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Topic: Synthesis of Disulfiram (Antabus)  (Read 12669 times)

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Offline RasmusL

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Synthesis of Disulfiram (Antabus)
« on: September 22, 2009, 04:36:07 PM »
Hello everyone, new on this forum  ;D

Today, I tried synthesizing Disulfiram by reaction of ethylamine with carbon disulfide.
Sadly, this all ended in an explosion (???), that I was completely unprepared for. Luckily nothing bad happened except some screwed up glassware, because some red crystals had formed instead of my wanted disulfiram.

I found this synthesis pathway in an article my school had, which states that the reaction only takes place in water, H2O2 and isopropanol. The article does NOT state any amounts, it only has a schematic drawing. My attempt was done without any of these, since I expected nothing to happen without the H2O2 catalyst.
I hope you can help me here. As you can see on wiki:
http://en.wikipedia.org/wiki/File:Disulfiram2.svg
the structure of disulfiram consists of 2 carbon disulfides in the center, and an ethylamine on each side.

I'm not really sure what I'm asking here.. But what went wrong? Or maybe a better synthesis path exists?

Thanks beforehand :)

By the way, I know this might sound REALLY unprepared, but my teacher actually made me do this ::) And she knows nothing about it.
« Last Edit: September 22, 2009, 05:01:37 PM by RasmusL »

Offline renge ishyo

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Re: Synthesis of Disulfiram (Antabus)
« Reply #1 on: September 22, 2009, 05:08:44 PM »
Here are a few bits of information I can offer.

The explosion can be easily explained because you mixed a concentrated nucleophile (ethylamine) with a concentrated electrophile (carbon disulfide...which is a more reactive version of carbon dioxide). These two species if they come in contact will react with one another readily in the presence of a small amount of aqueous catalyst (see carbamate formation in an organic chemistry textbook with sulfur replacing oxygen for the mechanism), so first off you should dissolve them in an appropriate solvent to dilute them before doing any further reactions to be safe.

CS2 has low solubility in water, which helps to explain why isopropanol is used as a solvent in the article as it is similar in structure to the reactant (more on this in a minute) and might help bring these two species together to react. Water is probably there to facilitate the presence of the highly polar H2O2 whose purpose seems to be to catalyze the formation of the sulfur-sulfur bond in the center of the desired product.

There are a bunch of things I want to point out to you before you go any further with this:

1) It is highly unlikely that you will get the desired product using the above reaction setup because at least based on what you stated you are using the wrong nucleophile. Diethylamine should be used and not ethylamine. Notice that the desired product contains two diethylamine groups not two ethylamine groups.

2) I would strongly recommend researching the scheme further to get more details about the reaction conditions before trying this again. It is quite dangerous to do chemistry with no knowledge of the general mechanism or of what purpose each reagent serves in the process. There is another reaction scheme for disulfiram mentioned in the wiki for example that could be a start to look for information of a useful synthetic scheme for this compound:

http://en.wikipedia.org/wiki/Disulfiram

Another thing you can do is contact the writer of the article and ask for more information on the reaction including amounts used, etc. You can also chemically analyze the failed product and determine it's structure to deduce what actually happened in that earlier attempt.

Offline RasmusL

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Re: Synthesis of Disulfiram (Antabus)
« Reply #2 on: September 22, 2009, 05:32:48 PM »
Thanks a lot for your answer. I agree that this was a stupid thing to try without more knowledge, but it seemed really hard to find information on this synthesis online.
The ethylamine part was a typo (well, several), I did use diethylamine :)

The only information the article had, was basically a drawing of this:
CS2 + diethylamine :rarrow: (above) H2O2, H2O, isopropanol @ 40-50C   disulfiram

I'd really like some more theory on the synthesis, but it's hard to obtain any. I don't have a lot of resources available, since this is just for a small assignment in 3rd year high-school.

Offline kiwi

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Re: Synthesis of Disulfiram (Antabus)
« Reply #3 on: September 22, 2009, 10:03:11 PM »
Given the extreme flammability of CS2 (a hot water pipe is sufficient to ignite it), the extreme toxicity of CS2 (inhalation, human LClo 4000 ppm/ 30m)  and the at times violent reaction of CS2 with oxidants (such as H2O2, the reaction with NOx is here http://www.youtube.com/watch?v=XAx0Ir9n4hI) I would say your teacher is irresponsible at best, and criminally negligent is not too much of a stretch. The chance of somebody becoming injured (or much much worse) is very high, especially with no knowledge of proper chemical procedure. Do not attempt to do this, and make it very clear to your teacher why.

Offline RasmusL

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Re: Synthesis of Disulfiram (Antabus)
« Reply #4 on: September 23, 2009, 03:26:16 AM »
Yeah I saw how dangerous CS2 was, I knew it was toxic and that's the reason I was working under a closed fume hood. (Of course, given both substances that was the only correct thing to do).

