Diazotization methods

Depending on the basicity and solubility of the amines being diazotized, the following diazotization methods find industrial use  

Certain aromatic amines require special diazotizing processes  

1 -Amino naphtho Is, such as l-amino-2-naphthol and several 1-aminonaphthol-sulfonic acids, such as l-amino-2-naphthol-4-sulfonic acid, are oxidized to the respective quinone by nitrous acid. Diazotization can, however, take place under normal conditions in the presence of catalytic quantities of metal salts, such as copper or zinc salts. 

The desired bis-diazotization with o-, m-, and p-phenylenediamine is achieved in glacial acetic acid with nitrosylsulfuric acid. 1,8-Naphthylenediamine can be bis-diazotized in an excess of acid. 

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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The amine 12 is very sensitive to the action of aqueous acids it could not be converted into trithiatriazepin-7-ol by various diazotization methods. 

These salts can be made easily since tetrafluoroboric acid (HBF4) and hexa-fluorophosphoric acid (HPF6) are commercially available. However, the main advantage of the diazonium salts with the anions of these acids is their stability, which is significantly higher than that of probably all other diazonium salts. 4-Nitrobenzenediazonium tetrafluoroborate is nowadays even a commercial product. Preparative diazotization methods with these two acids can be found in Organic Syntheses (tetrafluoroborate Starkey, 1943 hexafluorophosphate Rutherford and Redmont, 1973). 

Summarizing the discussion in this section, it is obvious that the various forms of diazotization methods became understandable only after the long historical development leading to the breakthrough by Hughes, Ingold, and Ridd in 1950 to 1958. 

Table 7 Conjugation of an amino-containing hapten to protein using the diazotization method Materials...

Grieve and Hey 13 obtained no markedly improved yields of biphenyl when they tried various reagents under different conditions. They did observe that the yield of biphenyl is just as good in the sodium diazotate method when the reaction is run at 30° as at 5-10°. This modification allows the use of components which are solid at the lower temperature but liquid at the higher one (30°). 

If the amine is basic enough to form a salt with dilute mineral acids in aqueous solution, the normal diazotization method of adding sodium nitrite in aqueous solution to a solution or suspension of the amine salt is satisfactory. Variations in die order of addition of die reagents are sometimes used, for example, when there is another functional group present which is sensitive to nitrous acid, or if die amine salt is very insoluble. Weakly basic amines can often be diazotized successfully either in concentrated sulfuric acid or in a mixture of sulfuric acid with acetic or phosphoric acid. It is likely that nitrosylsul fiiTic acid is formed on addition of sodium nitrite to concentrated sulfuric acid, and that this is the nitro sating agent when the amine is subsequently added. 

Another important diazotization method is the use of glacial acid for the nitrosation of alkylamines, because of the formation of an ion pair 7.12 between the acetate ion and the diazonium ion. In water the influence of acetate ion is small. 

Scheme 1 Electrophilic halogenation and diazotization methods in synthesis of nonactivated aromatic halides...

The modifications of the Knoevenagel diazotization method include the addition of isoamyl nitrite to an appropriate amine salt suspended in cold acetic acid and the diazotization of amine by the addition of a solution of N2O4 in ether. In addition, a specific method for the preparation of anhydrous diazonium tetrafluoroborate has been developed in which the amine is mixed with an alkyl nitrite and an excess amount of BF3 Et20. For this preparation, the excess BF3 can trap the alcohol and water produced during the diazotization, and the diazonium tetrafluoroborate precipitates from the reaction solution as it is formed. ... 

Other references related to the Knoevenagel diazotization method are cited in the literature. 

This method is considerably quicker than the diazotization method and has the added advantage that an atmosphere containing more than one isocyanate can be analyzed in one step. 

This method determines TDI together with the urea (3,3 -diisocyanato-4,-4 -dimethylcarbanilide) formed by the reaction of TDI with moisture. The urea concentration can be estimated by deducting the TDI content from the results of this method. The principle relies on a yellow colour being produced by both the above urea and TDI when added to a solution of sodium nitrite and boric acid in ethyl Cellosolve. This colour is measured in a spectrophotometer at 450 nm. The apparatus is similar to that described in the diazotization method. An ethyl Cellosolve solution is required to act as an absorber medium. It consists of 5 g of sodium nitrite and 10 g of powdered boric acid dissolved in 200 ml of water. This solution is diluted to 1 litre with ethyl Cellosolve. 

Knoevenagel (see Witt and Knoevenagel Diazotization Methods) Knoevenagel Condensation Knoop-Oesterlin Amino Acid Synthesis Knorr (see Koenigs-Knorr Synthesis)... 

Griess Diazo Reaction Witt and Knoevenagel Diazotization Methods... 

The bathochromic shift method has the advantage of being more specific than the diazotization method. Results obtained by this procedure agree well with these based on direct determination of elemental phosphorus (Table 2.3). 

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