Beckmann rearrangement trapping

Grignard reagents may themselves be used to induce the Beckmann rearrangement, trapping the reactive intermediate. A new and highly efficient one-step synthesis of 2-arylated 1-benzocines 440 by a Beckmann rearrangement was recently devised (equation 187). 

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. 

Various imidates 227 can be produced by trapping the electrophilic intermediate of the Beckmann rearrangement with a nucleophile (Nu ) other than water (equation 109). 

Pathway 2 of Scheme 9 corresponds to one of the most interesting developments in the Beckmann rearrangement chemistry. By trapping of the electrophilic intermediate with a nucleophile (Nu ) other than water, an imine derivative 227 is produced that may be used for further transformations. Carbon or heteroatom nucleophiles have been used to trap the nitrilium intermediate. Reducing agents promote the amine formation. More than one nucleophile may be added (for example, two different Grignard reagents can be introduced at the electrophilic carbon atom). Some of the most used transformations are condensed in Scheme 11. 

When the nucleophile is already present as a part of the starting oxime (for example, a heteroatom or a C=C double bond), intramolecular trapping of the electrophilic intermediate is possible and a new cycle is formed. This transformation is usually referred to as a Beckmann Rearrangement-Cychzation reaction. Two modes of ring closure may be possible, depending on the oxime structure (equations 111 and 112) ... 

Aromatic donble bonds may also be nsed effectively to trap the electrophilic intermediate (electrophilic aromatic snbstitntion). The Beckmann rearrangement-cyclization seqnence has fonnd ntihty in the synthesis of the isoquinoline nucleus . ... 

The electrophilic intermediate formed during the Beckmann rearrangement may be trapped by nucleophiles other than water. Strictly speaking, these reactions do not fit into the classical rearrangement reaction type. However, due to the fact that the carbon framework changes during the course of the reaction and to the similarities with the classical Beckmann rearrangement process, this topic will be analysed in the present chapter. 

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. 

The Beckmann rearrangement of oxime mesylates initiated by TiCU has been applied to the preparation of 1,2-dehydro-1-aminoalkylphosphonates, e.g. 201, through trapping of the intermediate with triethyl phosphite. Oximes of a-ketophosphonates are often difficult to reduce to the corresponding 1-aminoalk-... 

The vapour phase Beckmann rearrangement reaction was carried out using a continuous flow system operated at ambient pressure. Helium was used to entrain the oximes into the vapour phase from a saturator (2.2 torr). The rearrangement of the oxime took place in the u-tube pyrex reactor loaded with 100 mg of catalyst. In normal operation the total gas flow rate was 30 ml min. On leaving the reactor the gas stream was cooled, the products were trapped and analysed by off-line gas chromatography. 

Here is a more convincing example of the same fragmentation reaction the conditions, but not the results, are those of a Beckmann rearrangement. In this reaction, the ring structure means the cation cannot be trapped by the nitrile, and a fragmentation product is isolated. 

Trapping of the Beckmann Intermediate with Heteroatoms 43.13 Beckmann Rearrangement-rAlk ation Sequence... 

Generation of Electrophilic Cations. Complexation of Et2AlCl to ketones and aldehydes activates the carbonyl group toward addition of a nucleophilic alkyl- or allylstannane or allylsilane. Et2AlCl has been used to initiate Beckmann rearrangements of oxime mesylates. The ring-expanded cation can be trapped intermolecularly by enol ethers and cyanide and in-tramolecularly by alkenes (eq 5). ... 

EtAlCb catalyzes the Friedel-Crafts acylation of alkenes with acid chlorides, the formal [3 + 2] cycloaddition of alkenes with cyclopropane-1,1-dicarboxylates (eq 21), the Friedel-Crafts alkylation of anilines and indoles with ct-aminoacrylate esters, and the formation of allyl sulfoxides from sulfinyl chlorides and alkenes. EtAlCU induces the Beckmann rearrangement of oxime sulfonates. The cationic intermediates can be trapped with enol silyl ethers (eq 22). EtAlC is the preferred catalyst for addition of the cation derived from an a-chloro sulfide to an alkene to give a cation which undergoes a Friedel-Crafts alkylation (eq 23). ... 

---