Sciencemadness Discussion Board

Code for 'diester'?

Ritter - 20-6-2008 at 13:25

In War of Nerves by Jonathan B. Tucker (Anchor, 2006), he quotes one of the inventors describing the VX process flow developed at Edgewood as follows:

1. PCl3 + CH4 > CH3PCl2 (dichloro[methyl]phosphine) (code: SW)

2. SW + EtOH > 'diester' (diethyl methylphosphonite)

3. 'diester' + 2-(diisopropylamino)ethanol + > 'tranester' (code: QL) (O-ethyl O-2-diisopropylaminoethyl methylphosphonite)

4. QL + S8 (code: NE) or dimethyl polysulfide mixture (code: NM) > VX

Since most of the other components in this chain have 2-letter codes, I'm wondering if anyone knows the code for 'diester'?

[Edited on 20-6-2008 by Ritter]

[Edited on 20-6-2008 by Ritter]

[Edited on 21-6-2008 by Ritter]

Sauron - 20-6-2008 at 14:02

That's a sketchy, incomplete and at least partially very dubious scheme.

I can think of a few good ways to prepare MePCl2, but methane + PCl3 isn't one of them.

The transesterification process is well described in the open lit. in JACS and JOC papers by F.W.Hoffmann et al of Edgewood and in the UK patents. No mention is made that I recall of a transesterification catalyst.

My advice is to stick to the chemical literature and leave the scribblings of journalists and their fellow travellers to the masses.

Ritter - 20-6-2008 at 15:49

Quote:
Originally posted by Sauron
That's a sketchy, incomplete and at least partially very dubious scheme.

I can think of a few good ways to prepare MePCl2, but methane + PCl3 isn't one of them.


Thanks but I suggest you check the following references on exactly this process as described:

J Am Chem Soc 84, 851-854 (1962)
US3210418
US3519685
US3709932
Quote:
The transesterification process is well described in the open lit. in JACS and JOC papers by F.W.Hoffmann et al of Edgewood and in the UK patents. No mention is made that I recall of a transesterification catalyst.


I'd appreciate your sending some lit references. Pdfs would be appreciated. I could not locate a relevant UK patent to Friedrich Hoffmann in the EPO.

Transesterification reactions usually don't happen spontaneously. Patents I've seen on related substrates require a basic catalyst, as in an amine or an alkoxide. See US4146530 for example.
Quote:
My advice is to stick to the chemical literature and leave the scribblings of journalists and their fellow travellers to the masses.


Tucker's information came from an interview with Sigmund R. Eckhaus, one of the process' inventors & currently a consultant at the U.S. Arms Control & Disarmament Agency. I would think he knew what he was talking about in describing the Edgewood process that he helped develop. And Tucker has both a Ph.D. & is a chemical weapons specialist at the Center for Nonproliferation Studies. If you are not familiar with this book, I suggest you borrow a copy from the public library.

Here is the full text (p. 159 in his book) describing the synthesis of SW developed at Edgewood:
Quote:
It involved reacting phosphorous trichloride (PCl3) with methane gas (CH4) at high temperature for form the intermediate CH3PCl2, referred to by the code name "SW." Because this compound reacted violently with water, caught fire in the presence of moist air, and was highly corrosive, it had to be synthesized inside a coil of high-nickel steel from which the oxygen had been purged and replaced with inert nitrogen gas.


I would hardly categorize this type of obviously detailed information as the scribblings of journalists and their fellow travellers

[Edited on 20-6-2008 by Ritter]

Ritter - 20-6-2008 at 17:33

Since FMC Corp was one of the major contractors hired by the U.S. to build the VX plant, it is no coincidence that they should have filed patents on the process for making SW as described in Tucker's book. Ref their patent US3210418. See http://tinyurl.com/65fqow.

ScienceSquirrel - 20-6-2008 at 17:56

At one time I worked in a laboratory that routinely prepared phosphines for use as ligands and precursors to other chemicals.
We made MePCl2 on a multigram scale and we did not muck about with the methane and phosphorous trichloride reaction.
But it is very nasty stuff so making and handling it without acess to a good fume cupboard, manifold and Schlenk tubes is a bad idea.

Sauron - 20-6-2008 at 20:27

I don't think anyone is talking about actually making methyldichlorophosphine, and most especially not outside of a hood, and under inert atmosphere and anhydrous conditions.

What is being discussed is how it was done in the 50s and 60s.

I have previously described the preparation of MePCl2, UTFSE.

I have previously posted the UK patents. READ MY POST. The UK patents were not to F.W.Hoffmann, the JACS articles were by F.W.Hoffmann as principle author. Use the ACS Pubs search engine.

If you are such a font of knowledge on VX, why do you find it necessary to come here to this forum and ask for military code designations that are not in the open literature?

That is not amateur chemistry. Chemistry discussions are what this forum is about.

I for one won't be shovelling any pdf's your way, Ritter, because I don't know who you are or what your game might be.

There has been quite a proliferation of books on this general topic, and they often contradict each other as to details. It is best to rely on the CHEMICAL LITERATURE and not on polemics by non-chemists (including as I said, journalists and worse.)

By the way I used to supply Food Machinery Corporation aka FMC in San Jose CA with various items.

[Edited on 21-6-2008 by Sauron]

Sauron - 20-6-2008 at 20:53

I assume you are familiar with dichlor? MeP(O)Cl2

It is a trivial matter to prepare this compound, from PCl3, MeCl and AlCl3. The solid complex thus formed can be converted to dichlor or directly to diesters.

Dichlor can be converted to MeP(S)Cl2 by the action of various reagents.

This compound can be readily desulfurized to SW.

As dichlor formed one of the large scale process steps for production of GB and GD etc, and was thus on hand in bulk, this is a sensible way to prepare MePCl2 without recourse to high temperature processes.

The above is however not the convenient benchtop prep of MePCl2 that I have previously described and documented.

BTW the ACDA is a joke. Center for Nonproliferation Studies? Akin to the dance band on the Titanic. Doing a bangup job, they are. Ask the Iranians, the North Koreans, ask various Malaysian physicists. And I included CWC in this hypocrisy. Genies once loosed are notoriously hard to rebottle and Pandora's box, once opened, will never be refilled.

Sauron - 20-6-2008 at 22:12

ACS Pubs advanced search in Author field returns 27 hits for Friedrich W.Hoffmann (or without the middle initial) of Edgewood, many of them coauthored by Thomas C Simmons, someone I used to know personally and who was still at Edgewood in mid 80s.

The most pertinent of these is:

Organic Phosphorus Compounds. IV.1 A Study of the Transesterification of Dialkyl Alkylphosphonites
Friedrich W. Hoffmann, Robert G. Roth, Thomas C. Simmons
J. Am. Chem. Soc.; 1958; 80(22); 5937-5940. DOI: 10.1021/ja01555a012

-----------------

If you simply use the forum search engine you will find, if you search for methyldichlorophosphine, an article in the (password protected) References section on this prep.

MePCle is prepared conveniently in lab from the same comples of MeCl, PCl3 and AlCl3 as discussed above. Rather than hydrolysis to MeP(O)Cl2 or alcoholysis to a symmetrical diester of methylphosphonic acid, the complex is reduced with PhPCl2 in presence of POCl3.



[Edited on 21-6-2008 by Sauron]

Ritter - 21-6-2008 at 05:48

Quote:
Originally posted by Sauron
I don't think anyone is talking about actually making methyldichlorophosphine, and most especially not outside of a hood, and under inert atmosphere and anhydrous conditions.

What is being discussed is how it was done in the 50s and 60s.

I have previously described the preparation of MePCl2, UTFSE.


I was unable to find this post using the SEARCH function here. But there are a number of published ways to make SW. I did find where this CH4/PCl3 chemistry was posted by DDTea from a different source.

BTW, the correct nomenclature for this compound (at least the version generated by ChemDraw) is dichloro(methyl)phosphine.
Quote:
I have previously posted the UK patents. READ MY POST. The UK patents were not to F.W.Hoffmann, the JACS articles were by F.W.Hoffmann as principle author. Use the ACS Pubs search engine.


I'd read your post if I could find it. You're not being very helpful. Why the antagonism?
Quote:
If you are such a font of knowledge on VX, why do you find it necessary to come here to this forum and ask for military code designations that are not in the open literature?


I originally found this forum while searching for bits & pieces on VX chemistry, which has been discussed at length here. I came here to hopefully fill in some of the missing pieces and perhaps share some ideas I've had on alternative syntheses of various intermediates. I did not expect a negative reception on this topic or simply my presence. That's usually considered poor nettiquette.
Quote:
That is not amateur chemistry. Chemistry discussions are what this forum is about.


Well, VX chemistry has been discussed here at length as both a historical topic and a subject of amateur chemistry. I feel that QL is within reach of the amateur chemist. Imagine not making VX but making a non-toxic precursor that is only one simple step away from it! That would be a real technical & intellectual achievement.
Quote:
I for one won't be shovelling any pdf's your way, Ritter, because I don't know who you are or what your game might be.


Too bad you feel that way. But I can understand your negative reaction to my pointing out that you didn't know what you were talking about in terms of SW synthesis chemistry when you contradicted facts that I had previously confirmed by reading the patents.
Quote:
There has been quite a proliferation of books on this general topic, and they often contradict each other as to details. It is best to rely on the CHEMICAL LITERATURE and not on polemics by non-chemists (including as I said, journalists and worse.)




Since I have a degree in chemistry & over 40 years of experience in all aspects of the field, from sales & marketing of custom intermediates to starting & successfully running my own manufacturing company and to doing kilo-lab-scale R&D & manufacturing of custom intermediates to consulting on pharma IP, I agree completely that there is no substitute for the primary source literature. As the saying goes, a day in the library is worth a week in the lab. But this is an amateur interest for me. I don't have time or money to drive an hour each way to the chem library at the local university to copy articles, and most of the stuff we're talking about would be accessible online only via the ACS' DDS or File Beilstein on STN, both of which are very expensive. I hoped that this forum would give me access to knowledge & articles that had already been acquired, but I guess not. Too bad. You're turning a positive into a negative for no valid reason that I can discern.

Ritter - 21-6-2008 at 06:01

Quote:
Originally posted by Sauron
I assume you are familiar with dichlor? MeP(O)Cl2

It is a trivial matter to prepare this compound, from PCl3, MeCl and AlCl3. The solid complex thus formed can be converted to dichlor or directly to diesters.

Dichlor can be converted to MeP(S)Cl2 by the action of various reagents.

This compound can be readily desulfurized to SW.

As dichlor formed one of the large scale process steps for production of GB and GD etc, and was thus on hand in bulk, this is a sensible way to prepare MePCl2 without recourse to high temperature processes.

The above is however not the convenient benchtop prep of MePCl2 that I have previously described and documented.



Yes I am familiar with dichlor & the chemistry of its thio analog MeP(S)Cl2. Wonderful stuff but not really a fit topic for amateur chemistry mainly because it is pyrophoric. And making it involves high pressure chemistry (5000 psi SS autoclave) that is best done in the High Desert because of the sulfurous odors generated.

[Edited on 21-6-2008 by Ritter]

Ritter - 21-6-2008 at 06:04

Quote:
Originally posted by Sauron
The most pertinent of these is:

Organic Phosphorus Compounds. IV.1 A Study of the Transesterification of Dialkyl Alkylphosphonites
Friedrich W. Hoffmann, Robert G. Roth, Thomas C. Simmons
J. Am. Chem. Soc.; 1958; 80(22); 5937-5940. DOI: 10.1021/ja01555a012



I would appreciate getting a copy of this article. Thanks in advance!

Sauron - 21-6-2008 at 07:23

Sorry if I was testy. I am also a guy who will never see the green side of 50 again. Most of us here have degrees in chemistry, quite a few doctorates around here too, despite the amateur label.

