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Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
An Efficient, One-Pot Transamidation of 8-Aminoquinoline Amides Activated by Tertiary-Butyloxycarbonyl
Wengang Wu1, Jun Yi2, Huipeng Xu3
1College of Chemistry, Chemical Engineering and Materials Science of Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu 215123, China. 20155209006@suda.edu.cn.
Abstract:
The efficient, one-pot access to the transamidation of 8-aminoquinoline (8-AQ), notorious for its harsh removal conditions, has been widely employed as an auxiliary in C⁻H functionalization reactions due to its strong directing ability. In this study, the facile and mild Boc protection of the corresponding 8-AQ amide was critical to activate the amide C(acyl)⁻N bond by twisting its geometry to lower the amidic resonance energy. Both aryl and alkyl amines proceeded transamidation in one-pot, user-friendly conditions with excellent yields.
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Preparation of Amides
The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
Subsequently, the amine acts as a nucleophile that attacks the acylating agent to form a tetrahedral intermediate. In the...
Nomenclature of Secondary and Tertiary Amines
Amides to Carboxylic Acids: Hydrolysis
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Amines to Amides: Acylation of Amines
Next, the second equivalent of amine serves as a Brønsted base and deprotonates the quaternary...
Acid Halides to Amides: Aminolysis
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...

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