ULTRASOUND ASSISTED EXTRACTION and: ====================================== the most comprehensive , Phytochemical Data Documentation + ANALYSIS attached ! ====================================== UAE Protocol for Extracting Ephedrine-Type Alkaloids Materials and Equipment • Dried and powdered Herba Ephedrae • 70% ethanol (aqueous ethanol) • Ultrasound bath operating at 46 kHz • Thermometer • Filtration apparatus • Rotary evaporator • Freeze dryer or vacuum oven • Analytical balance • Glassware (beakers, flasks, etc.) Procedure 1. Sample Preparation : • Ensure the Herba Ephedrae is thoroughly dried and ground into a fine powder. 2. Solvent Preparation : • Prepare 70% ethanol by mixing ethanol with distilled water. 3. Weighing and Mixing : • Weigh the dried plant material accurately (e.g., 10 grams). • Place the powdered plant material in a beaker. • Add 70% ethanol at a solvent-to-material ratio of 20:1 (e.g., 200 mL for 10 grams of plant material). 4. Sonication : • Place the beaker with the mixture in the ultrasound bath. • Ensure the temperature of the ultrasound bath is maintained at 50°C. • Sonicate the mixture at 46 kHz for 30 minutes. • Stir the mixture occasionally to ensure even extraction. 5. Filtration : • After sonication, filter the mixture using a filtration apparatus to remove the plant debris. • Collect the filtrate in a clean flask. 6. Concentration : • Concentrate the filtrate under reduced pressure using a rotary evaporator. Set the water bath temperature to around 40°C to prevent degradation of the compounds. • Continue until the solvent is significantly reduced and you have a concentrated extract. 7. Drying : • Transfer the concentrated extract to a freeze dryer or a vacuum oven to remove any remaining solvent. • Ensure complete drying to obtain a powdered extract. 8. Storage : • Store the dried extract in a sealed container, preferably in a cool, dark place to maintain stability. Optimization Tips • Solvent Volume and Concentration : Adjust the solvent-to-material ratio and ethanol concentration if initial results are not satisfactory. • Sonication Time and Temperature : Experiment with longer sonication times and slightly higher temperatures if needed, but avoid temperatures that may degrade the alkaloids. • Repeat Extractions : Consider performing multiple extractions on the same plant material to maximize yield. Isolation of Ephedrine from Dried Extract Materials and Equipment • Dried extract of Herba Ephedrae • Hydrochloric acid (HCl) • Sodium hydroxide (NaOH) • Organic solvents (e.g., chloroform, diethyl ether) • Separatory funnel • Rotary evaporator • pH meter or pH paper • Ice bath • Filtration apparatus • Analytical balance • Recrystallization solvents (e.g., ethanol, acetone) • Glassware (beakers, flasks, etc.) Procedure 1. Preparation of Acidic Aqueous Solution : • Dissolve the dried extract in a minimal amount of distilled water. • Acidify the solution with dilute HCl (about 1-2 M) to a pH of around 2-3. This will convert ephedrine to its water-soluble hydrochloride salt. 2. Extraction of Non-Polar Compounds : • Transfer the acidic aqueous solution to a separatory funnel. • Extract with an organic solvent like chloroform or diethyl ether to remove non-polar impurities. Perform this step 2-3 times, discarding the organic layers each time. 3. Basification : • After the extraction, basify the aqueous layer by slowly adding NaOH solution (about 1-2 M) to a pH of around 11-12. This will convert ephedrine hydrochloride back to free base ephedrine. 4. Extraction of Ephedrine Base : • Extract the basified solution with an organic solvent such as chloroform or diethyl ether. Perform this step 2-3 times, combining the organic layers. 