To celebrate our 50th video,
we are going to do the reactions that a lot of viewers requested,
the synthesis of a phenethylamine ketone starting from propiophenone.
We've come up with a way that you can do this in one pot.
But be warned, the intermediate bromoketone is still extremely hazardous and irritant.
Plan the experiment and choose the apparatus carefully.
We're going to make the ephedrone analog which incorporates piperidine into its structure.
Note that this product is unlikely to be pharmacologically active.
We'll do this on a small scale and we'll use the dry 100 ml flask equipped with a magnetic stirrer.
Our starting material is 1.5 grams of propiophenone.
Ensure that this is dry as we've found that water inhibits the first reaction.
For information about how to make propiophenone, check out some of our other videos.
Add the propiophenone to the flask.
Then prepare 5 mL of dichloromethane and use this to wash the container.
Then add this to the flask.
Here's our second starting material.
Bromine solution in dichloromethane.
This solution contains around 0.45 grams of bromine for each gram of solution.
Weigh out 4 grams corresponding to 1.79.
Add 1.9 grams of bromine to the flask and add 1.5 grams of dichloromethane to each gram of solution.
Check out our other video for details of how to make this yourself.
Place the flask in a room-temperatured water bath and secure a glass pipette tube leading into the flask as shown connected to a hose.
We'll use this to blow air through the apparatus, but don't put the pipette tube under the surface of the liquid because otherwise it will cause too much DCM solvent to evaporate.
Okay, stirrin' is on and we're ready to rock.
Add one single drop of the DCM bromine solution to the flask.
This first drop is the slowest to react, but soon the color will fade.
As you slowly add the bromine drop by drop, you'll soon notice some smoke around the flask.
At this point switch on your vacuum pump and connect the output of the pump through a hose and use it to blow a bit of air through the apparatus.
Not too much, just enough to remove some smoke.
Not too much, just enough to remove some smoke.
Not too much, just enough to remove some smoke.
Wait until the color has faded before adding another drop.
Addition is complete in about 15 minutes.
At this point leave the flask stirrin' for another 20 minutes to ensure complete reaction.
And use the air blower occasionally to remove the hydrogen bromide smoke.
You've now created an alpha-bromo ketone.
It has a pleasant interesting aroma of elderflower.
It has a pleasant interesting aroma of elderflower.
It has a pleasant interesting aroma of elderflower.
And a second after you smell it, your eyes and face will start to burn.
It's very nasty indeed so use a lot of caution.
After 20 minutes is up use the air blower and keep going until the DCM solvent is removed and the yellow oil remains.
At this point you can remove the air blower.
We recommend that you make up the sodium hydroxide solution which you can use to soak the used apparatus in.
This will hydrolyze the homocytone.
Now for our third main ingredient.
This is 1.7 grams of piperidine hydrochloride.
This is our amine which will replace the bromine in the organic structure, creating our product.
This isn't exactly a household item, but we actually made this sample here starting from white peppercorns.
Check out our other video linked here to see how
Now measure out 3 mils of water.
You want to make a saturated solution of your amine salt.
Add this to the amine salt and stir.
Looking good.
Now place the flask containing the yellow oil into a cold water bath and get the temperature down to below 10 degrees C.
Add the amine salt solution to the flask.
At this point the amine is still a salt and the flask contents are still acidic with hydrobromic acid,
so no reaction will occur just yet.
Now measure out 1.2 grams of sodium hydroxide.
This needs to be enough to convert all the amine salt to the free base form
and neutralize the mole equivalent of hydrogen bromide.
Dissolve this in 3 mils of water and then cool the resulting hot solution down to below
10 degrees C.
Now we're ready to start adding this slowly drop wise to the flask.
As you add the first drop the local temperature increase combined with the amine free base
formation will generate a white smoke in the flask.
Add the sodium hydroxide solution slowly over about a 5 minute period.
Here's the flask on complete addition.
Doesn't look much different.
At this point, remove it from the water bath and heat it gently on the hot plate, with
vigorous stirring continuing.
We tested a tiny sample of the reaction.
Using indicator paper to test that the pH was around 13.
Continue heating on the hot plate until the temperature reaches 60 degrees C.
