Introduction
LSD is an unusually fragile molecule, and some comments are in order as to its stability and storage. As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely. There are two sensitive aspects of its structure. The position of the carboxamide attachment, the 8-position, is affected by basic, or high pH, conditions. Through a process called epimerization, this position can scramble, producing isolysergic acid diethylamide, or iso-LSD. This product is biologically inactive, and represents a loss of a proportionate amount of active product. A second and separate point of instability is the double bond that lies between this 8-position and the aromatic ring. Water or alcohol can add to this site, especially in the presence of light (sunlight with its ultraviolet energy is notoriously bad) to form a product that has been called lumi-LSD, which is totally inactive in man. Oh yes, and often overlooked, there may be only an infinitesimal amount of chlorine in treated tap water, but then there is only an infinitesimal amount of LSD in a typical LSD solution. And since chlorine will destroy LSD on contact, the dissolving of LSD in tap water is not appropriate.
There are many synthetic methods developed and reported for the preparation of LSD. All of them start with lysergic acid, and for that reason, it has been listed as a Schedule III controlled drug, as a depressant, under Federal law. The amide lysergamide, a component of several varieties of Morning glory seed, is also a controlled drug and, by law, a depressant.
The extraction procedure of Ergotamine from tablets is the same as in this method.
There are many synthetic methods developed and reported for the preparation of LSD. All of them start with lysergic acid, and for that reason, it has been listed as a Schedule III controlled drug, as a depressant, under Federal law. The amide lysergamide, a component of several varieties of Morning glory seed, is also a controlled drug and, by law, a depressant.
The extraction procedure of Ergotamine from tablets is the same as in this method.
Equipment and glassware:
- Round bottom flasks (RBF) 500 mL and 100 mL;
- Ice water bath;
- Retort stand and clamp for securing apparatus;
- Magnetic stirrer with heater;
- Vacuum source;
- Rotovap machine;
- Flash chromatography kit;
- Buchner flask and funnel (large) 5 L [Schott filter may be used for small quantities];
- Laboratory scale (0.01 — 100 g is suitable);
- Glass rod and spatula;
- pH indicator paper;
- Drip funnel 100 mL;
- 100 mL x3; 50 mL x2 Beakers;
- Reflux condenser;
- Separatory funnel, 500 mL.
Reagents:
- Ergotamine tartrate (ET) 10 g;
- Potassium hydroxide solution (KOH) 6.7 g in 100 mL H2O;
- Sulfuric acid ~100 mL 2.5 N (H2SO4);
- Diethyl ether (Et2O) ~200 mL;
- Ammonia (NH3) anhydrous ethanol solution 50 mL 15%;
- Aqueous ammonia (NH4OH) 50 mL of 1% + 200 mL 1 N;
- Diethylamine (Et2N) 7.1 g;
- Chloroform (CHCl3) ~350 mL;
- Phosphoryl chloride (POCl3) 3.4 g;
- Magnesium sulphate (MgSO4) anhydrous ~100 g;
- Hexane ~200 mL;
- Dry methanol (MeOH) ~100 mL;
- Dry d-Tartaric acid (0.232 g per 1 g of LSD base);
- Distilled water ~ 500 mL.
Boiling Point: N/A;
Melting Point: 200 °C;
Molecular Weight: 473.5 g/mole;
Density: N/A;
CAS Number: 17676-08-3.
Procedure
d-Lysergic acid hydrateA solution of 6.7 g KOH in 100 mL H2O, under an inert atmosphere and magnetically stirred, was brought to 75 °C, and 10 g ergotamine tartrate (ET) (1) added in 500 mL round bottom flask. The reaction mixture turned yellow as the ergotamine went into solution over the course of 1 h. The stirring was continued for an additional 3 h. The reaction mixture was cooled to about 10 °C with an external ice bath, and acidified to a pH of about 3.0 by the dropwise addition of 2.5 N H2SO4. White solids started to appear early in the neutralization; approximately 60 mL of sulfuric acid (H2SO4) was required. The reaction mixture was cooled overnight, the solids removed by filtration, and the filter cake washed with 10 mL Et2O. The dry solids were transferred to a beaker, suspended in 50 mL 15% ammonia in anhydrous ethanol, stirred for 1 h, and separated by decantation. This extraction was repeated, and the original decantation and the second extract combined and filtered to remove a few hundred milligrams of unwanted solids. The clear filtrate was stripped of solvent under vacuum, the residual solids dissolved in 50 mL of 1% aqueous ammonia, and this solution was acidified as before with 2.5 N H2SO4. The precipitated solids were removed by filtration and washed with Et2O until free of color. After drying under vacuum to a constant weight, there was obtained 3.5 g of d-lysergic acid hydrate (2), which should be stored in a dark, sealed container.
Lysergic acid diethylamide (LSD) free-base
A suspension of 3.15 g d-lysergic acid hydrate (2) and 7.1 g of diethylamine in 150 mL CHCl3 was brought to reflux with stirring. With the external heating removed, there was added 3.4 g POCl3 over the course of 2 min, at a rate sufficient to maintain refluxing conditions. The mixture was held at reflux for an additional 5 min, at which point everything had gone into solution. After returning to room temperature, the solution was added to 200 mL of 1 N NH4OH. The phases were separated, the organic phase dried over anhydrous MgSO4, filtered, and the solvent removed under vacuum. The residue was chromatographed over alumina with elution employing a 3:1 C6H6/CHCl3 mixture, and the collected fraction stripped of solvent under hard vacuum to a constant weight. This free-base solid (3) can be recrystallized from benzene to give white crystals with a melting point of 87-92 °C.
Lysergic acid diethylamide (LSD) tartrate
This base was dissolved in warm, dry MeOH, using 4 mL per 1 g of product. There was then added dry d-tartaric acid (0.232 g per 1 g of LSD base), and the clear warm solution treated with Et2O dropwise until the cloudiness did not dispel on continued stirring (use 100 mL RBF in this case). This opaqueness set to a fine crystalline suspension (this is achieved more quickly with seeding) and the solution allowed to crystallize overnight in the refrigerator. Ambient light should be severely restricted during these procedures. The product was removed by filtration, washed sparingly with cold methanol, with a cold 1:1 MeOH/Et2O mixture, and then dried to constant weight. The white crystalline product was lysergic acid diethylamide tartrate with two molecules of methanol of crystallization, with an m.p. of about 200 °C with decomposition, and weighed 3.11 g (66%).
Repeated recrystallizations from methanol produced a product that became progressively less soluble, and eventually virtually insoluble, as the purity increased. A totally pure salt, when dry and when shaken in the dark, will emit small flashes of white light.
Medicines containing Ergotamine
There is the list of medicine which are containing Ergotamine:- Brand names: Belcomp-PB, Cafatine PB, Micomp-PB, Ergocomp-PB
- Contain: Belladonna/caffeine/ergotamine/pentobarbital systemic
- Brand names: Bellergal-S, Spastrin, Eperbel-S, Bellamor
- Contain: Belladonna/ergotamine/phenobarbital
- Brand names: Cafergot, Cafetrate, Wigraine, Ercaf
- Contain: Caffeine/ergotamine systemic
There are many different medicines that contain ergotamine. You can search on Amazon or other search resource in your country.
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