Simply cooking up aniline in an excess of acetic acid will provide acetanilide.
I've been puzzling about acylations involving substituted anilines and I keep running into benzoylations wherein pyridine is used in the reaction
mixture. For what I ask? And why isn't the pyridine itself benzoylated? The methods I'm referring to employ acid chlorides and I'm trying to
minimize side reax and maximize yields so acid chlorides (acetyl-Cl) seem the better way to go but why the pyridine and are basic conditions supposed
to be maintained with diammines where one is tert?
[Edited on 5/2/2009 by Nicodem]Klute - 1-2-2009 at 09:45
The pyridine is there to react with the formed HX, driving the reaction forward, and preventing any side reactions do to the presence of a strong
acid. The pyridine itself isn't acylated because the formed salt is as reactive as the acylating agent (often an intermediate, hence the use of
pyridine, DMAP, imidazol etc as acylation catalysts)chemrox - 1-2-2009 at 11:07
so what would you use along with acetyl chloride? same thing?ziqquratu - 1-2-2009 at 12:32
The pyridine can be used as a base for the reaction, to mop up the acid generated as Klute mentioned. It is, however, usually far more important as a
catalyst - many acid chlorides can be surprisingly sluggish to react with amines or alcohols, but will react reasonably quickly with a pyridine. The
N-acyl pyridinium species thus formed is VERY reactive, and usually this is the actual acylating agent in the reaction. 4-dimethylaminopyridine (DMAP)
is an even better catalyst for the job than pyridine itself, although it is quite toxic.
In our lab, the standard protocol for acylations using acid chlorides involves about 10 mol% DMAP, with stoichiometric triethylamine to quench the
acid formed in the reaction (this mainly because DMAP is, for us, relatively expensive).chemrox - 1-2-2009 at 18:53
so if HX formation isn't a problem..i.e. one can use the acid salt to purify the product by recryx for example and then release the base, then one
could forgo the Et3N part but pyridine would be there in about 10 mol% as a catalyst? same ratio as DMAP?smuv - 1-2-2009 at 20:29
Acyl chlorides form ketenes in situ upon treatment with (relatively) non-nucleophilic bases; these are of course mega reactive.ziqquratu - 1-2-2009 at 22:56
No, you need a base to mop up the HX - it can cause you some big problems in some cases! I'm just saying, it's often the case that you don't want to
use stoichiometric pyridine - either for toxicity concerns, cost, or whatever. I suspect many hobbyists would have problems getting pyridine, so might
not want to waste it, for example.
My point was, the pyridine may serve both as catalyst and base, but if you want to conserve your pyridine you can use it purely as a catalyst along
with a second (usually cheaper and more available) stoichiometric base for taking care of the acid formed.chemrox - 2-2-2009 at 01:08
right I picked that up so the catalytic amount of pyridine is 10 mol%?Klute - 2-2-2009 at 11:23
Yes, that a good place to start. If you don't use any extra base to mop up the HX formed, your pyridine will be "blocked" as the HX salt and unable to
form the acyl pyridinium species... Better use Et3N, or even possibly an acetate (check that one in the litt though).chemrox - 2-2-2009 at 14:21
I've seen Et3N and NH4AcO .. however, if the pyridine is to be used as a catalyst why not use a molar excess and use it to take care of the HCl?
I'm assuming this will increase yield enough to be worthwhileKlute - 3-2-2009 at 09:28
You can of course use pyridine as the base too, using 1.1 eq for example. Usually it the most practical way to do so. Just depends if you have a good
access to pyridine I guess.chemrox - 3-2-2009 at 22:08
Is pyridine difficult for some folks to get? Too bad .. what a world..chemrox - 24-12-2013 at 15:34
I'd like to revisit this topic if we can. I tried stoichiometric pyridine with acyl halide in a familiar sequence the only difference being the
pyridine. I also tried adding acyl halide to neat pyridine. The results were precipitation of a solid and I doubt whether the intended acylation
even occurred. What is the complex I have? and how do I break it up? 6M HCl and 2M NaOH don't seem to affect it .. doesn't dissolve in 1,2-EtCl2 or
toluene. I'm guessing acetone or MeOH will dissolve it. So I may have a way to get the stuff out of the flask and manipulate it. I'd like to get
the pyridine complex out before I repeat the acylation with a simpler approach.