I have that Hoffmann article and others by him and Tom Simmons on CD somewhere but it is easier to get it from References. So I will do so. The UK patrnts are on same CD, I will dig them out.

When I criticized the rxn scheme as sketchy, and questioned the methane/PCl3 reaction, there was no mention of high temp conditions. Had tere been I would have not opened my mouth. When I started surveying OP military chemistry in the early 70s it was with a view toward monitoring and interdicting terrorist exploitation of CW. In the 80s when I was in Washington, there were only four analysts who raised the alarm about this threat. We were Harvey J.McGeorge, Neil Livingstone, Joe Douglass (of Edgewood) and myself. MCGeorge had been Secret Service WH details's tech agent for NBC, in the Ford and Carter admins. He was contributing editor for CW for Defense & Foreign Affairs magaine. In the recent past he was one of Hans Blix's inspectors in Iraq and the only one of that team to find anything. Joe and Neil wrote a book you may recall, THE POOR MAN'S ATOM BOMB. About subnational CW threat. All of us were laughed down by the rest of the intelligence community.

We were just prescient. After the Aum no one was laughing and an incredible scramble started as all the folks who said we were dead wrong and foolish, climbed all over each other and us to become instant chemical weapons experts.

So forgive my jaundiced eye and venting of spleen, I come by it honestly. I have been around long enough to have seen similar frenzied events regarding counterinsurgency and counterterrorism. Never a pretty sight.

I agree that MeP(S)Cl2 is not something an amateur ought to make in his garage. But it really does not take 5000 psi. It can be done at normal pressure with P2S5 (phosphorus pentasulfide) the most common thiation reagent. Or much more elegantly with Lawsson's reagent which is prepared from anisole and P2S5, see Org.Syn. These replace the pi-bonded O in dichlor with S.

Dichlor is no joy to work with but easier than SW, nicht wahr?

Not my first choice of route but there we are.

What keeps most of us from DOING any of this are two things: fear and common sense.

The Aum spent $11 million dollars on their lab and still their compound reeked, they had accidents, and when they tried to use VX tipped ammunition to kill Daisaku Ikeda, head of rival sect Soka Gakkai, the assassin poisoned himself with VX leaking from the projectiles.

One of my American collaeagues got the job of cleaning up the chemical mess the Aum left behind. I commented at the time that personally I'd rather Waltz across Cambodia (20 million land mines) wearing snow shoes.

Ritter - 21-6-2008 at 07:27

After looking at the available patent literature on 'diester' synthesis, perhaps the most interesting & least hazardous & obnoxious route would appear to be the one patented by Hoechst AG in 1992 (US5128495). Two moles of triethyl phosphite are reacted with one mole of PCl3 in the presence of a catalytic amount of hexamethylphosphoramide to produce diethyl phophorochloridate (diethyl chlorophosphite). This is then reacted with MeMgCl to replace the chlorine atom with a methyl group, giving 'diester.' See http://tinyurl.com/4j8roq

1. 2 P(OEt)3 + PCl3 > ClP(OEt)2

2. ClP(OEt)2 + MeMgCl > MeP(OEt)2

And all this is done at atmospheric pressure in a 4-neck flask. The only difficult parts to the chemistry are drying diglyme over metallic sodium & cooling to -20 deg. C prior to the Grignard addition. Vacuum distillation is in the 20-80mm Hg range. Yield is given as 87%.

If you have 'diester' you are only one step away from QL or an analog derived from a different 2-(dialkylamino)ethanol that would likely result in an extremely effective V-agent if carried to the end (which I do not suggest).

Ritter - 21-6-2008 at 07:39

Quote:
Originally posted by Sauron
Sorry if I was testy. I am also a guy who will never see the green side of 50 again. Most of us here have degrees in chemistry, quite a few doctorates around here too, despite the amateur label.

I have that Hoffmann article and others by him and Tom Simmons on CD somewhere but it is easier to get it from References. So I will do so. The UK patrnts are on same CD, I will dig them out.


Thank you, Sauron. I appreciate your courtesy.

Quote:
So forgive my jaundiced eye and venting of spleen, I come by it honestly. I have been around long enough to have seen similar frenzied events regarding counterinsurgency and counterterrorism. Never a pretty sight.


I understand completely. I have no home lab, though I once considered building one. And I do not advocate anyone even accidentally preparing noxious chemicals of any sort. That's a lot of effort simply to prove that Darwin was right.
Quote:
I agree that MeP(S)Cl2 is not something an amateur ought to make in his garage. But it really does not take 5000 psi. It can be done at normal pressure with P2S5 (phosphorus pentasulfide) the most common thiation reagent. Or much more elegantly with Lawsson's reagent which is prepared from anisole and P2S5, see Org.Syn. These replace the pi-bonded O in dichlor with S.

Dichlor is no joy to work with but easier than SW, nicht wahr?


These chemistries were all developed out of Cold War McCarthy-era hysteria & were never really optimized the way a big pharma company would do with difficult processes.

I appreciate your energy, enthusiasm & extensive background & look forward to enjoying mutual profitability on this board.

Sauron - 21-6-2008 at 07:46

The diester is already a potent AChe inhibitor.

Same is true of the phosphine oxide analog (G-agent precursor.)

Few of these intermediates are anything you want to be around. Efer read Schrader's monographs on his early works, like TEPP and OMPA?

Or Saunders classic? It's downloadable freely from forum library.

Sauron - 21-6-2008 at 08:04

Schrader worked for Baeyer developing pesticides. The G-agents were accidents, simply insecticides with too high a toxicity for higher mammalian species to be useful for anything but military use. So the OKH (German High Command) took them over. Fortunately Hitler had a horror of chemical warfare and did not give these a high priority.

Also the fluorine containing variants required technology the Germans did not posess in a facile form. The US did, coutesy of Dpont.

The V-agents came out of ICI pesticide work in a similar fashion. About a decade after Schrader. Cold War yes, McCarthyite no.

As I am sure you know those are first and second generation nerve agents. There are however at least two, maybe three generations more that are little discussed outside of highly classified circles. The Sovs started working on these in the late 60s and have never really stopped, they hide this work in agro-industry. A lot of that stuff is intended specifically to frustrate NATO MOPP gear, detectors, prophylaxis and therapy.

Oh yes it's a wicked old world.

Ritter - 21-6-2008 at 08:12

Quote:
Originally posted by Sauron
The diester is already a potent AChe inhibitor.

Same is true of the phosphine oxide analog (G-agent precursor.)


Makes sense & good to point out.
Quote:
Few of these intermediates are anything you want to be around. Efer read Schrader's monographs on his early works, like TEPP and OMPA?


No I haven't. I'm filling in down time between consulting projects & decided to pursue my long interest in nerve agent chemistry. I have pdfs of 120+ patents on these + summaries for each agent/intermediate that I'm slowly creating in ChemDraw. It's very interesting and almost overwhelming. But I'm picking up some valuable OP chemistry. So I'm definitely interested in reading the Schrader monographs The story of his experiences with Tabun are fascinating!
Quote:
Or Saunders classic? It's downloadable freely from forum library.


Again, no. Could you direct me to this library? Thanks!

BTW, is there a name for the final isomerization/rearrangement reaction in the VX synthesis? I had not encountered it before.

Ritter - 21-6-2008 at 08:23

Quote:
[The most pertinent of these is:

Organic Phosphorus Compounds. IV.1 A Study of the Transesterification of Dialkyl Alkylphosphonites
Friedrich W. Hoffmann, Robert G. Roth, Thomas C. Simmons
J. Am. Chem. Soc.; 1958; 80(22); 5937-5940. DOI: 10.1021/ja01555a012



I believe this paper may correspond to the patent US2907787 by Hoffmann & Moore. It states very clearly that the transesterification reaction of 'diester' with a beta-substituted ethanol does not require a catalyst. See http://tinyurl.com/43eot2.

This is what I love about this field: you learn something new every day!

[Edited on 21-6-2008 by Ritter]

Sauron - 21-6-2008 at 08:30

http://www.sciencemadness.org/library/index.html

Down the page you will find a pdf by B.C.Saunders, the title is very long but is usually abbreviated to "Phosphorus and Fluorine".

Saunders was effectively the British opposite number to Germany's Gerhard Schrader.

Careful. Two nn's in Hoffmann. That sort of error can upgefuck a search.

The tertiary aminoethanol transesterification does not require a base because it itself is a strong non-nucleophilic hindered base. Note the obvious relationship between the NN-di-Pri-2-aminoethanol and Hunig's Base.

Also note that in the conversion of SW to diester, that reaction is reversible unless an acid scavenging tertiary amine is employed. The most common is pyridine, but the better choice is diethylaniline. Its hydrochloride is easily filtered off and is not hygroscopic. See Ford-Moore's prepn of di-isopropyl methylphosphonate in Org.Syn. (from MeI and tri-isopropyl phosphite.) The author was a colleague of Saunders.

[Edited on 21-6-2008 by Sauron]

Ritter - 21-6-2008 at 08:49

Quote:
Originally posted by Sauron

See Ford-Moore's prepn of di-isopropyl methylphosphonate in Org.Syn. (from MeI and tri-isopropyl phosphite.) The author was a colleague of Saunders.

[Edited on 21-6-2008 by Sauron]


You can get the pdf here: http://www.orgsyn.org/orgsyn/pdfs/CV4P0325.pdf

Thanks for the reference!

Sauron - 21-6-2008 at 09:21

Here's the JACS peper.


Yes, that patent seems to correspond to the subject matter of the JACS article, it's same Hoffmann and Bel Air Md is bedroom community of Edgewood Arsenal. Itself pretty much a satellite of Aberdeen Proving Grounds. I spent a lot of time round there.

The JACS paper will have a lot more chemistry and a lot less legalese.

That thermal isomerization is well known in OP chemistry, RP(S)OR' being converted to RP(O)SR' just by heat. #13 is a wonderful element. As far as I know this isomerization does not have a name per se.

I have a scan I made of G.M.Kosolapoff's classic text ORGANOPHOSPHOTUS COMPOUNDS if you would like that. There are excellent reviews available that survey the literature where Kosolapoff left off c.1948-49.

[Edited on 22-6-2008 by Sauron]

Attachment: Organic Phosphorus Compounds.pdf (542kB)
This file has been downloaded 656 times

Sauron - 22-6-2008 at 12:33

In the Hoffmann JACS paper posted above there is no mention of any transesterification catalyst in the text, except in the sole instance of transesterification with phenol, in which a "catalytic amount" of sodium was added.

No catalyst is mentioned in the accompanying descriptions of redistribution reactions.

PainKilla - 22-6-2008 at 12:53

Sauron, please do post the "Organophosphorus Compounds" text, as there are few books on phosphorus available online.

Very many thanks!

Sauron - 22-6-2008 at 13:11

The pdf for the Kosolapoff book is in my 4shared folder in the /books subfolder, and you will find the link was posted in the New Books (Organic Chemistry) forum many months ago.

Also there is a scan of TOPICS IN PHOSPHORUS CHEMISTRY Vol 1 which may also be of interest.

I think that one is in there chapter by chapter as well as complete.

Enjoy! ------------

------------------

I dug up another Hoffmann paper from JACS, this one was reference 4 in the last such paper posted.

Buried in there you will find the detailed description of the preparation of the famous "diester" O,O-diethyl methyl phosphonite, from the methylphosphonous dichloride. Unsurprisingly to me, the alcoholysis was conducted in presence of exactly the tertiary base I mentioned above, and ether as solvent, with cooling. Isolation procedure and physical constants are provided.

The required dichloride was prepared by reduction of the CH2Cl-PCl3-AlCl3 solid complex, using Al (powder) in MeCN solvent as described in a contract final report by Shell Development Corp to the Army Chemical Center identified in a footnote. This might be available from DTIC or by FOIA. In any case I already posted a more convenient reduction using PhPCl2 and POCl3.



