Diazotisation reaction

Discussion. General procedures for the determination of nitrites are usually based upon some form of diazotisation reaction, often involving carcinogenic materials such as the naphthylamines. In the following method these compounds are avoided. 

The diazotisation reaction provides a classical example of the application of physical chemistry in the elucidation of the detail of organic... 

Shortly after Perkin had produced the first commercially successful dyestuff, a discovery was made which led to what is now the dominant chemical class of dyestuffs, the azo dyes. This development stemmed from the work of Peter Griess, who in 1858 passed nitrous fumes (which correspond to the formula N203) into a cold alcoholic solution of 2-aminO 4,6 dinitrophenol (picramic acid) and isolated a cationic product, the properties of which showed it to be a member of a new class of compounds [1]. Griess extended his investigations to other primary aromatic amines and showed his reaction to be generally applicable. He named the products diazo compounds and the reaction came to be known as the diazotisation reaction. This reaction can be represented most simply by Scheme 4.1, in which HX stands for a strong monobasic acid and Ar is any aromatic or heteroaromatic nucleus. 

For the diazotisation reaction to succeed, it is necessary that the amine should be completely converted into the hydrochloride before the addition of sodium nitrite, because any free amine can react with the diazonium salt to form a diazoamino compound (Scheme 4.7). This complication needs to be avoided in the case of amines, such as the dichloro anilines, which do not dissolve easily in dilute hydrochloric acid [17]. With such compounds it is convenient first to dissolve them in a hot acid solution, which is then cooled to 0-5 °C. This procedure ensures the absence of free amine, and even if the hydrochloride precipitates on cooling it readily redissolves as the diazotisation proceeds. Similar precautions are required with the nitroanilines and here an increased amount of mineral acid is advantageous [18]. 

Until recently most of the mechanistic studies on nitrosation have been concerned with N-nitrosation reactions of amines, including the diazotisation reactions of primary amines. Now, work has been extended to include both O- and S-nitrosation, so that comparisons can be made. Mechanistic studies have also been extended in recent years to include reactions of nitrogen oxides, nitrosamines, alkyl nitrites, thionitrites and transition metal nitrosyl complexes. Many of these reactions have been used preparatively for a long time, but little has been known about their detailed reaction mechanisms. 

This diazotisation reaction must be done at about 5 °C as the nitrous add made from the sodium nitrite and dilute hydrochloric acid decomposes easily above about 10 °C. 

This is a usefnl, bnt very hazardous preparative procedure for a number of 5-substituted tetrazoles and also, upon treatment with base, diazotetrazole, a source of atonfic carbon. It cannot be overemphasized how dangerous this diazotisation reaction is The low limit for possible spontaneous detonation in water is between 1 and 5% Even under very well-controlled conditions, during the synthesis of 5-nitrotetrazole by diazotization in the presence of excess nitrite, microdetonations occur in splashes on the walls of the vessel and often cause significant damage. However, the use of micro flow reactors (cf. 5.3) allow the reaction to be carried ont safely. ... 

Diazotisation is always carried out under strongly acidic conditions, but control of the degree of acidity is of particular importance in ensuring smooth reaction. The overall reaction equation for the diazotisation reaction using sodium nitrite and hydrochloric acid may be given as ... 

To ensure that the azo dyes and pigments are obtained in high yield and purity, careful control of experimental conditions is essential to minimise the formation of side products. It is a useful feature of both diazotisation and azo coupling reactions that they may be carried out in water as the reaction solvent. Temperature control, which is so critical in diazotisation reactions, is generally less important in the case of azo coupling. The reactions are normally carried out at or just below ambient temperatures. There is usually little advantage in... 

The solution of the aniline hydrochloride should be cooled to 5°C., and this temperature maintained throughout the addition of the sodium nitrite solution. External cooling has to be maintained, otherwise the heat of the reaction would cause the temperature to rise, with the consequent decomposition of the diazonium chloride and the production of phenol. If, on the other hand, the temperature is reduced to about o , diazotisation becomes extremely slow and unchanged nitrous acid may remain in the solution for an impracticably long time. 

Diazonium salts couple readily with aromatic primary amines, giving diazoamino compounds. If for instance an aqueous solution of aniline sulphate is diazotised with a deficiency of nitrous acid, only part of it is converted into benzenediazonium sulphate and the latter then couples with the unchanged aniline to give diazoaminobenzene. The reaction is carried out at the opti-CeHsNHj.HjSO + HONO = CbHsNjHSO, + zHaO... 