5. Drying and Concentration : • Dry the combined organic layers over anhydrous sodium sulfate (Na2SO4) to remove any water. • Filter the drying agent and concentrate the organic layer under reduced pressure using a rotary evaporator to obtain a crude ephedrine base. 6. Recrystallization : • Dissolve the crude ephedrine base in a minimal amount of a suitable recrystallization solvent (e.g., ethanol or acetone). • Slowly evaporate the solvent or cool the solution in an ice bath to induce crystallization. • Collect the crystals by filtration and dry them under reduced pressure. Ephedrine Base Solubility Overview Ephedrine Base: • Chemical Structure: Ephedrine (C₁₀H₁₅NO) is a basic compound with an amino group, making it soluble in polar solvents. • Form: It’s typically found as a free base in non-aqueous solvents and as a salt in aqueous solutions. Solubility in Common Solvents 1. Water: • Solubility: Ephedrine base has limited solubility in pure water. • Notes: Ephedrine salts (e.g., ephedrine hydrochloride) are more soluble in water. The free base form is less soluble due to its non-polar nature. 2. Ethanol: • Solubility: Ephedrine base is moderately soluble in ethanol. • Notes: Ethanol is often used in recrystallization or extraction processes. It dissolves ephedrine base effectively, especially when warm. 3. Methanol: • Solubility: Ephedrine base is quite soluble in methanol. • Notes: Methanol is similar to ethanol in terms of solubility and is also used for extraction and recrystallization. 4. Acetone: • Solubility: Ephedrine base has limited to moderate solubility in acetone. • Notes: Acetone is a good solvent for recrystallization but might require heating to fully dissolve ephedrine base. 5. Ethyl Acetate: • Solubility: Ephedrine base is moderately soluble in ethyl acetate. • Notes: This solvent is often used in liquid-liquid extractions and can be effective for separating ephedrine base from other components. 6. Hexane: • Solubility: Ephedrine base has very low solubility in hexane. • Notes: Hexane is non-polar, making it unsuitable for dissolving ephedrine base, which is more polar. 7. Chloroform: • Solubility: Ephedrine base has low to moderate solubility in chloroform. • Notes: Although chloroform is somewhat effective, it’s generally less preferred due to its hazardous nature. 8. Kerosene: • Solubility: Ephedrine base is very poorly soluble in kerosene. • Notes: Kerosene is a non-polar solvent and thus not suitable for dissolving ephedrine base. 9. Isopropanol (Isopropyl Alcohol): • Solubility: Ephedrine base is moderately soluble in isopropanol. • Notes: Isopropanol is similar to ethanol and methanol, making it useful for both extraction and purification. 10. 2-Methyl Tetrahydrofuran (2-MeTHF): • Solubility: Ephedrine base is moderately soluble in 2-MeTHF. • Notes: 2-MeTHF is a green solvent and can be effective in extractions where other solvents are less suitable. Summary of Solubility: • Highly Soluble: Methanol, ethanol • Moderately Soluble: Acetone, ethyl acetate, isopropanol, 2-MeTHF • Low to Very Low Solubility: Water, hexane, chloroform, kerosene Choosing a Solvent: • For Extraction: Ethanol, methanol, and ethyl acetate are good choices due to their moderate solubility and effectiveness in separating ephedrine from aqueous solutions. • For Purification (Recrystallization): Ethanol or acetone can be used, depending on the solubility requirements and the temperature at which recrystallization is performed. • For Green Chemistry: Solvents like 2-MeTHF are suitable due to their lower environmental impact. Solubility of Ephedrine Base in Aromatic Hydrocarbons 1. Benzene: • Solubility: Ephedrine base has low to moderate solubility in benzene. • Notes: Benzene is a non-polar solvent, and ephedrine base, being a polar compound, does not dissolve very well. Benzene is also highly toxic and carcinogenic, making it a less desirable choice. 2. Toluene: • Solubility: Ephedrine base has low to moderate solubility in toluene. • Notes: Toluene is slightly more polar than benzene, so it may dissolve a bit more ephedrine base. However, it is still less effective compared to more polar solvents. Toluene is less hazardous than benzene but still requires careful handling. 