[Edited on 23-6-2008 by Sauron]

Attachment: FWHoffmannJACS.pdf (722kB)
This file has been downloaded 870 times

Ritter - 22-6-2008 at 13:18

Quote:
Originally posted by Sauron
In the Hoffmann JACS paper posted above there is no mention of any transesterification catalyst in the text, except in the sole instance of transesterification with phenol, in which a "catalytic amount" of sodium was added.

No catalyst is mentioned in the accompanying descriptions of redistribution reactions.


See my post on this dated 21 June in this thread.

Sauron - 22-6-2008 at 13:42

No problem, just underscoring.

The following is reference 6 from the first Hoffmann paper above. It is a 1939 JACS paper describing the mechanism and practical aspects of the "redistribution reaction" and is necessary to fully comprehend Hoffmann's papers dealing with transesterification and redistribution prediction and control.

Incidentally I searched for Sigmund Eckhaus in the author field of ACS Publications search engine and found only a single entry in Ind.Eng.Chem dealing with paint filters. Not sure if same man or no.

My working hypothesis is that Friedrich W.Hoffmann was principle scientist on this project at Edgewood, while Eckhaus may be a chemical engineer involved in the process development (industrialization) rather than the basic chemistry and bench scale research. No denigration is intended; both are vital. But I am more interested in the chemistry and much less so in the scaleup and technology.

The following link is to a forum thread, the last three posts at bottom of page contain attachments of one US and two GB (UK) patents on VX. I posted these in December 2006.

The US Patent 3,911,059 dated 1975 is to Eckhaus, Davis, Moore (Thomas L.Moore, frequent collaborator with Hoffmann). One of Hoffmann's patents is cited as prior art and his papers on transesterification are cited in the patent text. One of the UK patents, q.v. is also cited.

We know that much of the actual work on VX in UK and US was done in the early 50s, but not allowed to be published, or secrecy orderes lifted on patents till very late 50s or later.

So note that 1973 represents a quarter of a century later date than the original work and, I would guess, this invention consists of improvements to the process. Most likely improvements made during the 1960s.

[Edited on 23-6-2008 by Sauron]

[Edited on 23-6-2008 by Sauron]

Attachment: redistribution.pdf (746kB)
This file has been downloaded 624 times

Sauron - 23-6-2008 at 00:38

Ritter,

What have you in that large patent collection or the 2006 book regarding preparation of the di-isopropyl-2-aminoethanol

And did you get my PMs regarding 4shared, Kosolapoff etc?

The Schrader articles are in German, from Angew.Chemie. I have them on a CD and will dig them out.

Ritter - 23-6-2008 at 06:31

Quote:
Originally posted by Sauron
Ritter,

What have you in that large patent collection or the 2006 book regarding preparation of the di-isopropyl-2-aminoethanol

And did you get my PMs regarding 4shared, Kosolapoff etc?

The Schrader articles are in German, from Angew.Chemie. I have them on a CD and will dig them out.


Many thanks!

Ritter - 23-6-2008 at 08:22

Quote:
Originally posted by Sauron
Schrader's paper from Angew Chem (in German)

[Edited on 23-6-2008 by Sauron]


I downloaded the file but Adobe Acrobat sent an error message that the file was damaged & could not be repaired. Could you check it on your end & then try posting it again?

Danke sehr!

Sauron - 23-6-2008 at 08:50

My copy is fine.

The forum must have messed it up, perhaps due to size.

Let me consider what to do about this.

I split the pdf into two parts.

Let's see if this works.

Here's first half.

[Edited on 24-6-2008 by Sauron]

Attachment: Pages from Schrader Prt 1.pdf (1MB)
This file has been downloaded 1592 times

Sauron - 23-6-2008 at 19:44

That works. I downloaded it to check.

So here's other half.

This one also downloaded OK.

If you have Adobe Acrobat Pro you can reassemble them into single pdf. That's what I used to break it in two.

You never did answer my question, Ritter, about lit. on preparation of N,N-di-isopropyl-2-aminoethanol.

[Edited on 24-6-2008 by Sauron]

Attachment: Pages from Schrader Prt 2.pdf (1.1MB)
This file has been downloaded 964 times

Sauron - 24-6-2008 at 23:46

Just as an addendum to the earlier discussion upthread, as I am no longer able to edit those posts, the VX process as described was incomplete because it proceededmonly so far as the thionation of QL (the transester). The final step in the prep of VX is the thermal isomerization of the resulting thiolated transester

MeP(=S)(OEt)(OCH2CH2N(Pri)2

to

MeP(=O)(OEt)(SCH2CH2N(Pri)2

Now if you go back and look at Amiton (code VG) you will see that it is in fact not precisely an analog:

(EtO)2P(=S)SCH2CH2N(Et)2

and thus is derived from phosphorus sulfochloride PSCl3 the sulfur analog of POCl3.



So seven variations into the original ICI insecticidal study, they were still looking at relatives of Parathion and Malathion (q.v.) and had not yet started alkylating the phosphorus atom.

Once they did, they were of course paralleling part of the G-agent series

RP(=O)(OR1)-X

So once they were onto

RP(=O)(OR1)S-CH2CH2-N(R2)2

the pertinent structural elements were three.

Alkyl ligand R linked to P

O-ester R1

Alkyl substituents R2 at N

A lot of further clues can be garnered from studying F.W.Hoffman's many papers in JACS and JOC.

The thermal isomerization of the alkylthiophosphonate O-esters to alkylphosphonate S-esters was first noticed during attempts to distill the former. Partial isomerization resulted, and the isomerized product was found to be several orders of magnitude more toxic than the already very toxic O-isomer. Similar phenomena were encountered with related insecticides such as Systox and Parathion.

Apart from its exploitation in the Eckhaus et al-patented production process this is also the basis of the binary VX2 system, in which the transester QL is mixed with rhombic sulfur or dimethyl polysulfide in the (cancelled) 8-inch artillery shell program.

A VX like analog of Amiton would be

EtP(=O)(OEt)SCH2CH2NEt2

which is probably part of the series but I don't know the code name.



[Edited on 25-6-2008 by Sauron]

Ritter - 25-6-2008 at 05:37

Quote:
Originally posted by Sauron
That works. I downloaded it to check.

So here's other half.

This one also downloaded OK.

If you have Adobe Acrobat Pro you can reassemble them into single pdf. That's what I used to break it in two.

You never did answer my question, Ritter, about lit. on preparation of N,N-di-isopropyl-2-aminoethanol.

[Edited on 24-6-2008 by Sauron]


Thanks for the downloads.

I checked on this yesterday & found nothing. I could guess at some prep methods. Forming the aklali metal salt of the amine with BuLi followed by addition of the chlorohydrin would be one. In situ formation of ethylene oxide by treating the chlorohydrin with 3 eq. of 2M NaOH at RT would be another. I think ethylene oxide is likely your best bet.

Ritter - 25-6-2008 at 05:43

Quote:
Originally posted by Sauron
Just as an addendum to the earlier discussion upthread, as I am no longer able to edit those posts, the VX process as described was incomplete because it proceeded only so far as the thionation of QL (the transester). The final step in the prep of VX is the thermal isomerization of the resulting thiolated transester


I thought the thionation/thermal isomerization occurred spontaneously. This was the basis for both the final manufacturing process & the binary shells/bombs.

Sauron - 25-6-2008 at 06:11

Eckhaus describes two discrete steps for these in his patent.

First the thiation, and then the isomerization. The addition of sulfur to the OP is almost always exothermic and usually done with external cooling. The isomerization time depends on temperature used, Eckhaus et al recommend higher temperatures and shorter rxn times.

How that relates to the binary, deponent knoweth not.

Ritter - 25-6-2008 at 07:46

Quote:
Originally posted by Sauron
Eckhaus describes two discrete steps for these in his patent.

First the thiation, and then the isomerization. The addition of sulfur to the OP is almost always exothermic and usually done with external cooling. The isomerization time depends on temperature used, Eckhaus et al recommend higher temperatures and shorter rxn times.

How that relates to the binary, deponent knoweth not.


I'll have to read Eckhaus more closely. I believe you can isolate the P=S intermediate but the whole point of the binary munitions was to use the heat of the reaction with S8 or CH3SSSSCH3 to accomplish the isomerization at the same time, in a matter of seconds.

In FM 3-11.9 they state (p. 11-71): 'Reacts with sulfur and sulfur compounds to produce VX or VX-like compounds.' footnoted as being from Nowlin, T.E. et al A New Binary VX Reaction-Two-Liquid System (U), EATR 4700, USA Munitions Command, Edgewood Arsenal, MD, November 1972. UNCLASSIFIED Report (AD524088). It also states that, not surprisingly, that QL reacts with selenium & selenium compounds. Since Se is just below S in the Periodic Table, seleno-VX would be the likely result.

Under QL toxicity, they give no data.

Ritter - 25-6-2008 at 11:12

Quote:
Originally posted by Sauron
Eckhaus describes two discrete steps for these in his patent.

First the thiation, and then the isomerization. The addition of sulfur to the OP is almost always exothermic and usually done with external cooling. The isomerization time depends on temperature used, Eckhaus et al recommend higher temperatures and shorter rxn times.

How that relates to the binary, deponent knoweth not.


I just read his patent & while Eckhaus claims the P=S & P=O compounds as discrete compounds, he did not isolate & characterize the P=S compound but instead kept it from isomerizing by using a DryIce/glycol bath to remove the heat formed in this very exothermic reaction. He then heated it to accomplish the isomerization in a second step.

The great amount of effort that Edgewood went to in developing the binary VX weapons was actually spearheaded in part by Eckhaus. From War of Nerves, p. 161:
Quote:
Given the lack of institutional support [by the U.S. Army's Chemical Corps] for binary weapons, Sigmund Eckhaus, the director of the VX pilot plant, had to "smuggle" samples of QL to the binary development team.


p. 160:
Quote:
Building on [Friedrich] Hoffmann's work...[ Edgewood] developed a concept for a binary VX bomb in which powdered sulfur would be injected into a liquid solution of QL.


In the binary weapons the heat of the sulfurization reaction also drove the P=S compound to isomerize immediately as it was formed to the P=O VX.

Ritter - 25-6-2008 at 11:31

Sigmund Eckhaus is apparently still with us. His name is in the list of donors on the AIChE's web site: http://www.aiche.org/About/Foundation/CentennialCelebrationA.... Tucker footnotes having interviewed him for his 2006 book.

Sauron - 25-6-2008 at 15:35

I did not get the notion from the Eckhaus patent, that the penultimate step (addn of S or Me2Sn to the QL, wis sufficiently exothermic to accomplish the isomerization in seconds. I would think that there is enough information in the literature (of P and S chemistry in general) to come up with an educated guess as to how many kcal or whatever units, we are talking about. Eckhaus gave a few examples of the time/temperature dependency in the patent, we can extrapolate from that.

There is certainly the possibility to consider that the rxn exotherm was assisted by external heating and/or that the kinetics were accelerated by catalysis, why not?

However, we are starting to cross the line from chemistry to something less welcome on this forum.

The transester QL was/is certainly quite toxic in its own right, just not so relative to VX proper. Arguendo, the binary designers may have settled for a mixture, incomplete isomerization, unlike the more leisurely isomerization (minutes) that could be induldged at the pilot plant.

I have obtained all six papers in the "Organic Phosphorus Compounds" series by F.W.Hoffmann et al in JACS. I compiled them into a single pdf of 3.5 Mb too large to post here but I can place it in my 4shared folder if you or other members would like to read it.

Part 1 concerns the preparation and use of the MeCl-PCl3-AlCl3 complex and its conversion to alkylphosphonate dichlorides,diesters or monoester chloridates. This is an extension of the seminal work of J.P.Clay in late 1940s, see attached from JOC.

As described upthread, reduction of same complex by various means, but most conveniently using PhPCl2 and POCl3, gives MePCl2.

Papers II through V describe in detail the preparation of various inorganic and OP esters and sulfur analogs and their transesterification.

