Polyphosphoric acid Beckmann rearrangement

Beckmann rearrangement of anthraquinone dioximes leads to 1.5-diazocine systems, a reaction which indirectly proves the C2-symmetry of the starting material.51,52 The reaction is induced preferentially by heating in polyphosphoric acid. 

For a review of Beckmann rearrangements with polyphosphoric acid, see Beckwith, A.L.J. in Zabicky, Ref. 253, p. 131. 

The most widely used route to l-benzazepin-2-ones involves the Beckmann or Schmidt reaction of the easily accessible 1-tetralones. Many biologically active compounds described in this review have been prepared on the basis of these reactions they have been fully reviewed [2], In the Beckmann reaction of 1-tetralone oximes, polyphosphoric acid is used as a catalyst-solvent in most instances. Aryl migration generally takes precedence over alkyl migration under these reaction conditions, and various 1-tetralone oximes substituted on the aromatic and/or aliphatic rings can be converted to the appropriate 2,3,4,5-tetrahydro-l//-l-benzazepin-2-ones (51) [5, 20-23, 36, 59, 65, 80, 107-112]. Both courses of the rearrangement occur in some instances, yielding l-benzazepin-2-ones (51) and the isomeric 2-benzazepine-l-ones, probably due to electronic effects of the substituents [90, 113, 114]. 

F yridinium oxime 394 in the presence of concentrated EECl gives oxazepine 395 in 61% yield (eqnation 172) . Beckmann rearrangement of 4-chromanone oximes in the presence of polyphosphoric acid or diisobntylalnminium hydride also afforded substituted benzoxazepinone ring. 

The synthesis of the benzazepinone portion of benazepril began with monobromination of 1-tetralone (35), followed by oxime formation to give 36 (Scheme 10.9). A Beckmann rearrangement mediated by polyphosphoric acid provided the ring-expanded lactam 37. Displacement of the a-bromine with potassium phthalimide installed the necessary... 

Beckmann rearrangement of 6-endo-chlorocamphor oxime (Vol. 7, p. 43) yields (220) and the cis- and frans-ring-fused (221), and camphor oxime rearranges with hydrazoic acid in polyphosphoric acid to yield (222). ... 

Beckmann rearrangement of quinuclidin-3-one oxime (103) in the presence of polyphosphoric acid or oleum proceeds with quinuelidine ring expansion and the formation of 3-oxo-l,4-diazabicyclo[3.2.2]-nonane (146).m,m... 

The reaction of ketone 243 with hydroxyamine resulted in the formation of oxime 244. Treatment of this oxime with polyphosphoric acid induced the Beckmann rearrangement of oxime 244 to form lactam 245 without detectable formation of isomeric lactam (Scheme 43) <1997JHG921>. Other examples of the Beckmann rearrangement of pyran and thiane derivatives have been reported <2004BML5907, 2004TL1051, 2005JOC10132>. 

The reaction of oxime 385 with polyphosphoric acid results in ring expansion via Beckmann rearrangement leading to the fused 1,4-benzothiazepine derivative 386 (Scheme 207) <1997JHC921, CHEC-III(13.09.10.2)286>. 

The reaction of lactim ethers with hydroxylamine results in lactam oximes.9,72,73, 78 This reaction became important when the lactam oximes were found to undergo the Beckmann rearrangement with polyphosphoric acid, yielding polymethyleneureas79 (Scheme 11). 

Dimethylaminoethyl-l-tetralone (59) may be generated from 4-phenyl-cyclohexanone by Beckmann rearrangement to 5-phenylcaprolactam (58), followed by hydrolysis, yV-methylarion, and polyphosphoric acid cyclization.(219) Conventional transformations afforded the desired 3-methylben-zomorphan (60), first synthesized from 4-phenylpyridine in 1968.(2(,)... 

Other Nitrogen-containing Derivatives of Ketones.—The Schmidt reaction of 6- and 7-oxo-steroids (with NaNj-polyphosphoric acid) gave the same lactams as the Beckmann rearrangements of the corresponding oximes. 

Most ketoximes will undergo the normal Beckmann rearrangement under the proper acidic or neutral conditions to yield an amide or a mixture of amides, and a wide variety of examples are listed in reviews. Polyphosphoric acid continues to be a common reagent for the Beckmann rearrangement. However, in view of the viscosity and utility in a large molar excess as a solvent, polyphosphoric acid has several drawbacks in the work-up step. A recent procedure suggests the use of xylene as a cosolvent. Under these conditions the reaction temperature is easily controlled and the yields are the same or better than those obtained in polyphosphoric acid alone. 

Probably the best-known rearrangement in which an aryl group migrates from carbon to nitrogen is the Beckmann rearrangement. Here, ketoximes are converted to A-substituted amides when treated with an acidic reagent, such as sulfuric or polyphosphoric acid, phosphorus pen-tachloride or thionyl chloride (SOC ). In the context of this chapter, the amides are hydrolysed to liberate the amine. The mechanism in acid media is believed to proceed as illustrated in Scheme 8.3, where the 1,2-shift from carbon to nitrogen is noted as the key step. 

Normal Beckmann rearrangements of the syn- and anti-oximes at C-3 in the 5a-series each involve specific migration of the trans-C-C bond, giving isomeric lactams. Beckmann rearrangements induced by polyphosphoric acid (PPA), however, have some unusual features. Saturated 3-oximes (e.g. 411) give small amounts (up to 5 % each) of the 1 -en-3-one (413) and 4-en-3-one, in addition... 

Compound 30 was prepared by the Beckmann rearrangement in polyphosphoric acid of the diphenylhydrazone 32 (R = Me). The reaction also worked for the benzyl analogue 32 (R = CH2Ph), but the 3-unsubstituted analogue could not be prepared from 32 (R = H), as this compound on acid treatment hydrolyzed back to the ketone 33. Phos-phoryl chloride converted 30 into the corresponding 4-chloroimidazo[l,5-ajquinoxaline. 

According to Horning and Stromberg,132 the Beckmann rearrangement gives particularly good results when carried out by means of polyphosphoric acid ... 

---