Note: Reuploaded due to multiple diagram errors.
For this video i’ll be making fenetoin which is an anti-seizure medication it’s often sold under the brand name dilantin and it’s also used to treat other things like heart arrhythmias and neuropathic pain one of the major benefits of phenytoin is that it can help control seizures but it doesn’t have the sedative effect that some of the other medications can have
It’s definitely by no means perfect though and has a slew of side effects ranging from nausea to things like liver damage what i think is cool is that the entire drug can be built from two natural sources bitter almond oil and urine bitter almond oil is nearly pure benzaldehyde and i’ll be using it directly without any purification i’ll start by reacting it with
Itself to make something called benzoin which will then be oxidized to benzyl using nitric acid for the last step i’ll react it with urea which i extracted from my own urine in a previous video if you’re interested in checking out that honestly pretty gross project there’s a link in the description before i start i just wanted to mention that i finally made some
T-shirts for the channel they’ll only be available for the next three days though and i’m not exactly sure when i’ll be selling them again so if you want to support the channel and pick one up you can go to the link on the screen here or click the one in the description anyway to start things off i needed to make the catalyst for the reaction which involved making
Two solutions for the first one i added 0.84 grams of sodium hydroxide to 7 mils of water it all dissolved with just a bit of mixing and then i temporarily placed it on the side for the second one i added 3.5 grams of thymine hydrochloride followed by eight ml of water i swirled it around until it all disappeared and then i added 35 mils of 95 ethanol both
Solutions were put in the freezer and i took them out when they were around zero c with some good stirring the base solution was slowly added to the thymine hydrochloride and a yellow color started to appear the reaction going on here was between the sodium hydroxide and the thymine hydrochloride to make just thymine which was the active catalyst when i was done
Adding it i let it stir for a bit and then i poured in 20 mils of the bitter almond oil before moving on i quickly checked the ph to make sure that it was between eight and nine this reaction can be quite sensitive and if it’s not within this bracket the yield would probably be affected based on my ph papers it all seemed to be good but they aren’t exactly super
Accurate so i guess we’ll see the entire beaker was then put in a water bath at around 60c after sitting there for about 15 minutes though i was concerned that too much ethanol would evaporate off so i put a flask with cold water on top of it as i mentioned earlier bitter almond oil is almost entirely made of benzaldehyde and under these conditions in the presence
Of the thymine catalyst tuben’s aldehyde molecules will condense together to form benzoin i left it in the water bath for about 90 minutes and then i took it out and let it cool as it cooled to room temperature benzoin slowly crystallized out to get out as much as possible i let it sit in a nice bath for about 30 minutes i then added it to my vacuum filter and
Pulled away the liquid the crude benz a wind was transferred to a beaker and i recrystallized it using 95 ethanol this was just done to clean it up a bit and to make it as pure as possible when everything had dissolved i took it off the hot plate let it cool and waited for the crystals to form when it got to about room temperature i put it in the freezer for a
Couple hours just to get out as much as possible the benzoin was again filtered off and i washed it with some ice cold ethanol i also left my pump on for about 20 minutes just to really dry it up my final yield of nice and dry benzoin was 4.95 grams which was a terrible percent yield of only 24 percent as far as i know this reaction isn’t super efficient but this
Is still a really low yield i’m not exactly sure why it was so low but i think it’s for a few reasons first of all this reaction is pretty sensitive to ph and if it’s either too high or too low it can affect the yield my ph papers weren’t super accurate so it was hard to get it in this bracket and it may have been outside it secondly i think i just used way too
Much ethanol to recrystallize it which resulted in a loss and the last reason is that bitter almond oil is usually nearly pure benzaldehyde but i didn’t purify it before using it so that might have affected things as well i considered redoing it to try to get a better yield but in the end i decided it wasn’t really worth it because i still had more than enough
To work with the next thing i needed to do was to oxidize it to benzyl into a beaker i poured 17 mils of concentrated nitric acid and added the benzoin in small portions i let it mix for a couple minutes and then i put the beaker in a water bath at around 70c as it heated up the nitric acid started reacting with the benzoin to make benzyl and nitrogen dioxide gas
Initially the nitrogen dioxide just caused the mixture to change to an orange color but eventually it does start letting off the nice orange red gas as a safety point one thing to keep in mind is that this stuff is really dangerous to breathe so it’s important to have proper ventilation when doing this i kept the reaction going until it looked like it wasn’t
