Need help extracting and isolating the active ingrediants in Benadryl Allergy an
ID: 904051 • Letter: N
Question
Need help extracting and isolating the active ingrediants in Benadryl Allergy and Sinus Headache Medication for research in an advanced chemistry lab.
The active ingrediants are:
Acetaminophen (pKa-9.38)
Diphenhydramine HCl (pKa~9) salt
Psuedophedrine HCl (pKa-9.22) salt
I have free roam off all the labroatory tools/glassware/chemicals so any procedure such as solid phase extraction, TLC, liquid-liquid extraction will work . thanks
p.s. last time I posted this i just got a copy and paste from Google or Wikipedia as an answer..please don't do that.
Explanation / Answer
Single-Phase Acid-Base Extraction of Dextromethorphan (DXM) from Cough Syrups
I see many post of the internet about how to extract DXM from cough syrups, and usually people do not understand them, and many have errors that can be very dangerous. I hope that by writing this document, many people with questions will be helped. Let me first start off by trying to explain how this will be accomplished.
There is a rule in chemistry that states “likes will dissolve in likes”, meaning that a nonpolar substance will dissolve in a nonpolar substance, and a polar substance will dissolve in a polar substance. Most of the bad stuff in cough syrups (coloring and such) is nonpolar. We will first get rid of this by dissolving it in another nonpolar substance (lighter fluid). Next we will convert the DXM salt (Dextromethorphan HBr) into its basic form (DXM freebase), by adding a strong base; sodium hydroxide (NaOH). DXM freebase is nonpolar, so we will dissolve this in the nonpolar solvent again, and then evaporate the solvent leaving the DXM freebase.
If the following procedure is followed accurately, you can assume around only 5% of the DXM will be lost in the procedure. Read the entire document and understand it before attempting to do it. If you have any questions, feel free to email me at ssabusivefw@yahoo.com.
WARNINGS
1. Do NOT try this procedure if the cough syrup contains any active ingredients other than Dextromethorphan Hydrobromide (DXM HBr) or Guaifenesin.
2. Sodium Hydroxide (NaOH) is used in this procedure. NaOH is caustic and extremely damaging to the eyes and skin. Wear proper safety gear during the procedure, including goggles and latex gloves.
3. Do in a well ventilated area due to the organic vapors from the nonpolar solvent.
Materials
1. Cough syrup containing DXM HBr (see Note 1)
2. Two clean plastic two-liter bottles with caps
3. Glass cup
4. Two gallon size plastic Ziploc™ bags
5. Nonpolar solvent (Naptha, Zippo™ lighter fluid, Ronson™ lighter fluid)
6. Sodium Hydroxide (NaOH) (see Note 2)
7. Distilled water
8. Scissors
9. Baking dish
10. Heat lamp
Directions
1. Form a solution of NaOH by placing 15ml (1tsp) of solid NaOH into 236ml (1cup) of distilled water. (Always add NaOH to the water) This will generate heat. Stir until all the NaOH is completely dissolved.
2. Empty the cough syrup into a two-liter bottle.
3. Add enough Naptha to make roughly a 6.35mm (¼ inch) layer deep of Naptha on top of the cough syrup per 4oz of cough syrup. (If you were using an 8oz bottle, the Naptha layer should be roughly 12.7mm, ½ inch, thick)
4. Cap the bottle and shake vigorously for at least 5 minutes. After the five minutes, let it stand until the layers have separated.
5. Pour the contents of the bottle into one of the bags, and seal it. Hold the bag by one of the top corners so that a bottom corners points straight down. Let the layers full separate again if needed.
6. Place a clean bottle beneath the corners that is pointing straight down, and cut the very tip of the corner off. Let the bottom layer pour into the bottle. Pinch the bag shut just before the top layer, making sure none of the top layer gets into the bottle. Discard what is remaining it the bag by letting it evaporate outdoors.
Most of the bindings and flavorings are now removed. You can repeat steps 3-6 to remove more excess stuff, but it is not necessary.
7. Add 15ml (1tsp) of the NaOH solution (that was prepared in step 1) to the two-liter bottle containing the cough syrup. You should see a rapid formation of a white precipitate. Swirl the bottle gently to mix thoroughly and the precipitate should redissolve.
