A potential greener protocol for peptide coupling reactions using recyclable/reusable ionic liquid [ $$\hbox {C}_{4}\hbox {-DABCO}][\hbox {N(CN)}_{2}$$ C 4 -DABCO ] [ N(CN) 2 ]

Abstract

Development of greener methodologies in synthetic organic chemistry has brought awareness in recent decades due to the ecological performance of green solvent media and catalytic systems. Here, we carried out the peptide bond formation reaction in one of the environmentally secure solvents, 'ionic liquids' in the presence of coupling reagent and in the absence of external base at room temperature, affording dipeptides in good to excellent yields.

Use of ionic liquids in amidation reactions for proteolysis targeting chimera synthesis

“…[38][39][40] The high efficiency of ILs as solvents and/or catalysts for the direct amidation of carboxylic acid and amine has already been reported in the literature, arousing considerable interest. [41][42][43][44][45][46][47][48] Additionally, ILs have been extensively used in pharmaceutical fields as reaction media for the synthesis of pharmaceutical compounds, 36,49,50 including non-steroidal anti-inflammatory drugs 51 and antiviral, 52,53 antimicrobial, 54,55 antimalarial, 56 and antitumor agents. 57,58 Here, a set of differently structured ILs were explored as reaction media for the synthesis of PROTAC 3a, including room-temperature ionic liquids (RTILs), such as 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide (…”

“…38–40 The high efficiency of ILs as solvents and/or catalysts for the direct amidation of carboxylic acid and amine has already been reported in the literature, arousing considerable interest. 41–48 Additionally, ILs have been extensively used in pharmaceutical fields as reaction media for the synthesis of pharmaceutical compounds, 36,49,50 including non-steroidal anti-inflammatory drugs 51 and antiviral, 52,53 antimicrobial, 54,55 antimalarial, 56 and antitumor agents. 57,58 Here, a set of differently structured ILs were explored as reaction media for the synthesis of PROTAC 3a , including room-temperature ionic liquids (RTILs), such as 1-methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide ([OMIM][NTf 2 ]), 1-methyl-3-octyl-imidazolium-hexafluorophosphate ([OMIM][PF 6 ]), 1-methyl-3-octyl-imidazolium-perchlorate ([OMIM][ClO 4 ]), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF 4 ]), 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF 6 ]) and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][NTf 2 ]) (Table 3, entries 4–9), and solid-state ionic liquids (SSILs), such as tributylmethylammonium methanesulfonate ([TBMA][MsO]) (Table 3, entry 10).…”

Liquid-Phase Peptide Synthesis (LPPS): A Third Wave for the Preparation of Peptides

“…Room-temperature ionic liquids (RTILs) are chemical entities characterized by negligible small vapor pressure, nonflammability, friction reduction, high chemical/thermal stability, and superior ionic conductivity and recyclability. , Ionic liquids (ILs), also referred to as “designer solvents”, can easily be fine-tuned depending on the choice of cations and anions, which allows them to phase separate from the organic and aqueous layers. − This property makes ILs ideal as reagents or solvents in green chemistry reactions. − ILs have found applications in peptide synthesis as a solvent (IL1–4), ,− additive (IL5), and soluble support (IL6–12). The use of ILs as solvent (IL1–4) has several advantages in peptide coupling in solution at rt due to the high solubility of amino acids and coupling reagents. ,− The most common ILs used for peptide synthesis are shown in Figure .…”

Green solvents for the formation of amide linkages

“…Finally, it was demonstrated that the developed catalytic system made up of ionic liquids and EDC•HCl could be recovered and reused up to four times without any significant loss of activity, further increasing the sustainability of the proposed protocol. 73 Another catalytic system has been successfully exploited by Zhang et al for the synthesis of versatile amides by the N-formylation and the N-acylation of aliphatic, aromatic, and heterocyclic amines. 74 Both transformations were carried out at 80 °C for 20 h and involved the use of 20% of a Brønsted acidic ionic liquid (BAIL) as both the metal-free catalyst and the reaction medium.…”