LOSSEN REARRANGEMENT

Mr. DILIP R. DAVHAREM.Pharm. IInd Sem. (Pharmaceutical Chemistry)UNIVERSITY DEPARTMENT OF PHARMACEUTICAL SCIENCES, RASHTRASANT TUKADOJI MAHARAJ

NAGPUR UNIVERSITY, NAGPUR

CONTENT. History. General Introduction. Reaction Mechanism. Reference.

HISTORY OF LOSSEN REARRANGEMENT History of Lossen rearrangement: In 1872 W. lossen reported

the pyrolysis of benzohydroxmate gave phenylisocyanate & benzoic acid.

Later he observed that potassium salt anisol benzohydroxomate was readily converted to diphenylurea, potassium anisate, & CO2 in boiling water.

In later transformation phenylisocyanate was product half to

which react with H2O to form aniline & CO2 & other reacted

with aniline to form diphenylurea.

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LOSSEN REARRANGEMENT

The Lossen rearrangement is the conversion of a betaxamic acid (1) to an isocyanate (3) via the formation of an O-acyl, sulfonyl, or phosphoryl intermediate hydroxamic acid O-derivative (2) and then conversion to its conjugate base. Here, 4-toluenesulfonyl chloride is used to form a sulfonyl Ortho-derivative of hydroxamic acid

The isocyanate can be used further to generate ureas in the presence

of amines (4) or generate amines in the presence of H2O (5).

REACTION MECHANISM FOR LOSSEN REARRANGEMENT The mechanism below begins with an O-

acylated hydroxamic acid derivative that is treated with base to form an isocyanate that generates an amine and CO2 gas in the presence of H2O. The hydroxamic acid acid derivative is first converted to its conjugate base by abstraction of a hydrogen by a base.

Spontaneous rearrangement kicks off a carboxylate anion to produce the isocyanate intermediate. The isocyanate in the presence H2O hydrolyzes and then decarboxylation via abstraction of a hydrogen by a base generates an amine and CO2 gas.

https://en.wikipedia.org/wiki/File:LossenRearangmentCHEMDRAW.jpg

REFERENCES S.N. Sanyal, Reactions, Rearrangements & Mechanisms,

volume I Nirali Publishing house PVT LTD, 3rd edition, Mumbai, India 2000-69 to 70.

Mukul C Ray, Reaction Mechanisms of Organic Chemistry, 1st edition, Published by M.T.G. Books New Delhi, India-259.

I.L.Finar, Organic chemistry,5th edition, published by Pearson Education Ltd, India- 232 to 233.

Arun Bhal, B.S. Bahl, Advanced Organic Chemistry, 7th edition, published by S.Chand Publishing House, Kolkata, India-139 to 145.

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Thank You