Fluoroacetates

[MrSamosa]

Fluoroacetates are a very interesting groups of poisons. They are derivatives of Fluoroacetic acid, which as its name implies is fluorinated Acetic Acid. They are very acutely toxic through ingestion and inhalation of the dust. Here are some LD50 values for Sodium Fluoroacetate:

ORL-RAT LD50 0.2 mg kg-1
IPR-MUS LD50 15 mg kg-1
SCU-RBT LD50 0.3 mg kg-1

Fluoroacetates work by interfering with the Krebs/Citric Acid cycle and reacting with Coenzyme A and Oxaloacetic Acid forming Fluorocitric Acid, which blocks the Krebs Cycle and causes a build up of Citric Acid. An interesting note: Fluorocitric Acid is itself a poison, which could cause secondary poison if say a wild animal eats another creature which has been poisoned. But of course, you wouldn't expect many humans to go about eating their dead <img border="0" title="" alt="[Wink]" src="wink.gif" /> .

I've heard a few things about Fluoroacetates, such as "their synthesis is straight-forward" and "is outlined in organic chemistry books," but I have not been able to find anything on their synthesis. Not on the Organic Synthesis database, not on google, nowhere. Does anybody have information about Fluoroacetates?

<small>[ July 24, 2002, 06:24 PM: Message edited by: MrSamosa ]</small>

[Rhadon]

I don't see a problem in making it if you are ready to risk it and can get the substances which are needed... Obviously, you'll either need fluoroacetic acid (or fluorine and acetic acid) for the synthesis. Do you have access to fluorine or HF?

Making fluoroacetic acid from fluorine and acetic acid should work exactly like making chloroacetic acid from chlorine and acetic acid. This synthesis is popular and you'll surely find it somewhere.
It should be as simple as leading F2 through boiling acetic acid with P as a catalyst. The problem is the toxicity of the unreacted F2 und that P ist hard to get (controlled substance in the US if I remember correctly).

If you actually want to do it, I think the easiest and cheapest way to get fluorine is the following:
(1) CaF2 + H2SO4 --&gt; 2 HF + CaSO4
(2) 2 HF + H2O2 --&gt; F2 + 2 H2O

EDIT: Step (2) doesn't work! See Pu239 Stuchtiger's post.

You can use any oxidizer in step (2), the stronger the better. Usually KMnO4 is used, but H2O2 is cheaper. When making chlorine, I use MnO2, because it is the cheapest. But I don't recommand using MnO2 here because the reaction would "consume" considerable amounts of your precious F-.

Rhadon

<small>[ July 25, 2002, 05:51 PM: Message edited by: Rhadon ]</small>

[A43tg37]

According to Rhodium's page on synthesizing chloroacetic acid ( <a href="http://www.rhodium.ws/chemistry/chloroacetic.html" target="_blank">http://www.rhodium.ws/chemistry/chloroacetic.html</a> ), Red P is not absolutely essential as a catalyst; one can also use sulfur. Even though it is somewhat less efficient, it is much cheaer and easier to obtain. Theoretically, it should work as a catalyst in making fluoroacetic acid as well.

[Rhadon]

The fluorination could also be done by electrolysis of a mixture of acetic acid and HF. This method should be the easiest by far. The idea is from Madscientist.

[MrSamosa]

The closest I have to HF right now is Ammonium Bifluoride 5% solution(NH4FHF..ABF from here on). It has one F-, the other F is bonded a Hydrogen. This is very close to HF, has a pH of about 2, and in water or cleaning solutions (which I have) forms HF. I suppose this could be used in some reactions though. What I was considering doing though was to react the ABF with Potassium Hydroxide to yield Potassium Fluoride. I'm not positive if this will work, the most information I can give related to this is that ABF reacts with bases to form Ammonia Gas and reacts with Acid to form HF. I would like to react the KF with H2O2 or another oxidizer, possibly Calcium Hypochlorite, to yield the necessary F2. I'd prefer using KF or NaF because they are easier to handle than HF. Can anyone see why this definately would not work? If it won't, I'm sure I can go to a Do It Yourself store and pick up some Wink Rust Remover (10% HF) and purify it.

