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Author: Subject: chloral hydrate synthesis
mantis
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Thanks!
I know this synthesis from lambdasyn, but I also read that a lot of people had big problems to syntheticize chloral hydrate. The reason was that they often get a unknown mix of chlorinated substances.
Punk
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Thanks for the warning before punk poisoned himself, punk will try the latter suggestions and report back in a few days or so.
Punk
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As far as chloral hydrate destroying the liver it cant be all that bad since doctors prescribe it.

Iodized table salt GC, fumes must have gone to the brain.
Punk
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What if a cell divider was used to keep the hydrogen out of the reaction? And what about adding a ph buffer to nutralize the sodium hydroxide that is produced?

Another thing is the chlorine produced from this electro setup doesnt smell potent like the lung burning gas created from acid/bleach maybe its not even strong enough to do the job. The electro chlorine smells weak like nearby pool.

[Edited on 5-3-2006 by Punk]
garage chemist
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Production of chloral hydrate by electrolysis is impossible.

Go to the pool shop and get some HCl and trichloroisocanuric acid or calcium hypochlorite. Then you'll be able to make some serious amounts of chlorine and actually have a chance for success.

Chloral hydrate isn't so bad for the liver, you're right.
But the byproducts in a nonprofessional synthesis are very much.

If you just want a sedative with the effects of chloral hydrate, consider making chlorobutanol (search, there's an excellent thread on this here). It's much easier to make a pure product with this, and it's even a bit more potent than chloral hydrate.
unionised
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"If you just want a sedative "
Drink the rum.
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Hmm, interested.

the way to -(OH)2 by trichloroacetaldehyde, i think a funny name. A hydrate can be too *H2O .
Important perhaps for other syntheses when ethanol is reacted with to the =O group and other chemicals to -CH(OH)2.

But how prepared the trichloroacetaldehyde, easy by the treatment of acetaldehyde with Cl2 or HCl, it would surely decompose by strong treatment or the endproduct is chloro or dichloroacetaldehyde.
Maybe is can prepared by trichloromethane and a other chemical or aldehyde and a slight acid.
I don´t know the method of the dehydration or oxidation of trichloroethanol walk fine when it threated with Na2Cr2O7 and H2SO4.

Sauron
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Doesn't Vogel have a prep for chloral? I'm sure I saw it in 3rd edition. I will go have a look.

Can't be worse than Smoothe's BS.

My idea of a chlorine generator is the classical conc HCl dripping onto permanganate (or MNO2) and you can calculate the amounts needed and therefore the reactor size. My modification is to employ a peristaltic pump to feed the acid at a steady controlled rate. Run the Cl2 which will contain some HCl and acid mist through the usual series of wash bottles as described in Vogel, and you have a really good supply of dry Cl2 for larger scale, lengthy chlorinations. The chlorine prep on Rhodium may not look it but they did get the ratios right if you compare to Vogel. (No not Smoothe's.)

Just a guess but I would say that the cooling at the start of chlorination of ethanol is to limit the oxidation to the aldehyde stage, else you make chloroacetic acid (and higher chlorinated acetic acids) instead of chloral. Then once you have achieved at least monochlorination and all ethanol has been oxidized as well, that's when the chlorination needs to be continued to room temperature and finally reflux.

I believe it is also possible to get at chloral from trichloroacetic acid by reduction. I will look into both these issues. I think I kept bumping into chloral preps a couple years ago when I was looking at unsym-dichloromethyl methyl ether.

Also I wonder whether UV would accelerate (catalyze) the chlorination of ethanol, this is after all a free radical chain isn't it? If so, then a radical initiator might also do same. UV being a pain in the butt when you are trying to hold the pot at o C.

As a reagent, chloral is interesting. As a drug of abuse it is way too harsh and toxic to contemplate. You will soon have the liver of a 75 year old alcoholic, there are dermatological complications associated with chloral addiction, and your breath will reek of pool cleaner.

The infamous Mickey Finn was administered in an alcoholic drink, to unsuspecting drunks. A relatively sober victim would notice the stench of chlorine coming off his cocktain and wonder how the bleach got in there. The ethanol and the chloral hydrtate of course potentiate each other and even if the bartender got the dosage right, if the victim is drunk enough he may very well wake up dead. I used to know a club owner on Bourbon Street (New Orleans) who did a stretych in prison for mickey finning a customer, who promptly expired. Bad show, that.
Sauron
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Well, unfortunately Vogel does not give a detailed procedure for chloral, merely alludes to is preparation (on pp 297-298) as proceeding like a haloform reaction.

He does describe a few reactions of chloral hydrate and give some physical constants.

Merck (12th) is a little more helpful. Monograph 9755 Trichloroacetaldehyde. Apart from half a dozen citations regarding chlorination of thanol which everyone appears to be familiar with, there's also a US patent on preparation from hypochlorous acid and trichloroethylene which may well bear scrutiny.

US 2,759,978 (1956)

which I will now go fetch and attach.