Paper VI, structure-activity relationships versus AChE inibition.

Paper IV has already been posted, it was the one describing the diester.

I think you will find these well worth your time and attention.



[Edited on 26-6-2008 by Sauron]

Attachment: jo01146a010.pdf (228kB)
This file has been downloaded 723 times

Sauron - 25-6-2008 at 15:45

PS Michael Crichton's work of fiction "Binary" is said to have badly rattled the Soviets. It has been cited as part of the rationale for their novichok program, although this strikes me as absurd on its face.

Why should binary VX be more intimidating than normal VX?

And the advantages of the Russian 3rd/4th/5th generation CW programs need no further justification. They positioned themselves for a treaty breakout before ever signing the (CWC) treaty. A de facto breach, certainly even if one accepts the rather thin de jure arguments that these compounds are not coverered by treaty.

Ritter - 25-6-2008 at 16:00

Quote:
Quote:
Originally posted by Sauron
I did not get the notion from the Eckhaus patent, that the penultimate step (addn of S or Me2Sn to the QL, wis sufficiently exothermic to accomplish the isomerization in seconds.


On the other hand, I did. This fact is the essence of the binary system: you need the heat generated by rxn #1 to drive rxn #2 while the weapon is in flight = seconds.
Quote:
The transester QL was/is certainly quite toxic in its own right, just not so relative to VX proper. Arguendo, the binary designers may have settled for a mixture, incomplete isomerization, unlike the more leisurely isomerization (minutes) that could be induldged at the pilot plant.


The Tucker book remarks that the CW Service was against binary VX because a weapon would not deliver 100% VX.
Quote:
I have obtained all six papers in the "Organic Phosphorus Compounds" series by F.W.Hoffmann et al in JACS. I compiled them into a single pdf of 3.5 Mb too large to post here but I can place it in my 4shared folder if you or other members would like to read it.

Part 1 concerns the preparation and use of the MeCl-PCl3-AlCl3 complex and its conversion to alkylphosphonate dichlorides,diesters or monoester chloridates. This is an extension of the seminal work of J.P.Clay in late 1940s, see attached from JOC.

As described upthread, reduction of same complex by various means, but most conveniently using PhPCl2 and POCl3, gives MePCl2.

Papers II through V describe in detail the preparation of various inorganic and OP esters and sulfur analogs and their transesterification.

Paper VI, structure-activity relationships versus AChE inibition.

Paper IV has already been posted, it was the one describing the diester.


I went to your 4shared folder & could not find the pdfs. Please give me a URL or some more info. Thanks!

Sauron - 25-6-2008 at 16:14

The pdf was uploadubg, now completed.

http://www.4shared.com/dir/2245331/5a78115f/sharing.html

No, I understand completely that the rxn time would have to be in (few) seconds, I just did not get any sense from the Eckhaus patent that such short time was feasible with procedure as described. The inventors described examples of isomerizations complete (substantially) in minutes. The temperatures IIRC were in the 100-200 C range. I see the need for much faster times, I just don't see the exotherm producing all that is required. Hence my speculations regarding auxiliary heating and/or some sort of kinetic manipulation (catalysis).

I admit I have not paid much attention to this, but, attention can be paid and I don't see anything occult about the thermodynamics. A little time with a MO package would certainly tell the tale.

Ritter - 25-6-2008 at 17:16

Quote:
Originally posted by Sauron

No, I understand completely that the rxn time would have to be in (few) seconds, I just did not get any sense from the Eckhaus patent that such short time was feasible with procedure as described.


They had to cool rxn #1 with a Dry Ice/glycol bath in order to prevent rxn#2 from taking place as soon as the P=S intermediate was formed. I do not know if the isomerization (rxm #2) is exothermic or not but the need for Dry Ice/glycol indicates some serious exothermy in rxn #1.

As Tucker had interviewed Eckhaus, I would believe what is in his book.

p. 179:
Quote:
[They] had used a propellant to fire a few grams of particulate sulfur directly into the QL solution, triggering the spontaneous chemical reaction that yielded VX. .....

The reaction worked perfectly, going to completion in about five seconds and generating VX and a great deal of heat.


[Edited on 25-6-2008 by Ritter]

Sauron - 25-6-2008 at 18:38

QL solution?

So the QL had to be solvated rather than reacting neat with sulfur?

This may explain the Army's objection, as any solvent would reduce the payload deliverable in a munition of a given size compared to a munition loaded with pure agent.

Anyway, it is not my intention to wax argumentative about the pros and cons of VX2. The chemistry is the same, and it's the chemistry that interests.

-----------------------------

Eckhaus' patent lawyer ought to be flogged or at least take a refresher course in something.

The patent example describes 3221 g of the transester as 1.37 moles.

And 425 g sulfur as 1.36 moles.

I submit that these are off by a factor of 10. And I may be nitpicking but that's gram-atoms of sulfur not moles.

13.7 moles of QL and 13.6 g-atoms S. It is obvious from the 4 liter flask that these amounts are correct.

Also it is clear that solvent is not required.

[Edited on 26-6-2008 by Sauron]

Ritter - 26-6-2008 at 06:11

Quote:
Originally posted by Sauron
QL solution?

So the QL had to be solvated rather than reacting neat with sulfur?

This may explain the Army's objection, as any solvent would reduce the payload deliverable in a munition of a given size compared to a munition loaded with pure agent.


That and their objection to the reaction (at least in the early stages of its development) not going entirely to completion before impact.
Quote:
Anyway, it is not my intention to wax argumentative about the pros and cons of VX2. The chemistry is the same, and it's the chemistry that interests.

-----------------------------

Eckhaus' patent lawyer ought to be flogged or at least take a refresher course in something.

The patent example describes 3221 g of the transester as 1.37 moles.

And 425 g sulfur as 1.36 moles.

I submit that these are off by a factor of 10. And I may be nitpicking but that's gram-atoms of sulfur not moles.

13.7 moles of QL and 13.6 g-atoms S. It is obvious from the 4 liter flask that these amounts are correct.

Also it is clear that solvent is not required
[Edited on 26-6-2008 by Sauron]


There is also a very important detail about this system that's disclosed in the patent that I will not post here so that I'm not writing a VX "cookbook."

Ritter - 26-6-2008 at 06:11

Quote:
Originally posted by Sauron
QL solution?

So the QL had to be solvated rather than reacting neat with sulfur?

This may explain the Army's objection, as any solvent would reduce the payload deliverable in a munition of a given size compared to a munition loaded with pure agent.


That and their objection to the reaction (at least in the early stages of its development) not going entirely to completion before impact.
Quote:
Anyway, it is not my intention to wax argumentative about the pros and cons of VX2. The chemistry is the same, and it's the chemistry that interests.

-----------------------------

Eckhaus' patent lawyer ought to be flogged or at least take a refresher course in something.

The patent example describes 3221 g of the transester as 1.37 moles.

And 425 g sulfur as 1.36 moles.

I submit that these are off by a factor of 10. And I may be nitpicking but that's gram-atoms of sulfur not moles.

13.7 moles of QL and 13.6 g-atoms S. It is obvious from the 4 liter flask that these amounts are correct.

Also it is clear that solvent is not required
[Edited on 26-6-2008 by Sauron]


There is also a very important detail about this system that's disclosed in the patent that I will not post here so that I'm not writing a VX "cookbook."

Ritter - 26-6-2008 at 07:33

I reread the sulfurization/isomerization procedure description and you are correct that a solvent was not used, at least in this lab work.

Sauron - 26-6-2008 at 09:21

There are any number of possible such points. However there is little danger in writing a "VX cookbook" as wannabe cooks will be dead faster than one can say acetylcholinesterase. No need to be coy. I've been looking at that patent since the early 1980s.

In one of Hoffmann's six part JACS series of papers, he describes a sulfurization reaction that was conducted in a solvent, employed a small amount of suspended AlCl3 and used a 100% excess of sulfur, the last two points being contrary to the teachings of the Eckhaus (et al) patent, which specifies a slight deficiency of sulfur (slight excess of QL) and makes no mention of any third substance. I mention this only to show that the sulfurization of phosphorus (III) compounds occurs in conditions not so narrow as the patent.

MePCl2 (and other alkyl or aryl dichlorophosphines) can be sulfurized to MeP(=S)Cl2. The half ester MeP(OEt)Cl and the diester MeP(OEt)2 can be sulfurized. All these reactions are highly exothermic. I don't think it is necessary to explain why doing so is not practical compared to waiting till after the transesterification, because the reason is obvious to anyone who has read and understood the literature. The sulfurization procedures are identical to those described by Eckhaus, or their variants as in Hoffmann. I am rather desultorily rereading Kosolapoff hoping to find how far back this reaction was known.

Thiation bu exchange of S for O was known as long ago as the mid 19th century using P2S5, examples can be found in Org.Syn. The desulfurization of resulting compounds to the alkyldichlorophospite using PhPCl2 is a much more contemporary discovery. In this fashion MeP(=O)Cl2 ->MeP(=S)Cl2 -. MePCl2. Maybe not the best way but there it is.

As you can see from the UK patents the ICI folks and their MOD counterparts had their own ideas about preparing VX; however they never got around to process engineering of it, did they? (Or any of the earlier V-agents save only Amiton, the illfated commercial application.)

Ritter - 26-6-2008 at 09:51

I have a strong hunch that if you dig around the Internet long enough you can find almost any bit of info.

This military publication, Guide to Scheduled Chemicals, (see http://dtirp.dtra.mil/products/products/129p.htm contains a wealth of info, including this gem:
Quote:
Diethyl methylphosphonite

Synonym: TR O,O-Diethyl ester of methlphosphonus acid
Schedule: 2B
CAS No: 15715-41-0
Synthesis: : Methylphosphonus dichloride and ethanol
Catalyst: : Ammonia
Use: Scheduled precursor to QL


Since this is from an official source, I think I've answered my original question at the top of this thread: the code for 'diester' appears likely to be TR.

And from the same page, and in keeping with the military's penchant for assigning code names to substances used in classified projects, we find a second gem:
Quote:
Chemical: KB
See: N,N-Diisopropyl-(beta)-aminoethanol


Also from the same page is this code for a by-product of the transester process:
Quote:
LT
See: Bis(2-diisopropylaminoethyl) methylphosphonite


and even more:
Quote:
Chemical: Methylphosphonothioic dichloride
Synonym: SWS Dichloromethylphosphine Phosphonothiotic dichloride, methyl
Schedule: 2B
CAS No: 676-98-2
Use: Scheduled precursor to YLS and VX



But wait, there is more on this:
Quote:
Chemical: O,O-Diethyl methylphosphonothionate
Synonym: TRS Diethyl methylphosphonothionate Methylphosphonothioic acid, O,O-diethyl ester
Schedule: 2B
CAS No: 6996-81-2
Use: Scheduled precursor to YLS


and still more:
Quote:
Chemical: O-Ethyl methylphosphonothiolic acid
Synonym: YLS Ethyl ThioMPA O-Ethyl methylphosphonothioic acid Methylphosphonothioic acid, O-ethyl-ester
Schedule: 2B
CAS No: 18005-40-8
Use: Scheduled precursor to VX; degradation product of VX (hydrolysis)


and yet more:
Quote:
Chemical: O-Ethyl methyl phosphinic acid
Synonym: Ethyl methylphosphinate YL Ethoxymethylphosphine oxide
Schedule: 2B
CAS No: 16391-07-4
Use: Scheduled precursor to VX; degradation product of QL (hydrolysis)



and more:
Quote:
Chemical: O-Ethyl O-2- diisopropylaminoethyl methylphosphonothionate
Synonym: CV O-Ethyl O-2-diisopropylaminoethyl methylphosphonothiolate phosphonothioic acid, methyl-, O- (2-diisopropylaminoethyl) O-ethyl ester
Schedule: 2B
CAS No: 71840-25-0
Use: Scheduled precursor to VX



CV is the reaction product of QL with sulfur. It rearranges under heating to give VX.

