[thuybui]

Dear alls,

I am looking for references related to studying selective amidation of primary amine in the presence of secondary amines
Any help would be appreciated,

[Dan]

By coincidence I saw something similar yesterday when I was having a poke through the literature. This is not exactly what you're looking for but the net result is the same: I saw a paper where a system containing a secondary and primary amine was acetylated at both positions, and then the secondary amine was selectively de-acetylated  (methanolysis) to leave only the NHAc.

Presumably the RNHAc is less susceptible to basic methanolysis due to the relatively acidic proton, whereas R₂NAc is cleaved more easily.

see: Schueller, A. M.; Heiker, F-R; Carbohydrate Research, 1990, 203, 308-313 

[orgopete]

By coincidence I saw something similar yesterday when I was having a poke through the literature. This is not exactly what you're looking for but the net result is the same: I saw a paper where a system containing a secondary and primary amine was acetylated at both positions, and then the secondary amine was selectively de-acetylated  (methanolysis) to leave only the NHAc.

Presumably the RNHAc is less susceptible to basic methanolysis due to the relatively acidic proton, whereas R₂NAc is cleaved more easily.

see: Schueller, A. M.; Heiker, F-R; Carbohydrate Research, 1990, 203, 308-313 

Interesting! I was just discussing the mechanism for a base catalyzed hydrolysis of an amide. I used an unsubstituted amide as an example and when I wrote it on the board, I knowingly ignored the deprotonation of an amide to give the anion. I went directly to the carbonyl addition necessary for the hydrolysis to succeed.

I presume the deprotonation reaction I ignored may be responsible for a decreased rate of hydrolysis compared to an amide from a secondary amine.

[thuybui]

THank you very much Dan and orgopete .

[thuybui]

Dear Dan and orgopete,
I have looked over the mechanism of themanolysis of amides. The methanolysis capabality depends on the positive charge on carbon-carbonyl. With amide from secondary, the electron push of methyl group can cause the decrease of positive charge on C-carbonyl, which can decrease the methanolysis rate of this amide compared to the other. That is my opinion, could you please explain more.
What do you mean under basic methanolysis? What are the reagents? methanol or methylat or others?
I reaed in other article, the diamine was amidated in the presence of methanol solvent and then isopropanol. The yield is high and no by-product was detected. Is is difficult to understand. Could you explain more?
Please see:
General Papers ARKIVOC 2007 (xiii) 41-46
ISSN 1424-6376 Page 41 ©ARKAT USA, Inc.
An improved and commercially viable process for the preparation
of Alfuzosin hydrochloride
Manne Satyanarayana Reddy*a, Bairy Kondal Reddya, Chepyala Kista Reddyb,
Muppa Kishore Kumara, Srinivasan Thirumalai Rajana and Venkatesh Mummadia
aDepartment of Research and Development, MSN Laboratories Limited Survey No. 317 and 323,
Rudraram, Patancheru, Medak District – 502 329, Andhra Pradesh, India
bDepartment of Chemistry P.G College of Science Saifabad, Hyderabad, India