Question

How can the lab experiment be adapted to make pharmaceutical grade Lidocaine

Answer 1

Lidocaine is an important member of Class 1b drugs used as local anesthetics.

Lidocaine can be prepared from 2,6-dimethylnitrobenzene.

Step 1 --- Reduction of 2,6-dimethylnitrobenzene with stannous chloride (precisely 3 equivalents) will lead to the formation of the ammonium salt.

Step 2 --- ammonium salt is reacted with an aqueous potassium hydroxide solution, liberating the free 2,6-dimethylaniline

Step 3 ---The reaction of 2,6-dimethylaniline with the slight excess of bifunctional α-chloroacetyl chloride leads to α-chloro-2,6-dimethylacetanilide (amine to amide conversion). The addition of sodium acetate solution avoids the formation of HCl which would protonate unreacted 2,6-dimethylaniline causing it to co-precipitate with the desired product.

step 4 ---In the last step, diethylamine is used for a nucleophilic substitution (SN2) on the remaining alkyl chloride. Diethylamine serves both as a nucleophile to form lidocaine, and as acid scavenger, leading to formation of NH2Et2 +Cl in this reaction. Diethylamine is used in excess here to improve the yield and speed up the reaction. The aqueous extraction of lidocaine with acid separates the unreacted chloroanilide and the lidocaine. Thereafter with addition of a strong base like aqueous potassium hydroxide, crude lidocaine is obtained.