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Aspirin to Tylenol Conversion · Acedra
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Aspirin to Tylenol Conversion
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0:00
a little over a year ago I made a series of videos where a converted aspirin to tylenol for those of you outside of North America tylenol is probably known as a cinnamon ofin or paracetamol the brand aspirin seems to be pretty universal around the world but it might also be known as a si I think the idea of converting one pain relieving drug to another is quite interesting but I don't think I did the best job of conveying that because the original series was
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spread out over several videos so I've decided to make a single summary video which covers the entire process that I did the reason why this conversion is even possible is because both of these medications are based around the same core molecule called phenol what this means is that if I'm able to degrade one of them back to phenol I can then build my way up to the other one this is the pathway that I came up with which started with aspirin and was based on reactions that I knew would work I
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decided to start with aspirin because breaking it down to phenol and then back up to tylenol is relatively straightforward the other way is possible but it's significantly harder for both the degradation and the synthesis parts in any case with that being said we can get things started the first step was to extract the actual aspirin from the pills which is chemically known as a siedel salicylic acid or a sa for short in total I use 200 pills which only contain 200 grams
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of aspirin the rest of the stuff in there is just a bunch of filler junk to have an efficient extraction the pills need to be powderized it is possible to do this with a mortar and pestle or a hammer but it's a pretty big pain I generally find that the easiest method to crush pills is to just use a coffee grinder all the pills were added in several batches and each time the powder was transferred to a beaker then on top of this I added 200 mils of acetone and turned on the hot plate
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the aspirin readily dissolved in the hot acetone but the other junk didn't I brought it to a boil for several seconds and then I filtered it off
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the solid stuff left in the beaker and whatever was caught by the filter was then washed with another 200 mils of boiling hot acetone this was done to just really make sure that I extracted as much as possible in the flask some of the aspirin started to precipitate as the acetone cooled down with just a little bit of mixing though everything goes back into solution now to isolate the aspirin I just needed to get rid of the acetone it is possible to just pour it out and let it evaporate on a dish
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but I decided to do the more proper method and do a distillation I cranked up the heat boiled off the acetone and collected it in the flask on the right in the original flask I was left with nearly dry a si but there was still a bit of acetone left to get rid of the last bit I could have set up the distillation again but I decided to just pump it on my vacuum I ran it for about 10 minutes and it didn't completely dry it up but it was a lot better than before just as a final purification step I
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decided to do a recrystallization it was transferred to a large flask and then I dissolved it in a minimal amount of boiling water there were some gooey bits floating around in it though so I had to filter it off I just passed it through a coffee filter into another large flask and then I took it off the hot plate as it cooled its solubility in water slowly decreased and it crystallized out once it was room-temperature I put it in the fridge for a couple hours and then
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filtered everything off the aspirin was washed a couple times with ice-cold water and then everything was transferred to a piece of paper to dry the final recovery was 94 grams which was extremely close to the theoretical hundred it is possible to get a hundred percent recovery here but because I recrystallized it some of it stayed dissolved in the water and that's probably where I lost most of it okay so now that the aspirin has been isolated it's time to get started with the actual
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synthesis stuff the first thing I needed to do was convert it to salicylic acid unfortunately I didn't have a single flask that was large enough so I had to do the reaction in two separate batches into each of them I loaded 47 grams of aspirin 650 mils of distilled water and 12 mils of concentrated hydrochloric acid the acid I'm using was just picked up from a local hardware store I put one of them in a heating mantle and cranked up the temperature above the flask I
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also connected a condenser column to reconned ends any water that escaped as the mixture heated up the aspirin slowly dissolved and I was eventually left with a crystal-clear solution when it got to the boiling point I turned on my timer and I continued boiling it for 30 minutes the reaction I'm doing here is known as an ester hydrolysis aspirins chemically known as acetyl salicylic acid and under these hot acidic conditions it's broken apart to form salicylic acid and acetic acid this
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reactions at equilibrium though which means that the products can react with themselves to reform the starting material as a result the reaction doesn't truly go to completion and there's still a bit of starting material left over however by including a huge excess of water and heating things it's possible to severely hinder the backwards reaction under these conditions it usually goes to like a 90 or 95 percent completion anyway after the 30 minutes the heating mantle was
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removed and the process was repeated for the second flask as the second reaction was heated up the other one cooled a nice salicylic acid crystals started to form after a reflux the other flasks for 30 min I let it cool and I waited for the crystals to form in this one as well when both of them had gotten to room temperature I filtered off the crystals they were all washed with some ice-cold distilled water and dumped onto a piece of paper to dry the final yield was
