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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: Xboss on October 23, 2009, 02:37:59 PM

Title: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on October 23, 2009, 02:37:59 PM

R-NH2 + Cl-SO2-Ar-NHCOCH3 ------> R-NH-SO2-Ar-NHCOCH3


here the solvents i used where ... Acetic anhydride and Pyridine ... i have one article which says pyridine alone isnt strong enough to help the removal of proton as HCl quickly ... but when used with ac. anhyd. it forms a "N-acetyl pyridium complex" .. since the acetate ion is a comparatively stronger base


WHAT THE HECK IS A "N-acetyl pyridium complex" ???

i have tried my BEST to structure out the mechanism without any success ..



PLEASE HELP ME GUYSSSSSSSS !!!!

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on October 23, 2009, 04:01:33 PM

Correcton .. its N-acetyl pyiridinium complex ...


btw for the info .. i'm a research student ... doing my masters in med chem ... My thesis defense is in ten days .. please help me .. this mechanism will be helpful .. thanks

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: dudeman on October 23, 2009, 04:19:36 PM

you need to edit your post. dont *Ignore me, I am impatient* your topic with another reply.

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Arctic-Nation on October 23, 2009, 04:47:44 PM

An N-acetyl pyridinium is a pyridine with an acyl (CH₃CO group attached to the nitrogen atom (any N-substituted pyridine compound is called a pyridinium). However, I do not know why you need to have acetic anhydride as a co-solvent. Pyridine in itself is a stronger base than acetate by about half an order of magnitude.

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on October 24, 2009, 03:11:05 AM

Thanks for the info ...


anyways ... When i used just pyridine as a solvent or pyridine + a neutral solvent ... the reaction took 6-8 hours to complete.... while when i used Acetic Anhydride and pyridine together ...


the reaction was completed within 2 hours and that too on a waterbath ...

Melting points confirmed that products achieved by both the methods were the same ... !!!

thank you for responding ...

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: movies on October 24, 2009, 03:19:55 PM

Are you certain that you got the right product?  Generally acetic anhydride + primary amine leads to acetamide pretty rapidly.

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on October 24, 2009, 03:28:36 PM

thanks for replying ... and yes i am sure .. cos as i said .. prepared a known compound by the above procedure and verified it by comparing the melting point .. and by IR data ..

but thats a very neat question i can expect during my thesis defense ... but i dont know how the frame out this answer properly .. as well as the mechanism !!!

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on November 02, 2009, 10:31:36 AM

okk ... after devouring books after books ... this is what happens ..


the first step is dissolving the amine in pyridine ... followed by addition of Acetic anhydride and the sulfonyl chloride ...  now usually the amine reacts with ac. anhy. to form acetamide ... but N on pyridine being more electronegative ... it attacks the carbonyl atom .. to form N-acetyl pyridinium complex ... thats ----> Pyr-N-COCH3 ...


that leaves CH3COOˉ .. Which indeed is a better base than Pyridine ... and abstracts the H from NH2 ... and forms ...

R-NH-SO2-Ar-NHCOCH3

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: movies on November 02, 2009, 06:10:16 PM

OAc^– is a stronger base than pyridine??

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: Xboss on November 03, 2009, 10:21:04 PM

indeed it is . pyridine itself is a weak base ...


as well as Ch3COOH is a weak acid ..

Title: Re: Synthesis of Sulfonamides using pyridine + Acetic anyhdride (HELP !)
Post by: movies on November 04, 2009, 01:30:52 PM

In water, the pK_a of acetic acid is 4.76, the pK_a of pyridinium (protonated pyridine) is 5.17, so in water solvent pyridine is the stronger base.

In what solvent is this reaction carried?