N-Alkylated 1,4-Diazabicyclo[2.2.2]octane–Polyethylene Glycol Melt as Deep Eutectic Solvent for the Synthesis of Fisher Indoles and 1H-Tetrazoles

Abstract

1,4-Diazabicyclo[2.2.2]octane (DABCO)-based ionic liquids (ILs) 2–4 were synthesized by the N-alkylation of DABCO using alkyl halides of varying chain lengths (C 2 , C 5 , and C 7 ). The N-alkylated DABCO-ILs were mixed with polyethylene glycols (PEGs) of varying molar masses as hydrogen bond donors (HBDs) to prepare new deep eutectic solvents (DESs). These DABCO–PEG-based DESs were successfully employed for the synthesis of a variety of indoles 7a–7h (by Fischer indole synthesis) and 1 H -tetrazoles 9a–9i (by click chemistry). For comparison, DESs of DABCO-ILs with different alcohols (as HBD) were also prepared and investigated for the synthesis of indoles. Although comparable yields were observed in DES-containing alcohols and PEGs, the use of PEG as HBD in DES (as an alternative to alcohols) provides a much safer, nonvolatile, and environmentally benign reaction medium for synthetic reactions. The first successful application of PEG-polymer-based DES as benign reaction media for organic syntheses offers exciting opportunities to be explored in the realm of green synthesis.

OPLS Force Field for Choline Chloride-Based Deep Eutectic Solvents

“…Accordingly, multiple fields have benefitted from their use, including biodiesel production, gas separation, , materials, , extractions, nanotechnology, and electrochemistry . As a medium for chemical reactions, DESs also possess numerous advantages, but are only beginning to emerge as potential alternatives to organic solvents. − DESs are made by mixing together a solid quaternary ammonium salt and a neutral hydrogen bond donor (HBD) and, like ionic liquids, often have melting points below 100 °C. While many combinations are available, DESs are frequently composed of the cost-effective choline chloride ion pair and an organic hydrogen bond donor such as urea or glycerol at ratios of 1:1, 1:2, or 1:3 (Figure and Table ).…”

Synthesis of 5‐Substituted‐1H‐Tetrazoles from Nitriles and Azides in a Betaine‐Diol‐Based Deep Eutectic Solvent

“…When acetate-based catalysts, such as Zn(OAc) 2 , Cu(OAc) 2 , and NH 4 OAc, were employed, the yield obtained was unsatisfactory compared to that obtained with the ZnCl 2 catalyst (Table 1, entries [11][12][13].…”

“…heterocyclic compounds, such as 1 j-1 n, afforded a good yield of the 5-substituted tetrazoles after 12 h (Table 2, entries [10][11][12][13][14]. However, the reaction of the less reactive substrates, such as cycloaliphatic or aliphatic nitriles 1 o and 1 p, with NaN 3 in DES did not proceed (Table 2, Entry 15 and 16).…”

“…In particular, Xie and co‐workers developed a synthetic method of 5‐substituted‐1H‐tetrazoles in the presence of molten tetrabutylammonium bromide (TBAB), which acts as both solvent and catalyst [11] . Moreover, Ghumro and co‐workers developed 1,4‐Diazabicyclo[2.2.2]octane (DABCO)‐based ionic liquids (ILs) with PEG 400 and employed them for the synthesis of a variety of tetrazoles [12] . Moin and co‐workers also reported the combination of morpholinium‐/piperidinium‐based ILs with diethylene glycolafforded good yields for tetrazoles [13] .…”

Piperidinium‐Based Deep Eutectic Solvents: Efficient and Sustainable Eco‐Friendly Medium for One‐Pot N‐Heterocycles Synthesis

“…[8] These DES are usually prepared by mixing organic quaternary nitrogen containing halide salts (cations and anions containing ionic liquids and quaternary ammonium salts) mixed with hydrogen bond donors (HBDs) species in which hydrogen attach with highly electronegative atoms as compared to hydrogen like oxygen and nitrogen, thus the partially positive hydrogens of hydrogen bond donor species interact with anions of ionic liquids forming an eutectic mixture. [7,9] IL based DES have multidimensional significance for organic synthetic chemistry, such as low melting point, high boiling points, liquid or molten state at room temperature, catalytic activity, low or no evaporation rate, high thermal stability, tunable miscibility, efficient recycling ability, non-flammability, and harmless for human health and environment; these qualities make ionic liquids based deep eutectic solvents as ideal green solvents. [7,8,10,11] Many recent studies have reported that DES are environment friendly so that they have very low toxicity level and can be made to be biodegradable.…”