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sixty-two point six grams which was 87 percent of the theoretical to get the overall efficiency of the process so far I just need to multiply the efficiency of each completed step so I multiply 0.94 by 0.87 which gives me 82% which isn't bad with every step though unless there are a hundred percent efficient this numbers gonna go down and just one inefficient step can be quite devastating when I first made this video I predicted that the final efficiency would be around 30% but that was way too
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optimistic you guys will see just how far off I was the next step is to convert the salicylic acid to that common precursor called phenol that I talked about earlier what's nice is that no other chemicals are required to do this and all I need to do is heat things up all the salicylic acid was dumped into a flask and I set up a short path distillation I forgot to put in the stir bar earlier so I quickly dropped one end then I turned on the stirring and I cranked up the heat the salicylic acid
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quickly melted and I was left with a dark liquid pure salicylic acid is colorless and the darkness is due to impurities this is okay though because this steps gonna clean it up anyway the major thing going on here is a reaction known as a decarboxylation as the salicylic acid is heated this carboxylic acid group that I've marked in red breaks off as carbon dioxide gas and leaves behind phenol at the same time there are a bunch of side reactions happening as well some of the salicylic
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acid reacts with phenol to form phenyl salicylate which then reacts with itself to form a bunch of other side products the major result of this is a loss of product and a diminished yield so although this process is easy to do and works quite well it's not very efficient the phenol that doesn't react with salicylic acid is boiled out of the flask and collected in the one on the right the most important part this process is keeping the heat high and preventing the phenol from
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crystallizing in the apparatus its melting point is around 40 C so it was important to keep the glass hotter than that if any phenol did start to freeze in it it's pretty easy to fix and I just had to blast it with a heat gun the boiling point of phenol is 182 C and everything below this temperature was collected the moment the temperature started to rise above this point the distillation was stopped left in the reaction flask there was a bunch of polymerized black tar which I just
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disposed of the phenol product that God was colorless but it still had a bunch of water and other impurities in it the major sign of this was that it didn't crystallize even when it cooled to room temperature which was well below its freezing point so just to clean it up i distilled it again initially some milky white stuff came over which definitely wasn't pure phenol it was probably an azeotrope of water and phenol and maybe some other stuff I just waited until the stuff
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coming over was at about a hundred and eighty C and then I swapped the flasks I collected everything between about a hundred and eighty and a hundred and eighty-three C and when the temperature started to rise I stopped the distillation this time as it cooled it crystallized into a solid chunk i used the heat gun to warm it up and remelted and then I transferred it to a container the final yield was twenty one point eight grams which represents a percent yield of about fifty one percent this
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isn't exactly the best yield but as I said the process isn't super efficient but it is easy in any case this was the first big hit to the overall efficiency and it brought it down from about eighty two percent to forty one percent okay so the degradation part is done and it's time to start building it up to tylenol aka paracetamol or acetaminophen what I needed to do was tack on a nitro group to the phenol by carrying out a nitration reaction I started by making
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the nitration solution which first involved dissolving sodium nitrate and water then I very carefully added sulfuric acid it was important to do this slowly and to also use an ice bath because it generated a lot of heat as the sulfuric acid was added it reacted with the sodium nitrate to make nitric acid an excess of sulfuric acid was used here so that the final result is basically a mixture of nitric and sulfuric acid in theory I could have just directly mixed the
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nitric and sulfuric acid but at the time I didn't have any nitric all of the phenol was removed from its container and transferred to a beaker I then poured in five mils of water and I put the beaker in some hot water to melt it the water was added here to prevent the phenol from freezing again once it was removed from the hot water bath when the phenol had completely liquefied I poured it into an addition funnel that was positioned above the nitration mixture I opened the addition funnel and I
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started adding the phenol drop-wise you can immediately see some brown stuff forming this whole reaction is kind of a dirty mess and this was just the beginning of the nightmare anyway this was the reaction that was going on as the phenol was added it was nitrated to form two products ortho nitro phenol and Parana trophy no the one I wanted was the para nitro phenol and the ortho one was just a side product keeping this reaction cold was extremely important because I only wanted to add one nitro
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group if the temperature were allowed to increase too much it might have started forming dye and tri nitro phenol which I definitely didn't want as the phenol was added the solution got darker and darker when I was eventually done adding it all I covered the top with some plastic wrap and I let it stir for two hours when I came back it had partially solidified and there were some nasty black chunks in there I added a hundred and fifty mils of water and then I ran the flask
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under some warm water to melt everything I very carefully poured off the upper red water layer and I tried to keep the black lower layer the goo that remained was washed again three times with 50 mils of water the nitrated phenols are nearly insoluble in water so they shouldn't really be washed away here all of this washing was really just to get rid of unreacted phenol acid and some other side products because I used cold water for the washing --zz things started to solidify again I probably
