Sauron
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Chlorination of MEK at 3-carbon
I want to prepare 3-chloro-2-butanone and want to minimize any byproducts.
The procedure described in Sartori's book for the bromo compounds is not helpful.
The attached US patent describes a selective chlorination by conc HCl or dry HCl that can be regulated to give either the mono-chloro product I
desire, or the dichloro product I am not interested in.
Catalyst is a solution of copper chlorides (Cu(I) and Cu(II) and oxygen or air.
Please see the patent and advise me how to instrument the setup to effect the required control.
Alternatively, recommend alternative preps.
I expect that N-chlorosuccinimide or TCCA would be good for this, and more convenient than Cl2.
The product is commercially available but mostly in tech grade.
[Edited on 28-12-2007 by Sauron]
Attachment: US3843731.pdf (153kB)
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chemrox
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possibly useful article
Hi Sauron- there are a few more agents in this paper and some data on their effectiveness. The nice thing is the paper seems specific to your
compound.
Attachment: method determin relative rates of reax halo agents with enols.pdf (273kB)
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chemrox
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and another paper
Here are a couple of more methods reported for making the material.
Attachment: Chlorination of Butanone.pdf (220kB)
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Sauron
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Thanks, chemrox.
Methods D and F in the second paper both employ sulfuryl chloride and give c.89% of the desired isomer, with fewer byproducts than the other
procedures. Method D simply has a tenfold excess of MEK to the chlorinating agent at reflux. Method F, a stoichiometric ration of MEK and SO2Cl2
diluted in fivefold n-pentane at 0C. F gives slightly better results. I think I would try using MEK as its own solvent and keeping the temperature at
) C, thus combining elements of the two methods for simplicity.
The authors seperated the isomers by VPC. I would use prep HPLC instead. However, this is ludicrously costly.
The first article suggests that procedures and reagents are available that produce ratios of isomers as high as 40 or more in favor of the
3-halobutanone. That is 97% or better and as pure as any on the market.
I will look through the first article more carefully.
Thanks again!
The first article indicates that various chloramines can be highly regioselective in the chlorination of MEK, typically giving 95% isomeric purity.
N-chlorodimethylamine, N-chloroisopropylamine and others were prepared and tested. A reference is given to bromination of MEK with NBS illminated by a
300W tunsgten lamp. This also provided the same order of selectivity. Most likely the same procedure would give similar results with NCS. The
reference is to a 1958 article in Acta Chem Scand for which I have been unable so far to obtain a DOI. I do not have a url for the home page of this
journal. Anyone knoe hoe to get there?
The full name is Acta Chemica Scandinavica
and the citation is C.Rappe, 22 219 (1968)
[Edited on 28-12-2007 by Sauron]
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not_important
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The times I made much of a halo-MEK I was taking it through Favorskii rearrangement and didn't care if the 1 or 3 carbon was halogenated.
But one time I did want the 3-halo exclusively and, not having access to reagents at the same level you do, did this
MEK =[H]=> 2-butanol
2-butanol =[vapour phase hot Al2O3]=> 2-butene
2-butene + 'HOCl' ==> 3-Cl-2-butanol
3-Cl-2-butanol =[O]=> 3-Cl-2-butanone
Obviously you could just purchase the 2-butanol or 2-butene.
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Sauron
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The Useless Reaction of the Year 2007 Award winner is from Canadian Journal of Chemistry.
Enol borinates are reacted with N-halosuccinimide to give high yield of a-haloketones, regiospecifically.
As I am after 3-chloro-2-butanone I looked into this. Unfortunatelt there are a few stumbling blocks.
To form the enol borinate, the appropriate diazomethyl ketone is reacted with the appropriate trialkylborane.
So for my C4 ketone the borane would be trimethylborane. This is unavailable commercially. It is a toxic pyrophoric gas bp -20 C.
