Hydroxamic acid derivatives 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 ... 

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... 

Rearrangement of O-acyl hydroxamic acid derivatives with base or heat to amines or urea derivatives (via isocyanates), or rearrangement of carboxylic acids via their hydroxamic acids to amines (see 1st edition). 

The Lossen rearrangement, discovered in 1872, is the transformation of a hydroxamic acid derivative to an isocyanate by using an activated hydroxamic acid 71 as the key intermediate tScheme 4.27)Z This activation can be achieved by O-acylation, O-arylation, or O-sulfonylation. From a mechanistic point of view, a base or a thermal treatment can initiate the reaction, giving a rearrangement of the corresponding anion 72 via a three-membered ring transition state 73. 

Unlike hydroxamic acids, A -hydroxyimides form stable 0-phosphoryloxy and O-sulfonyl derivatives. These hydroxyimides can be prepared from hydroxamic acid and isocyanates. As an example, cyclic A/-hydroximide 22 was prepared from dihydroxamic acid 20 through Lossen rearrangement and followed by self-condensation of intermediate 21. 

If the acid chloride prepared as in Schemes 10.35 and 10.36 is treated with hydroxylamine hydrochloride in pyridine solution, the corresponding hydroxamic acid is generated. When the hydroxamic acid (Scheme 10.37) is allowed to react with acetic anhydride, the O-acetate results and, on heating, the hydroxamic acid derivative undergoes decomposition (the Lessen rearrangement) to produce the same A -substituted isocyanate as previously seen. 

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. ... 

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

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. 

Conversions of compounds 116, 120 and 123 into IP-2-ones described above belong to Hofmann-, Curtius- and Lossen-type reactions. Therefore the parent amides, hydroxamic acids and o-aminopyridinecarboxylic acid azides, may formally be regarded as derivatives of monoaminopyridines. The above compounds rearrange into o-diamines with various degrees of ease, while benzenesulphonate 121 is transformed into intermediate isocyanate 122 under extremely mild conditions (68JOC2543). 

This reaction was first reported by Lossen in 1872. It is a thermal or alkaline conversion of hydroxamic acid into an isocyanate via the intermediacy of its O-acyl, sulfonyl, or phosphoryl derivative. In the presence of water, amine, or alcohol, the isocyanate is converted into amine, urea or urethane, respectively. Therefore, this reaction is generally known as the Lossen rearrangement. Occasionally, it is also referred to as the Lossen reaction, Lossen degradation, or Lossen transformation. ... 

Derivatives of Thioamides. (i) Syntheses,reactions, and physical properties of thiohydrazides. (ii) Syntheses and reactions of thio-hydroxamic acids. (iii) Syntheses, dimerization, trimerization, and reactions of thioacyl isocyanates. ... 

Disilylated hydroxamic acids (39), which are readily prepared from hydroxamic acids and hexamethyldisilazane, undergo thermolysis to the corresponding isocyanates (c/. Vol. 3, p. 181). This sequence thus constitutes a useful method for the conversion of carboxylic acid derivatives into amines (Scheme 52), and an alternative to the Hofmann reaction etc. 

The conversion of carboxylic acids and their derivatives into isoQranates is a synthetically useful and well-known transformation and two new methods now add to the available methodology. In one, amides are transformed electrochemically imder mild conditions to isocyanates, which are isolated or trapped as the corresponding carbonates. In the other method, adducts of nitrosocarbonylbenzenes (generated by oxidation of hydroxamic acids) and 9,10-dimethylanthracene are decomposed in benzene at 80 °C in the presence of triphenylphosphine, to give aryl isocyanates in high yield. ... 

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