Reactions of Polychlorinated Pyrimidines with DABCO

Abstract

The reaction of 2,4,5,6-tetrachloropyrimidine (4) and 4,5,6-trichloropyrimidine-2-carbonitrile (1) with DABCO (1 equiv.), in MeCN, at ca. 20 °C gives 2,4,5-trichloro-6-[4-(2-chloroethyl)piperazin-1-yl]pyrimidine (5) and 4,5-dichloro-6-[4-(2-chloroethyl)piperazin-1-yl]pyrimidine-2-carbonitrile (6) in 42% and 52% yields, respectively. The new compounds were fully characterized.

4,5,6-Trichloropyrimidine-2-carboxamide

“…A more efficient synthesis of pyrimidine 1 was subsequently developed, starting from the less readily available but highly reactive tetrachlorothiadiazine 3 via perchloro-9-thia-1,5,8,10-tetraazaspiro [5.5]undeca-1,4,7,10-tetraene (4) with a 53% overall yield [9] (Scheme 1). Other efforts to develop an independent synthesis of pyrimidine 1 [10,11] or investigate its chemistry [12] were also reported.…”

Synthesis of 4,5,6-trichloropyrimidine-2-carbonitrile from 4,6-dichloro-2-(methylthio)pyrimidine

“…However, the chemistry of the trichloropyrimidine 1 has remained unexplored due to its low yielding synthesis. To date, the known chemistry of trichloropyrimidine 1 is limited only to the nucleophilic displacement of the C4 chloride by DABCO to give piperazine 5, 8 and its involvement in the formation of the fused thiazole 6 from the degradation of tetrachlorothiadiazine 3 (Scheme 2). 9 Scheme 2.…”

Nitrogen-Containing Molecules: Natural and Synthetic Products including Coordination Compounds

“…The majority (13) of the published content was in the field of synthetic chemistry, including synthetic methodologies and studies on chemical reactions and reactivity, while two papers dealt with coordination chemistry and one with structural elucidation. In particular, contributions related to organic synthesis may be divided in the subfields of aromatic reactivity (2), reactivity of heterocycles (2), synthesis of heterocycles (6), and detailed routine synthesis of very important compounds (3). Two of these papers included biological evaluation experiments.…”

“…Kalogirou and Koutentis contributed with two communications on the reactivity of chlorinated pyrimidines. In their first paper, they focused on the displacement of carbon-2 or carbon-6 of polychlorinated pyrimidines using DABCO reagent (1,4-diazabicyclo[2.2.2]octane) with yields up to 52% [3]. The second publication demonstrates the synthesis of 2-cyanopyrimidines from the corresponding 2-thiomethyl pyrimidines starting from the 4,6-dichloro functionalized analogues.…”