Nitriles Beckmann rearrangements

The ketoxime derivatives, required as starting materials, can be prepared from the appropriate aromatic, aliphatic or heterocyclic ketone. Aldoximes (where R is H) do not undergo the rearrangement reaction, but rather an elimination of toluenesulfonic acid to yield a nitrile. With ketoxime tosylates a Beckmann rearrangement may be observed as a side-reaction. 

Not only do oximes undergo the Beckmann rearrangement, but so also do esters of oximes with many acids, organic and inorganic. A side reaction with many substrates is the formation of nitriles (the abnormal Beckmann rearrangement, 17-31). Cyclic ketones can be converted directly to lactams in one laboratory step by... 

A simple montmorillonite K 10 clay surface is one among numerous acidic supports that have been explored for the Beckmann rearrangement of oximes (Scheme 6.27) [54]. However, the conditions are not adaptable for the aldoximes that are readily dehydrated to the corresponding nitriles under solventless conditions. Zinc chloride has been used in the above rearrangement for benzaldehyde and 2-hydroxyacetophe-none, the later being adapted for the synthesis of benzoxazoles. 

Acidic zeolites, K-10 clay and silica are highly active and selective catalysts for the dehydration/Beckmann rearrangement reactions of aldoxhnes (benzaldoxime and 4-methoxybenzaldoxime) for the synthesis of nitriles and amides . 

A variety of ketones 249 can be directly converted into the secondary amides 253 (the expected product of a Beckmann rearrangement of the corresponding oximes 250) in high yield, by heating them with hydroxylamine hydrochloride and anhydrous oxalic acid (equation 75). Aromatic aldehydes afforded mixtures of nitriles and amides. The... 

Also, chlorosulfonic acid was demonstrated to be an efficient catalyst in the Beckmann rearrangement of a variety of ketoximes in refluxing toluene, and excellent conversion and selectivity was observed . This procedure can also be applied to the dehydration of aldoximes yielding the corresponding nitriles. 

Indium trifluoromethanesulfonate was found to be an effective high-yielding catalyst for the facile dehydration of aldoximes to nitriles and Beckmann rearrangement of ketoximes to anilides. ... 

Fragmentation of the intermediate or concerted formation of nitriles from the activated oxime (Scheme 9, pathway 3) this is the Beckmann fragmentation. In some circumstances this pathway becomes dominant, particularly when there are quaternary carbons adjacent to the oxime. This transformation has found particular utility in ring-cleavage processes (sometimes called abnormal or second-order Beckmann rearrangements). 

Under the same standard rearrangement conditions, the analogous a-chloroxime 340 gave a low yield of an azacardenolide 341 (14%) as a result of the normal Beckmann rearrangement the nitrile 342 was isolated as the major reaction product (equation 128). 

Some other syntheses of y-lactams by the Beckmann rearrangement were also tested without great success, the nitrile being the major product of the transformation (equations 130 and 131). 

Although the Beckmann fragmentation may be regarded as a limitation for the application of the Beckmann rearrangement, it provides a synthetic method to produce nitrile compounds. Some examples from the recent literature are collected in the next section. 

Another recent example of unsuccessful Beckmann rearrangement is shown in equation 212 and produced a benzopyran nitrile 491 . As in the previous example, mesomeric assistance by the oxygen atom turned the fragmentation very favourable. 

Nitriles may be prepared by dehydration of aldoximes an attempt to effect a Beckmann rearrangement on the oxime (481) of 5-methoxy-4-oxopyran-2-carboxaldehyde gives the nitrile (482) but under milder conditions only the chloride (483) and the chloronitrile (484) are obtained (75JHC219). 

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). 

Keywords aldoxime, p-toluenesulfonyl chloride, pyridine, alumina, Beckmann rearrangement, microwave irradiation, nitrile... 

Keywords oxime, Beckmann rearrangement, nitrile ylide, amide... 

Under the relatively mild conditions of chlorosulfonic acid in toluene, ketoximes undergo Beckmann rearrangement, whereas aldoximes dehydrate to nitriles.90... 

Oximes derived from p-silyl and P-stannyl ketones undergo unusual Beckmann rearrangement, giving rise to nitriles as predominant products. For example, Beckmann rearrangement of 3-trimethylsilylcyclohexanone oxime 88 (Scheme 15) proceeds to the formation of the acyclic alkenyl nitrile 89 as the major product.90 The nitrile is believed to be formed by fragmentation of the protonated oxime, giving the P-silyl—stabilized cation 90, followed by desilylation. Our... 

The participation of nitrilium salts has also been postulated42 in the Schmidt reaction and in some Beckmann rearrangements when concentrated sulfuric acid is employed. Hill43 has demonstrated recently that some Beckmann rearrangements carried out in a concentrated sulfuric acid medium are Ritter-type reactions in which the nitrile formed in situ from the oxime combines with a carbonium ion to yield a nitrilium salt, which, when diluted with water, leads to the N-alkylamide. 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

Each migrating tertiary group must have lost contact with the amide fragment it started out with. Each molecule falls to bits to give a f-alkyl cation and a nitrile the Beckmann rearrangement now goes via a fragmentation mechanism. 

The abnormal Beckmann rearrangement displayed by the oxime of 17-oxo-5a-androstan-3/3-yl acetate (248) to yield the 13,17-seco-nitrile (249) has provided the key step in a synthetic route to 17-oxo-18-nor-5a,13/8-androstan-3/S-yl acetate and its 13a-epimer.114 The reaction sequence is shown in Scheme 12. The 17-ketone (248) was converted via its oxime into the seco-nitrile in a yield of 52%. Treatment of the oxime by the more conventional toluene-p-sulphonyl chloride reagent... 

Beckmann rearrangement of a 17-oxime has also been used to furnish A13<18)-13,17-seco-5a-androstene-17-nitrile (249), which on methylation with methyl-lithium gave the ketone (256 R = H) and thence by hydride reduction the alcohol (257 R1 = H, R2 = OH, R3 = Me).115 Conversion of this alcohol into its tosylate and further hydride reduction furnished the exocyclic olefin A13(18)-13,17-seco-D-homoandrostene (257 R1 = R2 = H, R3 = Me). Reaction of the nitrile (249) with trideuteriomethyl-lithium gave the ketone (256 R = D) and conversion into the hydrocarbon as outlined above gave the olefin (257 R1 = R2 = H, R3 = CD3). Reduction of the ketone (256 R = H) with lithium aluminium deuteride furnished the alcohol (257 R1 = D, R2 = OH, R3 = Me) which could in turn be converted into... 

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