Chemical warfare agents GP and GV

[megalomania]

Since these are the new kids on the block, and there is very little information about them I decided to devote a little time on them. I am not exactly as to the proper code names of these compounds. In Chemical Abstracts it lists one as GV-4 and the other as both GV and GP. GV-4 is definetly the name for one, but I have seen the other referred to as GP/GV. Anyone know which is right?

The chemical weapons known as GP/GV and GV-4 are potent acetylcholinesterase inhibitors developed for battlefield use. Very little information exists about these compounds, other than that they do exist. It is likely these compounds were developed by the US or Great Britian in the early 1960s after the precursor compounds were first synthesized.

The nerve gas designated GP/GV is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)ethyl ester and has the structure given in attached pic 1:

The nerve gas designated GV-4 is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)propyl ester and has the structure given in attached pic 2:

Structurally these two compounds are very similar, differing only by an ethyl and propyl group respectively. In theory they are both synthesized from dimethylphosphoramidic difluoride and an amino alcohol in a simple esterification reaction typical of other binary nerve gasses. I have a reference published last year that confirms this reaction, but it does not provide experimental details, only an outline of the reaction. If I ran the reaction I would model it along the lines of sarin synthesis by gently refluxing a mixture of the amino alcohol with dimethylphosphoramidic difluoride.

Dimethylphosphoramidic difluoride is the key to this synthesis. I am eagerly awaiting a reference for the synthesis of this compound from Liebigs Annalen. When I get it I will post a synthesis work up. I suspect I may need to get an additional reference or two in order to make the precursor to dimethylphosphoramidic difluoride.

[megalomania]

Since these are the new kids on the block, and there is very little information about them I decided to devote a little time on them. I am not exactly as to the proper code names of these compounds. In Chemical Abstracts it lists one as GV-4 and the other as both GV and GP. GV-4 is definetly the name for one, but I have seen the other referred to as GP/GV. Anyone know which is right?

The chemical weapons known as GP/GV and GV-4 are potent acetylcholinesterase inhibitors developed for battlefield use. Very little information exists about these compounds, other than that they do exist. It is likely these compounds were developed by the US or Great Britian in the early 1960s after the precursor compounds were first synthesized.

The nerve gas designated GP/GV is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)ethyl ester and has the structure given in attached pic 1:

The nerve gas designated GV-4 is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)propyl ester and has the structure given in attached pic 2:

Structurally these two compounds are very similar, differing only by an ethyl and propyl group respectively. In theory they are both synthesized from dimethylphosphoramidic difluoride and an amino alcohol in a simple esterification reaction typical of other binary nerve gasses. I have a reference published last year that confirms this reaction, but it does not provide experimental details, only an outline of the reaction. If I ran the reaction I would model it along the lines of sarin synthesis by gently refluxing a mixture of the amino alcohol with dimethylphosphoramidic difluoride.

Dimethylphosphoramidic difluoride is the key to this synthesis. I am eagerly awaiting a reference for the synthesis of this compound from Liebigs Annalen. When I get it I will post a synthesis work up. I suspect I may need to get an additional reference or two in order to make the precursor to dimethylphosphoramidic difluoride.

[megalomania]

Since these are the new kids on the block, and there is very little information about them I decided to devote a little time on them. I am not exactly as to the proper code names of these compounds. In Chemical Abstracts it lists one as GV-4 and the other as both GV and GP. GV-4 is definetly the name for one, but I have seen the other referred to as GP/GV. Anyone know which is right?

The chemical weapons known as GP/GV and GV-4 are potent acetylcholinesterase inhibitors developed for battlefield use. Very little information exists about these compounds, other than that they do exist. It is likely these compounds were developed by the US or Great Britian in the early 1960s after the precursor compounds were first synthesized.

The nerve gas designated GP/GV is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)ethyl ester and has the structure given in attached pic 1:

The nerve gas designated GV-4 is named dimethylphosphoramidofluoridic acid 2-(dimethylamino)propyl ester and has the structure given in attached pic 2:

Structurally these two compounds are very similar, differing only by an ethyl and propyl group respectively. In theory they are both synthesized from dimethylphosphoramidic difluoride and an amino alcohol in a simple esterification reaction typical of other binary nerve gasses. I have a reference published last year that confirms this reaction, but it does not provide experimental details, only an outline of the reaction. If I ran the reaction I would model it along the lines of sarin synthesis by gently refluxing a mixture of the amino alcohol with dimethylphosphoramidic difluoride.

Dimethylphosphoramidic difluoride is the key to this synthesis. I am eagerly awaiting a reference for the synthesis of this compound from Liebigs Annalen. When I get it I will post a synthesis work up. I suspect I may need to get an additional reference or two in order to make the precursor to dimethylphosphoramidic difluoride.

[FUTI]

This sound interesting! Do you have any info will the product obtained from N,N-diethyl-aminoethanol work as well? I hope that other precursor can be made by some HMPT production modification.

[FUTI]

This sound interesting! Do you have any info will the product obtained from N,N-diethyl-aminoethanol work as well? I hope that other precursor can be made by some HMPT production modification.

[FUTI]

This sound interesting! Do you have any info will the product obtained from N,N-diethyl-aminoethanol work as well? I hope that other precursor can be made by some HMPT production modification.

[Chris The Great]

Very interesting. Over in the bicyclic phosphate thread, Samosa's reference about bicyclic phosphates also mentions these nerve agents, however the structure they provided did not have the oxygen between the phosphorus and the dimethylaminoalkyl group.

These agents are also of an interest to me, and the fact that there is in fact an oxygen there makes the synthesis much easier.

You could save some flourine (expensive) by mixing equal molar amounts of dimethylphosphoramidic difluoride and dimethylphosphoramidic dichloride, and refluxing that with the appropriate alcohol in a solvent with a base to remove the HCl generated. I believe this is a method of producing sarin that you mentioned in some thread.
This would keep nearly all the flourine attached to the nerve agent, and only chlorine would take part in the reaction.

I have this feeling I have some information on a relatively simple reaction that could yield these agents, but I can't remember how it goes offhand, or even if it is as simple as I think it is. I will look into it.

Anyway, the article Samosa posted about Bicyclic phosphates also has some information of the toxicity of GV http://www.asanltr.com/ASANews-98/chemistry.html

Also, it's nice to see some interest in nerve agents again, it's been quite quiet as of late.

[Chris The Great]

Very interesting. Over in the bicyclic phosphate thread, Samosa's reference about bicyclic phosphates also mentions these nerve agents, however the structure they provided did not have the oxygen between the phosphorus and the dimethylaminoalkyl group.

These agents are also of an interest to me, and the fact that there is in fact an oxygen there makes the synthesis much easier.

You could save some flourine (expensive) by mixing equal molar amounts of dimethylphosphoramidic difluoride and dimethylphosphoramidic dichloride, and refluxing that with the appropriate alcohol in a solvent with a base to remove the HCl generated. I believe this is a method of producing sarin that you mentioned in some thread.
This would keep nearly all the flourine attached to the nerve agent, and only chlorine would take part in the reaction.

I have this feeling I have some information on a relatively simple reaction that could yield these agents, but I can't remember how it goes offhand, or even if it is as simple as I think it is. I will look into it.

Anyway, the article Samosa posted about Bicyclic phosphates also has some information of the toxicity of GV http://www.asanltr.com/ASANews-98/chemistry.html

Also, it's nice to see some interest in nerve agents again, it's been quite quiet as of late.

[Chris The Great]

Very interesting. Over in the bicyclic phosphate thread, Samosa's reference about bicyclic phosphates also mentions these nerve agents, however the structure they provided did not have the oxygen between the phosphorus and the dimethylaminoalkyl group.

These agents are also of an interest to me, and the fact that there is in fact an oxygen there makes the synthesis much easier.

You could save some flourine (expensive) by mixing equal molar amounts of dimethylphosphoramidic difluoride and dimethylphosphoramidic dichloride, and refluxing that with the appropriate alcohol in a solvent with a base to remove the HCl generated. I believe this is a method of producing sarin that you mentioned in some thread.
This would keep nearly all the flourine attached to the nerve agent, and only chlorine would take part in the reaction.

I have this feeling I have some information on a relatively simple reaction that could yield these agents, but I can't remember how it goes offhand, or even if it is as simple as I think it is. I will look into it.

Anyway, the article Samosa posted about Bicyclic phosphates also has some information of the toxicity of GV http://www.asanltr.com/ASANews-98/chemistry.html

Also, it's nice to see some interest in nerve agents again, it's been quite quiet as of late.

