Pharmaceuticals Organic chemistry 3

1. REACTIONS OF SYNTHETIC
IMPORTANCE
REDUCTION,
OXIDATION and
REARRANGEMENT REACTIONS

2. REDUCTION
• Reduction of organic molecules has played an important role in
organic synthesis.
• Reduction is referred to as addition of hydrogen to an unsaturated
groups like carbon - carbon double bond or a carbonyl group.
• Typical example of reduction is conversion of ethylene into ethane
CH2=CH2→ CH3-CH3
• The concept of oxidation in terms of oxidation number is also useful
for reduction. In reduction the oxidation number changes from higher
oxidation states to lower oxidation state.
• Examples

5. Metal hydrides
➢ The reduction of metal hydrides proceeds by transfer of hydride ion to the
substrate.
➢ These selectively reduce a number of functional groups such as nitro, carbonyl,
carboxylic acid, nitrile, ester etc., in presence of carbon-carbon double bond.
➢ A number of complex hydrides have been used for reduction. The most common
are lithium aluminium hydride (LiAlH4) and sodium borohydride (NaBH4).
➢ These reagents serve as a source of hydride due to the presence of a polar metal-
hydrogen bond.
➢ Aluminium is less electronegative than boron, the Al-H bond in LiAlH4 is more
polar, thereby, making LiAlH4 a stronger reducing agent.

9. Mechanism
1) Nucleophilic attack by the hydride anion
2) The alkoxide is protonated

10. The following table summarizes some important characteristics of these useful reagents.

12. Clemmensen reduction is a chemical reaction described as a reduction of
ketones (or aldehydes) to alkanes using zinc amalgam and hydrochloric acid.
Clemmensen reduction is an organic reduction reaction shown by both
aldehydes and ketones, But Carboxylic acid (-COOH) group can't be reduced
by this method (but the -COOH group can be reduced by treating it with
soda lime [NaOH+ CaO] and then heating).
Here, C=O group of aldehydes and ketones is reduced to -CH2- by
clemmensen reduction. Zinc amalgam and concentrated hydrochloric acid
(Zn(Hg)/conc. HCl) is used as the reagent for Clemmensen reduction. (Note
By: alkenes and alkynes don't react with clemmensen reagent.)

14. Oppenauer oxidation
• The Oppenauer oxidation is an organic reaction used to convert a primary or secondary alcohol to a
ketone using another excess ketone reagent (such as acetone) and an aluminium isopropoxide catalyst.
• The reaction is the opposite of Meerwein–Ponndorf–Verley reduction.
• Oppenauer oxidation is used to prepare analgesics in the pharmaceutical industry such as morphine and
codeine. For instance, codeinone is prepared by the Oppenauer oxidation of codeine
• The Oppenauer oxidation is also used to synthesize hormones. Progesterone is prepared by the
Oppenauer oxidation of pregnenolone.
• A slight variation of the Oppenauer oxidation is also used to synthesize steroid derivatives. For example,
an efficient catalytic version of the Oppenauer oxidation which employs a ruthenium catalyst has been
developed for the oxidation of 5-unsaturated 3β-hydroxy steroids to the corresponding 4-en- 3-one
derivative.
• The Oppenauer oxidation is also used in the synthesis of lactones from 1,4 and 1,5 diols

18. Dakin Reaction
Dakin Reaction is the replacement of the aldehyde group in phenolic aldehydes or ketones by a hydroxyl group on
reaction with alkaline hydrogen peroxide and NaOH.
Dakin oxidation is most commonly used to synthesize benzenediols and alkoxy phenols.
Other synthetically use of dakin reaction is formation of Guaiacol, a precursor for several flavorants.
Synthesis of two antioxidants ie BHA and BHT.

19. MECHANISM
Alkaline
hydrolysis

20. Wolff Kishner Reduction
The reduction of aldehydes and ketones to alkanes.
Condensation of the carbonyl compound with hydrazine forms the hydrazone, and
treatment with base induces the reduction of the carbon coupled with oxidation of the
hydrazine to gaseous nitrogen, to yield the corresponding alkane.
Reaction of Aldehydes or Ketones with Hydrazine Produces a Hydrazone

21. MECHANISM
Wolff Kishner reduction mechanism begins with the formation of a hydrazone
anion which then releases the nitrogen atom to form a carbanion.
This carbanion then reacts with the water in the system to give a
hydrocarbon. Typically, diethylene glycol is used as a solvent for this method.

22. Schmidt Rearrangement
The Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl group to give an
amine or amide, with expulsion of nitrogen. It is named after Sir Karl Friedrich Schmidt.
Examples
The reaction is with carboxylic acids to give amines
Reaction
Hydrazoic acid, also known as hydrogen azide or azoimide,It is a
compound with the chemical formula HN3

23. MECHANSIM
SCHMIDT REARRANGEMENT

26. MECHANISM

27. BIRCH REDUCTION

29. 1,4- CYCLOHEXADIENE