Tetramethylenedisulfotetramine

[c0deblue]

Good to be back again after a long absense, and nice to see so many old familiar names!


Overview:

Tetramethylenedisulfotetramine, or TETS, C<SUB>4</SUB>H<SUB>8</SUB>N<SUB>4</SUB>O<SUB>4</SUB>S<SUB>2</SUB>, is a little known but extremely potent neurotoxic poison reported by the CDC to be 100 TIMES more toxic to humans than potassium cyanide. TETS is an odorless, tasteless, water soluble white crystalline powder that acts as a gamma-amino butyric acid (GABA) antagonist which binds noncompetitively and irreversibly to the GABA receptor on the neuronal cell membrane and blocks chloride channels. Exposure causes violent convulsions, ischemic neuropathy and other damage, with death following (for severe exposure) usually within three hours. The usual routes of TETS poisoning are by ingestion or inhalation, but there are reported cases of poisoning by skin absorption. Damage from exposure is essentially irreversible, and dosage is the only determinant of whether a victim dies or survives with irreparable neurological/brain damage. There is no known antidote for a lethal dose, and the only treatment for less-than-lethal doses (in China) is charcoal hemoperfusion and hemodialysis; neither of these are effective against lethal doses because they proceed at a much slower pace than the action of the poison. The incidence of TETS poisoning is sufficiently rare that the nature of the emergency is seldom even recognized by medical personnel, who in any case are unable to do much in the way of intervention. The CDC and the New York Poison Control Center report an LD50 for mammals of 0.1-0.3 mg/kg, with 7.0-10.0 mg the assured lethal dose in adult humans. Sounds like something the CIA might use. (Links to reports below, including complete chemical and physical characteristics).


So it looks as though hexamine, that readily-available old favorite of dabblers in energetic materials, may be the principal precursor in TETS production. While Tets is an order of magnitude less toxic than ricin, it acts so quickly and with such profound and irreversible effects at minute doses that the possibilities ought to send shivers down the spine of anyone who's ever fooled with hexamine or its precursors (Wonder what would happen if I added a few drops of this ... ? :eek: ) Of great concern is whether or not TETS might someday be the inadvertant and unrecognized (!) intermediate or byproduct of some ill-advised experiment. I'm thinking that one danger may lie along the lines of attempts to produce RDX via some variation or improvisation of a less-than-optimal synthesis involving sulphuric/nitric acid combinations, rather than the established method of nitration with 98% white nitric acid alone. For example, there are some processes (for substances other than RDX) that seek to minimize the risk of dangerous thermal runaway by pre-reacting any required sulphuric acid with the precursor chemical and allowing it to cool prior to nitration. If similar methods were to be experimentally employed for RDX production, mightn't the result potentially include as an intermediate or byproduct TETS or a close analogue?

I'm not that well-versed in the nuts and bolts of theoretical chemistry, so I thought I'd let the E&W whiz kids have a go at a TETS synthesis. This shouldn't be too difficult: although banned in China since the mid 1980s, TETS continues to be widely available due to high demand and a reported ease of production that puts it well within the capabilities of any backyard "entrepreneur" with kitchen utensils.

So the question is how do you go from

C<SUB>6</SUB>H<SUB>12</SUB>N<SUB>4</SUB> (hexamethylenetetramine - or its precursors)
to
C<SUB>4</SUB>H<SUB>8</SUB>N<SUB>4</SUB>O<SUB>4</SUB>S<SUB>2</SUB> (tetramethylenedisulfotetramine)?

The answer to this question would certainly be of great academic interest, as well as perhaps of literally VITAL importance to experimenters in knowing exactly what chemical combinations and methods to avoid when working with hexamine or its precursors!


Links to reports/physical characteristics on Tetramethylenedisulfotetramine: (suggest a copy-and-paste to URL bar to avoid referrer codes pointing back to E&W Forum)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5210a4.htm

http://www.dekker.com/servlet/product/DOI/101081CLT120022008/section/abstract_202 (click "Agree" to terms and conditions for report)

http://www.intox.org/databank/documents/chemical/tetradis/pim982.htm#7.2

http://aapse.ext.vt.edu:100/pdf00007.pdf (It appears this link is dead)

Additional information may be available using Searchword "Dushuquiang" - the Chinese name for the banned rodentcide containing anywhere from 6%-20% TETS.

Historical note: Dushuquiang (pronounced dooshoosheeang) has been responsible in China for the accidental as well as intentional deaths of many thousands. As recently as last year, the proprietress of a snack shop in a rural province indulged her drive for increased market share by visiting a competitor's snack shop and sabotaging some pastries with a sprinkling of Dushuquiang. Despite frantic emergency efforts and a familiarity by Chinese doctors with the symptoms of Dushuquiang poisoning, 42 people died after ingesting the undetectable powder.

EDIT
Nice going NBK. Also found the following in a Google search for "disulfo tetramine synthesis":

"... Tetramethylene disulfotetramine: a (not-so) novel rodenticide In 1949,
chemists at Bayer in Germany published the synthesis of tetramine. ... "

This appears only in the Google description and not on the linked webpage which contains only an abstract and subscriber link.

Google's descriptive text apparently is part of a PDF monograph titled "Rat poison and food security in the Peoples Republic of China: focus on tetramethylene disulfotetramine (tetramine)" which unfortunately is accessible only to subscribers. Doubtful that it includes an actual synthesis, but knowing a synthesis was published in 1949 by Bayer could be helpful.

[nbk2000]

Found this at http://www.chinaphar.com/1671-4083/25/534.htm

+++++++++++++++++++++

The acute poisoning of tetramine has the following characteristics: rapid incidence, severe state of convulsion, speedy lethality, and high mortality. The poisoning attack often happens 0.5 to 2 h after ingestion. The respiratory failure is the primary cause of death of tetramine. The EEG change has some relationship with toxicity. The dynamic monitoring of EEG is an important indicator for judgment and instruction of treatment[66]. The serologic examinations for liver functions and myocardial enzymes also reflect the toxic severity and damaging degrees of liver and heart, and are used to predict the prognosis[67].

