Rearrangement acylamino ketones

One of the major problems encountered in this synthesis is the difficulty of obtaining the starting materials (either the a-aminocarbonyl compounds or their acylated derivatives). The former may be prepared by Neber rearrangement of ketoxime tosylates with a base such as ethoxide or pyridine.46 a-Acylamino carbonyl compounds can be prepared directly by the reductive acetylation of oximino ketones.28 38 Balaban and his collaborators47-60 have developed an excellent method for the synthesis of a-acylamino ketones (5). They are obtained in yields of 50-90% by the reaction of azlactones (2-aryl-5-oxazolone, 4) with aromatic hydrocarbons in the presence of aluminum chloride under Friedel-Crafts conditions the reaction may proceed either intermolecularly or intramolecularly. 

Dialkylquinazolines 825 are available by microwave-assisted amination and ring closure of 2-acylamino phenyl-ketones 824 with ammonium formate <20070L69>. The 2-aminophenyl ketone precursors of the amides 824 are available by a photochemically induced Fries rearrangement of anilides 823, which enables a variety of different alkyl substituents to be incorporated at the 4-position of the quinazoline <20070L69>. 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Just as in benzene chemistry, Wolff-Kischner or Clemmensen reduction of ketones is a much-used route to alkyl-thiophenes, hypochlorite oxidation of acetyl-thiophenes a good route to thiophene acids, Beckmann rearrangement of thiophene oximes is a useful route to acylamino-thiophenes and hence amino-thiophenes, and esters and acids are interconvertible without complications. 

A device that has been frequently used to produce an ortto-acylamino-phenol synthon is to carry out a Beckmann rearrangement on an ort/to-hydroxyaryl ketone, the Beckmann intermediate cyclising in situ, as illustrated below. ... 

The 5-substituted 3-amino-l,2,4-oxadiazole (76) condensed with -di-ketones and /Fketoesters, giving the corresponding 3-enaminones (91). These compounds did not rearrange on melting, but with sodium ethoxide in DMF (a dipolar aprotic solvent which increased the nucleophilic power of anion 93) at 110°C they were converted into the 4-substituted 2-acylamino-5-acylimidazoles (92).60,61... 

---