2.
Subject – Pharmaceutical Organic Chemistry-
Topic: Birch Reduction
Group No:12
MAYURI KOLTE – 35
SHASHANK KUMBHAR - 36
AKANKSHA KUNJIR – 37
Guided By- Prof. Jayshree Jagtap Mam
Prof. Pooja Petkar Mam
Seth Govind Raghunath Sable College Of
Pharmacy,Saswad
3.
Introduction
History
Reagents
General reactions
Mechanism
Reaction kinetics
Effect of substituent
Catalytic hydrogenation Vs Birch reduction
Applications
Acknowledgement
References
Content
4.
DEFINATION :-
Reduction of aromatic rings with sodium(Na) ,
Potassium (K) or Lithium (Li) in liquid ammonia(NH3)
or amine(RNH2) in presence of alcohol , addition of
Hydrogen (H) take place at 1 & 4 positions to give
unconjugated diene . This is known as Birch reduction.
Reduction:-
Addition of Hydrogen(H) to an organic molecule or gain of electron e- is
regarded as reduction
BIRCH REDUCTION
5.
HISTORY
In 1944 Arthur Birch, building on earlier work by
Wooster and godfrey, developed the reaction while
working in the Dyson Perrins Laboratory at university
of oxford.
Birch`s original procedure used sodium and ethanol
Alfered L-wilds later discovered that lithium gives
better yield
7. Reagents :-
Alkali metals :- Na , K or Li in liquid NH3 (ELECTRON SOURCE)
Alcohol (Proton donor)
Solvents :-
Liquid ammonia (NH3) or Primary Amines (RNH2)
Choice of solvent :-
Benkar & Coworkers suggested that the use of primary amines as solvents because
Amine have higher boiling point (Ethyl amine – 17 ˚C) than NH3 (-33˚C ) which
Permits higher temperature for reactions .
This reduces the yield of 1˚ reduced products.
A photochemical Birch type reduction using OH ̄ (as electron source) in isopropyl
Alcohol has recently been reported.
8. Working of Reagent:-
Group 1 metal like Li or Na readily give up their single valance electron
as thy dissolve in liq.NH3 or amine.
NH3 + Na (NH3)……e ̄ (NH3) (deep blue solution) + Na⁺
These free electrons impart blue colour to the solution.
9. I) Reduction of conjugated dienes :-
II) Reduction of arenes :-
10. Mechanism:-
1. Transfer of one electron from metal to the benzene ring to produce a resonance
stabilized anion radical (Ia – Ib) in low concentration.
2. Anion radical accepts a proton from the alcohol to form a radical ( II ).
The strongly basic radical anion abstract a proton from alcohol to form radical
2. The addition of an electron from the metal to the radical produce an anion ( III )
3. Anion ( III ) which takes up a proton from the metal alcohol to give the dihydro
product
11. WHY 1 , 4 – DIHYDRO & NOT 1 , 2 – DIHYDRO
PRODUCT IS FORMED ?
In ( Ib ) , the steric repulsion between the anionic & radical centers is
minimum , therefore , adds a proton to give ( II ) & subsequently a
1 , 4 – dihydro product & not 1 , 2 – dihydro product is formed .
12. Rate of reaction :-
Krapcho and Buthnerby on the basis of a kinetic study , found that the
reaction was consistent with a THIRD ORDER rate law , being single
order in the concentration of substrate , alkali metal and alcohol .
The rate limiting step is :-
Protonation of radical atom
13. When Ammonia(NH3) becomes proton source …
At higher temperatures (50°C - 120°C) , ammonia becomes the proton source and
Alcohol need not be used .
The amide ion thus formed is a strong base and isomerises the 1 , 2 – dihydro
Product.
14. Reduction of 1 , 2 – dihydro product :-
The 1 , 2 – dihydro product has a conjugated double bond & hence undergoes
Further reduction to form a tetrahydro derivates .
Cyclohexone has a single olefinic bond which is unaffected by the reagent .
15. Effect of substituents :-
For monosubstituted benzenes , the reduction is highly regioselective and this
Is controlled by the polar nature of the substituent .
If electron withdrawing substituent (EWS) is attached :
•The EWS withdraws electron from the aromatic ring and decreases
electron cloud on Benzene ring.
•This stabilize the negative (-) charge of anion radical.
• This makes the ring more electron-accepting and hence the reaction is
facilitated .
16.
17. If electron donating substituent (EDS) is attached :
•The EDS donates electron to the aromatic ring and increases electron cloud at
Benzene ring.
•This EDS destabilize the negative (-) charge of anion radical.
18.
19. With substituted benzene , the electron – donating group remains on unsaturated
Carbon and the electron withdrawing group remains on the saturated carbon in
the products.
20. Note :-
I) The presence of bulky groups on the aromatic ring retards the reduction
, probably because of steric interference to solvation of radical anion.
II) Phenols are not reduced presumably they react with metal.
More elaborate studies have revealed that , Phenol may be reduced by
increasing the concentration of the metal four fold.
21. Catalytic hydrogenation Birch reduction
Difficult process Easy process
Requires reagent in large
concentration
Small concentration of
reagent is sufficient for
reaction to be carried out
Aromatic ring is reduced
totally.
Aromatic ring is not
reduced totally and
reaction steps at diene
stage
24. II) Birch reduction can partially reduce C≡C of internal
alkyene to form alkene
25. III) Synthesis of 3-oxocyclohexene
Reduction of m-anisic acid which earlier gave 3-oxocyclohexane carboxylic acid
can be controlled to yield 3-oxocyclohexene carboxylic acid in good yield.
26. IV) Synthesis of Non-conjugated hydrocarbons
A) From Naphthalene
B) From Anthracene
28. Acknowledgement
I thank Prof. Jayashree jagtap mam for explaining us the reaction very well.
I thank Prof. Pooja petkar mam for providing us information.
29. References:-
1) Prof . J. R. Jagtap , Name reaction of synthetic importance , sgrs
college of pharmacy, saswad
2) Stanley H Pine (2007) , Organic Chemistry , New Delhi , Tata McGraw-Hill
publishing company Ltd , Pg no. 110
3) P.S.Kalsi (2010) , Organic Reaction and Their Mechanisms , New Delhi ,
New Age International Ltd , Pg no. 514-515
4) Morrison , Boyd and S.K.Bhattacharjee (2011) , Organic Chemistry , South
Asia , Dorling Kindersley (India) Pvt Ltd , Pg no. 1003-1005
