Pesticides and Harmful Breakdown Products

[MrSamosa]

I've been researching a few readily-obtainable Organophosphate Pesticides and their potential as AntiCholinesterase agents.

The one that I spent the bulk of my time researching was Malathion. Malathion can be found at the local K-Mart (For those of us in the USA) in a 50/50 solution of Malathion/Water for about $11 USD. It is also sold as a dusting powder, but I'm not sure of the concentrations of that.

Ordinarily, Malathion is pretty harmless to mammals. But, through oxidation, a dangerous breakdown product called Malaoxon is formed. Malaoxon is an active Cholinesterase inhibitor. I know that Malaoxon is toxic to mammals...although I have not been able to find an LD50 or if it even has the potential for causing death. All I can really confirm is that it causes liver damage and has nasty interactions with other medicines, particularly ones that affect/are broken down by the liver. Now, how many people take Advil? <img border="0" title="" alt="[Wink]" src="wink.gif" />

Aside from drug interactions, Malaoxon is particularly toxic to children, the elderly, and the sick.

Another Pesticide I looked into was Parathion and its oxidation product Paraoxon, which is considerably more toxic than Malathion/Malaoxon. It is also odorless. I abandoned research into Parathion because it is not easily obtained and the EPA is considering banning it.

Here is the problem- what could be used to breakdown Malathion? Several different articles mentioned "different bacteria and microorganisms", but none mentioned specifically which organisms. I also read in another article that Malathion, even without the help of microorganisms, will break down to about 8% Malaoxon and other products. I'm sure there is a better way to break Malathion down to Malaoxon with halfway decent yields...to figure out a way would allow us to easily produce the "poor man's Nerve Gas".

[nbk2000]

Surely there's some chemical means of oxidation that could be used instead of bacteria or such.

[MrSamosa]

A quick look at the MSDS for 80.7% Malathion turned up this:

</font><blockquote><font size="1" face="Verdana, Arial, Helvetica">quote:</font><hr /><font size="2" face="Verdana, Arial, Helvetica">INCOMPATIBILITY WITH OTHER MATERIALS: Alkaline and Acidic conditions and materials. Oxidizing materials. Mildly corrosive to metals such as steel, iron and copper.</font><hr /></blockquote><font size="2" face="Verdana, Arial, Helvetica">Perhaps this is the way to chemically decompose Malathion? Very simple it seems. Just add an oxidizer. Another MSDS said to avoid reducing agents. I will have to buy some of this pesticide and do some experimenting...when I get some more money. I would appreciate if someone could help me though, because I don't have access to many chemicals or to any glassware.

<small>[ July 08, 2002, 01:55 PM: Message edited by: MrSamosa ]</small>

[pyromaniac_guy]

you may also want to consider sevin, 1-napthyl methylcarbamate as a cholinesterase inhibitor. The material is a common agent in the us, as well as extreemly inexpensive...

[MrSamosa]

From my initial searches on Google, Carbaryl Sevin looks very appealing as a Cholinesterase Inhibitor. But, what appeals to me even more is one of the precursors...Methyl Isocyanate. There was an accidental release of this in Bhopal, India which killed over 2,000 and wounded many thousands more.

Perhaps if Sevin were mixed in with DMSO, to allow it to better absorb through the skin? What I'm really trying to do is not simply BUY Pesticides and use them as Chemical Weapons, but to find ways to modify them to make them better. It's a bit more challenging, and I like challenges =).

[pyromaniac_guy]

Mr Samosa,
Even if it was absorbed through the skin better, sevin has a very low toxicity for higher forms of life, something like .2g per kg... You would definatly want to use it as a precursor to something a bit more fun if it is to have any use as a chemical warfare agent

[MrSamosa]

After looking into Sevin, I've come to the conclusion that it would not make a good chemical weapon...unless its detection properties are minimal or can be reduced. Carbaryl, or Sevin, is a carbamate. Applied to this topic, that means that it IS a Cholinesterase inhibitor, but the anti-cholinesterase effects are reversed after exposure stops. That means that in order to kill or seriously injure, one must be under constant exposure. In order to assure this, the detection properties must be minimized.

Malaoxon on the other hand is an Organophosphate. Although it may not be quite as toxic as Sevin, the effects last considerably longer. Also, generally Organophosphates tend to be more toxic than Carbamates.

I like Sevin though. It can probably still be made use of...

[MrSamosa]

I was thinking...what about a mixture of Carbaryl with an Organophosphate pesticide, or just mixtures of different Organophosphates? I like the idea of mixtures because the body mechanisms needed to breakdown one poison can be inhibited by the other, thus increasing the toxicity.

