Introduction
There are two methods of Ephedrine extraction. First one was taken from German patent and allow getting Ephedrine hydrochloride with high purity grade. This method is suitable for laboratory manufacturing more than for kitchen home lab. Second one is simple extraction method with ethanol and naphtha, which give quite dirty free base of ephedrine. Nevertheless, simple method may be carried out at home garage and product may be purified with recrystallization as in first method.
- 1000 mL x2; 250 ml x2 Beakers
- 100 mL x5; Erlenmeyer flasks;
- Glass rod;
- Glass column (d = 2.5 cm or wider, l = 70 cm);
- Cotton ball;
- 500 mL round bottom flask;
- Rotary evaporator;
- 500 ml Separating funnel;
- Conventional funnel;
- Filter paper;
- Hydrogen chloride gas production apparatus;
- Büchner funnel and flask;
- Water-jet aspirator;
- Laboratory scale (0.1 — 100 g is suitable);
- Spatula.
- Ephedra sinica Stapf 100 g;
- Sodium carbonate (Na2CO3) 50 g;
- Distilled water, 150 mL;
- Dichloromethane (CH2Cl2) ~1500 mL;
- Diethyl ether 50 mL;
- Hydrochloric acid 150 mL (HCl 0.5 N);
- Potassium carbonate (K2CO3) 50 g;
- Sodium hydroxide aq. solution (NaOH 1 N) ~100 mL;
- Sodium sulfate (Na2SO4) or magnesium sulfate (MgSO4) ~100 g;
- Acetone 30 mL;
- Methanol (MeOH) ~10 mL;
- Activated charcoal (optional) ~1 g;
Soluble in H2O 47.62 g/L (25 ºC), alcohol, ether, chloroform, and oils;
Boiling Point: 255 °C at 760 mm Hg (free base);Melting Point freebase: 37-39 ̊C;
Melting point HCI salt: 187-188 ̊C;
Molecular Weight: 165.236 g/mole;
Density: 1.124 g/cm3 (20 °C);
CAS Number: 299-42-3 (free base) and 50-98-6 (hydrochloride salt).
L-ephedrine hydrochloride from ephedra herb [50-98-6] C10H15NO HCl
Determination of content (optional):5 g of ground ephedra herb are mixed with 2 g of sodium carbonate and 7 mL of water and left to stand at room temperature for 3 hours. The mixture is treated three times with 50 ml of dichloromethane and stirred for at least 2 hours each time. The extract is pipetted off in each case. The organic phase is evaporated under vacuum (at 40 °C to 1 ml). After adding 20 mL of diethyl ether, it is extracted four times with 20 mL of 0.5 N hydrochloric acid, each time.
The combined hydrochloric acid phases are washed twice with 20 ml of ether, each time. After neutralization with 1 N sodium hydroxide solution (pH 7.5-8), it is extracted three times with 40 ml of dichloromethane and concentrated. The residue is taken up in 10 ml of water, and 3 ml of 0.1 N sodium hydroxide solution and 10 ml of 0.1 N I2/KI solution are added. The solution is stirred with gentle warming for 30 minutes. It is then carefully acidified with diluted HCl and a few drops of starch solution are added. The excess iodine is titrated with 0.1 N sodium thiosulphate solution until the color changes from blue to colorless.
Extraction procedure:
1. 100 g of powdered ephedra herb is added to a solution of 50 g of sodium carbonate in 150 ml of water in a 1000 ml beaker, mixed with a glass rod and left to stand for at least 2 hours.
2. A glass column (d = 2.5 cm or wider, l = 70 cm) is filled one third with dichloromethane and then filled in portions with the drug pulp. The drug should settle in the column without any air bubbles. The drug is covered with a glass cotton ball. (Please note: do not press the column filling too tightly).
3. It is percolated by continuously adding 1000 ml of dichloromethane (about two drops/sec). The percolate is concentrated portionwise in a 500 mL round bottom flask under vacuum to a volume of 5 mL.
4. 30 mL of ether are added to the extract, and it is shaken out three times with 50 ml of 0.5 N hydrochloric acid each time.
5. The combined hydrochloric acid extracts are filtered into a 500 ml separating funnel through a funnel with a pleated filter containing 50 g of potassium carbonate (add carefully). It must be filtered through carbonate slowly enough that the solution no longer reacts acidically (otherwise add carbonate). The carbonate is first rinsed with the methylene chloride for the extraction.
