Beckmann-like rearrangement

Beckmann like rearrangements have not been extensively explored but should translate this spiroannulation into a y-butyrolactam synthesis108). 

Nitrones (268), derived from ketones, undergo a Beckmann-like rearrangement when treated with tosyl chloride in pyridine. Unlike the Beckmann rearrangement, however, the reaction is independent of the nitrone configuration, and shows a preference for vinyl migration. The consequence, for a 4-en-3-one derivative, is the formation of the unusual enamine-lactam (270). The hydroxyl-amino-O-tosylate derivative (269) is considered a likely intermediate (see also Part II, Chap. 2, p. 353). 

Several other reactions of isatin derivatives will now be described. Isatin-2-oxime (93) underwent a Beckmann-like rearrangement to quinazoline-2,4-dione when heated with dilute sodium hydroxide (no yield given).107... 

The reaction likely proceeds through the oxime intermediate, which undergoes a metal-catalysed Beckmann-like rearrangement at 110 °C to form... 

The tetracyclic framework of homoberbine-like compound 210 was constructed by Beckmann rearrangement, reduction, and Pictet-Spengler cyclization (86JHC975). 

The most important route is the conversion of pyrimidines into 1,3,5-triazines. The first one-step transformation was effected by Taylor and Jefford (62JA3744) by heating the pyrimidine (179) with benzenesulfonyl chloride in pyridine (equation 106). The reaction may be considered as an example of an abnormal Beckmann rearrangement. The mechanism of the reaction of the 4-aminopyrimidine (180) is probably dependent on the nature of the 2-substituent (180, R). If R is an electron-releasing moiety, pathway B seems more likely (Scheme 109). The 4-hydroxypyrimidine (179 R = OH) behaves similarly. Many 2-cyano-1,3,5-triazines may be synthesized by this method. 

When the reaction is carried out in boiling DMSO, no significant gain in the yield of benzamide (30%) is observed. Since under these conditions the primary dehydration of aldoximes is evident, the formation of benzamide is most likely to result from hydration of the intermediate benzonitrile rather than by the Beckmann rearrangement scheme. 

A number of 1,4-diazocines have reacted to form imidazoles and fused-ring analogs. Beckmann rearrangement of the dioxime 171 yielded isoindolo-benzimidazole 172 (R = Cl, R = H) or 172 (R = H, R = Cl), most likely via rearrangement of an initially formed dichloro- 57 (57JCS1900). Dibenzo-diazocinedione 57, when heated with phosphorus pentachloride, afforded an... 

This reaction, like all Neber rearrangements, is limited by availability of the appropriate oxime tosylate. Substrates in which the aryl group contain an electron-donating function are unstable, since they have a propensity to undergo Beckmann rearrangement. However, this difficulty can be resolved by subsequent conversion of the a-amino acetals. For example, catalytic hydrogenation of 2,2-diethoxy-2-(p-bromophenyl)ethylaraine yields the known parent compound, 2,2-diethoxy-2-phenylethylamine These two a-amino acetals readily undergo hydrolysis and should be protected from moisture. 

CLXXXIII). The same series of reactions was subsequently applied to ethyl quininate (205), which fumiehed dihydroquinotoxine. Some twenty-five years later partial synthesis of quinotoxine itself was achieved in like manner by ProStenik and Prelog (90), who condensed ethyl quininate with -benzoylhomomeroquinene ethyl ester, derived by Beckmann rearrangement from iV-benzoylcinchotoxine oxime. 

Beckmann rearrangement provided the ring-expanded metallopyrazine imide 143, which showed metallochlorine-like optical properties. The demetallated derivative of 143 has a porphyrin-like optical spectrum In terms of further elaboration, the imide in 143 provides a functional group that can be derivatized. 

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. 

Usually, Beckmann rearrangement of oximes of ketones are converted into anilides by heating with acidic reagents like PCl, HCOOH, SOCI2 etc. However, solid-state Beckmann rearrangement has been reported. In this method oxime of a ketone is mixed with montmorillonite and irradiated for 7 min in a microwave oven to give corresponding anilide in 91% yield (Scheme 24). 

An integrated process, which combines catalytic EniChem TS-1, catalyzed direct ammoximation of cyclohexanone and Sumitomo Chemical vapour-phase Beckmann rearrangement, both exploiting MFI based zeolite-like materials, is now industrially used for greener caprolactam production from cyclohexanone without co-producing any ammonium sulfate (Fig. 15.2). ... 

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