Direct Way to Fluoroacetates

[simply RED]

I'm writing this again bacause of its significance as a direct - one reaction way to produce fluoroacetates.
All materials are readily available. The reaction has 100% yield.

Cl-CH2-COOH + AgF = AgCl + F-CH2-COOH

The reaction is done in water solution. With moderate heating.
AgCl falls as a precipitate.

AgF is prepared by AgOH and HF.
AgNO3 + NaOH = AgOH (Ag2O) + NaNO3
The precipitate of Ag2O is filtered and dissolved in 40% HF. (available commericialy here for 4 dolars liter).
This solution is directly applied in fluoroacetate synth.

AgNO3 costs 15 dolars for 50g here.
It is not a mass production reagent but anyway it could be the first thing to start with.

[FUTI]

Yes this is true....I research this subject in past. You could also use mercury-fluoride instead of silver-fluoride.

I look for its capability to quench the certain metabolic pathways....but this ability isn't directly linked to it's CW use since intermediates that are responsible for aresting e.g. metabolism of acetate have minor activity to nervous system. Did you look for explanation on that matter, I had no luck on that one?

[simply RED]

Fluoroacetates block the crebs cycle. (I don't remember which enzyme is inhibited.)
They have no direct action on the nervous system.

[megalomania]

The silver chloride could likely be recycled. I am not certain how it is done, but I know the labs always keep it.

[FUTI]

to Megalomania: Yes AgX containing solution can be recycled friend of mine did. He goes door to door from one to the other photolab and collected wasted fixating solution (don't soot me if it isn't english terminology) and after a small number of steps which I can proudly say I was a consulting member he did get elemental silver, after that it is easy. Bad side of the story the ass of the juvelery maker wanted to cheat the guy for the price of that silver offering him a really small fee for electrolitic pure silver.

to simple RED: I know what you mean, I read about it some times ago that acctualy a product from citric acid cycle an adduct made from acetate (in this case fluoro-acetate) is the one resposible for shuting proces down acting like suicide substrate. But I read that tests on pidgeons show that fluoro-acetate isn't active on nerve system while that adduct is very active. Researching I find some stories linking new chiral center action...meaning that one of two possible adduct is highly active in nerve system. Never finish that idea so when you mentioned it I couldn't resist and have to ask...thanks for the effort.

[Child-of-Bodom]

Fluoroacetates block the crebs cycle. (I don't remember which enzyme is inhibited.)

The aconitase enyme is inhibited, the cells transform fluoroacetate into fluorocitrate, which binds to aconitase, but does not relief anymore.
Here is a simpel diagram:
http://www.aw-bc.com/mathews/ch14/sp4961.gif

Most of the times, the victim dies because the aconitases in the heart muscle are inhibited...

Anyway, fluoroacetate is rather toxic, I was told 600mg was sufficiant to kill a 'normal' man, so 600/70 = 8.6mg/kg.

The drawback of it is, that it is very easy detected :( , citrate is present in a overdose in every single cell, which is observed in a very easy blood-test.

[FUTI]

Thanks Child-of-Bodom you confirmed some of mine statements if you look at C-2 of citrate derivate made in the proces it is chiral but some other things you said maybe lead to other conclusion from those I read and repeated here. Since brain consume most of nutrients and oxigen(=energy) in comparison to other organs, and those test I read are done on experimental animals and are very old results, maybe they concluded erroneously that adduct has some neuron linked activity when acctually it is only starving/fasting/slow death cell mechanism of the tissue exposed (I remember they injected substance into liquor inside cranial cavity). Diference in enantiomers action isn't conclusive evidence for action on receptors or signal conduction, it will work on metabolic enzymes too.

[MrSamosa]

I tried synthesizing Ethyl Fluoroacetate yesterday by this method. I'm not sure if I was successful; I was very nervous while I was working, even though I had the luxury of a fume hood (a gas mask is so much more comforting...but alas, I must get used to lab standards).

-I added NaF powder to about 25 mL of 1.0 M AgNO3 solution in an erlenmeyer flask until I had a usable amount of AgF precipitate. I decanted off as much of the remaining solution as I could.
*NOTE: in the future, I will use NaF solution instead of powder; it will be easier to see a precipitate that way--the solution I had became very foggy.

-To a small amount (maybe 10 mL) of Chloracetyl Chloride, I added 100% Ethanol until it stopped bubbling/fuming. There was probably an excess of Ethanol. The product was Ethyl Chloroacetate (this in and of itself can make one nervous; but on reflecting, I think I was overreacting). It was a clear, oily liquid. No comments on smell or taste here :)

-I poured the the Ethyl Chloroacetate into the erlenmeyer containing the AgF.
No reaction was visible. There was no hot plate in the fumehood I was working with, so I could not heat it. I did shake/stir/mix the contents as best I could, though. The end result was the liquid with some clumps of AgF still in it.