<small>[ July 24, 2002, 11:11 PM: Message edited by: MrSamosa ]</small>

[Pu239 Stuchtiger]

The element fluorine can only be liberated electrochemically. No oxidizer will react with HF and liberate F2.

Edit: Noticed that I had said something that was had already been posted...

<small>[ July 25, 2002, 12:28 AM: Message edited by: Pu239 Stuchtiger ]</small>

[kingspaz]

i'd just like to add that this is because fluorine has the highest electronegitivity and is therefore the most powerful oxidiser. if its the most powerful oxidiser then it cannot be oxidised by any other chemical. just thought i'd explain what Pu was saying.

[nbk2000]

Making it way too hard here.

Chlorine through acetic acid -&gt; chloroacetic acid

Chloroacetic acid + KF -&gt; Fluoroacetic acid + KCl

Though you're actually supposed to start out with methyl acetate, rather than straight acetic acid if you want the highly toxic methyl fluoroacetate.

[kingspaz]

would it be easier to use iodine as it would involve no bubbling?
also the CH2ICOOH would react with the KF much more easily.
CH2ICOOH + KF --&gt; CH2FOOH + KI
although iodine may not be reactive enough to work...i think also the reaction must be in light to work...i know it does when halogens react with alkanes.

[nbk2000]

The Gods have smiled upon their creations and give them the gift of knowledge.

Or in this case a horribly needed lesson in toxchem. :D

Here's some info I extracted from a file I have. I omitted a lot of the more technical and arcane stuff for clarity and brevity. This means only 1 chart and no citations or footnotes. You want all that, buy the DVD. :)

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The class of compounds known as "fluoroacetates" comprises the esters of fluoroacetic acid and of higher w-fluorocarboxylic acids, of the general formula:

F(CH2)COOR

Various other fluorine compounds, such as fluoroalcohols, a-fluoroacetamide, and their derivatives are generally included in this class. They are collectively named "fluoroacetates" because their toxic properties are similar to those of methyl fluoroacetate.

The discovery of this class of substances was reported in 1896 by Swarts, who prepared methyl fluoroacetate (Bull. soc. chim. 3, 15, 1134 (1896)). Over the next forty years several "fluoro-acetates" were described, but it was not until the high toxicity of 2-fluoroethanol and of fluoroacetic acid was recognized in 1936 that systematic study resulted.

The first compound investigated for possible chemical warfare use was methyl fluoroacetate. Many other "fluoroacetates" were prepared and tested for their toxicities, particularly in Poland and England. During World War II, it was planned to use these compounds especially as water contaminants, because of their stability in water solution and their lack of taste or odor.

The "fluoroacetates" are highly toxic when inhaled, injected, and to some extent when absorbed through the skin. They act as convulsant poisons with a delayed effect. Unlike the other haloacetates they do not possess lachrymatory properties, and unlike the fluophosphates (nerve gases) they are completely devoid of myotic activity.

<a href="http://server3001.freeyellow.com/nbk2000/Table_Fluoro_Toxicity.gif" target="_blank">Table listing various Fluoro compounds properties and LD50s (VERY LARGE .gif, but only 25K in size...photoshop people...learn it, live it, love it! <img border="0" title="" alt="[Wink]" src="wink.gif" /> )</a>

(Technicals details omitted for brevity)

1. Methods of preparation
It consists, in the case of methyl fluoroacetate, in heating at 190-200°C. for 10-15 hr. methyl chloroacetate with an excess of potassium fluoride in an autoclave. Yields of 60% and 90% are reported. Sodium fluoride under the same conditions gave very poor yields.

CICH2COOCH3+ KF -&gt; FCH2COOCH3 + KCl

Several other fluoroacetates have been prepared by using this method. The yields varied from 20 to 90 per cent. The best conditions for the reaction are:

(a) complete dryness of the starting materials, (b) large excess of potassium fluoride, 10 to 50 per cent, (c) strong agitation, and (d) high temperatures.

This method was used in the United States for the preparation of methyl fluoroacetate on a pilot-plant scale. Other methods for preparing alkyl fluoroacetates are based upon the following reactions:

(More obscure shit deleted for brevity)

(d) Ester interchange between ethyl fluoroacetate and an alcohol, such as 2-ethyl-1-hexanol or dodecyl alcohol, in the presence of p-toluenesulfonic acid as the catalyst. Yields varying from 60% to 80% were obtained (US patent#2409859 2-Ethyl Hexyl Fluoroacetate (highly toxic and easy to make)).

Properties and reactions:
The unsubstituted alkyl esters of w-fluorocarboxylic acids are generally colorless stable liquids of very faint fruit-like odors. Methyl fluoroacetate is practically odorless, concentrations of one part per million being undetectable, and it is completely miscible with most of the organic solvents as well as with mustard gas (2,2'-dichlorodiethyl sulfide). The solubility in water is about 15 per cent.

(Yet more stuff...detailing hydrolysis in water...yawn...)

Treatment of an aqueous solution of methyl fluoroacetate with an excess of calcium hydroxide (lime) and evaporation under vacuum yields a crystalline residue of calcium fluoroacetate. This salt, mixed with sulfuric acid and distilled under reduced pressure, gives a 90% yield of fluoroacetic acid.

When an excess of aqueous ammonia is added to methyl fluoroacetate, cooled in ice water, a crystalline precipitate of alpha-fluoroacetamide is obtained in quantitative yield. It is a stable compound and is as toxic as methyl fluoroacetate.

C. 2-FLUOROETHYL ESTERS OF w-FLUOROCARBOXYLIC ACID

2-Fluoroethyl fluoroacetate:
A 77.4 per cent yield of this fluoroacetate was obtained by refluxing for 30 min. a mixture of fluoroacetyl chloride with 2-fluoroethanol.

FCH2COCl + FCH2CH2OH -&gt; FCH2COOCH2CH2F + HCl

Properties:
2-Fluoroethyl fluoroacetate is a colorless liquid of very faint odor. The vapor pressures at 0°, 15°, and 30°C. are respectively 0.45, 1.28, and 3.29 mm. The 2-fluoroethyl esters of higher w-fluorocarboxylic acids are colorless mobile liquids with a pleasant fruit-like odor and fairly high boiling points.

Toxicological tests show that the 2-fluoroethyl esters are more toxic than the corresponding unsubstituted ethyl esters. 2-Fluoroethyl e-fluorocaproate is the most toxic compound of this series. It is eleven times as toxic as methyl fluoroacetate (mole for mole).

D. w-FLUOROALCOHOLS
A simpler method of synthesis was developed in 1943. It consists in heating ethylene chlorohydrin and potassium fluoride at 135°C. for 4 hr. in a rotating autoclave.

CICH2CH2OH + KF -&gt; FCH2CH2OH + KCl

The yield was 42 per cent. Sodium fluoride under the same conditions gave very poor yields. This reaction can also be carried out at atmospheric pressure by using high-boiling organic solvents, such as ethylene glycol, glycerol, diethylene glycol, or polyethylene glycol, either singly or in admixture. A 42.5 per cent yield of 2-fluoroethanol was obtained by reacting ethylene chlorohydrin with potassium fluoride at 170-180C. in a mixture of ethylene glycol and diethylene glycol (antifreeze).

(More tecnobabble)

2. Properties and reactions of 2- fluoroethanol

2-Fluoroethanol is a colorless liquid of very faint odor, resembling that of ethyl alcohol. The vapor pressures at 0°, 15°, and 30°C. are respectively 5.55, 14.3, and 40 mm. (96). It is miscible with water in all proportions and readily dissolves calcium chloride and calcium nitrate.

2-Fluoroethanol reacts with phosphorus trichloride, in the presence of pyridine, giving an unstated yield of tris(2-fluormethyl) phosphite, (FCH2CH2O)2P, a liquid acting as a depressant on the central nervous system.

