N,N-Dimethylpyridin-4-amine (DMAP) based ionic liquids: evaluation of physical properties via molecular dynamics simulations and application as a catalyst for Fisher indole and 1H-tetrazole synthesis

Abstract

The last few decades have seen a rapid increase in the use of ionic liquids (ILs) as a green alternative to traditional solvents in organic synthesis. The use of ILs as catalysts has also increased in recent years.Herein we the report synthesis of new N,N-dimethylpyridin-4-amine (DMAP) based ionic liquids (ILs) as new and efficient catalysts for the facile synthesis of indoles (via Fischer indole synthesis), and 1H-tetrazoles (via click chemistry). The method is environmentally friendly, requiring only minimum catalyst loading (0.2 equiv. for Fischer indole synthesis). In the case of 1H-tetrazole formation (via click chemistry), the reaction was carried out under a solvent free environment. Moreover, thermal studies (TGA, DTG and DSC) of DMAP-ILs (2, 3) have also been carried out to elicit their stability for temperature dependent reactions. Application of molecular dynamics simulations provided valuable insights into the structural and transport properties of these ionic liquids. An MP2 method was applied to evaluate the stability of the compound via binding energy calculations.

Quinine based ionic liquids: A tonic for base instability

“…The quinine ionic liquids produced higher yields than traditional bases (Table 3 entries 9, 10) and quinine itself (Table 3 entry 8). This suggests that the molecular functionality of the catalyst is important and it does not act solely as a base.…”

“…Basic ionic liquids of greater stability can be prepared by locating basicity on the cation [5], usually on free Lewis basic sites. Examples of this class includes ionic liquids synthesised from diaminoalkanes [6] and 4-dimethylaminopyridine (DMAP) [7,8]. Diaminoalkane ionic liquids suffer from a lack of selective alkylation which complicates their synthesis.…”

“…A mixture of mono and dialkylated species can be formed which are difficult to separate [6]. DMAP ionic liquids have reduced basicity due to withdrawal of electron density from the Lewis base by the cation [7,8]. We have previously had some success stabilising basic ionic liquids by using binary ionic liquids containing small amounts of alkoxide anions [9], and by heterogenising phosphonium hydroxide ionic liquids within silica and titania gels via the sol-gel process [10,11].…”

Morpholinium and Piperidinium Based Deep Eutectic Solvents for Synthesis of Pyrazole‐5‐Carbonitriles, Indoles and Tetrazoles: Bulk Properties via Molecular Dynamics Simulations

“…In DES, the ionic liquids and HBDs are associated to each other via hydrogen bonded networks, molecular dynamics (MD) simulations were used to study these interactions. Moreover, macroscopic properties, like transport and thermodynamic behaviour, as well as microscopic properties such as density, viscosity and effect of non‐bonded interaction on structural framework of ILs were also extensively studied via molecular dynamics simulations ,. In literature, only a limited number of simulation studies on DES were reported, that mainly focus on the understanding of interactions, such as electrostatic and hydrogen bonding, that confer unique characteristics to DES .…”

“…Transport properties of DES mixtures are of great importance due to their diverse applications which are based on these properties. In our previous studies, on ionic liquids, transport properties were determined by calculating mean square displacement (MSD), which was then used to compute diffusion coefficients for cations and anions. A similar method was adopted herein to calculate MSD for morpholinium based cation MoBr (C 7 ), bromide ion and HBDs in different DES mixtures.…”