It is prepared from methyl Grignard reagent (methylmagnesium iodide) and BF3 in n-butyl ether under N2.
So this already looking like no fun and costly.
I have not even looked into the diazomethyl ketone, which I think is diazoacetone in this instance. But in the back of my head is a whisper
"diazomethane" and warning bells warming up. Sure enough it is indeed diazoacetone and is prepared from acetyl chloride and diazomethane. Arghhh!
Anyone not know why diazomethan (CH2N2) is bad news?
It is toxic and prone to explode spontaneously; the special glassware designed for its reactions uses "Cleasr-Seal" joints free from any ground
surfaces since rough surfaces or sharp edges initiate explosion. Aldrich used to make a "macro scale" kit intended for 250 mmol work but no longer
sells this. So forget about kilo scale work with diazomethane. Even small scale work needs to be done in a good hood and behind a shield.
Now if only I wanted to make the corresponding a-chloro2-pentanone. Triethylborane is commercially available.
Sigh.
---------------
Thanks, not_important. I will look into starting with 2-butanol and going through the olefin, then treating with hypochlorite. I guess bubbling
through 10% Chlorox suffices? The chloroketone will be insoluble and seperate. Sounds good.
[Edited on 28-12-2007 by Sauron]
Attachment: CJC.pdf (214kB)
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Klute
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If it's not too undiscret, what do you plan to do with this haloketone? Just curious.
It's pretty funny, I was looking into 3-halogenation of MEK only two days ago for my raspberry ketone synth. I would be able to make the 3-isomer
using this chloroketone and phenol under light FC conditions. So then I could compare the smell of the two.
Please report back your results if you succeed in making this compound. The SO2Cl2 chlorination seems interesting as the reagent is relatively easy to
make and is very usefull in other reactions.
Good luck!
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Sauron
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3-halo-2-butanone is starting material for preparation of 4,5-dimethylthiazole.
Commercial 3-chloro-2-butanone is 95%-97% at best and remainder is 1-chloro-2-butanone and/or various dichloro-2-butanones. This can lead to problems
in the thiazole prep.
The boiling points are too close for fractionation to be of much use. Maybe with a 200 tp spinning band still, but I haven't got one of those.
The suggested route from sec-butyl alcohol (2-butanol) which is dehydrated to 2-butene, is simple and cheap. Treatment of the 2-butene vapor (it is a
gas) with HOCl soln (Clorox) produced the chlorohydrin. Oxidation of the chlorohydrin gives unambiguously the 3-chloro-2-butanone and nothing else.
This is a far more practicable route than trying to purify commercial 3-chloro-2-butanone via HPLC, which I am equipped to do - 3-4 grams at a time!
Maybe an ounce a day and at a cost of a dozen liters of HPLC grade solvent? Not likely.
The Canadian prep involves two kinds of unobtainium: trimethylborane (toxic, pyrophoric gas not commercially available) and diazomethane (toxic
explosive gas requiring special glassware an not amenable to scale-up). Another non-starter.
No, not_important's route is the best. Racemic sec-butyl alcohol is cheap.
I bet that 50% H2SO4 at a very mild temperature will dehydrate 2-butanol to 2-butene. See Vogel's procedure for methyl n-propyl carbinol (sec-amyl
alcohol).
And tert-butyl hypochlorite would be a far more effective reagent for preparing the chlorohydrin than sodium hypochlorite solution. It is easy to
prepare and as long as you keep it out of strong light, don't overheat, and eschew the use of any rubber, it is well behaved.
I thought about starting with 2,3-butanediol but it is too expensive, whereas the 2-butanol is really cheap.
Diacetyl (2,3-butanedione) could be reduced to the diol, monochlorinated, then oxidized. But this is still a bit costlier than the 2-butanol route and
same number of steps. So no advantage.
[Edited on 29-12-2007 by Sauron]
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not_important
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| Quote: | Originally posted by Sauron
...
