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Topic: How to get rid of this byproduct  (Read 5275 times)

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Offline Moz29386

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How to get rid of this byproduct
« on: June 07, 2012, 03:24:39 PM »

Dear all,

Currently for the above reaction, I am carrying out a basic solvent extraction as follows:

8 mL of saturated NaHCO3 is added followed by 8 mL of saturated NH4Cl. The organic layer is then extracted and washed 3 times with 3x10 mL of saturated sodium chloride (brine). This is then dried with MgSO4 and then dried using a rotary evaporator to yield reddish crystals.

My problem is that the reddish crystals are caused by the COMU by product (which is water soluble) and my actual product should be white crystals.
Can anyone give me a decent protocol to get rid of these impurities? Maybe acid base wash??

Many thanks.


Many thanks.

Offline fledarmus

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Re: How to get rid of this byproduct
« Reply #1 on: June 07, 2012, 03:40:30 PM »
That product shouldn't be very water soluble at all, and all of the COMU products are. What are you using for an organic solvent in your extraction? And are you washing with water at all? Washing only with saturated salt solutions may keep your aqueous phases from removing anything from your organic phase.

Offline Moz29386

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Re: How to get rid of this byproduct
« Reply #2 on: June 07, 2012, 03:53:29 PM »
That product shouldn't be very water soluble at all, and all of the COMU products are. What are you using for an organic solvent in your extraction? And are you washing with water at all? Washing only with saturated salt solutions may keep your aqueous phases from removing anything from your organic phase.

Hi thanks for your reply

I am not washing with water at the moment.

I just add Sodium bicarbonate (saturated) and ammonium chloride (saturated) this gives me two layers. The organic layer is extracted and then dried with MgSO4. This then dried under reduced pressure using a rotary evaporator to give the result impure red crystals.

Offline djt

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Re: How to get rid of this byproduct
« Reply #3 on: June 07, 2012, 04:47:29 PM »
Is the above reaction a simplified representation of more elaborate substrates? Would it not be easier to make (or even buy) the benzoyl chloride and react with Et3N/benzylamine? However, if it is simplified I would do as fledarmus suggests.

Offline Moz29386

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Re: How to get rid of this byproduct
« Reply #4 on: June 09, 2012, 01:59:22 PM »
Is the above reaction a simplified representation of more elaborate substrates? Would it not be easier to make (or even buy) the benzoyl chloride and react with Et3N/benzylamine? However, if it is simplified I would do as fledarmus suggests.

I will be doing a benzoyl chloride reaction. I am looking at first improving the yield using this method.

There must be a method for COMU extraction but I cant seem to find it online :(

Offline discodermolide

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Re: How to get rid of this byproduct
« Reply #5 on: June 09, 2012, 02:07:36 PM »
Is the above reaction a simplified representation of more elaborate substrates? Would it not be easier to make (or even buy) the benzoyl chloride and react with Et3N/benzylamine? However, if it is simplified I would do as fledarmus suggests.

I will be doing a benzoyl chloride reaction. I am looking at first improving the yield using this method.

There must be a method for COMU extraction but I cant seem to find it online :(

What's wrong with using the acid chloride and doing a Schotten-Baumann in a two-phase system with NaOH. That reaction is a titration, in fact I think benzoyl chloride is very cheap. Why use all these fancy expensive reagents and then run into problems with the work-up?

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Offline Moz29386

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Re: How to get rid of this byproduct
« Reply #6 on: June 09, 2012, 04:44:19 PM »
Is the above reaction a simplified representation of more elaborate substrates? Would it not be easier to make (or even buy) the benzoyl chloride and react with Et3N/benzylamine? However, if it is simplified I would do as fledarmus suggests.

I will be doing a benzoyl chloride reaction. I am looking at first improving the yield using this method.

There must be a method for COMU extraction but I cant seem to find it online :(

What's wrong with using the acid chloride and doing a Schotten-Baumann in a two-phase system with NaOH. That reaction is a titration, in fact I think benzoyl chloride is very cheap. Why use all these fancy expensive reagents and then run into problems with the work-up?



There's nothing wrong with it all.

Basically, this reaction is a basic platform for optimising the conditions for other reactions I will carry out.

I am doing a fragment based drug discovery method and some of the fragments have this amide and carboxyl function with complicated side chains. I could use thionyl chloride for the substituted carboxylic acids but then that means I would have to go through further procedures to obtain that. In addition to this, the lachrymatory nature of the benzoyl chloride makes it slightly unpractical.

I am just trying to fix this method first without giving up.

I've looked at Sigma Aldrich website and they dont have a protocol for the extraction.. so I'm asking here for help.


Offline discodermolide

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Re: How to get rid of this byproduct
« Reply #7 on: June 09, 2012, 08:25:56 PM »
Is the above reaction a simplified representation of more elaborate substrates? Would it not be easier to make (or even buy) the benzoyl chloride and react with Et3N/benzylamine? However, if it is simplified I would do as fledarmus suggests.

I will be doing a benzoyl chloride reaction. I am looking at first improving the yield using this method.

There must be a method for COMU extraction but I cant seem to find it online :(

What's wrong with using the acid chloride and doing a Schotten-Baumann in a two-phase system with NaOH. That reaction is a titration, in fact I think benzoyl chloride is very cheap. Why use all these fancy expensive reagents and then run into problems with the work-up?



There's nothing wrong with it all.

Basically, this reaction is a basic platform for optimising the conditions for other reactions I will carry out.

I am doing a fragment based drug discovery method and some of the fragments have this amide and carboxyl function with complicated side chains. I could use thionyl chloride for the substituted carboxylic acids but then that means I would have to go through further procedures to obtain that. In addition to this, the lachrymatory nature of the benzoyl chloride makes it slightly unpractical.

I am just trying to fix this method first without giving up.

I've looked at Sigma Aldrich website and they dont have a protocol for the extraction.. so I'm asking here for help.



I appreciate that, but if you get a hit and later on the compound lands in chemical development the first thing they will do is make the acid chloride and do a Schotten-Baumann, I know I've been there and done just that!
Anyway try adding some active charcoal when you re-crystalize the product. Filter while hot and let the product crystallize.You probably only have traces present. What about looking in the original literature where this coupling agent was described and send them an e-mail?

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Offline fledarmus

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Re: How to get rid of this byproduct
« Reply #8 on: June 11, 2012, 08:17:53 AM »
The side products of your reaction, while soluble in water, are not soluble in saturated salt solutions. Your product, while slightly soluble in water, would be much more soluble in an organic solvent like ether or ethyl acetate. Since you haven't mentioned a solvent, I assume you are running the reaction neat?

I would start my workup by diluting with either ethyl acetate or ether, wash with water to remove the COMU decomposition products, then wash with less-than-saturated solutions of sodium bicarbonate (to remove unreacted benzoic acid) and ammonium chloride or HCl (to remove unreacted benzylamine). Then strip off the solvent to recover what should be much cleaner product.

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