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woelen
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Toxicity of phosgene
Many times, people on sciencemadness are talking about the toxicity of phosgene and experiments (or synths) in which this gas is involved are avoided
like the plague. On the other hand, people are comfortably using chlorine (e.g. leading it through all kinds of liquids). For some members, working
with e.g. SOCl2 also is an option.
What makes phosgene so special, compared to other toxic/corrosive substances. IIRC it quickly hydrolyses to CO2 and HCl in water, so wouldn't it be of
the same level of toxicity as gaseous HCl? SOCl2 for instance is as toxic as HCl and SO2, because that are the gases, formed in contact with water
vapor, so I would expect COCl2 to be as toxic as HCl (CO2 is not toxic).
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Sauron
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That's easy. Phosgene is insidious, chlorine is not. If chlorine is present in harmful concentrations you will know it and you will not be able to
force yourself to remain in its presence even if you wanted to.
Phosgene is not reliably detectable by the nose (reported limit of detection 4 mg/m3 air) and is non-irritating in lethal concentrations, its action
is delayed, so you may be unaware that the hood is not working properly or that you are being exposed. The onset of pulmonary edema is 30-40 minutes
away, meanwhile you feel just fine.
It is possible to prepare test paper that will indicate the presence of phosgene and to place strips of such paper around the hood periphery.
Commercial phosgene detectors use the same test paper and color change. A method is described in Org.Syn. in one of the preps utilizing phosgene.
Several more are described in Sartori. Unfortunately in several instances these test papers are either not very specific (same color change is brought
about by HCl or Cl2 or sunlight) or else the test paper is short lived, or must be moistened with 50% alcohol to work. In short, this does not appear
to be a detection system one would care to bet his lungs on.
The insidiousness of phosgene is precisely why it was preferred as a war gas.
For these reasons phosgene if used at all, should be used in a good hood and with the worker wearing a SCBA.
BETTER - if prep calls for phosgene, use diphosgene instead, much less volatile liquid. Less reactive though. STILL BETTER - use solid nonvolatile
triphosgene, although it is less reactive than diphosgene.
The prep of diphosgene is in Org.Syn. and is the UV catalyzed chlorination of methyl chloroformate. That ester is best prepared by chlorination of
methyl formate in the cold and without UV irradiation (or bright light.) It can also be prepared by phosgenation of methanol but we are trying to
avoid phosgene, yes, like the plague.
That of triphosgenbe, an article from Angew.Chem. Intl Ed. by Eckert, has been posted by me previously. It is the UV catalyzed chlorination of
dimethyl carbonate in CCl4. Very high yield and easy workup.
You cannot judge the toxicity of anything by either its precursors or its degradation products.
Phosgene is formed from CO and Cl2. It is far more toxic than either.
SO2Cl2 is formed from SO2 and Cl2 and is far more aggressive than either.
[Edited on 10-8-2008 by Sauron]
[Edited on 10-8-2008 by Sauron]
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ScienceSquirrel
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During the First World War there were cases in which men inhaled phosgene in small doses over a period of time.
They would go to bed feeling fine, hours later they would get up, start coughing and the blisters in their lungs would burst and they would drown in
their own tissue fluid.
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Sauron
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As I said. Insidious.
Very very few of the industrial chemicals tested or used as war gases have this characteristic. Most are immediately irritating and so relatively
ineffective because troops will don masks.
Read Sartori.
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JohnWW
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| Quote: | | Originally posted by woelenWhat makes phosgene so special, compared to other toxic/corrosive substances. IIRC it quickly hydrolyses to CO2
and HCl in water, so wouldn't it be of the same level of toxicity as gaseous HCl? SOCl2 for instance is as toxic as HCl and SO2, because that are the
gases, formed in contact with water vapor, so I would expect COCl2 to be as toxic as HCl (CO2 is not toxic). |
I think COCl2 is much more likely to hydrolyse (except in the presence of a good supply of oxygen and an adsorbing metallic catalyst) to CO + HCl, not
CO2. This would certainly account for toxicity on the same level as CO. By comparison, CO2 and HCl can kill, in much larger concentrations, only by
suffocation and acidification.
