Amines ANRORC reaction

Briel et al. (90GEP282011) describe the transformation of thieno[3,2-d]-l,3-oxazin-4-ones 361 into thieno[3,4-d]pyrimidines 362 by heating with ammonia saturated DMF or with primary amines. This transformation is an example of an ANRORC reaction. 

Katritzky converted pyrylium salts 44 (formed from the reaction of enone 42 and ethyl pyruvate 43) to the corresponding pyridiniums (45) via ANRORC reaction with a primary amines. This strategy serves as an alternative to the Zincke-Konig method for the formation of substituted pyridinium salts. 

An important consequence of these results is that the overall amination process (37 to 39 ), which at first sight seems to follow a classical Sn(AE) pathway, is thus in fact a meta telesubstitution. This aminodehalogenation is one of the few reactions known that has proved to involve an Sn (ANRORC) mechanism, but that cannot be described as a degenerate ring... 

The reaction is one of the few examples of a degenerate ring transformation in pyrazine chemistry. Extensive investigations on the amination of 2-chloroquinoxaline have shown that in the formation of the 2-amino compound no Sn(ANRORC) process is involved (72RTC850). 

Comparison of this reactivity order with that found in the amination of 2-X-4-phenyl pyrimidines (SCH3 Br = Cl > F > SO2CH3 I > (013)3 > CN see Table 11.5 in Section ll,C,l,d) shows that these reactivity orders differ considerably. The fluoro substituent, especially, which has in the pyrimidine series about the same reactivity order as the chloro or bromo atom, shows in the 1,2,4-triazine series a low ANRORC activity. Comparison of both series of reactivities is, however, a delicate matter, mainly because the yields obtained for the amino compounds in the 1,2,4-triazine series are much lower than those obtained in the pyrimidine series, because of the occurrence of many side reactions, such as ring contraction, dehalogenation, ring transformations, and degenerate ring transformations... 

Only Sn(AE) and Sn(ANRORC) mechanisms require the formation of anionic ff-adducts. A great deal of attention has been paid to the correlation of the formation of these adducts with the mechanism of amination. However, inasmuch as a detailed account of the latter reaction is outside the scope of this chapter, we report only a few typical sequences proposed in the literature and suggest that the reader gain more information on this point from the outstanding work by van der Plas and his group. 

Diphenyl-l,3,5-triazine undergoes a Chichibabin-type amination reaction, the first example of this reaction to be reported for the 1,3,5-triazines. The 2-methylthio derivative (37 X = MeS) reacts exclusively via an Sn(ANRORC) mechanism rather than the SNAE mechanism (Scheme 21) (76RTC113). 

Phenyl-l,3,5-triazine has fewer sterically hindered positions of attack, and therefore can undergo amination by an Sjv(ANRORC) process. Indeed, Simig and van der Plas investigated the reaction by 1H NMR and showed that it does occur partially (ca. 55%) by this mechanism (76RTC125). 

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). 

Simig, G., Van der Plas, H. C. The SN(ANRORC) mechanism. XVII. An SN(ANRORC) mechanism in the amination of phenyl-1,3,5-triazine with potassium amide in liquid ammonia. A novel mechanism for the Chichibabin reaction. Red. Trav. Chim. Pays-Bas 1976, 95,125-126. 

Many aminations at C-3 have been found to occur via addition at C-5. Ring opening and ring closure constitute such reactions, which occur according to the Sn(ANRORC) mechanism. These reactions feature a so-called ring degenerate transformation (85T237), and will be dealt with in Section VI,A. 

Reaction of nucleophiles with 1,3,5-triazines usually results in ring cleavage. Substitution reactions of the parent system (271) have been limited to the Chichibabin amination, which provides 272, and the preparation of alkyltriazines 273 via an Sn (ANRORC) alkylation (84M16). 

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