The success of the Bart reaction when applied to nuclear- substituted anilines is often much affected by the pH of the reaction-mixture. Furthermore, the yields obtained from some m-substituted anilines, which under the normal conditions are usually low, arc considerably increased by the modifications introduced by Scheller, and by Doak, in which the diazotisation is carried out in ethanolic solution followed by reaction with arsenic trichloride in the presence of a cuprous chloride or bromide catalyst. 

The experimental conditions necessary for the preparation of a solution of a diazonium salt, diazotisation of a primary amine, are as follows. The amine is dissolved in a suitable volume of water containing 2 5-3 equivalents of hydrochloric acid (or of sulphuric acid) by the application of heat if necessary, and the solution is cooled in ice when the amine hydrochloride (or sulphate) usually crystallises. The temperature is maintained at 0-5°, an aqueous solution of sodium nitrite is added portion-wise until, after allowing 3-4 minutes for reaction, the solution gives an immediate positive test for excess of nitrous acid with an external indicator—moist potassium iodide - starch paper f ... 

The precipitated amine hydrochloride (or sulphate), if any, dissolves during the diazotisation to give a clear solution of the highly soluble diazonium salt. The general reaction may be written ... 

Some amines, such as the nitroanilines and the naphthylamines, give somewhat more stable diazonium compounds and may be diazotised at room temperature, when the reaction proceeds more rapidly. If the amine salt is only sparingly soluble in water, it should be suspended in the acid in a fine state of division (this is generally attained by cooling a hot solution and stirring vigorously), and it passes into solution as the soluble diazonium salt is formed. 

In the preparation of bromo compounds by the Sandmeyer reaction, the amine is generally diazotised in sulphuric acid solution (or in hydrobromic acid solution), and the resulting aryldiazonium sulphate (or bromide) is treated with a solution of cuprous bromide in excess of hydrobromic acid the addition... 

The controlled thermal decomposition of dry aromatic diazonium fluoborates to yield an aromatic fluoride, boron trifluoride and nitrogen is known as the Schiemann reaction. Most diazonium fluoborates have definite decomposition temperatures and the rates of decomposition, with few exceptions, are easily controlled. Another procedure for preparing the diazonium fluoborate is to diazotise in the presence of the fluoborate ion. Fluoboric acid may be the only acid present, thus acting as acid and source of fluoborate ion. The insoluble fluoborate separates as it is formed side reactions, such as phenol formation and coupling, are held at a minimum temperature control is not usually critical and the temperature may rise to about 20° without ill effect efficient stirring is, however, necessary since a continuously thickening precipitate is formed as the reaction proceeds. The modified procedure is illustrated by the preparation of -fluoroanisole ... 

An alternative method of removing the aniline is to add 30 ml. of concentrated sulphuric acid carefully to the steam distillate, cool the solution to 0-5°, and add a concentrated solution of sodium nitrite until a drop of the reaction mixture colours potassium iodide - starch paper a deep blue instantly. As the diazotisation approaches completion, the reaction becomes slow it will therefore be necessary to teat for excess of nitrous acid after an interval of 5 minutes, stirring all the whUe. About 12 g. of sodium nitrite are usually required. The diazotised solution is then heated on a boiling water bath for an hour (or until active evolution of nitrogen ceases), treated with a solution of 60 g. of sodium hydroxide in 200 ml. of water, the mixture steam-distilled, and the quinoline isolated from the distillate by extrsM-tion with ether as above. 

Chlorodiphenyl. Diazotise 32 g. of o-chloroaniline (Section IV,34) in the presence of 40 ml. of concentrated hydrochloric acid and 22 -5 ml. of water in the usual manner (compare Section IV,61) with concentrated sodium nitrite solution. Transfer the cold, filtered diazonium solution to a 1 5 htre bolt-head flask surrounded by ice water, introduce 500 ml. of cold benzene, stir vigorously, and add a solution of 80 g. of sodium acetate trihydrate in 200 ml. of water dropwise, maintaining the temperature at 5-10°. Continue the stirring for 48 hours after the first 3 hours, allow the reaction to proceed at room temperature. Separate the benzene layer, wash it with water, and remove the benzene by distillation at atmospheric pressure distil the residue under reduced pressure and collect the 2-chlorodiphenyl at 150-155°/10 mm. The yield is 18 g. Recrystalliae from aqueous ethanol m.p. 34°. 

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