[megalomania]

The chemical reaction in question is provided in the journal "Phosphorus, Sulfur and Silicon and the Related Elements." I didn't realize until just now this was a journal, I thought is was a book. It is available online, but only at the library. I hope it is available at least because this is one of those funky journals that does not publish electronic editions for the previous 12 months. It looks like this article is in issue 1 of 2004, so it may be out.

I do have a graphic for the reaction... One thing I don't quite understand is what that sodium atom is doing floating around there. I wonder if the amino alcohol is reacted with sodium metal to make an alkoxide? The article will clear it up I hope.

FUTI, I see no reason why one could not use N,N-diethyl-aminoethanol instead of N,N-dimethyl-aminoethanol. The toxicity would likely be lower, but it may be less hydrolyzable.

I also wonder why N,N-dimethyl-aminomethanol is not mentioned as I would think it would be the most toxic of all as this is the simplest possible molecular structure of this group. Maybe dimethylphosphoramidofluoridic acid 2-(dimethylamino)methyl ester is a chemical weapon and they just have not mentioned it. What chemicals are GO, GQ, GR, GS, GT, GU, GV-1, GV-2, and GV-3?

[megalomania]

The chemical reaction in question is provided in the journal "Phosphorus, Sulfur and Silicon and the Related Elements." I didn't realize until just now this was a journal, I thought is was a book. It is available online, but only at the library. I hope it is available at least because this is one of those funky journals that does not publish electronic editions for the previous 12 months. It looks like this article is in issue 1 of 2004, so it may be out.

I do have a graphic for the reaction... One thing I don't quite understand is what that sodium atom is doing floating around there. I wonder if the amino alcohol is reacted with sodium metal to make an alkoxide? The article will clear it up I hope.

FUTI, I see no reason why one could not use N,N-diethyl-aminoethanol instead of N,N-dimethyl-aminoethanol. The toxicity would likely be lower, but it may be less hydrolyzable.

I also wonder why N,N-dimethyl-aminomethanol is not mentioned as I would think it would be the most toxic of all as this is the simplest possible molecular structure of this group. Maybe dimethylphosphoramidofluoridic acid 2-(dimethylamino)methyl ester is a chemical weapon and they just have not mentioned it. What chemicals are GO, GQ, GR, GS, GT, GU, GV-1, GV-2, and GV-3?

[megalomania]

The chemical reaction in question is provided in the journal "Phosphorus, Sulfur and Silicon and the Related Elements." I didn't realize until just now this was a journal, I thought is was a book. It is available online, but only at the library. I hope it is available at least because this is one of those funky journals that does not publish electronic editions for the previous 12 months. It looks like this article is in issue 1 of 2004, so it may be out.

I do have a graphic for the reaction... One thing I don't quite understand is what that sodium atom is doing floating around there. I wonder if the amino alcohol is reacted with sodium metal to make an alkoxide? The article will clear it up I hope.

FUTI, I see no reason why one could not use N,N-diethyl-aminoethanol instead of N,N-dimethyl-aminoethanol. The toxicity would likely be lower, but it may be less hydrolyzable.

I also wonder why N,N-dimethyl-aminomethanol is not mentioned as I would think it would be the most toxic of all as this is the simplest possible molecular structure of this group. Maybe dimethylphosphoramidofluoridic acid 2-(dimethylamino)methyl ester is a chemical weapon and they just have not mentioned it. What chemicals are GO, GQ, GR, GS, GT, GU, GV-1, GV-2, and GV-3?

[Chris The Great]

I think the sodium is showing that the dimethylaminoethanol is not actually a alcohol, but a salt of the structure (Me)2NCH2CH2ONa. (if that is what a alkoxide is, sorry, my chem terms are not very good at all) This would remove the need to have a base to soak up the HF generated as there would be none, only NaF.

The NaF could then be used directly in other reactions, such as making the dimethylphosphoramidic difluoride, without having to extract it from something like triethylamine hydroflouride.

EDIT- I just remembered that the P-F bond is fairly strong, and so breaking it requires refluxing etc. However, Na and F would attract each other very strongly, so the reaction would not require much, if any, heating to get it to go to completion. At least, that's what I think. This would certainly make the reaction much safer.

[Chris The Great]

I think the sodium is showing that the dimethylaminoethanol is not actually a alcohol, but a salt of the structure (Me)2NCH2CH2ONa. (if that is what a alkoxide is, sorry, my chem terms are not very good at all) This would remove the need to have a base to soak up the HF generated as there would be none, only NaF.

The NaF could then be used directly in other reactions, such as making the dimethylphosphoramidic difluoride, without having to extract it from something like triethylamine hydroflouride.

EDIT- I just remembered that the P-F bond is fairly strong, and so breaking it requires refluxing etc. However, Na and F would attract each other very strongly, so the reaction would not require much, if any, heating to get it to go to completion. At least, that's what I think. This would certainly make the reaction much safer.

[Chris The Great]

I think the sodium is showing that the dimethylaminoethanol is not actually a alcohol, but a salt of the structure (Me)2NCH2CH2ONa. (if that is what a alkoxide is, sorry, my chem terms are not very good at all) This would remove the need to have a base to soak up the HF generated as there would be none, only NaF.

The NaF could then be used directly in other reactions, such as making the dimethylphosphoramidic difluoride, without having to extract it from something like triethylamine hydroflouride.

EDIT- I just remembered that the P-F bond is fairly strong, and so breaking it requires refluxing etc. However, Na and F would attract each other very strongly, so the reaction would not require much, if any, heating to get it to go to completion. At least, that's what I think. This would certainly make the reaction much safer.

[simply RED]

"This would certainly make the reaction much safer."

One drop is 50 mg (20 drops 1ml). Even worse, density more than 1 !!!
Only ONE TENTH of a drop is needed to kill you in case of these new nerve agents...
I can't immagine the precautions needed to be taken in case you want to make some...

Maybe the last reaction should be done as follows :
In a syringe first suck the first compound and then the second so they react in the syringe, or maybe an ampule or rubber stopper container. Anyway , new approach is needed so you don't be the victim of your VX .

[simply RED]

"This would certainly make the reaction much safer."

One drop is 50 mg (20 drops 1ml). Even worse, density more than 1 !!!
Only ONE TENTH of a drop is needed to kill you in case of these new nerve agents...
I can't immagine the precautions needed to be taken in case you want to make some...

Maybe the last reaction should be done as follows :
In a syringe first suck the first compound and then the second so they react in the syringe, or maybe an ampule or rubber stopper container. Anyway , new approach is needed so you don't be the victim of your VX .

[simply RED]

"This would certainly make the reaction much safer."

One drop is 50 mg (20 drops 1ml). Even worse, density more than 1 !!!
Only ONE TENTH of a drop is needed to kill you in case of these new nerve agents...
I can't immagine the precautions needed to be taken in case you want to make some...

Maybe the last reaction should be done as follows :
In a syringe first suck the first compound and then the second so they react in the syringe, or maybe an ampule or rubber stopper container. Anyway , new approach is needed so you don't be the victim of your VX .

[MrSamosa]

When looking at new molecules and trying to figure out their syntheses, I've been told to "look at the component structures and figure out where to get them." With that in mind, these new Nerve Agents remind me of Tabun, only with a Fluorine atom in place of a Cyanide group.

So maybe the syntheses of GV/GP could be approached the same way as that of Tabun, replacing NaF and Dimethylaminoethanol for NaCN and Ethanol.

And on the note of Dimethylaminoethanol, take a look at the structure of Diphenhydramine, the antihistamine/anticholinergic. Could the C-O-C structure in it be broken, perhaps leaving Dimethylaminoethanol?

[MrSamosa]

When looking at new molecules and trying to figure out their syntheses, I've been told to "look at the component structures and figure out where to get them." With that in mind, these new Nerve Agents remind me of Tabun, only with a Fluorine atom in place of a Cyanide group.

So maybe the syntheses of GV/GP could be approached the same way as that of Tabun, replacing NaF and Dimethylaminoethanol for NaCN and Ethanol.

And on the note of Dimethylaminoethanol, take a look at the structure of Diphenhydramine, the antihistamine/anticholinergic. Could the C-O-C structure in it be broken, perhaps leaving Dimethylaminoethanol?

[MrSamosa]

When looking at new molecules and trying to figure out their syntheses, I've been told to "look at the component structures and figure out where to get them." With that in mind, these new Nerve Agents remind me of Tabun, only with a Fluorine atom in place of a Cyanide group.

So maybe the syntheses of GV/GP could be approached the same way as that of Tabun, replacing NaF and Dimethylaminoethanol for NaCN and Ethanol.

And on the note of Dimethylaminoethanol, take a look at the structure of Diphenhydramine, the antihistamine/anticholinergic. Could the C-O-C structure in it be broken, perhaps leaving Dimethylaminoethanol?

[Chris The Great]

That method works very well, it's how I've thought out alot of reactions.