I'd really like to finish this project though, so maybe you can suggest an alternative route to disulfiram? Maybe the one from wikipedia is less risky, reaction sodium diethyldithiocarbamate with iodine to oxidize it to it's disulfide, which happens to be disulfiram.

Again, there's basiclly zero information on this reaction, so I don't really have any idea if it's violent?
« Last Edit: September 23, 2009, 03:42:05 AM by RasmusL »

Offline kiwi

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Re: Synthesis of Disulfiram (Antabus)
« Reply #5 on: September 23, 2009, 08:43:39 AM »
That reaction is less risky, since you no longer need to work with CS2 (provided you purchase the sodium diethyldithiocarbamate). Here is something that should work (I haven't tried it, but it should work, both the reagents are very water soluble while the product is not.)

In a fumehood, wearing gloves and safety glasses, add sodium diethyldithiocarbamate (1.13 g,) to water (5-10 mL, use the least amount needed to dissolve). Once its all dissolved, cool the mixture in a bath of ice, add more water if the thiocarbamate starts to precipitate. Mix 30% aqueous hydrogen peroxide (0.3 g) with water (3 mL), and add this solution a drop at a time to the cold thiocarbamate solution.  If all goes according to plan, disulfram will precipitate from the solution. Isolate it by filtration and let it air dry in the back of the fumehood.

Remember to work in the fumehood, always wear gloves and safety glasses, and don't handle/eat or otherwise use the disulfram. Give it to your teacher who will dispose of it properly. To reiterate, only do this procedure if you can obtain some sodium diethyldithiocarbamate WITHOUT attempting to make it. If you have any questions ask away. Above all, have fun - if you are this curious about synthetic chemistry now you'll make a good research chemist one day.

Offline RasmusL

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Re: Synthesis of Disulfiram (Antabus)
« Reply #6 on: September 23, 2009, 09:39:33 AM »
Thanks for all your help, I will discuss buying the sodium diethyldithiocarbamate with my teacher.

I'm not planning on using the disulfiram (;D), but I will probably have to devise some tests, for purity and yield. I will try to get some commercial disulfiram for comparison.

Also, yes I am quite interested in synthetic chemistry, which is why I'm doing this. I'm in the chemistry class in my highschool, including the class where I'm doing this.. My school calls it 'process', it's basically practical chemistry and currently we're on the subject of pharmaceuticals.

Offline orgopete

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Re: Synthesis of Disulfiram (Antabus)
« Reply #7 on: September 25, 2009, 10:51:28 AM »
I don't know what decomposition reaction occurred, but having made a number of trithiocarbonate esters a number of years ago, I found working with carbon disulfide quite easy. I am both surprised by the lack a failure and not surprised by some decomposition reaction taking place with the use of hydrogen peroxide.

I might question the stoichiometry used in the reaction as a possible problem. Be that as it may, I would look for a published procedure to make a disulfide from a dithiocarbamate. I would even guess that you would have a difficult time avoiding it formation in at least some small extent.

This is how I would guess you might perform the synthesis. Use one equivalent of diethylamine with one equivalent of NaOH, and then add one equivalent of carbon disulfide. This should give the sodium dithiocarbamate virtually as rapidly as it is mixed. Now, rather than hydrogen peroxide, use a fresh bottle of sodium hypochlorite (bleach). That should give the disulfide. This should require one half of an equivalent. However, this reaction will increase the pH and it may require buffering with something like acetic acid. You will not need to check for peroxides with this method while it probably should have been done with your peroxide method. 
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Offline Mawer0310

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Re: Synthesis of Disulfiram (Antabus)
« Reply #8 on: March 10, 2017, 03:15:21 AM »
Hey Rasmus!

Vi er en gruppe elever fra København som selv gerne vil syntetisere disulfiram ligesom du gjorde (for nogle år siden efterhånden). Er det evt. sådan at vi kan kontakte dig et sted og stille dig nogle spørgsmål? :)

- Magnus, 3.w, HTX Sukkertoppen

Offline Borek

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Re: Synthesis of Disulfiram (Antabus)
« Reply #9 on: March 10, 2017, 05:04:45 AM »
Vi er en gruppe elever fra København som selv gerne vil syntetisere disulfiram ligesom du gjorde (for nogle år siden efterhånden). Er det evt. sådan at vi kan kontakte dig et sted og stille dig nogle spørgsmål? :)

English please.

RasmusL was last seen on the forum 7 years ago, somehow I doubt he will read your post.
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Offline Mawer0310

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Re: Synthesis of Disulfiram (Antabus)
« Reply #10 on: March 16, 2017, 07:56:28 AM »
We're a group of students who are trying to make the same synthesis as Rasmus did some years back. We just wanted to know how his project went, and maybe have some kind of advice :) We are aware that he hasn't been online recently

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