SCHMIDT REARRANGEMENT, A NAMING REACTION. Mechanism of production of amines, imines, amides & nitrile from Aldehyde, ketone, tertiary alcohols, alkenes & carboxylic acid

1. SCHMIDT REARRANGEMENT
-SAKSHI BHATT
B.PHARM 4TH SEMESTER
Pharmaceutical Organic Chemistry
NAMING REACTION

2. • In a rearrangement reaction, an atom or group moves from one atom to another in the same
molecule i.e. connectivity of atoms changed within the molecule.
• Schmidt reactions refer to acid-catalyzed reactions of electrophiles, such as carbonyl compounds,
tertiary alcohols and alkenes which reacts with azide to produce amines, amides, imines & nitriles.
These substrates undergo rearrangement with extrusion of nitrogen.
• Basically,When Hydrazoic acid is treated in the presence of Conc H2SO4 , with
 Carboxylic acid  AMINE
 Alkenes  IMINE
 Tertiary Alcohol  IMINE
 Ketone  AMIDE
 Aldehyde  AMIDE & NITRILE

3. Mechanism for Producing Amines by Carboxylic acid
 Formation of an acylium ion by protonation of the carboxylic acid
 This acylium ion is now reacted with hydrazoic acid.
 Formation of a protonated azido ketone.
 Now, the protonated azido ketone and the R group undergo a rearrangement
reaction.
 The removal of dinitrogen leading to the formation of a protonated isocyanate.
 Addition of water forms carbamate.
 The carbamate is now deprotonated.
 The subsequent removal of CO2 by heat yields the required amine.

4. Mechanism for Producing Imines by Alkenes
Protonation to any of these carbon leading to the formation of carbocation
The HN3 will get attach to the positively charged carbon atom, carbocation.
The reaction is taken forward by the elimination of N2
 Followed by migration of alkyl group from carbon atom to nitrogen atom.
 The deprotonation occurs resulting in the formation of imine

5. Mechanism for Producing Imines byTertiary Alcohol
Protonation on the oxygen atom of hydroxy group
Elimination of water molecule resulting in the formation of carbocation.
The HN3 will attack to the carbocation, followed by attack of hydroxyl group
Elimination of the N2from the intermediate compound.
Migration of alkyl group from the carbon atom to the nitrogen atom
Formation of imine.

6.  Protonation of the ketone, leading to the formation of an O-H bond.
 Nucleophilic addition of the azide leads to the formation of an intermediate.
 Elimination of water, forming a temporary imine.
 Migration of alkyl group & removal of dinitrogen
 Water is used to attack the resulting compound
 The subsequent deprotonation yields a tautomer of the required amide.
 The relocation of a proton belonging to the tautomer of the amide gives the final amide
product.
Mechanism for Producing Amides by Ketone

7. Mechanism for Producing Nitrile by Aldehyde
Protonation on the oxygen atom.
Substitution by hydrazoic acid on carbocation.
The water molecule will release and the migration of hydrogen atom from carbon to
nitrogen will occur.
Elimination of dinitrogen.
Now, water is used to attack the resulting compound
Deprotonation yields a tautomer of the required amide.
Nitrile is yield by protonation and removing water molecule and then again deprotonation
gives the nitrile.

8. APPLICATIONS
• Synthesis of some medium-sized lactams (Caprolactam - used to make polymer)
• Cardiazole (heart stimulant) by excess HN3 forms substituted tetrazoles.
• Anticancer and antiprotozoals drugs like tetrahydro-benzo[1,4]diazepin-5-ones.
• The conversion of 3,5 dinitrobenzoic acid to 3,5- dinitroaniline which is used for detecting aldehyde
& ketone.
H2SO4

9. THANKYOU!!