In 2022,Ashworth, Ian W.; Frodsham, Lianne; Moore, Peter; Ronson, Thomas O. published an article in Journal of Organic Chemistry. The title of the article was 《Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions》.Application In Synthesis of 1-Methylpiperazine The author mentioned the following in the article:
An early synthetic step in the synthesis of adavosertib, AZD1775, is the SNAr reaction between 4-fluoronitrobenzene and 1-methylpiperazine in acetonitrile. A simple kinetics-based design of four reaction profiling experiments was used to investigate the kinetics of the reaction for the purpose of building a kinetic model. Fitting of the reaction profile data from two experiments conducted at 70°C with a different excess of 1-methylpiperazine showed the reaction to follow a third-order rate law with a second-order dependence upon 1-methylpiperazine. This was rationalized in terms of the reaction following a rate-limiting proton transfer mechanism (base catalyzed) in which the progress to product is driven by a proton transfer involving a second mol. of 1-methylpiperazine. The exptl. determined entropy of activation of -180 J K-1 is consistent with this mechanism. The formation of a low level impurity was found to be due to the presence of traces of piperazine in the 1-methylpiperazine, which was shown to react approx. 15 times faster than 1-methylpiperazine at 70°C. The rate constants for the 1-methylpiperazine catalyzed reaction of piperazine, 1-methylpiperazine, and the piperazine derived impurity were found to correlate in a Bronsted type anal. with the pKa’s (acetonitrile) of the amine nucleophile. In the experiment, the researchers used 1-Methylpiperazine(cas: 109-01-3Application In Synthesis of 1-Methylpiperazine)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Application In Synthesis of 1-Methylpiperazine
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics