this is the sixth and final installment
of this video series getting to this
point has kind of been a journey and I
want to recap everything I've done so
far the aspirin was first extracted then
it was hydrolyzed decarboxylated
nitrated and reduced this left me with a
molecule called pea amino phenol which
needs to be accelerated to form the
final paracetamol
so in terms of chemicals there isn't
much that I need on the right I have the
P amino phenol from the previous video
and on the Left I have some acetic
anhydride acetic anhydride is commonly
used to make illegal drugs so its sale
is pretty heavily controlled at least in
North America though you can get a small
amount from eBay but it comes at a
pretty hefty price the procedure that
I'm using for this video is sound on
line and I'll provide a link to it in
the description
to start things off all of the PME know
phenol was added to a flask
along with a little bit of water
PME no phenol is not very soluble in
water and what we want here is an evenly
mixed suspension once I felt like I had
a nice even suspension I added the
acetic anhydride after it's added the P
amino phenol should quickly dissolve
the stir bar wasn't doing a great job at
mixing things so I decided to do it
manually the procedure that I was
following said it would take about two
minutes for a precipitate to form but in
my case it took about five
in this reaction the PME know phenol is
being assimilated to form our final
paracetamol this type of reaction is
known as an acetylene and in the final
product we form an amide bond which I've
marked in red
in terms of the mechanism the first step
is the attack of the carbonyl by the
primary amine
the reason this occurs is because the
nitrogen has a free electron lone pair
that can attack the partial positive of
the carbonyl this leads to the formation
of this intermediate molecule and the
new carbon nitrogen bond the proton from
the nitrogen is then intermolecular li
transferred to the oxygen electrons on
the negatively charged oxygen then moved
to reform the carbonyl a carbon oxygen
bond is broken which leads to the
formation of the final paracetamol as
well as a molecule of acetic acid
so coming back to the preparation it
took about five minutes for some solid
to start forming the solar that's
precipitating out is our desired
paracetamol and as I continue to mix it
it seems like more appears it's then mix
for the next 15 minutes or so to make
sure that the reaction goes to
completion so 15 minutes later the
reaction should be more or less done and
I move on to filtering I turned on the
vacuum to pull away the brown liquid and
I wash the flask out a few times with
cold water the water helps get out any
paracetamol that remained in the flask
and it also washes the stuff that's
already in the filter it should help
wash away contaminants side products and
unreacted starting material with that
being said paracetamol is slightly
soluble in water so a minimal amount
should be used here so once I was done
with the washing steps I used a metal
spatula to scrape off the product I keep
the vacuum on to dry it up as much as
possible and I'm eventually left with a
powder that looks a lot like the pea
amino phenol that I started with pure
paracetamol is white or colorless so
what we have here must be pretty dirty
luckily it should be pretty easy to
clean this up and I just need to
recrystallize it from water
the dirty paracetamol is placed back
into the small flask and I add a little
bit of activated charcoal activated
charcoal is very good at getting out
colored impurities so it should help us
get rid of this brown color I then added
a somewhat arbitrary amount of water mix
things around and turned on the heating
I also quickly made a hog filtration set
up because the activated charcoal needs
to be filtered off I let the solution
boil for about 30 seconds and then I
filtered it off it might be hard to see
but the liquid coming through is nearly
colorless so it's looking good so far
once everything is filtered through I
wash the flask with a little bit of
water
I waited for everything to pass through
the filter and then I boiled things down
a little bit to get it more concentrated
I did a time-lapse and as it cools we
can see the crystals forming the
crystals are unfortunately still Brown
but on a positive note there are a lot
cleaner than before
once it cooled to room temperature I put
it in the fridge to fully crystallize
about an hour in the fridge I think it
precipitated as much as a paracetamol as
possible
the crystals were then isolated by
vacuum filtration and I washed them a
few times with ice-cold water
I kept the vacuum going to dry them up
and using a metal spatula I scraped them
off the filter
the crystals were transferred to a
filter paper and although they're not
super brown here they're still evidently
discolored
when I tested the melting point it was
way off from the theoretical so I did
another recrystallization after the
second recrystallization the melting
point was much closer to the theoretical
but it was still discolored so to purify
it even further I carried out a third
recrystallization after the third one I
was left with a very clean product I
tested the melting point and this time
it was pretty much exactly the
theoretical a very nice friend of mine
then ran a hydrogen and Amara on the
product so from the data in the graph
and from the melting point I can confirm
that I do have paracetamol the NMR here
is also quite clean so the product I
have is probably pretty pure I am only
detecting hydrogen's here though and
it's not going to pick up inorganic
things like metals at some point during
the preparation I use palladium on
carbon so it's possible for the final
product to contain some palladium but
it's not going to show up here with that
being said I'm going to go over this NMR
and NMR in general in more detail but
I'm going to do that in a separate video
so in the end the yield was 0.21 grams
which represents a killer percent yield
of 18 percent the major reason for the
low yield is because I did multiple
recrystallization each recrystallization
gave a more pure product but I lost
quite a bit in each one it's very normal
to lose some product when you
recrystallize but I think I lost a
little bit more than I should have
because I used way too much water
to get the efficiency of the series I
multiply out the individual efficiency
of each reaction to get an overall
percentage of 0.26 percent so with this
amazing method I was able to convert
about a hundred extra-strength aspirin
tablets to one regular strength
paracetamol in the end though this was
mostly just for fun and to explore the
chemistry I never really expected to get
a great yield an inherent problem with
synthetic pathways like this is that the
yield is sequentially whittled down with
each step that you have no matter how
efficient your steps are unless there
are a hundred percent efficient you're
going to lose something with each one
even if I got an 80 percent yield for
every single step my final percent yield
would only be 26% this is just one
reason among many why when you're
synthesizing something you want to use
the fewest steps possible anyway I guess
that's all I have to say about this
reaction this was the first real series
that I've done on this channel and it's
been pretty well received so I think
I'll do another one at this moment
besides Nile red I don't have any
particular ideas in mind so if you have
any please leave them in the comments
alongside this video or shortly after
I'm going to upload the NMR video that I
mentioned earlier I decided to separate
it off into its own video because I
thought it might be nice to do a little
introduction into NMR I'm going to do my
best to not make it too technical
because I want everyone to be able to
follow along the next video that I'll be
posting is the Cannizzaro reaction of
benzaldehyde what I do want you guys to
do though is vote for the next video
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decently large list at the end of the
video so please take a look at it and
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