Diethyl zinc mediated intramolecular metalloamination of N,N-dimethylhydrazines: expanding a novel approach to functionalized pyrrolidines and piperidines. Utilizing synthesis as a tool for medicinal chemistry, environmental remediation, and nonlinear optical chromophore construction

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Montana State University - Bozeman, College of Letters & Science


When attempting to develop a novel material for increased second-order nonlinear activity, a strategy was devised to rationally design an architecture that would allow for optimized acentric supramolecular organization. By coupling a liquid crystal tolane to a well-understood NLO chromophore via strategic synthesis, a set of novel chromophores was created. The ferroelectric liquid crystal-like molecules intrinsically favor unidirectional chromophore order while simultaneously containing a high beta chromophore along the polar axis. This system has shown potential for high terminal stability as well as increased nonlinear optical susceptibilities. Carbon tetrachloride poses a large threat to the environment and is the focus of ongoing remediation efforts. It is a well-known carcinogenic pollutant that has contaminated groundwater beneath former grain storage and industrial sites, such as the Department of Energy's Hanford site. Remediation through the use of a small molecule, PDTC, when complexed with copper has been shown to lead to complete dechlorination, resulting in conversion to non-toxic end-products (mostly CO 2) and complete removal of the problematic carbon-chlorine bonds. Synthetic chemistry was employed to develop a modified procedure for large-scale production of PDTC that eliminates harmful byproducts and excess toxic reagents used. Additionally, structural derivatives for increased water solubility have been envisaged from citrazinic acid, which could allow for aqueous destruction of carbon tetrachloride. In medicinal and pharmaceutical chemistry, routes to nitrogenous heterocycles are of great importance due to their prevalence in bioactive molecules. Diethylzinc mediated metalloamination/cyclization of unsaturated N,N-dimethylhydrazines with subsequent electrophilic functionalization could prove to be a powerful tool for constructing pyrrolidines and piperidines. This method was extended to the use of 1,2-disubstituted alkenes as N-Zn migratory insertion acceptors, including various vinylcyclopropyl hydrazines. The potential behind the irreversible cyclopropane scission and development of a new alkene make this class of substrates extremely desirable. The metalloamination-alkylation of N,N-dimethylhydrazinoalkenes was shown to be effectively catalyzed by CuBr x SMe 2, CuCN and CuI. This novel method obviates the prior methodology involving use of stoichiometric CuCN(LiCl) 2 as a promoter for the electrophilic functionalization.




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