Beckmann rearrangement intramolecularity

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

Zeolites have also been described as efficient catalysts for acylation,11 for the preparation of acetals,12 and proved to be useful for acetal hydrolysis13 or intramolecular lactonization of hydroxyalkanoic acids,14 to name a few examples of their application. A number of isomerizations and skeletal rearrangements promoted by these porous materials have also been reported. From these, we can underline two important industrial processes such as the isomerization of xylenes,2 and the Beckmann rearrangement of cyclohexanone oxime to e-caprolactam,15 which is an intermediate for polyamide manufacture. Other applications include the conversion of n-butane to isobutane,16 Fries rearrangement of phenyl esters,17 or the rearrangement of epoxides to carbonyl compounds.18... 

Beckmann rearrangement org chem An intramolecular change of a ketoxime into its isomeric amide when treated with phosphorus pentachloride. bek-man re-g ranj-mont ... 

When the nucleophile is already present as a part of the starting oxime (for example, a heteroatom or a C=C double bond), intramolecular trapping of the electrophilic intermediate is possible and a new cycle is formed. This transformation is usually referred to as a Beckmann Rearrangement-Cychzation reaction. Two modes of ring closure may be possible, depending on the oxime structure (equations 111 and 112) ... 

One of the most famous examples of intramolecular attack of oxygen on the nitriUnm ion intermediate was observed in the Beckmann rearrangement of Erythromycin oxime derivatives and was used in the discovery and synthesis of the commercial macrolide antibiotic Azithromycin 464. In fact, the Beckmann rearrangement of Erythromycin A 9( )-oxime 460 produced only small amounts (5%) of the expected amide 463, along with two isomeric imino ethers (461 and 462) in a fair yield (38 and 43%) (equation 198). 

Narasaka has utilized a Heck-type intramolecular aminopalladation of the olefinic moiety of r,5-unsaturated ketone 0-pentafluorobenzoyloximes 9 to afford 2,5-disubstituted pyrroles 10 (R = CH3, C02Et) <99CL45>. The use of the O-pentafluorobenzoyl group was found necessary to preclude competing Beckmann rearrangements. 

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. 

Intramolecular rearrangements provide dramatic evidence to the inadequacy of the theories of directed valence bonds. The Beckmann rearrangement of ketoximes into acid amides, represented by the scheme ... 

This surprising result was reported by B. Amit and A. Hassner, Synthesis, 1978, 932. The expected reaction was the Beckmann rearrangement (Chapter 37) but what actually happened was a Beckmann fragmentation (Chapter 38) followed by an intramolecular FriedetCrafts alkylation (Chapter 22). 

In the laboratory of J.D. White, the asymmetric total synthesis of the non-natural (+)-codelne was accomplished via intramolecular carbenoid insertion In the late stages of the total synthesis It was necessary to Install a 6-membered piperidine moiety. This transformation was accomplished utilizing a Beckmann rearrangement of the cyclopentanone oxime portion of one of the intermediates. Later the 6-membered lactam was reduced to the corresponding amine with LAH. To this end, an oxime brosylate (Bs) was prepared, which underwent a smooth Beckmann rearrangement in acetic acid to provide a 69% yield of two isomeric lactams in an 11 1 ratio in favor of the desired isomer. 

With dimethylacetylene dicarboxylate (DMAD) 1-acylimidazoles form novel functionalized derivatives as a consequence of electrophilic attack on the pyridine nitrogen followed by intramolecular transacylation (Scheme 112) <88CC1151,90JCS(P1)1821,92CB1939>. Ketoximes undergo Beckmann rearrangement and primary carboxamides are dehydrated to nitriles on treatment with (170)... 

Several structural modifications of the C-9 ketone of erythromycin have been explored oximes and hydrazones are less prone to intramolecular cydization, but they often have less antibiotic activity than erythromycin (140). Synthesis of more complex oxime derivatives resulted in the development of roxithromycin, the 9-[0-(2-methoxyethoxy)methyl]oxime (33) (141). Reduction of the oximes and hydrazones produced 9(S)-erythromycylamine (34) as the principal product, with minor amounts of the 9(R)-isomer (140) however, clinical studies showed that 9(5)-erythromycyclamine and its N-benzylidene derivative were poody absorbed in humans (142). Evaluation of more complex oxazine derivatives of erythromycylamine led to dirithromycin, the 2-(2-methoxyethoxy)ethylidene oxazine derivative (35) (143). A third route to modification of the ketone utilized a Beckmann rearrangement of the 9-oxime to expand the 14-membered ring to a 15-membered intermediate, which was subsequently reduced and AT-methylated to yield azithromycin (36) (144,145). The term azalide was proposed to denote these 15-membered azalactones (10,145). 

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