Pharmacologic and toxicologic studies Tetra-mine barely dissolves in water, slightly in acetone, and not in ethanol. It is stable in acidic and basic solutions. The saturated tetramine still keeps stable biological activity after five months of storage. It is absorbed through gastroenteric tract and respiratory tract. Tetra-mine stores in human body in its original form. No biological transformation of tetramine has been reported. Tetramine eliminates from urine via renal filtration. There was a report that serum tetramine was still detectable 10 d after ingestion. LD50 for the oral administration was 0.1-0.3 mg/kg in rats, and 0.1 mg/kg for men. The lethal dose for human is about 12 mg/kg. Due to the stability and severe toxicity, it easily leads to the second poisoning. The observation in animal experiments and human clinics shows that tetramine has severe neurotoxicity. But it is a stimulator of CNS, leading to convulsion and entasia. It has no effect on peripheral nervous system, skeletal muscle, and neuromuscular junction. Tetramine does not affect the parasympathetic systems in spleen, kidney, intestine, and bladder. Experiments on frog brain by damaging different brain region showed that the primary action site of tetramine was in brain stem. Removing cortex did not stop frog convulsion, while removing the region below medulla completely stopped its convulsive epilepsy[68]. g-Amino-butyric acid (GABA) is an inhibitory neurotransmitter in vertebrate and invertebrate animals. The convulsion caused by tetramine is related to its antagonism to GABA action[69]. Roberts et al used ventral ganglions in isolated arthropod horseshoe crab to test seven convulsive agents against GABA's inhibition and found that the potency of tetramine was 2705 times weaker than that of picrotoxinin[70]. Tetramine antagonized the depolarizing action of GABA to isolated rat jugular sympathetic ganglion, but it did not antagonize the action of carbachol. The action of tetramine against GABA is non-competitive and reversible but is not similar to the action of bicucullin[71]. Tetramine dose-dependently antagonized the inhibition of GABA on crab neuromuscular transmission[72]. Therefore, tetramine possibly also blocks GABA receptor or affects the receptor function by blocking amino acid channels[73]. When concentrations of amino acids in the brain of the mouse that exposed to tetramine were measured, the concentration of GABA increased while that of glutamic acid decreased, suggesting that the levels of these amino acids are related to the convulsion caused by tetramine[74]. Experiments with autoradiography showed that tetramine reduced the affinity of [3H]GABA with its receptors in rat brain sections of different regions, indicating that tetramine is the blocker of GABA receptor[74].

Treatment protocols

Exterminate sources and heteropathy When exposed to tetramine by oral ingestion, stomach wash-ing, diuretics, enemas, and catharsis should be used as soon as possible. Anticonvulsive agents can be used for heteropathy of the acute poisoning of tetramine. Diazepam and sodium phenobarbital are the first choice as the anticonvulsive agents. For severe patients, both diazepam and sodium phenobarbital cannot control the convulsion. A combination of diazepam, sodium phenobarbital and sedatives can be used. For patients with convulsion and abnormal surge in EEG, sodium valerate is also suggested to take[65].

Specific antidotes Experiments with six sulfhydryl agents as antidotes to treat the acute poisoning of tetramine were tested in teramine-exposed mice[75]. Na-DMPS and Na-DMS were that significantly decreased the number of convulsive animals, delayed the surge of convulsion, and reduced mortality (P<0.01), and Na-DMPS was more desirable. The excitation of CNS by the toxicant was also reduced (P<0.01). Na-DMPS showed excellent inhibition of tetanic convulsion on acute poisoning with tetramine in animals. In mice the LD50 of ig tetramine was 0.262 mg/kg and LD50 of ip Na-DMPS as antidote was 0.502 mg/kg (P<0.01). Rats after using ip Na-DMPS 0.8 mg/kg showed the elongation of latent period of convulsion (P<0.01) and lethal time (P<0.01), reduce of convulsive time (P<0.01) and decrease of mortaliy (P<0.05). In Na-DMPs treated rabbits, latent period and lethal time were elongated. Icv administration of trace of Na-DMPS also reduced the mortality and the incidence of convulsion of acute poisoning in mice and the emergence of tetanic convulsion wave in rats[76]. Satisfactory protective effect was found when Na-DMPS was given 20 min before poisoning (P<0.01). Na-DMPS had no antidotal effect on tetramine- exposed mice when in mixture. Either Na-DMPS or diazepam could rise LD50 of tetramine in mice and could reduce the convulsion and death rate of rats with acute tetramine poisoning. The combined administration of Na-DMPS and diazepam showed a better effect on antagonizing tetramine (P<0.01). Electroencephalogram showed that Na-DMPS given ip 30 min before poisoning could inhibit the occurrence of tetanic convulsion wave, which could be dispelled by iv diazepam[77]. Another combined therapy was studied about the antidotal effects of vitamin B6 combined with Na-DMPS which turned out to be an excellent way for acute tetramine poisoning. They suggested that this may be used to clinical work to rescue patients poisoned by tetramine[78]. A clinical trial compared Na-DMPS as an antidote in 11 patients with the acute poisoning of tetramine with regular hetero-pathy in 5 patients. It was found that Na-DMPS possessed unexpected effects and cured all 11 patients while 4 of 5 patients in heterpathy group died and the survivor suffered from memory damage[5]. Another clinical trial observed Na-DMPS as antidote to treat 39 patients with the acute poisoning of tetramine (20 severe poisoned and 19 medium poisoned)[79]. Initially, 0.125-0.25 g Na-DMPS was administrated intramuscularly. Based on the convulsion situation, 0.125 to 0.25 g Na-DMPS was repeated every 0.5 to 1 h until the convulsion was completely controlled[79]. After the new discovery of Na-DMPS as an antidote used for acute poisoning by tetramine, a lot of physicians adopted Na-DMPS and mostly considered this antidote to be specific[5,79,80], excellent, or more effective[81-91]. But its precise effects still lack general recognition, even denied antidotal effects[92,93]. It is necessary to do a large scale of clinical verification[91]. Fu and Wei et al reported Na-DMPS with vitamin B6 rescued patients poisoned by tetamine and were all alive[94,95]. Zhang et al studied Na-DMPS on the antagonism of tetramine to GABA receptor on mice, used automatic analyzer to determine the contents of free GABA and glutamic acid in brain and used autoradiography to observe the [3H]GABA bindings in the rat brain slices. In conclusion, the inhibitory effects of Na-DMPS on the antagoism of tetramine to GABA receptor are due to the increase in the GABA binding to its receptor in brain[74].