3. Xylene: • Solubility: Ephedrine base has low solubility in xylene. • Notes: Xylene is a non-polar solvent with similar characteristics to benzene and toluene. It is generally not suitable for extracting polar compounds like ephedrine base. 4. Other Aromatic Hydrocarbons: • Solubility: Similar to benzene, toluene, and xylene, other aromatic hydrocarbons would generally show low solubility for ephedrine base. • Notes: The non-polar nature of these solvents means they are not ideal for polar substances like ephedrine base. Advantages and Disadvantages of Using Aromatic Hydrocarbons Advantages: Solvent Strength: Aromatic hydrocarbons can sometimes dissolve non-polar or weakly polar compounds well. • Availability: They are widely used in industrial applications and are relatively easy to obtain. Disadvantages: • Solubility: Generally, aromatic hydrocarbons are less effective for dissolving polar compounds like ephedrine base. • Health Hazards: Benzene is highly toxic and carcinogenic; toluene and xylene are less toxic but still require careful handling and adequate ventilation. • Environmental Impact: Aromatic hydrocarbons can have significant environmental impacts and require proper disposal methods. Practical Considerations If you choose to use an aromatic hydrocarbon for extracting ephedrine base, it’s essential to consider: 1. Solubility Testing: Test the solubility of ephedrine base in the specific aromatic hydrocarbon you plan to use. This will ensure that the chosen solvent can effectively dissolve the compound. Alternative Approaches For extracting ephedrine base, polar solvents like ethanol, methanol, and ethyl acetate are generally preferred due to their better solubility for polar compounds. These solvents offer better safety profiles and are often more effective for this type of extraction. Summary • Benzene: Low to moderate solubility; highly toxic. • Toluene: Low to moderate solubility; less toxic than benzene. • Xylene: Low solubility; similar to benzene and toluene in terms of toxicity. Chemical Structure and Polarity ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ (Ephedra Isolate in Comparison to: N-Methyl-Amphetamin , the final Compound ) **** a.k.a ~> DESOXYEPHEDRINE *** ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 1. Ephedrine Base: • Structure: Ephedrine (C₁₀H₁₅NO) has a structure that includes a primary amine group, a hydroxyl group, and a phenyl ring. The primary amine group (–NH₂) and the hydroxyl group (–OH) are polar functional groups. • Polarity: Due to these polar groups, ephedrine base is relatively polar overall. The presence of these polar groups contributes significantly to its solubility in polar solvents like water, ethanol, and methanol. 2. Desoxyephedrine (N-Methylamphetamine ) -Base: • Structure: Desoxyephedrine (C₁₀H₁₅NO), also known as methamphetamine, lacks the hydroxyl group present in ephedrine. It only has a primary amine group and a phenyl ring. • Polarity: Without the hydroxyl group, desoxyephedrine is less polar than ephedrine. Its primary amine group still contributes to its polarity, but it is not as polar as ephedrine with the additional hydroxyl group. Solubility in Non-Polar Solvents • Polarity vs. Solubility: Non-polar solvents, such as aliphatic and aromatic hydrocarbons, interact poorly with polar compounds due to their inability to effectively solvate polar functional groups. Polar compounds are better solubilized in solvents that can interact with their dipole moments or hydrogen bonding capabilities. • Ephedrine Base: • Low Solubility in Non-Polar Solvents: The strong polar character of ephedrine base, due to both the amine and hydroxyl groups, makes it poorly soluble in non- polar solvents. Non-polar solvents cannot effectively interact with the polar groups in ephedrine base, leading to low solubility. • Desoxyephedrine (N-Methylamphetamine ) - Base: • Higher Solubility in Non-Polar Solvents: Desoxyephedrine, lacking the hydroxyl group, is less polar than ephedrine. The reduced polarity makes it more soluble in non-polar solvents, as there are fewer polar interactions that need to be overcome. Interaction with Solvents • Polar Solvents: Solubilize compounds based on hydrogen bonding and dipole interactions. Compounds with strong polar functional groups (like ephedrine with its hydroxyl group) dissolve well in these solvents. • Non-Polar Solvents: Solubilize compounds based on Van der Waals forces and hydrophobic interactions. Compounds with fewer polar groups or lower overall polarity (like desoxyephedrine) dissolve better in non-polar solvents. Summary 1. Ephedrine Base: • Structure: Includes both an amine and a hydroxyl group. • Polarity: Highly polar. • Solubility: Poor in non-polar solvents due to strong interactions with polar solvents. 