P-Aminobenzoic Acid Diazotization

NIPAGIN PREPARATION 1. The diazotization of the p-aminobenzoic acid a) The diazotization of the p-aminobenzoic acid Diazotization is a chemical process which results in the formation of the diazonium salts. The diazotization reaction involves the primary aromatic amines. They transform into diazonium salts under the action of the nitrous acid (HNO2), at low temperatures (0–50C), in the presence of strong mineral acids (HCl, H 2SO4) in excess (2,5–3 moles relative to 1 mol of amine) and in diluted aqueous solution. Diazotization is practically achieved by gradually adding, under continous stirring, small portions of a concentrated solution of sodium nitrite, the equivalent of a quantity of 1,02 -1,05 moles, to a cold mixture (0–5 0C) consisting of 1 mol of aromatic amine and 2,5–3 moles of diluted mineral acid (between 15–20%). The diazotization agent is the nitrosonium ion (N +=O), which results from the hetrolytic cleavage of the nitrous acid (obtained from the reaction between NaNO 2 and H2SO4), protonated by the strongly acidic medium. HO

N=O

+

+

H

H

O

+

+

N=O

N =O

+

H2O

H

Diazonium salts are generally crystallized substances, easily soluble in water, sparingly soluble in alcohol and ether, colourless, which become brown in contact with air. The reaction underlying the diazotization of the paminobenzoic acid is the following: COOH

+

NH2

COOH

HNO2 + H2SO4

+ 2 H2O

N

+

-

N ] HSO4

Necessary substances The p-aminobenzoic acid (Mr=137)..................... 13,7 g (0.10 moles) Sodium nitrite (Mr=69)............................................ 7 g (0.102 moles) Concentrated sulfuric acid (Mr=98; d=1.84)....... 10,7 ml (0.20 moles)

Working technique 13,7 g of p-aminobenzoic acid are placed over a solution of sulfuric acid (10.7 ml of 96% H2SO4 in 60 ml of distilled water) in a Berzelius beaker, under continous stirring, at high temperatures (on a water bath) in order to achieve its partial solubilization. It is stirred at elevated temperatures for a period of 15-30 minutes. The mixture is cooled down in an ice and salt bath, method which accelerates the cooling process up to 0–50C, and by adding 25 g of ice (instead of water). The following process extends over a period of 60 minutes and consists in the dropwise addition of a solution of sodium nitrite under continous stirring. The sodium nitrite solution is obtained by dissolving 7 g of NaNO2 in 15 ml of water. In order to perfect the reaction the reaction mixture is stirred for an additional period of 30 mnutes. The diazonium salt solution preserved at low temperatures will be used in the next phase (the final volume is 110 ml for 0.10 moles of p-aminobenzoic acid). b) The hydrolysis of the p-aminobenzoic diazonium salt The aromatic diazoderivatives (the diazonium salts) are relatively stable combinations but only at low temperatures (0–50C) and for a limited period of time. They are intermediate products used for the preparation of some organic substances which can take part in two types of reactions: 1) reactions involving the elimination of the diazo group (-N=N-) under the form of molecular nitrogen and its replacement with various substituents (hydrogen, hydroxyl, halogens, cyano, mercapto etc.); 2) reactions involving the retention of the diazo group (the diazonium aryl cation Ar-N=N+ being a weak electrophilic reactant), when the diazonium salts are coupled with the phenols or the aromatic amines, resulting in diazo- or azoaminoderivatives. The reaction of hydrolysis of the diazonium salt obtained in the diazotization stage is the following: COOH

COOH

+

N

+

H2O -

N ] HSO4

50 0 C

+

H2SO4 OH

N2

+

H2SO4

Necessary substances Diazonium salt solution (from the a phase).......................... 110 ml Concentrated sulfuric acid (Mr=98; d=1.84)..........5.2 ml (0,1 moles). Working technique A solution consisting of 5.2 ml H2SO4 96 % (approximately 0.1 moles) and 7,5 ml of water is introduced in a round-bottom flask equipped with a reflux condenser. The diazonium salt solution resulted from the previous phase is added over this solution and then the reaction mixture is heated on a water bath at a temperature of 40–50 0C until it finished releasing nitrogen. The content of the round-bottom flask is decanted in a Berzelius beaker and the reaction mixture is cooled down in an ice bath until the p-aminobenzoic acid crystallizes. The product is separated by means of filtration and the precipitate is washed directly on the filter with cold water until the pH reaches a value of 5 and it is dried at a temperature of 60–700C . The result is approximately 11.9 g p-hydroxybenzoic acid (η=88%) under the form of orange-brown crystals. The pure p-hydroxybenzoic acid appears under the form of colourless crystals with a value of the melting point of 210 0C. (In water, at a temperature of 150C, the product has a solubility of 0.44 g at 100 ml of solution).