Polyphosphoric acid, reaction with oximes

It is of interest to note that attachment of a basic side chain on carbon of an isomeric dibenzazepine affords a compound in which anticholinergic activity predominates, elantrine (50). Reaction of anthra-quinone (45) with the Grignard reagent from 3-chloro-N,N-dimethylaminopropane in THF in the cold results in addition to but one of the carbonyl groups to yield hydroxyketone 46. This is then converted to oxime 47 in a straightforward manner. Treatment of that intermediate with a mixture of phosphoric and polyphosphoric acids results in net dehydration of... 

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>. 

So now we start the synthesis. Available 46 was converted in two steps into 45 and an interesting reaction with chloral hydrate and hydroxylamine gave the amido-oxime 47, cyclised to 48 with polyphosphoric acid.5... 

Dihydro-4-methylcyclopent[b]indol-l(2H)-one oxime (1.53 g), polyphosphoric acid (409 g) and dioxan (15 ml) were heated at 110-120°C for 2.2 h under nitrogen. The reaction mixture was cooled, and treated with 2 N sodium carbonate solution (1 L). The suspension was extracted with ethyl acetate (4x400 ml) and the combined extracts were dried. Evaporation gave a solid (1.43 g) which was recrystallised from ethyl acetate/cyclohexane. This solid was purified by FCC, eluting with dichloromethane ethanol ammonia solution (200 10 1) to give a solid (1.26 g) which was recrystallised from ethanol to provide the title compound (960 mg), m.p. 234-238°C. 

A mixture of polyphosphoric acid and nitromethane converts fluorenone into phenanthridone at 250°. The reaction probably proceeds via the oxime, which can be isolated when the reaction is carried out at 190°.107 The same conversion can be achieved, though in lower yield, by the action of sodamide on fluorenone in liquid ammonia or (-butylamine. In this reaction biphenyl-2-carboxamide (isolated in 5% yield) is probably a precursor of phenanthridone, since the conversion of the amide to the latter in 40% yield has been demonstrated in a second experiment. The major product of the reaction with fluorenone in liquid ammonia is, not surprisingly, fluorenimine.108... 

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). 

The diazepine 85 (tetramethyleneurea) has been prepared by a variety of routes. Among these are the treatment of tetramethylene diisocyanate with water,70-72 the rearrangement of the oxime (86) in polyphosphoric acid,73,74 and the reaction of 1,4-diaminobutane with sulfur, methanol, and carbon monoxide at high pressure.75 A novel preparation of 85 involves the reaction of 1,4-diaminobutane with 87 to give the silylated diamine (88). Reaction of 88 with phosgene and triethylamine yielded the bistrimethylsilyldiazepine (89) which was then hydrolyzed in aqueous ethanol to give 85.76... 

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. 

HCl-HOAc-AcjO, POCls, BiCla, neat with FeCls, and polyphosphoric acid. The reaction has been done in supercritical water and in ionic liquids. A polymer-bound Beckman rearrangement has been reported. Sim-ply heating the oxime of benzophenone neat leads to A-phenyl benzamide. The oximes of cyclic ketones give ring enlargement and form the lactam,as in the formation of caprolactam (83) from the oxime of cyclohexanone. Heating an... 

Bromotellurenylbenzaldehyde (or its oxime) serves as the precursors to another tellurium-containing heterocyclic system, namely benzoisotellurazole 34 (78JHC865). The reaction of the aldehyde with ammonia proceeds through the formation of imine 35 followed by its dehydrobromination. The cyclization reaction of oxime 36 is catalyzed by polyphosphorous acid (Scheme 19). 

The parent heterocycle and its 5- and 6-monochloro derivatives have been recently prepared from the corresponding aminopyrazines. For example, reaction of 2-amino-6-chloropyrazine with dimethylformamide dimethylacetal gave the intermediate 7, which on reaction with hydrox-ylamine gave the oxime 8. Cyclization of the oximes with polyphosphoric acid afforded the s-triazolo[l,5-a]pyrazines in 61-76% yields. Attempts to methylate 2,5,6-triphenyl-s-triazolo[l,5-aJpyrazine with methyl iodide were unsuccessful. The 2-methyl derivative of the ring system, on treatment with hydrogen peroxide in acetic acid, gave the... 

Isatins are indole derivatives with broad use in synthetic dye production and are intermediates in the synthesis of other heterocyclic molecules/ They also possess a variety of biological activities/ Aksenov et al. reported a one-pot synthesis of isatins using ethyl nitroacetate with substituted benzenes such as anisole (159) in polyphosphoric acid fScheme 5.38)/ The process for isatin formation likely includes a hybrid between the Nef and Vilsmeier reactions of anisole 159 and nitro ester 160 to form the oxime intermediate 161, which then undergoes a Beckmann rearrangement to give the anilide 162. Subsequent intramolecular acylation yields isatin 163. 

The indeno[l,2-Z)]thiophene 27 was converted to 2-phenyl-4F7-indeno[l,2- )]thiophene-4-one oxime 28 by reaction with hydroxylamine in the presence of sodium acetate, which underwent the Beckmann rearrangement upon treatment with polyphosphoric acid to give 2-phenylthieno[3,2-c]quinoline-4(5/f)one 29. ... 

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