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ScienceSquirrel
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The rate of hydrolysis of phosgene is a lot slower than thionyl chloride or acetyl chloride.
They both fume in warm moist air, phosgene does not.
Most acid chlorides and chlorine have a rapid choking effect, phosgene does not.
Hence it is readily inhaled deep in to the lungs without immediate ill effect.
Phosgene casualties do not die of carbon monoxide poisoning. They die of pulmonary edema.
There was a case many years ago of a woman who was employed as a cleaner. She was given a bottle of carbon tetrachloride and set the task of removing
some stains. The woman was a very heavy smoker and as she worked she inhaled the carbon tetrachoride vapour through her cigarette where it pyrolysed
to phosgene. She went home feeling fine, on getting out of bed the following day the blisters burst and she died in minutes.
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woelen
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Sauron, I understand the issue about the insidiousness. Good to know that. Not that I had plans to do something with phosgene, but I just wondered.
JohnWW, I do not think that you are right. Hydrolysis is not a redox reaction and in your case, the carbon is reduced to the +2 oxidation state.
Conversion to CO and HCl only could be possible if something else is oxidized, but there is nothing to be oxidized, so no CO is formed.
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len1
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Ive yet to hear of anyone harmed by talking about phosgene. Its a perfectly safe compound for 95% or so of posts that never get beyond that here
[Edited on 10-8-2008 by len1]
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JohnWW
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Woelen: The C-Cl bond in COCl2 is more easily broken than a C-O bond. Also, in CO, the C resonates between being tetravalent as a carbanion (by far
the more favored canonical form, with the O as a tetravalent oxonium, there being three covalent bonds and an ionic bond) and being divalent as a
diradical (which is the far more chemically active canonical form, enabling CO to bond via the C atom to the Fe(III) in hemoglobin).
Besides, volatile chlorocarbon and bromocarbon compounds, including the likes of CCl4, CHCl3, CH2Cl2, CH3Cl, (CCl3)2O, CH3CCl3, etc., as well as
COCl2, are well-known as liver toxins, which would add to the toxicity of any COCl2 that is not hydrolysed.
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ScienceSquirrel
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| Quote: | Originally posted by len1
Ive yet to hear of anyone harmed by talking about phosgene. Its a perfectly safe compound for 95% or so of posts that never get beyond that here
[Edited on 10-8-2008 by len1] |
That about sums it up.
Out of the thousands of members on here there are only hundreds of regular posters and only a few dozen of them carry out practical chemistry on a
regular basis.
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Sauron
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I believe the thread author started off mentioning how we shun phosgene like the plague. Not everyone who actually gets some wet lab work done is
inclined to photograph the procedure and post it here.
Besides, about 98% of the time, setups are mundane, flask contents are water white, and there really isn't anything pictorially very interesting going
on.
As regards phosgene, the important thing to remember is: at home, just say no way. Even if you have a hood and a SCBA and a scrubber and a phosgene
detection system, have a care for your wife, your kids, your pets, and your neighbors.
Besides, you don't need phosgene to carry out phosgenation. Take the time to make some triphosgene (stable, solid, essentially nonvolatile phosgene
replacement.)
There's an Illustrated Guide suggestion for you, len1. Hexachlorodimethyl carbonate.
[Edited on 10-8-2008 by Sauron]
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len1
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Yes thanks, Ive already got that on.
What you get out of doing experiments is actually intimate knowledge of what youre talking about. Its a bit like watching softball on TV and imagining
oneself an expert. Theres a lot more to it than pictures.
As opposed to all these boasters with thousands of posts of 'Im going to do this and that' but than not one of 'Ive done it here are the results' -
b.....it
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Sauron
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Not everyone here is a lens-louse, len1. Your disdain for your fellow members is unbecoming. You are not a performer, and they are not your captive
audience. Feed them a diet of that sort of bile and they will turn on you.