I would use dimethylamine and chloroethanol to make the dimethylaminoethanol. Both are very easy to make OTC, dimethylamine can be made by hydrolising hexamine with HCl in the presence of formaldehyde, and chloroethanol from ethylene glycol and hydrochloric acid reacting in the vapour phase. I think there is a good procedure for chloroethanol on the forums, probably in a mustard gas thread.
It might work better using bromoethanol actually, the synthesis would probably be the same but using hydrobromic acid.

As for the Diphenhydramine, perhaps it could be hydrolised by refluxing in fairly dilute HCl? Maybe even 15%? The dimethylaminoethanol would come out as a salt, but that would make it very easy to seperate from the alcohol formed by the other half of the molecule.


As for the safety, it is much safer to react at room temperature compared to relfuxing the nerve agent. It is still a nerve agent and all appropriate safety measures must be taken to avoid painful death.

[Chris The Great]

That method works very well, it's how I've thought out alot of reactions.

I would use dimethylamine and chloroethanol to make the dimethylaminoethanol. Both are very easy to make OTC, dimethylamine can be made by hydrolising hexamine with HCl in the presence of formaldehyde, and chloroethanol from ethylene glycol and hydrochloric acid reacting in the vapour phase. I think there is a good procedure for chloroethanol on the forums, probably in a mustard gas thread.
It might work better using bromoethanol actually, the synthesis would probably be the same but using hydrobromic acid.

As for the Diphenhydramine, perhaps it could be hydrolised by refluxing in fairly dilute HCl? Maybe even 15%? The dimethylaminoethanol would come out as a salt, but that would make it very easy to seperate from the alcohol formed by the other half of the molecule.


As for the safety, it is much safer to react at room temperature compared to relfuxing the nerve agent. It is still a nerve agent and all appropriate safety measures must be taken to avoid painful death.

[Chris The Great]

That method works very well, it's how I've thought out alot of reactions.

I would use dimethylamine and chloroethanol to make the dimethylaminoethanol. Both are very easy to make OTC, dimethylamine can be made by hydrolising hexamine with HCl in the presence of formaldehyde, and chloroethanol from ethylene glycol and hydrochloric acid reacting in the vapour phase. I think there is a good procedure for chloroethanol on the forums, probably in a mustard gas thread.
It might work better using bromoethanol actually, the synthesis would probably be the same but using hydrobromic acid.

As for the Diphenhydramine, perhaps it could be hydrolised by refluxing in fairly dilute HCl? Maybe even 15%? The dimethylaminoethanol would come out as a salt, but that would make it very easy to seperate from the alcohol formed by the other half of the molecule.


As for the safety, it is much safer to react at room temperature compared to relfuxing the nerve agent. It is still a nerve agent and all appropriate safety measures must be taken to avoid painful death.

[FUTI]

I agree with simply RED...synthesis of these compounds is dangerous. I wouldn't advise anyone to try it in improvised facility. That is the reason why the armies switched their CW programs to binary weapons. It is to dangerous to produce new generation CW, but if you can made it by simple mixing of simple less-toxic precursors (benign looking "pesticides" or their precursors) during explosion it simplifies things a lot (and if it that toxic you coudn't care less about synthesis yield).

Even removal of old CW is pain in ***. If anyone care about that subject he can Google a little I believe that China and Japan have a long years dispute over WWII leftover CW ammo on Chinese soil (artilery shells and such things)...I believe China refused to sign a treaty of non-spreading CW and CW technology as long those CW leftovers are on their soil and they insist Japan take responsibility in its removal.

[FUTI]

I agree with simply RED...synthesis of these compounds is dangerous. I wouldn't advise anyone to try it in improvised facility. That is the reason why the armies switched their CW programs to binary weapons. It is to dangerous to produce new generation CW, but if you can made it by simple mixing of simple less-toxic precursors (benign looking "pesticides" or their precursors) during explosion it simplifies things a lot (and if it that toxic you coudn't care less about synthesis yield).

Even removal of old CW is pain in ***. If anyone care about that subject he can Google a little I believe that China and Japan have a long years dispute over WWII leftover CW ammo on Chinese soil (artilery shells and such things)...I believe China refused to sign a treaty of non-spreading CW and CW technology as long those CW leftovers are on their soil and they insist Japan take responsibility in its removal.

[FUTI]

I agree with simply RED...synthesis of these compounds is dangerous. I wouldn't advise anyone to try it in improvised facility. That is the reason why the armies switched their CW programs to binary weapons. It is to dangerous to produce new generation CW, but if you can made it by simple mixing of simple less-toxic precursors (benign looking "pesticides" or their precursors) during explosion it simplifies things a lot (and if it that toxic you coudn't care less about synthesis yield).

Even removal of old CW is pain in ***. If anyone care about that subject he can Google a little I believe that China and Japan have a long years dispute over WWII leftover CW ammo on Chinese soil (artilery shells and such things)...I believe China refused to sign a treaty of non-spreading CW and CW technology as long those CW leftovers are on their soil and they insist Japan take responsibility in its removal.

[MrSamosa]

Even removal of old CW is pain in ***.

I can't agree with you more on that idea. Even cleaning up after my little experiments with Chloropicrin was a pain, and often literally. Every single drop had to be thoroughly washed down with ethanol, water, napkins, and whatever I used to wipe down surfaces put in a few layers of ziplock baggies before being thrown away (No, this is not a viable means for dealing with disposal...but the way I figured, it won't only be in my trashbag for a few days). Then there was the problem that ethanol made Chloropicrin more volatile... But I digress.

GP and GV. From my understanding, the most effective Nerve Agents resemble Choline most closely, e.g.: VX. With that in mind, it would seem like GP is more effective than GV in two ways: it would be more toxic and it would have a lower molar mass, therefore letting it be more volatile. I'm speculating here and not basing any of this on toxicological data, which I don't have.

It is worth looking at Chapter V of Saunders about "Phosphorodiamidic Fluorides" and "Tabun and Sarin." The section I found of most interest was:

In view of the rapid toxic action and myotic effect of the dialkyl phosphorofluoridates and of the high toxicity of some of the phosphorodiamidic fluorides, we prepared and examined a 'hybrid' molecule containing the essential features of each type of compound...

Ethyl dimethylphosphoroamidofluoridate was prepared by a similar method [to ethyl phenylphosphoroamidofluoridate]. Its L.D. 50, on intravenous injection into rabbits and also on subcutaneous injection into mice, was 2.5 mg./kg. Toxicity was also determined by inhalation and a Ct (C = concentration, t = 10 min.) of 200 mg./min./cu.m. killed seven out of a batch of eleven rabbits, guinea-pigs, rats, and mice; a Ct of 100 mg./min./cu.m. killed four out of eleven. The compound also posessed myotic properties. Other compounds that we made in this series were much more toxic; and it will be seen that they bear some resemblance to tabun and sarin..."

That latter compound was (Me2N)(EtO)F-P=O --notice the similarity to GV and GP. By "other compounds," I'm going to assume they did the tests with the usual test class of alcohols: a secondary, a cyclic chain, methyl, propyl, a few halogenated ones here and there.

Maybe what we can gather here is that Aminoalcohols are much more toxic than other alkyl chains when attached to OP chains--if that's the case, it could be a lesson for all OP poisons.

[MrSamosa]

Even removal of old CW is pain in ***.

I can't agree with you more on that idea. Even cleaning up after my little experiments with Chloropicrin was a pain, and often literally. Every single drop had to be thoroughly washed down with ethanol, water, napkins, and whatever I used to wipe down surfaces put in a few layers of ziplock baggies before being thrown away (No, this is not a viable means for dealing with disposal...but the way I figured, it won't only be in my trashbag for a few days). Then there was the problem that ethanol made Chloropicrin more volatile... But I digress.

GP and GV. From my understanding, the most effective Nerve Agents resemble Choline most closely, e.g.: VX. With that in mind, it would seem like GP is more effective than GV in two ways: it would be more toxic and it would have a lower molar mass, therefore letting it be more volatile. I'm speculating here and not basing any of this on toxicological data, which I don't have.

It is worth looking at Chapter V of Saunders about "Phosphorodiamidic Fluorides" and "Tabun and Sarin." The section I found of most interest was:

In view of the rapid toxic action and myotic effect of the dialkyl phosphorofluoridates and of the high toxicity of some of the phosphorodiamidic fluorides, we prepared and examined a 'hybrid' molecule containing the essential features of each type of compound...

