Sustainable Triazine-Based Dehydro-Condensation Agents for Amide Synthesis

Abstract

Conventional methods employed today for the synthesis of amides often lack of economic and environmental sustainability. Triazine-derived quaternary ammonium salts, e.g., 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM(Cl)), emerged as promising dehydro-condensation agents for amide synthesis, although suffering of limited stability and high costs. In the present work, a simple protocol for the synthesis of amides mediated by 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and a tert-amine has been described and data are compared to DMTMM(Cl) and other CDMT-derived quaternary ammonium salts (DMT-Ams(X), X: Cl− or ClO4−). Different tert-amines (Ams) were tested for the synthesis of various DMT-Ams(Cl), but only DMTMM(Cl) could be isolated and employed for dehydro-condensation reactions, while all CDMT/tert-amine systems tested were efficient as dehydro-condensation agents. Interestingly, in best reaction conditions, CDMT and 1,4-dimethylpiperazine gave N-phenethyl benzamide in 93% yield in 15 min, with up to half the amount of tert-amine consumption. The efficiency of CDMT/tert-amine was further compared to more stable triazine quaternary ammonium salts having a perchlorate counter anion (DMT-Ams(ClO4)). Overall CDMT/tert-amine systems appear to be a viable and more economical alternative to most dehydro-condensation agents employed today.

Efficient Triazine Derivatives for Collagenous Materials Stabilization

“…With the intent to improve the environmental sustainability of the process, different nontoxic alcohols were used, such as ethanol and propan-2-ol, giving good even if slightly lower yields in amide III. Data reported in Table 1 show no significant difference between the alcoholic solvents used and the comparable data reported in literature with triazine condensation agents [ 46 ]. Further experiments were carried out in methanol, which has a lower boiling point and allows an easy recovery of the product.…”

“…According to a consolidated protocol reported in the literature [ 31 , 46 ], the first experiments to verify the activity of CDET and a tert -amine were carried out using as standard reaction the amidation of benzoic acid (I) with 2-phenylethylamine (II) ( Scheme 1 ).…”

“…According to literature data [ 44 , 46 , 47 ], counter anion exchange can favor the stability of triazine quaternary ammonium salts and thus improve their activity in condensation reactions. Raw et al and Kitamura et al report the synthesis and use of DMTMM(BF 4 ) and DMTMM(ClO 4 ) [ 47 , 48 ], while only one example is known of similar studies in the presence of in situ systems comparable to CDET/tert-amine [ 46 ]. Thus, further experiments were carried out to verify if counter anion exchange during condensation reaction could influence the reactivity of the CDET/tert-amine system.…”

“…Further experiments were carried out with CDET/ tert -amine systems to verify their efficiency as collagen cross-linking agents. According to literature [ 31 , 46 ], bovine collagen powder (BCP) was used as standard reference substrate for preliminary cross-linking (or tanning) tests.…”

A Novel Self-Assembly Strategy for the Fabrication of Nano-Hybrid Satellite Materials with Plasmonically Enhanced Catalytic Activity

“…Within the design strategy, we envisioned that the formation of covalent bonds between the primary amino groups on the AgNP@SiO 2 -NH 2 core and the carboxylate moieties on CdS@Pt QDs functionalised with MPA could be achieved by the use of the amide coupling reaction, activating the carboxylate of MPA with DMTMM. This reaction has been extensively used for the synthesis of peptides from amino acid precursors, combining, like in our case, primary amino groups and carboxylates to form amide bonds in aqueous media [ 25 , 26 , 27 ]. Controlling the pH of the solution is critical for this coupling reaction, and we ensured an optimal pH = 5.5 by using MES buffer (further details can be found in the Materials and Methods section).…”