HOPE AND PROSPECTS

In animals, there are many SH-group compounds, such as the minor, SH amino acids and SH-peptides, and the major, SH-enzymes and SH-proteins, which form the rich SH-group pools related to the biological life. The chemical structure is the foundation of the substance. Its special physico-chemical properties enable the SH-groups to regulate the cellular function, and to transfer the cellular signals[96]. In addition, it decreases the toxicants in body through special redox reactions. Beause the SH-groups and ions of heavy metal or metalloid can form the more stable chelating complex compounds. The SH group compound has been used as the antidote for some metallurgical and chemical industrial toxicants. Since the early war times, it has become the clinical therapy in the toxic war gas. With the development of pharmacology, toxiclolgy, and other related sciences, such as biochemistry and biophysics, etc, endogenic and exogenic SH compounds have been used as the specific antidotes, especially the Na-DMPS. Na-DMPS is an effective antidote against NTXI, CDM, bactericide 402, and tetramine. Due to lack of specific antidotes for a lot of pesticides especially, of non-metallic pesticides, it is urgent for pharmacologists and toxicologists to develop and solidify their researches on the antidotes against these pesticides. In addition to its effectiveness in the detoxication of heavy metals and metalloids by chelating action, Na-DMPS is also a specific antidote for several non-metallic pesticides. With the recent advance of scientific knowledge about the mechanisms of action of Na-DMPS about antidotal effects against pesticides other than chelating action, they shall widen its application in other pesticides, either low or high molecular weight, either inorganic or organic compounds and either great use for insecticides or raticides. China is a large agricultural nation, and many cases of poisoning by pesticides have taken place, especially in village. In recent years, it spreads to cities and affect social stabi-lity severely. For example there were more than 300 people poisoned and 42 died during the tetramine criminality in Nanjing city on 2002 Sep 14. Chinese researchers carried out the study on Na-DMPS for intoxication of pesticides and have found it has specific antidotal effect on many kinds of non-metallic pesticides. Great break through has been made not only in theory but also in practice and the research reaches international advanced level. These findings have been collected in the "Practic Internal Medicine", 11th ed[97]. The deve-loping which has been talked in the preface can meet the requirements of different clinical doctors. Chinese's finding that Na-DMPS can be used as specific antidote against tetramine and NTXI, has been edited by Ding Quan-Fu in "Pharmacology" 4th ed, normal textbook in the technical college of medical university[98]. More than 10 years ago Na-DMPS was adopted as antidote of SCS in the exprimental textbook in Wenzhou Medieal College and got very satisfactory results, which provided new antidotal knowledge and development for the doctors and medical students (personal communication). On the other hand, Na-DMPS can strengthen its antidotal effect against acute tetramime poisoning when combined with diazepam or vitamin B6, through the experimental researching and clinical observation. For example, atropine sulfate combined with pralidoxime chloride is the routine best choice, which is a combination of symptomatic therapy and causative therapy when treating the acute poisoning by organophosphorus insecticides. In poisoning by toxicants, the combined therapy is often used and has both theoretical and practial significances. Chen XY et al has recently reported Na-DMPS has protective effect against neuronal damage following ischemia and reperfusion in the rat brain[99]. Na-DMPS, as an exogenous dithiol compound icv significantly increased the latencyes and decreased the number of errors in cerebral ischemia reperfused mice. Meanwhile, Na-DMPS icv was found to be able to prevent the rise of malondialdehyde level induced by this experiment[100]. Sulfhydryl group compounds also have regulating actions to neuronal transmitters[101]. To explore the relationship between Na-DMPS and neurotransmitters or receptors will get brilliant achievement in neuropharmacology and neurotoxicology as against convulsion induced by tetramine and other central convulsants[73,74,102].

++++++++++++++++++++++

Lots of technobabble, but the gist of it is apparent.

Synthesis is the obvious first interest. There's a hint in the following statement from the same site.

"In 1933, it was first synthesized by sulfamide and formaldehyde"

Ammonia is an amine, and when reacted with formaldehyde forms hexamine.

Now, substitute sulfamide for ammonia, and you introduce a sulfur molecule into the hexamine, forming TETS?

EDIT:

In the Merck Index, 13th ed., it's listed as entry #9300.

Prep. from sulfamide, H2NSO2NH2, and formaldehyde in 60% H2SO4.

Now, what I'm wondering is, did they mean:

a) Sulfamide, [sulfamide formula], and formaldehyde? (2 chemicals)

OR

b) Sulfamide, [formula of something NOT sulfamide], and formaldehyde? (3 chemicals)

H2NSO2NH2 is the formula for sulfamide, according to the formula index in the back of the Merck, but it could be something else. Direct reading of the original references is needed. Mega? ;)

More info here:
http://www.inchem.org/documents/pims/chemical/pim982.htm

Seems it's also soluble in DMSO. How nice. :)

Company that'll make it for you as a research chemical:

www.neosyn.com/prepharm.html

CAS: 80-12-16

BIG listing of its properties and effects:

http://www.inchem.org/documents/pims/chemical/pim982.htm

A link to fluoride-based pesticide references found while searching:

http://www.fluoridealert.org/f-pesticides.htm

A blog page with a structural diagram:

http://blog.twblog.net/anion/archives/001716.html

Following the URL on the pic leads to a possible synthesis, but in taiwanese. :(

Being able to produce such a potent poison from such basic stock chemicals as ammonia, sulfur, formaldehyde, and such would greatly increase the potential for mass casualty jihad attacks by food poisoning, as we've seen already take place in china.

