Arylamine diazotization

Aryl diazonium ions prepared by nitrous acid diazotization of primary arylamines are substantially more stable than alkyl diazonium ions and are of enormous synthetic value Their use m the synthesis of substituted aromatic compounds is described m the following two sections... 

Diazotization of an arylamine followed by treatment with fluoroboric acid gives an aryl diazonium fluoroborate salt Heating this salt converts it to an aryl fluoride... 

Diazotization of a primary arylamine followed by treatment of the diazo mum salt with copper(l) bromide or copper(l) chloride yields the corre spending aryl bromide or aryl chloride... 

Diazotization (Section 22 16) The reaction by which a pn mary arylamine is converted to the corresponding diazo mum ion by nitrosation... 

Whereas reaction of hydrazones disubstituted in the 4,5-position of the selenazole rings with diazotized arylamines only gives formazans, compounds unsubstituted in the 5-position can be attacked there by the diazonium cation. In fact, the azo coupling in this position is decidedly quicker reaction of 5-benzylidenehydrazino-4-phenyl-... 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

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). 

For quantitative work, it is necessary to estimate the concentration of 5-amino-l-(P-D-ribofuranosyl)imidazole in aqueous solution. It seems that the only available method is the Bratton-Marshall assay, which was originally developed for the estimation of arylamines in biological fluids. The principle of the method is the spectrometric estimation of a salmon-pink colored dyestuff obtained by diazotation in situ, followed by coupling with /V-( 1 -naphthyl)ethyl-enediamine.65 The only remaining problem then is to know the molar extinction of this dye because pure samples of AIRs are not available. A value of 16800 at 520 nM was obtained for the dyes prepared from a model compound, 5-amino-l-cyclohexylimidazole-4-carboxylic acid (54), which is crystalline. A comparable molar extinction can be expected for the dye prepared from imidazole 55, if the carboxyl group does not exert too much influence on the chromophore. Actually, its influence is perceptible even with the naked eye, the dyestuff prepared from 53 having a somewhat different, wine-red color, with max>520 nM. The molar extinction for 55 is 17400 at 500 nM. When the decarboxylation of 54 was conducted under mild acidic conditions (pH 4.8, 50°C, 1 hour), estimation of 5-aminoimidazole 55 by the Bratton-Marshall method led to the conclusion that the reaction was almost quantitative.66 Similar conditions for the final decarboxylation were adopted in the preparation of samples of AIRs labeled with stable isotopes.58... 

The groups of Doyle and of Oae148 showed that the yields can be improved by the use of arylamines and alkyl nitrites in place of arenediazonium ion, i.e. by a one-pot diazotization-Meerwein procedure. A condition for good yields is, however, that the alkenes be activated by electron-withdrawing groups. 

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). 

Problem 18.36 Explain the following conditions used in coupling reactions (a) excess of mineral acid during diazotization of arylamines, (b) weakly acidic medium for coupling with ArNH, (c) weakly basic solution for coupling with ArOH. ... 

A very important advance was made in 1927, with the disclosure24 by Balz and Schiemann of a new synthetic route (which has ever since been named after them) from an arylamine to an aryl fluoride. After diazotization in the normal way, the readily available tetrafluoroboric acid, or a tetrafluoroborate salt, was added to precipitate the insoluble diazonium tetrafluoro-borate salt. This was then dried and heated it decomposed (usually at 100-150°C) to give a good yield of the corresponding aryl fluoride. 

The basic Balz-Schiemann reaction involves the preparation of an insoluble arenediazonium tetrafluoroborate 1, either by direct diazotization of arylamines in aqueous tetra-fluoroboric acid, or by addition of tetrafluoroboric acid or alkaline tetrafluoroborates to an aqueous solution of another arenediazonium salt. After filtration and air-drying, this solid diazonium tetrafluoroborate is decomposed either neat or suspended in an inert solvent. 

The Sandmeyer reaction (Section 22.17) Diazotization of a primary arylamine ArNH2 1. NaN02, HbO 2. CuX - ArX... 

Phenols may be prepared by diazotization of the corresponding aniline derivative. The problem simplifies itself, therefore, to the preparation of m-bromoaniline. Recognizing that arylamines are ultimately derived from nitroarenes, we derive the retrosynthetic sequence of intermediates ... 

The key to this problem is to recognize that the iodine substituent in m-bromoiodobenzene is derived from an arylamine by diazotization. 

Diazotization of primary arylamines followed by treatment with copper bromide converts them to aryl bromides. 

The synthesis of 2,4,6-trisubstituted 2,6-dihydropyrazolo[3,4-d]-l,2,3-triazoles by the oxidation of 5-amino-4-azopyrazoles is well documented <86DP289,87IJC(B)616,88JHC1663). In a typical procedure, diazotized arylamines were coupled with 5-aminopyrazoles affording the required 5-amino-4-azo compounds, which were readily oxidized to the desired bicycle <86DP289, 87IJC(B)616>. Scheme 10 illustrates the preparation of a symmetric bispyrazolo[3,4-J]-1,2,3-triazole (25e) <86DP289>. Alter-... 

On the other hand, 3,3-dialkyl-l-aryltriazenes can be easily obtained from the corresponding aromatic amines (by quenching the diazotized arylamine with a secondary amine, such as piperidine). Therefore, this reaction constitutes a mild alternative to the classic Balz-Schiemann thermal decomposition of aryldiazonium tetrafluoroborate salts, a method which in many cases is too drastic and tedious (see Section 1.1.8.5.). 

JA2587> both couple with diazotized 2,4-dichloroaniline and several other arylamines to produce the 8-arylazo derivative, and 2,6-diaminopurine also furnishes the 8-arylazopurine (154) with diazotized 2,4-dichloroaniline. 

Nitrous acid reacts with 1 ° alkylamines and arylamines to form diazonium salts. This reaction is called diazotization. 

Diazotization reaction (Section 25.13A) A reaction that converts 1 ° alkylamines and arylamines to diazonium salts. 

Primary arylamines rea t with nitrous acid, HNOg, to yield stable arene-diazonium salts, Ar-NsNX". This diazotization reaction is compatible with the presence of a wide variety of substituents on the aromatic ring. 

This behavior is typical of alkylamines. The arylamines behave similarly at higher than room temperatures. However, at temperatures of 5° or lower, the intermediate compounds, known as diazonium salts, are formed. Because of their great reactivity they are used in the preparation of a large and diversified number of compounds. The formation of the diazonium salts is known as diazotization of the arylamine ... 

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