Ethyl dimethylphosphoroamidofluoridate was prepared by a similar method [to ethyl phenylphosphoroamidofluoridate]. Its L.D. 50, on intravenous injection into rabbits and also on subcutaneous injection into mice, was 2.5 mg./kg. Toxicity was also determined by inhalation and a Ct (C = concentration, t = 10 min.) of 200 mg./min./cu.m. killed seven out of a batch of eleven rabbits, guinea-pigs, rats, and mice; a Ct of 100 mg./min./cu.m. killed four out of eleven. The compound also posessed myotic properties. Other compounds that we made in this series were much more toxic; and it will be seen that they bear some resemblance to tabun and sarin..."

That latter compound was (Me2N)(EtO)F-P=O --notice the similarity to GV and GP. By "other compounds," I'm going to assume they did the tests with the usual test class of alcohols: a secondary, a cyclic chain, methyl, propyl, a few halogenated ones here and there.

Maybe what we can gather here is that Aminoalcohols are much more toxic than other alkyl chains when attached to OP chains--if that's the case, it could be a lesson for all OP poisons.

[MrSamosa]

Even removal of old CW is pain in ***.

I can't agree with you more on that idea. Even cleaning up after my little experiments with Chloropicrin was a pain, and often literally. Every single drop had to be thoroughly washed down with ethanol, water, napkins, and whatever I used to wipe down surfaces put in a few layers of ziplock baggies before being thrown away (No, this is not a viable means for dealing with disposal...but the way I figured, it won't only be in my trashbag for a few days). Then there was the problem that ethanol made Chloropicrin more volatile... But I digress.

GP and GV. From my understanding, the most effective Nerve Agents resemble Choline most closely, e.g.: VX. With that in mind, it would seem like GP is more effective than GV in two ways: it would be more toxic and it would have a lower molar mass, therefore letting it be more volatile. I'm speculating here and not basing any of this on toxicological data, which I don't have.

It is worth looking at Chapter V of Saunders about "Phosphorodiamidic Fluorides" and "Tabun and Sarin." The section I found of most interest was:

In view of the rapid toxic action and myotic effect of the dialkyl phosphorofluoridates and of the high toxicity of some of the phosphorodiamidic fluorides, we prepared and examined a 'hybrid' molecule containing the essential features of each type of compound...

Ethyl dimethylphosphoroamidofluoridate was prepared by a similar method [to ethyl phenylphosphoroamidofluoridate]. Its L.D. 50, on intravenous injection into rabbits and also on subcutaneous injection into mice, was 2.5 mg./kg. Toxicity was also determined by inhalation and a Ct (C = concentration, t = 10 min.) of 200 mg./min./cu.m. killed seven out of a batch of eleven rabbits, guinea-pigs, rats, and mice; a Ct of 100 mg./min./cu.m. killed four out of eleven. The compound also posessed myotic properties. Other compounds that we made in this series were much more toxic; and it will be seen that they bear some resemblance to tabun and sarin..."

That latter compound was (Me2N)(EtO)F-P=O --notice the similarity to GV and GP. By "other compounds," I'm going to assume they did the tests with the usual test class of alcohols: a secondary, a cyclic chain, methyl, propyl, a few halogenated ones here and there.

Maybe what we can gather here is that Aminoalcohols are much more toxic than other alkyl chains when attached to OP chains--if that's the case, it could be a lesson for all OP poisons.

[megalomania]

AN interesting premise... What if we replaced the ethyl ester portion of VX with an aminoalcohol? Might it become yet more toxic? What if we used a fluorine substituted aminoalcohol, like HO-R-N-(R'F)2

[megalomania]

AN interesting premise... What if we replaced the ethyl ester portion of VX with an aminoalcohol? Might it become yet more toxic? What if we used a fluorine substituted aminoalcohol, like HO-R-N-(R'F)2

[megalomania]

AN interesting premise... What if we replaced the ethyl ester portion of VX with an aminoalcohol? Might it become yet more toxic? What if we used a fluorine substituted aminoalcohol, like HO-R-N-(R'F)2

[FUTI]

Imagination is woderfull thing...read and comment if you find this is worth of it.

I asked myself what will happen if we take GP and modify it in this way. Replace F- with O-NX2 (similar to novichok or whatever...) and as I'm supporter of choline theory use him (or something alike) instead of dimethylaminoethanol.

I assume that GP/GV agent work through a suicide substrate mechanism and that higher activity is result of closer resemblance of this agent to actual substrate. Look upon the data about sulfur containing nerve gases in this forum and you will find that similar structures having positive charge at the same distance e.g. -SR2+ have higher activity compared with neutral one e.g. -SR ....sulfur is at the position of nitrogen in aminoethanol in that case so that makes me very much convinced that choline resemblance have its share in this, as well as tetrahedral orientation of substituents around phosphor resembling the transition state for the hydrolysis of acetyl-choline. I didn't found much data about novichok mechanism of action so I don't know how will proposed modification of GP compound will afect its toxicity/activity. Idea behind this is to avoid use of fluorine compound (which makes it dificult to detect) and use substructure which makes compound resistant to normal detoxification protocol (and unfortunately harder to prepare). I'm curious is the mechanism of inactivation with novichok somewhat like covalent "acyl-enzyme complex" like agent-O-NX-O-Ser-Enzyme. The idea Mega had is when I think a little about it on the same line but he prefer alkylation instead. Mega I think that one you proposed have a few "bonus points". Major ones is multi-point attachment to targeted enzyme and formation of stronger carbon-N/O/S bond.

[FUTI]

Imagination is woderfull thing...read and comment if you find this is worth of it.

I asked myself what will happen if we take GP and modify it in this way. Replace F- with O-NX2 (similar to novichok or whatever...) and as I'm supporter of choline theory use him (or something alike) instead of dimethylaminoethanol.

I assume that GP/GV agent work through a suicide substrate mechanism and that higher activity is result of closer resemblance of this agent to actual substrate. Look upon the data about sulfur containing nerve gases in this forum and you will find that similar structures having positive charge at the same distance e.g. -SR2+ have higher activity compared with neutral one e.g. -SR ....sulfur is at the position of nitrogen in aminoethanol in that case so that makes me very much convinced that choline resemblance have its share in this, as well as tetrahedral orientation of substituents around phosphor resembling the transition state for the hydrolysis of acetyl-choline. I didn't found much data about novichok mechanism of action so I don't know how will proposed modification of GP compound will afect its toxicity/activity. Idea behind this is to avoid use of fluorine compound (which makes it dificult to detect) and use substructure which makes compound resistant to normal detoxification protocol (and unfortunately harder to prepare). I'm curious is the mechanism of inactivation with novichok somewhat like covalent "acyl-enzyme complex" like agent-O-NX-O-Ser-Enzyme. The idea Mega had is when I think a little about it on the same line but he prefer alkylation instead. Mega I think that one you proposed have a few "bonus points". Major ones is multi-point attachment to targeted enzyme and formation of stronger carbon-N/O/S bond.

[FUTI]

Imagination is woderfull thing...read and comment if you find this is worth of it.

I asked myself what will happen if we take GP and modify it in this way. Replace F- with O-NX2 (similar to novichok or whatever...) and as I'm supporter of choline theory use him (or something alike) instead of dimethylaminoethanol.

I assume that GP/GV agent work through a suicide substrate mechanism and that higher activity is result of closer resemblance of this agent to actual substrate. Look upon the data about sulfur containing nerve gases in this forum and you will find that similar structures having positive charge at the same distance e.g. -SR2+ have higher activity compared with neutral one e.g. -SR ....sulfur is at the position of nitrogen in aminoethanol in that case so that makes me very much convinced that choline resemblance have its share in this, as well as tetrahedral orientation of substituents around phosphor resembling the transition state for the hydrolysis of acetyl-choline. I didn't found much data about novichok mechanism of action so I don't know how will proposed modification of GP compound will afect its toxicity/activity. Idea behind this is to avoid use of fluorine compound (which makes it dificult to detect) and use substructure which makes compound resistant to normal detoxification protocol (and unfortunately harder to prepare). I'm curious is the mechanism of inactivation with novichok somewhat like covalent "acyl-enzyme complex" like agent-O-NX-O-Ser-Enzyme. The idea Mega had is when I think a little about it on the same line but he prefer alkylation instead. Mega I think that one you proposed have a few "bonus points". Major ones is multi-point attachment to targeted enzyme and formation of stronger carbon-N/O/S bond.

[Chris The Great]

I wouldn't replace the ethyl group on VX, as it is taking the place of the flourine. I would replace the methyl group, I would think that would be more toxic. But we are just guessing here so who knows...

The lack of flourine will also make the agent much easier to weaponize as it will not react with so many materials as the flourine tends to do.