Then switch off the heat and allow to cool back to room temperature again.
Here's our completed reaction mixture and the lappermattery effect of the intermedia
is now gone.
We now need to work this up.
Let's first get all organics into solution using 20 mils of dichloromethane.
Add to the flask and swirl it around vigorously.
Then add the mixture into a separating funnel.
Use an extra 5 mils of DCM to wash out the reaction flask.
The bottom layer is the DCM containing the organics.
Separate this off into a flask.
Then use a further 10 mils of DCM to extract the remaining aqueous layer.
Allow to separate.
Then separate off the bottom DCM layer and combine with the previous one.
We are now going to do an acid base extraction to get our product free from other organic
materials.
First place the dichloromethane solution back into the solution.
into a clean separating funnel now make up a solution of 20 mils of 10%
hydrochloric acid you can mix 6 mils of concentrated acid and add 14 mils of
water add this to the separating funnel this will convert our product back to
the salt form and make it soluble in the aqueous layer shake well and then allow
the layers to separate
separate off the bottom DCM layer in theory this now doesn't contain any
product but reserve it just in case anything went wrong now make up a
solution of 4 grams of sodium hydroxide in 25 mils of water and chill it down
add the cooled solution to the
separating funnel containing our aqueous product once the hydroxide has
neutralized excess hydrochloric acid the freebase product will start to separate
as a cloudy emotion again we did a quick pH test to verify that the pH is around
13 and hence all our product is free based will extract using 15
mils of dichloromethane
Add this to the separating funnel and give the mixture a vigorous shake to depict the product.
all the product into the organic layer the resulting mixture may take a while
to separate so be patient you can see that the cloudiness is all gone from the
top aqueous layer separate the bottom DCM layer containing our product add a
further 15 mils of dichloromethane to the funnel to break up any residual
emotion and extract again add some extra water if this helps as well remove
the bottom DCM layer and combine with the previous one then dry using a little
anhydrous magnesium sulfate pour the dried DCM product solution into a flask
and then evaporate off the solvent using the hot water bath and with a vacuum be
sure to remove all solvent
otherwise you may need to add more water if you don't have enough water to
use the crystallization step will fail you will be left with a yellow oil in
the flask this is our crude freebase product there was a very faint aroma of
piperidine in the background but not much
prepare a small amount of concentrated hydrochloric acid and add this drop wise
to the oil you'll only need a few drops and be very careful not to add too much
we used five drops in total now add a round two mils of acetone to the mixture
and then chill the flask in the freezer for thirty minutes or so the product
should crystallize out if it doesn't then either you use too much
hydrochloric acid or there is water present in the mixture or there is some
other solvent for organic impurity present
you
set up for filtration
and use a little acetone to transfer the contents of the flask into the filter.
And here's our first batch of product after washing with a little acetone and drying thoroughly.
0.49 grams of white crystal.
This isn't much so we decided to extract a second batch from the filtrate.
Since the hydrochloride salt of the product is very soluble in water,
any water present in the acetone or on the glassware will lead to losses of product.
We evaporated down the acetone filtrate in a small beaker on a hot plate.
We were left with a brown syrup which we allowed to cool to room temperature.
We added acetone to this to see if more product would crystallize after.
And there it is, pretty rapidly dropping out of the mixture.
Again we filtered this and used acetone to wash the beaker.
And a little acetone to wash the crystal.
And allowed them to dry.
Here's our second batch of product.
0.36 grams of white crystal but not quite as well formed as the first batch.
In total that's 0.85 grams of product which corresponds to a 35% yield on starting propiathanone.
This seems like a low yield, but we couldn't find any reference for this exact compound to compare against so who knows.
It's likely that there's still some product in the final filtrate and we could probably keep going and extract more.
But we're happy with this and it seems like a fairly pure product that we've obtained.
If you're tempted to try this reaction with primary amines, be warned that in the second reaction step these can cyclis under conditions of too much heat and too high pH to form pyrazines as impurities.
We chose piperidine which is a secondary amine to avoid this complexity, and also because the product is unlikely to be pharmacologically active.
We hope you enjoyed our 50th video. Stay tuned for more.
Thanks for watching.