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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: jeremie on January 10, 2018, 06:04:55 AM

Title: Synthesis a thiazole
Post by: jeremie on January 10, 2018, 06:04:55 AM

I want to synthesis a Isobutylthiazole methyl ester by first a reaction of condensation with isovaleronitrile and cysteine (solvant=methanol) to make a isobutylthiazoline acid carboxylic. Then a esterification with methanol and EDCI/DMAP to make isobutylthiazoline methyl ester. And finally a radical polymerisation with DBU/BrCCL3 or MnO2 activated to make Isobutylthiazole methyl ester.

Some article make this in N2 atmopshere and purify between each step, but i just want my product (Isobutylthiazole methyl ester) regardless of the purity and yield. So can i do this in presence of air. I know that EDCI and DBU are air sensitive, but what happens if i don't do it in N2 atmosphere ? And what happens if I don't purify between each step ?

Thank you and sorry for my english !

Title: Re: Synthesis a thiazole
Post by: wildfyr on January 10, 2018, 06:17:53 AM
DBU isn't very oxygen sensitive in my hands, I never took steps to store it away from air. It will probably absorb water to some extent. I dried mine over sieves for a few days.

EDC is rather hydrolytically unstable, not very oxygen sensitive.

I think the N2 in the case of these reactions is more to create a dry system with positive pressure to keep water out of the reaction, not oxygen.

I would definitely suggest against trying to do this as "one pot' The amount of garbage you will end up with is likely very high, and unless you plan quite carefully, there can be a multitude of sideproducts, some of which may prevent you from forming any product at all.

Organic chemistry is hard enough with pure materials, take the extra time to purify, and you usually increase your odds of success by doing things under water and oxygen free conditions. You should use dry solvents for these reactions (especially the EDC coupling).

Caveat: Some reactions need a bit of oxygen or water to work, but these are exceptions, and neither reaction you describe seems likely to need such catalysts.
Title: Re: Synthesis a thiazole
Post by: jeremie on January 10, 2018, 07:03:10 AM
Thanks you a lot !

Do you think i can do my esterification whitout EDCI/DBU ?
Title: Re: Synthesis a thiazole
Post by: wildfyr on January 10, 2018, 04:27:04 PM
Certainly. There is DCC/DMAP, or even just Fischer esterification with methanol and catalytic sulfuric acid. For the Fischer, you could run it under Dean-Stark conditions, or reflux in a manner that the vapor condenses over molecular sieves before flowing back in, or use trimethylorthoformate as a continuous drying agent.

Isn't EDC usually done with NHS? I like EDC/NHS because you can just do a water wash to get the byproducts off as long as conversion is high. I've never done it with DBU.
Title: Re: Synthesis a thiazole
Post by: kriggy on January 11, 2018, 07:37:23 PM
YOu need the inert atmosphere becaues the cysteine might get oxidized  by air to form cystine.

You can easily do the esterification with DCC/DMAP but its way simple to just reflux your compound in methanol with cat. H2SO4. Or you can even start using cysteine methyl ester so you dont have to run the esterification
Title: Re: Synthesis a thiazole
Post by: jeremie on January 12, 2018, 08:57:32 AM
Yes indeed if i success my condensation of my nitrile and the cysteine, i will try with a cysteine methyl ester, that will be easier !
Thanks you !  ;D