One interesting possibility is the nerve agent EA2192, which is VX but with the ethyl group replaced by a hydroxy group. If we replaced the methyl group on it with a dimethylamino group, we could potentially increase the toxicity (which is almost as high as VX already) and it would hydrolize over a thousand times more slowly than other nerve agents (EA2192 hydrolizes over 1000 times slower than VX, which from what I understand is fairly long lasting compared to some agents).
The hydroxy group also opens the possibility of preparing the nerve agent as a salt, which means no vapour. I am looking into this, it is certainly an interesting possibility. I would think it would act like cyanide salts and rapidly convert into the acid (volatile) form upon contact with an acid. Unfortunatly such nerve agents look more complex to synthesis, although I found a journal on making them. It only covered the main alcohol groups however, nothing on the amino type groups, most likely because these are nearly as toxic as V agents.

I though novichoks had the ONCX2 group, not an NX2 group, however that is an interesting idea.

All these ideas unfortunately probably won't get answers unless actual tests are done....and that would be, as already stated, extremely dangerous and a real pain to clean up. Even the nerve agent precursors are extremely toxic, which would be where the problem would be. I assume anyone doing toxicity tests would make only a few hundred micrograms at most, in solution inside a syringe and then immdietely injected into mice/rabbits/whatever.

[Chris The Great]

I wouldn't replace the ethyl group on VX, as it is taking the place of the flourine. I would replace the methyl group, I would think that would be more toxic. But we are just guessing here so who knows...

The lack of flourine will also make the agent much easier to weaponize as it will not react with so many materials as the flourine tends to do.


One interesting possibility is the nerve agent EA2192, which is VX but with the ethyl group replaced by a hydroxy group. If we replaced the methyl group on it with a dimethylamino group, we could potentially increase the toxicity (which is almost as high as VX already) and it would hydrolize over a thousand times more slowly than other nerve agents (EA2192 hydrolizes over 1000 times slower than VX, which from what I understand is fairly long lasting compared to some agents).
The hydroxy group also opens the possibility of preparing the nerve agent as a salt, which means no vapour. I am looking into this, it is certainly an interesting possibility. I would think it would act like cyanide salts and rapidly convert into the acid (volatile) form upon contact with an acid. Unfortunatly such nerve agents look more complex to synthesis, although I found a journal on making them. It only covered the main alcohol groups however, nothing on the amino type groups, most likely because these are nearly as toxic as V agents.

I though novichoks had the ONCX2 group, not an NX2 group, however that is an interesting idea.

All these ideas unfortunately probably won't get answers unless actual tests are done....and that would be, as already stated, extremely dangerous and a real pain to clean up. Even the nerve agent precursors are extremely toxic, which would be where the problem would be. I assume anyone doing toxicity tests would make only a few hundred micrograms at most, in solution inside a syringe and then immdietely injected into mice/rabbits/whatever.

[Chris The Great]

I wouldn't replace the ethyl group on VX, as it is taking the place of the flourine. I would replace the methyl group, I would think that would be more toxic. But we are just guessing here so who knows...

The lack of flourine will also make the agent much easier to weaponize as it will not react with so many materials as the flourine tends to do.


One interesting possibility is the nerve agent EA2192, which is VX but with the ethyl group replaced by a hydroxy group. If we replaced the methyl group on it with a dimethylamino group, we could potentially increase the toxicity (which is almost as high as VX already) and it would hydrolize over a thousand times more slowly than other nerve agents (EA2192 hydrolizes over 1000 times slower than VX, which from what I understand is fairly long lasting compared to some agents).
The hydroxy group also opens the possibility of preparing the nerve agent as a salt, which means no vapour. I am looking into this, it is certainly an interesting possibility. I would think it would act like cyanide salts and rapidly convert into the acid (volatile) form upon contact with an acid. Unfortunatly such nerve agents look more complex to synthesis, although I found a journal on making them. It only covered the main alcohol groups however, nothing on the amino type groups, most likely because these are nearly as toxic as V agents.

I though novichoks had the ONCX2 group, not an NX2 group, however that is an interesting idea.

All these ideas unfortunately probably won't get answers unless actual tests are done....and that would be, as already stated, extremely dangerous and a real pain to clean up. Even the nerve agent precursors are extremely toxic, which would be where the problem would be. I assume anyone doing toxicity tests would make only a few hundred micrograms at most, in solution inside a syringe and then immdietely injected into mice/rabbits/whatever.

[megalomania]

The reference for dimethylphosphoramidic difluoride is in. Seeing as it is from Liebigs Annalen the article is in German. I tried my best at translating the words and rewriting them to sound like proper English. I shall provide the original as well if anyone wants to double check my translation. I added words to my English version to make it sound correct. Notice the reaction is not specifically for dimethylphosphoramidic difluoride, but is for the general class of alkylphosphoramidic difluorides including R= ethyl, isopropyl, n-butyl, t-butyl, dimethyl, and diethyl phosphoramidic difluoride. The “amine” mentioned in the reaction uses those alkyl groups respectively as R2NH. We would want dimethylamine as our starting material, (CH3)2NH

Difluorphosphorsaure-alkylamide: In einen langhalsigen Rundkolben von 150ccm Inhalt gaben wir 30ccm Toluol und kondensierten dann unter Kuhlung mit flussigem Stickstoff darin 11.5g(0.11 Mol) Phosphoroxyfluorid. Der Rundkolben wurde hierauf in ein Trockeneis/Aceton-Bad gestellt, das Toluol geschmolzen und das festgebliebene POF3 im Toluol fein suspendiert. Zur erhaltenen Suspension gaben wir unter kraftigem Ruhren (Aceton/Trockeneis-Kuhlung) in kleinen Portionen eine abgekuhlte Losung von 0.2 Mol Amin in 50ccm Toluol zu. Es trat eine heftige. exotherme Reaktion ein; unter schwacher Gelbfarbung schied sich Alkylamin-hydrofluorid ab. Das auf Zimmertemperatur erwarmte Reaktionsgemisch haben wir rasch filtriert und das Alkylamin-hydrofluorid mit wenig Toluol gewaschen. Aus dem klaren Filtrat destillierten wir bei ca. 50 Torr das Toluol ab. Dann fraktionierten wir das zuruckgebliebene, orangefarbige Rohprodukt im Vakuum.

Alkylphosphoramidic difluoride: To a 150-mL long-necked round-bottom flask is added 30 mL of toluene cooled with liquid nitrogen, and 11.5 g (0.11 mol) of phosphorus oxyfluoride (POF3) is added. The flask is placed into a dry ice/acetone bath, which suspends the fine particles of solid POF3 in toluene. To this suspension we add a pre-cooled mixture of 0.2 mol of amine (we want dimethylamine) in 50 mL of toluene in small portions with vigorous shaking. A violent exothermic reaction occurs; the product alkylphosphoramidic difluoride will separate as a light yellow layer. The reaction mixture is filtered and allowed to rapidly warm to room temperature. In a separatory funnel the toluene layer is removed. The product layer is shaken with a little toluene and the toluene layer is combined with the rest. The clear toluene portion is distilled off at 50 torr pressure. The crude product layer is added to the undistilled portion and fractionally distilled under vacuum.

A note if I may: I know I wrote to distill off the toluene at 50 torr pressure, but our desired dimethylphosphoramidic difluoride boils at 47-49 C vs. toluene at 110 C. It may be our product is a viscous oil that is not affected by low pressure, or we actually distill off our product instead of toluene in this step.

Now the question becomes how to make phosphorus oxyfluoride. Merck does not list it, but it does list phosphorus oxychloride and oxybromide. Theoretically they should all be made the same way. Toluene and dimethylamine should not be problematic to obtain.

[megalomania]

The reference for dimethylphosphoramidic difluoride is in. Seeing as it is from Liebigs Annalen the article is in German. I tried my best at translating the words and rewriting them to sound like proper English. I shall provide the original as well if anyone wants to double check my translation. I added words to my English version to make it sound correct. Notice the reaction is not specifically for dimethylphosphoramidic difluoride, but is for the general class of alkylphosphoramidic difluorides including R= ethyl, isopropyl, n-butyl, t-butyl, dimethyl, and diethyl phosphoramidic difluoride. The “amine” mentioned in the reaction uses those alkyl groups respectively as R2NH. We would want dimethylamine as our starting material, (CH3)2NH

Difluorphosphorsaure-alkylamide: In einen langhalsigen Rundkolben von 150ccm Inhalt gaben wir 30ccm Toluol und kondensierten dann unter Kuhlung mit flussigem Stickstoff darin 11.5g(0.11 Mol) Phosphoroxyfluorid. Der Rundkolben wurde hierauf in ein Trockeneis/Aceton-Bad gestellt, das Toluol geschmolzen und das festgebliebene POF3 im Toluol fein suspendiert. Zur erhaltenen Suspension gaben wir unter kraftigem Ruhren (Aceton/Trockeneis-Kuhlung) in kleinen Portionen eine abgekuhlte Losung von 0.2 Mol Amin in 50ccm Toluol zu. Es trat eine heftige. exotherme Reaktion ein; unter schwacher Gelbfarbung schied sich Alkylamin-hydrofluorid ab. Das auf Zimmertemperatur erwarmte Reaktionsgemisch haben wir rasch filtriert und das Alkylamin-hydrofluorid mit wenig Toluol gewaschen. Aus dem klaren Filtrat destillierten wir bei ca. 50 Torr das Toluol ab. Dann fraktionierten wir das zuruckgebliebene, orangefarbige Rohprodukt im Vakuum.

