Amination of Phenyl-1,3,5-triazine

The ANRORC mechanism was first observed upon amination of phenyl-1,3,5-triazine (26) with potassium amide in liquid ammonia (76RTC125). When 26 was treated with excess potassium amide in liquid ammonia at -33°C for 40 hr, a low yield (9%) of 4-amino-2-phenyl-l,3,5-triazine (27) 

---

Furthermore, it was pointed out that, whereas the formation of the amino adduct is fast and the formation of the product slow, it is possible that an equilibrium exists among the starting materials, their 1 1 a-amino adducts, and their open-chain amidines (Scheme 11.54). When this is the case, one may expect that, if the amination of phenyl-1,3,5-triazine is stopped before complete conversion, the retrieved starting material should be N-labeled. This has indeed been found. This behavior is in agreement with that observed with the Chichibabin amination of 4- and 5-phenylpyrimidine. 

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. 

Substituted triazines have been subjected to amination with potassium amide in liquid ammonia. With 2,4-diphenyl-l,3,5-triazine (260), treatment with potassium amide in liquid ammonia afforded a typical Chichibabin product, 2-amino-4,6-diphenyl-I,3,5-triazine (261) (Scheme 89) (76RTC 113). Through labeling experiments, it was established that the amination was not occurring via an Sn(ANRORC) mechanism, but rather by an Sn(AE) process. However, Sn(ANRORC) does occur during the amination of phenyl-1,3,5-triazine, and this has been elaborated upon in Section II,B,1. 

The examples shown are illustrative of the many easy nucleophilic additions to the polyaza-azines both 3-phenyl-l,2,4,5-tetrazine and 1,3,5-triazine itself add ammonia and simple amines (contrast the requirement for hot sodamide (Chichibabin reaction) for pyridine (8.3.1.2)) and thus amino and alkyamino derivatives can be obtained via oxidative trapping with permanganate. 

Oxidation of 4,6-diphenyl- or 4,6-bis(4-chlorophenyl)-l,3,5-triazin-2-amine with Caro s acid at a temperature below 5 °C gives 4-amino-6-phenyl- or 4-amino-6-(4-chlorophenyl)-l,3,5-triazin-2-ol 1,3,5-trioxide 1, respectively, in varying yields. The 4-cblorophenyl derivative, however, needs to be heated up to 18-20°C for 20 minutes. If the temperature during the oxidation reactions rises above 35 C, complete decomposition of the triazine is observed.1... 

The initial product 2 loses N2 in a retro-DiELS-Alder reaction forming the 3,4-dihydropyridine 3, which aromatizes giving the pyridine derivative 4 by elimination of amine or alcohol. The geometry of the transition state of this [4+2] cycloaddition with inverse electron demand follows from the reaction of 3- or 6-phenyl-1,2,4-triazine 5 or 8 with enamines of cyclopentanone. It is apparently influenced by the secondary orbital interaction between the amino and phenyl groups. 3-Phenyl-1,2,4-triazine 5 favours the transition state 11. It leads first to the 3,4-dihydropyridine 6 which, on oxidation followed by a Cope elimination, affords the 2-phenyldihydrocyclopenta[c]pyridine 7. However, 6-phenyl-1,2,4-triazine 8 favours the transition state 12 leading to 3,4-dihydropyridine 9. Elimination of amine yields 5 -phenyldihydrocyclopenta[c]pyridine 10 ... 

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... 

Under similar conditions, 5-phenyltetrazole is converted to a complex mixture containing amine 164 (42%), 3,5-diphenyl triazole, and different phenyl-substituted triazines and tetrazines (62LA146). Electrophilic amination of 1,2,4-triazole by HOSA [80JCR(M)514] or by DNPH (89S269) leads to l-amino- and 4-aminotriazole with the great dominance of the first. This is the only method to synthesize unsubstituted 1-amino-s-triazole. It is known as the nitrene amination of 1,2,4-triazoles [Eq. (46)] [74AHC (17)213]. 

Treatment of 1-phenyl-3-(pyrrol-l-yl)pyrazol-4-amine with nitrous acid yields 1-phenylpyrrolo[5,1-c]pyrazolo[3,4-f ][l,2,4]triazine, an aromatic 1471-system.134... 

---