[Edited on 3-3-2007 by Sauron]

Attachment: 2759978[1].pdf (166kB)

Sauron
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Preferred conditions are >3 M HOCl (aq) and dry-ice/acetone temperatures, yield 30%

Still, interesting. They require removing elemental chlorine from the hypochlorous acid by blowing air through.

Worth a try?

Cf. Brauer, pp 308-309 procedure 1 for 25% HOCL (aq) from chlorine water (Cl2.6H20) and HgO. Isolation by vacuum distillation into a cold trap. This must be stored under -20 C and I suppose, used directly is best. See also p.299, prepn of Cl2O (hypochlorous anhydride) from HgO and Cl2. This is stored in CCl4. Addition of water gives HOCl.
(p309 procedure 2).

If I did the sums right in my head, a 25% soln of hypochlorous acid is c.5 M and this prep calls for slightly more than 3 M (like, 3.1 M). So, the required concentration is about 15-16%.

Note that the mercury chlorides produced can be conserved/recycled.

Also, there is a review specifically on chloral chemistry:

Chemistry of chloral

Chem. Rev. 75,3, 259 (1975)

which I have requested from References. There's a section on preparations.

[Edited on 3-3-2007 by Sauron]

[Edited on 3-3-2007 by Sauron]
Sauron
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Ah! Let me gloat. According to this 1975 Chem.Rev. piece, if the ethanol chlorination is begun at 20 C rather than 0 C you obtain not chloral but trichloroacetic acid.

So, the temperature control is specifically to limit oxidation to the aldehyde stage.

Per Org.Syn., chloral hydrate can be reduced (with Al(OEt)3 in EtOH) to trichloroethanol. So I repeat my assertion above in the thread, that trichloroacetic acid ought to be reducible to chloral (trichloroacetaldehyde). I believe we have selective reducing agents that knock carboxylic acids back to aldehydes and stop there and are inert to alpha-halogens.

The Chem.Rev article states that direct chlorination by the element, of ethanol is th best method of preparing chloral. So far I only have the first page but the section on preparations starts there and concludes on next page. It says that this process, using absolute ethanol but with traces of water, and basically unimproved since Leibig in 1832, gives 70-80% yields under best conditions. This is a whole lot better than 30% from tric and HOCl. Unless one has a whole lot of tric to dispose of.

Bad news for the druggies: there's a mutagenicity study referenced in Merck.

Good news for the rest of us: chloral is a versatile reagent and intermediate. It formerly was of great industrial importance fpr manufacture of DDT. See Org.Syn. for about a dozen preps in which it figures.

Also Org.Syn has a prep of bromal, starting from paraldehyde and Br2, with a catalytic amount of sulfur. So, a small amount of S or SCl2 might be of value in the chlorination of ethanol.

And I still suspect that UV (or bright sunlight) would accelerate the chlorination, just as it does for chlorination of acetic acid. Clearly the same mechanism is at work. As long as temperature control is not compomised I'd think there's no downside.
Sauron
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OK, thanks to @kmno$I have the Chem.Rev. piece and there's a gold mine in there. Anyone who is interested can now go retrieve it from page 15 in References. This flatly states that UV does not assist this chlorination; and that 100 C at the endgame is as important as ) C at the start. In fact by stopping the increase in temperature being input at 30 C only monochloroacetaldehyde is obtained and at 60 C only dichloroacetaldehyde. An electrochemical process is succesful and is detailed. It is possible to use acetaldehyde as substrate rather than ethanol but given the cost relative to ethanol this does not seem worthwhile. @gc, I trust this will be useful for you. Eclectic International Hazard Posts: 899 Registered: 14-11-2004 Member Is Offline Mood: Obsessive AFAIK, this was a fairly routine prep in organic chemistry college lab courses in the early part of the 20th century (along with barbitol). This is before it was assumed that anyone who could be a drug fiend, would be. Check organic lab texts published between 1910 and 1935. S.C. Wack bibliomaster Posts: 2419 Registered: 7-5-2004 Location: Cornworld, Central USA Member Is Offline Mood: Enhanced The only one that I found it in was Systematic Organic Chemistry, which was the source of the 1.4 figure that I posted earlier. Probably unsuitable for students due to the long time it takes to fully chlorinate. Sauron International Hazard Posts: 5351 Registered: 22-12-2006 Location: Barad-Dur, Mordor Member Is Offline Mood: metastable I remember seeing it in a lab manual for med tech undergrads taking a lab course in the 50s. No telling how far back it dated, and I no longer have it. That prep used ethanol and hypochlorite, rather than chlorine, so it likely gave a bunch of side products including chloroform. Chloral and chloral hydrate show up in Org.Syn. as regants but without any preparative details for making them. I'm not sure what that suggests. The stuff remained of industrial important till DDT was banned. It is still of some importance as a useful and versatile reagent (see review referenced above.) ------------ When faced with a chlorination or similar bi-phase rxn I like a tall form reaction vessel when possible. I found that locally I can buy 2 liter graduated cylinders with 45/40 standard taper joints at top, normally for PTFE stoppers. I replace these with an adapter to 29/42 ad add the gas inlet/outlet assy from a standard Corning gas washing bottle 500 ml size which has a 29/42 joint. To this I connect a tube with a fritted glass bubbler of medium porosity either permenently or by a section of an inert tubing. The length is such that the tip of the fritted section leaves just enough room at the bottom for a magnetic teflon spinbar. The advantage is that the gas (Cl2 or whatever is obliged to pass through a tall column of liquid. If a lot of gas still makes it out of the reaction mixture, connecting a second cylinder and even a third inline will maximize the utilization of the gas - better than having it go to waste in a scrubber. The cylinders can be inside a larger container for cooling, or can be heated by a bath, or by a wraparound mantle or heating tape, perferably with a thermocouple controller. They are Pyrex so I don't think a 100-120 C heat source is going to bother them. A setup like this is more efficient than a RB flask and is essentually off the shelf with just a wee bit of integration to accomplish. The 2L size can easily accomodate a stirred 1500 ml reaction charge. A Claisen adaper could be interposed for a reflux condenser to prevent escape of acetaldehyde in the early stages. [Edited on 21-9-2007 by Sauron] Attachment: 2669585[1].zip (286kB) This file has been downloaded 820 times Sandmeyer International Hazard Posts: 784 Registered: 9-1-2005 Location: Internet Member Is Offline Mood: abbastanza bene Chloral is a very useful chemical for isatin synthesis, to make it a controlled substance once again shows their ignorance in the matter of things. But nothing surprises me since the ban of tryptophan in favour of benzos and$\$RIs...

