Amines Lossen rearrangements

The amidase from Rhodococcus erythopolis strain MP50 was nsed to selectively convert racemic 2-phenylpropionamide into 5 -2-phenylpropiohydroxamate. This was converted into the isocyanate by Lossen rearrangement and then by hydrolysis to S-( )-phenylethyl-amine (Hirrlinger and Stolz 1997). 

Originally, the Lossen rearrangement specifically referred to the conversion of a hydroxamic acid to an amine with the loss of carbon dioxide ... 

Chandrasekhar and colleagues used Af-acyl-Af, 0-bis(ethoxycarbonyl)hydroxylamines in a similar procedure to prepare amines. Aromatic Af-hydroxyimide derivatives were used by Marzoni and Varney " and Giitschow " to synthesize benz[crf]indol-2(l//)-one and 1-benzoxazin-4-one derivatives, respectively, via Lossen rearrangements. Both Af-benzyloxy and A-mesyloxy derivatives were used. 

The hydroxamate anion 566 is invoked as intermediate in the formation of urea 568 from the iV-tosylated /3-lactam 564 by a Lossen rearrangement in the presence of a secondary amine 565 (equation 252). Apparently, attack of amine in an S/v2 fashion at the C(4) carbon of the /3-lactam 564 opened the ring to form hydroxamate anion 566, which then initiated a facile Lossen rearrangement to isocyanate 567 trapped with another molecule of base to give 568. 

Amides react with alkaline hypochlorite or hypobromite solutions to form primary amines having one less carbon atom. The reaction involves the hydrolysis of an isocyanate, which is seldom isolated. Isocyanates are also intermediates in the Curtius and Lossen rearrangements (methods 447 and 448). Although diese methods have a common mechanism and intermediate, they involve three separate and distinct types of starting materials and are, therefore, treated individually. A comparison of these reactions has been made. A detailed discussion of the Hofmann reaction, which includes conditions, typical procedures, and compounds prepared thereby, has been presented. ... 

Hydroxylamine-O-sulfonic acid can be also used for the Lossen rearrangement. Heating acids with hy-droxylamine-O-sulfonic acid in hot mineral oil or polyphosphoric acid affords amines, though the reaction conditions for this transformation still need to be optimized (equations 56 and 57). 

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,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... 

Lossen rearrangement. Conversion of a hy-droxamic acid, via a Hofmann-like arrangement, to an amine containing one less carbon than the original hydroxamic acid. 

Lossen rearrangement. Condensation of a carboxylic acid with this reagent followed by mild base treatment leads to primary amines with one less carbon. 

Since leaving group R COO leaves as R COO , the rearrangement is facilitated by the presence of electron-withdrawing groups in meta or para positions. Of these four related processes the Lossen rearrangement is the least useful in the synthesis of amines because of the unavailability of hydroxamic acids. 

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. ... 

The use of azides in the Curtius reaction is hazardous and the utility of the Hoffman and Lossen rearrangements is limited to preparation of aliphatic isocyanates, as aqueous media are employed (aromatic isocyanates react readily with water to form substituted ureas). Tertiary butyl hypochlorite can be used for non-aqueous Hoffman rearrangements but is costly. In practice mostly phosgenation of a primary amine is commercially important ... 

Hydroxamic acid 3 can be converted to activated hydroxamate 2 via reaction with a variety of electrophilic reagents. The Lossen rearrangement is then initiated by exposure of 2 to base or heat resulting in anion 10. Through a fast subsequent transformation via cyclic intermediate 12, isocyanate 1 is generated. This isocyanate 1 can be further converted to urea 13 or amine 15. 

Scheme 10.37. A representation of the Lossen rearrangement showing that the amine prepared from the corresponding carboxylic acid retains the absolnte configuration (see Lossen, W. Liebigs Ann. Chem., 1872,161, 347 as well as Yale, H. L. Chem. Rev., 1943,33, 219).

Degradation reactions of carboxylic acids and their derivatives to amines and their derivatives widi one less carbon unit involve reanangements of a carbon to an electron deficient nitrogen atom as key steps, namely the Hofmann Curtius (C), - Schmidt and Lossen rearrangements, as... 

Amines from carboxylic acids Lossen rearrangement... 

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. 

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