Odorless, tasteless, lethal in 10mg doses, with fractions of that leaving the victims permanent gimps....oh....too good to pass up. This would be just the thing for poisoning your weapons as per RTPB, as no effective antidote is available for it, and symptoms would be confusing, resulting in a kill from a flesh wound. :)

Of course, given the extremely toxic nature of the material, you'd have to be EXTREMELY careful in your preparation and handling of the material to prevent self-termination.

BTW, welcome back! Gods, it's been ages! I've dispaired of good discussions lately.

[simply RED]

mmmmmmmmmm
JUST GREAT !!!!!

[megalomania]

The synthesis of TETS looks like it follows the same mechanism as the formation of hexamethylenetetramine, a simple mixture of sulfamide and formaldehyde should do the trick. The role of sulfuric acid must be catalytic... I'll do some more research tomorrow, request the journal referenced in Merck, and report back. I do wonder how in the hell they came up with the acronum TETS, I would think it should be TMST or something.

The simplicity of the reaction is best exemplified by the fact that even though it is banned in China, it is still very much a hot commodity and sold cheap on the streets. Cheap and easy... I found a reference to a story about people getting sick after eating dogs that were killed by the poison; that's just disgusting.

Oh, and welcome back c0deblue!

[nbk2000]

It even has the capacity for use as an incapacitant.

Considering how effects manifest at several magnitudes less than the lethal dose, it wouldn't be too hard to specifically target a specific person with a dose that'd leave them hospitalized for a short spell, without killing them in the process.

Though, you'd have to be prepared for possible fatality.

The simplicity of the precursors, and a toxicity on par with organophosphates, makes it a possible additive for many other weapons, as a synergistic lethality enhancer.

A food additive, in low doses, to farm animals and crops to contaminate them and make them toxic to humans? Possible agri-terror agent?

[megalomania]

I found a synthesis today, although I don't care much for the acid they used...

Tetramethylenedisulfotetramine (8). A mixture of 4 (96 mg, 1mmol), 6 (152 mg, 2mmol), and trifluoroacetic acid (5 mL) was stirred at room temp (6 hrs). The solid that formed was filtered and dried to give 126 mg (96%) of 8: mp 252-254 C.

4 is sulfamide NH2SO2NH2
6 is dimethoxymethane CH2(OMe)2

Journal of Organic Chemistry Vol. 55 No. 25, 1990 pg 6098-6104
Intra- and Intermolecular a-Sulfamidoalkylation Reactions
Chai-Ho Lee and Harold Kohn

Other refs:
Dusenmund, J.;Schurreit, T. Arch. Pharm. (Weinheim) 1986, 319, 826.
Dusenmund, J. Ibid. 1977, 310, 600.
Hecht, G.; Henecka, H. Angew. Chem. 1949, 61, 365.
--------------

I suppose the good stuff is in the Angewandte Chemie article. Notice how this reaction involves only a mixture of two reactants with an acid. Just plain old stirring and the desired product precipitates. The aim of using dimethoxymethane was to insure maximum yields. This is also likely the reason they use such a strong acid as trifluoroacetic acid.

[nbk2000]

Found another reference to a synthesis procedure which was used to prepare a comparative standard for a poisoning case.

Mo J., His-Yuan C., Synthesis of tetramethylenetetramine disulfone, Yao Hsueh T'ung Pao, 7 (8) , (1959) 395. [English].

[megalomania]

I went ahead and requested the Yao Hsueh T'ung Pao (Chinese pharmaceutical bulletin) and Angewandte Chemie articles. Somebody remind me in a couple weeks what these articles are for :)

[nbk2000]

Merck says 60% sulfuric is used, so that replaces TFA, as who cares about maximum yield if you can't afford to use the astronomically expensive reagent?

And dimethoxymethane (DMM) is used as an inhalant abuse deterrent, so there's a 'plausible deniability' reason for buying it. :)

It's even OTC (at <5% w/ propellant gases and acetone) in K2r Spot Lifter-2/2003, Home inside, Customer Service# (800)251-4222.

Given how the synthesis posted by mega uses sub-gram quantities, and TETS is lethal in <10mg doses, you could easily make get a couple of grams of formal (AKA for DMM) from a can of the aerosol spot-remover, and make at least a dozen lethal doses of TETS from it. :)

A reference to DMM synthesis using exotic catalysts, that reference easier (less-efficient) processes.

http://iglesia.cchem.berkeley.edu/JPhysChemB_107_10840_2003.pdf


Current state-of-the-art DMM synthesis processes involve methanol oxidation to formaldehyde on silver or iron molybdate catalysts, followed by subsequent condensation reactions of methanol-formaldehyde mixtures using sulfuric acid or solid acid catalysts.1,2
..........
1. U.S. Patent 6,265,528
2. U.S. Patent 6,437,195

[thrall]

I think even formaldihyde(formalin) can be used as substitute of dimethoxymethane since it seems that the fuction of dimethoxymethane is to provide ---CH2---- and that same thing is provided by formadihyde but the TENDENCY is less.
Even merk says (first prepared by sulfamide, formaldyhyde and 60% sufuric acid..........) moreover it's solubility in water and acid both is very less and it's very stable compound so one can wait for a long time it takes to form in the formaldihyde method. Best part is that reaction occurs at room temparature so just mix and shake and wait.....filter the precipitate;).

[Polverone]

A Potential Industrial Process for Sulfamide
Ed. F. Degering, George C. Gross;
Ind. Eng. Chem.; 1943; 35(7); 751-753.

Brief summary of the relevant experimental bits:
75 ml of liquified anhydrous ammonia is chilled in a dry ice bath. To this is slowly added a solution of 20 ml of sulfuryl chloride in 210 ml of petroleum ether. During the addition, the flask contents are stirred vigorously (1000 RPM); the addition takes 20-40 minutes. Then the ammonia is allowed to evaporate, remaining pet ether decanted/evaporated, and the white residue extracted in a soxhlet apparatus with methyl acetate (best), ethyl acetate, acetone, or MEK for 2+ hours. The extract is evaporated under vacuum on a steam bath and allowed to crystallize; it can be dried under vacuum and recrystallized from water to obtain solid white sulfamide melting at 91-93 degrees. Dilute acid hydrolysis of crude product before extraction improves yields 10-15 percent.