So the synthesis of VX as worked out at Edgewood is SW > TR, TR + KB > QL + LT, QL + NM or NE > CV > VX.


[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

Ritter - 26-6-2008 at 10:38

From that same list of precursor chemicals, I found this:
Quote:
Chemical: Diethylphosphorachloridite
Synonym: DEPCI Phosphorochloridous acid, diethyl ester Diethyl chlorophosphite Ethyl phosphorochloridite
CAS No: 589-57-1
Use: Unscheduled precursor to Tabun


This is the product I posted on the 21st as being a precursor for 'diester' via Grignard reaction in a Hoechst AG patent. While they list it as being a Tabun precursor, we know it can also be a VX precursor.

Sauron - 26-6-2008 at 10:48

One is the half ester, an undesirable byproduct of the reaction of SW with ethanol in presence of a tertiary base.

The other is the diester, the main and desired product of that esterification.

The tertiary amine of choice is diethylaniline.

Methylphosphinous acid, MeP(OH)2 is another possible byproduct and degradation product, although I would expect it to rapidly oxidize to methylphosphonic acid MeP(=O)(OH)2 in the environment Also a degradation product of GB and GD and most G-agents save GA.

Another is the O-ethyl chloridate, MeP(OEt)Cl. Product of incomplete esterification of SW but wothout hydrolysis of the remaining chlorine to the acid.

In the case of MeP(OEt)OH or MeP(OH)Cl, the possibility exists for tautomerism between these tervalent structures and the pentavalent MeP(=O)(OEt)H and MeP(=O)(Cl)H which would also be undesirable.

Review the similar relationship bvetween trialkyl phosphites, dialkyl hydrogen phosphites, and dialkyl phosphates. See Saunders for how this underirable byproduct turned out to be useful. Treatment of the dialkyl hydrogen phosphite with N-chlorosuccinimide produced the dialkylphosphorochloridate, readily reacted with alcohol to get back to the trialkyl phosphite.

Ritter - 26-6-2008 at 11:22

I'm pleased that I was able to run down & identify the code names for all the Edgewood VX starting materials & process intermediates.

Apparently there are several routes to make VX. Have we covered EMPTA (O-ethyl methylphosphonothioic acid)? This is said to be either an intermediate or a hydrolysis product of the Iraqi VX process, though I thought they only had sarin & perhaps another G-agent only. It is the P=S isomer of YLS.

Another precursor is S-(2-diisopropylaminoethyl)methyl-phosphonthioic acid described in USH346 by Edgewood. See also US3903210 by them.

It is interesting to note that that chemical precursor schedule does not list methylphosphonothioic O,O-acid, one of the intermediates described in the patent.
Quote:
Chemical: S-2-Diisopropylaminoethyl methylphosphonothioic (acid)
Synonym: S-2-(Diisopropylamino) ethyl methylphosphonothioic EA 2192 Phosphonothioic methyl
Schedule: 2B
CAS No: 73207-98-4
Use: Scheduled precursor degradation product of VX (hydrolysis)



[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

[Edited on 26-6-2008 by Ritter]

Ritter - 26-6-2008 at 12:43

Gerhard Schrader did some work on V-agent-like insecticides while at Bayer. See US2918488 (1959) at http://tinyurl.com/6l6f39
.

[Edited on 26-6-2008 by Ritter]

Sauron - 26-6-2008 at 18:22

It seems like that military document is not always accurate, or was written and edited by non-chemists. Obviously that last acid you mentioned is a VX degredation product and has nothing to do with G-agent.s

As to the code designations, it raises more questions than it answers. Suddenly we have three-letter rather than two-letter codes to content with, and then there are the V-numeric codes.

At least in the latter case we can take a stab at an explanation.

I would guess that the code list starts at VA, we know Amiton is VG and that is still an early, non-alkylated (no C-P) structure. VX is pretty late in the series. Whewn they got to VZ they started into V1, V2 etc as an extension. Just surmise, but reasonable and it will have to do till harder intel comes along.

Anyway attaboy!

Part of the inherent wekness of CWC is that is is limited to past agents and past methods and precursors. Thus it has institutional blinders. It really is focused on large industrial production, and logistics.

Ritter - 26-6-2008 at 19:30

Quote:
Originally posted by Sauron
It seems like that military document is not always accurate, or was written and edited by non-chemists. Obviously that last acid you mentioned is a VX degredation product and has nothing to do with G-agent.s


If you read USH436, it describes this acid as a cholinesterase inhibitor, not a hydrolysis product. Apparently there were several routes to make VX. What about EMPTA?
Quote:
As to the code designations, it raises more questions than it answers. Suddenly we have three-letter rather than two-letter codes to content with, and then there are the V-numeric codes.

At least in the latter case we can take a stab at an explanation.

I would guess that the code list starts at VA, we know Amiton is VG and that is still an early, non-alkylated (no C-P) structure. VX is pretty late in the series. Whewn they got to VZ they started into V1, V2 etc as an extension. Just surmise, but reasonable and it will have to do till harder intel comes along.

Anyway attaboy!


Thanks. It was a rewarding experience. Thanks for the collaboration.

Sauron - 26-6-2008 at 20:35

With regard to the US patent (US5128495).

It is not necessary to treat diethyl hydrogen phosphite with two mols PCl3 in presence of the (very nasty) HMPA in order to obtain the diethyl chlorophosphite. The British (Saunders, Gerrard) found that NCS (N-chlorosuccinimide perferms this transformation. This was discovered in late 30s-early 40s and not published till postwar in J.Chem.Soc. and later referenced in Saunders book (q.v., in forum library.

This was an important breakthrough in the DFP program because they were reacting PCl3 with alcohols to obtain trialkyl phosphites, a reaction that required large amounts of costly pyridine. Without the tertiary base the main product was diethyl hydrogen phosphite (of whatever dialkyl hydrogen phosphite concerned.) So the observation that the P-H could be replaced by P-Cl via NCS was significant; the resulting compound could then be fluoridated directly to DFP pr another investigational dialkyl fluorophosphate.

Anyway, the patent illustrates a route to MePCl2 via Grignard for sure.

However, GA is a simpler matter. There the starting material is POCl3, rather ubiquitous and easy to make. The only other materials required are dimethylamine (readily made from DMF), ethanol and NaCN or KCN.

Usually, diethylamine is reacted with POCl3 in presence of equimolar pyridine or diethylaniline to make the dimethylphosphoroamidic dichloride. This is then reacted with a saturated ethanolic solution of NaCN to effect both the other additions at same time.

Variations of this are of course possible, but there is no need at all to get elaborate and expensive with a tervalent phosphorus reagent, so I think the staement that the diethyl hydrogen phosphite is a GA precursor, is an error in that military manual.



[Edited on 27-6-2008 by Sauron]

Sauron - 27-6-2008 at 04:55

I have been reading that document and I must say it is poorly organized and a pain to wade through. However it is certainly profitable from th standpoint of identifying some agents not previously mentioned or described in the open literature, and will doubtless precipitate a flurry of new editions of the various CW encyclopeadias, good, bad, and ugly.

There are a number of alternative synthetic routes of entry to VS precursors mentioned in there; I will cite just one or two for example. The reaction of methane with PF3 (both gaseous) to produce MePF2. Somewhat more practically, the reaction of PCl3 with MeI and sodium metal to produce MePCl2. Obviously MeCl and MeBr would react similarly.

The manual is on shaky ground in spots. It mentions the complex of AlCl3 and PCl3 as the Perrin-Kinnear complex, but fails to mention any alkyl halide which is an essential component, and insists that methylene chloride is a catalytic solvent for the complex formation. Perrin and Kinnear did describe the complex in J.Chem.Soc., but were not first to do so, the honor goes to J.P.Clay in JACS whom they cited. F.W.Hoffmann et al demonstrated in JACS that methylene chloride was not required; the complex forms without solvent in at least some cases, including the important one of [MePCl3][AlCl4].

Ritter - 27-6-2008 at 06:06

http://dtirp.dtra.mil/products/products/129p.htm
Quote:

======================================
Chemical: (N,N-Dimethylamino) ethyl chloride hydrochloride Synonym: 2-Dimethylaminic ethyl chloride hydrochloride Dimethylaminoethyl chloride hydrochloride
Schedule: 2B
CAS No: 4584-46-7
Use: Scheduled precursor to V1
==================================
Chemical: (N,N-Dipropylamino) ethyl chloride hydrochloride
Synonym: 1-Propanamine, N-(2- chloroethyl)-N-propyl-hydrochloride N-(2-Chloroethyl)-N-Propyl-1- propanamine hydrochloride (2-Chloro-ethyl)-dipropyl-amine hydrochloride
Schedule: 2B
CAS No: 4535-86-8
Use: Scheduled precursor to V2

====================================

Chemical: 2-(N,N-Diisopropylamino) ethyl chloride hydrochloride

Synonym: (2-Chloroethyl) diisopropylamine hydrochloride (.beta.-chloroethyl)diisopropylamine hydrochloride
Schedule: 2B
CAS No: 4261-68-1
Use: Scheduled precursor to VX, VS, V4, and V5 ==================================
N,N-Diisopropyl- (beta)-aminoethanol

Synonym: KB Ethanol, 2-(bis(1- methylethyl)amino) 2-(Bis(1-methylethyl) amino) ethanol (N,N-Diisopropylamino) ethanol
Schedule: 2B
CAS No: 96-80-0
Use: Scheduled precursor to QL, VX, VS, V4, and V5 ======================================
This is the first time I've seen V-agents listed with V# designations instead of V-letter codes.

[Edited on 27-6-2008 by Ritter]

Ritter - 27-6-2008 at 06:19

Quote:
Originally posted by Sauron
With regard to the US patent (US5128495).

It is not necessary to treat diethyl hydrogen phosphite with two mols PCl3 in presence of the (very nasty) HMPA in order to obtain the diethyl chlorophosphite. The British (Saunders, Gerrard) found that NCS (N-chlorosuccinimide perferms this transformation. This was discovered in late 30s-early 40s and not published till postwar in J.Chem.Soc. and later referenced in Saunders book (q.v., in forum library).


They used triethyl phosphite in that patent. Do you have a pdf of that JCS article?
Quote:
This was an important breakthrough in the DFP program because they were reacting PCl3 with alcohols to obtain trialkyl phosphites, a reaction that required large amounts of costly pyridine. Without the tertiary base the main product was diethyl hydrogen phosphite (of whatever dialkyl hydrogen phosphite concerned.) So the observation that the P-H could be replaced by P-Cl via NCS was significant; the resulting compound could then be fluorinated directly to DFP pr another investigational dialkyl fluorophosphate.

Anyway, the patent illustrates a route to MePCl2 via Grignard for sure.[


Don't you mean MeP(OEt)2?
Quote:
However, GA is a simpler matter. There the starting material is POCl3, rather ubiquitous and easy to make. The only other materials required are dimethylamine (readily made from DMF), ethanol and NaCN or KCN.

Usually, diethylamine is reacted with POCl3 in presence of equimolar pyridine or diethylaniline to make the dimethylphosphoroamidic dichloride. This is then reacted with a saturated ethanolic solution of NaCN to effect both the other additions at same time.

Variations of this are of course possible, but there is no need at all to get elaborate and expensive with a tervalent phosphorus reagent, so I think the staement that the diethyl hydrogen phosphite is a GA precursor, is an error in that military manual.

[Edited on 27-6-2008 by Sauron]


From Tucker, p. 111:
Quote:
....Edgewood....also worked on an industrial manufacturing process for Sarin [GB]. After failing to develop a simplified 4-step method, they decided to adopt the German 5-step approach known as the DMHP (dimethyl hydrogen phosphite) process.
So this may be an error in the military manual, as they go on to say that thev DMHP (or DEHP) process involves use of anhydrous HF, wehich is not involved with GA chemistry.

