Today we're finally making 1-octen-3-ol which is something I've been trying to make for a while now. It's
sometimes used as an artificial mushroom flavor but what I find interesting is
that it's a chemical attractive for biting insects. It's naturally present in
both human sweat and breath and this is one major way for insects like
mosquitoes to find us. I first tried to make it by the acrolein-
bromopentane route but unfortunately my acrolein polymerised before I could use it. Luckily for me though, the paper that I
was following had a secondary route that I could follow. This new route involved
two major steps. The first step is an aldol reaction and condensation and the second is known as a Meerwin-Pondorff-Veerley reduction or MPV reduction for
short. The aldol reaction and condensation will
give us someone called 1-octen-3-one which we'll then have to reduce to 1-octen-3-ol using the MPV reduction Here are the chemicals that are used for
both of the reactions. On the left we have the chemicals for the aldol
reaction and condensation and on the right we have the ones for the MPV
reduction. For the aldol stuff I use formaldehyde and 2-heptanone and both
were purchased online. I was able to get the formaldehyde for pretty cheap but
the 2-heptanone own cost me a ridiculous seventy dollars. For the MPV reduction I
made the aluminum isopropoxide in a previous video. The anhydrous iso-propyl
alcohol was prepared by adding some molecular sieves to some 99% isopropyl
alcohol that i purchased from a local company. For the aldol reaction and condensation
will need a three-necked round-bottom flask and an addition funnel. To the addition funnel we added 10
milliliters of ten percent sodium hydroxide solution 20 milliliters of
thirty-seven percent formaldehyde and 10 milliliters of water. I added the sodium
hydroxide first followed by the formaldehyde than the water but the
order really doesn't matter. To the round bottom flask and then
poured in 30 millilitres of 2-heptanone, which was the entire bottle, then
after all of the 2-heptanone had been added, I stoppered the flask. I turned on some strong stirring and
then I opened the addition funnel to slowly add the solution into the 2-heptanone. I added everything over the course of something like 30 minutes to
an hour, but I probably could have added it much quicker. Once everything has been added, the
addition funnel was removed and things were allowed to stir for about five
hours. This is the overall reaction scheme for
both the aldol reaction and the aldol condensation. The first part is the aldol
reaction where we react formaldehyde and 2-heptanone to produce an
intermediate. When the intermediate is heated, it will undergo a dehydration
reaction to form 1-octen-3-one That's just a very quick overview though
and I'm going to break it down mechanistically. As I just said a second ago the first
thing that occurs is the aldol reaction. In the first step we have a reaction
between an acidic hydrogen of the 2-heptanone and the sodium
hydroxide. The hydrogens that I've written out on the 2-heptanone are more acidic
because the resulting negative charge is stabilized. If you take a look at the
structures in the brackets, you'll see how the charges are stabilized. The negative charge on the carbon can rearrange and move to the oxygen. Because the negative charge isn't just sitting on the carbon and it can move around, the burden of the
negative charge is spread out and this makes it more stable. Just as a quick
side note it's also possible to deprotonate one of the hydrogens that
I have labeled in blue. To a certain extent this also occurs, and this is one major
source of side products. Moving forward with the reaction, our deprotonated 2-heptanone goes on to attack a formaldehyde. The bond between the oxygen and the carbon in the formaldehyde isn't super even and the electrons lie closer to the oxygen. This leaves a partial positive charge on
the carbon, which is attacked by the electron-rich 2-heptanone
intermediate. As a somewhat lengthy side note, it's also possible for the 2-heptanone to attack its own carbon oxygen bond instead of the formaldehyde. This is the reason why we mix the sodium hydroxide with the formaldehyde and not
the 2-heptanone. The formaldehyde has no acidic protons to deprotonate, so when
we mix it with sodium hydroxide nothing really happens. When the formaldehyde and base mixture is added, the 2-heptanone is deprotonated but it quickly reacts
with the formaldehyde. To a certain extent, some 2-heptanone will still
react with itself and this is another source of side products. Anyway, after the
intermediate attacks the formaldehyde we form a new carbon-carbon bond. The
negatively charged oxygen attacks a water molecule to form an alcohol group
and hydroxide that we used in the beginning is regenerated. There are two
main products of aldol reactions; a beta hydroxy aldehyde and beta hydroxy ketone. In this case we have a beta hydroxy
aldehyde but it's just an intermediate and we're going to be reacting it again
in just a minute. After five hours the reaction flask was
placed on a 50cc water bath and it was heated for another two hours. When the reaction mixture is heated, the
beta hydroxy aldehyde intermediate will undergo a dehydration reaction. Again, a
hydroxyl group picks up one of the acidic hydrogens and a negative charge
is formed. With a little bit of heat the electrons move to form a double bond and the hydroxyl group is popped off. This leads to the formation of the final
aldol product which is generally known as an alpha-beta unsaturated ketone. In
the 1-octen-3-one molecule, I've actually written the C for one of the
carbons so i could highlight the carbon that came from the formaldehyde under
normal circumstances though this C would not be written. Once we hit the two-hour mark, the water
bath was taken away and I let things stir overnight. In the morning the
contents of our reaction flask was transferred to a separatory funnel. In