8. Repeat step 7 until the precipitate does not redissolve with swirling.
9. Add 15ml (1tsp) more of the NaOH solution to the bottle.
10. Add Naptha again to make a 3.18mm (1/8 inch) thick layer of Naptha per 4oz bottle of cough syrup used. (Again, if using an 8oz bottle, the Naptha layer should be roughly 6.35mm, ¼ inch, thick)
11. Cap the bottle and shake vigorously for at least 5 minutes (the more you shake it the better the yield). Let it stand until the layers separate again. If the layers do not want to separate, add sodium chloride (table salt).
12. Pour the contents of the bottle into another plastic bag and seal it. Hold the bag by one of the top corners so that a bottom corner points straight down. Let the layers separate again.
13. Cut the very tip of the corner that is pointing straight down. Allow the bottom layer to drain out. Collect the top layer on the baking dish. This time, make sure none of the bottom layer gets onto the baking dish.
14. Let the liquid evaporate. You may heat it gently with an electrical heat source (hot plate) or a heat lamp (be careful not to put the heat lamp to close to the baking dish or you might burn it.) Do not boil it!
15. Scrape the DXM off the baking dish with a razor. This is DXM freebase. It should be a white crystalline powder. (See Note 3)
Notes
1. Following is a set of equations and tables that I used to determine which cough syrup had the best yield at the best price. Please be aware though, that you should avoid products that contain alcohol. The alcohol affects the extraction procedure, but it will still work if consumed in the syrup form. If you are aware of other product that is better, please send me the all the information that is included in the following table, and I will add it to the next revision. A little math knowledge is needed to understand how this information was obtained.
Brand
Size
Price
Dosage
Total Yield
Alcohol
Vicks 44
4oz
$4.69
30mg/15ml
236mg
None
Robitussin M.S.
4oz
$4.99
15mg/5ml
354mg
1.4%
CVS Tussin Cough
8oz
$5.19
($2.99 online)
15mg/5ml
708mg
1.4%
4oz = 118ml 15ml = 1 teaspoon
Yields
Vicks 44
(30mg/15ml)(118ml) = 236mg 236mg/4oz = 59mg/oz
Robitussin Maximum Strength & CVS Tussin Cough Yield
(15mg/5mg)(118ml) = 354mg 354mg/4oz = 88.5mg/oz
Pricing
Vicks 44
(59mg/1oz)(4oz/$4.69) = 50.32mg/$1
R.M.S.
(88.5mg/1oz)(4oz/$4.999) = 70.94mg/$1
CVS
(88.5mg/1oz)(8oz/$5.19) = 136.42mg/$1
*(88.5mg/1oz)(8oz/$2.99) = 236.79mg/$1 (If ordered online)*
2. Sodium hydroxide (NaOH) can be found in photography supply stores. If there is no such store near you, check online. Sodium hydroxide is a very common chemical and will not raise the suspicions of the government. You can also use Red Devil™ Lye. Make sure it is the pure, solid form though, otherwise is may be impure. Check the label. If you are still not sure, then do not risk it. The results can very easily be deadly.
3. If your baking dish is covered with an oily substance, you most likely extracted propylene glycol or something else, or if you think that you have not gotten anything, blow hot air, from a hair dryer, onto the surface of the dish until it completely dries. (DXM freebase plus propylene glycol can look a lot like glass). Also, guaifenesin converts to an oily layer if too much NaOH is used, so do not overdo it.
