Today we'll be preparing phlebotonic acid, an interesting heterocyclic compound synthesized

by the reaction of acetone and diethyl oxalate in the presence of a strong base.

We've drawn up the reaction scheme here so you can see how the carbons in the target molecule

originate. It's apparently useful to keep water out of the first stage of the reaction,

so we used an oven-dried 250 ml flask and Teclon magnetic stir bar.

We weighed out 14 G

of sodium ethoxide directly into the dry flask. This is a slight excess to what we need.

We prepared this reagent in a previous video. For more details, click the link shown.

We want to dissolve this in the minimum amount of ethanol possible,

so we're going to start with 30 ml and see how we go. Add the dry absolute ethanol to the flask.

Stir, stir, stir and then poke itAh-Aش, ah-Aish.

And then gently start stirring to get it to dissolve.

We added another 10 ml of ethanol, and most of the solid dissolved after 10 minutes.

Now for the diethyl oxalate.

We had some difficulty drying this because we discovered that over a period of time,

this compound has a habit of reactingurer.

with calcium chloride.

in calcium chloride.

We're not totally sure what happens, but it gives exp re如果你 effect website to see if the salt can react properly.

gives off a lot of HCl fumes.

So we washed the diethyl oxalate thoroughly with brine, and then dried it for a few days

using anhydrous magnesium sulfate.

Hopefully this will be dry enough.

We decanted the liquid and weighed out 26 grams of diethyl oxalate with a sickly sweet

fruity aroma.

And then added this to the flask containing our sodium ethoxide solution.

At this point the remaining sodium ethoxide solid went into solution.

Next we measured out 5.2 grams of dry acetone from a fresh bottle.

And we added 20 mils of absolute ethanol.

Remember to make up a solution.

We then set up the flask with a dry pressure equalized addition funnel on top.

If you're using a non-pressure equalized one you'll need some sort of vent from the flask

to allow pressure to escape.

We added the acetone in ethanol solution to this.

Then with stirring on at room temperature, we started a very slow addition of the acetone

solution.

We went slowly because too much of an acetone concentration in the mixture can cause side

reactions.

We want to keep the other reactants in large excess while the acetone is deprotonated and

reacts.

Our aim was for complete addition to take around 40 minutes, and with a small volume

of liquid to add this meant a slow drop rate.

The first sign of a reaction occurring was a slight yellow tint and a milky color appearing

in the mixture.

Soon this became much more intense as you can see.

We could also see a precipitate building up in the liquid.

Here we are half way through the addition.

And at this point we switched on the heating so that the temperature of the mixture is

going to rise during the second half of the addition.

By the end of the addition the temperature was around 60 degrees C.

And about 40 minutes in the addition is complete.

At this stage we removed the addition funnel and placed a thermometer in the reaction mixture

to monitor the temperature.

We bought the temperature up to between 70 and 75 degrees C, and then held the reaction

in place.

During this period the color darkened slightly and the mixture became thicker as more precipitate

was deposited as you can see here.

After an hour we allowed the mixture to cool and then let it overnight.

The next day the mixture was quite dense and could only just be stirred magnetically.

At this point we chilled the flask down to zero degrees C.

We placed 25 ml of concentrated hydrochloric acid into a small pooser and also chilled

this down to as cold as we could get.

Then we set up the dropper so we could add it slowly.

And with the cold reaction mixture stirred as well as we could, we slowly added the cold

concentrated hydrochloric acid.

By the end of the addition the temperature was around 20 degrees C.

see, and the mixture had turned an orange color. As you can see, a fairly heavy orange

colored precipitate formed. And we checked the pH of the mixture to make sure it was

strongly acid and all base had been neutralized. We then filtered the precipitate off using

a vacuum pump. The filtrate liquid was an intense red color with a yellow tint, and

as a warning hit, seeing everything it touched yellow, including the glass. We washed out

the flask with 20 mils of ice water and then used this to wash the precipitate.

Dry.

Drying took several hours on the pump, but we ended up with 13.5 grams of an orange solid

intermediate. This is our acetone double addition product. Now for the next step of the reaction

which is to hydrolyze the ester groups in this molecule and cyclase the compound into

calyponic acid. In hindsight we could probably increase the yield by boiling the ethanol

off the filtrate and seeing if we could collect more product.

This might be something.

feel inclined but watch out for the yellow stains this stuff takes no

prisoners okay now for part two we set out the 250 mil flask equipped with a

magnetic stir bar and added our 13.5 grams of intermediate product to this

then we measured out 40 mils of concentrated hydrochloric acid

and added this to the flask then we set this up on a hot plate stirrer with a

reflux condenser attached we're going to need to heat this for a while in order

to get all hydrolysis to occur and fumes of HCl will be given off so make sure

you use ventilation we initially heated the mixture to reflux point for two

hours there was a little bit of foaming in

the flask but not too much

after two hours of refluxing we added an additional 10 mils of concentrated

hydrochloric acid through the top of the condenser and then reflux for a further

hour and then after an hour we removed the condenser and allowed

the mixture to boil off a little bit since acid ester hydrolysis is a

reversible reaction we need to drive off the ethanol in order to get this to

completion total heating and hydrolysis time was

four hours towards the end of heating we noticed

that the mixture bubbled and foamed quite a lot and the color darkened

the dark boots slightly opalescent flaky material was seen on the sides of the flask

the dark boots slightly opalescent flaky material was seen on the sides of the flask

we chilled the flask down to zero degrees which seemed to increase the

amount of solid present and set up for filtration it took a bit of work with a

spatula to transfer it

we then washed out the chilled flask with 10 mils of ice-cold water and used

this to wash the precipitate in the filter

then we allowed the brown solid to dry thoroughly on the pump

the resulting brown paste was then oven dried at 120 degrees C to form a solid

here's the fully dried product 8.4 grams of a light brown fine powder

here's the fully dried product 8.4 grams of a light brown fine powder

at 120 degrees drying temperature we believe that this should be calyptonic

acid monohydrate if so this would give a yield from the starting acetone of 47%

if it's the dehydrated acid then that yield is 51% so in reality it probably

lies between these we're going to attempt to convert this into

glycemic acid by introducing a nitrogen into the ring this will be exciting alguns Eco R craniosul negroes

Because if it works it will give us a pyridine compound synthesized from relatively OTC starting

materials.

So stay tuned.