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Topic: Problem with synthesis of a ether from a urea-alcohol.  (Read 254 times)

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Offline rawa04

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Problem with synthesis of a ether from a urea-alcohol.
« on: November 10, 2020, 04:01:51 AM »
Hello.

During a synthesis project (in my master thesis) I have a problem forming an ether from an alcohol, and tert-butylbromoacetat.

I have synthesized an aliphatic unsymmetrical urea, with a primary alcohol. My next step is to synthesize (CH3(CH2)8-NH-CO-NH-(CH2)4-O-CH2-COOtbU.

The unsymmetrical urea is insoluble in most solvent. So I have tried using a two-phase system(50 % NaOH in water/toluene), with a phase-transfer compound. I have a huge problem with the formation of emulsion during work up, and have tried  a lot to fix the problem, but nothing seems to work.

The best i have done is  a 10 % yield.

I was wondering if you guys have any tips for formation, probably some other reactions?

I think my main problem is the solubility of the urea compound.

All tips willl help

Thanks!

Offline rawa04

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #1 on: November 10, 2020, 06:05:47 AM »
I may have posted this on the wrong forum, can moderator please transfer it to right forum?

Offline rolnor

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #2 on: November 10, 2020, 07:41:00 AM »
I think its better to make the urea as the last step. You can make a azide and alkylate this with the bromo-t-butylester, then make a aza-Wittig reagent from the azide and PPh3P, react this with CO2 and the resulting isocyanate with nonylamine to make the urea. These are very good steps, fast, high yield. The three last steps is made one-pot.

Offline rawa04

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #3 on: November 10, 2020, 09:26:38 AM »
Dear Rolnor,

I have also tried to make the urea in the last step, starting from 4-amino-butanol, first protecting the amine with boc, then reacting it with tert-butyl-bromoacetat, and lastly reacting it with CDI to form the amide, agian this gave a lot of biproducts, and it did not give my any excellent yield, mostly 10-20 %.

I will try to find the reagents for your suggestion.

Thanks for the help, and if you have any other ideas please tell me.


Offline rolnor

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #4 on: November 10, 2020, 12:54:56 PM »
To have a Boc-protected amine is not good, the amide-nitrogen is also possible to de-protonate and this can give by-products. With an azide you dont have these problems. It is really not so good to alkylate with a bromo-t-butylester, the ester have acidic alpha-protons that can interfere and the ester can also react with a alkoxide. You could have a unsaturated alkylhalide and then oxidize/cleave it to an carboxylic acid and convert it to a t-butylester.

Offline rawa04

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #5 on: November 11, 2020, 04:31:38 AM »
Dear Rolnor,

I have written your suggestion, and i canĀ“t find the ether group, what I want is  R-NH-CO-NH-(CH2)4-O-CH2-COOtbU,


I may have overseen it, but how do you suggest the ether bond is form the azo-wittig reaction

Offline rolnor

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Re: Problem with synthesis of a ether from a urea-alcohol.
« Reply #6 on: November 11, 2020, 04:48:06 AM »
If you have 1-bromo-4-butanol you make the azide with sodiumazide/DMF, then you alkylate this with allylbromide, then make the aza-Wittig, then cleave the allyl group to carboxylic acid.

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