[Edited on 10-3-2007 by Sandmeyer]

Sauron
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It's not so much Big Brother as Big Nanny and if youthink I'm wrong just watch Hillary run. She personifies Big Nanny. Mary Poppins with a law degree and a nasty agenda.

[Edited on 21-9-2007 by Sauron]
guy
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I am playing around with making chloral hydrate.

I am adding NaDCCA to a solution of Ethanol and 29% HCl. When I did this reaction (outside) late in the evening, I noticed it proceeded fairly slowly and the green color lasted for about 20 minutes before it faded and the reaction temperature did not change that much.

Today I did it in the afternoon with strong sunlight and the green color of chlorine was removed almost instantaneously and the reaction mixture got quite hot. This indicates that Cl2 is being broken into radicals and reacting with the ethanol or acetaldehyde. Cl2 breaks up at 493 nm so this seems quite plausible.
Sauron
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Yes you probably oxidized ethanol to acetaldehyde which promptly underwent the haloform reaction, which gets quite hot. You made chloroform not chloral.

That is what happens if you do not keep this reaction (targeting chloral hydrate) cold in the first stage.

[Edited on 21-9-2007 by Sauron]
chemrox
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I think you've got water in the mixture. Also, until you get a condenser (I'm amazed and impressed you've done all these other things without one), rig up a reflux with glass pot and lid inverted with ice on top taking care to keep the melted ice from getting into the mix. or use a long neck flask and funnel .. several ways to do this just think. BTW, how do you get the URL above? It took me to lambdasyn.com/ and no further.

Have you tried to find the original procedure? All the rhodium syns I've seen were excerpted from papers, patents or books.

You might look here:

Winter field, K. - practical course that pharmaceutical chemistry, 6 organic präparativen. Edition, Steinkopff Verl., 1965 • Schwabe and Paffrath - medicine regulation report, Stuttgart: Fischer 1995 • Kuschinsky, Lüllmann, Mohr - short text book of the pharmacology and toxicology, 13. Edition, Stuttgart: Thieme 1993

I got these from a lambdasyn translation ala Google so don't blame the refs on me but should be possible to track down.

[Edited on 20-9-2007 by chemrox]
guy
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 Quote: Originally posted by Sauron Yes you probably oxidized ethanol to acetaldehyde which promptly underwent the haloform reaction, which gets quite hot. You made chloroform not chloral. That is what happens if you do not keep this reaction (targeting chloral hydrate) cold in the first stage. [Edited on 21-9-2007 by Sauron]

Its possible to get haloform reaction in highly acidic conditions??
Sauron
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Ah, probably not.
chemrox
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I think he's half done and has wet chloral in the pot
Sauron
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The zip file I uploaded above, apparently has become corrupted.

It contained two US patents.

One is the file name so I reacquired it from freepatentsonline.com. It is attached. I am looking for the other patent file, or number so I can get it again too.

[Edited on 21-9-2007 by Sauron]

Attachment: 2669585.pdf (150kB)

Sauron
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And here are two more patents and a Chemical Reviews monograph on chloral, I found these in a folder on CD along with the other patent, so I am confident that one of these two was the second patent in the corrupted zip file..

I assembled these as a single pdf, rather than a zip for obvious reasons!

[Edited on 21-9-2007 by Sauron]

Attachment: chloral.pdf (1.4MB)