Aldehydes to bis(halo-alkyl) ethers

[MrSamosa]

This is a remarkably simple procedure I came across yesterday. So simple, in fact, that I could barely believe it! While going through an MSDS for my newly bought 37% Formaldehyde :) (I bought it from the Pet Store, if you're interested...sold in the Fish section as an anti-fungal for fish infections), I came across in the "Incompatabilities" section a passage saying, "Reaction with Hydrochloric Acid forms bis(chloromethyl) ether, an OSHA regulated Carcinogen."

If you have gone through War Gases, you will recall that a potential war gas was bis(chloro-ethyl) ether, and you would also recall that it is just as poisonous as Mustard Gas, but lacks the skin action due to its inability to penetrate the skin.

Now, this is where the weaponization comes in... Imagine this: React Acetaldehyde with Hydrochloric Acid to form bis(chloroethyl) ether, then dissolve that in DMSO (if possible, I have to check its solubilities :( ). Theoretically, you should have something very close to Mustard!

If it is intended simply as an inhalant, reacting said Aldehyde with Hydriodic Acid would be preferable, because the Iodine in place of the Chlorine atom makes the compound more poisonous.

I read of another reaction, done by some guy named Treitschke, who formed the bis(chloromethyl) ether using Paraformaldehyde and dried HCl Gas. But I could not find very in-depth information of his process, simply a brief mention of it :( .

I will be trying this with my formaldehyde over the weekend, and I will hopefully be able to report back myh results on monday.

btw- sorry for the series of new, and somewhat half-way researched posts. But, due to problems at home, I only have half an hour to do all my computer use at school! As such, I still come up with a series of ideas during my "down-time," but I do not have time to fully research them before posting. If you've noticed, I barely respond to any existing threads, although I'd really like to. So I sincerely apologize for my "flood" of new threads, but I hope their topics are worthy of a new thread :) .

[Einsteinium]

Actually the reaction between formaldehyde and HCl to produce chloroethers is very specific to formaldehyde. Higher aldehydes like acetaldehydes reacts through enols intermediates and you ends up with aldols. I uploaded a picture of both mechanism on the FTP (AldehydetoMustard.jpg) to show how it proceeds. Also, the bromo and iodo counterparts are easier to make, more toxic but less volatile and less cheap to make thus reducing their utility as war "gas" (more like vapours than gas). Good luck with formaldehyde/HCl if you ever try it.

[Edit: I should have mentionned that with acetaldehyde, the reaction with HCl dosen't stop at the aldol product, it condense further to paraldehyde, an illegal hypnotic drug <img border="0" title="" alt="[Wink]" src="wink.gif" /> ]

<small>[ April 05, 2003, 12:31 AM: Message edited by: Einsteinium ]</small>

[Mr Cool]

Aha, this explains why (CH₂O)_n's MSDS says that it absolutely must not be stored with conc. HCl... I was wondering why that was!
Now, time to mix some (CH₂O)_n with some conc. HCl :D .

[MrSamosa]

After going through Organic Synthesis Database, I found a very simple procedure for producing bis(holomethyl) ether. It proceeds as follows:

1. A mixture of Concentrated Sulfuric Acid and Paraformaldehyde (Or Formaldehyde; either way works just fine) are placed in an ice bath.

2. Slowly, Ammonium Chloride is added, while taking care to avoid the loss of HCl.

3. After a few hours (IIRC, 5 hours), the reaction is finished and the layer of bis(chloromethyl) ether is separated.

4. The product is then purified by neutralizing with Sodium Hydroxide and drying under a vacuum.

Since not everybody has Ammonium Chloride on hand, I imagine that Sodium Chloride could be substituted with the yields relatively unaffected. NaCl + H2SO4 has never failed before! :D

Now, here is the problem... My Formaldehyde is only 37%. 50% of this is water. Water is bad for bis(chloromethyl) ether, because it eventually breaks it down. So if possible, I would like to have this take place in as dry an environment as possible. Would it be possible to get rid of the water from the Formaldehyde solution without the use of distillation?

I was thinking that I could simply use an excess of H2SO4 in the Sulfuric/Formaldehyde mix, but I'm not sure how successful this would be. I always like to have a second opinion on my ideas, because my chemicals are expensive and difficult for me to come by :( .

I don't think I will actually be doing this anyway though... I am too afraid of getting lung cancer.

[Einsteinium]

I believe you would need quite an excess of sulfuric acid to achieve that, unfortunatly at theses concentrations it will simply cleave the ether leaving you with chloroalkylsulfates&Co.