Alkylphosphoramidic difluoride: To a 150-mL long-necked round-bottom flask is added 30 mL of toluene cooled with liquid nitrogen, and 11.5 g (0.11 mol) of phosphorus oxyfluoride (POF3) is added. The flask is placed into a dry ice/acetone bath, which suspends the fine particles of solid POF3 in toluene. To this suspension we add a pre-cooled mixture of 0.2 mol of amine (we want dimethylamine) in 50 mL of toluene in small portions with vigorous shaking. A violent exothermic reaction occurs; the product alkylphosphoramidic difluoride will separate as a light yellow layer. The reaction mixture is filtered and allowed to rapidly warm to room temperature. In a separatory funnel the toluene layer is removed. The product layer is shaken with a little toluene and the toluene layer is combined with the rest. The clear toluene portion is distilled off at 50 torr pressure. The crude product layer is added to the undistilled portion and fractionally distilled under vacuum.

A note if I may: I know I wrote to distill off the toluene at 50 torr pressure, but our desired dimethylphosphoramidic difluoride boils at 47-49 C vs. toluene at 110 C. It may be our product is a viscous oil that is not affected by low pressure, or we actually distill off our product instead of toluene in this step.

Now the question becomes how to make phosphorus oxyfluoride. Merck does not list it, but it does list phosphorus oxychloride and oxybromide. Theoretically they should all be made the same way. Toluene and dimethylamine should not be problematic to obtain.

[megalomania]

The reference for dimethylphosphoramidic difluoride is in. Seeing as it is from Liebigs Annalen the article is in German. I tried my best at translating the words and rewriting them to sound like proper English. I shall provide the original as well if anyone wants to double check my translation. I added words to my English version to make it sound correct. Notice the reaction is not specifically for dimethylphosphoramidic difluoride, but is for the general class of alkylphosphoramidic difluorides including R= ethyl, isopropyl, n-butyl, t-butyl, dimethyl, and diethyl phosphoramidic difluoride. The “amine” mentioned in the reaction uses those alkyl groups respectively as R2NH. We would want dimethylamine as our starting material, (CH3)2NH

Difluorphosphorsaure-alkylamide: In einen langhalsigen Rundkolben von 150ccm Inhalt gaben wir 30ccm Toluol und kondensierten dann unter Kuhlung mit flussigem Stickstoff darin 11.5g(0.11 Mol) Phosphoroxyfluorid. Der Rundkolben wurde hierauf in ein Trockeneis/Aceton-Bad gestellt, das Toluol geschmolzen und das festgebliebene POF3 im Toluol fein suspendiert. Zur erhaltenen Suspension gaben wir unter kraftigem Ruhren (Aceton/Trockeneis-Kuhlung) in kleinen Portionen eine abgekuhlte Losung von 0.2 Mol Amin in 50ccm Toluol zu. Es trat eine heftige. exotherme Reaktion ein; unter schwacher Gelbfarbung schied sich Alkylamin-hydrofluorid ab. Das auf Zimmertemperatur erwarmte Reaktionsgemisch haben wir rasch filtriert und das Alkylamin-hydrofluorid mit wenig Toluol gewaschen. Aus dem klaren Filtrat destillierten wir bei ca. 50 Torr das Toluol ab. Dann fraktionierten wir das zuruckgebliebene, orangefarbige Rohprodukt im Vakuum.

Alkylphosphoramidic difluoride: To a 150-mL long-necked round-bottom flask is added 30 mL of toluene cooled with liquid nitrogen, and 11.5 g (0.11 mol) of phosphorus oxyfluoride (POF3) is added. The flask is placed into a dry ice/acetone bath, which suspends the fine particles of solid POF3 in toluene. To this suspension we add a pre-cooled mixture of 0.2 mol of amine (we want dimethylamine) in 50 mL of toluene in small portions with vigorous shaking. A violent exothermic reaction occurs; the product alkylphosphoramidic difluoride will separate as a light yellow layer. The reaction mixture is filtered and allowed to rapidly warm to room temperature. In a separatory funnel the toluene layer is removed. The product layer is shaken with a little toluene and the toluene layer is combined with the rest. The clear toluene portion is distilled off at 50 torr pressure. The crude product layer is added to the undistilled portion and fractionally distilled under vacuum.

A note if I may: I know I wrote to distill off the toluene at 50 torr pressure, but our desired dimethylphosphoramidic difluoride boils at 47-49 C vs. toluene at 110 C. It may be our product is a viscous oil that is not affected by low pressure, or we actually distill off our product instead of toluene in this step.

Now the question becomes how to make phosphorus oxyfluoride. Merck does not list it, but it does list phosphorus oxychloride and oxybromide. Theoretically they should all be made the same way. Toluene and dimethylamine should not be problematic to obtain.

[MrSamosa]

Is there any reason why Phosphorus Oxyfluoride is used in this reaction to begin with? It would really make things more complicated than using Phosphorus Oxychloride would, given that POF3 is a gas.

If POF3 is made the same ways POCl3, that could entail reacting Phosphoric Acid with Carbonyl Fluoride at a high temperature or adding water to PF3...

Really, if POCl3 could be used, that would definitely be the better choice. In fact, it might not even require as much cooling as using POF3 would.

[MrSamosa]

Is there any reason why Phosphorus Oxyfluoride is used in this reaction to begin with? It would really make things more complicated than using Phosphorus Oxychloride would, given that POF3 is a gas.

If POF3 is made the same ways POCl3, that could entail reacting Phosphoric Acid with Carbonyl Fluoride at a high temperature or adding water to PF3...

Really, if POCl3 could be used, that would definitely be the better choice. In fact, it might not even require as much cooling as using POF3 would.

[MrSamosa]

Is there any reason why Phosphorus Oxyfluoride is used in this reaction to begin with? It would really make things more complicated than using Phosphorus Oxychloride would, given that POF3 is a gas.

If POF3 is made the same ways POCl3, that could entail reacting Phosphoric Acid with Carbonyl Fluoride at a high temperature or adding water to PF3...

Really, if POCl3 could be used, that would definitely be the better choice. In fact, it might not even require as much cooling as using POF3 would.

[simply RED]

Immagine the toxicity of POF3...

" POCl3 has the toxicity of phosgene."

[simply RED]

Immagine the toxicity of POF3...

" POCl3 has the toxicity of phosgene."

[simply RED]

Immagine the toxicity of POF3...

" POCl3 has the toxicity of phosgene."

[megalomania]

That is what I was thinking, go with POCl3, make dimethylphosphoramidochloridic acid 2-(dimethylamino)ethyl ester, and swap the chlorine with fluorine in an extra step. One of the methods of making sarin does that.

The cooling is apparently only necessary to condense the POF3 to the solid state in toluene. With POCl3 this could be done in a conventional salt-ice bath.

The rest of the article concerns a thio derivitative of the same molecule, R2N-PSF2. Dimethylphosphoramidothioic difluoride for example. I wonder if this would have any value? It is made from PSF3.

There is another issue worth bringing up for GP and GV compounds. According to an article in Phosphorus, Sulfur, and Silicon, 179:49–53, 2004 titled "IDENTIFICATION OF THE ISOMERIC TRANSFORMATION PRODUCT FROM 2-(DIMETHYLAMINO)ETHYL-(DIMETHYLPHOSPHORAMIDO)FLUORIDATE"
GV is unstable, and it rapidly converts to a much less toxic crystalline compound. GV is only stable at temperatures below -20 C. The conversion process takes 3 months as described in the article. This is probably why this particular nerve gas has not been heard of in military circles, it cannot be mass produced and stockpiled. The conversion happens even in the absence of air, light, or water, so storing this stuff is out of the question. A chemical shell or warhead would be the prefect reactor to convert it to the inert form.

This article also includes the outline of the synthesis for GV:

2-(Dimethylamino)ethyl-(dimethylphosphoramido)fluoridate (IV, CAS
141102-74-1) was synthesized by reaction of (dimethylamido)phosphoryldifluoride
with sodium 2-(dimethylamino)ethoxide and purified
by distillation in vacuo. Conversion of compound (IV) into the solid product
was performed in sealed ampoules in the dark at 21◦C for 3 months.


