Ring-opening reactions of 1,4-diazabicyclo[2.2.2]octane (DABCO) derived quaternary ammonium salts with phenols and related nucleophiles.
1,4-Diazabicyclo[2.2.2]octane (DABCO) has been evaluated as a starting material for the synthesis of 1-alkyl-4-(2-phenoxyethyl)piperazines and related derivatives. We found that 1-alkyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, resulting from the alkylation of DABCO, efficiently react with a variety of nucleophiles in polyethyleneglycol (PEG) or diglyme at high temperatures to give piperazine products resulting from the nucleophilic ring-opening reaction. The benzylation side reaction was found to be relevant with softer nucleophiles when using 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, while other types of alkylations were not observed. One-pot methodologies allow for the synthesis of piperazines directly from primary alcohols, alkyl halides or sulfonates, using phenols, or other nucleophile sources, and DABCO.
Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000, Ljubljana, Slovenia.
Nenad
N
Maraš
Slovenko
S
Polanc
Marijan
M
Kočevar
D005026:Ethylene Glycols / Q000737:chemistry*; D008738:Methyl Ethers / Q000737:chemistry*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012492:Salts / Q000737:chemistry
D005026:Ethylene Glycols; D008738:Methyl Ethers; D010636:Phenols; D010879:Piperazines; D000644:Quaternary Ammonium Compounds; D012492:Salts; D011092:Polyethylene Glycols; C007391:diglyme; C007306:triethylenediamine