N-Nitroso Group-Assisted Nucleophilic Aromatic Substitution of 6-Chloro­pyrimidines: A Facile and Efficient Synthesis of Pyrimidine-4,6- and -2,4-­diamines

Abstract

An N-nitroso group was used to activate chloropyrimidines toward nucleophilic substitution by amines. This permitted a simple, one-pot, high-yielding synthesis of pyrimidine-4,6-and -2,4-diamines.

The first example of the Fischer–Hepp type rearrangement in pyrimidines

“…In conclusion, the ability of N -substituted-6-chloropyrimidin-4-amines to undergo a N -nitrosation reaction facilitates a very useful and convenient synthetic possibility for the preparation of pyrimidinediamines [16] or 5-nitroso-4,6-pyrimidinediamines. An N -nitroso moiety, which assisted the nucleophilic displacement reaction, does not require harsh reaction conditions and it is a high-yielding process.…”

“…Preparation of the starting materials 1 , N -nitrosation and denitrosation reactions were performed according the methods published earlier [15–16]. …”

“…We also recognized that a 6-chloro substituent is activated by the N -nitroso moiety in position 4 of the pyrimidine ring which facilitates nucleophilic substitutions. Moreover, after completion of the substitution reaction, N -nitroso moieties can be easily removed by short heating in diluted sulfuric acid [16]. …”