PRESENTED BY

PRASANNA R. ANGANE.
M.Pharm. I-sem (Pharmaceutical chemistry)
GUIDED BY

Dr. S. G. WALODE.
Head of The Department (Pharmaceutical Chemistry) SINHGAD INSTITUTE OF PHARMACEUTICAL SCIENCES, LONAVALA, PUNE.
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 INTRODUCTION HISTORY GENERAL REACTION MECHANISM

OF THE REACTION STEREOCHEMISTRY APPLICATION REFERENCES

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INTRODUCTION 2
The 1,4-reduction of aromatic rings to the corresponding unconjugated Cyclohexadienes by alkali metals (Li, Na, K) dissolved in liquid ammonia. In the presence of an alcohol is called the Birch Reduction. Heterocycles, such as pyridines, pyrroles, and furans are also reduced under this condition.

When the aromatic compound is substituted, the regioselectivity of the reduction depends on the nature of the substituent

The Birch Reduction was reported in 1944 by the Australian chemist Arthur Birch (19151995) working in the Dyson Perrins Laboratory in the University of Oxford.

The original reaction reported by Arthur Birch in 1944 utilized sodium and ethanol. Subsequently A. L. Wilds noted that better yields result with lithium.

Benzene

1,4-dihydro cyclohexadiene

Step 1: Electron transfer from sodium

H
H H H
Benzene

H
H + Na H H H H + H Na+

H
Benzene anion radical
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Step 2: Proton transfer from methanol

H
H H H H H OCH3

Step 2: Proton transfer from methanol

H
H H H H H H OCH3 H H

H
H H H OCH3

Cyclohexadienyl radical

Step 3: Electron transfer from sodium

H
H H H H H + Na H

Cyclohexadienyl radical
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Step 3: Electron transfer from sodium

H
H H H H H + Na H H H H

H
H + H H Na+

Cyclohexadienyl anion
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Step 4: Proton transfer from methanol

OCH3 H H H

H
H H H H

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Step 4: Proton transfer from methanol OCH3 H H H H H H H H

OCH3 H H H

H H H

1,4-Cyclohexadiene
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STEREOCHEMISTRY 5,6,7

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Regioselectivity
OMe t BuOH Na or Li in Liq NH
3 -

OMe H H H H

COOH t BuOH Na or Li in Liq NH

3 -

COOH

H
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APPLICATION 2,8,9,10
1)
Me N OMe OMe Et CO 2Me N N H

K,NH3, t-BuOH

Chiral benzamide 2)
R CN H MOMO H H OMOM H3C H N H

Apovincamine

Li,NH3, EtOH
HCL / MeOH

H H HO H O

Galbulimima alkaloid
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3)
OMe
OMe

Me NaNH 3/THF, -78 C /THF, -78 C N O O CH 2 OMe

Me STEPS N H O Me O CH 2 OMe HOOC Me O

Me COOH Me

then add Mel 93% then add Mel 93%

Nemorensic acid

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4) Useful in synthesis of steroids. A) Synthesis of 19-nor testosterone

5) The synthesis and CNS depressant activity of 3-aminocyclohexa-1,4-diene-1-carboxylic acid and 3-[5-substituted1,3,4-thiadiazole-2-yl]-2-styryl 5,8 dihydroquinazoline-4 (3H)-ones
6)

Asymmetric Synthesis of the Core Structure of the Melodinus Alkaloids

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Benzoyl-CoA reductase: a biological birch reduction

Synthesis of trans-1,8,12,13-tetraoxadispiro[4.1.4.2] tridecanesa new class of peroxides

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REFERENCES
1) Carey.F.; Sundberg. R. Advanced Organic Chemistry, Part B : Reactions and Synthesis.; Springer publications.; Fifth edition.; pp- 445-448. 2) Kurti L.; Czako B. Strategic applications of named reactions in organic Synthesis.; Elsevier academic press.; pp- 60-61.

3) Sanyal S. Reaction Rearrangement and Reagent.; Bhararti Bhavan Publishers and Distributers.; fourth edition.; pp- 96-97.
4) March J. Advanced Organic Chemistry Reaction Mechanism And Structure.; fourth edition.; John Wiley and Sons.; pp- 779-783. 5) Kalasi P. Organic reaction & their mechanisms.; New age International publishers.; Second edition.; Pp-471-472.

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6) Nasipuri D., Stereochemistry of Organic Compounds: Principles and Applications In asymmetrical synthesis, New age international publishers, second edition, pp. 395-397. 7) http://en.wikipedia.org/wiki/birch_reduction

8) Charbe N.B., Mehere A.P., Shende S.G. Study of new developments in birch reduction process and their applications for the synthesis and CNS depressant activity of 3- aminocyclohexa-1,4-diene-1-carboxylic acid and 3-[5-substituted 1,3,4-thiadiazole-2-yl]-2-styryl 5,8 dihydroquinazoline-4 (3H)-ones International Journal of Drug Discovery, Volume 2, 2010, pp.17-25.
9) Arthur G. S. and Mingshi D. Asymmetric Synthesis of the Core Structure of the Melodinus Alkaloids Tetrahedron Letters volume 40,1999, pp.645-648.

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10) Kumar D. N., Sudhakar N., Venkateswara B. Synthesis of trans-1,8,12,13tetraoxadispiro[4.1.4.2]-tridecanesa new class of peroxides Tetrahedron Letters volume 47 2006 pp.771774 11) ACD/chemsketch(Free ware),File version-12.10 31258

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