But... you could simply polymerize your formalin into paraformaldehyde. I don't have a clean lab procedure for this, but here's what Dr. Vogel's says about it:
"By evaporating an aqueous solution [of formaldehyde] paraformaldehyde or paraform [CH₂O]_n, an amourphous white solid, is produced ; it is insoluble in most solvents"

It's from A.I. Vogel, A textbook of practical organic chemistry p.319 - Excellent reading, an old organic chem bible, you can get it here:
<a href="http://www.rhodium.ws/chemistry/vogel3.html" target="_blank">http://www.rhodium.ws/chemistry/vogel3.html</a>
(thanks Polverone!)

He also states that if you evaporate a 60% formaldehyde solution with sulfuric acid as a catalyst, it will polymerize to trioxane, the simpliest "crown ether", quite stable if my memory serves me well but I'm not certain. Overall it seems simple; ventilation, evaporation and filtration. I might try it on a very small scale using Cu/O₂ and methanol to produce some formalin since I have none on my hand at the time then post the results back here. BTW bis(chloromethyl)ether isn't of very high toxicity (I mean, for use as a chemical warfare agent), it find its use in many organic reactions as it introduces ether bridges cleanly, a friend of mine tells me that he did such a reaction once and wasn't particularly freaked out by the coumpound.

<small>[ April 09, 2003, 07:16 PM: Message edited by: Einsteinium ]</small>

[nbk2000]

30 grams of paraformaldehyde is mixed with 80 grams of concentrated sulphuric acid (98%) in a 300 mL flask. The mix is cooled in ice and continuously stirred while 155 grams of sodium bromide is added in small portions. Upon refluxing for 10 minutes, the para dissolves and an oily layer of dibromomethyl ether floats to the top. It is seperated and purifed by distillation.

It's a colorless liquid of very high density (2.2) and high volatility. Insoluble in water, it dissolved easily in ether and acetone.

By heating at 140 &deg; C, with more para and water, methyl bromide and formic acid is formed.

It's slightly more toxic than phosgene.

Para is available as a chemical toilet sanitizer. Cost $8/pound

Sulphuric acid as drain opener. Cost $15/gallon

Sodium bromide as spa chemical. Cost $2/2 oz. packet.

Given how everything needed to make it is readily available, it'd be a good candidate for use as a weapon for use against a single person, or small group of people. If you're willing to lose some product, and aren't concerned about high purity, you could make it in a wine bottle and siphon off the top layer for immediate use, skipping the need for reflux and distillation. Not too difficult for making something more toxic than phosgene, the gas that killed 80% of the soldiers who died from CW use in the Great War.

[megalomania]

Dichlorodiethyl ether has been used in the past as a chemical weapon, in WWI naturally, but it is not very useful. From a military perspective it doesn’t really do anything to you, no painful blisters, no choking gasping masses, no blinded victims to speak of. It is just lethal. It is rather like cyanide because you just up and die one day. This would make a more effective terrorist weapon as large groups of people could be exposed to the chemical for long periods of time since they would not freak. I suppose that would be a terror-less weapon. Consider the proposed system of masking the chemical weapon with pleasant odors and you have a candidate (to be used only on communist invaders of course).

They even used this stuff as an anesthetic in the long long ago, of course that was before they cared about peoples lives…

Dichlorodiethyl ether must be procured the old fashioned way, via a condensation reaction with ethylene chlorohydrin and sulfuric acid just like diethyl ether is made. I have been doing a lot of searching of the Internet for this information, but this is all I could come up with. If anyone has ready access to Faith, Keys, and Clark Industrial Chemicals it should say much the same. I don’t currently have a copy, so if someone would be so kind as to check…

I am hoping to use dichlorodiethyl ether as an intermediate in the preparation of THF prepared by all OTC sources. The same ethylene chlorohydrin that makes the ether can make ethylene oxide, which should extend the carbon chain by two via a Grignard reaction. The resulting dihydroxydibutyl ether can be broken forming two equivalents of 1,4-butanediol, which is readily cyclized with another condensation reaction forming THF.

I should mention I will be attempting to get the ethylene chlorohydrin by electrolyzing ethyl alcohol in salt solution. I don’t hold much hope that yields will be great this way, but this method is easier than other means of preparing ethylene chlorhydrin, from antifreeze for example. Being a cheap bastard with utilities included the alcohol route seems most economical.

[Einsteinium]

Wouldn't a simple radicalar chlorination (light-catalyzed, preferably) of diethylether vapours be simpler than the chlorohydrin route? The radicalar chlorination product wouldn't be as pure since much chlorination will happens at the carbon adjacent to the oxygen instead of the terminal carbon but I guess theses isomers would be quite toxic as well.

[nbk2000]

I assume dichlorodiethyl ether is another name for dichlorethyl ether?

