Base-catalyzed Hydrolysis of Ergocristine to Lysergic Acidby KrZ
Ergocristine base was obatined, and the subsequent base-catalyzed hydrolysis was a glowing success. The procedure here is very simple. Gloves should be worn at all times. Have a bucket of water to rinse the gloves in before you take them off so you will not contact the skin when trying to remove them, be careful cleaning all glassware.
33.5g KOH was dissolved in 500ml dH2O in a 1000ml flask, and the solution was stirred magnetically, heating was commenced and the temperature of the solution was allowed to reach 75°C. 50g of Ergocristine base was added in 2g fractions over a period of 30 minutes. The mix went from clear to a light golden yellow tint over the course of the addition. Everything was in solution after 50 minutes. The reaction was allowed to proceed for a total of 5 hours after complete addition. Heating was removed and the reaction flask placed in a room temp. water bath, and then in an ice bath, until the solution was at 5°C. 325 mL 2.5 N H2SO4 was placed in an addition funnel, the flask placed in the ice-bath and stirred, and the acid was added dropwise. As the volume added reached ~200 mL pH metering was commenced, and addition was halted when the pH reached 3.0, ~50 mL of acid remained in the addition funnel. The flask was sprayed out with a stream of nitrogen, stoppered, wrapped in aluminum foil, and stored at 0°C for 18 hours (dark, of course). The flask was then removed, swirled vigorously to mix the solids, and quickly poured onto the buchner funnel. 100 mL of Et2O was added to the flask, in two fractions, swirled, and poured over the filter cake. The filter cake was placed in a vacuum dessicator in the dark for two hours. The filter cake was scraped into 500 mL NH3/EtOH solution, and the filter paper rinsed with two syringes full of the NH3/EtOH solution. The solution was stirred for 90 minutes (lights off), decanted, the solids re-extracted with a second 500 mL NH3/EtOH fraction (90 min. stirring, lights off), and filtered to remove the remaing solids (weight 1440 mg). The pooled extracts were stripped of solvent under vacuum at the rotovap (lights off, temp. set then left in dark). The solids remaing in the flask were taken up in 500 mL of 1% Aq. Ammonia. 250 mL 2.5 N H2SO4 was placed in the addition funnel, and added slowly with stirring to a beaker containing the extract. The pH was monitored continuously and addition was halted as the pH reached 3.0, the beaker was covered and placed in the refrigerator overnight. The solids were stirred vigorously to suspend them and collected by vacuum filtration. The beaker was swirled with 100 mL Et2O and the briefly suspended solids poured over the filter cake. The filter cake was placed in the vacuum dessicator for two hours (in the dark), and then weighed at 16.48g, placed in a brown glass vial, sprayed with nitrogen, sealed, wrapped in foil, and stored in the freezer at -10°C. The yield equates to 73%.
15% NH3 in EtOH prep.
1000 mL of 15% Ammonia in Anhydrous Ethanol was prepared by the slow addition of NaOH to cold absolute ethanol containg NH4Cl (not dissolved), filtration, and drying of the formed water by adding 0.20g CaO/1g H2O formed, with stirring and cooling. The formed calcium hydroxide was filtered.
Regular lighting was used during the reaction. Two red photography lights were used during the rxn workup.