title: Templated synthesis of glycoluril hexamer and monofunctionalized cucurbit[6]uril derivatives.
abstract: We report that the p-xylylenediammonium ion (11) acts as a template in the cucurbit[n]uril forming reaction that biases the reaction toward the production of methylene bridged glycoluril hexamer (6C) and bis-nor-seco-CB[10]. Hexamer 6C is readily available on the gram scale by a one step synthetic procedure that avoids chromatography. Hexamer 6C undergoes macrocylization with (substituted) phthalaldehydes 12, 14, 15, and 18-in 9 M H(2)SO(4) or concd HCl at room temperature to deliver monofunctionalized CB[6] derivatives 13, 16, 17, and 19-that are poised for further functionalization reactions. The kinetics of the macrocyclization reaction between hexamer and formaldehyde or phthalaldehyde depends on the presence and identity of ammonium ions as templates. p-Xylylenediammonium ion (11) which barely fits inside CB[6] sized cavities acts as a negative template which slows down transformation of 6C and paraformaldehyde into CB[6]. In contrast, 11 and hexanediammonium ion (20) act as a positive template that promotes the macrocyclization reaction between 6C and 12 to deliver (±)-21 as a key intermediate along the mechanistic pathway to CB[6] derivatives. Naphthalene-CB[6] derivative 19 which contains both fluorophore and ureidyl C═O metal-ion (e.g., Eu(3+)) binding sites forms the basis for a fluorescence turn-on assay for suitable ammonium ions (e.g., hexanediammonium ion and histamine).
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, United States.
authors.forename: Derick
authors.initials: D
authors.lastname: Lucas
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Minami
authors.forename: Greg
authors.initials: G
authors.lastname: Iannuzzi
authors.forename: Liping
authors.initials: L
authors.lastname: Cao
authors.forename: James B
authors.initials: JB
authors.lastname: Wittenberg
authors.forename: Pavel
authors.initials: P
authors.lastname: Anzenbacher
authors.forename: Lyle
authors.initials: L
authors.lastname: Isaacs
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines
chemical_list: D000480:Alkynes; D001952:Bridged-Ring Compounds; D007093:Imidazoles; C454805:cucurbit(6)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C092018:glycoluril; D006574:Heterocyclic Compounds, 2-Ring; D048289:Imidazolidines