Sauron - 27-6-2008 at 07:05

No, not MeP(OEt)2.

The Brits (late 30s-early to mid 40s) were focused on dialkyl fluorophosphates, particularly DFP, diisopropyl fluorophospate, or what we now call phosphonofluoridate.

(PriO)2POF

These compounds are about as toxic as HCN and much less so than G agents; however they are AChE inhibitors and played an important role in development of future insecticides and OP military agents. There is no C-P bond. See Saunders' book.

Saunders also benefitted from British intelligence of Schrader's work and prepared tabun and sarin in his lab very early on by routes differing from Schrader's own. (Soman of course did not come into the picture till a few years later.)

The significance of dialkyl hydrogen phosphites in G-agent production is related to the role of these compounds in the Michaelic-Arbusov reaction. In this reaction an alkyl halide such as MeI is reacted with a trialkyl phosphite such as tri-isopropyl phosphite under suitable conditions and alkylation and rearrangement occurs. The product is MeP(=O)(OPri)2

In a modification of this reaction the di-dsopropyl hydrogen phosphite can be used instead.

The alkylphosphonic diester can be exploited in several different ways to end up with G-agents such as GB, GD, GE, GF etc.

One or both alkoxy groups can be replaced by chlorine.

If both alkoxy groups are replaced a different alcohol can be reacted with the alkylphosphonic dichloride to obtain the desired alkylphosphonochloridate ester.

The final step is to replace the Cl with F.

Alternatively if the alkoxy group already present is the desired one then only one is replaced with chlorine, and then exchanged for fluorine.

On the industrial scale the usual chlorinating agent is phosgene and the usual fluorinating agent is anhydrous HF but of course there are other choices.

The Germans had a lot of problems handling fluorine and neat HF but for obvious reasons having to do with Dupont and the UF6 diffusion process, the US did not.

The process engineering of G-agents is beyond my ken, as I am not a CE. On the bench scale there are many options, again we are constrained by our old friends fear and common sense from going beyond doodling on paper.

Ritter - 27-6-2008 at 08:12

Quote:
Originally posted by Sauron
No, not MeP(OEt)2.



That Hoechst patent that you reference has to do with converting trialkyl phosphites with PCl3 & hexamethylphosphoramide into chlorophosphites which are then converted to alkyl phosphite esters (such as MeP(OEt)2)via coupling with alkyl Grignard reagent. It has nothing to do with alkyl(chloro)phosphines.

Sauron - 27-6-2008 at 08:27

My point was that if you want dialkyl chlorophosphites you do not need to jump through all those hoops.

If you react PCl3 with an alcohol (three moles) in absence of tertiary base you get c.80% yield of the (RO)2P-OH which is tautomer of (RO)2P(=O)-H and that is the dialkyl hydrogen phosphite. Now treating with Cl2, on a large scale, or NCS on a bench scale gets you the (RO)2P(=O)Cl. Again high yield.

I'll have to read the patent but it sounds like a more complex answer to a simple problem.

The military manual implied that the alkylation of the product of this gave SW not DC, unless I read it wrong. DC is not a V agent precursor, but a G agent one.

[The reason that in the reaction of PCl3 with alcohol, in absence of tertiary base like pyridine, the HCl formed cleaves the labile third alkoxy group, producing alkyl chloride and the dialkyl hydrogen phosphite.

The situation is much worse with PBr3. In that case you get a mixture of alkyl dihydrogen phosphite, dialkyl hydrogen phosphite and phosphorous acid, along with lots of alkyl bromide. This is why the conventional wisom is that PBr3 is good for making alkyl bromides and useless for making trialkyl phosphites. The conventional wisdom is not quite right, as it turns out. But there we are.

[Edited on 28-6-2008 by Sauron]

Attachment: Pages from phosphorus_fluorine_toxicity.pdf (190kB)
This file has been downloaded 681 times

Ritter - 27-6-2008 at 10:27

Quote:
Originally posted by Sauron
My point was that if you want dialkyl chlorophosphites you do not need to jump through all those hoops.

If you react PCl3 with an alcohol (three moles) in absence of tertiary base you get c.80% yield of the (RO)2P-OH which is tautomer of (RO)2P(=O)-H and that is the dialkyl hydrogen phosphite. Now treating with Cl2, on a large scale, or NCS on a bench scale gets you the (RO)2P(=O)Cl. Again high yield.


The P=O compound you show is a phosphonate, not a phosphonite. The compound desired is (RO)2PCl. As far as I know there are only 2 known ways to get it: one, reaction of SW with EtOH in the presence of organic base, or two, by alkyl Grignard replacement of the chlorine in (RO)2PCl. Since SW is difficult to make and I believe pyrophoric in air, the second (Hoechst) approach seems more attractive.
Quote:
I'll have to read the patent but it sounds like a more complex answer to a simple problem.


Please.
Quote:
The military manual implied that the alkylation of the product of this gave SW not DC, unless I read it wrong. DC is not a V agent precursor, but a G agent one.


SW is methyl(dichloro)phosphine, made from MeCl & PCl3. It is the Edgewood starting point for VX. DC (dichlor) is a G-agent precursor & a phosphonate (P=O) compound.

Ritter - 27-6-2008 at 11:20

I found this snippet on the Iraqi EMPTA VX process:
Quote:
O-ethyl methylphosphonothioic acid [EMPTA] on reaction with N,N-diisopropylethyl chloride in the presence of...


The last part is likely a catalyst/acid acceptor. The net result is esterification of the EMPTA to form CV, the immediate precursor of VX that is thermally isomerized to form VX.

To prepare EMPTA, TR (diester) is reacted with sulfur to form O,O-diethyl methylphosphonothioate. This is then half-hydrolyzed with NaOH to form the half acid/half ester. The rest of the chemistry from there to VX is in the open literature (US3781387).[Edited on 27-6-2008 by Ritter]

[Edited on 28-6-2008 by Ritter]

Sauron - 27-6-2008 at 18:50

I will go retrieve the patent and post it here.

I think I see your point.

Saunders used dialkyl hydrogen phosphite to make the pentavalent dialkyl phosphonochloridate,

Hoechst made tervalent dialkoxychlorophosphine, and alkylated that via Grignard to TR. ((RO)2PMe)

OK, clear.



[Edited on 28-6-2008 by Sauron]

Attachment: US5128495.pdf (342kB)
This file has been downloaded 566 times

Sauron - 28-6-2008 at 00:05

Here's a route to dichlor (DC, methyldichlorophosphine oxide) I'd forgotten:

(MeO)2P(=)-H -> (MeP(=O)(OH))2O

by heating to 300 C

Chlorination (classically by PCl5, other reagents are surely possible) gives MeP(=O)Cl2

Since DC can be thiated then dethiated to SW, this is potentially a route to both G and V agents.

See Saunders p.92-93.

Dimethyl hydrogen phosphite (for that is what it is) can also be exploited by conversion to the chloridate, then its sodium salt, reaction of the sodium salt with MeCl to yield MeP(=O)(OMe)2 which can then be chlorinated, transesterified, etc. Classically, fluorinated directly to DF (MeP(=O)F2, difluor) then partially esterified with the preferred alcohol (2-propyl, or pinacolyl, etc.)

These are most likely the 4-step and 5-step routes to GB mentioned briefly in Tucker's book.

[Edited on 28-6-2008 by Sauron]

Sauron - 28-6-2008 at 06:18

A preliminary mining of that manual for CWC inspectors, reveals complete structures or partial structures for:

VE
VG (Amiton)
VM
VS
VX

To which can be added VR "russian V-agent")

Structures for the above are in Wikipedia and are entirely consistent with information released in this manual.

and

V1
V2
V4
V5

Also PP-VX

These, AFAIK have not been described elsewhere. I cannot say whether the numbered V-agents precede VA or follow VZ. Insufficient information as yet.

V1 all we are told is that the ethanolamine is N,N-dimethyl. V2, N,N-diethyl. V4 and V5 have same ethanolamine as VX (N,N-di-isopropyl.)

PP-VX is a VX homolog where the alkyl group on P is n-propyl, all other elements of structure unchanged.

CWC defines V-agents in the schedule precisely.

R1 is alkyl in C-P bond where alkyl = methyl, ethyl, n-propyl or isopropyl

The two alkyl groups of the aminoethyl side chain are methyl, ethyl, n-propyl or isopropyl

The alkoxy group is up to C10. Cycloalkyls are included. No limitation on isomers is mentioned. This means that the number of alcohols possible is quite large. But it is worth noting that in the case of VX the alcohol is ethanol. VX is allegedly yje most potent member of the series.

I would infer that there must exist a classified version of this manual, in which chemical weapons not declassified are described so that insectors with appropriate clearance can be properly trained to look for indications of their development, manufacture, or stockpiling.





Most of those are not new revelations.

Ritter - 28-6-2008 at 06:47

Quote:
Originally posted by Sauron
Here's a route to dichlor (DC, methyldichlorophosphine oxide) I'd forgotten:

(MeO)2P(=)-H -> (MeP(=O)(OH))2O

by heating to 300 C

Chlorination (classically by PCl5, other reagents are surely possible) gives MeP(=O)Cl2

Since DC can be thiated then dethiated to SW, this is potentially a route to both G and V agents.

See Saunders p.92-93.

Dimethyl hydrogen phosphite (for that is what it is) can also be exploited by conversion to the chloridate, then its sodium salt, reaction of the sodium salt with MeCl to yield MeP(=O)(OMe)2 which can then be chlorinated, transesterified, etc. Classically, fluorinated directly to DF (MeP(=O)F2, difluor) then partially esterified with the preferred alcohol (2-propyl, or pinacolyl, etc.)

These are most likely the 4-step and 5-step routes to GB mentioned briefly in Tucker's book.

[Edited on 28-6-2008 by Sauron]


Now that we are exchanging graphic files, please send this type of contribution to me in that format.

Sauron - 28-6-2008 at 08:39

Here are the pages from Saunders on tabun and sarin. His graphical schemes are there. No need to redraw them.

There is a different path to the TR diester, not via SW, and one that is facile and employs no CWC scheduled reagents. I already sent you the details.

No PCl3, no Grignard. The plumbing may be exotic.

[Edited on 29-6-2008 by Sauron]

Attachment: Pages from phosphorus_fluorine_toxicity.pdf (152kB)
This file has been downloaded 615 times

Ritter - 28-6-2008 at 10:38

Quote:
Originally posted by Sauron

There is a different path to the TR diester, not via SW, and one that is facile and employs no CWC scheduled reagents. I already sent you the details.

No PCl3, no Grignard. The plumbing may be exotic.

[Edited on 29-6-2008 by Sauron]


I have not received them. If you are referring to that U2U JACS ref, I'd appreciate receiving a pdf.

[Edited on 28-6-2008 by Ritter]

Sauron - 28-6-2008 at 17:14

I sent you complete citation of JACS article twice. by URL.

When I have the pdf I will post it here.

I posted pages from Saunders above.

So no need to draw graphical sceme again.

Methane and PF3 react (conditions not known yet) to form MePF2 and HF.

MePF2 reacts with ethanol (2 mols), product is TR diester.

This is right out of military manual.

See Brauer (forum library, Handbook of Preparative Inorg.Chem.) for prepn PF3; also different prep from JACS article I am waiting for.

Alkylation of PF3 higher or lower temp than PCl3? I don't know ywt. PF3 is as you would expect, a gas.

All information I have is from open sources. I am retired, and will not be filing any more patents. This is a chemistry forum. Anything we can discuss between us we can post here. There's nothing confidential about any of this as far as I am concerned. Chemical journals, patent archives, books, nothing secret or sinister. Unless libraries are sinister. Is knowledge sinister?

Ritter - 28-6-2008 at 17:25

Quote:
Originally posted by Sauron
I sent you complete citation of JACS article twice. by URL.


Not received here.
Quote:


When I have the pdf I will post it here.

