Lossen reaction

In the Lossen reaction a hydroxamic acid derivative (usually an 0-acyl derivative) is deprotonated by base, and rearranges via migration of the group R to give an isocyanate 2. Under the usual reaction conditions—i.e. aqueous alkaline solution—the isocyanate reacts further to yield the amine 3. The Lossen reaction is closely related to the Hofmann rearrangement and the Curtins reaction. 

The Lossen reaction is of limited importance in synthetic organic chemistry one reason for that is the poor availability of the required hydroxamic acid derivatives. Some hydroxamic acids are even unreactive." ... 

The related Lossen reaction was used in studies on the core of a Salmonella lipopolysaccharide.105 Aldehyde groups formed on periodate oxidation were oxidized to carboxylic acid groups, these were esterified, the esters were treated with hydroxylamine, and the products finally subjected to the Lossen reaction by treatment with a water-soluble carbodiimide. 

The fourth related rearrangement reaction is the Lossen reaction, which generally occurs by base treatment of 0-substituted hydroxamic acids which possess electron-withdrawing functions at the oxygen atom (e.g. O-acylhydroxamic acids), giving amines via isocyanates (equation 6). Preliminary 0-activation (e.g. O-acylation) of hydroxamic acids is essential for a smooth rearrangement, otherwise it will not occur, ilie Lossen reaction is not as useful as the other three rearrangements since hydroxamic acids are not readily available. 

The Lossen reaction 4 5 is the rearrangement of hydroxamic acids, which are prepared from acids, acyl chlorides and esters. It is usually conducted under alkaline conditions. Initial attachment of electron-withdrawing groups to the oxygen atom of the hydroxamic acids is essential to conduct the reaction the... 

Short heating of 4-quinolinecarbohydroxamic acid (205) with formamide affwds 4-aminoquinoline (207) via the isocyanate (206), while use of a large excess of formamide and increasing the temperature slowly give N-(4-quinolyl)urea (208) exclusively, as shown in Scheme 32. Intermediacy of 0-formates or equivalents has been suggested in the above modification of the Lossen reaction. ... 

N// -Dicyclohexylcarbodiimide (DCC) also mediates the Lossen reaction of hydroxamic acids under neutral conditions.In the conversion of the hydroxamic acid (209) to the tricyclic compound (210), the Lossen rearrangement is accompanied by an intramolecular cycloaddition (equation 54). 

As in the Curtius and Lossen reactions, when alcohol is employed as a solvent, a urethan is formed. 

An earlier proposed structure for the bis oxime of N-acetylisatin was shown to be erroneous. The correct structure (60) was deduced from its chemical reactions and by synthesis from methyl o-N-acetamidobenzoyl-formate and hydroxylamine.162 The hydroxamic acid (60) underwent a Lossen reaction to form the 4-isocyanato derivative, which cyclized to the oxadiazoloquinazoline 61. The structure of the latter was confirmed by an X-ray analysis.163... 

---