Chemical Properties
White Solid
Uses
2,4-Dichloropyrimidine was used in the synthesis of medicinally important 4-aryl-5-pyrimidinylimidazoles.
Preparation
Obtained by chlorination of uracil. Add uracil, phosphorus trichloride, and xylene amine into the reaction pot, heat to 130 ℃, reflux for about 45min, slightly cool, put in crushed ice, that is, the precipitation of purple solid, filtered while hot and not dissolved, washed with ice water, vacuum drying, a kind of purple crude, decolorized with petroleum ether (boiling range of 60-90 ℃), recrystallized, obtained 2,4-dichloropyrimidine.
General Description
2,4-Dichloropyrimidine is a human skin sensitizer. It undergoes effective one-pot, regioselective double Suzuki coupling reaction to yield diarylated pyrimidines.
Reactivity Profile
The reaction of N-substituted cyclic amines with 2,4-dichloroquinazoline and 2,4-dichloro-5-methyl-pyrimidine afforded 2-amino-4-chloroquinazolines and 2-amino-4-chloro-5-methylpyrimidines, respectively—the reaction of these amines with 2,4-dichloropyrimidine 3a afforded not only 2-amino-4-chloropyrimidines but also the isomeric 4-amino-2-chloropyrimidines. An effective one-pot, regioselective double Suzuki coupling of 2,4-dichloropyrimidine has been developed. This method enables the quick and efficient synthesis of diarylated pyrimidines. The choice of solvent proved critical to the success of this reaction sequence, with alcoholic solvent mixtures affording much greater reactivity and correspondingly lower temperatures than polar aprotic solvents[5-6].
References
[1] DR. AGNES FIZIA. Cyclopalladation in the Periphery of a NHC Ligand as the Crucial Step in the Synthesis of Highly Active Suzuki–Miyaura Cross-Coupling Catalysts[J]. Chemistry - A European Journal, 2017. DOI:
10.1002/chem.201702877.
[2] FABIAN BRUENING Lucie E L. Highly Regioselective Organocatalytic SNAr Amination of 2,4-Dichloropyrimidine and Related Heteroaryl Chlorides[J]. European Journal of Organic Chemistry, 2017. DOI:
10.1002/ejoc.201700459.
[3] ANDERSONSAMANTHA C HandyScott T. One-pot Double Suzuki Couplings of Dichloropyrimidines.[J]. Synthesis-Stuttgart, 2010. DOI:
10.1055/s-0030-1258150.
[4] TOMá? KUBELKA. Synthesis of 2,4-Disubstituted Pyrimidin-5-yl C-2′-Deoxyribonucleosides by Sequential Regioselective Reactions of 2,4-Dichloropyrimidine Nucleosides[J]. European Journal of Organic Chemistry, 2010. DOI:
10.1002/ejoc.201000164.
[5] Kenji Yoshida, M. Taguchi. “Reaction of N-substituted cyclic amines with 2,4-dichloroquinazoline, 2,4-dichloropyrimidine, and its 5-methyl derivative.” Journal of The Chemical Society-perkin Transactions 1 102 1 (1992): 919–922.
[6] Samantha C Anderson, Scott T Handy. “One-pot Double Suzuki Couplings of Dichloropyrimidines.” Synthesis-Stuttgart 2010 16 (2010): 2721–2724.
