Beckmann degradation

Keto steroids can be obtained in excellent yields via the Beckmann degradation of 17a-hydroxy-or 16a,17a-epoxy-20-ketopregnanes. In the case of the 17-hydroxy compounds, substituents at C-16 readily survive e.g., 16 -Br, 16jS-Cl, Iba-OAc). The 16,17-oxido-20-oximinopregnanes produce 16a-acetoxy-17-ketones. 

Examples of Beckmann degradation reactions with assistance by mesomeric donation of electron lone pairs (example Y = N, O, S) or n electrons (example R = Ph or aromatic group) are well documented in the literature ... 

New azacyclic diterpenoid compounds were also prepared in good yields by ring expansion and only one isomer of the lactam 363 product was obtained (equation 142). However, when the oxime was tosylated, a nitrile compound resulting from ring opening was obtained in good yield (72%) as a result of the Beckmann degradation reaction. 

The ready availability and low cost of A -20-keto steroids from the degradation of sapogenins has led to intensive study of methods for the preparation of androstanes via these intermediates. The simplest, most practical and most widely used method on a production scale is the Beckmann rearrangement of -20-oximinopregnenes ... 

A diazodiphenoquinone is also produced as a chemical artifact (Knackmuss and Beckmann 1973). There are, however, a nnmber of unresolved features of the degradation, including the mechanisms for production of 2,6-dihydroxypyridine and oxidative fission of the pyridine ring. 

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. 

Gates and Malchick utilized the Beckmann rearrangement for their purposes (Scheme 24).217) When the Hofmann degradation of 142 and 143, followed by catalytic dehydrogenation over 5 % palladium on asbestos at 300—310 °C, afforded not 1-vinylpentalene but azulene, the workers concluded that the former was thermodynamically unstable relative to the latter. 

The configuration of the oxime is important to the course of the reaction. Thus, while the j8-oxime (11) gives the indoxazene or its degradation products, the a-oxime (12) undergoes a Beckmann rearrangement, finally yielding benzoxazole (13). This difference in reaction pathway between stereoisomeric oximes was used in the determination of their configurations.7,8 22,23... 

The first 34 residues of human parathyroid hormone (PTH) [190] were identified from the Cl mass spectra of their phenylthiohydantoin derivatives by repeated Edman degradations on a Beckmann Sequencer [163]. In a similar way as part of the characterisation of ovine hypothalmic luteinizing hormone-releasing factor (LRF), the trimethylsilyi derivatives of the phenylthiohydantoins from Edman degradation were confirmed by MS [191]. 

Schopf sought to obtain direct evidence for the location of the side-chain at C-13 by subjecting dihydrocodeinone oxime to a Beckmann transformation, when, if the side-chain is located at C-13 [liv], an aldehyde [lv] would be the product, whereas if the point of attachment is C-14 [lvi] a ketone [lvii] would be formed. Neither the oxime nor its methyl ether yielded the desired proof directly, and it was only after a sequence of further degradations that the conclusion was drawn that the product was [lv], indicating C-13 as the point of attachment of the side-chain [85] (see Chap. X). 

Beckmann rearrangement of the oxime (59), prepared from (56), gives the two amines (60). Ruschig degradation" (treatment of the iV-chloro-derivative with NaOMe) gives the nitriles (61). 

Here again, these thiophene derivatives are much less stable than their benzenoid counterparts, unless the ring is provided with other substitution. " The unsubstituted amino-thiophenes (thiophenamines) can be obtained by reduction of the nitro-thiophenes, "" but in such a way as to isolate them as salts - usually hexachlorostannates - or via Beckmann rearrangements " or Hofmann degradation, " as acyl-derivatives, which are stable. 3,4-Dinitration of 2,5-dibromothiophene, then reduction, produces 3,4-diaminothio-phene. " " Many substituted amines have been prepared by nucleophilic displacement of halogen in nitro-halo-thiophenes. In so far as it can be studied, in simple cases, and certainly in substituted amino-thiophenes the amino form is the only detectable tautomer. " ... 

Further work has been described on the formation of aza-steroids by the cyclisation of methine bases obtained by Hofmann degradation of perhydro-azepines. Thus, Beckmann rearrangement of the cholestan-3-, -4-, -6-, and -7-one oximes followed by lithium aluminium hydride reduction afforded the 4- and... 

Of special interest are the methods which serve for the degradation of the ketones to derivatives of homomeroquinene (XXXIX). The Beckmann rearrangement of the toxine oximes (XL) proceeds in both... 

Phosphorus oxide chloride pyridine Ketones from a>hydroxyoximes Degradation by Beckmann rearrangement... 

---