-I did not have any time to do tests on the product to confirm the presence of ethyl fluoroacetate. But on disposal of the mixture [destroyed with NaOH solution and poured down the drain], I noticed a fruity/ethereal odor. My guess is that it was from the Ethyl Chloroacetate, but I haven't been able to find anything regarding the smell of the Fluoroacetate.

Anyhow, I hope this will give some useful information. I know I used reagents not readily available to the amateur to make Ethyl Chloroacetate... Maybe later I'll test a more practical route. But from this procedure, if I were using a fumehood with a hotplate, the synthesis of Fluoroacetates is piss easy.

[hereno]

-I added NaF powder to about 25 mL of 1.0 M AgNO3 solution in an erlenmeyer flask until I had a usable amount of AgF precipitate. I decanted off as much of the remaining solution as I could.
*NOTE: in the future, I will use NaF solution instead of powder; it will be easier to see a precipitate that way--the solution I had became very foggy.


How would you get a precipitate when AgF is FAR more soluble then NaF?

[MrSamosa]

How would you get a precipitate when AgF is FAR more soluble then NaF?

Well then, that could explain the lack of reaction when I added the ethyl chloroacetate :p

I made the ASSumption that Silver Fluoride behaved the same way as the Chloride, Bromide, and Iodide in that it would be practically insoluble in water.. Oh how wrong I was--AgF forms a nice hydrate. The 'precipitate' I saw was probably excess NaF that failed to dissolve in a saturated solution.

The trouble is there is no HF available... Would Na+ or NO3- ions readily react with the Chloroacetate? If not, then I'll try using the Ag+, Na+, F-, NO3- solution. And an even better idea, I'll try using calculations. :cool:

Also, on reading the section on Ethyl Chloroacetate in "The War Gases," it looks like it would be a good idea to keep the water solution quite acidic to prevent the decomposition of Chloroacetic acid to Hydroxyacetic Acid, which is of no interest to us. Maybe dissolve the AgOH in an excess of HF.

[simply RED]

You could obtain HF by distilling H2SO4/CaF2 or KF.
As not very conc HF is needed, the HF conducting tube could be put directly in icy water.
AgF is soluble in water - while AgX (X - halogen but not F) is not, that's why the reaction goes so easily.

[simply RED]

Using ester of chloroacetic acid is a good idea, as the ester is insoluble in water. In this case I would recommend the isopropyl ester, beeing less volatile than the EtOH ester.

I found interesting reference info about this reaction :
"Silver acetate could form as a precipitate - when reagents mixed. In the end of the reaction, some nitric acid should be added - !!!all silver salts of organic acids are soluble in 2% HNO3!!! while AgCl and AgBr are practically insoluble (in 2% HNO3)."

So if in the end of the reaction there is a precipitate when HNO3 is added - it is 100% sure you have succesfully made fluoroacetate.

Another chemical of interest is fluoro ethanol , beeing "deadly metabolised" to fluoroacetic acid.
And an interesting ester FCH2-CO-O-CH2-CH2F :) .

----

Btw, i tried today the action of NH4HF2 (ammonium hydrogen fluoride) solution on a hamster. 3 ml 20% solution was applied on the skin. The rodent was in a jar.
It died in 10 minutes - becoming wet with the solution and bleeding from the eyes, nose and mouth.

NH4HF2 is a non-hygroscopic (at least not very) solid soluble in water without releasing HF.

[inFinie]

AgX, the argentohalogenides :eek: decompose under sunlight to the halogen and Ag(s) powder. Maybe this can be called recycling from fixating solutions.

[simply RED]

Multi{kilo} synthesis of fluoroacetates is possible with another method.
18-Crown-6 is a crown ether that makes KF soluble in benzene or toluene.
The price of 18-Crown-6 may not matter because it is only a catalyst. (actually the mix and the catalyst depletes with concentration of Br-)

Saturate 10% (the exact number is a guess for now) Crown Ether solution in toluene with KF. (Actually there is no problem if solid phase is presented but anyway). Add to this the calculated chloroacetic acid (better bromoacetic) and heat the mix.

KF + BrCH2-COOH =[crown]=} K(+){crown} + Br(-) + FCH2-COOH
F(-) is a very bad leaving group and the equation is completely "moved" to the right.

Use water to extract the fluoroacetic acid. Then turn to fluoroacetate with Na2CO3. Then add acetone to the water-Facetate mix to precipitate the product.
Last step would be just to filter it...

The idea came to my mind yesterday while reading for crown ethers:

[[[[Liotta, C.L.; Harris, H.P. "Chemistry of naked anions. I. Reactions of the 18-crown-6 complex of potassium fluoride with organic substrates in aprotic organic solvents" J. Amer. Chem. Soc. 1974, 96, 2250-2252.]]]]