Which is the real len1, they will ask? The dedicated pedagogue who selflessly leads by example? Or the sneering, arrogant prig who is so clearly
contemptuous of all who do not emulate his shining self?
In case you did not notice, the thread topic is TOXICITY OF PHOSGENE. Would you propose an Illustrated Guide to Pulmonary Edema? A mini-WWI
re-enactment? Come on, show us all why and how we should NOT make phosgene at home and drown in our own body fluids!
Some things are best left unreduced to experiment, and this is one of them.
[Edited on 10-8-2008 by Sauron]
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Pyrovus
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The other danger of phosgene, in addition to its hydrolysis, is the fact that it is also a very strong acylating agent. The carbon centre is strongly
electrophilic, and chloride is a very good leaving group, meaning that phosgene will readily add to any nucleophilic organic molecules (such as the
bases in DNA). Not only will this lead to cell death in the short term, but in the long run you also have to worry about cancer. Thus, the toxicity of
phosgene is much more akin to that of mustard gas or dimethyl sulphate, than of chlorine or HCl.
Never accept that which can be changed.
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BromicAcid
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| Quote: | Originally posted by Sauron
Phosgene is not reliably detectable by the nose (reported limit of detection 4 mg/m3 air) and is non-irritating in lethal concentrations, its action
is delayed, so you may be unaware that the hood is not working properly or that you are being exposed. |
Commercial phosgene detectors alarm at 0.1 ppm and 0.2 ppm. 0.1 ppm is the OSHA 8 hour exposure limit and at even this low of a level phosgene does
have an odor so long as you know what it smells like (and it smells very faintly sweet at this level). At 0.2 ppm the odor is just as faint, this is
the upper limit to what a person can work at for a short period of time (15 minutes). At 2.0 ppm phosgene has a strong odor, and is in the IDLH (Check out the information at the CDC website for detailed info)). Point being that although you can smell it, to be able to quantify it using
your olfactory senses is folly, and you will likely end up getting yourself seriously injured.
| Quote: | | It is possible to prepare test paper that will indicate the presence of phosgene and to place strips of such paper around the hood periphery.
Commercial phosgene detectors use the same test paper and color change. |
I've seen the paper phosgene detectors in operation. They use a roll of ticker tape that travels through the machine and measures the phosgene at
intervals, they work very good for high concentrations. The FID style personal detectors are much better though, they have a fast response time but a
long relaxation time (once they go off, even after moving away from the source they will continue to alarm for some time). They are small and
somewhat affordable. But their detection limits max out at 2.0 ppm because they are for saving lives and not just measuring phosgene concentrations.
Also of note are the phosgene badges which are available. They are stored in a refrigerator and are one time use. You put them on at the beginning
of your shift and they change color slowly during the shift if you get phosgene exposure. Then at the end of your shift you compare them to the
standard to see if you stayed under 0.1 ppm for the day as a weighted average. Problem is they have a very slow response time and even when held in a
stream of phosgene they are slow to change so they are no help of you are trying to save yourself, only if you are trying to meet OSHA requirements.
As Sauron said, and everyone else, phosgene is insidious because its lethal effects are not known and can be delayed for more than 24 hours.
Diphosgene and triphosgene are somewhat better but under most effective reaction conditions they do break down to form phosgene and can also pose a
hazard for workup for this reason.
SCBA works well for handling phosgene but don't overlook supplied air, providing you can set your intake in a safe place.
Note that scrubbing effluent with caustic has to be done in an efficient column at high pH ~14. Phosgene is somewhat hydrophobic, the neutralization
is not as instantaneous as some of us would like to believe. Ammonia solutions make much better scrubbers because the nucleophilic attack on the
phosgene is much faster to form urea and ammonium chloride.
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Sauron
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All good sound advice.
My advocacy os triphosgene and diphosgene as replacements for phosgene, take second place to my preference to avoid phosgenation entrely whenever
possible.
For an example see the current thread on ethyl centralite. Nothat one is a five finger exercise, I have no particular use for centralite.
