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.