Diazotization of an amine

The reaction, called diazotization of an amine goes as follows Nitrous acid is pro-tonated by a strong acid to form the nitrosonium ion, Nitrosonium ion reacts with the primary amine to form AAnihosoammomum, an unstable compound., V-ni-trosoammonium deprotonates to form AAnitrosoamine. W-nitrosoamine tautomerizes to diazenol. In die presence of acid, diazenol dehydrates to diazonium... 

The diazonium group car be easily replaced by a variety of other groups, making the diazotization of an amine a useful reaction. 

Mechanism 19-6 Diazotization of an Amine 910 19-17 Reactions of Arenediazonium Salts 911 Summary Reactions of Amines 915 19-18 Synthesis of Amines by Reductive Amination 918 19-19 Synthesis of Amines by Acylation-Reduction 920... 

R—N=N. This procedure is called diazotization of an amine. Diazonium salts are the most useful products obtained from the reactions of amines with nitrous acid. The mechanism for diazonium salt formation begins with a nucleophilic attack on the nitrosonium ion to form an A-nitrosoamine. 

The most important reaction of the diazonium salts is the condensation with phenols or aromatic amines to form the intensely coloured azo compounds. The phenol or amine is called the secondary component, and the process of coupling with a diazonium salt is the basis of manufacture of all the azo dyestuffs. The entering azo group goes into the p-position of the benzene ring if this is free, otherwise it takes up the o-position, e.g. diazotized aniline coupled with phenol gives benzeneazophenol. When only half a molecular proportion of nitrous acid is used in the diazotization of an aromatic amine a diazo-amino compound is formed. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

The basic principle of all diazotizations of aromatic amines with a hydroxy- or a sulfonamido group in the 4-position relative to the amino group involves a deprotonation of the OH or NH group, respectively, after diazotization of the amino group. There is also a case of a deprotonation of a CH group in the 4-position of an aniline derivative, namely in the diazotization of 4-aminophenylmalononitrile (2.41) which, by the sequence of steps shown in Scheme 2-23, yields 3-diazo-6-dicyanomethylene-1,4-cyclohexadienone (2.42), as found by Hartzler (1964). This product can also be represented by a zwitterionic carbanion-diazonium mesomeric structure. 

Schmid (1936 a) was the first to observe a third-order reaction in the diazotization of aromatic amines in the presence of sulfuric acid, and he proposed the kinetic equation of Scheme 3-3. In subsequent work (1936b, 1937 Schmid and Muhr, 1937), he investigated the course of the reaction in dilute hydrochloric or hydrobromic acid, which could be described by incorporating an extra term for the halide ion with only a first-order dependence on (HNO2), as in Scheme 3-4. 

It is worth noting, however, that the prototropic equilibrium between the N-nitrosoamine (3.7) and the diazohydroxide (3.9) has been determined semiquan-titatively for the analogous diazotization of an aliphatic amine. Fishbein and coworkers (Hovinen et al., 1992) determined an upper limit for the nitrosoamine equilibrium concentration (<1.5% see also Zollinger, 1995, Sec. 7.2). 

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 production of azo pigments relies almost exclusively on the azo coupling reaction [1,2] to afford the azo group. Diazotization of an aromatic amine yields a diazonium compound, which subsequently reacts with a coupling component ( coupling ). 

The diazonium ions 13 with electron-withdrawing substituents are not h texoaromatic compounds and therefore do not strictly come within the scope of this chapter. They are formally related to the alkenediazonium ions. Nevertheless, they are discussed here because in their properties they bear a close resemblance to heteroaromatic and arenedi-azonium ions rather than to alkenediazonium ions. In particular they can be obtained by direct diazotization of the amines, they are stable in an aqueous medium and they are capable of undergoing an azo coupling reaction. 

The rates of diazotizations in nitrosylsulfuric acid can be increased favorably by the addition of acetic or propionic acid. A mixture of the two acids is frequently used as an additive in diazotizations of heteroaromatic amines, as it has a lower melting point than acetic acid (0 °C or lower), but little is mentioned about it in the scientific literature... 

Diazotization of the amine by an organic nitrite, such as butyl nitrite in acidic medium, and subsequent coupHng of the product with an active aromatic amine... 

Diazatrimethine dyes have been prepared by oxidative coupling of a heterocyclic hydrazine with an active methylenic heterocycle as in the yellow dye (31). Alternatively they may be prepared by diazotization of an aromatic or heteroaromatic amine followed... 

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-... 

An important neutral leaving group is N9, Diazotization of alkyl amines (Equation 5.11) leads to the unstable alkyl diazonium ions, which immediately lose nitrogen, leaving carbocations. 

Aryl azides (such as 13) can be easily prepared from their corresponding amines (12) in one or two steps. Three examples are given in Scheme 2a. The most common method is the diazotization of the amine with sodium nitrite under acidic conditions (giving diazonium species 14), followed by addition of sodium azide in an aqueous medium (route i in Scheme 2a) [44], In 2003, the synthetic method was improved by application of triflyl azide (TfN3), which allowed a one-step conversion and gave improved yields (route ii in Scheme 2a) [45]. Recently, the development of sulfonyl azides 15 (with R = imidazole [46] or R = benzotriazole [47]) was reported these proved to be more stable reagents and allowed a conversion under mild conditions (route iii in Scheme 2a). 

Aromatic fluorination chemistry has a remarkably long history, and the first successful synthesis of aryl C-F bonds was reported in 1870 [22], Significant developments in the area in the early part of the 20th century included the discovery of Balz-Schiemann reaction [23,24] involving diazotization of an aromatic amine in the presence of tetrafluoroboric acid and the reaction scheme is shown in Fig. 4. The above reaction produces large quantities of waste (such as NaBF4,... 

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