Beckmann reaction pathway

Unlike the Beckmann rearrangement, the outcome of the Neber rearrangement does not depend on the configuration of the starting oxime derivative E- as well as Z-oxime yield the same product. If the starting oxime derivative contains two different a-methylene groups, the reaction pathway is not determined by the configuration of the oxime, but rather by the relative acidity of the a-methylene protons the more acidic proton is abstracted preferentially. ... 

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 synthetic uses of hydrazones and oximes for carbon-bond formation differ little from those of imines as their anions represent enolate equivalents except for certain methods that have been developed for asymmetric induction. Conversely, the formal replacement of the carbon substituent of imines by a heteroatom (nitrogen for hydrazones and oxygen for imines) opens reaction pathways such as the Beckmann rearrangement of oximes and the Wolff-Kishner and Shapiro reductions of hydrazones that have no analogy in the chemistry of imines. 

When the Beckmann reaction was performed with mesylated oxime intermediate 113, lactam 112, from the Beckmann rearrangement, was obtained as the sole product tScheme 5.261. thus shutting down the Beckmann fragmentation pathway.This reaction is similar to what White and coworkers observed during their morphine synthesis. Beckmann reaction of an intermediate brosylated oxime in acetic acid provided the desired lactam, whereas the reaction of the corresponding oxime under acidic conditions did not yield any lactam... 

Several pathways may be possible for the Beckmann fragmentation reaction (equations 68 and 69). Stepwise processes may occur (equation 68), but stereospecific concerted fragmentations are also common (equation 69). Stepwise processes may follow different routes, but in most cases the fragmentation may have the same intermediate as the Beckmann rearrangement the nitrilium ion. 

A simplified mechanism for the Beckmann rearrangements and important related reactions is shown hi Scheme 9. Summarizing the mechanism section, the key step of the reaction is the migration of an a-carbon group to the electronically deficient nitrogen atom of the oxime. A nitrilium ion in some cases or an imidate in others are key intermediates in the reaction. Their destiny determines the course of the transformation. Basically, three different pathways may be possible and can be synthetically exploited ... 

Water attack on the electrophihc carbon to produce an amide after tautomerization this reaction is the classical Beckmann rearrangement (Scheme 9, pathway 1). 

The intermediate may be trapped by other nucleophiles (different from water) and diverse products may be obtained. The interception of the intermediate may occur inter- or intra-moleculary, the latter providing a helpful tool to produce a new ring system (Scheme 9, pathway 2). These reactions are sometimes referred to, respectively, as Beckmann rearrangement-addition and Beckmann rearrangement-cyclization reactions. 

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. 

In strong acids, or when treated with reagents such as thionyl chloride or phosphorus pentachloride, an oxime will react to give a rearranged amide. This is known as the Beckmann rearrangement. When the reaction gives products other than amides, these products are referred to as abnormal products. One such abnormal pathway is illustrated in Problem 4.14. 

The first photochemical Beckmann rearrangement of aromatic aldoximes was reported in 1963. Subsequently, cyclohexanone oxime was shown to rearrange, upon photolysis, to caprolactam. Although the presence of oxaziridines in the solutions of photolyzed oximes was demonstrated, no oxaziridines have been isolated from these reaction mixtures presumably because of the general instability of oxaziridines that have no substituents on the ring nitrogen. The qualitative results are consistent with the intermediacy of oxaziridines in the photolysis of oximes to amides, yet the possibility of the reactions following other pathways cannot be ruled out. ... 

Further study of the photo-Beckmann rearrangement of oximes suggests that the reaction occurs by way of a concerted pathway from an excited singlet oxaziridine intermediate.84 Thus, in the rearrangement of syn- or anti-5jS-cholestan-6-one oximes (107), which are photochemically interconvertible, the original configuration at C-5 is retained in both lactam products (108) and (109). 

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