title: Cu(II)-ion-catalyzed solvolysis of N,N-bis(2-picolyl)ureas in alcohol solvents: evidence for cleavage involving nucleophilic addition and strong assistance of bis(2-picolyl)amine leaving group departure.
abstract: The kinetics and products for solvolysis of N-p-nitrophenyl-N',N'-bis(pyridin-2-ylmethyl) urea (7a), N-methyl-N-p-nitrophenyl-N',N'-bis(pyridin-2-yl methyl) urea (7b), and N-phenyl-N',N'-bis(pyridin-2-yl-methyl) urea (DPPU) (7c) promoted by Cu(II) ion in methanol and ethanol were studied under (s)(s)pH-controlled conditions at 25 °C. Methanolysis and ethanolysis of these substrates proceeds rapidly at a 1:1 ratio of substrate:metal ion, the half-times for decomposition of the Cu(II):7a complexes being ~150 min in methanol and 15 min in ethanol. In all cases, the reaction products are the Cu(II) complex of bis(2-picolyl)amine and the O-methyl or O-ethyl carbamate of the parent aniline, signifying that the point of cleavage is the bis(2-picolyl)-N-C=O bond. Reactions of the Cu(II):7b complexes in each solvent proceed about 3-5 times slower than their respective Cu(II):7a complexes, excluding an elimination mechanism that proceeds through an isocyanate which subsequently adds alcohol to give the observed products. The reactions also proceed in other solvents, with the order of reactivity ethanol > methanol >1-propanol >2-propanol > acetonitrile (with 0.2% methanol) > water spanning a range of 150-fold. The mechanism of the reactions is discussed, and the reactivity and mode of cleavage are compared with that of the M(II)-promoted ethanolytic cleavage of a mono-2-picolyl derivative, N-p-nitrophenyl-N'-(pyridin-2-yl-methyl) urea (4a), which had previously been shown to cleave at the aniline N-C=O bond. The large estimated acceleration of the rate of attack of ethoxide on 7b of at least 2 × 10¹⁶ provided by associating Cu(II) with the departing group in this urea is discussed in terms of a trifunctional role for the metal ion involving Lewis acid activation of the substrate, intramolecular delivery of a Cu(II)-coordinated ethoxide, and metal-ion-assisted leaving group departure.
authors: Department of Chemistry, Queen's University , Kingston, Ontario, Canada K7L 3N6.
authors: Mei-Ni
authors: MN
authors: Belzile
authors: Alexei A
authors: AA
authors: Neverov
authors: R Stan
authors: RS
authors: Brown
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D006868:Hydrolysis; D012997:Solvents; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000438:Alcohols; D000588:Amines; D012997:Solvents; D003300:Copper; D014508:Urea