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lysergic acid diethylamide full synthesis

#1 Synthesis of LSD-25 from Ergot Alkaloids or LSA
(including sections on isomerization, seperation, purification, and crystallization)

NOTE: The chemicals and reactions described below are potentially dangerous, even to an organic chemist in a well-equipped labaratory.

A) Synthesis of LSD-25
(iso-and dextro-lysergic acid diethylamide)

PREPARATORY: Obtain one Red and one Yellow photographic safety light and one Weak, Long-wave ultraviolet light. These are used to prevent the hydrolysis of lysergic acid compounds.

NOTE: Aluminum foil must be used to cover the Chemicals when light is present. Rubber gloves must be worn; these compounds are extremely poisionous.

USING YELLOW LIGHT

Place 1 volume of Ergot Alkaloid in a small roundbottom flask. Add 2 volumes of Anhydrous(Contains no water) Hydrazine and use the Reflux distillation process for exactly 30 minutes. Maintain atmospheric pressure by using a fractionating column.

After Refluxing, add 1.5 volumes of purified water to the mixture and boil gently for 15 minutes. After boiling is complete, cool the mixture in a refrigerator until the mixture has become solid. The solid material obtained is iso-lysergic acid hydrazine.

USING RED LIGHT

Chill all regents(Chemicals) to be used at 0 celsius. Place an open flask in an ice bath. Add 100ml of concentrated Hydrochloric acid(chilled to 0 celsius) being careful to maintain a temperature of 0 celsius.

Add 100ml of a 0.1(1/10th Normal) solution of Sodium Nitrate(chilled to 0 celsius) and stir vigorously for 3 minutes.

Continue stirring and add dropwise 130ml of Hydrochloric acid while maintaining 0 celsius.

When the acid addition is complete, continue stirring for 5 minutes, then neutralize the solution with Sodium bicarbonate using a saturated water solution of the bicarbonate.

Extract the solution with Ether, remove the water layer, and dissolve the gummy substance in Ether. Add this to the Ether layer.

Add 3 grams of diethylamine for every 30ml of the Ether extract.

Let the solution stand in complete darkness and gradually warm up to 20 celsius for 24 hours.

Evaporate the solution in a vacuum.

The material remaining is a mixture of inactive iso-lysergic acid diethylamide and the active lysergic acid diethylamide(LSD-25). The inactive isomer must now be converted(isomerized) into active isomer to greatly increase the yield, since the inactive compund predominates in the synthesis.

B) Isomerization of iso-LSD into active LSD-25

USING RED LIGHT

Dissolve the synthesized material into the minimum amount of Ethyl Alcohol.

Mix a 4 normal solution of Potassium hydroxide in Ethanol. The amount of solution needed is twice the volume of the iso-LSD/ethanol solution.

Add the two solutiontogether and let the mixture sit for 4 hours at normal room temperature.

Neutralize the mixture with dilute Hydrochloric acid, then make it slightly basic with Ammonia Hydroxide.

Extract the mixture with Chloroform, sperate the Chloroform layer and extract this 4 times witha 25% volume of purified water

Evaporate the Chloroform in a vacuum. Discard the water extracts. The material left after evaporation is a mixture of iso-LSD and LSD-25, the active LSD-25 predominating.

The mixture may now be seperated by chromatography and the iso-LSD again, isomerized by the above process.

C) Seperation, Purification and Crystallization of LSD-25

USING A DARK ROOM

The material obtained from the isomerization process is now dissolved in a solution prepared from 3 part Benzene/! part Chloroform. Use 50ml Solvent per 1 gram LSD material.

Mix a slurry basic alumina in Benzene. Pack it into a 1 inch Chromatography column until it fills 6 inches

When the slurry settles, drain the Benzene/Chloroform down to the level of the basic alumina and carefully add an equal amount of LSD/solvent solution

USING A WEAK,LONG-WAVE ULTRAVIOLET LIGHT(to follow the blue band only)

Drain the solution through the column. The fastest-moving Blue Flourescent band contains the LSD-25.
Collect this fraction and evaporate in a vacuum. The syrup remaining will crystallize spontaneously, but slowly. DO NOT HEAT.

Use the Ultraviolet light only when necessary to follow the Blue band in order to avoid Decomposition of the compounds.

Dissolve the syrup or crystals in Tartaric acid solution and Recrystallize to form the stable end product(dextro-Lysergic Acid Diethylamide tartrate).

The material remaining in the column may be removed with Methanol, evaporated in a vacuum and recycled through the isomerization and subsequent procedures by itself or combined with fresh material.
Also, all leftover solutions and residues mmay be neutralized with sodium bicarbonate, Evaporated in a vacuum and extracted with Ammoniacal Chloroform, the extract evaporated to dryness and the residue reused.

End of part 1