Is nucleophilic cleavage chemistry practical for 4-membered heterocycles?
A computational study at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level of the ammonolysis of halogen substituted azetidines, oxetanes and thietanes was performed in the gas phase and in the commonly used solvent, acetonitrile. Using the free energy of activation of a benchmark reaction for evaluation of synthetic viability, several haloazetidines and oxetanes that possessed the required reactivity were identified; however, no substituted thietane investigated herein was determined to be synthetically useful under the mild conditions selected for this study. In the case of the azetidines, the side reaction of displacement of halide ion was determined to be the preferred reaction course in acetonitrile; however, the amino product of the reactions of the 2-haloazetidines cleaved at an acceptable rate under mild conditions. For the oxetane derivatives investigated, 2-fluorooxetane proved to be a direct source of ring cleavage product. Nucleophilic cleavage of halogen-substituted azetidines and oxetanes is predicted to be a viable source of functionalized three-carbon moieties under mild conditions in organic synthesis.
Banks
Harold D
HD
U.S. Army Edgewood Chemical Biological Center, APG, Maryland 21010-5424, USA. harold.banks@us.army.mil
D000097:Acetonitriles / Q000737:chemistry; D000641:Ammonia / Q000737:chemistry; D005027:Ethylene Oxide / Q000737:chemistry; D006219:Halogens / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D013696:Temperature
D000097:Acetonitriles; D006219:Halogens; D006576:Heterocyclic Compounds, 4 or More Rings; D000641:Ammonia; D005027:Ethylene Oxide; C032159:acetonitrile