There are detailed diagrams of apparatus, effects of varying parameters on yield, instructions for scaling up, etc. in the original article. This problem basically reduces to that of assembling the right apparatus and making/obtaining sulfuryl chloride.

[megalomania]

The Angewandte Chemie article is in, but of course it is in German, so rather than translate it I will post a scan of the article and let you good people have at it. I also found a procedure in volume 1 of Preparatory Manual of Inorganic Chemistry for sulfamide. I'll post these as soon as I hook up my scanner...

[megalomania]

I have scanned in the Angewandte Chemie article. The Yao Hsueh T'ung Pao article is still pending. I have attached the article as well as an excerpt from the Handbook of Preparative Inorganic Chemistry concerning the synthesis of sulfamide.

I hope someone out there will be willing to provide a German translation, at least of the actual parts relating to the synthesis.

[c0deblue]

Here are two PDF files - an English translation of the Angewandte Chemie article, and the German original. I don't think any critical information or meanings were changed in transposing it to make it readable, but perhaps someone fluent in German could double check it. For comparison purposes, both documents are column-and-page identical to the original scan.

Some observations:

1. Sulfamide-formaldehyde polymers are toxic only when reduced to particles small enough to be ingested, inhaled or absorbed, and then only to the extent of their actual TETS content. The described synthesis, on the other hand, produces pure TETS without the polymerization that normally binds it in a plastic matrix and renders it inert. This suggests that the function of the acid in TETS synthesis is strictly one of inhibiting the usual polymeric cross-linking, thereby allowing post-reaction separation of TETS crystals from a still-liquid medium.

2. If this is the case, almost any strong mineral acid should work. The article's authors synthesized TETS alternatively using concentrated hydrochloric acid and 60% sulfuric acid, apparently with equal success. The Lee-Kohn article posted earlier by Mega describes a synthesis using trifluoroacetic acid. Looks like the exact acid may not be critical at all, as long as it's strong enough and in sufficient quantity to inhibit polymerization.

3. The ratio of acid to be used isn't given in the article, but if the above analysis is correct the exact amount isn't critical. A quick way to find out might be to follow the described synthesis using urea instead of sulfamide. If the acid interferes with polymerization, an effective acid ratio could then be determined. The 1mol:2mol:5ml ratio given in the Lee-Kohn article might be a good starting point.

Don't know about you, but I wouldn't want to be anywhere around this stuff. Of course it might be different if one had a (willing) assistant. "Here, pulverize these crystals for me. Use that big mortar and pound it up real fine." :eek:

[megalomania]

Ahh, good. I was just going to bump this thread and see if a translation was underway.

Where exactly did you get those PDF's c0deblue? Did you make those yourself or are they from some online journal database? Having an archive of old Angewandte Chemie articles, in English no less, would be a wonderful thing!

[c0deblue]

Heh heh, no, unfortunately there's no online Angewandte Chemie database - at least nothing free. No translations anywhere either that I know of, and even the German versions available by subscription run many thousands for access. I had to make these the old-fashioned way - Photoshop your original scan, do initial OCR followed by a day of careful proofing and correcting due to the poor original, do initial setup of the German version in MS Word, run it through Systran and GE Trans, use various dictionaries to fill in a huge number of unrecognized words and run it through Systran again for improved context recognition, transpose the German construction to make it readable in English, set up the translation in a second Word document and conform it with the first, format everything and finally create PDFs from the Word files. No free lunch, as they say, but at least there's now something respectable for the RogueSci database.

Still hoping someone will double check the translation though, since the only thing I know about German is that it's bloody difficult. :(

[nbk2000]

If you could make a polymer of high TETS content, that'd make it safer to handle, while still making it useable as a weapon by explosive pulverization or thermal distillation (if it's volatile).

Hell, just storing it would make it polymerization good, 'cause you could keep it in the form of a plastic figurine sitting on the shelf, harmless as could be, and simply shave a little off the bottom when you have an annoying houseguest to get rid of. ;)

Cops are always testing powders and such, not plastic keychain fobs and candleholders. :p

[SweNMFan]

Just found something..

http://webbook.nist.gov/cgi/cbook.cgi?ID=63-74-1&Units=SI
Cut and paste ...

Benzenesulfonamide, 4-amino-

* Formula: C6H8N2O2S
* Molecular Weight: 172.21
* CAS Registry Number: 63-74-1

Other Names: Sulfanilamide; p-Aminobenzenesulfamide; p-Aminobenzenesulfonamide; p-Aminobenzenesulfonylamide; p-Aminophenylsulfonamide; p-Anilinesulfonamide; p-Sulfamidoaniline; p-Sulfamoylaniline; A-349; Albexan; Albosal; Ambeside; Aniline-p-sulfonic amide; antiStrept; Astreptine; Astrocid; Bacteramid; Bactesid; Collomide; Colsulanyde; Copticide; Deseptyl; Dipron; Ergaseptine; Erysipan; Estreptocida; Exoseptoplix; F 1162; Fourneau 1162; Gerison; Gombardol; Infepan; Lusil; Lysococcine; Neococcyl; Orgaseptine; Prontalbin; Prontosil album; Prontosil i; Prontosil white; Prontylin; Pronzin album; Proseptal; Proseptine; Proseptol; Pysococcine; Pabs; Rubiazol A; Sanamid; Septamide album; Septanilam; Septinal; Septolix; Septoplex; Septoplix; Stopton album; Stramid; Strepamide; Strepsan; Streptagol; Streptamid; Streptasol; Streptocid; Streptocid album; Streptocide; Streptocide white; Streptoclase; Streptocom; Streptol; Strepton; Streptopan; Streptosil; Streptozol; Streptozone; Streptrocide; Sulfamidyl; Sulfamine; Sulfana; Sulfanalone; Sulfanidyl; Sulfanil; Sulfanilimidic acid; Sulfocidine; Sulfonamide; Sulfonamide p; Sulfonylamide; Sulphanilamide; Sulphonamide; Therapol; Tolder; White streptocide; 1162 F; 4-Aminobenzenesulfonamide; 4-Aminophenylsulfonamide; 4-Sulfamoylaniline; Benzenesulfonamide, p-amino-; Streptamin; Sulfocidin; Sulfanilamide Vaginal Cream; 4-(Aminosulfonyl)aniline; p-Aminobenzensulfonamide

