Rearrangement of 2-alkylpyrimidines to 2-aminopyridines

Direction of the Primary Nucleophilic Attack in the Kost—Sagitullin Rearrangement.

“…We should note that dilution of the solution of this compound in CCl 4 does not lead to shift in the carbonyl group frequency. This unequivocally indicates the existence of an intramolecular rather than intermolecular hydrogen bond, which is possible only upon addition of the hydroxyl group at C (2) .…”

Kost-Sagitullin Rearrangement and Other Isomerization Recyclizations of Pyrimidines. (Review)

“…The Kost-Sagitullin rearrangement was first discovered and studied under the leadership of Prof. A. N. Kost in derivatives of pyridine and pyrimidine [5,[64][65][66][67][68][69][70][71][72][73][74][75][76][77]. Such recyclizations were realized both in N-alkylazinium salts and in annelated azine systems containing a bridging nitrogen atom (common to the two heterocycles).…”

“…The action of an aqueous solution of ammonia led to N-demethylation with the formation of 4,6-dimethylpyrimidine (19), while an aqueous solution of methylamine gave a mixture of amines 20 and 21. Reaction with hydrazine also did not lead to the expected Kost-Sagitullin rearrangement, and 3,5-dimethylpyrazole was isolated [5,66] According to the presented examples, the first stage in the recyclization of the pyrimidines takes place normally; ring opening occurs, but degradation is then usually observed. The reason for this may be either insufficient electron density at the carbon atom (the atom at which attack by the terminal carbonyl group of the intermediate should occur) or the presence of water in the solution, which promotes hydrolysis.…”

“…The reason for this may be either insufficient electron density at the carbon atom (the atom at which attack by the terminal carbonyl group of the intermediate should occur) or the presence of water in the solution, which promotes hydrolysis. In fact it was found that the introduction of electron-accepting groups (phenyl and ester groups) into the side chain (compounds 24 and 25) and the exclusion of water (realization of the reaction in an alcohol solution of methylamine) led to isomerization to the 2-methylaminopyridine derivatives 26 and 27 with partial demethylation (the formation of compound 28) [5,66]. The introduction of a nitrile group into the side chain had a more significant effect.…”

“…Another somewhat less studied type of isomerization recyclization in the pyrimidine ring is the KostSagitullin rearrangement, discovered in the seventies of the last century at M. V. Lomonosov Moscow State University [5,[64][65][66][67]. This reaction, its modifications, and the concurrent transformations that accompany the process have been studied in detail in recent years.…”