I posted pages from Saunders above.

So no need to draw graphical sceme again.

Methane and PF3 react (conditions not known yet) to form MePF2 and HF.

MePF2 reacts with ethanol (2 mols), product is TR diester.

This is right out of military manual.

See Brauer (forum library, Handbook of Preparative Inorg.Chem.) for prepn PF3; also different prep from JACS article I am waiting for.

Alkylation of PF3 higher or lower temp than PCl3? I don't know ywt. PF3 is as you would expect, a gas.

All information I have is from open sources. I am retired, and will not be filing any more patents. This is a chemistry forum. Anything we can discuss between us we can post here. There's nothing confidential about any of this as far as I am concerned. Chemical journals, patent archives, books, nothing secret or sinister. Unless libraries are sinister. Is knowledge sinister?


Sorry to bother you by sending you those graphic files. It won't happen again.

I worked the better part of my career in organofluorine chemistry & believe me, it is no improvement over the routes discussed earlier. HF & fluoride ion are things to be avoided unless there is no other way to get there.

Sauron - 28-6-2008 at 19:48

I can't understand why my PMs fail to reach you.

Phosphorus-Halogen Compounds from Phosphorus Pentoxide and Halides. Properties of Phosphorus Trifluoride and Phosphorus Oxyfluoride*
Grady Tarbutton, E. P. Egan, , Jr. S. G. Frary
J. Am. Chem. Soc.; 1941; 63(7); 1782-1789. DOI: 10.1021/ja01852a002

This paper teaches that PF3 and POF3 are produced in high yield by heating P2O5 and CaF2 (or other fluoride salts) as a solid mixture to 400-600 C. The physical properties of these gases are described.

Analogously P2O5 and NaCl (yes table salt) produce POCl3 along with a small amount of PCL3 (10-25%) which appeared to be the result of reduction of POCl3 by iron from the inner surface of the autoclave.

I agree with you about the "thrills" of working with HF neat. I did not say PF3 was an improvement as a starting material, only an alternative. As this is a paper exercise such reagents are no barrier.

You should see the novichoks, really scary precursors there like carbonyl chloride fluoride oxime. Ugh.

I was not discomfitted about receiving your skc files. You asked me to regard them as confidential and NFP and so I shall. I simply asked why? As nothing new seemed to be present.

Why don't you request the password for References from Polverone? It is a very useful resource. Also, write (PM) MadHatter and ask him to set up a user account and pw for you for his ftp site. You will be surprised what a treasure trove is there.

This route to POCl3 and maybe PCl3 is one I have been sitting on for about a year. I have another back door method to POCl3 as well also from P2O5 but the required reagent is costlier than NaCl.

[Edited on 29-6-2008 by Sauron]

Ritter - 28-6-2008 at 20:44

Quote:
Originally posted by Sauron
I was not discomfitted about receiving your skc files. You asked me to regard them as confidential and NFP and so I shall. I simply asked why? As nothing new seemed to be present.


Not to worry. I won't be sending you anything that I personally generate again. Personally-generated content is usually considered privileged if its creator requests that status.
Quote:
Why don't you request the password for References from Polverone? It is a very useful resource. Also, write (PM) MadHatter and ask him to set up a user account and pw for you for his ftp site. You will be surprised what a treasure trove is there.


I may. This board is not very 'user friendly' in defining these options.
Quote:
This route to POCl3 and maybe PCl3 is one I have been sitting on for about a year. I have another back door method to POCl3 as well also from P2O5 but the required reagent is costlier than NaCl. [Edited on 29-6-2008 by Sauron]


I was hoping to collaborate with you on this topic since you & I seem to be the only ones here with the background & interests to contribute anything of value. But as it seems that you are not really in a position to do so, no problem. Enjoy your retirement just as much as I am enjoying mine.

[Edited on 28-6-2008 by Ritter]

[Edited on 28-6-2008 by Ritter]

Sauron - 28-6-2008 at 21:29

I spent 28 years as a very senior defense journalist - not because my background was journalism but because it was defense. You made no mention of any proposed collaboration till now; in fact you said you were not writing a book on this. Oh, well, another chance at a Pulitzer down the crapper, I suppose.

Here as promised is the JACS paper by Grady Tarbutton.

[Edited on 29-6-2008 by Sauron]

Attachment: tarbutton.pdf (807kB)
This file has been downloaded 512 times

Ritter - 29-6-2008 at 05:23

Quote:
Originally posted by Sauron
You made no mention of any proposed collaboration till now; in fact you said you were not writing a book on this. Oh, well, another chance at a Pulitzer down the crapper, I suppose.


I believe I mentioned it in one our PMs. I am not writing a book but instead attempting to make sense of the literature on this subject, starting with the previously missing code for 'diester.' I am in the process of creating ChemDraw files to summarize the chemistry in each of the main patents I have collected as well as large ChemDraw files summarizing & comparing the synthetic alternatives for each of the principle starting materials in the V-agent series as well as an overall process flow for VX, which is what I sent you.

As you were quick to send me your email & reinstall your ISIS Draw, I expected this to be a 2-way exchange. Guess not.

Since you and I are apparently the only ones with the technical experience to contribute to this thread, the word collaboration came to mind when it came to exchanging graphical files. And as far as exchanging graphic files on this chemistry goes, trying to wade through some of the linear nomenclature you post gets very time consuming. Organic chemistry is a 2-D visual science, not a linear one.
Quote:
Here as promised is the JACS paper by Grady Tarbutton.


Thanks. As I expected it is a hopelessly academic exercise & of little synthetic application.

[Edited on 29-6-2008 by Ritter]

Sauron - 29-6-2008 at 07:21

A hopeless academic exercise perhaps insofar as producing PF3 is concerned, since the main product is POF3.

I think it is not so academic when it comes to POCl3. Since the alternative is via PCl5 and therefore requires elemental P and a lot of Cl2, the Tarbutton procedure looks pretty attractive.

I understand the frustrations of trying to represent OP structures in Hill notation. I have posted many many .skc files as jpgs on this forum. I just did not fathom why you reckoned that we needed to take our conversation private.

In the past there have been other members interested in this general topic. I don't know why this thread has been so one-on-one.

Did you download the pages from Saunders I posted?

Ritter - 29-6-2008 at 08:45

Quote:
Originally posted by Sauron

I understand the frustrations of trying to represent OP structures in Hill notation. I have posted many many .skc files as jpgs on this forum. I just did not fathom why you reckoned that we needed to take our conversation private.


You never expressed curiosity about that before. As you can see from the 2 files I sent you, I put quite a bit of effort into the background reseach before generating them. I have a natural inclination to be protective of my work.

Quote:
In the past there have been other members interested in this general topic. I don't know why this thread has been so one-on-one.


I have no idea. Looking at the number of views, there is a high level of interest in this topic. But if I'm having difficulty following your Hill notation posts, then subscribers who aren't graduate chemists may have been discouraged to participate.
Quote:
Did you download the pages from Saunders I posted?
I honestly don't remember. I have the Hoffmann papers. I have requested a password for the library but have not yet received it.

Sauron - 29-6-2008 at 18:34

Hill notation is common on this forum and I am surprised you have such difficulty with it. Others generally do not, and once again you seem to underestimate the number of graduate chemists (and Ph.D.'s) here.

for example

MeP(=O)(OEt)SCH2CH2N(Pri)2

which happens to be VX.

a methyl group bonded directly to P

A pi bonded O to P

An ethoxy group to P

and a -S-ethylamino-di-isopropyl side chain bonded to P

Now what is so tough about that?

Patents, journals etc use same notation, so do books, catalogs etc.

It is faster than generating a skc and converting to jpg to post here. I have done that many many times in other threads.

I don't think other members are refraining from posting because of my notation. I think they are refraining because they have little to add. I've been active here for more than a year and a half, and interest in OP chemistry has not been excessive.

From the start of this thread you have been more interested in the military codes (particularly the ones you lacked) than anything else. Well, from a purely historical viewpoint I can imagine that is interesting. But those codes convey no chemical information whatsoever. So to chemists they are meaningless. Chemists do not refer to dichloromethylphosphine as SW. What's that? Tunsten sulfide?

I applaud your ferreting out of the diester code from that inspector's manual. So you were able to complete your graphic, with CAS numbers, ChemDraw generated IUPAC nomenclature and the Army codes. I am a little vague about why you appeared at first to be ignorant of the thermal isomerization which is plainly detailed in Eckhaus' patent. Because it is crucial to the process, and that is true whether it takes place in tandem with the sulfurization step, or, by dint of external chilling, is done seperately. Without understanding the isomerization, one would expect the final product to be the P=S and O-di isopropylaminoethyl on.

The importance of the isomerization was observed at least as early as the development of Parathion, and again with Systox, and again with Amiton. These are the pedigree, the ancestry of VX. In each of these commercial insecticides, isomerization resulted in the formation of the the same shift to -S-ester and O pi bonded to P. This had same profound effect on toxicity, increasing it by "several orders of magnitude" relative to -O-ester and P=S.

Incidentally there is some confusion in the lit. and on Wiki regarding the structure of Amiton. See the graphical illustrations of these isomerizations below



[Edited on 30-6-2008 by Sauron]

isomp1.jpg.jpg - 51kB

Sauron - 29-6-2008 at 19:55

And here's Systox:

[Edited on 30-6-2008 by Sauron]

isomp2.jpg - 33kB

Sauron - 29-6-2008 at 20:08

Amiton and Systox were in fact mixtures of both isomers, the isomerization took place partially in the purification process and then gradually at room temperature, over time. Only later research elaborated this as the cause for anomalous toxocity increases over early tox studies with the pure O-isomer.

Similar problems arose with parathion which is

(EtO)2P(S)-OPh-4-NO2.

Sources which report the structure of Amiton and/or Systox as

(EtO)2P(=S)SR

where R = -CH2CH2SEt or -CH2CH2NEt2

are in error.

See both Saunders and Hoffmann to support this position.

[Edited on 30-6-2008 by Sauron]

Ritter - 30-6-2008 at 06:43

Quote:
Originally posted by Sauron
Hill notation is common on this forum and I am surprised you have such difficulty with it. Others generally do not, and once again you seem to underestimate the number of graduate chemists (and Ph.D.'s) here.


I have not worked with linear notation very much since college. While I am familiar with it, 2-D graphical representations are the standard format used today. Understanding a Hill notation listing in the Aldrich catalog is one thing, but trying to follow some of your multi-step OP posts necessitates my having to visually convert each notation into a 2-D structure so that I can understand what ytou are trying to convey.
Quote:
Now what is so tough about that?

Patents, journals etc use same notation, so do books, catalogs etc.

It is faster than generating a skc and converting to jpg to post here. I have done that many many times in other threads.


I think you are just trying to be argumentative. I do not wish to participate on that level. Professional chemists are required to submit 2-D graphics in their lab notebooks & journal article submissions.
Quote:
I don't think other members are refraining from posting because of my notation. I think they are refraining because they have little to add. I've been active here for more than a year and a half, and interest in OP chemistry has not been excessive.

From the start of this thread you have been more interested in the military codes (particularly the ones you lacked) than anything else. Well, from a purely historical viewpoint I can imagine that is interesting. But those codes convey no chemical information whatsoever. So to chemists they are meaningless. Chemists do not refer to dichloromethylphosphine as SW. What's that? Tunsten sulfide?

I applaud your ferreting out of the diester code from that inspector's manual. So you were able to complete your graphic, with CAS numbers, ChemDraw generated IUPAC nomenclature and the Army codes. I am a little vague about why you appeared at first to be ignorant of the thermal isomerization which is plainly detailed in Eckhaus' patent. Because it is crucial to the process, and that is true whether it takes place in tandem with the sulfurization step, or, by dint of external chilling, is done seperately. Without understanding the isomerization, one would expect the final product to be the P=S and O-di isopropylaminoethyl on.