The third from the end is a intresting one.. :D

And Merck

Porofor® BSH
Monograph Number: 7679
Title: Porofor® BSH
CAS Registry Number: 80-17-1
CAS Name: Benzenesulfonic acid hydrazide
Additional Names: benzenesulfohydrazide; phenylsulfohydrazide
Molecular Formula: C6H8N2O2S
Molecular Weight: 172.21.
Percent Composition: C 41.85%, H 4.68%, N 16.27%, O 18.58%, S 18.62%
Line Formula: C6H5SO2NHNH2
Literature References: Ref: Lober, Angew. Chem. 64, 65 (1952).
Properties: Crystals, dec 103-104° with the evolution of nitrogen. May be stored indefinitely at temps up to 80°. Sensitive to moist oxidizing agents.
Use: Gas generating agent for use in making foam rubber and foam plastics.

[c0deblue]

SweNMFan: Thanks for the contribution and research, but while it would be great to be able to list an alternative for Sulfamide, I somehow doubt that this is it. I'd certainly welcome being corrected if you have a well-reasoned case for how Sulfonamide could be used in TETS synthesis. Sulfamide and Sulfonamide are different substances, although some references fail to draw a clear distinction. It was exactly this ambiguity that led the authors of the Angewandte Chemie article to state in a footnote concerning Sulfamide: "Not to be confused with Sulfonamide or its derivatives."

On the other hand, the T'ung Pao article that Mega is still waiting for refers to TETS as "tetramethylenetetramine disulfone", so perhaps there's a possibility after all. Maybe that article will shed further light on the subject.

[megalomania]

I asked about the T'ung Pao article Friday because I have neither received a notice that it is in nor did I get a rejection notice that they could not find it. The guy checked the database of outstanding requests, but did not find an order for it. So, it looks like the T'ung Pao article has fallen through the cracks somewhere. I won't be able to request iy again until after the new year since it is Christmas break at the library.

[SweNMFan]

The Sulfamide ??

http://www.pfaltzandbauer.com/cgi-bin/details.pl?type=cas&order=chemname&chem=7803-58-9&page=1&item=S11000

$72.00 / 5 G !!


And

http://www.spectrumchemical.com/retail/product.asp?catalog%5Fname=Chemicals&product%5Fid=1060339#

$25.85 / 5 G

It doesn't seem restricted in any way..

[megalomania]

c0deblue, would you be willing to start a new thread describing exactly how you did that translation? There are so many non-English references available that it would be nice to have some process of machine translating them, at least the bulk of the words. There are a million things I want to get from the Beilstein Index, Chemische Berichte, Annalen, Angewandte Chemie, and various patents that I just ignore because the thought of going through by hand and translating the words would be too time consuming. Your process sounds like it could speed things up greatly.

PS. Sorry about the scan, I edited and compressed it quite a lot to get it to fit on the board.

[c0deblue]

Mega: I'll write something up and post it in The Water Cooler. Might take a day or so before I can get to it.

SweNMFan: The U.S. prices for Sulfamide and everything else are absurd. $25.85 for a 5 g quantity???!!! The REAL value of the stuff is reflected in the import price currently quoted for the chemical industry in India - Sulfamide $11.80 USD per kg at point of entry, and there are probably lots of Asian makers who would ship it for less than that. The money grubbing middlemen in this country price everything as though it was going to be used as the international gas chromatography standard or something. Oh for the days when you could just go to an industrial chem supplier and pick up a bucket of this and a carboy of that and still have enough left in your pocket for lunch!

[nbk2000]

RDX is made by reacting formaldehyde/AcO/AN, and RDX is bound into plastic matrixs' as PBXN's, and sulfamide reacts with formaldehyde to form TETS, so....

Would it be possible to form TETS in-situ with RDX, using an excess of formaldhyde to react with the additional sulfamide? This may be better added afterwards, but hey...

Or using a sulfamide/formaldehyde resin to make a PBXN that, upon detonation, disperses TETS in an aersolized form? Sounds like just the thing for an anti-personnel weapon.

Explosive for blast/frag, and TETS to contaminate wounds and target area, to both ensure kills and deny area. Considering how piss easy it is to make (once you've got sulfamide), how could you NOT use it? :)

Found a place in the US that sells a half-key of sulfamide for $70. Not a huge bargain, but much less than the bastard 5gram rip-offs.

[megalomania]

I believe amides react with anhydrides to form imides as well as cyclic imides. Amides also react with ammonia salts, although I don't know if that includes ammonium nitrate or just organic salts.

With the stated decomposition temperature (in Merck) of 255-260 degrees C I wonder if the heat of an explosion would not render it largely inert. Perhaps one of the cooler temperature explosives would work? Encasing an explosive charge with a shell of tetramethylenedisulfotetramine may be a better option than a plasticized matrix. This would certainly be a better compound to use than osmium tetroxide for both toxicity and economic reasons.

By the way, I see this thread is number 8 on google for tetramethylenedisulfotetramine.

[FUTI]

problem with price of chemicals is that when you buy something from respectable / reliable source that charge a lot of money is that you can complain and press charges agains them if they fucked the substance you ordered (so they guaranted for purity). In the case of India and other countries with all respect I have it is not the case. But they are so cheap that a large number of US companies are importing their "products" and just doing final purification step as it turns out to be more economic then to set up a whole new line for a new product. So if you want something for research buy from "brand name company" for else you can buy from "no-name" company as you going to purify it before doing anything.

