title: Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins.
abstract: Batch synthesis of sulphobutyl ether β-cyclodextrin (also known as SBE-β-CD or SBECD) is a process effectively divided into three main stages, i.e. initial reagent dissolution, a sulphoalkylation reaction and final reaction quenching. This reaction is followed by downstream processing and purification, and ultimate isolation of the solid SBECD material. However, a feature associated with using this synthetic method is that a high proportion of lower substituted SBECD is observed. There is therefore a need to provide an improved synthetic method for producing higher substituted cyclodextrins. The authors here present a Continuous Tank Reactor (CTR) method for preparing sulphobutyl ether-cyclodextrins. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then involves separately contacting the activated cyclodextrin with an 1,4-butane sultone to form sulphoalkyl ether-cyclodextrin. The activation reaction is carried out in batch synthesis mode and the sulphoalkylation reaction is carried out under continuous flow conditions resulting in a novel method for the synthesis of highly derivatised cyclodextrins. The work is particularly concerned with producing controlled substitution in sulphobutyl ether β-cyclodextrins and novel compositions of highly substituted sulphoalkyl ether β-cyclodextrins are described.
authors.affiliation: Medway Centre for Formulation Science, Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Tammy
authors.initials: T
authors.lastname: Savage
authors.affiliation: Medway Centre for Formulation Science, Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK. Electronic address: J.Mitchell@Greenwich.ac.uk.
authors.forename: John
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Medway Centre for Formulation Science, Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Vivek
authors.initials: V
authors.lastname: Trivedi
authors.affiliation: Medway Centre for Formulation Science, Engineering and Science, University of Greenwich at Medway, Chatham Maritime, Kent ME4 4TB, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wicks
authors.affiliation: School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Waters
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin
keywords: CD-screen-DAP; Continuous Tank Reactor; Cyclodextrin; Evaporative light scattering detection; SBE-β-CD; SBECD; Sulphobutyl ether β-cyclodextrin