Nitrilium ions cyclization

Ring closures based upon electrophilic processes are uncommon. The cationic cyclization in Scheme 29a proceeds via transformation of the commencing oxime into a nitrilium ion (81CC568). Schemes 29b (82CB706) and 29c (82CB714) exemplify the application of intramolecular acylation. 

The protonated azirine system has also been utilized for the synthesis of heterocyclic compounds (67JA44S6). Thus, treatment of (199) with anhydrous perchloric acid and acetone or acetonitrile gave the oxazolinium perchlorate (207) and the imidazolinium perchlorate (209), respectively. The mechanism of these reactions involves 1,3-bond cleavage of the protonated azirine and reaction with the carbonyl group (or nitrile) to produce a resonance-stabilized carbonium-oxonium ion (or carbonium-nitrilium ion), followed by attack of the nitrogen unshared pair jf electrons to complete the cyclization. 

Pschorr cyclization of diazotized A-mesyl-o-aminodiphenylamine yields A-mesyl-5,7-dihydro-6H-dibenz[c,e]azepine (73AJC1307). Diazonium compounds also feature in the preparation of 1 lH-dibenz[6,e]azepines via nitrilium ions (Scheme 21) (72CB1634), and in the only synthesis reported so far of a tribenz[6,rf,/]azepine (10 R=Ph) (72CB880). 

The more common process commences in the normal way, with addition of nitrile and carbenium ion generating a nitrilium species. However, the latter now undergoes intramolecular cyclization with a nucleophilic group in the same molecule to produce a heterocycle of structure (37 Scheme 15). The less common reaction involves initial intramolecular formation of a cyclic nitrilium ion which is then quenched by an external nucleophile, giving products of type (38). 

Reaction of aryl nitrilium ions (40) or imidoyl chlorides (41) with benzonitrile produced the nitrilium species (42), which underwent Friedel-Crafts reaction yielding the quinazoline system (43 Scheme 17). Generation and cyclization of nitrilium species using Friedel-Crafts reagents has since found widespread favor in heteroaromatic synthesis and such procedures have been reviewed in detail. An illustration of its use for a nonbenzenoid aromatic system is given in equation (31). ... 

Other examples from this study indicate that the reaction path followed by the nitrilium ion depends very much on the nature of the nucleophiles present. Thus, the allylindole (106) produced the imidate (107) through reaction of the nitrilium ion wiA methanol in preference to the electron-rich heterocyclic system (equation 45). In contrast, alcohol (108) underwent effective intramolecular cyclization (equation 46). 

This reaction corresponds to the Bischler-Napieralski synthesis of isoquinoline (see p 343) and proceeds as an intramolecular S Ar process by way of nitrilium ions as intermediates. By an anlogous reaction, biphenyl-2-isocyanates 29, derived from 2-aminobiphenyl, on treatment with polyphosphoric acid, cyclize to yield phenanthridones 30. 

This process is similar to the Ritter reaction for the preparation of amines from nitriles and olefins. The first step is the regioselective formation of a carbenium ion from the diol 13 followed by addition to the nitrile. The resulting nitrilium ion 15, following attack on the remaining OH group, cyclizes and gives dihydro-1,3-oxazine 14. 

It is relevant to point out that Fodor and co-workers have shown that nitrilium cations are intermediates in the Bischler-Napieralski cyclization whenever secondary amides are used. A nitrilium ion was trapped as its crystalline hexafluoroantimonate salt. ... 

As a mechanistic rationale, LEwis-acid mediated nitrile N-alkylation (11 —> 12) could be the primary step the nitrilium ion 12 undergoes cyclization via the hydrazone moiety to afford 1,3,5-trisubstituted 1,2,4-triazoles 13. 

The B-N reaction could have two other plausible mechanistic pathways. Path (a) involves the generation of a dichlorophosphoryl imine-ester intermediate, which upon cyclization, leads to elimination with imine formation (Scheme 7) (07MI290). Path (b) includes the formation of a nitrilium ion intermediate followed by cyclization to dihydroisoquino-line (97JCS(P1)2217) (Scheme 8).This mechanistic deviation is due to the ambiguity over the timing for the elimination of the carbonyl oxygen in the amide precursor. Presently, it is often assumed that different conditions affect the predominance of one mechanism over the other. Under certain... 

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