An interesting two-step sequence was described that uses tetrabutylammonium chloride (TBAC) as catalyst. This sequence was reported in an earlier 2019 patent.
In the first reaction TBAC is a source of catalytic chloride that is soluble in an organic liquid to perform a reaction and in the second step the TBAC, which is not isolated from the first reaction appears to serve as a phase-transfer catalyst to transfer and activate inorganic sulfide as a nucleophile.
In the first reaction, we assume that the chloride from TBAC opens the ring of epichlorohydrin to form mostly 1,3-dichloropropoxide that attacks phosgene to form the intermediate chloroformate in high yield and high regioselectivity. The chloride liberated from the phosgene regenerates TBAC.
The first reaction uses no added solvent and the crude product was used in the next step without isolation. An interesting two-condenser system was used, presumably to contain the phosgene.
Since the reaction mixture from the first step was used without workup in the second step, the tetrabutylammonium phase-transfer catalyst was still present in the second reaction and available to transfer, activate the inorganic sulfide for the nucleophilic displacement of two chlorides to form the 1,3-oxathiolane-2-one ring. As long as the regioselectivity of the first reaction was high, then the ring closure in the second step should afford the right product. One may assume that the use of 1.0 equiv sulfide with no excess avoided further reaction of the final chloromethyl group.
Interestingly, the inventors chose to use tetramethylammonium chloride with DMF as the solvent for the subsequent esterification of the 5-(chloromethyl)-1,3-oxathiolane-2-one with sodium acetate or sodium methacrylate. These esterifications required higher temperatures (100 deg C and 120 deg C), which is common but they gave relatively low conversions (23% and 48% by GC). We wonder if the inventors tried using more organophilic phase-transfer catalysts and less polar solvents, especially with quat bromides or quat iodides that usually reduce the temperature required for PTC esterifications.
When your company needs to optimize process conditions for PTC esterifications, now contact Marc Halpern of PTC Organics to explore collaboration through PTC Process Consulting.