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should have just remelted it but I instead tried transferring it as a solid to the other flask I was able to use up to 250 mils of water to help me out but it was still a major pain with everything transferred over the mixture was set up for a distillation as the water was boiled off the yellow ortho nitro phenol was carried over with it once I collected about a hundred and fifty mils of water in the flask on the right I added a hundred 50 mils more to the boiling flask and continued the
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distillation near the end the condenser started getting all jammed up with solidified own nitro phenol to fix this I just turned the water pump off and I let the water stagnate in the condenser without a fresh supply of cold water cooling things the hot water vapour was allowed to travel down the condenser and it slowly cleaned things up eventually the water coming over was crystal clear and there was no yellow tinge to it at this point the distillation was done so I turned off the heating and I
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dismantled the apparatus on the left is the original boiling flask which still contains my desired para nitro phenol on the right is relatively pure ortho nitro phenol mixed in with water they were both still quite hot here so I let them cool to room temperature and then I left them both overnight in the fridge in the morning I quickly filtered off the ortho nitro phenol and washed it with some water then I transferred it to a piece of paper to dry but I didn't really have
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a use for it so once it was dry I just put it away in storage when I took a look at the other flask I was happy to see that some crystals had formed unfortunately though there was a solid tar chunk at the bottom that I had to deal with most of it was probably garbage but some peanuts or phenol was mixed into it I filtered off the crystals and the tar separately but I ended up combining them anyway into the flask I added about a gram of activated charcoal which is good at picking up
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colored impurities on top of this I poured in a hundred mils of 2% hydrochloric acid then I brought it to a boil and kept boiling it for about two minutes I filtered off the activated charcoal and I did my best to leave the tar at the bottom of the flask some of it was still transferred over though I let the flask cool to room temperature and then I place it in the freezer when it took it out I was really happy to see that a bunch of nice crystals formed I vacuumed filtered off the para nitro
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phenol and I left the tar at the bottom of the flask all of the water was pulled through and I watch the crystals a couple times with some ice-cold water the product that I got here wasn't super pure but it'll be cleaned up in the next couple steps the final yield was extremely low and I only got one point eight two grams which is a six percent yield so not exactly amazing the yield of the ortho nature phenyl was much better but it was still only 25% although this reaction wasn't very
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efficient at all I think in the end it still was the easiest way for me to do it anyway with the crazy low yield of this step as well as the last one the overall process efficiency was knocked down to a killer 2.5 percent moving on the next step was to reduced the Nitro group to an amine which is NH 2 instead of no.2 there are several ways to do this but I decided to use the sodium borohydride and Palladium on carbon method it just seemed to be the cleanest and easiest into a flask I added point
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seven five grams of sodium hydroxide drain cleaner followed by 18 mils of water I dropped in a magnetic stir bar turned on the stirring and waited for it all to dissolve when I had a nice clear solution I dumped in 1.0 one grams of sodium borohydride and I stirred this until it all dissolved as well then on top of all of this I added 90 milligrams of Palladium on carbon catalyst i cooled this mixture to 13c and i slowly added the p nitro phenol in small portions the addition generates a bit of
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heat and it's important to keep the temperature as close to 13 C as possible sometimes the temperatures started to get too low though and I had to take it out of the ice path then when it started to heat up again I just added it back the reaction I'm doing here is generally known as a reduction where the peanut Roux phenol is being converted to P amino phenol the sodium borohydride acts as a carrier of hydrogen gas which is catalytically released by the Palladium
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on carbon the Palladium on carbon then acts again to catalyze the actual reduction reaction between the hydrogen gas and the P nitro phenol if you look closely you can see there's quite a bit of bubbling going on which is all the hydrogen that's being generated for those of you who are wondering palladium on carbon is basically just extremely small particles of palladium stuck on to bits of carbon powder this makes a very small amount of palladium have a huge surface area which is much more
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efficient than just adding solid plate iam metal on top of this it's also a lot cheaper after everything was added I washed the sides of the flask and the thermometer with a small amount of water I then continued mixing it for another 30 minutes when I came back all of the solid peanut Ruffino had disappeared and the solution had become completely black the reaction was done at this point and I started to slowly add 28 mils of dilute hydrochloric acid this decomposed
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any unreacted sodium borohydride and converted it to boric acid sodium chloride and hydrogen gas it also reacted with the P amine of phenol itself and converted it to P amino phenol hydrochloride which is much more water-soluble this reaction caused a lot of bubbling and I was afraid it would overflow so I transferred it to a beaker I continued adding the rest of the acid and it eventually stopped bubbling I used some Universal pH papers and I saw that it was around 1 which is highly
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acidic and exactly what I wanted to get rid of all the carbon that was floating around I just filtered it off some of the carbon managed to make it through though so I filtered it again unfortunately the whole filtration process took quite a long time and the P amino phenol and it started to decompose and the solution became purple P amino phenol is quite sensitive to light so this step should really be done as fast as possible in hindsight I probably should have done a vacuum filtration
