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Barbituric acid synthesis - Video Tutorial

Barbituric acid synthesis

Today is the 4th of December, the Feast of St. Barbara.

151 years ago on this day Adolf von Bayer discovered how to synthesize barbituric acid,

the parent molecule for barbiturate sedatives, all named after St. Barbara.

So in honor of the German chemist and to commemorate the day, we're going to synthesize barbituric

acid using the diethylmelonate we prepared in the previous video.

First we're going to get it as pure as we can.

We've got about 10 ml of diethylmelonate here in a small flask, and we've set up for

simple distillation.

It's really important to use pure reagents for this reaction, as well as being extremely

careful to ensure that all reagents and apparatus are dry.

We're using the thermometer so we can check the temperature of the vapors and make sure

we save only the pure diethylmelonate which boils at around 200 degrees C.

We're heating and the liquid starts to crackle at first a bit like a hot oil bath.

We start to collect a small amount of liquid, only about 1 ml or so at around 80 degrees

C.

This has a very characteristic aroma and is ethyl acetate, an impurity due to acetic acid

being present.

We're going to add a small amount of diethylmelonate to the mixture, probably due to malonic acid

decomposition.

Then the temperature increases and we start to get a main liquid vapor front coming up

the glass.

The temperature shoots up to about 140 degrees C and we get a few mils of a rather unpleasant

smelling liquid coming over.

Then the temperature increases again and we get distillation of a clear fruity sweet.

This is our pure diethylmelonate distilling.

In order to ensure the pure product we didn't complete the distillation, but collected enough

of the liquid that we could work with.

We didn't want any decomposition products potentially forming and coming over, making

our distillate impure again.

Here's our stock.

Here's the starting material.

Exactly 4 grams of fruity smelling diethylmelonate which is a slightly oily liquid.

We placed this into a small dry beaker and reserved it ready for the reaction.

OK here's our reaction setup.

We're using a hot plate for heating and a small flat bottomed flask sitting on this.

At the moment we don't have a magnetic stirrer in there, but we recommend that you use one

of these.

We've got the small ebig condenser attached to the flask.

And on top of this we've got an adapter connected to a drying tube containing anhydrous calcium

chloride.

It is essential that all the glassware is completely dry.

Oven dry everything.

Then assemble the apparatus while the glass is still hot.

Then leave to cool.

Let's get going.

First we've measured out 20 mils.

Of absolute ethanol into a dry measuring cylinder.

Again, the ethanol must be anhydrous for this reaction to work.

With the condenser temporarily removed, we add this into the flask.

OK here we go.

We've closed it back up again to ensure that no moisture gets in.

Now we've measured out a block of sodium metal.

Weighing around 1.5 grams.

We're going to use a sharp knife and quickly trip the sides to remove any oxide any hydroxide

build up.

Then we quickly add the remaining sodium block weighing just over 1 gram to the flask.

This reacts with the ethanol and bubbles away producing hydrogen gas.

The mixture also heats up and starts to reflux very slightly.

The sodium metal takes an hour or so to dissolve.

And towards the end it helps to switch on the heat so that the mixture refluxes.

OK.

While we're waiting for this to react we're going to prepare the other reagents we need

for the reaction.

In this reaction diethylmelonate condenses with a molecule of urea to give our product.

We took some urea powder and placed it into a makeshift desiccator containing anhydrous

calcium chloride for a few days in order to make sure it was completely dry.

Then we weighed 2.2 grams of the dry urea powder into a dry beaker.

And added 15 mils of absolute ethanol.

We've got the hot plate switched on and we're now going to heat the urea and ethanol until

the urea goes into solution.

We've covered the top of the beaker to stop moisture getting in.

The urea will dissolve.

But it requires the ethanol to be nearly boiling.

And here's our diethylmelonate from the distillation we did.

We've placed it into a small beaker with a few granules of anhydrous calcium chloride

to make extra sure it's properly dry.

Our sodium has now completely reacted and we've got a slightly viscous cloudy sodium

ethoxide solution now.

So first.

We add the diethylmelonate to the reaction flask.

And now we're just waiting for the urea to dissolve in the ethanol.

That boiling point has all dissolved.

And now our urea solution in ethanol goes into the reaction flask.

. . . within about 10 seconds.

it starts to form in the flask and this becomes quite thick so now we need to

heat the flask to reflux temperature and keep this going for a few hours in

order for the reaction to complete there's just one catch the ethanol and

the heavy precipitate create a mixture which bumps very violently to counteract

this we place a small magnetic stirred bar in the beaker and set it stirring at

high speed this didn't stop bumping entirely but it does reduce the

magnitude we left this to reflux gently for the next two hours there wasn't any

further visible change to the reaction mixture during this time it's still a

relatively

liquid slurry during the last 15 minutes we prepared the beaker containing

20 mils of water and placed this on the hot plate when the temperature of the

water is about 60 degrees C then it's ready two hours are now up and we've

removed the drying tube from the condenser as you can see from the

indicator paper there's an alkaline reaction from the vapor this is due to

a small amount of ammonia being formed in the mixture as a result of area

hydrolyzing under the alkaline conditions however there is not much now

we add the warm water to the flask through the condenser

there's no obvious reaction or heat evolution we allowed the mixture to cool

slightly and then dismantle it and put it in the freezer for another three-низle for another half hour.

the majority of the apparatus okay our product should be in this mixture and

since it's acidic it will be dissolved as the sodium salt here's about eight

mils of concentrated hydrochloric acid in a small beaker and with a dropper so

we can add it to the reaction mixture

on addition the white precipitate starts to become lighter in volume the mixture

at this stage is still strongly alkaline as you can see from the indicator paper

so we keep adding the hydrochloric acid slowly and soon the precipitate

disappears forming a clear solution

now the mixture is strongly acidic so we are finished with acidification our

product should now be present in the solution is free barbituric acid this is

still somewhat water-soluble so in order to get it to crystallize we need to

chill the solution down to nearly freezing point

for an extended time period after only

an hour or so of chilling some white

crystals are already visible in the

mixture as you can see let the mixture

chill in the coldest part of the fridge

but without freezing for six hours here

we are six hours later the cream colored

solid has fallen to the bottom of the

flask

So we set up for filtration.

We're using our grade for fine center as it looks as though the crystals are quite small.

We wash with a small amount of ice water and then let them to dry thoroughly on the pump.

Here's our dried product.

2.3 grams of fluffy cream colored tiny crystals of barbituric acid.

Barbituric acid is colorless so this will need re-crystallization to obtain a completely pure sample.

This is a crude yield of 72% which is about the same as the literature suggests.

And this is a great result as it shows our drying precautions worked well.

Here's a small amount of water in a beaker.

Let's add some of the product.

Some dissolves but as you can see it's not that soluble.

Now let's add a little bit of sodium hydroxide.

Now the solid dissolves forming the sodium salt of barbituric acid.

Overall a very satisfying experiment and it was by sheer coincidence that we had the opportunity to do it at exactly the right time of year.

Depending on who you believe that is.

Thanks for watching and stay tuned because it won't be long before our 100th video.

And we've got something special planned.

See you next time.