Nitrogen compounds diazotization

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. 

Triazatrimethines are prepared by alkylation of linear triazene groups (diazoamino compounds) connecting an aromatic ring with a heterocyclic radical containing nitrogen. Thus, diazotization of an aromatic amine and coupling with, for example, a 2-aminoben-... 

Blomstrand then mentioned that Griess had found that in acidic solution, instead of diazoaminobenzene, a salt of "diazobenzol" is formed, a discovery which had led to azo compounds, which even in 1869 were already technically important. Of course Kekule had theoretically explored all these new organic nitrogen compounds and, "with his ordinary perspicacity completely disentangled their constitution" (2, p. 271), as Blomstrand ironically expressed it. He then cornered Kekule by comparing Kellie s way of describing the the diazotization of aniline with his own ... 

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... 

There are several methods for generation of benzyne in addition to base-catalyzed elimination of hydrogen halide from a halobenzene, and some of these are more generally applicable for preparative work. Probably the most convenient method is diazotization of o-aminobenzoic acid. Concerted loss of nitrogen and carbon dioxide follows diazotization and generates benzyne. Benzyne can be formed in this manner in the presence of a variety of compounds with which it reacts rapidly. 

This diazotization is typical of many aminoazoles the diazonium ions formed are relatively strong acids. The pATa values of five di-, tri-, and tetrazolediazonium ions are reported to be between 3 and 4, i. e., about 10 units lower (more acidic) than those of the respective unsubstituted heterocycles (Vilarrasa et al., 1974). Therefore, deprotonation of the diazonium ion is easy and, depending on reaction conditions, yields either the diazonium salt or its conjugate base, the diazo compound. The electrophilic reactivity of the P nitrogen atom in the diazo group of the base is lower than the reactivity of the diazonio group of the cation (Diener and Zollinger, 1986 see Sec. 12.2). 

Aminopyridines, aminopyridine oxides, and 3-aminoquinoline are obviously diazotized by analogous mechanisms. Kalatzis (1967 b) studied the diazotization of 4-aminopyridine over a very large range of acid concentrations (0.0025-5.0 m HC104). This compound is comparable to 2-aminothiazole in its acid-base properties the heterocyclic nitrogen is easily protonated at pH 10, whereas the amino group is a very weak base (pKa = -6.5). Therefore, the kinetics indicate that the (mono-protonated) 4-aminopyridinium ion reacts with the nitrosyl ion. The... 

Neither the 2- nor 4-aminopyridine-l-oxides nor their substitution products can be protonated at the heterocyclic nitrogen. The findings regarding the diazotization kinetics of these compounds indicate that, under the reaction conditions studied by Kalatzis and Mastrokalos (1977), two simultaneous mechanisms take place. In the first of these, nitrosyl ions attack the free amine, whereas in the second they attack the protonated amine. 

More recently, Stepanov et al. (1989) investigated the acid-base properties of the zwitterion 3.22 which is obtained in the diazotization of 5-amino-3-nitro-l,2,4-triazole. Under alkaline conditions the (Z)-diazoate dianion 3.23 is formed. It can be isomerized thermally to give the (E)-diazoate dianion 3.24. If the solution of this compound is acidified, the primary addition of a proton takes place at the anionic ring nitrogen yielding 3.25, and subsequently the hydrogen-bond-stabilized (Z)-iso-mer (3.26). Further acidification gives the nitrosoamine (3.27). 

The reversibility of aromatic diazotization in methanol may indicate that the intermediate corresponding to the diazohydroxide (3.9 in Scheme 3-36), i. e., the (Z)-or (is)-diazomethyl ether (Ar — N2 — OCH3), may be the cause of the reversibility. In contrast to the diazohydroxide this compound cannot be stabilized by deprotonation. It can be protonated and then dissociates into a diazonium ion and a methanol molecule. This reaction is relatively slow (Masoud and Ishak, 1988) and therefore the reverse reaction of the diazomethyl ether to the amine may be competitive. Similarly the reversibility of heteroaromatic amine diazotizations with a ring nitrogen in the a-position may be due to the stabilization of the intermediate (Z)-diazohydroxide, hydrogen-bonded to that ring nitrogen (Butler, 1975). However, this explanation is not yet supported by experimental data. 

As shown by Heindel and Corley (1979), ring closure also takes place if the nucleophilic nitrogen is part of a heterocycle, as in the diazotization of 5-amino-3-methyl-2-H-l,2,4-benzothiadiazine-l, 1-dioxide (6.50). In the tricyclic compound 6.51 formed initially, the thiadiazinedioxide ring is opened rapidly in water, forming 1-acetyl-7-aminosulfonyl-l-i/-benzo-l,2,3-triazole (6.52). 

Type II nitrosamines have two reaction pathways. One pathway involves nucleophilic attack at the carbon of C=0 to generate a tetrahedral intermediate which decomposes to an active diazotate ion (R-N=N-0 ). The other pathway involves the nucleophililc attack on the nitrogen of the nitroso group resulting in denitrosation (Scheme 3.5). The nucleophile can be a biologically prevalent thiol, therefore type II compounds are often used as NO donors for the formation of S-nitrosothiols [67, 68]. 

A special approach to [l,2,4]triazolo[3,2-c][l,2,4]triazine derivatives is the transformation of 3-diazo[l,2,4]triazoles, easily available by diazotation of aminotriazoles. These compounds already contain the five nitrogen atoms in the correct sequence in order to form the desired bicyclic ring system and, thus, their reaction with proper bifunctional reagents can give rise the cyclized products in one single step. Such transformations are collected in Scheme 50. 

This diazotization reaction is compatible with the presence of a wide variety of substituents on the benzene ring. Arenediazonium salts are extremely important in synthetic chemistry, because the diazonio group (N=N) can be replaced by a nucleophile in a radical substitution reaction, e.g. preparation of phenol, chlorobenzene and bromobenzene. Under proper conditions, arenediazonium salts react with certain aromatic compounds to yield products of the general formula Ar-N=N-Ar, called azo compounds. In this coupling reaction, the nitrogen of the diazonium group is retained in the product. 

T. Urbanski, Szyc-Lewanska et al. [18] have recently found that dinitrobenzene-diazo-oxide can be prepared by oxidation of picramic acid with chromium trioxide in the presence of sulphuric acid at 55-60°C. One part of picramic acid is fully oxidized by chromic acid to yield gaseous products CO, C02, N02, NH3 and H20. Nitrogen dioxide acts further as a diazotizing agent on undecomposed picramic acid to yield the diazo compound. The yield of this reaction does not exceed 31% of theoretical calculated on the picramic acid used. 

Diazonium compounds are generally stable only in aqueous solution at low temperatures. When heated, they frequently decompose by eliminating nitrogen to form the corresponding phenol. Some amines, however, can be diazotized at temperatures up to 40 °C. Metal ions also accelerate the decomposition of diazonium compounds. Therefore, diazotization is usually carried out in wooden vats or iron stirring vessels with an acid-proof lining or rubber coating. 

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