the procedure that I'm following, the next step is to neutralize the sodium
hydroxide using hydrochloric acid but let's pretend that I totally didn't
forget to do this. The layers in the separatory funnel were
allowed to separate and the lower aqueous layer was drained off. The
aqueous layer still contains some of our product and we're gonna have to extract
it a few times using toluene. The upper layer, which contains our
product, residual 2-heptanone and other side products is drained into a
separate flask. Now it's time to extract our aqueous
layer and to do this we pour it back into a separatory funnel. The aqueous layer is then washed three
times using 15 milliliters of toluene each time. The procedure for washing things is
pretty simple: the separatory funnel is capped and taken off the stand and we
shake it vigorously. Sometimes some pressure will build up, so while the
separatory funnel is tilted backwards we occasionally open the stopcock. Once we
feel like we've mixed things adequately, we can place it back on the stand and
allow the layers to separate. The lower aqueous layer is drained back
into the Erlenmeyer flask and the upper toluene layer is poured into the flask
with the rest of our product. The aqueous layer is returned to the
separatory funnel, we add 15 milliliters more of toluene and the washing steps
are repeated two more times. All of our product which is combined
with the toluene washings are added back to the separatory funnel. To get everything out of the flask we
wash it with a little bit of toluene and then add about 25 milliliters of
saturated salt solution. Like before, I cap the separatory funnel
take it off, shake it, vent it and then put it back on the stand for the layers
to separate. The purpose of this step is to remove water from the organic layer
by osmotically pulling it into the saturated salt solution. Once the layers have separated you can
see that the organic layer is a lot less opaque and white. The bottom aqueous layer is drained off
and discarded and our upper layer which contains our product is poured out into
an Erlenmeyer flask. The organic solution that we have here
is still slightly opaque so to dry it further I add some hydrogen magnesium
sulfate. I mix things around and then let it
stand for about 30 minutes and were left with a nice clear solution. The solution is then filtered through a
little bit of cotton to separate out the magnesium sulfate. Once most of our crude product has
passed through the flask and the magnesium sulfate is washed with a
little bit of toluene. Once we're finished filtering things, I
removed the funnel and I set things up for a vacuum distillation. So this is what our setup looks like. On
the left we have our flasks with the heating mantle and on the right we have
our cow adaptor connected to the vacuum. The cow adapter is very useful in vacuum
distillations because it allows us to swap the flask without removing the
vacuum. In most distillations we have to collect more than one fraction and when
it's under vacuum it kind of becomes a pain to swap things out. With this
adapter we can keep everything under vacuum and simply turn it and the flask
that the liquid goes into will change. The purpose of this distillation isn't
to isolate our 1-octen-3-one and it's simply to remove toluene and any much
higher boiling point side products. With heating and vacuum on we bring
things to a boil and we start to collect our first fraction which is toluene. Our
desired ketone fraction comes over between 60 and 85°C at a pressure of 15
millimeters of mercury. The temperature that our fraction comes over at though
is really dependent on the pressure and my pressure is not 15 millimeters of
mercury. My vacuum pulls out around 37 millimeters of mercury, so my fraction came over between 85 and
110°C. Once we reach the end of our toluene
fraction, the temperature will start to increase and we have to change our
collection flask. For me this occurred at around 85°C and now I collect everything
up until about 110°C. The stuff that were collecting here in
the middle flask contains our desired product as well as some side products. Again at some point the distillation
slowed down and the temperature increased so I swapped to the third
flask. In the end I'll be combining the second
and third fraction so this separation is really unnecessary; I was just trying to see if i was able
to isolate 1-octen-3-one. Just for the record though I wasn't. Eventually the temperature rose to about
a 110 or 115°C so I stopped the
distillation. In the distillation flask were left with
a lot of thick yellow goo and this was discarded. In the second and third flask we have
are slightly opaque mixtures of 1-octen-3-one and side product ketones. The next thing that we want to do is
carry out our MPV reduction. To start things off, we add both of the ketone
fractions to a larger round bottom flask. On top of the ketone fractions I then
poured in a hundred and fifty milliliters of anhydrous isopropanol, Then weighed out about 3.1 grams of
aluminum eyes isopropoxide and added about 15 milliliters of anhydrous isopropanol
to it. Using a glass rod I mix things around
and try to break up any large chunks. The aluminum isopropoxide suspension
that we made was then added to the reaction flask a small amount of isopropanol was used
to wash the crystallizing dish as well as the funnel. I then set things up for a fractional
distillation, and to show the whole apparatus I used a very skillful moving
shot. A heating mantle is placed under the
flask and we turn it on to get the distillation started. At first our
reaction mixture is going to be opaque with aluminum isopropoxide floating
around but as we heat things up everything should eventually dissolve. It
also takes on a yellow color but I'm not exactly sure why it does this. The column is insulated with some
aluminum foil to keep it hot so the vapors can make it over. Not too long after starting we'll start
