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.