panziandi
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chloroacetonitrile
I am looking at preparing chloroacetonitrile. Now I have looked on Orgsyn and found the preparation from chloroacetamide by P2O5 dehydration which is
by far my favorite option...
chloroacetonitrile
...Now I have chloroacetic acid so preparation of the amide can be acompilished. However I am out of P2O5, perhaps phosphoryl chloride could be used
(bp 106 bp product 125)?
Alternatively I had contemplated chlorination of acetonitrile itself perhaps with UV, iodine or peroxide initiator? I have not found any references to
this though.
My third option of course is to buy it but that takes the fun out of it and sets me back a fair amount of £s!
Does anybody have any ideas or anything that I have missed?
Cheers 
(p.s. I'm looking to see if anybody has experience of this preparation or yields with the phosphoryl chloride route?)
[Edited on 3-6-2008 by panziandi]
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Sauron
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My advice is to replenish your supply of P2O5 and use the Org Syn prep.
Chloroacetamine is rather nasty and so is ClCH2CN, I trust you have a hood and know what you are doing?
[Edited on 3-6-2008 by Sauron]
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Nicodem
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Yes, you can use POCl3, at least according to JP62289552:
| Quote: | Chem. Abstr., 109, 54333:
Nitriles were prepd. by dehydration of acid amides with POCl3 in a mixed solvent of N,N-di-substituted anilines or N-substituted anilines and
halohydrocarbons or arom. hydrocarbons. Thus, POCl3 was added dropwise to a suspension of ClCH2CONH2 in C6H6/PhNMe2 at 60 over 2 h and the reaction
mixt. was kept for 1.5 h to give 95% ClCH2CN, vs. 70% for C6H6 as a solvent. |
...and JP62289551:
| Quote: | Chem. Abstr., 109, 92296:
Nitriles of b.p. 150 were prepd. by dehydration of amides with POCl3 in a mixed solvent of N,N-di-substituted anilines or N-substituted anilines and
halohydrocarbons or arom. hydrocarbons followed by simple distn. of the resulting reaction mixt. Thus, POCl3 was added dropwise to suspension contg.
ClCH2CONH2 in C6H6/PhNMe2 at 60 over 5 h, the reaction mixt. was kept for 2 h, and then subjected to simple distn. at 100 under 40 torr. The obtained
distillate was rinsed with aq. NaOH and subjected to rectification to give 71% ClCH2CN, vs. 50% for reaction mixt. which was neutralized at pH 8
before rectification. |
Direct chlorination of acetonitrile is described in DE4111906.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
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panziandi
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Thank you for voicing concern over the hazards. I do indeed have a hood and
the scale will be quite small looking for 25mL product.
P2O5 dehydration is quoted as having upto 70% yield whereas POCl3 method you have referenced seems to have the potential for a 95% yield which is
obviously interesting.
I have in the past looked at chlorination directly (eg of acetic acid) but inevitably chlorination past the monochloroacetyl compounds always seems to
be a problem, thank you for the reference though.
So from the looks of it the P2O5 method and POCl3 method are high yielding and much more worthwhile.
Thanks again for the replies
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Sauron
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I'd regard the Org.Syn. procedure as rock solid, while the patents (any patents and not just the cited ones) are somewhat like a bog with quicksand in
spots. The inventors oftem omit tidbits whike the patent lawyers obscure and obfuscate further. At best I'd regard a patent procedure as
investigational like a partially obscured map.
That being said, POCl3 ought to do the job. The devil as usual is hiding amidst the details.
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panziandi
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Vogel says that dehydration of primary amides may also be dehydrated with thionyl chloride.
2CH3(CH2)4C0NH2 =SOCl2=> 2CH3(CH2)4CN + H2S03 + 2HCl
So I'll have to weigh up the pros and cons of the thionyl chloride, phosphoryl chloride and phos pentoxide methods.
I agree with you Sauron that patents are often to be taken with a pinch of salt, don't reveal anyting because the writers want the money... that being
said having a closer look at the patents POCl3 methods above, it appears that the tertiary amines are acting as HCl scavengers thus increasing the
yield (if we assume the patent is correct).
Has anybody had experience with preparing this particular nitrile?
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Sauron
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How much risk of failure you want to chance depends on how much chloroacetamide you have and how easily you can get or make more. While you can buy
chloroacetamide, just as you can buy chloroacetonitrile, I have the impression you will make both yourself.
One line from good old Vogel with a generalization does not equal a detailed, annotated and referenced Org.Syn. procedure. So unless/until you can
find a comparably complete literature prep of your specific target using thionyl chloride - I'd still say replenishing your supply of P2O5 is the
shortest distance between two points amd path of least resistance.
It would really piss me off to lose a precious intermediate for the sake of expediency about a dehydrating reagent.
Sic gorgeamus a los subjectatus nunc.
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garage chemist
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I've dehydrated benzamide (amide of benzoic acid, obtained by reaction of same with an urea melt) to benzonitrile (PhCN) using thionyl chloride.
A catalyst, either DMF or benzyltriethylammonium chloride (selfmade from triethylamine and benzyl chloride) is necessary to give high yield, though
the reaction does work without it. SOCl2 is used in 1,5-fold excess, everything is heated at 80°C until no more benzamide crystals appear upon
cooling.
The product (liquid, insoluble in water) is preferrably purified via steam distillation, as this eliminates any sulfur chloride impurities arising
from decomposition of SOCl2 (decomposes slightly at 80°C).
No steam has to be led into the pot, I just periodically added water and boiled it off until no more oil came over with the water.
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panziandi
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Well I have sodium monochloroacetate and chloroacetic acid so chloroacetamide can be made from them. I can buy the chloroacetonitrile but it is fairly
expensive and I don't need very much of it so it's more worth my while making it. I agree that the best way forward looks like to go with orgsyn as it
is the only detailed peer reviewed method to date...
But as I have access to POCl3 and SOCl2 I would be willing to risk a go with these too, possibly?! I finish university soon so will give this
synthesis a shot when I get home.
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