Separation of Active Components from Excedrin ES Purpose: The purpose of this lab is to isolate the active components present in Exedrin ES tablets, namely acetaminophen, aspirin, and caffeine. To accomplish this, you will take advantage of the different chemical characteristics of these three components. From the structures below, you can see that aspirin contains a carboxylic acid group, while the caffeine contains a basic N atom (circled). So it should be relatively easy to dissolve these two components in an organic solvent and then extract them with an aqueous acid or base. HO O O O CH3 N N N N O O CH3 H3C CH3 HN O CH3 OH aspirin caffeine acetaminophen (acetylsalicyclic acid) (p-hydroxyacetanilide) CH2Cl2 soluble CH2Cl2 soluble CH2Cl2 insoluble The acetaminophen contains a phenol (OH directly attached to an aromatic ring) and an amide functionality. At first glance, the amide group may appear to be basic because it contains a nitrogen atom. However, contributing resonance forms for amides results in decreased electron density on the N atom, making the N less basic than amines. In addition, acetaminophen has additional resonance forms which distribute the electron density to carbon atoms, further reducing the basicity of the N atom. Phenols are slightly N O CH3 OH H N + O - CH3 OH H CH - N + O CH3 OH H C - N + O CH3 OH H HC - N + O CH3 OH H resonance forms of acetaminophen, showing increased positive charge on N atom compared to amines acidic and many phenols are acidic enough to react with NaOH to form water soluble salts. However acetaminophen and aspirin have different solublities in methylene chloride and this difference can be used to separate acetaminophen from the other two active ingredients in Excedrin ES. Methylene chloride is not soluble in water and will form a separate liquid layer when shaken with water and allowed to settle in a separatory funnel. The two phases can be separated, thereby creating two fractions: one containing substances soluble in methylene chloride and one containing substances soluble in water. By adjusting the pH of the aqueous phase by adding NaOH or HCl, the nature of organic substance, and hence its solubility in water, can be manipulated. HO O O O CH3 N N N N O O CH3 H3C CH3 NaOH O O - O O CH3 Na+ water soluble CH2Cl2 soluble HCl HCl NaOH N N N NH + O O CH3 H3C CH3 CH2Cl2 soluble water soluble Cl- . You will use the properties described above to separate the components of Excedrin ES. As you follow the procedure, you will use your knowledge of the properties of each substance to determine the effect of each step on the separation scheme and the identity of the component(s) present at each step of the scheme. Based on these two properties, we can develop a scheme to separate these three compounds. First, use an organic solvent to dissolve the aspirin, and the caffeine. Since the acetaminophen is less soluble in organic solvents, it has effectively been isolated from the other two. Now we will extract the organic layer with an aqueous acid. The acid will react with the caffeine to produce a salt that is water soluble. Remove the aqueous layer and make it basic to regenerate the caffeine. The caffeine is once again soluble in organic solvent and so can be separated from the aqueous phase. Finally, extract the original organic layer with an aqueous base. It will react with the aspirin to produce a salt that is water soluble. Remove the aqueous layer and make it acidic to regenerate the aspirin. The aspirin is once again soluble in organic solvent and so can be separated from the aqueous phase. Unfortunately, there is no such thing as a 100% efficient extraction. Because of this you will not extract all of the original components. In addition, each crude product you collect will contain small amounts of one or more of the other compounds. To further purify you crude compounds, you will need to recrystallize them using the procedures you learned in previous labs. Equipment/supplies ExcedrinES: 2 tablets/student Methylene chloride (~27ml/student) Ethanol (~5 mL/student) 5% HCl (~10mL/student) 3M NaOH (~10mL/student) aspirin standard caffeine standard acetaminophen standard 25mL E. flasks 5/student small beaker 5/student 1 hot plate/stirrer stir bar boiling stick (3/student) TLC plates iodine chamber acetic acid/butyl acetate developing solvent Procedure I Sample Preparation 1. Carefully weigh 2 Excedrin ES tablets and grind the tablets into powder using a mortar and pestle. 2. Transfer the resulting powder into a clean, 25 mL Erlenmeyer flask and add ~7 mL methylene chloride. (Note: methylene chloride is a suspected carcinogen, handle with care!