I doubt this will work as I plan, but maybe the Malaoxon would increase the Carbaryl's effects? Maybe the Carbaryl will cause the quicker, more severe injuries while the Malaoxon prevents the body from detoxifying the poisons? It's hard to put in words what I'm thinking, so I hope you are able to understand it.

However, in an MSDS for 57% Malathion and the rest being a mixture of Xylene, T-Mulz Light Aromatic, Cumene, and Trimethyl Benzene , it says it is incompatible with Carbaryl =(. Oh well, this is brain storming...can't expect too much from it yet.

EDIT- I keep forgetting to mention this: Malaoxon is 40 times more acutely toxic than Malathion <img border="0" title="" alt="[Eek!]" src="eek.gif" /> .

<small>[ July 12, 2002, 08:11 PM: Message edited by: MrSamosa ]</small>

[MrSamosa]

I'm sorry to make 3 posts in a row in this thread, but I like to break my thoughts down into smaller, to-the-point, one-general-idea posts.

I have found another Insecticide that is of much interest. It is Diazinon and is an Organothiophosphate. You can find it in K-Mart under the name "K-brand Diazinon". It is 22% Diazinon combined with Petroleum Distillates. As is, it's LD50 isn't TOO bad... 300-400 mg/kg for rats. The results vary significantly, some state it to be much lower than that. Diazinon, like Malathion and other Organothiophosphates, has an oxidized form called "Diazoxon" which is an active cholinesterase inhibitor and significantly more potent. Both Diazinon and Diazoxon can be toxic through dermal exposure, thus making them more versatile chemicals. Like other Organophosphates, Diazoxon (this is the form that is of interest to us) is Lipid soluble. As a weapon, this is worth noting because it allows it to better penetrate the Central Nervous System and cause prolonged seizures, hyperthermia, and other fun things.

The way Diazinon has been oxidized in lab tests was by using 5% Sodium Hypochlorite or with Calcium Hypochlorite (not sure of the concentrations with this). Other articles simply state that "An excess of Chlorine in water" will do the job. The first way seemed strange to me, because I thought that the Sodium Hypochlorite would destroy organophosphates? Correct me if I'm wrong...

Also, if there is low water and the Diazinon is in acidic conditions, it breaks down to tetraethylpyrophosphate (TEPP), which is extremely toxic.

On the core Phosphate molecule of Diazinon, there are two Ethyl Groups attatched to the Phosphate group. A PDF file I found stated "Ethanol AChEs are rarely toxic due to their short duration of action." Since I'm an idiot when it comes to OP Chemistry, can someone tell me if it would be possible to replace the Ethyl Groups with another alcohol?

<small>[ July 16, 2002, 06:46 AM: Message edited by: MrSamosa ]</small>

[A-BOMB]

Except there is one thing wrong with that, they pulled Diazaon off the shelf. Because I'll been looking for it and now they all sell this Diazion replacement and I asked a clerk there and he said the Diazion was too lethal and some idiot got poisoned by it and so I bought a can of the replacement and it don't kill bugs worth shit! And It costs more too!

[MrSamosa]

I can find Diazinon just fine here in Maryland...22%, 5%, 2%, it's all over the place. I guess I better stock up on it before it's no longer sold in K-Mart. I'm going to buy some tomorrow to do some testing. Sucks for you all though, who can't get a hold of it...I'll focus more time on Malathion then, for your sake.

[A43tg37]

Here in Georgia (at least where I'm at) Diazinon is still fairly plentiful as the liquid form, but the pellet/granule form is getting harder and harder to find (not that that really matters; the liquid would almost certainly be more useful in any synthesis). One form of Diazinon that particularly interests me is a paint additive called "Bug Stuff". Whereas most pesticide Diazinon is 22-30% pesticide and the rest inert ingredients, Bug Stuff is 87% Diazinon. The only disadvantage is that it is comparitively more expensive, selling in paint and wallpaper stores for around $4 for a one ounce (easily pocketable) bottle, but at that high of purity, it might well be easier to use in producing TEPP or Diazoxon.

[A-BOMB]

Well here in Pennsylvaina I've trying to find grandual form for killing ants and I can't find it anywhere (home depot,lowes,k-mart,wallymart,etc...etc...etc) you are lucky but I am luckier my grandfather still has a small can of DDT if anyone is interested.

[MrSamosa]

Anyhow, I just bought 1 Quart (32 oz) of 22.4% Diazinon from K-Mart. They don't have much left, unfortunately...but I don't know many gardeners who want the stuff anyway. They all do their best to avoid it, which is good for me.