Letting off any more gas which took about an hour i took it out of the water bath let it cool for a few minutes and without stirring it separated into two distinct layers the bottom portion is just the water and acid and the upper parts the benzyl to force the benzyl to solidify i turned on the stirring and i dumped in 50 mils of ice cold water i let it stir for
A few minutes and then i put it in the freezer to get out as much as possible the crude benzyl was quickly filtered off and i transferred everything to a beaker i poured in a small amount of ethanol and turned on the stirring and heating it eventually got to the boiling point and i added some water to knock down the solubility when i got to what i felt was a good
Balance between the ethanol and water i took it off the hot plate and let it crystallize then just like before i put it in the freezer for a bit and filtered it off i also watched the beaker and the crystals with a small amount of ice cold ethanol i dumped them on some paper to dry for about a day or so and the final yield was 4.2 grams which is a percent yield of
About 86 percent okay so now for the last step where the benzyl is converted to the final phenytoin to start things off i just quickly made a concentrated solution of potassium hydroxide by dissolving 3.2 grams in 6 ml of water i swirled it a bit to get it all to dissolve and then this was placed on the side for the moment and i moved on to setting up the reaction
So into the flask i dumped 2 grams of the benzyl that i just made then on top of this i added 0.96 grams of urea the reason i only used 2 grams of benzyl instead of the full 4.2 that i just made was because i wanted to use less urea this reaction isn’t very efficient with it and i only recovered several grams for my urine so i have to be sparing anyway on top of
This i poured in 50 mils of 95 ethanol and stirred it for a few minutes for things to dissolve then i added the concentrated potassium hydroxide solution that i made like a minute ago it caused an immediate change in color and a lot of the stuff that was still undissolved started to disappear just like the other ones this reaction needed to be heated and i set
It up for a reflux i placed the heating mantle below it and above it i attached the cold water condenser so i turned on the heating and i brought it to a boil and i kept boiling it for about two hours the major reaction that was going on here was between the benzyl the urea and the potassium hydroxide to make potassium phenytoin the mixture initially got a lot
Darker and this was only about 20 minutes in at some point though it started to lighten up again and this is what it looked like near the end when it was done i took it off heating and i let it cool a bit then i dumped it into 50 mils of ice cold water the flask was also washed with a bit of water to make sure i got out as much as possible i let it stir for a
Couple minutes and a precipitate appeared which was a side product to get rid of it it was pretty easy and i just filtered it through a cotton ball at this point all my product was in the form of potassium phenytoin which was soluble in the solution to get it out i added dilute hydrochloric acid to convert it to regular phenytoin which was insoluble i kept that
In the acid and i knew i was done when i got to a ph of around one or two then i put the whole mixture in the freezer for a couple hours to separate off the phenytoin i added it to my vacuum filter and pulled away the liquid i washed it with some ice cold water to get rid of any acid that remained and then i transferred it to a beaker on top of it i added a stir
Bar and some ethanol and i turned on the heating i then kept adding more in small amounts until it was all dissolved i took it off the hot plate and as it cooled some really nice white crystals formed when it eventually got to room temperature i put it in the freezer overnight in the morning i filtered it off and washed it with a small amount of freezing ethanol
I left the vacuum on to dry it up as much as possible and then i dumped it onto some paper and left it there for about a day my final yield here was 1.18 grams which was a percent yield of about 49 to confirm that this was in fact phenytoin i took the melting point of it and compared it to the theoretical it was extremely close which told me that it was phenytoin
And that it was relatively pure all the fenetone that i have here is in its unsalted form which is insoluble in water and has to be administered by iv to take it in pill form it needs to be converted to assault usually sodium phenytoin it’s actually quite simple to do that and i would just have to react it with a bit of dilute sodium hydroxide and then evaporate off
The water if i were to convert it with a hundred percent yield to sodium phenytoin it would give me about 1.3 grams the average daily adult dose of this drug is 300 milligrams so what i have here is about four days worth if i’d used all the benzyl that i had though it would have been around eight so assuming the efficiency of the process stays the same i can make a
Month supply from about 75 mils of the bitter almond oil i think my yields for each step were generally pretty low though so it could probably be done with much less also in my opinion using urea for my own urine was cool but it really wasn’t ideal it’s a much better idea to get the urea from an easier and cleaner source like instant cold packs anyway i think that’s
About it i hope you guys enjoyed the video and i’ll see you on the next one 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 five dollars or more you’ll get your name at the end like you see here thank you
Transcribed from video
Turning my own pee into medicine By NileRed