2. Desoxyephedrine Base: • Structure: Lacks the hydroxyl group, only contains an amine and phenyl ring. • Polarity: Less polar. Solubility: Higher in non-polar solvents due to reduced polarity. Conclusion | Physical Properties observational gathered Data (polarity specifics) The key factor affecting the solubility of ephedrine base versus desoxyephedrine base in non-polar solvents is the presence or absence of polar functional groups. Ephedrine’s additional hydroxylgroup increases its polarity, making it less soluble in non-polar solvents. In contrasdesoxyephedrine, with fewer polar functional groups, interacts more favorably with non-polar solvents. Sophisticated ADD-ON | finish THE COMPOSITION ------------------------------------ ----------------------------------- Salting Out | PRO- TECHNIQUE -------------------- --------------------------- THE “ CLEVER SOLUTION “ with Acetone / (EtOH or i-PrOH work as well) for Ephedrine Extraction Principle: • Salting Out : Adding sodium chloride to the aqueous phase reduces the solubility of organic compounds in water, thus driving them into the organic solvent (acetone in this case). This process increases the efficiency of the extraction. Protocol Using Acetone and Sodium Chloride 1. Basification : • Prepare the dried extract in a minimal amount of distilled water. • Basify the solution by adding NaOH (1-2 M) until the pH reaches 11-12. This converts ephedrine to its free base form. 2. Salting Out : • Add a saturated solution of sodium chloride to the basified aqueous solution. Continue adding solid sodium chloride until no more dissolves, indicating saturation. This helps to "salt out" the ephedrine, making it more available for extraction by acetone. 3. Extraction with Acetone : • Transfer the saturated, basified aqueous solution to a separatory funnel. • Add an equal volume of acetone to the separatory funnel. • Shake the funnel gently, then allow the layers to separate. Acetone will form the upper organic layer. • Separate the acetone layer and repeat the extraction process 2-3 times to ensure maximum recovery of ephedrine. 4. Drying : • Combine the acetone extracts. • Dry the combined extracts over anhydrous sodium sulfate (Na2SO4) to remove any residual water. • Filter the drying agent and collect the acetone solution. 5. Concentration : • Concentrate the acetone solution under reduced pressure using a rotary evaporator to obtain the crude ephedrine base. 6. Recrystallization : • Dissolve the crude ephedrine base in a minimal amount of a suitable recrystallization solvent (e.g., ethanol or acetone). • Slowly evaporate the solvent or cool the solution in an ice bath to induce crystallization. • Collect the crystals by filtration and dry them under reduced pressure. Considerations • Layer Separation : Ensure complete separation of the aqueous and organic layers to maximize recovery • Purity : Multiple extractions and thorough drying will improve the purity of the ephedrine. This in-depth Compendium on Plant Alkaloids ***************************************** [ of the HERBA EPHEDRAE Spec. Family ] with a Vast DOCUMENTATION of Experiments for NOVEL Phytochemistry Applications | all Data Properties were gathered in LAB-Setting , by OBSERVATION and TESTING I proudly DEDICATE my Reference Work on “ EPHEDRA type ALKALOID Preparations “ ____________________________________ → from HERB <-- TO CRYSTAL METH _____________________________________ TO ALL MY CLANDESTINE ALCHEMISTS , dwelling at the infamous BB-GATE DUNGEON (esp.G!)