Does anyone know what kind of protection I should take as I run my tests on it (different ways of oxidizing it, ways to purify the Diazinon)? I will make solutions of Sodium Hypochlorite and Sodium Hydroxide for decontamination. For clothing, all I have are some cheap plastic gloves (i know this won't do shit, but it makes me feel more secure), a C-5/ M-69 Canadian Gas Mask with a relatively new NATO Filter, some Jungle Boots, and a WindBreaker I wear to cover my arms and shirt. As I work, I plan to have a mirror and flashlight to test how my eyes respond to light every few minutes... I will be working in my garage which is quite warm this time of year, so I will have the Diazinon in an ice-bath most of the time, to prevent it from evaporating.

EDIT- I've dreamt about one test...by freezing the pesticide. In my dream, I froze 100 mL in a normal freezer, in an attempt to separate the Daizinon from the other chemicals. I don't know what these "inert ingredients" are, but they give the insecticide a creamy-white color, almost like milk. It smelled like a mixture of grass and epoxy. Freezing failed to separate the liquids.

Does anyone have other ideas? I was thinking maybe using Cooking Oil (a Lipid) to try to separate them. The Cooking Oil is a lipid, which Diazinon is soluble in and hopefully the other chemicals aren't. I just want some ideas so I don't waste my precious dream-time =).

<small>[ July 17, 2002, 05:47 PM: Message edited by: MrSamosa ]</small>

[Boob Raider]

I don't have many ideas .. but from what it sounds like ..... the milky appearance could be due to an emulsifier and something water based to dilute the diazion with. So I would suggest instead of using cooking oil or something that non-volatile .... use petrol, or diesel or something. Oh btw in India, many pestisides were sold in solutions with kerosene, so petrol should work.
Oh and here is another synthetic toxin (I was searching on Yahoo) :
DIOXIN
Aromatic compound, any of a group of contaminants produced in making herbicides (e.g., Agent Orange), disinfectants, and other agents. They have two benzene rings connected by a pair of oxygen atoms; when substituents on the rings are chlorine atoms, the molecules are particularly toxic. The best known, usually called simply dioxin, is 2,3,7,8-tetrachlorodibenzo-p-dioxin, or 2,3,7,8-TCDD. It is extremely stable chemically, does not dissolve in water but does in oils (and thus accumulates in body fat). Its human toxicity is disputed and the subject of continuing research.

[nbk2000]

Dioxin isn't immediately toxic to humans though. Sure, it may cause cancer, but that's not the topic on hand.

It IS, however, extremly toxic to animals, birds especially. In Italy many years ago, there was a dioxin release of a few dozen kilos. Birds 50 miles downwind just fell out of the sky, dead. <img border="0" title="" alt="[Eek!]" src="eek.gif" />

Horses, cows, dogs, cat, etc...dropping dead for miles.

People...nothing. Oh sure, the cancer and luekemia (SP?) rate went up a few percent, but so what?

Dioxin does have some humble orgins though. Seems you can make it by chlorinating DDT, which is itself made from chloral hydrate, made by chlorinating alcohol.

[MrSamosa]

Who ever said Chemical Weapons have to be used against people :cool: . What I see from Dioxin is a weapon of economic warfare. I believe Winston Churchill was worried about this during WW2, I can't remember his exact quote though. Basically he was concerned about herbicides wiping out their crops, biological agents for killing cattle, poisons in the water, etc. etc. If you can destroy a food supply though, that is an easy way of affecting a large population...and the dispersal seems like it would be easier. Killing plants is easier than killing people.

Think of unconventional uses! <img border="0" title="" alt="[Wink]" src="wink.gif" />

[megalomania]

Both the Malathion and Diazinon structures have the makings of thiosarin. Not really thiosarin itself actually, but a close derivative. One would have to selectively remove the esters, and then rebuild the molecule in your image (faster, stronger, and better than before, the 6 million dollar molecule…). Just off the top of my head I would say hydrolysis to a carboxylic acid may be the way to go. You could saponify Malathion to reduce it to a diol. That diol should react with HF to attach a F on there (not selectively, you will get a mix of mono and di fluorinated products). You could then reconvert the remaining OH of the phosphonyl into a suitable ester.

Oh I forgot the pyrimidide part (the substituted sulfide arylamine attached to the phosphorus). I am not sure how to knock off that –S–X portion of the molecule off hand. The reason I chose Malathion as a better starting material is because of it though. I suspect it can be removed with little trouble. Less so than Diazinon, which would make quite the mess with three esters to remove. I gather sulfides react the same as ethers do, which would mean HF acid may not be the best as it will attach an F as well. Instead of HF for attaching that fluorine you could SOF2 or PF3, and then use another HX acid to break the sulfide apart while attaching a more readily reacted halogen. Another way to go would be to remove the sulfide first with HX, attach an alkyl group to that, convert the esters to alcohols, replace one of those with fluorine, and reform an ester with your choice of alcohol. Viola, sarin or soman. Actually thiosarin or thiosoman. I am just brainstorming as well, some research will be required here.