The importance of the isomerization was observed at least as early as the development of Parathion, and again with Systox, and again with Amiton. These are the pedigree, the ancestry of VX. In each of these commercial insecticides, isomerization resulted in the formation of the the same shift to -S-ester and O pi bonded to P. This had same profound effect on toxicity, increasing it by "several orders of magnitude" relative to -O-ester and P=S.


I have limited experience with OP chemistry, which is one of the reasons I became interested in VX. Are you just trying to make points by being critical of someone's lack of expertise in a certain area? That's not very nice.

[Edited on 30-6-2008 by Ritter]

Sauron - 30-6-2008 at 07:06

No, just trying to understand some apparent non sequiturs.

I pointed you at free downloads of Saunders book on P and F compounds from forum library, and Kosolapoff's book reviewing OP chemistry from 19th century through middle of the 20th. I hope you availed yourself of these, which will get you well up to speed at least through the period when VX was being developed at ICI.

Once you have access to References there is an excellent book in there on the formation of C-P bonds, quite recently published.

I have an excellent review on the Michaelis-Arbusov reaction, would you like to read it?

OP chemistry and phosphorus chemistry in general can get a little strange in places, organophosphorus-sulfur compounds to my mind is one of these areas, and VX is in there. Organic chemistry is far to vast for anyone to be a generalist any more. We hop from one little island of specialization to another and hope we don't get our feet wet. Continuing education is nothing to be shy about, or to criticize. We are all of us playing catch-up, all the time.

[Edited on 30-6-2008 by Sauron]

Attachment: cr00044a004.pdf (2.5MB)
This file has been downloaded 1428 times

Ritter - 30-6-2008 at 08:33

Since I found the information I was looking for at the start of this thread, I now consider this thread closed.

Sauron - 30-6-2008 at 08:57

And I now consider you a pious fraud.

[Edited on 30-6-2008 by Sauron]

Ritter - 30-6-2008 at 10:31

Quote:
Originally posted by Sauron
And I now consider you a pious fraud.

[Edited on 30-6-2008 by Sauron]


Why the unnecesary hostility? Didn't I find the code for 'diester' on my own? End of story, end of thread.

PainKilla - 30-6-2008 at 10:52

I just want to add that I find this thread to be very interesting, at least, where the chemistry was involved. I am quite against the weaponization of such agents but chemistry is chemistry, and I am sure even these compounds have some medicinal uses (well relatives anyway).

I'd always thought that the chemistry of these agents had been relatively restricted (classified) but it seems that patents, for once, actually have some validity behind them and are useful for reading (although, some of the notation within is a bit trifling to sort through).

Sauron, out of curiosity, did you pick up your knowledge of these agents through industry experience, or academic coursework, or simply from reading lots of references? As you mentioned, it is quite difficult to become an expert at organic chemistry, but even so, an introduction to all realms would be nice, and so I wonder if there is a good place to start (for the chemically inclined)...

Thanks!

Sauron - 30-6-2008 at 16:34

Neither industrial experience nor academic work. I was academically trained as a research organiker, including of course being "socialized" to the literature, C.A., Beilstein etc. Tose are the tools.

Frankly, in hindsight, it is very clear to me that if I had elected to get into pesticides, plant protection chemistry, I would have ended up learning about never agents anyway because all the "great" nerve agents were accidental offshoots of such research. Simply, insecticides that turned out to be too potent to use, and then the military sat up and took notice. That was true of Schrader's work at Baeyrt. That was true of Ghost and Newman's work at Imperial Chemical Industries. Or, getting away from the OPs, it was true of BZ the incapacitant, which grew out of work in the pharm industry to develop a better smasmolytic. Read the work of Dr.Leo Abood, it's all there. The stuff had unexpected side effects, at first they tried to exploit it in psychotherapy and found that the drug they thought thay had (Ditran) was rearranging to something else, more potent. They followed that to its logical conclusion and the quinuclidinal benzilates were born.

And yes all of them, even the nastiest, have had beneficial consequences. I personally consider vesicants like mustard to be crimes against the genome, because of how they work (by crosslinking DNA and preventing replication and repair). But with that knowledge came the birth of cancer chemotherapy.

The nerve agents advanced enzymology, and are used in opthamology, treatment of myasthemia gravis etc. (See Saunders.)

Even the early CW agents were just industrial chemicals, or chemicals developed as possible industrial compounds, which turned out to be nasty. This was true of all the chemical weapons in WWI. All of them. Chemists remembered footnotes in old journals or doctoral dissertations about this nasty sulfur compound or this stinking arsenical.

I could tell you about one less than lethan agent, now used to incapacitate terrorists. You would not believe the chemistry it came out of. It's a cannabinoid.

On the other hand when that terrible hostage incident in the CIS happened, they used carfentanyl to do the same thing and managed to kill 30% of the hostages with it, too. One does not think of the fentanyls as chemical weapons, but there we are.

So what specialization can you go into that will NOT have potential for perversion into a military weapon? That's the tough question.

Sauron - 30-6-2008 at 16:52

Ritter, you do not have the authority to close this or any other thread. So don't pretend that you do.


[Edited on 1-7-2008 by Sauron]

Polverone - 30-6-2008 at 18:34

Let's keep this thread on-topic. If you have a problem with another member's behavior, report it to a moderator.

Formatik - 30-6-2008 at 21:34

Quote:
Originally posted by PainKilla
I just want to add that I find this thread to be very interesting, at least, where the chemistry was involved. I am quite against the weaponization of such agents but chemistry is chemistry, and I am sure even these compounds have some medicinal uses (well relatives anyway).


That can be said of at least diisopropyl fluorophosphate, F-P(O)(OC3H7)2, which is quite volatile and has a lethality along the lines of HCN, but its toxicological action is like the classical nerve gases. Its medicinal use is as a miotic in glaucoma therapy.

Sauron - 30-6-2008 at 22:29

DFP was developed by Saunders (q.v.) as a military agent, it is regarded as a first generation OP agent along with octamethylpyrophosphoroamidate (OMPA), tetraethyl pyrophosphate (TEPP) etc. These paved the way to the second generation tabun, sarin and soman, the G-agents (G for Germany) and these pointed the way to the V-series (V for venemous) which came along about a decade later. But as I mentioned, this was all serendipity, the chemists were after pesticides, high mammalian toxicity was undesirable. Still the world situation made militarization unavoidable.

The scary part is that there are at least two maybe three generations of nerve agents that we know very little about. The state parties involved (Russia and USA) have a conspiracy of silence going, they don't even use consistent euphemisms for these shadowy weapons which are, arguably according to the Russians, excluded from CWC and other treaties purportedly banning CW.

We can't begin to understand this threat without knowing what came before.

If we leave aside DFP, which is about as toxic as HCN (not very as OP agents go) there are striking similarities between all of the 2nd and 3rd generation OP agent structures.

The heart of every one of these is a pentavalent phosphorus with a pi bond to oxygen and a sigma bond to an alkoxy group.

Agents of the GA type have a diaminoalkyl group sigma bonded to P and a highly electron withdrawing group such as a nitrile (-CN) also sigma bonded to P. In the case of GA itself, the substance is N,N-dimenthyl-O-ethylphosphorocyanoamidate (see below).

Other known homologs such as G11, simply replace the methyl groups with n-propyls.

The larger group of G-agents have an alkyl group directly sigma bonded to P, the alkyls being methyl, ethyl, n-propyl or isopropyl. The alkoxy groups are preferably secondary such as isopropyl or pinacolyl or cyclohexyl. The very characteristic electron withdrawing substituent is fluorine. Examples are sarin GB, soman GD and cyclosarin GF.

The V-series differ from the above only in that there is no electron withdrawing substituent. Instead there is a highly characteristic -S-CH2CH2NR2 side chain. The most potent known member of the series, VX, is shown upthread. In its instance R = isopropyl, the alkoxy group is ethyl and the alkyl group is methyl.

The GA agents are in general nonpersistant, meaning that they breakdown to relatively nontoxic products in the environment rather rapidly, the -CN or -F bonds being labile to hydrolysis. GD is hindered so semipersistant especially in cold climates.

G-agents as a generalization are 10-20 times more toxic than HCN.

V-agents are c10 times more toxic than G-agents, they are quite persistant, difficult to decontaminate, but are not very volatile and primarily operate as aerosols or by skin absorption.

The 4th/5th and 6th generation agents about which little is known for certain, are believed to be OP agents, of same order of toxicity as VX, and are designed to defeat MOPP gear, detection systems, and prophylaxis as well as therapeutic agents (antidotes taken before and after exposure respectively.) The Soviet Union is believed to have developed these weapons starting in late 1950s and continuing ever since, even after the fall of communism, under cover of various agrochemical research institutes not subject to CWC inspection. What information is in the open literature is fragmentary, and often unverifiable. For some insight into this see my Novichok thread. This Russian word means Newcomers.



[Edited on 1-7-2008 by Sauron]

OP.jpg - 75kB

Sauron - 1-7-2008 at 20:35

Here are two examples of homologous structures in the G and V series. AFAIK these structures have never been illustrated in the open literature before now. They were described but not illustrated in the military training manual for CWC inspectors posted by ritter, let's give credit where it is due.

G11 is also referred to as P-GA or propyl-GA.


In addition to PP-VX shown below there is also P1-VX, which is the isopropylphosphine oxide derivative rather than the n-propyl.

[Edited on 2-7-2008 by Sauron]

homologs1.jpg - 55kB

Sauron - 2-7-2008 at 00:17

Two more agents in the G series that AFAIK have not been previously illustrated structurally in the open literature.

GE "ethyl sarin" has a CAS number [1189-87-3] so maybe I am wrong.

Again, from US Army manual of CWC scheduled chemicals courtesy of ritter.

There is also an "ethyl GD" (ethyl soman) which is O-pinacolyl ethylfluorophosphine oxide. Also known as E-GD, this agent carries CAS registry no. [97931-20-9]. The highly hindered ester imparts semipersistance (resistance to hydrolysis in the envirment) to the fluorine moiety. Pinacolyl alcohol is the product of reduction of pinacolone, the rearrangement product of pinacol. Few who have been classically trained in organic chemistry will forget having dimerized acetone to pinacol and rearranged it to pinacolone.


[Edited on 2-7-2008 by Sauron]

homologs2.jpg - 92kB

Sauron - 2-7-2008 at 00:53

The US Army manual also makes reference to "isopropyl GA" "isopropyl GD" and "isopropyl GF" which in each case are the 2-propylphosphine oxide esters homologous to the familiar GA tabun, GD soman and GF cyclosarin agents respectively. These are also referred to as I-GA, I-GD and I-GF. Propyl GA shown earlier is also referred to as P-Ga, not to be confused with the pro golf association! It is reasonable to assume that other alkyl homologs of G-agents may be similarly identified.

For example PriP(=O)(O-cyclohexyl)F is I-GF

If anyone wants these illustrated explicitly let me know.

[Edited on 2-7-2008 by Sauron]

Sauron - 7-7-2008 at 18:44

It has come to my attention that my claim upthread to be the first to illustrate the structures of a number of the G and V series agents and their homologs is partially incorrect.

Compendium of Chemical Warfare Agents by S.Hoening does show some (but far from all) of these, particularly the agents with G and V codes.

Structure graphics for the following, however, do appear to be novel in the open literature:

E-GA, E-GD, E-GF ethyl homologs of alkyl groups in G series
P-GA, P-GB, P-GD, P-GF n-propyl homologs
I-GA, I-GB, I-GD, I-GF 2-propyl homologs
G-11 or G11 N,N-di-n-propyl homolog of GA
PP-VX n-propyl homolog of alkyl group on phosphorus in VX

No CAS Registry numbers were published for these structures. All are within the regulated envelope of CWC. Certain other homologs are obviously implied particularly in the V-series. I have omitted their structural drawings for lack of their mention in any open source document (at least to my knowledge) thus far.