This is an fantastic thread...I have nothing to add:)

[SweNMFan]

Rewrote the preparation of sulfamide from Handbook of Preparative Inorganic Chemistry vol 1...

The main problem is how to make -80C and maintain it for 3-4 hours.. :mad:

[c0deblue]

"The main problem is how to make -80C and maintain it for 3-4 hours.. "

A cooling bath of dry ice and acetone or alcohol gives a temperature of about -79C. Presumably the specified -80C has little to do with the reaction and is primarily to keep the liquified NH3 well below its -33C boiling point and to minimize volatilization. For this purpose, anything -60C or lower ought to work. A wide mouth thermos of appropriate size should maintain the cooling bath for the required period, particularly if the reactor vessel is mounted in a cork stopper (with a suitable pressure vent).

[SweNMFan]

Ok.. To sum it up.

To make TETS one needs sulfamide and formaldehyde and a acid.

Sulfamide is insanely expencive so that one have to syntesise and that is done
by reacting liquid ammonia with Sulfuryl chloride in a cold bath of dryice and ethanol.

Sulfuryl chloride is nearly impossible to find as it is higly toxic so one have to make that as well. Could be done reacting fumes from burning Sulphur and Chlorine gas thru activated charcoal

Liquid ammonia is also hard to find nowdays so that too have to be made..

Dry Ice and ethanol is atleast easy to find ;)

[nbk2000]

Considering how toxic TETS is, $100/pound (includes shipping) for sulfamide isn't too expensive, as the resulting product would make tens of thousands of lethal doses. :)

Imagine how many poison bullets, darts, and frags you could make with that. :D

What's the thermal stability of TETS? Subliminate-able?

[SweNMFan]

I still haven't found a cheaper source than the $29/5g :(

But I got my hands on a used Soxhlet extractor and a few other usefull glasswares.. so if I one day could synth sulfamide I can atleast purify it.. hmm maybe I should grow some Fusarium tricinctum and extract T-2 instead..

[nbk2000]

Seems the buggers are developing effective anitdotes for TETs. :(

Generally seems to be a combination of a derivative of BAL (British Anti-Lewiste), sodium dimercaptopropane sulfonate , and Vitamin B6.

Though recognition of symptoms in time for effective treatment in western nations where TETS is not (yet) a common means of poisoning remains to be seen. :p

But having an effective prophalytix pre-treatment for yourself is good.

From http://www.chinaphar.com/1671-4083/25/534.htm:


Ying BY, Chen ZZ, Chen ZK, Zhang SQ, Lin W. A clinical study on Na-DMPS in the emergency treatment of acute tetramine intoxication. Chin J Intern Med 2000; 30: 100-2.

Haskell AR, Voss E. The pharmacology of tetramine (Tetramethylenedisulfotetramine). J Am Pharm Assoc (Sci ed) 1957; 46: 239-42.

Smythies JR. Relationship between the chemical structure and biological activity of convulsants. Ann Rev Pharmacol 1974; 14: 9-22.

Roberts CJ, James VA, Collins JF, Walker RJ. The action of seven convulsants as antagonists of the GABA of limulus neurons. Comp Biochem Physiol 1981; 70: 91-6.

Bowery NG, Brown DA, Collins JF. Tetramethylenedisul-photetramine, an inhibitor of g-aminobutyric acid induced depolarization of isolated superior cervical ganglion of the rat. Br J Pharmacol 1975; 55: 422-4.

Large WA. Effect of tetramethylenedisulfotetramine on the membrane conductance increase produced by g-aminobutyric acid at the crab neuromuscular junction. Br J Pharmacol 1975; 53: 598-9.

Zhang CY, Zhu TJ, Chen XY, Hu GX, Lin D. The convulsive effects and mechanism of tetramethylenedisulpho-tetramine. J Health Toxicol 2001; 15: 5-7.

Zhang CY, Zhu TJ, Hu GX, Chen XY, Liu DX, Chen ZK. Effect of sodium dimercaptopropanesulfonate on antagonism tetramethylenedisulphotetramine to GABA receptor. Acta Pharmacol sin 2001; 22: 435-9.

Zhu TJ, Zhang CY, Chen XY, Hu GX, Chen ZK. Protective effects of sulfhydryl compounds on acute poisoning with tetramine in mice. J Wenzhou Med Coll 2000; 30: 3-4.
Zhang CY, Zhu TJ, Chen XY, Hu GX, Chen ZK. Antidotal effects of sodium dimercaptopropane sulfonate on acute poisoned animals with tetramethylenedisulphotetramine. J Wenzhou Med Coll 2000; 30: 179-81.

Hu GX, Chen XY, Zhou HJ, Lin D, Zhu TJ. Protective effects of sodium dimercaptopropanesulfonate with and without combined administration of diazepam on acute poisoned animals with tetramethylenedisulphotetramine. J Labour Med 2001; 18: 288-90.

Qiu ZW, Lan M, Zhuang JH, Xia YJ, Huang SQ. Antidotal effects of vitamin B6 and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylenedisulpho-tetramine in animals. Chin J Intern Med 2002; 41: 186-8.

Ying BY, Fan X, Zhang SQ, Chen LM, Zhuang R, Lin W. Observation of therapeutic effects on Na-DMPS in antidotal treatment of acute tetramine poisoning. Chin J Intern Med 2000; 59: 767-8.

Chen SQ, Zhu GF. Experience of antidotal effects of sodium dimercaptopropane sulfonate against acute poisoning of tetramine in children. Pediatr Emerg Med 2002; 9: 165.

Jin LY, Zhang HS. Observation of therapeutic effects of sodium dimercaptopropane sulfonate against tetramine poisoning in 11 cases. Chin J Pract Pediatr 2002; 17: 308.

Liang YJ, Chen J, Zhang W. Analysis of neuropsychic disorders were caused by tetramethylenedisulphotetramine poisoning in 12 cases. J Intern Inten Med 2002; 8: 206.

Liao Y, Tang XH. Song JG, Zhong BX. Clinical observation of acute severe tetramine poisoning in 15 patients. Chin Occup Med 2002; 29: 52.

