Beckmann rearrangement 356 Subject

The previous referred inconveniences have prompted an increasing interest in the development of alternative, essentially neutral and more environmental-friendly catalysts to promote the rearrangement of O-unsubstituted oximes. The development of highly efficient and selective transformations and also of processes for catalyst recovery and its reuse are the aim of some of the more recent studies. Much of this work is being done in industry to improve current production processes and is the subject of new patent applications. During the last two decades environment concerns have led to the development of green, simple and cost-effective catalytic systems for the Beckmann rearrangement. 

The same strategy had application in several other heterocyclic compounds, to obtain either amine or carboxylic acid derivatives. A process for the production of 4-amino-5-methylpyrazole derivative 325 using the Beckmann rearrangement as a key step was the subject of a new patent ° (equation 119). 

Pollini and colleagues converted D(—)-quinic acid in five steps into a chiral oxime 395, R = H in an enantiomeric pure form and subjected this oxime to a Beckmann rearrangement (equation 161). Even though the reaction lacked selectivity, 395 was useful in the synthesis of the chiral epoxide 396, a key intermediate in the synthesis of (—)-Balanol 397. The same authors also prepared the isomeric epoxide 398. 

Later the estrone produced for commercial purposes was obtained from diosgenin. Diosgenin was first oxidized to its l,4,6-triene-3-one derivative, which was aromatized by pyrolysis at 500-600°C,50 subjected to the Marker degradation and the 17-acetyl group removed by Beckmann rearrangement of the 20-oxime. The overall Syntex process51 for the manufacture of Norethindrone from diosgenin (XVIII) is outlined in Scheme 5. 

J.D. White et al. reported the total synthesis of ( )-ibogamine via the catalytic asymmetric Diels-Alder reaction of benzoquinone. The azatricyclic framework of the molecule was established by converting the bicyclic ketone to the anti oxime and then subjecting it to a Beckmann rearrangement in the presence of p-toluenesulfonyl chloride to afford the 7-membered lactam. Elaboration of this lactam into the azatricyclic core of ibogamine and later to the natural product itself was accomplished in a few additional steps. 

The conventional process (Figure 2.32a) involves the reaction of cyclohexanone tvith hydroxylamine sulfate (or another salt), producing cyclohexanone oxime that is subjected to the Beckmann rearrangement in the presence of stoichiometric amounts of sulfuric acid or oleum. The overall process generates about 4.5 kg of ammonium sulfate per kg of caprolactam, divided roughly equally over the two steps. The Sumitomo process (Figure 2.32b) instead produces virtually no waste and allows caprolactam to be obtained in >98% yield (based on cyclohexanone 93% based on FI2O2). 

After separation, the oxime hydrochloride is subjected to the Beckmann rearrangement in the presence of oleum ... 

The active site for the Beckmann rearrangement is still the subject of controversy. What is the acid strength suitable for lactam production-strong, weak or intermediate It has even been suggested that neutral sites are responsible for the rearrangement. For the zeolite catalysts, does the reaction occur inside the pore or on the external surface If the reaction occurs on the external surface, what is the role of the zeolite structure ... 

Intramolecular rearrangements of polymers with ketone groups were subjects of several studies. The Schmidt and Beckmann rearrangements were carried out on copolymers of ethylene and carbon... 

In the traditional approach to s-caprolactam (Fig. 15.2), cyclohexanone reacts with hydroxylamine sulfate to obtain cyclohexanone oxime. The latter is then subjected to an oleum-catalyzed Beckmann rearrangement, affording the desired g-caprolactam. This complex approach is penalized by its complexity, the necessity to avoid emissions of nitrous oxides (NOx) and sulfur oxides (SOx), and mainly by... 

Usually, the cyclohexanone intermediate is made from the oxidation of cyclohexane. However, cyclohexanone is also made from phenol (Honeywell) or toluene (BASF, DSM). With the new processes, ammonia is oxidized to nitrous oxide (NjO), which is hydrogenated in the presence of sulfuric acid into hydroxylamine sulfate, which in turn is reacted with cyclohexanone to form cyclohexanone oxime. This chemical product is subjected to a Beckmann rearrangement with oleum to produce caprolactam. 

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