Migration to Electron-Deficient Nitrogen

FIGURE 18.15 Reaction of the norbornyl cation with acetate. 

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Another important reaction involving migration to electron-deficient nitrogen is the Beckmann rearrangement, in which oximes are converted to amides.282... 

Another important reaction involving migration to electron-deficient nitrogen is the... 

Our consideration of rearrangements to electron-deficient heteroatoms must be brief. In discussing migrations to electron-deficient nitrogen, we first discuss three rearrangements that occur in carbonyl derivatives, the Beckmann, Hofmann, and Schmidt rearrangements, and then consider rearrangements of nitrenium ions. 

Rearrangement of NJV-dilmloanunesf N,N-Dichloro-tri-n-butylcarbinamine (2), prepared by treatment of tri-n-butylcarbinamine (I) with calcium hypochlorite, when treated with aluminum chloride in methylene chloride at - 30°, followed by acid hydrolysis, gives di-n-butyl ketone (3) and n-butylaminc (4) in high yield. The reaction is considered to involve alkyl migration to electron-deficient nitrogen. 

Hofmann rearrangement. Migration to electron-deficient nitrogen... 

We have depicted the pinacol rearrangement as a two-step process with an actual carbonium ion as intermediate. There is good evidence that this is so, at least when a tertiary or benzylic cation can be formed. Evidently the stability of the incipient cation in the transition state permits (SNl-lihe) loss of water without anchimeric assistance from the migrating group. This is, we note, in contrast to what happens in migration to electron-deficient nitrogen or oxygen. 

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. One of the most useful of these reactions is the Curtius rearrangement 16 This reaction has the same relationship to acylnitrene intermediates that the Wolff rearrangement does to acylcar-benes. The initial product is an isocyanate, which can be isolated or trapped by a nucleophilic solvent. 

Rearrangements to Electron-Deficient Nitrogen and Oxygen Centers Migration of an alkyl group was discussed in Section 6.2.1.2. The well-known... 

Cinnamaldoxime 65 in the presence of different H-zeolites, K-10 montmorillonite clay, amorphous SiOT-AhOa and y-alumina underwent the Beckmann rearrangement via the migration of the awft-styiyl moiety to electron-deficient nitrogen followed by an intramolecular cyclization to afford the isoquinoline 66 as the major product. Cinnamonitrile 67 and cinnamaldehyde were obtained as minor products. 

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. 

The Wolff rearrangement has a close formal resemblance to the Hofmann and related reactions (p. 122), in which migration takes place to an electron-deficient nitrogen atom to form an isocyanate, RN=C=0, intermediate. 

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 ... 

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. 

The Hofmann rearrangement also involves a migration to an electron-deficient nitrogen. In this case, an amide is treated with Cl2 or Br2 in aqueous base, resulting in the formation of an amine with one less carbon. The original carbonyl carbon is lost as carbon dioxide. The mechanism is shown in Figure 22.7 and an example is provided by the following equation ... 

Nitrenes, like carbenes, are immensely reactive and electrophilic, and the same Wolff-style migration takes place to give an isocyanate. The substituent R migrates from carbon to the electron-deficient nitrogen atom of the nitrene. Isocyanates are unstable to hydrolysis attack by water on the carbonyl group gives a carbamic acid which decomposes to an amine. 

Methoxy-N-chloromorphinan may be prepared in 78% yield by treatment of 3-methoxymorphinan with sodium hypochlorate.(139) Upon silver ion catalyzed rearrangement, it gave 13% of 146. The alkyl migration to the electron-deficient nitrogen was proposed as being mediated by a nitrenium ion transition state (145). 

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