The Synthesis and Some Reactions of Chloropyrimidines

Aromatic aldehyde thiosemicarbazones in the synthesis of hydrazones of the pyrimidine series

“…Unambiguous proof for the structure of 4a and 4b is provided by the presence of the molecular ion peak in the mass spectrum of 4a and by the coincidence of physicochemical and spectral parameters of samples of 4b obtained from chloropyrimidine 2 (method a) and by independent synthesis [condensation of 4-hydrazinyl-6-methylpyrimidin-2amine (5) [6] with 4-nitrobenzaldehyde, followed by treatment of 4-[(4-nitrobenzylidene)hydrazinyl]-6methylpyrimidin-2-amine (6) The above contradiction between the observed reaction direction and calculated charge distribution can be rationalized assuming intramolecular rearrangement of initially formed intermediate A with elimination of thiocyanic acid molecule (Scheme 3). A similar mechanism was proposed previously [7] for the reaction of 2-thioxohexahydropyrimidine-4,6-diones with hydrazonoyl halides, leading to the formation of [1,2,4]triazolo[4,3-a]pyrimidines. The rearrangement of intermediate A yields hydrazinylpyrimidine B which undergoes deformylation in situ by the action of hydrogen chloride present in the reaction mixture.…”

“…Yield 0.57 g (81%), mp 267°C (decomp., from EtOH-DMF, 15 : 1); published data [9]: mp 249°C; R f 0.82. 1 …”

“…6-Chloro-4-methylpyrimidin-2-amine (1) reacts with binucleophiles (hydroxylamine [1], N 1 -unsubstituted semi-and thiosemicarbazides [2]) to give the corresponding 6-methylpyrimidine-2,4-diamine derivatives. The goal of the present work was to study the reaction of N-(4-chloro-6-methylpyrimidin-2-yl)formamide (2) [3] with aromatic aldehyde thiosemicarbazones 3a and 3b [4].…”

Synthesis of Hydroxylamines

“…35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of N-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine 83,84 , quinoline 83 , pyrimidine 85,86 , pyridazine 87 , pyrazine 88 , purine 89, 90 and 1,3,5-triazine 91 systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino 92,93 or methoxy 94 are also common.…”

Preparation and biological properties of 2-thio-containing pyrimidines and their condensed analogs

“…Thus, Sauter with his colleagues 27 Chowdhury and Shibata 28 published results of the study in which they used a similar approach for pyrimidine derivative formation. Authors used 2-isothiocyanatoacetate (14) as electrophilic reagent and various o-amino nitriles 15, 17-19 or o-amino ester 16 as 1,4-binucleophiles (Scheme 5). In all cases the appropriate condensed pyrimidine derivatives 20-24 were obtained.…”