-keep the flask under a snorkel hood) 3. Add a magnetic stir bar and stir the contents on a magnetic stirrer/hot plate for 5 minutes with gentle warming. The caffeine and aspirin are soluble in the methylene chloride whereas the acetaminophen and binders are not. II Isolation of crude acetaminophen 4. Filter the material through a small Buchner funnel (pre-weigh the filter paper) and wash the solids with ~5mL additional methylene chloride. (this helps remove any methylene chloride soluble material still entrained (trapped) in the solids). Allow the solids to dry for 5 minutes and then weigh the filter paper/solids. Determine the mass of the solids. Label the solids ‘A’ 5. While the solids in step 4 are drying, transfer the filtrate from step 4 to a separatory funnel (make sure the stopcock is in the closed position). Label the filtrate ‘B’ 6. Transfer the solids ‘A’ in the funnel to a clean 25 mL Erlenmeyer flask and add ~5-7 mL ethanol. Add a boiling stick (provided) and gently boil the contents on a hot plate. Filter the contents while still warm by gravity filtration (pre-weigh the filer paper) into a small pre-weighed beaker and wash the contents of the filter paper with ~ 5mL warm ethanol. Place the filter paper on a watch glass and allow to air dry. Label the solids ‘C’. Obtain the weight of solids ’C’ when dry. 7. Concentrate the ethanol solution in the beaker to dryness by gently heating to a boil. Be careful not to over heat the material. After cooling, weigh the contents of the beaker. Calculate the amount of crude acetaminophen recovered. Label this ‘D’ III Isolation of aspirin 9. Add ~5mL 5% HCl to the separatory funnel described in step 5. Cap the separatory funnel and invert the funnel. While in the inverted position, open the stopcock to release any pressure buildup. Repeat this process once more, and then agitate the funnel to thoroughly mix the contents. Open the stopcock once more in the inverted position. Then close the stopcock and place the separatory funnel in a ring support and allow the layers to separate. 10. Drain the methylene chloride layer into a clean 25mL Erlenmeyer flask; drain the aqueous layer into another 25mL Erlenmeyer flask. Label the methylene chloride layer ‘E’ and the aqueous layer ‘F’ 11. Return the methylene chloride layer ‘E’ to the separatory funnel and repeat step 9. 12. Drain the aqueous layer from step 11 into flask ‘F’. Return the methylene chloride layer to flask ‘E’ 13. Remove trace amounts of water from the methylene chloride layer (E) by adding small amounts of anhydrous magnesium sulfate (MgSO4) until the MgSO4 easily disperses and remains suspended in the liquid. Allow the mixture to stand for 5 minutes. 14. Filter the MgSO4 suspension through a Kim-wipe placed in a short gravity funnel suspended over a pre-weighed beaker. The Kim-wipe should remove the magnesium sulfate. The filtrate in the beaker should be clear. If not, re-filter. 15. Evaporate the methylene chloride on a hot plate at low setting (2-3). Weigh the solids that remain in the beaker (‘E’) IV Isolation of caffeine 16. Transfer the contents of flask ‘F’ to the separatory funnel. Slowly add 10% NaOH(aq) with gentle swirling until the solution is basic to litmus paper. (use a glass rod to sample the mixture and touch the end of the rod to a piece of litmus paper) 17. Add 5mL methylene chloride to the separatory funnel and shake the contents to mix the contents. Allow the contents to settle into two phases. 18. Drain the methylene chloride layer into flask ‘G’ 19. Add 5mL fresh methylene chloride to the contents of the separatory funnel and repeat step 17. 20. Drain the methylene chloride layer into flask ‘G’; drain the aqueous layer into flask ‘H’ 21. Dry the methylene chloride layer and filter as described in steps 13-14 (make sure to pre-weigh the beaker.) 22. Evaporate the methylene chloride layer as described in step 15 . Weigh the residue (‘G’) VI Purification of crude substances. 23. Re-crystallize the crude solid ‘D as follows: Add ~2-3mL water and heat to near boiling. Add additional water slowly until the solids dissolve. Allow the solution to cool and then place in an ice bath. Recover the solids by vacuum filtration (Buchner funnel). Allow the solids to dry and obtain the mass. 24. Recrystallize the crude aspirin as follows: Add 2-3 mL of 95% ethanol to the beaker containing the crude aspirin and warm (do not boil) the mixture to dissolve the crystals. If the crystals do not all dissolve, add 2-3 mL more of the ethanol and continue to warm the mixture. When the crystals are all dissolved, add 8-10 mL of warm water, cover the beaker with a watch glass, and let the solution cool slowly. Crystals of aspirin will form. Complete the recrystallization by cooling in an ice bath. 25. Recrystallize the crude caffeine by adding just enough hot water to dissolve the crude material. Allow the resulting solution to cool to room temperature. Place the mixture in an ice bath to complete the recrystallization. VII Charactaerization of isolated substances 26. Obtain melting points for each of the separated components of Excedrin ES. Since caffeine sublimes readily, the capillary holding the caffeine sample.
Brand
Size
Price
Dosage
Total Yield
Alcohol
Vicks 44
4oz
$4.69
30mg/15ml
236mg
None
Robitussin M.S.
4oz
$4.99
15mg/5ml
354mg
1.4%
CVS Tussin Cough
8oz
$5.19
($2.99 online)
15mg/5ml
708mg
1.4%
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