6. In this, the solution is shaken out four times with 75 ml of dichloromethane each time.
7. The combined organic phases are dried over sodium sulfate and concentrated in portions in a 250 ml flask on a rotary evaporator. The resulting yellow-orange oil is taken up in a mixture of 20 ml of diethyl ether and 20 ml of dichloromethane.
8. Dried hydrogen chloride gas is introduced into this solution. The apparatus for HCl generation consists of a multi-necked round-bottom flask with a stirrer, which is charged with sodium chloride and sulfuric acid (from a dropping funnel). To dry it, the gas is again passed through a washing bottle with a sodium chloride and sulfuric acid. The introduction into the alkaloid solution takes place with a Pasteur pipette. Empty safety washing bottles are installed in mirror image between all vessels so that no mixing can occur even if solutions are accidentally sucked back (see figure below). The excess gas is fed into a wash bottle with 10% NaOH solution (vent!).
[G.Patton note: You, probably, can substitute these 8-9 steps with addition of HCl conc. solution until precipitate stop forming. After, neutralize solution by NaOH aq solution to pH 7. Evaporate water under vacuum with minimum heating to get crystals.]
The combined hydrochloric acid phases are washed twice with 20 ml of ether, each time. After neutralization with 1 N sodium hydroxide solution (pH 7.5-8), it is extracted three times with 40 ml of dichloromethane and concentrated. The residue is taken up in 10 ml of water, and 3 ml of 0.1 N sodium hydroxide solution and 10 ml of 0.1 N I2/KI solution are added. The solution is stirred with gentle warming for 30 minutes. It is then carefully acidified with diluted HCl and a few drops of starch solution are added. The excess iodine is titrated with 0.1 N sodium thiosulphate solution until the color changes from blue to colorless.
Extraction procedure:
1. 100 g of powdered ephedra herb is added to a solution of 50 g of sodium carbonate in 150 ml of water in a 1000 ml beaker, mixed with a glass rod and left to stand for at least 2 hours.
2. A glass column (d = 2.5 cm or wider, l = 70 cm) is filled one third with dichloromethane and then filled in portions with the drug pulp. The drug should settle in the column without any air bubbles. The drug is covered with a glass cotton ball. (Please note: do not press the column filling too tightly).
3. It is percolated by continuously adding 1000 ml of dichloromethane (about two drops/sec). The percolate is concentrated portionwise in a 500 mL round bottom flask under vacuum to a volume of 5 mL.
4. 30 mL of ether are added to the extract, and it is shaken out three times with 50 ml of 0.5 N hydrochloric acid each time.
5. The combined hydrochloric acid extracts are filtered into a 500 ml separating funnel through a funnel with a pleated filter containing 50 g of potassium carbonate (add carefully). It must be filtered through carbonate slowly enough that the solution no longer reacts acidically (otherwise add carbonate). The carbonate is first rinsed with the methylene chloride for the extraction.
6. In this, the solution is shaken out four times with 75 ml of dichloromethane each time.
7. The combined organic phases are dried over sodium sulfate and concentrated in portions in a 250 ml flask on a rotary evaporator. The resulting yellow-orange oil is taken up in a mixture of 20 ml of diethyl ether and 20 ml of dichloromethane.
8. Dried hydrogen chloride gas is introduced into this solution. The apparatus for HCl generation consists of a multi-necked round-bottom flask with a stirrer, which is charged with sodium chloride and sulfuric acid (from a dropping funnel). To dry it, the gas is again passed through a washing bottle with a sodium chloride and sulfuric acid. The introduction into the alkaloid solution takes place with a Pasteur pipette. Empty safety washing bottles are installed in mirror image between all vessels so that no mixing can occur even if solutions are accidentally sucked back (see figure below). The excess gas is fed into a wash bottle with 10% NaOH solution (vent!).
[G.Patton note: You, probably, can substitute these 8-9 steps with addition of HCl conc. solution until precipitate stop forming. After, neutralize solution by NaOH aq solution to pH 7. Evaporate water under vacuum with minimum heating to get crystals.]
9. After about 5 minutes, an off-white precipitate of alkaloid hydrochlorides forms. The supply of hydrogen chloride is stopped, and all hose connections are disconnected from to prevent the liquids from being sucked back.
10. The alkaloid mixture is filtered off using a Büchner funnel.
11. About 30 ml of acetone are added to a 250 ml beaker and the mixture is heated on a water bath while adding methanol (about 10 ml) in portions until residue has completely dissolved.
12. A spatula tip of activated charcoal is added, boiled and the hot solution filtered. Just enough acetone is added to the still hot filtrate until the crystals begin to precipitate.