to get some vapors coming over and we want to maintain the temperature at
around 75°C. We maintain the temperature here because
this is below the boiling point of isopropyl alcohol but above that of
acetone; the reaction is an equilibrium reaction and by slowly removing the
acetone we push it towards completion. Now I'd like to just quickly go over the
reaction mechanism. The carbonyl group of the1-octen-3-one starts things
off by attacking the aluminum isopropoxide in one concerted step and
isopropoxide group in the aluminum isopropoxide donates a hydrogen to the
carbonyl and it's then itself kicked off as acetone. A random isopropyl alcohol
molecule then comes along and attacks the aluminum. The isopropyl alcohol group
that just detached donates its hydrogen to the oxygen in red and the bond
between the red oxygen and the aluminum is broken. This leads to the formation of our final
1-octen--3-ol product and it regenerates the aluminum isopropoxide
catalyst. The proper way to know the endpoint of
this reaction is to test the distillate for the presence of acetone a common and
easy way to do this is to use something called 2,4-dinitrophenylhydrazine
but unfortunately I didn't have any of this. Because I had no way of testing whether
there was acetone left in the distillate, I just kept the distillation going until
it looked like I had about 30 milliliters left. The distillation apparatus was
dismantled and we were left with this orange liquid in the reaction flask. Now it's time for the workup and the
first thing that we do is add 50 milliliters of twenty percent sulfuric
acid. After adding the sulfuric acid, I stir
things for a few minutes and then I let the layers separate. It separates pretty cleanly with a clear
aqueous layer on the bottom and a slightly yellow organic layer on top. To separate our desired organic layer
from the aqueous layer, we transfer everything into a separatory funnel. The lower aqueous layer was drained into
an Erlenmeyer flask and it can be discarded. The organic layers then washed with
about twenty milliliters of distilled water. Just like before things were mixed
thoroughly and then placed back on the stand to separate. Once the layers of separated, we then
drain off our lower water washing. The organic layer is then poured out
into a beaker. It has some water in it and we need to
dry it up so just like before we add a little bit of magnesium sulfate. After we let it stand for a while we're
left with a nice clear solution and it's time to filter off the magnesium sulfate. Just like before the magnesium sulfate
is separated by filtering it through a little bit of cotton. Once we're done filtering, we set things
up for a vacuum distillation. Unfortunately I don't have a cow adapter
that's the appropriate size so this time I have to hotswap things. As we heat things up will start to
collect our distillate and things came over in three main fractions the first
fraction that came over was mostly just isopropanol the second one I believe was
2-hepten-3-ol and are desired product came over in the last one. At the end of the distillation you can
see here the incredible yield of product that I got. I transferred all of the product to a
small amber glass vial and the total weight came out to be about 0.5
grams. This corresponds to an incredible yield of about two percent. To make
matters even better this is a crude yield and it probably
only is 50% 1-octen-3-ol. As a test I left out some of the 1-octen-3-ol outside, but it didn't seem to attract many bugs. I watched it over the
course of a few hours and unfortunately the only thing that happened was a
spider drowning during the filming, though I had at least ten flies swarming
everywhere they weren't biting insects but there was definitely an above-normal
amount but I'm not sure if this was a coincidence or directly related. I did a
little Google searching and I found a paper that tested the ability of the 1-octen-3-ol to attract insects. Their experimental procedure was a
little bit more structured, and it didn't just involve pouring out some 1-octen-3-ol onto a plastic spoon but it didn't really seem to work well for them
either. The 1-octen-3-ol seemed to work the best when it was combined with
another insect attractant like CO2. I was honestly a little bit disappointed when
I found out that it didn't just attract bugs like crazy. I think the most
disappointing part though is that later on I found that I could have just bought
the 1-octen-3-ol. A perfume site actually sells it for cheaper than I
bought the 2-heptanone for so I ended up buying some and now I have about 80
milliliters. At some point I'm going to oxidize the 1-octen-3-ol back to
1-octen-3-one. If you recall, this was an intermediate in this preparation but
it's also a cool molecule on its own. This chemical is responsible for the
metallic scent of blood and the metallic smell you get when you touch metal. In
either case you're not really smelling metal at all and you're actually just
smelling 1-octen-3-one. That's kind of it for now, and I'll post a new video
soon. As usual I'd like to extend a big thanks to all my supporters on Patreon
and especially those who donate five dollars are more anyone who donates in
support when Patreon gets to see my videos 24 hours before I release it to
youtube and if you donate five dollars more you get your name at the end of the
video like you see here. In the next few months though I want to
work on my Patreon page lot and I want to get more rewards going and maybe even
get some higher tier ones and I want to also offer some Patreon exclusive content. Also as usual here's the videos that I've currently filmed and the ones that
plan to work on if you have any suggestions or ideas please feel free to
leave them in the comments.
So instead of spreading nasty, oily DEET on yourself, you can have your friends put this on themselves instead?
Nope nope nope nope nope nope nope