ANRORC Addition of Nucleophile, Ring

ANRORC addition of nucleophile, ring opening and ring closure... 

Another stimulating transformation of benzylamines to benzyl iodides is based on the smooth ANRORC (Addition of Nucleophile, Ring Opening and Ring Closure) reaction of the former with 4,6-diphenylpyran-2-thione followed by quaternization with methyl iodide and thermal decomposition (equation 174)1097. 

An apparent exception to the relative unreactivity of 3-halo-isoquinolines is provided by the reaction of 3-bromoisoquinoline with sodium amide. Here, a different mechanism, known by the acronym ANRORC (Addition of Nucleophile, Ring Opening and Ring Closure), leads to the product, apparently of direct displacement, but in which a switching of the ring nitrogen to become the substituent nitrogen, has occurred. 

The recyclization of monocyclic pyrylium salts % occurs in accordance with the addition of nucleophile-ring opening-ring closure (ANRORC) mechanism (78ACR462) which starts with the a-addition of the nucleophile2 (Scheme 4). 

Just as in aryl halides, the halogen can be replaced by hydrogen and by a metal, or be involved in transition metal-catalyzed processes (covered in Section 3.2.3.11.2). Three of the mechanisms of such nucleophilic substitutions are familiar from benzene chemistry via arynes, SrnI processes, and Pd(0)-catalyzed sequences. However, of the two further mechanisms of nucleophilic replacement, the ANRORC (Addition of Micleophile, Ring Opening, Ring Closure) is unique to heterocycles, and Sae reactions occur only with strongly activated benzenoid systems. 

The reaction of strongly basic amide anions, R -N-R, with chloro- or bromopyridines, -pyrimidines, and other heterocycles can lead to ring opening and subsequent ring closure to result in substituted amino-N-heterocycles (addition of nucleophile, ring opening, ring closure = ANRORC). 

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... 

As indicated in CHEC-II <1996CHEC-II(7)431 >, displacement of a good leaving substituent by a nucleophile is readily accomplished. In several cases, ring opening and recyclization in an ANRORC mode (addition of nucleophile by ring opening and recyclization) occurs. 

A final nonaryne mechanism of cine-substitution is also based on the tendency of certain heteroaromatic compounds to add nucleophiles. Instead of elimination (AEa mechanism) or substitution followed by elimination (ASE mechanism), however, the initial addition product 134 undergoes a sequence of ring opening to 135, elimination to 136, and ring closure to 137. This variation of the ANRORC mechanism of nucleophilic aromatic substitution was recently proposed to explain at least part of the cine-amination of 4-substituted-5-halopyrimidines (138) previously thought to proceed via an aryne 139. 

ANRORC Addition of the nucleophile, ring opening, and ring closure in... 

With [ N2]hydrazinium hydrogen sulfate and potassium hydroxide, the 2, 3, 5 -tri-0-acetyl-l-( N-amino) (3- N) inosine 54 is obtained (Scheme III.29). The reaction follows the same reaction pathway as described in Scheme III.28 addition of the nucleophile at C-6, ring opening between C(6) and N(l), and ring closure with elimination of nitrous oxide and water. This Sn(ANRORC) reaction provides us with an good entry to N-ring-labeled purines. 

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