887947-03-7Relevant academic research and scientific papers
Reactivity of activated versus nonactivated 2-(bromomethyl)aziridines with respect to sodium methoxide: A combined computational and experimental study
Goossens, Hannelore,Vervisch, Karel,Catak, Saron,Stankovic, Sonja,D'Hooghe, Matthias,De Proft, Frank,Geerlings, Paul,De Kimpe, Norbert,Waroquier, Michel,Van Speybroeck, Veronique
scheme or table, p. 8698 - 8709 (2012/01/05)
The difference in reactivity between the activated 2-bromomethyl-1- tosylaziridine and the nonactivated 1-benzyl-2-(bromomethyl)aziridine with respect to sodium methoxide was analyzed by means of DFT calculations within the supermolecule approach, taking into account explicit solvent molecules. In addition, the reactivity of epibromohydrin with regard to sodium methoxide was assessed as well. The barriers for direct displacement of bromide by methoxide in methanol are comparable for all three heterocyclic species under study. However, ring opening was found to be only feasible for the epoxide and the activated aziridine, and not for the nonactivated aziridine. According to these computational analyses, the synthesis of chiral 2-substituted 1-tosylaziridines can take place with inversion (through ring opening/ring closure) or retention (through direct bromide displacement) of configuration upon treatment of the corresponding 2-(bromomethyl)aziridines with 1 equiv of a nucleophile, whereas chiral 2-substituted 1-benzylaziridines are selectively obtained with retention of configuration (via direct bromide displacement). Furthermore, the computational results showed that explicit accounting for solvent molecules is required to describe the free energy profile correctly. To verify the computational findings experimentally, chiral 1-benzyl-2-(bromomethyl)aziridines and 2-bromomethyl-1-tosylaziridines were treated with sodium methoxide in methanol. The presented work concerning the reactivity of 2-bromomethyl-1- tosylaziridine stands in contrast to the behavior of the corresponding 1-tosyl-2-(tosyloxymethyl)aziridine with respect to nucleophiles, which undergoes a clean ring-opening/ring-closure process with inversion of configuration at the asymmetric aziridine carbon atom.
An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles from common chiral aziridines
Chan Kim, Jong,Choi, Hwan Geun,Kim, Min Suk,Ha, Hyun-Joon,Lee, Won Koo
experimental part, p. 8108 - 8114 (2010/10/21)
An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles was successfully achieved via Pd-catalyzed intramolecular C-N bond formation between the nitrogen originated from the aziridine and the halogen containing aromatic carbon. This reaction has a broad substrate scope to provide various enantiomerically pure (3,4-dihydro-2H-benzo[b][1,4]oxazin-3-yl) methanols, 2-hydroxymethyl-1,2,3,4-tetrahydroquinolines and (1,2,3,4- tetrahydroquinoxalin-2-yl)methanols from common chiral aziridines in good yields.
Nucleophilic substitution of (sulfonyloxymethyl)aziridines: an asymmetric synthesis of both isomers of mexiletine
Han, Sang-Mi,Ma, Sang-ho,Ha, Hyun-Joon,Lee, Won Koo
experimental part, p. 11110 - 11114 (2009/04/11)
The nucleophilic substitution reactions of 1-[1′(R)-α-methylbenzyl]-(2R)- and (2S)-(sulfonyloxymethyl)aziridines were carried out with various nucleophiles including N3-, MeO-, CN-, SCN-, and diarylcuprates. The reaction pathway is influenced by the stereochemistry of the substrates, nucleophiles, and also the structure of the leaving groups. When the reaction site is less sterically hindered for the reactive nucleophiles to approach to the substrate 1-[1′(R)-α-methylbenzyl]-(2S)-(p-toluenesulfonyloxymethyl)aziridines, product is obtained as a single isomer while all the other starting materials afford a mixture of two isomers from two different reaction pathways. Application of this method enabled us to prepare both isomers of orally effective antiarrhythmic agent mexiletine.
Regio- and stereospecific ring opening of 1,1-dialkyl-2-(aryloxymethyl) aziridinium salts by bromide
D'hooghe, Matthias,Van Speybroeck, Veronique,Waroquier, Michel,De Kimpe, Norbert
, p. 1554 - 1556 (2008/02/11)
Enantiomerically pure 2-(aryloxymethyl)aziridines are efficiently transformed into chiral N-(2-bromo-3-aryloxypropyl)amines via a regio- and stereospecific ring opening of the intermediate aziridinium salts, and the experimental results are rationalized o
