and Ridd, 1958). Alternatively it can be the deprotona-... 

In Sections 3.1 to 3.3 the discussion of the mechanism of diazotization concentrated on the rate-determining part of the reaction which, in most cases, does not include steps occurring after the formation of the A-nitrosoamine. The various pathways of nitrosation are summarized in Scheme 3-35. The transformation of the N-nitrosoamine will be discussed in Section 3.4. 

As discussed in the three preceding sections, the key intermediate in diazotizations is the A-nitroso derivative of the primary amine, the formation of which is usually the rate-determining step of diazotization. The subsequent steps are faster and therefore not easily accessible to study. The sequence of protonation, deprotonation, protonation, and dehydration in Scheme 3-36 seems to be the most reasonable mechanism. 

In general, however, reduction by ethanol is recommended only in cases where one has a reliable analytical method for distinguishing between products resulting from hydrogen- or ethoxy-substitution. For all other cases we recommend Kornblum s dediazoniation in an aqueous solution of hypophosphorous acid, in some cases in the presence of a catalyst, e.g., 0.05-0.10 mol% CuS04. The procedure is notable for its simplicity of operation. In Organic Syntheses the diazotization and hydro-de-diazoniation of 3,3 -dimethyl- and 3,3 -dimethoxybenzidine are described by Kornblum (1955) and the formation of 2,4,6-tribromobenzoic acid by Robison and Robison (1963). 

In Section 3.4 we discussed the problem of reversibility of diazotization of aromatic and heteroaromatic amines. Simple stoichiometric considerations indicate that the reverse reaction (ArNJ -> ArNH2) may take place under strongly acidic conditions. Experimentally the reverse reaction was found only with heteroaromatic diazonium salts (Kavalek et al., 1989). Reaction conditions of hydroxy-de-diazonia-tion are comparable to those used for the reverse reactions of diazotization (e.g., 10 m H2S04, but at 0°C for the formation of 2-amino-5-phenyl-l,3,4-thiadiazol from the corresponding diazonium salt, Kavalek et al., 1979). So far as we know, however, amines have never been detected in aromatic hydroxy-de-diazoniations, not even in small amounts. 

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