Sciencemadness Discussion Board

What are some OTC thiols for thioketal formation?

Loptr - 20-3-2019 at 13:28

As the title suggests, what are some OTC thiols that might be used for thioketal formation from ketones?

Any ideas are welcome. I am aware they can be synthesized using the alkyl dihalide or tosylate, and thiourea, and probably a few other reagents, but am curious what is readily available.

I can't imagine there are a lot of them, since thiols tend to stink. :cool:

[Edited on 20-3-2019 by Loptr]

clearly_not_atara - 20-3-2019 at 15:00

I've considered using alpha-lipoic acid, possibly after decarboxylating it somehow. Decarboxylated ALA is just 1,3-heptanedithiol, a practically perfect choice for ketal formation, since it is the same as 1,3-propanedithiol but less volatile and thus easier to handle and less smelly.

I do not know how to decarboxylate lipoic acid, but I do have a jar of it sitting on a shelf.

Loptr - 20-3-2019 at 15:27

Quote: Originally posted by clearly_not_atara  
I've considered using alpha-lipoic acid, possibly after decarboxylating it somehow. Decarboxylated ALA is just 1,3-heptanedithiol, a practically perfect choice for ketal formation, since it is the same as 1,3-propanedithiol but less volatile and thus easier to handle and less smelly.

I do not know how to decarboxylate lipoic acid, but I do have a jar of it sitting on a shelf.


You would also have to reduce that S-S bond, but interesting none the less.

UC235 - 20-3-2019 at 16:23

Quote: Originally posted by Loptr  
Quote: Originally posted by clearly_not_atara  
I've considered using alpha-lipoic acid, possibly after decarboxylating it somehow. Decarboxylated ALA is just 1,3-heptanedithiol, a practically perfect choice for ketal formation, since it is the same as 1,3-propanedithiol but less volatile and thus easier to handle and less smelly.

I do not know how to decarboxylate lipoic acid, but I do have a jar of it sitting on a shelf.


You would also have to reduce that S-S bond, but interesting none the less.


S-S bonds reduce relatively easily. I do it every day at work with proteins. The problem is keeping it that way.

Loptr - 21-3-2019 at 06:13

According to the ScienceMadness Wiki, aluminum sulfide will react with alcohols to produce the corresponding thiol. The yields leave something to be desired, though, I can't complain because the reaction would be cheap. The requisite aluminum sulfide shouldn't be too difficult to prepare, but does require elevated temperatures.

Following this logic, 1,3-propanediol would be the starting alcohol to prepare 1,3-propanedithiol, which is now readily available, and I so happen to have on hand.

http://www.sciencemadness.org/smwiki/index.php/Aluminium_sul...
Quote:

Aluminium sulfide will react with alcohols at high temperature to give their respective thiols. such as: With methanol, it forms methanethiol and dimethyl sulfide, the yield being 40-45 % and 15% for each product, at 300 °C; reaction with ethanol gives ethanethiol at temperatures between 310-360 °C, with a 39% yield. At 310 °C it reacts with propanol to give propanethiol, with a 32.5 % yield. Reaction with ethers gives thioethers.


[Edited on 21-3-2019 by Loptr]

Loptr - 21-3-2019 at 06:27

How foul is 1,3-propanedithiol, by the way. Is this something that wouldn't be considered socially acceptable to those around, or can the smell be managed? I ask because I do wonder about higher MW thioacetalizing reagents, and if I am underestimating it.

Thoughts?

[Edited on 21-3-2019 by Loptr]

The Volatile Chemist - 21-3-2019 at 10:24

Well, dodecanethiol is used for surface spectroscopy standardization - and it still stinks, despite the relatively high MW. it's probably a little more volatile than the 1,3-propanedithiol, though, so I don't know how smelly it'd be.

clearly_not_atara - 21-3-2019 at 19:27

Dodecanethiol bp: 268 C
1,3-propanedithiol bp: 169 C

Wiki: "This liquid, which is readily available commercially, has an intense stench."

I'd be more concerned about Al2S3 generating H2S upon contact with atmospheric moisture, though.

Loptr - 22-3-2019 at 04:50

The aluminum sulfide in air isn't bad actually. I have made some before by burning a mixture of aluminum powder and sulfur. Now drop it into some water and that is another story.

Now that I think about it some more, I would likely just make 1,3-dibromopropane from 1,3-propanediol, and then follow the procedure on orgsyn to prepare the di-Bunte salt, and then hydrolyze to the dithiol.

http://www.orgsyn.org/demo.aspx?prep=CV6P0235

[Edited on 22-3-2019 by Loptr]

Boffis - 26-3-2019 at 09:00

I have prepared 1,4-butane-dithiol from 1,4-dibromobutane and either thiosemicarbazide or thiourea, this gives an odourless bis-isothiuronium bromide salt which can be decomposed with hydrazine solution to give the dithiol and either a diaminoguanidine or aminoguanidine salt respectively. The dithiol is an unfortunate byproduct but is easily extracted and recovered. It is certainly smelly but nothing like as bad as some of the lighter monothiols. I am going to try and convert it into a macrocyclic thioether. If you only want to prepare the dithiol you should use thiourea because its cheap and carry out the hydrolysis with sodium hydroxide. Neutralize excess alkali and extract with DCM.

Loptr - 26-3-2019 at 15:50

Quote: Originally posted by Boffis  
I have prepared 1,4-butane-dithiol from 1,4-dibromobutane and either thiosemicarbazide or thiourea, this gives an odourless bis-isothiuronium bromide salt which can be decomposed with hydrazine solution to give the dithiol and either a diaminoguanidine or aminoguanidine salt respectively. The dithiol is an unfortunate byproduct but is easily extracted and recovered. It is certainly smelly but nothing like as bad as some of the lighter monothiols. I am going to try and convert it into a macrocyclic thioether. If you only want to prepare the dithiol you should use thiourea because its cheap and carry out the hydrolysis with sodium hydroxide. Neutralize excess alkali and extract with DCM.


Thanks for the feedback! I was thinking about using thiosulfate.

I am in the middle of building a new lab with lots of ventilation where I can experiment more with things that give off smells and bad gases. In addition to a fume hood, imagine a whole house fan in a detached garage leading to a vent on the roof. I should be able to leave it on low to have constant extraction of corrosive gases that have always been an issue causing rust in the most unsightly places.

:cool:

[Edited on 27-3-2019 by Loptr]

Loptr - 27-3-2019 at 04:22

Different day, new post. That doesnt count as double posting does it?

Is there a benefit to using thiourea over thiosulfate?