EDIT: oops, I completly confused those compounds. The arylamine part is actually on Diazinon. This dosn't change anything I said above, I should then say first remove the sulfide-ester. The arylamide of Diazinon is just one of the three esters that is removed just like the other two. I should also like to emphasize why I disliked Diazinon, it is because I feel yield would be lower if you had to deal with 3 identical -OH functional groups. These could not be selectively converted, wheras with Malathion you can remove the sulfide, and then deal with only two -OH groups.

<small>[ August 27, 2002, 01:18 AM: Message edited by: megalomania ]</small>

[megalomania]

I have decided to explain what I mean graphicially, with a graphic :)

<img src="http://www.roguesci.org/images/malscheme.gif" alt=" - " />

In this proposed reaction we first remove the sulfide by replacing it with a halogen. Since HCl reacts very poorly, and HF not all all, we preferably use HI or HBr. I think HBr would be easier to get a hold of. We then react the halide with lithium dimethylcuprate (easily prepared) to replace the Br with a methyl group. An alternate process to this would be to react the halide with some sodium cyanide to give yourself a tabun structure. In our third step we saponify and aciduate the ester to form a thiophosphoryl diol. If you are following the tabun route you would use dimethylamine instead of saponifying thus making an amide. You would get a diamide to some degree. In our fourth reaction we wish to get a phosphonofluoridothionate. Unfortunatly it is rather difficult to attach a fluorine directly to phosphorus, but we can easily exchange with a bromine ion. We then brominiate with Ph3Br2 and react that product with ammonium fluoride in acetonitrile. You might be able to get such an exchange with chlorine, first chlorinating with PCl5, and then replacing with F with ZnF2. It is rather difficult to replace a chlorine with a fluorine, which is why the bromine route is preferable. This would lead us to a dihalogenated product, not good. I do not know what yields you would get, but assuming the halogenation process is not very efficient, you could separate out the dihalogenated product and hydrolyse it back into a diol and try again, so there is no waste at least. Our final step is to add some oh so rare and hard to obtain ethyl or isopropyl alcohol (pinacolyl alcohol for the truly resourceful). There then is thiosarin with isopropyl, thiosoman with pinicolyl alcohol, and of course all of the other unnamed derivitaves with all the other types of alcohols (like cyclothiosarin with cyclohexanol).

Now then my chemistry assumes these reactions will work with phosphorus. These reactions are derived from carbon chemistry. Except, that is, for the phosphonofluoridothionate part which is real. I obtained that information from the journal ‘Bulletin Academie Polonaise des Sciences Serie des Sciences Chimiques’ Vol. 17 No. 2 pg 75-77, 1969 by B. Pliszka-Krawiecka, M. Mikolajczyk, and J. Michalski. That is quite the name for a journal. Why, it occurs to me that none of the chemicals involved here are particularly hard to obtain or prepare. We have no harsh temperatures, or super pressures. The only problem I foresee is attaching a single fluorine instead of two in the fourth step.

After further research I have found that thioesters can be easily replace by reacting with an alcohol. With this method we can remove the sulfide portion simply by adding an alcohol, which gives us a triester. In fact this gives us a similar molecule to Diazinon. I shall have to look into using that substance and route later.

[MrSamosa]

Haven't heard from this therad in a long time, have we? But, I have some more useful information to contribute. I came a cross this link not too long ago, and it has some good information on entomology, insecticides, and cholinesterase inhibition-- including tables and detailed explanations of reactions: http://wcb.ucr.edu/wcb/schools/CNAS/entm/tmiller/1/modules/page25.html

Relating to this thread, they discussed how to change the P=S bond to a P=O bond. In their tests, they used Brominated Water-- not something too difficult for the amateur. In the case of Diazinon undergoing degradation to TEPP, do you suppose that H2O2 could accomplish this? Being an oxidizer, it could be used to replace the Sulfur. Following the oxidation, it becomes H2O, and could thus be used to further Hydrolize the resulting Diazoxon... or is my logic flawed here?

After looking freshly at Mega's graphic, I see something interesting- could the leaving group on some insecticides be replaced with a more reactive one?? For example, could the worthless carboxlyic acid in Malathion be substituted with a more reactive Halogen, as Mega says?? Because if that's true, then simple Diethyl Thiophosphonobromide/iodide/etc. would themselves be potent and relatively stable cholinesterase inhibitors, and with much less effort than continuing the synthesis to full-blown Thiosarin.