+++++++++++++++++++++++++++++++++++++++

It'd seem to me that the easiest thing to make would be 2-fluoroethanol by refluxing of EtC and KF in glycerine or ethylene glycol. The EtC can be prepared via the processes in my "antifreeze mustard gas" post (search the archives) using easily obtainable antifreeze and pool acids.

Another possiblility is to make MeFAc using a similar process of refluxing MeClAc with KF in a solvent, thus removing the need for an autoclave (looks around room...nope...don't see it. Must have left mine at work :p ) Might get crappy yeilds, or it may not work, but it'd be worth trying before investing in an autoclave.

<small>[ July 25, 2002, 01:52 PM: Message edited by: nbk2000 ]</small>

[Rhadon]

Correcting myself:

Quoting Pu239 Stuchtiger:
</font><blockquote><font size="1" face="Verdana, Arial, Helvetica">quote:</font><hr /><font size="2" face="Verdana, Arial, Helvetica">No oxidizer will react with HF and liberate F2</font><hr /></blockquote><font size="2" face="Verdana, Arial, Helvetica">Pu239 Stuchtiger, you're probably right. I thought that HCl and HF can be treated similar in this respect, but they apparently can't.

<small>[ July 25, 2002, 05:48 PM: Message edited by: Rhadon ]</small>

[MrSamosa]

To NBK- Do you think you could do me, and all the other forumites, a big favor (ahh, as if you do not do enough for us; giving us knowledge, writing PDFs...)?

I find the idea of Mustard from AntiFreeze very interesting, and I'm sure there are plenty of others who feel the same. However, I am having much trouble finding it in the Archives. My guess is that since some of the 2001 Archives, from August-December are inaccessable (atleast on my computer), the topic was probably made during those months; hence my inability to reach it.

So, what I am asking is if you could please repost that topic for all the new-comers of the Forum to see :) . If not, thanks anyway.

[nbk2000]

Here's the relevant portion about preparing chlorohydrin. You'll have to go to the FTP and download the older archvies since the original article was back in sep '00.

++++++++++++++++++++++++++++++++++++++++++++++++++ +++++++++++++++++++++++++++

Ethylene glycol is placed in a distillation apparatus and heated up to 148° C and at the same time a slow current of dry hydrogen chloride gas is passed through it. The water and chlorohydrin formed distill s off and is collected.

Gradually the temperature of the bath is increased to approximately 160° C till the chlorohydrin distillation is complete. The processing of 100 grams of glycol takes about 16 hours to complete.

The distillation product is first freed from hydrochloric acid by washing with sodium carbonate and then washed with 2-3 times it's volume of ethyl ether.

The ether solution is removed and completely dried over freshly melted sodium carbonate. Two distillations supply one pure product boiling between 128° C and 131° C. Yield, about 60 % of the theoretical.

[MrSamosa]

Unfortunately, I don't have access to distillation apparatus...maybe I will build one of those improvised ones later. Anyhow, I've found a mixture of Hydrochloric Acid and Hydrofluoric Acid. I have plenty of HCl right now so what I'm interested in is the HF. My plan to separate the two is to add 27% H2O2 to release Chlorine Gas and form HF dissolved in H2O. Seeing as the H2O2 will not react with the HF, I figured this method would work pretty well. My next step would be to freeze the solution in an attempt to separate the HF and H2O, since HF has a significantly lower melting point than water.

Sorry if this is another stupid idea where basic knowledge of chemistry would show would not work, but can anyone tell me what is wrong with it, or atleast a better way to go about with the separation?

[rikkitikkitavi]

sounds like a good idea in theory, but it have some practical drawbacks.

I have used HCl+H2O2 extensivly to process PCB:s , since it is a very effcicent etching solution. Left standing it produces Cl2 only slowly, like most reactions where the products are gaseous, unless the reactants are of high concentration. The mix was usable after a one week period.

Boiling might increase rate of reaction though I never did that of course. Try it out :)

There is the possibility to neutralize the acid-mix with CaCO3. CaF2 is almost insoluble so it preciptates. The HF can be reformed with
H2SO4 (CaF2+H2SO4 =&gt; CaSO4 + 2HF (g)

/rickard