Amides from Beckmann rearrangement

Primary amides may be produced by a Beckmann rearrangement both from E or Z oximes which are commonly obtained from the corresponding carbonyl compound (aldehyde). Retrosynthetic analysis follows equation 98. 

The stereochemical use of the Beckmann rearrangement in assigning configuration to ketoximes has already been referred to, and it also has a large-scale application in the synthesis of the textile polymer Nylon-6 from cyclohexanone oxime (78) via the cyclic amide (lactam, 79) ... 

The common name caprolactam comes from the original name for the Ce carboxylic acid, caproic acid. Caprolactam is the cyclic amide (lactam) of 6-aminocaproic acid. Its manufacture is from cyclohexanone, made usually from cyclohexane (58%), but also available from phenol (42%). Some of the cyclohexanol in cyclohexanone/cyclohexanol mixtures can be converted to cyclohexanone by a ZnO catalyst at 400°C. Then the cyclohexanone is converted into the oxime with hydroxylamine. The oxime undergoes a very famous acid-catalyzed reaction called the Beckmann rearrangement to give caprolactam. Sulfuric acid at 100-120°C is common but phosphoric acid is also used, since after treatment with ammonia the by-product becomes... 

In the presence of a catalytic amount of an antunony(V) salt (SbCU SbFe ), generated from antimony(V) chloride and silver hexafluoroantimonate, the Beckmann rearrangement of several ketoxime trimethylsilyl ethers proceeds smoothly to give the corresponding amides or lactams in good yields . ... 

The Beckmann rearrangement of cyclohexanone oxime catalysed by solid metaboric acid (286) has also been investigated (equation 94). When ketoximes, mixed with 286 (formed from boric acid at 100°C/0.1 Torr), are heated (140°C/7-42 h) the corresponding amides or lactams are produced in excellent yields (62-92%). Under the... 

Activated Fly ash , an industrial waste pollutant, is found to be a good catalyst in Beckmann rearrangement promoted by microwaves under solvent-free conditions. The amides are obtained from the corresponding ketoximes in high yields (75-94%). 

However, the stereochemistry of the oxime cannot be easily controlled and this may be a drawback for the synthetic utility of the Beckmann rearrangement. When a mixture of oximes is obtained from the ketone and when the isomerization of the oxime cannot be prevented during the rearrangement reaction, a mixture of amides is obtained. In other less favourable cases, the intended oxime cannot be obtained and the wrong amide will result from the rearrangement reaction. 

Amines 297 and/or carboxylic acids 298 may be obtained by amide hydrolysis and the latter compound may be produced from a ketone by a Beckmann rearrangement (equation 103). Therefore, the Beckmann rearrangement of a ketone oxime followed by amide hydrolysis provides a synthetic method to cleave the C—C bond between the carbon... 

Novel a,/ -unsaturated amide derivatives at C(4) of chromones 335 were synthe-sized (equation 124). Oximes 332 and 333 rearranged in the presence of PCI5 into the same amides 335 in high yields. Spiroisoxazolines 334, formed from oxime 332 by acid treatment, also produce 335 under Beckmann rearrangement conditions. 

Conversion of oximes derived from cyclobutyl ketones to amides represents the classic Beckmann rearrangement. One example of this reaction is the formation of optically active 7,7-dimethyl-2-azabicyclo[4.1.1]octan-3-one (1) from 6,6-dimethylbicyclo[3.1.1]heptan-2-one oxime, which is readily derived from /3-pinene.40... 

Trimethylsilyl polyphosphate (PPSE),1 The reagent is prepared from P205 and [(CHj),Si]20. It is a colorless, volatile liquid, soluble in the usual organic solvents. It is comparable to polyphosphate ester for the Beckmann rearrangement of oximes to amides (3, 230 231). but it is prepared more easily. 

Xanthone is unreactive towards hydrazine and phenylhydrazine. The oxime is obtained by reaction of xanthione (xanthene-9-thione) with hydroxylamine, or from xanthone and hydroxylamine in pyridine. When the oxime is heated in water with phenylhydrazine, the phenylhydrazone is formed. In acid solution, xanthone reacts normally with 2,4-dinitro-phenylhydrazine but xanthone-1 -carboxylic acid (435) gives the pyridazinone (436), possibly via the hydrazone (57JCS1922). When the oxime is heated with phosphorus pentachloride it undergoes a Beckmann rearrangement to give the amide (437) (70MI22300). 

The fact that under the same conditions acetophenone oxime does not form amides, but remains intact, also provides evidence against the classical Beckmann rearrangement. The conditions found can be employed for preparing amides from nitriles and aldoximes, especially when the latter contain fragments unstable to acids. In the absence of DMSO, benzaldoxime is dehydrated with alkali only at the boiling point (200°C). 

It should be noted that amines may be formed by hydrolysis of amides arising from the intramolecular Beckmann rearrangement of ketoximes (p. 1047) this rearrangement is a further example of the migration of a nucleophilic carbon species from a carbon to an electron-deficient nitrogen. 

Oximes of cyclojjentanone and cyclohexanone undergo the Beckmann rearrangement to cyclic amides from which amino acids may be obtained, e.g., S-aminovaleric acid (71-80%) and e-aminocaproic acid (92%). ... 

The conversion of ketones to amides by the Schmidt reaction has been mentioned elsewhere (method 362). Since the hydrolysis of the amides so obtained proceeds readily, the two steps provide a convenient synthesis of amines from ketones. The yields are often higher than those obtained from the Beckmann rearrangement with subsequent hydrolysis (method... 

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