More important to me are various peptide reagents for protecting groups, such as benzyl chloroformate (Z reagent), Boc2O and Boc-ON. The Z reagent is
now virtually unobtainable. Boc2O (Boc-anhydride) has a short shelf life and turns into expensive tert-butanol. Boc-ON is stable but expensive.
Everyone of these requires a phosgenation step. (See Org.Syn.) So, I'd go with diphosgene or triphosgene and take appropriate measures in workup.
But if at all possible, I'd go a long way round to avoid phosgenation.
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Klute
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Can't benzyl chloroformate be prepared in-situ from benzyl chloride and carbon monoxide? Granted, hardly a safe substitution, but I recall seeing this
at several occasions.
Why is benzyl chloroformate unobtainable? Does it release phsogene? I'm not much of a peptide chemist myself..
\"You can battle with a demon, you can embrace a demon; what the hell can you do with a fucking spiritual computer?\"
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woelen
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Is there a possibility that experiments with oxalyl chloride produce phosgene? All the things, described above, look very scary and not something I
would like to handle (I do not have the suitable equipment, my protection is working outside when it is not raining). I, however, only use quantities
of 0.1 or 0.2 ml of oxalyl chloride, so not much phosgene can be formed in my experiments (if any), but if there are reactions with oxalyl chloride,
which can release phosgene, then I certainly would like to know. I do not heat my oxalyl chloride, I just use it in dilute solutions in DCM or
ethylacetate or methylacetate.
In one of my experiments, I obtained a lot of colorless gas, and I tried igniting this. This gas did not burn, but when the flame of my cigarette
lighter is kept in the stream of gas, then a lot of soot is produced. Could this be due to presence of phosgene? I once made pure CO with formic acid
and sulphuric acid, and that burns with a nice blue flame.
All this stuff about phosgene has made me somewhat scared of working with oxalyl chloride as well.
[Edited on 10-8-08 by woelen]
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Sauron
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Sartori describes decomposition of oxalyl chloride to CO and phosgene under three conditions:
-- vapor phase 600 C in a tube over a bed of something or other (pumice I think)
-- contact with AlCl3
-- UV irradiation
So store it in brown bottles out of sunlight. Avoid the other conditions, that ought to be easy.
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woelen
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Sauron, thanks for this clear answer. The oxalyl chloride is stored in a brown bottle, in a dark place, so that is not a problem. The others are not
an issue at all, I don't do that in my experiments and heating things to 600 C I never do at all.
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Ozone
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My oxalyl chloride label states that it contains: Phosgene <1%. The better grade (mine is 98 %, Aldrich) is much more expensive, but does not
declare phosgene content.
It came in an amber bottle in a bag in a can in a box which was in a silver mylar bag.
Honestly, I just transfer with care in the hood (as long as it's in solution, it's far less intimidating). I made some DNPO last week, no problem.
Working only with small amounts can greatly minimize the risks (particularly on work-up, here I was much more worried about the 2,4-DNP, which, in
toluene, goes right nitrile gloves.).
BUT--I do this kind of work in a university lab. It is not at all safe to do at home (although there are some really nice hoods on display here) even
with a hood because the thing has to vent somewhere. Somehow I have not yet seen a burner or scrubber applied to the vent of an amateur hood. These
safety features are required--the ass you save might not be your own. That said,
When I need phosgene (and triphosgene will not work for one reason or another), I get it as a 5% (IIRC) solution in either hexanes or ether. I
dispense the solution via cannula whilst cold from the freezer (you ought to see how fast the scroungers close your freezer when they see that in
there .
Cheers,
O3
-Anyone who never made a mistake never tried anything new.
--Albert Einstein
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7-cartridge
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Even if phosgene is intraperitoneal injection, pulmonary edema happens.
Many people know only the inhalational toxicity.
http://www.journalarchive.jst.go.jp/japanese/jnlabstract_ja....
(Japanese)
The contents of the paper.
Phosgene was injected in the abdominal cavity of a rabbit (weight of about 2 kg).
In the case of 0.5 ml, a rabbit died one hour later and four hours later.
