ANRORC mechanism heterocycles

In certain cases, the SrnI mechanism has been found (p. 856). When the substrate is a heterocyclic aromatic nitrogen compound, still a different mechanism [the Sn(ANRORC) mechanism], involving opening and reclosing of the aromatic ring, has been shown to take place. 

In the 1,2,4-triazole series, base-induced degenerate rearrangements have been reported with the aroylarylazo-l,2,4-triazolium salts 185 (87MI3) (Scheme IV.72). The reaction product is 3-aroyl-l-aryl-1,2,4-triazole 187, and its formation can be described as involving an ANRORC mechanism, initiated by an addition of the nucleophile at C-5, ring opening into 186, and subsequent heterocyclization with the former CNN side chain of the rearranging 1,2,4-triazole. 

There are two important general types of reaction by which six-membered heterocycles containing two or more heteroatoms can be transformed into other six-membered heterocyclic systems, namely reactions which involve an ANRORC mechanism, and reactions which proceed by a Diels-Alder/retro-Diels-Alder type of mechanism. Transformation of 1,3-oxazinones and -thiazinones into pyrimidones (equations 193 and 194) has been extensively used, especially in the conversion of isatoic anhydride into quinazolinones (e.g. equation 195). 2,4-Diaryl-l,2,3,5-oxathiadiazines, which are readily accessible by reaction of sulfur trioxide with aryl isocyanates, are useful precursors to pyrimidines and 1,3,5-triazines (equation 196). 

One of the most important reactions of TAs is their transformation into pyrimidin-4-ones, which proceeds under the action of ammonia and amines according to the ANRORC mechanism. For thiazinones 39 it was suggested (81H851) that the first step is a nucleophilic addition of ammonia to the 2 position of the heterocyclic ring (Scheme 91). 

The first ring-degenerate transformation in heterocyclic chemistry was discovered in 1898 by E. Fischer, who found that treatment of 2-chloro-7-methyladenine with base does not yield the expected 7-methylisoguanine but 7-methylguanine (6). This can undoubtedly be considered as a ring-degenerate transformation by a nucleophilic displacement according to a S ,(ANRORC) mechanism. 

The elegant work of H. C. van der Plas and colleagues provides proof that the Sn(ANRORC) mechanism (addition of the nucleophile to the heterocycle, ring opening, and ring closure) operates in some Chichibabin reactions under homogeneous conditions (85T237). 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

Dehydroheteroarenes like (10) and (11) have also been proposed as intermediates in nucleophilic substitution.23-25 Some of these reactions were evaluated uncritically and operation of other mechanisms like addition-elimination (AE) and ring opening-ring closure (ANRORC) can now be demonstrated in many such cases. Nevertheless, there is conclusive evidence for heteroaryne intermediacy in some reactions of heterocyclic halides. From the preparative point of view, nucleophilic coupling of such intermediates has found only limited applications.26-28 Reactive intermediates with an additional formal bond between nonadjacent atoms, like (12) and (13), have also been postulated but again hold little synthetic interest. 

The second mechanism is an Sn(ANRORC)—addition of nucleophile to the heterocycle, ring opening and ring closure. It was proposed by and heavily investigated and reviewed by H. C. Van der Plas and co-workers as a possible mechanism for some Chichibabin amination cases under homogenous conditions. The hypothesis comes from his extensive... 

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