13. The mother liquor is carefully pipetted off the product, which precipitates on cooling (at least 6 hours); the crystals are washed with a little acetone and air dried.
If there is still no TLC-uniform product, the product is dissolved in 15 times the amount of methanol, treated with 100 times the amount of acetone and recrystallized at about 4 °C overnight.
10. The alkaloid mixture is filtered off using a Büchner funnel.
11. About 30 ml of acetone are added to a 250 ml beaker and the mixture is heated on a water bath while adding methanol (about 10 ml) in portions until residue has completely dissolved.
12. A spatula tip of activated charcoal is added, boiled and the hot solution filtered. Just enough acetone is added to the still hot filtrate until the crystals begin to precipitate.
13. The mother liquor is carefully pipetted off the product, which precipitates on cooling (at least 6 hours); the crystals are washed with a little acetone and air dried.
If there is still no TLC-uniform product, the product is dissolved in 15 times the amount of methanol, treated with 100 times the amount of acetone and recrystallized at about 4 °C overnight.
Second (simplified) extraction way to Ephedrine free base
Equipment and glassware:
- Pyrex pots ~750 mL x2;
- Heating plate (or stove);
- Filter with filter paper;
- Sponge cake pan, 2.5 cm deep.
Reagents:
- Ephedra sinica Stapf;
- Ethyl alcohol (EtOH) ~2.25 L;
- 750 mL Naphtha.
a) Fine powder placed in a four quart Pyrex pot, about 750 mL of ethyl alcohol (EtOH) to cover the powder. For this process, use Ever Clear from local spirit hut. The pot and alcohol to be warmed at ~32 °C (don’t bring to boil as it will destroy the Ephedrine). After allowing to steep for 10 minutes, remove the pot from the stove.
b) After 15 minutes filter the mush through a #15 gold filter with a coffee filter inside the gold filter (you can use a laboratory glass funnel or another filter sieve) then set the mush aside.
c) The filtered solution is poured into a 2.5 cm deep sponge cake pan covered with cheese cloth and allow to dry. Allow the solution to dry for 12 hours, leaving only a fine white powder (which shows to be 70% Ephedrine and 30% misc, mostly oils that the alcohol couldn’t break down).
2nd step:
a) Same as before, placed it in a four quart Pyrex pot. To the pot add 750 mL Naphtha, shake it vigorously 5-10 min and let it soak for three days.
b) Filter the mush the same way as above. Set the Naphtha solution aside for the second batch. Allow the mush to dry for three days.
c) Transfer the mush to a fresh Pyrex and cover with 750 mL ethyl alcohol, shake it vigorously 5-10 min and allow soaking for two days. Filter the mush, as you already know how to mark the solution “A” so that you can recognize it later.
d) Then place mush back in Pyrex and cover with another 750 mL ethanole this time, shake it vigorously 5-10 min and allow soaking for one day filter as you know how and then trash.
e) Now combine the second solution with the first into a 2.5 cm sponge cake pan to dry. Dry it for one day, leaving behind fine white powder.
Result 99% (not approved) Ephedrine free base, so total of Ephedrine extracted from 453 g of Ma Huang is 9.6 grams.
b) After 15 minutes filter the mush through a #15 gold filter with a coffee filter inside the gold filter (you can use a laboratory glass funnel or another filter sieve) then set the mush aside.
c) The filtered solution is poured into a 2.5 cm deep sponge cake pan covered with cheese cloth and allow to dry. Allow the solution to dry for 12 hours, leaving only a fine white powder (which shows to be 70% Ephedrine and 30% misc, mostly oils that the alcohol couldn’t break down).
2nd step:
a) Same as before, placed it in a four quart Pyrex pot. To the pot add 750 mL Naphtha, shake it vigorously 5-10 min and let it soak for three days.
b) Filter the mush the same way as above. Set the Naphtha solution aside for the second batch. Allow the mush to dry for three days.
c) Transfer the mush to a fresh Pyrex and cover with 750 mL ethyl alcohol, shake it vigorously 5-10 min and allow soaking for two days. Filter the mush, as you already know how to mark the solution “A” so that you can recognize it later.
d) Then place mush back in Pyrex and cover with another 750 mL ethanole this time, shake it vigorously 5-10 min and allow soaking for one day filter as you know how and then trash.
e) Now combine the second solution with the first into a 2.5 cm sponge cake pan to dry. Dry it for one day, leaving behind fine white powder.
Result 99% (not approved) Ephedrine free base, so total of Ephedrine extracted from 453 g of Ma Huang is 9.6 grams.
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