The Canadian prep involves two kinds of unobtainium: trimethylborane (toxic, pyrophoric gas not commercially available) and diazomethane (toxic
explosive gas requiring special glassware an not amenable to scale-up). Another non-starter.
... |
What, you've no wish to become the Fiery EyE?
Well, I did this some 30 ears ago, and even if I did take notes they're long lost on one continent or another. What I remember is that the route was
based off of examples in "laboratory methods" or "practical organic chem" books from the 1900s to 1940s.
The dehydration step is critical. You want to get E2 elimination for Saytzeff orientation, maximising the 2-butene over 1-butene. The 1-butene can
vary from 1% or so up tp 15%, depending on catalyst and conditions' obviously for the goal here much of 1-butene is a no go. Alumina is good for E2,
the roughly 10 C difference in boiling points made it practical to remove much of the 1-alkene that did form.
The other potential problem is halogenation of the methyl group on the 2-butene, as those are allylic hydrogens. The less free halogen in the 'HOCl'
source the better. I think I used the chloride plus mercuric or zinc oxide method, either being more accessible to me than the typical reagents of
today (cold climates have their uses).
Can't remember which oxidation method I used, sorry.
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Sauron
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See my remarks upthread. I am looking at Vogel's procedure for preparing 2-pentene from 2-pentanol (sec-amylalcohol to "amylene") using 50% vol H2SO4
(equal volumes conc acid and water) and very mild heat. 2-butanol ought to require even more dilute acid and lower temperature than the pentanol.
both of the 2-butenes (cis and trans) boil close to 0 ( 0 and 3.7 C). I will have to look up 1-butene's bp. (It is -6.5 C)
I'd make t-Butyl hypochlorite to prepare the chlorohydrin.
If I butene is going to be a significant contaminant then we have our choice of seperating at the olefin stage, or at the chlorohydrin stage.
The book you took this from sounds like one of the Gattermann volumes in the forum library. I'll have a look.
Well, no, it is not Gattermann's "Laboratory Methods in Organic Chemistry" after all.
I am afraid that without any details as to temperature and dwell time, this procedure is not useful to me. Perhaps I can purchase a cylinder of pre
2-butene from Thai Industrial Gases and go from there. But, if there is more than a few percent of 1-butene present, then I am no better off than with
95% 3-chloro-2-butanone, so might as well buy that instead
[Edited on 30-12-2007 by Sauron]
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chemrox
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| Quote: | Originally posted by Sauron
The Canadian prep involves two kinds of unobtainium: trimethylborane (toxic, pyrophoric gas not commercially available) and diazomethane (toxic
explosive gas requiring special glassware an not amenable to scale-up). Another non-starter.
|
in case you want to try it:
btw- thanks for starting the most interesting thread in a few weeks or so...
[Edited on 29-12-2007 by chemrox]
Attachment: syn. organoboranes.pdf (551kB)
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Sauron
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Thanks. H.C.Brown's original procedure for trimethylborane is in Brauer's books (and in JACS). It uses bromomethane to prepare methylmagnesium bromide
and that is reacted in absolute n-butyl ether with BF3. In a variation almost as efficient, the BF3 is in the form of its etherate rather than a gas,
and Et2) is solvent.
The bottleneck is not particularly the Me3B but the diazoacetone, which requires diazomethane. Anyone want to work with diazomethane on a molar or
multi-molar scale? I'd have to want the product really really badly, and have no other options.
And there are other options.
But thanks.
The paper you provided gives two routes to Me3B, one through (MeO)3B and the other from BCl3. Iodomethane is the other reactant. I'll check Brauer
where I remember seeing a prep for trimethobyborane. Interesting.
But the diazomethane is the hassle. Vogel has a prep for Diazald (though of course he does not call it by its Aldrich reg.trademark). It is made from
tosyl chloride, dimethylamine and is no big deal (skin sensitizer though.) The problem with diazomethane is not making it, it is surviving afterwards.
