Catalytic and Sustainable Amide Bond Formation using a DABCO/Dichlorotriazine System

Abstract

Amides are one of the most important functional groups in organic chemistry and play essential roles in both the pharmaceutical industry and life sciences. However, due to the natural reactivity of carboxylic acids and amines, their direct coupling is challenging and often leads to reactions that are not atom-economic and produce large amounts of nonrecoverable by-products. Despite the impressive number of coupling reagents available, sustainable methods for amide bond formation are still needed. To address this challenge, a new catalytic approach for the direct preparation of amides from carboxylic acids and amines is reported here. This method combines organocatalysis with a substoichiometric amount of activating agent under mild conditions (open air, room temperature, green solvents). This method was applied with good efficiency on a wide range of substrates, without epimerization of chiral stereocenters and on SPPS.

A Catalytic Approach for the Synthesis of Peptide−Oligonucleotides Conjugates in Aqueous Solution or On‐Column

“…Our investigation began with the application on CPG-beads of our previously reported reaction conditions for practical supported synthesis. [39] Optimization of the reaction was performed on a hexathymidine DNA sequence modified at its 5' extremity by an amino group introduced using a commercially available 5'-amino modifier phosphoramidite (ODN1) and FmocÀ Leucine as the acid partner (see ESI for details). The carboxylic acid was preactivated using our new CDMT/DABCO system prior addition on the CPG beads.…”

“…[34] In the context of small organic molecules chemistry, sustainable methods for the formation of amides are particularly required considering the high environmental impact of classical methods involving low atom economy activating agents such as HATU or EDCI. Greener approaches involving mechanochemistry, [35][36][37] neat reactions [38] or catalysis [39][40][41][42][43] have also been recently developed. The nature of the solvents used is also an important parameter and amide synthesis in water represents an alternative to highly toxic and hazardous solvents that are commonly used.…”

“…Recently, we reported a catalytic and sustainable approach for the direct coupling between an amine and a carboxylic acid using DABCO as catalyst and 2,4-dichloro-6-methoxy-1,3,5triazine (DCMT) as substoichiometric activating agent. [39] Considering the advantages of this catalytic method using cheap and non-hazardous reactants, we set out to explore its extension to the preparation of POCs both on solid support in anhydrous conditions and in aqueous conditions using in each case 2chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and catalytic amounts of DABCO (Figure 1b).…”

Synthesis and Estimation of the Insecticide and Antibacterial Activities for Some New Amide Derivatives

“…The amide functional group is one of the most important in organic synthesis, with a wide range of applications in different fields. For example, therapeutic peptides have demonstrated their effectiveness in pharmaceutical chemistry [2], and approximately 25% of marketed drugs and two-thirds of drug candidates contain at least one amide function. Furthermore, the use of amides in material and polymer chemistry is of great importance, such as for OLED applications, dentistry, or nanocomposites.…”