what is the purpose of the sodium acetate solution in the amide synthesis of acetophenetidin This is a topic that many people are looking for. amritsang.org is a channel providing useful information about learning, life, digital marketing and online courses …. it will help you have an overview and solid multi-faceted knowledge . Today, amritsang.org would like to introduce to you CHEM261 Synthesis of Phenacetin PreLab. Following along are instructions in the video below:
Is our organic chemistry laboratory introduction to the preparation of the molecule fine aciton and and were going to use introduce a new reaction mechanism for this one that havent yet covered in class. A nucleophilic acyl. Substitution.
And so weve got it were making a new compound. Via a new mechanism. Okay so the reaction.
Were going to do is a nucleophilic acyl substitution. Just for some background fen aciton was originally produced in 1887 as an analgesic and it was on the market and in the united states until 1983 at which time evidence showed that while it was an effective analgesic. Its similar to aspirin and what it does long term use could lead to some consequences.
There was some increased incidence of kidney failure or possibly kidney related cancers. So some cant increase cancer risk of appeared and so in the early 80s. It was withdrawn from the market in most places so were going to start with this molecule for oxy.
So theres our ethyl group right f. Oxy. And then amino benzene is called annalen.
So its a for oxy annalen or whats called para phonetic. Remember with substitutions on a benzene ring. Youve got ortho meta para.
So it can be paraffin. Editing. And were going to react that with this molecule.
Which is acetic anhydride acetic anhydride is what you would get if you took two molecules of acetic acid and linked them together by removing water all right if we take out water and link. Whats left together you get lets see it again hydride and acetic anhydride is good for this because we have right we have the acyl group right so something with a carbonyl is an acyl group.
If it is attached to something that can be at least a decent leaving group or a potential leaving group right and so since our leaving group here would be the acetate ion and hydrides here or acetic anhydride is an excellent choice for this acyl substitution right so our fourth oxy annalen or paraffin editing is going to act as the nucleophile right to attack our acyl group in a nucleophilic acyl substitution. Okay so just to go through the mechanism of a nucleophilic acyl substitution so right heres our nucleophile. Which in this case will be our our paraffin.
Our voxi allan right so. Our nucleophile attacks. The carbonyl now a nucleophilic attack on a carbonyl first results in opening up the pi bond to make an intermediate.
Which is tetrahedral and so in that intermediate. There are the original nucleophile. Which could be a leaving group or the original group that could be a leaving group.
And what generally happens is whichever is the better leaving group is the one that leaves and so normally you have a stronger base attack and a weaker base leave and as that leaves it allows the pi electrons to come back reform. The carbonyl. The carbon goes back to being sp2 and your nucleophile has replaced your leaving group so this tetra this tetrahedral intermediate right this tetrahedral intermediate is characteristic of nucleophilic acyl substitutions.
Okay so heres the specific mechanism using the molecules that were using in this lab. Right so here is your f oxy. Annalen.
Alright acting as nucleophile attacking the carbon eel alright. Lets go ahead and put some color to this right so alright. It acts as a nucleophile attacks.
The carbon eel that opens up to create the tetrahedral intermediate. With now two groups that are potential leaving groups attached to our original carbon. And so if we want to make this an even better leaving group right oxygens become better leaving groups that we can protonate them so if we get an intramolecular proton transfer that is the acidic ammonium nitrogen protonates the oxygen now this oxygen becomes a better and even better leaving group and certainly a better leaving group than this nitrogen that would leave as a negatively charged nitrogen and so now right our electrons can fall back and as they fall back the leaving group is pushed off and so you end up.
Then with your substituted product. Your acetate group.
Now on the nitrogen let me write that out right. That group would be in a sat. Eel or acetyl group.
And the leaving group was acetic acid. Certainly you know we name it. As a scenic acid.
Is it is certainly a weak enough base and looking quickly. I can see that we need to add a couple of electrons. There so that our full octet is shown on the oxygen that was on the leaving group.
