Synthesis of Thio VX - Original Article

[simply RED]

This is an original article (from 1972) concerning the synthesis of thio VX.
I'm typing it transalted from russian.
[my comment]
(C2H5O)2EtP=O + PCl5 = Et(Cl)P(OEt)=O [ + POCL3 + EtCl ]

1. Synthesis of (Et)(Cl)P(OEt)=O
14,5 g (C2H5O)2EtP=O is dissolved in 33ml absolute CCl4. 15,3 g PCl5 is added to this solution and the mix is allowed to stay overnight at room temperature [knowing of our (economic) conditions - this could be very cold :) ]. Yield 11,8 g. Boiling temp: 82-84 deg Celsius (11 mm Hg).

2. Synthesis of CH3-CH2-S-CH2-CH2-S-P=O(OEt)(Et)
Suspension of 1,14g Na metal in 30ml benzene is added to 6,1g EtSEtSH. The mix is heated 3 hours to 80-85 deg Celsius. The mixture is cooled to room temp and 7,8 grams (Et)(Cl)P(OEt)=O are added.
Then the mix is heated for 8 hours to 85 deg.
The mixture is then dissolved in very little water and extracted many times with benzol.
Benzol is dried with Na2SO4 and evaporated in vacuum.
[At this step you have material with LD50~50 mg/kg]

3. Final step - ["Charging" of the S atom].
0,05 mols CH3-CH2-S-CH2-CH2-S-P=O(OEt)(Et) is dissolved in very little benzol. 0,05 mols (CH3O)2SO2 is added to it. The mix is boiled 2 hours with condenser [fumes condense and go back to the mother liquid] with CaCl2 tube. [you have VX now - BEWARE!!!]
The solvent is evaporated, the yield is mixed with diethyl ether and left overnight. After the ether is decanted, pure [VX] is produced as a viscous liquid. Overal yield (from all steps) 66%.

Institute of elementorganic chemistry scientific academy CCCP and Tashkent uni. V.I. Lenin
19.IX.1972

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Comments:
Et(EtO)2P=O could be substituted with (EtO)3P=O producing a product with the same potency.
Step 1:
One majour drawback...
No instruction is given how to separate Et(Cl)P(OEt)=O from POCL3. Maybe fraction destilation in vacuum where POCl3 should pass first?
bp POCl3 108 degC 760 mm Hg ; bp Et(Cl)P(OEt)=O 85 deg - 11 mm Hg...
Step 2:
Would't it be easier directly to add Et-S-Et-SNa to the Et(Cl)P(OEt)=O?
(NaOH + R-SH = NaSR + H2O)
(R-P-Cl + NaSR - R-P-SR + NaCl)
Step 3:
(RSR + (CH3O)2SO2 = RCH3(S+)R [(CH3O)OSO2-)]
I thought it will react at room temp, now it's obvious it should be boiled 2 hours in benzene.
It should be done much wiser to minimize the chance of accident. Like making special vessel for the reaction.
There is no need to purify the product...

The toxicity of benzene will not be the only problem here, I guess... :)


Quite interesting idea I had the last night -- concerning tetraethyl pyrophosphate (TEPP) (already with LD-50 = 1 mg/kg).
((EtO)2(P=O)-O-(P=O)(EtO)2). It should react with thio choline or CH3-CH2-S-CH2-CH2-SH producing the same VX and OH-P=O(EtO)2. The last could be neutralised with some diluted base to "freeze" the reaction, and thats it... Do you have info on TEPP synthesis?

[akinrog]

I don't want to object you but does VX contain two isopropyl alcohol groups ((CH3)2C-O) instead of Butyl alcohol (C2H5O-) groups? Regards.

[simply RED]

This one is exactly with etoxy groups (C2H5O). Etoxy groups make it more potent than metoxy groups.
There are hundreds of VX formulas.

[simply RED]

wrong message wrong message 1234

[oneup]

why do you want to make this stuff? do you actually want to kill someone :s

[festergrump]

Learning is FUN. Discussion is important to the learning process. You'd prefer to re-discover it by accident, perhaps? Shhhhh!!!

[Chris The Great]

Nerve agents are an interesting aspect that so far has not yet been experimented with by "amateurs" and is really only researched by several people here. I'd say there are only four forum members who actually have a strong interest and have done large amounts of research into the topic: Samosa, SimplyRED, Megalomania and myself. I am not sure if nbk has done large amounts of in-depth research on nerve agents specifically but he certainly has done alot of CW research in general.

From what I have read about V-agent toxicity mechanism, methoxy should actually be more deadly due to steric effects (smaller groups allow it to attach more easily to the cholinesterase, ie ethoxy > isopropoxy for V agents). It must have some other drawback, since I have not seen it mentioned in anything I've read (ALOT). It could be more susceptable to hydrolysis or something.
The nitrogen analogs are more toxic than the sulfur analogs (the topic of this thread) but are more difficult to make. Nonetheless, the 'charged' sulfur analogs are still extremely toxic!

Does anyone have an easy synthesis for EtSEtSH?

Also, I would imagine PCl5 could be replaced with COCl2 for selective chlorination, as in the sarin procedure (only difference is with sarin you have isopropoxy groups instead of ethoxy groups). This makes the procedure alot cheaper, and COCl2 is alot easier to make OTC than PCl5.

[FUTI]

methyl esters have alternative way of hydrolysis through Sn2 attack on methyl group...maybe that is the reason why it is not used? I guess that it would still inhibit the enzyme, but that enzyme inhibited in this way is maybe easier to "regenerate" than the "acyl-enzyme VX type" complex we all know.