Yes, my dear organic chemists, all the beautiful things have to finish and, what I'm going to describe today is the last of the experiments we performed during our lab course. However, while non-organic chemists may be jumping happily, in the knowledge that, from last week, I'll be back to the "normal service", I must point out this is not the end of the "Laboratoire Organique" series: I'm preparing not one, not two but (ready for this!?) THREE special episodes which will certainly entertain you like nothing else before!
Em, well, I should calm myself now, shouldn't I?
OK, the last experience I present what was described to us as the (only) dangerous experiment, because involved the most toxic substances we had handled so far. And, in fact, although so dramatically warned, there was a incident, but you'll have to read the whole story to know what happened. Ah, ah, ah, ah, ah!
Today, ladies and gentlemen, we synthesize p-Nitroacetanilide from Acetanilide.
I know, as usual, the reaction is not that difficult: you just
nitrate acetanilide (which we, due to our endemic lack of time, hadn't synthesized but, annoyingly, bought). The main purpose, though, wasn't the synthesis per se: what our professor(s) wanted us to learn was how to purify the final product through
Flash Chromatography.
We began by dissolving
5.0084 g of acetanilide, in a 250 mL beaker, with
5 mL of concentrated acetic acid. However, this is almost impossible, given the
poor solubility of acetanilde in that solvent, so, having stirred this mixture for a long time, we ended up with a
dense amalgam which, to be honest, looked more like
honey rather than a
liquid.
The beaker was placed on ice and we added (drop by drop)
10 mL of concentrated sulphuric acid. Keeping the reagents cool we tried to avoid not only the nasty effects of the
exothermic nitration, but also the
hydrolysis of the amide which, as it turned out, led to a considerable amount of byproducts (namely, derivatives of
aniline, bearing a
nitro group).
But there's more. While my colleague was carefully adding the acid, I set to prepare the
nitration mixture: in a nutshell, 2.2 mL of
concentrated nitric plus
1.4 mL of concentrated sulphuric acid.
This reagent was in a test tube I placed
on ice too. To prevent us from inhaling an awful lot of
toxic nitrogen dioxide, we were told to be extra careful not to add it too quickly, but gently dropwise.
Finally, the beaker was left on the bench, at room temperature, to allow
nitration to occur. During our 40 minutes wait, we stirred the solution every so often.
To quench the reaction, 50 mL of water were used and, subsequently, we waited for 15 minutes before filtering it with a Büchner funnel.
We kept the filtered solution and then washed, thrice, the yellow precipitate with three aliquots of 50 mL of water. each time verifying whether the pH of the wash waters was neutral. These three aqueous solutions were, in the end, discarded.
We raised the pH of the first, yellow, filtered solution with NaOH (10%) and performed a liquid-liquid extraction in a sep funnel with 10 mL of dichloromethane. Because the aqueous phase contained a lot of aniline derivatives, dichloromethane became bright yellow, which made the separation pretty easy.
The organic phase was first dried with sodium sulphate and then concentrated to 2 mL. We labelled it solution A.
We weighed our crude product and, predictably, our yield was a mind-blowing 133% (8.9056 g), which was obviously a result of the percentage of water still present.
However, we put a bit of this highly impure product in a test tube where 3 mL of dichloromethane dissolved it. We dried this solution as well and named it solution B.
For our solution C, we recrystallized a tip of a narrow microspatula of p-nitroacetanilide (and other byproducts) with ethanol. In the beginning, we yielded a yellowish suspension, but, placing the test tube in a hot bath and then allowing the solution to cool to room temperature, we obtained our crystals.
This solution was filtered, this time a Hirsch funnel was enough, and labelled solution C. Our last solution, D, was yielded dissolving a small quantity of the pure crystals in dichloromethane and removing any trace of water with sodium sulphate.
We completed our synthesis with a TLC (mobile phase: toluene/ethyl acetate 4/1), which proved how beautifully pure our p-nitroacetanilide crystals were.
Moreover, we determined the melting point of these purified product (212°C), which nicely matched that found in literature (215°C). By the way, this assay wanted to make sure we hadn't got everything wrong: o-nitroacetanilide has, in fact, a completely different melting point (92-94°C).
For the grand finale, however, we had to try to purify our crude product through
flash chromatography. Now, although we were more than just guided by our professors (who actually prepared everything and witnessed the whole thing, while we solely had to manually collect the samples and staining the TLC layers), I can at least describe the procedure.
First of all, however, this being a lab course, there was just one column for each of the two labs, we were divided in groups of 4 couples each and queued: anyhow, every couple gave
1.5 g of crude product, which were placed in a 250 mL round-bottom flask, dissolved with
80 mL of dichloromethane (plus 5 mL of extra ethanol), dried with
sodium sulphate and transferred in another round-bottom flask (through a funnel with some cotton in the middle).
In the flask we also put
8 g of silica gel for flash chromatography (40-63 µm; mesh: 230-400) and concentrated the whole mixture: we begin setting the temperature at 40°C and then raised it to 60°C, until the only thing in the flask was a powder.
The column was packed with a bit of cotton right over the bottom valve and a volume of silica gel to fill two thirds of the column. A layer of sand was then placed on top of the gel and the
mobile phase (the same t
oluene/ethyl acetate 4/1 solution used for the first
TLC and for those carried out during the
flash chromatography) was poured in the column.
The
flow controller was placed on top of the column and connected to a small
compressor: the mobile phase went through the
stationary phase as the professor closed the bleed port with a finger. With some mobile phase still covering the
sand layer, we loaded the system: someone (don't blame me, I was having
a cup of tea: it was 5 o'clock) removed the
dry powder from the inner surface of the round-bottom flask, placed it on a piece of weighing paper and put it on top of the
stationary phase.
So, we were ready to start the
chromatography: sticking to what described in the
original paper (and due to dire financial crisis of our university) we manually collected the samples in 25 mL test tubes placed in a rack.
While some of us looked after the column, a series of
TLCs were carried out to assay the quality of our purification: please notice that
sample #1 is the dead volume of the system.
Now, there's a distinct possibility the sole reason you have read the post is because you want to know about the
incident. Well, towards the end of the first day (this experiment covered two days),
we heard the noise of glassware exploding coming from the other lab: their flash chromatography column. Eyewitnesses reported that a
lab assistant had just checked the
compressor, which wasn't working well, when, as a student opened the
flow controller, the
solvent reservoir in between the
controller and the
column suddenly exploded. Other people who were working there claim the
upper part of the column actually burst.
Fortunately, the column was behind a
hood, so,
nobody got hurt.
So, here we are. This concludes our syntheses: I hope the
organic chemists, who have begun reading this blog, thanks to these syntheses, will go on visiting this site.
Moreover, don't miss the three, forthcoming, ass-kicking
specials that, I hope, will provide
a proper sent-off to "pure" organic chemistry on this pages.
Stay tuned!
.jpg "Nitroacetalinide(s)")
