video tutorial Chelidonic acid synthesis from diethyloxalate and acetone

Name: video tutorial - Chelidonic acid synthesis from diethyloxalate and acetone
Uploaded: 2025-12-11T09:03:43.864Z
Duration: 11 min 7 s
Description: We prepared this reagent in a previous video. For more details, click the link shown.

Target: synthesize phlebotonic acid via condensation of acetone with diethyl oxalate in the presence of a strong base (sodium ethoxide) using dry ethanol as solvent.
Reagent preparation: sodium ethoxide (14 g) dissolved in minimal dry ethanol; diethyl oxalate dried (brine wash, MgSO4) and weighed (26 g).
Reaction setup: acetone (5.2 g) in absolute ethanol (20 mL) prepared; mixture added slowly to the sodium ethoxide/diethyl oxalate system with temperature control starting at room temperature.
Reaction progression: slow acetone addition over ~40 minutes; gradual color change to yellow/milky and precipitation observed; initial heating to maintain reaction while adding acetone; final temperature ~60–75 °C.
Workup: after addition, cool and acidify with cold concentrated HCl; orange precipitate forms; filtration yields 13.5 g of acetone double addition intermediate.
Hydrolysis and cyclization: hydrolyze esters in intermediate with 40 mL concentrated HCl in a 250 mL flask under reflux for 4 hours, with additional HCl added later; drive off ethanol to push completion.
Product isolation: after cooling and filtration, brown solid is dried to yield 8.4 g of calyptonic acid intermediate (monohydrate if dried at 120 °C; dehydration gives the acid).
Estimated overall yield: 47% (monohydrate) to 51% (anhydrous acid) from starting acetone; actual lies between these values.
Future step: convert to glycemic acid by nitrogen insertion to form a pyridine ring, enabling synthesis of a pyridine derivative from relatively OTC starting materials.
Notes: precautions include handling HCl fumes and avoiding yellow staining; some steps may benefit from solvent removal to improve yield.