In the case of 0.3 ml, one rabbit died six hours later, and one rabbit still lived 72 hours later.
In the case of 0.1 ml, all rabbits lived 72 hours later.
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DDTea
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I remember reading the introduction to a book about phosgenation reactions. Pretty much, it stated that a lot of the reluctance of chemists to handle
phosgene is unnecessary. When we grill meats, a fair amount of acrolein is emitted in the smoke. Acrolein has similar inhalation toxicity as
phosgene, yet we don't think about personal protective equipment as we grill. When handled reasonably, phosgene is perfectly safe to handle and opens
doors to a lot of exciting, useful synthetic chemistry.
However, "reasonably" is a very vague word. I didn't finish reading the book, so I can't say much more on the matter.
"In the end the proud scientist or philosopher who cannot be bothered to make his thought accessible has no choice but to retire to the heights in
which dwell the Great Misunderstood and the Great Ignored, there to rail in Olympic superiority at the folly of mankind." - Reginald Kapp.
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BromicAcid
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Author Andrew Dequasie has a wonderful quote on working with boron hydrides and derivatives in his book "The Green Flame":
| Quote: | | Each job has hazards of its own. In general, we know that we can handle our own dog, no matter how apprehensive our neighbors may feel about the
creature. On the other hand, we do hope that our neighbors will keep that vicious brute of theirs on a chain. |
I have been a phosgene chemist now going on five years, day in and day out I am refluxing phosgene but I see nothing life threatening about it, I've
been well trained and safety systems are in place. There are a number of toxic compounds we work with in our profession and hobby that have the
capacity to kill, but phosgene lends itself to a special class of compounds that can deliver a lethal dose easily in the event of an accident.
A concentration of 50 PPM is considered lethal after a short exposure, to put this in perspective if you were in a box 6'x6'x7' and 1.48 grams of
liquid phosgene were placed into that box you would be in this range. In gaseous form that would be ca. 350 mL. If you have a setup generating
phosgene or a flask full of phosgene you have your lethal dose there. And if something were to go with you close by, forget that room scenario, the
room is now only the space in your lungs. The above value is from "Phosgene and Related Carbonyl Halides" and it is described as 'Rapidly Fatal'.
One or two lung fulls might be enough to do you in. But it wouldn't feel that way, a little stingy, very sweet, and your eyes would burn, but you'd
feel better in a few minutes.
If you barely smell it, it's likely not enough to kill you, if you smell it pretty good the same might hold true. But the fact remains that if
something goes wrong and you have a release your time might expire.
@ DDTea, you may have been reading the above mentioned Phosgene and Related Carbonyl Halides, the first hundred pages or so are on the phobias
associated with phosgene throughout history including snippets of comic books and poems written during phosgene attacks from WWI. In comparing
acrolein toxicity one study using rats exposed them to acrolein at 4 PPM, 6 hours a day, 5 days a week for 62 days, mortality rate was ca. 50%.
Compare that at 5 PPM the mortality rate after just 1 hour is 50% with phosgene. Still I guess the main difference is that at least in this topic we
are not talking about harvesting and concentrating acrolein, afterall it is only the dose that determines the poison.
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eyeofjake
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As a weapons specialist, I have to say that it can be deadly....and it can't. Chemical weapons vary in effectiveness heavily by weather, environment,
temp, and delivery. Phosgene is lethal, but it isn't a fast killer. It can take several days before pulmonary edema finally kills you. Good chem
agents kill or injury a soldier on the field immediately as they are no longer fighting. Phosgene was weaponized as grenades. Since phosgene wouldn't
destroy electronics like cyanide, a grenade of it would end a tank crew fast. Yet, out in the open you would have to lay down a ton as it mixes with
air and drops it's lethality.
Despite all this, a simple wind gust would make the weapon you use your death. Spray some of it and then a gust of wind blows it your way......bad
day. I don't like dealing with chem weapons really. I hate getting into a SCALP suit and wear a gas mask for hours. It's not fun. So I wouldn't be
mixing it up in the house or in an enclosed area.
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