That settles the rogue sodium ion in the graphic I provided, the starting material we want is sodium 2-(dimethylamino)ethoxide. We should be able to make that by adding sodium metal to dimethylaminoethanol.

I have a suspicion these guys screwed up when they published the details of this synthesis. Obviously GV is a state secret, why else is there no other published data about making it until now?

[megalomania]

That is what I was thinking, go with POCl3, make dimethylphosphoramidochloridic acid 2-(dimethylamino)ethyl ester, and swap the chlorine with fluorine in an extra step. One of the methods of making sarin does that.

The cooling is apparently only necessary to condense the POF3 to the solid state in toluene. With POCl3 this could be done in a conventional salt-ice bath.

The rest of the article concerns a thio derivitative of the same molecule, R2N-PSF2. Dimethylphosphoramidothioic difluoride for example. I wonder if this would have any value? It is made from PSF3.

There is another issue worth bringing up for GP and GV compounds. According to an article in Phosphorus, Sulfur, and Silicon, 179:49–53, 2004 titled "IDENTIFICATION OF THE ISOMERIC TRANSFORMATION PRODUCT FROM 2-(DIMETHYLAMINO)ETHYL-(DIMETHYLPHOSPHORAMIDO)FLUORIDATE"
GV is unstable, and it rapidly converts to a much less toxic crystalline compound. GV is only stable at temperatures below -20 C. The conversion process takes 3 months as described in the article. This is probably why this particular nerve gas has not been heard of in military circles, it cannot be mass produced and stockpiled. The conversion happens even in the absence of air, light, or water, so storing this stuff is out of the question. A chemical shell or warhead would be the prefect reactor to convert it to the inert form.

This article also includes the outline of the synthesis for GV:

2-(Dimethylamino)ethyl-(dimethylphosphoramido)fluoridate (IV, CAS
141102-74-1) was synthesized by reaction of (dimethylamido)phosphoryldifluoride
with sodium 2-(dimethylamino)ethoxide and purified
by distillation in vacuo. Conversion of compound (IV) into the solid product
was performed in sealed ampoules in the dark at 21◦C for 3 months.


That settles the rogue sodium ion in the graphic I provided, the starting material we want is sodium 2-(dimethylamino)ethoxide. We should be able to make that by adding sodium metal to dimethylaminoethanol.

I have a suspicion these guys screwed up when they published the details of this synthesis. Obviously GV is a state secret, why else is there no other published data about making it until now?

[megalomania]

That is what I was thinking, go with POCl3, make dimethylphosphoramidochloridic acid 2-(dimethylamino)ethyl ester, and swap the chlorine with fluorine in an extra step. One of the methods of making sarin does that.

The cooling is apparently only necessary to condense the POF3 to the solid state in toluene. With POCl3 this could be done in a conventional salt-ice bath.

The rest of the article concerns a thio derivitative of the same molecule, R2N-PSF2. Dimethylphosphoramidothioic difluoride for example. I wonder if this would have any value? It is made from PSF3.

There is another issue worth bringing up for GP and GV compounds. According to an article in Phosphorus, Sulfur, and Silicon, 179:49–53, 2004 titled "IDENTIFICATION OF THE ISOMERIC TRANSFORMATION PRODUCT FROM 2-(DIMETHYLAMINO)ETHYL-(DIMETHYLPHOSPHORAMIDO)FLUORIDATE"
GV is unstable, and it rapidly converts to a much less toxic crystalline compound. GV is only stable at temperatures below -20 C. The conversion process takes 3 months as described in the article. This is probably why this particular nerve gas has not been heard of in military circles, it cannot be mass produced and stockpiled. The conversion happens even in the absence of air, light, or water, so storing this stuff is out of the question. A chemical shell or warhead would be the prefect reactor to convert it to the inert form.

This article also includes the outline of the synthesis for GV:

2-(Dimethylamino)ethyl-(dimethylphosphoramido)fluoridate (IV, CAS
141102-74-1) was synthesized by reaction of (dimethylamido)phosphoryldifluoride
with sodium 2-(dimethylamino)ethoxide and purified
by distillation in vacuo. Conversion of compound (IV) into the solid product
was performed in sealed ampoules in the dark at 21◦C for 3 months.


That settles the rogue sodium ion in the graphic I provided, the starting material we want is sodium 2-(dimethylamino)ethoxide. We should be able to make that by adding sodium metal to dimethylaminoethanol.

I have a suspicion these guys screwed up when they published the details of this synthesis. Obviously GV is a state secret, why else is there no other published data about making it until now?

[Chris The Great]

I found a ref for these compounds from sometime in 1960. They both broke down very quickly, the O-ethyl agent in days and the isopropyl agent in months. The author even stated that they had no use at all for CW, but could be useful for medical experiments.
Toxicity was hard to determine unless they where reacted with methyl iodide for form the trimethylammonium iodide salt, since they hydrolyse nearly instantly (ie in seconds) in water. The salts where extremely toxic but still hydrolyzed very rapidly.

So basically, these are old news, and completely useless for CW use. I will post the exact synth details as well as all the info on breakdown/hydrolysis.

I found the article completely by accident, it was refferenced by a article on VX I had just gotten, and was in the same journal, by the same author. Acta chemica scandanavia or something like that. Some dumbass screwed up the microfilm so there were a few pages of it in the middle of nowhere... luckily I found all the pages completely by accident while rewinding the microfilm to get to the article. :cool:
So the info is out there mega, it's just hiding in some obscure microfilm copy of an obscure journal spliced out of order and not referrenced by anyone since they all thought it to be useless.

Sorry for the let down, I was really excited when I found the article, but then got dissappointed after reading it.

[megalomania]

I would be interested in knowing what that reference is if you still have it. From what you say it seems as if those compounds hydrolyze in seconds when passed directly into water. It is possible they may last several minutes, or even hours, in the open air depending what the humidity is at the time and if released indoors or outdoors.

Imagine a situation where your troops release the chemical weapon into an enemy bunker, and then follow up with a forced entry a few minutes later. The gas would have killed or incapacitated the subjects in seconds, and would subsequently have become non-lethal. No need for bulky protective suits or masks for your men. Another example is you making a quick getaway from the feds during a raid, they get gassed, and in a few minutes you make your escape.

[nbk2000]

To Dipterex:

Regurgitation of links from other threads, and posting them repeatedly over several days, doesn't earn you any gratitude from me. :mad:

Newbies step out of the sandbox of the Water Cooler and into the 'real' Forum sections at their own risk.

Guess you stepped on a mine hidden under the grass. :p

[Chris The Great]

I still have it, I am slow in typing it up. Rest assured it will get posted eventually, hopefully sooner rather than later. It just slips my mind will all sorts of other stuff going on.

There is a slight difference between what was in the journals and GV/GP, in that the agents described by the journal have a methyl group instead of a dimethylamino group. This doesn't make much of a difference for hydrolysis though, since it takes place at the P-F bond.

The reference is Methyl-fluoro-phosphorylcholines: Two synthetic Cholinergic Drugs and Their Tertiary Homologues, L. E. Tammelin, Acta Chemica Scandinavica 11 (1957) pages 859-865

[nbk2000]

2-Dimethylaminoethanol [AKA N-N-Dimethylaminoethanol](DMAE), C4H11NO, CAS #108-01-0

This is listed as an chemical exempt from the CW export control list.

Is this the same Dimethylaminoethanol being discussed above?

If CAS #108-01-0 is useable as a CW precursor, I found a place that sells it in ounce quantities for less than $6. Cheap enough for making a couple grams of G-agent.

[Chris The Great]

Identical. :D

The other option is synthesis, chloroethanol (formed by chlorinating antifreeze, IIRC you, NBK, have done this before when synthesizing mustard) reacting with dimethylamine (ammonium chloride and formaldehyde, or hexamine, formaldehyde and HCl) under heat and pressure to keep in the dimethylamine will give the hydrochloride salt of dimethylaminoethanol.
Add to NaOH to get the freebase.
The bromide would work even better, in which HBr is used instead of HCl. To get that, add HCl to NaBr from your local hot tub supplier (or Walmart). You could probably just mix and heat the two without needing to react them as gases like with HCl.

I would definately choose purchasing over synthesizing for "trial runs" or if you only want to make a small amount of agent.
The synthesis I just described is simple on paper but will undoutably be quite involved and have numerous problems, especially if you only want a small amount.

For VX analogs (more toxic and more stable) you'd need to convert to a thiol. I posted what was below but then remembered GP doesn't have the sulfur in it. That makes synthesis straight from the purchased compound possible. So being able to buy it is definately a big time saver for the synthesis.