Okay. Now theres a problem with this reaction. And the problem is that this group is really strongly nucleophilic and when it acts as a nucleophile.
We saw it deprotonate and when it deprotonates. It becomes a nucleophile again so if you put this in with an excess of acetic anhydride. It attacks once goes through the nucleophilic substitution.
When that nitrogen is deprotonated. It attacks. A second molecule goes to the nucleophilic acyl substitution.
Again and so its very easy to get a diacetyl product. Now. This is easy enough to occur that even if we just you know note this even if we just pour the acetic anhydride directly into the paraffin editing in that moment.
Before the acetic anhydride can disperse. You get a local high concentration of the acetic anhydride and in that local high concentration.
This reaction starts before. You can disperse the acetic anhydride in the solution and so you start making this product that you dont want before you can do anything else. That is if you just add the acetic anhydride.
So we have to take specific measures to try to counteract this reaction. So the one thing. We know is we cant directly pour our acetic hydride into a solution of our fanatic dean.
Thats not gonna work okay so one of the things that we do is were gonna do the reaction in an acidic solution. Were gonna start off in an acidic solution. If we put the phonetic in in an acidic solution.
Then we protonate it and if we protonate it no when its protonated. We have no unshared pairs. So it is not nucleophilic in this reaction right so by doing it in an acidic solution.
We block the finetti diene from attacking and then we get no reaction when we put in our acetic anhydride right so thats one thing we start off in an acidic solution. And then we cant get the reaction now the problem is eventually we want the reaction how are we going to do that well were gonna add our finetti diene right the ethoxy annalen in acidic solution. Were gonna add the acetic anhydride and let disperse and then were going to add a weak base right.
Were gonna add a weak base all right sodium acetate. When we add the weak base sodium acetate. It is a strong enough base to deprotonate the finetti diene when we deprotonate the finetti diene.
We expose the unshared pair of electrons and once we expose the unshared pair of electrons. We can get the nucleophilic attack that will make our product. But since weve allowed the acetic anhydride now to disperse evenly through the solution before we let the reaction start.
We dont get that high concentration of acetic anhydride and so we get only one substitution sort of a slick way of not letting the reaction start until. We want it to start and so that is going to be essential to getting the right product.
So just some points. Some technical points. We need to follow the procedure really carefully because amounts and order of order of addition of reagents is important right so a couple of things one bigger on that so one thing.
Aromatic. Amino compounds tend to be oxidized. If you let them sit around and when they are oxidized.
They create compounds that are yellow to brown. And so just the fact that you know weve been using these materials. The bottles have been open before means we probably have some oxidation products.
So if you get to the end and your solution is not clear you can put it a little bit of activated charcoal in these yellow and brown products adhere to the activated charcoal and the charcoal will remove them before you start making your product. So as i said before order of addition of reagents is critical right especially youve got to acidify the food before you add. The acetic anhydride right also in this case.
The amount right this the amount or as we like to talk about the stoichiometry right of the hydrochloric acid the stoichiometry of the hydrochloric acid and of the sodium acetate are critical to getting us a successful reaction right you really want those in in the proper. One to one relationship right you wont have enough hydrochloric acid to protonate your finetti diene. But not too much right if you put in too much its going to take more sodium acetate than you think.
And you wont completely d. Protonate your phonetic diene and if you dont deprotonate your phonetic diene. You dont get near 100 yield right.
So whats really important right as its really remember stoichiometry is about mole to mole ratio right so its really critical that you cant calculate how many moles of each thing you need of each reactant is required now at the end of this were going to do a recrystallization. So you know we harp on recrystallization you know how do you know how to put in the minimum amount of solvent right what are the specific steps in recrystallization. But really read because this is a different kind of recrystallization.
Were going to use a mixed solvent system ethanol and water right and so youre going to have to make note of the slight differences in technique when were using the ethanol water recrystallization versus a single solvent recrystallization which is what weve done in the past. So. This is your this was your prelab preparation for our synthesis of van.
A certain if you have any questions. Please ask before the start of your lab period. .
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