------------------
I am still unable to find a sufficiently selective dehydration for 2-butanol; most selectivity so far is 9:1 2-butene over 1-butene.
In contract, chlorination of MEK with various reagents is said to be as high as 24 to 40:1 in favor of the 3-chloro-2-butanone over
1-chloro-2-butanone.
And commercial 3-chloro-2-butanone runs 95% (Acros) to 97+% (Aldrich/Fluka) which corresponds to selectivities of 19:1 to 40:1. The Acros product is
$30-something/100 g, the purer Aldrich is double that.
These are viable alternatives to playing chemical Russian roulette with diazomethane on a prep scale.
Another viable option is to purchase pure 2-butene in a cylinger and go from there.
Aldrich when they were still selling bottled gases, offered mixed 2-butenes at 99%, and same purities of cis-2-butene and trans-2-butene. I bet that
our local gas vendor TIG (Thai Industrial Gases) sells 2-butene (mixed cis and trans is fine for my purpose) in which case, all I need to do is whip
up some t-Butyl hypochlorite and away we go.
[Edited on 30-12-2007 by Sauron]
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Sauron
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I found an old paper in J.Chem.Soc. Transactions (1919, pp.1404-1410) which states that 2-butene (or as they called it, b-butylene) can be prepared
from n-butanol, rather than sec-butyl alcohol, and be free from isobutene and contain only small amounts of 1-propene (a-butylene).
The catalyst was "glacial phosphoric acid" on ignited pumice. Reaction was conducted through a 2 x 150 cm copper tube heated electrically. 280-400 C
which is heating tape country
This is a very happy encounter if I can replicate these results.
The author used the 2-butene to make MEK. Simply, he rehydrated the alkene to sec-butyl alcohol by absorbing it in sulfuric acid (diluted with water
to below 78% to avoid polymerization) and stirred this mix under autogeous pressure, simple as that. The 2-butanol he oxidized to MEK. Voila.
2-butanone from 1-butanol. Go figure.
I would instead take the 2-butene, react it with tert-butyl hypochlorite, and then oxidize the resulting 3-chloro-2-butanol to 3-chloro-2-butanone.
I seem to recall an Org.Syn. prep in which the 1,3-dichloro-2-propanol was oxidized by very conventional means (chromic/sulfuric acid I think) to the
1,3-dichloroacetone. Therefore I do not think the compound I wish to oxidize will be a problem as regards lability of the halogen.
I take "glacial phosphoric acid" to mean anhydrous H3PO4 (* SEE NOTE BELOW!)the preparation of which is detailed in Brauer. The author of the
J.Chem.Soc. paper says that catalyst on pumice support is active indefinitely, being occasionally recharged by burning a small piece of WP in a
current of air at the mouth of the reaction tube thus depositing phosphorus pentoxide into the catalyst.
To me this suggests that polyphosphoric acid ought to be well worth a try. PPA is after all just anhydrous H3PO4 with extra P4O10, effectively
>100% phosphoric acid. Right?
Anyway here is the paper. Please have a look, I'd appreciate comments about the dehydration of n-butanol to 2-butene selectively.] I have been getting
tired eyes reading more contemporary papers talking about Bronstead acid and Lewis acid sites on chi-alumina, niobium oxide, tungsten oxide, Mo/Zr
oxides, various exotic zeolites, etc. - none of which gave the selectivity I am after. This old work from 89 years gone before GCs, before MS, appears
to be just what the doctor ordered and eminently practicable.
--------------------
* Glacial phosphoric acid is apparently an ambiguous term. Some sources define it as I thought, anhydrous H3PO4. Most however say it is metaphosphoric
acid, and others hedge their bets and say it could be either. How annoying. I will have to delve into this more deeply.
[Edited on 31-12-2007 by Sauron]
Attachment: ct9191501404.pdf (413kB)
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