For conversion to the thiol, some methods of synthesizing those have been recently discussed in the thread "long term area denial". The alcohol group can easily be converted to a halogen with the corresponding acid (maybe) or the thionyl halide (ie thionyl chloride, bromide, etc) for the methods that require it.
Personally, I would react with chlorosulfuric acid to get the sulfuric acid ester, then react that with a base (to get a salt) and then a hydrogen sulfide to give a sulfate and the desired thiol:
(CH3)2NCH2CH2OH + HSO3Cl -> [(CH3)2NCH2CH2OSO3H]HCl
[(CH3)2NCH2CH2OSO3H]HCl + 2NaOH -> (CH3)2NCH2CH2OSO3Na + NaCl
(CH3)2NCH2CH2OSO3Na + NaSH -> Na2SO4 + (CH3)2NCH2CH2SH

Thiols do not react with phosphorus chlorides normally, but on the addition of a base such as triethylamine the reaction proceeds readily and in high yeild.

[sprocket]

One interesting possibility is the nerve agent EA2192, which is VX but with the ethyl group replaced by a hydroxy group. If we replaced the methyl group on it with a dimethylamino group, we could potentially increase the toxicity (which is almost as high as VX already) and it would hydrolize over a thousand times more slowly than other nerve agents (EA2192 hydrolizes over 1000 times slower than VX, which from what I understand is fairly long lasting compared to some agents).

EA2192 which is one of the hydrolisation products of VX (~35% in distilled water) is indeed nearly as toxic as VX, but with one significant difference; it doesn't penetrate the skin. This is most likely an effect of the hydroxyl group, so replacing the methyl group won't make it skin penetrating.

Since V-type nerve agents have low volatility (10mg/m³ for VX at 25°C) the main route of exposure is skin contact, making penetration an important factor.

It might not be completely useless though, we're still talking about an extremely toxic substance. Potential uses are long term indoor area denial and poisonous projectiles.

[inviernomudo]

Hello.

There are some very interesting articles in Acta chemica scandinavica 50 years ago. Perhaps they are of some interest. I will check if they are accessible in our biblioteca.


- B. Hansen. The Addition of Dimethylamine to Propylene Sulphide. Acta Chem.Scandinavica 13 (1):151-158, 1959.
- B. Hansen. The Preparation of Thiocholine Esters. Acta Chem.Scandinavica 13 (1):159-162, 1959.
- L.-E. Tammelin. Methyl-fluoro-phosphorylcholines. Acta Chem.Scandinavica 11 (5):859-865, 1957.
- L.-E. Tammelin. Isomerisation of w-Dimethylaminoethyl-diethyl-thionophosphate. Acta Chem.Scandinavica 11 (10):1738-1744, 1957.
- L.-E. Tammelin. Dialkoxy-phosphorylthiocholines, Alkoxy-methyl- phosphorylthiocholines and Analogous Choline Esters. Acta Chem.Scandinavica 11:1340-1349, 1957.


(Double posting is a No-No here, that results in banning. Only thing that saved you was the citations. Don't do it again. NBK)

[megalomania]

A compound on the order of toxicity as VX, but without the skin penetration would still be a valuable toxin under the right circumstances. As an airborne spray it would still be lethal if inhaled. It sounds like it could contaminate a water supply. It would still serve as a highly effective area denial weapon (would you want to walk through it?). Perhaps it could be absorbed into an inert powder and spread as a dusty agent?

This may also serve as an effective “training” weapon. Since it lacks the ability to kill just by getting it on you, one would require less rigorous lab skills and expensive equipment in making this substance. It would also be safer to store, transport, and deploy in the field. One could essentially train themselves in chemical warfare and hone their art of weaponization using such a compound.

VX with training wheels :)

Hmm, since VX takes about 3 weeks of environmental exposure in summer weather before it is rendered harmless, decreasing its hydrolyzability 1000 fold should make for one hell of a long cleanup. I am not saying it would sit around for years since heat and sunlight play a role as well, but a few months of contamination could be feasible. Considering area denial is essentially a matter of economic cost (the longer you can’t use a structure the more inconvenience, aka money, it costs you), and the safest cleanup tactic with VX is to just let it sit, having something that increases that inconvenience make for a more effective weapon.

Just a thought, would the usual application of DMSO possibly make EA2192 be able to penetrate the skin?

[Chris The Great]

Thanks for the refs... I'll pick them up next time I am at the university. And I'll try to convert what I have found into pdfs, though at the moment I'm not exactly sure the best way to go about doing so. Mega probably has most of the refs but I'm sure the rest of you would appreciate them.


It might be possible to use DMSO... I remember I saw something before about skin penetration with this compound. I can't remember where, but I'll look through my files later and see if I can dig up anything, maybe a ref on it.

EA2192 is already a "dusty" agent, it is a non-volatile solid at STP. It is very soluble in water, so although it does NOT get hydrolysized, it would wash away quite easily, like salt. So soil or water supply contaimination would probably work, but area denial except in very dry areas probably will prove to be ineffective. It is also only ~15% (or thereabouts IIRC) as toxic as VX by the oral route, and being a dust inhalation might not be that effecient.
The fact it is a solid does make it much easier to prepare and handle however. It would make an effective "training" agent, assuming that the synthesis works out similarily (it might precipitate out from the non-polar solvents generally used in the preparations).

I am just entering my exam weeks right now, so no guarantees on the speed of the data delivery, but I'll get it eventually.


It is good to see you back Mega :D

[nbk2000]

Why not combine agents?

Have the hydrolysis product (GVo) mixed with mustard or other vesicant.

Anyone who gets the liquid on them will die quickly from the absorbed GVo carried through their skin by the mustard, just like a nerve agent.

After the liquid vesicant mist has settled, it creates an immediate vapor hazard afterwhich, once that's evaporated away, the GVo dust remains behind to furthur contaminate and blow around.

Since it's water-soluble, there's your weaponization solvent. :D

Or, dissolve in water, absorb into carrier agent, dehydrate and powder, disperse IN target. I'm thinking buildings here.

Imagine explosively dispersing a few pounds of talcum powder in an office building.

Now imagine having to attempt removal of literally every trace of said powder as, at even 15% of the toxicity of VX, the stuff is far more toxic than cyanide, and anyone scuffing their feet across the carpet will kick up a lethal dose. :p

Inhalation is almost always more effective than ingestion, as the lungs present a far more rapid absorption route, with no destructive acids or enzymes to degrade the poison.

Win, win! :)

[Chris The Great]

I like the idea with mustard! That would probably be very effective.

My doubt about inhalation is that the human body is pretty good with stopping small fibers from reaching the lungs. Obviously, get it small enough and they'll get in (asbestos) however if the particles are too large they would get stuck in the nose and throat, and perhaps only give moderate toxicity to those affected. OTOH it might end up being very effective.
The talcum powder idea would be effective in any case though, for a terror weapon. Even if the casualties aren't that high, the cost of cleanup would be enormous.
AND since the agent is non-volatile, most detection methods would not pick it up! Only if they tested the powder directly, which their fancy electronic sniffers are not meant to do.

I have had an idea just now. The most likely reason EA2192 is so resistant to hydrolysis is that hydrolysis takes place by attack from OH- ions. Since EA2192 is an acid, the main "nerve gas" part of the molecule will be negative when the hydrogen dissociates into H3O+. Since it's negative, there isn't any way for the OH- to easily attack it since like charges repel.
It is likely that by preparing the sodium/potassium salt of the compound, it would be in the dissociated form even more, and hence even less vunerable to hydrolysis. OTOH the increased concentration of OH- ions in the water might remove any gain from this. It would be something to try if you did use it to poison the water supply.

[inviernomudo]

Hello again.
I will do some research in the next future after studying some publications. Very interesting are some Russian literature about possible novichok precursor molecules.
Sokolov et al. "Reaction of 1,1-dichloro-1-nitrosoethane with phosphorus oxychloride in the presence of zinc", Russian Chemical Bulletin, 37:1506, (1988)
and
Sokolov et al. "O-alkylchloroformimino O-alkyl methylphosphonates" Russian Chemical Bulletin, 37:989-991, (1988)
Compounds we are talking about are (CH3)(RO)PO-ON=CR'Cl

Another interesting article:
Wu and Casida "Ethyl Octylphosphonofluoridate and Analogs: Inhibitors of Neuropathy Target Esterase", Chem.Res.Toxicol., 8:1070-1075 (1995)
with a synthesis for some phosphorofluoridates.

[FullMetalJacket]

.. Just wow.

Just when i thought I was getting into the upper echelons of knowledge and... whammo. I read a thread like this. I'm about as out of depth as I was reading haemotology textbooks in grade school because I wanted to see if I could give my teacher sickle-cell anemia. Time to go to the library, methinks.