An efficient mechanochemical synthesis of amides and dipeptides using 2,4,6-trichloro-1,3,5-triazine and PPh₃

Abstract

Scheme 1 Proposed mechanism for amidation mediated by TCT-PPh 3 system. This journal is

A high‐efficient method for the amidation of carboxylic acids promoted by triphenylphosphine oxide and oxalyl chloride

“…The product (0.81 g, 72% yield) was obtained as a white solid; mp 154.1‐155.0°C [Duangkamol et al . 153‐154°C]; 1 H NMR (500 MHz, CDCl 3 ): δ 7.89 (d, J = 7.4 Hz, 2H), 7.75 (s, 1H), 7.56 (d, J = 7.3 Hz, 3H), 7.51 (t, J = 7.5 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H); 13 C NMR (125 MHz, DMSO) δ 165.5, 156.0, 135.5, 132.7, 131.8, 128.8, 128.0, 122.4, 114.2, 55.6; HRMS (FT ICR‐MS) m/z: [M+H] + calcd for C 14 H 13 NO 228.10191; found 228.10134.…”

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

“…Indeed, liquid reaction mixtures enable efficient agitation when using a conventional batch reactor equipped with either magnetic stirring bar or impeller, and automated handling such as pumping and filtration. Since Lamaty and co-workers have shown in their seminal work that peptide synthesis could be performed in a ball-mill (BM) [9], various solvent-free or solvent-less peptide synthesis strategies have been developed [10][11][12][13][14][15][16][17]. While these approaches enable to circumvent the use of toxic solvents and bases [18][19][20], no comparison between ballmilling and conventional approaches was performed, discussed and communicated.…”

Making Solid‐Phase Peptide Synthesis Greener: A Review of the Literature

“…Boc removal was done by using gaseous HCl, thus avoiding solvent use throughout. Other mechanochemical syntheses of dipeptides by using 2,4,6‐trichloro‐1,3,5‐triazine and PPh 3 under solvent‐drop grinding conditions, synthesis of N ‐protected amino acids in the absence of solvents, and the synthesis of α,β‐ and β,β‐ dipeptides from β‐UNCAs ( N ‐urethane‐protected N ‐carboxy anhydrides) in solvent‐free conditions have also been reported, thus making the use of ball milling an interesting and environmentally benign alternative to the standard peptide synthesis protocol.…”

“…Boc removal was done by using gaseous HCl, thus avoiding solvent use throughout. Otherm echanochemicals yntheses of dipeptides by using 2,4,6-trichloro-1,3,5-triazine and PPh 3 under solvent-drop grinding conditions, [22] synthesis of N-protected amino acids in the absence of solvents, [23] and the synthesis of a,b-a nd b,b-d ipeptides from b-UNCAs( N-urethane-protected N-carboxy anhydrides) in solvent-freec onditions [24] have also been reported, thus making the use of ball milling an interesting and environmentally benign alternative to the standardp eptides ynthesis protocol. Morales-Sernas et al have employed heterogeneous catalysts such as hydrotalcite minerals in the presence of WSCD (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide) and HOBt and by using CH 2 Cl 2 to synthesize peptides.…”