A selective process for N-alkylation in competition with O-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes
Hr. Bjorsvik et al., A selective process for N-alkylation in competition with O-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes, ORG PROC R, 5(5), 2001, pp. 472-478
This paper describes a selective process for the N-alkylation of substrates
that contain 1,2-diol groups. The developed approach utilises temporary pr
otection of the diol groups by boric acid, Borax, or metaborate. The introd
uction of the boron-containing groups into the substrate may provide, in ad
dition to affording the intended protection of the hydroxyl groups that may
otherwise act as nucleophilic sites, the advantages of improved solubility
of the substrate in water that is used as solvent. Moreover the N-alkylati
on and the deprotection of the diols are performed in one pot, and the form
ation of undesired O-alkylated by-products is significantly reduced. The pa
per gives examples from the synthesis of several X-ray contrast agents used
in medical imaging diagnostics: iohexol (Ominipaque, Nycomed Imaging); iop
entol (Imagopaque, Nycomed Imaging); iodixanol (Visipaque, Nycomed Imaging)
; ioversol (Optiray, Mallinckrodt).