Pharma gyan Pandit

Diazotization Titration

The process of forming diazonium compounds or salts is called diazotation, diazoniation, or diazotization Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group with the characteristic structure of R-N₂ + X ^- where R can be any organic residue such alkyl or aryl and X is an inorganic or organic anion such as a halogen The reaction was discovered by Peter Griess in 1858, who subsequently discovered several reactions of the new compound.

Diazonium salts have been developed as important intermediates in the organic synthesis of dyes Diazotization titrations are carried out for the estimation of drugs containing primary aromatic amino group Several drugs contain either primary aromatic amino group or they can be converted to have such groups by simple reaction like hydrolysis or reduction.

Condition for diazotization rate of titration: Different amino compound react with HONO at different rates NaNO₂ added from the burette needs time to react with amino group accumulating in the solution Amines are classified as rapidly, slowly diazotisable depending on the rate of conversion into azo compounds.

Slow diazotisable compounds include compounds that contain sulpha groups, nitrous oxide group, or carboxylic group in aromatic ring or besides aromatic ring Eg: isomeric nitro aniline, sulphanilic acid and anthranilic acid Fast diazotisable compounds do not contain any substituent group other than amino group but some times they may contain –CH₃ or –OH group along with NH₂ group. Eg : aniline, toluidine and aminophenol Adding KBr to the solution can increase the rate of titration.

Temperature: The diazonium compounds formed are unstable and readily decompose at elevated temperature. This can lead to side reaction and give wrong result. To eliminate this problem, this titration is carried out at low temperature (0-5 ⁰C). Optimum temperature for most amine is 10-15 ⁰C, when they form relatively stable diazo compounds.

PRINCIPLE The first involved is addition of sodium nitrite to hydrochloric acid cause formation of nitrous acid.

              NaNO₂ + HCl ---------à HONO + NaCl

This nitrous acid diazotises the aromatic amino group.

After the end point , excess nitrous acid formed is shown by instant formation of blue colour with starch iodide paper.

               KI + HCl------àHI+ KCl

               2HI +2HONO-------àI₂ ↑ +2NO +2H₂O

Starch iodide paper is prepared by immersing a filter paper in starch mucilage and potassium iodide solution The iodine formed reacts with starch mucilage to give the blue colour. I₂ + Starch blue color (end point) The end point can also be determined by dead stop end point and potentiometric technique.

It is important to check the acidity at the end of the titration. If there is no excess of acid present in the solution, starch –iodide paper will not detect excess HNO₂ and so will not indicate the end point.

Types of diazotisation titrations

Direct titrations: These are carried out by treating 1 mole of the drug with 3 moles of acid solution. Ice can be used to lower the temperature to about 0-5°c. 0.1M sodium nitrite is added in small amounts and titration is carried out. The end point is determined by any one of the techniques as said before.

Reverse method: In this method a solution of amine and sodium nitrite are run into a solution of acid. This method is used when the diazonium salts are insoluble. Eg: naphtylamine sulphonic acids form insoluble diaonium salts due to formation of zwitter ions.

Special method: Aminophenol are readily oxidized by nitrous acid to quinones For such substances , the titration is carried out in the presence of copper sulphate which forms diazo-oxide These diazo-oxides are more stable and undergo coupling reaction.

Applications:

The first use of diazonium salts was to produce water-fast dyed fabrics A more common process uses a paper coated with diazo It is also applicable in nano technology.

It is also used in the preparation of hydrocarbons , aryl halide , aryl cyanide , and aryl hydrazines It is used in the assay of sulpha drugs like dapsone , sulphonamides It is also used in the assay of various drugs like benzocaine , procainamide , procaine , suramin , sodium amino salicylate.