Nitrilium ions rearrangement

The main intermediate of the rearrangement may be a nitrilium ion (225) in some cases or an imidate (226) in others. The resulting intermediate reacts with water to produce the amide (218) after tautomerization. If other nucleophiles (Nu ) are present, they can intercept the reactive intermediates (both inter- or intra-molecularly) and several different imino-substituted derivatives (227) can be formed. These rearrangement-addition reactions will be analysed later in this chapter as they can effectively broaden the scope of the Beckmann rearrangement reaction (Sections VI.D.2 and VI.E.2). 

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. 

The formation of a very electrophilic intermediate 258 from 256 and 257 is proposed (equation 78). The hydroxyl group of the oxime adds to 259, giving a reactive cationic species 260 that rearranges and affords the nitrile 261 (in the case of aldoxime, equation 79), or the amide 262 upon hydrolytic workup (equation 80). The conversion of 260 to the nitrilium ion should occur through a concerted [1,2]-intramolecular shift. This procedure can be applied in the conversion of aldoximes to nitriles. It was observed that the stereochemistry of the ketoximes has little effect on the reaction, this fact being explained by the E-Z isomerization of the oxime isomers under the reaction conditions. 

Rearrangement of 273 with simultaneous loss of triphenylphosphine oxide 274 produces the intermediate nitrilium ion 225 that affords the corresponding amide 218. Aldoximes are easily converted to their corresponding nitriles 219 under the same reaction conditions. 

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 ... 

The Beckmann rearrangement of cyclic oximes results in lactams. This is exemplified in Figure 14.42 with the generation of e-caprolactam, the monomer of nylon-6. The nitrilium ion... 

The Beckmann rearrangement of cyclic oximes results in lactams. This is exemplified in Figure 11.38 with the generation of e-caprolactam, the monomer of nylon-6. The nitrilium ion intermediate cannot adopt the preferred linear structure because it is embedded in a seven-membered ring. Therefore, in this case the intermediate might better be described as the resonance hybride of the resonance forms A (C=N+ triple bond) and B (C+=N double bond). The C,N multiple bond in this intermediate resembles the bond between the two C atoms in benzyne that do not carry H atoms. 

Nitrilium ions are generally indicated as discrete intermediates in the Beckmann rearrangement of oximes (equation 37, Y = OH2) and in the Schmidt rearrangement (equation 37, Y = N2) of ketones and aldehydes with hydrogen azide. The first stage of these reactions has been defined as an ionization by rearrangement process through a transition state of type 183 (Smith, 1963). 

However, a considerable difference should be noted between a-hydroxyalkyl nitrilium ions 24 which contain an intramolecular nucleophilic center (OH group), and N-alkylnitrilium ions 26 which are the intermediates of a Ritter reaction45. The transformation of ions 24 into the N-acyliminium ions 25 (equation 11) is evidently an intramolecular rearrangement (see Sections V.B and V.C), while the nitrilium salts 26 can be converted into ions 25 only by an oxidative dehydrogenation of amides 273 (equation 12). 

Jochims and coworkers48 138 139 cf equations 79, 80 and 84) as well as Lukyanov and colleagues49 cf equation 15) suggested that oxazetium salts like 344 and 346 are intermediates (or transition states) in these rearrangements. However, at the same time the opinion was advanced137 that the conversions of both nitrilium ions 285 and carboxonium ones 288 into A-acyliminium cations 289 are a second type of acid-catalyzed rearrangement of carbonyl compounds. 

The Beckmann rearrangement is one of the typical reactions of oxime derivatives and the N-substituted nitrilium ion intermediates have been widely exploited as synthetic intermediates for the preparation of nitrogen-containing heterocycles, " while few examples have been reported for the nucleophilic substitution on the sp nitrogen atom of oximes. Even though, in some of them, carbon-nitrogen bond formation is realized, these reactions have not been well generalized as synthetic tools. ... 

The mechanism leading to adduct G presents clear analogies with that of the well established Ugi MCR, in which the isocyanide attacks the electrophilic carbon of an iminium ion for this reason, this process could be called the Ugi-Reissert reaction (Scheme 31). However, in this transformation, the adduct arises after a final hydration of the nitrilium ion, instead of undergoing the Mumm rearrangement as in the traditional Ugi reaction [188]. The novelty here lies in the use of M-acylazinium salts as a new source of reactive iminium ions for Ugi-type processes. 

If the rearrangement of oxime sulfonates is induced by organoaluminum reagents,the nitrilium ion intermediate 82 is captured by the nucleophile originally attached to the Al. By this means an oxime can be converted to an imine, an imino thioether (R-N=C-SR), or an imino nitrile (R-N=C-CN). " In the last case, the nucleophile comes from added trimethylsilyl cyanide. The imine-producing reaction can also be accomplished with a Grignard reagent in benzene or toluene. " ... 

One synthetically interesting development in the Beckmann rearrangement is the trapping of the intermediate nitrilium ion with heteroatom nucleophiles other than water, since the resulting imine derivatives may be further manipulated into various amine derivatives. 

---