Tertiary amides are used as solvents in a variety of industrial chemical processes, and their recycling for reuse in these processes is of significant commercial value. Depending on the type of reaction performed in the tertiary amide, such recycling may require the removal of reaction byproducts not easily separated from it in a cost-effective manner. One example of such byproducts includes carboxylic acids. In some cases, these must be removed from used solvent as part of recycling, and in other cases they must be removed from the solvent while it is still in use to dissolve process intermediates. The latter situation frequently compounds the difficulty of removing the acids, since potentially sensitive intermediates may be present. The commercial preparation of sucralose is an example of a process where carboxylic acids need to be removed from a tertiary amide solvent, both alone and in the presence of sensitive process intermediates.
Sucralose (4,1′,6′-trichloro-4,1′,6′-trideoxygalactosucrose), a high-intensity sweetener made from sucrose, can be used in many food and beverage applications.
A number of different synthesis routes for the preparation of sucralose have been developed in which the reactive hydroxyl in the 6 position is first blocked with an acyl group to form a sucrose-6-ester. The acyl group is typically acetyl or benzoyl, although others may be used. The sucrose-6-ester is then chlorinated to replace the hydroxyls at the 4, 1′ and 6′ positions to produce 4,1′,6′-trichloro-4,1′,6′-trideoxygalactosucrose 6-ester (referred to herein as sucralose-6-ester), followed by hydrolysis to remove the acyl substituent and thereby produce sucralose. Several synthesis routes for formation of the sucrose-6-ester involve tin-mediated acylation reactions, with illustrative examples being disclosed in U.S. Pat. Nos. 4,950,746; 5,023,329; 5,089,608; 5,034,551; and 5,470,969, all of which are incorporated herein by reference.
Various chlorinating agents may be used to chlorinate the sucrose-6-ester, and most commonly a Vilsmeier-type salt such as Arnold's Reagent will be used. One suitable chlorination process is disclosed by Walkup et al. (U.S. Pat. No. 4,980,463), incorporated herein by reference. This process uses a tertiary amide, typically N,N-dimethyl formamide (“DMF”), as the chlorination reaction solvent. After the chlorination is complete, adducts of Arnold's reagent on the base sucrose moiety and excess chlorinating reagent are neutralized (“quenched”) with aqueous base to provide the sucralose-6-ester in an aqueous solution, accompanied by the tertiary amide solvent and salts resulting from reactions of the chlorination reagent. The sucralose-6-ester is then deacylated to produce sucralose. One suitable deacylation process is taught by Navia et al, U.S. Pat. No. 5,498,709, the entire disclosure of which is incorporated herein by reference.
In such processes, carboxylic acids need to be removed at various points in the process. Accordingly, facile means of removing these acids are of commercial value.