1,4,7,10,13,16-Hexaoxacyclooctadecane (18-Crown-6) is an effective agent for the solubilization of KF in polar and non-polar, aprotic org. solvents. This solubilized fluoride, which we have termed naked fluoride, is both a potent nucleophile and base and provides a facile and efficient means of obtaining a wide variety of org. fluoride compds. in high yields.

I do not have the whole article yet, only this part...

-----------------------
http://physchem.ox.ac.uk/~rodgers/www/Chemistry/Ligands.html
. Another use of the macrocyclic effect is to increase the nucleophilicity of fluoride salts. For example, KF in benzene is not very soluble and not very nucleophilic because it tends to exist as ion-pairs. Adding crown-6 ether increases the solubility ten-fold {{{it means ten times?}}} and raises the nucleophilicity of the fluoride ion (by solvating the potassium cation and therefore breaking up the ion-pairing) .
----------------------

[simply RED]

http://science.kennesaw.edu/~apanu/Carey%20ppt%20/16_04_08.ppt

A presentation I will highly recommend!
(only [O]xigen is mistaken with [C]arbon)

[simply RED]

Another method of making fluoroethanol is:
Ethylene oxide + HF - both in water solution - as concentrated as possible.

CH2--CH2 (O)to bothCH2 + HF = FCH2-CH2OH
The rection mixture should be heated in water solution (never tried anyway).
The yield is easily determined by titration the remaining HF after the reaction
is complete.

This method of epoxide openeing with HF is used in synthetic steroide chemistry.

[nbk2000]

If the solution of KF salt in crown-ethered benzene was used as an electrolyte, I wonder how corrosive this would be? Is it even conductive?

I remember a method of disarming metal cased UXO's that used a copper tube hooked up to a 12v car battery that had an electrolyte of salt water pumped through it by a windshield wash pump.

It would 'drill' a hole through hard steel artillery shells at the rate of a millimeter per minute. Now, if plain ol salt water can do that, surely a fluorine free-radical could do far better!

Of course, I'm not thinking of 'drilling' artillery shells, but much more profitable things. ;)

[simply RED]

Quite interesting question!
So, F- ion travels to the anode where it gives off electron and become... fluorine radical . If the solvent is benzene the resault is not going to be good as benzene reacts with F . CCl4 may give better resaults (F reacts faster with metal than with CCl4). Some metal fluorides are not soluble in organic solvent - which is a primary problem (they will act like isolator stopping the corrosion)...

Another problematic part is what happens whem K+[Crown] reaches the katode. Theory suggests - if the voltage is high enough the K+ will receive electron, detach from the Crown and bind to the katode as potassium metal.

I do not have information how high the voltage must be.

[simply RED]

NBK, hardly anyone here knows the answer of your question.
Half of the specialists start showing big omish formulas, others state the answe is in some "tablic data".
You could make a doctors degree with such experiments :P ....

[MrSamosa]

Another method of making fluoroethanol is:
Ethylene oxide + HF - both in water solution - as concentrated as possible.

CH2--CH2 (O)to bothCH2 + HF = FCH2-CH2OH
The rection mixture should be heated in water solution (never tried anyway).
The yield is easily determined by titration the remaining HF after the reaction
is complete.

This method of epoxide openeing with HF is used in synthetic steroide chemistry.

I'm assuming the next step is implied--oxidize Ethylene Fluorohydrin to Fluoroacetic Acid with KMnO4. However, when we adapt this to garage scale and techniques, this is almost going in loops...and is quite dangerous! Ethylene Oxide is toxic like phosgene and ridiculously flammable.

Ethylene Oxide would be obtained from Ethylene Glycol via NBK's Chlorohydrin synthesis, followed by elimination with NaOH. See the redundancy? We could oxidize the Chlorohydrin and then do the substitution on that with HF.

[simply RED]

Very dangerous chemicals indeed! HF is no better!

Why should you oxidize the fluoroethanol? Alcohol dehydrogenase-P450 will do this.

Anyway, oxidizing the half part and esterifying the acid with FCH2-CH2OH is going to give the most desirable product. (assuming what lab is needed for this - the process is not quite perespective)

If (cyclic-CH2-CH2-0-) and HF react very fast in cold - a possibility for binary weapon is emmerging.

[FUTI]

There is some mixed oxidative esterification setup involving alcohol, oxidant (chromate) and sulphuric acid. It would give exactly what simply RED said.

[simply RED]

"There is some mixed oxidative esterification setup involving alcohol, oxidant (chromate) and sulphuric acid. It would give exactly what simply RED said."

Very interesting! Do you have the real procedure?

[FUTI]

I can't find exact procedure for reaction with fluoro-ethanol...but I think it must be something like getting of butyl-butirate from butanol and that procedure you can find in Organic Synthesis. :confused: Check it twice anyway as I'm not sure it is the same and it wouldn't be nice to have an accident involving those substance.:eek: