The usual procedure for making acid chlorides from carboxylic acids with COCl2 is use of a small amount of DMF catalyst, but this results in a side
product that is a potent carcinogen. This carcinogen is no joke. Mice developed skin tumors after one dermal exposure.
If I work outside, and don't have a fume hood, is there a way to totally avoid exposure? Obviously I would use an organic vapors respirator, gloves,
lab coat, goggles. Would a large fan be sufficient to blow vapors away? I normally take my glassware indoors for cleaning, so should I be rinsing them
with acetone outdoors first?
My other option is to just use DBU instead of DMF as the catalyst, which was described in the paper. I'll probably just do this, but in general it's
good to know how to minimize carcinogen exposure at home. I'm worried I won't live to see 2100 because of this hobby.karlos³ - 23-9-2020 at 11:07
Not a real answer on your question, though what I'm saying might make your issue obsolete.
I assume you aren't planning to make such a more complex molecule, nor is a hydroxamic acid the target?
You just want to prepare an acid chloride, nothing else?
What is your target acid chloride precisely?
I'm asking, because if you just want to make an acid chloride, you don't need DMF or DBU at all, especially if the acid you're chlorinating is a
simple molecule.
For example, I've chlorinated oleic acid with oxalyl chlorided without any issues in DCM, on two occasions.
You just let it react, ideally in a distillation setup and distill the fumes and the DCM off under mild heating to drive the reaction forward.
I did the same with SOCl2 too and that worked fine as well.
Also did the same with a certain substituted hydrocinnamic acid, both with SOCl2 and (COCl)2, without any catalyst either, of course.
I really don't know what the DMF or DBU would be useful for at all if you don't want to make a hydroxamic acid like they did in that paper?
Definitely it has no advantage in the simple formation of an acid chloride, so I don't understand why you think you would need one?Cou - 23-9-2020 at 11:08
I plan on making simple aliphatic acid chlorides, such as butyryl chloride from butyric acid, nonanyl chloride from nonanoic acid.karlos³ - 23-9-2020 at 11:10
Then its all fine if you use only the (COCl)2 as it is without a catalyst.
The reaction is driven forward when you distill the resulting gaseous byproducts off.
I've seen that a catalytic amount of DMF is recommended, yeah, but it works well without that already.
At least I had no problems to make the mentioned acid chlorides with it without any catalyst.
Just let the acid react with oxalyl chloride in dry DCM overnight, and the next day you strip the volatiles off, the residue will consist of a good
yield of acid chloride then.
[Edited on 23-9-2020 by karlos³]Cou - 23-9-2020 at 12:00
for some reason, some procedures use DMF, and some don't. I notice the first procedure, with no DMF, heats the reaction to 70 C, whereas the others,
which use DMF, work at room temp. That could be the only difference.
If you're going to use a catalyst, then you should use DBU. from what i've read, Dimethylcarbamoyl chloride is a really serious carcinogen, not like
"eh just don't breath it in every day and you barely increase your cancer risk by 1%"
[Edited on 9-23-2020 by Cou]karlos³ - 23-9-2020 at 13:10
I am actually quite satisfied with the yields I've gotten without catalytic DMF or DBU.
It might make the reaction time shorter and the general outcome higher I assume, but it doesn't seem to be worthwhile enough to me, especially if the
dimethylcarbamoyl chloride is such a nasty carcinogen.
I've seen much cheaper bases in use by the way, like pyridine.
The yield table given in your referenced document should be taken with a grain of salt also, since you are not going to make hydroxamic acids nor do
you start from a more complex molecule.
I think you can substitute, if you really want to employ a catalyst at all, not just with DBU but any of the other potential catalysts.
On a simple substrate like your butyric acid as example, it will probably not matter much at all, the outcome will be just as well as with any of the
potential catalysts.
Don't think I will ever try to employ a catalyst in the synthesic of acid chlorides with oxalyl chloride myself though.
On oleic acid I get yields up into the 80s% of amide after reaction of the crude acid chloride with ammonia, so I wonder how much this could be
improved even with the use of a catalyst?
Because with SOCl2, the reaction hasn't worked substantially better at all.
On the other acid I've chlorinated twice with (COCl)2, the yields were likewise high as well of crude acid chloride, and when further reacted with
NaN3 followed by the curtius rearrangement, gave the same outcome to a former trial using SOCl2 for the same reactions.
I really don't see the reason why a catalyst would be used or even needed here to be honest.
Although now I wonder how likely the formation of that carcinogen is in a vilsmeier-haack formylation?
I've occasionally seen procedures with SOCl2 instead of POCl3, and I was already thinking if oxalyl chloride might be a suitable substitute as well.
But I guess now with that knowledge on hand, definitely not!
I think oxalyl chloride probably would be too mild anyway to work here, so one would end up only with a soup full of a potent carcinogen instead of
the desired (chloromethylene)dimethyliminium chloride as it would be the case with SOCl2 or POCl3...Sulaiman - 23-9-2020 at 16:57
source] This carcinogen is no joke. Mice developed skin tumors after one dermal exposure.
If I work outside, and don't have a fume hood, is there a way to totally avoid exposure?...
based on gasses
such as SO2. NO2. Cl2 etc. working outdoors without a mask in suburbia
No, you cannot totally avoid exposure,
winds change direction
accidents happen
not just you but other humans and animals - possibly 10's metres away.
My neighbours would tolerate the odd whiff of 'chemicals' and I assured them that I would not let anything 'dangerous' get to them.
That is a basic guide for my hobby Chemistry.
Even so, I often get a whiff of noxious gasses myself.
(so far no comments from neighbours)
So, unless you can control the area around the experiment, (or fume cupboard vent) you can't be sure.
[Edited on 24-9-2020 by Sulaiman]Cou - 23-9-2020 at 17:00
I live in the middle of a large agricultural parcel, not in cookie cutter suburbia, lucky me.Sulaiman - 23-9-2020 at 17:07