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instead anyway to get out the P amino phenol all I had to do was convert it back to its freebase form which isn't very soluble in water to do this I just needed to carefully add baking soda and make sure it didn't bubble over at some point one of the additions caused a very distinct color change and this told me I was close to the neutralization point with only a bit more baking soda the solution started to become cloudy because P amino phenol was precipitating
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out I kept adding small amounts and I knew it was done when it didn't result in any bubbling I tested the pH and saw that it was around 7 which was perfect the product just needed to be filtered off and again I did a gravity filtration I really should have done a vacuum one though because the degradation here is quite significant I washed the product with a bit of water and then it was allowed to dry to try and limit its decomposition I turned off the lights after a few hours I scraped off the
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filter paper and then I left it out for a couple more hours when it was totally dry I waited and the yield was 0.82 grams which is a percent yield of 58% so now the overall process efficiency is about 1.5 percent ok so this brings us now to the final step all the P amino phenol was added to a flask with the stir bar and I poured in 7.4 mils of water I turned on the stirring and when I had an even suspension I added point nine mils of acetic anhydride immediately almost all the P amino
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phenol disappeared and the solution became a dark red black color the reaction that's going on here is in a set elation where the P mean of phenol is reacting with the acetic anhydride to form tylenol it also produces acetic acid as a side product it's generic chemical name is based on its structure and called para acetyl amino phenol the brand name tylenol and most of its common names are derived directly from it about five minutes after the acetic anhydride was added these cinnamon
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offend started to precipitate from the mixture I then mix it occasionally over the course of about 15 minutes when the reaction was done I added it to my filter funnel and I turned on the vacuum pump I washed the flask and the acetaminophen a few times with cold water the powder I was left with was dark and dirty so it needed to be cleaned up I put it all into a small flask and added a bit of activated charcoal I poured in a small amount of water mixed it around and turned on the
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heating when it started boiling I set things up for a hot filtration and I filtered off the activated charcoal I needed to do a hot filtration here because the water in the flask was close to saturated with a cinnamon ofin and if it cooled too much while filtering it could crystallize out and mess things up by having water boil under the funnel the steam that's led off keeps everything nice and hot when everything had passed through I washed the flask with a small amount of boiling water
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then I kept everything on the hot plate for just a little while longer to boil off some of the water and concentrate the solution I took it off the hot plate and let it cool and crystals of a cinnamon ofin started forming but they were still off-color so I filtered them off and did two more recrystallization --zz using activated charcoal after the last one I was left with some nice and clean looking crystals the final yield was 0.2 in grams which was less than the amount
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that would go into a single regular strength tylenol tablet so basically I was able to convert 200 extra-strength aspirins into one really weak Tylenol the percent yield of this step was extremely low at around 18% I probably lost most of my product doing the multiple recrystallization z' in a couple of them i think i used a lot more water than i actually needed in any case this puts the final efficiency of the process at an impressive 0.26 percent so my original prediction of 30
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percent wasn't that far off i just kind of misplaced the a mole by two spots just to confirm that really this was in fact a cinnamon ofin I did a melting point test and it was almost exactly the theoretical I also ended up doing one other quick test I transferred a small amount of it into a vial added some water and shook it around I then added a couple drops of ferric chloride and there was immediately a small color change this test is simply known as the ferric
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chloride test and a positive result like we have here indicates that a phenyl group is present and since Tylenol has a phenyl group in it this is a good sign the result from this test along with the melting point didn't definitively prove that this was Tylenol but it was extremely unlikely that it could be anything else I wanted to be a hundred percent certain though so I sent a sample to my friend and he ran a proton NMR the graph that was generated matched perfectly with a cinnamon ofin and it
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was also pretty clean this tells me the product that I have is relatively pure at least in terms of organic impurities there couldn't theory be some inorganic stuff in there that I just can't see but I don't really think that's likely in the end did this project was mostly just for fun and to see if I could even do it I do think the idea of converting one drug to another is cool but I think the whole idea of planning and designing my own pathway is even cooler even though I
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do stuff like this all the time it still blows my mind that it's possible to systematically build and degrade things on the molecular level I hope you guys liked this video in general and that it gave you insight as to what multi-step organic synthesis can be like synthetic pathways like this are extremely common in industry and they're used to produce most drugs as well as many flavorings vitamins and supplements in the future I plan to do another project like this
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where I synthesize caffeine I think it's also something like six or seven steps but I won't be posting it as a series and I'll probably make it into a video like this or maybe I'll split it into two parts if it gets too long as usual a big thanks goes out to all my supporters on patreon everyone who supports me can see my videos at least 24 hours before I post them to YouTube also everyone on patreon can directly message me and if you support me with $5 or more you'll get your name at the end
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like you see here
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