154117-92-7Relevant articles and documents
Facile aromatic nucleophilic substitution (SNAr) reactions in ionic liquids: An electrophile-nucleophile dual activation by [Omim]Br for the reaction
Zhang, Xiao,Lu, Guo-Ping,Cai, Chun
, p. 5580 - 5585 (2016/10/21)
A facile aromatic nucleophilic substitution (SNAr) reaction in recyclable [Omim]Br under relatively mild conditions has been described. An electrophile-nucleophile dual activation by [Omim]Br is also discovered based on control experiments, 1H NMR and IR spectroscopies. This chemistry provides an efficient and metal-free approach for the generation of Caryl-X (XS, N, O) bonds, many of which are significant synthetic intermediates or drugs, making this methodology attractive to both synthetic and medicinal chemistry.
Highly selective hydrolysis of chloropyrimidines to pyrimidones in 12 N hydrochloric acid
Padilla, Amphlett G.,Pearlman, Bruce A.
supporting information, p. 921 - 926 (2012/12/23)
A chromatography-free process for synthesis of 6-piperazinyl-2,4-bis- pyrrolidinylpyrimidine in isomerically pure form is described. The key step is the purification of a crude 6-chloro-2,4-bis-pyrrolidinylpyrimidine/2-chloro-4, 6-bis-pyrrolidinylpyrimidine isomer mixture (generated by reaction of 2,4,6-trichloropyrimidine with pyrrolidine) by a highly selective acid-catalyzed hydrolysis of the 2-chloro isomer to the pyrimidone. The 2-chloro isomer hydrolyzes 350 times faster than the 6-chloro isomer in 6 N HCl and 1750 times faster in 12 N HCl. To put these rate ratios in perspective, the 2-chloro isomer reacts with amines and alkoxides only ～ 10-17 times faster than does the 6-chloro isomer. A mechanistic investigation using methodological tools developed by Bunnett established that the transition state for hydrolysis of the 6-chloro isomer involves two more molecules of water (each acting as a base) than does the transition state for hydrolysis of the 2-chloro isomer. As the concentration of HCl increases from 3 N to 6 N to 12 N, there are fewer unprotonated water molecules. Thus, the transition state that involves the greater number of unprotonated water molecules (6-chloro-2,4-bis- pyrrolidinylpyrimidine) is expected to be increasingly disfavored with increasing acid concentration, as is observed. The optimized process was run successfully on production scale.