Chen GL. Analysis of tetramine poisoning in 24 cases. Zhejiang Clin Med J 2001; 3: 133.

Zhang YZ, Fan QJ, Lu C, Yin LS. An epidemiological investigative analysis of tetramine poisoning. Pract Prevent Med 2001; 8: 42.

Wang ZY, Zhang QF, Lu HQ. Clinical observation of treatment of tetramine poisoning with sodium dimercaptopropane sulfonate. Clin Med 2001; 21: 27-8.
Nai YF. Congregate acute poisoning by tetramine in 88 cases. Clin Focus 2003; 18: 105-6.

Li YR, Zhu SQ. Analysis of acute tetramethylenedisulpho-tetramine in 15 cases. J Intern Inten Med 2002; 8: 27, 31.

Xing Y, Xu H. Report of congregate poisoning by tetramine in 68 cases. Chin J Pract Pediatr 2002; 17: 315.

Bai XH, Zhang WW. Clinical analysis of acute tetramine poisoning in 21 cases. Clin Med 2002; 22: 16.

Meng XK. Advances in studies of poisoning by tetramine. Chin J Crit Care Med 2002; 22: 245-66.

Lin ZB, Xing Y, Xu H, Lu CZ, Zhang YX. The congregate intoxication of prohibitive rodenticides and emergent treatment in children. Chin J Crit Care Med 2002; 22: 403-5.

Shi L, Feng JZ. Inquiry of emergent rescue on acute poisoning by tetramine (additional report in 32 cases). Clin Emerg J 2002; 3: 184.

Fu JX, Zong Y, Qin GR. Advances in diagnosis and treatment of poisoning by rodenticides. Chin J Crit Care Med 2002; 22: 59-61.

Wei SK, Lin SJ, Huang X, Xie LL. Sodium dimercaptopro-pane sulfonate combined with vitamin B6 to rescue acute tetramine poisoning in 13 cases. (Observation and nurse of treatment). Jiujiang Med J 2001; 15: 179.

Zhang CY, Zhu TJ, Chen ZK. Protective action of mercapto- compounds on cellular injury. J Wenzhou Med Coll 2000; 30 Suppl; 27-9.

Shi DM. Antidotes. In: Ding QF, chief editor. Pharma-cology. 4th ed. Beijing: People's Medical Publishing House; 2001. p 314.

Zhang CY, Zhu TJ, Chen XY, Hu GX, Chen ZK. Actions on sodium dimercaptopropane sulfonate against convulsions lnduced by tetramethylenedisulfotetramine. Chin Pharm J 2001; 36: 736-8.

[megalomania]

It makes one wonder if they are researching the cure if only because they are weaponizing TETS...

[SweNMFan]

I still think that here in the west a doctor wouldn't suspect TETS in the first place. More likely to sent the patient to a CAT or MRI scanner to check for brain damage/ tumors..

[nbk2000]

Mega, I had the same thought, as how could the chinks miss the obvious utility of such a thing? After all, the nerve agents came to use after their utility as weapons was recognized during their development as pesticides. So too must TETS after its use as a 'humacide' in so many mass poisonings in china.

[Emc2]

All is great info, but attachments posted by megalomania seem to be not available. I did register and loged-in to read it, however it still shows an error message when I try to view them.

[Emc2]

All is great info, but attachments posted by megalomania seem to be not available. I did register and loged-in to read it, however it still shows an error message when I try to view them.

[nbk2000]

Incorrect.

I just now downloaded both of them, so the problem is on your end. :p

[MrSamosa]

Taking a shot in the dark here regarding Sulfamide preparation:

Amides can be prepared by reacting Ammonia/Amines with Acyl Chlorides, which is the method that the posted synthesis uses; but they can also be prepared by reacting ammonia/amine with the acid anhydride.

What I'm getting at is making Sulfamide by reacting Sulfur Dioxide (or Trioxide?) directly with Ammonia. This would cut out the steps of working with nasty Chlorine fumes and the even nastier Sulfuryl Chloride.

EDIT: Sorry, this won't work. From http://www.tramfloc.com/tf88.html :

When a sulfur dioxide leak occurs, it is easily detected by the sharp, pungent odor of the vapor. The location of the leak may be determined by means of ammonia vapor dispensed from a squeeze bottle, or by the use of an ammonia swab. When the ammonic comes in contact with the sulfur dioxide vapor, dense white fumes of ammonium sulfate form near the leak.

And on sulfur trioxide: http://pubs.acs.org/cgi-bin/abstract.cgi/jpcafh/2003/107/i27/abs/jp034531w.html

Apparently it forms some weird clusters/complex.

[FUTI]

AFAIR 25% NH3 water solution mixed with concentrated H2SO4 makes enough heat to evaporate all water and leave solid ammonium-sulfate. This is industrial procedure for some batch type large reactors though, but knowing this I assume that mixing of ammonia and SO3 won't produce sulfamide if even a trace of water is present and reaction for producing of sulfamide from those reactants isn't posible without formation of water and...you can guess the rest of the story.

For those complex type compounds look for Karl-Fischer titration of water and you will find more or less the same stuff. Sulfur oxides love amines of all kinds.

[meyer25]

Has anybody thought of preparing sulfamide by pyrolising ammonium sulfamate (used as acidic cleaner and herbicide)

H₂N-SO₃^-NH₄⁺?

Or heating it with some dehydrating agent, such as tin tetrachloride?

[nbk2000]

As it turns out, there's a patent for making Sulphamide using gaseous Ammonia and Sulphur Trioxide crystals. :)

US2117626

Gets about a 25% yield.

Combine with that other patent for decomposing ammonium sulphate into sulfur trioxide, old chemical techniques of decomposing ammonium sulphate into anhydrous ammonia gas, and you've got a pretty OTC means of making it. :)

[Telkor]

I wonder if it's possible tor produce it (or at least something similar) using Sulfamic Acid. The structure's quite similar to Sulfamide, one NH2 ist replaced by OH. It's much cheaper and might react similar.