[Mr Cool]

Dichlorodiethyl ether refers to CH₂Cl-CH₂-O-CH₂-CH₂Cl, which would be the same as di(chloroethyl) ether.
Dichloroethyl ether could be this, or CHCl₂-CH₂-O-CH₂-CHCl₂ (+ isomers).
That's what I reckon.

[megalomania]

Light catalyzed addition of chlorine to ether will work, and it more or less favors the formation of dichlorodiethyl ether. There will naturally be byproducts if the reaction runs long enough, which must be purified. I suppose it is 6 of one, half a dozen of the other between chlorination and epoxidation. I have other uses for both chlorhydrin and ethylene oxide, so I favor that route because I have them on hand. Epoxidation leads to a higher yield and purer product if you have the precursors. I think it is favored industrially because of this.

The chlorination route may perhaps appeal to a broader audience because of the more simplistic OTC nature of the reactants. Ether is easy enough to make in large quantities, and chlorine generating compounds can be had by all. I think I will have to try this just to satisfy my curiosity.

I suppose I should call the product 2,2'-dichlorodiethylether, although by convention just saying dichloroether is assumed to be the same thing.

[simply RED]

http://ntp-db.niehs.nih.gov/NTP_Reports/NTP_Chem_HS_HTML/NTP_Chem1/Radian111-44-4.html
It seems not to have the toxicity of S and N mustards, but the formula looks quite like s mustard, only the S is substituted with O.
It must be irritant.

[MrSamosa]

Symptoms of exposure to this compound include irritation of the eyes, skin,
eyes, stomach and respiratory tract; coughing, nausea, retching, lung lesions,
pulmonary edema, dermatitis, conjunctivitis, lachrymation and liver and kidney
injuries.

Save for the skin necrosis and blistering, notice how similar the effects of 2,2'-Dichloroethyl Ether are against the body. The big difference, it would seem, is that their is less of a delay between exposure and onset of symptoms. I believe for Mustard, the delay is between 1-3 hours for the symptoms to appear, and blistering begins to appear about a day after exposure.

In terms of use as a weapon, 2,2'-Dichloroethyl Ether seems to have more use as a solvent for more potent agents than as a weapon in itself.

However, if I should say so again, 2,2'-Dichloroethyl Ether seems to have great potential use should a way be found for it to penetrate the epidermis. However, I cannot say this for sure, because I cannot find any information regarding its action against cells. Mustard causes skin necrosis by interfering with intra-cellular chemical exchanges, and I can't find any information regarding 2,2'-Dichloroethyl Ether doing this. I am just assuming it does, because of the similar structure :) . But, so it goes, to assume is to make an ass of u and me ;) .

[nbk2000]

If I remember correctly, the reason DDE doesn't have the same effect as mustard is because it's not lipid soluble, meaning that it's not absorbed into the fatty molecules of the skin, thus unable to breach the skin to effect the cellular structure of the skin in any meaningful way.

If it was able to get through the outer layers of the epidermis, then it would be absorbed into the watery parts of the skin tissue, where it would cause damage.

Combining an orticant (skin/pore inflammatory) like CN/CX, or perhaps mechanical abrasives like fiberglass dust, would be one possible means of getting the agent through the skin into the deeper tissues. I don't know if the MW is within the range for DMSO to carry it through.

The skin, while seemingly porous, is in fact more like a seive. It can block molecules above a certain size range, while letting smaller ones through. It's similiar to the way that the porous protective clothing of NATO is vulnerable to agents of certain particle size.

If the particles are very small, their brownian behavior makes them unable to penetrate, lacking sufficient mass/energy to act like dust, being more like gases, thus too "volatile" to penetrate.

Whereas more massive particles are too big to fit through the pores.

So the particles have to be "just right" to have sufficient mass to penetrate, while still being small enough to fit through the pores.

Then there's the furthur complication of water/fat solubilities, alkyation clevage, yada yada...all the stuff that the Big Boys have spent untold billions and years to research.

For all that, Mustard gas is still the King of the war gases, since nerve agent vapors are protected against by simple masks, whereas mustard vapor requires full body protection. OPA's are complicated to make, compared to mustard, which (as anyone who read my article on it) can be made from anti-freeze in buckets and such.

DDE should best be thought of as a lung injurant, rather than a vesicant, since that'd be it's primary kill mode.

Also, there's the time/exposure ratio to realize. Unlike HCN, which the body can detoxify (below a certain threshold) for an indefinate period of time, exposure to other chemicals (like DDE) cause cumulative damage. The lower the concentration, the longer the exposure required to effect a kill, but the greater the probability of doing so since the target would be fatally exposed without having experienced any irritation that could give warning.

Thus, for DDE, you'd either want to use sudden mega-dosing to give lethal exposure in a few seconds (directly being sprayed upon/explosive dispersal in confined space), or a very low level exposure over the period of many hours so that the target never notices (gassed while sleeping).