Hydroxamic acids isocyanates

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 0-acyl derivatives of hydroxamic acids give isocyanates when treated with bases or sometimes even just on heating, in a reaction known as the Lossen rearrangement. The mechanism is similar to that of 18-13 and 18-14 ... 

Treatment of O-acylated hydroxamic acids with base provides isocyanates. 

Finally, the Lessen rearrangement provides a practical procedure for replacing the hydroxamic group of a hydroxamic acid (12) by an amino group (14) (equation 2). The initial rearrangement product is an isocyanate (13) which readily reacts with nucleophiles, for example with OH and NH functionalities to give amines (14) and ureas (15). 

To improve the product yields in Lossen rearrangement, mesyloxycarbamates have been used as alternative reagents . The use of A-acyl-O-mesylhydroxamic acids (558) avoids the competing formation of self-condensation by-products (560). These are obtained from the accumulation of isocyanate (559) before complete consumption of the hydroxamic acid (557) as observed in the classical Lossen rearrangement (equation 249). 

Surprisingly, however, monoalkylaminium cation radicals 104 have not been studied well. Newcomb found that they could not be prepared from respective PTOC carbamates due to instability of the precursors, nevertheless, the problem was solved via the isocyanate condensation with a different thio-hydroxamic acid 105a, as shown in Scheme 44. These deriva-... 

H)-Oxazolones are formed by the spontaneous cyclization of /3-oxo isocyanates (equation 134). Similarly, o-hydroxyphenyl isocyanate, produced by the Curtius rearrangement of the azide of salicylic acid or by the action of sodium hypochlorite on salicylamide, forms benzoxazolone (equation 135). An analogous reaction is the formation of IV-phenyl-benzoxazolone by the action of thionyl chloride on the hydroxamic acid shown in equation (136) (78TL2325). Pyrolysis of aryl azidoformates affords benzoxazolones by nitrene insertion (equation 137) (81CC241). 

Azine approach. DCC dehydration of the 3-oxoquinazoline-4-hydroxamic acid (602) gives an isocyanate (603) via a Lossen rearrangement addition of the AT-oxide oxygen to the isocyanate group effects the cyclization. The same product is formed by the phosgene reaction with 4-amino-2-methylquinazoline 3-oxide (76TL3615). 

However, hydroxamic acids, such as 474, react with carbodiimides to produce a nitrene intermediate 475, which undergoes the Lossen rearrangement to give an isocyanate 476." " The latter reacts with the starting hydroxamic acid to give the adduct 477. 

Alkali salts of hydroxamic acids and their derivatives undergo a re> arrangement to give isocyanates. The method has had little synthetic application it has been reviewed. ... 

Rearrangement of O-acyl hydroxamc acxl derivatives with base or heat to amines or urea derivatives (via Isocyanates) or rearrangement of cartioxylic acids via their hydroxamic acids to amines... 

In the presence of base, acyl derivatives of hydroxamic acids undergo the Lessen rearrangement to yield isocyanates or amines. 

Phosgenation of hydroxamic acids affords nitrile carbonates which has been suugested as isocyanates precursors (Ref. 233). 

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. 

A further example is the Lossen rearrangement, in which an O-acyl derivative of hydroxamic acid, RCONHOCOR, gives an isocyanate on treatment with hydroxide ion, which in turn may be hydrolysed to the amine. Illustrate this reaction pathway. 

Lossen rearrangement The O-acyl derivative of a hydroxamic acid gives an isocyanate when treated with a base or, sometimes, just heat. 

Lossen Rearrangement,78 The thermal decomposition of hydroxamic acid derivatives leads to isocyanates or, in aqueous solution, to amines. This reaction is usually called the Lossen rearrangement. Its mechanism... 

The Hofmann-degradation of acid amides (60-80%, via N-bromoamides) as well as the Lossen-degradation of hydroxamic acids by [l,2,l]-elimination of HBr, or H20, respectively, leads to isocyanates (Scheme 4), which usually yield primary amines RNH2 by solvolysis 36). 

---